Calistru, Ana Maria; Lisboa, Carmen; Cruz, Maria João; Delgado, Luis; Poças, Licínio; Azevedo, Filomena
Urticarial vasculitis is characterized clinically by urticaria-like skin lesions and histologically by leukocytoclastic vasculitis. It may be idiopathic or associated with various conditions such as infections, hematologic disorders, drugs, and connective tissue diseases, primarily systemic lupus erythematosus; an association with mixed connective tissue disease (MCTD) has rarely been reported. We present a case of hypocomplementemic urticarial vasculitis in a patient with MCTD that responded to hydroxychloroquine after a period of corticosteroid dependence.
... IgA Vasculitis (Henoch-Schönlein Purpura) Hypersensitivity Vasculitis (Leukocytoclastic) Kawasaki Disease Microscopic Polyangiitis Polyarteritis Nodosa Polymyalgia Rheumatica Takayasu’s Arteritis ...
Estrada Rodríguez, J L; López Serrano, C; Belchi Hernández, J; Florido López, F; Martínez Gómez, W
A patient with hypocomplementemic urticarial vasculitic syndrome (HUV) is presented. This is an immunological pathology, limited to skin or multisystemic, that requires a differential diagnosis with erythematosus systemic lupus on the same occasions. The ever-present symptom is skin participation, such as urticaria-angioedema or fixed exanthema; biopsy shows necrotizing venulitis with polymorphonuclear infiltration and leukocytoclastic powder. Typical laboratory data are: diminished C3, C4 and C1q; C1 inhibition can be low or normal; the more characteristic finding is the presence of C1q associated immunocomplexes. Leukocytoclastic necrotizing vasculitis was found in the skin biopsy. During the course of illness (three years) the patient presented moderate cutaneous symptoms and asthma, without other systemic participation. During this period, antihistamines and, occasionally, corticoids were administered with improvement. Moreover, the patient presented urticaria related to ampicillin ingestion, and furthermore, the presence of anaphylaxis to beta-lactam was diagnosed in vivo and specific IgE was found in the laboratory study. This feature was previously observed by other authors; however, we cannot determine why the IgE-mediated allergy to beta-lactam and a complement pathology like HUV are related.
Urticaria is common in children. Urticarial vasculitis (UV) is a potentially more serious, rare variant. The youngest reported case was 12 months of age. A systemically well, 19-month-old girl presented with her mother who was concerned about the development of a rash. On presentation, the child had normal vital signs, was alert, and was well and playing with toys. There was a widespread urticarial rash (raised, pruritic, and erythematous) that was most apparent on the trunk with minimal rash on the legs. Overlying this urticarial rash in a similar distribution was a blotchy, palpable purpuric rash and associated hyperpigmentation. Investigations revealed a normal level of haemoglobin, white cells, platelets, and electrolytes. Renal function, international normalised ratio, and activated partial thromboplastin time were all normal. There was no blood or protein in the urine. The erythrocyte sedimentation rate was mildly elevated at 19 mm/hour. Complement results (including C1q) obtained later were normal. This case is striking not only because of the rarity of UV in children but also due to the unique diagnostic and prognostic challenges that it raises. PMID:27818822
Vasculitis; Systemic Vasculitis; Behcet's Disease; CNS Vasculitis; Cryoglobulinemic Vasculitis; Eosinophilic Granulomatosis; Temporal Arteritis; Wegener Granulomatosis; Henoch-Schoenlein Purpura; Microscopic Polyangiitis; Polyarteritis Nodosa (PAN); Takayasu's Arteritis; Urticarial Vasculitis
Bock, Vanessa L; Friedlander, Michael; Waring, Dale; Kossard, Steven; Wood, Glenda K
Hormonal therapy with either tamoxifen or aromatase inhibitors is commonly used to treat women with breast cancer in both the adjuvant and recurrent disease setting. Cutaneous adverse reactions to these drugs have been rarely reported in the literature. We report an unusual case of urticarial vasculitis following the aromatase inhibitor anastrozole that localised to the unilateral trunk and mastectomy scar, and review the literature on the cutaneous adverse effects of hormonal therapy for breast cancer.
Cryoglobulinemic Vasculitis (CV); Drug-induced Vasculitis; Eosinophilic Granulomatosis With Polyangiitis (EGPA); IgA Vasculitis; Isolated Cutaneous Vasculitis; Granulomatosis With Polyangiitis (GPA); Microscopic Polyangiitis (MPA); Polyarteritis Nodosa (PAN); Urticarial Vasculitis; Vasculitis
Vasculitis; Behcet's Disease; CNS Vasculitis; Cryoglobulinemic Vasculitis; Eosinophilic Granulomatosis With Polyangiitis (EGPA); Churg-Strauss Syndrome (CSS); Granulomatosis With Polyangiitis (GPA); Wegener's Granulomatosis; IgA Vasculitis; Henoch-Schoenlein Purpura (HSP); Microscopic Polyangiitis (MPA); Polyarteritis Nodosa (PAN); Takayasu Arteritis (TAK); Urticarial Vasculitis; Systemic Vasculitis
There are a number of vasculitides that are not confined to a specific vessel size, do not have characteristic features, and/or are not secondary to another disease. Most of these vasculitides are rare in childhood. Behçet disease is representative of this group as it involves vessels of any size on both the arterial and venous side. In addition to renal vascular involvement, Behçet disease may involve the kidney through glomerulonephritis, secondary amyloidosis and, rarely, tubulointerstital involvement. Vasculitis secondary to infections, malignancy, and drugs are not common among children. However, vasculitis may be associated with a number of rheumatic diseases in childhood and the auto-inflammatory syndromes (periodic fever syndromes). Auto-inflammatory syndromes are diseases characterized by periodic attacks of clinical and laboratory inflammation. Studies carried out during the past decade have provided valuable information on the mechanism of inflammation and innate immunity in general. This group of vasculitides is associated with secondary amyloidosis of the kidney if not treated. Hypocomplementemic urticarial vasculitis is an interesting vasculitic disease with frequent kidney involvement. Here, we introduce the reader to the wide scope of these diseases; although rare, such diseases represent a challenge to the nephrologist.
... damage to blood vessels, primarily in the skin. Causes Hypersensitivity vasculitis is caused by an allergic reaction to ... affects people older than age 15. Often, the cause of the problem cannot be found even with ... vasculitis may look like necrotizing vasculitis , which can ...
Weiss, Pamela F
Childhood vasculitis is a challenging and complex group of conditions that are multisystem in nature and often require integrated care from multiple subspecialties, including rheumatology, dermatology, cardiology, nephrology, neurology, and gastroenterology. Vasculitis is defined as the presence of inflammation in the blood vessel wall. The site of vessel involvement, size of the affected vessels, extent of vascular injury, and underlying pathology determine the disease phenotype and severity. This article explores the classification and general features of pediatric vasculitis, as well as the clinical presentation, diagnostic evaluation, and therapeutic options for the most common vasculitides.
... RV) is an unusual complication of longstanding, severe rheumatoid arthritis. The active vasculitis associated with rheumatoid disease occurs ... a manifestation of “extra-articular” (beyond the joint)rheumatoid arthritis and involves the small and medium-sized arteries ...
Brown, Kevin K.
Pulmonary vasculitis describes a number of distinct disorders that are pathologically characterized by the destruction of blood vessels. The clinical manifestations of each disorder are defined by the size, type, and location of the affected vasculature. The clinical approach to these disorders rests upon an astute clinician considering the diagnosis and identifying the specific patterns of clinical, radiologic, laboratory, and pathologic abnormalities. Lung involvement is most commonly seen with the primary, idiopathic, small-vessel, or antineutrophil cytoplasmic antibody–associated vasculitides; Wegener's granulomatosis, microscopic polyangiitis, and Churg-Strauss syndrome. However, primary, idiopathic medium and large-vessel vasculitis, primary immune complex–mediated vasculitis, and secondary vasculitis are all capable of presenting with lung involvement. In this article, we focus on the more common, antineutrophil cytoplasmic antibody–associated disorder, vasculitides. PMID:16493151
... Alert Bracelet More information on CNS Vasculitis Patient Information Book Vasculitis Terms A – Z VF Medical Consultants YouTube Education ... Mission The Vasculitis Foundation supports and empowers ...
Treatment of vasculitis depends on etiology and type of vasculitis. Gluccocorticoids are drug of choice in treatment of systemic vasculitis. While in vasculitis of large vessels treatment with gluccocorticoids is often sufficient, in ANCA associated vasculitis almost always intial combination of gluccocorticoids and immunosupresive drugs (cyclofosfamide in severe forms; azatioprin and metotrrexate in moderate disease) is needed. Maintance therapy of ANCA associated vasculitis is methotrexate or azatioprin. From biologic therapy, in gigantocellular vasculitis treatment with tocilizumb has a great expectation, while in ANCA associated vasculitis recently rituximab was approved by regulatory agencies, and it is nontinferior to cyclofosfamide in induction of remission and prefarable in relapsing disease.
Wegeners Granulomatosis (Granulomatosis With Polyangiitis); Microscopic Polyangiitis; Churg Strauss Syndrome (Eosinophilic Granulomatosis With Polyangiitis); Polyarteritis Nodosa; Takayasu Arteritis; Primary CNS Vasculitis; Unclassified Vasculitis
Gusdorf, Laurence; Bessis, Didier; Lipsker, Dan
Abstract Neutrophilic urticarial dermatosis (NUD) resembles urticaria clinically but is a neutrophilic dermatosis histopathologically. The majority of patients with NUD have an underlying systemic condition, mainly, autoinflammatory disorders such as cryopyrin-associated periodic syndromes, Schnitzler syndrome, and adult-onset Still disease, but a few also have systemic lupus erythematosus (LE). Here, we confirm these data and we report relevant clinical and histopathological data of 7 patients with LE and NUD. We retrospectively retrieved the medical records of all patients with LE in whom skin biopsy showed NUD in registers of Strasbourg and Montpellier University hospitals since 2000. All were female and aged between 13 and 45 years. Skin lesions were typically rose or red macules or slightly elevated papules occurring in a wide distribution. Individual lesions resolved within 24 hours and were not or only slightly itchy. Every patient had associated signs, most of the time polyarthritis and/or fever. NUD was the presenting mode of LE in 2 patients. NUD was misdiagnosed as a classic lupus flare and led to therapeutic intensification with the introduction of immunosuppressive drugs in 4 patients. Histopathological findings consisted of intense neutrophilic interstitial and perivascular infiltrate with leukocytoclasia and without fibrinoid necrosis of vessel walls. Direct immunofluorescence testing showed a lupus band in 4 patients. Antinuclear antibodies were always positive, anti-dsDNA antibodies were positive in 5 patients, and anti-Ro/SSA antibodies in 6 patients. Immunosuppressive drugs such as prednisone, hydroxychloroquine, mycophenolate mofetil, and methotrexate were never effective to treat NUD. Antihistamines were effective in 1 patient and dapsone or colchicine was effective in 5 patients. NUD is not exceptional in patients with systemic LE and is easily misdiagnosed as an acute LE flare. Furthermore, we show that conventional immunosuppressive LE
Sharma, Poonam; Sharma, Sanjeev; Baltaro, Richard; Hurley, John
The systemic vasculitides are characterized by inflammation of blood vessel walls. Vessels of any type, in any organ can be affected, resulting in a broad spectrum of signs and symptoms. The heterogenous nature of vasculitides presents a diagnostic challenge. The American College of Rheumatology classification criteria and the Chapel Hill Consensus Conference nomenclature are the most widely used to distinguish different forms of vasculitis. The Chapel Hill Consensus Conference nomenclature defines 10 primary vasculitides based on vessel size (large, medium, and small). The diagnosis relies on the recognition of a compatible clinical presentation supported by specific laboratory or imaging tests and confirmatory histology. Antineutrophilic cytoplasmic antibody testing has been of particular benefit in defining a subgroup of small vessel vasculitides. Treatment is based on clinical presentation and the pattern of organ involvement. Glucocorticoids are the primary treatment for many forms of vasculitis. Additional immunosuppressive agents, including methotrexate and cyclophosphamide, are sometimes required. Newer approaches, such as the use of anti-tumor necrosis factor or B cell therapies, are being tried in resistant cases. Patients can experience considerable treatment-related toxicity, especially infection from immunosuppressive therapy and adverse effects from steroids (e.g., osteoporosis, diabetes mellitus, cataract). Vitamin D and calcium prophylaxis are recommended in patients on long-term steroid therapy.
... other signs develop that point to arteritis. Mostly Medium Vessel Vasculitis These types of vasculitis usually, but not always, affect the body’s medium-sized blood vessels. Buerger's Disease Buerger's disease , also ...
Casella, G; Bronzino, B; Cutrino, L; Montani, N; Somma, A; Baldini, V
The incidence of gastrointestinal involvement is relatively observed in patients with vasculitis processes. Vasculitis can be primary (necrotising or hypersensitivity) or secondary to another primary disease. Gastrointestinal involvement is present in up to 50% of the various forms of systemic vasculitis. Primary or secondary vasculitic process, according to the classification in necrotizing and hypersensitivity vasculitis, are described in this paper. A review of the literature on the the subject is also presented.
Lally, Lindsay; Sammaritano, Lisa R
The major manifestations of antiphospholipid syndrome (APS) are caused by thrombosis within the venous or arterial vasculature, whereas the vascular lesions in systemic vasculitis result from an inflammatory infiltrate in the vessel wall. There is an association between vascular thrombosis and inflammation, however, as vasculitis can occur in APS and thromboembolic complications are seen in systemic vasculitis. Although differentiating between vasculitis and antiphospholipid-associated thrombosis can be difficult, it may be crucial to do so given the different therapeutic implications for immunosuppression or anticoagulation. This article explores the relationship between thrombosis and inflammation as it relates to APS and systemic vasculitis.
Mertz, L E; Conn, D L
A large variety of vasculopathic syndromes are uncommonly associated with malignancies. Vasculitis is usually manifested by skin lesions and is generally associated with hematologic malignancies rather than solid tumors. Evidence of autoantibodies, immune complexes, and complement consumption is typically absent. Myelodysplastic syndromes can be confidently linked to vasculitis on the basis of recent literature. The temporal relationship of malignancy to vasculitis development is variable except that vasculitis generally follows the discovery of hairy cell leukemia and splenectomy. Vasculitis may occasionally be a complication of chemotherapy, radiation therapy, and bone marrow transplantation. Occasionally, malignant disorders may mimic vasculitic syndromes. The etiopathogenesis of vasculitis in patients with malignant disorders is unknown. The recent literature on vasculitis and malignancy addresses predominantly case reports and small patient cohorts and identifies clinical characteristics rather than pathogenic mechanisms.
... Clinical Trials Links Related Topics Aneurysm Blood Tests Kawasaki Disease Raynaud's Smoking and Your Heart Send a link ... of vasculitis. For example, the standard treatment for Kawasaki disease is high-dose aspirin and immune globulin. Immune ...
Kumar, Ashok; Goel, Anshul; Lapsiwala, Mehul; Singhal, Suman
Systemic rheumatoid vasculitis (SRV) can develop in rheumatoid arthritis of long duration and high disease activity. It most commonly manifests as cutaneous vasculitis and mononeuritis multiplex. This can involve any organ of the body and carries very high mortality. We report a case of a young male who had rheumatoid arthritis for the past 15 years and became refractory to standard drugs and anti-TNF agents. He subsequently developed SRV, which started as mononeuritis multiplex. Disease progressed to result in gangrene of hands and feet despite receiving intravenous cyclophosphamide. Intravenous immunoglobulin and rituximab also could not provide any response. Prolonged ICU stay resulted in critical care neuromyopathy. Central nervous system vasculitis developed even after repeated infusions of intravenous immunoglobulins and at last he died of complications. In this case report, we have presented rare and chronic protracted presentation of rheumatoid vasculitis involving skin, nerves, brain and testis, which was refractory to the recommended therapies. PMID:28031844
Baig, Zahid Farooq; Raja, Khalid Mahmood; Abbas, Fahad
Vasculitis (Wegeners Granulomatosis and Microscopic Polyangiitis) and Tuberculosis share many features including constitutional symptoms and respiratory tract involvement. The presence of kidney involvement with new onset azotaemia and active urine sediment support the diagnosis of vasculitis. We describe two cases that were diagnosed to be suffering from tuberculosis and placed on anti-tuberculosis therapy. On further workup they were found to be suffering from pauci- immune glomerulonephritis and recovered well with treatment.
Banan, Parastoo; Butler, Gregory; Wu, Jason
Urticarial dermatitis is a poorly understood skin condition while it seems to be much more common than the paucity of reports suggest. It manifests with severely pruritic papules and plaques that resemble eczematous and urticarial lesions morphologically. The key clues to diagnosis are the urticarial appearance and overlap with an eczematous reaction. Here, we present a series of 19 cases (13 women and six men) with urticarial dermatitis clinically and histologically. The patients' average age was 58 and most of the cases were idiopathic. Trunk and proximal extremities were the most common sites involved followed by the distal extremities. Poor response to potent topical corticosteroids and antihistamines was usual and many patients required oral prednisone or other immunosuppressant agents or phototherapy.
Martínez Aguilar, N E; Guido Bayardo, R; Vargas Camaño, M E; Compañ González, D; Miranda Feria, A J
Viruses have been implicated in vasculitis. To determine activity of viral infection associated with vasculitis. 17 patients with vasculitis had been in immunological and antiviral antibodies evaluation. Twenty five healthy controls sex and age matched with hematic biometry (BH) and AA. All subjects were negative to HIV and HBV. Viral activity was demonstrated in eight patients; vascular purpura (5), Takayasu disease (1), polyarteritis nodosa (1), erythema nodosum (1). None subject of control group had IgM activity. Antibodies response of IgG in patients were of lesser intensity than in control group. 14 abnormalities in BH were found in patients and 4 in control group. Immune response in patients, measured by lymphocyte subpopulations and circulating immune complexes was abnormal. In conclusion 47% showed viral activity, but the dominant feature was abnormal immune response in 82%.
Boudghène-Stambouli, O; Mérad-Boudia, A; Ghernaout-Benchouk, S
Brucellosis is an anthropozoonosis caused by a Gram negative bacillus of the Brucella gender. Skin manifestations have been reported in 1.5 to 11 p. 100 of the cases. Allergic vasculitis is rare. Recently a 24-year-old man was hospitalized for signs of infection. He had been treated with tetracycline. The clinical picture was suggestive of brucellosis and the Wright test was positive at 1/1,280. There were violet and purpuric papulae on the limbs, arthritis of the knee and ankle joints and renal involvement (haematuria, proteinuria). Histology revealed fibrinoid and leukocytoclastic vasculitis of the small veinules of the subpapillary plexus. Outcome was favourable with rifampicin, doxycycline and adjuvant dapsone, together with bed rest. Several types of skin manifestations have been reported in brucellosis although cases of allergic vasculitis are rare.
Berman, Mark; Paran, Daphna; Elkayam, Ori
The use of cocaine continues to grow worldwide. One of the possible side-effects of cocaine is vasculitis. Two distinct vasculitic syndromes have been described due to cocaine. One is cocaine-induced midline destructive lesion, secondary to a direct vasoconstrictor effect of cocaine, inducing ischemic necrosis of the septal cartilage and perforation of the nasal septum, mimicking findings of granulomatosis with polyangiitis in the upper airways. The other is ANCA-associated vasculitis, attributed to the levamisole component that contaminates about 70% of the cocaine. This type of vasculitis may be myeloperoxidase (MPO) and proteinase 3 (PR3) positive, and its main manifestations are typical cutaneous findings, arthralgia, otolaryngologic involvement, and agranulocytosis. A high degree of suspicion and awareness is needed in order properly to diagnose and treat these patients. PMID:27824551
Kim, Jeong-Min; Lim, Kyung-Min; Kim, Hoon-Soo; Ko, Hyun-Chang; Kim, Moon-Bum
Background Urticarial dermatitis, which is characterised by persistent wheals with eczematous papules and plaques, is frequently misdiagnosed and difficult to treat. Patients commonly experience intolerable pruritus which may greatly affect their quality of life. Objective The objective of this study is to characterize the clinical patterns of pruritus in patients with urticarial dermatitis and to determine the effectiveness of cyclosporine treatment. Methods This prospective study included 50 histopathologically confirmed patients with urticarial dermatitis. A face-to-face structured questionnaire was given to all patients, and they were treated with low-dose cyclosporine (1~3 mg/kg/d) for at least 2 weeks. Results The majority of patients (80.0%) had moderate to severe pruritus. Most patients experienced exacerbation of the itch in the evening (74.0%), with the extremities (upper, 86.0%; lower, 94.0%) being the most commonly involved sites. Due to severe pruritus, patients complained about reduced social contact, quality of life and difficulties in falling asleep et al. Cyclosporine significantly reduced the mean itch score and extent of erythema, and improved interference with daily activities and sleep. Conclusion Our study highlights the detailed description and characteristics of pruritus in patients with urticarial dermatitis. And we recommend alternative and effective therapeutic option of low-dose cyclosporine. PMID:28392640
Carlson, J Andrew; Cavaliere, L Frank; Grant-Kels, Jane M
Vasculitis is histologically defined as inflammatory cell infiltration and destruction of blood vessels. Vasculitis is classified as primary (idiopathic, eg, cutaneous leukocytoclastic angiitis, Wegener's granulomatosis) or secondary, a manifestation of connective tissue diseases, infections, adverse drug eruptions, or a paraneoplastic phenomenon. Cutaneous vasculitis, manifested as urticaria, purpura, hemorrhagic vesicles, ulcers, nodules, livedo, infarcts, or digital gangrene, is a frequent and often significant component of many systemic vasculitic syndromes such as lupus or rheumatoid vasculitis and antineutrophil cytoplasmic antibody-associated primary vasculitic syndromes such as Churg-Strauss syndrome. In most instances, cutaneous vasculitis represents a self-limited, single-episode phenomenon, the treatment of which consists of general measures such as leg elevation, warming, avoidance of standing, cold temperatures and tight fitting clothing, and therapy with antihistamines, aspirin, or nonsteroidal anti-inflammatory drugs. More extensive therapy is indicated for symptomatic, recurrent, extensive, and persistent skin disease or coexistence of systemic disease. For mild recurrent or persistent disease, colchicine and dapsone are first-choice agents. Severe cutaneous and systemic disease requires more potent immunosuppression (prednisone plus azathioprine, methotrexate, cyclophosphamide, cyclosporine, or mycophenolate mofetil). In cases of refractory vasculitis, plasmapheresis and intravenous immunoglobulin are viable considerations. The new biologic therapies that work via cytokine blockade or lymphocyte depletion such as tumor alpha inhibitor infliximab and the anti-B-cell antibody rituximab, respectively, are showing benefit in certain settings such as Wegener's granulomatosis, antineutrophil cytoplasmic antibody-associated vasculitis, Behçet's disease, and cryoglobulinemic vasculitis.
Silveira, Luis H
Systemic vasculitides were initially reported as acute, progressive, severe, and life-threatening diseases. The introduction of glucocorticoids and cyclophosphamide for the treatment of vasculitis improved survival dramatically, but morbidity has remained high. Damage develops as a consequence of recurrent or persistent active vasculitis or its treatment. It is defined as the accumulation of nonhealing scars that are unlikely to respond to immunosuppressive therapy. Damage assessment is essential in systemic vasculitis because it may facilitate patient stratification in clinical trials and possibly in clinical practice. Moreover, it may avoid unnecessary use of immunosuppressive therapy. The Vasculitis Damage Index, developed and validated in 1997, has been very useful in solving many matters in systemic vasculitis and is currently the only validated damage-assessment tool available. However, the vasculitis community has recognized that there is a growing need to improve the evaluation of damage in vasculitis. The development of a Combined Damage Assessment index, which would permit a more appropriate and standardized approach to disease assessment applicable to systemic vasculitis, has been proposed.
Castañer, Eva; Alguersuari, Anna; Andreu, Marta; Gallardo, Xavier; Spinu, Cristina; Mata, Josep M
Vasculitis is a destructive inflammatory process affecting blood vessels. Pulmonary vasculitis may develop secondary to other conditions or constitute a primary idiopathic disorder. Thoracic involvement is most common in primary idiopathic large-vessel vasculitides (Takayasu arteritis, giant cell arteritis, Behçet disease) and primary antineutrophil cytoplasmic autoantibody-associated small-vessel vasculitides (Wegener granulomatosis, microscopic polyangiitis, Churg-Strauss syndrome). Primary pulmonary vasculitides are rare, and their signs and symptoms are nonspecific, overlapping with those of infections, connective tissue diseases, and malignancies. The radiologic findings in primary pulmonary vasculitis vary widely and can include vessel wall thickening, nodular or cavitary lesions, ground-glass opacities, and consolidations, among others. Diffuse alveolar hemorrhage usually results from primary small-vessel vasculitis in the lungs. To diagnose vasculitis, medical teams must recognize characteristic combinations of clinical, radiologic, laboratory, and histopathologic features.
Many pathophysiological process components are known to be implicated in lower limb ulcerations, among which vascular lesions have a major role. Vasculitis denotes a heterogeneous group of clinical entities which all are characterized by the inflammatory process of arterial and venous walls of any size and in any organ, quite frequently in the skin. Vasculopathy, on the other hand, refers to vascular and capillary lesions caused by, for example, some medications. The classification of vasculitides according to the size of the blood vessels involved serves for proper understanding the issue among clinicians and researchers, and not as a diagnostic tool. According to histologic finding obtained by examination of blood vessel biopsy specimen, vasculitides are divided into three groups: lymphocytic, leukocytoclastic and granulomatous. Livedoid vasculitis (livedo reticularis) most commonly affects women and is generally localized on lower extremities. The etiology oflivedoid vasculitis may imply autoimmune diseases, capillary obstruction with cryoglobulins, or antiphospholipid syndrome. Livedoid vasculopathy is a hyalinization disease of the vasculature, with thromboses and ulcerations on lower extremities, and of unknown etiology. Livedoid vasculopathy has been singled out as a separate disease that usually does not occur consequentially to other primary diseases. Livedoid vasculopathy typically affects women (71%) at a mean age of 45 (range 10-85) years; bilateral involvement of both lower limbs is present in 80.8%, disease manifested with ulcerations in 68.9%, ulcerations followed by development of atrophie blanche in 71.1%, transcutaneous oximetry reduction is found in 74.1%, factor V mutation (Leiden heterozygotes) in 22.2%, reduced protein C activity in 13.3%, prothrombin gene mutation (G20210A) in 8.3%, positive lupus anticoagulant in 17.9%, positive anticardiolipin antibodies in 28.6%, and elevated homocysteine level in 14.3% cases; blood vessel histology shows
Wilken, Reason; Ho, Derek; Petukhova, Tatyana; Jagdeo, Jared
Q-switched lasers, such as the neodymium:yttrium-aluminum-garnet (Nd:YAG) laser, are the gold standard for tattoo removal. Allergy to tattoo pigment is well-documented, but adverse allergic reactions during or shortly after laser tattoo removal are rare with few reports in the medical literature. Here we describe an intraoperative, localized urticarial reaction that developed during treatment of a tattoo using a 1064-nm Nd:YAG laser. As laser tattoo removal becomes increasingly popular amongst our patients, it is important for dermatologists to be aware of urticarial allergic reactions as well as their management. We outline our recommendations for medical management of this condition and hope that these guidelines will facilitate patient care by dermatologists who encounter this immune skin reaction to laser tattoo removal
Pastuszczak, Maciej; Celińska-Löwenhoff, Magdalena; Sułowicz, Joanna; Wojas-Pelc, Anna; Musiał, Jacek
Abstract Leukocytoclastic vasculitis (LCV) is a heterogenous group of disorders that may manifest as a mild disease isolated to the skin or be a part of life-threatening systemic vasculitis. According to the 2012 Chapel Hill Consensus Conference nomenclature, patients presenting symptoms of LCV confined only to the skin should be defined as suffering from a single-organ cutaneous small vessel vasculitis (SoCSVV). SoCSVV is a benign disease with a good clinical outcome but with a significant risk of relapse and skin ulcer formation. The aim of the current study was to characterize SoCSVV and to identify factors that may be associated with the risk of recurrence and skin ulcers. Medical records of patients with LCV hospitalized at the Department of Dermatology at University Hospital in Cracow in the years 2010 to 2015 were analyzed. A total of 24 patients fulfilled criteria of SoCSVV. Drugs and preceding infections were identified as precipitating factors in 40% and 20% of cases, respectively. Skin lesions other than palpable purpura (i.e., macules, urticarial vasculitis, or ulcers) were identified in almost half of the patients. Interestingly, the presence of macules independently increased the risk of skin ulcer formation (odds ratio = 16; 95% confidence interval: 1.5–176.6; P = 0.0075) in the multivariate logistic regression analysis. One-quarter of patients with SoCSVV experienced relapse during the 6-month follow-up. The greater number of affected skin areas was an independent risk factor of recurrence (odds ratio = 5; 95% confidence interval: 2–45; P = 0.02). SoCSVV was usually associated with drugs and preceding infections. The disease relapses in approximately one-quarter of the patients. The more severe the skin involvement in the course of SoCSVV, the higher is the risk of recurrence. PMID:28328827
Eosinophilic Granulomatosis With Polyangiitis (Churg-Strauss) (EGPA); Churg-Strauss Syndrome (CSS); Granulomatosis With Polyangiitis (Wegener's) (GPA); Wegener Granulomatosis (WG); Microscopic Polyangiitis (MPA); ANCA-Associated Vasculitis (AAV); Vasculitis
Kaye, B.R.; Fainstat, M.
A case of cerebral vasculitis in a previously healthy 22-year-old man with a history of cocaine abuse is described. Cerebral angiograms showed evidence of vasculitis. A search for possible causes other than cocaine produced no results. The authors include cocaine with methamphetamines, heroin, and ephedrine as illicit drugs that can cause cerebral vasculitis.
Abdellatif, A A; Waris, S; Lakhani, A; Kadikoy, H; Haque, W; Truong, L D
Vascular lesions are encountered frequently in renal biopsy specimens of patients with systemic lupus erythematosus (SLE) and can present in a variety of morphologic forms. True renal lupus vasculitis (TRLV) is one of the rare vascular lesions associated with lupus nephritis that has been infrequently reported in the medical literature. The primary focus on glomerular pathology and collective classification of the vascular lesions under lupus vasculopathy is one of the reasons why this form of inflammatory vasculitis has been under-recognized as a separate disease entity. Here we have comprehensively reviewed the literature on renal vascular involvement in SLE for a better understanding of the epidemiology, morphologic features, pathogenesis, clinical course and treatment of TRLV. It can be morphologically differentiated from other forms of renal vascular lesions in lupus nephritis, i.e. arteriosclerosis, uncomplicated vascular immune deposits, non-inflammatory necrotizing vasculopathy, and thrombotic microangiopathy. Despite close similarities with antineutrophil cytoplasmic autoantibody associated vasculitis (AASV), there are certain morphological differences that warrant a thorough investigation of the possible pauci-immune mechanism of pathogenesis. The vasculitis follows a severe clinical course in general with rapid progression to renal failure, although favorable outcomes have been reported in certain cases. The standard use of steroids and cytotoxic drugs has yielded variable results in the treatment of TRLV. Current treatment modalities being used in lupus nephritis and AASV have been compared in this article with focus on drugs acting on the inflammatory cells implicated in TRLV pathogenesis.
Hilhorst, Marc; van Paassen, Pieter
In patients with GN or vasculitis, ANCAs are directed against proteinase 3 (PR3) or myeloperoxidase (MPO). The differences between PR3-ANCA-associated vasculitis (AAV) and MPO-AAV described in the past have been supplemented during the last decade. In this review, we discuss the differences between these two small-vessel vasculitides, focusing especially on possible etiologic and pathophysiologic differences. PR3-AAV is more common in northern parts of the world, whereas MPO-AAV is more common in southern regions of Europe, Asia, and the Pacific, with the exception of New Zealand and Australia. A genetic contribution has been extensively studied, and there is a high prevalence of the HLA-DPB1*04:01 allele in patients with PR3-AAV as opposed to patients with MPO-AAV and/or healthy controls. Histologically, MPO-AAV and PR3-AAV are similar but show qualitative differences when analyzed carefully. Clinically, both serotypes are difficult to distinguish, but quantitative differences are present. More organs are affected in PR3-AAV, whereas renal limited vasculitis occurs more often in patients with MPO-AAV. For future clinical trials, we advocate classifying patients by ANCA serotype as opposed to the traditional disease type classification. PMID:25956510
Numata, T.; Yamamoto, S.; Yamura, T.
The mite antigen-induced histamine release from leucocytes of chronic urticarial patients was enhanced in the presence of deuterium oxide, which stabilizes microtubules. This enhancing effect of deuterium oxide on the histamine release from leucocytes may provide a useful means for the detection of allergens in vitro in chronic urticaria.
Mulloy, Karen B
Work in Department of Energy (DOE) facilities has exposed workers to multiple toxic agents leading to acute and chronic diseases. Many exposures were common to numerous work sites. Exposure to crystalline silica was primarily restricted to a few facilities. I present the case of a 63-year-old male who worked in DOE facilities for 30 years as a weapons testing technician. In addition to silica, other workplace exposures included beryllium, various solvents and heavy metals, depleted uranium, and ionizing radiation. In 1989 a painful macular skin lesion was biopsied and diagnosed as leukocytoclastic vasculitis. By 1992 he developed gross hematuria and dyspnea. Blood laboratory results revealed a serum creatinine concentration of 2.1 mg/dL, ethrythrocyte sedimentation rate of 61 mm/hr, negative cANCA (antineutrophil cytoplasmic antibody cytoplasmic pattern), positive pANCA (ANCA perinuclear pattern), and antiglomerular basement membrane negative. Renal biopsy showed proliferative (crescentric) and necrotizing glomerulonephritis. The patient's diagnoses included microscopic polyangiitis, systemic necrotizing vasculitis, leukocytoclastic vasculitis, and glomerulonephritis. Environmental triggers are thought to play a role in the development of an idiopathic expression of systemic autoimmune disease. Crystalline silica exposure has been linked to rheumatoid arthritis, scleroderma, systemic lupus erythematosus, rapidly progressive glomerulonephritis and some of the small vessel vasculitides. DOE workers are currently able to apply for compensation under the federal Energy Employees Occupational Illness Compensation Program (EEOICP). However, the only diseases covered by EEOICP are cancers related to radiation exposure, chronic beryllium disease, and chronic silicosis. PMID:14644669
Perez-Alamino, Rodolfo; Maldonado-Ficco, Hernán
The systemic vasculitis is a heterogeneous group of diseases characterized by the inflammation of blood vessels. The development of advanced diagnostic tests and genetic studies have resulted in greater improvement in our understanding of vasculitis pathogenesis and thus in the development of newer therapies. However, there is still an unmet need in the management of systemic vasculitis, focused on developing of new biomarkers that would enable distinction between active disease from damage or infection and predict treatment response and prognosis.
Behcet's Disease; Churg-Strauss Syndrome; Vasculitis, Central Nervous System; Giant Cell Arteritis; Wegener Granulomatosis; Henoch-Schoenlein Purpura; Microscopic Polyangiitis; Polyarteritis Nodosa; Takayasu's Arteritis
Kim, Jee-Eun; Park, Su-Yeon; Sinn, Dong In; Kim, Sung-Min; Hong, Yoon-Ho; Park, Kyung Seok; Lee, Kwang-Woo
Background Livedoid vasculitis is a chronic dermatological problem with an unclear etiology. Clinical findings are petechiae with painful ulcers in both lower extremities, which heal to become hyperpigmented and porcelain-white satellite lesions. There are only a few reported cases of livedoid vasculitis presenting in combination with peripheral neuropathy. Case Report We report the first case of a Korean patient presenting with mononeuritis multiplex combined with livedoid vasculitis, which was confirmed by electrophysiological and pathological studies. Conclusions Our report supports the possible vaso-occlusive etiology of livedoid vasculitis in multifocal ischemic neuropathy. PMID:22259622
Carlson, J Andrew
Vasculitis is defined as inflammation directed at vessels, which compromises or destroys the vessel wall leading to haemorrhagic and/or ischaemic events. Skin biopsy is the gold standard for the diagnosis of cutaneous vasculitis, whose manifestations include urticaria, infiltrative erythema, petechiae, purpura, purpuric papules, haemorrhagic vesicles and bullae, nodules, livedo racemosa, deep (punched out) ulcers and digital gangrene. These varied morphologies are a direct reflection of size of the vessels and extent of the vascular bed affected, ranging from a vasculitis affecting few superficial, small vessels in petechial eruptions to extensive pan-dermal small vessel vasculitis in haemorrhagic bullae to muscular vessel vasculitis in lower extremity nodules with livedo racemosa. Skin biopsy, extending to subcutis and taken from the earliest, most symptomatic, reddish or purpuric lesion is crucial for obtaining a high-yielding diagnostic sample. Based on histology, vasculitis can be classified on the size of vessels affected and the dominant immune cell mediating the inflammation (e.g. neutrophilic, granulomatous, lymphocytic, or eosinophilic). Disruption of small vessels by inflammatory cells, deposition of fibrin within the lumen and/or vessel wall coupled with nuclear debris allows for the confident recognition of small vessel, mostly neutrophilic vasculitis (also known as leukocytoclastic vasculitis). In contrast, muscular vessel vasculitis can be identified solely by infiltration of its wall by inflammatory cells. Extravasation of red blood cells (purpura) and necrosis are supportive, but not diagnostic of vasculitis as they are also seen in haemorrhagic and/or vaso-occlusive disorders (pseudovasculitis). Vasculitic foci associated with extravascular granulomas (palisaded neutrophilic and granulomatous dermatitis), tissue eosinophilia, or tissue neutrophilia signal the risk for, or co-existence of systemic disease. This essential histological information
Miloslavsky, Eli M; Stone, John H; Unizony, Sebastian H
The need to distinguish true primary systemic vasculitis from its multiple potential mimickers is one of the most challenging diagnostic conundrums in clinical medicine. This article reviews 9 challenging vasculitis mimickers: fibromuscular dysplasia, calciphylaxis, segmental arterial mediolysis, antiphospholipid syndrome, hypereosinophilic syndrome, lymphomatoid granulomatosis, malignant atrophic papulosis, livedoid vasculopathy, and immunoglobulin G4-related disease.
Hague, Cameron; Bicknell, Simon
Very little has been published about single-organ vasculitis of the testicle in the radiological literature. Consequently, it is a diagnosis that is unfamiliar to most radiologists. This case report describes the sonographic, pathologic, and laboratory findings of testicular vasculitis and reviews the available literature with regard to this subject. PMID:28246567
... topics/vas/. Accessed July 16, 2014. Longo DL, et al. Harrison's Online. 18th ed. New York, N. ... resourceID=4. Accessed July 16, 2014. Gwathmey KG, et al. Vasculitic neuropathies. Lancet Neurology. 2014;13:67. ...
... Fellows Evidence-Based Practice for Academic Researchers Responsible Data Management in Research Career Planning Treatments Patient and Caregiver ... Fellows Evidence-Based Practice for Academic Researchers Responsible Data Management in Research Career Planning Treatments Patient and Caregiver ...
Lidar, Merav; Lipschitz, Noga; Langevitz, Pnina; Shoenfeld, Yehuda
Infectious agents have been implicated in the etiopathogenesis of various vasculitides via numerous and overlapping mechanisms including direct microbial invasion of endothelial cells, immune complex mediated vessel wall damage and stimulation of autoreactive B and/or T cells through molecular mimicry and superantigens. While the causative role of hepatitis B virus in polyarteritis nodosa and hepatitis C virus in mixed cryoglobulinemia is clearly established, evidence for the association of other infectious agents with vasculitis, including human immunodeficiency virus, parvovirus B19, cytomegalovirus, varicella zoster virus, Staphylococcus aureus, rickettsiaceae, Treponema pallidum and Borrelia burgdorferi, among numerous others, is accumulating. The spectrum of association of infectious agents; bacteria, viruses and parasites, with systemic vasculitides, will be reviewed herewith.
Novakovich, Elaine; Grayson, Peter C
Advances in clinical care for patients with vasculitis have improved survival rates and created new challenges related to the ongoing management of chronic disease. Lack of curative therapies, burden of disease, treatment-related side effects, and fear of relapse contribute to patient-perceived reduction in quality of life. Patient-held beliefs about disease and priorities may differ substantially from the beliefs of their health care providers, and research paradigms are shifting to reflect more emphasis on understanding vasculitis from the patient's perspective. Efforts are ongoing to develop disease outcome measures in vasculitis that better represent the patient experience. Health care providers who care for patients with vasculitis should be sensitive to the substantial burdens of disease commonly experienced by patients living with the disease and should strive to provide comprehensive care directed towards the medical and biopsychological needs of these patients.
Ely, H; Bard, J W
Two patients with idiopathic livedo vasculitis responded favorably to therapy with pentoxifylline. One patient had responded to fibrinolytic therapy with phenformin and ethylestrenol before phenformin was taken off the market. Pentoxifylline (Trental) has multiple mechanisms of action, including stimulation of prostacyclin synthesis, decreased aggregation of platelets, increased deformability of red blood cells, increased mobility of neutrophils, and increased fibrinolysis. All of these factors may contribute to its successful use in the treatment of idiopathic livedo vasculitis.
Iglesias Gammara, Antonio; Coral, Paola; Quintana, Gerardo; Toro, Carlos E; Flores, Luis Felipe; Matteson, Eric L; Restrepo, José Félix
A literature review utilizing Fepafem, Bireme, LiLacs, Scielo Colombia, Scielo Internacional, former MedLine, Pubmed, and BVS Colombia as well as manual searches in the libraries of major Latin American universities was performed to study vasculitis in Latin America. Since 1945, a total of 752 articles have been published by Latin American authors. However, only a minority are devoted to primary vasculitides, and even fewer have been published in indexed journals. Approximately 126 are in OLD, Medline, Pubmed, Bireme, and Scielo. Most publications are from Mexico, followed by Brazil and Colombia. Systematic studies of the epidemiology of primary idiopathic vasculitis are available for a few countries, i.e. Brazil, Mexico, Colombia, Chile, and Peru. Takayasu arteritis and ANCA-associated vasculitis are the best studied forms of vasculitis in Latin America. Interest and expertise in vasculitis is growing in Latin America, as reflected in the increased number of published articles from this region of the world in the last decade. Racial and environmental factors are possibly responsible for the differential expression of various types of primary vasculitis observed in Latin America. With time, the unique features, epidemiology, and better treatment strategies for idiopathic vasculitides in Latin America will emerge.
Vital, Anne; Vital, Claude
One characteristic histological lesion on biopsy specimens is mandatory to establish the diagnosis of vasculitis. Combined nerve and muscle biopsies, by the same cutaneous incision, improve significantly the percentage of positive results. Nerve fragments should be taken in every patient presenting sensory manifestations. Such vasculitic lesions are present in medium-sized arterioles and/or small vessels, and correspond mainly to 4 necrotizing vasculitis: panarteritis nodosa (PAN), microscopic polyangiitis (MPA), Churg and Strauss syndrome and Wegener granulomatosis. Microvasculitis should be added to these classical entities, because it corresponds to small vessel wall infiltration by inflammatory cells, as observed in PAN and MPA, but without any necrosis. Microvasculitis has to be differentiated from the inflammatory cell infiltrates surrounding small vessels. However, such perivascular inflammatory cell infiltrates enable the diagnosis of probable vasculitis when associated with clusters of neo-vessels, hemosiderin deposits, or a focal damage of nerve fibers. Grossly, one third of vasculitis diagnosis is confirmed on muscle fragments, a second third on nerve fragments, and the last third on both nerve and muscle fragments. Moreover, in the search for vasculitis, an unpredicted diagnosis of lymphoma or amyloidosis is occasionally established on the neuro-muscular biopsy.
Mirouse, Adrien; Savey, Léa; Domont, Fanny; Comarmond, Cloé; Barete, Stéphane; Plaisier, Emmanuelle; Rouvier, Philippe; Cacoub, Patrice; Saadoun, David
Abstract Rationale: Vemurafenib, an inhibitor of mutated B-rapidly accelerated fibrosarcoma, is frequently used in the treatment of melanoma and Erdheim–Chester disease (ECD) patients. Inflammatory adverse effects have been increasingly reported after vemurafenib treatment. Patient concerns and diagnose: We report 6 cases of vemurafenib-associated vasculitis, of whom a personal case of a 75-year-old man with history of ECD who developed purpura and rapidly progressive pauci-immune glomerulonephritis during treatment with vemurafenib. Intervention: In the 5 others cases from the literature, all patients presented skin vasculitis, and with joint involvement in 60% of them. Vemurafenib treatment was stopped (n = 3), continued at reduced doses (n = 1), or continued at the same dose (n = 2). Outcomes: Three patients (50%) received corticosteroids combined with cyclophosphamide (n = 1), and all achieved remission of vasculitis. One patient experienced vasculitis relapse after vemurafenib therapy was restarted. Lessons: Systemic vasculitis is a rare vemurafenib-associated adverse event that may be life-threatening. PMID:27861332
Giant Cell Arteritis; Takayasu's Arteritis; Polyarteritis Nodosa; Wegener's Granulomatosis; Microscopic Polyangiitis; Churg-Strauss Syndrome; Behcet's Disease; Kawasaki Disease; Henoch-schoenlein Purpura; Vasculitis, Central Nervous System; Drug-induced Necrotizing Vasculitis
Eleftheriou, Despina; Brogan, Paul A
Considerable therapeutic advances for the treatment of vasculitis of the young have been made in the past 10 years, including the development of outcome measures that facilitate clinical trial design. Notably, these include: a recognition that some patients with Kawasaki Disease require corticosteroids as primary treatment combined with IVIG; implementation of rare disease trial design for polyarteritis nodosa to deliver the first randomised controlled trial for children; first clinical trials involving children for anti-neutrophil cytoplasmic antibody (ANCA) vasculitis; and identification of monogenic forms of vasculitis that provide an understanding of pathogenesis, thus facilitating more targeted treatment. Robust randomised controlled trials for Henoch Schönlein Purpura nephritis and Takayasu arteritis are needed; there is also an over-arching need for trials examining new agents that facilitate corticosteroid sparing, of particular importance in the paediatric population since glucocorticoid toxicity is a major concern.
Warren, Donald; Speck, Laura; Jackson, Julie
Tumor necrosis factor (TNF)-alpha antagonists are a common treatment modality for autoimmune disorders, but their use can be associated with many side effects, including various dermatologic conditions. Certolizumab pegol, a newer TNF antagonist that lacks the Fc portion of the IgG antibody, has recently been approved to treat psoriatic arthritis, rheumatoid arthritis, and Crohn's disease. Though other TNF antagonists have been associated with leukocytoclastic vasculitis, this finding has not yet been reported with certolizumab pegol. We present a case report of leukocytoclastic vasculitis caused by certolizumab pegol.
Abdulqader, Yasir; Al-Ani, Muhsen; Parperis, Konstantinos
Rheumatoid vasculitis is a rare and late complication of rheumatoid arthritis and may affect small-to-medium-sized vessels. Here, we report a case of a 49-year-old man who presented with amaurosis fugax in the left eye, symmetric polyarthritis, Raynaud's symptoms and paraesthesia in both lower extremities. The patient subsequently experienced right foot drop, nail fold infracts and gangrene of his right second toe. He was found to have a high titre of rheumatoid factor and treatment with rituximab and high dose of corticosteroids led to significant improvement of his symptoms. This is rare case describing the early onset of rheumatoid vasculitis in a patient with rheumatoid arthritis.
Pillai, Sreeja Hareendranathan; Sreedharan, Sapna Erat; Menon, Girish; Kannoth, Santhosh; PN, Sylaja
Primary angiitis of the central nervous system (PACNS) is a rare disorder affecting both medium- and small-sized vessels. Intracranial haemorrhages though less reported are in the form of parenchymal haemorrhage and subarachnoid haemorrhage. We report a case of PACNS with intraventricular haemorrhage due to aneurysms secondary to progression of vasculitis. PMID:27570401
Salama, Alan D.; Little, Mark A
This review seeks to provide an update on the experimental models that have been developed recapitulating clinical ANCA associated vasculitis. The recent insights regarding the application of the models in the study of pathogenesis, and the therapeutic implications of this, are covered in the article by van Timmeren and Heeringa in this issue. Recent findings Rodent models of both MPO- and PR3 ANCA associated vasculitis have been developed, which have provided important insights into the pathogenesis of ANCA associated pulmonary and renal disease. The vast majority of in vivo work in this field has concerned MPO-ANCA associated disease, although the last year has seen some advances in modelling of anti-PR3 disease. As with all experimental animal models they are flawed in one way or another, by virtue of the means by which they are induced, but they have already provided novel directions for future intervention in these complex diseases. To date there are no good models that replicate the granulomatous lesions found in granulomatosis with polyangiitis (GPA, formerly Wegener’s), or the development of vasculitis lesions in organs other than the lungs or kidneys. However, use of a combination of the available models should allow greater understanding of the critical requirements for disease and how these may be potentially monitored and modified in patients. Summary ANCA associated vasculitis can be induced in various forms in susceptible rodents. Further refinements are required for the full spectrum of disease phenotype to be replicated in animals, but critical new targets have been proposed based on use of molecular blocking agents and transgenic animals to elucidate disease pathways. PMID:22089094
Jumean, Khalid; Arqoub, Ahmad Abu; Hawatmeh, Amer; Qaqa, Firas; Bataineh, Ayham; Shaaban, Hamid
Warfarin is typically prescribed for patients with thromboembolic diseases and atrial fibrillation. In addition to the complications of bleeding, allergic skin reaction is one of its rare adverse effects. We herein report a case of a 79 year old male patient with leukocytoclastic vasculitis and proteinuria secondary to warfarin. The warfarin was discontinued and oral prednisone therapy was initiated. The cutaneous lesions and the proteinuria resolved thereafter. PMID:27453863
Bartels, C. M.; Bridges, A. J.
Rheumatoid vasculitis is a rare but serious complication of rheumatoid arthritis. Herein we examine the pathophysiology, epidemiology, clinical diagnosis, and treatment of rheumatoid vasculitis. Seropositivity, specific HLA variations, and tobacco use are among the genetic and environmental predictors of rheumatoid vasculitis. Fortunately, recent reports have noted declines in the prevalence of rheumatoid vasculitis. Nevertheless, proper recognition of systemic manifestations may assist in pathologically confirming the diagnosis, determining the extent of disease, and guiding treatment. Contemporary treatment reports are discussed in the context of the ongoing debate regarding whether new agents may trigger, treat, or even prevent rheumatoid vasculitis. Evolving genetic, histopathologic, and immunologic studies partnered with ongoing clinical experience with biologics offer promise to inform future prevention and treatment of rheumatoid vasculitis. PMID:20842467
Mitchell, M S; Gifford, R H; Bertino, J R; Kenney, J D; Malawista, S E
With the great interest in recent years in the use of immunosuppressive/antiinflammatory drugs for the treatment of severe systemic inflammatory disorders, it is surprising that, except in Wegener's granulomatosis, the use of methotrexate (MTX) in disseminated vasculitides has been neglected. We have treated three patients with MTX, each with a different form of severe, corticosteroid-resistant, life-threatening, disseminated vasculitis. One had a nonspecific vasculitis characterized by excruciating muscle pain, weakness, and atrophy; the second had rheumatoid vasculitis with extensive skin ulceration and four-limb mononeuritis multiplex; the third had polyarteritis nodosa with hypertension, eventually fatal renal disease, and severe peripheral neuropathy. Treatment in each case was associated with a dramatic, favorable change in a course previously marked by relentless deterioration; two patients are alive 4 and 5 years later, without MTX. The purpose of this preliminary report is to indicate the possible efficacy of MTX in a wider group of disorders than those to which it is generally limited at present, and to stimulate its further evaluation.
Puéchal, Xavier; Guillevin, Loïc
Current data on therapeutic immunomodulation used to treat systemic vasculitides are reviewed in this paper, which also discusses ongoing and future developments in the field. In vasculitides associated with anti-neutrophil cytoplasmic antibodies, rituximab is a validated induction treatment that can serve as an alternative to cyclophosphamide and must be followed by maintenance treatment. In addition, the usefulness of rituximab as maintenance treatment was established recently. Immunoglobulins can be helpful adjuncts, most notably in patients with severe immunodepression. Plasmapheresis is indicated in patients with severe renal failure and may have a role in the treatment of alveolar hemorrhage syndromes. Mepolizumab has produced encouraging preliminary results in eosinophilic granulomatosis with polyangiitis (Churg-Strauss). Rituximab can be used in cryoglobulinemic vasculitis associated with hepatitis C virus infection when antiviral therapy fails or the disease is severe. Very low doses of interleukin-2 may be helpful in refractory forms. Rituximab is also an option in essential mixed cryoglobulinemia with uncontrolled vasculitis despite glucocorticoid and/or immunosuppressive treatment. In polyarteritis nodosa associated with the hepatitis B virus, a combination of short-course glucocorticoids, plasmapheresis, and antiviral therapy produces excellent outcomes. Intravenous immunoglobulins are used to treat Kawasaki disease, in which they diminish the incidence of coronary artery aneurysms. Several prospective controlled trials are currently assessing tocilizumab in giant-cell arteritis. Rituximab has useful effects in systemic vasculitis associated with rheumatoid arthritis. In Goodpasture's syndrome, plasmapheresis is indicated to clear the antibodies to glomerular membrane antigen, which can induce glomerulonephritis.
Gong, Eun Jeong; Kim, Do Hoon; Chun, Joo Hyun; Ahn, Ji Yong; Choi, Kwi-Sook; Jung, Kee Wook; Lee, Jeong Hoon; Choi, Kee Don; Song, Ho June; Lee, Gin Hyug; Jung, Hwoon-Yong; Kim, Jin Ho; Song, In Hye; Kim, Yong-Gil
Background/Aims Gastrointestinal involvement in vasculitis may result in life-threatening complications. However, its variable clinical presentations and endoscopic features, and the rarity of the disease, often result in delayed diagnosis. Methods Clinical characteristics, endoscopic features, and histopathological findings were reviewed from medical records. Results Of 6,477 patients with vasculitis, 148 were diagnosed as primary vasculitis with upper gastrointestinal involvement. Of these, 21 cases (14.2%) were classified as large-vessel vasculitis, 17 cases (11.5%) as medium-vessel vasculitis, and 110 cases (74.3%) as small-vessel vasculitis. According to the specific diagnosis, IgA vasculitis (Henoch-Schönlein purpura) was the most common diagnosis (56.8%), followed by Takayasu arteritis (14.1%), microscopic polyangiitis (10.1%), and polyarteritis nodosa (6.8%). Gastrointestinal symptoms were present in 113 subjects (76.4%), with abdominal pain (78.8%) the most common symptom. Erosion and ulcers were striking endoscopic features, and the second portion of the duodenum was the most frequently involved site. Biopsy specimens were obtained from 124 patients, and only eight (5.4%) presented histopathological signs of vasculitis. Conclusions Diagnosis of vasculitis involving the upper gastrointestinal tract is difficult. Because of the widespread use of endoscopy, combining clinical features with endoscopic findings may facilitate making appropriate diagnoses; however, the diagnostic yield of endoscopic biopsy is low. PMID:27226428
Importance. Infections can cause leukocytoclastic vasculitis. Observations. We report the case of a patient with a left ventricular assist device who presented with acute kidney injury and biopsy proven leukocytoclastic vasculitis. Blood cultures grew Listeria monocytogenes. The patient's rash improved with treatment of the underlying Listeria infection. Conclusion. Clinicians should be aware that there are a number of broad categories of disease associated with the histologic finding of vasculitis, including infection. It is important to keep in mind the risk factors of a particular patient when formulating a differential diagnosis. This is the first reported case of Listeria bacteremia causing leukocytoclastic vasculitis. PMID:27313916
Sánchez-Guerrero, J; Gutiérrez-Ureña, S; Vidaller, A; Reyes, E; Iglesias, A; Alarcón-Segovia, D
In a study of 222 patients with vasculitis, we identified 11 who had an associated neoplasia. Seven had hematological neoplasia and 4 had solid malignant tumors. In 4 patients vasculitis gave the first evidence of the neoplasia or of its recurrence. Nine of our patients had cutaneous vasculitis. The other 2 had vasculitis involving the intestine and resulted in acute abdomens. These 2 patients needed prednisone treatment for the vasculitis. Neoplasia should be considered in patients with vasculitis without an apparent cause.
Carpenter, Delesha M.; Meador, Amy E.; Elstad, Emily A.; Hogan, Susan L.; DeVellis, Robert F.
Objectives Our objective is to explore how vasculitis, affects patients’ friendships and social participation. Methods Vasculitis patients (n=221) completed an online questionnaire that asked if, and how, relationships with friends have changed since receiving a vasculitis diagnosis. Participants’ written responses were imported into Atlas.ti, and two independent researchers used both structured and unstructured coding to identify themes. After reaching 100% consensus on the themes present in each participant’s responses, the coders determined how themes were interrelated across participants. Results Over half of patients (52%) expressed that vasculitis negatively impacted their friendships and 25% noted a negative impact on their social participation. At limes, this negative impact was related to structural changes in patients’ social networks due to loss of friendships. Reduced social participation was also associated with friends’ inability to understand vasculitis and its effects, vasculitis-related fatigue, and lifestyle changes such as not being able to drink alcohol and avoiding infection-prone events. Additionally, patients withdrew from social engagements due to fatigue or because of physical symptoms and side effects. Conclusion The unique circumstances associated with a rare chronic illness like vasculitis can create significant barriers to friendships, including loss of these relationships. Interventions designed to help patients cope with the social impact of vasculitis are implicated, especially if they increase patients’ ability to engage in dialogue about their illness with their friends. PMID:22325346
Levine, James W; Gota, Carmen; Fessler, Barri J; Calabrese, Leonard H; Cooper, Sheldon M
There is a well established link between type II mixed cryoglobulinemia (MC) and hepatitis C virus (HCV) infection, and HCV is believed to be the cause of cryoprotein formation and tissue deposition. Successful treatment of HCV infection has resulted in resolution of cryoglobulinemia and vasculitis. We describe 4 patients who had persistent MC and vasculitis despite successful eradication of HCV with antiviral therapy.
Quéméneur, Thomas; Mouthon, Luc; Cacoub, Patrice; Meyer, Olivier; Michon-Pasturel, Ulrique; Vanhille, Philippe; Hatron, Pierre-Yves; Guillevin, Loïc; Hachulla, Eric
Abstract Although the presence of antineutrophil cytoplasmic antibodies (ANCA) has been reported in patients with systemic sclerosis (SSc), the association of SSc and systemic vasculitis has rarely been described. We obtained information on cases of systemic vasculitis associated with SSc in France from the French Vasculitis Study Group and all members of the French Research Group on Systemic Sclerosis. We identified 12 patients with systemic vasculitis associated with SSc: 9 with ANCA-associated systemic vasculitis (AASV) and 3 with mixed cryoglobulinemia vasculitis (MCV). In all AASV patients, SSc was of the limited type. The main complication of SSc was pulmonary fibrosis. Only 2 patients underwent a D-penicillamine regimen before the occurrence of AASV. The characteristics of AASV were microscopic polyangiitis (n = 7) and renal limited vasculitis (n = 2). Anti-myeloperoxidase antibodies were found in 8 of the 9 patients. The Five Factor Score was above 1 in 3 of the 9 patients. Of the 3 patients with MCV, Sjögren syndrome was confirmed in 2. We compared our findings with the results of a literature review (42 previously reported cases of AASV with SSc). Although rare, vasculitis is a complication of SSc. AASV is the most frequent type, and its diagnosis can be challenging when the kidney is injured. Better awareness of this rare association could facilitate earlier diagnosis and appropriate management to reduce damage. PMID:23263715
Donovan, Christopher P; Pecen, Paula E; Baynes, Kimberly; Ehlers, Justis P; Srivastava, Sunil K
A 31-year-old woman with a history of anti-synthetase syndrome-related myositis and interstitial lung disease presented with acute-onset blurry vision and rash on her hands and feet. Visual acuity was hand motion in her right eye and 20/40 in her left eye. Dilated fundus exam showed extensive retinal vasculitis, diffuse intraretinal hemorrhages, and subretinal fluid. Optical coherence tomography revealed significant macular thickening, and fluorescein angiography revealed vascular leakage with peripheral nonperfusion. Aggressive systemic immunosuppression was initiated, with gradual resolution of her disease during 8 months of follow-up. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:874-879.].
Kalfa, Melike; Kocanaoğulları, Hayriye; Karabulut, Gonca; Emmungil, Hakan; Çınar, Celal; Yılmaz, Zevcet; Gücenmez, Sercan; Kabasakal, Yasemin
Segmental arterial mediolysis (SAM) is a rare, nonarteriosclerotic, noninflammatory vascular disease and mostly affects medium-to-large sized abdominal arteries as well as presents with hemorrhages in the abdominal cavity. We report the case of a patient with SAM of the celiac, right renal, jejunal branch of the superior mesenteric, left gastric, and splenic arteries who was diagnosed by excluding other causes and in whom transcatheter embolization was performed in two different sessions, but he died because of an undefined reason. SAM mimics systemic vasculitis and causes abdominal pain; it should be considered because abdominal hemorrhage or arterial infarction can result in death.
Kalfa, Melike; Kocanaoğulları, Hayriye; Karabulut, Gonca; Emmungil, Hakan; Çınar, Celal; Yılmaz, Zevcet; Gücenmez, Sercan; Kabasakal, Yasemin
Segmental arterial mediolysis (SAM) is a rare, nonarteriosclerotic, noninflammatory vascular disease and mostly affects medium-to-large sized abdominal arteries as well as presents with hemorrhages in the abdominal cavity. We report the case of a patient with SAM of the celiac, right renal, jejunal branch of the superior mesenteric, left gastric, and splenic arteries who was diagnosed by excluding other causes and in whom transcatheter embolization was performed in two different sessions, but he died because of an undefined reason. SAM mimics systemic vasculitis and causes abdominal pain; it should be considered because abdominal hemorrhage or arterial infarction can result in death. PMID:27733945
Rho, Young Hee; Choi, Seong Jae; Lee, Young Ho; Ji, Jong Dae; Song, Gwan Gyu
We have recently reported on two cases of scleroderma patients with ANCA-associated vasculitis for the first time in Korea. In order to explore the nature of this disease combination, we pooled together all the previously known cases and statistically analyzed them. Out of the 50 selected cases, survival analysis was done for comparison of the scleroderma disease period and the clinical factors associated with ANCA-associated vasculitis (AAV). Kaplan-Meier analysis revealed that patients having anti-topoisomerase antibody (anti-Scl-70) and, probably, PR-3 ANCA are at a higher risk for developing AAV than patients without both anti-topoisomerase antibody and anti-centromere antibody (ACA), and patients with MPO-ANCA. Multivariate Cox regression analysis revealed having anti-topoisomerase antibody as a risk factor for developing AAV [OR 3.1 (95% CI 1.11-8.55), P=0.031]. We suggest that having anti-topoisomerase antibodies may play a role among scleroderma patients in developing AAV.
Lambert, Jessica; Rodriguez, Alexis; Pearcy-Baluyot, Mischelle; Shahi, Sanjeet K
Cutaneous leukocytoclastic vasculitis (LCV) is a systemic condition that can be associated with iritis. LCV is characterized as a small-vessel vasculitis of the cutaneous area. The disease demonstrates purple lesions on the skin due to the destruction of small cutaneous blood vessels. These lesions are palpable and most often coalesce forming larger patches on the surface of the skin. During early stages of LCV, the disease can be undetected due to the infrequency and small size of the skin lesions. As such, the patient might go undiagnosed for years while having symptoms of LCV or iritis of unknown etiology. This article discusses the correlation seen with LCV and iritis. We report a case on a patient that presented to our clinic with a history of bilateral chronic iritis. After extensive laboratory testing, we concluded that the chronicity of her iritis was due to her LCV. The correlation between LCV and iritis was not evident for several years in our patient. We also discuss the correlation with systemic Sjogren's syndrome and LVC and how these two separate diseases are linked in many patients. We will illustrate the importance of serological testing, imaging, and skin lesion biopsy for the diagnosis of LCV.
Riangwiwat, Tanawan; Wu, Chris Y; Santos-Ocampo, Alberto S; Liu, Randal J; McMurtray, Aaron M; Nakamoto, Beau K
Waldenström macroglobulinemia (WM) is an indolent B cell lymphoproliferative disorder with monoclonal IgM secretion. We present a patient with WM who presented with multifocal acute cortical ischemic strokes and was found to have central nervous system (CNS) vasculitis. Workup was negative for cryoglobulins and hyperviscosity syndrome. Immunosuppression with intravenous steroids and cyclophosphamide stabilized the patient's mental status and neurologic deficits. On followup over 7 years, patient gained independence from walking aids and experienced no recurrences of CNS vasculitis. To our knowledge, CNS vasculitis in a WM patient, in the absence of cryoglobulins, has not been reported. Immunosuppression is the preferred treatment.
Navarro, J. F.; Quereda, C.; Rivera, M.; Navarro, F. J.; Ortuño, J.
A 68 year old man presented with a systemic necrotizing vasculitis and elevated levels of anti-neutrophil cytoplasmic antibody (ANCA) which responded to treatment with steroids and cyclophosphamide, with a decrease in the titre of ANCA until its disappearance. Four months later he presented with weakness, loss of weight, aphonia and dysphagia. A computerized tomography scan showed a solid mass in the anterior mediastinum, and histological studies revealed an undifferentiated adenocarcinoma. Vasculitis improved although the malignancy progressed and ANCA was persistently negative. Our case demonstrates an association between ANCA and paraneoplastic vasculitis. Images Figure 2 PMID:8016013
Loricera, Javier; Calvo-Río, Vanesa; Ortiz-Sanjuán, Francisco; González-López, Marcos A.; Fernández-Llaca, Hector; Rueda-Gotor, Javier; Gonzalez-Vela, Maria C.; Alvarez, Lino; Mata, Cristina; González-Lamuño, Domingo; Martínez-Taboada, Victor M.; González-Gay, Miguel A.; Blanco, Ricardo
Abstract Cutaneous vasculitis may be associated with malignancies, and may behave as a paraneoplastic syndrome. This association has been reported in a variable proportion of patients depending on population selection. We conducted the current study to assess the frequency, clinical features, treatment, and outcome of paraneoplastic vasculitis in a large unselected series of 766 patients with cutaneous vasculitis diagnosed at a single university hospital. Sixteen patients (10 men and 6 women; mean age ± standard deviation, 67.94 ± 14.20 yr; range, 40–85 yr) presenting with cutaneous vasculitis were ultimately diagnosed as having an underlying malignancy. They constituted 3.80% of the 421 adult patients. There were 9 hematologic and 7 solid underlying malignancies. Skin lesions were the initial clinical presentation in all of them, and the median interval from the onset of cutaneous vasculitis to the diagnosis of the malignancy was 17 days (range, 8–50 d). The most frequent skin lesions were palpable purpura (15 patients). Other clinical manifestations included constitutional syndrome (10 patients) and arthralgia and/or arthritis (4 cases). Hematologic cytopenias (11 cases) as well as immature peripheral blood cells (6 cases) were frequently observed in the full blood cell count, especially in those with vasculitis associated with hematologic malignancies. Specific treatment for vasculitis was prescribed in 10 patients; nonsteroidal antiinflammatory drugs (4 patients), corticosteroids (3 patients), chloroquine (1 patient), antihistamines (1 patient), and cyclophosphamide (1 patient). Ten patients died due to the malignancy and 6 patients recovered following malignancy therapy. Patients with paraneoplastic vasculitis were older, more frequently had constitutional syndrome, and less frequently had organ damage due to the vasculitis than the remaining patients with cutaneous vasculitis. In summary, cutaneous paraneoplastic vasculitis is an entity not uncommonly
Riangwiwat, Tanawan; Wu, Chris Y.; Santos-Ocampo, Alberto S.; Liu, Randal J.
Waldenström macroglobulinemia (WM) is an indolent B cell lymphoproliferative disorder with monoclonal IgM secretion. We present a patient with WM who presented with multifocal acute cortical ischemic strokes and was found to have central nervous system (CNS) vasculitis. Workup was negative for cryoglobulins and hyperviscosity syndrome. Immunosuppression with intravenous steroids and cyclophosphamide stabilized the patient's mental status and neurologic deficits. On followup over 7 years, patient gained independence from walking aids and experienced no recurrences of CNS vasculitis. To our knowledge, CNS vasculitis in a WM patient, in the absence of cryoglobulins, has not been reported. Immunosuppression is the preferred treatment. PMID:27818812
Lotti, T M; Comacchi, C; Ghersetich, I
Cutaneous necrotizing vasculitis (CNV) is a complex multisystem disease generally involving the skin and mucous membranes, often accompanied by renal, gastrointestinal, pericardial, neurological, and articular signs and symptoms. CNV may be idiopatical or occur in association with a drug, infection, or underlying disease. CNV has been shown in patients with chronic infections (viral, bacterial, protozoa, helminthic), serum sickness, a variety of collagen vascular diseases (systemic lupus erythematous, Sjögren's syndrome, rheumatoid arthritis, Behçet's disease) hyperglobulinemic states, cryoglobulinemia, bowel bypass syndrome, ulcerative colitis, cystic fibrosis, primary biliary cirrhosis and HIV infection. Association with malignancies is not frequent. Lymphoproliferative disorders (Hodgkin's disease, mycosis fungoides, lymphosarcoma, adult T-cell leukemia, multiple mieloma) and solid tumors (lung cancer, colon carcinoma, renal, prostate, head and neck cancer and breast cancer) may be associated with CNV. Whenever possible, treatment is directed at the elimination of the cause. In other cases after adequate laboratory screening local and systemic therapy are recommended.
Kim, Hye Won; Song, Yeong Wook
We investigated the clinical features of Korean patients with anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) by reviewing the literature. The characteristics of AAV in Korean patients were as follows: (1) granulomatous and limited disease is prevalent in granulomatosis with polyangiitis (Wegener's) (GPA), (2) ANCA positivity is lower in GPA (56.6-68.9%) and eosinophilic granulomatosis with polyangiitis (EGPA) (5.9-8.3%), whereas it is higher in microscopic polyangiitis (MPA) (69-94%), (3) C-ANCA/proteinase 3 (PR3)-ANCA positivity is 71.5-100% in GPA and P-ANCA/myeloperoxidase (MPO)-ANCA positivity reached 94-100% in patients with MPA, (4) renal involvement or progression to end-stage renal disease was lower in Korean patients with GPA and EGPA than in Caucasians with GPA and EGPA (according to data provided in reports). The data provided here may need to be confirmed in large-scale studies.
Marques, Rui Moreira; Cabral, Ana Rita; Monteiro, Antonio; Henriques, Pedro
Churg-Strauss syndrome (CSS) is a rare syndrome characterized by sinusitis, asthma and peripheral eosinophilia. This vasculitic syndrome affects medium and small-sized vessels, the lung being the most commonly affected organ, followed by the skin. The authors report a case of a 59-year-old male with a past history of asthma and allergic rhinitis. He presented necrohemorragic lesions in the distal phalanx of the 2nd, 3rd and 4th fingers of the left-hand and petechial lesions in the plant of both feet, accompanied by asthenia, anorexia and weight loss. The analytical study revealed leukocytosis with eosinophilia, elevated inflammatory parameters and p-ANCA positive antibodies. The diagnosis of CSS was established based on clinical and histopathological data. Cutaneous manifestations of hemorragic vasculitis are rare in CSS syndrome but can be the first manifestation of the disease. The recognition of this presentation is important for the early diagnosis and treatment of this syndrome. PMID:25386301
Plasma exchange, or plasmapheresis, is a treatment method that developed over a period of two decades and involves the removal and replacement of a patient's circulating plasma. The aim of treatment is to remove disease-associated molecules and therefore interrupt disease progression. This article summarizes the developmental history of this treatment and then looks in more detail at data on the use of plasma exchange in treating antineutrophil antibody (ANCA)-associated vasculitis. The eight randomized trials and the Cochrane Systematic Review on treating renal vasculitis are summarized to show that plasma exchange may be effective in this disease, specifically in reducing the development of end-stage kidney disease (ESKD) by approximately 40%. The plasma exchange and glucocorticoid dosing in the treatment of anti-neutrophil cytoplasm antibody associated vasculitis (PEXIVAS) study is a currently enrolling study aiming to answer some of the outstanding questions relating to the use of this treatment in ANCA-associated vasculitis.
Basnyat, Shristi; Eid, Hala; Kuzyshyn, Halyna; Feinstein, David
The clinical presentation of Systemic Lupus Erythematosus (SLE) is diverse and vasculitis can be a potential manifestation. Cutaneous lesions involving small vessels are the most frequent presentation. However, medium and large vessel vasculitis may present with life-threatening visceral manifestations. We present a unique case of pelvic vasculitis mimicking a pelvic mass as an initial presentation of SLE. There are case reports of systemic vasculitis involving the female genital tract with giant cell arteritis (GCA), polyarteritis nodosa (PAN), and granulomatous with polyangiitis and microscopic polyangiitis (GPA/MPA), among others, but only a few cases attributed to SLE. Awareness of this condition and a prompt diagnosis are warranted as this is a severe and potentially life-threatening condition. PMID:28127489
... Weight loss Fatigue (tiredness) General aches and pains Organ- or Body System-Specific Signs and Symptoms Vasculitis can affect specific organs and body systems, causing a range of signs and symptoms. Skin ...
Sacks, Sarah; Steuer, Alan
We report regarding a male patient who presented with a systemic vasculitis that was consistent with a diagnosis of polyarteritis nodosa. At presentation, he had no features of inflammatory arthritis but had a high rheumatoid factor titer and low C4 level. Withdrawal of immunosuppression after 6 years resulted in the development of classical rheumatoid arthritis (RA). This case supports previous reports that revealed that vasculitis may predate the development or occur very early in the course of articular RA. PMID:28293454
Castañer, Eva; Alguersuari, Anna; Gallardo, Xavier; Andreu, Marta; Pallardó, Yolanda; Mata, Josep Maria; Ramírez, José
Vasculitis is an inflammatory destructive process affecting blood vessels. Pulmonary vasculitis may be secondary to other conditions or constitute a primary, and in most cases idiopathic, disorder. Underlying conditions in the secondary vasculitides are infectious diseases, connective tissue diseases, malignancies, and hypersensitivity disorders. The most widely used approach to classifying the primary vasculitides is based on the size of the affected vessels (large, medium, small). Thoracic involvement is most commonly seen with primary idiopathic large-vessel vasculitides (Takayasu arteritis, giant cell arteritis, Behçet disease) and primary small-vessel antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides (Wegener granulomatosis, microscopic polyangiitis, Churg-Strauss syndrome). The radiologic manifestations of primary pulmonary vasculitis are extremely variable and include vessel wall thickening, nodular or cavitary lesions, ground-glass opacities, and consolidations. Diffuse alveolar hemorrhage is a clinical syndrome that usually results from primary small-vessel vasculitis in the lungs. Although chest radiography is often the first imaging study performed in patients with pulmonary involvement by vasculitis, chest radiographs often fail to show the exact pattern and extent of thoracic involvement and CT is more useful in assessment of the thoracic findings. The pulmonary primary vasculitides are rare disorders, and their diagnoses are among the most demanding challenges in medicine because their signs and symptoms are nonspecific and overlap with those of infections, connective tissue diseases, and malignancies; thus, diagnosis of vasculitis relies on recognition of characteristic combinations of particular clinical, radiologic, laboratory, and histopathologic features.
Al-Ani, Bahjat; Fitzpatrick, Martin; Al-Nuaimi, Hamad; Coughlan, Alice M.; Hickey, Fionnuala B.; Pusey, Charles D.; Savage, Caroline; Benton, Christopher M.; O’Brien, Eóin C.; O’Toole, Declan; Mok, Ken H.; Young, Stephen P.; Little, Mark A.
Current biomarkers of renal disease in systemic vasculitis lack predictive value and are insensitive to early damage. To identify novel biomarkers of renal vasculitis flare, we analysed the longitudinal urinary metabolomic profile of a rat model of anti-neutrophil cytoplasmic antibody (ANCA) vasculitis. Wistar-Kyoto (WKY) rats were immunised with human myeloperoxidase (MPO). Urine was obtained at regular intervals for 181 days, after which relapse was induced by re-challenge with MPO. Urinary metabolites were assessed in an unbiased fashion using nuclear magnetic resonance (NMR) spectroscopy, and analysed using partial least squares discriminant analysis (PLS-DA) and partial least squares regression (PLS-R). At 56 days post-immunisation, we found that rats with vasculitis had a significantly different urinary metabolite profile than control animals; the observed PLS-DA clusters dissipated between 56 and 181 days, and re-emerged with relapse. The metabolites most altered in rats with active or relapsing vasculitis were trimethylamine N-oxide (TMAO), citrate and 2-oxoglutarate. Myo-inositol was also moderately predictive. The key urine metabolites identified in rats were confirmed in a large cohort of patients using liquid chromatography–mass spectrometry (LC-MS). Hypocitraturia and elevated urinary myo-inositol remained associated with active disease, with the urine myo-inositol:citrate ratio being tightly correlated with active renal vasculitis. PMID:27905491
Fishbein, Gregory A; Fishbein, Michael C
Pulmonary vasculitides are a diverse group of limited and systemic disorders associated with inflammation of pulmonary vessels and parenchyma. These diseases often have distinctive clinical, serological, and histopathological features-extrapulmonary sites of involvement, circulating autoantibodies, predispositions for small or large vessels, and others. Some have characteristic inflammatory lesions; others are characterized by the absence of such lesions. Frequently pathological findings overlap, rendering classification, and diagnosis a challenge. The anti-neutrophil cytoplasmic antibody (ANCA)-associated small-vessel diseases constitute the major pulmonary vasculitides. These include Wegener granulomatosis (WG), Churg Strauss syndrome (CSS), and microscopic polyangiitis (MPA). Less frequently, diseases such as polyarteritis nodosa, Takayasu arteritis, Behçet syndrome, and connective tissue diseases may involve pulmonary vessels, but these entities are better associated with extrapulmonary disease. Diffuse alveolar hemorrhage (DAH) is a severe manifestation of pulmonary vasculitis. DAH is most commonly seen in small-vessel vasculitides, specifically MPA and WG. Other syndromes associated with DAH include Goodpasture syndrome, Henoch-Schönlein purpura, and systemic lupus erythematosus. Less commonly, DAH may be secondary to infection or drugs/toxins. Furthermore, in the absence of discernable systemic disease, DAH may be idiopathic-referred to as isolated pulmonary capillaritis (IPC) or idiopathic pulmonary hemosiderosis (IPH), depending on the presence of capillaritis.
De Vita, S; Soldano, F; Isola, M; Monti, G; Gabrielli, A; Tzioufas, A; Ferri, C; Ferraccioli, G F; Quartuccio, L; Corazza, L; De Marchi, G; Casals, M Ramos; Voulgarelis, M; Lenzi, M; Saccardo, F; Fraticelli, P; Mascia, M T; Sansonno, D; Cacoub, P; Tomsic, M; Tavoni, A; Pietrogrande, M; Zignego, A L; Scarpato, S; Mazzaro, C; Pioltelli, P; Steinfeld, S; Lamprecht, P; Bombardieri, S; Galli, M
Background To develop preliminary classification criteria for the cryoglobulinaemic syndrome or cryoglobulinaemic vasculitis (CV). Methods Study part I developed a questionnaire for CV to be included in the formal, second part (study part II). Positivity of serum cryoglobulins was defined by experts as an essential condition for CV classification. In study part II, a core set of classification items (questionnaire, clinical and laboratory items, as agreed) was tested in three groups of patients and controls—that is, group A (new patients with the CV), group B (controls with serum cryoglobulins but lacking CV) and group C (controls without serum cryoglobulins but with features which can be observed in CV). Results In study part I (188 cases, 284 controls), a positive response to at least two of three selected questions showed a sensitivity of 81.9% and a specificity of 83.5% for CV. This questionnaire was employed and validated in study part II, which included 272 patients in group A and 228 controls in group B. The final classification criteria for CV, by pooling data from group A and group B, required the positivity of questionnaire plus clinical, questionnaire plus laboratory, or clinical plus laboratory items, or all the three, providing a sensitivity of 88.5% and a specificity of 93.6% for CV. By comparing data in group A versus group C (425 controls), the same classification criteria showed a sensitivity 88.5% and a specificity 97.0% for CV. Conclusion Classification criteria for CV were developed, and now need validation. PMID:21571735
Rao, Mana; Agrawal, Abhinav; Parikh, Manan; Banayat, Rikka; Thomas, Maria Joana; Guo, Tianhua; Lee, Andrew
Mycoplasma is a virulent organism that is known to primarily infect the respiratory tract; however, affection of the skin, nervous system, kidneys, heart and bloodstream has been observed in various forms, which include Stevens Johnson syndrome, erythema multiforme, toxic epidermal necrolysis, encephalitis, renal failure, conduction system abnormalities and hemolytic anemia. Small vessel vasculitis is a lesser-known complication of mycoplasma pneumonia infection. We report a case of mycoplasmal upper respiratory tract infection with striking cutaneous lesions as the presenting symptom. Mycoplasmal infection was confirmed by serology testing, skin biopsy was suggestive of leukocytoclastic vasculitis. This case brings forth an uncommon manifestation of mycoplasmal infection with extra-pulmonary affection, namely small vessel vasculitis. PMID:25874067
Katsumata, Yasuhiro; Kawaguchi, Yasushi; Yamanaka, Hisashi
The association between interstitial lung disease (ILD) and anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), particularly microscopic polyangiitis (MPA), has been described in a number of case reports and case series reports in the last 2 decades. In addition, patients with pulmonary fibrosis and ANCA positivity but without other manifestations of systemic vasculitis have also been reported. Pulmonary fibrosis was clinically manifested at the time of diagnosis in the majority of AAV patients that developed this condition. Moreover, ANCA-positive conversion occurs in patients initially diagnosed with idiopathic pulmonary fibrosis, and as a result, other manifestations of systemic vasculitis develop in some of these patients. There is significant predominance of myeloperoxidase (MPO)-ANCA and MPA in patients with AAV and ILD. Radiological and pathological findings generally demonstrate usual interstitial pneumonia (pattern) in the lungs of these patients. In most studies, AAV patients with ILD have a worse prognosis than those without it. PMID:26448696
Korkmaz, Pınar; Kıdır, Mehtap; Namdar, Nazlı Dizen; Özmen, Ahmet; Uyar, Cemile; Değer, Ayşe Nur
Brucellosis is a zoonosis that affects several organs or systems. Skin involvement is nonspecific and it is reported to range between 0,4 and 17% of the patients with brucellosis. Here, we defined a 36-year-old female patient presented to our clinic with a clinical picture of recurrent attacks of vasculitis due to brucellosis for the first time. Skin involvement and vasculitic lesions as a finding of skin involvement are nonspecific in brucellosis. Therefore, in the regions like Turkey where brucellosis is endemic, brucellosis should be kept in mind necessarily in the differential diagnosis of vasculitis. PMID:27042369
Korkmaz, Pınar; Kıdır, Mehtap; Namdar, Nazlı Dizen; Özmen, Ahmet; Uyar, Cemile; Değer, Ayşe Nur
Brucellosis is a zoonosis that affects several organs or systems. Skin involvement is nonspecific and it is reported to range between 0,4 and 17% of the patients with brucellosis. Here, we defined a 36-year-old female patient presented to our clinic with a clinical picture of recurrent attacks of vasculitis due to brucellosis for the first time. Skin involvement and vasculitic lesions as a finding of skin involvement are nonspecific in brucellosis. Therefore, in the regions like Turkey where brucellosis is endemic, brucellosis should be kept in mind necessarily in the differential diagnosis of vasculitis.
Lucas, Alexandra; Maung, Ko Ko; Ratts, Ryan
Intracranial abscesses are rare complications of Streptococcus pneumoniae infections, and to our knowledge, there have been no case reports of post-infectious vasculitis developing in such patients. Here we describe the case of a 48-year-old post-splenectomy male who developed post-infectious vasculitis following S. pneumoniae otitis media complicated by mastoiditis, osteomyelitis, meningitis, and intracranial abscess. Clinicians ought to be aware of the possible adverse outcomes of invasive S. pneumoniae and the limitations of current treatment options. PMID:28191299
Sawalha, Amr H; Dozmorov, Mikhail G
Systemic vasculitides are poorly understood inflammatory diseases of the blood vessels that are frequently associated with significant organ damage. Genetic risk variants contribute to the susceptibility of vasculitis, but functional consequences of these genetic variants are largely unknown. Most genetic risk variants in immune-mediated diseases, including systemic vasculitis, are localized to non-coding genetic regions suggesting they might increase disease risk by influencing regulatory elements within the genome. Long range regulatory interactions pose an additional obstacle in localizing functional consequences associated with risk variants to specific genes or cell types. We used cell-type specific enrichment patterns of histone changes that mark poised, primed, and active enhancers, and DNase hypersensitivity to identify specific immune cells mediating genetic risk in vasculitis. Our data suggest that genetic risk variants in ANCA-associated vasculitis are significantly enriched in enhancer elements in Th17 cells, supporting a role for Th17 cells in this disease. Primed and active enhancer elements in B cells can be potentially affected by genetic risk variants associated with Kawasaki disease. Genetic risk in Behçet's disease and Takayasu arteritis might affect enhancer elements in multiple cell types, possibly explained by influencing enhancers in hematopoietic stem cells. Interestingly, our analyses indicate a role for B cells in Kawasaki disease, Behçet's disease, and Takayasu arteritis, and suggest that further work to characterize the involvement of B cells in these diseases is warranted.
Espitia, Olivier; Dréno, Brigitte; Cassagnau, Elisabeth; Didier, Quentin; Quillard, Thibaut; Nicol, Christelle; Le Bouch, Yann; Planchon, Bernard; Pistorius, Marc-Antoine
Although exercise-induced vasculitis (EIV) is usually misdiagnosed, it is not uncommon. Occurring mostly after prolonged exercise, especially in hot weather, EIV is an isolated cutaneous vasculitis with stereotypical presentation. This article reviews the clinical characteristics, treatments, and outcomes of EIV based on the published literature. We report 99 patients who developed EIV after walking, dancing, swimming, or hiking especially during hot weather, including the records of 16 patients with EIV treated at our hospital from 2007 to 2015. Erythematous or purpuric plaques arise on the lower legs, without the involvement of compression socks or stockings. Symptoms include itch, pain, and a burning sensation. EIV is an isolated cutaneous vasculitis. Lesions resolve spontaneously after 10 days. When triggering conditions persist, relapses are frequent (77.5 %). Histopathology demonstrates leukocytoclastic vasculitis in 95 % of cases with C3 or immunoglobulin M deposits in 88 and 46 % of cases, respectively. Blood investigations are negative. EIV appears to be a consequence of venous stasis induced by an acute failure of the muscle pump of the calf and thermoregulation decompensation. Both appear after prolonged and unusual exercise in hot weather. Treatment is not codified; topical corticosteroids may reduce symptoms and wearing light clothes might limit lesion occurrence.
Galesic, Kresimir; Ljubanovic, Danica; Horvatic, Ivica
Context Vasculitis is a clinicopathological entity characterized by inflammation and necrosis of blood vessels. Evidence Acquisitions Directory of Open Access Journals (DOAJ), Google Scholar, Pubmed (NLM), LISTA (EBSCO) and Web of Science have been searched. Results Two major autoantigens for ANCA are myeloperoxidase (MPO) and proteinase 3 (PR3), which are proteins in the primary granules of neutrophils and in the lysosomes of monocytes. They are expressed in mature neutrophils of patients with ANCA, while absent in healthy subjects. Conclusions The kidney is the most commonly affected vital organ in ANCA-associated vasculitis, and patient outcomes are largely determined by the severity of renal disease at diagnosis and by its response to treatment. PMID:24475421
Bowlt, K; Cattin, I; Stewart, J
Feline hyperthyroidism can be treated medically, surgically or with radioactive iodine. Carbimazole inhibits both triiodothyronine and thyroxine synthesis in the thyroid gland and reported side effects include mild eosinophilia, leucopenia and lymphocytosis, thrombocytopenia, elevated liver enzyme activities, gastrointestinal signs and skin abnormalities. This case report describes a cat with carbimazole-associated apparent hypersensitivity vasculitis causing digital and tail necrosis, with multiple renal infarcts. Withdrawal of carbimazole resulted in stable disease.
Retamozo, Soledad; Brito-Zerón, Pilar; Ramos-Casals, Manuel
Cryoglobulinemia is a heterogeneous systemic autoimmune disease with a wide variety of causes, symptoms and outcomes, and different etiopathogenic pathways involved in the vasculitic organ damage. The discovery of the hepatitis C virus (HCV) in 1989 changed radically the focus of research of the so-called "essential" cryoglobulinemia. Cryoglobulins can be detected in 25-30% of patients with HCV, overwhelmingly representing mixed cryoglobulins. However, only 10-15% of patients present with cryoglobulinemic vasculitis, with a broad spectrum of symptoms including mild or life-threatening manifestations. Consequently, not all patients can be uniformly treated. The key therapeutic points in HCV+ patients with cryoglobulinemic vasculitis cover different aspects. The first is to treat the underlying cause of cryoglobulinemia whenever possible, hence the use of antiviral therapies must always be considered in these patients. An individualized diagnostic approach to assess the number of organs involved and the severity of organ involvement is also essential in the therapeutic planning. This complex clinical scenario leads to an equally complex therapeutic scenario. There are three main treatment strategies for HCV-associated cryoglobulinemic vasculitis: conventional immunosuppression, antiviral treatment and biological therapies. The most recent studies are suggesting a change from the classical therapeutic approach (monotherapeutic regimens) to combination/sequential regimens, including treatments targeting the virus and those directed against the induced autoimmune disease, with the aim of blocking the various etiopathogenic pathways involved.
Nakano, Hiromasa; Ozaki, Shoichi
The vasculitides are defined by the presence of leukocytes in vessel walls with reactive damage to mural structures. Vasculitis may occur as a primary process or may be secondary to another underlying disease. In general, the affected vessels vary in size, type, and location in association with the specific vasculitic disorder. Classically, vasculitic syndromes have been categorized by the predominant sizes of the blood vessels and types of vessel most commonly affected among patients with the disorder. Currently, antineutrophil cytoplasmic antibody (ANCA) testing plays a critical role in the pathogenesis, diagnosis, and classification of vasculitides. Two types of ANCA assay (indirect immunofluorescence assay and enzyme-linked immunosorbent assay (ELISA)) are in wide use. Two major immunofluorescence patterns are observed, the C-ANCA and P-ANCA patterns. In vasculitis, the two relevant target antigens for ANCA are proteinase 3 (PR3) and myeloperoxidase (MPO). Antibodies with target specificities for PR3 and MPO are called PR3-ANCA and MPO-ANCA, respectively. Vasculitides associated with serum positivity for ANCA that affect small to medium-sized vessels are commonly known as ANCA-associated vasculitis and include Wegener's granulomatosis, microscopic polyangiitis, and Churg-Strauss syndrome. In this article, the pathogenesis of ANCA will be reviewed as well as the pitfalls regarding its clinical application.
Hoffman, Gary S
In the field of autoimmunity, much has been learned from studying circulating and tissue bound immune-reactive cells, cytokines and antibodies. However, what has brought those cells to the site of injury, for most forms of vasculitis remains a mystery. Might the etiology of at least certain forms of vasculitis be related to generation of neoantigens in the native vessel, making that vessel the target of a pathogenic immune response? How might one explain organ targeting and patterns of disease that are so critical to the diagnostic process? Embryologists have demonstrated great diversity in the vasculature of different organs. Unique quantitative and qualitative features become apparent in vascular territories as early as the third week of gestation. These differences are later amplified by the effects of further development, aging, infection, spontaneous mutations and other co-morbidities. Based on data from these observations a testable hypothesis would be that many forms of vasculitis may begin with emergence of new antigens within affected vessel walls and the resulting immune response may in fact be a normal reaction to perceived foreign protein(s).
García-Patos, V; Barnadas, M A; Domingo, P; Esquius, J; de Moragas, J M
We report a patient with an upper respiratory tract infection who presented outbreaks of erythematosus-purpuric macules and papules (the pathological substrate of which was a leukocytoclastic vasculitis with numerous intravascular thrombi) coinciding with two autolimited febrile episodes. In serial hemocultures B meningococcus was identified oral antibiotic treatment was given achieving a good clinical evolution. Although both episodes could be considered as a meningococcemia without sepsis, they could also correspond to the initial phase of a chronic meningococcemia. The possible etiopathogenesis of the cutaneous lesions is discussed and the therapeutic and prognostic repercussion of an early identification of these forms of meningococcal disease, which are poorly expressed clinically, are highlighted.
Sreih, Antoine G; Mandhadi, Ranadeep; Aldaghlawi, Fadi; Khan, Asad; Irshad, Vajiha; Finn, Katherine; Block, Joel A
This study aims to compare the severity and outcomes of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) between Hispanics and Caucasians living in the same geographical area. All patients diagnosed with AAV at two academic institutions in Chicago from January 2006 to December 2012 were retrospectively and prospectively identified. Disease activity was measured with the Birmingham Vasculitis Activity Score (BVAS), and disease damage was measured with the Vasculitis Damage Index (VDI). Student's t test and chi-square tests were employed; p ≤ 0.05 was considered significant. Seventy patients with AAV were identified; 15 patients were excluded. Fifty-five patients were included in the study: 23 Hispanics and 32 Caucasians, 35 patients with granulomatosis with polyangiitis (Wegener's), 12 with microscopic polyangiitis, 7 with eosinophilic granulomatosis with polyangiitis, and 1 with renal-limited vasculitis. Compared to Caucasians, Hispanics had a higher BVAS at presentation (16.3 ± 7.6 versus 10.7 ± 7.5, p = 0.006), a higher VDI at presentation (2.90 ± 1.50 versus 2.06 ± 1.30, p = 0.030), and a cumulative VDI (3.90 ± 1.70 versus 2.50 ± 1.90, p = 0.010). Renal involvement was more common among Hispanics (85 % of Hispanics versus 48 % of Caucasians, p = 0.01). Seventy percent of Hispanics had acute renal failure (mean creatinine = 3.37 ± 4.4 mg/dl) of whom seven (50 %) required dialysis, versus 25 % of Caucasians (mean creatinine = 1.78 ± 1.57 mg/dl, p = 0.03) and only two requiring dialysis. Compared to Caucasians, Hispanics with AAV present with more severe disease and higher damage indices. Larger studies are required to confirm these findings and delineate the respective roles of environment and genetics in the pathogenesis of the disease.
Bouiller, Kévin; Audia, Sylvain; Devilliers, Hervé; Collet, Evelyne; Aubriot, Marie Hélène; Leguy-Seguin, Vanessa; Berthier, Sabine; Bonniaud, Philippe; Chavanet, Pascal; Besancenot, Jean-François; Vabres, Pierre; Martin, Laurent; Samson, Maxime; Bonnotte, Bernard
Abstract In this study, outcomes of patients with leukocytoclastic vasculitis (LCV) were analyzed focusing on clinical, histopathology and laboratory findings, relapses, and survival. Data from patients with cutaneous vasculitis diagnosed between January 1, 2000, and December 31, 2010, at Dijon University Hospital (France) were retrospectively reviewed. LCV was defined as perivascular neutrophilic infiltrate, endothelial cell nuclear swelling, extravasation of red blood cells, and/or fibrin deposition in vessels. Patients were classified according to the 2012 Chapel Hill Consensus Conference. Relapses were defined as the recurrence of vasculitis symptoms after a period of remission >1 month. Time to relapse and/or death was calculated from the date of diagnosis. Univariate and multivariate (Cox model) analyses were performed. A total of 112 patients (57 males and 55 females), with a mean age of 60 ± 19 (18–98) years, were analyzed. Overall follow-up was 61 ± 38 months. At diagnosis, all patients had skin lesions, purpura being the most common (n = 83). Lesions were associated with systemic involvement in 55 (51%) patients. Only 41 (36.6%) patients received specific treatment: glucocorticoids in 29 of 41 (70.7%) and immunosuppressants in 9 of 41 (22%). Sixty-two patients (55%) had LCV due to underlying causes, 29 (25.9%) had single-organ cutaneous small vessel vasculitis (SoCSVV), and 21 (18.8%) had unclassifiable LCV. Twenty patients of the cohort (18%) experienced relapse, 14 ± 13 (1–40) months after the diagnosis of LCV. None of the 29 patients with SoCSVV relapsed. Independent risk factors for relapse were vascular thrombosis in the biopsy [hazard ratio (HR) = 4.9; P = 0.017], peripheral neuropathy (HR = 9.8; P = 0.001), hepatitis (HR = 3.1; P = 0.004), and positive antineutrophil cytoplasm antibodies (ANCA, HR = 5.9 P = 0.005). In contrast, SoCSVV was a protective factor for relapse (HR = 0.12; P = 0.043). The 1-, 3-, and 6-year overall
Kobak, Senol; Yilmaz, Hatice; Karaarslan, Ahmet; Yalcin, Murat
A 26-year-old male patient presented to our rheumatology clinic with pain, swelling and limitation of movement in his right ankle, and also purpuric skin lesions in the lower extremity pretibial region. He was asked questions, and he said that he had been having chronic low back pain and morning stiffness for the last few years. His physical examination revealed that he had arthritis in his right ankle, purpuric skin lesions in pretibial regions of both legs, and bilateral FABERE/FADIR positivity. The sacroiliac joint imaging and MRI revealed bilateral sacroiliitis findings, and the lateral heel imaging revealed enthesitis. HLA-B27 was positive. Skin biopsy from lower skin lesions was reported to be consistent with leukocytoclastic vasculitis. Based on clinical, laboratory, radiological, and pathological examinations, the patient was diagnosed with ankylosing spondylitis and leukocytoclastic vasculitis. Administration of corticosteroid, salazopyrin, and nonsteroid anti-inflammatory medications was started. Notable clinical and laboratory regression was observed during his checks 3 months later. PMID:24653851
Khoury, Paneez; Grayson, Peter C; Klion, Amy D
Eosinophils are multifunctional granular leukocytes that are implicated in the pathogenesis of a wide variety of disorders, including asthma, helminth infection, and rare hypereosinophilic syndromes. Although peripheral and tissue eosinophilia can be a feature of many types of small-vessel and medium-vessel vasculitis, the role of eosinophils has been best studied in eosinophilic granulomatosis with polyangiitis (EGPA), where eosinophils are a characteristic finding in all three clinical stages of the disorder. Whereas numerous studies have demonstrated an association between the presence of eosinophils and markers of eosinophil activation in the blood and tissues of patients with EGPA, the precise role of eosinophils in disease pathogenesis has been difficult to ascertain owing to the complexity of the disease process. In this regard, results of clinical trials using novel agents that specifically target eosinophils are providing the first direct evidence of a central role of eosinophils in EGPA. This Review focuses on the aspects of eosinophil biology most relevant to the pathogenesis of vasculitis and provides an update of current knowledge regarding the role of eosinophils in EGPA and other vasculitides.
Hilhorst, Marc; Shirai, Tsuyoshi; Berry, Gerald; Goronzy, Jörg J.; Weyand, Cornelia M.
Granuloma formation, bringing into close proximity highly activated macrophages and T cells, is a typical event in inflammatory blood vessel diseases, and is noted in the name of several of the vasculitides. It is not known whether specific properties of the microenvironment in the blood vessel wall or the immediate surroundings of blood vessels contribute to granuloma formation and, in some cases, generation of multinucleated giant cells. Granulomas provide a specialized niche to optimize macrophage–T cell interactions, strongly activating both cell types. This is mirrored by the intensity of the systemic inflammation encountered in patients with vasculitis, often presenting with malaise, weight loss, fever, and strongly upregulated acute phase responses. As a sophisticated and highly organized structure, granulomas can serve as an ideal site to induce differentiation and maturation of T cells. The granulomas possibly seed aberrant Th1 and Th17 cells into the circulation, which are known to be the main pathogenic cells in vasculitis. Through the induction of memory T cells, aberrant innate immune responses can imprint the host immune system for decades to come and promote chronicity of the disease process. Improved understanding of T cell–macrophage interactions will redefine pathogenic models in the vasculitides and provide new avenues for immunomodulatory therapy. PMID:25309534
Smoller, B R; McNutt, N S; Contreras, F
While histopathologic analysis may offer some clues as to the pathogenesis of vasculitis, observations must be interpreted with caution, as there is considerable overlap in the histologic pattern. In most cases, a predominantly neutrophilic vasculitis affecting small dermal venules suggests a relatively acute, immune complex-mediated reaction. Less commonly, this histologic pattern may be seen in non-immunologically mediated processes, such as in the presence of bacterial toxins or malignant hypertension, or in more chronic disease states, such as granuloma faciale or erythema elevatum diutinum. A predominantly lymphocytic vasculitis may represent several pathogenetic mechanisms. In lesions more than 24 to 48 hours old, a lymphocytic vasculitis may represent a resolving phase of an immune complex-mediated neutrophilic vasculitis. Alternatively, this histologic pattern may be seen de novo in conditions with a presumed cell-mediated immunologic pathogenesis. Lymphocytic vasculitis may also be seen in rickettsial infections such as Rocky Mountain spotted fever. The pathogenesis of granulomatous vasculitis remains poorly understood and is thought to be induced by a combination of circulating immune complexes and a cell-mediated immune response.
Mayor, Helen; Reidy, John
Fatigue is a common symptom associated with vasculitis and contributes significantly to impaired quality of life. Motivational control theory suggests a role for perseverative cognition and goal adjustment in fatigue. Therefore, this study investigated these potential predictors of fatigue in individuals with vasculitis. A total of 249 participants completed online questionnaires assessing fatigue, perseverative cognition, goal disengagement and goal reengagement, in addition to demographic and disease-related variables. Hierarchical regression analysis found only pain, sleep disturbance, disease activity and perseverative cognition to significantly predict fatigue. This highlights the importance of psychological factors in determining fatigue in those with vasculitis.
Groothuis, D.R.; Mikhael, M.A.
In this report we describe a patient with a benign glioma treated with surgery and radiation. After a period of stability he developed subacute bacterial endocarditis, and deteriorated neurologically. Computed tomographic scans did not show recurrent tumor. An angiogram showed vasculitis restricted to the previously irradiated area. Secondary to subacute bacterial endocarditis was the presence of high levels of circulating immune complexes. His neurological status was unchanged after antibiotics, but improved after treatment with dexamethasone. We interpret the clinical course as an immune-complex-mediated vasculitis superimposed on a subclinical radiation vasculitis. This case supports the hypothesis that immune mechanisms may be involved in delayed radiation injury to the nervous system.
Hoffman, G S
The era prior to 1990 was a time of careful observation of disease presentation, course, outcomes and meticulous pathology studies. These mainly single-centre studies introduced new life-saving therapies for drugs still used effectively today. In the 1970-1980s, cyclophosphamide (CyP) added to glucocorticosteroids (GCS) was shown to be life-saving. The trade-off was often severe adverse events. Some forms of vasculitis were found not as ominous as thought initially. Some could be treated with safer drugs [e.g. methotrexate (MTX)]. However, whether mild or severe, patients were not cured. From 1990 to the present large collaborative networks have provided studies were not possible heretofore. Randomized controlled trials captured and manipulated vast amounts of data, banked biological specimens and shared these resources and intellectual capital, moving the field forward at an extraordinary pace. We now know that even for severe forms of granulomatosis and polyangiitis [granulomatosis with polyangiitis (GPA), Wegener's granulomatosus (WG)], microscopic polyangiitis (MPA) and Churg-Strauss syndrome (CSS), we do not need to use CyP for extended periods. We have learned recently that rituximab is as effective as CyP for severe WG and MPA. We should never again see the permanent toxicities born from years of chronic CyP use. However, short courses of CyP remain useful and can be life-saving. Step-down therapy from CyP is now a standard of care, perhaps to be replaced by rituximab in the future. If one accepts the premise that there are few cures at present for idiopathic large- and small-vessel vasculitis, we will serve our patients well if we can determine the most effective initial therapy that leads to a maintenance strategy for remission with least risk. Ultimately, we wish to identify causes of vasculitis so they can be used as a wedge to secure cures. Unmet needs and strategies are as follows: (1) to increase the numbers of vasculitis-trained physicians; (2) to
Singh, Lavleen; Singh, Geetika; Bhardwaj, Swati; Sinha, Aditi; Bagga, Arvind; Dinda, Amit
Dense deposit disease is caused by fluid-phase dysregulation of the alternative complement pathway and frequently deviates from the classic membranoproliferative pattern of injury on light microscopy. Other patterns of injury described for dense deposit disease include mesangioproliferative, acute proliferative/exudative, and crescentic GN. Regardless of the histologic pattern, C3 glomerulopathy, which includes dense deposit disease and C3 GN, is defined by immunofluorescence intensity of C3c two or more orders of magnitude greater than any other immune reactant (on a 0-3 scale). Ultrastructural appearances distinguish dense deposit disease and C3 GN. Focal and segmental necrotizing glomerular lesions with crescents, mimicking a small vessel vasculitis such as ANCA-associated GN, are a very rare manifestation of dense deposit disease. We describe our experience with this unusual histologic presentation and distinct clinical course of dense deposit disease, discuss the pitfalls in diagnosis, examine differential diagnoses, and review the relevant literature.
Kallenberg, Cees G M
Anti-neutrophil cytoplasmic autoantibodies (ANCA) directed to proteinase 3 (PR3-ANCA) and myeloperoxidase (MPO-ANCA) are sensitive and specific markers for their associated diseases, granulomatosis with polyangiitis (GPA, formerly Wegener's granulomatosis) and microscopic polyangiitis (MPA), respectively. Clinical observations suggest but do not prove that ANCA are involved in the pathogenesis of GPA and MPA. In vivo and in vitro experimental data strongly suggest if not prove that MPO-ANCA underlie the pathological lesions seen in MPO-ANCA associated MPA. This is less clear for PR3-ANCA associated GPA in which, besides small-vessel vasculitis, granulomatous inflammation is apparent. Here, cellular immunity appears to play an additional role. Insight into the pathogenetic events involved in these diseases has resulted in new ways of treatment that target the specific pathways that underlie the development of the lesions.
A fundamental change in management of antineutrophil cytoplasmic antibody-associated vasculitis in the past 10 years is the early focussed use of aggressive immunosuppression, using regimens comprised of widely available medications. Using a clinical framework to quantify morbidity, we can induce remission in most patients within 3-6 months using glucocorticoids plus methotrexate, cyclophosphamide or rituximab, with additional plasmapheresis when indicated. Difficulty in maintaining remission probably relates to the difference between true pathophysiological remission and the absence of clinical, serological or radiological evidence of disease activity. For surviving patients, the cumulative problems of relapse, burden of disease, or its treatment are coupled with pre-existing diseases or new conditions arising since diagnosis. Initial early control should reduce subsequent damage, but what effect it will have on relapse is not clear. In the absence of a cure, future trials should focus on reducing toxicity and comorbidity as well as controlling disease.
Singh, Lavleen; Bhardwaj, Swati; Sinha, Aditi; Bagga, Arvind; Dinda, Amit
Dense deposit disease is caused by fluid-phase dysregulation of the alternative complement pathway and frequently deviates from the classic membranoproliferative pattern of injury on light microscopy. Other patterns of injury described for dense deposit disease include mesangioproliferative, acute proliferative/exudative, and crescentic GN. Regardless of the histologic pattern, C3 glomerulopathy, which includes dense deposit disease and C3 GN, is defined by immunofluorescence intensity of C3c two or more orders of magnitude greater than any other immune reactant (on a 0–3 scale). Ultrastructural appearances distinguish dense deposit disease and C3 GN. Focal and segmental necrotizing glomerular lesions with crescents, mimicking a small vessel vasculitis such as ANCA-associated GN, are a very rare manifestation of dense deposit disease. We describe our experience with this unusual histologic presentation and distinct clinical course of dense deposit disease, discuss the pitfalls in diagnosis, examine differential diagnoses, and review the relevant literature. PMID:26361799
Jennette, J. C.; Wilkman, A. S.; Falk, R. J.
Anti-neutrophil cytoplasmic autoantibodies (ANCA) react with constituents of neutrophil primary granules and monocyte lysosomes. Indirect immunofluorescence microscopy using alcohol-fixed neutrophils demonstrates two ANCA types: one causing cytoplasmic staining (C-ANCA), and a second causing artifactual perinuclear staining (P-ANCA) that frequently has specificity for myeloperoxidase. Using indirect immunofluorescence microscopy (IIFM) and enzyme immunoassays (EIA), sera from over 300 patients with renal disease, with and without systemic vasculitis, were analyzed. Of 76 patients with pauci-immune glomerulonephritis with crescents or necrosis, 87% had ANCA by IIFM (38% of C-ANCA type, 49% of P-ANCA type), and 78% had ANCA by EIA. Of 55 patients with nonlupus immune complex-mediated glomerulonephritis, only 11% had ANCA by IIFM and 5% had ANCA by EIA. Of 24 patients with anti-GBM antibody-mediated glomerulonephritis, none had ANCA. Renal and extrarenal lesions were studied in 81 patients with ANCA-associated glomerulonephritis. These patients formed a pathologic continuum ranging from renal-limited to widespread systemic vascular injury, including patients with primary crescentic glomerulonephritis, Wegener's granulomatosis, and polyarteritis nodosa. In ANCA-positive patients the frequency of C-ANCA and P-ANCA correlated with disease distribution. P-ANCA was most frequent with renal-limited disease and C-ANCA was most frequent when there was lung and sinus involvement. It is proposed that ANCA are not only useful diagnostic markers, but may also be directly involved in a novel pathogenetic mechanism that is a frequent cause of crescentic glomerulonephritis and systemic necrotizing vasculitis. Images Figure 1 Figure 4 Figure 5 Figure 6 Figure 7 PMID:2683800
de Boysson, Hubert; Martin Silva, Nicolas; de Moreuil, Claire; Néel, Antoine; de Menthon, Mathilde; Meyer, Olivier; Launay, David; Pagnoux, Christian; Guillevin, Loïc; Puéchal, Xavier; Bienvenu, Boris; Aouba, Achille
Abstract A few reports suggest combination of ANCA-associated vasculitis (AAV) and neutrophilic dermatoses (ND). We aimed to describe the main characteristics of patients presenting with both AAV and ND in a French cohort and through a systematic literature review, and to discuss the possible common pathogenic process involved. We conducted a retrospective study of patients with both conditions. Patients were selected via the French Internal Medicine Society (SNFMI) and the French Vasculitis Study Group (FVSG). A literature review focusing on a combination of both conditions, concentrated only on publications with well-established diagnoses and individual detailed data. Seventeen patients diagnosed with AAV and ND were identified in this cohort. Twelve patients had granulomatosis with polyangiitis (GPA), 4 had microscopic polyangiitis (MPA) and one had eosinophilic GPA (EGPA). Eight patients, all with GPA, displayed pyoderma gangrenosum (PG). Sweet's syndrome was observed in 6 patients (4 with MPA, one with GPA and one with EGPA) and erythema elevatum diutinum in the other three (2 with GPA and 1 with MPA). The literature review identified 33 additional patients with both conditions, including 26 with GPA. Altogether, of the 50 patients (17 from our study and 33 from the literature review), 33 (66%) patients presented with PG associated with GPA in 29 cases (89%). Corticosteroids were the first-line treatment in conjunction with an immunosuppressive agent in most cases. Outcomes were good and a total of 15 patients experienced a relapse. Patients who relapsed were more likely to have ear, nose and throat manifestation than patients who did not [12/15 (80%) relapsing patients vs. 15/35 (43%) non-relapsing patients; p = 0.03)]. In our stud, the most frequent association concerned GPA and PG. ND should be considered and specifically researched within the spectrum of cutaneous manifestations observed in AAV. PMID:26986103
Stein, R.L.; Martino, C.R.; Weinert, D.M.; Hueftle, M.; Kammer, G.M.
The authors present a case of isolated central nervous system vasculitis documented by cerebral arteriography in which remission, using a treatment regimen of prednisone and cyclophosphamide, was guided by serial arteriography during a 15-month period.
Belaconi, Ionela Nicoleta; Toma, Claudia Lucia; Bogdan, Miron Alexandru
The antineutrophil cytoplasm antibody (ANCA)-associated vasculitis are heterogeneous, multisystem, autoimmune diseases characterized by necrotizing small and medium vessel vasculitis and the association with ANCA. The diagnosis and management of these patients may be challenging due to the variability of clinical features, the possibility of life-threatening events (acute renal failure or pulmonary hemorrhage) and the relative rarity of these syndromes. ANCA-associated vasculitis include granulomatosis with polyangiitis, microscopic polyangiitis and eosinophilic granulomatosis with polyangiitis. The treatment requires significant immunosuppression and there are frequent treatment related side effects. Although the standard protocol with cytotoxic agents and glucocorticoids has dramatically improved patient outcome, its toxic profile remains a major problem. Recent progress in evidence base and consensus in understanding the pathogenic mechanism and the quantification of disease activity further improved patient's life. Special attention was paid in refining immunosuppressive treatment to minimize his toxicity. This review will focus on evidence based treatment of ANCA-associated vasculitis.
Sy, Alice; Khalidi, Nader; Dehghan, Natasha; Barra, Lillian; Carette, Simon; Cuthbertson, David; Hoffman, Gary S.; Koening, Curry L.; Langford, Carol A.; McAlear, Carol; Moreland, Larry; Monach, Paul A.; Seo, Philip; Specks, Ulrich; Sreih, Antoine; Ytterberg, Steven R.; Van Assche, Gert; Merkel, Peter A.; Pagnoux, Christian
Background Published small case series suggest that inflammatory bowel disease [IBD; Crohn’s disease (CD) or ulcerative colitis (UC)] and vasculitis co-occur more frequently than would be expected by chance. Objectives To describe this association by an analysis of a large cohort of carefully studied patients and through a systematic literature review. Methods Patients with both IBD and vasculitis enrolled in the Vasculitis Clinical Research Consortium (VCRC) Longitudinal Studies, followed in Canadian Vasculitis research network (CanVasc) centers and/or in the University of Toronto’s IBD clinic were included in this case series. A systematic literature review of patients with IBD and vasculitis involved a PubMed search through February 2014. The main characteristics of patients with Takayasu arteritis (TAK) and IBD were compared to those in patients with TAK without IBD followed in the VCRC. Results The study identified 32 patients with IBD and vasculitis: 13 with large-vessel vasculitis [LVV; 12 with TAK, 1 with giant cell arteritis (GCA); 8 with CD, 5 with UC]; 8 with ANCA-associated vasculitis [AAV; 6 granulomatosis with polyangiitis (GPA), 2 with eosinophilic granulomatosis with polyangiitis (EGPA)]; 5 with isolated cutaneous vasculitis; and 6 with other vasculitides. Patients with LVV and AAV were mostly female (18/21). The diagnosis of IBD preceded that of vasculitis in 12/13 patients with LVV and 8/8 patients with AAV. The review of the literature identified 306 patients with IBD and vasculitis: 144 with LVV (133 TAK; 87 with IBD preceding LVV), 19 with AAV [14 GPA, 1 EGPA, 4 microscopic polyangiitis (MPA)], 66 with isolated cutaneous vasculitis, and 77 with other vasculitides. Patients with IBD and TAK were younger and had more frequent headaches, constitutional symptoms, or gastrointestinal symptoms compared to those patients in the VCRC who had TAK without IBD. Conclusions These findings highlight the risk of vasculitis, especially TAK, in patients
Gomez, Alexandra; Dholaria, Kevin; Arosemena, Leopoldo R.; Ladino-Avellaneda, Marco A.; Barisoni, Laura; Bhamidimarri, Kalyan R.
Intestinal involvement of cryoglobulinemia is an uncommon manifestation and marker of severe vasculitis. We describe the case of a woman admitted to our service for management of acute renal failure and progressive gastrointestinal symptoms after initiating hepatitis C virus treatment with ribavirin and sofosbuvir 4 weeks prior. With an undetectable hepatitis C viral load and persistent symptoms despite hepatitis C virus therapy cessation, an upper endoscopy revealed duodenal sloughing, erythema, and bleeding, sparking suspicion for recurrence of cryoglobulinemic vasculitis. PMID:27807586
Tervaert, J W Cohen
Premature atherosclerosis has been observed during the course of different systemic inflammatory diseases such as rheumatoid arthritis and sytemic lupus erythematosus. Remarkably, relatively few studies have been published on the occurrence of accelerated atherosclerosis in patients with vasculitis. In giant cell arteritis (GCA), mortality because of ischaemic heart disease is not increased. In addition, intima media thickness (IMT) is lower in patients with GCA than in age-matched controls. In contrast, IMT is increased significantly in Takayasu arteritis, another form of large vessel vasculitis occurring in younger patients. In Takayasu arteritis and in Kawasaki disease, a form of medium-sized vessel vasculitis, accelerated atherosclerosis has been well documented. In small vessel vasculitis because of anti-neutrophil cytoplasmic autoantibodies-associated vasculitis, cardiovascular diseases are a major cause of mortality. IMT measurements reveal conflicting results. During active disease these patients experience acceleration of the atherosclerotic process. However, when inflammation is controlled, these patients have atherosclerotic development as in healthy subjects. Several risk factors, such as diabetes and hypertension, are present more often in patients with vasculitis compared with healthy controls. In addition, steroids may be pro-atherogenic. Most importantly, many patients have impaired renal function, persistent proteinuria and increased levels of C-reactive protein, well-known risk factors for acceleration of atherosclerosis. Enhanced oxidation processes, persistently activated T cells and reduced numbers of regulatory T cells are among the many pathophysiological factors that play a role during acceleration of atherogenesis. Finally, autoantibodies that may be relevant for acceleration of atherosclerosis are found frequently in elevated titres in patients with vasculitis. Because patients have an increased risk for cardiovascular events, vasculitis
Hashimoto, Hirotsugu; Hara, Kei; Matsumoto, Jun; Nashiro, Tamaki; Nagano, Masaaki; Kusakabe, Masashi; Kurata, Atsushi; Kuroda, Masahiko; Suzuki, Yoshio; Horiuchi, Hajime
Necrotizing arteritis is a complex lesion of pulmonary hypertension, as are plexiform lesions, and is classically recognized as grade 6 in the Heath and Edwards grading scheme for hypertensive pulmonary vascular disease. The vascular changes observed in intralobar pulmonary sequestration have been reported to be similar to those observed in pulmonary hypertension, such as plexiform lesions. However, necrotizing arteritis occurring in an intralobar sequestration of a patient without systemic vasculitis syndrome has never been reported to our knowledge. Here, we report a case of a 38-year-old woman with pulmonary sequestration detected on a medical checkup. She was treated with surgery, and subsequent pathological analyses revealed necrotizing vasculitis in her sequestrated lung. We suspected systemic vasculitis syndromes, such as Takayasu arteritis, polyarteritis nodosa, and antineutrophil cytoplasmic antibody-associated vasculitis. However, physical and blood examination did not show any other abnormalities, and hence, she did not have systemic vasculitis syndrome. Immunohistochemical analyses of the resected specimen showed that inflammatory cells of the arteries were mainly composed of T lymphocytes. T-lymphocytic inflammation with little neutrophil and histiocyte infiltration may be a pathological feature of necrotizing arteritis observed in pulmonary sequestration. This is the first case to our knowledge of necrotizing arteritis in an intralobar pulmonary sequestration of a patient without systemic vasculitis syndrome.
Lee, Yeonhee; Lee, Sang Taek; Cho, Heeyeon
Anti-neutrophil cytoplasmic antibodies (ANCA) are associated with systemic vasculitis. The pathophysiology of ANCA-associated vasculitis (AAV) has not been clearly proven, and drug-induced ANCA-associated vasculitis has been reported. Wilson's disease is an inborn error of copper metabolism caused by a mutation in the copper transporting gene ATP7B, and traditional treatment is based on copper chelation with agents such as D-penicillamine. There have been rare reports that prolonged D-penicillamine therapy might cause adverse renal events such as membranous nephropathy and minimal change disease, but it is questionable if D-penicillamine induces ANCA-associated vasculitis. We describe 2 patients with Wilson's disease treated with D-penicillamine who presented with ANCA (+) vasculitis and renal involvement. The 2 patients also showed positive results for antinuclear antibody (ANA). Their kidney biopsy findings were compatible with crescentic/necrotizing glomerulonephritis, pauci-immune type. After diagnosis of AAV, D-penicillamine was stopped. Patients were then treated with plasmapheresis and immunosuppressants, including methylprednisolone pulse therapy and intravenous cyclophosphamide. One patient progressed to end-stage renal disease and the other showed persistent proteinuria. These cases suggest that D-penicillamine may induce ANA (+) ANCA (+) vasculitis with severe renal involvement in pediatric patients, and plasmapheresis combined with immunosuppressant should be considered.
Thom, Vivien; Schmid, Sabrina; Gelderblom, Mathias; Hackbusch, Romy; Kolster, Manuela; Schuster, Simon; Thomalla, Götz; Keminer, Oliver; Pleß, Ole; Bernreuther, Christian; Glatzel, Markus; Wegscheider, Karl; Gerloff, Christian
Objective: To explore the possibility of using interleukin-17 (IL-17) production by CD4+ T cells in the CSF as a potential biomarker for cerebral vasculitis in stroke patients. Methods: In this consecutive case study, we performed prospective analysis of CSF and blood in patients admitted to a university medical center with symptoms of stroke and suspected cerebral vasculitis. Flow cytometry was performed for intracellular detection of inflammatory cytokines in peripheral blood lymphocytes and expanded T cells from CSF. Results: CSF CD4+ lymphocytes from patients with cerebral vasculitis showed significantly higher levels of the proinflammatory cytokine IL-17 compared to patients with stroke not due to vasculitis or with other, noninflammatory neurologic diseases. There was no difference in the production of interferon-γ in the CSF and no overall differences in the relative frequencies of peripheral immune cells. Conclusions: Intracellular IL-17 in CSF cells is potentially useful in discriminating cerebral vasculitis as a rare cause in patients presenting with ischemic stroke. Classification of evidence: This study provides Class II evidence that an increased proportion of IL-17-producing CD4+ cells in CSF of patients presenting with stroke symptoms is indicative of cerebral vasculitis (sensitivity 73%, 95% confidence interval [CI] 39–94%; specificity 100%, 95% CI 74%–100%). PMID:27144213
Mavrogeni, Sophie; Markousis-Mavrogenis, George; Kolovou, Genovefa
Antineutrophil cytoplasmic antibody (ANCA)-related vasculitis is a systemic small-vessel vasculitis, including 3 clinical syndromes: granulomatosis with polyangiitis, known as Wegener's granulomatosis (WG), microscopic polyangiitis (MPA) and the Churg-Strauss syndrome (CSS). ANCA-related vasculitis usually presents with severe kidney or pulmonary disease, has a mortality of 28% at 5 years, and also contributes to increased morbidity in vasculitis patients. Cardiac involvement in this entity may have different forms, including coronary vessels, pericarditis, myocarditis, endocarditis, myocardial infarction and subendocardial vasculitis that can contribute to reduced life expectancy. Cardiovascular magnetic resonance using oedema and fibrosis imaging can early reveal, noninvasively and without radiation, heart involvement during vasculitis, undetected by other imaging techniques and guide further risk stratification and treatment of these patients.
Monov, Simeon; Hristova, Ruska; Dacheva, Rositza; Toncheva, Reni; Shumnalieva, Russka; Shoumnalieva-Ivanova, Viara; Monova, Daniela
Abstract Rationale: Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by autoantibody production, complement activation, and deposition of immune complexes in tissues and organs. SLE can involve any region of the visual system. Although ocular manifestations are not part of the classification criteria for SLE, they can be observed in up to one-third of the patients with SLE. They are rarely reported at the time of disease onset. Retinal vasculitis is usually associated with active generalized disease. Due to its low frequency, we report a case of acute necrotizing retinal vasculitis as onset of SLE. Patient concerns and diagnosis: A 25-year-old white female was referred to the rheumatology clinic with gradually and rapid deterioration of the vision due to abnormal vessel permeability in the right fundus with edema along the vessels, occlusion of arterial branches in the middle periphery with leakage of the dye in these areas and indentical but less prominent changes with cotton wool spots in the papillomacular area and extensive hemorrhages in the left eye. The onset of malar rash, arthralgias and positive antinuclear, anti-double stranded DNA, anti-ribosomal P and anti-β2 glycoprotein I antibodies with decreased C4 complement levels, as well as the positive lupus-band test confirmed the diagnosis of SLE. Interventions: Aggressive immunomodulating therapy with high-dose methylprednisolone, intravenous immunoglobulin, and cyclophosphamide was used for suppression of the disease activity followed by azathioprine as maintaince therapy. Outcomes: Substantial improvement and partial resorption of the vasculitic changes, including central retinal artery and vein, was achieved prominently in the left eye. The study was conducted in accordance with the Declaration of Helsinki and written informed consent was obtained from the patient. Because of this, there is no need to conduct special ethic review and the ethical approval is not necessary
Söderberg, Daniel; Segelmark, Mårten
A group of pauci-immune vasculitides, characterized by neutrophil-rich necrotizing inflammation of small vessels and the presence of antineutrophil cytoplasmic antibodies (ANCAs), is referred to as ANCA-associated vasculitis (AAV). ANCAs against proteinase 3 (PR3) (PR3-ANCA) or myeloperoxidase (MPO) (MPO-ANCA) are found in over 90% of patients with active disease, and these ANCAs are implicated in the pathogenesis of AAV. Dying neutrophils surrounding the walls of small vessels are a histological hallmark of AAV. Traditionally, it has been assumed that these neutrophils die by necrosis, but neutrophil extracellular traps (NETs) have recently been visualized at the sites of vasculitic lesions. AAV patients also possess elevated levels of NETs in the circulation. ANCAs are capable of inducing NETosis in neutrophils, and their potential to do so has been shown to be affinity dependent and to correlate with disease activity. Neutrophils from AAV patients are also more prone to release NETs spontaneously than neutrophils from healthy blood donors. NETs contain proinflammatory proteins and are thought to contribute to vessel inflammation directly by damaging endothelial cells and by activating the complement system and indirectly by acting as a link between the innate and adaptive immune system through the generation of PR3- and MPO-ANCA. Injection of NET-loaded myeloid dendritic cells into mice results in circulating PR3- and MPO-ANCA and the development of AAV-like disease. NETs have also been shown to be essential in a rodent model of drug-induced vasculitis. NETs induced by propylthiouracil could not be degraded by DNaseI, implying that disordered NETs might be important for the generation of ANCAs. NET degradation was also highlighted in another study showing that AAV patients have reduced DNaseI activity resulting in less NET degradation. With this in mind, it might be that prolonged exposure to proteins in the NETs due to the overproduction of NETs and/or reduced
Butts, G Tyler; Bishop, Phyllis R; Wyatt, Julie P
An adolescent female with long-standing, difficult-to-control ulcerative colitis developed leukocytoclastic vasculitis, a rare cutaneous extra-intestinal manifestation of the inflammatory bowel disease. The authors provide a literature review on leukocytoclastic vasculitis complicating ulcerative colitis. Furthermore, the clinical features of leukocytoclastic vasculitis are compared and contrasted with the more common cutaneous extra-intestinal manifestations of inflammatory bowel disease, erythema nodosum, and pyoderma gangrenosum. PMID:27489650
Wall, Anji E; Weaver, Sheena M; Litt, Jeffrey S; Rae, Lisa
The purpose of this case report and review of the literature is to provide an exploration of the clinical symptoms, diagnosis, prevention, and management of propylthiouracil (PTU)-associated vasculitis in the intensive care setting. A PubMed search of the available literature was conducted using the MeSH search terms "propylthiouracil" and "vasculitis." The literature search returned 121 articles. Twenty-five were excluded because they were not in English. Fifty-nine case reports or case studies describing PTU-associated vasculitis were included. Data extracted from each case study included patient age, sex, autoimmune markers, laboratory tests, length of time on PTU, treatment for vasculitis, and patient outcomes. The authors reviewed 128 cases of PTU-associated vasculitis. The majority were women (8.8:1 F:M ratio), and the most common presenting symptoms were rash (51.6%), fever (46.9%), and arthralgia (43.8%). In addition to discontinuing PTU, the most common treatment was steroids (71.9%). Eight patients (6.3%) progressed to end-stage renal disease; two (1.6%) required intubation for respiratory failure; and five (3.9%) died of various organ systems failure related to vasculitis development. A high index of suspicion for vasculitis should be maintained, especially when presented with skin manifestations in the presence of PTU therapy. Screening with myeloperoxidase-antinuclear cytoplasmic antibodies is most sensitive. Positive screening should prompt a thorough clinical investigation. In cases of severe skin manifestations, the focus should be on aggressive wound care. Our case report is unique, not only in the size and extent of cutaneous involvement, but also as the first description of mortality secondary to cutaneous manifestations.
Li, Xia; Zhao, Jiuliang; Wang, Qian; Fei, Yunyun; Zhao, Yan
Abstract Reports of hypertrophic pachymeningitis associated with myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) localized exclusively in the spine were quite rare. Two cases of ANCA-associated systemic vasculitis (AASV) presenting with hypertrophic spinal pachymeningitis (HSP) causing low back pain and numbness are described. Two patients showed prominent systemic and local inflammatory reactions manifested as fever, elevated levels of erythrocyte sedimentation rate and C-reactive protein, and markedly increased levels of total protein of cerebrospinal fluid. The gadolinium (Gd)-enhanced T1-weighted magnetic resonance imaging scan of spinal cord demonstrated diffuse spinal dura matter thickening. Additionally, simple microscopic hematuria was found in 1 case suggestive of renal involvement and the other 1 complicated with interstitial lung disease. Then, a diagnosis of HSP secondary to AASV was made. Combination therapy of corticosteroids and cyclophosphamide produced a rapid improvement in the clinical symptoms and laboratory parameters. Followed up for 6 months, 1 case relapsed when the dosage of prednisone was tapered to 10 mg daily. Since the patient refused rituximab-based regimen, an immunosuppressive triple-therapy (corticosteroid, cyclophosphamide, and azathioprine) was initiated and brought control of the disease during the subsequent 6 months of follow-up. HSP is a relatively rare form of central nervous system involvement of AASV. Early recognition and intervention are of great significance since the pathogenesis of HSP starts with an inflammatory and fibrosing process. PMID:26579814
Weyand, Cornelia M.; Goronzy, Jörg J.
Summary Vasculitis of the medium and large arteries, most often presenting as giant cell arteritis (GCA), is an infrequent, but potentially fatal type of immune-mediated vascular disease. The site of the aberrant immune reaction, the mural layers of the artery, is strictly defined by vascular dendritic cells, endothelial cells, vascular smooth muscle cells and fibroblasts which engage in an interaction with T cells and macrophages to ultimately cause luminal stenosis or aneurysmal wall damage of the vessel. A multitude of effector cytokines, all known as critical mediators in host-protective immunity, has been identified in the vasculitic lesions. Two dominant cytokine clusters, one centering on the IL-6/IL-17 axis, the other on the IL-12/IFN-γ axis, have been connected with disease activity. These two clusters appear to serve different roles in the vasculitic process. The IL-6/IL-17 cluster is highly responsive to standard corticosteroid therapy, whereas the IL-12/IFN-γ cluster is resistant to steroid-mediated immunosuppression. The information exchange between vascular and immune cells and stabilization of the vasculitic process involves members of the NOTCH receptor and ligand family. Focusing on elements in the tissue context of GCA, instead of broadly suppressing host immunity, may allow for a more tailored therapeutic approach and spare patients the unwanted side-effects of aggressive immunosuppression. PMID:24189842
Uçmak, Feyzullah; Uçmak, Derya; Beştaş, Remzi; Anli, Ruken Azizoğlu; Adanir, Haydar
Brucellosis is globally the most prevalent multisystem infection of zoonotic origin, while it is still one of the most important public health problems in Turkey as non-pasteurised milk and dairy products are consumed. Early diagnosis is vital to prevent the possibly lethal complications caused by the disease. However, diagnosis might be delayed as the disease does not have a single and typical manifestation and presents with various symptoms of different systems. Brucellosis and associated splenic infarct have rarely been studied, there being few cases in the literature. One of the rare involvements in this disease is dermatological involvement, which has been found in less than 10 percent of brucellosis cases. In this study, we discuss a 17 year old male patient who was admitted to our hospital due to fever, abdominal pain, arthralgia and rash on legs, diagnosed with brucellosis through brucellosis tube agglutination test and found to have splenic infarct upon examination and leukocytoclastic vasculitis according to the skin biopsies in the light of the present literature.
Hammar, Samuel P; Williams, M Glenn; Dodson, Ronald F
The authors report a case of a 39-year-old woman who sustained an injury to her left knee requiring arthroscopic surgical medial menisectomy and ganglionic block for reflex sympathetic dystrophy syndrome. Approximately 1 year after injury, the patient presented with an elevated white blood cell count and fever and was diagnosed to have a psoas muscle abscess, which was treated with antibiotics. She was also taking 4 different oral medications that contained microcrystalline cellulose as a filter. Approximately 1 month after being diagnosed with the psoas muscle abscess, the patient developed shortness of breath, marked weakness, diaphoresis, and intermittent emesis. She became hypotensive and tachyneic and expired. Postmortem examination showed granulomatous vasculitis with extensive occlusions of pulmonary arteries by birefringent crystalline material identified to be cellulose histochemically and by analytical electron microscopy evaluation. This case report describes the ultrastructural and chemical features of various medicinal tablet fillers and compares them to pure samples. This report also demonstrates the usefulness of analytical electron microscopy in accurately identifying birefringent material in lung tissue.
Houben, Eline; Bax, Willem A.; van Dam, Bastiaan; Slieker, Walentina A.T.; Verhave, Gideon; Frerichs, Fenneke C.P.; van Eijk, Izhar C.; Boersma, Wim G.; de Kuyper, Guido T.M.; Penne, Erik L.
Abstract Currently no validated diagnostic system for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is available. Therefore, diagnosing AAV is often challenging. We aimed to identify factors that lead to a clinical diagnosis AAV in ANCA positive patients in a teaching hospital in The Netherlands. In this study, all patients that tested positive for ANCA proteinase 3 (PR3) and/or myeloperoxidase (MPO) between 2005 and 2015 were analysed. Patients with a clinical diagnosis of AAV were compared with patients without a clinical diagnosis of AAV. Clinical symptoms and laboratory variables at presentation, including the ANCA titre, were collected for both patients with and without AAV. Clinical and laboratory variables related with AAV were investigated, using multivariable logistic regression. Two hundred thirty seven consecutive patients with a positive ANCA were included, of whom 119 were clinically diagnosed with AAV. Of the 118 ANCA positive patients without AAV, 87 patients had an alternative diagnosis, including inflammatory bowel disease (n = 24), other rheumatic diseases (n = 23), infection (n = 11), malignancy (n = 4), and other diagnoses (n = 25). In a multivariable regression model, a high ANCA titre (odds ratio [OR] 14.16, 95% confidence interval [CI] 6.93–28.94) and a high number of affected organ systems (OR 7.67, 95% CI 3.69–15.94) were associated with AAV. MPO and PR3 ANCA can be positive in a variety of diseases that mimic AAV. A higher ANCA titre and multiple affected organ systems may help to discriminate between AAV and other systemic illnesses in anti-PR3 and anti-MPO positive patients. A diagnostic scoring system incorporating these factors should be considered. PMID:27749588
Merkel, Peter A; Herlyn, Karen; Mahr, Alfred D; Neogi, Tuhina; Seo, Philip; Walsh, Michael; Boers, Maarten; Luqmani, Raashid
The past decade has seen a substantial increase in the number and quality of clinical trials of new therapies for vasculitis, including randomized, controlled, multicenter trials that have successfully incorporated measures of disease activity and toxicity. However, because current treatment regimens for severe disease effectively induce initial remission and reduce mortality, future trials will focus on any of several goals including: (a) treatment of mild-moderate disease; (b) prevention of chronic damage; (c) reduction in treatment toxicity; or (d) more subtle differences in remission induction or maintenance. Thus, new trials will require outcome measure instruments that are more precise and are better able to detect effective treatments for different disease states and measure chronic manifestations of disease. The OMERACT Vasculitis Working Group comprises international clinical investigators with expertise in vasculitis who, since 2002, have worked collaboratively to advance the refinement of outcome measures in vasculitis, create new measures to address domains of illness not covered by current research approaches, and harmonize outcome assessment in vasculitis. The focus of the OMERACT group to date has been on outcome measures in small-vessel vasculitis with an overall goal of creating a core set of outcome measures for vasculitis, each of which fulfills the OMERACT filter of truth, discrimination, feasibility, and identifying additional domains requiring further research. This process has been informed by several ongoing projects providing data on outcomes of disease activity, disease-related damage, multidimensional health-related quality of life, and patient-reported ratings of the burden of vasculitis.
Ramirez, G A; Maugeri, N; Sabbadini, M G; Rovere-Querini, P; Manfredi, A A
Vascular inflammation contributes to the defence against invading microbes and to the repair of injured tissues. In most cases it resolves before becoming apparent. Vasculitis comprises heterogeneous clinical entities that are characterized by the persistence of vascular inflammation after it has served its homeostatic function. Most underlying mechanisms have so far remained elusive. Intravascular immunity refers to the surveillance of the vasculature by leucocytes that sense microbial or sterile threats to vessel integrity and initiate protective responses that entail most events that determine the clinical manifestations of vasculitis, such as end-organ ischaemia, neutrophil extracellular traps generation and thrombosis, leucocyte extravasation and degranulation. Understanding how the resolution of vascular inflammation goes awry in patients with systemic vasculitis will facilitate the identification of novel pharmacological targets and bring us a step closer in each patient to the selection of more effective and less toxic treatments. PMID:24128276
Alba, Marco A; Flores-Suárez, Luis F
Since cyclophosphamide was introduced for the treatment of ANCA-associated vasculitis, the mortality of these diseases has decreased considerably. However, such treatment is related to acute and chronic serious adverse effects, which contribute to the morbidity and mortality of such diseases. Therefore, one of the main challenges in the treatment of such conditions is to find newer and effective therapies with a safer profile. Rituximab (RTX), an anti-CD20 monoclonal antibody stands at the top of new options for the treatment of ANCA-associated vasculitis, and is the strongest candidate to establish itself as a first choice therapeutic agent. Here, we review the rationale of RTX treatment in ANCA-associated small vessel vasculitis, and the current evidence of both its efficacy and toxicity.
Swe, Thein; Pervil-Ulysse, Mona; Baqui, AAM A.
Cocaine is a popular recreational drug in the United States, and up to 70% of the seized cocaine contains levamisole which is an antihelminthic that can cause cutaneous vasculitis with necrosis and positive antineutrophil cytoplasmic antibodies (ANCAs). Here, we report a unique case of recurrent cocaine-induced vasculitis in a patient who smokes cocaine for more than 20 years. A 38-year-old woman complained of painful erythematous rash in her right arm and right thigh which appeared some hours after smoking cocaine. Physical examination revealed tender, erythematous base, retiform purpura with necrosis and bullae. Serological test showed high atypical perinuclear ANCA titer of 1:320 and antimyeloperoxidase antibody level of 20.4 U/mL. Cocaine-induced vasculitis should be one of the differential diagnoses in cocaine abusers who present with painful rash and areas of necrosis. Early diagnosis is important since it is an emerging public health concern. PMID:28217616
Brigita, Jonaitytė; Rūta, Kibarskytė; Edvardas, Danila; Marius, Miglinas; Dmitrij, Šeinin; Rokas, Stulpinas; Jurgita, Mitrikevičienė; Vygantas, Gruslys; Virginija, Šileikienė; Rolandas, Zablockis
ANCA-associated vasculitis (AAV) is an inflammatory systemic disorder affecting small to medium sized vessels and likely leading to any organ dysfunction. Adequate treatment is important to avoid mortality or severe organ damage. In most cases initial treatment (induction therapy) allows to achieve remission. Induction therapy leads to immunosuppression and may cause severe infections. However, in vasculitis patients even an intensive immunosuppressive therapy is rarely complicated by an invasive fungal infection. We present a case in a 29-year old male patient with newly diagnosed AAV. He suffered a fatal pulmonary complication of the induction immunosuppressive treatment. Pathological (infectious) changes in the lungs were misinterpreted as progression of the vasculitis and he died due to disseminated angioinvasive aspergillosis. A clinical course, imaging and histopathology of this case are described and discussed. PMID:28356801
Singh, Gunveen; Hodgson, Tim; Clarke, David E
Introduction Pyridostigmine is an acetylcholinesterase inhibitor commonly used in the treatment of myasthenia gravis. We describe a patient who developed a rash after recently being started on pyridostigmine and give a general review of leukocytoclastic vasculitis. Case Presentation A 91-year-old man was diagnosed with ocular myasthenia gravis. He was started on pyridostigmine, and 2 weeks later he developed a rash. The rash was biopsied and found to be secondary to leukocytoclastic vasculitis; the pyridostigmine was stopped, loratadine was started, and the rash resolved. Discussion Leukocytoclastic vasculitis is commonly caused by a hypersensitivity reaction to medications, or it can be associated with certain medical conditions. We present a brief review of the most common medications and medical conditions known to cause this reaction, but to our knowledge this is the first description of pyridostigmine causing this reaction. PMID:28080955
Madeira, Catarina; Pinto, Joana; Pestana, Joana
A 71-year-old woman presented with constitutional signs and lower extremity palpable purpura after being prescribed a four-day course of 500 mg of ciprofloxacin two times daily for a gastrointestinal infection. She was admitted for inpatient treatment. During the third hospital day, she presented with an episode of abundant hematemesis while her skin lesions remained unchanged. Upper endoscopy revealed multiple lesions consistent with vasculitis and histological examination of the skin biopsy disclosed a leukocytoclastic vasculitis. The patient was successfully treated with prednisone following ciprofloxacin discontinuation. Complete resolution of the lesions on drug withdrawal strongly suggested drug toxicity, which was further supported by a score of 8 in the Naranjo Adverse Drug Reaction Probability Scale. Awareness that the development of skin and gastrointestinal lesions following administration of ciprofloxacin may be a manifestation of ciprofloxacin-induced vasculitis can help early detection, treatment, and lead to an overall good prognosis. PMID:28070469
Berlit, P; Kraemer, M
Cerebral vasculitis is a rare cause of juvenile stroke. It may occur as primary angiitis of the central nervous system (PACNS) or as CNS manifestation in the setting of systemic vasculitis. Clinical hints for vasculitis are headache, stroke, seizures, encephalopathy and signs of a systemic inflammatory disorder. Diagnostic work-up includes anamnesis, whole body examination, laboratory and cerebral spinal fluid (CSF) studies, magnetic resonance imaging (MRI), angiography and brain biopsy. Due to the rarity of the disease, exclusion of more frequent differential diagnoses is a key element of diagnostic work-up. This review summarizes the steps that lead to the diagnosis of cerebral vasculitis and describes the red flags and pitfalls. Despite considering the dilemma of angiography-negative vasculitis and false-negative brain biopsy in some cases, it is important to protect patients from ‘blind’ immunosuppressive therapy in unrecognized non-inflammatory differential diagnosis. PMID:24117125
van Schaik, Jan; Crobach, Stijn L. P.; van Rijswijk, Catharina S. P.; Rotmans, Joris I.
The combination of alpha-1 antitrypsin (AAT) deficiency, ANCA-vasculitis, and aortic aneurysm has been rarely described in literature. We report an eventually fatal case in a 70-year-old patient who initially presented with giant cell arteritis and ANCA associated glomerulonephritis. Several years later, he presented with aortic dissection due to large vessel vasculitis, raising the suspicion of AAT deficiency, as two first-line relatives had chronic obstructive pulmonary disease, while they never smoked. This diagnosis was confirmed by AAT electrophoresis and immunohistochemistry on a temporal artery biopsy. Considering AAT deficiency in these cases might lead to a more timely diagnosis. PMID:28367219
Kitajima, Takamasa; Marumo, Satoshi; Shoji, Tsuyoshi; Huang, Cheng-Long; Yuba, Yoshiaki; Fukui, Motonari
Chronic pulmonary arterial obstructions are caused mostly by chronic pulmonary artery thromboembolism and rarely by vasculitis or intimal sarcoma of the pulmonary artery. We herein report an unusual case of a 42-year-old woman with a solitary obstruction of the pulmonary artery in the right lower lobe of her lung. Because we could not exclude the possibility of intimal sarcoma, middle and lower lobectomy was performed. The resected specimens revealed large vessel vasculitis (LVV) and an isolated lesion in the right lower lobe pulmonary artery. LVV should therefore be considered in the differential diagnosis for single pulmonary arterial stenosis or obstruction.
Wang, Fang; Liu, Juan-Hua; Zhao, Yu-Kun; Luo, Di-Qing
Cutaneous reactions associated with interferons (IFNs) treatment are either localized or generalized. The most common presentation of localized reactions at IFNs injection site is usually an erythematous patch or plaque. Local leukocytoclastic vasculitis presenting with cutaneous necrosis is extremely rare. We report a 19-year-old man with hepatitis B who had local leukocytoclastic vasculitis induced by interferon-gama injection at the injection site. After changing the injection sites and using the combined treatment of prednisone and colchicine, the previous lesion healed and no other cutaneous lesion occurred. We also made a mini review of such cases.
Hu, S; Birg, A; Hovaida, M; Gavin, M W; McCarthy, D
IgA vasculitis is primarily a pediatric disease that is rarely encountered in adults. With adults, gastrointestinal manifestations are quite common, yet are nonspecific and may overlap with other diseases, particularly Crohn's disease, which can make the diagnosis a challenging task. Treatment is controversial given the disease course is usually self-limited with few serious complications. We present a case of IgA vasculitis in an adult patient with limited extraintestinal findings illustrating the complexity of arriving at the correct diagnosis.
Sofi, Fayaz; Ahmad, Mushtaq; Kuchay, Abid
Background Aerococcus viridans organisms are Gram-positive cocci that are widely distributed in hospital environments and room air. These bacteria have infrequently been encountered as human pathogens causing bacteremia, endocarditis and urinary tract infections. The significance of these bacteria may be overlooked due to their fastidious growth, and they are often confused with other strains of streptococci or staphylococci. Case report We present a case of Aerococcus viridans manifesting as cutaneous vasculitis in an immunocompetent patient. A 30-year-old female patient was admitted to hospital after two weeks history of fever, chills and papular rash over the limbs and trunk. The clinical diagnosis of vasculitis was made. Investigations revealed elevated leucocytosis (21.7 × 109/l) with 81% of neutrophils, and an elevated erythrocyte sedimentation rate or 60 mm/h. Serum anti-neutrophil cytoplasmic antibodies (ANCAs) were not found. Blood culture showed growth of Aerococcus viridans. Histopathological assessment of skin biopsy revealed cutaneous vasculitis. Conclusions To date, no clinical case report of this kind has been reported implicating Aerococcus viridans in cutaneous vasculitis. Increased awareness and more studies of this genus should lead to the identification of its potential role in human infections. PMID:28115783
Murray, Nigel P.; Ruíz, Amparo; Reyes, Eduardo
Hypernephroma can present as a variety of paraneoplastic, nonmetastatic conditions, including vasculitis, and rarely a lupus-type anticoagulant. Nephrectomy leads to the resolution of the systemic complaints. Malignancy, in this case hypernephroma, can present as an immune-mediated paraneoplastic syndrome which resolves after removal of the underlying tumor. PMID:22919534
Cid, M C; Grant, D S; Hoffman, G S; Auerbach, R; Fauci, A S; Kleinman, H K
Angiogenesis is an important process in chronic inflammatory diseases. We observed that sera from patients with systemic vasculitis stimulated angiogenesis in an in vitro model using human umbilical vein endothelial cells cultured on a basement membrane (Matrigel) substrate. After 40% ammonium sulfate precipitation, angiogenic activity remained in the low molecular weight fraction and could be inactivated by heat. SDS-page of serum FPLC fractions exhibiting maximal angiogenic activity demonstrated two prominent species of 45 and 16-20 kD in patients' sera. These bands were much less apparent in sera obtained from control subjects. Amino-terminal sequencing of the 45-kD protein demonstrated that it was haptoglobin. Purified haptoglobin stimulated angiogenesis in a dose-dependent manner. The angiogenic activity of vasculitis patients' sera was partially inhibited by an antihaptoglobin antibody. Furthermore, serum haptoglobin levels in vasculitis patients correlated both with disease and angiogenic activity. Haptoglobin angiogenic activity was confirmed in two in vivo models using an implanted disc and a subcutaneous injection of basement membrane. Stimulation of angiogenesis is a newly recognized biological function of haptoglobin. The increased levels of haptoglobin found in chronic inflammatory conditions may play an important role in tissue repair. In systemic vasculitis, haptoglobin might also compensate for ischemia by promoting development of collateral vessels. Images PMID:7680672
Wu, Chan; Dong, Fang-tian; Chen, You-xin; Wang, Qian; Dai, Rong-ping; Zhang, Hua
Making accurate and timely diagnosis is often challenging when patients with a systemic disease first present with ocular manifestations. The possibility that vasculitis associated with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) can be misdiagnosed as cysticercosis has not been discussed in the literatures.
Zeng, Mingbing; Liu, Xialin; Liu, Yizhi
Patient: Female, 20 Final Diagnosis: Eosinophilic granulomatosis with polyangiitis Symptoms: Fever • skin rashes • eosinophilic cholecystitis • retinal vasculitis Medication: — Clinical Procedure: — Specialty: Ophthalmology Objective: Rare co-existance of disease or pathology Background: Eosinophilic granulomatosis with polyangiitis (EGPA), also known as Churg-Strauss syndrome (CSS), is a rare vasculitis of unknown etiology. Most of the patients have a long history of asthma and then develop autoimmune inflammation of small and medium-sized blood vessels, with consequent reduction of blood flow to various organs and tissues. EGPA can cause disorders in multiple systems; the most seriously affected organs are the retina, kidney, brain, cardiovascular system, and skin. Case Report: The patient was hospitalized for high fever and skin rashes and then developed right upper abdominal pain, decreased visual acuity, coma, and convulsions. Laboratory investigations showed marked eosinophilia (9412/mm3). Following cholecystectomy, histopathological examination revealed a marked inflammatory cell infiltrate composed mainly of eosinophils. Retinal vasculitis and medium and peripheral vascular closure were confirmed by fundus fluorescence angiography (FFA). The coma and convulsions were controlled successfully by high-dose methylprednisolone. After gradual tapering of the methylprednisolone, the patient’s blood count recovered to a normal level, and the other systematic disorders disappeared; however, she was left with irreversible blindness. Conclusions: EGPA can cause eosinophilic cholecystitis, retinal vasculitis, and neuropathy in the short term and calls for effective treatments in order to avoid binocular blindness. PMID:27857032
Anti-neutrophil cytoplasmic antibodies (ANCA) have been associated with a spectrum of vasculitis that includes granulomatous polyangiitis (formerly known as Wegener's granulomatosis), microscopic polyangiitis, the Churg-Strauss syndrome, primary pauciimmune necrotizing and crescentic glomerulonephritis and related forms of vasculitis. In vitro, in vivo and clinical evidence support the conclusion that ANCA participate in the pathophysiology of this disease spectrum. Rituximab is a potent tool that can interrupt B cell-mediated immunity without major compromise of T cell-mediated immunity. Thus, it has great appeal as a tool to interrupt antibody-mediated autoimmune disease. The results of two prospective randomized trials confirm that rituximab can be effective as part of induction therapy for active ANCA-associated vasculitis. The safety profile for rituximab appears favourable relative to cyclophosphamide and steroids. However, there remain many patients who require individualized adjustments of ancillary therapy, as breakthrough disease, relapses and infectious complications do occur. Based on our current knowledge, rituximab should now be incorporated as part of induction therapy in many patients with ANCA-associated vasculitis. However, more work is needed to determine how rituximab may best be integrated into the overall immunosuppression of these patients.
Ames, P R; Cianciaruso, B; Bellizzi, V; Balletta, M; Lubrano, E; Scarpa, R; Brancaccio, V
A 43-year-old man presented with oliguria and hypertension. Renal arteriography showed bilateral renal artery occlusion. Circulating antiphospholipid antibodies were found together with a change in natural anticoagulant plasma levels. Immunofluorescence of examined vessels showed immune complex vasculitis. We discuss the pathogenetic mechanism leading to the development of this rare occlusive event.
ABSTRACT BACKGROUND Anti-neutrophil cytoplasmic autoantibodies (ANCA) specific for myeloperoxidase (MPO) or proteinase 3 (PR3) are detectable in >90% of patients with ANCA-associated vasculitis (AAV). ANCA titers do not correlate well with disease activity. In vivo and in vi...
Wolf, G; Porth, J; Stahl, R A
Three cases of venous thrombosis with pulmonary embolism in two patients associated with underlying antineutrophil cytoplasmic autoantibody (ANCA)-positive vasculitis and reactivated cytomegalovirus (CMV) infection are described. In vitro studies previously have shown that infection of endothelium with CMV increases the release of procoagulant factors and stimulates the expression of adhesion molecules. Because the endothelial cell plays a pivotal role in maintaining the equilibrium between procoagulant and anticoagulant states, injury by ANCA-positive vasculitis and additional infection with CMV may ignite a local thrombosis easily. Although venous thrombosis is uncommon in CMV infection (eg, in the immunosuppressed state after organ transplantation), the combination of vasculitis and reactivated CMV infection may have contributed to injury of the vessel wall with subsequent development of thrombosis. A better awareness of this association could improve morbidity and may lead to prevention of potentially life-threatening pulmonary embolism. Patients with ANCA-positive vasculitis and CMV infection may profit from prophylactic anticoagulant therapy with heparin or low-molecular-weight heparin.
Nickerson, Ashley; Marik, Paul Ellis
We present a 47-year-old Caucasian fire fighter who developed multisystem organ failure in the setting of a positive antineutrophil cytoplasmic autoantibody (myeloperoxidase) as well as confirmed Rocky Mountain spotted fever by skin biopsy PCR. This case provided a diagnostic challenge, a rare association of a Rickettsia infection and autoimmune vasculitis as well as a unique management approach.
Li, Xiao-Jing; Zhou, Min; Li, Xiao-Hui; Xu, You-Hua; Liu, Hong; Yang, Mo
The objective of this study was to investigate the effect of Tanshinone IIa on IL-1beta, IL-6 and TNF-alpha cytokines in immune vasculitis and platelets, as well as their relationship. The model of immune vasculitis of rabbits were established by intravenous injection of bovine serum albumin twice. Experiment was divided into 4 groups: control group, model group, tanshinone IIa-treated group and aspirin-treated group. The platelet count, platelet aggregation of peripheral blood were determined. The levels of serum IL-1beta, IL-6, TNF-alpha were detected by ELISA. The pathological changes of immune vasculitis were analyzed by hematoxylin & eosin staining, elastic fibers staining and electron microscopy. The results showed that the levels of IL-1beta and TNF-alpha in model group were significantly higher than those in normal group (p < 0.05), while the level of IL-6 was not significantly different between various groups. The serum level of IL-1beta was correlated with platelet number, while serum levels IL-1beta and TNF-alpha were both correlated with the platelet aggregation. The treatment with tanshinone IIa could significantly decrease the serum levels of IL-1beta, TNF-alpha and platelet number, and the efficacy of tanshinone IIa was same as aspirin. The tanshinone IIa and aspirin both could alleviate the vessels damage in patients with immune vasculitis. It is concluded that the tanshinone IIa may diminish the inflammation damage of vessels in patients with immune vasculitis through the inhibition of cytokines and platelets.
Walsh, Michael; Catapano, Fausta; Szpirt, Wladimir; Thorlund, Kristian; Bruchfeld, Annette; Guillevin, Loic; Haubitz, Marion; Merkel, Peter A.; Peh, Chen Au; Pusey, Charles; Jayne, David
Background Plasma exchange may be effective adjunctive treatment for renal vasculitis. We performed a systematic review and meta-analysis of randomized control trials of plasma exchange for renal vasculitis. Study Design Systematic review and meta-analysis of manuscripts identified from electronic databases, bibliographies, and studies identified by experts. Data was abstracted in parallel by two reviewers. Setting & Population Adults with idiopathic renal vasculitis or rapidly progressive glomerulonephritis Selection Criteria for Studies Randomized controlled trials that compared standard care with standard care plus adjuvant plasma exchange in adult patients with either renal vasculitis or idiopathic rapidly progressive glomerulonephritis. Intervention Adjuvant plasma exchange Outcome Composite of end-stage renal disease or death. Results We identified 9 trials including 387 patients. In a fixed-effects model the pooled relative risk of end-stage renal disease or death was 0.80 for patients treated with adjunctive plasma exchange compared to standard care alone (95% confidence interval 0.65 to 0.99; p=0.04). No significant heterogeneity was detected (p=0.5; I2=0%). The effect of plasma exchange did not differ significantly across the range of baseline serum creatinine values (p=0.7) or number of plasma exchange treatments (p=0.8). The relative risk for end-stage renal disease was 0.64 (95% confidence interval 0.47 to 0.88; p=0.006) while the relative risk for death alone was 1.01 (95% confidence interval 0.71 to 1.4; p=0.9). Limitations Although the primary result was statistically significant, there is insufficient statistical information to reliable determine if plasma exchange reduces the composite of end-stage renal disease or death. Conclusions Plasma exchange may reduce the composite endpoint of end-stage renal disease or death in renal vasculitis. Further trials are required given the limited data available. PMID:21194817
Koike, Haruki; Sobue, Gen
Vasculitis can be primarily or secondarily to various underlying diseases. It frequently affects the nervous system, and neurological deficits may remain even after disease remission. Because the progression of vasculitides is usually acute to subacute, early initiation of treatment is important from the viewpoint of patients' functional status. However, early diagnosis may be difficult, particularly in patients with central nervous system vasculitis. Hence, it is important to understand the wide-ranging clinical manifestations of vasculitides. Here, we summarize the 2012 revised International Chapel Hill Consensus Conference nomenclature of vasculitides from the standpoint of central nervous system vasculitis.
Ye, Hua; Gao, Ying; Guo, Xiao-Hui; Zhao, Ming-Hui
Substantial evidences suggested that propylthiouracil (PTU) could induced anti-myeloperoxidase (MPO) antibodies in sera from patients with hyperthyroidism, however, only a subgroup of the PTU-induced anti-MPO antibody positive patients developed clinical evident vasculitis. The aim of this study is to compare the titres and affinities of PTU induced anti-MPO antibodies in sera from patients with hyperthyroidism with and without clinical vasculitis. Anti-MPO antibody positive sera from patients diagnosed hyperthyroidism with (n = 13) and without (n = 14) clinical evident vasculitis were collected. The titre was determined by MPO-ELISA and expressed as logarithm value (lgT). The affinity constant (aK) of anti-MPO IgG was measured by antigen inhibition assay. The titre and aK values were compared between patients with and without vasculitis. In patients with vasculitis, the mean lgT of anti-MPO antibodies was 3.62 +/- 0.66; the median aK was 4.47 x 10(7)M(-1). In patients without vasculitis, the mean lgT was 2.54 +/- 0.29; the median aK was 0.14 x 10(7)M(-1), and both were significant lower than those in patients with vasculitis (t = 5.464; P = 0.000 & z = -4.373; P = 0.000, respectively). We concluded that the titre and affinity of anti-MPO antibodies might be associated with the development of clinical vasculitis in patients with PTU-induced ANCA.
Gözüküçük, Murat; Gürsoy, Aslı Yarcı; Kankaya, Duygu; Atabekoglu, Cem
Single-organ vasculitis (SOV) has rarely been reported to involve the female genital tract but mostly the uterine cervix. A 39-year-old woman was diagnosed to have a high-grade cervical intraepithelial lesion and was treated by large loop excision of the transformation zone. Histopathological evaluation of the excised specimen confirmed the diagnosis of cervical intraepithelial neoplasia grade III accompanied by human papillomavirus infection. The excised second specimen showed the evidence of vasculitis of medium-sized vessels of the cervix, which is a quite rare form of SOV. It seems to be important to be aware of the localized form of polyarteritis nodosa limited to the female genital tract to prevent unnecessary immunosuppressive therapies. PMID:28386466
Hussain, Nasir; Mustafa, Usman; Davis, James; Thakkar, Shivani; Ali, Alaa M; Mirrakhimov, Aibek E; Barbaryan, Aram; Rowley, Guy Anthony
Leukocytoclastic vasculitis (LCV) is a small-vessel vasculitis with a reported incidence rate of 30 cases per million persons per year. It usually presents as a palpable purpuric skin rash on legs, though any part of the body can be affected. LCV rash may have an associated burning sensation or pain and in some cases may involve internal organs. In some cases, LCV rash may present as nodules, recurrent ulcerations or asymptomatic lesions. The diagnosis of LCV is usually made on skin biopsy. Etiological triggers may not be identified in as many as half of the cases. Treatment is usually conservative and includes identification and removal or treatment of the etiological trigger except in cases with internal organ involvement where systemic steroids and immunosuppressant may be necessary. In this article we present a case of indomethacin-associated LCV that improved with discontinuation of the offending agent.
McCluggage, W G; Armstrong, D J; Maxwell, R J; Ellis, P K; McCluskey, D R
A 24 year old male who suffered from the Wiskott-Aldrich syndrome developed intra-abdominal bleeding on two occasions. Radiological investigations showed aneurysmal dilatation of branches of the hepatic and superior mesenteric arteries. The second abdominal bleed necessitated laparotomy and the bleeding was localised to the kidneys. Right nephrectomy was performed and histological examination showed a necrotising vasculitis, mainly involving medium and small sized renal blood vessels. Steroids, immunosuppressive treatment, and control of blood pressure resulted in resolution of the vasculitic process and prevented further haemorrhage. Vasculitis and aneurysm formation are rarely described complications of Wiskott-Aldrich syndrome and may account for the life threatening haemorrhage which occurs in this condition. Images PMID:10560364
Montoliu, J; Darnell, A; Grau, J M; Torras, A; Revert, L
Six HBsAg negative patients with cirrhosis of the liver (CL) presented with recurrent bouts of palpable purpura in the legs due to small vessel leucocytoclastic vasculitis. In addition, all patients had renal failure, proteinuria and microhaematuria. Renal biopsy disclosed either diffuse proliferative (3 cases) or focal necrotising glomerulonephritis with crescents (2 cases). One patient had IgM-IgG mixed cryoglobulinaemia (type II). Four patients died of complications of their CL. Hepatocellular carcinoma was found in 1 case. In the patient without renal biopsy renal function improved following steroids and cyclophosphamide. The pathogenesis of this syndrome of cutaneous vasculitis with severe glomerular involvement in CL is unknown but could be immune-complex mediated.
Miller, Matthew A; Lenci, Lucas T; Reddy, Chittaranjan V; Russell, Stephen R
We present the case of a 75-year-old man who had uneventful cataract surgery and administration of intracameral vancomycin for endophthalmitis prophylaxis, followed by the same procedure in the fellow eye 1 week later. The patient subsequently developed bilateral hemorrhagic occlusive retinal vasculitis, resulting in profound vision loss in both eyes. A second case of hemorrhagic occlusive retinal vasculitis previously reported from our institution is summarized. That case was characterized by a far milder course, with rapid resolution of vision loss. The 2 cases illustrate the broad range of toxicity potentially associated with intracameral vancomycin, suggest that bilateral administration results in a worse prognosis, and indicate that this disorder may be underrecognized due to the potential for a mild course. We recommend that intracameral vancomycin not be used for endophthalmitis prophylaxis.
Goto, Kimihiko; Nakai, Kentaro; Fujii, Hideki; Nishi, Shinichi
Antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis is a life-threatening disease characterized by rapidly progressive glomerulonephritis (RPGN) and diffuse alveolar hemorrhage (DAH). Glucocorticoids and immunosuppressants are commonly used to treat this disease but may induce irreversible side effects, particularly in elderly patients. We herein report the case of a 76-year-old woman with RPGN. After methylprednisolone pulse therapy, DAH occurred, and she required ventilatory support. After plasma exchange, her serum creatinine level improved, and she was discharged with home oxygen therapy. Immunosuppressive agents other than glucocorticoids were not required. In conclusion, plasma exchange with glucocorticoid therapy may be effective in treating severe ANCA-associated vasculitis in elderly patients. PMID:28050000
Zeineddine, Nabil; Felix, Richard; Goldstein, Mark
Levamisole is an antihelminthic drug banned by the US Food and Drug Administration (FDA) in 2000 because of its dangerous side effects. Over the past few years, it has been identified as an adulterant in cocaine and reported to cause cutaneous vasculitis in cocaine users. The health burden of levamisole is serious since it is estimated that over 5 million Americans use cocaine and that 70% of the cocaine used in the USA contains levamisole. In this paper we report the case of a 23-year-old female cocaine user that presented with purpuric rash and skin necrosis, found to have positive c-ANCA and anti-proteinase 3 antibodies. Her skin biopsy showed fibroconnective tissue with signs of necrosis, acute and chronic inflammation, and thrombus formation. She was diagnosed with levamisole-induced vasculitis and successfully treated with withdrawal of cocaine use and local wound care. PMID:27579207
Ribeiro, Sofia; Domingues, Vital; Faria, Raquel M; Mendonça, Teresa
Invasive pneumococcal disease (IPD) is a potential life-threatening situation that requires immediate recognition and treatment. Cerebrovascular complications are uncommon and have been reported less frequently in adults than in children. We report a case of 59-year-old man with IPD complicated by cerebral vasculitis, transient central diabetes insipidus and spondylodiscitis. Each of these complications is rare and needs specific approach. Their association is even rarer and to the best of our knowledge this is the first case reported.
van der Geld, Y M; Stegeman, C A; Kallenberg, C G M
Pauci-immune idiopathic small-vessel vasculitis is strongly associated with the presence of antineutrophil cytoplasm autoantibodies (ANCA). Antibodies to PR3 predominate in patients with Wegener's granulomatosis; antibodies to myeloperoxidase (MPO) are found more frequently in patients with microscopic polyangiitis. There is increasing in vivo and in vitro evidence for a pathogenic role of ANCA in systemic vasculitis based on associations of ANCA with disease activity. If ANCA are pathogenic, why is the course of disease different from one patient to another? Antibodies can recognize different binding sites (epitopes) on their corresponding antigens. Differences in binding specificity may influence the pathogenic potential of the antibodies. Differences between epitope specificity of ANCA between patients or changes in epitope specificity of ANCA in time in an individual patient may, accordingly, result in differences in disease expression. This review will focus on epitope specificity of autoantibodies in systemic autoimmune diseases and especially on the epitope specificity of PR3- and MPO-ANCA. We will discuss whether PR3-ANCA or MPO-ANCA recognize different epitopes on PR3 and MPO, respectively, and whether the epitopes recognized by ANCA change in parallel with the disease activity of ANCA-associated vasculitis. Finally, we will speculate if the direct pathogenic role of ANCA can be ascribed to one relapse- or disease-inducing epitope. Characterization of relapse- or disease-inducing epitopes bound by PR3-ANCA and MPO-ANCA is significant for understanding initiation and reactivation of ANCA-associated vasculitis. Elucidating a disease-inducing epitope bound by ANCA may lead to the development of epitope-specific therapeutic strategies.
Trask, R S; Bond, I P
This paper presents the first conceptual study into creating a Plantae-inspired vascular network within a fibre-reinforced polymer composite laminate, which provides an ongoing self-healing functionality without incurring a mass penalty. Through the application of a 'lost-wax' technique, orthogonal hollow vascules, inspired by the 'ray cell' structures found in ring porous hardwoods, were successfully introduced within a carbon fibre-reinforced epoxy polymer composite laminate. The influence on fibre architecture and mechanical behaviour of single vascules (located on the laminate centreline) when aligned parallel and transverse to the local host ply was characterized experimentally using a compression-after-impact test methodology. Ultrasonic C-scanning and high-resolution micro-CT X-ray was undertaken to identify the influence of and interaction between the internal vasculature and impact damage. The results clearly show that damage morphology is influenced by vascule orientation and that a 10 J low-velocity impact damage event is sufficient to breach the vasculature; a prerequisite for any subsequent self-healing function. The residual compressive strength after a 10 J impact was found to be dependent upon vascule orientation. In general, residual compressive strength decreased to 70 per cent of undamaged strength when vasculature was aligned parallel to the local host ply and a value of 63 per cent when aligned transverse. This bioinspired engineering study has illustrated the potential that a vasculature concept has to offer in terms of providing a self-healing function with minimum mass penalty, without initiating premature failure within a composite structure.
Nielsen, Amy Almaraz; Smith, Benn E; Engel, Andrew G; Bosch, Erich Peter
A 52-year-old man presented with a severe head drop and proximal extremity weakness. Magnetic resonance imaging of the cervical spine showed T2 hyperintensity in cervical paraspinal muscles. Electrodiagnostic studies revealed an axial myopathy isolated to paraspinal muscles. A splenius capitis muscle biopsy confirmed an acute myopathy associated with nonsystemic vasculitis. The patient improved on steroids, intravenous immunoglobulin, and monthly pulse doses of cyclophosphamide. Our case emphasizes that a subgroup of patients with dropped head syndrome have treatable conditions.
Geetha, Duvuru; Specks, Ulrich; Stone, John H; Merkel, Peter A; Seo, Philip; Spiera, Robert; Langford, Carol A; Hoffman, Gary S; Kallenberg, Cees G M; St Clair, E William; Fessler, Barri J; Ding, Linna; Tchao, Nadia K; Ikle, David; Jepson, Brett; Brunetta, Paul; Fervenza, Fernando C
Rituximab (RTX) is non-inferior to cyclophosphamide (CYC) followed by azathioprine (AZA) for remission-induction in severe ANCA-associated vasculitis (AAV), but renal outcomes are unknown. This is a post hoc analysis of patients enrolled in the Rituximab for ANCA-Associated Vasculitis (RAVE) Trial who had renal involvement (biopsy proven pauci-immune GN, red blood cell casts in the urine, and/or a rise in serum creatinine concentration attributed to vasculitis). Remission-induction regimens were RTX at 375 mg/m(2) × 4 or CYC at 2 mg/kg/d. CYC was replaced by AZA (2 mg/kg/d) after 3-6 months. Both groups received glucocorticoids. Complete remission (CR) was defined as Birmingham Vasculitis Activity Score/Wegener's Granulomatosis (BVAS/WG)=0 off prednisone. Fifty-two percent (102 of 197) of the patients had renal involvement at entry. Of these patients, 51 were randomized to RTX, and 51 to CYC/AZA. Mean eGFR was lower in the RTX group (41 versus 50 ml/min per 1.73 m(2); P=0.05); 61% and 75% of patients treated with RTX and 63% and 76% of patients treated with CYC/AZA achieved CR by 6 and 18 months, respectively. No differences in remission rates or increases in eGFR at 18 months were evident when analysis was stratified by ANCA type, AAV diagnosis (granulomatosis with polyangiitis versus microscopic polyangiitis), or new diagnosis (versus relapsing disease) at entry. There were no differences between treatment groups in relapses at 6, 12, or 18 months. No differences in adverse events were observed. In conclusion, patients with AAV and renal involvement respond similarly to remission induction with RTX plus glucocorticoids or CYC plus glucocorticoids.
Okubo, Yusuke; Nochioka, Kotaro; Sakakibara, Hiroshi; Hataya, Hiroshi; Terakawa, Toshiro; Testa, Marcia; Sundel, Robert P
At the national level, IgA vasculitis-related hospitalizations among children in the USA are scarce. Furthermore, nationwide epidemiology and hospital course of children with IgA vasculitis have not been fully described in the USA, and disparities by race/ethnicity remain unknown. Hospital discharge records of patients aged 19 years or younger were obtained from the 2003, 2006, 2009, and 2012 Kids' Inpatient Database, and they were weighted to estimate the annual hospitalization rates with respect to age, gender, and race/ethnicity in the USA. Annual hospitalization rates were calculated using weighted case estimates and US census data. Negative binomial regression was used to ascertain the factors associated with length of hospital stay. Total annual hospitalization rates showed a significant decreasing trend, ranging from 2.45 per 100,000 children in 2003 to 1.89 per 100,000 children in 2012 (p < 0.001). The peak ages of the hospitalized children with IgA vasculitis were 2 and 7 years, and male-to-female ratios were 1.38-1.44. Factors associated with length of hospital stay were patients' ages (10-14 and 15-19 years), race/ethnicity (Hispanic, Asian, and Pacific Islander), comorbid electrolyte abnormality, GI hemorrhage, intussusception, renal symptoms, and GI symptoms. The annual hospitalization rates for IgA vasculitis are declining in the USA across multiple age groups. GI and renal manifestations are associated with increased length of hospital stay.
Medina, G; González-Pérez, D; Vázquez-Juárez, C; Sánchez-Uribe, M; Saavedra, M A; Jara, L J
Vasculitis in systemic lupus erythematosus (SLE) has a broad spectrum of clinical manifestations from cutaneous to visceral involvement and its prognosis ranges from mild to life-threatening. We report the case of a previously healthy 17-year-old woman with eight months' history of arthralgias and myalgias. Subsequently, she developed facial and lower limbs edema, and hair loss. Two weeks before admission to a secondary level hospital, she developed fever up to 40°C followed by abdominal pain, rectal bleeding, hematemesis and blisters on both legs, reason for which she was hospitalized. With active bullous SLE with rapidly progressive glomerulonephritis suspected, she was treated with methylprednisolone pulses without response. After one week of treatment, she was transferred to a tertiary level hospital. On admission she presented acute arterial insufficiency of the lower extremities, respiratory failure with apnea, metabolic acidosis and shock; six hours later she died. Autopsy findings showed active diffuse lupus nephritis and diffuse systemic vasculitis that involved vessels from the skin, brain, myocardium, spleen, iliac and renal arteries. In addition, serositis of the small intestine and colon, acute and chronic pericarditis, pericardial effusion and myocarditis were found. Immunologic tests confirmed SLE diagnosis. In this case the fulminant course was the result of SLE high disease activity, visceral vasculitis of several organs and late diagnosis, referral and treatment. Early diagnosis, and opportune referral to the rheumatologist for intensive treatment can improve the outlook in these patients.
Ponte, C; Sznajd, J; O'Neill, L; Luqmani, R A
The systemic vasculitides are a group of rare, chronic, relapsing, but often progressive inflammatory conditions. They are associated with a significant burden of morbidity both due to scarring from the disease itself and as a consequence of treatment with glucocorticoids and other potent immunosuppressive agents. Careful assessment of disease activity is critical to guide appropriate use of these potentially toxic therapies. It is also important to differentiate features of active disease from those attributable to damage, which will not respond to immunosuppression. As these are chronic complex conditions, the impact on a patient's functional ability and quality of life are also important considerations. Given the lack of a reliable biomarker for assessment of disease activity or damage in systemic vasculitis, clinical tools developed and validated for use initially in clinically trials are key outcome measures in the evaluation of these patients. While the conduct of randomised clinical trials in vasculitis has been significantly enhanced by the development and use of validated outcome measures, regular use of validated disease activity and damage measurements as part of routine care offers a structured approach, which can serve as the basis of justifying treatment decisions. The authors review the concepts of clinical assessment tools used in the evaluation of patients with systemic vasculitis in the setting of clinical practice, clinical trials and long term databases with particular emphasis on disease activity, damage, prognosis and function.
V, Dharma Rao; Rampure, Dilip; S, Rama Rao
Anti-tuberculosis drugs frequently result in cutaneous adverse reactions but Isoniazid is known to have least toxic potential for cutaneous reactions. We report a rare case of Isoniazid induced cutaneous leucocytoclastic vasculitis. A 64-year-old male was diagnosed to have Pott’s spine with multiple vertebral body involvement (D8-12 vertebrae). Subsequently, he was treated with first line anti-TB drugs i.e., Isoniazid, Rifampicin, Pyrazinamide and Ethambutol. On the fourth day of treatment with Anti Tuberculosis Treatment (ATT), the patient developed an erythematosus rash over right upper limb not associated with itching or pain, non-blanchable macules and papules over bilateral shins on lower limbs, petechiae on both forearms and hyper pigmented, scaly rash over right axilla and buttocks. The skin biopsy report was consistent with cutaneous leukocytoclastic vasculitis. Although rare, Isoniazid among anti-tuberculosis drugs should be considered as potential cause of drug-induced cutaneous leukocytoclastic vasculitis in the differential diagnosis of erythematosus rash with petechiae. PMID:25302231
Yates, M; Watts, R A; Bajema, I M; Cid, M C; Crestani, B; Hauser, T; Hellmich, B; Holle, J U; Laudien, M; Little, M A; Luqmani, R A; Mahr, A; Merkel, P A; Mills, J; Mooney, J; Segelmark, M; Tesar, V; Westman, K; Vaglio, A; Yalçındağ, N; Jayne, D R; Mukhtyar, C
In this article, the 2009 European League Against Rheumatism (EULAR) recommendations for the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) have been updated. The 2009 recommendations were on the management of primary small and medium vessel vasculitis. The 2015 update has been developed by an international task force representing EULAR, the European Renal Association and the European Vasculitis Society (EUVAS). The recommendations are based upon evidence from systematic literature reviews, as well as expert opinion where appropriate. The evidence presented was discussed and summarised by the experts in the course of a consensus-finding and voting process. Levels of evidence and grades of recommendations were derived and levels of agreement (strengths of recommendations) determined. In addition to the voting by the task force members, the relevance of the recommendations was assessed by an online voting survey among members of EUVAS. Fifteen recommendations were developed, covering general aspects, such as attaining remission and the need for shared decision making between clinicians and patients. More specific items relate to starting immunosuppressive therapy in combination with glucocorticoids to induce remission, followed by a period of remission maintenance; for remission induction in life-threatening or organ-threatening AAV, cyclophosphamide and rituximab are considered to have similar efficacy; plasma exchange which is recommended, where licensed, in the setting of rapidly progressive renal failure or severe diffuse pulmonary haemorrhage. These recommendations are intended for use by healthcare professionals, doctors in specialist training, medical students, pharmaceutical industries and drug regulatory organisations.
Vydyula, Ravikanth; Allred, Charles; Huartado, Mariana; Mina, Bushra
A 34-year-old female presented with fever and abdominal pain. Past medical history includes Crohn's and Behcet's disease. Examination revealed multiple skin ulcerations, oral aphthae, and bilateral coarse rales. She developed respiratory distress with diffuse bilateral alveolar infiltrates on chest radiograph requiring intubation. PaO2/FiO2 ratio was 132. The chest computed tomography revealed extensive nodular and patchy ground-glass opacities. Bronchoalveolar lavage demonstrated a predominance of neutrophils. Methylprednisolone 60 mg every 6 h and broad-spectrum antimicrobials were initiated. No infectious etiologies were identified. Surgical lung biopsy demonstrated diffuse alveolar damage (DAD) mixed with lymphocytic and necrotizing vasculitis with multiple small infarcts and thrombi consistent with Behcet's vasculitis. As she improved, steroids were tapered and discharged home on oral cyclophosphamide. Pulmonary involvement in Behcet's is unusual and commonly manifests as pulmonary artery aneurysms, thrombosis, infarction, and hemorrhage. Lung biopsy findings demonstrating DAD are consistent with the clinical diagnosis of adult respiratory distress syndrome. The additional findings of necrotizing vasculitis and infarcts may have led to DAD. PMID:25378849
Marco, Helena; Mirapeix, Eduard; Arcos, Emma; Comas, Jordi; Ara, Jordi; Gil-Vernet, Salvador; Puig, Josep; Vinyas, Odette; Perello, Manel; Oppenheimer, Federico; Poveda, Rafael; Ibernón, Meritxell; Díaz, Montserrat; Ballarin, Jose
The survival after renal transplantation of patients with antineutrophil cytoplasmic antibody (ANCA)-associated to systemic vasculitis is as good as in other diseases, although most of the reports are based on small numbers of patients. Furthermore, it is not known whether comorbidities (cardiovascular [CV] disease and cancer) are more frequent than in general population. We report our experience and the analysis of the published data on this topic. The outcome after transplantation in 49 patients with ANCA-associated small vessel vasculitis was compared with a control group. The relapse rate of vasculitis was 0.01 per patient per year. Comparison with the control patients revealed no difference in long-term outcome, CV mortality or incidence of malignancies. In the published literature, patients with ANCA at transplantation and with Wegener's granulomatosis are at greater risk of relapse. Taking our own results together with the review of the literature, we conclude that patient and graft survival rates compare favorably with those in control group that the recurrence rate is very low and that there is no increase in the incidence of cancer or in CV mortality. Patients with ANCA at transplantation and with Wegener's granulomatosis have a higher relapse rate.
Yi, Xiao-Yan; Wang, Yao; Li, Qi-Fu; Li, Rong; Yang, Shu-Min; Zhou, Guo-Qing; Wang, Zhi-Hong
Abstract Background: Propylthiouracil is the most common drug used to treat hyperthyroidism. However, this drug could cause a severe disease, antineutrophilic cytoplasmic antibody-associated vasculitis (AAV), which was usually misdiagnosed. Methods: We reported a 60-year-old woman of propylthiouracil-induced AAV manifested as blood coagulation disorders. The patient was admitted because of hyperthyroidism and leukopenia. At the time of hospitalization, she suffered from dry cough, erythema and knee joints ache, and gradually became febrile. And then BP decreased and PLT was reduced with coagulation disorders. ANCA: c-ANCA positive (1:100), p-ANCA positive (1:320), MPO-IgG positive, PR3-IgG positive, GBM-IgG negative. Erythrocyte sedimentation rate and C-reactive protein increased markedly. Chest high-resolution computed tomography (HRCT) showed that scattered spots, patch and ground-glass opacity. Results: Finally, we made a terminal diagnosis of PTU-induced AAV possibly. After drug withdrawal and use of steroid, the patient recovered well and then accepted RAI therapy. As the patient was given imipenem-cilastatin before the reduction of PLT and coagulation disorders, we considered that the hematologic disorders might be caused by antibiotics or a clinical presentation of the vasculitis itself. Conclusion: Drug-induced vasculitis is relatively good prognosis, but early diagnosis and timely withdrawal of associated drugs are the key to the treatment. PMID:27741122
Horai, Yoshiro; Miyamura, Tomoya; Takahama, Soichiro; Hirata, Akie; Nakamura, Masataka; Ando, Hitoshi; Minami, Rumi; Yamamoto, Masahiro; Suematsu, Eiichi
A 63-year-old-man was diagnosed in March 2002 with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis because of mononeuritis multiplex, interstitial pneumonia and a positive finding for myeloperoxidase (MPO)-ANCA. Although treated with prednisolone and oral cyclophosphamide, he suffered repeated remission and deterioration of his conditon, which was complicated by hypertrophic pachymeningitis and sinusitis. In July 2006, he was diagnosed with an exacerbation of ANCA-associated vasculitis because of pyrexia, general malaise, numbness in his face and legs, and elevated serum CRP level. Steroid pulse therapy was thus initiated and the patient's clinical symptoms improved. However, serum CRP levels elevated again (5.18 mg/dl) in September 2006. We began administration of rituximab (500 mg/bodyx4 times) in November 2006 and his symptom and laboratory data significantly improved. The dose of prednisolone was slowly decreased without suffering a relapse. Rituximab has been administered every one year, and good disease control has been achieved. Diagnosis of Wegener's granulomatosis was made from the findings of a nodular lesion in the left lung. Rituximab should be considered for patients with refractory ANCA-associated vasculitis.
Both, M.; Jahnke, T.; Reinhold-Keller, E.; Reuter, M.; Grimm, J.; Biederer, J.; Brossmann, J.; Gross, W.L.; Heller, M.; Mueller-Huelsbeck, S.
The purpose of this study was to evaluate the safety and effectiveness of percutaneous transluminal angioplasty for occlusive arterial disease associated with vasculitis. Eleven patients(10 women, 1 man; ages 35-82 years) with the diagnosis of vasculitis of the large vessels underwent interventional treatment during intraarterial angiography. The causes included giant cell arteritis(n = 8) and Takayasu arteritis (n = 3).Thirty-three occlusive lesions (including brachiocephalic and renalarteries, and arteries of upper and lower extremities) were treated with balloon angioplasty and/or stent placement. Follow-up included clinical examination, angiography, and color duplex ultrasound.Technical success was 100% (25/25) for stenoses and 50% (4/8) for occlusive lesions, representing all lesions combined from different anatomic locations. Dissection (n = 3) and arterial rupture with retroperitoneal hematoma (n = 1) was found in three patients. During follow-up (mean 12 months), restenoses(n = 8) and re-restenoses (n = 1)occurred in 8 vascular areas. Three of these lesions were treated with repeated PTA (n = 4). The cumulative primary clinical success rate was 67.6%, cumulative secondary success rate 74.4%, and cumulative tertiary success rate 75.9%. Interventional therapy in systemic vasculitis provides promising results in technical success rates and followup. Angioplasty may result in arterial injury, but the rate of complications is low.
Tseng, Chien-Chi; Chen, San-Ni; Hwang, Jiunn-Feng; Lin, Chun-Ju; Chen, Huan-Sheng
A 45-year-old man, a case of acquired immunodeficiency syndrome, received a highly active antiretroviral therapy at the outpatient service for 4 years without regular follow-up. He experienced progressively blurred vision for 6 months and a cutaneous zoster on his back 3 months ago. He was diagnosed with progressive outer retinal necrosis by polymerase chain reaction-restriction fragment length polymorphism using an aqueous humor sample, which revealed an existence of varicella zoster virus. He was given a combination of systemic, intravitreal antiviral and a highly active antiretroviral therapy. Occlusive vasculitis, an unusual finding for progressive outer retinal necrosis, developed in both eyes 1 week after the secondary intravitreal injection. Unfortunately, his vision deteriorated to no light perception in both eyes within 2 weeks. Progressive outer retinal necrosis is characterized clinically as showing minimal or no inflammation in the aqueous and vitreous humors, absence of retinal vasculitis, and patches of yellowish spots located deep in the retina. Physicians should pay attention to this rare case of progressive outer retinal necrosis associated occlusive vasculitis with very poor prognosis in spite of aggressive treatment.
Jung, David H; Nadol, Joseph B; Folkerth, Rebecca D; Merola, Joseph F
The association of sensorineural hearing loss and vertigo with inflammatory eye disease, usually interstitial keratitis, has been called Cogan's syndrome. The pathogenesis of Cogan's syndrome is unknown, but it has been assumed to be an immune mediated disorder with vasculitis. The histopathology of the inner ear in Cogan's syndrome has been described in 6 case reports. Although common pathologic findings in these reports include degeneration of the auditory and vestibular neuroepithelium, endolymphatic hydrops, fibrosis, and new bone formation, direct pathologic evidence of a vasculitis has not been published. A possible reason for this failure to identify vasculitis was a substantial delay (range, 4-40 years) between the onset of symptoms and examination of the otopathology. In the current case report, the patient had both auditory and vestibular symptoms and interstitial keratitis with a time delay of only 2 to 4 weeks between symptoms and death. Evidence of a vasculitis as a possible underlying etiology included H&E histopathology and anti-CD45 immunostaining of vessels both in the auditory and vestibular systems, supporting the hypothesis of a vasculitis as a mechanism in this disorder.
Biscetti, Federico; Carbonella, Angela; Parisi, Federico; Bosello, Silvia Laura; Schiavon, Franco; Padoan, Roberto; Gremese, Elisa; Ferraccioli, Gianfranco
Abstract Systemic vasculitides represent a heterogeneous group of diseases that share clinical features including respiratory distress, renal dysfunction, and neurologic disorders. These diseases may often cause life-threatening complications requiring admission to an intensive care unit (ICU). The aim of the study was to evaluate the validity and responsiveness of Birmingham Vasculitis Activity Score (BVAS) score to predict survival in patients with systemic vasculitides admitted to ICU. A retrospective study was carried out from 2004 to 2014 in 18 patients with systemic vasculitis admitted to 2 different Rheumatology divisions and transferred to ICU due to clinical worsening, with a length of stay beyond 24 hours. We found that ICU mortality was significantly associated with higher BVAS scores performed in the ward (P = 0.01) and at the admission in ICU (P = 0.01), regardless of the value of Acute Physiology And Chronic Health Evaluation (APACHE II) scores (P = 0.50). We used receiver-operator characteristic (ROC) curve analysis to evaluate the possible cutoff value for the BVAS in the ward and in ICU and we found that a BVAS > 8 in the ward and that a BVAS > 10 in ICU might be a useful tool to predict in-ICU mortality. BVAS appears to be an excellent tool for assessing ICU mortality risk of systemic vasculitides patients admitted to specialty departments. Our experience has shown that performing the assessment at admission to the ward is more important than determining the evaluation before the clinical aggravation causing the transfer to ICU. PMID:27902615
Veronese, F.V.; Dode, R.S.O.; Friderichs, M.; Thomé, G.G.; da Silva, D.R.; Schaefer, P.G.; Sebben, V.C.; Nicolella, A.R.; Barros, E.J.G.
Levamisole has been increasingly used as an adulterant of cocaine in recent years, emerging as a public health challenge worldwide. Levamisole-associated toxicity manifests clinically as a systemic vasculitis, consisting of cutaneous, hematological, and renal lesions, among others. Purpura retiform, cutaneous necrosis, intravascular thrombosis, neutropenia, and less commonly crescentic nephritis have been described in association with anti-neutrophil cytoplasmic antibodies (ANCAs) and other autoantibodies. Here we report the case of a 49-year-old male who was a chronic cocaine user, and who presented spontaneous weight loss, arthralgia, and 3 weeks before admission purpuric skin lesions in the earlobes and in the anterior thighs. His laboratory tests on admission showed serum creatinine of 4.56 mg/dL, white blood count 3,800/μL, hemoglobin 7.3 g/dL, urinalysis with 51 white blood cells/μL and 960 red blood cells/μL, and urine protein-to-creatinine ratio 1.20. Serum ANCA testing was positive (>1:320), as well as serum anti-myeloperoxidase and anti-proteinase 3 antibodies. Urine toxicology screen was positive for cocaine and levamisole, with 62.8% of cocaine, 32.2% of levamisole, and 5% of an unidentified substance. Skin and renal biopsies were diagnostic for leukocytoclastic vasculitis and pauci-immune crescentic glomerulonephritis, respectively. The patient showed a good clinical response to cocaine abstinence, and use of corticosteroids and intravenous cyclophosphamide. Last serum creatinine was 1.97 mg/dL, white blood cell count 7,420/μL, and hemoglobin level 10.8 g/dL. In levamisole-induced systemic vasculitis, the early institution of cocaine abstinence, concomitant with the use of immunosuppressive drugs in severe cases, may prevent permanent end organ damage and associate with better clinical outcomes. PMID:27119429
Sepsis is a potentially life-threatening complication of an infection where cutaneous lesions often represent one of the early signs. A myriad of microorganisms including bacteria, fungi, yeasts, viruses, protozoas, helminths and algae can be implicated. A broad spectrum of clinical and histopathologic findings can be observed in the skin and the common denominator is a thrombotic vasculopathy. The pathogenesis of cutaneous septic vasculitis (SV)/vasculopathy is complex and includes five main mechanisms: disseminated intravascular coagulation, direct invasion and occlusion of blood vessel walls by microorganisms, hypersensitivity reaction with immune complex deposition into blood vessel walls, embolism from a distant infectious site and vascular effects of toxins. Herein we describe the clinicopathologic findings of some selected cases of SV recently observed in our hospital, including purpura fulminans, necrotizing fasciitis, cutaneous meningococcemia, malignant syphilis and disseminated alternaria infection. Histopathologically, a wide spectrum of histopathologic changes was observed in skin specimens from the various entities, involving the intensity and composition of the inflammatory infiltrate, the degree of vascular changes and the presence of microorganisms, that ranged from a predominant not inflammatory, thrombotic-occlusive vasculopathy in purpura fulminans to leukocytoclastic vasculitis like changes in cutaneous meningococcemia to a dermal angiomatosis-like pattern in disseminated Alternaria infection. The different pathologic presentations may be related to the microorganism involved, the main pathogenetic mechanism that induced the vascular injury and the individual immunologic burden. Early skin biopsy for histopathologic examination and microbiologic culture is a cornerstone in the diagnosis of life-threatening diseases that present with cutaneous septic vasculitis. Ancillary techniques, such as immunohistochemistry and polymerase chain reaction are
Lipitsä, Tiina; Naukkarinen, Anita; Laitala, Joel; Harvima, Ilkka T
The complement factor C3 and chymase released from tryptase(+), chymase(+) mast cells may be involved in the pathogenesis of cutaneous leukocytoclastic vasculitis. To study whether mast cells contain C3 in vasculitis and whether chymase interacts with C3, cryosections from vasculitis biopsies were double-stained histochemically for C3c in tryptase(+) mast cells, as well as for chymase and vessel wall C3c, or they were treated with 5 µg/ml rh-chymase for 24 h followed by immunofluorescence (IF) analysis of C3c, IgG, IgM and IgA. The effect of rh-chymase on purified human C3, C3a and IgG was studied using SDS-PAGE electrophoresis and LAD2 mast cell cultures. The results show that 34.2 ± 17.9, 37.4 ± 15.5 and 43.4 ± 18.6 % (mean ± SD) of the mast cells express C3c immunoreactivity in the healthy skin, initial petechial (IP) and palpable purpura (PP) lesions, respectively. About 9.4-12.1 % of the chymase(+) mast cells were in apparent contact with C3c(+) vessels in IP and PP. The treatment of cryosections with rh-chymase decreased the IF staining of C3c, but not that of immunoglobulins. In SDS-PAGE, 1-10 µg/ml rh-chymase degraded the alpha- and beta-chains of C3, but did not degrade IgG. Unexpectedly, the rh-chymase treatment of C3 produced fragments that resulted in the release of tryptase and histamine from LAD2 cells. However, rh-chymase degraded C3a and consequently inhibited C3a activity on LAD2. In conclusion, mast cells can be one source for C3 in the early and late phases of vasculitis pathogenesis. However, rh-chymase degraded native C3, vessel wall C3c, and biologically active C3a. Therefore, chymase may control C3-related pathology.
Biasibetti, Elena; Sferra, Chiara; Lynen, Godelieve; Di Giulio, Giuseppe; De Meneghi, Daniele; Tomassone, Laura; Valenza, Federico; Capucchio, Maria Teresa
The Authors describe a severe vasculitis with fibrinoid necrosis of the meningeal arteries observed in two brains of indigenous short-horn zebu (Bos indicus) cattle, with bovine cerebral theileriosis (BCT) caused by a tick-transmitted hemoprotozoan, Theileria taurotragi, from Northern Tanzania. In the Author's opinion, the role of T. taurotragi infection in the angiocentric and angiodestructive detected features remains to be evaluated. A possible immunopathologic cancerous mechanism, secondary to the lymphoid deregulation, could be involved. This report suggests further studies to better characterize the lymphoid cell involvement in the pathogenesis of the meningeal vascular lesions by T. taurotragi.
Manenti, Lucio; Urban, Maria Letizia; Maritati, Federica; Galetti, Maricla; Vaglio, Augusto
Complement alternative pathway (cAP) hyperactivation seems to be involved in ANCA-associated vasculitis (AAV). We here describe a case of AAV with severe activation of cAP that developed acute renal failure. No mutation predisposing to cAP dysregulation was identified. We treated our patient with the standard immunosuppressive therapy, but disease progression was only reversed after the addition of eculizumab, a monoclonal antibody against C5; the patient eventually achieved an almost complete renal function recovery. A review of the available literature about the role of complement targeted therapies in the treatment of AAV is discussed.
García Cosmes, Pedro; Fraile Gómez, Pilar; Lewczuk, Kamil; Rodríguez González, Marta; Ruiz Ferreras, Elena; Tabernero Fernández, Guadalupe
Renal disease secondary to vasculitis associated with anti-neutrophil cytoplasmic antibodies (ANCA) can lead to chronic renal disease requiring renal replacement therapy. In these patients, kidney transplantation offers excellent long-term rates of allograft and patient survival; consequently, they can be trasplanted when the clinical disease activity has remitted. However, the risk of disease relapses in the renal allograft remains, although at lower rates due to modern immunosuppressive regimens. We describe the case of a male patient with extracapillary glomerulonephritis type III C-ANCA (+) who developed a recurrence in the renal allograft 8 years after transplantation. Intensive immunosupression with plasmapheresis controlled the disease.
Hachiya, Kenta; Wakami, Kazuaki; Yoshida, Atsuhiro; Suda, Hisao; Ohte, Nobuyuki
We herein report an unusual case of an infected descending aortic pseudoaneurysm with luminal pathognomonic oscillating vegetation with serological findings and clinical features mimicking anti-proteinase 3-antineutrophil cytoplasmic antibody-associated vasculitis. The positive blood cultures and imaging findings, including a pseudoaneurysm and vegetations in the aorta, suggested the presence of an infected aortic aneurysm. The patient was successfully treated with antibiotics and endovascular aortic repair. A precise diagnosis is crucial in order to avoid inappropriate therapy such as immunosuppressive treatment, which could result in life-threatening consequences in a patient with an infected aortic aneurysm. PMID:27904110
Murakami, Masanori; Shimane, Kenichi; Takahashi, Hiroshi; Tomiyama, Junji; Nagashima, Masakazu
We here report a rare case of dual antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in a 38-year-old Japanese woman previously diagnosed with mixed connective tissue disease. The patient was found to be positive for myeloperoxidase- and proteinase 3-ANCA, and was diagnosed with AAV following admission to hospital with fervescence, polyarthralgia, purpura, and asymmetric numbness of the extremities. Examination of her genetic background revealed that she carried HLA-DR9, which confers risk of both diseases in Japanese populations.
Nozari, Neda; Divsalar, Parisa
This case report demonstrates fatal gastrointestinal vasculitis as a rare presentation of systemic lupus erythematosus. A 34-year-old woman presented with abdominal pain and diarrhea. Anti nuclear antibody was positive and high titre of anti-ds DNA antibody was also reported. Treatment with corticosteroid and supportive cares were started; however, her condition worsened. Eventually, she was considered as a candidate for diagnostic laparoscopy. Immediately after laparoscopy, she developed respiratory distress along with upper gastrointestinal bleeding. Soon after, the patient died because of disseminated intravascular coagulation . PMID:25093065
Manusow, Joshua S; Khoja, Leila; Pesin, Nataly; Joshua, Anthony M; Mandelcorn, Efrem D
We report on a 36-year-old woman treated with the anti PD-1 antibody Pembrolizumab for metastatic cutaneous melanoma in the first line setting. She achieved a complete response and then relapsed with metastases to the vitreous cavity with an associated angiographically determined retinal vasculitis. Vitreous metastasis without choroidal involvement is unusual and may be due to individual cell extravasation, vitreous hemorrhage containing malignant cells, or direct spread through the optic nerve. This finding highlights the need for immune sanctuary sites to be monitored in the presence of PD-1 inhibition and we hypothesize that the use of PD-1 inhibitor potentiated the patient's angiographically determined retinal vasculitis.
Rarok, Agnieszka A; Huitema, Minke G; van der Leij, Marcel J; van der Geld, Ymke M; Berthold, Heike; Schmitt, Jacky; Stegeman, Coen A; Limburg, Pieter C; Kallenberg, Cees G
The presence of antineutrophil cytoplasmic autoantibodies with specificity for proteinase 3 (PR3-ANCA) usually is detected by enzyme-linked immunosorbent assay (ELISA) with purified PR3 as a substrate. We studied the technical performance of direct and capture ELISA using a recombinant proteolytically inactive form of PR3 produced in the baculovirus expression system for the detection of PR3-ANCA in 114 patients with systemic vasculitis at diagnosis. We found that ELISA using recombinant PR3 produced in insect cells is a promising alternative for ELISA with native PR3. We found a correlation between tests using recombinant or native PR3, as well as correlation of the ELISA results with ANCA titers measured by the indirect immunofluorescence technique. However, the specificity for ANCA-associated vasculitis of ELISA with recombinant PR3 was lower than ELISA using native PR3. Compared with the direct assay, capture ELISA is a more sensitive method for PR3-ANCA detection, with both native and recombinant PR3, and its results depend on the monoclonal antibody used to capture the antigen.
Yoshida, Naohiro; Iino, Yukiko
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is histologically characterized by systemic necrotizing vasculitis and is clinically classified into two phases, systemic or localized. Recently, otological symptoms such as otitis media and hearing loss, not previously often associated with AAV, have been reported in AAV cases. In these cases we propose a diagnosis of otitis media with AAV (OMAAV). The ANCA titer is important for the diagnosis of OMAAV, and in most cases rapid progressive hearing loss is observed as localized AAV. Peripheral facial nerve palsy or hypertrophic pachymeningitis are coupled with 25% of cases and 18% of cases respectively. Proteinase 3-ANCA (PR3-ANCA) positive otitis media causes granulomatous formation or middle ear effusion in the middle ear, on the other hand myeloperoxidase-ANCA (MPO-ANCA) positive otitis media predominantly presents as otitis media with effusion. The early diagnosed case and the sensorineural hearing loss not progressed deaf could be recovered by the immunosuppressive therapy. Delayed diagnosis of AAV occasionally leads to progression to the irreversible phase; therefore, diagnosis at the early-localized stage is important for treating AAV. In this review, we discuss the current understanding of this newly proposed concept of OMAAV.
Watanabe, Kae; Rajderkar, Dhanashree A.; Modica, Renee F.
Pediatric polyarteritis nodosa is rare systemic necrotizing arteritis involving small- and medium-sized muscular arteries characterized by aneurysmal dilatations involving the vessel wall. Aneurysms associated with polyarteritis nodosa are common in visceral arteries; however intracranial aneurysms have also been reported and can be associated with central nervous system symptoms, significant morbidity, and mortality. To our knowledge extracranial involvement of the vertebral arteries has not been reported but has the potential to be deleterious due to fact that they supply the central nervous system vasculature. We present a case of a 3-year-old Haitian boy with polyarteritis nodosa that presented with extracranial vessel involvement of his vertebral arteries. After thorough diagnostic imaging, including a bone scan, ultrasound, Magnetic Resonance Imaging/Angiography, and Computed Tomography Angiography, he was noted to have vertebral artery vasculitis, periostitis, subacute epididymoorchitis, arthritis, and myositis. He met diagnostic criteria for polyarteritis nodosa and was treated with cyclophosphamide, methylprednisolone, and tocilizumab, which resulted in improvement of his inflammatory markers, radiographic findings, and physical symptoms after treatment. To the authors' knowledge, this is the first report of vertebral artery vasculitis in polyarteritis nodosa as well as successful treatment of the condition using the combination cyclophosphamide and tocilizumab for this condition. PMID:27018080
Huang, Qing; Liu, Yu-lan
The male patient reported here presented as gangrene and central diabetes insipidus (CDI), who had characteristics of vasculitis. The patient complained about polydipsia and polyuria half a year ago, and then developed tingling, pain and blackish discoloration of some fingers and toes 3 month ago. He also had Raynaud's phenomenon. After admission, his laboratory examination showed the rise of erythrocyte sedimentation rate, C-reactive protein, immunoglobulin, β2-glycoprotein I and the activity of rheumatoid factors, lupus anticoagulant test. his pituitary gland showed loss of posterior signal on magnetic resonance imaging. In addition, his vasopressin test was active. However, there was no sufficient evidence to diagnose any specific disease; as a consequence the patient was diagnosed as idiopathic systemic necrotizing vasculitis (SNV). For SNV, the patient was treated with glucocorticoid 40 mg/d and impact therapy of cyclophosphamide 0.4 g every 2 weeks. He also received symptomatic treatment for gangrene and CDI. Cutaneous involvement leading to gangrene was widely reported in SNV, however pituitary involvement in SNV leading to CDI was rare. The prognosis of this patient was poor.
Sabayan, B; Zolghadrasli, Abdolali
Acute disseminated encephalomyelitis (ADEM) is defined as a multifocal, monophasic, demyelinating, and inflammatory disease involving the central nervous system. It typically begins within 6 weeks of an antigenic challenge such as infection or immunization. Perivenous inflammation, edema and demyelination are the pathological hallmarks of ADEM. Reactivity of T-cells against myelin components such as myelin basic protein has been found in children with ADEM. The triggers for immune responses in ADEM are not known, but the two most widely accepted hypotheses are molecular mimicry and self-sensitization secondary to CNS infection. Inflammatory cytokines including tumor necrosis factor alpha (TNFalpha), interleukin 2 (IL2) and interferon gamma (INFgamma) are thought to be important in lesion formation in ADEM. Due to the active role of inflammatory cytokines in the pathogenesis of ADEM, any disease contributing to systemic formation of inflammatory cytokines can potentially be an etiologic factor for the initiation of ADEM. In vasculitis and rheumatologic diseases the number of T-cells, T helper type 1 cytokines and other inflammatory cytokines such as TNFalpha increase substantially. We present this hypothesis that in such setting of inflammation, adhesion molecules are up-regulated on the brain capillary endothelium by cytokines and other inflammatory mediators, altering the permeability of the brain blood barrier and so allowing for inflammatory cell migration. The migratory cells attack the basic myelin protein and the final result is the demyelination seen in ADEM. So we propose that vasculitis and rheumatologic diseases may play role in the pathogenesis of ADEM.
D'Cruz, D P; Houssiau, F A; Ramirez, G; Baguley, E; McCutcheon, J; Vianna, J; Haga, H J; Swana, G T; Khamashta, M A; Taylor, J C
Using an ELISA, anti-endothelial cell antibodies (AECA) have been found in sera obtained at the time of renal biopsy in 46 out of 57 patients (81%) with systemic lupus erythematosus (SLE) and nephritis (mean binding index (BI) = 84% +/- 52.8) compared with 22 out of 50 SLE patients (44%) without nephritis (mean BI = 45% +/- 35.9). Seventy normal human sera had a mean BI of 10% +/- 9.8. The highest levels were seen in patients with diffuse proliferative glomerulonephritis (WHO grade IV) and in patients with proteinuria and nephrotic syndrome. When the biopsies were assessed for activity and chronicity scores, AECA were associated with active renal lesions (P less than 0.001). AECA levels correlated with low complement levels but not with anti-DNA antibodies to extractable nuclear antigens (ENA), anti-cardiolipin or anti-neutrophil cytoplasmic antibodies. The presence of AECA conferred a positive predictive value of 0.68 for the presence of nephritis. Twenty-five patients had active vasculitis at the time of assay and the highest AECA values were seen in patients with both nephritis and vasculitis. No correlation was seen with serum immunoglobulin levels and immune complexes did not bind significantly to the endothelial surface. The possible role of these antibodies as a marker in lupus nephritis is discussed.
Giscombe, R; Grunewald, J; Nityanand, S; Lefvert, A K
Wegener's granulomatosis (WG) and polyarteritis nodosa (PAN) are systemic necrotizing vasculitides of unknown etiology. These disorders run a fatal course if untreated. T lymphocytes are implicated in the pathogenesis of WG, since they have been found to infiltrate affected organs, and sIL-2R correlates with disease activity. To elucidate further the role of T cells in necrotizing vasculitis, we have used a panel of 12 TCR V-specific MoAbs to investigate the number of cells expressing certain V alpha and V beta gene segments in the CD4+ and CD8+ subsets of altogether 11 patients with WG or PAN. In the group of patients, we found abnormal expansions of T cells using particular TCR V alpha or V beta gene products. These T cell expansions were more numerous, of a dramatically higher magnitude, and frequently more often found in the CD4 subset, compared with T cell expansions identified in healthy individuals. In long-term studies of the T cell expansions for up to 18 months, a heterogeneous pattern was revealed, with no obvious correlation to clinical features such as disease activity or treatment. Studies of TCR V gene usage in this group of patients may help in understanding the pathogenesis of necrotizing vasculitis, and in the identification of unknown antigens, and may open the possibility to a highly selective immunotherapy by targeting disease-mediating T cells. PMID:7648706
Immunoglobulin (Ig)A vasculitis (IgAV), formerly known as Henoch-Schönlein purpura, is one of the most common vasculitis caused by an IgA-mediated immune complex. It occurs most frequently in childhood and less commonly in adulthood. As for the treatment of IgAV in adults, there are few studies dealing with the administration and efficacy of intravenous pulse steroid therapy or combination therapy using prednisolone (PSL) and immunosuppressive drugs. Mizoribine (MZB) is a newly developed immunosuppressive drug with few adverse effects; however, there are currently few studies using MZB in adult patients with IgAV. In this study, we evaluated the efficacy of MZB combined with a course of PSL in adult patients with IgAV. Five patients with adult onset IgAV were enrolled in the study. All patients received oral PSL (initial dose 30-50 mg/day), and MZB was administered orally at a single morning dose of 150 mg. We investigated the clinical manifestations and prognosis of these patients receiving the combination therapy of MZB and PSL retrospectively. All patients showed complete or partial remission of proteinuria and microscopic hematuria with the combination therapy of MZB and PSL. Furthermore, no significant adverse effects were observed. Although this study had an uncontrolled small group, our results indicate that the combination of MZB with PSL could be a possible new treatment for adult patients with IgAV.
Floyd, M; Tesar, J T
The effect of IgM rhematoid factor (RF) on reversepassive cutaneous Arthus reaction in rats was studied. The RF was obtained from the serum cryoglobulin of a patient with symptoms of purpura, arthralgia and digital gangrene. The cryoglobulins was of IgG-IgM type and when given i.v it induced a prompt hypocomplementaemia in experimental animals. The purified RF also induced low serum complement levels when injected i.v. along with complexes of non-complement-fixing, aggregated IgG. A reverse passive Arthus reaction was induced by intradermal injection of IgG anti-bovine serum albumin (BSA), followed by an i.v. dose of antigen (Ag). The cutaneous inflammatory reaction was aggravated by simultaneous administration of IgM RF intradermally, but not by IgM without antibody (Ab) properties. Intradermal injection of low concentrations of non-complement-fixing IgG anti-BSA, along with normal human IgM, followed by i.v. injection of BSA, resulted in a complete lack of cutaneous inflammation. At higher Ab concentrations there was only a mild inflammation. However, when IgM RF was substituted for normal IgM and injected with non-complement-fixing anti-BSA, an effective reverse passive cutaneous Arthus reaction and vasculitis was induced. The inflammatory response was greatly suppressed by decomplementation of animals by cobra venom factor. This study provides evidence favouring an inflammatory, complement-dependent role for RF in vasculitis. PMID:157238
Choudhry, Wajid M; Nori, Uday S; Nadasdy, Tibor; Satoskar, Anjali A
Diagnostic kidney biopsies sometimes yield clinically unsuspected diagnoses. We present a case of a 69-year-old woman with established ANCA-associated vasculitis (AAV) of 4 years duration who was in clinical remission following cytotoxic therapy and was on maintenance immunosuppression. She presented to the hospital with acute kidney injury (AKI), symptoms suggestive of a systemic vasculitis, and in addition had hypercalcemia, metabolic alkalosis. A relapse in the AAV was suspected but a diagnostic kidney biopsy showed acute tubular necrosis, patchy interstitial inflammation, and calcium phosphate deposits. It was found that the patient recently started consuming large doses of over-the-counter calcium-containing antacids and vitamin Dcontaining multivitamin supplements. Cessation of these drugs led to improvement of renal function to baseline. This case highlights several teaching points: (1) the kidney biopsy can prove to be critically important even in cases where there appears to be a more obvious clinical diagnosis, (2) AK due to calcium-alkali syndrome has characteristic histopathological changes, and (3) that the triad of hypercalcemia, metabolic alkalosis, and AKI is exclusively associated with the ingestion of excessive quantities of calcium-containing antacids. The physician should keep this in mind, and pro-actively seek pertinent medication history from the patient. A brief review of calcium-alkali syndrome is given.
Tejedor, Ana; Solé, Manel; Prieto-González, Sergio; Alba, Marco Antonio; Grau, Josep Maria; Cid, Maria Cinta; Hernández-Rodríguez, José
We report the case of a 45-year-old patient who presented with acute dilated cardiomyopathy. During admission the patient was consecutively diagnosed with cryoglobulinaemic vasculitis and beriberi. In both diseases, cardiac involvement may occur as dilated cardiomyopathy. Thiamin deficiency was the final cause for the severe cardiac manifestations (cardiac acute beriberi or Shoshin syndrome), which returned to normal after thiamin supplementation.
Papireddy, Muralidhar; Gao, John
Background. Renal-limited myeloperoxidase vasculitis with simultaneous rheumatoid arthritis is reported as a rare occurrence. Review of literature suggests that most patients had a diagnosis of rheumatoid arthritis for several years prior to presenting with renal failure from myeloperoxidase vasculitis. Case Presentation. A 58-year-old Caucasian male presented to the hospital experiencing malaise, fevers, decreased oral intake, nausea, and vomiting for one week duration. His past medical history consisted of newly diagnosed but untreated rheumatoid arthritis, hypertension, and non-insulin-dependent diabetes mellitus. He was found to have acute renal failure, proteinuria, and hypoglycemia. Standard therapy, including intravenous fluids, did not improve his acute renal failure. A vasculitis workup resulted in a positive myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA). Renal biopsy revealed crescentic glomerulonephritis (GN) pauci-immune type, suggestive of MPO-ANCA-associated vasculitis (MPO-AAV). Treatment consisted of prednisone, cyclophosphamide, and seven cycles of plasmapheresis, in addition to hemodialysis for uremia. Upon discharge, he received hemodialysis for another week and continued treatment with cyclophosphamide and prednisone. Conclusion. Patients with longstanding rheumatoid arthritis may develop renal failure due to nonsteroidal anti-inflammatory medication use and AA type amyloidosis; however, necrotizing glomerulonephritis with crescent formation has been rarely reported. This stresses the importance of early recognition and swift initiation of treatment. PMID:27891268
Khatibi, Kasra; Heit, Jeremy J; Telischak, Nicholas A; Elbers, Jorina M; Do, Huy M
A young patient with PAPA (pyogenic arthritis, pyoderma gangrenosum, and acne) syndrome developed an unusual cerebral arterial vasculopathy/vasculitis (CAV) that resulted in subarachnoid hemorrhage from a ruptured dissecting posterior cerebral artery (PCA) aneurysm. This aneurysm was successfully treated by endovascular coil sacrifice of the affected segment of the PCA. The patient made an excellent recovery with no significant residual neurologic deficit.
Khatibi, Kasra; Heit, Jeremy J; Telischak, Nicholas A; Elbers, Jorina M; Do, Huy M
A young patient with PAPA (pyogenic arthritis, pyoderma gangrenosum, and acne) syndrome developed an unusual cerebral arterial vasculopathy/vasculitis (CAV) that resulted in subarachnoid hemorrhage from a ruptured dissecting posterior cerebral artery (PCA) aneurysm. This aneurysm was successfully treated by endovascular coil sacrifice of the affected segment of the PCA. The patient made an excellent recovery with no significant residual neurologic deficit.
Bello, Luis; Mimessi, Galie; Gómez, Maximiliano
There are cases of patients having urticaria that do not respond satisfactorily to antihistamine treatment suggested by guidelines. In order to expand the search for associated factors, research about possible related infections have been performed. This paper describes the case of two patients evaluated in our center for hives resistant to standard treatment in which syphilis was diagnosed, with remission of urticaria when specific antibiotic treatment was established.
... and ulcers that do not heal Muscles and joints: Joint pain Leg pain Muscle weakness Brain and nervous ... URAC, also known as the American Accreditation HealthCare Commission (www.urac.org). URAC's accreditation program is an ...
... the past more » View All News Connect with us on social media! Join VF Donate Next Page » ... our community through education, awareness and research. Contact Us Click here to send us an email! Mail: ...
... most frequently listed as being associated with the development of HV include: penicillin, cephalosporin, sulfonamide, some medicines used to control blood pressure (loop and thiazide-type diuretics), phenytoin and allopurinol. Infections that may be ...
Sowa, Mandy; Grossmann, Kai; Knütter, Ilka; Hiemann, Rico; Röber, Nadja; Anderer, Ursula; Csernok, Elena; Bogdanos, Dimitrios P.; Borghi, Maria Orietta; Meroni, Pier Luigi; Schierack, Peter; Reinhold, Dirk; Conrad, Karsten; Roggenbuck, Dirk
Anti-neutrophil cytoplasmic antibodies (ANCA) are the serological hallmark of small vessel vasculitis, so called ANCA-associated vasculitis. The international consensus requires testing by indirect immunofluorescence (IIF) on human ethanol-fixed neutrophils (ethN) as screening followed by confirmation with enzyme-linked immunosorbent assays (ELISAs). This study evaluates the combination of cell- and microbead-based digital IIF analysis of ANCA in one reaction environment by the novel multiplexing CytoBead technology for simultaneous screening and confirmatory ANCA testing. Sera of 592 individuals including 118 patients with ANCA-associated vasculitis, 133 with rheumatoid arthritis, 49 with infectious diseases, 77 with inflammatory bowel syndrome, 20 with autoimmune liver diseases, 70 with primary sclerosing cholangitis and 125 blood donors were tested for cytoplasmic ANCA (C-ANCA) and perinuclear ANCA (P-ANCA) by classical IIF and ANCA to proteinase 3 (PR3) and myeloperoxidase (MPO) by ELISA. These findings were compared to respective ANCA results determined by automated multiplex CytoBead technology using ethN and antigen-coated microbeads for microbead immunoassays. There was a good agreement for PR3- and MPO-ANCA and a very good one for P-ANCA and C-ANCA by classical and multiplex analysis (Cohen's kappa [κ] = 0.775, 0.720, 0.876, 0.820, respectively). The differences between classical testing and CytoBead analysis were not significant for PR3-ANCA, P-ANCA, and C-ANCA (p<0.05, respectively). The prevalence of confirmed positive ANCA findings by classical testing (IIF and ELISA) compared with multiplex CytoBead analysis (IIF and microbead immunoassay positive) resulted in a very good agreement (κ = 0.831) with no significant difference of both methods (p = 0.735). Automated endpoint-ANCA titer detection in one dilution demonstrated a very good agreement with classical analysis requiring dilution of samples (κ = 0.985). Multiplexing by Cyto
Graham-Brown, M. P. M.; Aljayyousi, R.; Baines, R. J.; Burton, J. O.; Brunskill, N. J.; Furness, P.; Topham, P.
We report the case of a 40-year-old female transplant patient with undiagnosed ANCA-associated vasculitis (AAV) and renal allograft dysfunction who achieved disease remission with restoration of transplant function following induction therapy with rituximab. There are currently no trial data looking at the use of rituximab for induction of remission of renal transplant patients with AAV. Although recurrence of AAV following renal transplantation is rare, such patients have invariably had multiple previous exposures to induction and maintenance immunosuppressive regimens, often limiting treatment options post-transplantation. In this case, rituximab was well tolerated with no side effects, and was successful in salvaging transplant function. Optimal treatment regimens for relapsed AAV in the transplant population are not known, and clinical trials are needed to evaluate the efficacy and safety of rituximab at inducing and maintaining disease remission in relapsed AAV following transplantation. PMID:27699052
Trieste, Leopoldo; Palla, Ilaria; Baldini, Chiara; Talarico, Rosaria; D'Angiolella, Lucia; Mosca, Marta; Turchetti, Giuseppe
This article attempts to perform an evaluation of the state of the art of the economic and societal burden of systemic vasculitis (VAs). Due to the rarity of these diseases and their variable clinical picture, few data are available in the literature on their health economic issues, and only some papers have been published that marginally examine the problem. Since VAs are severe conditions with a high medical and societal impact and determine high healthcare resource consumption, studies able to define societal, quality of life and economic burden of these pathologies are needed. Policy makers, private and public organisations involved in the care of VAs need data to programme future investment or make cost-effectiveness analysis for introducing new drugs or protocols.
Kirchner, J; Raab, H P; Länger, F; Wigand, R; Mitrou, P; Jacobi, V
Antineutrophil cytoplasmatic antibodies (ANCA)-associated vasculitides (Wegener's granulomatosis, microscopic polyangiitis, Churg-Strauss syndrome) show quite variable courses. Clinical features of the full blown generalized systemic vasculitis are usually found in the respiratory tract and the kidney. Pulmonary involvement of Wegener's granulomatosis shows commonly nodules and cavitations but also diffuse alveolar hemorrhage. We report the case of a 57 year-old man suffering from dyspnea, thoracal pain, arthralgia, purpura, scleritis and tinitus. Specimen of the kidney showed segmental glomerulosclerosis and tubulointerstitial nephritis. Because of the presence of cANCA Wegener's disease was assumed. Pulmonary infiltrates developed under immunosuppressive treatment with cyclophosphamid. As differential diagnosis of the pulmonary infiltrates, we considered invasive pulmonary aspergillosis as well as infiltrates due to Wegener's granulomatosis. In spite of maximal therapeutic management of patient died of respiratory and cardiovascular failure. The findings at autopsy showed distinct invasive pulmonary aspergillosis and perifocal hemorrhage.
Lazarus, B.; John, G. T.; O’Callaghan, C.; Ranganathan, D.
Anti-neutrophil cytoplasmic antibody-associated vasculitis is an uncommon inflammatory disease of small to medium-sized vessels that frequently presents with rapidly progressive glomerulonephritis and renal failure though it can affect any organ system. If untreated, the vast majority of patients will die within a year. Current treatments improve prognosis but affected patients remain at a substantially higher risk of death and adverse outcomes. We review the classification of the disease, our understanding of the pathogenesis and epidemiology, and propose future directions for research. We also evaluate the evidence supporting established treatment regimens and the progress of clinical trials for newer treatments to inform the design of future studies. PMID:27051131
Malenica, Branko; Rudolf, Marija; Kozmar, Ana
Antineutrophil cytoplasmic antibodies (ANCA) are a heterogeneous group of circulating antibodies directed toward the cytoplasmic constituents of neutrophils and monocytes. ANCA have been described in various diseases including idiopathic systemic vasculitides, connective tissue diseases, inflammatory bowel diseases, autoimmune liver diseases, infectious diseases, and some drugs. ANCA recognize different target antigens such as proteinase 3 (PR3-ANCA), myeloperoxidase (MPO-ANCA), cathepsin G, lactoferrin, bactericidal/permeability-increasing protein (BPI), and some others. However, only PR3-ANCA and MPO-ANCA are closely associated with systemic vasculitides, in particular Wegener's granulomatosis, microscopic polyangiitis and its renal limited manifestation, and Churg-Strauss syndrome. Both in vitro and in vivo experimental data strongly support a pathogenic role for ANCA in vasculitis and glomerulonephritis.
Shah, Jay; Poonawala, Husain; Keay, Susan K; Serulle, Yafell; Steven, Andrew; Gandhi, Dheeraj; Cole, John W
Infections are rare but important causes of stroke. Among these, varicella zoster virus has been known to cause ischemic stroke. During an attack of herpes zoster ophthalmicus, it has been hypothesized that the virus replicates in the trigeminal ganglion and travels via the trigeminal nerve centrally to cause cerebral vasculopathy. Here we present a case of a 69 year-old Caucasian immunocompromised woman who suffered recurrent ischemic infarcts within the same vascular distribution following an episode of zoster ophthalmicus three months prior. An imaging technique termed black-blood magnetic resonance imaging was utilized to aid in the diagnosis of cerebral vasculitis. The case is used to provide a literature review of the pathogenesis, diagnosis, and treatment of cerebral varicella zoster vasculopathy. In situations where an isolated unilateral cerebral vasculopathy is identified, neurologists are urged to consider varicella zoster as a treatable etiologic agent, as untreated vasculopathy can lead to further strokes. PMID:27065314
Spriggs, Maria; Reeder, Chris
A 59-yr-old female Nile hippopotamus (Hippopotamus amphibius) was diagnosed and treated for severe dermatitis. Lesions included large areas of depigmentation, erosions, and ulcerations on glabrous skin areas, limbs, and perineal region. Histopathologic lesions included a markedly edematous, focally eroded, ulcerative to necrotic epidermis; foci of keratinocyte apoptosis; and a mixed suppurative dermatitis. Most of the dermal vessels had variable hyalinized walls with plump endothelial cells and frequent intramural neutrophils, and some vessels had vascular thrombi consistent with vasculitis. Culture of the lesions yielded beta-hemolytic Streptococcus, Morganella morgannii, and Enterococcus sp. The hippopotamus was successfully treated with sulfamethoxazole and trimethoprim, amoxicillin, and pentoxifylline for more than 2 mo, and the condition did not recur over the subsequent 16 mo.
Rain, Carmen; Yáñez, Tatiana; Rada, Gabriel
Adding rituximab to the treatment with corticosteroids has been proposed as a therapeutic alternative for inducing remission in anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis, especially when fertility is a concern, or when there is contraindication or intolerance to cyclophosphamide. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified only one systematic review including three pertinent randomized controlled trials. We combined the evidence using meta-analysis and generated a summary of findings following the GRADE approach. We concluded rituximab may slightly increase induction of remission rate, but it may also increase the risk of infection. It is not clear whether it increases the risk of cancer, or whether increases or decreases mortality because the certainty of the evidence is very low.
Poulton, Caroline J.; Nachman, Patrick H.; Hu, Yichun; McGregor, JulieAnne G.; Jennette, J. Charles; Falk, Ronald J.; Hogan, Susan L.
Objectives Antineutrophil cytoplasmic antibody small-vessel vasculitis (ANCA-SVV) is an autoimmune systemic process increasingly recognised since the advent of antibody testing for the disease. Prompt diagnosis and institution of immunosuppressive therapy has been shown to improve patient outcome. The goal of this study was to better understand how patients navigate the health care system from symptom presentation to biopsy diagnosis, and to study the effects of prompt versus delayed diagnosis. Methods Disease symptoms and number of physicians seen prior to renal biopsy were assessed for 127 ANCA-SVV patients. Direct, delayed, and quest pathways to diagnosis and treatment of vasculitis were defined for both patients and providers. Kruskal-Wallis and Fisher exact tests were used to evaluate continual measures and compare categorical variables across pathways. Results Among patients who sought direct care, physician delay in referral to a nephrologist was common (49/127, 71%, p=0.0023). Patients who delayed seeking care also experienced a delayed diagnosis 57% of the time (p=0.0023). Patients presenting with prodromal flu or upper respiratory involvement were more likely to have a delay/quest patient pathway (56% and 55%, respectively) than a direct patient pathway (44%, p=0.033 and 45%, p=0.019, respectively). There was a trend for patients with more severe loss of renal function to have a more direct referral to a nephrologist. Conclusion Delay in diagnosis of ANCA SVV may be due to lack of or non-specific symptoms, especially in patients who present with non-renal manifestations of disease. Better algorithms are needed to identify extra-renal manifestations, expedite diagnosis and improve patient outcomes. PMID:23343774
Kauffmann, R H; Herrmann, W A; Meijer, C J; Daha, M R; Vanes, L A
Sixty-two patients with allergic vasculitis and histological evidence of leukocytoclastic vasculitis were examined to determine whether clinical features, such as course and degree of systemic involvement, could be related to the class of the immunoglobulins in immune complexes (IC) in both the circulation and the vessel wall. Circulating IC were detected with the 125I-C1q-binding assay (C1q-BA), an anti-IgA inhibition binding assay (a-IgA-Inh BA) and the conglutinin-binding assay (Con-BA). Stabilized heat-aggregated IgG, IgA and IgM were used to determine the immunoglobulin class specificity of these assays. With the C1q-BA only aggregated IgG were detected, with the a-IgA-Inh Ba only aggregates containing IgA. With the Con-BA IgG, IgA or IgM in reactive aggregates were identified with class-specific antibodies. For patients with acute cutaneous vasculitis all assays were negative. The a-IgA-Inh BA was frequently positive in sera of patients with chronic cutaneous and acute systemic vasculitis; in the latter group conglutinin-binding IC of the IgG, IgA and IgM class were also detected. Levels in the C1q-BA were high for patients with chronic systemic vasculitis. Comparison of the results of the IC assays with the immunofluorescence studies of the cutaneous vessel walls of the same patients showed agreement between the results of the C1q-BA and deposition of IgG and the results of the a-IgA-Inh BA and IgA deposition. The class of immunoglobulin in conglutinin-binding IC did not correspond as well with the immunoglobulins in vessel walls. This study shows that certain clinical features of allergic vasculitis are related to the composition of the IC in the circulation and in the vessel wall. PMID:7438561
Moreno, Alan D.; Joseph, Nora; Kim, George; Fimmel, Claus J.
Relapse of hepatitis C virus (HCV) genotype 1 infection after combination therapy with sofosbuvir and ledipasvir is unusual. We report a treatment-naïve, non-cirrhotic patient in whom the relapse of genotype 1b HCV infection was accompanied by de novo cryoglobulinemic vasculitis and glomerulonephritis, requiring hemodialysis for acute renal failure. Sequence analysis revealed several resistance-associated variants in the HCV NS5a gene but not in NS3/4A. The patient’s vasculitis was successfully treated with immunosuppression and plasmapheresis, followed by retreatment of HCV with a combination of sofosbuvir, simeprevir, and ribavirin. The patient achieved sustained virological response, recovered his renal function, and remains in remission from cryoglobulinemia. PMID:28184378
Hafiz, Shahd; Albeity, Abdurahman; Almoallim, Hani
Antineutrophil cytoplasmic antibody- (ANCA-) associated vasculitis (AAV) is a multisystem autoimmune disease affecting mainly microscopic blood vessels due to circulating autoantibodies against neutrophil cytoplasmic antigens. We report a case of a 57-year-old female patient presenting with hemoptysis, sinusitis, and conjunctivitis. Based on lung biopsy, the diagnosis of antineutrophil cytoplasmic antibody- (ANCA-) associated vasculitis (AAV) was established. She was put on rituximab as induction and maintenance therapy. She responded initially to rituximab as induction therapy but failed to respond in the maintenance course of the drug. Rituximab was stopped and mycophenolate mofetil was administered. She responded as laboratory c-ANCA titers turned negative and symptoms subsided. There are no randomized clinical trials addressing rituximab effect in induction and remission at the same time. This case report doubts the efficacy of the use of rituximab therapy for both induction and maintenance of remission at the same time, waiting for the results of the ongoing trials. PMID:27006851
De Blasi, T; Aguilar Marucco, D; Cariti, G; Maiello, A; De Rosa, F G; Di Perri, G
HCV infection may be related to many extrahepatic manifestations including mixed cryoglobulinemia (MC). Clinical manifestations commonly associated to MC include arthralgia, purpura, vasculitis, peripheral neuropathy and renal function abnormalities. Treatment with interferon often leads to remission, especially in virological responders, or to disappearance of MC-related clinical manifestations. We report on a patient with chronic hepatitis C, deficit of G6P-DH, type II MC, who developed a cryoglobulinemic vasculitis with purpura, renal impairment and arterial hypertension, during treatment with PEG-interferon a-2b plus amantadine. The occurrence of purpuric lesions and MC-related nephropathy with increased cryocrit despite negative viremia, in a patient previously asymptomatic, during interferon treatment, is unusual.
Garge, Shaileshkumar S.; Vyas, Pooja D.; Modi, Pranav D.; Ghatge, Sharad
Cerebral vasculitis secondary to Crohn's disease (CD) seems to be a very rare phenomenon. We report a 39-year-old male who presented with headache, vomiting, and left-sided weakness in the known case of CD. Cross-sectional imaging (computed tomography and magnetic resonance imaging,) showed right gangliocapsular acute infarct with supraclinoid cistern subarachnoid hemorrhage (SAH). Cerebral digital substraction angiography (DSA) showed dilatation and narrowing of right distal internal carotid artery (ICA). Left ICA was chronically occluded. His inflammatory markers were significantly raised. Imaging features are suggestive of cerebral vasculitis. Arterial and venous infarcts due to thrombosis are known in CD. Our case presented with acute subarachnoid hemorrhage in supraclinoid cistern due to rupture of tiny aneurysm of perforator arteries causing SAH and infarction in right basal ganglia. Patient was treated conservatively with immunosuppression along with medical management of SAH. PMID:25506170
Takahashi, Masatoshi; Katada, Fumiaki; Sato, Susumu; Shibayama, Hidehiro; Fukutake, Toshio; Murayama, Shigeo
The patient was a 78-year-old man. Three years before admission, he developed transient peripheral neuropathy and purpura, and at admission, he presented with livedo reticularis of both his lower extremities and with mononeuritis multiplex. Vasculitis was not observed, and antiphospholipid antibodies were detected. The nerve and skin biopsies revealed no inflammation; axonal degeneration accompanied by thrombi was found in his arterioles and venules. Based on these findings, he was diagnosed with ischemic peripheral neuropathy due to primary antiphospholipid syndrome. Administration of anticoagulant therapy resulted in an improvement in symptoms; however, two months later, a relapse occurred, and the patient contracted an infection while undergoing immunosuppressive therapy. The infection became fulminant, and the patient succumbed to multiple organ failure. The autopsy revealed a systemic arterial and venous embolism; however, no vasculitis was observed. Antiphospholipid syndrome, which is responsive to antithrombotic treatment, should be considered as a differential diagnosis of mononeuritis multiplex.
Manners, P; Robbins, P
Chronic recurrent multifocal osteomyelitis (CRMO), of unknown etiology, is characterized by recurring non-suppurative lesions of bone in multiple sites, and has been considered to be self-limiting. Reported therapies include prolonged antibiotics, corticosteroids and anti-inflammatory medications. This case is presented to illustrate the following: 1) CRMO may be severe, on-going, and unresponsive to treatment; 2) it may be associated with Crohns' disease; 3) the use of granulocyte colony-stimulating factor (G-CSF) may be associated with severe gastrointestinal vasculitis. A male was treated from ages 11-20 years for CRMO (manifesting as multiple bone lesions), with therapies of variable efficacy (anti-inflammatories, antibiotics, corticosteroids, gammaglobulin and methotrexate). With increasing disruption to his life, a 10-day course of granulocyte colony-stimulating factor (G-CSF) was given with benefit seen on magnetic resonance imaging (MRI). With exacerbation of symptoms one month later, G-CSF was re-commenced but ceased after 3 weeks because of abdominal pain, rectal blood loss, and progression of bone lesions with subsequent removal of portions of ileum, colon and appendix, which showed vasculitis. Months later, a colonoscopy revealed perianastomotic ulcers and continuing gastroenterological ulceration not unlike Crohn's disease. With azathioprine, gut and bone symptoms improved. We conclude that 1) CRMO may adversely affect life for years; 2) proven treatments are unavailable; 3) gastroenterological vasculitis/ Crohn's may be associated with CRMO; 4) MRI is useful for monitoring CRMO; 5) In this patient, G-CSF seemed beneficial initially, but later, vasculitis (possibly Crohn's) manifested, leading to bowel resection; 6) Crohn's disease may have been present for years, masked by corticosteroid, and unmasked by reduction of steroids and use of G-CSF.
Monach, Paul A; Warner, Roscoe L; Tomasson, Gunnar; Specks, Ulrich; Stone, John H; Ding, Linna; Fervenza, Fernando C; Fessler, Barri J; Hoffman, Gary S; Iklé, David; Kallenberg, Cees GM; Krischer, Jeffrey; Langford, Carol A; Mueller, Mark; Seo, Philip; St. Clair, E William; Spiera, Robert; Tchao, Nadia; Ytterberg, Steven R; Johnson, Kent J; Merkel, Peter A
Objective To identify circulating proteins that distinguish between active anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and remission in a manner complementary to markers of systemic inflammation. Methods Twenty-eight serum proteins representing diverse aspects of the biology of AAV were measured before and 6 months after treatment in a large clinical trial of AAV. Subjects (n=186) enrolled in the Rituximab in ANCA-Associated Vasculitis (RAVE) trial were studied. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels were available for comparison. The primary outcome was the ability of markers to distinguish severe AAV (Birmingham Vasculitis Activity Score for Wegener’s granulomatosis (BVAS/WG)≥3 at screening) from remission (BVAS/WG=0 at month 6), using areas under receiver operating characteristic (ROC) curve (AUC). Results All subjects had severe active vasculitis (median BVAS/WG=8) at screening. In the 137 subjects in remission at month 6, 24 of the 28 markers showed significant declines. ROC analysis indicated that levels of CXCL13 (BCA-1), matrix metalloproteinase-3 (MMP-3) and tissue inhibitor of metalloproteinases-1 (TIMP-1) best discriminated active AAV from remission (AUC>0.8) and from healthy controls (AUC>0.9). Correlations among these markers and with ESR or CRP were low. Conclusions Many markers are elevated in severe active AAV and decline with treatment, but CXCL13, MMP-3 and TIMP-1 distinguish active AAV from remission better than the other markers studied, including ESR and CRP. These proteins are particularly promising candidates for future studies to address unmet needs in the assessment of patients with AAV. PMID:22975753
Luterbacher, R.; Trask, R. S.; Bond, I. P.
The effect of including hollow channels (vascules) within cross-ply laminates on static tensile properties and fatigue performance is investigated. No change in mechanical properties or damage formation is observed when a single vascule is included in the 0/90 interface, representing 0.5% of the cross sectional area within the specimen. During tensile loading, matrix cracks develop in the 90° layers leading to a reduction of stiffness and strength (defined as the loss of linearity) and a healing agent is injected through the vascules in order to heal them and mitigate the caused degradation. Two different healing agents, a commercial low viscosity epoxy resin (RT151, Resintech) and a toughened epoxy blend (bespoke, in-house formulation) have been used to successfully recover stiffness under static loading conditions. The RT151 system recovered 75% of the initial failure strength, whereas the toughened epoxy blend achieved a recovery of 67%. Under fatigue conditions, post healing, a rapid decay of stiffness was observed as the healed damage re-opened within the first 2500 cycles. This was caused by the high fatigue loading intensity, which was near the static failure strength of the healing resin. However, the potential for ameliorating (via self-healing or autonomous repair) more diffuse transverse matrix damage via a vascular network has been shown.
Moog, Philipp; Thuermel, Klaus
A 54-year-old patient presented to his general practitioner because of strong muscle pain in both thighs. Inflammatory parameters (CRP 16.3 mg/dL) and white blood cells (15 g/L) were elevated. The patient reported a weight loss of 10 kg in 4 weeks. There was no fever or any other specific symptoms. Urine dipstick examination and computed tomography of the chest were unremarkable. Because of increasing symptoms, the patient was referred to our department. Magnetic resonance tomography showed diffuse inflammatory changes of the muscles of both thighs. Neurological examination and electrophysiology revealed axonal sensorimotor neuropathy and ground-glass opacities of both lungs had occurred. Serum creatinine increased to 229 μmol/L within a few days, with proteinuria of 3.3 g/g creatinine. Kidney biopsy showed diffuse pauci-immune proliferative glomerulonephritis. Proteinase 3-specific antineutrophil cytoplasmic antibodies were markedly increased. Birmingham Vasculitis Activity Score was 35. Within 2 days, serum creatinine further increased to 495 μmol/L. Plasma exchange, high-dose glucocorticosteroids, and hemodialysis were started. The patient received cyclophosphamide 1 g twice and rituximab 375 mg/m2 four times according to the RITUXVAS protocol. Despite ongoing therapy, hemodialysis could not be withdrawn and had to be continued over 3 weeks until diuresis normalized. Glucocorticosteroids were tapered to 20 mg after 2 months, and serum creatinine was 133 μmol/L. However, nephritic urinary sediment reappeared. Another dose of 1 g cyclophosphamide was given, and glucocorticosteroids were raised for another 4 weeks. After 6 months, the daily prednisolone dose was able to be tapered to 5 mg. Serum creatinine was 124 μmol/L, proteinuria further decreased to 382 mg/g creatinine, and the Birmingham Vasculitis Activity Score was 0. Maintenance therapy with rituximab 375 mg/m2 every 6 months was started. At the last visit after 8 months, the patient was still in
Cheung, Y; Brogan, P; Pilla, C; Dillon, M; Redington, A
Background: Polyarteritis nodosa is a necrotising vasculitis of the medium sized and small muscular arteries. The inflammatory and subsequent reparative processes may alter the arterial mechanical properties. The effect of vasculitic damage on arterial distensibility has never been explored however. Aim: To determine the normal values and the effect of childhood vasculitis on arterial distensibility in children and teenagers. Methods: Distensibility of the brachioradial arterial segment was studied using pulse wave velocity (PWV ∝1/√distensibility), in 13 children with polyarteritis nodosa at a median age of 11.8 (range 4.9–16) years. As a control group, 155 healthy schoolchildren (6–18 years, 81 boys) were studied. PWV was assessed using a photoplethysmographic technique; blood pressure was measured by an automatic sphygmomanometer (Dinamap). Data from patients were expressed as z scores adjusted for age and compared to a population mean of 0 by a single sample t test. Determinants of PWV in normal children were assessed by univariate and multivariate linear regression analyses. Results: Age, height, weight, and systolic blood pressure correlated individually with the brachioradial PWV. Multivariate analysis identified age as the only independent determinant. Ten of the patients were in clinical remission, while three had evidence of disease activity at the time of study. The PWV in the patient group as a whole was significantly greater than those in healthy children (mean z score +0.99). Raised C reactive protein concentration (>2 mg/dl) in the three patients with active disease was associated with a higher PWV when compared to those in remission (z score +2.78 v +0.45). The diastolic blood pressure of the patients was higher than those of the controls (z score +1.04) while the systolic pressure was similar (z score -0.36). Conclusions: PWV in the brachioradial arterial segment increases gradually during childhood independent of body weight, height, mass
Slot, M C; Theunissen, R; van Paassen, P; Damoiseaux, J G M C; Cohen Tervaert, J W
Many patients surviving vasculitis are prone to accelerated atherosclerosis and often have enhanced levels of antibodies to oxidized low-density lipoprotein (oxLDL). To measure anti-oxLDL antibodies, oxidation of LDL is achieved with copper (Cu) or malondialdehyde (MDA). Because, in vivo, LDL may be oxidized with myeloperoxidase (MPO) or its product hypochlorite, we measured anti-hypochlorite LDL antibodies in patients with vasculitis, haemodialysis patients and healthy controls. A newly developed enzyme-linked immunosorbent assay (ELISA) was used to detect antibodies to oxLDL as modified by hypochlorite. Results are compared with data obtained by standard LDL oxidation using MDA–LDL or Cu–LDL as substrate. Results were compared between anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) patients (n = 93), haemodialysis (HD) patients (n = 59) and healthy controls (HC; n = 43). Furthermore, patients with MPO–ANCA-associated vasculitis (n = 47) were compared with patients with proteinase 3 (PR3)–ANCA associated vasculitis (n = 46). Optimal cut-off points were determined by receiver operator characteristic (ROC) curve analysis. Anti-oxLDL antibodies are enhanced in AAV patients (MDA–LDL and hypochlorite–LDL) and in HD patients (hypochlorite–LDL), when compared to HC. Furthermore, patients with MPO–ANCA-associated vasculitis had higher levels of antibodies to hypochlorite–LDL than patients with PR3–ANCA-associated vasculitis. Our newly developed assay, in which hypochlorite–LDL is used as substrate, seems a more sensitive assay than traditional assays to measure oxLDL antibodies. Furthermore, our results suggest that enhanced MPO-mediated LDL oxidation occurs in patients with MPO–ANCA. PMID:17521320
Domiciano, Talita P.; Wakita, Daiko; Jones, Heather D.; Crother, Timothy R.; Verri, Waldiceu A.; Arditi, Moshe; Shimada, Kenichi
Interleukin-1β (IL-1β) is a highly inflammatory cytokine that significantly contributes to both acute and chronic inflammatory diseases. The secretion of IL-1β requires a unique protease, caspase-1, which is activated by various protein platforms called inflammasomes. Data suggests a key role for mitochondrial reactive oxygen species for inflammasome activation. Flavonoids constitute a group of naturally occurring polyphenolic molecules with many biological activities, including antioxidant effects. In this study, we investigated the effect of three flavonoids, quercetin (QUC), naringenin, and silymarim on inflammasome activation. We found that QUC inhibits IL-1β secretion by both the NLRP3 and AIM2 inflammasome in a dose dependent manner, but not the NLRC4 inflammasome. QUC inhibition of the inflammasome was still observed in Atg16l1 knockout macrophages, indicating that QUC’s effect was autophagy independent. Since QUC inhibited both NLRP3 and AIM2 inflammasomes but not NLRC4, we assessed ASC speck formation. QUC reduced ASC speck formation and ASC oligomerization compared with controls. Additionally, QUC inhibited IL-1β in Cryopyrin-Associated Periodic Syndromes (CAPS) macrophages, where NLRP3 inflammasome is constitutively activated. In conclusion, QUC inhibits both the NLRP3 and AIM2 inflammasome by preventing ASC oligomerization and may be a potential therapeutic candidate for Kawasaki disease vasculitis and other IL-1 mediated inflammatory diseases. PMID:28148962
Fatma, Lilia Ben; Rais, Lamia; Mebazza, Amel; Azzouz, Haifa; Beji, Somaya; Krid, Madiha; Smaoui, Wided; Maiz, Hedi Ben; Zouaghi, Karim; Zitouna, Moncef; Osmane, Amel Ben; Moussa, Fatma Ben
The association between Kaposi's sarcoma (KS) and human herpes virus eight (HHV-8) infection is rarely reported in hemodialysis (HD) patients. We report here the rare association of KS, HHV-8 and hepatitis C virus (HCV) infection as well as syphilis in a HD patient. We report the case of a 72-year-old woman who presented with microscopic polyangiitis with alveolar hemorrhage and pauci-immune necrosing and crescentic glomerulonephritis as well as renal failure requiring HD. Biological tests showed positive HCV and syphilis tests. The patient was treated by HD and intravenous pulse, followed by oral corticosteroids and six cyclophosphamide monthly pulses with remission of the alveolar hemorrhage, but without renal functional recovery as the patient remained HD dependent. Five months after the first treatment administration, she developed extensive purpuric lesions on her lower limbs, abdomen face and neck. A skin biopsy showed KS. The HHV-8 test was positive, with positive polymerase chain reaction-HHV8 in the serum and skin. After immunosuppression withdrawal, the KS skin lesions regressed rapidly without relapse after 12 months of follow-up, but alveolar hemorrhage relapsed after 16 months of follow-up. Our case showed that the immunosuppressed state related to multiple factors such as aging, vasculitis, HHV-8, HCV, syphilis, immunosuppressive therapy and HD may all have contributed to the development of KS in our patient.
File, Ibolya; Trinn, Csilla; Mátyus, Zsolt; Ujhelyi, László; Balla, József; Mátyus, János
Relapsing polychondritis (RP) is a rare autoimmune disease with chronic inflammatory/destructive lesions of the cartilaginous tissues. In one third of the cases it is associated with other autoimmune disorders, mostly with anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV). We report three cases of RP with p-ANCA positive AAV. In the first patient RP developed 1.5 years after the onset of AAV. In the others the signs of RP were present before the onset of severe crescent glomerulonephritis. Patients responded well on steroid and cyclophosphamide. In dialysis dependent cases plasmapheresis was also used successfully. During the 2 and 1.5 years of follow up, they were symptom-free, and had stable glomerular filtration rate. The first patient died after four years of follow-up due to the complications of sudden unset pancytopenia, which raises the possibility of associated hemophagocytic syndrome. In the setting of RP or AAV physicians should always be aware of the possibility of sudden or insidious appearance of the other disease. PMID:25516870
Bertram, Anna; Lovric, Svjetlana; Engel, Alissa; Beese, Michaela; Wyss, Kristin; Hertel, Barbara; Park, Joon-Keun; Becker, Jan U; Kegel, Johanna; Haller, Hermann; Haubitz, Marion; Kirsch, Torsten
ANCA-associated vasculitides are characterized by inflammatory destruction of small vessels accompanied by enhanced cleavage of membrane-bound proteins. One of the main proteases responsible for ectodomain shedding is disintegrin and metalloproteinase domain-containing protein 17 (ADAM17). Given its potential role in aggravating vascular dysfunction, we examined the role of ADAM17 in active proteinase-3 (PR3)-positive ANCA-associated vasculitis (AAV). ADAM17 concentration was significantly increased in plasma samples from patients with active PR3-AAV compared with samples from patients in remission or from other controls with renal nonvascular diseases. Comparably, plasma levels of the ADAM17 substrate syndecan-1 were significantly enhanced in active AAV. We also observed that plasma-derived ADAM17 retained its specific proteolytic activity and was partly located on extracellular microparticles. Transcript levels of ADAM17 were increased in blood samples of patients with active AAV, but those of ADAM10 or tissue inhibitor of metalloproteinases 3, which inhibits ADAMs, were not. We also performed a microRNA (miR) screen and identified miR-634 as significantly upregulated in blood samples from patients with active AAV. In vitro, miR-634 mimics induced a proinflammatory phenotype in monocyte-derived macrophages, with enhanced expression and release of ADAM17 and IL-6. These data suggest that ADAM17 has a prominent role in AAV and might account for the vascular complications associated with this disease.
Draibe, Juliana Bordignon; Fulladosa, Xavier; Cruzado, Josep Maria; Torras, Joan; Salama, Alan David
Anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) is characterized by a variable disease course, with up to 50% of patients having one relapse within 5 years and many progressing to end-stage organ damage despite modern treatment strategies. Moreover, complications arising from treatment dominate the causes of mortality and morbidity both early and late during disease, especially in the elderly and those with severe renal involvement, and there is additional uncertainty as to how long treatment should be continued. There is, therefore, an urgent clinical need to identify robust biomarkers to better predict treatment responses, risk of disease relapse and eventual complete clinical and immunological quiescence. To date, no such biomarkers exist, but better understanding of disease pathogenesis and the underlying immune dysfunction has provided some potential candidates linked to the discovery of new antibodies, different leukocyte activation states, the role of the alternative complement pathway and markers of vascular activation. With all promising new biomarkers, there is the need to rapidly replicate and validate early findings using large biobanks of samples that could be brought together by leaders in the field. PMID:27478594
Liu, Huifang; Xiong, Jiachuan; Zhang, Jun; Zhang, Ying; Nie, Ling; Wang, Yiqin; Zhao, Jinghong
Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a life-threatening condition that causes renal failure. Multiple myeloma (MM) is a malignant proliferation of monoclonal plasma cells in the blood that can also cause renal failure. The two diseases have high morbidity and mortality rates in the elderly, with a poor prognosis. A 64-year-old female presented to Xinqiao Hospital (Chonqing, China) with fatigue and a poor appetite that had been apparent for 6 weeks. Laboratory tests revealed a serum creatinine level of 10.31 mg/dl, a cytoplasmic ANCA titer of 1:10, a positive result for myeloperoxidase and a serum globulin level of 3.96 g/dl. A renal biopsy revealed crescent glomerulonephritis, combined with the rapid progression of renal function. Based on these observations (ANCA titer, crescent glomerulonephritis and rapid progression of renal function) a diagnosis of AAV was established. MM was confirmed by serum immunofixation electrophoresis combined with bone marrow aspiration. The present study discusses what is, to the best of our knowledge, the first case of AAV coexisting with MM in order to highlight it as a clinical concern. PMID:27602144
Bertram, Anna; Lovric, Svjetlana; Engel, Alissa; Beese, Michaela; Wyss, Kristin; Hertel, Barbara; Park, Joon-Keun; Becker, Jan U.; Kegel, Johanna; Haller, Hermann; Haubitz, Marion
ANCA-associated vasculitides are characterized by inflammatory destruction of small vessels accompanied by enhanced cleavage of membrane-bound proteins. One of the main proteases responsible for ectodomain shedding is disintegrin and metalloproteinase domain-containing protein 17 (ADAM17). Given its potential role in aggravating vascular dysfunction, we examined the role of ADAM17 in active proteinase-3 (PR3)-positive ANCA-associated vasculitis (AAV). ADAM17 concentration was significantly increased in plasma samples from patients with active PR3-AAV compared with samples from patients in remission or from other controls with renal nonvascular diseases. Comparably, plasma levels of the ADAM17 substrate syndecan-1 were significantly enhanced in active AAV. We also observed that plasma-derived ADAM17 retained its specific proteolytic activity and was partly located on extracellular microparticles. Transcript levels of ADAM17 were increased in blood samples of patients with active AAV, but those of ADAM10 or tissue inhibitor of metalloproteinases 3, which inhibits ADAMs, were not. We also performed a microRNA (miR) screen and identified miR-634 as significantly upregulated in blood samples from patients with active AAV. In vitro, miR-634 mimics induced a proinflammatory phenotype in monocyte-derived macrophages, with enhanced expression and release of ADAM17 and IL-6. These data suggest that ADAM17 has a prominent role in AAV and might account for the vascular complications associated with this disease. PMID:25788529
Murthy, S N; DePace, D M; Shah, R S; Podell, R
Substance P has been implicated as a neuronal mediator of inflammation in various inflammatory conditions. However, the exact role played by substance P in inflammatory bowel diseases or in experimental colonic vasculitis has not been clearly understood. In this study, we examined the effect of close superior mesenteric artery injection of substance P under prevailing inflammatory conditions induced by intravenous human albumin antialbumin immune complex followed by intracolonic perfusion of 2.5% formaldehyde in rats or intracolonic perfusion of 5% alcohol alone. The immune complex- and formaldehyde-treated rats showed severe microvascular changes such as microvascular plugging by red blood cells, endothelial breakage and extravasation of plasma proteins and red blood cells. The bolus injection of 10(-8) M substance P reduced extravasation of Evans blue dye by 50% and the tissue wet to dry ratio by 20% in immune complex- and formaldehyde-perfused rats. Myeloperoxidase activity was not changed. Substance P also significantly inhibited (44%) the extravasation in alcohol-perfused rats. Pretreatment of immune complex- and formaldehyde-treated rats with substance P antagonist reversed the effect of substance P. These findings suggest that the most immediate effect of substance P may be vasodilation and clearing of vascular plugs induced by immune complex and formaldehyde. This effect of substance P differs from its chronic effect, which causes vasodilation and extravasation.
Akbaryan, Mahmood; Darabi, Farideh; Soltani, Zahra
Dermatomyositis is an idiopathic inflammatory myopathy that cause skin and muscle complications. The ethiology is not understood well yet. Released cytokines including interferon and interleukins are suggested to make inflammatory responses in the skin or muscle. Muscle weakness and skin lesions including heliotrope rash, shawl sign and Gottron’s papules are the most common symptoms. A biopsy (muscle or skin) is always the most reliable method for diagnosis. Corticosteroids in association with immunosuppressive agents are used as standard treatment. The patient was a 30 years old woman who got involved with dermatomyositis for 10 years. She has been under therapy with Methotrexate, Prednisolon and Azathioprine until she came to us suffering from progressive skin lesions. Experiments and examinations were normal except the lesions and detected lipoatrophy. Because of immune cells infiltration and observations necrotizing vasculitis was diagnosed. After three month of high dose prednisolon and intravenous cyclophosphamide therapy the lesions vanished remarkable. True and immediate diagnosis gives physicians the chance not only to assess the best treatment but have adequate time to apply the procedure. However shortening the therapy and diminishing morbidity of the disease need more investigations and efforts. PMID:28190982
Wagner, Wolfgang; Fehrmann, Astrid
The objective of this study was to present a previously unknown association of visual loss and Meniere-like vestibuloauditory symptoms in Eales' disease (idiopathic retinal vasculitis) and to give a survey of other conditions affecting both the retina and inner ear. A 32-year-old man diagnosed with Eales' disease presented with recurrent deteriorations of visual acuity and simultaneous recurrent vestibuloauditory symptoms strongly reminiscent of Meniere's disease. Both the recurrent low frequency hearing losses and the losses of visual acuity could be restituted repeatedly by high dose i.v. corticosteroids. A literature review reveals that in a number of other retinopathic diseases associated with Meniere-like symptoms, microvasculopathy is also the pathomechanism. A common pathogenetic cause, e.g., autoimmune-mediated microvasculitis of retinal periphlebitis and vestibulocochlear symptoms, in this case is suggested. The presented case adds new evidence to microvasculopathy being a pathogenetic factor in Meniere's disease. In cases of coincidence of vestibulocochlear symptoms and retinal perivasculitis, a therapeutic attempt with high-dose corticosteroids is advisable.
Akbaryan, Mahmood; Darabi, Farideh; Soltani, Zahra
Dermatomyositis is an idiopathic inflammatory myopathy that cause skin and muscle complications. The ethiology is not understood well yet. Released cytokines including interferon and interleukins are suggested to make inflammatory responses in the skin or muscle. Muscle weakness and skin lesions including heliotrope rash, shawl sign and Gottron's papules are the most common symptoms. A biopsy (muscle or skin) is always the most reliable method for diagnosis. Corticosteroids in association with immunosuppressive agents are used as standard treatment. The patient was a 30 years old woman who got involved with dermatomyositis for 10 years. She has been under therapy with Methotrexate, Prednisolon and Azathioprine until she came to us suffering from progressive skin lesions. Experiments and examinations were normal except the lesions and detected lipoatrophy. Because of immune cells infiltration and observations necrotizing vasculitis was diagnosed. After three month of high dose prednisolon and intravenous cyclophosphamide therapy the lesions vanished remarkable. True and immediate diagnosis gives physicians the chance not only to assess the best treatment but have adequate time to apply the procedure. However shortening the therapy and diminishing morbidity of the disease need more investigations and efforts.
Domiciano, Talita P; Wakita, Daiko; Jones, Heather D; Crother, Timothy R; Verri, Waldiceu A; Arditi, Moshe; Shimada, Kenichi
Interleukin-1β (IL-1β) is a highly inflammatory cytokine that significantly contributes to both acute and chronic inflammatory diseases. The secretion of IL-1β requires a unique protease, caspase-1, which is activated by various protein platforms called inflammasomes. Data suggests a key role for mitochondrial reactive oxygen species for inflammasome activation. Flavonoids constitute a group of naturally occurring polyphenolic molecules with many biological activities, including antioxidant effects. In this study, we investigated the effect of three flavonoids, quercetin (QUC), naringenin, and silymarim on inflammasome activation. We found that QUC inhibits IL-1β secretion by both the NLRP3 and AIM2 inflammasome in a dose dependent manner, but not the NLRC4 inflammasome. QUC inhibition of the inflammasome was still observed in Atg16l1 knockout macrophages, indicating that QUC's effect was autophagy independent. Since QUC inhibited both NLRP3 and AIM2 inflammasomes but not NLRC4, we assessed ASC speck formation. QUC reduced ASC speck formation and ASC oligomerization compared with controls. Additionally, QUC inhibited IL-1β in Cryopyrin-Associated Periodic Syndromes (CAPS) macrophages, where NLRP3 inflammasome is constitutively activated. In conclusion, QUC inhibits both the NLRP3 and AIM2 inflammasome by preventing ASC oligomerization and may be a potential therapeutic candidate for Kawasaki disease vasculitis and other IL-1 mediated inflammatory diseases.
Edgell, Randall C.; Sarhan, Ahmed E.; Soomro, Jazba; Einertson, Collin; Kemp, Joanna; Shirani, Peyman; Malmstrom, Theodore K.; Coppens, Jeroen
Background Central nervous system vasculitis (CNSV) is a rare disorder, the pathophysiology of which is not fully understood. It involves a combination of inflammation and thrombosis. CNSV is most commonly associated with headache, gradual changes in mental status, and focal neurological symptoms. Diagnosis requires the effective use of history, laboratory testing, imaging, and biopsy. Catheter angiography can be a powerful tool in the diagnosis when common and low-frequency angiographic manifestations of CNSV are considered. We review these manifestations and their place in the diagnostic algorithm of CNSV. Summary We reviewed the PubMed database for case series of CNSV that included 5 or more patients. Demographic and angiographic findings were collected. Angiographic findings were dichotomized between common and low-frequency findings. A system for incorporating these findings into clinical decision-making is proposed. Key Message CNSV is a diagnostic challenge due to the absence of a true gold standard test. In the absence of such a test, catheter angiography remains a central piece of the diagnostic puzzle when appropriately employed and interpreted. PMID:27781050
Pepper, Ruth J.; Chanouzas, Dimitrios; Tarzi, Ruth; Little, Mark A.; Casian, Alina; Walsh, Michael; Pusey, Charles D.; Harper, Lorraine
Summary Background and objectives Induction therapy with oral cyclophosphamide (CYP) has been a mainstay of treatment in patients with severe renal failure secondary to ANCA-associated vasculitis (AAV). Recent evidence proposes using pulsed intravenous CYP in less severe disease to minimize adverse events. It is unclear if this can be translated to those with dialysis-dependent renal insufficiency. Design, setting, participants, & methods All AAV patients presenting between 2005 and 2010 requiring dialysis at presentation were retrospectively analyzed. Patients were treated with plasma exchange, corticosteroids, and intravenous CYP. Rate of dialysis independence at 3 and 12 months and adverse effects were assessed and compared with the outcome of the plasmapheresis, prednisolone, and oral CYP arm of the randomized MEPEX (methylprednisolone versus plasma exchange) trial. Results Forty-one patients were included. At 3 months, 3 (7.3%) patients had died on dialysis, 12 (29.3%) remained dialysis dependent, and 26 (63.4%) were dialysis independent (creatinine, 2.5 mg/dl; GFR, 26 ml/min per 1.73 m2). Four patients subsequently reached ESRD at a median time of 83 days. Thirty-seven (90%) patients reached 1 year follow-up, 13 (35%) remained dialysis dependent, and 24 (65%) had independent renal function. Eleven patients (27%) had episodes of leukopenia (white cell count <4×109/L) during CYP therapy and 17 (41%) experienced infectious complications. This compares favorably with the dialysis-dependent cohort treated with plasmapheresis in the MEPEX study in which 51% were alive with independent renal function at 1 year. Conclusions Intravenous CYP used with corticosteroids and plasmapheresis may be an effective alternative to oral CYP in patients with dialysis-dependent AAV. PMID:23160261
Pamuk, Ömer Nuri; Dönmez, Salim; Calayır, Gökçe Büşra; Pamuk, Gülsüm Emel
Epidemiological data about antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is very limited. Until now, there has been no study about the epidemiology of AAV in Turkey. In this study, we evaluated the frequency of AAV in the northeastern part of Turkey. The general clinical features of patients diagnosed with AAV at our center within the last 10 years (2004-2014) were retrospectively recorded down. The incidence rates and the prevalence per 1,000,000 population aged ≥16 years were calculated. In addition, we evaluated the clinical features and survival rates of AAV patients. There were 30 patients with granulomatous polyangiitis (GPA), 15 with microscopic polyangiitis (MPA), and 5 with eosinophilic polyangiitis (EGPA). The overall prevalence of AAV in our region was 69.3/1,000,000 in individuals ≥16 years. Males had a similar prevalence (73.2/1,000,000) with females (65.4/1,000,000). The mean annual incidence rate was 8.1/million for all AAV. The annual incidence of AAV in females was 6.9/million; in males, it was 9.2/million. The annual incidence for GPA was calculated as 4.8/1,000,000, the incidence for MPA was 2.4/1,000,000, and the incidence for CSS was 0.8/1,000,000. Ten-year survival of patients with AAV was 65.3 %. The only independent poor prognostic factor in Cox's multivariate analysis was advanced age at the time of diagnosis (OR 7.5, 95 % CI 10.6-526, p = 0.043). The frequency of all AAV in northwestern Turkey was similar to that in southern Europe; however, it was lower than the frequency in Northern Europe.
Guilpain, Philippe; Jeannin, Pascale; Pignon, Pascale; Blanchard, Simon; Garo, Erwan; Jaillon, Sébastien; Chevailler, Alain; Renier, Gilles; Puéchal, Xavier; Bottazzi, Barbara; Mantovani, Alberto; Delneste, Yves; Augusto, Jean-François
Objectives Pentraxin 3 (PTX3), in common with myeloperoxidase and proteinase 3, is stored in human neutrophil granules and is expressed on apoptotic neutrophil surface. We therefore investigated the presence of anti-PTX3 autoantibodies (aAbs) in the sera of antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) patients. Methods Presence of anti-PTX3 autoantibodies was analysed by a specific enzyme-linked immunosorbent assay in sera from 150 patients with microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA), and eosinophilic granulomatosis with polyangiitis (EGPA), and in sera of 227 healthy subjects (HS), 40 systemic sclerosis (SSc) patients, and 25 giant cell arteritis patients (GCA). Using indirect immunofluorescence on fixed human neutrophils, we also analyzed the staining pattern associated with the presence of anti-PTX3 aAbs. Results Anti-PTX3 aAbs were detected in 56 of 150 (37.3%) of the AAV patients (versus 12 of 227 (5.3%) of HS, p<0.001) and, interestingly, in 7 of 14 MPO and PR3 ANCA negative AAV patients. Moreover, by indirect immunofluorescence on fixed neutrophils, anti-PTX3 aAbs gave rise to a specific cytoplasmic fluorescence pattern distinct from the classical cytoplasmic (c-ANCA), perinuclear (p-ANCA), and atypical (a-ANCA) pattern. Anti-PTX3 aAbs levels were higher in patients with active AAV as compared to patients with inactive disease. Conclusion Our work suggests that PTX3 is as a novel ANCA antigen. Anti-PTX3 aAbs appear thus as a promising novel biomarker in the diagnosis of AAV, including in patients without detectable MPO and PR3 ANCA. PMID:26797217
Cadir, Bilge; Karahan, Nermin; Nasir, Serdar; Aydin, M. Asim; Turkaslan, S. Suha
Fibrosarcoma of the paranasal sinuses is extremely rare pathology and there is limited report in the literature. We report synchronous presentation of maxillary sinus fibrosarcoma and gemistocytic astrocytoma which is, to our knowledge, unique in the literature. Both tumors metastases to other organ rarely and the metastatic spread of gemistocytic astrocytoma to fibrosarcoma or vice versa have also not been reported in the literature yet. This report discusses the clinical course of the disease, outcome of the treatment approach and survival as well as an unusual occurrence of leukocytoclastic vasculitis during the course of radiotherapy in such unusual presentation. PMID:19756200
Nagaeva, T A; Balasheva, I I; Saratikov, A S; Bocharova, M N; Mikhalenko, A N
Twenty-four children aged 3-15 years were examined, 16 of these with cutaneous and articulo-cutaneous hemorrhagic vasculitis (HV) and 8 normal controls. The patients were divided into 2 groups: 10 patients treated by basic therapy and 6 children whose treatment protocols were supplemented by membranoprotector locheine. The children were repeatedly examined 1 month after discharge from hospital. Scanning electron microscopy of peripheral blood erythrocytes provides valuable diagnostic data on erythrocyte membrane morphology and function in children with HV and can serve as a method for monitoring the efficiency of new approaches to therapy of this disease.
Garrido Rasco, Rocío; García Hernández, Francisco José; González León, Rocío; Castillo Palma, María Jesús; Ocaña Medina, Celia; Sánchez Román, Julio
Peritoneal vasculitis is a rare and severe clinical manifestation of systemic lupus erythematosus. We report a patient who presented with ascites due to peritoneal vasculitis and cutaneous, articular, hematological and renal inflammatory activity. Treatment with glucocorticoids and immunosuppressive drugs was ineffective. In view of the resistance to different therapies, 4 weekly infusions of 375mg/m2 of rituximab (RTX) were started, in association with cyclophosphamide pulses during the first and the third weeks. With this treatment strategy, the patient reached a complete response which was achieved in later flares of inflammatory activity (the second and third flares were multisystemic and with ascites again, and the fourth flare with nephritis).
Grande, Andrew; Grewal, Sanjeet; Tackla, Ryan; Ringer, Andrew J.
Background: This case report represents one of the estimated 17,000 aneurysms clipped annually in the United States, often with nickel-containing clips. The authors highlight the development of life-threatening allergic vasculitis in a 33-year-old woman after aneurysm clipping. Case Description: After suffering subarachnoid hemorrhage, the patient had coil embolization at another facility for rupture of a right internal carotid artery (ICA) aneurysm. An incidental finding, an unruptured left posterior communicating artery aneurysm unamenable to coiling, was then successfully clipped via a left pterional craniotomy. Arriving in our emergency department 11 days later, she progressively declined during the next weeks, facing deteriorating clinical status (i.e. seizures) and additional infarctions in the left frontal lobe, midline shift, and new infarctions in the bilateral frontal lobe, right sylvian, right insular regions, and posterior cerebral artery distribution. During decompressive surgery, biopsy findings raised the possibility of lymphocytic vasculitis; consultations with rheumatology, allergy, and immunology specialists identified that our patient had a nickel allergy. After reoperation to replace the nickel-containing clip with one of a titanium alloy, the patient had an uncomplicated postoperative course and was discharged 6 days later to a rehabilitation facility. Conclusions: Nickel-related allergies are more common than appreciated, affecting up to 10% of patients. Fortunately, severe reactions are rare; nevertheless, vascular neurosurgeons should be aware of this potential complication when using cobalt alloy aneurysms clips. The use of titanium alloy clips eliminates this risk. PMID:25071940
Tattoli, Lucia; Krocker, Klaus; Sautter, Julia; Tsokos, Michael
Ambiguous findings during external examination of a deceased in combination with dubious autopsy findings can raise doubts concerning the manner and cause of death. We report the case of a 35-year-old female deceased who had suffered from a borderline personality and depressive disorder with suicidal ideation. At the death scene, the body showed massive facial swelling accompanied by complete reddening of the skin of the face, with patchy skin abrasions on the forehead and neck, and purple bruise-like discolorations distributed symmetrically over both shoulders, elbows, hands, hips, knees, lower legs, and feet, raising the suspicion of underlying massive external blunt force injury. Police investigators strongly suspected sexual homicide. At autopsy, dissection in layers revealed massive subcutaneous hemorrhages as the cause of the reddish skin discolorations. Toxicological analyses showed fatal levels of lamotrigine with additional proof of zopiclone, zolpidem, diphenhydramine, O-desmethylvenlafaxine, pregabalin, tramadol, and modafinil in venous blood. Histologically, both the macroscopically impressive purple skin changes with underlying bleeding into the subcutaneous tissue and the skin abrasions were due to leukocytoclastic vasculitis, a form of acute hypersensitivity vasculitis that was a reaction to the multiple therapeutic drugs that the woman had taken shortly before death. The manner of death was classified as suicide, and sexual homicide was ruled out.
Schneider, David A.; Frevert, Charles W.; Nelson, Danielle D.; Morrison, W. Ivan; Knowles, Donald P.
Respiratory failure and death in East Coast Fever (ECF), a clinical syndrome of African cattle caused by the apicomplexan parasite Theileria parva, has historically been attributed to pulmonary infiltration by infected lymphocytes. However, immunohistochemical staining of tissue from T. parva infected cattle revealed large numbers of CD3- and CD20-negative intralesional mononuclear cells. Due to this finding, we hypothesized that macrophages play an important role in Theileria parva disease pathogenesis. Data presented here demonstrates that terminal ECF in both Holstein and Boran cattle is largely due to multisystemic histiocytic responses and resultant tissue damage. Furthermore, the combination of these histologic changes with the clinical findings, including lymphadenopathy, prolonged pyrexia, multi-lineage leukopenia, and thrombocytopenia is consistent with macrophage activation syndrome. All animals that succumbed to infection exhibited lymphohistiocytic vasculitis of small to medium caliber blood and lymphatic vessels. In pulmonary, lymphoid, splenic and hepatic tissues from Holstein cattle, the majority of intralesional macrophages were positive for CD163, and often expressed large amounts of IL-17. These data define a terminal ECF pathogenesis in which parasite-driven lymphoproliferation leads to secondary systemic macrophage activation syndrome, mononuclear vasculitis, pulmonary edema, respiratory failure and death. The accompanying macrophage phenotype defined by CD163 and IL-17 is presented in the context of this pathogenesis. PMID:27195791
Jaunmuktane, Zane; Sheerin, Una-Marie; Phadke, Rahul; Brandner, Sebastian; Milonas, Ionnis; Dean, Andrew; Bajaj, Nin; McNicholas, Nuala; Costello, Daniel; Cronin, Simon; McGuigan, Chris; Rossor, Martin; Fox, Nick; Murphy, Elaine; Chataway, Jeremy; Houlden, Henry
Background Hereditary diffuse leukoencephalopathy with neuroaxonal spheroids (HDLS) is a hereditary, adult onset leukodystrophy which is characterised by the presence of axonal loss, axonal spheroids and variably present pigmented macrophages on pathological examination. It most frequently presents in adulthood with dementia and personality change. HDLS has recently been found to be caused by mutations in the colony stimulating factor-1 receptor (CSF1R) gene. Methods In this study, we sequenced the CSF1R gene in a cohort of 48 patients from the UK, Greece and Ireland with adult onset leukodystrophy of unknown cause. Results Five pathogenic mutations were found, including three novel mutations. The presentations ranged from suspected central nervous system (CNS) vasculitis to extrapyramidal to cognitive phenotypes. The case histories and imaging are presented here, in addition to neuropathological findings from two cases with novel mutations. Conclusion We estimate that CSF1R mutations account for 10% of idiopathic adult onset leukodystrophies and that genetic testing for CSF1R mutations is essential in adult patients presenting with undefined CNS vasculitis or a leukodystrophy with prominent neuropsychiatric signs or dementia. PMID:25935893
Anti-neutrophil cytoplasmic antibody (ANCA) - associated vasculitis (AAV) is a life-threatening autoimmune disease characterized by an antibody-mediated glomerulonephritis and necrotizing vasculitis. Apart from antibodies, T cells are also involved in disease pathogenesis. This review stresses the hallmarks of T cell-mediated pathology in AAV and highlights the characteristics of lesional and circulating T cells in the immune response in AAV. Circulating effector T-cell populations are expanded and are in a persistent state of activation. Circulating regulatory T-cell subsets are less well characterized but seem to be impaired in function. Lesional effector T cells are present in granulomas, vasculitic lesions, and nephritis. Lesional T cells usually show pro-inflammatory properties and promote granuloma formation. Apart from T cells, dendritic cells are abundantly present at the sites of inflammation and locally orchestrate the immune response. Targeting the above-mentioned T cell-mediated disease mechanisms will potentially provide powerful therapeutic tools for AAV. PMID:20236453
Lerkvaleekul, Butsabong; Treepongkaruna, Suporn; Saisawat, Pawaree; Thanachatchairattana, Pornsri; Angkathunyakul, Napat; Ruangwattanapaisarn, Nichanan; Vilaiyuk, Soamarat
Henoch-Schönlein purpura (HSP) is generally a self-limited vasculitis disease and has a good prognosis. We report a 4-year-old Thai boy who presented with palpable purpura, abdominal colicky pain, seizure, and eventually developed intestinal ischemia and perforation despite adequate treatment, including corticosteroid and intravenous immunoglobulin therapy. Imaging modalities, including ultrasonography and contrast-enhanced computed tomography, could not detect intestinal ischemia prior to perforation. In this patient, we also postulated that vasculitis-induced mucosal ischemia was a cause of the ulcer, leading to intestinal perforation, and high-dose corticosteroid could have been a contributing factor since the histopathology revealed depletion of lymphoid follicles. Intestinal perforation in HSP is rare, but life-threatening. Close monitoring and thorough clinical evaluation are essential to detect bowel ischemia before perforation, particularly in HSP patients who have hematochezia, persistent localized abdominal tenderness and guarding. In highly suspicious cases, exploratory laparotomy may be needed for the definite diagnosis and prevention of further complications. PMID:27468201
Ji, Guiyi; Zeng, Xuemei; Sandford, Andrew J; He, Jian-Qing
Antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) is a pauci-immune necrotizing vasculitis that involves small vessels. Herein, we report an extremely rare case of rifampicin (RFP)-induced AAV. A 42-yearold female was transferred to the West China Hospital due to cough with phlegm for 3 months, fever for 1 month, and fatigue for 2 weeks. The patient was diagnosed with pulmonary tuberculosis (TB) and received anti-TB treatment with isoniazid, RFP, ethambutol, and pyrazinamide (PZA) at her local hospital. After 5 days of anti-TB treatment, her creatinine level rose to 420.2 μmol/L from a normal level prior to anti-TB treatment. Serum proteinase 3 (PR3)-ANCA was positive. After discontinuing the anti-TB drugs and administering protective renal treatment, her renal function improved, whereas PR3-ANCA remained positive. With RFP rechallenge after transfer to our hospital, the patient developed oliguria. Her urine volume increased gradually after RFP was discontinued 3 days later. Therefore, RFPinduced AAV was suspected. Eventually, the patient received prednisone and anti-TB therapy, including isoniazid, ethambutol, PZA, and moxifloxacin. After 2 months, PZA was discontinued. During 6 months of normal, and PR3-ANCA became negative at 4 months. This outcome is characteristic of RFP-induced AAV.
Salvarani, Carlo; Brown, Robert D.; Christianson, Teresa; Miller, Dylan V.; Giannini, Caterina; Huston, John; Hunder, Gene G.
Abstract Primary central nervous system vasculitis (PCNSV) is an uncommon condition in which lesions are limited to vessels of the brain and spinal cord. Because the clinical manifestations are not specific, the diagnosis is often difficult, and permanent disability and death are frequent outcomes. This study is based on a cohort of 163 consecutive patients with PCNSV who were examined at the Mayo Clinic over a 29-year period from 1983 to 2011. The aim of the study was to define the characteristics of these patients, which represents the largest series in adults reported to date. A total of 105 patients were diagnosed by angiographic findings and 58 by biopsy results. The patients diagnosed by biopsy more frequently had at presentation cognitive dysfunction, greater cerebrospinal fluid total protein concentrations, less frequent cerebral infarcts, and more frequent leptomeningeal gadolinium-enhanced lesions on magnetic resonance imaging (MRI), along with less mortality and disability at last follow-up. The patients diagnosed by angiograms more frequently had at presentation hemiparesis or a persistent neurologic deficit or stroke, more frequent infarcts on MRI and an increased mortality. These differences were mainly related to the different size of the vessels involved in the 2 groups. Although most patients responded to therapy with glucocorticoids alone or in conjunction with cyclophosphamide and tended to improve during the follow-up period, an overall increased mortality rate was observed. Relapses occurred in one-quarter of the patients and were less frequent in patients treated with prednisone and cyclophosphamide compared with those treated with prednisone alone. The mortality rate and degree of disability at last follow-up were greater in those with increasing age, cerebral infarctions on MRI, angiographic large vessel involvement, and diagnosis made by angiography alone, but were lower in those with gadolinium-enhanced lesions on MRI and in those with
Sheep-associated malignant catarrhal fever (SA-MCF) caused by ovine herpesvirus-2 (OvHV-2), a '-herpesvirus, is an often fatal disease characterized by lymphoproliferation, vasculitis, and mucosal ulceration in American bison (Bison bison), cattle (Bos taurus), and other clinically susceptible speci...
Mauro, Liberatore; Manuela, Morreale; Valentina, Megna; Sara, Collorone; Chondrogiannis, Sotirios; Maria, Drudi Francesco; Christos, Anagnostou; Liana, Civitelli; Ada, Francia; Maffione, Anna Margherita; Marzola, Maria Cristina; Rubello, Domenico
Background: The diagnosis of vasculitis in the brain remains a quite difficult achievement. To the best of our knowledge, there is no imaging method reported in literature which is capable of reaching to a diagnosis of vasculitis with very high sensitivity. Aim: The aim of this study was to determine whether perfusion brain single photon emission computed tomography (SPECT) can be usefully employed in monitoring the treatment of vasculitis, allowing treating only potentially responder patients and avoiding the side effects on patients who do not respond. Materials and Methods: Twenty patients (two males and 18 females) suffering from systemic lupus erythematosus (SLE; n = 5), Behcet's disease (BD; n = 5), undifferentiated vasculitis (UV; n = 5), and Sjogren's syndrome (SS; n = 5) were included in the study. All patients underwent a wide neurological anamnestic investigation, a complete objective neurological examination and SPECT of the brain with 99mTc-hexamethyl-propylene-aminoxime (HMPAO). The brain SPECT was then repeated after appropriate medical treatment. The neurological and neuropsychiatric follow-up was performed at 6 months after the start of the treatment. Results: Overall, the differences between the scintigraphic results obtained after and before the medical treatment indicated a statistically significant increase of the cerebral perfusion (CP). In 19 out of 200 regions of interest (ROI) studied, the difference between pre- and post treatment percentages had negative sign, indicating a worsening of CP. This latter event has occurred six times (five in the same patients) in the UV, 10 times (eight in the same patients) in the SLE, never in BD, and three times (two in the same patient) in the SS. Conclusion: The reported results seem to indicate the possibility of identifying, by the means of a brain SPECT, responder and nonresponder (unchanged or worsened CP) patients, affected by autoimmune vasculitis, to the therapy. PMID:25973400
Lee, Youngho; Wakita, Daiko; Dagvadorj, Jargalsaikhan; Shimada, Kenichi; Chen, Shuang; Huang, Ganghua; Lehman, Thomas J.A.; Fishbein, Michael C.; Hoffman, Hal M.; Crother, Timothy R.; Arditi, Moshe
Objective Kawasaki disease (KD) is the most common cause of acute vasculitis and acquired cardiac disease among US children. We have previously shown that both TLR2/MyD88 and IL-1β signaling are required for the Lactobacillus casei cell wall extract (LCWE)-induced KD vasculitis mouse model. The objectives of this study were to investigate the cellular origins of IL-1 production, the role of CD11c+ Dendritic Cells (DCs) and macrophages and the relative contribution of hematopoietic and stromal cells for IL-1 responsive cells, as well the MyD88 signaling in LCWE-induced KD mouse model of vasculitis. Approach and Results Using mouse knockout models as well as antibody depletion, we found that both IL-1α and IL-1β were required for LCWE-induced KD. Both DCs and macrophages were necessary and we found that MyD88 signaling was required in both hematopoietic and stromal cells. However, IL-1 response and signaling was critically required in non-endothelial stromal cells, but not hematopoietic cells. Conclusions Our results suggest that IL-1α and IL-1β as well as CD11c+ DCs and macrophages are essential for the development of KD vasculitis and coronary arteritis in this mouse model. Bone marrow chimera experiments suggest that MyD88 signaling is important in both hematopoietic and stromal cells, while IL-1 signaling and response is required only in stromal cells, but not in endothelial cells. Determining the role IL-1α and IL-1β and of specific cell types in the KD vasculitis mouse model may have important implications for the design of more targeted therapies and understanding of the molecular mechanisms of KD immunopathologies. PMID:26515418
Lim, Mie-Jin; Kwon, Seong Ryul; Lee, Seunghee; Park, Won
Polyarteritis nodosa (PAN) related to hepatitis B is an uncommon vasculitis that is sometimes associated with the rapid progression of distal ischemia. A few recent reports have proposed the use of antiviral therapy. However, there is not yet a consensus for the standard treatment of this disease entity and none of these treatments have been focused on fast symptomatic improvement. We describe here a 39-year-old female patient with PAN related to hepatitis B infection who completely recovered from the acutely progressing ischemic manifestations of her distal extremities with the use of alprostadil infusion (prostaglandin E1). The reactivation of her hepatitis B infection after glucocorticoid and cyclophosphamide therapy was successfully managed by the antiviral lamuvudine therapy. Most importantly, the vasodilator together with the conventional therapy may be desirable in the early stages of the disease before irreversible ischemic tissue damage can occur.
Sijia, Li; Shuangxin, Liu; Wei, Shi; Yanhai, Cui
One month previously, a 28-year old male underwent an emergency modified Bentall procedure because of Marfan syndrome with acute aortic dissection Stanford Class A. Computed tomography of the chest did not reveal severe graft stenosis of the anastomosis. To explore the cause of anaemia, renal dysfunction and macroscopic haematuria, the patient was tested for antineutrophil cytoplasmic antibody (ANCA)-associated systemic vasculitis (AASV). Antimyeloperoxidase antibodies (MPO)-ANCA and antiproteinase 3 antibodies (PR3)-ANCA were strongly positive. Corticosteroid therapy was applied, followed by cyclophosphamide and azathioprine. In response to treatment, the MPO-ANCA and PR3-ANCA levels gradually decreased, proteinuria was alleviated and haemoglobin levels returned to normal after 6 months. This is the first report to highlight haemolytic anaemia and AASV with Marfan syndrome after surgery for aortic dissection.
Faurschou, Mikkel; Berden, Annelies; Flossmann, Oliver; Bajema, Ingeborg; Hoglund, Peter; Smith, Rona; Szpirt, Wladimir; Westman, Kerstin; Pusey, Charles D.; Jayne, David R.W.
Background and objectives Treatment with azathioprine within 3 months of remission induction with cyclophosphamide is a common treatment strategy for patients with ANCA-associated vasculitis. This study comprised patients undergoing long-term follow-up who were randomly allocated to azathioprine after 3–6 months or after 12 months of cyclophosphamide treatment. Design, setting, participants, & measurements Patients from 39 European centers between 1995 and 1997 with a new diagnosis of ANCA-associated vasculitis that involved the kidneys or another vital organ were eligible. At the time of diagnosis, participants were randomly allocated to convert to azathioprine after 3–6 months (the azathioprine group) or after 12 months of cyclophosphamide (the cyclophosphamide group). Patients who did not achieve a remission within 6 months were excluded. This study assessed relapses, ESRD, and death during long-term follow-up. Results Patients were allocated to the azathioprine group (n=71) and the cyclophosphamide group (n=73). Of these patients, 63 (43.8%) developed a relapse, 35 (24.3%) developed a renal relapse, 13 (9.0%) developed ESRD, and 21 (14.6%) died. Although there were worse outcomes in the azathioprine group, none were statistically significant. The subdistribution hazard ratio [sHR] for relapse was 1.63 (95% confidence interval [95% CI], 0.99 to 2.71), the composite of relapse or death hazard ratio [HR] was 1.59 (95% CI, 1.00 to 2.54), the ESRD sHR was 1.71 (95% CI, 0.56 to 5.19), and the death HR was 0.75 (95% CI, 0.32 to 1.79). Conclusions It remains uncertain whether converting to azathioprine after 3–6 months of induction cyclophosphamide therapy is as effective as converting after 12 months. Outcomes are still poor for this group of patients and further research is required to determine the optimal timing of maintenance therapy. PMID:24970876
WEIDEBACH, W; VIANA, V S T; LEON, E P; BUENO, C; LEME, A S; ARANTES-COSTA, F M; MARTINS, M A; SALDIVA, P H N; BONFA, E
The aim of the present study was to analyse in rats the ability of C-ANCA-positive IgG fraction in triggering inflammatory response on pulmonary tissue. Wistar rats (n = 18) were injected via the the internal jugular vein with 20 mg of total C-ANCA-positive IgG fraction isolated from serum of three different Wegener's granulomatosis patients obtained before therapy. Similarly, control rats were treated with IgG fraction from two rheumatoid arthritis patients (n = 7), IgG from six normal human sera (n = 15) or saline (n = 18), respectively. Animals were sacrificed after 24h of injection for histological analysis of the lungs. Vasculitis and inflammatory infiltrate were consistently absent in rats injected with rheumatoid arthritis IgG or saline and in 14/15 of normal IgG treated animals. In contrast, marked vasculitis was observed in all 18 animals injected with C-ANCA-positive IgG fraction. The histological features were characterized by the presence of a perivascular pleomorphic cellular sheath, particularly around small vessels, endothelial adherence and diapedesis of polymorphonuclear leucocytes and presence of granuloma-like lesions. A dose–response relationship was observed between protein concentration of C-ANCA IgG sample and the intensity of the inflammatory response in the animals. In addition, IgG fraction with undetectable C-ANCA, obtained from one patient in remission after treatment, was not able to reproduce the pulmonary tissue alterations induced by its paired IgG that was positive for C-ANCA taken before therapy. The experimental model described herein may be useful to characterize more effectively the pathogenic mechanism of C-ANCA in Wegener's disease. PMID:12100022
Luan, Jiangwei; Zhao, Peiwei; Yue, Xin; Yu, Chunhua; Laing, Xiaohui; Zhao, YuLan
IgA vasculitis (IgAV), previously named as Henoch–Schönlein purpura, is the most common systematic vasculitis with unknown etiology. Lack of appropriate study system and/or animal model limits the understanding of its molecular pathogenesis and hinders the identification of targets for rational therapy, especially for its long-term complication, IgAV nephritis (IgAVN). In this study, we applied comparative analysis of serum proteomes to obtain an insight about disease pathogenesis. This study has utilized high sensitivity nanoscale ultra performance liquid chromatography-mass spectrometry (nanoLC-MS/MS) to investigate the alterations in serum proteomic profiles in patients with IgAV (n=6), IgAVN (n=6) and healthy subjects (n=7). The differentially expressed proteins were subjected to functional pathway analysis by PANTHER and DAVID software. We identified 107 differentially expressed proteins among three different groups, and functional analysis suggested that, in addition to earlier reported pathways, such as acute phase response, immune response, complement and blood coagulation pathways, hemostasis and Wnt signaling pathway were probably involved in pathogenesis of IgAV. A few differentially abundant proteins identified, such as C4a, serum amyloid A, angiotensinogen, and kininogen 1, were further validated by ELISA. More importantly, we found that angiotensinogen concentration is correlated with IgAVN and could be used as a potential marker for the progression of IgAV. This is the first report of analyzing the proteomic alterations in IgAV patients and the differentially proteins identified in this study may enhance understanding of the pathology of IgAV and a few of them may be used to monitor disease progression. PMID:26098644
[Two cases of severe cutaneous vasculitis with thrombocytopenia associated with hepatic cirrhosis: autoimmune and infective-inflammatory component with endothelial lesion and restrictive pulmonary pattern in one case].
de Andrade Júnior, D R; Warth, M do P; Morrone, L F; Calich, I; de Andrade, D R
Two clinical cases of female patients with hepatic cirrhosis and autoimmune multisystemic involvement with infectious intercurrent are reported. Case 1 presented infective endocarditis and erysipelas on the left thigh. In the course of the clinical picture a cutaneous vasculitis developed in the same place together with autoimmune thrombocytopenia, leukopenia and pulmonary restrictive picture with inflammatory pattern. There are also elevate immune complexes and complement consumption. Case 2 presented erysipelas on the left thigh cutaneous vasculitis and complement consumption. In Case 1 the infective endocarditis was treated with antibiotic therapy during 4 weeks followed by 1 mg/kg corticoid (Prednisone) with thrombocytopenia and leukopenia reversion. Case 2 presented an improvement with antibiotic only. The relation between chronic liver diseases and systemic autoimmune phenomena is commented, special attention being paid to the cutaneous, hematological and pulmonary affection.
Fujita, Yoshimasa; Fujii, Takao; Shimizu, Hironori; Sato, Tomomi; Nakamura, Takuji; Iwao, Haruka; Nakajima, Akio; Miki, Miyuki; Sakai, Tomoyuki; Kawanami, Takafumi; Tanaka, Masao; Masaki, Yasufumi; Fukushima, Toshihiro; Okazaki, Toshiro; Umehara, Hisanori; Mimori, Tsuneyo
Here, we established CD4(+)αβTh1 clones specific for rat vascular smooth muscle antigen (VSMAg) that induced vasculitis lesions in the lungs of MRL/Mp-Fas(+/+) mice following adoptive transfer. Six different T cell clones, MV1b1 (Vβ1), MV1b4 (Vβ4), MV1b8.3 (Vβ8.3), MV1b61 (Vβ6), MV1b62 (Vβ6), and MV1b63 (Vβ6), were isolated from the MV1 T cell line from the regional lymph nodes of immunized MRL/Mp-Fas(+/+) mice; the three (Vβ6) clones had unique CDR3 amino acid sequences. Following stimulation with VSMAg-pulsed antigen presenting cells, MV1b61 and MV1b62 failed to secrete interferon-γ and tumor necrosis factor-α, although the other four clones secreted high levels of both cytokines. In adoptive transfer experiments, MV1b61 and MV1b62 did not induce organ involvement including pulmonary vasculitis. In contrast, MV1b1, MV1b4, MV1b8.3, and MV1b63 induced perivascular mononuclear cell infiltration in pulmonary small arteries. These clones may provide useful tools for investigating the underlying mechanisms of vasculitis syndromes and for developing therapeutic strategies.
Chen, Bo; Yang, Xiaoqing; Sun, Shihai; Guo, Weina; Li, Xiaosheng; Zhang, Lei; Guo, Zhongliang; Han, Jie; Li, Ning
Introduction Propylthiouracil (PTU) is commonly used to treat hyperthyroidism and can induce antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Although this is a rare side effect, ANCA-associated vasculitis can progress to severe disease if its diagnosis and treatment are delayed, leading to a poor prognosis. Case Presentation A 43-year-old woman with Graves’ disease developed pulmonary vasculitis and diffuse alveolar hemorrhage (DAH) associated with ANCA against myeloperoxidase and proteinase-3 that was confirmed by computed tomography (CT) and bronchoscopy and treated with PTU. The symptoms and signs of alveolar hemorrhage were rapidly resolved after PTU withdrawal and treatment with corticosteroids. After 6 months of follow-up, the patient maintained complete ANCA-negative clinical remission status, as confirmed by normal CT and bronchoscopy findings. To our knowledge, this is the first documented case of bronchoscopic comparison of PTU-induced DAH before and after steroid treatment. Conclusions Patients treated with PTU should be closely monitored and followed up, even if the drug has been used for several years. When patients develop progressive dyspnea with alveolar opacities on chest imaging that cannot be explained otherwise, alveolar hemorrhage should be an important differential diagnosis while investigating the case. Early diagnosis and prompt discontinuation of the PTU treatment are essential for improving patient outcomes. PMID:27257510
Oshima, Yoichi; Hoshino, Junichi; Suwabe, Tatsuya; Hayami, Noriko; Yamanouchi, Masayuki; Sekine, Akinari; Ueno, Toshiharu; Mizuno, Hiroki; Yabuuchi, Junko; Imafuku, Aya; Kawada, Masahiro; Hiramatsu, Rikako; Hasegawa, Eiko; Sawa, Naoki; Takaichi, Kenmei; Hayashi, Nobukazu; Fujii, Takeshi; Ubara, Yoshifumi
A 41-year-old man was referred to our hospital for the evaluation of hypergammaglobulinemia (IgG 2898 mg/dL and IgA 587 mg/dL), inflammation (CRP 6.7 mg/dL and serum interleukin-6 (IL-6) 15.1 ng/L), and anemia (Hb 10.9 mg/dL). Castleman's disease (CD) was diagnosed by axillary lymph node biopsy. Five months later, painful purpura (multiple palpable 5 mm lesions) developed on his legs, gradually spreading to the upper limbs, thighs, and trunk, accompanied by arthralgia of the wrists, ankles, and knees. Skin biopsy revealed leukocytoclastic vasculitis with IgA deposits in dermal vessels. Accordingly, IgA vasculitis (Henoch-Schönlein purpura) was diagnosed. Tocilizumab (an anti-IL-6 receptor antibody) was administered intravenously at 8 mg/kg and treatment was repeated at monthly intervals. His purpura and clinical findings specific to CD improved rapidly. CD is well known to cause various skin lesions. The findings in this case indicate that overproduction of IL-6 contributes to IgA vasculitis (Henoch-Schönlein purpura) as well as to the pathogenesis of CD.
Levamisole-induced vasculitis is a relatively new entity in people who use cocaine. We describe a 44-year-old woman with a history of cocaine use who presented with a complaint of a painful rash of 2-3 month’s duration on her extremities, cheeks, nose, and earlobes. She had not experienced fever, weight loss, alopecia, dry eyes, oral ulcers, photosensitivity, or arthralgia. Examination revealed tender purpuric eruptions with central necrosis on her nose, cheeks, earlobes, and extremities. Laboratory investigations revealed neutropenia, an elevated erythrocyte sedimentation rate (ESR), presence of lupus anticoagulant, low complement component 3 (C3), and presence of perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA). A urine toxicology screen was positive for cocaine, and gas chromatography–mass spectrometry was positive for levamisole. Skin biopsy showed leukocytoclastic vasculitis and small vessel thrombosis. Necrotic lesions of the nose led to its self-amputation. Large bullae on the lower extremities ruptured, leading to wound infection and extensive necrosis that required multiple surgical debridements. When necrosis progressed despite debridement, bilateral above-knee amputation of the legs was performed. Once new lesions stopped appearing, the patient was discharged home. Two months later, she had a recurrence related to cocaine use. To the best of our knowledge, this is only the second reported case of levamisole-induced vasculitis that required above-knee amputation. PMID:23186390
Bakashvili, N; Swaak, A J G; Tervaert, J W Cohen; Dees, A
A 55-year-old man, with no previous history, presented with extreme fatigue and fever and was admitted to hospital. He had progressive renal dysfunction and his serum anti-neutrophil cytoplasmic antibodies (ANCA) were markedly elevated. Renal histology was consistent with ANCA-associated vasculitis. The patient was successfully treated with cyclophosphamide and prednisolone. The classification and management of the ANCA-associated vasculitides are described. The classification was guided by the clinical presentation, serology and results of tissue biopsies. The ANCA inflammation had affected the middle sized and small vessels of especially the upper and lower airways, and the kidneys. The antibodies were directed at proteinase-3 (PR3) or myeloperoxidase (MPO). PR3-ANCA is predominantly found in Wegener's granulomatosis, while MPO-ANCA is related to microscopic polyangiitis. Tissue studies showed granulomatous inflammation of the airways which is typical of Wegener's disease. This type of inflammation is absent in microscopic polyangiitis. The initial treatment schedule consists of prednisone 1 mg/kg daily and oral cyclophosphamide 2 mg/kg daily. In the remission phase, the cyclophosphamide is replaced by azathioprine. It is not yet known how long maintenance treatment should be continued and which parameters have prognostic value.
Tarkowski, A; Jonsson, R; Sanchez, R; Klareskog, L; Koopman, W J
MRL lpr/lpr (MRL/1) mice spontaneously develop a widespread renal vasculitis. The majority of the cells in vasculitic lesions are bright Ly-1, L3T4 and la-positive in contrast to the cells found in lymph nodes and spleens of the old MRL/1 mice. However, despite differences in phenotypical patterns, B and T cells from arteritic lesions do not differ from mononuclear cells (MNC) eluted from MRL/1 lymph nodes with regard to the frequency of IgG secreting cells and the proliferative responses to Concanavalin A (Con A). Co-culture experiments with congeneic MRL+/+ (MRL/n) spleen cells indicate that the poor response to Con A of the MNC eluted from vasculitic lesions is, unlike the case of lymph node MNC, due to suppressive action of vasculitic cells on the indicator cell population. Further support for the activation status of infiltrating MHC in kidney vasculitic lesions, expressed by high in vivo uptake of 3H-thymidine, was obtained by autoradiography performed on frozen sections. The observed differences in phenotypic patterns and functional features between lymph node MNC and infiltrating vasculitic MNC indicate that different immune mechanisms may be responsible for the development of lymphadenopathy and vasculopathy, respectively in MRL/1 mouse. Images Fig. 2 Fig. 3 Fig. 4 PMID:3293853
The purpose of this study was to describe a presumed case of Epstein–Barr virus (EBV)-associated retinal vasculitis in a 42-year-old female with sudden unilateral vision loss and successful treatment with acyclovir therapy. Diagnostic vitreous biopsy of the right eye was performed to test for EBV and other known infectious causes of retinitis and evaluate vitreous cells and serological testing. Vitreous polymerase chain reaction viral DNA testing result was positive for EBV but negative for herpes simplex virus, varicella-zoster virus, and cytomegalovirus. Serologic testing was negative for toxoplasma gondii, syphilis, tuberculosis, and HIV. Histopathologic analysis of vitreous cells revealed atypical lymphocytes. Fluorescein angiography showed disk leakage, occluded retinal artery, peripheral vascular leakage, and ischemic area of the right eye. Intravenous acyclovir, 10 mg/kg/d, was prescribed for 14 days followed by oral acyclovir for 3 months. All lesions have become quiet. EBV may be a cause of retinal disease, and intravenous acyclovir is a successful treatment choice. PMID:27524923
Sanchez, Carlos; Rebolledo, Alejandra; Gahona, Junior; Rojas, Mauricio; Jiménez, Raquel; Bojórquez, Aurora
Nearly 20% of SLE corresponds to the pediatric population, and 75% of them have kidney involvement representing an important etiology of chronic kidney disease. A correlation between SLE and ANCA-associated vasculitis has been identified as an overlapping syndrome. Kidney allograft recurrence is rare in SLE when disease control is achieved and with nowadays immunosuppression treatment. Histologic transformation is unusual, especially when there are negative serologic markers and no immune complex deposition reported in native kidneys. A 17-year-old female with crescentic glomerulonephritis, p-ANCA-positive antibodies with pauci-immune pattern in kidney biopsy develops end-stage renal disease requiring hemodialysis. Deceased donor kidney transplant was performed receiving triple immunosuppression thereafter. Thirteen months later serum creatinine rises without evidence of infection, urinary obstruction, or clinical and serologic disease relapse. Allograft biopsy reports mesangial proliferation and "full-house" immunofluorescence. The role of ANCA in SLE physiopathology is controversial, and its relation with lupus nephritis is also discordant. ANCA could represent an important factor in the heterogeneity of systemic lupus erythematosus and lupus nephritis.
Ma, Jane; Clements, Philip J.
This paper describes one patient with Antineutrophil Cytoplasmic Antibody- (ANCA-) associated vasculitis who initially presented with multiple ischemic fingers and toes. On further evaluation, the patient was also found to have pulmonary-renal involvement and episcleritis. The diagnosis was supported with a positive cANCA (anti-proteinase 3) and a bronchoscopy consistent with diffuse alveolar hemorrhage. Although the patient refused a tissue biopsy, clinical presentation including nasal ulceration, sinus congestion, and epistaxis and anti-proteinase 3 antibody were more consistent with Granulomatosis with Polyangiitis (GPA) rather than Microscopic Polyangiitis (MPA) or Eosinophilic Granulomatosis with Polyangiitis (EGPA) based on the recently presented ACR/EULAR Provisional 2017 Classification Criteria for GPA (Luqmani et al., 2016). The patient responded well to therapy including high dose steroids and cyclophosphamide, with improvement of all organs involved and had no further digital ischemia or gangrene on follow-up. We include a review of the English literature summarizing presentation, management, and outcome of 16 similar cases. PMID:28348913
Jarrot, Pierre-Andre; Chiche, Laurent; Hervier, Baptiste; Daniel, Laurent; Vuiblet, Vincent; Bardin, Nathalie; Bertin, Daniel; Terrier, Benjamin; Amoura, Zahir; Andrés, Emmanuel; Rondeau, Eric; Hamidou, Mohamed; Pennaforte, Jean-Loup; Halfon, Philippe; Daugas, Eric; Dussol, Bertrand; Puéchal, Xavier; Kaplanski, Gilles; Jourde-Chiche, Noemie
Abstract The aim of the study was to report the clinical, biological, and pathological characteristics of patients with glomerulonephritis (GN) secondary to systemic lupus erythematosus (SLE)/antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) overlap syndrome. A nationwide survey was conducted to identify cases of SLE/AAV overlap syndrome. Data were collected from SLE and AAV French research groups. Inclusion criteria were diagnosis of both SLE and AAV according to international classification criteria and biopsy-proven GN between 1995 and 2014. Additional cases were identified through a systematic literature review. A cohort of consecutive biopsy-proven GN was used to study the prevalence of overlapping antibodies and/or overlap syndrome. The national survey identified 8 cases of SLE/AAV overlap syndrome. All patients were female; median age was 40 years. AAV occurred before SLE (n = 3), after (n = 3), or concomitantly (n = 2). Six patients had rapidly progressive GN and 3/8 had alveolar hemorrhage. All patients had antinuclear antibodies (ANA); 7/8 had p-ANCA antimyeloperoxidase (MPO) antibodies. Renal biopsies showed lupus nephritis (LN) or pauci-immune GN. Remission was obtained in 4/8 patients. A literature review identified 31 additional cases with a similarly severe presentation. In the GN cohort, ANCA positivity was found in 30% of LN, ANA positivity in 52% of pauci-immune GN, with no correlation with pathological findings. The estimated prevalence for SLE/AAV overlap syndrome was 2/101 (2%). In patients with GN, SLE/AAV overlap syndrome may occur but with a low prevalence. Most patients have an aggressive renal presentation, with usually both ANA and anti-MPO antibodies. Further studies are needed to assess shared pathogenesis and therapeutic options. PMID:27258503
Ernst, Diana; Bearlecken, Niklas; Ernst Schmidt, Reinhold; Witte, Torsten
Background: Whilst large vessel vasculitis (LVV) predominantly occurs in isolation, associations with other infectious and non-infectious diseases have been reported. Limited data describing associations with various autoimmune diseases (AI), including spondyloarthritis exists. The aim of this study was to characterize the association of LVV and spondyloarthritis or its associated diseases (SpAD). Methods: A single centre, retrospective study of patients ≥50yrs with first presentation LVV between 01.06.2008-01.06.2015 was performed. Patients were categorized according to SpA or associated disease, other AI or idiopathic LVV (iLVV). Clinical, laboratory and imaging findings were compared. Kaplan-Meyer survival analysis, with relapse taken as the primary end-point, was performed. Results: LVV was confirmed in 62 pts, of who 16/62 (26%) had SpA or associated disease. In these patients, LVV presented earlier (59.2 SpAD vs. 68.1 AI and 70.3yrs iLVV; p=0.01) and occurred predominantly in spring compared to autumn and winter in non-SpA patients, was associated with more centralised pattern of distribution (p=0.05) and was more likely to exhibit a refractory course (p=0.05). Overall relapse rates were similar across groups. Smoking-status influenced age of onset in all groups, being associated with earlier onset. Conclusion: A clear association between LVV and SpAD exists. LVV associated with SpAD has a particular phenotype characterised by earlier onset, thorax-limited disease and increased risk of a refractory course. Given on-going LVV treatment trials further genetic and pathophysiological characterization appears warranted, to evaluate potential variation in treatment response and optimize future care. PMID:28077977
Kawashima, Nozomu; Kawada, Jun-ichi; Nishikado, Yuichi; Kitase, Yuma; Ito, Sanae; Muramatsu, Hideki; Sato, Yoshiaki; Kato, Taichi; Natsume, Jun; Kojima, Seiji
ABSTRACT Rare progression to renal failure imposes a burden on children with IgA vasculitis (Henoch–Schönlein purpura, HSP). An abnormal urinalysis on day 7 (7d-UA) may be a surrogate marker for persistent nephritis, but this has not been established. We retrospectively analyzed the risk factors for persistent nephritis in a cohort of 138 children. Of 35 children with abnormal 7d-UA, 24 (69%) had an abnormal urinalysis 6 months after the diagnosis of HSP, which was significantly more than 6 of 103 children (6%) with normal 7d-UA (P < 0.0001). The negative predictive values for normal urinalysis and negative proteinuria 6 months after diagnosis were 0.94 (95% confidence interval [CI], 0.90–0.97) and 0.98 (95% CI, 0.95–0.99), respectively. When children with abnormal urinalysis 6 months after diagnosis were compared with those without, the following factors were significantly associated: age at diagnosis, abnormal urinalysis at diagnosis, abnormal 7d-UA, complement C3, steroid treatment, and presence of abdominal pain. However, multivariate analysis revealed that abnormal 7d-UA was the only significant risk factor for abnormal urinalysis 6 months after diagnosis (odds ratio 54.3, 95% CI 15.3–275, P = 1.89 × 10−6). Abnormal 7d-UA may be an independent risk factor for persistent nephritis, but this should be confirmed in a prospective study. PMID:28008191
Other Specified Inflammatory Disorders of Skin or Subcutaneous Tissue; Pyoderma Gangrenosum; Erosive Pustular Dermatosis of the Scalp; Sweet's Syndrome; Behcet's Disease; Bowel-associated Dermatosis-arthritis Syndrome; Pustular Psoriasis; Acute Generalized Exanthematous Pustulosis; Keratoderma Blenorrhagicum; Sneddon-Wilkinson Disease; IgA Pemphigus; Amicrobial Pustulosis of the Folds; Infantile Acropustulosis; Transient Neonatal Pustulosis; Neutrophilic Eccrine Hidradenitis; Rheumatoid Neutrophilic Dermatitis; Neutrophilic Urticaria; Still's Disease; Erythema Marginatum; Unclassified Periodic Fever Syndromes / Autoinflammatory Syndromes; Dermatitis Herpetiformis; Linear IgA Bullous Dermatosis; Bullous Systemic Lupus Erythematosus; Inflammatory Epidermolysis Bullosa Aquisita; Neutrophilic Dermatosis of the Dorsal Hands (Pustular Vasculitis); Small Vessel Vasculitis Including Urticarial Vasculitis; Erythema Elevatum Diutinum; Medium Vessel Vasculitis
Schwartz, J; Gonzalez, J; Rosenberg, R; Fujihara, K; Cottrill, C M; Klainer, A S; Bisaccia, E
The clinical spectrum of retroviruses is expanding rapidly. Human T-cell lymphotropic virus type I (HTLV-I) was the first retrovirus to be described, and its role had been established in adult T-cell leukemia/lymphoma and tropical spastic paraparesis. We report the case of a 35-year-old woman with HTLV-I and the unusual combination of cutaneous T-cell lymphoma, tropical spastic paraparesis, cerebral vasculitis, and protein S deficiency. We discuss the relationship of all her diseases to HTLV-I.
Black, A K
Typical urticarial lesions are transient cutaneous swellings of sudden onset, often itchy, persisting for less than 24 hours and resolving to leave normal appearing skin. Angioedema lesions are similar subcutaneous lesions. Atypical urticarias persist for longer than 24 hours, may be painful and bruised in appearance and accompanied with severe systemic symptoms. Conditions where prolonged weals are present include delayed pressure urticaria and urticarial vasculitis. These conditions do not respond well to antihistamine therapy. In delayed pressure urticaria, weals appear after a delay of hours at sites of sustained pressure on the skin and occur in association with ordinary chronic 'idiopathic' urticaria. Weals of urticarial vasculitis show histological features of venulitis, and can be accompanied by arthralgia and abdominal pain. Rarely, the condition is due to infective or autoimmune disease. Urticarial diseases, sometimes with features of urticarial vasculitis, and with associated systemic features include Schnitzler's Syndrome, Still's disease and Muckle-Wells syndrome. The latter syndrome is linked with chromosome 1q44, as is autosomal dominant cold urticaria, an unusual physical urticaria. Persistent cholinergic erythema, a variant of cholinergic urticaria, has been mistaken for a drug eruption or cutaneous mastocytosis. Rarely, food and exercise induced urticaria and anaphylaxis occur when exercise follows a specific food or any meal within a few hours. The early stages of inflammatory disease may be mistaken for urticaria and angioedema, but lesions usually persist for longer than 48 hours and are accompanied by epidermal changes.
O'Brien, Eóin C; Abdulahad, Wayel H; Rutgers, Abraham; Huitema, Minke G; O'Reilly, Vincent P; Coughlan, Alice M; Harrington, Mark; Heeringa, Peter; Little, Mark A; Hickey, Fionnuala B
ANCA vasculitis encompasses several autoimmune conditions characterised by destruction of small vessels, inflammation of the respiratory tract and glomerulonephritis. Most patients harbour autoantibodies to myeloperoxidase (MPO) or proteinase 3 (PR3). Clinical and experimental data suggest that pathogenesis is driven by ANCA-mediated activation of neutrophils and monocytes. We investigated a potential role for distinct monocyte subsets. We found that the relative proportion of intermediate monocytes is increased in patients versus control individuals, and both MPO and PR3 are preferentially expressed on these cells. We demonstrate that MPO and PR3 are expressed independently of each other on monocytes and that PR3 is not associated with CD177. MPO expression correlates with that of Fc receptor CD16 on intermediate monocytes. Monocyte subsets respond differently to antibodies directed against MPO and PR3, with anti-MPO but not anti-PR3 leading to increased IL-1β, IL-6 and IL-8 production. In concordance with the observed higher surface expression of MPO on intermediate monocytes, this subset produces the highest quantity of IL-1β in response to anti-MPO stimulation. These data suggest that monocytes, specifically, the intermediate subset, may play a role in ANCA vasculitis, and also indicate that substantial differences exist between the effect of anti-MPO and anti-PR3 antibodies on these cells.
Nelson, Danielle D; Taus, Naomi S; Schneider, David A; Cunha, Cristina W; Davis, William C; Brown, Wendy C; Li, Hong; O'Toole, Donal; Oaks, J Lindsay
American bison (Bison bison) are particularly susceptible to developing fatal sheep-associated malignant catarrhal fever (SA-MCF) caused by ovine herpesvirus-2 (OvHV-2), a γ-herpesvirus in the Macavirus genus. This generally fatal disease is characterized by lymphoproliferation, vasculitis, and mucosal ulceration in American bison, domestic cattle (Bos taurus), and other clinically susceptible species which are considered non-adapted, dead-end hosts. The pathogenesis and cellular tropism of OvHV-2 infection have not been fully defined. An earlier study detected OvHV-2 open reading frame 25 (ORF25) transcripts encoding the viral major capsid protein in tissues of bison with SA-MCF, and levels of viral transcript expression positively correlated with lesion severity. To further define the cellular tropism and replication of OvHV-2 infection in vascular lesions of bison, immunofluorescence studies were performed to identify cell type(s) expressing ORF25 protein within tissues. Cytoplasmic and not nuclear ORF25 protein was demonstrated in predominantly perivascular fibroblasts in six bison with experimentally-induced SA-MCF, and there was no evidence of immunoreactivity in vascular endothelium, smooth muscle, or infiltrating leukocytes. The cytoplasmic distribution of viral major capsid protein suggests that viral replication in perivascular fibroblasts may be abortive in this dead-end host. These findings provide a novel foundation for defining the pathogenesis of vasculitis in non-adapted hosts with SA-MCF.
Kato, Eishi; Isobe, Yuka; Mizuno, Akiko; Wakayama, Hisashi; Ogasawara, Tomohiko; Suzuki, Masayuki; Shimizu, Shigeki; Niimi, Takashi; Sato, Shigeki; Ueda, Ryuzo
A 36-year-old man was admitted to our hospital in 1994 because of fever, and abdominal CT showed multiple low-density areas in the liver. Although granulomas were found in a liver biopsy specimen, a definitive diagnosis could not be established. With complaints of oral and genital ulcerations and erythema nodosum, Behçet disease was diagnosed in 1995 and he was treated with colchicine and cyclosporin. In May 1997 he had fever, leg edema, and proteinuria, and a renal biopsy revealed secondary amyloidosis. Cavitary lesions were found on a chest X-ray for the first time, but these later disappeared spontaneously. In October 2002, nodular shadows, cavitary lesions, and a mediastinal tumor appeared on a chest X-ray film. The nodular shadows in the lung fields had transformed into cavity lesions, resulting in the disappearance of the shadows. Specimens obtained from an open lung biopsy showed necrotizing granulomas and destructive vasculitis of the lung, and aneurysm of the brachiocephalic trunk caused by destructive vasculitis. Because multiple nodular shadows with cavitary lesions in Behçet disease, as in this case, have never been reported, we think this is a rare case.
Calle Toro, Juan S; Davalos, Diana M; Charry, Jose D; Arrunategi, Ana M; Tobon, Gabriel
Approximately 80% of patients with hepatitis C virus infection develop chronic liver disease as cirrhosis, and 40% develop autoimmune complications as mixed cryoglobulinemia (MC). Gastrointestinal involvement in MC is rare, and even more so is hepatic involvement. We report a case of an 87-year-old woman with a 10-year history of blood transfusion-acquired hepatitis C virus infection, without treatment. She consulted the emergency department for diffuse abdominal pain, associated with vomiting. After 2 weeks of hospitalization in the intensive care unit, a diagnosis of MC was made; cirrhosis and secondary mesenteric and hepatic vasculitis were confirmed by a diagnostic laparoscopy. Unfortunately the condition of the patient worsened with sepsis and resulted in death in the fourth week from admission. This case highlights the importance of having in mind gastrointestinal tract vasculitis as a medical cause of abdominal pain in patients with chronic hepatitis C virus infection and using data laboratory tests, images, and histopathologic studies to aid with the diagnosis.
Ma, Tian-Tian; Zhang, Lu-Xia; Chen, Min; Zhao, Ming-Hui
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of life-threatening disorders, and frequently affects the kidneys. This study investigated whether the circulating neutrophil extracellular traps (NETs) levels were associated with disease activity of AAV. We collected serum samples from 34 patients with AAV in active stage and 62 patients with AAV in remission. Cell free DNA in serum was quantified using the Quant-iT PicoGreen assay. NETs associated MPO-DNA complexes, citrullinated-histone H3-DNA (cit-H3-DNA) complexes and the concentration of deoxyribonuclease I (DNase I) were quantified using ELISA. The activity of DNase I was quantified using radial enzyme-diffusion method. Associations between circulating levels of NETs with clinico-pathological parameters were analyzed. Serum levels of NETs in active AAV patients were significantly higher than those in healthy controls, and the level of cell free DNA correlated with C-reactive protein (CRP). However, no correlation was found between MPO-DNA complexes or cit-H3-DNA complexes level and CRP. Also there was no significant correlation between NETs level and initial serum creatinine, estimated glomerular filtration rate (eGFR), crescents formation or Birmingham Vasculitis Activity Score (BVAS). Furthermore, there was no significant difference of serum levels of cell free DNA or MPO-DNA complexes between active stage and remission of AAV. In conclusion, circulating levels of NETs cannot be used as a biomarker to assess disease activity in AAV patients. PMID:26840412
Sheep-associated malignant catarrhal fever (SA-MCF) caused by ovine herpesvirus-2 (OvHV-2) is a fatal disease associated with lymphoproliferation, lymphocytic vasculitis, and mucosal ulceration in clinically susceptible species. SA-MCF is an important threat to American bison (Bison bison) due to th...
Pullerits, R; Ljevak, M; Vikgren, J; Bokarewa, M
The aim of the study was to evaluate long-term clinical and immunological effects of anti-B cell treatment in patients with antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis refractory to conventional immunosuppressive treatment. Rituximab (RTX) was added to the ongoing immunosuppressive treatment in 29 patients with refractory ANCA-associated vasculitis. The disease activity was measured using Birmingham Vasculitis Activity Score/Wegener's granulomatosis (BVAS/WG score), and clinical laboratory variables were recorded. The median BVAS/WG score before treatment was 6 (IQR 3-8), and 28 patients (97%) had disease flare classified either severe (62%) or limited (34%). Six of 29 patients (21%) achieved a complete remission, and 12 (41%) had a treatment response with ≥50% decrease in BVAS/WG score at 6 months. Fourteen patients (64%) with kidney involvement achieved remission, and in seven patients (50%), no flare was seen during the follow-up period. Three patients had renal flare and were successfully re-treated with RTX. Seventeen patients had disease symptoms from airways and eyes at RTX initiation, whereas only 29% displayed ≥50% treatment response. Limited clinical improvement was seen in patients with endobronchial lesions and trachea-subglottic granulomatous disease. RTX is a potent therapeutic option for ANCA-associated vasculitis refractory to conventional treatment. Best response may be expected in patients with vasculitic manifestations.
... Systematic Evidence Reviews & Clinical Practice Guidelines Resources Continuing Education Researchers Funding Training & Career Development Division of Intramural Research Research Resources Research Meeting Summaries Technology Transfer Clinical Trials What Are Clinical Trials? Children & ...
... kidneys. EKG (Electrocardiogram) An EKG is a simple, painless test that records the heart's electrical activity. You ... is affecting your heart. Echocardiography Echocardiography is a painless test that uses sound waves to create a ...
Takayasu arteritis is a chronic granulomatous disease of the aorta and its major branches that usually affects women during the second and third decades of life, but it has been reported in young children. This review details the clinical, pathological and radiological features, differential diagnoses and management of the condition, focusing chiefly on the disease in children. The recent definition of Takayasu arteritis is discussed. The condition should be considered in patients with unexplained arterial hypertension or unexplained inflammatory syndromes without signs of localization. Since the disease may be life-threatening and progressive, early recognition is necessary to initiate appropriate therapy. Patients with persistent ischaemic symptoms including hypertension might benefit from revascularization procedures. PMID:19844748
McCormick, J N; Wojtacha, D; Edmond, E
A patient with rheumatoid arthritis, vasculitis, peripheral neuropathy, cutaneous ulceration, and digital gangrene was studied. Circulating immune complexes were detected by C1q binding although serum complement levels were within the normal range. Immunofluorescent staining of buffy coat cells with specific antisera showed the presence of IgG and IgM in phagocytosed inclusions but complement C3 was not detected. A monoclonal antibody specific for cytomegalovirus detected antigens in phagocytosed inclusions on one occasion. These results may suggest that cytomegalovirus antigens are a hitherto unidentified component of serum complexes in patients with rheumatoid arthritis and may contribute to the pathogenesis of the vasculitic complications of rheumatoid arthritis by participating in immune complex formation. Images PMID:1316744
Radford, D J; Lord, J M; Savage, C O S
The ability of antineutrophil cytoplasm autoantibodies (ANCA) from patients with systemic vasculitis to stimulate protein kinase C (PKC) and tyrosine kinases was examined in human neutrophils. Using the superoxide dismutase-inhibitable reduction of ferricytochrome C, the kinetics of ANCA-induced superoxide (O2−) production were characterized and subsequently manipulated by specific inhibitors of PKC and tyrosine kinases. With this approach, ANCA IgG, but not normal IgG or ANCA F(ab′)2 fragments caused a time and dose dependent release of O2− from TNF-α primed neutrophils. The kinetics of ANCA-induced O2− production showed an initial 10–15 min lag phase compared to the N-formyl-l-methionyl-l-leucyl-l-phenylalanine response, suggesting differences in the signalling pathways recruited by these two stimuli. Inhibitor studies revealed that ANCA-activation involved members of both the Ca2+-dependent and -independent PKC isoforms and also tyrosine kinases. ANCA IgG resulted in the translocation of the βII isoform of PKC at a time corresponding to the end of the lag phase of O2− production, suggesting that PKC activity may be instrumental in processes regulating the activity of the NADPH oxidase in response to ANCA. Tyrosine phosphorylation of numerous proteins also peaked 10–15 min after stimulation with ANCA but not normal IgG. These data suggest that PKC and tyrosine kinases regulate O2− production from neutrophils stimulated with autoantibodies from patients with systemic vasculitis. PMID:10540175
Guest, Ian; Sell, Stewart
We systematically examined by immune-histology the lungs of some widely used mouse models of asthma. These models include sensitization by multiple intraperitoneal injections of soluble ovalbumin (OVA) or of OVA with alum, followed by three intranasal or aerosol challenges 3 days apart. Within 24 hours after a single challenge there is fibrinoid necrosis of arterial walls with deposition of immunoglobulin and OVA and infiltration of eosinophilic polymorphonuclear cells that lasts for about 3 days followed by peribronchial B-cell infiltration and slight reversible goblet cell hypertrophy. After 2 challenges, severe eosinophilic vasculitis is present at 6 hours, increases by 72 hours and then declines; B-cell proliferation and significant goblet cell hypertrophy and hyperplasia (GCHTH) and bronchial smooth muscle hypertrophy recur more prominently. After 3 challenges, there is significantly increased induced bronchus associated lymphoid tissue (iBALT) formation, GCHTH and smooth muscle hypertrophy. Elevated levels of Th2 cytokines: IL-4, IL-5 and IL-13, are present in bronchial lavage fluids. Sensitized mice have precipitating antibody and positive Arthus skin reactions but also develop significant levels IgE antibody to OVA but only 1 week after challenge. We conclude that the asthma like lung lesions induced in these models is preceded by immune complex mediated eosinophilic vasculitis and iBALT formation. There are elevations of Th2 cytokines that most likely produce bronchial lesions that resemble human asthma. However, it is unlikely that mast cell activated atopic mechanisms are responsible as we found only a few presumed mast cells by toluidine blue and metachromatic staining limited to the most proximal part of the main stem bronchus, and none in the remaining main stem bronchus or in the lung periphery. PMID:26006019
Negi, Vir Singh; Devaraju, Panneer; Misra, Durga Prasanna; Jain, Vikramraj K; Usdadiya, Jignesh Babulal; Antony, Paul T; Gulati, Reena
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with multiple etiological factors. Mannose-binding lectin (MBL) plays a key role in innate immunity by activating antibody-independent lectin complement pathway, opsonisation, phagocytosis, and immune complex (IC) clearance. Genetic polymorphisms in the promoter and coding regions of MBL gene affect the circulatory levels and biological activity of MBL. Defects in MBL can lead to defective opsonisation and, hence, hamper clearance of apoptotic debris, the persistence of which can drive autoantibody formation in lupus. The exon1 variants at codon 52, 54, and 57 have been reported to augment the risk of SLE in different ethnic populations. Three hundred South Indian Tamil patients with SLE and 460 age-, sex-, and ethnicity-matched controls were genotyped for three polymorphisms at codon 52, 54, and 57 in exon1 of MBL gene by Taqman real-time PCR. The three polymorphisms in exon1 of MBL were observed not to confer risk of developing SLE. However, MBL codon 54 rs1800450 polymorphism was associated with the development of medium vessel vasculitis and gangrene (OR-2.29, CI 95% 1.08-4.83, p = 0.02), whereas, the ancestral allele G conferred protection (OR-0.44, CI 95% 0.21-0.93, p = 0.02). Genetic variants in the exon1 of MBL gene per se are not risk factors for SLE in South Indian Tamils. However, the association of codon 54 (rs1800450) with medium vessel vasculitis suggests that it may be a genetic modifier of clinical phenotype in SLE.
Systemic urticaria are defined as urticaria, most often chronic, associated with systemic diseases. At present time, urticarial vasculitis and neutrophilic urticarial dermatosis associated to autoinflammatory syndromes are not considered to be subtypes of chronic spontaneous urticaria due to their distinctly clinical and histological characteristics as well different pathomechanisms. Sometimes, chronic urticaria is associated to thyroid autoimmunity. However, the majority of cases of chronic spontaneous urticaria have no discernible cause and further investigations are not necessary, as already suggested by some authors and French consensus conference more than 10 years ago.
Sayegh, Johnny; Poli, Caroline; Chevailler, Alain; Subra, Jean-François; Beloncle, François; Deguigne, Pierre Antoine; Beauvillain, Céline; Augusto, Jean-François
A prompt immunosuppressive treatment initiation is crucial in ANCA-associated vasculitis (AAV) to minimize organ injury. The aim of the present work was to analyze the accuracy of emergency ANCA screening to identify rapidly patients with AAV. In our Institution, emergency ANCA screening is based on a telephone call between a Clinician and a Biologist. Indirect immunofluorescence (IIF) for ANCA detection was performed using a commercial kit (Euroimmun(®) Granulocyte Mosaic 12). Positive serums for c- or p-ANCA at IIF are subsequently screened for antigenic specificity (MPO or PR3) by an immunodot technique (immunodot, D-Tek(®).) Positive samples with atypical c- or p-ANCA pattern at IIF are subsequently screened for antigenic specificity by ELISA. Data were retrieved from patients' medical records and confronted to emergency ANCA screening results. Between 2005 and 2012, 114 patients were screened. IIF was positive in 27.2% of patients, but c-/p-ANCA anti-MPO/-PR3 was detected in 13.2% of patients. The sensibility and specificity of IIF combined with immunodot for newly diagnosed AAV were 83.3 and 100%, respectively. Ten patients were newly diagnosed with AAV. In these patients, a specific AAV treatment was initiated less than 24 h following ANCA screening. Emergency ANCA screening based on a clinical gating policy was relevant to identify patients with AAV diagnosis, and was associated with a rapid treatment initiation.
Alexander, E L; Moyer, C; Travlos, G S; Roths, J B; Murphy, E D
We have recently described 2 histopathologic types of inflammatory vascular disease (IVD) in patients with Sjögren's syndrome (SS): neutrophilic IVD (NIVD) and mononuclear IVD (MIVD). Autoimmune MRL/Mp mice, which have many features of SS, spontaneously develop IVD which is histopathologically indistinguishable from that observed in human SS patients. Both MRL/Mp-+/+ and MRL/Mp-lpr/lpr mice develop MIVD which evolves into NIVD and results in decreased survival; the transition to NIVD is accelerated by the lpr gene. The presence of the lpr gene on other genetic backgrounds does not result in a similar acceleration of IVD and associated decreased survival. Thus, the spontaneous autosomal recessive mutation lpr appears to modulate the development of IVD in a strain of mice with an underlying propensity for vasculitis. Based on our observations on IVD in SS patients and MRL/Mp mice, we propose a new model which may enhance our understanding of the immunopathogenesis of IVD in connective tissue disease.
Chen, Yinghua; Yang, Liu; Li, Kang; Liu, Zhengzhao; Gong, Dehua; Zhang, Haitao; Liu, Zhihong; Hu, Weixin
Our aim was to investigate the clinical efficacy of double filtration plasmapheresis (DFPP) in the treatment of antineutrophil cytoplasmic autoantibody-(ANCA) associated vasculitis (AAV) with severe renal involvement. Fifteen AAV patients who had severe renal failure (median SCr 5.6(IQR 5.2-9.0) mg/dL) and needed initial renal replacement therapy (RRT) were treated with DFPP and immunosuppressive therapy. Two plasma volumes were processed during each DFPP session. The changes of serum ANCA and renal function were investigated. After the DFPP treatment for three to five sessions, serum MPO-ANCA level decreased from 250.0 ± 86.9 RU/mL to 70.5 ± 64.7RU/mL (P = 0.00), with a median reduction rate of 67.6%. Eleven patients (73.3%) no longer needed from RRT 3 months after DFPP treatment, while another four patients remained on dialysis. During the follow up for median 10 (IQR 6-24) months, SCr level decreased to normal in one patient, one patient progressed into ESRD. The 1 year renal survival rate was 62.9%. Five (33.3%) patients were complicated with pulmonary infection. DFPP combined with immunosuppressive therapy could increase the renal recovery rate through rapidly decreasing serum ANCA levels for AAV patients with severe renal failure, but its clinical efficacy and impact on long-term renal survival require further studies.
Yamashita, Kyoko; Haga, Hironori; Kobashi, Yoichiro; Miyagawa-Hayashino, Aya; Yoshizawa, Akihiko; Manabe, Toshiaki
There have been a few reports on lung diseases associated with an increased number of infiltrating IgG4-positive plasma cells or lung involvement of IgG4-related sclerosing disease, although their characteristic histologic features have not been well described. Herein, we present 3 cases of interstitial lung disease with common histology and abundant IgG4-positive cell infiltration. Patient 1, a 65-year-old man, was incidentally noted to have a nodular lesion in the left hilar region. In patient 2, a 78-year-old man with dyspnea on effort, computed tomography revealed multifocal consolidation adjacent to the pleura in both lower lobes. Patient 3, a 74-year-old man, underwent lung biopsy for right-sided pleural effusion of unknown etiology. The histologic findings of the 3 individuals were characterized by expansion of the interstitium by dense lymphoplasmacytic infiltrate with prominent vascular involvement, which was indistinguishable from grade 1 lesion of lymphomatoid granulomatosis (LYG-G1). In situ hybridization for Epstein-Barr virus-encoded small RNA (EBER) revealed few or no EBER-positive lymphocytes. Vascular involvement showed subendothelial lymphoplasmacytic infiltrate, including numerous IgG4-positive plasma cells. The percentages of IgG4-positive to IgG-positive plasma cells were 85%, 47%, 46%, respectively. Similar vascular lesions have been described in previous reports of lung complications in IgG4-related sclerosing diseases. Some of these lesions were diagnosed as LYG-G1 without EBER-positive cells. In conclusion, LYG-G1-like lesion characterized by lymphoplasmacytic vasculitis might be a characteristic feature of IgG4-related lung disease.
Aybar, L T; McGregor, J G; Hogan, S L; Hu, Y; Mendoza, C E; Brant, E J; Poulton, C J; Henderson, C D; Falk, R J; Bunch, D O
Pathogenesis of anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis is B cell-dependent, although how particular B cell subsets modulate immunopathogenesis remains unknown. Although their phenotype remains controversial, regulatory B cells (Bregs ), play a role in immunological tolerance via interleukin (IL)-10. Putative CD19(+) CD24(hi) CD38(hi) and CD19(+) CD24(hi) CD27(+) Bregs were evaluated in addition to their CD5(+) subsets in 69 patients with ANCA-associated vasculitis (AAV). B cell IL-10 was verified by flow cytometry following culture with CD40 ligand and cytosine-phosphate-guanosine (CpG) DNA. Patients with active disease had decreased levels of CD5(+) CD24(hi) CD38(hi) B cells and IL-10(+) B cells compared to patients in remission and healthy controls (HCs). As IL-10(+) and CD5(+) CD24(hi) CD38(hi) B cells normalized in remission within an individual, ANCA titres decreased. The CD5(+) subset of CD24(hi) CD38(hi) B cells decreases in active disease and rebounds during remission similarly to IL-10-producing B cells. Moreover, CD5(+) B cells are enriched in the ability to produce IL-10 compared to CD5(neg) B cells. Together these results suggest that CD5 may identify functional IL-10-producing Bregs . The malfunction of Bregs during active disease due to reduced IL-10 expression may thus permit ANCA production.
Vaglio, Augusto; Gnappi, Elisa; Maggiore, Umberto; Allegri, Landino; Allinovi, Marco; Urban, Maria L.; Delsante, Marco; Galetti, Maricla; Nicastro, Maria; Pilato, Francesco P.; Buzio, Carlo
Background and objectives Complement alternative pathway (cAP) activation has recently been recognized as a key pathogenic event in ANCA-associated vasculitis (AAV). cAP dysregulation is also a major determinant of thrombotic microangiopathies (TMA), which can in turn complicate AAV. We explored the prognostic significance of cAP activation and of histologic evidence of TMA in a cohort of patients with renal AAV. Design, setting, participants, & measurements We studied 46 patients with AAV diagnosed between January 1990 and December 2011 at the Nephrology Unit of Parma University Hospital; 30 of them had undergone renal biopsy. We analyzed serum levels of C3 (sC3) and C4 (sC4) and, for 19 patients who had frozen plasma, plasma Bb and C5b-9 levels. We also reviewed all kidney biopsy specimens, specifically searching for histologic signs of TMA, and performed immunofluorescence or immunohistochemistry for C3d, C4d, Bb and C5b-9. Results sC3 was below the lower limit of normal in 35% of the patients, whereas C4 was low in only 2%. Patients with low sC3 tended to be older (P=0.04) and to have lower eGFR at diagnosis (P=0.06). The median follow-up was 78 months (interquartile range, 18–135 months); 18 patients reached ESRD (10 of 14 and 8 of 26 in the low and normal sC3 groups, respectively). Death-censored renal survival was lower in the low sC3 group than in the normal sC3 group (log-rank test, P=0.01). Eight of the 30 patients who had undergone biopsy (27%) had histologic signs of TMA; these signs were more frequent in patients with low sC3 (5 of 10 versus 3 of 20; P=0.04). Notably, patients with histologic signs of TMA had a dramatically worse death-censored renal survival than patients without TMA (log-rank test, P=0.01), with ESRD occurring in 8 of 8 patients with TMA versus 8 of 22 patients without TMA. Conclusions Low sC3 levels and histologic signs of TMA are associated with a poor renal prognosis in patients with AAV. PMID:26542163
Dixon, William G; Kersley-Fleet, Lianne; Bruce, Ian N; Chinoy, Hector; Barton, Anne; Lunt, Mark; Watson, Kath; Hyrich, Kimme L
Objective To compare the risk of lupus-like events (LLEs) and vasculitis-like events (VLEs) in tumour necrosis factor-α inhibitor (TNFi)-treated patients with rheumatoid arthritis (RA) to those receiving non-biological disease-modifying antirheumatic drugs (nbDMARDs). Methods Patients were recruited to the British Society for Rheumatology Biologics Register—RA, a national prospective cohort study. Two cohorts recruited between 2001 and 2015: (1) patients starting first TNFi (adalimumab, etanercept, infliximab and certolizumab) (n=12 937) and (2) biological-naïve comparison cohort receiving nbDMARDs (n=3673). The risk of an event was compared between the two cohorts using Cox proportional-hazard models, adjusted using propensity scores. Rates of LLE/VLE were compared between TNFi and nbDMARD patients. Results The crude incidence rates for LLEs were: TNFi 10/10 000 patient-years (pyrs) (95% CI 8 to 13) and nbDMARD 2/10 000 pyrs (95% CI 1 to 6); for VLEs: TNFi 15/10 000 pyrs (95% CI 12 to 19) and nbDMARD 7/10 000 pyrs (95% CI 4 to 12). The risk of both events was highest in the first year of TNFi treatment. After adjusting for differences in baseline characteristics, there was no difference in risk of LLEs (adjHR 1.86; 95% CI 0.52 to 6.58) or VLEs (adjHR 1.27; 95% CI 0.40 to 4.04) for TNFi compared to nbDMARD-treated patients. Infliximab conferred the highest overall risk, followed by etanercept, although 95% CIs overlapped following adjustment. Conclusions In one of the largest biological registers, the absolute risk of both events is low. The addition of TNFi to nbDMARD does not alter the risk of either event in patients with RA selected for TNFi. This is the first study to assess the risk of these outcomes in a prospective, observational cohort. PMID:28123776
QASIM, F J; THIRU, S; GILLESPIE, K
d-penicillamine (DP) and gold salts which are used as immune-modulating agents in the treatment of rheumatoid arthritis are known to be capable of causing autoimmune manifestations. Most autoimmune diseases in man are dominated by Th1-type responses, and one might presume that effective immunotherapy counteracts Th1 activity, perhaps by causing a shift to a Th2 response. The mechanism of action of gold and DP is not clear, but some clues may be obtained from their effects in animal models. DP, gold salts and mercuric chloride (HgCl2) are known to induce Th2-dominated autoimmune syndromes in genetically susceptible rodent strains, and we have demonstrated recently that HgCl2 up-regulates messenger RNA (mRNA) for IL-4 in the Brown Norway (BN) rat. In the BN rat HgCl2 treatment is also associated with the development of vasculitis, and anti-myeloperoxidase (MPO) antibodies are found in the serum. The present study examined and confirmed the hypothesis that, since gold and DP induce an autoimmune syndrome similar to HgCl2 in the BN rat, they may also induce vasculitis and an up-regulation in mRNA for IL-4. Tissue injury was assessed macroscopically and histologically on day 5 and day 15 after the start of injections with gold, DP or HgCl2, serum titres of IgE and presence of anti-MPO antibodies were determined using ELISA, and a semi-quantitative assay using reverse transcription-polymerase chain reaction was used to assay the level of mRNA for IL-4 in spleen and caecum. The relative degree of tissue injury reflected the potency of induction of IgE by the three agents (HgCl2 being most potent and DP least potent). The lesions were identical histologically, supporting the premise that the vasculitis is a manifestation of the autoimmune syndrome rather than non-specific HgCl2 toxicity. Both gold and DP induced less up-regulation of mRNA for IL-4 than HgCl2. HgCl2 (but not gold or DP) induced anti-MPO antibodies. It would be interesting to examine patients treated with
Impaired activation of the fibrinolytic system in children with Henoch-Schönlein purpura: beneficial effect of hydrocortisone plus Sigma-aminocaproic acid therapy on disappearance rate of cutaneous vasculitis and fibrinolysis.
Prandota, J; Pankow-Prandota, L; Kotecki, L
Systemic vasculitis is a predominant clinical symptom in Henoch-Schönlein purpura (HSP), and some studies suggested that decreased blood fibrinolytic activity, as well as blood platelets, is of importance in the development of cutaneous vasculitis. Although patients with HSP have normal blood coagulation, little is known about the fibrinolytic system. On the other hand, it is known that the focus of Sigma-aminocaproic acid (EACA) activity in vivo is probably the blood platelet-vessel wall interaction or a vascular component alone. The aim of this study was, therefore, to investigate blood coagulation and fibrinolytic system as well as the effect of hydrocortisone (H) plus EACA therapy (Group I) on plasma antithrombin-III (AT-III), alpha1-proteinase inhibitor (alpha1-PI), alpha2-antiplasmin (alpha2-A), alpha2-macroglobulin (alpha2-M) activity, fibrinogen and plasminogen concentrations in plasma, euglobulin clot lysis time (ELT), and disappearance rate of cutaneous vasculitis in 14 children with HSP aged 7.6 +/- 3.1 (SD) years. Ten patients (8.6 +/- 2.5 years old) were treated with H alone (Group II), and 8 healthy, age-matched children served as controls. Plasma proteinase inhibitor activity was estimated with the kinetic method using Boehringer chromozyme tests before administration of H (9.2 +/- 3.3 mg/kg/d, i.v.) plus EACA (140 +/- 52 mg/kg/d, p.o.) for 5.93 +/- 2.05 days, and 24 hours after the last dose of EACA, as well as before and after treatment with H alone (8.25 +/- 1.74 mg/kg/24 h, i.v.) for 7.1 +/- 1.2 days. It was found that patients with HSP had the initial fibrinogen and plasminogen plasma concentrations significantly increased compared with the controls (Group I: 3.93 +/- 1.3 g/L and 124 +/- 38%; Group II: 4.24 +/- 0.89 g/L and 134 +/- 42% vs. 2.96 +/- 0.34 g/L, and 90 +/- 14%, respectively). Also, there was a marked decrease of the initial plasma alpha2-A activity in Group II compared with the controls (0.69 +/- 0.29 vs. 0.94 +/- 0.11 IU
Nelson, Danielle D; Davis, William C; Brown, Wendy C; Li, Hong; O'Toole, Donal; Oaks, J Lindsay
Sheep-associated malignant catarrhal fever (SA-MCF) caused by ovine herpesvirus-2 (OvHV-2), a gamma-herpesvirus in the Macavirus genus, is a fatal disease associated with lymphoproliferation, lymphocytic vasculitis, and mucosal ulceration in clinically susceptible species. SA-MCF is an important threat to American bison (Bison bison) due to their high susceptibility to this disease. Currently, the pathogenesis of disease in SA-MCF is poorly understood, and the immunophenotype of lymphocytes that infiltrate the vascular lesions of bison and cattle with SA-MCF has been only partially defined. Previous single-color immunohistochemistry studies have demonstrated that CD8(+) cells and CD4(+) cells predominate within vascular infiltrates in cattle and bison. The CD8(+) cells detected in the vascular lesions of cattle and bison were assumed to be cytotoxic alphabeta T lymphocytes. However, polychromatic immunophenotyping analyses in this study showed that CD8(+)/perforin(+) gammadelta T cells, CD4(+)/perforin(-) alphabeta T cells, and B cells infiltrate vascular lesions in the urinary bladder, kidney, and liver of six bison with experimentally-induced SA-MCF. CD8(+) alphabeta T cells and WC1(+) gammadelta T cell cells were only infrequently and inconsistently identified. This study confirmed our hypothesis that the predominant CD8(+) lymphocytes infiltrating the vascular lesions of bison with SA-MCF are cytotoxic lymphocytes of the innate immune system, not CD8(+) alphabeta T cells. Results of the present study support the previous suggestions that MCF is fundamentally a disease of immune dysregulation.
Hewins, Peter; Belmonte, Frances; Jennette, J Charles; Falk, Ronald J; Preston, Gloria A
Antibodies recognizing the complement of the middle of PR3 (cPR3m) occur in ~30% of PR3-ANCA-vasculitis patients and immunization of animals with a peptide complementary to the middle of PR3 (cPR3m) induces not only anti-complementary PR3 antibodies, but also anti-PR3 antibodies derived through an anti-idiotypic response. PR3 epitopes recognized by patient ANCA however, are not restricted to the middle of PR3. This prompted us to test for antibodies that react with proteins complementary to the terminal regions of PR3 (cPR3C and cPR3N) in PR3-ANCA patients. Anti-cPR3C reactivity was detected in 28% of patients but anti-cPR3N reactivity in only 15%. Ranked anti-cPR3C and anti-cPR3m reactivity correlated in the cohort, whereas there was no significant relationship between cPR3C and cPR3N reactivity. Serial samples from three patients’ revealed that anti-cPR3C and anti-cPR3m reactivity followed a similar pattern over time. Serial samples from a fourth patient demonstrated an anti-cPR3N response without concurrent cPR3m or cPR3C reactivity. Epitope determination by mass spectrometry identified a thirteen amino acid sequence on cPR3C that contained a common binding site recognized by antibodies from three patients. This peptide sequence contains a “PHQ” motif which was reported to be the basis for cross-reactivity of anti-cPR3m antibodies with plasminogen. Why these antibodies are detected in only ~30% of the patients remains unclear. The data reveal it is not due to lack of inclusion of flanking regions of complementary PR3 during screening. Instead, quite unexpectedly, the data demonstrate that patients’ antibodies react with a restricted epitope that exists in both cPR3m and cPR3C. PMID:20712431
The CD4 Lymphocyte Count is a Better Predictor of Overall Infection Than the Total Lymphocyte Count in ANCA-Associated Vasculitis Under a Corticosteroid and Cyclophosphamide Regimen: A Retrospective Cohort.
Shi, Yi-Yun; Li, Zhi-Ying; Zhao, Ming-Hui; Chen, Min
Patients with antineutrophil cytoplasmic autoantibody associated vasculitis (AAV) have a high prevalence of infection during immunosuppressive therapy, and the total lymphocyte count (TLC) has been demonstrated to be an independent predictor of infection. The current study investigated the value of the TLC and its subsets, particularly the CD4 count, for predicting infections of AAV in a single Chinese cohort.A total of 124 AAV patients were retrospectively recruited in our department from December 1997 to October 2013. Multivariate Cox models with the CD4 count or TLC measured at three typical time points, that is, at baseline, at the beginning of immunosuppressant dose reduction, and at the last visit before infection or censoring, or with the measurements included as time-varying covariates, were compared to select the most predictive time point for infection. A time-dependent area under the receiver operating characteristic curve (AUC(t)) for the TLC (AUC(t)TLC) and the CD4 count (AUC(t)CD4count) measured at the most predictive time point were calculated and compared.During an average follow-up of 11.5 (range 0.5-142) months, 55 of the 124 patients (44.3%) experienced a microbiologically confirmed infection. Independent predictors of overall infection were initial creatinine clearance (P = 0.02 and 0.04), pulmonary interstitial fibrosis (P = .04 and .05), pulmonary nodule or cavity (P = 0.002 and .002), CD4 count (P < 0.001) or TLC (P = 0.05) from the last visit. The comparison of Cox models fitted at different time points confirmed the last visit to be the most predictive one for overall infection. The predictive value of the CD4 count or TLC from the last visit measured by AUC showed that the AUC(t)CD4count (62.8-70.2%) was almost always higher than AUC(t)TLC (55.2-58.1%) during the first 2 years of immunosuppressive therapy (P = 0.01-0.2). In terms of different pathogens, both the CD4 count and TLC performed well for non
Satish, S.; Rajesh, R.; Shashikala, S.; Kurian, G.; Unni, V. N.
While meningoencephalitis due to cryptococcus is well known in immunocompromised patients, disseminated cryptococcosis and cryptococcemia is rare outside the setting of advanced HIV infection. We report a case of disseminated cryptococcosis occurring in a patient with Wegener’s granulomatosis on immunosuppressive medications. PMID:21072158
Antineutrophil cytoplasm antibody (ANCA)-associated vasculitides are small-vessel vasculitides that include granulomatosis with polyangiitis (formerly Wegener’s granulomatosis), microscopic polyangiitis, and eosinophilic granulomatosis with polyangiitis (Churg–Strauss syndrome). Renal-limited ANCA-associated vasculitides can be considered the fourth entity. Despite their rarity and still unknown cause(s), research pertaining to ANCA-associated vasculitides has been very active over the past decades. The pathogenic role of antimyeloperoxidase ANCA (MPO-ANCA) has been supported using several animal models, but that of antiproteinase 3 ANCA (PR3-ANCA) has not been as strongly demonstrated. Moreover, some MPO-ANCA subsets, which are directed against a few specific MPO epitopes, have recently been found to be better associated with disease activity, but a different method than the one presently used in routine detection is required to detect them. B cells possibly play a major role in the pathogenesis because they produce ANCAs, as well as neutrophil abnormalities and imbalances in different T-cell subtypes [T helper (Th)1, Th2, Th17, regulatory cluster of differentiation (CD)4+ CD25+ forkhead box P3 (FoxP3)+ T cells] and/or cytokine–chemokine networks. The alternative complement pathway is also involved, and its blockade has been shown to prevent renal disease in an MPO-ANCA murine model. Other recent studies suggested strongest genetic associations by ANCA type rather than by clinical diagnosis. The induction treatment for severe granulomatosis with polyangiitis and microscopic polyangiitis is relatively well codified but does not (yet) really differ by precise diagnosis or ANCA type. It comprises glucocorticoids combined with another immunosuppressant, cyclophosphamide or rituximab. The choice between the two immunosuppressants must consider the comorbidities, past exposure to cyclophosphamide for relapsers, plans for pregnancy, and also the cost of rituximab. Once remission is achieved, maintenance strategy following cyclophosphamide-based induction relies on less toxic agents such as azathioprine or methotrexate. The optimal maintenance strategy following rituximab-based induction therapy remains to be determined. Preliminary results on rituximab for maintenance therapy appear promising. Efforts are still under way to determine the optimal duration of maintenance therapy, ideally tailored according to the characteristics of each patient and the previous treatment received. PMID:27733943
Koster, Matthew J.; Warrington, Kenneth J.
Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs) are near universally fatal conditions if untreated. Although effective therapeutic options are available for these diseases, treatment regimens are associated with both short- and long-term adverse effects. The recent identification of effective B-cell-targeted therapy with an anti-CD20 monoclonal antibody has transformed the treatment landscape of AAV. Questions, nevertheless, remain regarding the appropriate timing, dose, frequency, duration, and long-term effects of treatment. The aim of this article is to provide an overview of the current information, recent advances, ongoing clinical trials, and future treatment possibilities in AAV. PMID:27347395
McKinney, Eoin F; Willcocks, Lisa C; Broecker, Verena; Smith, Kenneth G C
The small-vessel vasculitides are a group of disorders characterised by variable patterns of small blood vessel inflammation producing a markedly heterogeneous clinical phenotype. While any vessel in any organ may be involved, distinct but often overlapping sets of clinical features have allowed the description of three subtypes associated with the presence of circulating anti-neutrophil cytoplasmic antibodies (ANCA), namely granulomatosis with polyangiitis (GPA, formerly known as Wegener's Granulomatosis), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (eGPA, formerly known as Churg-Strauss syndrome). Together, these conditions are called the ANCA-associated vasculitidies (AAV). Both formal nomenclature and classification criteria for the syndromes have changed repeatedly since their description over 100 years ago and may conceivably do so again following recent reports showing distinct genetic associations of patients with detectable ANCA of distinct specificities. ANCA are not only useful in classifying the syndromes but substantial evidence implicates them in driving disease pathogenesis although the mechanism by which they develop and tolerance is broken remains controversial. Advances in our understanding of the pathogenesis of the syndromes have been accompanied by some progress in treatment, although much remains to be done to improve the chronic morbidity associated with the immunosuppression required for disease control.
Rheumatoid fac- rheumatoid arthritis , and with increasing fre- tor, antinuclear antibody , VDRL, antibody to the quency in hematologic...Goldsweig (Hoffmann-La Roche) nia. In addition, numbness, paresthesias, and sen- and Ms. D. Davis (Genentecn) in the interferon antibody assays. sory
Carruthers, David; Sherlock, Jonathan
The vasculitides associated with antineutrophil cytoplasmic antibodies (ANCAs) present to and are managed by a wide spectrum of physicians, reflecting the multi-organ nature of the conditions. Treatment strategies for these primary inflammatory vascular diseases have varied based on the outcomes of different clinical trials and practice reviews. The individual drugs used and their route of administration, dose, and duration of therapy have varied and have been the source of much debate. Advances in our understanding of disease immunopathogenesis, clinical assessment and outcome have formed the basis for several recent good-quality clinical trials. Now, with the results of these large-scale multicentre collaborative studies, there is a firmer evidence base to guide management decisions for individual patients. This evidence base, reviewed here, has led to the publication of treatment guidelines which importantly encompass many of the broader aspects of disease management.
Cozzi, A; Doria, A; Gisondi, P; Girolomoni, G
Skin and joint manifestations are part of the clinical spectrum of many disorders. Well-known associations include psoriatic arthritis and arthritis associated with autoimmune connective tissue diseases. This review focuses on less common associations where skin lesions can provide easily accessible and valuable diagnostic clues, and directly lead to the specific diagnosis or limit the list of possibilities. This may also affect health care resources as diagnostic tests are often low-specific, highly expensive and poorly available. This group of diseases can be divided into two subsets, based on the presence/absence of fever, and then further classified according to elementary skin lesions (macular, urticarial, maculo-papular, vesico-bullous, pustular, petechial and nodular). In most instances joint involvement occurs as peripheral migrating polyarthritis. Erythematosus macular or urticarial rashes occur in most febrile disorders such as monogenic autoinflammatory syndromes, Schnitzler's syndrome, Still's disease and rheumatic fever and afebrile diseases as urticarial vasculitis. Pustular rash may be observed in chronic recurrent multifocal osteomyelitis (CRMO) and pyogenic arthritis with pyoderma gangrenosum and acne (PAPA) syndrome (both febrile) as well as in Behcet's disease and Synovitis, acne, pustulosis, hyperostosis and osteitis syndrome (both non-febrile). Papular lesions are typical of secondary syphilis, sarcoidosis, interstitial granulomatous dermatitis, papular petechial of cutaneous small-vessel vasculitis and nodular lesions of polyarteritis nodosa and multicentric reticulohistiocytosis all of which are afebrile. Differential diagnosis includes infections and drug reactions which may mimic several of these conditions. To biopsy the right skin lesion at the right time it is essential to obtain relevant histological information.
Stojan, G; Petri, M
C1q is the first component of the classical complement pathway. Both clinically validated in-house ELISA assays as well as commercial ELISA kits are used for detection of anti-C1q antibodies. Anti-C1q autoantibodies can be detected in a wide range of autoimmune diseases and are highly sensitive for hypocomplementemic uticarial vasculitis. In SLE, anti-C1q are strongly associated with proliferative lupus nephritis, and their absence carries a negative predictive value for development of lupus nephritis of close to 100%. Anti-C1q in combination with anti-dsDNA and low complement has the strongest serological association with renal involvement. The anti-C1q titers correlate with global disease activity scores in patients with renal involvement, and higher titers seem to precede renal flares. After the successful treatment of a renal flare, anti-C1q has the tendency to decrease or even become undetectable. The main obstacle to the inclusion of anti-C1q in the classification criteria and clinical management of SLE is the lack of standardized laboratory assays.
Halkier-Sørensen, L; Thestrup-Pedersen, K
We have studied the influence of cold exposure on itch, erythema and wheal, in response to histamine scratch tests, in 14 volunteers. Cooling of the skin to less than 20 degrees C, by application of an ice cube for 30 min on the inside of the forearm, abolished itch and reduced erythema by approximately 50%, whereas the size of the wheal was unaffected by cooling. The observations bear significance for an explanation of the well-known observation that cold relieves itch. A normal itch response seems to require a continuous metabolic process in the skin, which is inhibited at temperatures less than 20 degrees C. The skin symptoms, itching and erythema, among workers in the fish processing industry are mainly localized to the forearms and backs of the hands, but only seldom to the fingers and palms, although they are in direct contact with fish products. Skin temperature measurements have shown that the temperature on the fingers and palms is less than 20 degrees C, while the temperature on the backs of the hands and forearms ranges from 25 to 30 degrees C. We therefore conclude that the skin temperature is an important factor for the location of skin symptoms among workers in the fish processing industry.
Issa, Abdelfatah Abou; Simman, Richard
Lovenox is a trade name for Enoxaparin. It is a low molecular weight heparin (LMWH) and has other trade names like Clexane and Xaparin. It is an anticoagulant used to prevent and treat venous thromboembolism events (VTE) like deep vein thrombosis or pulmonary embolism, and is given as a subcutaneous injection. General speaking, the most common skin reactions as a result of enoxaparin use are: urticarial, ecchymosis, and even skin necrosis due to vasculitis. These side effects are usually located at the injection site. New studies have pointed out the side effect that could occur a distance from the site of Lovenox injection. In our case extensive skin and subcutaneous tissue necrosis developed at the abdominal wall injection site.
Kinyas, Şeref; Esgin, Haluk
Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system. A 40-year-old female patient with a 12-year history of MS was admitted to our clinic with blurred vision and floaters in her right eye for about 1 month. Here, we share the findings and the management of intermediate uveitis and retinal periphlebitis in an MS case being treated with interferon beta-1a for 7 years. PMID:27800257
... the Central and Peripheral Nervous Systems Fact Sheet Table of Contents (click to jump to sections) What ... Information Page NINDS Epilepsy Information Page NINDS Familial Periodic Paralyses Information Page NINDS Farber's Disease Information Page ...
Antineutrophil cytoplasmic autoantibodies (ANCAs) directed to proteinase 3 (PR3-ANCA) or myeloperoxidase (MPO-ANCA) are strongly associated with the ANCA-associated vasculitides—Wegener’s granulomatosis, microscopic polyangiitis, and Churg-Strauss syndrome. Clinical observations, including the efficacy of B-cell depletion via rituximab treatment, support—but do not prove—a pathogenic role for ANCA in the ANCA-associated vasculitides. In vitro experimental studies show that the interplay of ANCA, neutrophils, the alternative pathway of the complement system, and endothelial cells could result in lysis of the endothelium. A pathogenic role for MPO-ANCA is strongly supported by in vivo experimental studies in mice and rats, which also elucidate the pathogenic mechanisms involved in lesion development. Unfortunately, an animal model for PR3-ANCA–associated Wegener’s granulomatosis is not yet available. Here, cellular immunity appears to play a major role as well, particularly via interleukin-17–producing T cells, in line with granulomatous inflammation in the lesions. Finally, microbial factors, in particular Staphylococcus aureus and gram-negative bacteria, seem to be involved in disease induction and expression, but further studies are needed to define their precise role in disease development. PMID:20878509
This study evaluates bullous cutaneous reactions and sequential histopathology in an individual sensitized to bed bug bites in an effort to better understand the allergic response and histology associated with these bites. There was a progression of the inflammatory response across time ranging from...
Caswell, Jeff L; Nykamp, Stephanie G
Two, full sibling, Welsh springer spaniel presented at 8 and 18 mo of age with rapidly progressive ataxia, recumbency, and pyrexia. The spinal cord contained extensive subdural hemorrhage and, in 1 dog, suppurative and necrotizing arteritis in the dura. The findings suggest a familial form of canine juvenile polyarteritis syndrome.
Avila, Julio; Acosta, Elisa; Machargo, María-del-Valle; Arteaga, María-Francisca; Gallego, Eduardo; Cañete, Haridian; García-Pérez, José-Javier; Martín-Vasallo, Pablo
Background Systemic vasculitides constitute a heterogeneous group of diseases of autoimmunological origin characterized by inflammation of blood vessels and antibodies that react against autoantigens in a process that ultimately affects blood vessel walls. An important number of these patients present kidney disease. An endeavour of this area of research is the identification of autoantigens involved in these diseases. Accordingly, we used serum from a patient suffering from a microscopic polyangiitis, P-ANCA positive, manifesting a clinically atypical renal necrotizing glomerulonephritis and interstitial nephropathy for the identification of autoantigens; we also determined the prevalence of corresponding autoantibodies in other vasculitides, diabetic microangiopathy and in general population. Methods The patient's serum was used as a probe for the immunoscreening method SEREX to screen a human brain cDNA expression library. Results Four positive clones were isolated and sequenced. Clones Jos002 code for protein HDAC5, Jos014 for TFC4, Jos107 for RTF1, and Jos313 for POLDIP3 polymerase. The four proteins are of nuclear localization. None of them had been reported as autoantigen. Recombinant proteins were synthesised and checked as antigens by western blot with different sera from controls and patients affected with other vasculitides and diabetic microangiopathy as well. Only the serum from the patient origin of this study recognized all recombinant proteins. Conclusion We identify four nuclear proteins, HDAC5, TFC4, RTF1 and POLDIP3 polymerase as new autoantigens that could be used as markers in the diagnosis of subfamilies in immune diseases, although we cannot determine the role of these proteins in the aetiopathogenic process. PMID:18625050
Zidi, A; Ben Miled Mrad, K; Hantous, S; Nouira, K; Mestiri, I; Mrad, S
Thoracic involvement of Behcet's disease is unusual but serious. It is related to the well known vascular tropism of the disease. It may involve the superior vena cava, pulmonary arteries, aorta and subclavian vessels. Imaging is useful for diagnosis and assess the degree of thoracic involvement. CT scan and MRI are obviously more accurate than angiography. The spectrum of thoracic manifestations of the disease is presented based on a review of 22 cases.
Matteson, Eric L
Adolf Kussmaul is well known for his contributions to the science of medicine and the specialty of rheumatology. A much-loved teacher and respected physician and researcher, Kussmaul's desire to understand disease, his careful clinical observations, and his innovative thinking in medical technology mark him as a pioneer in modern rheumatology.
Morović-Vergles, Jadranka; Culo, Melanie-Ivana; Sutić, Anamarija
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides are rare diseases, with the average of 30 new cases per million inhabitants per year. Their main characteristic is systemic involvement with necrosis of the vessel walls (histological changes showing necrosis of the media and inflammation of adventitia and intima). In some forms granulomas may be found surrounding the vessels. ANCA-associated vasculitides include granulomatosis with polyangiitis (GPA, previously called Wegener's), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA, previously called Churg-Straus). Honorific eponyms are now changing to a disease-descriptive or etiology-based nomenclature. ANCA-associated vasculitides are a distinctive group of vasculitides because they dominantly involve small sized vessels, sometimes even medium sized vessels, are associated with antineutrophil cytoplasmic antibodies with high risk of developing glomerulonephritis and respond well to immunosuppresion with cyclophosphamide.
Mareen, P; Van De Walle, S; Bernaert, P; Vanhouteghem, H; Dierick, J
We report on one patient with Wegener's granulomatosis (WG) and two patients with microscopic polyangiitis (MPA). The patient with WG had signs of a respiratory infection and showed a c-ANCA pattern with proteinase 3 (PR3) specificity. The patients with MPA presented with pulmonary haemorrhage and signs of renal damage and showed a p-ANCA pattern with myeloperoxidase (MPO) specificity. In the three patients histopathological findings confirmed the diagnosis. We discuss the clinical indications of ANCA testing and the current terminology for reporting ANCA results (c-ANCA, p-ANCA, c-ANCA (atypical) and atypical ANCA). The target antigens and diseases associated with these different patterns are considered. Finally we focus on the value of ANCA and more specific PR3-ANCA and MPO-ANCA in the diagnosis of WG and MPA. The new application domain of ANCA in Crohn's disease and ulcerative colitis is also discussed.
Ferreira, Catarina; Costa, Teresa; Marques, Ana Vieira
Propylthiouracil is a drug used to treat hyperthyroidism. It can cause several side effects including pulmonary disorders that, although rare, can be severe. The authors describe the case of a woman treated with propylthiouracil who developed diffuse alveolar haemorrhage with severe respiratory failure and anaemia, which improved with discontinuation of the antithyroid drug and on starting systemic corticosteroid therapy. PMID:25661751
Vega, Luis E; Espinoza, Luis R
It is important to recognize factors that might predict poor outcome and prognosis in patients with AAV. The predictors reported in the literature encompass genetic, histopathological, and clinical ones. Genetic studies (genetic predictors) have found genes that are associated with prediction of poor response to treatment, deterioration of renal function, and risk of mortality. Histopathological studies (histopathological predictors) have shown that sclerotic renal lesions are associated with increased risk of progression to end-stage renal disease and death. Lastly, scores (clinical predictors) obtained with tool as FFS, Maldini risk score, VDI, and emerging new biomarkers could potentially be helpful in assessment of prognosis in the future.
Tokura, Y; Yagi, H; Yanaguchi, H; Majima, Y; Kasuya, A; Ito, T; Maekawa, M; Hashizume, H
IgG4-related disease (IgG4-RD) is a recently established clinical entity characterized by high levels of circulating IgG4, and tissue infiltration of IgG4(+) plasma cells. IgG4-RD exhibits a distinctive fibroinflammatory change involving multiple organs, such as the pancreas and salivary and lacrimal glands. The skin lesions of IgG4-RD have been poorly characterized and may stem not only from direct infiltration of plasma cells but also from IgG4-mediated inflammation. Based on the documented cases together with ours, we categorized the skin lesions into seven subtypes: (1) cutaneous plasmacytosis (multiple papulonodules or indurations on the trunk and proximal part of the limbs), (2) pseudolymphoma and angiolymphoid hyperplasia with eosinophilia (plaques and papulonodules mainly on the periauricular, cheek and mandible regions), (3) Mikulicz disease (palpebral swelling, sicca syndrome and exophthalmos), (4) psoriasis-like eruption (strikingly mimicking psoriasis vulgaris), (5) unspecified maculopapular or erythematous eruptions, (6) hypergammaglobulinaemic purpura (bilateral asymmetrical palpable purpuric lesions on the lower extremities) and urticarial vasculitis (prolonged urticarial lesions occasionally with purpura) and (7) ischaemic digit (Raynaud phenomenon and digital gangrene). It is considered that subtypes 1-3 are induced by direct infiltration of IgG4(+) plasma cells, while the other types (4-7) are caused by secondary mechanisms. IgG4-related skin disease is defined as IgG4(+) plasma-cell-infiltrating skin lesions that form plaques, nodules or tumours (types 1-3), but may manifest secondary lesions caused by IgG4(+) plasma cells and/or IgG4 (types 4-7).
Anti-neutrophil cytoplasm autoantibody (ANCA)-associated diseases are autoimmune conditions characterized by necrotizing inflammation of small blood vessels. The immunogenesis and etiology of these conditions are unknown, but our knowledge of the immunopathogenesis has increased considerably in recent years. In this review, we discuss the animal models currently used to investigate the mechanisms of vascular injury and to test novel therapies. We outline their advantages and limitations and propose potential directions for future research. PMID:21371348
Kaul, A; Agrawal, V; Bhaduaria, D; Agrawal, Vikas; Prasad, Narayan; Gupta, Amit; Sharma, R K
More than 50% of patients with systemic lupus erythematosus (SLE) have renal involvement at presentation or during their illness. Lupus nephritis (LN) encompasses several patterns of renal disease, including glomerular, tubulointerstitial, and vascular pathologies. The presence and significance of renal vascular lesions (VLs) are often overlooked. VLs in LN are not rare with an incidence of 10%-40% on renal biopsies from various studies and their presence is often labeled as poor prognostic markers. The current treatment protocol for LN is mainly based on the glomerular pathology, and no guidelines/consensus exists for treatment of LN with VLs. We describe the clinical presentation, course, response to therapy, and outcomes in five patients with SLE with histological evidence of renal VLs.
Isada, Carlos M
Infectious diseases are a significant cause of morbidity and mortality in immunosuppressed patients, including those with connective tissue diseases. Both disease and treatment contribute to a predisposition to infection in immunocompromised patients. Significant infection and morbidity occur in 25% to 50% of these patients with a median mortality of 5.2% due to common bacterial infections, such as pneumonia or bacteremia, and opportunistic fungal infections such as Pneumocystis. The lungs, skin, urinary tract, blood, and central nervous system are commonly affected. Pathogens such as Pneumocystis jirovecii, Histoplasma capsulatum, Aspergillus species, herpes zoster, JC virus, Nocardia asteroides, and Nocardia species are increasingly prevalent in immunocompromised patients. Improved recognition, diagnosis, and prevention of these infections are needed to enhance outcomes in these patients.
Ohlsson, Susanne M; Linge, Carl Petrus; Gullstrand, Birgitta; Lood, Christian; Johansson, Asa; Ohlsson, Sophie; Lundqvist, Andrea; Bengtsson, Anders A; Carlsson, Fredric; Hellmark, Thomas
Anti-neutrophil cytoplasmic antibody associated vasculitides (AAV) are conditions defined by an autoimmune small vessel inflammation. Dying neutrophils are found around the inflamed vessels and the balance between infiltrating neutrophils and macrophages is important to prevent autoimmunity. Here we investigate how sera from AAV patients may regulate macrophage polarization and function. Macrophages from healthy individuals were differentiated into M0, M1, M2a, M2b or M2c macrophages using a standardized protocol, and phenotyped according to their expression surface markers and cytokine production. These phenotypes were compared with those of macrophages stimulated with serum from AAV patients or healthy controls. While the healthy control sera induced a M0 macrophage, AAV serum promoted polarization towards the M2c subtype. No sera induced M1, M2a or M2b macrophages. The M2c subtype showed increased phagocytosis capacity compared with the other subtypes. The M2c polarization found in AAV is consistent with previous reports of increased levels of M2c-associated cytokines.
HOLLAND, M; TAKADA, K; OKUMOTO, T; TAKAHASHI, N; KATO, K; ADU, D; BEN-SMITH, A; HARPER, L; SAVAGE, C O S; JEFFERIS, R
The triad of small vessel vasculitides (SVV) comprise Wegener's granulomatosis (WG), microscopic polyangiitis (MPA) and Churg–Strauss syndrome (CS). All three are associated with presence of circulating IgG antineutrophil cytoplasm antibodies (ANCA) which target autoantigens contained, primarily, within neutrophil azurophilic granules. The widely accepted model of pathogenesis suggests that ANCA activate cytokine-primed neutrophils within the microvasculature, leading to by-stander damage to endothelial cells, and rapid escalation of inflammation with recruitment of mononuclear cells. Activation may be initiated, in vitro, by the coligation of the PR3 or MPO antigen, translocated to the cell surface, and FcγRIIa/FcγRIIIb receptors. This suggests that the IgG subclass profile of ANCA and, possibly, its glycosylation status could influence the inflammatory mechanisms activated. The glycosylation status of total IgG isolated from the sera of patients with WG (13), MPA (6) and CSS (1) was determined by analysis of the released oligosaccharides. A deficit in IgG galactosylation is demonstrated for all patient samples, compared to controls. The mean percentage values for the agalactosylated (G0) oligosaccharides were 57% (SD ± 9·71), 47% (SD ± 4·25) and 28% (SD ± 4·09) for WG, MPO and control samples, respectively. The G0 levels for polyclonal IgG isolated from the sera of both WG and MPA patients were significantly increased compared to controls (P < 0·0001). The major glycoform present therefore is agalactosylated (G0) IgG. In previous studies the G0 glycoform of IgG has been shown to bind and activate mannan binding lectin, and hence to activate the complement cascade, and to facilitate mannose receptor binding and the uptake of IgG complexes by macrophages and dendritic cells. Both of these activities could impact on the processing and presentation of self-antigens in autoimmune disease. PMID:12100039
Alba, Marco A; Flores-Suárez, Luis Felipe
ANCA-associated vasculitides (AAV) are chronic autoimmune diseases characterized by inflammation and destruction of small vessels. Rituximab is now licensed for use as a remission-induction agent in the treatment of these disorders. During recent years, several non-controlled studies have suggested that rituximab may be of value in maintaining disease remission in AAV. In these series, 3 techniques have been tried: "watch-and-wait", repeated cycles in fixed intervals, or administration based on proposed biomarkers. More importantly, the results of the MAINRITSAN trial showed that this anti-CD20 agent is superior to azathioprine for preventing major relapses in AAV. This review summarizes current information regarding the effectiveness, timing, dosing, duration and safety of rituximab as a valid option for remission maintenance.
... because, as he told her, one of the benefits of being in a research study is gaining information about the newest ideas in treatment options. “In the beginning, I went to the NIH in Bethesda, Maryland, four times a year for routine lab work, including blood samples, totaling 18 vials each time, ...
[Hypocomplementary membrano-proliferative glomerulonephritis in a Malagasy patient with schistosomiasis mansoni (detection of bilharzial antigen on glomerular basement membrane using monoclonal antibodies)].
Rajaonarivelo, P; Rajaona, H R; Alix, J L; Couderc, P; Daveau, C; Santoro, F; Nogueira-Quetroz, J A; Lovens, M; Capron, A; Cordonnier, D
Schistosomiasis due to Schistosoma mansoni affects more than 40 millions people all over the world. Renal involvement is observed mainly in endemic areas. We report a case of hypocomplementemic membrano-proliferative glomerulonephritis in a malagasy man who suffered also from hepatosplenic bilharziosis. The relation between Schistosoma mansoni and the nephropathy was proved by indirect immunofluorescence test using a monoclonal antibody directed against the caecum of adult Schistosoma mansoni.
Szczęch, Justyna; Rutka, Maja; Samotij, Dominik; Zalewska, Agnieszka
Introduction Lupus erythematosus (LE) shows a wide variety of clinical manifestations, skin involvement being one of the most important. Aim To analyze the clinical presentation of cutaneous variants of lupus erythematosus in terms of skin lesion spectrum and extracutaneous involvement. Material and methods A total of 64 patients with cutaneous LE (CLE) were included. The study was based on the “Core Set Questionnaire” developed by the European Society of Cutaneous Lupus Erythematosus (EUSCLE). Clinical severity of skin lesions was evaluated with the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI). All results were subjected to statistical analysis. Results Fifteen (23.4%) patients had an acute CLE (ACLE), 26 (40.6%) subacute CLE (SCLE) and 21 (32.8%) chronic CLE (CCLE). Two (3.2%) individuals only demonstrated urticarial vasculitis as a cutaneous manifestation of LE and these patients were excluded. Patients with ACLE were characterized by the earliest onset of the disease (mean age of 31.9 ±15.0 years; p < 0.001). On average, 4.8 ±1.8 criteria of systemic LE were found in the ACLE group compared to 2.7 ±1.3 criteria in SCLE and 2.5 ±1.5 criteria in CCLE (p < 0.001). The highest activity of skin lesions according to CLASI was found in the SCLE group (p = 0.002). On the other hand, the most severe skin damage was observed in CCLE (p < 0.01). Conclusions Each variant of CLE differs significantly from the others in respect of various aspects of clinical manifestations. Due to a number of different variants of LE skin lesions, a unified classification of CLE still remains a challenge. PMID:26985173
Takayasu arteritis is a rare disease affecting especially young females. Nonspecific symptoms make the diagnosis difficult; cases in which a diagnosis has not been made for a long period are not rare. However, recent progress in imaging modalities including magnetic resonance angiography, computed tomography angiography, and positron emission tomography have allowed making specific diagnoses in the early stage. Although specific serological markers of this disease are not known, many biomarkers specific to arterial inflammation are being developed and applied for diagnosing this disease. Also, advances in immunosuppressive treatment including new biological agents could alter the clinical outcome of the disease. According to these changes in diagnosis and treatment, the prognosis of Takayasu arteritis has been improving.
Respiratory failure and death in East Coast Fever (ECF), a clinical syndrome of African cattle caused by the apicomplexan parasite Theileria parva, has historically been attributed to pulmonary infiltration by infected lymphocytes. However, immunohistochemical staining of tissue from T. parva infect...
Cannon, Martha J; Silkstone, Malcolm A; Kipar, Anja M
This report describes a clinical case of feline infectious peritonitis (FIP) with multisystemic involvement, including multiple nodular cutaneous lesions, in a cat that was co-infected with feline coronavirus and feline immunodeficiency virus. The skin lesions were caused by a pyogranulomatous-necrotising dermal phlebitis and periphlebitis. Immunohistology demonstrated the presence of coronavirus antigen in macrophages within these lesions. The pathogenesis of FIP involves a viral associated, disseminated phlebitis and periphlebitis which can arise at many sites. Target organs frequently include the eyes, abdominal organs, pleural and peritoneal membranes, and central nervous tissues, but cutaneous lesions have not previously been reported.
Savige, Judy; Trevisin, Michelle; Hayman, Matthew; Pollock, Wendy
Antineutrophil cytoplasmic antibodies (ANCA) levels have been thought to follow disease activity, with levels being high at presentation, declining with treatment and increasing just before relapse. However, we have shown that ANCA often persist for many years in patients with clinically inactive Wegener's granulomatosis. ANCA assays are less sensitive for treated disease than for active disease, and the levels in treated patients produce different results in different assay systems. ANCA often persist for years without relapse, and the risk of relapse probably depend on levels that are critical for any individual patient. The capture enzyme-linked immunosorbent assays may be more sensitive in detecting early relapse. Relapse is more common when ANCA levels are high but, although elevated, ANCA levels are lower in relapse than at presentation. Standardized ANCA levels for the definitions of remission and relapse may not be possible, and the optimal ANCA testing protocol for treated disease remains unclear.
Misra, Durga Prasanna; Sharma, Aman; Kadhiravan, Tamilarasu; Negi, Vir Singh
Takayasu's arteritis (TA) and Giant cell arteritis (GCA) comprise the large vessel vasculitides (LVV). Patients with LVV are treated with disease-modifying anti-rheumatic drugs (DMARDs), both conventional (cDMARDs) and biologic (bDMARDs). We undertook a scoping review to assess the effectiveness of cDMARDs in TA and GCA. We could identify 11 studies in TA and 18 studies in GCA. There were only 3 randomized controlled trials on methotrexate, one on hydroxychloroquine and two on cyclosporine in GCA, the others being case series (including all studies on TA). Most of these studies had small patient numbers (median 15 in TA and 27 in GCA). Outcome measures reported in different studies were heterogenous. Overall, methotrexate, leflunomide, azathioprine, mycophenolate mofetil and cyclophosphamide were effective in TA (low quality of evidence). Methotrexate (high quality of evidence), hydroxychloroquine and cyclosporine (moderate quality of evidence) appeared to be ineffective in GCA. Azathioprine (moderate quality of evidence), leflunomide, mycophenolate mofetil, cyclophosphamide and dapsone (low quality of evidence) were effective in GCA. There exists a paucity of high quality evidence to guide use of cDMARDs in TA and GCA. There is an unmet need to conduct large multi-centric randomized placebo-controlled trials to accurately assess the utility on cDMARDs in LVV.
Aortitis; Cutaneous Vasculitis; Eosinophilic Granulomatosis With Polyangiitis; Giant Cell Arteritis; Granulomatosis With Polyangiitis (Wegener's); Henoch-Schonlein Purpura; IgA Vasculitis; Microscopic Polyangiitis; Polyarteritis Nodosa; Takayasu Arteritis; Churg-Strauss Syndrome
Vasculitis is a clinicopathologic process characterized by inflammation and necrosis of blood vessels. Classification schemes for systemic vasculitis depend on the size of the involved blood vessels, the anatomic site, and the clinical manifestations. The most common primary types of vasculitis are Wegeners granulomatosus, polyarteritis nodosa, and Churg-Strauss vasculitis. There is limited information on pregnancy outcome and medication use in these patients because most of the primary vasculidities occur in older individuals and they are more common in men.
Hacard, Florence; Nosbaum, Audrey; Bensaid, Benoit; Nicolas, Jean-François; Augey, Frédéric; Goujon, Catherine; Bérard, Frédéric
Most angioedemas are histaminergic and correspond to deep urticarial swelling. Recurrent histaminergic angioedema led to the diagnosis of chronic urticaria, even when there are no superficial associated hives. Chronic urticaria is a benign disease, and autoimmune in 40 % of cases. The occurrence of angioedema in chronic urticaria is not a sign of severity. The occurrence of angioedema in chronic urticaria is associated with a longer duration of urticarial disease. NSAIDs and/or systemic corticotherapy are classic triggers of angioedema in chronic urticaria. In the absence of clinical endpoints, there is no need to make further assessment in chronic urticaria good responders to antihistamines.
Urticarial wheals and angioedema are 2 different clinical symptoms. Both belong to various disease entities, and may occur in combination or be isolated. Increased vasodilation and vasopermeability is a common feature. Histamine and bradykinin are well-known mediators. For clinical purposes, 3 groups of diseases can be differentiated: diseases with urticaria and angioedema, diseases with angioedema alone, and diseases with urticarial lesions without angioedema. The article presents an overview of these groups and the role of the main mediators, and the clinical features of urticaria and angioedema.
Hasei, K; Ichihashi, M
A 42-year-old woman acquired solar urticaria approximately ten minutes after exposure to sunlight. Urticaria developed from visible light emitted from a projector lamp after a similar time lag. Monochromatic rays between 400 and 500 nm induced immediate urticaria by irradiation, with four times the minimal urticarial dose. Urticaria that was induced by monochromatic rays of the projector lamp was completely inhibited by immediate reirradiation of test sites with light waves longer that 530 nm. Radiant heat exposure from an electric hair dryer at 50 degrees C had no suppressive effects on the development of urticarial lesions.
Kutlu, A; Karabacak, E; Aydin, E; Ozturk, S; Bozkurt, B
In this case report, successful use of omalizumab in the treatment of chronic urticarial and angioedema in a 24-year-old female patient with an allergic reaction history to almost every drug including steroids and antihistamines was presented. She also had allergy against a large number of foods, which were confirmed by oral provocation, specific Immunoglobulin E and allergy skin test.
Vasculitis can affect the peripheral nervous system alone (nonsystemic vasculitic neuropathy) or can be a part of primary or secondary systemic vasculitis. In cases of pre-existing systemic vasculitis, the diagnosis can easily be made, whereas suspected vasculitic neuropathy as initial or only manifestation of vasculitis requires careful clinical, neurophysiological, laboratory and histopathological workout. The typical clinical syndrome is mononeuropathia multiplex or asymmetric neuropathy, but distal-symmetric neuropathy can frequently be seen. Standard treatments include steroids, azathioprine, methotrexate and cyclophosphamide. More recently the B-cell antibody rituximab and intravenous immunoglobulins have shown to be effective in some vasculitic neuropathy types.
Rheumatoid Arthritis; Spondyloarthritis; Psoriatic Arthritis; Systemic Lupus Erythematosus; Antiphospholipid Syndrome; Sjogren Syndrome; Scleroderma; Myositis; Vasculitis; Mastocytosis; Various Autoimmune and/or Systemic and/or Rare Diseases
Vasculitis can affect the peripheral nervous system alone (nonsystemic vasculitic neuropathy) or can be a part of primary or secondary systemic vasculitis. In cases of pre-existing systemic vasculitis, the diagnosis can easily be made, whereas suspected vasculitic neuropathy as initial or only manifestation of vasculitis requires careful clinical, neurophysiological, laboratory and histopathological workout. The typical clinical syndrome is mononeuropathia multiplex or asymmetric neuropathy, but distal-symmetric neuropathy can frequently be seen. Standard treatments include steroids, azathioprine, methotrexate and cyclophosphamide. More recently the B-cell antibody rituximab and intravenous immunoglobulins have shown to be effective in some vasculitic neuropathy types. PMID:25829955
Bousquet Muylaert, Bianca Pinheiro; Braga, Bruna Backsmann; Esteves, Eduarda Braga; Garbelini, Luciana Elisa Barandas; Michalany, Alexandre Ozores; de Oliveira Filho, Jayme
Lupus tumidus is considered a rare subtype of chronic cutaneous lupus erythematosus, characterized by erythema and bright urticarial erythematous-violaceous lesions that leave no scars after regression. Histopathology reveals perivascular and periannexal lymphohistiocytic infiltrates in the papillary and reticular dermis and interstitial mucin deposition. Treatment is based on photoprotection, topical corticosteroids and antimalarials. We report two cases of lupus tumidus, which deserve attention for their low frequency in the literature, in addition to their relevance as a differential diagnosis among dermatologic disorders.
Corpus, L D; Corpus, K M
Cat fleas, Ctenocephalides felis Bouchet, were collected at a Mississippi child care facility after reports of large numbers of adult fleas occurring on children and personnel. One building yielded 161 (99 percent) of the fleas collected. Urticarial lesions due to flea bites occurred on the legs of six children. Flea presence was due to cats occupying the crawl space. Fleas were eradicated by eliminating entry of cats and using residual insecticides throughout the facility.
Ter Poorten, Maryanna C; Prose, Neil S
The incidence of skin disease secondary to infestation with the human bedbug, Cimex lectularius, has increased dramatically in the United States and in the United Kingdom. We describe a child with a recurrent pruritic eruption of urticarial, erythematous papules on the face, neck, and extremities. The etiology of her cutaneous lesions was discovered to be a bedbug infestation in the home. The epidemiology, entomology, presentation, and treatment of bedbugs and their bites are discussed.
Galicia-Curiel, María Fernanda; Quintanar, J Luis; Jiménez, Mariela; Salinas, Eva
Mast cells and histamine participate in toxic effects of hairs from some caterpillars. This study reports that a crude extract of Morpheis ehrenbergii caterpillar hairs induces in vitro mast cells activation, triggers the release of histamine and causes a rapid urticarial reaction in the rat skin. Heating of the extract abolishes the inflammatory reaction. These results suggest that the use of antihistamines may improve the adverse skin reactions caused by the Mexican caterpillar M. ehrenbergii.
portion " Post Transfusion Data" of Section III - Record of Transfusion, must be completed and signed. The first copy of the completed SF 518 must be placed...hemoglobinuria, hemoglobinemia; 2) one 7 ml lavender top tube and two 7 ml red top tubes; 3) one freshly voided post -reaction urine; 4) the blood container and...anaphylactic, septic or infectious and post -transfusion hepatitis. Simple urticarial reactions with no change in vital signs need not be reported. The details
Hawkins, Kellie L.; Janoff, Edward N.; Janson, Robert W.
Immunologic phenomena can complicate chronic infections with Coxiella burnetii (Q fever), including immune complex deposition causing vasculitis, neuropathy, and glomerulonephritis. We describe the case of a man with Q fever endocarditis, mixed cryoglobulinemia, and life-threatening vasculitis driven by immune complex deposition who was successfully treated with B cell depleting therapy (rituximab). PMID:28203574
Baratta, John M.; Dyck, P. James B.; Brand, Patricio; Thaisetthawatkul, Pariwat; Dyck, Peter J.; Engelstad, JaNean K.; Goodman, Brent
Objective: To report 3 patients with minocycline-induced autoimmunity resulting in peripheral nerve vasculitis. Methods: We report 3 patients who, during minocycline treatment for acne vulgaris, developed subacute onset of pain and weakness caused by vasculitis in single and multiple mononeuropathy patterns. Results: Each patient underwent either a nerve or muscle biopsy that confirmed vasculitis. One patient additionally developed systemic symptoms (including fever, fatigue, and night sweats) and another had a posterior circulation stroke. Symptoms developed with either early or prolonged use of minocycline. Despite withdrawal of minocycline, patients needed long-term immunotherapy to gain neurologic improvement. Conclusions: Our findings suggest that the typical neuropathy associated with minocycline use is painful single or multiple mononeuropathy due to peripheral nerve vasculitis, which may also be accompanied by presumed CNS vasculitis (presenting as stroke). PMID:26601119
Gadde, Shilpa; Lee, Belinda; Kidd, Laura; Zhang, Rubin
Antineutrophil cytoplasmic antibodies (ANCA) are well known to be associated with several types of vasculitis, including pauci-immune crescentic glomerulonephritis, a form of rapid progressive glomerular nephritis (RPGN). ANCA vasculitis has also been reported after administration of propylthiouracil, hydralazine, cocaine (adulterated with levimasole), allopurinol, penicillamine and few other drugs. All previously reported cases of drug-associated ANCA glomerulonephritis were in native kidneys. Sofosbuvir is a new and effective drug for hepatitis C virus infection. Here, we report a case of ANCA vasculitis and RPGN following sofosbuvir administration in a kidney transplant recipient. It also represents the first case of drug-associated ANCA vasculitis in a transplanted kidney. Further drug monitoring is necessary to elucidate the degree of association and possible causal effect of sofosbuvir and perinuclear ANCA vasculitis. PMID:27872837
Although "biocompatible" polymeric elastomers are generally nontoxic, nonimmunogenic, and chemically inert, implants made of these materials may trigger acute and chronic inflammatory responses. Early interactions between implants and inflammatory cells are probably mediated by a layer of host proteins on the material surface. To evaluate the importance of this protein layer, we studied acute inflammatory responses of mice to samples of polyester terephthalate film (PET) that were implanted intraperitoneally for short periods. Material preincubated with albumin is "passivated," accumulating very few adherent neutrophils or macrophages, whereas uncoated or plasma- coated PET attracts large numbers of phagocytes. Neither IgG adsorption nor surface complement activation is necessary for this acute inflammation; phagocyte accumulation on uncoated implants is normal in hypogammaglobulinemic mice and in severely hypocomplementemic mice. Rather, spontaneous adsorption of fibrinogen appears to be critical: (a) PET coated with serum or hypofibrinogenemic plasma attracts as few phagocytes as does albumin-coated material; (b) in contrast, PET preincubated with serum or hypofibrinogenemic plasma containing physiologic amounts of fibrinogen elicits "normal" phagocyte recruitment; (c) most importantly, hypofibrinogenemic mice do not mount an inflammatory response to implanted PET unless the material is coated with fibrinogen or the animals are injected with fibrinogen before implantation. Thus, spontaneous adsorption of fibrinogen appears to initiate the acute inflammatory response to an implanted polymer, suggesting an interesting nexus between two major iatrogenic effects of biomaterials: clotting and inflammation. PMID:8245787
Huang, C-Y; Trask, R S; Bond, I P
A study of the influence of embedded circular hollow vascules on structural performance of a fibre-reinforced polymer (FRP) composite laminate is presented. Incorporating such vascules will lead to multi-functional composites by bestowing functions such as self-healing and active thermal management. However, the presence of off-axis vascules leads to localized disruption to the fibre architecture, i.e. resin-rich pockets, which are regarded as internal defects and may cause stress concentrations within the structure. Engineering approaches for creating these simple vascule geometries in conventional FRP laminates are proposed and demonstrated. This study includes development of a manufacturing method for forming vascules, microscopic characterization of their effect on the laminate, finite element (FE) analysis of crack initiation and failure under load, and validation of the FE results via mechanical testing observed using high-speed photography. The failure behaviour predicted by FE modelling is in good agreement with experimental results. The reduction in compressive strength owing to the embedding of circular vascules ranges from 13 to 70 per cent, which correlates with vascule dimension.
Huang, C.-Y.; Trask, R. S.; Bond, I. P.
A study of the influence of embedded circular hollow vascules on structural performance of a fibre-reinforced polymer (FRP) composite laminate is presented. Incorporating such vascules will lead to multi-functional composites by bestowing functions such as self-healing and active thermal management. However, the presence of off-axis vascules leads to localized disruption to the fibre architecture, i.e. resin-rich pockets, which are regarded as internal defects and may cause stress concentrations within the structure. Engineering approaches for creating these simple vascule geometries in conventional FRP laminates are proposed and demonstrated. This study includes development of a manufacturing method for forming vascules, microscopic characterization of their effect on the laminate, finite element (FE) analysis of crack initiation and failure under load, and validation of the FE results via mechanical testing observed using high-speed photography. The failure behaviour predicted by FE modelling is in good agreement with experimental results. The reduction in compressive strength owing to the embedding of circular vascules ranges from 13 to 70 per cent, which correlates with vascule dimension. PMID:20150337
Patnala, Guru Prasad; Sunandini, Anila P; Rayavarapu, Rama; Yandapalli, Padmasri Somala
Erythema elevatum diutinum (EED) is a rare form of vasculitis characterized clinically by red-violet brown papules, plaques, and nodules mainly involving the extensor surfaces; histologically by leukocytoclastic vasculitis in early lesions, and fibrosis and cholesterolosis in late lesions. EED has been associated with many systemic disorders including infections, autoimmune disorders, and both benign and malignant hematological disorders. As it is a rare form of vasculitis and only 250 cases reported till date, we report a case of EED in association with IgA monoclonal gammopathy with partial response to dapsone treatment.
Esdaile, J.; Hawkins, D.; Gold, P.; Freedman, S. O.; Duguid, W. P.
Review of four cases of relapsing polychondritis (RP) seen at one hospital in the 12-year period 1963 to 1974 revealed that one patient had aortic insufficiency with large artery involvement, two others had involvement of medium and large arteries and the fourth may have had mucocutaneous vasculitis. Valvular disease has occurred in 9% of all cases of RP reported in the literature and, if vasculitis beyong the aortic root is included, 25% of cases of RP manifested inflammatory vascular disease. The frequency of pseudotumour of the orbit and cochlear-labyrinthine dysfunction is also high and may be a manifestation of vasculitis. PMID:870159
Babar, Faizan; Posner, Jeffery N.; Obah, Eugene A.
Hydralazine has been used since the 1950s for the management of hypertension. Evidence for hydralazine-associated vasculitis dates to pre-ANCA (antineutrophil cytoplasmic antibodies) era. This abstract describes two cases of ANCA-positive pauci-immune glomerulonephritis (GN) in challenging scenarios where diagnosis was misconstrued. A comprehensive literature review was done to understand the pathogenesis of drug-induced pauci-immune GN. We have described key diagnostic features that are helpful in distinguishing idiopathic ANCA vasculitis from drug-induced vasculitis. Additionally, we have also described different treatments meant to provide therapy options with the least side effects. PMID:27124161
Babar, Faizan; Posner, Jeffery N; Obah, Eugene A
Hydralazine has been used since the 1950s for the management of hypertension. Evidence for hydralazine-associated vasculitis dates to pre-ANCA (antineutrophil cytoplasmic antibodies) era. This abstract describes two cases of ANCA-positive pauci-immune glomerulonephritis (GN) in challenging scenarios where diagnosis was misconstrued. A comprehensive literature review was done to understand the pathogenesis of drug-induced pauci-immune GN. We have described key diagnostic features that are helpful in distinguishing idiopathic ANCA vasculitis from drug-induced vasculitis. Additionally, we have also described different treatments meant to provide therapy options with the least side effects.
Katz, S M; Korn, S; Umlas, S L; DeHoratius, R J
In the past, necrotizing vasculitis has been considered to be one of the dominant intrarenal vascular abnormalities in systemic lupus erythematosus (SLE). To test the validity of this statement, 70 consecutive renal biopsies from patients with SLE were reviewed. Light microscopy (LM) and immunofluorescence (IF) studies documented abnormalities, including thrombosis and nephrosclerosis, in 30 patients (43 percent), but no cellular infiltration of the vessel walls or other evidence of acute necrotizing vasculitis was seen. It is concluded that while intrarenal vasculopathy with thrombosis and nephrosclerosis is a common finding in SLE, our data and recently published studies suggest that acute necrotizing vasculitis occurs rarely, if at all, in SLE nephritis.
Patnala, Guru Prasad; Sunandini, Anila P.; Rayavarapu, Rama; Yandapalli, Padmasri Somala
Erythema elevatum diutinum (EED) is a rare form of vasculitis characterized clinically by red-violet brown papules, plaques, and nodules mainly involving the extensor surfaces; histologically by leukocytoclastic vasculitis in early lesions, and fibrosis and cholesterolosis in late lesions. EED has been associated with many systemic disorders including infections, autoimmune disorders, and both benign and malignant hematological disorders. As it is a rare form of vasculitis and only 250 cases reported till date, we report a case of EED in association with IgA monoclonal gammopathy with partial response to dapsone treatment. PMID:27559509
... Churg and Strauss discovered that the presence of granulomas as well as the abundance of eosinophils distinguished ... vasculitic) are occasionally found in the GI tract Granuloma sometimes found in spleen Heart Vasculitis lesions in ...
Behcet's syndrome is a disease that involves vasculitis, which is inflammation of the blood vessels. It causes problems in many parts of the body. The ... National Institute of Arthritis and Musculoskeletal and Skin Diseases
... skull Bulging of a blood vessel in the brain ( aneurysm ) Abnormal connection between the arteries and veins in ... Editorial team. Related MedlinePlus Health Topics Arteriovenous Malformations Brain Aneurysm Vascular Diseases Vasculitis X-Rays Browse the Encyclopedia ...
Diabetic Foot; Varicose Ulcer; Pressure Ulcer; Surgical Wound Dehiscence; Vasculitis; Skin Ulcer; Leg Ulcer; Wounds and Injuries; Pyoderma; Peripheral Arterial Disease; Diabetic Neuropathies; Lymphedema; Venous Insufficiency; Diabetes Complications; Amputation Stump
Iannella, Giannicola; Greco, Antonio; Granata, Guido; Manno, Alessandra; Pasquariello, Benedetta; Angeletti, Diletta; Didona, Dario; Magliulo, Giuseppe
Granulomatosis with polyangiitis (GPA) is an autoimmune systemic necrotizing small-vessel vasculitis associated with the presence of anti-neutrophil cytoplasmic antibodies (ANCA). Oto-neurological manifestations of ANCA-associated vasculitis according to PR3-ANCA positivity and MPO-ANCA positivity are usually reported. Facial nerve palsy is usually reported during the clinical course of the disease but it might appear as the presenting sign of GPA. Necrotizing vasculitis of the facial nerve 'vasa nervorum' is nowadays the most widely accepted etiopathogenetic theory to explain facial damage in GPA patients. A central role for PR3-ANCA in the pathophysiology of vasculitis in GPA patients with oto-neurological manifestation is reported. GPA requires prompt, effective management of the acute and chronic manifestations. Once the diagnosis of GPA has been established, clinicians should devise an appropriate treatment strategy for each individual patient, based on current clinical evidence, treatment guidelines and recommendations.
... Matters NIH Research Matters August 12, 2013 Mutated Genes in Schizophrenia Map to Brain Networks Schizophrenia networks in the prefrontal ... Vasculitis Therapy as Effective as Standard Care Mutated Genes in Schizophrenia Map to Brain Networks Connect with Us Subscribe to ...
... t o s i s , Microscopic polyangiitis, Churg-Strauss syndrome, Behcet’s disease, and others. The decision to recommend MTX is ... MTX if you have moderate to severe kidney disease. Please consult the Vasculitis Center ...
Juvenile Idiopathic Arthritis; Systemic Lupus Erythematosus; Mixed Connective Tissue Disease; Juvenile Ankylosing Spondylitis; Juvenile Dermatomyositis; Localized Scleroderma; Systemic Sclerosis; Vasculitis; Sarcoid; Fibromyalgia, Primary; Auto-inflammatory Disease; Idiopathic Uveitis Idiopathic
Romero, J J; Herrera, P; Cartelle, M; Barba, P; Tello, S; Zurita, J
We report the first case of recently characterized species M. monacense associated with chronic nodular vasculitis, infecting a young woman. This case represents the first isolation of M. monacense from Ecuador. The isolate was identified by conventional and molecular techniques.
Granulomatosis with polyangiitis (GPA), previously known as Wegener's granulomatosis, is a rare disease. It is a type of vasculitis, or inflammation of the blood vessels. The inflammation limits the flow of ...
Rheumatoid Arthritis; Spondyloarthritis; Systemic Lupus Erythematosus (SLE); Dermatomyositis (DM); DMixed Connective Tissue Disease; Systemic Vasculitis; Systemic Sclerosis (SSc); Sjögren's Syndrome; Antiphospholipid Syndrome; Juvenile Idiopathic Arthritis; Juvenile SLE; Juvenile DM
... Loss of axon tissue Metabolic neuropathies Necrotizing vasculitis Sarcoidosis Risks Allergic reaction to the local anesthetic Discomfort ... Neurosarcoidosis Peripheral neuropathy Primary amyloidosis Radial nerve dysfunction Sarcoidosis Tibial nerve dysfunction Review Date 6/1/2015 ...
... disorders Uremia (a result of kidney failure ) Von Willebrand disease (a bleeding disorder) Risks There is very little ... vasculitis Platelet count Polycythemia vera Prerenal azotemia Von Willebrand disease Review Date 1/27/2015 Updated by: Yi- ...
... symptoms include: Chest pain when taking a breath (pleurisy) Dry eyes and mouth (Sjogren syndrome) Eye burning, ... replacement Hypersensitivity vasculitis Joint pain Knee joint replacement Pleurisy Ulcers Patient Instructions ACL reconstruction - discharge Ankle replacement - ...
Baqir, Misbah; Usman, Mohammed Haris Umer; Adenwalla, Humaira N; Aziz, Saqib; Noor, Fazle; ul- Islam, Tasbir; Ahmed, Mansoor; Hotiana, Mateen
We report a case of Crohn's disease that was associated with marked dermatologic manifestations depicting necrotizing vasculitis around the ankles. On further evaluation, this patient was found to have aortic narrowing, which fit the criteria for Takayasu's arteritis.
... vasculitis), lupus or sickle cell anemia Cocaine or methamphetamine use Colon cancer (rare) The role of medications ... may recommend these imaging tests: Ultrasound and abdominal CT scans, to provide images of your colon that ...
... adults with cutaneous lesions of vasculitis. http://www.uptodate.com/home. Accessed March 10, 2015. Raffini L. Evaluation of purpura in children. http://www.uptodate.com/home. Accessed March 10, 2015. Boos SC, ...
... vessel vasculitis such as hypertension from renal artery stenosis, aortic regurgitation from aortitis, or stroke from carotid artery ... active disease. Diagnosis is confirmed by angiography showing stenosis and dilation of the aorta, its branches, or both. Thickening of the aortic ...
Benson, C.H.; Pennebaker, J.B.; Harisdangkul, V.; Songcharoen, S.
A patient with known systemic lupus erythematosus had fever and symptoms of a lower urinary tract infection. Bone scintigraphy showed left ureteral perforation and necrosis with no demonstrable nephrolithiasis. It is speculated that this episode was due to lupus vasculitis.
Sampaio, Luzia; Silva, Lã Gia; Terroso, Georgina; Nadais, Goreti; Mariz, Eva; Ventura, Francisco
Vasculitic neuropathy corresponds to the occurrence of vasculitis at the level of vasa nervorum, resulting in ischemic damage of the peripheral nerve and axonal degeneration. Vasculitic neuropathy commonly occurs in association with systemic diseases and may be the initial manifestation or arise in the course of established disease. Although rare, vasculitis can be confined to the peripheral nervous system - non-systemic vasculitic neuropathy. This paper aims to review the classification, diagnosis and treatment of vasculitic neuropathy.
Van Haare Heijmeijer, Sophie; Wilmes, Dunja; Aydin, Selda; Clerckx, Caroline; Labriola, Laura
Infective endocarditis (IE) and small-vessel vasculitis may have similar clinical features, including glomerulonephritis. Furthermore the association between IE and ANCA positivity is well documented, making differential diagnosis between IE- and ANCA-associated vasculitis particularly difficult, especially in case of culture-negative IE. We report on one patient with glomerulonephritis secondary to culture-negative IE caused by Bartonella henselae which illustrates this diagnostic difficulty. PMID:26819786
Kalinke, D U; Wüthrich, B
A 58 year old patient with hepatitis virus C (HCV) infection had a secondary polyclonal IgG-IgM cryoglobulinemia with a benign 20 year course. Clinically the patient suffered from progressive pigmented purpura (PPP). Histologic evaluation revealed a lymphocytic vasculitis. Food containing tartrazine triggered flares of the PPP, as demonstrated with controlled oral provocation testing. In most of the previously described cases of HCV and type III cryoglobulinemia, the typical cutaneous finding was palpable purpura with leukocytoclastic vasculitis.
Rupala, Ketankumar; Mittal, Varun; Gupta, Rajiv; Yadav, Rajiv
Pheochromocytoma has atypical presentation in 9%–10% of patients. Atypical presentations include myocardial infarction, renal failure, and rarely cerebrovascular events. Various etiologies for central nervous system (CNS) involvement in pheochromocytoma have been described in the literature. A rare association of CNS vasculitis-like features has been described with pheochromocytoma. We report a rare case of pheochromocytoma detected on evaluation for CNS vasculitis-like symptoms. PMID:28197038
Torraca, Pedro de Freitas Silva; de Castro, Bruna Corrêa; Hans Filho, Günter
The Henoch-Schönlein purpura is the vasculitis associated with deposits of immunoglobulin A in small vessels. Its association with cytoplasmic antineutrophil cytoplasmic antibodies is possible, but rare. This vasculitis is uncommon in adults and the main clinic manifestations are purpuric lesions in lower limbs with gastrointestinal symptoms and renal involvement. The present work describes a rare case of Henoch-Schönlein purpura in an adult with cytoplasmic antineutrophil cytoplasmic antibodies. PMID:27828648
Bastug, Demir E.; Dominic, Anthony; Ortiz, Orlando; DiBartolomeo, Anthony G.; Kotzan, Jeffrey M.; Abraham, F. Matthew
A 31-year-old woman with Cogan syndrome (a rare form of systemic vasculitis) was evaluated for a cold, painful left foot with diminished pulses. Arteriography demonstrated thrombosis of the left popliteal artery with evidence of vasculitis. Thrombolytic therapy was begun with initial success but eventual rethrombosis. After reinitiating thrombolytic therapy combined with intraarterial vasodilator therapy, successful angioplasty was performed with sustained results, at 6-month follow-up.
Mahmoodian, Reihaneh; Haghighi, Anoosheh; Vakili, Masoud; Shahriari-Ahmadi, Ali; Hajsadeghi, Shokoufeh; Arabi, Mohsen
Secondary systemic vasculitis and nonbacterial endocarditis are rare events. We report a case presented with different manifestations of underlying malignancy such as systemic vasculitis, non bacterial endocarditis and DIC (disseminated intravascular coagulopathy). Efforts to find the source of malignancy was unsuccessful and due to patient's unwillingness for further evaluation, finally under the diagnosis of metastatic disease of unknown primary, patient is receiving cyclic chemotherapy. PMID:24505550
Pang, S; Fiume, M Z
incidence of urticarial reactions was performed with 17.5% Ammonium, Potassium, and Sodium Persulfate under occlusive patches. At this concentration and exposure conditions, a mixture of these Persulfates was not sensitizing, and application of Ammonium, Potassium, and Sodium Persulfate did not result in an urticarial reaction. In normal use (i.e., not occluded and rinsed off), it was expected that a concentration greater than 17.5% would also be safe. Given the clinical reports of urticarial reactions, however, manufacturers and formulators should be aware of the potential for urticarial reactions at concentrations of Persulfates greater than 17.5%. Based on the available data, the Cosmetic Ingredient Review (CIR) Expert Panel concluded that Ammonium, Potassium, and Sodium Persulfate are safe as used as oxidizing agents in hair colorants and lighteners designed for brief discontinuous use followed by thorough rinsing from the hair and skin.
Zhao, Cathy Y.; Murrell, Dedee F.
Bullous pemphigoid (BP) is the commonest subtype of autoimmune blistering disease in most countries of the world. It occurs most frequently in elderly patients and is characterised clinically by large, tense blisters in the skin preceded by urticarial plaques and pruritus. Immunopathologically, it is characterised by autoantibodies directed against the 180 kD antigen (BP180) and the 230 kD antigen (BP230). New knowledge regarding BP is being continually uncovered. This article reviews the recent advances in BP, including newer diagnostic tests, standardised outcome measures and emerging therapeutic options, as well as the evidence supporting their use. PMID:26918143
Colosio, C; Tomasini, M; Cairoli, S; Foà, V; Minoia, C; Marinovich, M; Galli, C L
A case of triphenyltin acetate (TPTA) poisoning is described. The patient, who had been exposed mainly to cutaneous absorption, showed acute stages of an urticarial eruption, signs of hepatic injury, slight glucose intolerance, and electroencephalographic abnormalities. Concomitant with the highest concentrations of tin in plasma and the peak of tin excretion in urine, neutrophils did not show the normal increase in actin polymerisation after stimulation with a chemotactic peptide (100 nM fMLP). The peak of urinary excretion of tin occurred between the fifth and the sixth day after poisoning; subsequently, the rate of excretion became slow, suggesting biphasic kinetics with the possibility of a cumulative trend. Images PMID:1825604
Siddalingappa, Karjigi; Murthy, Sambasiviah Chidambara; Herakal, Kallappa; Kusuma, Marganahalli Ramachandra
Cutaneous larva migrans or creeping eruptions is a cutaneous dermatosis caused by hookworm larvae, Ancylostoma braziliense. A 2-month-old female child presented with a progressive rash over the left buttock of 4 days duration. Cutaneous examination showed an urticarial papule progressing to erythematous, tortuous, thread-like tract extending a few centimeters from papule over the left gluteal region. A clinical diagnosis of cutaneous larva migrans was considered. Treatment with albendazole led to complete resolution, confirming the diagnosis. This is to the best of our knowledge, the youngest age at which this condition is being reported. PMID:26538729
Abraham, Tina; Frith, John; Tcheurekdjian, Haig; Hostoffer, Robert
Cold urticaria and cholinergic urticaria are two distinct entities. The presentation of exclusive cold-induced cholinergic urticaria is very rare. The patient described herein had experienced urticaria in the exclusive setting of exercising in a cold environment. Urticarial testing including laboratory and in-office testing was all negative. The patient has prevented urticaria symptoms with oral antihistamine therapy. Pure cold-induced cholinergic urticaria is rarely described in literature. This form of urticaria has yet to be described in a pediatric patient. PMID:28025628
Özdemir, Özhan; Atalay, Cemal Resat; Asgarova, Vusala; Ilgin, Bunyamin Ugur
Pemphigoid gestationis (PG) is a rare autoimmune blistering disease of pregnancy caused by antibasement membrane zone auto-antibodies. The usual clinical findings are multiple pruritic urticarial papules and plaques, target lesions, vesicles, and blisters that occur during the second and third trimesters of pregnancy or in the immediate postpartum period. The disease is often treated with topical corticosteroids and oral antihistaminics. In more severe cases, systemic corticosteroids are needed. Herein, we report a case of resistant PG that responded to treatment with cyclosporine. PMID:28250977
Yamamoto, K; Kijima, M; Takahashi, T; Yoshimura, H; Tani, O; Kojyou, T; Yamawaki, Y; Tanimoto, T
Six strains of Erysipelothrix rhusiopathiae were isolated from farmed wild boars with acute septicemic erysipelas during the period from 1983 to 1998 in Japan. All isolates belonged to serovar 1a or 2 (predominant serovars in swine). The 50 per cent lethal dose values of those isolates ranged from 10(1.3)to 10(6.2)colony forming units in mice. In swine, all isolates were virulent, capable of inducing localized or generalized urticarial lesions after intradermal inoculation. All of the isolates were resistant to oxytetracycline and/or dihydrostreptomycin. These observations suggest that E. rhusiopathiae strains isolated from wild boars may have aetiological significance in swine erysipelas.
Vasculitic peripheral neuropathy (VPN) occurs due to ischemic changes of peripheral nerves, resulting from a deficit of vascular blood supply due to damaged vasa nervorum leading to vasculitis. VPN usually manifests as sensorimotor or sensory disturbances accompanied by pain, presenting as a type of multiple mononeuropathy, with a scattered distribution in distal limbs. VPN may also present as a mononeuropathy, distal symmetric polyneuropathy, plexopathy, or radiculopathy. The rapidity of VPN is variable, ranging from days to months, with symptoms occasionally changing with the appearance of new lesions. Careful history taking and neurological examination provides an exact diagnosis. The most common cause of VPN is primary vasculitis predominantly affecting small vessels, including vasa nervorum, anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, and polyarteritis nodosa. Similar vasculitic processes can also result from a systemic collagen disorder or secondary vasculitis. Electrophysiological studies and pathological investigation of biopsied peripheral nerves and muscles are important for diagnosis of vasculitis. Serological tests, including ANCA, are useful for diagnosis of vasculitis. Accurate neurological examinations are essential for diagnosis and evaluation of clinical course.
Jokar, Mohammadhassan; Mirfeizi, Zahra
Vasculitides are a heterogeneous group of more than 20 diseases defined by inflammation and destruction of blood vessels. We aimed to study the demographic characteristics of the primary vasculitides in the North East of Iran. We retrospectively studied the medical records of patients diagnosed with any kind of vasculitis at the Clinic and Department of Rheumatology of the Imam Reza Hospital, Mashhad, Iran between January 1, 2002, and December 31, 2012. Patients were classified according to the American College of Rheumatology 1990 criteria for the classification of vasculitis and the 2012 Revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. A total of 721 patients (51.5% male, 48.5% female) with a diagnosis of primary vasculitis was identified. The frequency distributions of vasculitic disorders were as follows: Behcet’s disease, 63.6%; cutaneous leukocytoclastic angiitis, 8.2%; granulomatosis with polyangiitis (Wegener’s), 6.8%; Takayasu’s arteritis. 6%; giant cell arteritis, 4%; polyarteritis nodosa, 2.1%; microscopic polyangiitis, 0.6%; eosinophilic granulomatosis with polyangiitis (Churg-Strauss), 1.8%; cryoglobulinemic vasculitis, 0.3%; and IgA vasculitis (Henoch-Schonlein purpura), 3.5%. In our population, the most common forms of vasculitis are Behcet’s disease, cutaneous leukocytoclastic angiitis, and granulomatosis with polyangiitis (Wegener’s). PMID:26170524
The Schnitzler syndrome is a rare and underdiagnosed entity which is considered today as being a paradigm of an acquired/late onset auto-inflammatory disease. It associates a chronic urticarial skin rash, corresponding from the clinico-pathological viewpoint to a neutrophilic urticarial dermatosis, a monoclonal IgM component and at least 2 of the following signs: fever, joint and/or bone pain, enlarged lymph nodes, spleen and/or liver, increased ESR, increased neutrophil count, abnormal bone imaging findings. It is a chronic disease with only one known case of spontaneous remission. Except of the severe alteration of quality of life related mainly to the rash, fever and pain, complications include severe inflammatory anemia and AA amyloidosis. About 20% of patients will develop a lymphoproliferative disorder, mainly Waldenström disease and lymphoma, a percentage close to other patients with IgM MGUS. It was exceedingly difficult to treat patients with this syndrome until the IL-1 receptor antagonist anakinra became available. Anakinra allows a complete control of all signs within hours after the first injection, but patients need continuous treatment with daily injections. In many aspects, the Schnitzler syndrome resembles the genetically determined auto-inflammatory syndromes involving activating mutations of the NLRP3 inflammasome. This latter point and its consequences will be addressed. PMID:21143856
Cooke, Andrew; Bulkhi, Adeeb; Casale, Thomas B
Chronic urticaria (CU) is a common condition faced by many clinicians. CU has been estimated to affect approximately 0.5%–1% of the population, with nearly 20% of sufferers remaining symptomatic 20 years after onset. Antihistamines are the first-line therapy for CU. Unfortunately, nearly half of these patients will fail this first-line therapy and require other medication, including immune response modifiers or biologics. Recent advances in our understanding of urticarial disorders have led to more targeted therapeutic options for CU and other urticarial diseases. The specific biologic agents most investigated for antihistamine-refractory CU are omalizumab, rituximab, and intravenous immunoglobulin (IVIG). Of these, the anti-IgE monoclonal antibody omalizumab is the best studied, and has recently been approved for the management of CU. Other agents, such as interleukin-1 inhibitors, have proved beneficial for Schnitzler syndrome and cryopyrin-associated periodic syndromes (CAPS), diseases associated with urticaria. This review summarizes the relevant data regarding the efficacy of biologics in antihistamine-refractory CU. PMID:25926715
Homburger, H.A.; Smith, J.R.; Jacob, G.L.; Laschinger, C.; Naylor, D.H.; Pineda, A.A.
To enable the detection of IgG class, anti-IgA antibodies and to investigate the possible occurrence of IgE class, anti-IgA antibodies, we developed a solid phase immunoradiometric assay, which uses purified IgA coupled covalently to microcrystalline cellulose as an immunosorbent. Radiolabeled, Fc specific anti-IgG and anti-IgE antibodies were used to detect specific aIgA after incubation of test sera or controls with the immunosorbent. IgG-aIgA were detected by the IRA in 100 and 67% of control sera with class specific and limited specificity aIgA. The IRA was sensitive to approximately two ng of class specific IgG-aIgA. IgG-aIgA also were detected by IRA in 7.9% of sera from patients with urticarial transfusion reactions and 73% of sera from patients with ataxia telangiectasia and IgA deficiency. Sera from 50 normal blood donors did not have detectable IgG-aIgA. Tests for IgE-aIgA were negative in all cases, including control sera with class specific IgG-aIgA. We conclude that the IRA is a sensitive and reproducible method for detection of class specific and limited specificity IgG-aIgA, and that IgE-aIgA do not mediate urticarial transfusion reactions.
The Schnitzler syndrome is a rare and underdiagnosed entity which is considered today as being a paradigm of an acquired/late onset auto-inflammatory disease. It associates a chronic urticarial skin rash, corresponding from the clinico-pathological viewpoint to a neutrophilic urticarial dermatosis, a monoclonal IgM component and at least 2 of the following signs: fever, joint and/or bone pain, enlarged lymph nodes, spleen and/or liver, increased ESR, increased neutrophil count, abnormal bone imaging findings. It is a chronic disease with only one known case of spontaneous remission. Except of the severe alteration of quality of life related mainly to the rash, fever and pain, complications include severe inflammatory anemia and AA amyloidosis. About 20% of patients will develop a lymphoproliferative disorder, mainly Waldenström disease and lymphoma, a percentage close to other patients with IgM MGUS. It was exceedingly difficult to treat patients with this syndrome until the IL-1 receptor antagonist anakinra became available. Anakinra allows a complete control of all signs within hours after the first injection, but patients need continuous treatment with daily injections.In many aspects, the Schnitzler syndrome resembles the genetically determined auto-inflammatory syndromes involving activating mutations of the NLRP3 inflammasome. This latter point and its consequences will be addressed.
Batur, Abdussamet; Dorum, Meltem; Yüksekkaya, Hasan Ali; Koc, Osman
Behcet's disease is a multisystemic vasculitis of unknown etiology with a chronic relapsing course. Vasculitis in Behcet's disease with predominant vascular involvement is the only vasculitis that affects both arteries and veins of any size. Involvement of the renal artery and inferior vena cava is rare among the arteries and veins, respectively. When disease affect the veins, it is in the form of thrombosis. Arterial complications include aneurysms, stenosis and occlusions. Both rupture of arterial aneurysm and occlusion of suprahepatic veins, causing Budd-Chiari syndrome, are associated with a high mortality rate. Vascular involvement is more common in male patients than in female patients. Men and patients with a younger age of onset present with a more severe prognosis. In this case report, we describe a very rare cause of intrarenal arterial aneurysm's rupture with previous Budd-Chiari syndrome due to Behcet's disease and successful angiographic embolization of actively bleeding aneurysm.
Spísek, Radek; Kolouchová, Elena; Jensovský, Jirí; Rusina, Robert; Fendrych, Pavel; Plas, Jaroslav; Bartůnková, Jirina
Wegener granulomatosis (WG) is a systemic vasculitis of small and medium vessels. It predominantly affects the upper and/or lower respiratory airway and kidneys. Its pathogenesis is not fully understood. WG relatively frequently affects the nervous system (in 30-50% according to the different studies). Most frequently, it manifests as necrotizing vasculitis that leads to the peripheral neuropathies or to the cranial nerves palsy. Impairment of the central nervous system (CNS) is less frequent and occurs in 2-8% of patients. Three major pathogenetic mechanisms were described: CNS vasculitis, spreading of granulomas from the adjacent anatomical areas (paranasal cavities, orbit etc.), and new formation of granulomas in brain tissue. This case report describes patients in whom WG manifested in the form of localized skin involvement and combined CNS involvement that included pituitary gland. Atypical presentation of WG impedes and slows down the process of diagnosis and emphasizes the need for collaboration between medical specialists.
Ocaña Pérez, E; Peña Casas, A M; del Campo Muñoz, T; Avila Casas, A; Luque Barona, R
Wegener's granulomatosis belongs to the group of small vessel vasculitis associated with anti-neutrophil cytoplasmic antibodies characterized by granulomatous inflammation and necrotising vasculitis in various organs with particular involvement of the upper and lower respiratory tracts and kidneys. Wegener's granulomatosis is a rare disorder in childhood and early diagnosis of this disease is critical to the long-term prognosis of the disease. The presence of positive cytoplasmic antineutrophil cytoplasmic antibody staining or a high titre of proteinase 3 antibodies were added as new criteria of vasculitis in childhood. This article presents a case of Wegener's granulomatosis, with the presence of anti-neutrophil cytoplasm antibodies with cytoplasmic pattern with absence of anti-proteinase 3 antibodies and presence of high levels of anti-cathepsin G antibodies, rarely described in Wegener's granulomatosis.
Chen, Pei-Hsuan; Chiang, Bor-Luen; Lu, Meng-Yao; Yang, Yao-Hsu
Mucosa-associated lymphoid tissue lymphoma (MALToma) is a type of B-cell lymphoma. Case reports of childhood thymic MALToma and its association with vasculitis are rarely found in the related literature. Herein, we present a report of an 11-year and 10-month-old girl who was initially diagnosed with cutaneous vasculitis characterized by nonthrombocytopenic palpable purpura, positive antinuclear antibody and anti-SSA (Ro) antibody. Eight months later, a thymic mediastinal mass was found. Surgical excision was performed and results of pathological analysis revealed an extranodal marginal zone CD20(+) B-cell MALToma. Benign response to the chemotherapeutic regimen of Berlin-Frankfurt-Münster group NHL-BFM 90 R2 without relapse was noted in 2 years of follow-up. For the first time, our case demonstrated some clinical evidence of the association between vasculitis and childhood MALToma.
García-Nava, Marcos; Mateos-Toledo, Heidegger; Guevara-Canseco, Ana Patricia Georgina; Infante-González, Cesar Eduardo; Reyes-Nava, Diego Alberto; Estrada-Castro, Emilio
Microscopic polyangiitis (MPA) is a systemic disease included in the Chapel Hill 2012 Classification as necrotizing vasculitis affecting capillaries, venules and arterioles. It usually expresses antineutrophil cytoplasmic antibodies (ANCA) and has a perinuclear immunofluorescence pattern and correlation with anti-myeloperoxidase (MPO) antibodies. Capillaritis with alveolar hemorrhage is the most common manifestation of lung disease. Interstitial lung disease (ILD) is uncommon, with usual interstitial pneumonia being the predominant pattern. However, other patterns such as organizing pneumonia have been described. No guidelines exist for treating patients with ILD and, currently, ANCA-associated vasculitis (AAV) is managed along the lines of small vessel vasculitis. The prognosis with this association is uncertain, with possibilities of relapse and a fatal outcome. We present a case in which ILD was the first manifestation of MPA, without alveolar hemorrhage, with subsequent renal involvement and, in which, the established treatment produced a significant clinical improvement.
Kogan, E A; Grusha, Ya O; Ismailova, D S; Novikov, P I; Abramova, Yu V; Meshkov, A D; Rizopulu, E F
Orbital granulomatosis with polyangiitis (Wegener's granulomatosis, GPA), which is characterized by granulomatous inflammation with small-vessel vasculitis, can develop in local and generalized forms of the disease. The introduction of current immunosuppressive therapy regimens has improved the prognosis of the disease; however, there are immunosuppressive treatment-refractory forms of GPA, the morphology of which has been inadequately investigated. The paper describes a clinical case of refractory GPA involving the orbit, as evidenced by histological and immunohistochemical examinations. The specific feature of the case is the development of severe fibrosis with the accumulation of mainly type III collagen and the persistence of granulomatous inflammation and productive-destructive vasculitis.
Tsetsou, S; Michel, P; Ribi, C; Hirt, L; Kawasaki, A; Hugli, O; De Leval, L; Bart, P-A; Waeber, G; Meuli, R; Raffoul, W; So, A; Du Pasquier, R
Giant cell arteritis (GCA) is a subacute/chronic vasculitis and represents the most common form of systemic vasculitis in people over the age of 50 years. The absence of clear and specific diagnostic criteria with the highly variable clinical presentation is a diagnostic challenge requesting a multidisciplinary approach. Yet, GCA is an emergency and the treatment must be initiated very rapidly due to the risk of blindness. This article presents a review of GCA as well as the diagnostic and therapeutic institutional guidelines of the University Hospital of Lausanne.
Roscoe, Clay; Kinney, Rebecca; Gilles, Ryan; Blue, Sky
Behçet's disease is an autoimmune systemic vasculitis that can occur after exposure to infectious agents. Behçet's disease also has been associated with HIV infection, including de novo development of this condition during chronic HIV infection and resolution of Behçet's disease symptoms following initiation of antiretroviral therapy. We describe a patient who presented with systemic vasculitis with skin and mucous membrane ulcerations in the setting of acute HIV infection, who was eventually diagnosed with Behçet's disease, demonstrating a possible link between acute HIV infection, immune activation and development of autoimmunity.
Vacula, I; Ambrózy, E; Makovník, M; Stvrtina, S; Babál, P; Stvrtinová, V
Cryoglobulinemia is a rather rare condition accompanying quite a broad spectrum of different states and diseases. Mixed or polyclonal cryoglobulins can be seen in patients with autoimmune disorders, chronic infections and lymphoproliferative disorders. Monoclonal cryoglobulins are often revealed in patients with multiple myeloma or Waldenström's macroglobulinemia. Cryoglobulinemia is in most cases asymptomatic. Cryoglobulinemic vasculitis is an immune complex-mediated systemic disorder involving mostly small, but sometimes also larger vessels. In this report, we describe a case of a patient presented with gangrene of almost all fingers and toes, who was finally diagnosed and treated as cryoglobulinemic vasculitis due to multiple myeloma.
Ng, Felix; Chiong, Fabian Joon Kiong; Buchanan, Russell; Burrell, Louise M
Behçet disease (BD) is a rare relapsing, multisystem vasculitis characterised by recurrent oral and genital ulcers, and uveitis. As an autoimmune small vessel vasculitis, BD can involve other organs including the skin, joints, nervous system, kidney and the gastrointestinal tract. This report describes a 40-year-old woman who presented with an uncommon feature of BD, namely myositis, and who went on to develop myocarditis and polymicrobial necrotising fasciitis. To the best of our knowledge, this is the first reported case of an immunocompromised-associated infection occurring in BD without concurrent immunosuppressive therapy.
Massasso, David; Gibson, Kathryn
A young male immigrant from Syria with a vasculitic-appearing leg rash, asymmetrical polyarthritis, microscopic haematuria, and raised inflammatory markers was provisionally diagnosed with Henoch-Schönlein purpura. Skin biopsy showed leukocytoclastic vasculitis. Low-grade fevers persisted despite non-steroidal anti-inflammatory therapy, and Brucella sp. was subsequently grown from both blood and synovial fluid aspirates. Further tests gave positive results for B. abortus, and triple antibiotic therapy produced a rapid clinical response. Cutaneous vasculitis has rarely been described in brucellosis, and this is the first report in the English medical literature of brucellosis mimicking Henoch-Schönlein purpura.
Mascaró, José M; Baselga, Eulalia
Erythema induratum of Bazin is a chronic, nodular eruption that usually occurs on the lower legs of young women. It has been regarded as a manifestation of tuberculin hypersensitivity, a type of tuberculid occurring on the legs, whereas nodular vasculitis represents the nontuberculous counterpart. The number of reports of erythema induratum of Bazin is decreasing in most developed countries in accordance with the decreased incidence of tuberculosis. The etiopathogenesis of erythema induratum of Bazin and its relation to tuberculosis are still controversial, because mycobacteria cannot be cultured from the skin lesions. Most authors currently consider erythema induratum of Bazin (nodular vasculitis) a multifactorial disorder with many different causes, tuberculosis being one of them.
Grünholz, Daniela; Poblete, María Paz; Ovalle, Loreto; Wainstein, Eduardo; Rubio, Gloria; Manríquez, María; Kalbhenn, Karin
Large vessel vasculitis and particularly Temporal Arteritis are systemic diseases that may affect the aorta and its major branches, mainly involving extra cranial branches of the carotid artery. We report a 72-year-old man presenting with weight loss, fever and malaise. Positron emission computed tomography (PET CT) showed an extensive inflammation of the aorta and its major branches. Temporal artery biopsy confirmed the presence of vasculitis with granulomas. Treatment with a high dose of steroids had an excellent clinical response. This case underscores the utility of PET CT in the assessment of this disease.
Shibuya, Hideki; Sano, Hiroko; Osamura, Kou; Kujime, Kosei; Hara, Kei; Hisada, Tetsuya
A 68-year-old man, who had worked for processing quartz-containing stones for more than 50 years, complained of low-grade fever and arthralgia. Mediastinal lymph nodes were markedly swollen on chest computed tomography. Pathological findings of the lymph node were compatible with silicosis, with a high titer of myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA). During follow-up with prednisolone treatment, pleuritis and uveitis developed as manifestations of vasculitis. Thus, he was diagnosed with MPO-ANCA-associated vasculitis with occupational silica exposure, possibly microscopic polyangiitis (MPA). This case is rare, because pleuritis was the only pulmonary manifestation, without interstitial pneumonia, alveolar hemorrhage or glomerulonephritis.
Gera, Chanchal; Jose, Wesly; Malhotra, N; Malhotra, Vinita; Dhanoa, Jasbir
Behçet's disease (BD) is a multi-system inflammatory disorder which presents with recurrent orogenital ulceration, uveitis, and erythema nodosum. Medium vessel vasculitis of upper limb is extremely rare and it is only reported in patients with Behçet's disease on long follow up. Mean duration from diagnosis of disease to development of vasculitis is 5.8 years. We present a patient who presented with gangrene of fingers with absent radial pulse and during course of his illness he developed features of Behçet's disease. Diagnosis was established by clinical features and histopathology and patient was treated with steroids and colchicine.
Narayanan, Coimbatore; Varadraj, Govindraj; Nandeesh, Bevinahalli
Mononeuritis multiplex is a common manifestation of many illnesses which includes Hansen’s disease and certain types of systemic vasculitis. The Antineutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis (AAV) is a group of rare diseases which show typical characteristic inflammatory cell infiltration and blood vessel wall necrosis. AAV syndromes include Granulomatosis with Polyangiitis (GPA), Microscopic Polyangiitis (MPA) and Eosinophilic Granulomatosis with Polyangiitis (EGPA). We describe a patient who presented with mononeuritis multiplex and had features of overlap between EGPA and MPA. The patient was treated with standard regimen of steroids and pulsed cyclophosphamide and she achieved excellent clinical remission. PMID:28273992
Gonen, Korcan Aysun; Erfan, Gamze; Oznur, Meltem; Erdogan, Cuneyt
Henoch-Schönlein purpura (HSP) is a systemic vasculitis affecting small vessels. It is the most common systemic vasculitis in children, and is rare in adults. Serious gastrointestinal complications are more common in childhood. Infections and drugs are the most prominent factors in the aetiology. Wall thickening in segments of the small intestine is commonly seen in imaging studies in gastrointestinal system (GIS) involvement. Simultaneous involvement of small intestine and colon is rare. An HSP case involving small intestine and colon in an adult patient due to the use of rosuvastatin, an antihyperlipidaemic agent, is presented, and is first of its kind reported in the literature.
Henoch-Schonlein Purpura (HSP) is a small vessel vasculitis mediated by IgA-immune complex deposition. It is characterized by the clinical tetrad of non-thrombocytopenic palpable purpura, abdominal pain, arthritis and renal involvement. Pathologically, it can be considered a form of immune complex-mediated leukocytoclastic vasculitis (LCV) involving the skin and other organs. Though it primarily affects children (over 90% of cases), the occurrence in adults has been rarely reported. Management often involves the use of immunomodulatory or immune-suppressive regimens. PMID:21619657
Ugan, Yunus; Doğru, Atalay; Şencan, Hüseyin; Şahin, Mehmet; Ercan Tunç, Şevket
Familial Mediterranean fever (FMF) is an autoinflammatory disorder with autosomal recessive inheritance, characterized by recurrent fever and episodes of serositis. The condition is known to be caused by mutations in the MEFV (Mediterranean FeVer) gene, located in the short arm of chromosome 16. While more than 310 sequence variants in the MEFV gene have been described to date, the diagnosis is still established clinically. FMF may be accompanied by sacroiliitis and various forms of vasculitis. The most common forms of associated vasculitis are Henoch-Schonlein purpura and polyarteritis nodosa (PAN). We have presented here a fairly rare case of FMF, accompanied by both sacroiliitis and PAN. PMID:27143975
Hellemans, S.; Dens, J.; Knockaert, D.
The Churg-Strauss syndrome (CSS) is a rare systemic disease characterised by vasculitis and peripheral eosinophilia in patients with an atopic constitution. Cardiac involvement is an important cause of morbidity and mortality yet coronary involvement is very rarely documented. We report the case of a 38 year old man presenting with fulminant heart failure. Coronary arteriography demonstrated extensive focal vasculopathy consistent with vasculitis. The diagnosis of CSS was established based upon the classical diagnostic criteria and corticosteroid treatment resulted in a spectacular remission of disease activity. Images PMID:9227307
Kawasaki, Tomisaku; Naoe, Shiro
We describe a short history of Kawasaki disease. In 1967, we published a paper entitled 'Infantile acute febrile mucocutaneous lymph node syndrome with specific desquamation of the fingers and toes. Clinical observation of 50 cases'; this was the first report on what is now called Kawasaki disease. Since then, many reports on cardiology, treatment, epidemiology, pathology and etiology of Kawasaki disease have been published. Furthermore, a recent Chapel Hill Consensus Statement on Kawasaki disease in the classification of vasculitis is given, along with a figure on the relationship and classification of childhood vasculitis by autopsy material.
Sussman, G L; Davis, K; Kohler, P F
Although penicillin is nontoxic, it is highly immunogenic and is the most common drug that causes allergic reactions. A previous reaction to penicillin has been shown to be unreliable in predicting sensitivity in 75% to 90% of patients. To more accurately test for penicillin allergy, diagnostic skin test reagents have been developed; these include the major determinant (benzylpenicilloyl-polylysine) and the minor determinant mixture (penicillin G potassium, benzylpenicilloate sodium and benzylpenicilloyl-N-propylamine). Penicillin skin testing has been shown to be safe and useful in predicting immediate IgE-mediated reactions (overall predictive value 99%). Reactions that occur when patients are challenged with penicillin are mild or accelerated urticarial reactions. We outline a practical and rational therapeutic approach based on the current understanding of penicillin allergy. PMID:3518897
Missall, Tricia A; Pruden, Samuel; Nelson, Christine; Fohn, Laurel; Vidal, Claudia I; Hurley, M Yadira
A 23-year-old Chinese man presented with a 3-year history of a pruritic eruption. On examination, pink urticarial papules associated with hyperpigmented reticulated patches were noted on his neck, back, and upper chest. Histopathology revealed vacuolar interface dermatitis and numerous gram-negative rods within a dilated hair follicle. The organisms were reactive with anti-Helicobacter pylori immunohistochemisty. The histologic findings and clinical presentation support the diagnosis of prurigo pigmentosa. Additional testing demonstrated a positive urease breath test and serum H. pylori IgG antibodies. The patient was referred to gastroenterology and treated with appropriate antibiotics. After treatment, esophagogastroduodenoscopy revealed chronic gastritis without evidence of H. pylori infection and his skin showed reticulated hyperpigmented patches without evidence of active inflammatory papules. Although previous reports have associated prurigo pigmentosa to H. Pylori gastritis, this is the first report of H. pylori organisms identified in a skin biopsy of prurigo pigmentosa.
Koch, A; Tchernev, G; Chokoeva, A A; Lotti, T; Wollina, U
Since 2005, an 82-year-old female patient suffered from relapsing, generalized urticarial rash with relapsing fever episodes, arthralgias and burning tibial pain sensations. She unintentionally lost about 10 kg of body weight within 9 months. Systemic treatment with desloratadine, ranitidine, prednisolone and later, ciclosporin A was started. All these efforts could not control the symptoms but caused adverse effects including glaucoma and hypertension. Several years later a therapy with interleukin-1 inhibitor anakinra 100 mg s.c. once daily was started. The patient became symptom-free within 24 h after the first injection. With a follow up of three years the patient remained completely symptom-free with no fever or burning sensations. Later on, the dosage was reduced to 100 mg s.c. every other day. Anakinra reduces pro-inflammatory cytokine release due to lipopolysaccharide stimulation. In a long-term use the drug does not lose effectiveness.
Limsuwan, Ticha; Demoly, Pascal
Drug hypersensitivity reactions (HSRs) are the adverse effects of drugs which, when taken at doses generally tolerated by normal subjects, clinically resemble allergy. Immediate-reaction of drug HSRs are those that occur less than 1 hour after the last drug intake, usually in the form of urticaria, angioedema, rhinitis, conjunctivitis, bronchospasm, and anaphylaxis or anaphylactic shock. Acute urticarial and angioedema reactions are common clinical problems frequently encountered by internists and general practitioners. They are not specific to drug allergic reaction, and can be caused by various pathogenic mechanisms. Despite the benign course of urticaria and angioedema, a mucocutaneous swelling of the upper respiratory tract could be life-threatening by itself or a feature of anaphylaxis. This article reviews acute symptoms of drug HSR-related urticaria, angioedema, anaphylaxis, and anaphylactic shock, and how clinicians should approach these problems.
Connor, Suzy; Child, Nick; Burdon-Jones, David; Connor, Andrew
A 43-year-old man with no cardiac history presented with chest pain followed by cardiac arrest. He was successfully defibrillated and underwent primary percutaneous coronary angioplasty to a culprit coronary artery lesion. He later re-presented with a diffuse urticarial rash and lip swelling, reporting that these symptoms had been present for 4 weeks before his cardiac arrest and voicing concern that a further cardiac arrest may be imminent. A diagnosis of post-viral or idiopathic autoimmune urticaria and angioedema was made. Given the absence of cardiac symptoms before the development of the rash, it was hypothesised that coronary artery spasm precipitated by histamine release due to his dermatological condition contributed to his myocardial infarction and cardiac arrest. The final diagnosis was therefore cardiac arrest secondary to type II Kounis syndrome, resulting from idiopathic autoimmune or post-viral urticaria and angioedema.
Wrangsjö, Karin; Boman, Anders; Lidén, Carola; Meding, Birgitta
IgE-mediated allergy to natural rubber latex was first noted from rubber gloves in 1979. The initial reports in dermatological journals described contact urticarial reactions; later, severe generalized allergic reactions and asthma were documented. A considerable proportion of the people involved in medical and dental care were found to be sensitized to latex. This article describes and surveys a broad range of primary prevention measures at the local and national levels. Examples are given from paediatrics, dental education, and medical care. National strategies and position papers on latex allergy are presented in which medical professionals, manufacturers and public authorities have cooperated. Special reference is paid to the European work to standardize medical gloves, which led to document EN 455:3.
Kawakami, Yukari; Gokita, Mari; Fukunaga, Atsushi; Nishigori, Chikako
Adrenergic urticaria (AU) is a rare type of stress-induced physical urticaria characterized by widespread pruritic urticarial papules. Diagnosis can be made by i.d. injection of adrenaline or noradrenaline, which produces the characteristic rash. Although the lesions of AU typically respond to beta-blockers such as propranolol, the therapeutic options for AU are limited. Here, we report a case of AU that was resistant to beta-blockers and successfully treated with clotiazepam. The clinical picture of AU resembles that of cholinergic urticaria (CU), however, positive noradrenaline test and negative acetylcholine skin test were useful for the differential diagnosis of AU and CU. Although his symptoms were resistant to several therapeutic methods including olopatadine (H1 antagonist), lafutidine (H2 antagonist) and propranolol, the severity and frequency of his attacks and his subjective symptoms were reduced by oral clotiazepam, an anxiolytic benzodiazepine. Dermatologists should be aware that anxiolytic benzodiazepines may be a therapeutic option in AU.
Berry, Tammy; Walsh, Erica; Berry, Ryan; DeSantis, Emily; Smidt, Aimee C
A 2-year-old African American, Hispanic boy presented with well-defined, violaceous, annular dermal plaques without scale over the upper extremities, face, lower extremities, and buttocks. The clinical presentation and laboratory studies were consistent with a diagnosis of subacute cutaneous lupus erythematous (SCLE). SCLE presenting in childhood is exceedingly rare, with only eight cases previously reported. It is important to clinically differentiate SCLE from other eruptions more common to children, such as atopic dermatitis, urticarial drug eruptions, and psoriasis vulgaris, because progression to systemic lupus erythematous (SLE) may occur. SLE needs to be closely followed. We present the first case (to our knowledge) of SCLE in a child of African American or Hispanic descent and provide a table of other documented pediatric presentations of SCLE for comparison.
Juhlin, L; de Vos, C; Rihoux, J P
A single oral dose of cetirizine, 10 mg, a new H1 antagonist with minimal sedative effects and devoid of anticholinergic activities, was administered to eight healthy subjects. It markedly inhibited the wheal and flare induced 4 hours later by intracutaneously injected histamine and compound 48/80. Dermographism was produced by different pressures (100 to 500 gm/15 mm2) in 10 patients with factitial urticaria. Four hours after 10 mg of cetirizine, the whealing was absent in eight patients and markedly reduced in the other two subjects. In 12 patients with cold urticaria, wheals were induced by 30 seconds to 12 minutes application of an ice cube. Four hours after 10 mg of cetirizine, the urticarial reaction had disappeared in five patients and was decreased in the other patients. No itching was experienced in any of the patients after cetirizine, but the tested areas had an erythema lasting for 20 to 60 minutes.
Morais-Almeida, M; Marinho, S; Gaspar, A; Arêde, C; Loureiro, V; Rosado-Pinto, J
Physical urticaria includes a heterogeneous group of disorders characterized by the development of urticarial lesions and/or angioedema after exposure to certain physical stimuli. The authors present the case of a child with severe acquired cold urticaria secondary to infectious mononucleosis. Avoidance of exposure to cold was recommended; prophylactic treatment with ketotifen and cetirizine was begun and a self-administered epinephrine kit was prescribed. The results of ice cube test and symptoms significantly improved. Physical urticaria, which involves complex pathogenesis, clinical course and therapy, may be potentially life threatening. Evaluation and diagnosis are especially important in children. To our knowledge this is the first description of persistent severe cold-induced urticaria associated with infectious mononucleosis in a child.
Urano, Y; Shikiji, T; Sasaki, S; Fukuhara, K; Arase, S
A 14-year-old Japanese girl had a lifelong history of skin lesions developing after generalized exposure to cold air; the lesions were often accompanied by systemic symptoms such as fever and chills. The skin lesions were non-pruritic, maculopapular, erythematous eruptions and were neither urticarial nor angioedematous. An ice-cube test was negative. Laboratory examinations showed marked leucocytosis during an acute attack. On the basis of clinical features, histological findings and laboratory data, although these symptoms were sporadic, the most likely diagnosis was familial polymorphous cold eruption, which has also been referred to as familial cold urticaria. Serum levels of granulocyte colony-stimulating factor and interleukin 6 were significantly elevated during an acute attack after cold exposure, suggesting that both cytokines played important parts in the development of her condition.
Derraik, José G B; Sirvid, Phil J; Rademaker, Marius
New Zealand has very few arthropods that pose a threat to human health. While most New Zealand spiders are considered harmless, the bite effects of most species are unknown. Here, we describe a case of a bite by a native spider, in which a young man was bitten after rolling over in his bed. The spider was collected and identified as Trite planiceps (Salticidae, black headed jumping spider), a native species commonly encountered around homes. The initial reaction was a relatively painful, sting-like, sensation, followed by the appearance of two red puncture marks and an urticarial wheal. Symptoms eventually disappeared after 72 hours, and he has had no further dermatological problems. Trite planiceps is considered to be a rather docile spider with regard to humans, but even a docile species may still bite defensively as a last resort. Notes on this species and on treatment of spider bites are provided.
Sarrabay, Guillaume; Grandemange, Sylvie; Touitou, Isabelle
Cryopyrin-associated periodic syndrome are rare autosomal dominantly inherited diseases. They include three overlapping phenotypes: familial cold autoinflammatory syndrome, Muckle-Wells syndrome, and chronic infantile neurological cutaneous articular syndrome/neonatal onset multisystem autoinflammatory syndrome (NOMID/CINCA). Recurrent fevers, joint pain, and urticarial skin rash are the main clinical features of these conditions. Renal amyloidosis and sensorineural complications may occur. Gain-of-function mutations in NLRP3 gene are responsible for the overactivation of the NLRP3 inflammasome, a multimolecular complex involved in the inflammatory process. Missense mutations are almost always encountered, particularly in exon 3, which encodes the nucleotide-binding domain. Mosaicism is not rare, especially in CINCA/NOMID. Next-generation sequencing will grant access to new insights about NLRP3 implication in oligogenic and multifactorial diseases.
After describing the cutaneous and histo-pathological symptoms of allergic vasculazities, the author describes: Gougerot's tri-symptomatic disease, its differential diagnoses, and its various aetiologies. The pathology of the latter leads us to consider immune complexes, but our study does not deal with it in detail. Purpura rheumatica produces gammaglobulins A. Urticarial vasculazities may or may not be accompanied by anomalies of the complementary system; they may be transposed auto-immune disorders such as lupus erythematosus; their development is fairly unpredictable., Acute hemorrhagic oedema of the skin of nurslings also has allergic vasculazities at its basis. The author also mentions the transitory state between these different pictures, notably polyarteritis nodosa, granulomatotic pulmonary angitis of Churg and Strauss, and Wegener's granulomatosis.
Delaunay, Pascal; Blanc, Véronique; Del Giudice, Pascal; Levy-Bencheton, Anna; Chosidow, Olivier; Marty, Pierre; Brouqui, Philippe
Bedbugs are brown and flat hematophagous insects. The 2 cosmopolite species, Cimex lectularius and Cimex hemipterus, feed on humans and/or domestic animals, and recent outbreaks have been reported in occidental countries. Site assessment for bedbug eradication is complex but can be assured, despite emerging insecticide resistance, by hiring a pest-control manager. The common dermatological presentation of bites is an itchy maculopapular wheal. Urticarial reactions and anaphylaxis can also occur. Bedbugs are suspected of transmitting infectious agents, but no report has yet demonstrated that they are infectious disease vectors. We describe 45 candidate pathogens potentially transmitted by bedbugs, according to their vectorial capacity, in the wild, and vectorial competence, in the laboratory. Because of increasing demands for information about effective control tactics and public health risks of bedbugs, continued research is needed to identify new pathogens in wild Cimex species (spp) and insecticide resistance.
Karagöz, Ergenekon; Selek, Mehmet Burak; Aydın, Ersin; Hatipoğlu, Mustafa; Turhan, Vedat; Acar, Ali; Öncül, Oral; Görenek, Levent
Toxocariasis is a worldwide human helminthiasis, especially seen in temperate and tropical climate regions around the world. The diagnosis of this disease is performed on the basis of clinical symptoms and laboratory findings. Albendazole is one of the treatment choices for toxocariasis, with a currently recommended regimen of 10 mg/kg/day in two doses (400 mg twice daily) for 5 days. However, there is no precise consensus about the duration of the treatment. In this article, we report a case of toxocariasis; the patient visited our infectious disease polyclinic with complaints of long-term itching and urticarial skin lesions that were resistant to routine treatment and that recurred. Then, recurrent disease was resolved and skin lesions were diminished after prolonged albendazole therapy.
Blanc, Véronique; Del Giudice, Pascal; Levy-Bencheton, Anna; Chosidow, Olivier; Marty, Pierre; Brouqui, Philippe
Bedbugs are brown and flat hematophagous insects. The 2 cosmopolite species, Cimex lectularius and Cimex hemipterus, feed on humans and/or domestic animals, and recent outbreaks have been reported in occidental countries. Site assessment for bedbug eradication is complex but can be assured, despite emerging insecticide resistance, by hiring a pest-control manager. The common dermatological presentation of bites is an itchy maculopapular wheal. Urticarial reactions and anaphylaxis can also occur. Bedbugs are suspected of transmitting infectious agents, but no report has yet demonstrated that they are infectious disease vectors. We describe 45 candidate pathogens potentially transmitted by bedbugs, according to their vectorial capacity, in the wild, and vectorial competence, in the laboratory. Because of increasing demands for information about effective control tactics and public health risks of bedbugs, continued research is needed to identify new pathogens in wild Cimex species (spp) and insecticide resistance. PMID:21288844
Gundersen, S G; Ravn, J; Haagensen, I
A 34-year-old male developed acute Katayama fever with fever, diarrhoea, joint pains, headache, urticarial rash and eosinophilia 18 days after falling into and spending 15 min in the water during water-skiing in the outlet of the Volta river. Low anti-schistosomal antibody titres were found by the immunofluorescence assay after 4 weeks, and the first Schistosoma mansoni eggs were found in faeces after 6 weeks. Both symptoms and eosinophilia increased the first days after treatment with oxamniquine, after which he improved gradually. Examination of frozen sera by the newly developed Magnetic Beads Antigen Capture-EIA (MBAC-EIA) later demonstrated a peak in schistosomal circulating anodic antigen (CAA) levels of diagnostic significance already 4 weeks after he was infected.
Gunawardena, Mudalige Don Vajira Malin; Weerasinghe, Anura; Herath, Jagath; Amarasena, Naomali
Myocardial infarction occurring during the course of type I hypersensitivity constitutes Kounis syndrome. We report a case of a 38-year-old man who presented with anterior ST elevation myocardial infarction and peripheral blood eosinophilia. He had rhinitis and malaise for several days prior to presentation. There was no urticarial rash or pruritus to suggest hypersensitivity. Coronary angiogram revealed only mild plaque disease. Blood investigations revealed moderate eosinophilia and elevated IgE levels. CT of the thorax revealed fluid extravasation at multiple sites. Screening for a possible secondary cause for eosinophilia revealed hypersensitivity to multiple antigens. A diagnosis of Kounis syndrome was made. Within days of starting steroids and antihistamines, the patient's eosinophil count returned to normal with improvement of clinical picture. This case differs from classical Kounis syndrome as there was no acute allergic reaction (except atopic rhinitis). Fluid extravasation at multiple sites has not been described in previous cases. PMID:25608982
Delorenze, Lilian Mathias; Branco, Letícia Guedes; Cerqueira, Luiza Fiszon; Vasques, Wellington Batista; Salles, Simone de Abreu Neves; Vilar, Enoi Guedes
Pruritic folliculitis of pregnancy is a rare disease of unknown etiology. It occcurs primarily during pregnancy, usually with spontaneous resolution postpartum. It is characterized by a benign dermatosis, with papular and pustular follicular lesions that first appear on the torso and occasionally spread throughout the body. We report the case of a patient in the 27th week of pregnancy, with a two-month evolution of pruritic and papular erythematous lesions on her lower back. Differential diagnosis includes other pregnancy-specific dermatoses: gestational pemphigoid, pruritic urticarial papules and plaques of pregnancy (PUPPP), prurigo of pregnancy, and (PUPPP) and prurigo of pregancy. Histopathological tests showed changes consistent with pruritic folliculitis of pregnancy. This case is relevant due to its rare nature and its clinical and histopathological characteristics. PMID:28300898
Hossler, Eric W
Caterpillars and moths (order Lepidoptera) are uncommonly recognized causes of adverse cutaneous reactions, such as localized stings, papular dermatitis, and urticarial wheals. These reactions are typically mild and self-limited; however, in South America, the sting of Lonomia caterpillars can cause a potentially fatal hemorrhagic diathesis related to massive fibrinolysis. In addition, ocular inflammation and prominent arthralgias have been reported to be caused by caterpillar exposures. Therapies for mucocutaneous reactions to Lepidoptera are largely empiric, with the exception of antivenin against Lonomia obliqua envenomation. Part II of this two-part series on caterpillars and moths reviews the varied symptoms caused by Lepidopteran exposures, reviews the differential diagnosis, and discusses appropriate treatment algorithms.
Scala, E; Giani, M; Pirrotta, L; Guerra, E C; Cadoni, S; Girardelli, C R; De Pità, O; Puddu, P
Anisakis simplex (AS), a fish and cephalopodes parasite, may cause allergic reactions in humans on eating and/or handling contaminated fish. We present a case of occupational hypersensitivity to AS in a woman employed in a frozen-fish factory. She showed both generalised urticarial rash and asthmatic symptoms after work place exposure. All these symptoms immediately disappeared after work place exposure was ceased. The presence of a positive skin prick test and high specific IgE values confirmed a hypersensitivity to anisakis. This is the first case reported of both occupational generalised urticaria and allergic airborne asthma due to AS in the same patient. We suggest that AS could be an important cause of occupational asthma and/or urticaria in the fish industry.
Ferre, Elise M.N.; Rose, Stacey R.; Rosenzweig, Sergio D.; Burbelo, Peter D.; Romito, Kimberly R.; Niemela, Julie E.; Rosen, Lindsey B.; Break, Timothy J.; Gu, Wenjuan; Hunsberger, Sally; Browne, Sarah K.; Hsu, Amy P.; Rampertaap, Shakuntala; Swamydas, Muthulekha; Collar, Amanda L.; Kong, Heidi H.; Chascsa, David; Simcox, Thomas; Pham, Angela; Bondici, Anamaria; Natarajan, Mukil; Monsale, Joseph; Kleiner, David E.; Quezado, Martha; Alevizos, Ilias; Moutsopoulos, Niki M.; Yockey, Lynne; Frein, Cathleen; Soldatos, Ariane; Calvo, Katherine R.; Adjemian, Jennifer; Similuk, Morgan N.; Lang, David M.; Stone, Kelly D.; Uzel, Gulbu; Bishop, Rachel J.; Holland, Steven M.; Olivier, Kenneth N.; Fleisher, Thomas A.; Heller, Theo; Winer, Karen K.
Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare primary immunodeficiency disorder typically caused by homozygous AIRE mutations. It classically presents with chronic mucocutaneous candidiasis and autoimmunity that primarily targets endocrine tissues; hypoparathyroidism and adrenal insufficiency are most common. Developing any two of these classic triad manifestations establishes the diagnosis. Although widely recognized in Europe, where nonendocrine autoimmune manifestations are uncommon, APECED is less defined in patients from the Western Hemisphere. We enrolled 35 consecutive American APECED patients (33 from the US) in a prospective observational natural history study and systematically examined their genetic, clinical, autoantibody, and immunological characteristics. Most patients were compound heterozygous; the most common AIRE mutation was c.967_979del13. All but one patient had anti–IFN-ω autoantibodies, including 4 of 5 patients without biallelic AIRE mutations. Urticarial eruption, hepatitis, gastritis, intestinal dysfunction, pneumonitis, and Sjögren’s-like syndrome, uncommon entities in European APECED cohorts, affected 40%–80% of American cases. Development of a classic diagnostic dyad was delayed at mean 7.38 years. Eighty percent of patients developed a median of 3 non-triad manifestations before a diagnostic dyad. Only 20% of patients had their first two manifestations among the classic triad. Urticarial eruption, intestinal dysfunction, and enamel hypoplasia were prominent among early manifestations. Patients exhibited expanded peripheral CD4+ T cells and CD21loCD38lo B lymphocytes. In summary, American APECED patients develop a diverse syndrome, with dramatic enrichment in organ-specific nonendocrine manifestations starting early in life, compared with European patients. Incorporation of these new manifestations into American diagnostic criteria would accelerate diagnosis by approximately 4 years and
Urticaria is a common disorder that adversely affects quality of life; work-related and recreational activities are restricted, while rest, sleep, and emotions are seriously disturbed in a significant proportion of patients. The pathogenic mechanisms vary, but cutaneous mast-cell activation with release of histamine and other vasoactive or proinflammatory mediators is thought to be the final common pathway for lesion induction in most cases. A subsequent, but incompletely understood, late-phase allergic reaction seems to prolong the inflammatory process, particularly in certain chronic forms of the disorder. Although histamine is considered an important mediator of urticaria, additional substances, including the cysteinyl leukotrienes (LTs), are putative mediators of the immediate urticarial responses and the inflammatory events that follow in some types of urticaria. A second-generation antihistamine, mizolastine, which exhibits dual activity with selective H1-receptor antagonism and, as shown in animal studies, anti-5-lipoxygenase activity, represents an advance in the treatment of urticaria. It has rapid, potent and sustained action. At the recommended 10-mg dose, mizolastine suppresses the histamine-induced wheal reaction as early as 1 h after oral administration. Compared to placebo, mizolastine significantly reduces overall patient discomfort and pruritus in patients with chronic idiopathic urticaria. Double-blind, placebo-controlled studies have also shown mizolastine to be at least as effective as other second-generation antihistamines. Furthermore, with long-term use of mizolastine over 1 year, a reduction in pruritus and the number of urticarial episodes was maintained with no evidence of tachyphylaxis or tolerance. Mizolastine has also been shown to be an effective treatment for cold-induced urticaria, causing significant delay in the whealing response to the ice-cube test and also reducing the wheal diameter.
Ferre, Elise M N; Rose, Stacey R; Rosenzweig, Sergio D; Burbelo, Peter D; Romito, Kimberly R; Niemela, Julie E; Rosen, Lindsey B; Break, Timothy J; Gu, Wenjuan; Hunsberger, Sally; Browne, Sarah K; Hsu, Amy P; Rampertaap, Shakuntala; Swamydas, Muthulekha; Collar, Amanda L; Kong, Heidi H; Lee, Chyi-Chia Richard; Chascsa, David; Simcox, Thomas; Pham, Angela; Bondici, Anamaria; Natarajan, Mukil; Monsale, Joseph; Kleiner, David E; Quezado, Martha; Alevizos, Ilias; Moutsopoulos, Niki M; Yockey, Lynne; Frein, Cathleen; Soldatos, Ariane; Calvo, Katherine R; Adjemian, Jennifer; Similuk, Morgan N; Lang, David M; Stone, Kelly D; Uzel, Gulbu; Kopp, Jeffrey B; Bishop, Rachel J; Holland, Steven M; Olivier, Kenneth N; Fleisher, Thomas A; Heller, Theo; Winer, Karen K; Lionakis, Michail S
Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare primary immunodeficiency disorder typically caused by homozygous AIRE mutations. It classically presents with chronic mucocutaneous candidiasis and autoimmunity that primarily targets endocrine tissues; hypoparathyroidism and adrenal insufficiency are most common. Developing any two of these classic triad manifestations establishes the diagnosis. Although widely recognized in Europe, where nonendocrine autoimmune manifestations are uncommon, APECED is less defined in patients from the Western Hemisphere. We enrolled 35 consecutive American APECED patients (33 from the US) in a prospective observational natural history study and systematically examined their genetic, clinical, autoantibody, and immunological characteristics. Most patients were compound heterozygous; the most common AIRE mutation was c.967_979del13. All but one patient had anti-IFN-ω autoantibodies, including 4 of 5 patients without biallelic AIRE mutations. Urticarial eruption, hepatitis, gastritis, intestinal dysfunction, pneumonitis, and Sjögren's-like syndrome, uncommon entities in European APECED cohorts, affected 40%-80% of American cases. Development of a classic diagnostic dyad was delayed at mean 7.38 years. Eighty percent of patients developed a median of 3 non-triad manifestations before a diagnostic dyad. Only 20% of patients had their first two manifestations among the classic triad. Urticarial eruption, intestinal dysfunction, and enamel hypoplasia were prominent among early manifestations. Patients exhibited expanded peripheral CD4(+) T cells and CD21(lo)CD38(lo) B lymphocytes. In summary, American APECED patients develop a diverse syndrome, with dramatic enrichment in organ-specific nonendocrine manifestations starting early in life, compared with European patients. Incorporation of these new manifestations into American diagnostic criteria would accelerate diagnosis by approximately 4 years and
Two cases of sheep-associated malignant catarrhal fever (MCF) in pigs were diagnosed on a small farm in New York State, and in Kentucky, U.S.A. In both cases initial diagnosis was based on histopathological changes representing typical lymphoproliferative vasculitis in multiple tissues of the affect...
Churg-Strauss syndrome is a systemic and pulmonary vasculitis, defined by its association with severe asthma and with hypereosinophilia of the blood and tissues. The systemic vasculitis is a small-vessel vasculitis frequently associated with purpura, mononeuritis multiplex, and, more rarely, with rapidly progressive glomerulonephritis or diffuse alveolar hemorrhage. Its prevalence of 7 to 13 per million population makes it one of the rarest of the systemic vasculitides. Anti-MPO (antimyeloperoxidase) pANCA (ANCA with a perinuclear fluorescence pattern) is present in 35-40% of cases and appears to determine a subgroup of patients with a higher frequency of renal damage, alveolar hemorrhage, and central nervous system damage. Cardiac involvement is an important cause of morbidity and the leading cause of mortality in Churg-Strauss syndrome. Treatment is based on corticosteroid therapy and immunosuppressive drugs (cyclophosphamide and azathioprine) and is determined according to validated prognostic criteria (Five-Factor Score). Complete remission occurs in almost 90% of cases, and the 10-year survival rate has reached 79.4%. Relapses are frequent (25% of cases) and even after recovery from vasculitis, most patients (90%) still have asthma requiring corticosteroid treatment.
SAATCI, Ali Osman; AYHAN, Ziya; ONEN, Fatos; OZBEK, Zeynep; DURAK, Ismet
This case report involves a 32-year-old man with Behçet’s disease who had simultaneous bilateral anterior uveitis, unilateral nodular scleritis, and occlusive vasculitis with retinal hemorrhages. Although scleritis is not a classical feature of Behçet’s disease, a diagnosis of Behçet’s disease should be considered in patients with scleritis.
Ahn, Eric; Luk, Adriana; Chetty, Runjan; Butany, Jagdish
Systemic vasculitis is often not considered as a possible diagnosis by clinicians because of its low prevalence compared with other more common diseases. Vasculitis can affect any end organ, and it is therefore often missed early on in disease progression. Gastrointestinal (GI) manifestations of vasculitis are considered rare and the presentation is often nonspecific. However, if there is significant involvement of the major vessels of the gastrointestinal system, life-threatening sequelae, including perforation and bowel ischemia, may occur. This makes early and immediate management crucial to improve long-term morbidity and mortality. Diagnosis of various GI vasculitides often relies on correlation of clinical manifestations with pathology and additional investigations. This paper reviews the various vasculitides that affect the GI tract, including systemic lupus erythematosus, mixed connective tissue disease, Henoch Schönlein purpura, polyarteritis nodosa, Churg-Strauss syndrome, Wegener's granulomatosis, microscopic polyangiitis, enterocolic lymphocytic phlebitis, and Behcet's disease. Segmental arterial mediolysis, mistakenly believed to be a vasculitis, is also discussed.
Extensive fat deposits below subcutis Vasculization of hair follicles Seasonally regulated hair shedding Structure of the collagenous tissue...comparison (p-values) of skin thickness between breeds. Segments in gray indicate statistically different variances (F- test ) or means (t- test ...2004, Pg. 475). Note that keratinocytes produce keratin, the primary constituent for hair . Melanosomes enter the hair when it is being formed
Nandu, A; Salu, P; Caspers, L; Gordts, F; Sennesael, J
Cogan's syndrome is a systemic inflammatory disease that associates typical (interstitial keratitis) and atypical (such as anterior uveitis) ocular manifestations to vestibulo-auditory dysfunction. It has also a systemic vascular association of vasculitis type. We report a case of a 64 years old woman who presented an atypical form with anterior uveitis.
Kim, J E; Kolh, E M; Kim, D K
Takayasu's arteritis (TA) is a vasculitis of large and medium sized arteries. Involvement of bone in TA is very rare. We report a case of young woman who presented with multiple painful bone lesions which were identified as periostitis with new bone formation associated with TA. Our case is unique in that bony involvement in TA could occur independent of vascular stenosis.
Kumar, Nitin; Vaish, A K
We report here a case of a 13-year-old boy with Churg Strauss Syndrome who presented with acute right sided hemiplegia with slurred speech due to cerebral infarction most likely due to cerebral vasculitis. The boy was treated with steroids and aspirin and improved. This case in interesting as Churg Strauss Syndrome is not so common in pediatric age group.
Sureda Ramis, B; Bautista, J; Martínez Navarro, M L
A 57-year-old patient nonimmunosuppressed who had zoster ophthalmicus associated to contralateral hemiplegia is presented. We noticed on the CT scan an infarction of left caudate nucleus, as well as in the angiography signs of vasculitis. We comment on the clinical and diagnosis features and suggest possible benefit effects of the treatment with acyclovir.
Govett, G S; Amedee, R G
Wegener's granulomatosis is an uncommon systemic vasculitis with granuloma formation that has many manifestations in the head and neck. The otolaryngologist may be the first physician called upon to examine such a patient. Although this disease was previously fatal, treatment with cyclophosphamide and steroids has produced response rates of 93%.
Vasculitis Study 12 2. Hepatitis B Vaccine Study 13 3. Structure of HLA-DR Antigens 13 H. REFERENCES 16 4 2 A. ABSTRACT The objective of this contract is...during the next contract year. B. STUDIES ON THE RECIPIENTS OF HEPATITIS B VACCINE , ANALYSIS OF NON RESPONDERS During the past two years field trials
Wobeser, Bruce K
During a widespread anthrax outbreak in Canada, miniature horses were vaccinated using a live spore anthrax vaccine. Several of these horses died from an apparent immune-mediated vasculitis temporally associated with this vaccination. During the course of the outbreak, other miniature horses from different regions with a similar vaccination history, clinical signs, and necropsy findings were found.
Basaran, M; Sever, K; Kafali, E; Ugurlucan, M; Alpagut, U; Dayioglu, E
Behçet's disease is an inflammatory vasculitis which affects the arteries and veins. The vascular pathologies are the rare complications of this disease. We present here a patient with Behçet's disease who has been hospitalized several times because of plurifocal vascular manifestations.
Ugurlucan, Murat; Sayin, Omer Ali; Surmen, Benguhan; Kafali, Eylul; Basaran, Murat; Alpagut, Ufuk; Dayioglu, Enver; Onursal, Ertan
Behcet's disease is an autoimmune multisystemic disorder based on vasculitis. In this disease, the most important predictor of morbidity and mortality is the vascular complications. Appropriate surgical interventions are critical and must be planned strategically. Here, we will describe a very rare complication of the disease; spontaneous aortic pseudoaneurysm in a 33-year-old patient.
Harre, R.G.; Conrad, G.R.; Seabold, J.E.
A patient with known Behcet's disease demonstrated intense colonic localization of In-111 labeled leukocytes. Gastrointestinal involvement had not been previously manifested, but extensive colonic inflammation was documented by endoscopy. This case illustrates the utility of In-111 labeled leukocyte imaging for detecting active bowel disease in a debilitated patient with documented Behcet's vasculitis.
Healthy Volunteer; Rheumatoid Arthritis; Ankylosing Spondylitis; Systemic Lupus Erythematosus/Antiphospholipid Syndrome; FMF; Cryopyrin-Associated Periodic Syndromes /TNF-receptor Associated Periodic Syndrome; Vasculitis; Uveitis; Myositis; Crohn's Disease; Ulcerative Rectocolitis; Type 1 Diabetes; Unclassified IAD Knee and/or Hip Arthritis, Muscular Dystrophy
Minnee, R C; van den Berk, G E L; Groeneveld, J O; van Dijk, J; Turkcan, K; Visser, M J; Vahl, A C
We present a patient with Wegener's granulomatosis (WG) with involvement of the abdominal aorta, testis, peripheral nerve system, and skin. A 51-year-old man presented at our outpatient clinic with lower back pain. He had a history of smoking, hypertension, and an embryonal carcinoma of the left testis, treated 13 years ago with orchidectomy and chemotherapy. One month earlier, he underwent a partial orchidectomy of the right testis due to testicular swelling. Abdominal computed tomography showed a 3.8 cm wide aneurysm of the distal part of the aorta with inflammation. One week later he was admitted to the hospital with numbness of his hands and feet. Physical examination showed signs of peripheral microemboli. Serological laboratory tests revealed elevated antineutrophil cytoplasmic antibody titers with positive reactions against proteinase-3, indicating Wegener's disease. The chest X-ray was normal. Pathological examination of the right testis showed necrotizing vasculitis of a small artery. He was treated with cyclophosphamide and prednisolone. WG with extrapulmonary involvement occurs infrequently, and reports of manifestations of WG in aorta, testis, the peripheral nerve system, and skin are even more uncommon. Small- and medium-vessel vasculitis can precede large-vessel vasculitis or occur in the absence of small-vessel involvement. Therefore, WG should be included in the work-up of large-vessel vasculitis, which can give rise to periaortic inflammation.
Nobles, Irma J.; Khan, Safdar
A 5-year-old spayed female Bernese mountain dog, with a chief complaint of vomiting and melena ingested approximately 200 nutritional joint supplement tablets. Despite aggressive therapy, the patient developed a coagulopathy, pancreatitis, peritonitis, acute kidney injury, and was euthanized. Postmortem examination revealed myocardial necrosis, pneumonia, centrilobular hemorrhage and necrosis of the liver, vasculitis, and acute tubular necrosis. PMID:25829554
Mbéthé, G L Gaundong; Diéval, C; Lafitte, A; Roger-Schmeltz, J; Longy-Boursier, M; Mercié, P
Wegener's granulomatosis (WG) is a rare systemic necrotizing granulomatous vasculitis affecting small- to medium-sized vessels, associated with antineutrophil cytoplasm antibodies (ANCA), mainly anti-proteinase 3. Rarely, ANCA may be directed against myeloperoxidase. We report a 58-year-old woman who developed an uveitis as the presenting manifestation of Wegener's granulomatosis who highlight the usefulness of internist and ophthalmologist collaboration.
Turner, R.A.; Wise, C.M.
This book contains 23 papers. Some of the titles are: Diagnostic Radiology in the Rheumatic Diseases; Laboratory Testing in Rheumatology; Arthritis Nursing and the Team Approach in the Management of Rheumatic Disease; The Surgical Management of Arthritis; Vasculities; Neoplasms of Bone and Joints; and Rheumatic Disease of Childhood.
BACKGROUND Relapse is a major clinical problem in ANCA vasculitis that causes increased morbidity and mortality. Compared to MPO-ANCA patients, patients with PR3-ANCA run a significantly increased risk of experiencing relapses. We hypothesized that a relapsing patient is produ...
Sharma, Arpit; Deshmukh, Shraddha; Dabholkar, Jyoti
Wegeners granulomatosis is a necrotizing granulomatous vasculitis with multisystemic involvement. We present two cases of Wegener's presenting with otological manifestations as the first symptom. These symptoms are subtle and diagnosis may be easily overlooked. Hence a high index of suspicion is required. Early diagnosis and treatment goes a long way in improving the outcomes and in preventing further complications.
Reddy, Raja Shekhar; Biyyani, Sappati; Pauskar, Privi; Fahmy, Nabil M; King, James F
Wegeners granulomatosis (WG) is a pauci-immune systemic vasculitis involving small to medium sized blood vessels of the respiratory tract and renal vasculature. We report a 34-year-old lady with extensive gastrointestinal tract, pancreas and thyroid involvement. Literature review revealed only two prior reports of esophageal involvement, two reports of pancreatic involvement and few cases of thyroid involvement.
Abdel-Hadi, O.; Greenstone, M. A.; Hartley, R. B.; Kidner, P. H.
A 29-year-old man with previous Henoch-Schönlein disease presented with multiple systemic emboli and a myocardial infarction. Subsequent investigation by angiography showed normal coronary arteries. This appears to be the first reported case of Henoch-Schönlein disease and myocardial infarction probably due to coronary vasculitis. Images Fig. 1 PMID:7301688
Carlson, J Andrew; Chen, Ko-Ron
Cutaneous pseudovasculitis represents a heterogeneous collection of disorders that are capable of simulating cutaneous vasculitis and can be broadly classified into diseases that produce hemorrhage (petechiae, purpura, and ecchymoses) or vessel occlusion with resultant livedo, cyanosis, ulcers, digital necrosis, and/or gangrene. Overlap is not uncommon, but if present, one mechanism dominates. Hemorrhagic pseudovasculitis is due to vessel wall dysfunction (incompetence), which can be related to diverse factors that include vessel wall deposition of metabolic substances (amyloid, calcium), nutritional deficiencies (scurvy), nonvasculitic inflammatory purpura (pigmented purpuric dermatitis, arthropod, viral and drug reactions), degeneration of the vessel wall and supporting stroma (senile/solar purpura), direct vessel wall invasion of infective organisms, coagulation-fibrinolytic disorders (eg, thrombocytopenia), and vessel wall trauma. Cyanotic-infarctive pseudovasculitis is due vaso-occlusion by emboli, thrombi, or fibrointimal hyperplasia (endarteritis obliterans) and includes varied conditions such as purpura fulminans, Coumadin necrosis, antiphospholipid antibody syndrome, cardiac myxoma, cholesterol embolization, calciphylaxis, and radiation arteritis. Delayed and inappropriate diagnosis of pseudovasculitis leads to incorrect management and exposure to potentially deleterious treatment modalities such as corticosteroids and cytotoxic agents. The diagnosis of a pseudovasculitic disorder requires a high index of suspicion and should always be part of the differential diagnosis of vasculitis. Skin biopsy is a crucial step in differentiating pseudovasculitis from authentic vasculitis; absence of histologic evidence of vasculitis, particularly after multiple biopsies, should direct evaluation and diagnosis towards pseudovasculitis.
Boulagnon, Camille; Kovacs, Ovidiu-Bujor; Patey, Martine
We report a case of pseudotumoral nasal septum and hard palate perforation in a 42-years-old man. The diagnosis retained after differential diagnosis exclusion was necrotic midfacial lesion due to chronic inhalation of cocaine. This condition can mimic vasculitis, primary tumors and granulomatous infections. Differential diagnosis and pathophysiology of this condition will be discussed in this anatomo-clinical case.
Buxton, N; McConachie, N S
Amphetamines taken by any route can cause cerebral vasculitis and intracranial haemorrhage. 8 cases were seen in a neurosurgical unit over 3.5 years. The published work indicates that those who experience these complications, mainly young adults, have poor outcomes. PMID:11089483
Romero, J.J.; Herrera, P.; Cartelle, M.; Barba, P.; Tello, S.; Zurita, J.
We report the first case of recently characterized species M. monacense associated with chronic nodular vasculitis, infecting a young woman. This case represents the first isolation of M. monacense from Ecuador. The isolate was identified by conventional and molecular techniques. PMID:26933504
Ovine herpesvirus 2 (OvHV-2) is a gammaherpesvirus in the genus Macavirus that is carried asymptomatically by sheep. Infection of poorly adapted animals with OvHV-2 results in sheep associated malignant catarrhal fever, a fatal disease characterized by lymphoproliferation and vasculitis. There is no...
Hamzaoui, Amira; Litaiem, Noureddine; Smiti Khanfir, M.; Ayadi, Sofiene; Nfoussi, Haifa; Houman, M. H.
Ischemic colitis is one of the most common intestinal ischemic injuries. It results from impaired perfusion of blood to the bowel and is rarely caused by vasculitis. We report a case of ischemic colitis revealing polyarteritis nodosa (PAN) in a 55-year-old man. Histological examination of the resected colon led to the diagnosis of PAN. PMID:24382967
Cook, Amanda L; Rouster-Stevens, Kelly; Williams, Derek A; Hines, Michael H
Behcet's disease is a rare autoimmune vasculitis characterized by oral aphthosis, genital ulcers, and ocular and cutaneous lesions. Vascular involvement usually affects the veins more commonly than the arteries, and coronary arterial involvement is extremely rare. We report an adolescent with Behcet's disease who developed a large pseudoaneurysm of the left anterior descending coronary artery requiring a coronary arterial bypass graft.
Purpura, Schoenlein-Henoch; Graft Versus Host Disease; Anemia, Hemolytic, Autoimmune; Rheumatoid Arthritis; Churg-Strauss Syndrome; Hypersensitivity Vasculitis; Wegener's Granulomatosis; Systemic Lupus Erythematosus; Giant Cell Arteritis; Pure Red Cell Aplasia; Juvenile Rheumatoid Arthritis; Polyarteritis Nodosa; Autoimmune Thrombocytopenic Purpura; Takayasu Arteritis
Drolet, Richard; Denicourt, Martine; D’Allaire, Sylvie
This report describes an uncommon variant of humpy-back syndrome associated with multiple rib fractures and multisystemic vasculitis in several nursing piglets and, for the first time, a skin disease in swine consistent with alopecia areata. Both conditions were observed concurrently on the farm and occasionally in the same piglets. PMID:23372194
Quiceno, G Andres; Cush, John J
Rheumatic complaints are common in the geriatric population. However, uncommonly autoimmune or musculoskeletal complaints and disorders may arise as a consequence of pharmacotherapy. These rare events include stain myopathy, drug-induced lupus, arthralgias, vasculitis, or tight skin syndromes. This article discusses the possible iatrogenic causes of rheumatic conditions, potential inciting agents, and the various types of rheumatic manifestations seen in the elderly.
Quiceno, G Andres; Cush, John J
Rheumatic complaints are common in the geriatric population. However, uncommonly autoimmune or musculoskeletal complaints and disorders may arise as a consequence of pharmacotherapy. These rare events include statin myopathy, drug-induced lupus, arthralgias, vasculitis, or tight skin syndromes. This article will discuss the possible iatrogenic causes of rheumatic conditions, potential inciting agents, and the various types of rheumatic manifestations seen in the elderly.