Sato, Yasuharu; Yoshino, Tadashi
IgG4-related disease is a recently recognized systemic syndrome characterized by mass-forming lesions, mainly in exocrine tissue, that consist of lymphoplasmacytic infiltrates and sclerosis. There are numerous IgG4+ plasma cells in the affected tissues, and the serum IgG4 level is elevated in these patients. Ocular adnexal IgG4-related disease frequently involves bilateral lacrimal glands, and obliterative phlebitis is rare. Moreover, some malignant lymphomas, especially mucosa-associated lymphoid tissue lymphoma, arise from ocular adnexal IgG4-related disease. It is known that hyper IL-6 syndromes, such as multicentric Castleman's disease, rheumatoid arthritis, and other autoimmune diseases, fulfill the histological diagnostic criteria for IgG4-related disease; therefore, hyper IL-6 syndromes and IgG4-related disease cannot be differentially diagnosed by immunohistochemical staining alone. However, upon laboratory examination, hype IL-6 syndromes show elevation of the CRP level, polyclonal hyper gamma-globulinemia, anemia, and hypoalbuminemia. These findings are quite different from IgG4-related disease, which is not characterized by elevated serum IgA, IgM, and CRP levels. Therefore, laboratory findings are crucial for the differential diagnosis.
Sato, Yasuharu; Ohshima, Koh-Ichi; Takata, Katsuyoshi; Huang, Xingang; Cui, Wei; Ohno, Kyotaro; Yoshino, Tadashi
IgG4-related disease is a recently proposed clinical entity with several unique clinicopathological features. A chronic inflammatory state with marked fibrosis, which can often be mistaken for malignancy, especially by clinical imaging analyses, unifies these features. In the present report, we describe a case of IgG4-producing mucosa-associated lymphoid tissue lymphoma mimicking IgG4-related disease. The patient was a 55-year-old male who was being followed for right orbital tumor over 1.5 years. The lesion had recently increased in size, so a biopsy was performed. Histologically, the lesion was consistent with IgG4-related disease ; however, IgG4+ plasma cells showed immunoglobulin light-chain restriction and immunoglobulin heavy chain gene rearrangement was detected in the lesion. Therefore, the lesion was diagnosed as IgG4-producing mucosa-associated lymphoid tissue lymphoma. In conclusion, in histological diagnosis of IgG4-related disease, it is important to examine not only IgG4-immunostain but also immunoglobulin light-chain restriction.
Ikeda, Tetsuya; Oka, Masahiro; Shimizu, Hideki; Hatakeyama, Mayumi; Kanki, Haruhisa; Kunisada, Makoto; Tsuji, Goh; Morinobu, Akio; Kumagai, Shunichi; Azumi, Atsushi; Negi, Akira; Nishigori, Chikako
We describe two cases of IgG4-related disease associated with skin manifestations with IgG4-positive plasma cells. The first patient was a 52-year-old woman with a 3-year history of IgG4-related sialadenitis who presented with pruritic, indurated erythematous lesions on the auricle, postauricular and submandibular regions and neck. A skin biopsy showed infiltration of IgG4-positive plasma cells in the subcutaneous tissue. The second patient was a 53-year-old woman with IgG4-related lesions in the ocular adnexal tissues and nasal cavity who presented with pruritic, indurated erythema on the cheek and submandibular region. Histopathological examination of a skin biopsy revealed a dense, patchy infiltrate comprised of lymphocytes, IgG4-positive plasma cells and eosinophils around blood vessels and sweat glands in the entire dermis and subcutis. The skin lesions in these cases were considered to be skin manifestations of IgG4-related disease. The findings of these two cases together with the three reported cases of IgG4-related disease with skin manifestations in the literature suggest that IgG4-related skin lesions may appear on the scalp, face, neck, auricle and postauricular regions during the course of IgG4-related disease.
Cornell, Lynn D
IgG4-related kidney disease is a term that refers to any form of renal involvement by IgG4-related disease (IgG4-RD), a recently recognized systemic immune-mediated disease. The most common renal manifestation is IgG4-related tubulointerstitial nephritis (IgG4-TIN), which presents as acute or chronic renal insufficiency, renal mass lesions, or both. On biopsy, IgG4-TIN shows a plasma cell-rich interstitial inflammatory infiltrate with increased IgG4+ plasma cells, along with expansile interstitial fibrosis; tubular basement membrane immune complex deposits are common. IgG4-TIN usually shows a brisk response to immunosuppressive therapy. Glomeruli may be affected by IgG4-RD, usually in the form of membranous glomerulonephritis. Other patterns of glomerular disease include IgA nephropathy, membranoproliferative glomerulonephritis, and endocapillary or mesangioproliferative immune complex glomerulonephritis. IgG4-related plasma cell arteritis has also been observed in the kidney. This review describes the histopathologic and immunophenotypic patterns of renal involvement by IgG4-RD, with associated clinical, radiographic, and serologic features.
González-Moreno, Juan; Losada López, Inés; Ortego Centeno, Norberto
IgG4-related disease is a recently described clinicopathological entity showing a wide spectrum of clinical manifestations that share a common pathology. Its most characteristic feature is the formation of inflammatory tumors in different organs, which makes differentiation mainly with neoplastic diseases fundamental. The inflammatory process is typically comprised of IgG4 lymphoplasmacytic cells. The pathophysiological role of the immunoglobulin is not clear. The treatment of choice is corticosteroids. This article aims to summarize the main features of the disease.
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).
Yamamoto, Motohisa; Takahashi, Hiroki; Shinomura, Yasuhisa
IgG4-related systemic disease/systemic IgG4-related disease has been established as a new systemic disease entity. It is characterized by high serum IgG4 concentrations and abundant IgG4-bearing plasma cell infiltration in the involved organs. The chronic inflammation can attack lacrimal glands, salivary glands, the thyroid, lung, pancreas, kidney, and prostate. The concept includes Mikulicz's disease, Riedel's thyroiditis, pulmonary fibrosis, pulmonary pseudotumor, autoimmune pancreatitis, a part of tubulointerstitial nephritis, and chronic prostatitis. It is important to note that these lesions can occur at different times and sites. So, it is necessary to reconfirm the disease definition and entity in each specialized field. The diagnosis of this disease is confirmed by the above serological and histopathological characteristics. There are clinical diagnostic criteria of Mikulicz's disease (the Japanese Medical Society for Sjögren's Syndrome) and autoimmune pancreatitis (the Japanese Ministry of Health, Labour and Welfare, and the Japan Pancreas Society). They are convenient and useful. Glucocorticoid improves the physical abnormalities, and the initial dose of prednisolone is 30 mg/day, tapered in 5-mg reductions every two weeks. Nevertheless, there are some cases unable to achieve complete remission.
Goto, Hiroshi; Takahira, Masayuki; Takahira, Masahiro; Azumi, Atsushi
Immunoglobulin G4 (IgG4)-related disease is a novel clinical entity characterized by infiltration of IgG4-immunopositive plasmacytes and elevated serum IgG4 concentration accompanied by enlargement of and masses in various organs, including the lacrimal gland, salivary gland, and pancreas. Recent studies have clarified that conditions previously diagnosed as Mikulicz disease as well as various types of lymphoplasmacytic infiltrative disorders of the ocular adnexa are consistent with a diagnosis of IgG4-related disease. Against this background, the diagnostic criteria for IgG4-related ophthalmic disease have recently been established, based on both the clinical and the histopathologic features of the ocular lesions. This article reviews these new criteria with reference to the comprehensive diagnostic criteria for IgG4-related disease for all systemic conditions reported in 2012.
Stone, John H; Khosroshahi, Arezou; Hilgenberg, Alan; Spooner, Amy; Isselbacher, Eric M; Stone, James R
We describe herein a patient who developed a dissection of the ascending aorta in the setting of IgG4-related systemic disease, linking IgG4-related systemic disease with a newly-recognized subset of noninfectious aortitis. At the time of aortic surgery, a transmural lymphoplasmacytic infiltrate was detected in the patient's aorta, with a principal focus of inflammation within the media. Immunohistochemical studies demonstrated that >50% of the plasma cells in the lesion stained for IgG4. By in situ hybridization, the plasma cells showed polytypic staining for kappa and lambda light chains, consistent with a polyclonal plasma cell infiltrate. Serologic evaluation revealed that the patient's IgG4 levels were elevated nearly 10-fold. Four years before aortic surgery, the patient had undergone a mediastinal lymph node biopsy. Reexamination of the lymph node revealed features consistent with IgG4-related systemic disease, which had not been recognized at the time of the original biopsy. Glucocorticoid therapy for the IgG4-related systemic disease yielded a prompt response. Recognition that IgG4-related systemic disease can involve the ascending as well as the descending abdominal aorta indicates the need for a change in the way idiopathic aortitis is regarded. This case offers new potential considerations for short- and long-term management of noninfectious aortitis, because of the frequent good response of IgG4-related systemic disease to glucocorticoid treatment without additional therapy. Treatment of the aortitis may prevent progression of the IgG4-related systemic disease to involvement of other organs. IgG4-related systemic disease should be considered in all patients with aortitis judged to be of unknown etiology.
Sato, Yasuharu; Takeuchi, Mai; Takata, Katsuyoshi; Ohno, Kyotaro; Iwaki, Noriko; Orita, Yorihisa; Goto, Naoe; Hida, Akira I; Iwamoto, Toshiyuki; Asano, Naoko; Ito, Toshihiro; Hanakawa, Hiroyuki; Yanai, Hiroyuki; Yoshino, Tadashi
IgG4-related disease is a recently recognized systemic syndrome characterized by mass-forming lesions with lymphoplasmacytic infiltration, increase in the number of IgG4(+) cells in affected tissues and elevation of serum IgG4 levels. In 2009, we were the first to report skin lesions in patients with IgG4-related disease, but no large case series has been reported and clinicopathological findings remain unclear. To clarify these features, we herein report 10 patients (9 men and 1 woman; median age, 64 years; age range, 46-81 years) with IgG4-related skin disease. All patients had erythematous and itchy plaques or subcutaneous nodules on the skin of the head and neck, particularly in the periauricular, cheek, and mandible regions, except for one patient, whose forearm and waist skin were affected. In addition, eight patients had extracutaneous lesions: these were found on the lymph nodes in six patients, the lacrimal glands in three patients, the parotid glands in three patients, and the kidney in one patient. Histologically examined extracutaneous lesions were consistent with IgG4-related disease; five of six lymph node lesions showed progressively transformed germinal centers-type IgG4-related lymphadenopathy. Cases of IgG4-related skin disease were classified into two histological patterns: those exhibiting a nodular dermatitis pattern and those with a subcutaneous nodule pattern. The infiltrate was rich in plasma cells, small lymphocytes, and eosinophils; the majority of the plasma cells were IgG4(+). The IgG4(+) cell count was 49-396 per high-power field (mean±s.d., 172±129), with an IgG4(+)/IgG(+) cell ratio ranging from 62 to 92%. Serum IgG4 levels were elevated in all examined patients. In conclusion, patients with IgG4-related skin disease had uniform clinicopathology. Lesions were frequently present on the skin of the periauricular, cheek, and mandible regions, and were frequently accompanied by IgG4-related lymphadenopathy.
Chougule, Abhijit; Bal, Amanjit; Das, Ashim; Singh, Gurpreet
IgG4 related disease (IgG4RD) is a recently recognised condition characterised by mass forming lesions associated with storiform fibrosis, obliterative phlebitis, lymphoplasmacytic infiltrate rich in IgG4 positive plasma cells and elevated serum IgG4 levels. Although rare, mammary involvement has been reported as IgG4 related sclerosing mastitis, the morphological counterpart of a growing family of IgG4 related diseases. A total of 17 cases belonging to mass forming benign inflammatory breast lesions such as plasma cell mastitis, granulomatous lobular mastitis, non-specific mastitis and inflammatory pseudotumour were investigated as a possible member of IgG4 related sclerosing mastitis. Clinical, radiological, histopathological and immunohistochemistry findings were noted in all cases. Cases diagnosed as inflammatory pseudotumour showed all the histopathological features of IgG4RD along with increased number of IgG4 positive plasma cells and IgG4/IgG ratio >40%. However, only a few IgG4 positive cells were seen in plasma cell mastitis, granulomatous lobular mastitis and non-specific mastitis cases. These cases also did not fulfill the morphological criteria for the diagnosis of IgG4 related diseases. IgG4RD should be excluded in plasma cell rich lesions diagnosed on core biopsies by IgG4 immunostaining. This can avoid unnecessary surgery as IgG4 related diseases respond to simple and effective steroid treatment.
Martínez-de-Alegría, Anxo; Baleato-González, Sandra; García-Figueiras, Roberto; Bermúdez-Naveira, Anaberta; Abdulkader-Nallib, Ihab; Díaz-Peromingo, José A; Villalba-Martín, Carmen
Immunoglobulin G4 (IgG4)-related disease is a relatively recently proposed clinical-pathologic entity that is characterized by fibro-inflammatory lesions rich in IgG4-positive plasma cells and, often but not always, elevated serum IgG4 concentrations. IgG4-related disease was recognized as a systemic disease in 2003, when extrapancreatic manifestations were identified in patients with autoimmune pancreatitis. Since then, the disease has been reported as affecting virtually every organ system and has been identified in the biliary tree, salivary and lacrimal glands, periorbital tissues, lungs, lymph nodes, thyroid gland, kidneys, prostate gland, testicles, breasts, and pituitary gland. Its pathogenesis is poorly understood, but findings are consistent with both an autoimmune and an allergic disorder. Although definitive diagnosis requires histopathologic analysis, imaging plays an important role in demonstrating infiltration and enlargement of involved organs. Because of the systemic nature of the disease, imaging workup of IgG4-related disease should always include whole-body examinations to detect multiorgan involvement. Patients often present with subacute development of a mass in or diffuse enlargement of the affected organ, sometimes mimicking a neoplastic process. In every anatomic location, several inflammatory and neoplastic entities must be considered in the differential diagnosis. Because IgG4-related disease usually shows a marked response to corticosteroid therapy, radiologists should be familiar with its clinical and imaging manifestations to avoid a delay in diagnosis and unnecessary surgical interventions.
Dum, Travis W.; Lee, Eugene K.
IgG4-related disease is a newly recognized fibroinflammatory disorder that has the ability to affect nearly every organ system. It is characterized by tumefactive lesions and fibrosis and closely mimics neoplasms. Only one case of IgG4-related bladder mass has been reported in the literature, but there are no reports of IgG4-related disease in a urachal mass. Herein, we report a 26-year-old male who initially presented with symptoms of recurrent UTI. Work-up revealed a 6 cm urachal tumor, a 1.4 cm pulmonary lesion, and mediastinal lymphadenopathy; all metabolically active on PET scan and suspicious for urachal adenocarcinoma. Lung lesion fine needle aspiration and TURBT pathology revealed inflammation but no evidence of malignancy. The patient underwent a partial cystectomy and umbilectomy with pathology demonstrating dense plasmacytic cells, a high rate of immunohistochemistry staining positive for IgG4 plasma cells, a storiform pattern of fibrosis, and an obliterative phlebitis. Furthermore, the patient had an elevated serum IgG4 level of 227 mg/dL (range 2.4–121 mg/dL). IgG4-related disease is a newly recognized fibroinflammatory disorder that can mimic neoplastic processes and a high index of suspicion and accurate tissue pathology is necessary for an accurate diagnosis. PMID:25202466
Pradhan, Dinesh; Pattnaik, Niharika; Silowash, Russell; Mohanty, Sambit Kumar
IgG4-related disease (IgG4-RD) is a recently recognized systemic autoimmune disorder characterized by high levels of serum IgG4 and dense infiltration of IgG4-positive plasma cells in multiple organs. The condition was first described as a disease of the pancreas, and has since been recognized in various organ systems including the kidneys. IgG4 related kidney disease (IgG4-RKD) signifies any form of renal involvement by IgG4-RD. The most common renal involvement by IgG4-RD is tubulointerstitial nephritis. Glomerular disease, in particular membranous glomerulonephritis, may also be seen. Other co-existent glomerular diseases such as IgA nephropathy, membranoproliferative glomerulonephritis, and mesangioproliferative immune complex glomerulonephritis may be identified. IgG4-related plasma cell arteritis has also been noted in the kidney. As with IgG4-RD in general, IgG4 related kidney disease (IgG4-RKD) usually occurs in middle-aged to elderly men. Common findings in IgG4-RKD are plasma cell-rich interstitial inflammatory infiltrate either in a focal or diffuse pattern with increased IgG4+ plasma cells, expansile swirling interstitial fibrosis, high levels of serum IgG and IgG4, hypocomplementemia, high serum IgE levels and/or peripheral blood eosinophilia. By immunofluorescence, most of the cases show IgG4 dominant tubular basement membrane immune complex deposits. Similar to IgG4-RD, IgG4-RKD often shows a rapid response to steroid therapy. In this review, we discuss the current knowledge on IgG4-RKD and its clinical relevance.
Kawano, Mitsuhiro; Saeki, Takako
Purpose of review IgG4-related disease (IgG4-RD) is a recently recognized systemic inflammatory disorder that can affect most organs/tissues such as sarcoidosis. The kidney is a frequently affected organ with tubulointerstitial nephritis (TIN), the representative lesion of IgG4-RD. This review focuses on the latest knowledge of IgG4-related kidney disease (IgG4-RKD). Recent findings A wide range of renal manifestations of IgG4-RD, that is TIN, membranous glomerulonephritis (MGN) and other glomerular lesions, and pyelitis, are collectively referred to as IgG4-RKD. Clinically, decreased renal function, or characteristic imaging findings such as multiple low-density lesions on contrast-enhanced computed tomography or diffuse thickening of the renal pelvic wall, are typical presenting features. Although a rapid response to corticosteroid therapy is a very important feature of IgG4-TIN, in cases in which renal function is moderately to severely decreased before therapy, only partial recovery of renal function is obtained. Summary TIN with characteristic imaging findings is a typical manifestation of IgG4-RKD in the interstitium, while MGN is a representative manifestation of the glomerular lesions. Although IgG4 is a central feature of IgG4-RD, the recent discovery of IgG4-negative IgG4-RD raises questions about the causative role of the IgG4 molecule in this context. PMID:25594543
Zhang, Lizhi; Smyrk, Thomas C
Autoimmune pancreatitis (AIP) is a rare form of chronic pancreatitis that is characterized by lymphoplasmacytic infiltrate, storiform fibrosis, obliterative phlebitis, and increased IgG4+ plasma cells. Serum IgG4 levels usually are elevated. Patients with AIP frequently have disease affecting other organs or sites; these tissues show similar histologic changes, including increased IgG4+ plasma cell infiltrate and response to corticosteroid therapy. A new clinicopathologic concept of IgG4-related systemic disease (ISD) has been proposed. These diseases often are not limited to the pancreas, and the pancreas may not be involved at all. In this article, we review the literature and our own experience to detail the clinicopathologic features of AIP and extrapancreatic lesions in ISD. PMID:20606730
Perugino, Cory A.; Wallace, Zachary S.; Meyersohn, Nandini; Oliveira, George; Stone, James R.; Stone, John H.
Abstract Objectives: IgG4-related disease (IgG4-RD) is an immune-mediated fibroinflammatory condition that can affect multiple organs and lead to tumefactive, tissue-destructive lesions. Reports have described inflammatory aortitis and periaortitis, the latter in the setting of retroperitoneal fibrosis (RPF), but have not distinguished adequately between these 2 manifestations. The frequency, radiologic features, and response of vascular complications to B cell depletion remain poorly defined. We describe the clinical features, radiology findings, and treatment response in a cohort of 36 patients with IgG4-RD affecting large blood vessels. Methods: Clinical records of all patients diagnosed with IgG4-RD in our center were reviewed. All radiologic studies were reviewed. We distinguished between primary large blood vessel inflammation and secondary vascular involvement. Primary involvement was defined as inflammation in the blood vessel wall as a principal focus of disease. Secondary vascular involvement was defined as disease caused by the effects of adjacent inflammation on the blood vessel wall. Results: Of the 160 IgG4-RD patients in this cohort, 36 (22.5%) had large-vessel involvement. The mean age at disease onset of the patients with large-vessel IgG4-RD was 54.6 years. Twenty-eight patients (78%) were male and 8 (22%) were female. Thirteen patients (36%) had primary IgG4-related vasculitis and aortitis with aneurysm formation comprised the most common manifestation. This affected 5.6% of the entire IgG4-RD cohort and was observed in the thoracic aorta in 8 patients, the abdominal aorta in 4, and both the thoracic and abdominal aorta in 3. Three of these aneurysms were complicated by aortic dissection or contained perforation. Periaortitis secondary to RPF accounted for 27 of 29 patients (93%) of secondary vascular involvement by IgG4-RD. Only 5 patients demonstrated evidence of both primary and secondary blood vessel involvement. Of those treated with
Arnon, Ella; Yaakobi, Alona; Cohen, Yuval; Tiosano, Beatrice
A rare case of IgG4-related disease (IgG4-RD) manifesting as nodular scleritis is presented in a 20-year-old female. Patient complained of left eye pain and redness for one week. Ocular examination together with ancillary testing led to the diagnosis of nodular scleritis. Since the patient did not show apparent improvement after one week of systemic steroidal treatment, she underwent a biopsy of the affected area revealing histopathological characteristics of IgG4-RD. Long-term treatment with corticosteroids and a steroid-sparing agent (methotrexate) led to significant improvement in signs and symptoms. This case highlights the significance of IgG4-RD in the differential diagnosis of scleritis and raises the question as to whether various organs affected by IgG4-RD may have different underlying pathophysiological mechanisms in which pathogenic T cells play a role. PMID:28149653
Ebbo, Mikael; Patient, Matthieu; Grados, Aurelie; Groh, Matthieu; Desblaches, Julien; Hachulla, Eric; Saadoun, David; Audia, Sylvain; Rigolet, Aude; Terrier, Benjamin; Perlat, Antoinette; Guillaud, Constance; Renou, Frederic; Bernit, Emmanuelle; Costedoat-Chalumeau, Nathalie; Harlé, Jean-Robert; Schleinitz, Nicolas
Abstract IgG4-related disease (IgG4-RD) is characterized by variable tissue or organ involvements sharing common pathological findings. Orbital or orbital adnexa involvement of the disease has been reported in a few case series. The aim of our study was to characterize and analyze ophthalmic manifestations from a nationwide French case-series. Patients with IgG4-RD and orbital or orbital adnexa involvement included in the French multicentric IgG4-RD case-registry were identified. Only patients fulfilling “modified” comprehensive diagnostic criteria with pathological documentation were retained for the study. Clinical, biological, pathological, radiological findings and data regarding the response to treatment were retrospectively analyzed. According to our data registry, the frequency of IgG4-related ophthalmic disease (IgG4-ROD) was 17%. Mean age at diagnosis was 55.1 ± 7.1 years with a male/female ratio of 2.2. The 19 cases of IgG4-ROD consisted of lacrimal gland (68.4%), soft tissue (57.9%), extra-ocular muscles (36.8%), palpebral (21.1%), optical nerve (10.5%), orbital bone (10.5%), and mononeuritis (V1 and/or V2, 10.5%) involvements. IgG4-ROD was bilateral in 57.9% of cases. Extra-ophthalmic manifestations were reported in 78.9% of cases. All patients responded to prednisone but two-thirds of patients relapsed within a mean (SD) of 9.8 (3.5) months and 72.2% required long-term glucocorticoids and/or immunosuppressive agents. Eight patients were treated by rituximab with a favorable response in 87.5% of cases. Lacrimal involvement is the most frequent ophthalmic manifestation of IgG4-RD and is frequently associated with extra-orbital manifestations. Despite initial favorable response to steroids, the long-term management of relapsing patients needs to be improved. PMID:28272212
Brito-Zerón, Pilar; Ramos-Casals, Manuel; Bosch, Xavier; Stone, John H
IgG4-related disease (IgG4-RD) is an emerging immune-mediated disease with the capability of involving essentially any organ. The epidemiology of this disease has not been explored in detail. A majority of patients reported in the literature to date are from Japan, but the condition has been described all across the world and there is no strong evidence to suggest a predilection for Asian populations. The mean age at diagnosis is approximately 60 years and there is a decided male predominance for many clinical features, with an overall male:female ratio of 8:3. A cardinal feature of IgG4-RD is single or multiple organ swelling that often raises concern for malignancy. IgG4-RD should be suspected in patients presenting with unexplained enlargement or swelling of one or more organs. Presenting features vary substantially according to the specialty to which patients present first; in addition, the disease can be diagnosed unexpectedly in pathological specimens or identified incidentally on radiology studies. Involvement of major organs is common and IgG4-RD may lead to organ failure, particularly in the pancreas, liver and biliary tree, kidneys, thyroid gland, lungs, and aorta. The diagnosis of IgG4-RD relies on the coexistence of various clinical, laboratory and histopathological findings, although none is pathognomonic by itself.
Detlefsen, S; Klöppel, G
At an international consensus conference in 2011, multifocal chronic fibrosing inflammatory processes, which are associated with elevated IgG4 serum levels and/or tissue infiltration with IgG4 positive plasma cells, were recognized as a distinct disease entity called IgG4-related disease (IgG4-RD). As IgG4-RD responds well to steroid treatment but imitates a tumor in many organs, particularly in the pancreas, a biopsy for confirmation of the diagnosis is often warranted. The histological criteria for IgG4-RD as defined in 2011 are based on the following main features: 1) dense lymphoplasmacytic infiltrate, 2) storiform fibrosis and 3) obliterative phlebitis. The diagnosis is further supported by immunohistochemical demonstration of an increased infiltration of IgG4-positive plasma cells and an elevated IgG4/IgG ratio. The morphological criteria of IgG4-RD are in most cases detectable in biopsies and can significantly contribute to the diagnosis of this disease, in concert with clinical, serological (elevated serum IgG4 level) and radiological features.
Takeuchi, Mai; Sato, Yasuharu; Yasui, Hiroshi; Ozawa, Hiroaki; Ohno, Kyotaro; Takata, Katsuyoshi; Gion, Yuka; Orita, Yorihisa; Tachibana, Tomoyasu; Itoh, Tomoo; Asano, Naoko; Nakamura, Shigeo; Swerdlow, Steven H; Yoshino, Tadashi
IgG4-related lymphadenopathy with increased numbers of Epstein-Barr virus (EBV)-infected cells has been reported but not fully described. We analyzed 31 cases of IgG4-related lymphadenopathy and 24 cases of extranodal IgG4-related diseases for their possible relationship with EBV. Other types of reactive lymph nodes (22) and angioimmunoblastic T-cell lymphoma (AITL) (10) were also studied for comparison. EBV-encoded RNA (EBER) in situ hybridization revealed EBER(+) cells in 18 of 31 cases (58%) of IgG4-related lymphadenopathy. Increased EBER(+) cells were found in only 4 of 22 (18.1%) non-IgG4-related reactive lymphoid hyperplasia in patients of a similar age (P=0.002) and in only 5 of 24 (21%) extranodal IgG4-related biopsies (P=0.006). Interestingly, all patients with EBER(+) progressively transformed germinal center-type IgG4-related lymphadenopathy had systemic lymphadenopathy and/or extranodal involvement. AITL also is associated with EBV, and IgG4-related lymphadenopathy sometimes mimics the morphology of AITL; however, the number of IgG4(+) cells in AITL was significantly less than that in IgG4-related lymphadenopathy (P<0.001). Increased numbers of regulatory T cells are seen in IgG4-related disease; however, there was not a significant difference between the EBER(+) and EBER(-) cases. In conclusion, the presence of increased numbers of EBV-infected cells in IgG4-related lymphadenopathy, compared with other reactive lymphadenopathy or extranodal IgG4-related disease, suggests that there may be a relationship at least between nodal IgG4-related disease and EBV. It is important to avoid overdiagnosing these cases as malignant lymphomas or EBV-related lymphoproliferative disorders.
Smit, Wouter; Barnes, Eleanor
IgG4-related disease (IgG4-RD) is increasingly recognised in Western societies as a multi-system, inflammatory, fibrosing disease of unknown aetiology that typically, though not exclusively, presents in older men. The clinical manifestations are diverse and almost any organ may be affected. The cardinal histological features are a lymphoplasmacytic infiltrate, storiform fibrosis, obliterative phlebitis and an abundance of IgG4+ plasma cells in affected organs. Serum IgG4 levels are elevated in approximately 70% of patients and are a useful biomarker when present. IgG4-RD is frequently misdiagnosed as malignancy. Making the correct diagnosis is important as the disease is usually steroid responsive, although relapse rates are high. Second-line immunosuppressive agents and B-cell depletion therapy have also been used in retreatment strategies. Recent data suggests that the disease is associated with both progressive organ failure and malignancy. The biological mechanisms driving IgG4-RD remain unclear but this is currently an area of intense scientific investigation. Broadly, IgG4+ B cells are thought to exhibit a regulatory phenotype, but it is not known if these are pathogenic or simply represent a bystander effect. Extending our understanding of the role of IgG4 immunoglobulins in health and disease, the assessment of B and T cell immune phenotype, and large genetic studies of IgG4-RD may enhance our understanding of disease pathogenesis. Ultimately it may be that there is not a single, simple unifying aetiology and so careful stratification of disease by clinical phenotype will be required in multi-centre prospective clinical cohorts. These cohorts will also be essential for the study of treatment outcomes with novel therapies.
Brito-Zerón, Pilar; Kostov, Belchin; Bosch, Xavier; Acar-Denizli, Nihan; Ramos-Casals, Manuel; Stone, John H.
Abstract To review the reported evidence on the therapeutic management of IgG4-related disease (IgG4-RD) in clinical practice. A systematic search of the literature was conducted. The primary outcome measured was the rate of efficacy of first-line therapeutic approaches. Secondary outcomes measured included the rate of disease relapse, the outcome of untreated patients, the rate of patients without drug therapy at the end of follow-up, the rate of side effects, and mortality. The MOOSE, AHRQ, STROBE, and GRACE recommendations/statements were followed. The results of the systematic search strategy yielded 62 studies that included a total of 3034 patients. Complete information about first-line therapeutic regimens was detailed in 1952 patients, including glucocorticoid-based regimens in 1437 (74%), drug-free regimens in 213 (11%), and other therapies in 38 (2%). No therapy (wait and see management) was reported in 264 (13%) patients. The efficacy of monotherapy with glucocorticoids was specified in 1220 patients, of whom 97% had a therapeutic response. Relapses, however, were reported in 464/1395 (33%) patients despite typically short follow-up periods. Therapeutic efficacy was reported in 219/231 (95%) of relapses treated with glucocorticoids, 56/69 (81%) of those treated with azathioprine, 16/22 (72%) of those treated with other immunosuppressive agents, and in the 9 cases treated with rituximab (100%). In 14 studies, the authors detailed the outcome of 159/246 patients with wait-and-see management; spontaneous improvement or resolution was reported in 68 (43%) cases. Wide heterogeneity was observed with respect to the first-line therapeutic approaches used for the different organ-specific disease subsets, including significant differences in the mean dose of glucocorticoids used. Nearly 70% of reported IgG4-RD patients are treated with oral glucocorticoids in monotherapy. However, the therapeutic management is heavily influenced by geographical, epidemiological
Inoue, Akiko; Wada, Kota; Matsuura, Kentaro; Osafune, Hiroshi; Ida, Yutaro; Kosakai, Arifumi; Edamatsu, Hideo
IgG4-related disease was recently proposed under the classification of systemic chronic inflammatory disease. In the field of otolaryngology, organ-specific diagnostic criteria have been established for the occurrence of this condition in the salivary glands, but not in the sinonasal cavity. Here we report a case involving a 70-year-old man with IgG4-related disease in the sinonasal cavity. The patient, with the chief complaint of nasal bleeding, first visited a physician. However, the patient experienced recurrent bleeding with intranasal structure loss and was subsequently referred to our hospital. His IgG4 level was elevated, and histopathological examination of a tissue sample obtained from the edematous sphenoid sinus showed increased IgG4-positive plasma cells and storiform fibrosclerosis. A definitive diagnosis of IgG4-related rhinosinusitis was made on the basis of comprehensive criteria for IgG4-related disease. The disease showed a progressively destructive course that was clearly different from that of chronic sinusitis and represented a very rare case of IgG4-related rhinosinusitis. IgG4-related disease originating in the sinonasal cavity is rare, and, to the best of our knowledge, this is the first primary case of IgG4-related disease that originated in one side of the sinonasal cavity and showed progressive destruction.
Sekulic, Miroslav; Pichler Sekulic, Simona; Movahedi-Lankarani, Saeid
IgG4-related disease has been previously described to involve numerous organs and anatomic sites, however, involvement of the ovary has not yet been reported in the literature. In this case report we describe an ovary involved with an inflammatory process with histopathologic features supportive of involvement by IgG4-related disease: a dense lymphoplasmacytic infiltrate with an eosinophilic component, obliterative phlebitis, and a prominent proportion of IgG-positive cells with IgG4 expression by immunohistochemistry (40%-50%). The differential diagnosis for this case would include eosinophilic perifolliculitis involving the ovary, another rare entity that shares the eosinophilic component of IgG4-related disease. In short, we present the first description of IgG4-related disease of the ovary providing morphologic characterization and immunohistochemical studies supporting the diagnosis.
Takahashi, Hiroki; Yamamoto, Motohisa; Suzuki, Chisako; Naishiro, Yasuyoshi; Shinomura, Yasuhisa; Imai, Kohzoh
IgG4-related disease is a distinct clinical entity, whose characteristic features are the following; Serum IgG4 is prominently elevated, IgG4-positive plasma cells infiltrate in involved tissues, various mass-forming lesions with fibrosis develop in a timely and spatial manner and the response to corticosteroids is prompt and good. IgG4-related diseases mainly target two organs. One is the pancreas (autoimmune pancreatitis; AIP), and the other comprises the lacrimal and salivary glands, the clinical phenotype is Mikulicz's disease (MD). MD has long been considered a manifestation of Sjögren's syndrome (SS). However, we noticed several clinical differences in case of MD from SS; no deflection of female sex differences, mild sicca syndrome, good response to corticosteroids, no positivity of anti-SS-A/SS-B antibodies. In addition, elevated level of serum IgG4 and abundant infiltration of plasma cells expressing IgG4 were reported in MD patients. Those are common features of IgG4-related diseases. MD often coexisted with IgG4-related diseases such as AIP, retroperitoneal fibrosis, and IgG4-associated nephropathy. Based on those findings, it has been considered to recognize IgG4-related diseases including MD as a new clinical entity. The etiology of IgG4-related systemic diseases remains to be elucidated. It is necessary to accumulate and analyze larger data from patients worldwide.
IgG4-related disease is well-known, and while the functions of cytokines which affect IgG4 production are being clarified, it remains unclear what causes it. There are many clinicopathological characteristics of IgG4-related disease and, therefore, comprehensive criteria are used for diagnosis. Notably, histopathological findings are the most important of these, with which we cannot make a definite diagnosis. The model disease of an IgG4-related disease is autoimmune pancreatitis (AIP). Currently, AIP is classified into type 1 (AIP1) and type 2 (AIP2). AIP1 is IgG4-related while AIP2 is not. AIP1 sometimes has localized mass formation, making it difficult to distinguish between AIP1 and pancreatic cancer. Thus, upon biochemical and immunological examination, the IgG4 level is the most useful for the diagnosis, although the levels of IL-2R, β2MG, C4, and monoclonal rheumatoid factor are also useful for the assessment of disease. In addition, histopathological findings are also important to diagnose AIP1. Typical AIP1 cases show lymphoplasmacytic infiltration including IgG4-positive plasma cells with storiform fibrosis. A careful analysis of cases with the typical features of IgG4-related disease will lead to the elucidation of the mechanism behind IgG4-related disease.
Leivo, Tiina; Koskenmies, Sari; Uusitalo, Marita; Tynninen, Olli
IgG4-related disease is a recently defined inflammatory process characterized by IgG4-bearing plasma cells in the involved tissues. The most common sites of involvement are the pancreas, hepatobiliary tract, salivary glands, lymph nodes, retroperitoneum and orbit, especially the lacrimal glands. Other ocular or ocular adnexal sites are rare. To our knowledge, there is one reported case of a conjunctival involvement. We describe a patient, who had an IgG4-RD mimicking chalazion in the upper eyelid, confined to the tarsus, with multiple skin lesions on the trunk. This is a case report of a 55-year-old female. A 55-year-old female presented with an upper eyelid lesion, which was clinically diagnosed as chalazion and drained three times. Histopathological diagnoses were chalazion and inflammation with mixed cells, respectively. Additionally, the patient had had skin nodules on the trunk for several years. Finally, after a third recurrence, the tarsal eyelid lesion was completely excised. The tarsal pathology specimen showed 85 IgG4 positive plasma cells per HPF and the IgG4/IgG ratio was 0.64, suggesting a probable IgG4-related disease. The re-examined skin lesions resembled histologically the eyelid lesion. It is essential to be aware of IgG4-related disease, including in recurrent chalazia.
IgG4 related disease of the head and neck region represents one of the more common manifestations of IgG4 related disease. Involvement of the submandibular and parotid glands, the orbit and thyroid represent some of the more common sites involved by IgG4 related disease. Eosinophilic angiocentric fibrosis, Mikulicz disease and Riedel thyroiditis are also members of the family of IgG4 related disease. Clinically, the disease is characterized by tumefactive lesions, often multicentric, that show a swift response to immunosuppressive therapy. An elevated serum IgG4 represents the only validated blood based biomarker. However, elevated serum IgG4 is detected in only half the patients with this disease. Histology continues to represent the gold standard for the diagnosis of IgG4 related disease: storiform-type fibrosis and obliterative phlebitis constitute characteristic features of this disease. A definitive diagnosis of IgG4 related disease also requires the presence of elevated numbers of IgG4 positive plasma cells as well as an IgG4 to IgG ratio of greater than 40 %. In isolation, elevated numbers of IgG4 positive plasma cells represents a non-specific feature, detected in a variety of other inflammatory as well as neoplastic diseases. Attention to the clinical context, histological features, as well as an elevated IgG4 to IgG ratio is critical to avoiding overdiagnosis of IgG4 related disease.
Yamada, Rin; Horiguchi, Shin-ichiro; Yamashita, Toshinari; Kamisawa, Terumi
IgG4-related disease (IgG4-RD) is characterised by high serum concentrations of IgG4, dense lymphoplasmacytic infiltrates, storiform fibrosis and increased IgG4-positive plasma cells in tissues. This systemic disease occurs in various organs metachronously, but IgG4-related mastitis appears extremely rare. We report a case of IgG4-related mastitis, radiologically considered to represent breast cancer mainly composed of intraductal component and requiring histological differentiation from mucosa-associated lymphoid tissue (MALT) lymphoma. The breast mass disappeared with steroid therapy. When patients have a breast mass, regardless of the presence or absence of IgG4-RD, IgG4-related mastitis should be considered in addition to breast cancer. If histological findings show dense lymphoplasmacytic infiltrates, IgG4-related mastitis should be suspected in addition to malignant lymphoma, and lack of monoclonality should be confirmed. To avoid unnecessary surgery or chemotherapy, knowledge and accurate diagnosis of the entity of IgG4-related mastitis is necessary.
Della-Torre, E; Lanzillotta, M; Doglioni, C
Immunoglobulin G4-related disease (IgG4-RD) is a fibroinflammatory condition that derives its name from the characteristic finding of abundant IgG4+ plasma cells in affected tissues, as well as the presence of elevated serum IgG4 concentrations in many patients. In contrast to fibrotic disorders, such as systemic sclerosis or idiopathic pulmonary fibrosis in which the tissues fibrosis has remained largely intractable to treatment, many IgG4-RD patients appear to have a condition in which the collagen deposition is reversible. The mechanisms underlying this peculiar feature remain unknown, but the remarkable efficacy of B cell depletion in these patients supports an important pathogenic role of B cell/T cell collaboration. In particular, aberrant T helper type 2 (Th2)/regulatory T cells sustained by putative autoreactive B cells have been proposed to drive collagen deposition through the production of profibrotic cytokines, but definitive demonstrations of this hypothesis are lacking. Indeed, a number of unsolved questions need to be addressed in order to fully understand the pathogenesis of IgG4-RD. These include the identification of an antigenic trigger(s), the implications (if any) of IgG4 antibodies for pathophysiology and the precise immunological mechanisms leading to fibrosis. Recent investigations have also raised the possibility that innate immunity might precede adaptive immunity, thus further complicating the pathological scenario. Here, we aim to review the most recent insights on the immunology of IgG4-RD, focusing on the relative contribution of innate and adaptive immune responses to the full pathological phenotype of this fibrotic condition. Clinical, histological and therapeutic features are also addressed. PMID:25865251
Della-Torre, E; Lanzillotta, M; Doglioni, C
Immunoglobulin G4-related disease (IgG4-RD) is a fibroinflammatory condition that derives its name from the characteristic finding of abundant IgG4(+) plasma cells in affected tissues, as well as the presence of elevated serum IgG4 concentrations in many patients. In contrast to fibrotic disorders, such as systemic sclerosis or idiopathic pulmonary fibrosis in which the tissues fibrosis has remained largely intractable to treatment, many IgG4-RD patients appear to have a condition in which the collagen deposition is reversible. The mechanisms underlying this peculiar feature remain unknown, but the remarkable efficacy of B cell depletion in these patients supports an important pathogenic role of B cell/T cell collaboration. In particular, aberrant T helper type 2 (Th2)/regulatory T cells sustained by putative autoreactive B cells have been proposed to drive collagen deposition through the production of profibrotic cytokines, but definitive demonstrations of this hypothesis are lacking. Indeed, a number of unsolved questions need to be addressed in order to fully understand the pathogenesis of IgG4-RD. These include the identification of an antigenic trigger(s), the implications (if any) of IgG4 antibodies for pathophysiology and the precise immunological mechanisms leading to fibrosis. Recent investigations have also raised the possibility that innate immunity might precede adaptive immunity, thus further complicating the pathological scenario. Here, we aim to review the most recent insights on the immunology of IgG4-RD, focusing on the relative contribution of innate and adaptive immune responses to the full pathological phenotype of this fibrotic condition. Clinical, histological and therapeutic features are also addressed.
Galeano, Dario; Zanoli, Luca; Scarfia, Viviana Rosalia; L'Imperio, Vincenzo; Malatino, Lorenzo; Fatuzzo, Pasquale; Granata, Antonio
IgG4 related disease is a systemic fibro-inflammatory disorder characterized by multiple organ and multiple tissue lesions. The real pathogenesis is currentlyactually unknown. For these reasons many authors compare IgG4 related disease to sarcoidosis. Lesions are often localized in the pancreas, salivary and lacrimal glands, biliary ducts, retroperitoneum and in many other organs. The diagnosisis difficult because of mild symptoms and the possibility of mimicking other severe diseases. Therefore, histopathology together with clinical and radiological typical findings are mandatory tools for diagnosis. Steroidtherapy usually enables disappearance of tumor like lesions and complete recovery. Kidney has an extensive organ involvement in the contextof IgG4-related disease. Historically, tubule - interstitial nephritis(TIN) is considered the main renal feature of renal lesions, however recent studies extend the spectrum of renal lesions also to glomerular tuft. These findings allow to introduce in the nosography the term of IgG4related kidney disease (IgG4 RKD). This review focuses on renal involvement in IgG4related disease, in order to help nephrologists to improve their clinical, diagnostic and therapeutic approach to this emerging pleiotropic clinical pattern.
IgG4-related disease is a chronic and fibroinflammatory disorder, which is characterized with elevated levels of serum IgG4, and prominent infiltration of IgG4-bearing plasma cells in the involved organs. It often affects with lacrimal glands, salivary glands, pancreas, kidneys, lungs, and retroperitoneal cavity. Now, the first line of the induction therapy for IgG4-related disease is glucocorticoid, but almost patients need the maintenance treatment and experience the relapse. It is recently reported that biologic agents, including rituximab and abatacept, are effective for the relapse of IgG4-related disease. It is clear that the tapering effect of glucocorticoid is better than conventional oral immunosuppressants. We can use it in safely if we choose the appropriate cases. The investigator-initiated trial of rituximab for IgG4-related disease is scheduled in Japan. This article reviews the new strategies for the treatment of IgG4-related disease with our data of SMART registry, and discuss the problems of each biologic agents for IgG4-related disease.
Frydman, James; Grunner, Shahar; Kluger, Yoram
IgG4-related disease is a recently recognized entity linked initially to autoimmune pancreatitis and has been subsequently described in nearly every organ system. Men over the age of 50 represent the most affected demographic group and a comprehensive set of diagnostic criteria has been developed to aid treating clinicians. Though elevated levels of IgG4 in the serum are suggestive of the disease, definitive diagnosis is made on histopathology. Treatment is tailored to the clinical presentation with corticosteroid therapy known to have proven efficacy. Gastric manifestations of the IgG4-related disease primarily come in two varieties, notably chronic ulceration or pseudotumor formation. Autoimmune pancreatitis conveys increased risk for IgG4-related disease of the stomach, which is independent of Helicobacter pylori status. In this case report, we present an acute gastric-pericardial fistula secondary to IgG4-related disease that required urgent operative management. To our knowledge, this is the first report in the medical literature describing this complication of IgG4-related disease.
Tan, Hongyi; Li, Haitao; Hu, Yongbing; Niu, Ruichao; Pan, Pinhua; Hu, Chengping
IgG4-related disease (IgG4-RD) is a chronic progressive autoimmune disease. Solely lung involved IgG4-RD is extremely rare. Herein, we reported a case of IgG4-related disease as mimicking tuberculosis. A 52-year-old male patient was admitted due to cough and hemoptysis for two months and fever for 1 month. The pre-admission diagnosis in another hospital was secondary pulmonary tuberculosis, but the quadruple anti-tuberculosis therapy was ineffective and the disease condition continued to deteriorate. The percutaneous lung biopsy was carried out after admission and the pathological diagnosis was IgG4-related disease. The patient's disease condition was improved following hormonal therapy.
Du, Haitao; Wu, Yinqiao; Yan, Li; Wu, Benyan; Wan, Jun
IgG4-related disease is a newly recognized systemic disease characterized by involving a wide range of organs. It includes the pancreas, biliary tree, salivary glands, periorbital tissues, upper aerodigestive tract, retroperitoneum, mediastinum, aorta, soft tissue, skin, central nervous system, breast, kidneys, prostate, lungs and lymph nodes. The elevated serum titer of immunoglobulin G4 (IgG4), which is the least common (3 % to 6 %) of the 4 subclasses of IgG, is a special marker for IgG4-related disease. However, its entity is still unknown. This article reviewed the literature to learn the IgG4-related diseases and their current status of diagnostic approaches. PMID:27847453
IgG4-related disease is a newly recognized systemic fibroinflammatory disorder. We report a 36-year-old man who presented with intractable right nasal pain and frontal headache for 1 month. Computed tomography revealed an ill-defined lesion with bony erosion over the right anterior ethmoid sinus and middle turbinate. The lesion was resected through endoscopic anterior ethmoidectomy and middle turbinectomy. IgG4-related disease was definitively diagnosed according to histopathological features. Prednisolone was administered postoperatively. IgG4-related disease presenting with destructive sinonasal lesion mimicking malignancy is rare. Awareness is essential to avoid delayed diagnosis or unnecessary invasive intervention, because the disorder responds to glucocorticoid and immunosuppressant therapy.
Lu, Zeyuan; Yin, Jianyong; Bao, Hongda; Jiao, Qiong; Wu, Huijuan; Wu, Rui; Xue, Qin; Wang, Niansong; Zhang, Zhigang; Wang, Feng
Introduction IgG4-related disease (IgG4-RD) is a fibroinflammatory disorder that may involve almost each organ or system. IgG4-related kidney disease (IgG4-RKD) refers to renal lesions associated with IgG4-RD. The most frequent morphological type of renal lesions is IgG4-related tubulointerstitial nephritis (IgG4-TIN) which is associated with increased IgG4-positive plasma cell infiltration and interstitial fibrosis. Case Report Herein, we present a rare case with coexisting IgG4-RKD and acute crescent glomerulonephritis with concomitant severe tubulointerstitial lesions instead of classic IgG4-TIN. Conclusion IgG4-RKD and acute crescent glomerulonephritis can occur in the same patient. This case may give us a clearer viewpoint of the disease. PMID:27504450
Izumi, Yasumori; Takeshita, Hayato; Moriwaki, Yuji; Hisatomi, Keiko; Matsuda, Masakazu; Yamashita, Natsuki; Kawahara, Chieko; Shigemitsu, Yoshika; Iwanaga, Nozomi; Kawakami, Atsushi; Kurohama, Hirokazu; Niino, Daisuke; Ito, Masahiro; Migita, Kiyoshi
A 50-year-old woman was referred to our hospital for shoulder joint stiffness. She had a history of polyclonal hypergammaglobulinemia and an elevated C-reactive protein level. Her laboratory data revealed an elevated serum immunoglobulin G4 (IgG4) level, hypergammaglobulinemia, and rheumatoid factor positivity in the absence of anticyclic citrullinated peptide antibody. [18(F)]-Fluorodeoxyglucose positron emission tomography showed significant [18(F)]-fluorodeoxyglucose uptake in multiple lymph nodes (axillary, hilar, para-aortic, and inguinal). Biopsy of the inguinal lymph node showed expansion of the interfollicular areas by heavily infiltrating plasma cells, consistent with multicentric Castleman disease (MCD). Immunohistochemical analysis revealed a 37.3% IgG4-positive:IgG-positive plasma cell ratio, indicating overlapping IgG4-related disease. However, serological cytokine analysis revealed elevated levels of interleukin-6 (9.3 pg/ml) and vascular endothelial growth factor (VEGF) (1210 pg/ml), which are compatible with MCD. Corticosteroid treatment resolved the serological and imaging abnormalities. IgG4-related disease can mimic MCD, and it is crucial to distinguish between these two diseases. Serum interleukin-6 and VEGF levels may help to discriminate MCD from IgG4-related disease.
Chen, Luke YC; Wong, Patrick CW; Noda, Shinji; Collins, David R; Sreenivasan, Gayatri M; Coupland, Robert C
Key Clinical Message Polyclonal hyperviscosity syndrome (HVS) is rare and has been reported in various disorders of immune dysregulation and lymphoid hyperplasia. IgG4-Related Disease (IgG4-RD) is an emerging disorder often associated with exuberant hypergammaglobulinemia, and this review of seven cases establishes IgG4-RD as an important cause of polyclonal HVS. PMID:25914812
Li, Luocheng; Wang, Zhiwei; Xu, Peng; Ruan, Yongle; Jiang, Wanli; Wu, Zhiyong
As a designated entity within medicine, immunoglobulin G4 (IgG4)-related disease is relatively new. It is immune-mediated origin, characterized by a tendency for formation of tumefactive lesions, the infiltration of IgG4-positive plasma cells, and frequent but not invariable elevations of IgG4 levels in the serum. IgG4-related cardiac mass accompanying aortic intramural hematoma is an extremely rare clinical presentation. Herein we present the case of a patient who was admitted to our department complaining of severe chest pain. Computed tomographic angiography examination revealed a cardiac mass accompanying an aortic intramural hematoma. He underwent a surgical resection of the cardiac mass and a replacement of the ascending aorta with Hemashield Platinum graft and made an uneventful recovery. A diagnosis of an IgG4-related disease was made based on laboratory results and pathological examination. Corticosteroids were administered postoperatively. This case shows that the heart itself can also be a potential site for IgG4-related disease.
Luiz, Henrique Vara; Gonçalves, Diogo; Silva, Tiago Nunes da; Nascimento, Isabel; Ribeiro, Ana; Mafra, Manuela; Manita, Isabel; Portugal, Jorge
Hashimoto's thyroiditis (HT) has been characterized for many years as a well-defined clinicopathologic entity, but is now considered a heterogeneous disease. IgG4-related HT is a new subtype characterized by thyroid inflammation rich in IgG4-positive plasma cells and marked fibrosis. It may be part of the systemic IgG4-related disease. We report a case of a 56-year-old Portuguese man who presented with a one-month history of progressive neck swelling and dysphagia. Laboratory testing revealed increased inflammatory parameters, subclinical hypothyroidism and very high levels of thyroid autoantibodies. Cervical ultrasound (US) demonstrated an enlarged and heterogeneous thyroid gland and two hypoechoic nodules. US-guided fine needle aspiration cytology was consistent with lymphocytic thyroiditis. The patient was submitted to total thyroidectomy and microscopic examination identified typical findings of HT, marked fibrosis limited within the thyroid capsule and lymphoplasmacytic infiltration, with >50 IgG4-positive plasma cells per high-power field and an IgG4/IgG ratio of >40%. After surgery, serum IgG4 concentration was high-normal. Symptoms relief and reduction in laboratory inflammatory parameters were noticed. Thyroid function is controlled with levothyroxine. To our knowledge we report the first case of IgG4-related HT in a non-Asian patient. We also perform a review of the literature regarding IgG4-related disease and IgG4-related HT. Our case highlights this new variant of the well known HT, and helps physicians in recognizing its main clinical features, allowing for proper diagnosis and treatment.
Jokisch, Friedrich; Kleinlein, Irene; Haller, Bernhard; Seehaus, Tanja; Fuerst, Heinrich; Kremer, Marcus
IgG4-related disease is a newly identified syndrome characterized by high serum IgG4 levels and increased IgG4-positive plasma cells in involved organs. The incidence of IgG4-related thyroiditis in the Caucasian population of Europe is unknown. We investigated formalin-fixed thyroid gland samples of 216 patients (191 Hashimoto's thyroiditis, 5 Riedel's thyroiditis, and 20 goiters, as controls), morphologically, and immunohistochemically. Cases were divided into two groups: IgG4-related Hashimoto's thyroiditis (24 cases) together with Riedel thyroiditis (1 case) and 171 non-IgG4-related thyroiditis. Compared to the non-IgG4-related cases, IgG4-related thyroiditis showed a higher IgG4/IgG ratio (0.6 vs. 0.1, p < 0.0001), a higher median IgG4 count (45.2 vs. 6.2, p < 0.0001), an association with younger age (42.1 vs. 48.1 years, p = 0.036), and a lower female-to-male ratio (11:1 vs. 17.5:1). Fibrous variant of Hashimoto's thyroiditis was diagnosed in 23 of the 24 IgG4-related cases (96 %) and in 13 of 167 (18 %, p > 0.001) non-IgG4-related cases. The single case of IgG4-related Riedel's thyroiditis also showed a higher median IgG4 plasma cell count (56.3 vs. 14.3) and a higher IgG4/IgG ratio (0.5 vs. 0.2) than the four cases of non-IgG4-related Riedel's thyroiditis. Our data suggests the incidence of IgG4-related disease (IgG4-RD) of the thyroid gland in Europe is considerably lower than that observed in other studies. A significant elevation of IgG4-positive plasma cells was only found in a small group of Hashimoto's thyroiditis and then accompanied by intense fibrosis, indicating an association with IgG4-RD. Morphologically, IgG4-RD of the thyroid gland differs from that in other organ systems, exhibiting a dense fibrosis without intense eosinophilia or obliterative phlebitis.
Mavrogeni, Sophie; Markousis-Mavrogenis, George; Kolovou, Genovefa
Immunoglobulin 4-related disease (IgG4-related disease) is a systemic inflammatory disease that presents with increases of serum IgG4. It may affect various systems, including the cardiovascular (CV) system. Assessment of serum IgG4 levels and involved organ biopsy are necessary for diagnosis. IgG4-related disease is characterized by fibrosclerosis, lymphocytic infiltration and presence of IgG4-positive plasma cells. The disease usually responds to treatment with corticosteroids and/or immunosuppressive medication. CV involvement may manifest as cardiac pseudotumors, inflammatory periaortitis, coronary arteritis and/or pericarditis. IgG4-related cardiovascular disorders can severely affect patient prognosis. Various imaging techniques, including echocardiography, Computed Tomography (CT), 18FDG-PET, Cardiovascular Magnetic Resonance (CMR) and cardiac catheterisation, have been successfully used for early disease detection and follow-up. Echocardiography and vascular ultrasound are the most commonly used non-invasive, non-radiating imaging techniques for the evaluation of IgG4-related CV disease. Periaortitis/periarteritis can be also assessed by CT, showing a soft tissue thickening around arteries. Coronary artery aneurysms can be easily diagnosed by coronary CT. In case of active periarterial or coronary artery inflammation, 18FDG-PET will show FDG uptake at the area of the lesion. CMR, due to its capability to perform function and tissue characterisation, can offer an integrated imaging of aorta, coronary arteries and the heart, assessment of disease acuity, extent of fibrosis and guide further treatment. However, multimodality imaging may be necessary for assessment of disease activity and fibrosis extent in those cases with multifocal CV involvement.
DaCosta, Joanna; Younis, Saad
This report describes a case of reversible topiramate-induced maculopathy in a 32-year-old female patient with IgG4-related disease. The patient presented with decreased vision associated with anterior uveitis and cystoid macula edema, which was unresponsive to oral and topical steroids. Following topiramate cessation, both cystoid macula edema and vision improved. The ocular side effects of topiramate and putative pharmacological mechanisms for topiramate-induced maculopathy in the context of IgG4-related disease are discussed. This report highlights that neurologists and ophthalmologists should be aware that patients presenting with topiramate-associated maculopathy should be advised to discontinue topiramate promptly to prevent irreversible loss of vision. PMID:27354829
Hsing, Ming-Tai; Hsu, Hui-Ting; Cheng, Chun-Yuan; Chen, Chien-Min
Hypophysitis is a rare inflammatory disorder that can mimic a pituitary tumor clinically or radiologically. Furthermore, immunoglobulin G4 (IgG4)-related systemic disease is only a just recently characterized disorder. It can manifest as a systemic disease involving multiple organs, including the pancreas, salivary glands, lungs, liver, bile duct, gallbladder, kidneys, and retroperitoneum. It is characterized by a high serum level of IgG4 clinically and dense lymphoplasmacytic infiltration with sclerosis and phlebitis histologically. Herein, we report the case of a man 66 years of age who presented with nausea, vomiting, and poor appetite with a body weight loss of 4 kg. Image study revealed a pituitary infundibulum mass, right-posterior mediastinal and paraspinal masses, as well as infiltrating masses in bilateral kidneys. Therefore, he received a thoracoscopic biopsy for the right-posterior mediastinal and paraspinal masses and a pathologic examination reported an IgG4-related inflammatory pseudotumor. Then, transsphenoidal removal of the infundibulum mass was performed. Histologically, the infundibulum mass represented a IgG4-related hypophysitis manifested as an infiltration of plasma cells, lymphocytes, histiocytes, and some eosinophils with a fair number of IgG4-immunoreactive plasma cells. After the operation was complete, the patient took 5 mg of prednisolone every 2 days for 3 months. A follow-up computed tomography scan revealed improvement of the infiltrating masses in the bilateral kidneys.
Larson, Brent K; Balzer, Bonnie; Goldwasser, Jerome; Dhall, Deepti
Calcifying fibrous tumor is a rare benign mass lesion characterized by bland spindle cells embedded in abundant collagenous matrix, interspersed dystrophic or psammomatous calcifications, and lymphoplasmacytic infiltrate. It shares several clinical and morphologic features with IgG4-related disease, a newly recognized fibroinflammatory disorder. Characteristic histologic features of IgG4-related lesions include dense fibrosis and abundant lymphoplasmacytic infiltrate, similar to calcifying fibrous tumor. They contain high numbers of IgG4-positive plasma cells in the tissue. Patients also often have elevated serum IgG4 levels. We report the case of a patient with an ileal calcifying fibrous tumor that contained 69 IgG4-positive plasma cells per high-power field and an IgG4-to-IgG ratio of 56% in lesional plasma cells. The patient's serum IgG4 level was 185 mg/dL, more than double the normal value. Altogether, these features suggest that calcifying fibrous tumor could be an unrecognized lesion of IgG4-related disease.
Migita, Kiyoshi; Miyashita, Taiichiro; Mizuno, Aya; Jiuchi, Yuka; Ito, Masahiro; Matsuo, Manabu; Izumi, Yasumori; Takeoka, Atsushi; Nishino, Ayako; Hayashi, Mikio
We describe herein a patient who presented with immunoglobulin G4-related disease (IgG4-RD) involving the testis and prostate as well as the submandibular glands. Massive infiltration of IgG4-expressing plasma cells was observed in testis and prostate tissues. Serum concentrations of B cell activating factor belonging to the tumor necrosis factor family (BAFF) were elevated in parallel with serum IgG4 concentrations, and infiltration of BAFF-receptor (BAFF-R)-expressing B cells and BAFF-expressing lymphoid cells was observed around the ectopic lymphoid foci in the affected urogenital tissues. To date, testicular involvement in a patient diagnosed with IgG4-RD had not been reported, making this the first reported case of IgG4-related epididymo-orchitis. These findings suggest that the immune mechanism underlying ectopic lymphoneogenesis in IgG4-RD may involve enhanced BAFF/BAFF-R interactions among lymphoid cells.
Sato, Yasuharu; Inoue, Dai; Asano, Naoko; Takata, Katsuyoshi; Asaoku, Hideki; Maeda, Yoshinobu; Morito, Toshiaki; Okumura, Hirokazu; Ishizawa, Shin; Matsui, Shoko; Miyazono, Takayoshi; Takeuchi, Tamotsu; Kuroda, Naoto; Orita, Yorihisa; Takagawa, Kiyoshi; Kojima, Masaru; Yoshino, Tadashi
Progressively transformed germinal centers is a benign condition of unknown pathogenesis characterized by a distinctive variant form of reactive follicular hyperplasia in lymph nodes. We recently reported Ig G4-related disease in progressively transformed germinal centers. However, no large case series has been reported and clinicopathologic findings remain unclear. Here, we report 40 Japanese patients (28 men, 12 women; median age, 56 years) with progressively transformed germinal centers of the lymph nodes who fulfilled the histological diagnostic criteria for IgG4-related disease (IgG4(+) progressively transformed germinal centers), with asymptomatic localized lymphadenopathy involving the submandibular nodes in 24, submandibular and cervical nodes in 14, cervical nodes only in 1, and cervical and supraclavicular nodes in 1. In all, 16 (52%) of 31 examined patients had allergic disease. Histologically, the lymph nodes demonstrated uniform histological findings, namely marked follicular hyperplasia with progressively transformed germinal centers, and localization of the majority of IgG4(+) plasma cells in the germinal centers. Serum IgG4, serum IgE and peripheral blood eosinophils were elevated in 87%, 92% and 53% of examined patients, respectively. Eighteen patients subsequently developed extranodal lesions (including five who developed systemic disease), which on histological examination were consistent with IgG4-related disease. IgG4(+) progressively transformed germinal centers presents with uniform clinicopathological features of asymptomatic localized submandibular lymphadenopathy, which persists and/or relapses, and sometimes progresses to extranodal lesions or systemic disease. Nine patients were administered steroid therapy when the lesions progressed, to which all responded well. We suggest that IgG4(+) progressively transformed germinal centers should be included in the IgG4-related disease spectrum.
Zoshima, Takeshi; Yamada, Kazunori; Hara, Satoshi; Mizushima, Ichiro; Yamagishi, Masakazu; Harada, Kenichi; Sato, Yasuharu; Kawano, Mitsuhiro
Multicentric Castleman disease is a benign lymphoproliferative disorder with heterogenous clinical symptoms and involves systemic organs in addition to lymph nodes. Elevated serum IgG4 levels and IgG4-positive plasma cell (IgG4+PC) infiltrates have been reported in lymph nodes, lung and skin in some multicentric Castleman disease cases, resembling IgG4-related disease (IgG4-RD) histologically. However, no report has been available regarding IgG4+PC infiltration in the kidneys of multicentric Castleman disease. Here, we report 2 cases of multicentric Castleman disease complicated by IgG4-related disease (IgG4-RD) histologically. However, there has been no report published on PC-rich tubulointerstitial nephritis, lymphadenopathy, with numerous IgG4+PC infiltration, and elevated serum IgG4 levels, mimicking IgG4-RD. The blood examinations revealed systemic inflammation and elevated C-reactive protein and interleukin-6 levels. Corticosteroid therapy was partially effective in both cases, and combination therapy of corticosteroid and tocilizumab was needed in both cases. Moreover, after triple therapy with corticosteroid, rituximab and cyclophosphamide were used in 1 case to tame the severe inflammation. The present cases suggest that if continuously elevated serum C-reactive protein levels and partial corticosteroid responsiveness are encountered, multicentric Castleman disease should be considered rather than IgG4-RD as a differential diagnosis even if serum IgG4 is elevated and IgG4+PCs infiltrate systemic organs.
Buelli, Simona; Perico, Luca; Galbusera, Miriam; Abbate, Mauro; Morigi, Marina; Novelli, Rubina; Gagliardini, Elena; Tentori, Chiara; Rottoli, Daniela; Sabadini, Ettore; Saito, Takao; Kawano, Mitsuhiro; Saeki, Takako; Zoja, Carlamaria; Remuzzi, Giuseppe; Benigni, Ariela
The pathophysiology of glomerular lesions of membranous nephropathy (MN), including seldom-reported IgG4-related disease, is still elusive. Unlike in idiopathic MN where IgG4 prevails, in this patient IgG3 was predominant in glomerular deposits in the absence of circulating anti-phospholipase A2 receptor antibodies, suggesting a distinct pathologic process. Here we documented that IgG4 retrieved from the serum of our propositus reacted against carbonic anhydrase II (CAII) at the podocyte surface. In patient's biopsy, glomerular CAII staining increased and co-localized with subepithelial IgG4 deposits along the capillary walls. Patient's IgG4 caused a drop in cell pH followed by mitochondrial dysfunction, excessive ROS production and cytoskeletal reorganization in cultured podocytes. These events promoted mitochondrial superoxide-dismutase-2 (SOD2) externalization on the plasma membrane, becoming recognizable by complement-binding IgG3 anti-SOD2. Among patients with IgG4-related disease only sera of those with IgG4 anti-CAII antibodies caused low intracellular pH and mitochondrial alterations underlying SOD2 externalization. Circulating IgG4 anti-CAII can cause podocyte injury through processes of intracellular acidification, mitochondrial oxidative stress and neoantigen induction in patients with IgG4 related disease. The onset of MN in a subset of patients could be due to IgG4 antibodies recognizing CAII with consequent exposure of mitochondrial neoantigen in the context of multifactorial pathogenesis of disease. PMID:26137589
Buelli, Simona; Perico, Luca; Galbusera, Miriam; Abbate, Mauro; Morigi, Marina; Novelli, Rubina; Gagliardini, Elena; Tentori, Chiara; Rottoli, Daniela; Sabadini, Ettore; Saito, Takao; Kawano, Mitsuhiro; Saeki, Takako; Zoja, Carlamaria; Remuzzi, Giuseppe; Benigni, Ariela
The pathophysiology of glomerular lesions of membranous nephropathy (MN), including seldom-reported IgG4-related disease, is still elusive. Unlike in idiopathic MN where IgG4 prevails, in this patient IgG3 was predominant in glomerular deposits in the absence of circulating anti-phospholipase A2 receptor antibodies, suggesting a distinct pathologic process. Here we documented that IgG4 retrieved from the serum of our propositus reacted against carbonic anhydrase II (CAII) at the podocyte surface. In patient's biopsy, glomerular CAII staining increased and co-localized with subepithelial IgG4 deposits along the capillary walls. Patient's IgG4 caused a drop in cell pH followed by mitochondrial dysfunction, excessive ROS production and cytoskeletal reorganization in cultured podocytes. These events promoted mitochondrial superoxide-dismutase-2 (SOD2) externalization on the plasma membrane, becoming recognizable by complement-binding IgG3 anti-SOD2. Among patients with IgG4-related disease only sera of those with IgG4 anti-CAII antibodies caused low intracellular pH and mitochondrial alterations underlying SOD2 externalization. Circulating IgG4 anti-CAII can cause podocyte injury through processes of intracellular acidification, mitochondrial oxidative stress and neoantigen induction in patients with IgG4 related disease. The onset of MN in a subset of patients could be due to IgG4 antibodies recognizing CAII with consequent exposure of mitochondrial neoantigen in the context of multifactorial pathogenesis of disease.
Stone, John H; Brito-Zerón, Pilar; Bosch, Xavier; Ramos-Casals, Manuel
IgG4-related disease (IgG4-RD) is a systemic disease characterized by the infiltration of IgG4-bearing plasma cells and, more importantly, distinctive histopathological features: storiform fibrosis, obliterative phlebitis, a lymphoplasmacytic infiltrate, and mild-to-moderate tissue eosinophilia. The diagnostic approach is complex and relies on the coexistence of various clinical, laboratory, and histopathological findings, none of which is pathognomonic in and of itself. IgG4-related disease should be suspected in patients presenting with unexplained enlargement or swelling of 1 or more organs or tissue organs. Four laboratory abnormalities often provide initial clues to the diagnosis of IgG4-RD: peripheral eosinophilia, hypergammaglobulinemia, elevated serum IgE levels, and hypocomplementemia. Elevated serum IgG4 levels provided critical information in identifying the first cases of IgG4-RD, but recent studies have reported substantial limitations to the measurement of serum IgG4 concentrations, precluding reliance on serum IgG4 concentrations for diagnostic purposes. In contrast, new studies have suggested a promising role of flow cytometry studies in the diagnosis and longitudinal management of IgG4-RD. Demonstration of the classic histopathological features of IgG4-RD remains crucial to diagnosis in most cases, and biopsy proof is preferred strongly by most disease experts before the initiation of treatment. Of note, the multiorgan nature of IgG4-RD was first established in 2003. This review intends to provide most recent knowledge about the clinical, laboratory, radiological, and pathological characteristics of IgG4-RD that may guide the physician to establish an early diagnosis. We searched PubMed and MEDLINE for relevant articles published between January 1, 2000, and November 1, 2014, using the search terms IgG4 and IgG4-related.
Ferry, Judith A; Klepeis, Veronica; Sohani, Aliyah R; Harris, Nancy Lee; Preffer, Frederic I; Stone, John H; Grove, Arthur; Deshpande, Vikram
Although chronic inflammatory disorders of the ocular adnexa are relatively common, their pathogenesis is in many cases poorly understood. Recent investigation suggests that many cases of sclerosing orbital inflammation are a manifestation of IgG4-related disease; however, most patients reported have been Asian, and it is not clear whether the results of studies from the Far East can be reliably extrapolated to draw conclusions about Western patients. We evaluated 38 cases previously diagnosed as orbital inflammatory pseudotumor or chronic dacryoadenitis to determine whether our cases fulfill the criteria for IgG4-RD (IgG4-related dacryoadenitis when involving the lacrimal gland, and IgG4-related sclerosing orbital inflammation when involving orbital soft tissue). Fifteen patients had IgG4-related dacryoadenitis or orbital inflammation. These patients included 9 men and 6 women, aged 24 to 77 years (median, 64 y). Lesions involved orbital soft tissue (8 cases), lacrimal gland (6 cases), and canthus (1 case). In 1 case, focal in situ follicular neoplasia was seen in a background of IgG4-RD. In another case, a clonal IGH gene rearrangement was detected. Four patients with IgG4-RD had evidence of IgG4-RD in other anatomic sites. Five patients, 1 man and 4 women, aged 26 to 74 years (median 50 y) had orbital lesions (2 involving lacrimal gland, 3 involving soft tissue) suspicious for, but not diagnostic of, IgG4-RD. Of 16 patients with IgG4-RD or probable IgG4-RD with information available regarding the course of their disease, 11 patients experienced recurrent or persistent orbital disease. However, no patient developed lymphoma, and no patient died of complications of IgG4-RD. Eighteen patients had lesions not representing IgG4-RD. They included 6 male and 12 female individuals aged 6 to 77 years (median, 47 y). These patients had a variety of diseases, including granulomatosis with polyangiitis (3 cases), Rosai-Dorfman disease (1 case), nonspecific chronic
Agaimy, A; Ihrler, S
Immunoglobulin G4 (IgG4)-related disease (also known as hyper-IgG4 disease) is a recently defined emerging condition with highly heterogeneous clinicopathological features and variable disease manifestations. This disorder is characterized by unifocal or multifocal (multiorgan) involvement by tumefactive plasma cell-rich inflammatory infiltrates associated with prominent fibrosclerosis. This not uncommonly interferes with organ function resulting in diverse clinical symptoms. The autoimmune pancreatitis represents the prototype of this disease; however, to date almost all organs have been reported to be involved in this disorder. In the head and neck area several presentations of this disease may be encountered in salivary glands, lacrimal glands, thyroid gland, lymph nodes, soft tissue of the neck, ear and sinonasal tract. However, IgG4 positive plasma cells are occasionally prominent in non-specific chronic inflammatory conditions of the head and neck and the oral cavity unrelated to autoimmune diseases or systemic disorders, thus representing diagnostic pitfalls. The diagnosis of IgG4-related disease should be based on a combination of typical histological, clinical and serological findings.
Deshpande, Vikram; Zane, Nicolas A; Kraft, Stefan; Stone, John H; Faquin, William C
IgG4-related disease (IgG4-RD) is a recently recognized entity that causes progressive fibrosis and formation of mass lesions. IgG4-RD can be diagnosed histologically by its hallmarks of storiform fibrosis, prominent lymphoplasmacytic infiltrate, and obliterative phlebitis, accompanied by the infiltration of excessive numbers of IgG4-positive plasma cells as well as elevations in serum IgG4 concentrations. A recent publication reported a case of IgG4-RD in the mastoid sinus, representing a new anatomic location for this disease. We report two additional cases of IgG4-RD occurring in the mastoid and causing clinical mastoiditis. The presenting symptoms were varied-tinnitus, hearing loss, and cranial nerve palsies. All three cases showed a dense lymphoplasmacytic infiltrate, storiform type fibrosis as well as elevated numbers of IgG4 positive plasma cells. The three patients responded to immunosuppressive therapy that included steroids and Rituximab. We further investigated 162 consecutive mastoiditis cases at our institution in order to determine the frequency of IgG4-RD as a previously unrecognized cause of mastoiditis. Within this latter cohort we identified nine cases of mastoiditis that had two of the histologic features of IgG4-RD, specifically storiform fibrosis and a dense lymphoplasmacytic infiltrate. Two of these cases showed >50 IgG4-positive plasma cells per high-power field with IgG4-IgG ratio of >40 %, thus fulfilling histological criteria for IgG4-RD. However, both were due to severe acute or chronic infection. In conclusion, we reaffirm IgG4 related mastoiditis as a distinct but uncommon cause of recurrent mastoiditis. The diagnosis of IgG4-related mastoiditis should be rendered with caution, and only after the exclusion of potential mimickers, particularly infection.
Wolfson, Anna R.; Hamilos, Daniel L.
IgG4-related disease was only recently discovered, so its description, management, and new discoveries related to its etiology are rapidly evolving. Because IgG4 itself is a unique antibody which is intimately related to the diagnosis of the disease, the role of plasmablasts in the pathophysiology remains an active area of discussion. Recent studies have uncovered a possible role for CD4-positive cytotoxic T lymphocytes, T follicular helper cells, and M2 macrophages. The clinical presentation is variable and can be vague, as this disease affects many organs and new presentations are continuing to be described. The diagnosis depends on clinical and histopathological assessment. The mainstay of treatment is with glucocorticoids, but rituximab has recently shown promise. Monitoring disease activity using imaging modalities (including positron emission tomography) and serum markers is imperative, as relapses are common. IgG4-related disease spans many medical disciplines but is a treatable condition with which all clinicians should be familiar. PMID:28299186
Saqib, Amina; Nalluri, Nikhil; Raza, Muhammad R; Goldstein, Mark
IgG4-related disease is characterized by multi-system inflammation and possible elevation in serum immunoglobulin-G4 level. Treatment regimens include glucocorticoids, disease-modifying anti-rheumatic agents and recently, rituximab infusions have been reported to be effective in treatment-refractory disease. We present a case of a 64-year-old male presenting with acute abdominal pain and scleral icterus. An abdominal ultrasound demonstrated extensive biliary ductal dilatation. A computed tomography (CT) scan and a magnetic resonance cholangiopancreatography (MRCP) revealed a 4.8 cm pancreatic head mass. He underwent an exploratory laparotomy, and a pathologic examination of the mass revealed a dense lymphoplasmacytic infiltrate. The patient’s IgG subclass 2 level was elevated. A review of the patient’s medical records revealed that, in 1992, he presented with bilateral periorbital discomfort not severe enough to require intervention. In 2006, he presented with bilateral periorbital swelling and discomfort. A magnetic resonance imaging (MRI) scan showed gross enlargement of the lacrimal glands, and a biopsy revealed a dense lymphoplasmacytic infiltrate. He was treated with corticosteroids, cyclosporine and methotrexate. The regimen was repeated in 2009 for recurrent symptoms. Hence, on our encounter, a diagnosis of IgG4-related disease was made and he was treated with rituximab that resulted in complete remission. PMID:28367391
Wibmer, Thomas; Kropf-Sanchen, Cornelia; Rüdiger, Stefan; Blanta, Ioanna; Stoiber, Kathrin M; Rottbauer, Wolfgang; Schumann, Christian
IgG4-related lung disease is commonly associated with autoimmune pancreatitis. Recently, isolated IgG4-related interstitial lung disease (ILD) without other organ involvement has newly been reported in two cases with clinical features of nonspecific interstitial pneumonitis (NSIP).We report the first case of an isolated IgG4-related ILD in a 78-year-old man with dry cough and dyspnea, whose clinical findings proved to be different from NSIP. Serum IgG4 levels were increased. Chest CT scan revealed bilateral consolidations especially in the lower lobes, enlarged mediastinal and hilar lymph nodes and pleural effusions. Video-assisted thoracoscopic (VATS) lung biopsy revealed a pattern similar to usual interstitial pneumonia (UIP) and an abundant IgG4-positive plasma cell infiltration. He was effectively treated by steroid therapy.Increasing recognition of IgG4 related diseases has led to a growing number of new entities. The novel concept of isolated IgG4-related ILD as a pulmonary manifestation of a systemic IgG4-related disorder should be taken into account as a possible differential diagnosis of ILD and mass-forming lesions, even when no other organ manifestation is clinically apparent at the time of diagnosis. Lung specific diagnostic criteria and algorithms are required to enhance diagnostic accuracy in cases of possible IgG4-related ILD.
IgG4-related lung disease is commonly associated with autoimmune pancreatitis. Recently, isolated IgG4-related interstitial lung disease (ILD) without other organ involvement has newly been reported in two cases with clinical features of nonspecific interstitial pneumonitis (NSIP). We report the first case of an isolated IgG4-related ILD in a 78-year-old man with dry cough and dyspnea, whose clinical findings proved to be different from NSIP. Serum IgG4 levels were increased. Chest CT scan revealed bilateral consolidations especially in the lower lobes, enlarged mediastinal and hilar lymph nodes and pleural effusions. Video-assisted thoracoscopic (VATS) lung biopsy revealed a pattern similar to usual interstitial pneumonia (UIP) and an abundant IgG4-positive plasma cell infiltration. He was effectively treated by steroid therapy. Increasing recognition of IgG4 related diseases has led to a growing number of new entities. The novel concept of isolated IgG4-related ILD as a pulmonary manifestation of a systemic IgG4-related disorder should be taken into account as a possible differential diagnosis of ILD and mass-forming lesions, even when no other organ manifestation is clinically apparent at the time of diagnosis. Lung specific diagnostic criteria and algorithms are required to enhance diagnostic accuracy in cases of possible IgG4-related ILD. PMID:23509921
Campbell, Sabrina N; Rubio, Edmundo; Loschner, A Lukas
IgG4-related disease (IgG4-RD) is a recently recognized systemic disease characterized by tumefactive lesions in various organ systems. The list of organs that can be involved continues to expand, and recently computed tomography (CT) descriptions of the pulmonary lesions found in the disease have been described. The clinical symptoms are nonspecific and may include cough, dyspnea, chest pain, and fever. The appropriate clinical presentation along with elevated serum IgG4 concentrations and pathologic evidence of lymphoplasmacytic infiltrates with abundant IgG4-positive plasma cells and storiform fibrosis is consistent with the disease. Steroids are used to treat this disease in addition to immunosupressives such as cyclosporine or rituxumab for steroid refractory disease. The pulmonary manifestations and imaging features can often mimic malignancy, and as such knowledge of the diagnostic, clinicopathologic, and radiographic features of the disease is required in order to provide appropriate diagnostic workup and treatment.
Keenan, Joseph C; Miller, Elizabeth; Jessurun, Jose; Allen, Tadashi; Kim, Hyun Joo
IgG4 related disease has been recently proposed as a unifying term for a group of inflammatory conditions previously referred to by a plethora of other names. The common denominator for these entities is the histopathologic finding of lymphocytic infiltrates rich in IgG4 producing plasma cells, often accompanied by storiform fibrosis and obliterative phlebitis. Many medical conditions have been attributed to IgG4-related disease,but few reports of IgG4-related lung disease have been published, and it remains a rare condition about which little is known. In this report, we describe the clinical and pathologic features of six patients with IgG4-related disease of the lung. Patients were followed 1-5 years following their diagnosis. We describe unique features of IgG4-related lung disease, including one patient who presented with alveolar hemorrhage and a positive anti-neutrophil cytoplasmic antibody and two patients whose disease improved after treatment with mycophenylate mofetil. Two patients presented with pulmonary pseudotumor. We conclude that the clinical presentation of IgG4-related lung disease varies widely, and histopathology remains the key to diagnosis.
Ardila-Suarez, Oscar; Abril, Andy; Gómez-Puerta, José A
IgG4-related disease is the term used to refer to a condition characterized by a lymphoplasmacytic infiltrate, fibrosis and an increased number of IgG4+ cells present in tissue, in most cases, with an elevated serum IgG4 level. This disease frequently affects the pancreas, salivary glands and lymph nodes, but can involve almost any tissue. Its etiology and the exact role of the different inflammatory cells in the damage to the target organ is still unclear. As yet, there is no international consensus about diagnostic criteria for the disease, but there are important advances in its treatment and in the quest to achieve remission. We include a review of the history, possible pathogenesis, clinical manifestations, diagnostic approach and available therapeutic approaches.
Ohno, Keiko; Matsuda, Yoko; Arai, Tomio; Kimura, Yurika
IgG4-related disease (IgG4-RD) is a recently recognized clinical disease entity characterized by elevated serum IgG4, tumefaction, tissue infiltration of IgG4-positive plasma cells and fibrosis. IgG4-RD may occur, either synchronously or metachronously, in a variety of organs throughout the body. We describe herein two representative cases of the nasal manifestations of IgG4-RD, characterized by diffuse, crusty, erosive lesions on nasal mucosa. Oral steroid administration was effective in treating these nasal manifestations. We report a decrease in IgG4 positive plasma cell infiltrates in nasal mucosa biopsy specimens after steroid therapy, demonstrating that infiltration of IgG4-positive cells is reversible.
Li, Yaqiong; Zhou, Gengyin; Ozaki, Takashi; Nishihara, Eijun; Matsuzuka, Fumio; Bai, Yanhua; Liu, Zhiyan; Taniguchi, Emiko; Miyauchi, Akira; Kakudo, Kennichi
A form of Hashimoto's thyroiditis with lymphoplasmacytic sclerosing changes and increased numbers of IgG4-positive plasma cells has recently been reported in the literature. These histopathological features suggest that this subtype of Hashimoto's thyroiditis may be closely related to IgG4-related disease. Therefore, this unique form of IgG4-related Hashimoto's thyroiditis, which is referred to as IgG4 thyroiditis, has its own clinical, serological, and sonographic features that are distinct from those associated with non-IgG4 thyroiditis. IgG4 thyroiditis shares similarities with the well-known fibrous variant of Hashimoto's thyroiditis; however, the detailed histopathological features of IgG4 thyroiditis have not been well established. Based on immunostaining results, 105 patients with Hashimoto's thyroiditis were divided into an IgG4 thyroiditis group (n=28) and a non-IgG4 thyroiditis group (n=77). As in our previous reports, IgG4 thyroiditis was associated with a patient population of a younger age, a lower female-to-male ratio, rapid progression, higher levels of thyroid autoantibodies, subclinical hypothyroidism, and diffuse sonographic echogenicity. Histopathologically, this group revealed severe lymphoplasmacytic infiltration, dense stromal fibrosis, marked follicular cell degeneration, numerous micro-follicles, and notable giant cell/histiocyte infiltration. Importantly, the IgG4-related group did not completely overlap with fibrous variant of Hashimoto's thyroiditis. Four cases (14%) in the IgG4 thyroiditis group presented only mild fibrosis in the stroma, whereas 29 cases (38%) in the non-IgG4 thyroiditis group met the diagnostic criteria for fibrous variant of Hashimoto's thyroiditis. Furthermore, we observed three patterns of stromal fibrosis in Hashimoto's thyroiditis: interfollicular fibrosis, interlobular fibrosis, and scar fibrosis. The IgG4 thyroiditis group was significantly associated with the presence of predominant interfollicular fibrosis. In
Wang, Zhiwei; Feng, Ruie; Chen, Yu; Duan, Miao; Wang, Man; Jin, Zhengyu; Rumboldt, Zoran; Zhang, Zhuhua
The submandibular gland is one of the most frequently affected salivary gland in IgG4-related systemic disease, usually demonstrate homogeneous attenuation on CT imaging as reported, but without much pathological comparison of many cases. This article is to investigate and analyze the typical CT findings and pathologic characteristics of IgG4-related systemic disease (IgG4-RSD) of submandibular gland. A retrospective analysis of the preoperative CT findings in patients with IgG4-RSD of submandibular glands who underwent surgical resection between January 2010 and February 2014 was performed. Twenty patients (16 women) were identified, with a mean age of 58.1±10.2 years. All patients presented with painless submandibular gland swelling. Diffuse gland enlargement, with clear margins and homogeneous density, was found on non-enhanced CT scans in all cases. There were no calcifications or stones within the involved glands. Based on contrast-enhanced CT appearance the patients could be divided into two groups: 11 cases showed homogeneous gland enhancement; and multiple hyperenhancing foci, with a crazy-paving pattern, were detected in 9 cases, which were in consistent with the pathologic findings. The maximum submandibular gland diameter on transverse images was significantly larger (P=0.008) in patients with crazy-paving appearance (32±4 mm) compared to patients with homogeneous enhancement (28±3 mm). It is concluded that the submandibular glands with IgG4-RSD can be characterized by either homogenous appearance or crazy-paving pattern on contrast-enhanced CT imaging.
Raparia, Kirtee; Molina, Claudia P; Quiroga-Garza, Gabriela; Weilbaecher, Donald; Ayala, Alberto G; Ro, Jae Y
In this study, we investigate the hypothesis that IgG4-related autoimmune reaction is involved in the formation of inflammatory aortic aneurysms (IAA). We obtained 23 cases of IAA and 11 cases of atherosclerotic aortic aneurysms (AAA) as control group. We evaluated the expression of IgG4 in both IAA study cases and AAA control cases. In addition, immunohistochemical expression of C-Kit, CD21, CD34, S-100 protein, SMA, vimentin, p53, beta-catenin, and ALK-1, and EBV-LMP1 expression by in situ hybridization were performed only in IAA cases. Of the 23 patients, 20 were males and 3 were females (M: F ratio 6.7:1); age ranged from 43 to 81 years (average 64.3 years). Histologically, all 23 cases of IAA formed a mass that displayed inflammatory myofibroblastic tumor-like features. All lesions stained strongly and diffusely for vimentin and SMA (100%); 17 stained strongly and focally for CD34 (74%); and all were negative for C-Kit, CD21, S-100 protein, p53, beta-catenin, EBV-LMP1, and ALK-1. The numbers of infiltrating IgG4-positive plasma cells in IAA cases exceed that of AAA cases. Score 3 (>50 plasma cells/one 40X field) of IgG4-positive plasma cells was only seen in IAA cases (13/23, 57%), whereas none of the 11 cases of AAA showed score 3 IgG4-positive plasma cells (P=0.0018, Fischer‘s exact test). Our findings suggest that IAA may be an aortic manifestation of the IgG4-related sclerosing disease. The high number of positive plasma cells, >50 plasma cells/one 40X field is more specific for the IAA than for AAA; however, lesser number can be seen in both IAA and AAA patients. PMID:23411750
Gianfreda, Davide; Musetti, Claudio; Nicastro, Maria; Maritati, Federica; Cobelli, Rocco; Corradi, Domenico; Vaglio, Augusto
Abstract Immunoglobulin-G4 (IgG4)-related disease (IgG4RD) is a fibro-inflammatory disorder characterized by tissue-infiltrating IgG4+ plasma cells, and, often, high serum IgG4. Several autoimmune, infectious, or proliferative conditions mimic IgG4RD. Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis, characterized by foamy histiocytic infiltration, fibrosis, and chronic inflammation. ECD and IgG4RD manifestations may overlap. A patient presented with huge fibrous retroperitoneal masses causing compression on neighboring structures; the case posed the challenge of the differential diagnosis between IgG4RD and ECD mainly because of a prominent serum and tissue IgG4 response. Retroperitoneal biopsy led to the diagnosis of ECD; the V600E BRAF mutation was found. Treatment with the BRAF inhibitor vemurafenib was started. Treatment failed to induce mass regression and the patient died after 3 months of therapy. Prompted by this case, we examined serum and tissue IgG4 in a series of 15 ECD patients evaluated at our center, and found that approximately one-fourth of the cases have increased IgG4 in the serum and often in the tissue. The differential diagnosis between IgG4RD and ECD can be challenging, as some ECD patients have prominent IgG4 responses. This suggests the possibility of common pathogenic mechanisms between ECD and IgG4RD. PMID:27227923
Nakata, Ruka; Yoshimura, Shunsuke; Motomura, Masakatsu; Tsujino, Akira; Hayashi, Tomayoshi; Hara, Minoru
IgG4-related disease is a systemic disease characterized by lesions with IgG4 positive plasma cell infiltration in the involved organs and a raised serum IgG4 level. We report a patient of 70-year-old male presented orbital inflammation of IgG4-related disease. The patient developed right eye pain, double vision, and reduced eye sight. MRI image revealed mild right ocular proptosis and swelling of right carvenous sinus, bilateral intraorbital extraocular muscles and right optic nerve. Right optic nerve showed ring-like enhancement. IgG4-related disease was suspected with increased serum IgG4 level of 355 mg/dl, mediastinal lymphadenopathy and prostate enlargement. Transbronchial lung biopsy and prostate needle biopsy were administered with negative results. The eye related symptoms resolved with time, but serum IgG4 continuously increased. IgG4-related disease was diagnosed by nasal mucosa biopsy, which showed IgG4 positive plasma cells within the inflammatory infiltrate. This report emphasizes the usefulness of nasal mucosa biopsy for the diagnosis of IgG4 related disease with lesions difficult to approach.
Lei, Wen-Hui; Xin, Jun; Shao, Chu-Xiao; Mao, Ming-Feng; Zhu, Chao-Yong; Wu, Chui-Fen; Jin, Lie
Immunoglobulin G4-related disease is a recently recognized systemic disease that can affect any organ or tissue in the body, including the kidneys. IgG4-related kidney disease (IgG4-RKD) is an important part of immunoglobulin G4-related disease. The most common renal manifestation of IgG4-RKD is tubulointerstitial nephritis and glomerular lesions. There, however, is few case of IgG4-RKD mimicking malignant ureter tumor leading to severe hydronephrosis. We herein report an unusual case of IgG4-RKD mimicking malignancy.A 66-year-old Asian man presented to the nephrologist with soreness of loins, anorexia, and acute kidney injury in 2010. His renal function spontaneously improved after 2 weeks' hemodialysis without systemic steroid therapy. Four years later, he presented to the urologist with severe left hydronephrosis because of marked thickness of the left ureter wall. As a ureteral malignancy could not be ruled out, laparoscopic nephroureterectomy was performed.IgG4-related kidney disease was confirmed by the histologic examination. Then, repeat laboratory test showed almost complete recovery of renal function after initiation of steroidal therapy.This case highlights the rare possibility of IgG4-RKD mimicking malignant ureter tumor. Nephrologist and pathologists should be aware of the possibility that hydronephrosis with ureter obstruction may be involved in IgG4-RKD.
Ochoa, Minerva Lazos; Gabiño López, Belem; Cabello, Raúl Romero; Feregrino, Raúl Romero
IgG4-related disease (IgG4RD) is a chronic recurring fibro-inflammatory pathology that is considered to be of autoimmune origin. Histopathology is considered to be the gold standard method for diagnosis. IgG4RD affects multiple organs. IgG4RD was first identified in the pancreas and was called autoimmune pancreatitis (AIP). During the following years, the disease spectrum was expanded and it was realised that the extrapancreatic lesions can precede, coexist or appear after the diagnosis of AIP. At present, several illnesses such as Mikulicz disease, Küttner tumour, multifocal fibrosclerosis, etc, are considered to be part of the IgG4RD spectrum. The symptoms of the disease tend to appear over months and years and diagnosis is achieved on average 13.5 months (4–60 months) after the onset. The purpose of this report was to provide information about a case that was sadly fatal but that permitted a complete histopathological study of the damaged tissues. PMID:23645656
Stone, John H
IgG4-related disease (IgG4-RD) is a fibroinflammatory condition that can affect essentially any organ. The disease shows similar histopathology findings across organ systems, consisting of a lymphoplasmacytic infiltrate enriched in IgG4-positive plasma cells, storiform fibrosis, and obliterative phlebitis. IgG4 itself appears to be a reactive phenomenon rather than the primary disease driver. Recent investigations have focused on the interactions between cells of the B cell lineage and a novel CD4+ SLAMF7+ cytotoxic T cells capable of promoting fibrosis. Plasmablasts appear to play a crucial role along with B cells in the presentation of antigen to this T cell. IgG4-RD is marked by responsiveness to glucocorticoids, but frequent disease relapse, the inability to taper glucocorticoids completely, and steroid toxicity are problematic. Targeted treatment approaches against the B cell lineage appear promising, and therapeutic efforts focused upon the CD4+ SLAMF7+ cytotoxic T cell may also be feasible.
Farooq, Tahir Ali; Mudhar, Hardeep; Sandramouli, S
IgG4-related orbital disease is a recognised cause for orbital inflammation. As its awareness increases and diagnostic accuracy improves there will be an increased number of cases being identified. This unique case demonstrates for the first time, with histological evidence, a case of a non-lacrimal IgG4-related orbital disease with concurrent IgG4-related mastitis. We describe a 47 year old who presented with a supraorbital swelling and mass. This was initially successfully treated with oral steroids and was later excised on recurrence. Immunohistochemical and blood serum analysis confirmed IgG4-related orbital disease. On systemic enquiry she was found to have a mass of the breast, which was shown to be IgG4-related mastitis. She is currently asymptomatic with no sign of recurrence and is under long-term surveillance. This case highlights the importance of systemic work up in patients presenting with orbital foci of IgG4 disease.
Beltrame, Rafael Coimbra Ferreira; Friderichs, Maurício; Fior, Bárbara Rayanne; Schaefer, Pedro Guilherme; Thomé, Gustavo Gomes; Silva, Dirceu Reis da; Barros, Elvino José Guardão; Seligman, Renato; Veronese, Francisco Veríssimo
The IgG4-related disease has a wide clinical spectrum where multiple organs can be affected, and the diagnosis depends on typical histopathological findings and an elevated IgG4 expression in plasma cells in the affected tissue. We describe the clinical presentation and evolution of a patient with acute tubulointerstitial nephritis, severe kidney failure and systemic manifestations such as lymphadenomegaly and chronic pancreatitis. The diagnosis was confirmed by the clinical picture and kidney and lymph node histopathology, in which immunohistochemistry of the lymphoid tissue showed policlonality and increased expression of IgG4, with a IgG4/total IgG ratio > 80%. The patient was treated with prednisone at a dose of 60 mg/day, followed by mycophenolate mofetil, and showed clinical and renal function improvement at 6 months of follow-up. The high index of suspicion of IgG4-related disease with multisystem involvement and the early treatment of this condition are essential to improve the prognosis of affected patients. Resumo A doença relacionada à IgG4 tem um espectro clínico amplo em que múltiplos órgãos podem ser afetados, e o diagnóstico depende de achados histopatológicos típicos e elevada expressão de IgG4 em plasmócitos no tecido afetado. Descrevemos o quadro clínico e a evolução de um paciente com nefrite túbulo-intersticial aguda, insuficiência renal grave e manifestações sistêmicas como linfoadenomegalias e pancreatite crônica. O diagnóstico foi confirmado pelas características clínicas e pela histopatologia renal e de linfonodo, na qual a imunohistoquímica mostrou tecido linfoide com policlonalidade e expressão aumentada de IgG4, com uma relação IgG4/IgG total > 80%. O paciente foi tratado com prednisona na dose de 60 mg/dia, seguido de micofenolato mofetil, e apresentou melhora clínica e da função renal depois de 6 meses de tratamento. O alto índice de suspeição da doença relacionada ao IgG4 com comprometimento multissist
Koarada, S; Tashiro, S; Nagao, N; Suematsu, R; Ohta, A; Tada, Y
Four patients with IgG4-related disease (IgG4-RD) showed increased percentages of RP105-negative B cells in the peripheral blood. Case 1: A 66-year-old man having retroperitoneal fibrosis had 18.8% of RP105-negative B cells. Oral prednisolone improved the affected lesions and the percentage of RP105-negative B cells decreased (3.2%) after the treatment. Case 2: A 53-year-old man with retroperitoneal fibrosis had 27.9% of RP105-negative B cells. Case 3: A 38-year-old man with follicular hyperplasia showed increased percentage of RP105-negative B cells (8.3%). Case 4: A 60-year-old man with interstitial nephritis had 27.5% of RP105-negative B cells. The treatment decreased the numbers of RP105-negative B cells. Increased numbers of RP105-negatvie B cells is possibly associated with disease activity of IgG4-RD. Analysis of expression of RP105 on B cells may be helpful in evaluation of disease activity of IgG4-RD.
Rossi, Giovanni Maria; Rocco, Rossana; Accorsi Buttini, Eugenia; Marvisi, Chiara; Vaglio, Augusto
Retroperitoneal fibrosis (RPF) is a rare disease characterised by fibrous tissue proliferation in the retroperitoneum, with encasement of the ureters and large vessels of the abdomen as the most destructive of potentially severe complications. It can either be idiopathic, or secondary to infections, malignancies, or the use of certain drugs. The idiopathic form accounts for approximately 75% of the cases, and is usually responsive to immunosuppressive therapy. In recent years, the emergence of a new clinical entity, IgG4-related disease (IgG4-RD), shed light on many fibro-inflammatory disorders once thought to be separate clinical entities, although frequently associated in the so-called multifocal fibrosclerosis. Among these, together with sclerosing pancreatitis and cholangitis, pseudotumour of the orbit, idiopathic mediastinal fibrosis and other conditions, is idiopathic retroperitoneal fibrosis (IRF). Both IRF and IgG4-RD can be associated with a wide variety of disorders, usually governed by immune-mediated (and particularly auto-immune) mechanisms. In our review, we discuss the clinical and therapeutic challenges IRF presents to the internist, as well as the meaning of its recent inclusion in the IgG4-RD spectrum from a clinical practice standpoint.
Immunoglobulin G4-related disease (IgG4-RD) in the pancreatobiliary system manifests as sclerosing cholangitis (SC), hepatic inflammatory pseudotumors, and type 1 autoimmune pancreatitis (AIP). The pathology of IgG4-RD involves an inflammatory process and fibrogenic pathway, the combination of which damages the affected organs. Fibroinflammatory injury is characterized by three microscopic findings: a diffuse lymphoplasmacytic infiltrate rich in IgG4-positive plasma cells, obliterative phlebitis, and storiform fibrosis. Although the diagnosis of IgG4-related pancreatocholangitis is relatively straightforward in surgical specimens, the current clinical requirement is to diagnose patients using biopsy samples, which remains challenging. Histological differential diagnoses include primary SC, follicular cholangitis/pancreatitis, SC with granulocytic epithelial lesions, and type 2 AIP. Although the massive infiltration of IgG4-positive plasma cells is a histological hallmark of IgG4-RD, many other immune cells (e.g., Th2 lymphocytes, regulatory T cells, and M2 macrophages) appear to be strongly involved in orchestral immune reactions.
Laco, Jan; Örhalmi, Július; Bártová, Jolana; Zimandlová, Dana
Herein we present a case of a 65-year-old woman with enterocolic lymphocytic phlebitis (ELP) who presented with anemic syndrome and in whom severe stenosis of the right flexure of large bowel was detected. The microscopic examination revealed fibrosis of the submucosa and lymphoplasmacytic phlebitis of small veins and venules, whereas arteries were spared. There were 110 IgG4-positive and 160 IgG-positive plasma cells in 1 high-power field, respectively, with corresponding IgG4/IgG ratio of 0.69. The IgG4 serum level was 2.42 g/L. According to the currently proposed criteria, this ELP case is the first that may be diagnosed as definite IgG4-related disease (IgG4-RD). Although based on the sole case description, taken together with a recent review and a case report, we presume that a subset of ELPs is a manifestation of IgG4-RD.
Zaarour, Mazen; Weerasinghe, Chanudi; Eter, Ahmad; El-Sayegh, Suzanne; El-Charabaty, Elie
We report a case of a 71-year-old Filipino female who was admitted to the hospital for abdominal pain, vomiting and diarrhea of 8 days duration. The patient was found to have marked acute kidney injury (AKI), which required hemodialysis in the next 3 days. Extensive workup revealed hematuria, subnephrotic range proteinuria, elevated anti-nuclear antibody (ANA) and elevated total immunoglobulin G (IgG) levels, with normal IgG4 and anti-dsDNA levels. On kidney biopsy, mild membranous glomerulonephritis was found, along with autoimmune tubulointerstitial nephritis (TIN) with a "full-house" pattern of immune deposits. These findings were suggestive of lupus interstitial nephritis. However, IgG4+ plasma cells were detected in the interstitium by immunostaining, favoring a diagnosis of IgG4-related kidney disease (IgG4-RKD). Our case highlights the difficulty in differentiating lupus nephritis (LN) from IgG4-RKD in some patients, raising the suspicion that these two entities can co-exist.
Zaarour, Mazen; Weerasinghe, Chanudi; Eter, Ahmad; El-Sayegh, Suzanne; El-Charabaty, Elie
We report a case of a 71-year-old Filipino female who was admitted to the hospital for abdominal pain, vomiting and diarrhea of 8 days duration. The patient was found to have marked acute kidney injury (AKI), which required hemodialysis in the next 3 days. Extensive workup revealed hematuria, subnephrotic range proteinuria, elevated anti-nuclear antibody (ANA) and elevated total immunoglobulin G (IgG) levels, with normal IgG4 and anti-dsDNA levels. On kidney biopsy, mild membranous glomerulonephritis was found, along with autoimmune tubulointerstitial nephritis (TIN) with a “full-house” pattern of immune deposits. These findings were suggestive of lupus interstitial nephritis. However, IgG4+ plasma cells were detected in the interstitium by immunostaining, favoring a diagnosis of IgG4-related kidney disease (IgG4-RKD). Our case highlights the difficulty in differentiating lupus nephritis (LN) from IgG4-RKD in some patients, raising the suspicion that these two entities can co-exist. PMID:26015827
IgG4-related disease (IgG4-RD) is a recently recognized chronic fibrotic inflammation, which can affect almost every organ, and may come to clinical attention first due to visible organ swelling or organ dysfunction, or is identified incidentally by imaging and specific biopsy. The disorder has an allergic background and is immune-mediated. Up-regulated responses of T helper 2 and T regulatory cells and their cytokines play a major role in disease progression. About 30-50% of patients are atopic or have mild eosinophilia. IgG4-RD predominantly affects middle-aged male patients. The cornerstones of diagnosis of the disease are compatible clinical features and typical histopathology. Swelling of salivary and lacrimal glands, lymphadenopathy, and type 1 autoimmune pancreatitis (AIP) are the most common manifestations of the disease. However, other tissues and organs, such as retroperitoneum, lung, kidney, aorta, upper airways, thyroid gland, meninges, heart, mesenterium and skin may be involved. Typical histopathology is lymphoplasmacytic infiltration abundant in IgG4-positive plasma cells, storiform-type fibrosis, and obliterative phlebitis. Elevated serum IgG4 concentration supports the diagnosis. Characteristic imaging features such as a "capsule-like rim" surrounding the pancreatic lesions is highly specific to type 1 AIP. 18F-fluorodeoxyglucose positron emission tomography/computed tomography enables mapping the sites of inflammation, permits evaluation of the extent of the disease, helps in guiding biopsy decision, and may be used in monitoring response to treatment. Glucocorticoids alone or in combination with B-cell depletion with rituximab induces prompt clinical response to IgG4-RD. This article reviews the current understanding, different clinical manifestations, and approaches to diagnosis and treatment of IgG4-RD.
Du, Hongwu; Shi, Lili; Chen, Peng; Yang, Weikang; Xun, Yiping; Yang, Chunhe; Zhao, Lanqing; Zhou, Yabin; Chen, Guangyu
Objective IgG4-related disease (IgG4-RD) is a chronic systemic disease involved in many organs and tissues. As only limited autoantigens have been found since the beginning of this century, the aim of this study was to reveal new candidate autoantigens of IgG4-RD. Methods Multiple cell lines including HT-29, EA.hy926, HEK 293 and HepG2 were used to test the binding ability of circulating autoantibodies from IgG4-RD sera. The amino-acid sequence was then analyzed by matrix-assisted laser desorption/ionization time-of-flight tandem (MALDI-TOF/TOF) mass spectrometry. After the cloning and expression of recombinant putative autoantigen in a bacterial expression system, the corresponding immuno assay was set up and utilized to observe the prevalence of serum autoantibodies in a large set of confirmed clinical samples. Results One positive autoantigen was identified as prohibitin. ELISA analysis showed that a majority of patients with IgG4-RD have antibodies against prohibitin. Anti-prohibitin antibodies were present in the sera of patients with definite autoimmune pancreatitis (25/34; 73.5%), Mikulicz’s disease (8/15; 53.3%), retroperitoneal fibrosis (6/11; 54.5%), other probable IgG4-RD (26/29; 89.7%) and Sjögren’s syndrome (4/30; 13.3%) but not in apparently healthy donors (1/70; 1.4%). Conclusions An association between prohibitin and patients with some IgG4-RD was observed, although the results were quite heterogeneous among different individuals within autoimmune pancreatitis, Mikulicz’s disease and retroperitoneal fibrosis. PMID:25932630
Fernández-Codina, Andreu; Martínez-Valle, Fernando; Pinilla, Blanca; López, Cristina; DeTorres, Inés; Solans-Laqué, Roser; Fraile-Rodríguez, Guadalupe; Casanovas-Martínez, Arnau; López-Dupla, Miguel; Robles-Marhuenda, Ángel; Barragán-González, María Jesús; Cid, Maria Cinta; Prieto-González, Sergio; Brito-Zerón, Pilar; Cruces-Moreno, María Teresa; Fonseca-Aizpuru, Eva; López-Torres, Manuel; Gil, Judith; Núñez-Fernández, Manuel Jesús; Pardos-Gea, José; Salvador-Cervelló, Gonzalo
Abstract IgG4-related disease (IgG4-RD) is a rare entity consisting of inflammation and fibrosis that has been described in multiple organs. Concrete diagnostic criteria have been established recently and there is a lack of large series of patients. To describe the clinical presentation, histopathological characteristics, treatment and evolution of a series of IgG4-RD Spanish patients. A retrospective multicenter study was performed. Twelve hospitals across Spain included patients meeting the current 2012 consensus criteria on IgG4-RD diagnosis. Fifty-five patients were included in the study, 38 of whom (69.1%) were male. Median age at diagnosis was 53 years. Thirty (54.5%) patients were included in the Histologically Highly Suggestive IgG4-RD group and 25 (45.5%) in the probable IgG4-RD group. Twenty-six (47.3%) patients had more than 1 organ affected at presentation. The most frequently affected organs were: retroperitoneum, orbital pseudotumor, pancreas, salivary and lachrymal glands, and maxillary sinuses. Corticosteroids were the mainstay of treatment (46 patients, 83.6%). Eighteen patients (32.7%) required additional immunosuppressive agents. Twenty-four (43.6%) patients achieved a complete response and 26 (43.7%) presented a partial response (<50% of regression) after 22 months of follow-up. No deaths were attributed directly to IgG4-RD and malignancy was infrequent. This is the largest IgG4-RD series reported in Europe. Patients were middle-aged males, with histologically probable IgG4-RD. The systemic form of the disease was frequent, involving mainly sites of the head and abdomen. Corticosteroids were an effective first line treatment, sometimes combined with immunosuppressive agents. Neither fatalities nor malignancies were attributed to IgG4-RD. PMID:26266361
Karram, Sarah; Kao, Chia-Sui; Osunkoya, Adeboye O; Ulbright, Thomas M; Epstein, Jonathan I
Idiopathic granulomatous orchitis (IGO) is rare, thought to result from an autoimmune reaction to spermatogenic elements. Its relationship to IgG4-related disease (IgG4-RD) has not been evaluated. Sixteen orchiectomy specimens (1984-2012) with a prominent intratubular granulomatous reaction were reviewed: IGO (n = 6); intratubular germ cell neoplasia unclassified (IGCNU) with a granulomatous reaction and associated seminoma (GS, n = 6); and unclassified intratubular granulomatous orchitis not fitting into a specific entity (UGO, n = 4). Men with IGO were 32 to 86 years old, presenting with a mass suspicious for malignancy. Only one patient had a history of an inflammatory disease. Clinical follow-up was available for 2 patients with IGO, and both had no evidence of systemic IgG4-RD. All IGO cases had an epithelioid granulomatous reaction confined to seminiferous tubules, an extensive interstitial lymphoplasmacytic inflammation, 3 of 6 had prominent interstitial fibrosis, and 3 of 6 cases had plasma cells with an IgG4+/IgG+ ratio >40%. In GS, 10% to 100% of tubules with IGCNU had a granulomatous reaction, which in 3 cases replaced IGCNU cells. In contrast to IGO, GS had more intratubular multinucleated giant cells, more peritubular sclerosis, fewer interstitial plasma cells, and no interstitial fibrosis. Of the 4 UGO cases, most had predominantly interstitial with less intratubular granulomatous inflammation. Only 1 non-IGO case had elevated tissue IgG4 (GS case). It is critical and sometimes difficult to distinguish GS from IGO. IGO shares some features with IgG4-RD, yet current evidence does not support its classification as a localized manifestation of IgG4-RD occurring in the testis.
De Virgilio, Armando; de Vincentiis, Marco; Inghilleri, Maurizio; Fabrini, Giovanni; Conte, Michela; Gallo, Andrea; Rizzo, Maria Ida; Greco, Antonio
Hypertrophic pachymeningitis (HP) is a rare disorder that causes thickening of the dura mater. Inflammatory lesions may be located in the cerebral or spinal dura mater or, less frequently, in both locations simultaneously. Numerous clinico-pathological entities cause thickening of the pachymeninges. Indeed, HP is a potential manifestation of many different diseases, but the diagnosis often remains uncertain. Cases in which the pachymeningitis has no known aetiology are termed "idiopathic" HP (IHP). Recently, it has been suggested that IgG4-related disease represents a subset of cases previously diagnosed as idiopathic hypertrophic pachymeningitis. Little is known regarding the pathogenic events of IHP. In a general theory, the inflammatory infiltrate, mainly consisting of B and T lymphocytes, activates fibroblasts and induces collagen deposition, leading to tissue hypertrophy and increased dural thickness. Clinical manifestations of IHP depend upon the location of the inflammatory lesions and compression of the adjacent nervous structures. Three central pathological features are lymphoplasmacytic infiltration, obliterative phlebitis, and storiform fibrosis. MRI is the examination of choice for the preliminary diagnosis of IHP. Histopathological examination of a biopsy specimen of the dura mater would finally confirm the diagnosis. The differential diagnosis for HP is broad and includes infections, autoimmune disorders, and neoplasia. Currently, there is no consensus about treatment for patients with IHP. There is a preference for glucocorticoid treatment on diagnosis followed by the addition of other immunosuppressive agents in the event of a recurrence. Rituximab is used in patients who did not respond to glucocorticoids or to conventional steroid-sparing agents.
Igawa, Takuro; Hayashi, Toshiaki; Ishiguro, Kazuya; Maruyama, Yumiko; Takeuchi, Mai; Takata, Katsuyoshi; Yoshino, Tadashi; Sato, Yasuharu
We herein report a case in which an IgG4-producing lymphoma arose in a patient with a previous diagnosis consistent with an IgG4-related disease. A 43-year-old man presented with enlarged cervical lymph nodes and was treated with steroids and radiation for what was initially assumed to be Kimura's disease, although the lesions were later histologically re-diagnosed as IgG4-related lymphadenopathy. Fourteen years later, when the patient was 58-years-old, he presented with retroperitoneal fibrosis and swollen lymph nodes. The suspicious lesions were not histologically examined as the patient did not give consent. However, the serum IgG4 concentration was high (1400 mg/dL) and he was clinically diagnosed with systemic IgG4-related disease. Although steroid administration reduced the size of the lesions, tapering the dose finally resulted in systemic, prominently enlarged lymph nodes. Analysis of the biopsy specimen revealed that these multiple lymph node lesions were marginal zone B cell lymphomas that themselves expressed IgG4. Complete remission was achieved after a total of six courses of chemotherapy including rituximab. This case suggests that the infiltrating IgG4-expressing cells observed in IgG4-related disease can clonally expand to malignant lymphomas.
Fang, W L; Wang, H J; Lu, Y W; Feng, R E; Bu, X N; Fang, Q H
Objective: To investigate the clinical data of a patient with IgG(4)-related disease involving the trachea and paratracheal soft tissue and review the literature so as to improve the understanding level of the disorder. Methods: To analyze the clinical manifestation, laboratory examination, imaging, histopathology, treatment and prognosis of a patient with IgG(4)-related disease trachea and paratracheal soft tissue involved, who was admitted to the Department of Respiratory and Critical Care Medicine at Beijing Chaoyang Hospital. The relevant literatures were reviewed. Results: A 18-year-old female was admitted with chief complaint of cough, dyspnea, and neck mass. Neck CT suggested that tracheal stenosis was caused by surrounded soft tissue. Paratracheal mass biopsy showed dense collagen fibers with infiltration of many lymphocytes and plasma cells. Immunohistochemical stain found that IgG(4)-positive plasma cells were >50/high power field (HPF) and a ratio of IgG(4)/IgG positive cells was over 40% .The level of serum IgG(4) was significantly increased (2 930 mg/L). She was diagnosed as IgG(4)-related disease. The patient was treated with 80 mg intravenous methylprednisolone per day for three days, then prednisone 40 mg daily oral. Her dyspnea was significantly relieved.One month later, CT scan showed that the cervical tracheal stenosis was significantly improved. We identified 20 cases of IgG(4)-related disease involving the trachea and paratracheal soft tissue from databases, in which only 1 case was similar as this patient. The other 19 cases were of extratracheal involvement. Elevated serum IgG(4) was detected in 11/12 patients. Most patients were treated with glucocorticoid, some combined with immunosuppressive agents and rituximab. The clinical outcome was good. Conclusion: IgG(4)-related disease involving the trachea and paratracheal soft tissue is a rare condition. Serum IgG(4) level and histopathology should be considered for diagnosis. Glucocorticoid is
Brito-Zerón, Pilar; Kostov, Belchin; Bosch, Xavier; Acar-Denizli, Nihan; Ramos-Casals, Manuel; Stone, John H
To review the reported evidence on the therapeutic management of IgG4-related disease (IgG4-RD) in clinical practice.A systematic search of the literature was conducted. The primary outcome measured was the rate of efficacy of first-line therapeutic approaches. Secondary outcomes measured included the rate of disease relapse, the outcome of untreated patients, the rate of patients without drug therapy at the end of follow-up, the rate of side effects, and mortality. The MOOSE, AHRQ, STROBE, and GRACE recommendations/statements were followed.The results of the systematic search strategy yielded 62 studies that included a total of 3034 patients. Complete information about first-line therapeutic regimens was detailed in 1952 patients, including glucocorticoid-based regimens in 1437 (74%), drug-free regimens in 213 (11%), and other therapies in 38 (2%). No therapy (wait and see management) was reported in 264 (13%) patients. The efficacy of monotherapy with glucocorticoids was specified in 1220 patients, of whom 97% had a therapeutic response. Relapses, however, were reported in 464/1395 (33%) patients despite typically short follow-up periods. Therapeutic efficacy was reported in 219/231 (95%) of relapses treated with glucocorticoids, 56/69 (81%) of those treated with azathioprine, 16/22 (72%) of those treated with other immunosuppressive agents, and in the 9 cases treated with rituximab (100%). In 14 studies, the authors detailed the outcome of 159/246 patients with wait-and-see management; spontaneous improvement or resolution was reported in 68 (43%) cases. Wide heterogeneity was observed with respect to the first-line therapeutic approaches used for the different organ-specific disease subsets, including significant differences in the mean dose of glucocorticoids used.Nearly 70% of reported IgG4-RD patients are treated with oral glucocorticoids in monotherapy. However, the therapeutic management is heavily influenced by geographical, epidemiological, and clinical
Kazantseva, I A; Lishchuk, S V; Gribunov, Yu P; Shestakova, I N; Pavlov, K A
The paper presents the data available in the literature on IgG4-related disease (IgG4-RD) concurrent with malignancies at different sites, as well as possible common pathogenetic mechanisms of their development and morphological diagnostic criteria for IgG4-RD. The authors give their own observation of gastric signet ring cell carcinoma concurrent with morphologically verified IgG4-RD.
Geyer, Julia T; Niesvizky, Ruben; Jayabalan, David S; Mathew, Susan; Subramaniyam, Shivakumar; Geyer, Alexander I; Orazi, Attilio; Ely, Scott A
IgG4-related disease is a newly described systemic fibroinflammatory process, characterized by increase in IgG4-positive plasma cells. Its pathogenesis, including the role of IgG4, remains poorly understood. Plasma cell myeloma is typically associated with a large monoclonal serum spike, which is frequently of IgG isotype. We sought to identify and characterize a subset of IgG4-secreting myeloma, as it may provide a biological model of disease with high serum levels of IgG4. Six out of 158 bone marrow biopsies (4%) from patients with IgG myeloma expressed IgG4. Four patients were men and two were women, with a mean age of 64 (range 53-87) years. Imaging showed fullness of pancreatic head (1), small non-metabolic lymphadenopathy (1), and bone lytic lesions (6). Two patients developed necrotizing fasciitis. All had elevated serum M-protein (mean 2.4, range 0.5-4.2 g/dl), and none had definite signs or symptoms of IgG4-related disease. Four myelomas had plasmablastic morphology. Four had kappa and two had lambda light chain expression. Three cases expressed CD56. Two patients had a complex karyotype. In conclusion, the frequency of IgG4 myeloma correlates with the normal distribution of IgG4 isoform. The patients with IgG4 myeloma appear to have a high rate of plasmablastic morphology and could be predisposed to necrotizing fasciitis. Despite high serum levels of IgG4, none had evidence of IgG4-related disease. These findings suggest that the increased number of IgG4-positive plasma cells is not the primary etiologic agent in IgG4-related disease. Elevated serum levels of IgG4 is not sufficient to produce the typical disease presentation and should not be considered diagnostic of IgG4-related disease.
Lee, Lennard Y W; Yap, Hsiu; Sampson, Steve; Ford, Brian; Hayman, Grant; Marsh, James; Bansal, Amolak S
Isolated IgG4 tubulointerstitial nephritis (TIN) is a rare disorder characterized by raised serum IgG4 levels and histological findings of dense lymphoplasmacytic infiltrates rich in IgG4 positive plasma cells. We report a case of isolated IgG4 TIN that presented with acute kidney injury in an 84 year old man with a polyclonal increase in his total IgG and a raised IgE of 381 kUA/L but without evidence of systemic autoimmunity. We draw a parallel with IgG4-related autoimmune pancreatitis and show raised levels of circulating regulatory T cells. Importantly the plasma levels of the T regulatory cell cytokine, IL10, the TH1 cytokines IL12 and IFNγ, the proinflammatory TNF α and immune regulatory IL27 were all highly raised. Furthermore, the level of IL21 that promotes IgG4 production was also very significantly elevated. These results suggest efforts of the immune system to reduce inflammation and suppress an exaggerated Th2 response. A raised serum IgG in the setting of acute kidney injury and in the absence of autoimmunity and chronic infection should encourage an assessment of the IgG subclasses. Prompt steroid treatment of those with a raised IgG4 may reduce ongoing renal damage.
Wei, Tzu-Wei; Lien, Ching-Feng; Hsu, Tun-Yen; He, Hong-Lin
Chronic sclerosing sialadenitis typically involves the submandibular gland. It usually occurs in the middle-aged and elderly adults with a slight male predominance. Recent evidences have suggested that it is an entity of IgG4-related sclerosing disease and has distinct histopathological features, such as a dense lymphoplasmacytic infiltrate, sclerosis and obliterative phlebitis. It is important to discriminate this entity from other diseases, trying to give effective treatment to the patients. In this report, we described a patient having chronic sclerosing sialadenitis in the submandibular gland. PMID:26339446
Kawano, Mitsuhiro; Suzuki, Yasunori; Yamada, Kazunori; Mizushima, Ichiro; Matsumura, Masami; Nakajima, Kenichi; Yamagishi, Masakazu; Yamaguchi, Yutaka
We describe a 62-year-old woman with Sjögren's syndrome (SS) presenting with tubulointerstitial nephritis (TIN) and lymphadenopathy mimicking IgG4-related disease (IgG4-RD). Computed tomography revealed multiple swollen lymph nodes. Biopsy of the largest lymph node showed reactive lymphadenopathy with dense IgG4 positive plasma cell (IgG4 + PC) infiltration. Renal biopsy showed chronic plasma cell-rich TIN with IgG4 + PC infiltration. This case suggests that Immunoglobulin G4 immunostaining does not always support the diagnosis of IgG4-RD in the differential diagnosis between SS and IgG4-RD.
Storgaard, Anders; Detlefsen, Sönke
Immunoglobulin G4-related disease (IgG4-RD) is an inflammatory and fibrotic disease with the potential to produce diffuse enlargement, massforming lesions or stenoses in a wide range of organs. Elevation of serum IgG4 concentration and high levels of IgG4-positive cells in the inflamed tissue are common denominators. Type 1 autoimmune pancreatitis is one of the main manifestations, and its recognition preceded the definition of IgG4-RD as a novel clinical entity. The aetiology, pathophysiology, epidemiology and clinical long-term outcome of IgG4-RD are not fully elucidated. Steroids are effective in most patients, sometimes combined with other antiinflammatory drugs.
Sakai, Toshiyuki; Kondo, Masahide; Yoshii, Shintaro; Tomimoto, Hidekazu
We report a patient of 32-year-old female with central IgG4-related disease. She developed headache and visual disturbance. On examination, she revealed diabetes insipidus, retrobulbar neuritis, hyperreflexia and limb weakness. Her laboratory findings showed serum IgG4 elevation, pleocytosis and protein elevation in cerebrospinal fluid. Chest CT showed a nodular lesion in the S8 of the left lung. Cranial and spinal magnetic resonance images with gadolinium contrast material showed cranial, cervical and lumbosacral hypertrophic pachymeningitis associated with infundibulo-hypophysitis. Pathological findings of the left frontal dura mater revealed lymphoplasmacytic inflammatory cell infiltrate with dense fibrosis. IgG4 immunohistochemistry showed no IgG4 + plasma cells within the inflammatory infiltrate. During treatment with intravenous pulse methylprednisolone followed by oral prednisolone, she revealed recovery of visual acuity with improvement of hypertrophic pachymeningitis and normalization of serum IgG4. This is a first report of IgG4-related hypertrophic pachymeningitis which involved cranial, cervical and lumbosacral regions as well as infundibulo-hypophysitis in a young female.
Jalilian, Chris; Prince, H Miles; McCormack, Chris; Lade, Stephen; Cheah, Chan Y
Immunoglobulin type gamma 4 (Ig)G4-related disease (IgG4-RD) is a relatively recently described clinical entity characterised by elevated levels of serum IgG4 and tissue infiltration of IgG4+ plasma cells in various organ systems. Cutaneous involvement is rare but is becoming increasingly appreciated; typically presenting as erythematous papules and/or nodules that are commonly pruritic. We report a case of IgG4-RD presenting with persistent pruritic papules and unilateral parotid swelling. His serum IgG4 level was elevated and a histological examination of his skin biopsies found a lymphoplasmacytic infiltration with an excess of IgG4+ non-clonal plasma cells. The patient was intolerant of oral prednisolone, however complete resolution of the cutaneous lesions was achieved with the anti-CD20 antibody, rituximab.
Delgado-García, Guillermo; Sánchez-Salazar, Sergio; Rendón-Ramírez, Erick; Castro-Medina, Mario; Sáenz-Ibarra, Bárbara; Barboza-Quintana, Álvaro; Loredo-Alanis, María Azalea; Hernández-Barajas, David; Galarza-Delgado, Dionicio
Coronary involvement in IgG4-related disease (IgG4-RD) has been scarcely reported, and myocardial ischemia as its presenting feature is even rarer. Here, we describe an additional case with novel and relevant observations. The patient was a previously healthy, middle-aged woman who presented to the clinic with new-onset typical angina. One tumefactive lesion encasing the left anterior descending artery was found during her workup. The most common underlying malignancies with secondary cardiac involvement were rationally ruled out. Symptoms persisted despite medical treatment, and she was therefore referred to surgery. Tumor excision was successfully performed, and she received coronary bypass grafting. IgG4-related coronary arteritis with pseudotumor formation was subsequently diagnosed following the comprehensive diagnostic criteria. This condition was clinically classified as active and circulating plasmablasts were found to be increased (5480/mL), even when these were determined 38 days after surgery. A PET/CT revealed an additional hypermetabolic lymph node. She was therefore treated with rituximab as induction therapy (two 1000 mg doses, administered 15 days apart). Three months later, her disease remained clinically inactive. Circulating plasmablasts were repeated and these had dropped to 0/mL. We thereafter review the current and pertinent literature on the topic, emphasizing the previous cases with similar presenting features (n = 7). We lastly suggest that IgG4-RD should be part of the differential diagnosis of any patient with tumefactive lesions surrounding the coronary arteries, since it can initially presented as sudden cardiac death.
Chong, Sze Yee; Coleman, Lee; MacGregor, Duncan; Hardikar, Winita; Oliver, Mark R.
We report 3 children who presented with fever and abdominal pain, deranged liver function tests, and on abdominal ultrasound were found to have an enlarged pancreas, substantial abdominal lymphadenopathy, and extrahepatic biliary duct dilatation. After ruling out malignancy, probable immunoglobulin G4-related disease (IgG4RD) associated with autoimmune pancreatitis was considered. This condition was first described in the adults and often mimics pancreatic cancer. It can involve multiple organs, either synchronously or metachronously, and is rarely reported in children. The disorder mostly responds to corticosteroid therapy and other immune suppression. We highlight the difficulty in diagnosing autoimmune pancreatitis/IgG4-related disease in children and illustrate the difference between pediatric and adult presentation. PMID:27622194
Lang, David; Zwerina, Jochen; Pieringer, Herwig
Immunoglobulin G4-related disease (IgG4-RD) represents an immune-mediated fibroinflammatory condition with a characteristic histopathological appearance that can affect various organs. Although numerous single-organ manifestations have been described more than a century ago, its systemic nature and unique features were only discovered in the last 2 decades, when IgG4-RD emerged as a new entity of disease. IgG4-RD is usually considered a rare disease, but its true epidemiology has not yet been fully clarified. Also, despite recent advances in the identification of the underlying immunological processes, its pathophysiology is only incompletely understood till now. The diagnostic workup of IgG4-RD is complex and usually requires a combination of clinical examination, imaging, histological, and serological analyses. However, no finding alone is specific for IgG4-RD. Therefore, its diagnosis requires careful interpretation of examination results in context with the patient’s clinical appearance as well as the exclusion of a broad variety of differential diagnoses. The past years brought rapid advances concerning this novel disease entity: diagnostic criteria, further insights into the underlying immunological processes, new biomarkers, and novel therapeutic approaches were proposed and widened the knowledge in the field of IgG4-RD. Still, a greater number of questions remain unanswered, and many recent developments require further discussion and proof from clinical trials. This review should give an overview on current knowledge and future perspectives in epidemiology, pathophysiology, diagnosis, and therapy of IgG4-RD. PMID:26929632
Schneider, Frank; Veraldi, Kristen L.; Levesque, Marc C.; Colby, Thomas V.; S. Yi, Eunhee
We report a case of immunoglobulin(Ig)G4-related disease with the radiologic and histopathological manifestations resembling usual interstitial pneumonia (UIP). The patient was a 62-year-old man who presented with progressive dyspnea of insidious onset. High resolution computed tomography of the chest showed lower-lobe predominant peripheral reticulation and traction bronchiectasis but no honeycomb change. Microscopic examination of the surgical lung biopsy showed characteristic features of UIP including architectural distortion by fibrosis with peripheral and paraseptal accentuation, scattered fibroblast foci and microscopic honeycomb change. In addition there were prominent multifocal lymphoplasmacytic infiltrates with a marked increase of IgG4-positive plasma cells (79 per high power field in hot spots) and high IgG4/IgG ratio (up to 67%). The serum IgG4 level was elevated at 760 mg/dl (reference range 9-89), with normal levels for the other IgG subclasses and negative serologic markers for autoimmune diseases. The patient’s symptoms improved significantly with oral corticosteroid treatment. PMID:27053971
Corujeira, Susana; Ferraz, Catarina; Nunes, Teresa; Fonseca, Elsa; Vaz, Luísa Guedes
Immunoglobulin G4-related disease (IgG4-RD) is an increasingly recognized syndrome that can appear with multiple organ involvement, typically with tumor-like swelling, lymphoplasmacytic infiltrate rich in IgG4-positive plasma cells, and elevated serum IgG4 concentrations. We report the case of a 22-month-old female child with failure to thrive and recurrent respiratory tract infections since 8 months of age. Physical examination was normal except for pulmonary auscultation with bilateral crackles and wheezes. Laboratory tests revealed elevated erythrocyte sedimentation rate, and elevated serum IgG and IgG4 with polyclonal hypergammaglobulinemia. Thoracic CT and MRI showed multiple mediastinal lymphadenopathies and a nodular posterior mediastinal mass in right paratracheal location with bronchial compression. Initial fine needle aspiration biopsy was compatible with reactive lymphadenopathy but after clinical worsening a thoracoscopic partial resection of the mass was performed and tissue biopsy revealed lymphoplasmacytic infiltrate and increased number of IgG4-positive plasma cells and a ratio of IgG4/IgG positive cells above 40%. Glucocorticoids therapy was started with symptomatic improvement, reduction in the size of the mass, and decrease of serum IgG4 levels after 6 weeks. There are very few reports of IgG4-RD in children. Long-term follow-up is necessary to monitor relapses and additional organ involvement.
Takeshima, Ken; Inaba, Hidefumi; Ariyasu, Hiroyuki; Furukawa, Yasushi; Doi, Asako; Nishi, Masahiro; Hirokawa, Mitsuyoshi; Yoshida, Akira; Imai, Ryoukichi; Akamizu, Takashi
Riedel's thyroiditis (RT) is a rare chronic fibrosing disorder characterized by a hard, infiltrative lesion in the thyroid gland, which is often associated with multifocal fibrosclerosis. Immunoglobulin G4-related disease (IgG4-RD) is typified by infiltration of IgG4-positive plasma cells into multiple organs, resulting in tissue fibrosis and organ dysfunction. In order to evaluate the clinicopathological features of RT and its relationship with IgG4-RD, we performed a Japanese literature search using the keywords "Riedel" and "Riedel's thyroiditis." We used the electronic databases Medline and Igaku Chuo Zasshi, the latter of which is the largest medical literature database in Japan. The diagnosis of RT was based on the presence of a fibroinflammatory process with extension into surrounding tissues. Only 10 patients in Japan fulfilled RT diagnostic criteria during the 25-year period between 1988 and 2012. Two patients with confirmed IgG4/IgG immunohistochemical findings demonstrated 43 and 13 IgG4-positive plasma cells per high-power field, respectively, and the IgG4-positive/IgG-positive plasma cell ratios of 20% and less than 5%. Of the 10 patients with RT, two received glucocorticoids, one of whom experienced marked shrinkage of the thyroid lesion. One patient had extra-thyroid involvement in the form of retroperitoneal fibrosis. Although the clinicopathological features of RT suggest that IgG4-RD may be the underlying condition in some cases, further investigation is needed to clarify the etiology of RT in relation to IgG4-RD.
Divatia, Mukul; Kim, Sun A
Immunoglobulin G4-related systemic disease (IgG4-RSD) is a recently defined emerging entity characterized by a diffuse or mass forming inflammatory reaction rich in IgG4-positive plasma cells associated with fibrosclerosis and obliterative phlebitis. IgG4-RSD usually affects middle aged and elderly patients, with a male predominance. It is associated with an elevated serum titer of IgG4, which acts as a marker for this recently characterized entity. The prototype is IgG4-related sclerosing pancreatitis or autoimmune pancreatitis (AIP). Other common sites of involvement are the hepatobiliary tract, salivary gland, orbit, and lymph node, however practically any organ can be involved, including upper aerodigestive tract, lung, aorta, mediastinum, retroperitoneum, soft tissue, skin, central nervous system, breast, kidney, and prostate. Fever or constitutional symptoms usually do not comprise part of the clinical picture. Laboratory findings detected include raised serum globulin, IgG and IgG4. An association with autoantibody detection (such as antinuclear antibodies and rheumatoid factor) is seen in some cases. Steroid therapy comprises the mainstay of treatment. Disease progression with involvement of multiple organ-sites may be encountered in a subset of cases and may follow a relapsing-remitting course. The principal histopathologic findings in several extranodal sites include lymphoplasmacytic infiltration, lymphoid follicle formation, sclerosis and obliterative phlebitis, along with atrophy and destruction of tissues. Immunohistochemical staining shows increased IgG4+ cells in the involved tissues (>50 per high-power field, with IgG4/IgG ratio >40%). IgG4-RSD may potentially be rarely associated with the development of lymphoma and carcinoma. However, the nature and pathogenesis of IgG4-RSD are yet to be fully elucidated and provide immense scope for further studies. PMID:22187229
Bakhit, Mudathir S; Fujii, Masazumi; Jinguji, Shinya; Sato, Taku; Sakuma, Jun; Saito, Kiyoshi
Lower cranial nerve sheath tumors are relatively rare, and cases of schwannoma collision tumors have rarely been reported, with most of the reported cases describing schwannoma and meningioma collision tumors. We report a very rare case of a cerebellopontine angle collision tumor of the 9(th) cranial nerve schwannoma with an IgG4 plasma cell pseudotumor. IgG4 plasma cell pseudotumors comprise a group of diseases called IgG4-related diseases (IgG4-RDs). These diseases usually affect organs such as the pancreas and salivary gland. Few cases of nervous system IgG4-RDs have been reported. Under intraoperative microscopy, the tumor in our case did not appear different from usual cases of schwannoma, but histopathology showed significant infiltration of IgG4 plasma cells. IgG4-RDs have a distinctive histopathological pattern; however, their pathophysiology remains unclear. Special attention must be paid to the diagnosis of such diseases because they mimic other diseases and can be missed.
Takano, Kenichi; Yamamoto, Motohisa; Takahashi, Hiroki; Himi, Tetsuo
IgG4-related disease (IgG4-RD) is a chronic inflammatory disorder, characterized by elevated serum IgG4 levels as well as abundant infiltration of IgG4-positive plasmacytes and fibrosis in various organs, including the head and neck region. In particular, the salivary glands, orbit, and thyroid are common sites of disease involvement. IgG4-RD is diagnosed based on various clinical, serological, and histopathological findings, none of which are pathognomonic. Hence, various differential diagnoses, which exhibit elevated serum IgG4 levels and infiltration of IgG4-postive cells into tissues, need to be excluded, especially malignant diseases and mimicking disorders. Systemic corticosteroids are generally effective in inducing IgG4-RD remission; however, recurrent or refractory cases are common. In addition, although the pathogenic mechanisms of IgG4-RD remain unclear, an antigen-driven inflammatory condition is believed to be involved. Recent studies have indicated the important pathogenic role of B cell/T cell collaboration and innate immunity in this disease. Nevertheless, additional research and discussions are needed to resolve many remaining questions. In this review, we provide an overview of the recent insights on the history, clinical features, diagnosis, and treatment of IgG4-RD in the head and neck region. Furthermore, we have also addressed the pathogenesis of this disease.
Okazaki, Kazuichi; Yanagawa, Masahito; Mitsuyama, Toshiyuki; Uchida, Kazushige
Recent studies have proposed nomenclatures of type 1 autoimmune pancreatitis (AIP) (IgG4-related pancreatitis), IgG4-related sclerosing cholangitis (IgG4-SC), IgG4-related cholecystitis, and IgG4-related hepatopathy as IgG4-related disease (IgG4-RD) in the hepato-bilio-pancreatic system. In IgG4-related hepatopathy, a novel concept of IgG4-related autoimmune hepatitis (AIH) with the same histopathological features as AIH has been proposed. Among organs involved in IgG4-RD, associations with pancreatic and biliary lesions are most frequently observed, supporting the novel concept of "biliary diseases with pancreatic counterparts." Targets of type 1 AIP and IgG4-SC may be periductal glands around the bile and pancreatic ducts. Based on genetic backgrounds, innate and acquired immunity, Th2-dominant immune status, regulatory T (Treg) or B cells, and complement activation via a classical pathway may be involved in the development of IgG4-RD. Although the role of IgG4 remains unclear in IgG4-RD, IgG4-production is upregulated by interleukin 10 from Treg cells and by B cell activating factor from monocytes/basophils with stimulation of toll-like receptors/nucleotide-binding oligomerization domain-like receptors. Based on these findings, we have proposed a hypothesis for the development of IgG4-RD in the hepato-bilio-pancreatic system. Further studies are necessary to clarify the pathogenic mechanism of IgG4-RD.
Takeuchi, Mai; Sato, Yasuharu; Ohno, Kyotaro; Tanaka, Satoshi; Takata, Katsuyoshi; Gion, Yuka; Orita, Yorihisa; Ito, Toshihiro; Tachibana, Tomoyasu; Yoshino, Tadashi
IgG4-related disease is a systemic disorder with unique clinicopathological features and uncertain etiological features and is frequently related to allergic disease. T helper 2 and regulatory T-cell cytokines have been reported to be upregulated in the affected tissues; thus, the production of these cytokines by T helper 2 and regulatory T cells has been suggested as an important factor in the pathogenesis of IgG4-related disease. However, it is not yet clear which cells produce these cytokines in IgG4-related disease, and some aspects of the disorder cannot be completely explained by T-cell-related processes. To address this, we analyzed paraffin-embedded sections of tissues from nine cases of IgG4-related submandibular gland disease, five cases of submandibular sialolithiasis, and six cases of normal submandibular gland in order to identify potential key players in the pathogenesis of IgG4-related disease. Real-time polymerase chain reaction analysis confirmed the significant upregulation of interleukin (IL)4, IL10, and transforming growth factor beta 1 (TGFβ1) in IgG4-related disease. Interestingly, immunohistochemical studies indicated the presence of mast cells expressing these cytokines in diseased tissues. In addition, dual immunofluorescence assays identified cells that were double-positive for each cytokine and for KIT, which is expressed by mast cells. In contrast, the distribution of T cells did not correlate with cytokine distribution in affected tissues. We also found that the mast cells were strongly positive for IgE. This observation supports the hypothesis that mast cells are involved in IgG4-related disease, as mast cells are known to be closely related to allergic reactions and are activated in the presence of elevated non-specific IgE levels. In conclusion, our results indicate that mast cells produce T helper 2 and regulatory T-cell cytokines in tissues affected by IgG4-related disease and possibly have an important role in disease
Xu, Wen-long; Ling, Ying-chun; Wang, Zhi-kai; Deng, Fang
An elevated serum IgG4 level is one of the most useful factors in the diagnosis of IgG4-related disease (IgG4-RD). In this study, we performed a meta-analysis of the published articles assessing the diagnostic accuracy of serum IgG4 concentrations for IgG4-RD. The databases of MEDLINE/PubMed, EMBASE and Web of Science were systematically searched for relevant studies. Sensitivities and specificities of serum IgG4 in each study were calculated, and the hierarchical summary receiver operating characteristic (HSROC) model with a random effects model were employed to obtain the individual and pooled estimates of sensitivities and specificities. In total, twenty-three studies comprising 6048 patients with IgG4-RD were included in the meta-analysis. The pooled sensitivity was 85% with a 95% confidence interval (CI) of 78–90%; the pooled specificity was 93% with a 95% CI of 90–95%. The HSROC curve for quantitative serum IgG4 lies closer to the upper left corner of the plot, and the area under the curve (AUC) was 0.95 (95% CI 0.93, 0.97), which suggested a high diagnostic accuracy of serum IgG4 for the entity of IgG4-RD. Our study suggests that serum IgG4 has high sensitivity and specificity in the diagnosis of IgG4-RD. PMID:27558881
Mattoo, Hamid; Stone, John H; Pillai, Shiv
IgG4-related disease (IgG4-RD) is a systemic condition of unknown cause characterized by highly fibrotic lesions, with dense lymphoplasmacytic infiltrates containing a preponderance of IgG4-expressing plasma cells. CD4(+) T cells and B cells constitute the major inflammatory cell populations in IgG4-RD lesions. IgG4-RD patients with active, untreated disease show a marked expansion of plasmablasts in the circulation. Although the therapeutic depletion of B cells suggests a role for these cells in the disease, a direct role for B cells or IgG4 in the pathogenesis of IgG4-RD is yet to be demonstrated. Among the CD4(+) T-cell subsets, Th2 cells were initially thought to contribute to IgG4-RD pathogenesis, but many previous studies were confounded by the concomitant history of allergic diseases in the patients studied and the failure to use multi-color staining to definitively identify T-cell subsets in tissue samples. More recently, using an unbiased approach to characterize CD4(+) T-cell subsets in patients with IgG4-RD - based on their clonal expansion and ability to infiltrate affected tissue sites - CD4(+) CTLs have been identified as the major CD4(+) T-cell subset in disease lesions as well as in the circulation. CD4(+) CTLs in affected tissues secrete pro-fibrotic cytokines including IL-1β, TGF-β1, and IFN-γ as well as cytolytic molecules such as perforin and granzymes A and B. In this review, we examine possible mechanisms by which activated B cells and plasmablasts may collaborate with the expanded CD4(+) CTLs in driving the fibrotic pathology of the disease and describe the lacunae in the field and in our understanding of IgG4-RD pathogenesis.
Allen, Steven G; Soliman, Amr S; Toy, Kathleen; Omar, Omar S; Youssef, Tamer; Karkouri, Mehdi; Ayad, Essam; Abdel-Aziz, Azza; Hablas, Ahmed; Tahri, Ali; Oltean, Hanna N; Kleer, Celina G; Merajver, Sofia D
Idiopathic granulomatous mastitis (IGM) is a benign, frequently severe chronic inflammatory lesion of the breast. Its etiology remains unknown and reported cases vary in their presentation and histologic findings with an optimal treatment algorithm yet to be described owing mainly to the disease's heterogeneity. IgG4-related disease (IgG4-RD) is a newly recognized systemic fibroinflammatory condition characterized by a dense lymphoplasmacytic infiltrate with many IgG4-positive plasma cells, storiform fibrosis, and obliterative phlebitis. Immunosuppressive therapy is considered to be an effective first-line therapy for IgG4-RD. We sought to clarify and classify chronic mastitis according to the histologic findings of IgG4-RD mastitis with respect to IGM and to develop a robust diagnostic framework to help select patients for optimal treatment strategies. Using the largest collection to date (43 cases from Egypt and Morocco), we show that despite sharing many features, IGM and IgG4-RD mastitis are separate diseases. To diagnostically separate the diseases, we created a classification schema-termed the Michigan Classification-based upon our large series of cases, the consensus statement on IgG4-RD, and the histologic description of IGM in the literature. Using our classification, we discerned 17 cases of IgG4-RD and 8 cases of IGM among the 43 chronic mastitis cases, with 18 indeterminate cases. Thus, our Michigan Classification can form the basis of rational stratification of chronic mastitis patients between these two clinically and histopathologically heterogeneous diseases.
Hara, Satoshi; Kawano, Mitsuhiro; Mizushima, Ichiro; Harada, Kenichi; Takata, Takuma; Saeki, Takako; Ubara, Yoshifumi; Sato, Yasuharu; Nagata, Michio
IgG4-related kidney disease (IgG4-RKD) occasionally progresses to chronic renal failure and is pathologically characterized by IgG4-positive lymphoplasmacyte-rich tubulointerstitial nephritis with storiform fibrosis (bird's-eye pattern fibrosis). Although radiology reveals a heterogeneous distribution of affected areas in this disease, their true distribution within the whole kidney is still unknown because of difficulty in estimating this from needle biopsy samples. Using 5 autopsy specimens, the present study histologically characterized the distribution and components of interstitial inflammation and fibrosis in IgG4-RKD. Interstitial lymphoplasmacytic infiltration or fibrosis was observed in a variety of anatomical locations such as intracapsular, subcapsular, cortical, perivascular, and perineural regions heterogeneously in a patchy distribution. They tended to be more markedly accumulated around medium- and small-sized vessels. Storiform fibrosis was limited to the cortex. Immunostaining revealed nonfibrillar collagens (collagen IV and VI) and fibronectin predominance in the cortical lesion, including storiform fibrosis. In contrast, fibril-forming collagens (collagen I and III), collagen VI, and fibronectin were the main components in the perivascular lesion. In addition, α-smooth muscle actin-positive myofibroblasts were prominently accumulated in the early lesion and decreased with progression, suggesting that myofibroblasts produce extracellular matrices forming a peculiar fibrosis. In conclusion, perivascular inflammation or fibrosis of medium- and small-sized vessels is a newly identified pathologic feature of IgG4-RKD. Because storiform fibrosis contains mainly nonfibrillar collagens, "interstitial fibrosclerosis" would be a suitable term to reflect this. The relation between the location and components of fibrosis determined in whole kidney samples provides new clues to the pathophysiology underlying IgG4-RKD.
Wang, Chenqiong; Wu, Xuefen; Miao, Ye; Xiong, Hui; Bai, Lin; Dong, Lingli
Objective Elevated serum IgG4 levels are an important hallmark for diagnosing IgG4-related disease (IgG4-RD), but can also be observed in other diseases. This study aimed to compare two different testing methods for IgG4: ELISA and nephelometric assay. Both assays were used to measure serum IgG4 concentrations, and to assess the prevalence of high serum IgG4 levels in both IgG4-RD and non-IgG4-RD diseases. Methods A total of 80 serum samples were tested using the nephelometric assay and ELISA method that we established. Serum IgG4 concentrations were determined by ELISA for 957 patients with distinct diseases, including 12 cases of IgG4-RD and 945 cases of non-IgG4-RD. Results IgG4 levels from 80 selected serum samples examined by ELISA were in agreement with those detected using the nephelometry assay. Meanwhile, the serum IgG4 concentrations measured by ELISA were also consistent with the clinical diagnoses of patients with IgG4-RD during the course of disease. The Elevated levels of serum IgG4 (>1.35 g/L) were detected in all IgG4-RD (12/12) patients, and the prevalence of high IgG4 serum levels was 3.39% in non-IgG4-RD cases. Among them, the positive rates of serum IgG4 were 2.06% in patients with carcinoma and 6.3% in patients with other non-IgG4 autoimmune diseases. Conclusion Our established ELISA method is a reliable and convenient technique, which could be extensively used in the clinic to measure serum IgG4 levels. High levels of IgG4 were observed in IgG4-RD. However, this phenomenon could also be observed in other diseases, such as carcinomas and other autoimmune diseases. Thus, a diagnosis of IgG4 disease cannot only be dependent on the detection of elevated serum IgG4 levels. PMID:25885536
Acevedo Ribó, Mercedes; Ahijado Hormigos, Francisco Javier; Díaz, Francisco; Romero Molina, Marta; Fernandez Rojo, Maria Angeles; Garcia Rubiales, Maria Antonia; García Diaz, Eugenio
This case report describes a patient with a previous history of autoimmune pancreatitis secondary to IgG4-related disease, who developed an overt nephrotic syndrome due to membranous nephropathy, surprisingly idiopathic. In all the previously described cases with both concurrent diseases, membranous nephropathy was considered to be secondary to the IgG4-related disease based on the absence of anti-PLA2R1 autoantibodies, and nephrotic syndrome usually remitted after treatment with steroids alone. However, in our patient positivity of serum anti-PLA2R1 autoantibodies together with a normal serum IgG4 level, and the absence of the other most commonly associated diseases were compatible with an idiopathic membranous nephropathy. Combination treatment with steroids and cyclophosphamide was successful. We hypothesize about causality or coincidental diseases and the importance of a correct classification. .
Cárdenas-Perilla, R; Monturiol-Duran, J; Simó-Perdigó, M; Barios-Profitós, M; Castell-Conesa, J
IgG4-related diseases are a group of recently identified entities that include disorders that were previously known by other names, such as Mikulicz disease, Küttner's tumor, Riedel thyroiditis, among others, as well as some new ones described in the last years. These pathologies are a challenge for the medical community in terms of diagnosis and characterization due to their wide spectrum of clinical presentation. Functional imaging can provide a new approach to the comprehension of physiopathology, staging and targeting site of biopsy of IgG4-related diseases. In this clinical note, we describe five patients who underwent ¹⁸F-FDG PET-CT and correlate their findings with previous reports.
Nishihara, Eijun; Hirokawa, Mitsuyoshi; Ito, Mitsuru; Fukata, Shuji; Nakamura, Hirotoshi; Amino, Nobuyuki; Miyauchi, Akira
Background IgG4-related disease is a novel disease entity characterized by diffuse lymphoplasmacytic infiltration rich in IgG4-positive plasma cells and fibrosis into multiple organs. There is still controversy over whether some thyroid diseases are actually IgG4-related disease. The objective of this study was to elucidate the clinicopathological features of Graves’ disease with diffuse lymphoplasmacytic infiltration in the thyroid. Patients and Methods Among 1,484 Graves’ disease patients who underwent thyroidectomy, we examined their histopathological findings including the degree of lymphoplasmacytic and fibrotic infiltration and levels of IgG4-positive plasma cells in the thyroid. Their clinical pictures were defined by laboratory and ultrasonographic evaluation. Results A total of 11 patients (0.74%) showed diffuse lymphoplasmacytic infiltration in the stroma of the thyroid gland. Meanwhile, other patients showed variable lymphoid infiltration ranging from absent to focally dense but no aggregation of plasma cells in the thyroid gland. Based on the diagnostic criteria of IgG4-related disease, 5 of the 11 subjects had specifically increased levels of IgG4-positive plasma cells in the thyroid. Fibrotic infiltration was present in only 1 patient developing hypothyroidism after anti-thyroid drug treatment for 4 years, but not in the other 10 patients with persistent hyperthyroidism. Obliterative phlebitis was not identified in any of the 11 subjects. Thyroid ultrasound examination showed 1 patient developing hypothyroidism who had diffuse hypoechogenicity, but the other hyperthyroid patients had a coarse echo texture. Conclusions In our study, Graves’ disease patients with persistent hyperthyroidism who had diffuse lymphoplasmacytic infiltration rich in IgG4-positive plasma cells in the thyroid showed no concomitant fibrosis or obliterative phlebitis. PMID:26218874
Quattrocchio, Giacomo; Roccatello, Dario
IgG4-related disease (IgG4-RD) is a recently recognized disorder, often with multiple organ involvement, characterized by dense tissue infiltration of IgG4-positive plasma cells, storiform fibrosis, obliterative phlebitis and frequently elevated serum IgG4 concentration. The kidney can be involved either directly or indirectly. The most frequent direct renal manifestations of IgG4-RD are IgG4-related tubulointerstitial nephritis (TIN) and membranous glomerulonephropathy. Retroperitoneal fibrosis (RPF) is another condition that is frequently IgG4-related and that can indirectly affect the kidney causing ureteral obstruction and hydronephrosis. Contrast-enhanced computerized tomography, magnetic resonance imaging and (18)F-fluorodeoxyglucose positron emission tomography/computed tomography show different imaging findings and are useful tools for monitoring therapeutic response. Steroid treatment is the first line of therapy, but relapsing or refractory forms of the disease are frequently observed and require more aggressive therapeutic approaches. At our centre, we treated three cases of aggressive IgG4-related TIN and two cases of IgG4-related RPF with an intensified, immune suppressive protocol, obtaining good results without severe adverse effects.
Baer, Alan N; Gourin, Christine G; Westra, William H; Cox, Darren P; Greenspan, John S; Daniels, Troy E
IgG4-related disease has been recently defined as a distinct clinic-pathologic entity, characterized by dense IgG-4 plasmacytic infiltration of diverse organs, fibrosis, and tumefactive lesions. Salivary and lacrimal glands are a target of this disease and, when affected, may clinically resemble Küttner tumor, Mikulicz disease, or orbital inflammatory pseudotumor. In some patients, the disease is systemic, with metachronous involvement of multiple organs, including the pancreas, aorta, kidneys, and biliary tract. We report a 66-year-old man who presented with salivary gland enlargement and severe salivary hypofunction and was diagnosed with IgG4-related disease on the basis of a labial salivary gland biopsy. Additional features of his illness included a marked peripheral eosinophilia, obstructive pulmonary disease, and lymphoplasmacytic aortitis. He was evaluated in the context of a research registry for Sjögren syndrome and was the only 1 of 2594 registrants with minor salivary gland histopathologic findings supportive of this diagnosis.
Lu, Zhang; Tongxi, Liu; Jie, Luo; Yujuan, Jiao; Wei, Jiang; Xia, Liu; Yumin, Zheng; Xin, Lu
The aim of this study is to study the clinical, laboratory, imaging pathology, and prognosis features of IgG4-related spinal pachymeningitis. We worked with a 55-year-old man suffering from IgG4-related spinal pachymeningitis who had the most widespread lesion in his dura mater. We also review previous related studies and discuss the clinical characteristics of this rare disease. In total, eight IgG4-related spinal pachymeningitis patients have been reported in the literature since 2009. They were mostly male patients, 51.7 ± 11.9 years old on average. Cervical and thoracic vertebrae were the most common sites for lesions. The most prominent symptom was varying numbness and weakness of the limbs and/or body associated with spinal cord compression. There was one patient (1/5) with elevated serum IgG4 levels and three patients (3/3) with increased cerebrospinal fluid (CSF) IgG4 index. Positive histopathologic findings are the strongest basis for a diagnosis. All the patients with IgG4-related spinal pachymeningitis responded well to glucocorticoid therapy. IgG4-related spinal pachymeningitis is an orphan disease that mainly occurs in cervical and thoracic vertebrae. Older males are the most susceptible group. Serum IgG4 levels were consistently normal in these cases, so analysis of CSF for IgG4 production (IgG4 index) could become a useful tool. Pathological findings remain the gold standard for diagnosis. Most patients responded favorably to glucocorticoid treatment.
Kato, Eisuke; Takayanagi, Noboru; Ishiguro, Takashi; Kagiyama, Naho; Shimizu, Yoshihiko; Sugita, Yutaka
Presently, 6 cases of IgG4-related pleuritis have been reported. We encountered a patient who developed chylothorax due to IgG4-related disease. To our knowledge, such patients have not been reported. This patient developed right-sided chylothorax and left-sided non-chylothorax lymphocyte-predominant pleuritis. Elevated serum and pleural IgG4 concentrations and histopathological analysis of pleural biopsy confirmed the diagnosis of IgG4-related pleuritis. Left-sided pleuritis improved with corticosteroid therapy, but right-sided chylothorax persists. IgG4-related disease can be one cause of chylothorax.
Yamamoto, Motohisa; Tabeya, Tetsuya; Naishiro, Yasuyoshi; Yajima, Hidetaka; Ishigami, Keisuke; Shimizu, Yui; Obara, Mikiko; Suzuki, Chisako; Yamashita, Kentaro; Yamamoto, Hiroyuki; Hayashi, Toshiaki; Sasaki, Shigeru; Sugaya, Toshiaki; Ishida, Tadao; Takano, Ken-Ichi; Himi, Tetsuo; Suzuki, Yasuo; Nishimoto, Norihiro; Honda, Saho; Takahashi, Hiroki; Imai, Kohzoh; Shinomura, Yasuhisa
IgG4-related disease (IgG4-RD) is a novel disease entity that includes Mikulicz's disease, autoimmune pancreatitis (AIP), and many other conditions. It is characterized by elevated serum IgG4 levels and abundant IgG4-bearing plasmacyte infiltration of involved organs. We postulated that high levels of serum IgG4 would comprise a useful diagnostic tool, but little information is available about IgG4 in conditions other than IgG4-RD, including rheumatic diseases. Several reports have described cutoff values for serum IgG4 when diagnosing IgG4-RD, but these studies mostly used 135 mg/dL in AIP to differentiate from pancreatic cancer instead of rheumatic and other common diseases. There is no evidence for a cutoff serum IgG4 level of 135 mg/dL for rheumatic diseases and common diseases that are often complicated with rheumatic diseases. The aim of this work was to re-evaluate the usual cutoff serum IgG4 value in AIP (135 mg/dL) that is used to diagnose whole IgG4-RD in the setting of a rheumatic clinic by measuring serum IgG4 levels in IgG4-RD and various disorders. We therefore constructed ROC curves of serum IgG4 levels in 418 patients who attended Sapporo Medical University Hospital due to IgG4-RD and various rheumatic and common disorders. The optimal cut-off value of serum IgG4 for a diagnosis of IgG4-RD was 144 mg/dL, and the sensitivity and specificity were 95.10 and 90.76%, respectively. Levels of serum IgG4 were elevated in IgG4-RD, Churg-Strauss syndrome, multicentric Castleman's disease, eosinophilic disorders, and in some patients with rheumatoid arthritis, systemic sclerosis, chronic hepatitis, and liver cirrhosis. The usual cut-off value of 135 mg/dL in AIP is useful for diagnosing whole IgG4-RD, but high levels of serum IgG4 are sometimes observed in not only IgG4-RD but also other rheumatic and common diseases.
Akiyama, Mitsuhiro; Kaneko, Yuko; Hayashi, Yutaro; Takeuchi, Tsutomu
Immunoglobulin G4-related disease (IgG4-RD) is a recently recognized new disease entity characterized by elevated serum IgG4 and infiltration of IgG4 plasma cells in affected tissues. Histological examination is essential for definitive diagnosis, as other pathological conditions can also present with serum IgG4 elevation. However, IgG4-RD frequently involves vital or internal organs that are difficult to perform biopsies. We herein report a unique case of IgG4-RD involving vital organs that could be successfully diagnosed by alternative lip biopsy, an accessible, little invasive procedure, despite no apparent manifestation demonstrating the involvement in labial salivary gland.A 60-year-old man with swelling of both submandibular glands and elevated serum creatinine level visited our hospital. His labial salivary glands appeared normal. His blood test showed high serum IgG4, and positron-emission computed tomography revealed abnormal uptake in submandibular glands, periaorta, and left kidney with hydronephrosis. We suspected him of IgG4-RD; however, the involved organs were difficult to approach for histological examination. Alternatively, we performed lip biopsy and proved massive infiltration of IgG4 plasma cells leading to the diagnosis with IgG4-RD. Treatment with prednisolone resulted in the remarkable improvement of organ involvements and the normalization of serum IgG4 level after 3 months. Prednisolone was gradually tapered without the relapse of disease.The early recognition and diagnosis of IgG4-RD is clinically important because delay in the treatment initiation leads to fibrosis with irreversible organ damage. Our case highlights the possibility that lip biopsy is a promising option for histological examination in patients with IgG4-RD in whom affected organs are difficult to access, leading to early diagnosis with appropriate treatment.
Li, Dujuan; Kan, Yunzhen; Fu, Fangfang; Wang, Shuhuan; Shi, Ligang; Liu, Jie; Kong, Lingfei
Immunoglobulin G4-related disease (IgG4-RD) is a recently described inflammatory disease involving multiple organs. Prostate involvement with IgG4-RD is very rare. In this report, we describe a case of IgG4-related prostatitis progressed from localized IgG4-related lymphadenopathy. This patient was present with urine retention symptoms. MRI and CT examination revealed the prostatic enlargement and the multiple lymphadenopathy. Serum IgG4 levels were elevated. Prostatic tissue samples resected both this time and less than 1 year earlier showed the same histological type of prostatitis with histopathologic and immunohistochemical findings characteristic of IgG4-RD. The right submandibular lymph nodes excised 2 years earlier were eventually proven to be follicular hyperplasia-type IgG4-related lymphadenopathy. This is the first case of IgG4-RD that began as localized IgG4-related lymphadenopathy and progressed into a systemic disease involving prostate and multiple lymph nodes. This patient showed a good response to steroid therapy. This leads us to advocate a novel pathogenesis of prostatitis, and a novel therapeutic approach against prostatitis. Pathologists and urologists should consider this disease entity in the patients with elevated serum IgG4 levels and the symptoms of prostatic hyperplasia to avoid ineffective medical or unnecessary surgical treatment. PMID:26617921
Li, Dujuan; Kan, Yunzhen; Fu, Fangfang; Wang, Shuhuan; Shi, Ligang; Liu, Jie; Kong, Lingfei
Immunoglobulin G4-related disease (IgG4-RD) is a recently described inflammatory disease involving multiple organs. Prostate involvement with IgG4-RD is very rare. In this report, we describe a case of IgG4-related prostatitis progressed from localized IgG4-related lymphadenopathy. This patient was present with urine retention symptoms. MRI and CT examination revealed the prostatic enlargement and the multiple lymphadenopathy. Serum IgG4 levels were elevated. Prostatic tissue samples resected both this time and less than 1 year earlier showed the same histological type of prostatitis with histopathologic and immunohistochemical findings characteristic of IgG4-RD. The right submandibular lymph nodes excised 2 years earlier were eventually proven to be follicular hyperplasia-type IgG4-related lymphadenopathy. This is the first case of IgG4-RD that began as localized IgG4-related lymphadenopathy and progressed into a systemic disease involving prostate and multiple lymph nodes. This patient showed a good response to steroid therapy. This leads us to advocate a novel pathogenesis of prostatitis, and a novel therapeutic approach against prostatitis. Pathologists and urologists should consider this disease entity in the patients with elevated serum IgG4 levels and the symptoms of prostatic hyperplasia to avoid ineffective medical or unnecessary surgical treatment.
Manabe, Akihiro; Igawa, Takuro; Takeuchi, Mai; Gion, Yuka; Yoshino, Tadashi; Sato, Yasuharu
Plasma cell-type Castleman disease (PCD) is often encountered when differentiating IgG4-related disease (IgG4-RD). Given that serum IgA is often elevated in Castleman disease, we investigated whether IgA expression levels in histological specimens can be used to differentiate between the two diseases. Lymph node lesions obtained from 12 IgG4-RD and 11 PCD patients were analysed by immunohistochemistry with anti-IgG, -IgG4, and -IgA antibodies. In addition to all 12 cases of IgG4-RD, 8/11 cases (72.7 %) of PCD also met the diagnostic criteria of IgG4-RD (serum IgG4 ≥135 mg/dl and IgG4/IgG-positive cells ≥40 %). IgA-positive cells were sparsely and densely distributed in IgG4-RD and PCD cases, respectively. The median number of IgA-positive cells ± SD in all 12 cases of IgG4-RD was 31 ± 37 cells per three high-powered fields (3HPFs) (range 4-118 cells/3HPFs). In contrast, the median number of IgA-positive cells, which was significantly higher in all 11 cases of PCD, was 303 ± 238 cells/3HPFs (range 74-737 cells/3HPFs) (P < 0.001). In conclusion, our findings indicate that in cases where serum analysis-based data are unavailable, anti-IgA immunostaining can be used for differential diagnosis of IgG4-RD.
Ebbo, Mikael; Patient, Matthieu; Grados, Aurelie; Groh, Matthieu; Desblaches, Julien; Hachulla, Eric; Saadoun, David; Audia, Sylvain; Rigolet, Aude; Terrier, Benjamin; Perlat, Antoinette; Guillaud, Constance; Renou, Frederic; Bernit, Emmanuelle; Costedoat-Chalumeau, Nathalie; Harlé, Jean-Robert; Schleinitz, Nicolas
IgG4-related disease (IgG4-RD) is characterized by variable tissue or organ involvements sharing common pathological findings. Orbital or orbital adnexa involvement of the disease has been reported in a few case series. The aim of our study was to characterize and analyze ophthalmic manifestations from a nationwide French case-series.Patients with IgG4-RD and orbital or orbital adnexa involvement included in the French multicentric IgG4-RD case-registry were identified. Only patients fulfilling "modified" comprehensive diagnostic criteria with pathological documentation were retained for the study. Clinical, biological, pathological, radiological findings and data regarding the response to treatment were retrospectively analyzed.According to our data registry, the frequency of IgG4-related ophthalmic disease (IgG4-ROD) was 17%. Mean age at diagnosis was 55.1 ± 7.1 years with a male/female ratio of 2.2. The 19 cases of IgG4-ROD consisted of lacrimal gland (68.4%), soft tissue (57.9%), extra-ocular muscles (36.8%), palpebral (21.1%), optical nerve (10.5%), orbital bone (10.5%), and mononeuritis (V1 and/or V2, 10.5%) involvements. IgG4-ROD was bilateral in 57.9% of cases. Extra-ophthalmic manifestations were reported in 78.9% of cases. All patients responded to prednisone but two-thirds of patients relapsed within a mean (SD) of 9.8 (3.5) months and 72.2% required long-term glucocorticoids and/or immunosuppressive agents. Eight patients were treated by rituximab with a favorable response in 87.5% of cases.Lacrimal involvement is the most frequent ophthalmic manifestation of IgG4-RD and is frequently associated with extra-orbital manifestations. Despite initial favorable response to steroids, the long-term management of relapsing patients needs to be improved.
London, Jonathan; Martin, Antoine; Soussan, Michael; Badelon, Isabelle; Gille, Thomas; Uzunhan, Yurdagul; Giroux-Leprieur, Bénédicte; Warzocha, Ursula; Régent, Alexis; Galatoire, Olivier; Dhote, Robin; Abad, Sébastien
Adult onset asthma and periocular xanthogranuloma (AAPOX) is a rare non-Langerhans histiocytosis characterized histopathologically by a periocular infiltration of foamy histiocytes and Touton giant cells. Benign hyperplasia with plasma cell infiltration is classically described in eyelids or lymph nodes of AAPOX patients. It is also a characteristic feature of IgG4-related disease (IgG4-RD), a new entity defined by an IgG4-bearing plasma cell infiltration of organs.To determine if AAPOX syndrome shares clinical, biological, and histopathological characteristics with IgG4-RD, we used the comprehensive clinical diagnostic criteria for IgG4-RD in a retrospective case series of three consecutive patients with histologically-proven AAPOX. Patients who were diagnosed with AAPOX at a French academic referral center for orbital inflammation between November 1996 and March 2013 were enrolled. Biopsies from ocular adnexa or other organs were systematically reexamined. For each patient, clinical and serological data, radiologic findings, and treatment were retrospectively analyzed.Two AAPOX patients fulfilled all of the diagnostic criteria for a definite IgG4-RD. One patient who lacked the serological criteria fulfilled the criteria of a probable IgG4-RD.These 3 cases of AAPOX patients fulfilled the IgG4-RD comprehensive clinical diagnostic criteria. To our knowledge, this is the first observational case report study to clearly show a strong relationship between IgG4-RD and AAPOX syndrome.
Ohta, Miho; Moriyama, Masafumi; Maehara, Takashi; Gion, Yuka; Furukawa, Sachiko; Tanaka, Akihiko; Hayashida, Jun-Nosuke; Yamauchi, Masaki; Ishiguro, Noriko; Mikami, Yurie; Tsuboi, Hiroto; Iizuka-Koga, Mana; Kawano, Shintaro; Sato, Yasuharu; Kiyoshima, Tamotsu; Sumida, Takayuki; Nakamura, Seiji
IgG4-related disease (IgG4-RD) is a novel systemic disease entity characterized by elevated serum IgG4 and tissue infiltration of IgG4-positive plasma cells accompanied by severe fibrosis. Although recent studies demonstrated that innate immune cells including monocytes and macrophages might promote local fibrosis and IgG4 production, the pathological mechanism remains unclear. In this study, we sought to identify the disease-associated genes, especially innate immune molecules. Gene expression was analyzed by DNA microarray in submandibular glands (SMGs) from patients with IgG4-RD (n = 5), chronic sialoadenitis (CS) (n = 3), and controls (n = 3). Differentially expressed genes (DEGs) were validated by real-time polymerase chain reaction (PCR) and immunohistochemical staining in IgG4-RD (n = 18), CS (n = 4), Sjögren syndrome (n = 11), and controls (n = 10). Gene expression patterns in the 3 groups were quite different from each other by the pvclust method and principal components analysis. In IgG4-RD, 1028 upregulated genes and 692 downregulated genes were identified as DEGs (P < 0.05). Gene Ontology (GO) term analysis indicated that the upregulated DEGs in IgG4-RD encoded proteins involved in T/B cell activation and chemotaxis. PCR validated significantly higher expression of macrophage receptor with collagenous structure (MARCO), a pattern-recognition receptor, in IgG4-RD compared with the other groups (P < 0.01). Immunohistochemical analysis confirmed that the expression pattern of MARCO was similar to that of the M2 macrophage marker CD163. MARCO was identified as a disease-associated molecule in IgG4-RD by DNA microarray. Moreover, M2 macrophages might contribute to the initiation of IgG4-RD via MARCO.
Ohta, Miho; Moriyama, Masafumi; Maehara, Takashi; Gion, Yuka; Furukawa, Sachiko; Tanaka, Akihiko; Hayashida, Jun-Nosuke; Yamauchi, Masaki; Ishiguro, Noriko; Mikami, Yurie; Tsuboi, Hiroto; Iizuka-Koga, Mana; Kawano, Shintaro; Sato, Yasuharu; Kiyoshima, Tamotsu; Sumida, Takayuki; Nakamura, Seiji
Abstract IgG4-related disease (IgG4-RD) is a novel systemic disease entity characterized by elevated serum IgG4 and tissue infiltration of IgG4-positive plasma cells accompanied by severe fibrosis. Although recent studies demonstrated that innate immune cells including monocytes and macrophages might promote local fibrosis and IgG4 production, the pathological mechanism remains unclear. In this study, we sought to identify the disease-associated genes, especially innate immune molecules. Gene expression was analyzed by DNA microarray in submandibular glands (SMGs) from patients with IgG4-RD (n = 5), chronic sialoadenitis (CS) (n = 3), and controls (n = 3). Differentially expressed genes (DEGs) were validated by real-time polymerase chain reaction (PCR) and immunohistochemical staining in IgG4-RD (n = 18), CS (n = 4), Sjögren syndrome (n = 11), and controls (n = 10). Gene expression patterns in the 3 groups were quite different from each other by the pvclust method and principal components analysis. In IgG4-RD, 1028 upregulated genes and 692 downregulated genes were identified as DEGs (P < 0.05). Gene Ontology (GO) term analysis indicated that the upregulated DEGs in IgG4-RD encoded proteins involved in T/B cell activation and chemotaxis. PCR validated significantly higher expression of macrophage receptor with collagenous structure (MARCO), a pattern-recognition receptor, in IgG4-RD compared with the other groups (P < 0.01). Immunohistochemical analysis confirmed that the expression pattern of MARCO was similar to that of the M2 macrophage marker CD163. MARCO was identified as a disease-associated molecule in IgG4-RD by DNA microarray. Moreover, M2 macrophages might contribute to the initiation of IgG4-RD via MARCO. PMID:26886650
Zhang, Pingchuan; Cornell, Lynn D
Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is a fibroinflammatory disorder that can involve nearly any organ. The disorder has increasingly become known as a distinct clinical entity during the last decade. IgG4-related tubulointerstitial nephritis (IgG4-TIN) is the most common manifestation of IgG4-RD in the kidney. Many patients with IgG4-TIN are diagnosed after IgG4-RD has been recognized in other organ systems, but the kidney may also be the first or only site involved. The presenting clinical features of IgG4-TIN are most commonly kidney insufficiency, kidney mass lesion(s), or both. On biopsy, IgG4-TIN shows a dense lymphoplasmacytic infiltrate, increased IgG4+ plasma cells, storiform fibrosis, and often tubular basement membrane immune complex deposits. Elevation of serum IgG4 often accompanies IgG4-RD; however, it is not specific in reaching the diagnosis. Like IgG4-RD in other organs, IgG4-TIN characteristically responds promptly to steroids, although there is a high relapse rate on discontinuation of immunosuppression. The pathogenesis of IgG4-RD is not understood.
Furukawa, Sachiko; Moriyama, Masafumi; Miyake, Kensuke; Nakashima, Hitoshi; Tanaka, Akihiko; Maehara, Takashi; Iizuka-Koga, Mana; Tsuboi, Hiroto; Hayashida, Jun-Nosuke; Ishiguro, Noriko; Yamauchi, Masaki; Sumida, Takayuki; Nakamura, Seiji
IgG4-related disease (IgG4-RD) is characterized by elevated serum IgG4 and marked infiltration of IgG4-positive cells in multiple organs. Interleukin-33 (IL-33) is a recently described cytokine that is secreted by damaged epithelial cells, macrophages, and dendritic cells, and potently activates helper T type 2 (Th2) immune responses, which have been suggested to play a major role in IgG4 production of IgG4-RD. Here, we assessed the expression of IL-33 and related molecules in the salivary glands (SGs) of patients with IgG4-RD versus that in patients with Sjögren’s syndrome (SS) and controls. Expression of IL-33 and its receptor (ST2) was strongly detected around ectopic germinal centers (GCs) in the SGs from patients with IgG4-RD, whereas IL-33 was expressed only in epithelial cells in patients with SS and controls. Moreover, IL-33 and CD68+/CD163+ macrophages were mainly distributed around ectopic GCs in patients with IgG4-RD. Double immunofluorescence staining showed that IL-33 expression co-localized with CD68+/CD163+ macrophages. Finally, mRNA expression levels of IL-33 showed a positive correlation to those of Th2 cytokines (IL-4 and IL-13) in patients with IgG4-RD. Our data suggest that IL-33 produced by M2 macrophages might contribute to the pathogenesis of IgG4-RD via aberrant activation of Th2 immune responses. PMID:28205524
Grados, Aurélie; Ebbo, Mikael; Piperoglou, Christelle; Groh, Matthieu; Regent, Alexis; Samson, Maxime; Terrier, Benjamin; Loundou, Anderson; Morel, Nathalie; Audia, Sylvain; Maurier, François; Graveleau, Julie; Hamidou, Mohamed; Forestier, Amandine; Palat, Sylvain; Bernit, Emmanuelle; Bonotte, Bernard; Farnarier, Catherine; Harlé, Jean-Robert; Costedoat-Chalumeau, Nathalie; Vély, Frédéric; Schleinitz, Nicolas
IgG4-related disease (IgG4-RD) is a fibro-inflammatory disorder involving virtually every organ with a risk of organ dysfunction. Despite recent studies regarding B cell and T cell compartments, the disease’s pathophysiology remains poorly understood. We examined and characterized subsets of circulating lymphocytes in untreated patients with active IgG4-RD. Twenty-eight consecutive patients with biopsy-proven IgG4-RD were included in a prospective, multicentric study. Lymphocytes’ subsets were analyzed by flow cytometry, with analysis of TH1/TH2/TH17, TFH cells, and cytokine release by peripheral blood mononuclear cells. Results were compared to healthy controls and to patients with primary Sjögren’s syndrome. Patients with IgG4-RD showed an increase of circulating T regulatory, TH2, TH17, and CD4+CXCR5+PD1+ TFH cell subsets. Accordingly, increased levels of IL-10 and IL-4 were measured in IgG-RD patients. TFH increase was characterized by the specific expansion of TFH2 (CCR6−CXCR3−), and to a lesser extent of TFH17 (CCR6+CXCR3−) cells. Interestingly, CD4+CXCR5+PD1+ TFH cells normalized under treatment. IgG4-RD is characterized by a shift of circulating T cells toward a TH2/TFH2 and TH17/TFH17 polarization. This immunological imbalance might be implicated in the disease’s pathophysiology. Treatment regimens targeting such T cells warrant further evaluation. PMID:28348556
Szántó, Antónia; Szabó, Katalin; Nagy, Gábor; Molnár, Csaba; Zeher, Margit
Differential diagnosis of patients with Sjögren's syndrome (SS), IgG4-related disease (IgG4-RD) and SS patients having high risk for lymphoma (LHR) can be challenging. Some patients with IgG4-RD might be misdiagnosed as having SS. There are special symptoms of SS that raise the possibility of IgG4-RD whereas other symptoms identify patients as having LHR. The purpose of this study was to characterize and compare patients with SS, possible IgG4-RD and SS patients with LHR. Sixty-five SS patients were divided into 4 subgroups according to having possible IgG4-RD (n = 15), LHR (n = 16), eligible for both aforementioned groups (n = 20) and not eligible for either group (n = 14), respectively. Four patients fulfilled the diagnostic criteria for IgG4-RD. The serum levels of IgG4 were significantly higher in patients suspicious for IgG4-RD compared to that of LHR patients (0.46 g/l vs. 0.12 g/l, p = 0.032). Shared features of the patient groups (salivary gland swelling (SGS) and lymphadenopathy), were separately analysed: SGS patients had higher IgG4/IgG ratio (p = 0.036), lymphadenopathic patients had higher IgG4 levels (p = 0.042). Some patients may be "hidden" under the diagnosis of SS. Although patients with LHR and patients with possible IgG4-RD share some symptoms, they differ significantly regarding IgG4 levels and IgG4/IgG ratio.
Yamamoto, Hiroshi; Suzuki, Toshiro; Yasuo, Masanori; Kobayashi, Orie; Tsushima, Kenji; Ito, Michiko; Urushihata, Kazuhisa; Yamazaki, Yoshitaka; Hanaoka, Masayuki; Koizumi, Tomonobu; Uehara, Takeshi; Kawakami, Satoshi; Hamano, Hideaki; Kawa, Shigeyuki; Kubo, Keishi
A 78-year-old man with cryptogenic chronic bilateral lymphoplasmacytic pleuritis, diagnosed based on left parietal pleural biopsy specimens obtained by pleuroscopy, developed acute left bacterial pleuritis. The left pleural effusion was neutrophil dominant, however, the right pleural effusion showed lymphoplasmacytic infiltration. Laboratory examinations revealed that his serum IgG4 concentration was increased, with a higher level of IgG4 in the right pleural effusion. Re-evaluation of the previous biopsy specimens using an immunostaining method revealed numerous IgG4-positive plasma cell infiltrations with IgG4-positive/IgG-positive plasma cells at 85.4%. Accordingly, the new diagnosis of this patient was considered to be chronic bilateral IgG4-related pleuritis.
Wang, Q; Ping, F Y; Pan, H B
IgG4-related disease is a novel clinical entity which can affect single or multiple organs. IgG4-related sialadenitis is referred to the salivary gland involvement of IgG4-related disease, with or without other organ involvement. IgG4-related sialadenitis is characterized by painless swelling or enlargement of salivary glands, high serum IgG4 level, abundant IgG4+ plasma cells infiltration with fibrosis histologically, and good response to glucocorticoids. With review of related articles, highlight and provide an overview of the most recent and focused findings and concepts of this disease, including the most significant pathogenic process based on kinds of immunocytes, cytokines, as well as participation of epithelial-mesenchymal transition, the clinical value of elevated serum IgG4 concentration and pathological role of infiltrated IgG4+ plasma cells, the potential relationship with salivary gland malignant tumor, the applying and usefulness of positron emission tomography-CT, the diagnostic utility of lip biopsy, treatment, prognosis, and also future perspectives.
Hara, Satoshi; Kawano, Mitsuhiro; Mizushima, Ichiro; Yamada, Kazunori; Fujita, Kentaro; Harada, Kenichi; Matsumura, Masami; Yamagishi, Masakazu; Sato, Yasuharu; Yamaguchi, Yutaka; Nakanuma, Yasuni; Nagata, Michio
We describe a 74-year-old Japanese man with systemic fibroinflammatory conditions closely resembling those of immunoglobulin G4-related disease (IgG4-RD). Radiology and histology showed characteristics of IgG4-related tubulointerstitial nephritis, despite normal serum IgG4 value and scanty IgG4-positive plasma cell infiltration in each organ. This case suggests that a condition closely mimicking IgG4-RD may develop without IgG4-positive plasma cells and those exceptional cases should also be taken into account in the differential diagnosis of IgG4-RD.
Rodriguez, Eduardo A.; Williams, Frederick K.
Patient:Female, 55 Final Diagnosis: Autoimmune pancreatitis Symptoms: Abdominal pain • weight loss Medication: Prednisone Clinical Procedure: Admitted to the hospital Specialty: Gastroenterology and Hepatology Objective: Challenging differential diagnosis Background: Autoimmune pancreatitis is an IgG4-related fibroinflammatory condition often associated with obstructive jaundice, as most lesions are located at the head of the pancreas. IgG4 level can help in the diagnosis, but it is normal in nearly 30% of affected patients. Case Report: A 55-year-old woman presented with a 5-month history of 20-pound unintentional weight loss and intermittent abdominal pain. She had an unremarkable abdominal exam and significant findings included a small, non-mobile rubbery left axillary lymph node. Complete blood count, complete metabolic panel, amylase, anti-smooth muscle antibody, antimitochondrial antibody, carcinoembryonic antigen, Ca 19-9, complement C3 and C4, antinuclear antibody, anti-Smith double-strand antibody, and IgG4 were all within normal limits. CT of the abdomen showed a mass in the junction of the body and tail of the pancreas and endoscopic ultrasound showed it as encasing the splenic artery. Fine-needle aspiration cytology demonstrated follicular hyperplasia, obliterative phlebitis, storiform fibrosis, and negative staining for IgG4 and malignancy. Left axillary lymph node biopsy demonstrated follicular hyperplasia. PET scan revealed hypermetabolic uptake of the pancreas tail, bone marrow, and spleen, as well as diffuse lymphadenopathy. Bone marrow biopsy showed follicular hyperplasia and was negative for malignancy. The patient was started on 40 mg of oral prednisone for possible autoimmune disease. During follow-up, she reported progressive improvement and a repeat PET scan 6 months later showed marked improvement. Conclusions: A normal IgG4 value should not decrease the clinical suspicion of IgG4-related disease. If clinical, histological, and
Bernreuther, Christian; Illies, Christopher; Flitsch, Jörg; Buchfelder, Michael; Buslei, Rolf; Glatzel, Markus; Saeger, Wolfgang
IgG4-related disease is an immune-mediated disease with manifestations in most organ systems among them the pituitary gland. To date, few cases of histologically confirmed cases of IgG-related hypophysitis have been reported. The aim of this study was to retrospectively determine the prevalence of IgG4-related hypophysitis among cases previously diagnosed as primary hypophysitis (lymphocytic hypophysitis, granulomatous hypophysitis and hypophysitis not otherwise specified). Histological and immunohistochemical analysis revealed that 12 of 29 cases (41.4%) previously diagnosed as primary hypophysitis fulfilled the criteria for IgG4-related disease and, thus, IgG4-related hypophysitis should always be considered in the differential diagnosis of primary hypophysitis. All cases of IgG4-related hypophysitis showed a dense lymphoplasmacytic infiltrate with more than 10 IgG4-positive cells per high power field and a ratio of IgG4/IgG-positive cells of more than 40%, whereas storiform fibrosis was an inconsistent histological feature and was also seen in few cases of non-IgG-related hypophysitis, thus lacking sensitivity and specificity. Obliterative phlebitis was not seen in any case. Thus, histological criteria defined for IgG4-related disease in other organs should be modified for IgG4-related hypophysitis, accordingly.
Rotondo, Fabio; Qaddoura, Amro; Syro, Luis V; Karamchandani, Jason; Munoz, David G; Arroyave, Mariam J; Ospina, William P; Cusimano, Michael D; Kovacs, Kalman
We report two different cases of IgG4-related hypophysitis. In the first case, a pituitary lesion was accompanied by lymphocytic meningitis possibly mimicking tuberculous meningitis. The second case was unassociated with involvement of other organs. No histologic differences were noted between the two cases indicating that the morphologic features of the hypophysial lesion do not depend on the presence of other lesions. The pathogenesis of IgG4 hypophysitis is not known, and further study is necessary to explore the cause, progression, and influencing factors of this disease.
Feely, Michael M; Gonzalo, David H; Corbera, Montserrat; Hughes, Steven J; Trevino, Jose G
An increased awareness of IgG4-related diseases has led to an escalation in the number of sites known to be involved by this fibroinflammatory disease. We report three cases of IgG4-related cholecystitis which were thought to represent biliary malignancies both clinically and radiographically. All three cases underwent surgery tailored towards presumed malignant neoplasms. Only following pathologic examination was the true nature of the disease identified. Recognition of the clinical, radiographic, and pathologic presentation of IgG4-related cholecystitis is essential for the consideration of this disease process prior to surgical management for suspected gallbladder malignancies. However, the pre-operative diagnosis remains challenging and extensive surgical intervention is often necessary given the distressing presentation of IgG4-related cholecystitis.
Kase, Satoru; Noda, Mika; Ishijima, Kan; Yamamoto, Teppei; Hatanaka, Kanako; Ishida, Susumu
Immunoglobulin (IgG) 4-related disease is characterized by elevated serum IgG4 and tissue infiltration by IgG4-positive plasma cells. We report a case of IgG4-related inflammation of the orbit simulating extranodal marginal zone B-cell lymphoma (EMZL). A 72-year-old female complained of bilateral eyelid swelling for three years. A MRI scan demonstrated two kinds of lesions, tumor 1, presenting with a predominantly low density, and tumor 2, of relatively high density. Laboratory tests showed high serum IgG4 concentrations, measuring 991 mg/dl. Partial resection of each tumor was conducted in September 2011. Based on the clinicopathological findings, tumors 1 and 2 were diagnosed as IgG4-related inflammation and EMZL, respectively. The patient initially received oral prednisolone at 30 mg/per day, followed by irradiation with a total dosage of 30 Gy to both eyes. The bilateral tumors consequently diminished, and she is currently well with no recurrence or systemic involvement. In conclusion, EMZL can arise from massive IgG4-related orbital inflammation. Since IgG4-related inflammation can represent multiple nodular lesions, biopsies from multiple sites within the lesion are required to make a correct diagnosis in selected cases. Oral prednisolone combined with radiotherapy is an effective treatment for patients with IgG4-related ophthalmic disease simulating EMZL.
Culver, Emma L; Vermeulen, Ellen; Makuch, Mateusz; van Leeuwen, Astrid; Sadler, Ross; Cargill, Tamsin; Klenerman, Paul; Aalberse, Rob C; van Ham, S Marieke; Barnes, Eleanor; Rispens, Theo
Background IgG4-related disease (IgG4-RD) is a systemic fibroinflammatory condition, characterised by an elevated serum IgG4 concentration and abundant IgG4-positive plasma cells in the involved organs. An important question is whether the elevated IgG4 response is causal or a reflection of immune-regulatory mechanisms of the disease. Objectives To investigate if the IgG4 response in IgG4-RD represents a generalised polyclonal amplification by examining the response to common environmental antigens. Methods Serum from 24 patients with IgG4-RD (14 treatment-naive, 10 treatment-experienced), 9 patients with primary sclerosing cholangitis and an elevated serum IgG4 (PSC-high IgG4), and 18 healthy controls were tested against egg white and yolk, milk, banana, cat, peanut, rice and wheat antigens by radioimmunoassay. Results We demonstrated an elevated polyclonal IgG4 response to multiple antigens in patients with IgG4-RD and in PSC-high IgG4, compared with healthy controls. There was a strong correlation between serum IgG4 and antigen-specific responses. Responses to antigens were higher in treatment-naive compared with treatment-experienced patients with IgG4-RD. Serum electrophoresis and immunofixation demonstrated polyclonality. Conclusions This is the first study to show enhanced levels of polyclonal IgG4 to multiple antigens in IgG4-RD. This supports that elevated IgG4 levels reflect an aberrant immunological regulation of the overall IgG4 response, but does not exclude that causality of disease could be antigen-driven. PMID:25646372
Kasashima, Satomi; Zen, Yoh; Kawashima, Atsuhiro; Konishi, Keiko; Sasaki, Hisao; Endo, Masamitsu; Matsumoto, Yasushi; Kawakami, Kengo; Kasashima, Fuminori; Moriya, Makio; Kimura, Keiichi; Ohtake, Hiroshi; Nakanuma, Yasuni
Inflammatory abdominal aortic aneurysm (AAA) is a member of a family of disorders referred to as "chronic periaortitis" together with retroperitoneal fibrosis. Retroperitoneal fibrosis is included in IgG4-related disease, which is characterized by numerous infiltrating IgG4-positive plasma cells and high serum IgG4 concentrations. However, the relationship between IgG4-related disease and inflammatory AAA has not been documented. In this study, we examined the clinicopathologic characteristics of inflammatory (10 cases) and atherosclerotic (22 cases) AAAs, based on the hypothesis that inflammatory AAA might be related to IgG4-related disease. Cases of inflammatory AAA could be classified into 2 groups based on immunostaining of IgG4. Four patients showed diffuse infiltration of abundant IgG4-positive plasma cells (IgG4-related cases), whereas the remaining 6 cases of inflammatory AAA and all cases of atherosclerotic AAA had only a few IgG4-positive plasma cells (non-IgG4-related cases). IgG4-related inflammatory AAA was pathologically characterized by the frequent infiltration of eosinophils, lymph follicle formation, perineural inflammatory extension, and inconspicuous infiltration of neutrophils compared with non-IgG4-related inflammatory AAA. Obliterative phlebitis, which is venous occlusion with inflammatory cell infiltration, is observed in all IgG4-related cases. In addition, serum IgG4 concentrations were significantly higher in IgG4-related inflammatory AAA (109 to 559 mg/dL, normal range: 4 to 110 mg/dL) than non-IgG4-related inflammatory AAA (32 to 59 mg/dL) and all atherosclerotic AAA (12 to 83 mg/dL). In conclusion, inflammatory AAAs might be classified into 2 groups: IgG4-related or nonrelated. The former might be one of the IgG4-related diseases, and could be included in IgG4-related periaortitis together with retroperitoneal fibrosis.
Inoue, Tadahisa; Okumura, Fumihiro; Mizushima, Takashi; Nishie, Hirotada; Iwasaki, Hiroyasu; Anbe, Kaiki; Ozeki, Takanori; Kachi, Kenta; Fukusada, Shigeki; Suzuki, Yuta; Watanabe, Kazuko; Sano, Hitoshi
We encountered a case of localized IgG4-cholecystitis mimicking gallbladder cancer with focal/segmental type1 autoimmune pancreatitis (AIP). In this case, we were unable to exclude a diagnosis of gallbladder cancer and thus performed radical cholecystectomy. Type1 AIP is often associated with gallbladder lesions, accompanied by generally diffuse, circumferential thickening of the gallbladder wall. Although localized IgG4-related cholecystitis is extremely rare, differentiating this condition from gallbladder cancer is often very difficult.
Ishida, Mitsuaki; Hodohara, Keiko; Furuya, Aya; Fujishiro, Aya; Okuno, Hiroko; Yoshii, Miyuki; Horinouchi, Akiko; Shirakawa, Ayaka; Harada, Ayumi; Iwai, Muneo; Yoshida, Keiko; Kagotani, Akiko; Yoshida, Takashi; Okabe, Hidetoshi
IgG4-related sclerosing disease is an established disease entity with characteristic clinicopathological features. Some recent reports have demonstrated that this disease can occur in the respiratory system including the pleura. Herein, we describe the first documented case of concomitant occurrence of IgG4-related pleuritis and periaortitis. A 71-year-old Japanese female with a history of essential thrombocythemia presented with persistent cough and difficulty in breathing. Computed tomography demonstrated thickening of the right parietal pleura, pericardium, and periaortic tissue and pleural and cardiac effusions. Histopathological study of the surgical biopsy specimen of the parietal pleura revealed marked fibrous thickening with lymphoplasmacytic infiltration. Phlebitis was noted, however, only a few eosinophils had infiltrated. Immunohistochemical study revealed abundant IgG4-positive plasma cell infiltration and high ratio of IgG4-/IgG-positive plasma cells (84%). Therefore, a diagnosis of IgG4-related pleuritis was made with consideration of the elevated serum IgG4 level (684 mg/dL). Recently, the spectrum of IgG4-related sclerosing disease has expanded, and this disease can occur in the pleura, pericardium, and periaortic tissue. Although histopathological analysis of the pericardium and periaortic tissue was not performed in the present case, it was suspected that thickening of the pericardium and periaortic tissue was clinically due to IgG4-related sclerosing disease. Our clinicopathological analyses of IgG4-related pleuritis and pericarditis reveal that this disease can present as dyspnea and pleural and pericardial effusion as seen in the present case, therefore, it is important to recognize that IgG4-related sclerosing disease can occur in these organs for accurate diagnosis and treatment.
Cai, Y I; Li, Han-Zhong; Zhang, Yu-Shi
IgG4-related disease is a recently recognized clinical entity. It is characterized by diffuse organ swelling or mass formation, a dense lymphoplasmacytic infiltrate rich in IgG4-positive plasma cells with fibrosis and typically an increased serum IgG4 concentration, which may affect various organs. An 80-year-old woman with an otherwise unremarkable previous medical history was revealed to have a renal mass that was indicative of renal malignant carcinoma, for which a radical nephrectomy was performed. The mass was diagnosed as an IgG4-related inflammatory pseudotumor, which was histopathologically confirmed. The patient is currently well without evidence of IgG4-related disease at 3 months post-surgery, and did not require any additional therapy.
Bélissant, Ophélie; Guernou, Mohamed; Rouvier, Philippe; Compain, Caroline; Bonardel, Gérald
A 17-year-old adolescent girl was admitted with chronic arthralgia, Raynaud phenomenon, pericarditis, and evidences of chronic diffuse inflammation. F-FDG PET/CT scan was performed to search systemic vasculitis and showed diffuse moderate uptake in the kidneys. We suggested the existence of a nephritis, but the ultrasonography result was normal, and no treatment was introduced. Another F-FDG PET/CT scan was performed 7 months later to explore abdominal pain. It showed again diffuse intense uptake in both kidneys. A proteinuria was highlighted, and renal biopsy allowed to diagnose IgG4-related disease.
Ohshima, Koh-Ichi; Sato, Yasuharu; Yoshino, Tadashi
There are no reports on the effect of anti-allergic agents against IgG4-related disease. We herein report a case of IgG4-related dacryoadenitis that is believed to have regressed due to the administration of anti-allergic agents. A 57-year-old woman consulted us because of bilateral temporal upper eyelid swelling and induration. She had also been suffering from allergic rhinitis and allergic conjunctivitis for 20 years. We performed an incisional biopsy of the lesion. With respect to the pathology, extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue type was strongly suspected. On obtaining consent from the patient, follow-up alone was to be continued without radiation therapy. In addition to the observation of lacrimal gland lesions, the administration of epinastine hydrochloride at a dosage of 20 mg/day and 0.01% betamethasone eye drops twice a day to both eyes was commenced in order to treat both allergic rhinitis and allergic conjunctivitis. The lacrimal gland lesion decreased in size over time, becoming predominantly normal 7 years after the commencement of agent administration. We therefore re-examined the blood and pathology specimens. As a result, the serum IgG4 level was found to have increased to 540 mg/dl, while IgG4/IgG was 36.2%. The pathological diagnosis was revised to IgG4-related dacryoadenitis. The hypotheses of spontaneous remission and/or the effect of epinastine hydrochloride administration can be proposed regarding the mechanism by which the lacrimal gland lesion decreased in size. [J Clin Exp Hematop 53(1): 53-56, 2013].
unnecessary tests and procedures. 2. Case Presentation A 28-year-old female with no significant past medical history presented to her primary care...removed, again without an obvious etiology. Rheumatology was then consulted and expanded the differential to include systemic lupus erythematosus...count on cytometry Mycobacterial infection AFB culture of lymph node (negative) Systemic lupus erythematosus ANA panel (1 : 160) Anti-dsDNA and anti
Although now considered to be a member of the systemic entity of immunoglobulin G4- (IgG4-) related disease, IgG4-related pancreatitis is generally referred to as type 1 autoimmune pancreatitis (AIP). Type 1 AIP was established based on a pathological background of lymphoplasmacytic sclerosing pancreatitis, high serum IgG4 concentration, and abundant IgG4-bearing plasma cell infiltration. The characteristic clinical features of type 1 AIP, such as elderly male preponderance, obstructive jaundice, and mass-forming lesions in the pancreas, often mimic those of pancreatic cancer. However, because AIP responds favorably to corticosteroid treatment, careful differentiation from pancreatic cancer is required. An AIP diagnosis is currently based on the 2011 International Consensus Diagnostic Criteria for AIP, which are based on high sensitivity, selectivity, and accuracy. Over the long term, AIP can progress to a chronic condition, with pancreatic stone formation and atrophy resembling that of chronic pancreatitis. Although AIP has been linked to the complication of malignancies, it remains controversial whether an association exists between the disease and tumor formation.
Fragoulis, G E; Zampeli, E; Moutsopoulos, H M
IgG4-related disease (IgG4-RD) has emerged as a new entity in the last decade. It comprises numerous conditions previously thought to be unrelated. Macroscopically, these diseases cause diffuse organ swelling and formation of pseudotumorous masses. Histopathologically, they are characterized by a lymphoplasmacytic infiltrate with increased IgG4+ plasma cells and storiform fibrosis. Despite rapid progress within the last years, our knowledge on these conditions is still fragmented. To date, more than forty organs have been reported to be included in IgG4-RD, and salivary gland involvement is amongst the most common organs affected [IgG4-related sialadenitis (IgG4-RS)]. Interestingly, IgG4-RS shares commonalities with Sjögren's syndrome (SS), like glandular enlargement, sicca symptoms, arthralgias, hypergammaglobulinemia, hypocomplementemia, and circulating antinuclear antibodies. Nonetheless, they differ in that the incidence of anti-Ro and anti-La reactivity is not frequently found in patients with IgG4-RS, their salivary glands are infiltrated by a large number of IgG4+ plasma cells and IgG4-RS symptoms respond promptly to steroids. The aim of this review was to describe the clinical, serological, histopathological and pathophysiological aspects of IgG4-RS in the context of IgG4-RD and highlight the differences between IgG4-RS and SS.
Ramasamy, Vijaya B P; Trefor, Rhiannon; Rajamani, Kaushik; Santosh, Divya; Griffiths, David; Donovan, Kieron
Immunoglobulin G4-related disease (IgG4-RD) is a systemic inflammatory condition that may involve any organ in the body, including the kidneys. However, renal parenchymal lesions are not seen frequently and the treatment strategy remains unclear. We describe a case of IgG4-related renal mass, which resolved spontaneously. The patient presented with right loin pain, constitutional symptoms and raised inflammatory markers. Magnetic resonance imaging (MRI) showed a large infiltrative mass centered on the right renal hilum and biopsy demonstrated histological changes in keeping with IgG4-RD. A careful 'watch-and-wait' approach was taken and at six months following initial presentation, the patient's symptoms had fully resolved and inflammatory markers had normalised. Repeat MRI showed almost complete resolution of the mass. We propose that a careful 'watch-and-wait' approach could be considered as an alternative to immune suppression for IgG4-related renal masses, especially if they are not causing symptoms or organ compromise.
Harano, Yumi; Honda, Kazufumi; Akiyama, Yurika; Kotajima, Lisa; Arioka, Hiroko
Immunoglobulin (Ig) G4-related systemic syndrome is a recently described entity characterized by elevated serum IgG4 and tissue infiltration of IgG4-positive plasma cells. Pituitary gland can be involved as hypophysitis. We report a case of a 72-year-old man, who presented with general fatigue and weakness. Laboratory tests revealed diabetes insipidus as well as hypopituitarism including adrenal insufficiency, hypogonadism, and hypothyroidism. His serum IgG4 was elevated. MR images showed enlargement of the pituitary stalk. Multiple nodules in bilateral kidneys were pointed out in the abdominal CT. Histological examination of the nodules showed increased IgG4-positive plasma cells. We diagnosed him with IgG4-related kidney disease and hypophysitis. After treatment with hydrocortisone, his symptoms improved. The follow-up images showed that almost all renal nodules disap-peared and his pituitary stalk was shrinking. Our case appears to be very sensitive to glucocorticoid and suggests the possibility of treating IgG4-related hypophysitis successfully with a lower dose of glucocorticoid.
Hasosah, Mohammed Y.; Satti, Mohamed B.; Yousef, Yasmin A.; Alzahrani, Daifullah M.; Almutairi, Sajdi A.; Alsahafi, Ashraf F.; Sukkar, Ghassan A.; Alzaben, Abdullah A.
Sclerosing mesenteritis (SM) is a rare, benign inflammatory disorder of unknown etiology, affecting the membranes of the digestive tract that involves lymphoplasmacytic inflammation, fat necrosis, and fibrosis of the mesentery. We report a child patient with a history of recurrent abdominal pain and fever who was found to have an intra-abdominal mass suspicious for malignancy. A tissue biopsy revealed the diagnosis of SM associated with IgG4-related systemic disease. The patient is currently maintained on 5 mg prednisone daily and no recurrence of symptoms was noted during the 24-month follow-up period. We emphasize, therefore, that SM can present clinical challenges and the presence of SM should cue clinicians to search for other coexisting autoimmune disorders that can have various outcomes. PMID:25434322
Ishida, Mitsuaki; Hodohara, Keiko; Yoshida, Keiko; Kagotani, Akiko; Iwai, Muneo; Yoshii, Miyuki; Okuno, Hiroko; Horinouchi, Akiko; Nakanishi, Ryota; Harada, Ayumi; Yoshida, Takashi; Okabe, Hidetoshi
IgG4-related sclerosing disease is an established disease entity with characteristic clinicopathological features. Recently, the association between IgG4-related sclerosing disease and the risk of malignancies has been suggested. IgG4-related autoimmune pancreatitis with pancreatic cancer has been reported. Further, a few cases of extraocular malignant lymphoma in patients with IgG4-related sclerosing disease have also been documented. Herein, we describe the first documented case of anaplastic large cell lymphoma (ALCL) following IgG4-related autoimmune pancreatitis and cholecystitis and diffuse large B-cell lymphoma (DLBCL). A 61-year-old Japanese male, with a past history of DLBCL, was detected with swelling of the pancreas and tumorous lesions in the gallbladder. Histopathological study of the resected gallbladder specimen revealed diffuse lymphoplasmacytic infiltration with fibrosclerosis in the entire gallbladder wall. Eosinophilic infiltration and obliterative phlebitis were also noted. Immunohistochemically, many IgG4-positive plasma cells had infiltrated into the lesion, and the ratio of IgG4/IgG-positive plasma cells was 71.6%. Accordingly, a diagnosis of IgG4-related cholecystitis was made. Seven months later, he presented with a painful tumor in his left parotid gland. Histopathological study demonstrated diffuse or cohesive sheet-like proliferation of large-sized lymphoid cells with rich slightly eosinophilic cytoplasm and irregular-shaped large nuclei. These lymphoid cells were positive for CD30, CD4, and cytotoxic markers, but negative for CD3 and ALK. Therefore, a diagnosis of ALK-negative ALCL was made. It has been suggested that the incidence of malignant lymphoma may be high in patients with IgG4-related sclerosing disease, therefore, intense medical follow-up is important in patients with this disorder.
Decker, Lauren; Crawford, Angela M; Lorenzo, Gamaliel; Stippler, Martina; Konstantinov, Konstantin N; SantaCruz, Karen
IgG4-related hypophysitis is a rare, inflammatory process of the pituitary that mimics more commonly seen pituitary tumors. We report a case of IgG4-related hypophysitis in a 16-year-old female with diabetes insipidus who was found to have IgG4-related hypophysitis based on tissue diagnosis. This entity has not been previously described in a pediatric patient. Recognition of certain inflammatory processes of the pituitary may lead to alternative means of diagnosis and medical management without a biopsy.
Decker, Lauren; Crawford, Angela M; Lorenzo, Gamaliel; Stippler, Martina; Konstantinov, Konstantin N
IgG4-related hypophysitis is a rare, inflammatory process of the pituitary that mimics more commonly seen pituitary tumors. We report a case of IgG4-related hypophysitis in a 16-year-old female with diabetes insipidus who was found to have IgG4-related hypophysitis based on tissue diagnosis. This entity has not been previously described in a pediatric patient. Recognition of certain inflammatory processes of the pituitary may lead to alternative means of diagnosis and medical management without a biopsy. PMID:28083451
Ota, Masao; Umemura, Takeji; Kawa, Shigeyuki
Autoimmune pancreatitis (AIP) is a unique form of chronic pancreatitis characterized by high serum IgG4 concentration and a variety of complicating extra-pancreatic lesions. AIP has the features of a complex disease that is caused by multifactorial genes. However, the genetic factors underlying AIP have not been elucidated conclusively. Association studies by the candidate-gene approach and genome-wide association studies (GWAS) have revealed several susceptibility genes for AIP, including HLA DRB1*04:05-DQB1*04:01, FCRL3, CTLA4, and KCNA3, albeit in small-scale analyses. Thus, GWAS of large sample sizes and multinational collaborative meta-analyses are needed to identify the precise genetic variants that are associated with AIP onset. Systems genetics approaches that integrate DNA sequencing, expression quantitative trait locus (eQTL) mapping, proteomics, and metabolomics will also be useful in clarifying the pathogenesis of AIP.
Seki, Nobuhiko; Yamazaki, Norikazu; Koizumi, Jun-ichi; Takano, Ken-ichi; Abe, Ayumi; Ikeda, Tatsuru; Noguchi, Hiroko; Himi, Tetsuo
Progressively transformed germinal centers (PTGC), a lymph node process unfamiliar to most otolaryngologists, is a morphological variant of reactive lymphofollicular hyperplasia of lymph nodes. Immunoglobulin (Ig)G4-related disease (IgG4-RD) is a newly identified condition, characterized by hyper-IgG4-γ-globulinemia and mass-forming or hypertrophic lesions associated with infiltration of IgG4(+) plasma cells in the affected organs. Recently, a case study of PTGC was reported that fulfilled the diagnostic criteria of IgG4-RD (IgG4(+) PTGC) . A 68-year-old male was referred to our hospital with swelling in the left submandibular region. Palpation revealed swollen lymph nodes, the largest of which measured 5cm in diameter. (18)F-fluorodeoxyglucose (FDG)-positron emission tomography/computed tomography identified lymphadenopathy with high (18)F-FDG uptake in the left submandibular region. We strongly suspected malignant lymphoma, and excisional biopsy of the submandibular lymph node was performed under general anesthesia. Pathological findings were consistent with IgG4(+) PTGC, and serological examination demonstrated elevated levels of IgG4. These findings were consistent with IgG4-RD. The patient did not have systemic lesions; therefore, he has not undergone corticosteroid therapy. IgG4(+) PTGC should be considered as a differential diagnosis for cervical lymphadenopathy by otolaryngologists as well as pathologists.
Shin, Sang-Wook; Kim, Yongsoo; Jeong, Woo Kyoung; Kim, Jinoo; Kim, Min Yeong; Oh, Young Ha; Pyo, Ju Yeon
A 58-year-old man with right upper quadrant pain was referred to the radiology department. The patient underwent computed tomography and magnetic resonance imaging, which suggested the diagnosis of gallbladder cancer invading the liver. After surgical removal of the gallbladder, and the adjacent liver parenchyma was performed, the histologic diagnosis of IgG4-related cholecystitis was made.
Fukuhara, Takataro; Tomiyama, Takashi; Yasuda, Kaneki; Ueda, Yoshihiro; Ozaki, Yoshio; Son, Yonsu; Nomura, Shosaku; Uchida, Kazushige; Okazaki, Kazuichi; Kinashi, Tatsuo
The serine/threonine kinase Mst1 plays important roles in the control of immune cell trafficking, proliferation, and differentiation. Previously, we reported that Mst1 was required for thymocyte selection and regulatory T-cell functions, thereby the prevention of autoimmunity in mice. In humans, MST1 null mutations cause T-cell immunodeficiency and hypergammaglobulinemia with autoantibody production. RASSF5C(RAPL) is an activator of MST1 and it is frequently methylated in some tumors. Herein, we investigated methylation of the promoter regions of MST1 and RASSF5C(RAPL) in leukocytes from patients with IgG4-related autoimmune pancreatitis (AIP) and rheumatoid arthritis (RA). Increased number of CpG methylation in the 5′ region of MST1 was detected in AIP patients with extrapancreatic lesions, whereas AIP patients without extrapancreatic lesions were similar to controls. In RA patients, we detected a slight increased CpG methylation in MST1, although the overall number of methylation sites was lower than that of AIP patients with extrapancreatic lesions. There were no significant changes of the methylation levels of the CpG islands in the 5′ region of RASSF5C(RAPL) in leukocytes from AIP and RA patients. Consistently, we found a significantly down-regulated expression of MST1 in regulatory T cells of AIP patients. Our results suggest that the decreased expression of MST1 in regulatory T cells due to hypermethylation of the promoter contributes to the pathogenesis of IgG4-related AIP. - Highlights: • Mst1 controls immune cells trafficking, cell proliferation and differentiation. • Autoimmune pancreatitis (AIP) is an idiopathic pancreatitis affecting multiple organs. • Decreased MST1 expression and increased CpG methylation of promoter of MST1 in AIP. • Slight increased CpG methylation of MST1 in rheumatoid arthritis patients. • MST1 contributes pathogenesis of IgG4-related AIP.
Bhagat, Priyanka; Bal, Amanjit; Das, Ashim; Singh, Navneet; Singh, Harkant
IgG4-related inflammatory pseudotumor (IPT) and inflammatory myofibroblastic tumor (IMT) share morphological features like a prominent fibroblastic/myofibroblastic proliferation and the presence of inflammatory cells. Since IPT is managed conservatively and IMT is treated by surgical excision, it is important to differentiate these two lesions. The aim of this study is to highlight morphological and immunohistochemical features that distinguish IPT and IMT. Clinicopathological characteristics of cases diagnosed as pulmonary IPT or IMT from 1997 to 2013 were reviewed. The histological features were studied on hematoxylin and eosin-stained sections. Immunohistochemistry was done for IgG, IgG4, ALK-1, SMA, desmin, and CD34 for classification into IPT and IMT. Of the ten patients, seven were male and the age ranged from 4 to 58 years. The tumor size ranged from 1.5 to 4.0 cm in diameter. Histologically, proliferation of bland-looking spindle cells along with fibrosis and an inflammatory infiltrate comprising of lymphocytes and plasma cells were the common morphological features of both lesions. The spindle cell proliferation was more marked in IMT whereas lymphoplasmacytic infiltrate was more prominent in IPT. Obstructive phlebitis was observed only in cases of IPT. IgG4 expression was noted in IPT, and the number of IgG4-positive plasma cells and the ratio of IgG4+/IgG+ plasma cells were significantly lower in IMT than in IgG4-related IPT. Expression of anaplastic lymphoma kinase (ALK) was observed only in IMT, but not in IgG4-related IPT. The proportion of proliferating spindle cells, lymphoplasmacytic infiltrate, obstructive phlebitis, IgG4+ plasma cells and the ratio of IgG4+/IgG+ plasma cells, and ALK expression are helpful in differentiating these morphologically similar but biologically different lesions, which require different treatment modalities.
Hashimoto's thyroiditis emerges in patients who have genetic preponderance such as SNPs of CTLA-4 and risk factors such as excess intake of iodine, pregnancy or postpartum period, and smoking. Such risk factors also affect the entire clinical course. One of the major outcomes in Hashimoto's thyroiditis appears to be increased in cardio-vascular risks through subclinical hypothyroidism and concomitant metabolic syndrome, but in most cases, treatment with L-T4 has little effects on cardio-vascular benefit or quality of life. The pregnant women also have risks for obstetric complications and postpartum thyroid dysfunction. The women who have anti-TPO antibodies, type 1 diabetes, or previous history of post-partum thyroid dysfunction are recommended to be measured their TSH. It is noteworthy that Hashimoto's thyroiditis is sometimes complicated with encephalopathy, papillary carcinoma, or IgG4-related thyroiditis. IgG4-related thyroiditis is partly similar but partly discerned from a variant of Hashimoto's thyroiditis. The pathogenetic roles of this variant on autoimmune-based thyroiditis remain unclear.
Chougule, Abhijit; Bal, Amanjit; Das, Ashim; Agarwal, Ritesh; Singh, Navneet; Rao, Katragadda L N
IgG4-related disease is a recently recognized systemic condition characterized by tumefactive lesions at various sites. Inflammatory pseudotumor (IPT), a tumefactive mass lesion with an unknown etiology, belongs to the spectrum of IgG4-related disease. Inflammatory myofibroblastic tumor (IMT), previously considered under the umbrella of IPT, is now classified as a clonal neoplasm. Previously, both the terms were used interchangeably, because of overlapping morphologic features. This study was carried out to compare the morphologic and the immunohistochemical features of these entities and to study the role of IgG4 in their pathogenesis. Thirty-nine cases comprising of IMT (n=18) and IPT (n=21) were retrieved, and their clinical, morphologic, and immunohistochemical features were studied. IMT was more common in children as compared with IPT. IMT cases showed the proliferation of myofibroblastic cells accompanied by a variable inflammatory infiltrate, whereas IPT cases showed predominantly stromal fibrosis and a lymphoplasmacytic infiltrate with a subset of cases showing a storiform fibrosis and obliterative phlebitis. Anaplastic lymphoma kinase-1 (ALK-1) was positive in 12 of the 18 (66.7%) IMT cases, whereas none of the IPT cases showed ALK-1 immunoreactivity. IPT cases showed significantly increased IgG4+ plasma cells (mean, 127.8/high-power fields vs. 17.8/high-power fields) and a higher IgG4/IgG ratio (mean, 48.2% vs. 10.7%) as compared with IMT. Fluorescence in situ hybridization analysis was positive for ALK rearrangement in 6 of the 9 IMT cases tested. In conclusion, most of the IPT cases can be considered as IgG4 related on the basis of their histopathologic features and immunohistochemistry criteria. However, IMT represents a myofibroblastic neoplasm with ALK-1 overexpression and is clearly not IgG4 related.
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.
Liu, Wei; Chen, Weijie; He, Xiaodong; Qu, Qiang; Hong, Tao; Li, Binglu
Abstract IgG4-related sclerosing cholangitis (IgG4-SC) is a rare biliary manifestation in which many other organs might be affected. The purpose of our study was to investigate the different clinical characteristics and initial steroid response between IgG4-SC patients with and without other organs affected. A series of patients with IgG4-SC in the period from January 2006 to December 2015 at our hospital were included. The pancreas and major salivary glands were screened, and the initial corticosteroid therapy was given. Clinical information was collected and analyzed including demographics, clinical presentation, IgG4 serology, imaging features, and treatment outcomes. The study identified 72 IgG4-SC patients, including 60 males and 12 females. The mean age was 59.8 years old. Among these IgG4-SC patients, 10 patients had only bile duct involved, 42 patients had 2 organs involved and 20 patients had multiple organs involved. In patients with multiple organs involved, more complaints were given (mean 2.9 kinds), higher serum IgG4 levels were found (23458 ± 19402.7 mg/L), and more stricture lesions of biliary tract were shown. All 72 patients exhibited a disease response within 4 to 6 weeks of starting steroids. The remission rate in the multiple lesions group was lower (60%), and the recurrence rate is higher (83.3%). The relapse-free survival was 20.0 months in the single lesion group, which is longer than that in the multiple lesions group (3.1 months, P < 0.05). The IgG4-SC patients with multiple organs affected had more complaints, higher serum IgG4 levels, and poor response to initial steroids. PMID:28328835
Vanegas-Garcia, A L; Calle-Lopez, Y; Zapata, C H; Alvarez-Espinal, D M; Saavedra-Gonzalez, Y A; Arango-Viana, J C
Introduccion. La enfermedad relacionada con IgG4 es una entidad clinica multisistemica recientemente descrita y que se presenta con diferentes manifestaciones clinicas. Los organos que estan afectados con mayor frecuencia son el pancreas, la via biliar y las glandulas salivales, y es menos frecuente la afeccion del sistema nervioso central. Caso clinico. Mujer de 33 años con alteraciones cognitivas, alucinaciones, cefalea, sindrome convulsivo, sinusitis maxilar con afeccion osea y evidencia de paquimeningitis y panhipopituitarismo, con biopsia meningea que confirmo una enfermedad relacionada con IgG4, tras haberse descartado causas secundarias. Se inicio tratamiento con glucocorticoides y azatioprina, sin recaidas despues de 12 meses de seguimiento. Conclusiones. Se debe considerar el diagnostico de enfermedad relacionada con IgG4 en casos de paquimeningitis hipertrofica e hipofisitis, incluso sin que se acompañen de otras manifestaciones sistemicas, siempre que se hayan descartado otras causas mas frecuentes. El tratamiento de eleccion son los glucocorticoides, y puede ser necesario añadir otro inmunosupresor como ahorrador de esteroides y para evitar las recaidas. Se necesitan estudios prospectivos para evaluar las diferentes manifestaciones clinicas y paraclinicas y establecer los resultados del tratamiento a largo plazo.
Konstantinova, Anastasia M; Shelekhova, Ksenya V; Stewart, Colin J; Spagnolo, Dominic V; Kutzner, Heinz; Kacerovska, Denisa; Plaza, Jose A; Suster, Saul; Bouda, Jiri; Pavlovsky, Michal; Kyrpychova, Liubov; Michal, Michal; Guenova, Emmanuella; Kazakov, Dmitry V
Extramammary Paget disease (EMPD) is a rare neoplasm usually presenting in the anogenital area, most commonly in the vulva. Adnexal involvement in primary EMPD is a very common feature and serves as a pathway for carcinoma to spread into deeper tissue. The depth of carcinomatous spread along the appendages and the patterns of adnexal involvement were studied in 178 lesions from 146 patients with primary EMPD. Hair follicles and eccrine ducts were the adnexa most commonly affected by carcinoma cells. The maximal depth of involvement was 3.6 mm in this series. When planning topical therapy or developing novel local treatment modalities for EMPD, this potential for significant deep spread along adnexa should be taken into account.
Wright, Jason D.; Kostolias, Alessandra; Ananth, Cande V.; Burke, William M.; Tergas, Ana I.; Prendergast, Eri; Ramsey, Scott D.; Neugut, Alfred I.; Hershman, Dawn L.
Objective To perform a population-based analysis to compare the complications and cost of laparoscopic and robotically assisted adnexal surgery. Methods A nationwide database was utilized to analyze the use and outcomes of robotically assisted adnexal surgery from 2009–2012. Multivariable mixed effects regression models were developed to examine predictors of use of robotic surgery. After propensity score matching, complications and cost were compared between robotically assisted and laparoscopic surgery. Results 87,514 women were identified. From 2009 to 2012, performance of robotic-assisted oophorectomy increased from 3.5% (95% CI, 3.2–3.8%) to 15.0% (95% CI, 14.4–15.6%), while robotically assisted cystectomy rose from 2.4% (95% CI, 2.0–2.7%) to 12.9% (95% CI, 12.2–13.5%). The overall complication rate was 7.1% (95% CI, 4.0–10.2%) for robotically assisted vs. 6.0% (95% CI, 2.9–9.1%) for laparoscopic oophorectomy (OR=1.20; 95% CI, 1.00–1.45) (P=0.052). Robotic-assisted oophorectomy was associated with a higher rate of intraoperative complications (3.4% vs. 2.1%, OR=1.60; 95% CI, 1.21–2.13). The overall complication rate was 3.7% (95% CI −0.8–8.2%) after robotically assisted versus 2.7% (95% CI, −1.8–7.2%) for laparoscopic cystectomy (OR=1.38; 95% CI, 0.95–1.99). The intraoperative complication rate was higher for robotically assisted cystectomy (2.0% vs. 0.9%, OR=2.40; 95% CI, 1.31–4.38). Compared to laparoscopy, robotically assisted oophorectomy was associated with $2504 (95% CI, $2356–$2652) increased total costs and robotically assisted cystectomy $3310 (95% CI, $3082–$3581) higher costs. Conclusion Use of robotically assisted adnexal surgery increased rapidly. Compared to laparoscopic surgery, robotically assisted adnexal surgery is associated with substantially greater costs and a small, but statistically significant, increase in intraoperative complications. PMID:25437715
Sánez, Henry Aristóteles Mateo; Taboada-Pérez, Grecia Carolina; Hernández-Arroyo, Lysandra; Mateo-Madrigal, Melissa; Mateo-Madrigal, Victoria
Adnexal torsion is a gynecological emergency caused by the torsion of the ovary over its pedicle producing lymphatic and venous stasis, later it develops into ischemia and necrosis, when is not treated. Until recently, the treatment for adnexal torsion has been adnexectomy. This paper report three cases treated successfully with conservative treatment. It is essential to establish a protocol for adnexal torsion management where radical treatments are abandoned and conservative surgeries, such as detorsion and plication, are performed. We suggest as a first choice management adnexal detorsion, in case malignity is suspected to have intraoperative pathologic analysis, and based on the results to decide to preserve the adnexal or remove it for definitive cure.
Fernández Lorente, Loreto; Álvarez, Dolores López; López, Virginia García; Kollros, Vesna Abujder; Ariza, Aurelio; Gálvez, Alejandro; Bonet, Josep
This is a case report of a 73-year-old man with new-onset acute renal failure while being investigated for pulmonary infiltrates and mediastinal lymphadenopathies. Urine tests showed tubular range proteinuria with no microhaematuria. Immunology tests showed elevated serum IgG and hypocomplementaemia (classical pathway activation). Renal biopsy and clinical-pathological correlation were crucial in this case, reinforcing their important role in the final diagnosis of acute kidney injury.
Rodríguez-Castro, Emilio; Fernández-Lebrero, Aida; López-Dequidt, Iria A; Rodríguez-Osorio, Xiana; López-González, Francisco J; Suárez-Peñaranda, José M; Arias, Manuel
Introduccion. La paquimeningitis hipertrofica es un trastorno infrecuente que produce un engrosamiento focal o difuso de la duramadre. Puede ser idiopatica o secundaria a procesos infecciosos, autoinmunes o neoplasicos. La recientemente descrita 'enfermedad relacionada con IgG4' podria ser la causa de bastantes cuadros considerados criptogenicos. Caso clinico. Mujer de 54 años, con historia de asma bronquial, que consulto por cefalea, vertigo y perdida de audicion por su oido izquierdo. En la resonancia magnetica cerebral con gadolinio se objetivo engrosamiento y realce dural, que se extendia desde la pared lateral del seno cavernoso izquierdo y la parte medial del lobulo temporal al angulo pontocerebeloso y parte del tentorio homolaterales. El liquido cefalorraquideo presentaba 10 leucocitos/µL (90% mononucleares), con 1 g/L de proteinas y sin consumo de glucosa. El estudio anatomopatologico mostro fibrosis y un infiltrado linfoplasmocitario, con 16 celulas plasmaticas IgG4+ por campo de gran aumento. El resto de estudios analiticos y microbiologicos resultaron normales o negativos. La tasa plasmatica de IgG4 estaba dentro de los limites normales. Tratada con esteroides, se produjo mejoria clinica acompañada de la practica desaparicion de las alteraciones detectadas en la neuroimagen. Conclusiones. La paquimeningitis hipertrofica como manifestacion de la enfermedad relacionada con IgG4 puede diagnosticarse basandose en los hallazgos de la resonancia magnetica si la IgG4 plasmatica esta elevada. En casos dudosos, habra que recurrir a la biopsia meningea. La corticoterapia suele ser eficaz y representa la primera linea terapeutica.
Sasaki Yatabe, Midori; Watanabe, Kimio; Hayashi, Yoshimitsu; Yatabe, Junichi; Morimoto, Satoshi; Ichihara, Atsuhiro; Nakayama, Masaaki; Watanabe, Tsuyoshi
The clinical picture of IgG4-related disease (IgG4-RD) is diverse because various organs can be affected. We describe the case of a 56-year-old man with acute renal failure and tuberoinfundibular hypophysitis due to IgG4-RD. Steroid therapy lowered the serum IgG4 level and ameliorated renal dysfunction, bilateral hydronephrosis and retroperitoneal fibrosis. However, polyuria from post-obstructive diuresis and unmasked central diabetes insipidus ensued. The patient's polyuria continued despite the administration of a therapeutic dose of glucocorticoid; the patient's pituitary swelling and anterior pituitary dysfunction were partially ameliorated. The pituitary swelling recurred seven months later. In patients with IgG4-RD, the manifestation of polyuria after steroid therapy should prompt suspicion of post-obstructive diuresis and the unmasking of central diabetes insipidus. PMID:28049999
Overlap of Post-obstructive Diuresis and Unmasked Diabetes Insipidus in a Case of IgG4-related Retroperitoneal Fibrosis and Tuberoinfundibular Hypophysitis: A Case Report and Review of the Literature.
Sasaki Yatabe, Midori; Watanabe, Kimio; Hayashi, Yoshimitsu; Yatabe, Junichi; Morimoto, Satoshi; Ichihara, Atsuhiro; Nakayama, Masaaki; Watanabe, Tsuyoshi
The clinical picture of IgG4-related disease (IgG4-RD) is diverse because various organs can be affected. We describe the case of a 56-year-old man with acute renal failure and tuberoinfundibular hypophysitis due to IgG4-RD. Steroid therapy lowered the serum IgG4 level and ameliorated renal dysfunction, bilateral hydronephrosis and retroperitoneal fibrosis. However, polyuria from post-obstructive diuresis and unmasked central diabetes insipidus ensued. The patient's polyuria continued despite the administration of a therapeutic dose of glucocorticoid; the patient's pituitary swelling and anterior pituitary dysfunction were partially ameliorated. The pituitary swelling recurred seven months later. In patients with IgG4-RD, the manifestation of polyuria after steroid therapy should prompt suspicion of post-obstructive diuresis and the unmasking of central diabetes insipidus.
Yuk, Jin-Sung; Shin, Ji-Yeon; Park, Won I.; Kim, Dae Woon; Shin, Jung Whan; Lee, Jung Hun
Abstract The purpose of this study was to determine the effect of pregnancy on adnexal torsion (AT). We conducted a matched case-control study using the Korean Health Insurance Review and Assessment Service–National Inpatients Sample (HIRA-NIS) from 2009 to 2011. AT patients were defined as women with both a diagnostic code (N835) and a surgical code for AT. The AT patients were randomly matched 1:4 with women without AT by age and year of claim. In total, 545 AT cases and 2180 controls were enrolled from a total of 1,843,451 women. After adjustment for such covariates as age, pregnancy was found to be associated with a lower rate of AT (adjusted odds ratio 0.314, 95% confidence interval [CI] 0.237–0.416, P value <0.01) and ovarian hyperstimulation syndrome was associated with a higher rate of AT (adjusted odds ratio 20.091, 95% CI 3.607–111.908, P value <0.01). We found that pregnancy is a negative risk factor for AT. However, a further study is needed to elucidate the mechanisms underlying these results. PMID:27310967
... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Ovarian adnexal mass assessment score test system... immunological Test Systems § 866.6050 Ovarian adnexal mass assessment score test system. (a) Identification. An ovarian/adnexal mass assessment test system is a device that measures one or more proteins in serum...
... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Ovarian adnexal mass assessment score test system... immunological Test Systems § 866.6050 Ovarian adnexal mass assessment score test system. (a) Identification. An ovarian/adnexal mass assessment test system is a device that measures one or more proteins in serum...
... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Ovarian adnexal mass assessment score test system... immunological Test Systems § 866.6050 Ovarian adnexal mass assessment score test system. (a) Identification. An ovarian/adnexal mass assessment test system is a device that measures one or more proteins in serum...
Scribner, Dennis R.; Weiss, Patrice M.
Introduction: Single-site laparoscopy is gaining acceptance in many surgical fields including gynecology. The purpose of this report is to demonstrate the technique and outcome for removing a large adnexal mass through a single site. Case Description: A 41-y-old female was referred to gynecology oncology for increased abdominal girth for 3 mo. An ultrasound confirmed a benign-appearing, 37-cm left adnexal mass. The mass was removed through a single-site laparoscopic incision with the aid of drainage and a morcellator. The operating time was 84 min. The patient was discharged 2 h and 35 min later with full return to normal activity in 5 d. Conclusion: Large, benign-appearing adnexal masses can be managed safely with superior cosmetic results using single-site laparoscopy. PMID:23925036
Torres, Kara Melissa Tiangco; Junkins-Hopkins, Jacqueline M.
Acantholytic dyskeratosis (AD) is a histologic pattern seen in Darier's disease or dyskeratosis follicularis, warty dyskeratoma, and transient AD. This pattern is characterized by suprabasilar clefting, acantholysis, and formation of corps ronds and grains. We present a case of AD that is unique based on its genital location and cystic architecture. A 53-year-old woman presented with an otherwise asymptomatic cyst on her left vulva of uncertain duration. On microscopic examination, there were fragments of cystic epithelium with areas of hypergranulosis, acantholysis, corps ronds, and corps grains formation. These features are felt by the authors to be a unique presentation of a follicular adnexal neoplasm. PMID:27559500
Kashani, Irwin; Rajak, Saul N; Kearney, Daniel J; Andrew, Nicholas H; Selva, Dinesh
IgG4-related ophthalmic disease is increasingly widely recognized. Moreover, IgG4 staining can occur in other inflammatory diseases. The authors report a case of IgG4 staining of an enlarged, inflamed levator palpebrae superioris in a patient with a past history of thyroid eye disease. A 78-year-old woman with quiescent hyperthyroidism had clinical and radiological evidence of levator palpebrae superioris inflammation without superior rectus involvement. A biopsy was consistent with IgG4-related ophthalmic disease. There was a marked but incomplete response to an orbital injection of triamcinolone. The authors discuss the association between thyroid eye disease and IgG4 staining and the diagnostic issues that arise when IgG4-related ophthalmic disease criteria are fulfilled in patients with other orbital inflammatory conditions.
Glanc, Phyllis; Benacerraf, Beryl; Bourne, Tom; Brown, Douglas; Coleman, Beverly G; Crum, Christopher; Dodge, Jason; Levine, Deborah; Pavlik, Edward; Timmerman, Dirk; Ueland, Frederick R; Wolfman, Wendy; Goldstein, Steven R
The First International Consensus Conference on Adnexal Masses was convened to thoroughly examine the state of the science and to formulate recommendations for clinical assessment and management. The panel included representatives of societies in the fields of gynecology, gynecologic oncology, radiology, and pathology and clinicians from Europe, Canada, and the United States. In the United States, there are approximately 9.1 surgeries per malignancy compared to the European International Ovarian Tumor Analysis center trials, with only 2.3 (oncology centers) and 5.9 (other centers) reported surgeries per malignancy, suggesting that there is room to improve our preoperative assessments. The American College of Obstetricians and Gynecologists Practice Bulletin on "Management of Adnexal Masses," reaffirmed in 2015 (Obstet Gynecol 2007; 110:201-214), still states, "With the exception of simple cysts on a transvaginal ultrasound finding, most pelvic masses in postmenopausal women will require surgical intervention." The panel concluded that patients would benefit not only from a more conservative approach to many benign adnexal masses but also from optimization of physician referral patterns to a gynecologic oncologist in cases of suspected ovarian malignancies. A number of next-step options were offered to aid in management of cases with sonographically indeterminate adnexal masses. This process would provide an opportunity to improve risk stratification for indeterminate masses via the provision of alternatives, including but not limited to evidence-based risk-assessment algorithms and referral to an "expert sonologist" or to a gynecologic oncologist. The panel believed that these efforts to improve clinical management and preoperative triage patterns would ultimately improve patient care.
Karaköse, Oktay; Pülat, Hüseyin; Oğuz, Serhat; Zihni, İsmail; Özçelik, Kazım Çağlar; Yalta, Tülin Deniz; Eken, Hüseyin
Abstract Introduction: Ancient schwannoma is a rare tumor of the peripheral nerve sheath. As degenerative properties are defined histologically, it can be wrongly interpreted as malignant. Case presentation: The case presented here is of a giant ancient schwannoma with a pelvic retroperitoneal location, which was mimicking an adnexal mass. Conclusion: In the rarely seen cases in the retroperitoneum, it may reach very large dimensions. PMID:27472696
Alsaad, K O; Obaidat, N A; Ghazarian, D
Skin adnexal neoplasms comprise a wide spectrum of benign and malignant tumours that exhibit morphological differentiation towards one or more types of adnexal structures found in normal skin. Most adnexal neoplasms are relatively uncommonly encountered in routine practice, and pathologists can recognise a limited number of frequently encountered tumours. In this review, the first of two, the normal histology of the skin adnexal structures is reviewed, and the histological features of selected but important benign and malignant tumours and tumour‐like lesions of pilosebaceous origin discussed, with emphasis on the diagnostic approach and pitfalls in histological diagnosis. PMID:16882696
Jung, Sung Il; Park, Hee Sun; Yim, Younghee; Jeon, Hae Jeong; Yu, Mi Hye; Kim, Young Jun
Objective To evaluate the increased value of using coronal reformation of a transverse computed tomography (CT) scan for detecting adnexal torsion. Materials and Methods This study included 106 woman suspected of having adnexal torsion who underwent CT with coronal reformations and subsequent surgical exploration. Two readers independently recorded the CT findings, such as the thickening of a fallopian tube, twisting of the adnexal pedicle, eccentric smooth wall thickening of the torsed adnexal mass, eccentric septal thickening of the torsed adnexal mass, eccentric poor enhancement of the torsed adnexal mass, uterine deviation to the twisted side, ascites or infiltration of pelvic fat, and the overall impression of adnexal torsion with a transverse scan alone or combined with coronal reformation and a transverse scan. The areas under the receiver operating characteristic curves (AUCs), sensitivity, specificity, and positive predictive value were used to compare diagnostic performance. Results Fifty-two patients were confirmed to have adnexal torsion. The addition of coronal reformations to the transverse scan improved AUCs for readers 1 and 2 from 0.74 and 0.75 to 0.92 and 0.87, respectively, for detecting adnexal torsion (p < 0.001 and p = 0.004, respectively). Sensitivity of CT for detecting twisting of the adnexal pedicle increased significantly for readers 1 and 2 from 0.27 and 0.29 with a transverse scan alone to 0.79 and 0.77 with a combined coronal reformation and a transverse scan, respectively (p < 0.001 and p < 0.001, respectively). Conclusion Use of a coronal reformation with transverse CT images improves detection of adnexal torsion. PMID:26175583
Seo, Jung Chul; Kwon, Oh-Chang; Kwon, Hyo-Jung; Chung, Dae-Kyoo; Cho, Yoon-Jeong; Lee, Geon Ho
We report the case of a 30-year-old woman with a right adnexal mass resembling an ovarian cyst who declined diagnostic laparoscopy and requested treatment with acupuncture. The patient was treated with Saam acupuncture for 14 weeks. After treatment, transvaginal sonography revealed disappearance of the right adnexal mass. No adverse effects of the Saam acupuncture treatment were reported.
Charlotte, Frédéric; Doghmi, Kamal; Cassoux, Nathalie; Ye, Hongtao; Du, Ming-Qing; Kujas, Michèle; Lesot, Annette; Mansour, George; Lehoang, Phuc; Vignot, Nicole; Capron, Frédérique; Leblond, Véronique
To better characterize ocular adnexal marginal zone lymphoma of mucosa-associated lymphoid tissue (MZL-MALT), we analyzed the clinical and pathologic features of 23 patients (11 men, 12 women, median age 66 years). The tumor was confined to one ocular structure in 18 cases (conjunctiva, n=8; orbit, n=8; or lacrimal gland, n=2). Concurrent extraorbital disease was detected by the staging procedure in five patients, and preferentially involved other MALT sites. Histogenetic B cell marker studies, available in 13 cases, showed an early post-germinal center (GC) phenotype (BCL-6(-)/IRF4(+)/CD138(-)) (n=5) or a late post-GC phenotype (BCL-6(-)/IRF4(+)/CD138(+)) (n=8), which could be helpful for discrimination from other types of small-B cell lymphoma. BCL10 was positive in 12 of 13 patients tested, with nuclear (n=4) or cytoplasmic (n=8) immunoreactivity. These staining patterns ruled out t(1;14)(p22;q32) translocation. T(11;18)(q21;q21), another MZL-MALT-specific translocation, was detected by reverse transcriptase polymerase chain reaction in four of 15 patients tested. Clinical outcome was excellent but the overall relapse rate was 26.1% with a median follow-up of 39 months (range 6-132 months). Regardless of the disease stage at diagnosis, combined chemotherapy and radiotherapy seemed to be more effective than chemotherapy alone in ocular adnexal MZL-MALT, as persistent complete remission was achieved in nine patients receiving combination therapy, while six of 14 patients treated with chemotherapy alone relapsed.
Sarac, Momir; Marjanovic, Ivan; Bezmarevic, Mihailo; Zoranovic, Uros; Petrovic, Stanko; Mihajlovic, Miodrag
Most primary aortoduodenal fistulas occur in the presence of an aortic aneurysm, which can be part of immunoglobulin G4 (IgG4)-related sclerosing disease. We present a case who underwent endovascular grafting of an aortoduodenal fistula associated with a high serum IgG4 level. A 56-year-old male underwent urgent endovascular reconstruction of an aortoduodenal fistula. The patient received antibiotics and other supportive therapy, and the postoperative course was uneventful, however, elevated levels of serum IgG, IgG4 and C-reactive protein were noted, which normalized after the introduction of steroid therapy. Control computed tomography angiography showed no endoleaks. The primary aortoduodenal fistula may have been associated with IgG4-related sclerosing disease as a possible complication of IgG4-related inflammatory aortic aneurysm. Endovascular grafting of a primary aortoduodenal fistula is an effective and minimally invasive alternative to standard surgical repair. PMID:23155348
Whilst the outcomes for patients with ovarian cancer clearly benefit from centralised, comprehensive care in dedicated cancer centres, unfortunately the majority of patients still do not receive appropriate specialist treatment. Any improvement in the accuracy of current triaging and referral pathways whether using new imaging tests or biomarkers would therefore be of value in order to optimise the appropriate selection of patients for such care. An analysis of current evidence shows that such tests are now available, but still await recognition, acceptance and widespread adoption. It is therefore to be hoped that present guidance relating to the classification of ovarian masses will soon become more "evidence-based". These promising tests include the International Ovarian Tumour Analysis (IOTA) LR2 model and ultrasound-based Simple Rules (SR). Based on a comprehensive recent meta-analysis both currently offer the optimal "evidence-based" approach to discriminating between cancer and benign conditions in women with adnexal tumours needing surgery. LR2 and SR are reliable tests having been shown to maintain a high sensitivity for cancer after independent external and temporal validation by the IOTA group in the hands of examiners with various levels of ultrasound expertise. They also offer more accurate triage compared to the existing Risk of Malignancy Index (RMI). The development of the IOTA ADNEX model represents an important step forward towards more individualised patient care in this area. ADNEX is a novel test that enables the more specific subtyping of adnexal cancers (i.e. borderline, stage 1 invasive, stage II-IV invasive, and secondary metastatic malignant tumours) and shares similar levels of accuracy to IOTA LR2 and SR for basic discrimination between cancer and benign disease. The IOTA study has made significant progress in relation to the classification of adnexal masses, however what is now needed is to see if these or new diagnostic tools can assist
Cavaco-Gomes, João; Jorge Moreira, Cátia; Rocha, Anabela; Mota, Raquel; Paiva, Vera; Costa, Antónia
Adnexal masses can be found in 0.19 to 8.8% of all pregnancies. Most masses are functional and asymptomatic and up to 70% resolve spontaneously in the second trimester. The main predictors of persistence are the size (>5 cm) and the imagiological morphocomplexity. Those that persist carry a low risk of malignancy (0 to 10%). Most malignant masses are diagnosed at early stages and more than 50% are borderline epithelial neoplasms. Ultrasound is the preferred method to stratify the risk of complications and malignancy, allowing medical approach planning. Pregnancy and some gestational disorders may modify the levels of tumor markers, whereby their interpretation during pregnancy should be cautious. Large masses are at increased risk of torsion, rupture, and dystocia. When surgery is indicated, laparoscopy is a safe technique and should ideally be carried out in the second trimester of pregnancy. PMID:27119043
Basile, John R; Lin, Yi-Ling
The microcystic adnexal carcinoma (MAC) is a rare, slow-growing but locally aggressive neoplasm arising in the midface and lips of middle-aged adults. The MAC is histologically characterized by deeply infiltrating nests and islands of basaloid or squamous cells forming cysts and ductal structures, proliferating in a dense sclerotic stroma and occasionally exhibiting perineural invasion. We describe a salivary gland adenocarcinoma arising in the lower lip, characterized by ductal structures and cords, 3-5 cell layers in thickness, set in a dense fibrous stroma and also invading nerves, thus mimicking a MAC in both its clinical and its histopathologic appearance. The diagnostic dilemma presented by this lesion is discussed, along with a differential diagnosis and brief review of the literature.
Ognong-Boulemo, Audrey; Dohan, Anthony; Hoeffel, Christine; Stanek, Agatha; Golfier, François; Glehen, Olivier; Valette, Pierre-Jean; Rousset, Pascal
Given the unique intra-peritoneal anatomic location of the adnexa, tubo-ovarian diseases can commonly spread into the peritoneal cavity. Peritoneal seeding may occur in a spectrum of adnexal conditions including infectious diseases, endometriosis, and benign or malignant primary or secondary ovarian tumors. CT is usually the imaging modality on which the concomitant involvement of the peritoneum and the ovary is depicted. The first diagnosis to be considered by the radiologist is generally peritoneal carcinomatosis from ovarian cancer but other conditions cited above have also to be borne in mind and may be suggested on the basis of careful assessment of CT findings or on further MR findings. MRI may indeed help characterize the lesions in some cases. The purpose of this review is to describe the clinical and imaging patterns of peritoneal involvement that may be found in association with different ovarian lesions. Familiarity with these patterns and diagnoses will help the radiologist narrow the differential diagnosis and make an accurate diagnosis, thus facilitating patient management and avoiding unnecessary invasive treatment.
Panagopoulos, P.; Domi, V.; Christodoulaki, C.; Sioutis, D.; Papantoniou, N.
Appendiceal tumors are rare, late diagnosed neoplasms that may not be differentiated from adnexal masses even by advanced imaging methods and other diagnostic procedures. They may be asymptomatic and remain undiagnosed until surgery. We report a case of an 80-year-old postmenopausal woman presenting with a pelvic mass and a history of weight loss. The patient underwent laparotomy which revealed an appendiceal mucocele, for which she received a full oncological procedure. The histology report showed a low-grade appendiceal mucinous neoplasm, and the patient underwent six cycles of chemotherapy. Appendiceal tumors should be kept in mind in patients with adnexal mass. PMID:28286683
... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 866 Medical Devices; Immunology and Microbiology Devices; Classification of Ovarian Adnexal Mass Assessment Score Test System; Correction AGENCY: Food...
Inskip, Mike; Magee, Jill
We present a case report of a microcystic adnexal carcinoma on the cheek of a 67-year-old man. Clinical, dermatoscopic and dermatopathologic images are presented. A search of the literature has not discovered any previously published dermatoscopy images of microcystic adenexal carcinoma. PMID:25692080
Cho, Bo Ra; Han, Jae Won; Kim, Tae Hyun; Han, Ae Ra; Hur, Sung Eun; Lee, Sung Ki
Objective Investigation of initial 51 cases of single port access (SPA) laparoscopic surgery for large adnexal tumors and evaluation of safety and feasibility of the surgical technique. Methods We retrospectively reviewed the medical records of the first 51 patients who received SPA laparoscopic surgery for large adnexal tumors greater than 10 cm, from July 2010 to February 2015. Results SPA adnexal surgeries were successfully completed in 51 patients (100%). The mean age, body mass index of the patients were 43.1 years and 22.83 kg/m2, respectively. The median operative time, median blood loss were 73.5 (range, 20 to 185) minutes, 54 (range, 5 to 500) mL, and the median tumor diameter was 13.6 (range, 10 to 30) cm. The procedures included bilateral salpingo-oophorectomy (n=18, 36.0%), unilateral salpingo-oophorectomy (n=14, 27.45%), and paratubal cystectomy (n=1, 1.96%). There were no cases of malignancy and none were insertion of additional ports or conversion to laparotomy. The cases with intraoperative spillage were 3 (5.88%) and benign cystic tumors. No other intraoperative and postoperative complications were observed during hospital days and 6-weeks follow-up period after discharge. Conclusion Our results suggest that SPA laparoscopic surgery for large adnexal tumors may be a safe and feasible alternative to conventional laparoscopic surgery. PMID:28217669
González-Guerra, Elena; Kutzner, Heinz; Rutten, Arno; Requena, Luis
Calretinin is a calcium-binding protein member of the EF-hand family. The presence of calretinin has been demonstrated in certain stages of the cellular cycle in a wide variety of normal and neoplastic tissues. The main aims of our study were (1) to investigate what structures of the normal skin and cutaneous adnexal proliferations express immunoreactivity for calretinin and (2) to determine the value of immunohistochemical expression for calretinin as a marker for follicular, sebaceous, apocrine, and eccrine differentiation in cutaneous adnexal proliferations. We studied 139 biopsy specimens, including 10 cases of normal skin of different locations and 129 benign and malignant cutaneous adnexal proliferations. In normal skin, we found that calretinin is expressed in the innermost cell layer of the outer root sheath in anagen hair follicle, in both the duct and sebolemma of the sebaceous gland, in the secretory portion of eccrine glands, and in mast cells of the stroma. In cutaneous adnexal proliferations, we found strong immunoreactivity for calretinin in tricholemmal cysts, tricholemmomas/inverted follicular keratoses, tumors of follicular infundibulum, and in some basal cell carcinomas. Focal positivity was also seen in trichoadenomas, trichoblastomas/trichoepitheliomas, pilomatricomas, proliferating tricholemmal tumors, pilar sheath acanthomas, trichofolliculomas, follicular hybrid cysts, cutaneous mixed tumors, steatocystomas, sebaceous hyperplasias, and sebaceomas. These results demonstrate that immunohistochemical study for calretinin may be helpful to identify the innermost cell layer of the outer root sheath in anagen hair follicle and the cutaneous adnexal proliferations showing differentiation toward this structure. Calretinin immunoreactivity supports eccrine differentiation in some sweat gland neoplasms, and it is also useful in identifying neoplasms with ductal sebaceous differentiation.
Verma, Varun; Shen, Defen; Sieving, Pamela C.; Chan, Chi-Chao
Given the fact that infectious agents contribute to around 18% of human cancers worldwide, it would seem prudent to explore their role in neoplasms of the ocular adnexa: primary malignancies of the conjunctiva, lacrimal glands, eyelids, and orbit. By elucidating the mechanisms by which infectious agents contribute to oncogenesis, the management, treatment, and prevention of these neoplasms may one day parallel what is already in place for cancers such as cervical cancer, hepatocellular carcinoma, gastric mucosa-associated lymphoid tissue lymphoma and gastric adenocarcinoma. Antibiotic treatment and vaccines against infectious agents may herald a future with a curtailed role for traditional therapies of surgery, radiation, and chemotherapy. Unlike other malignancies for which large epidemiological studies are available, analyzing ocular adnexal neoplasms is challenging as they are relatively rare. Additionally, putative infectious agents seemingly display an immense geographic variation that has led to much debate regarding the relative importance of one organism versus another. This review discusses the pathogenetic role of several microorganisms in different ocular adnexal malignancies, including human papilloma virus in conjunctival papilloma and squamous cell carcinoma, human immunodeficiency virus in conjunctival squamous carcinoma, Kaposi sarcoma-associated herpes virus or human herpes simplex virus-8 (KSHV/HHV-8) in conjunctival Kaposi sarcoma, Helicobacter pylori (H. pylori,), Chlamydia, and hepatitis C virus in ocular adnexal mucosa-associated lymphoid tissue lymphomas. Unlike cervical cancer where a single infectious agent, human papilloma virus, is found in greater than 99% of lesions, multiple organisms may play a role in the etiology of certain ocular adnexal neoplasms by acting through similar mechanisms of oncogenesis, including chronic antigenic stimulation and the action of infectious oncogenes. However, similar to other human malignancies
Moulla, Alexandra A; Magdy, Nesreen; Francis, Nicholas; Taube, Janis; Ronnett, Brigitte M; El-Bahrawy, Mona
Mature teratoma of the ovary is the most common primary ovarian tumor accounting for 15% (10%-20%) of all ovarian neoplasms. Skin and skin adnexal structures are the most common elements identified in mature teratomas. Benign and malignant skin tumors can arise in ovarian teratomas, the most common being epithelial tumors. Melanocytic and adnexal tumors developing in a teratoma are rare and can be easily overlooked. We report 3 cases and review melanocytic and skin adnexal tumors encountered in ovarian teratomas.
Masutani, Hironori; Okuwaki, Kosuke; Kida, Mitsuhiro; Yamauchi, Hiroshi; Imaizumi, Hiroshi; Miyazawa, Shiro; Iwai, Tomohisa; Takezawa, Miyoko; Koizumi, Wasaburo
To our knowledge, patients with immunoglobulin G4-related sclerosing cholangitis (IgG4-SC) associated with autoimmune hemolytic anemia (AIHA) have not been reported previously. Many patients with IgG4-SC have autoimmune pancreatitis (AIP) and respond to steroid treatment. However, isolated cases of IgG4-SC are difficult to diagnose. We describe our experience with a patient who had IgG4-SC without AIP in whom the presence of AIHA led to diagnosis. The patient was a 73-year-old man who was being treated for dementia. Liver dysfunction was diagnosed on blood tests at another hospital. Imaging studies suggested the presence of carcinoma of the hepatic hilus and primary sclerosing cholangitis, but a rapidly progressing anemia developed simultaneously. After the diagnosis of AIHA, steroid treatment was begun, and the biliary stricture improved. IgG4-SC without AIP was thus diagnosed.
Rao, Arun; Ullal, Sonali; Krishna, Gowtham
Introduction Suspicious adnexal masses are common clinical problems in gynaecological practice. A reliable diagnostic tool for the early detection of the ovarian malignancy is essential. Aim To validate a new scoring system –Pelvic Mass Score (PMS) in predicting the nature of the adnexal mass pre-operatively. Materials and Methods A prospective observational study was carried out in 100 consenting women with an undiagnosed adnexal mass requiring operative intervention. Among them 62 patients had mass with a feeding vessel in which the Doppler velocimetry study values were available. The PMS was determined in these 62 patients. A score of 29 or more was taken as suggestive of malignancy. The results were compared with the histopathological diagnosis to confirm malignancy. The chi-square test was applied to test the significance. Results Among the 62 patients with vascular mass, 31 had histopathological diagnosis of malignancy. The statistical analysis of the data with PMS with 29 as cut-off revealed 100% sensitivity and 100% Negative Predictive Value (NPV) as there was no false negative case detected. But the specificity and Positive Predictive Value (PPV) was poor; 45.2% and 64.6% respectively. Based on the Receiver Operating Characteristic (ROC) curve, if we redefine cut-off as 69, specificity increases to 80.6% with a sensitivity of 90.3%, the PPV and NPV being 82.35 and 89.29 respectively. Conclusion The present study concludes that, in suspicious vascular adnexal masses PMS can be used as a reliable diagnostic score to predict malignancy if we redefine the existing cut-off of 29 to 69. PMID:28050448
Kawai, Nobuyuki; Kanematsu, Masayuki; Kawaguchi, Shimpei; Kojima, Toshihisa; Furui, Tatsuro; Morishige, Ken-ichirou; Matsuo, Masayuki
Background The usefulness of T2*-weighted (T2*W) imaging for the detection of adnexal torsion has yet to be determined. Purpose To assess the usefulness of T2*W imaging for detecting and differentiating adnexal torsion. Material and Methods Eight patients with eight ovaries with torsion and 44 patients with 72 ovaries without torsion were included in this study. All patients underwent 1.5-T magnetic resonance imaging (MRI) including T2*W images. The frequency and distribution of hypointensity on T2*W images were compared between ovaries with torsion and ovaries without torsion. Results Hypointensity on T2*W images was significantly more frequent in ovaries with torsion than in ovaries without torsion (75% vs. 36%; P < 0.05). Among patients with hypointensity on T2*W images, the frequency of diffuse hypointensity was significantly higher in ovaries with torsion than in ovaries without torsion (83% vs. 0%; P < 0.01); whereas the frequency of focal hypointensity was significantly lower in ovaries with torsion than in ovaries without torsion (17% vs. 100%; P < 0.01). Conclusion The presence and distribution of hypointensity on T2*W images may play a supplementary role in the detection of adnexal torsion. PMID:27478621
Minig, Lucas; Otaño, Lucas; Cruz, Pilar; Patrono, María Guadalupe; Botazzi, Cecilia; Zapardiel, Ignacio
OBJECTIVE: To evaluate the feasibility and safety of laparoscopic surgery for treating adnexal masses during the first trimester of pregnancy. STUDY DESIGN: An observational study of a prospective collection of data of all pregnant women who underwent laparoscopic surgery for adnexal masses during the first trimester of pregnancy between January 1999 and November 2012 at the Obstetrics and Gynecology Department of the Italian Hospital of Buenos Aires, Buenos Aires, Argentina was performed. RESULTS: A total of 13 women were included. The median (range) gestational age at the moment of surgical procedure was 7 weeks (range: 5-12 weeks). The main indication of surgery was cyst torsion in four cases (30.7%) and rupture of ovarian cysts in four cases (30.7%). Other indications included persistent ovarian cyst in three patients (23%) and heterotopic pregnancy in two cases (15.3%). Neither surgical complications nor spontaneous abortions occurred in any of the cases and the post-operative period was uneventful in all the cases. No cases of intrauterine growth retardation, preterm delivery, congenital defects, or neonatal complications were registered. CONCLUSION: The treatment of complicated adnexal masses by laparoscopic surgery during the first trimester of pregnancy appears to be a safe procedure both for the mother and for the foetus. Additional research on a larger number of cases is still needed to support these conclusions. PMID:26917915
Khan, Lubna; Malukani, Kamal; Malaiya, Siddharth; Yeshwante, Prashant; Ishrat, Saba; Nandedkar, Shirish S.
Purpose: To evaluate the role of fine needle aspiration (FNAC) as a diagnostic tool in cases of orbital and ocular adnexal masses. Cytological findings were correlated with histopathological diagnosis wherever possible. Methods: FNAC was performed in 29 patients of different age groups presenting with orbital and ocular adnexal masses. Patients were evaluated clinically and investigated by non-invasive techniques before fine needle aspiration of the masses. Smears were analyzed by a cytologist in all cases. Further, results of cytology were compared with the histopathological diagnosis. Results: The age of patients ranged from 1 to 68 years (mean: 29.79±19.29). There were 14 males and 15 females with a male to female ratio of 0.93:1. Out of 29 cases, 26 aspirates were cellular. Cellularity was insufficient in three (10.34%) aspirates. Out of 26 cellular aspirates, 11 were non-neoplastic while 15 were neoplastic on cytology. Subsequent histopathologic examination was done in 21/26 cases. Concordance rate of FNAC in orbital and ocular adnexal mass lesions with respect to the precise histologic diagnosis was 90%. Conclusion: When properly used in well-indicated patients (in cases where a diagnosis cannot be made by clinical and imaging findings alone), FNAC of orbital and periorbital lesions is an invaluable and suitable adjunct diagnostic technique that necessitates close cooperation between the ophthalmologist and cytologist. However, nondiagnostic aspirates may sometimes be obtained, and an inconclusive FNAC should not always be ignored. PMID:27621787
Smiljanic, M; Milosevic, R; Antic, D; Andjelic, B; Djurasinovic, V; Todorovic, M; Bila, J; Bogdanovic, A; Mihaljevic, B
Orbital and ocular andexal Mucosa-Associated Lymphoid Tissue Lymphoma (MALT) or ocular adnexal MALT lymphoma (OAML) is the most common of all eye non-Hodgkin lymphomas. Autoimmune inflammatory disorders and chronic infections are important etiological factors and CD5 and CD43 (sialophorin) tumor markers are significant negative prognostic factors. Disease signs and symptoms can occur a long time before diagnosis. Varieties of treatment options are available. The aim of this retrospective analysis was to compare the efficiency of different treatment options and to investigate disease outcome. Twenty OAML patients, diagnosed in the Clinic of Hematology, Clinical Centre of Serbia, between 2003 and 2013, were enrolled. In most cases, OAML developed in the eighth decade with greater incidence in the male population. Median age was 67.5 years. The median period between the appearance of local signs and symptoms and diagnosis was 7 months. The dominant sign at presentation was swelling of involved tissue (40%). The most common was orbital involvement (55%). All patients had localized disease. Observed laboratory parameters on presentation showed low disease activity. Sialophorin prognostic significance was not registered. Our patients were initially treated differently but there was no significant difference in progression-free survival (PFS) due to initial treatment option (p = 0.2957). Median PFS was 22 months (3-89), and 5-year PFS was 60%. Median overall survival (OS) was 43 months (1-105) and 5-year OS 95%. Eight patients (40%) relapsed and one patient died due to non-hematological complications. In our experience, most modern induction treatment options appear to result in the same, favorable outcome.
Uehara, Takeshi; Ikeda, Shu-ichi; Hamano, Hideaki; Kawa, Shigeyuki; Moteki, Hideaki; Matsuda, Kazuyuki; Kaneko, Yasunori; Hara, Eiji
A 66-year-old Japanese man with an 11-year history of Mikulicz's disease (MD) received continuous corticosteroid administration. At age 58, a left renal pelvic mass was identified and diagnosed as an IgG4-related inflammatory pseudotumor. The patient underwent an operation to remove the tumor. Subsequently, he contracted repeated pulmonary infections and eventually died of severe gastrointestinal bleeding. Autopsy revealed systemic lymph node swelling and infiltration in some organs, and diffuse large B-cell lymphoma (DLBCL) was diagnosed. These findings suggest that an IgG4-related disease can be causally related to the development of malignant lymphoma through the occurrence of mucosa-associated lymphoid tissue lymphoma.
Gupta, Rajib K; Patton, Kurt T
Hyalinizing cholecystitis (HC) is a recently described rare subtype of chronic cholecystitis characterized by dense, paucicellular collagenous transmural fibrosis, which usually replaces the mucosa and muscularis propria. Immunoglobulin (Ig)G4-associated cholecystitis is also a newly described cholecystitis variant characterized by transmural or extramural lymphoplasmacytic inflammation, lymphoid follicles, storiform fibrosis, phlebitis, and increased tissue IgG4-positive plasma cells. We describe a case of cholecystitis in an elderly white man who harbored features of both HC and IgG4-associated cholecystitis. In retrospect, the patient also had a significantly elevated serum IgG4 level. To the best of our knowledge, an association between HC and IgG4-related disease has not been previously described in the literature. Although not entirely conclusive, our observations raise the possibility that some cases of HC represent the end stage of IgG4-related disease.
Suh-Burgmann, Elizabeth; Kinney, Walter
Although ultrasound has so far been found to be ineffective as a screening tool for ovarian cancer, it is commonly used as a means of evaluating or following ovarian or adnexal masses once they are detected. We review the use of serial ultrasound for the management of adnexal masses and propose an approach to monitoring based on an understanding of the overall risk of cancer among the population in question and an assessment of how the potential benefit of monitoring compares with potential risk. In our approach, masses that are symptomatic, large (>10 cm), associated with an elevated CA 125 level or overt signs of malignancy, or that are determined to have a worrisome appearance by stringent ultrasound criteria should be evaluated surgically. Women with masses that have none of these characteristics should be offered monitoring. Short-term initial ultrasound monitoring carries significant potential benefit in terms of aiding detection of early malignancy and avoidance of unnecessary surgery. However, if a mass remains stable but persistent, the potential benefit of ongoing monitoring wanes with time, whereas the potential harms, in terms of patient anxiety, cost, and the risk of incidental findings and unnecessary surgery increase. Therefore, monitoring of stable lesions should be limited in duration in order to limit potential harms from overtreatment and overdiagnosis. PMID:26904503
Buechner, Stanislaw; Erne, Paul; Resink, Therese J.
Background T-cadherin is an atypical glycosylphosphatidylinositol-anchored member of the cadherin superfamily of adhesion molecules. The role of T-cadherin in biology of the skin is poorly understood. Expression of T-cadherin in basal keratinocytes and dermal blood vessels of the healthy epidermis has been demonstrated, but studies on expression in skin appendages are rare. Methods We conducted an immunohistochemical analysis of T-cadherin expression in the epidermis and adnexal structures of normal skin. Results T-cadherin expression is restricted to basal keratinocytes of the epidermis. The basal cell layer of sebaceous glands was T-cadherin positive, whereas sebocytes were negative. Within apocrine glands, only myoepithelial cells were T-cadherin positive. In contrast, both the secretory coils and excretory ducts of eccrine glands were T-cadherin positive. In terminal hair follicles, the outer root sheath layers strongly expressed T-cadherin throughout different regions of the follicle, with the strongest immunoreactivity at the bulge and suprabulbar regions. T-cadherin and CK15 stem cell marker similarly localized within the bulge and suprabulbar region. T-cadherin and CD34 stem cell marker similarly localized at the suprabulbar level. Conclusion The specific patterns of T-cadherin expression in the epidermis and adnexal structures suggest an important guardian role in skin homeostasis. PMID:27904857
... abdomen (abdominal cavity) and the tissues lining it. Did You Know... The ovary sometimes twists, causing sudden, ... is removed (called oophorectomy). Resources In This Article Did You Know 1 Did You Know... Noncancerous Gynecologic ...
Jain, Shivi; Verma, Ashish; Jain, Madhu; Trivedi, Sameer; Shukla, Ram C; Srivastava, Arvind
A surgical swab retained in the body after surgery is known as ‘Gossypiboma’. The purpose of this report is to highlight an intramural vesical gossypiboma mimicking an invasive adnexal malignancy. A 28-year-old multiparous, with open-tubal ligation three years ago, presented with painless hematuria and a nontender mass on vaginal examination. USG suggested ‘pelvic endometriosis’ infiltrating into the bladder and cystoscopy showed no intraluminal extension of the mass. Contrast-enhanced computed tomography (CECT) and magnetic resonance imaging (MRI) misdiagnosed it as invasive malignancy of the fallopian tube. Exploratory laparotomy found it to be an intramural vesical gossypiboma. A pelvic gossypiboma infiltrating into the wall of the urinary bladder may easily be misinterpreted as an invasive pelvic malignancy on imaging and may make one consider unwarranted radical surgery. PMID:25969644
Jackson, Amanda M; Hope, Erica R; Phippen, Neil T
Surgery for suspected ovarian torsion sometimes reveals unexpected sources of pelvic pain, such as internal hernias, adhesions, or anatomic defects. A 23-year-old nulligravida with Alagille syndrome was taken to the operating room with suspected ovarian torsion. Intraoperatively, the right adnexa bulged out of a right-sided, posterior peritoneal cleft that incarcerated most of the enlarged ovary. No ovarian torsion was identified. The left adnexa appeared to be normal; however, it dwelled within a left-sided posterior peritoneal cleft. The bilateral posterior peritoneal defects that housed the adnexa were likely of congenital etiology. Although adnexal incarceration is a rare finding at surgery for suspected ovarian torsion, it should be part of the differential diagnosis when evaluating acute pelvic pain.
Fei, Yunyun; Shi, Juhong; Lin, Wei; Chen, Yu; Feng, Ruie; Wu, Qingjun; Gao, Xin; Xu, Wenbing; Zhang, Wen; Zhang, Xuan; Zhao, Yan; Zeng, Xiaofeng; Zhang, Fengchun
To investigate clinical and radiological features of IgG4-related disease (IgG4-RD) patients with intrathoracic involvement. A prospective cohort study was performed and IgG4-RD patients were enrolled from January 2011 to March 2015 in Peking Union Medical College Hospital, in which the clinical and radiological characteristics of IgG4-RD patients with intrathoracic involvement were summarized. Out of total 248 cases with IgG4-RD, 87 cases had intrathoracic lesions, including 58 male cases and 29 female cases, with average age of 54.19 ± 13.80 years. Hilar and mediastinal lymphadenopathy were the most common manifestations of IgG4-related intrathoracic disease, accounting for 52.9% (46/87). Other imaging findings of pulmonary disease included: solid nodular (25.3%), round-shaped ground-glass opacities (9.2%), alveolar-interstitial type (20.7%), bronchovascular type (23.0%), pleural effusion (4.6%), and pleural nodules or thickening (16.1%). Only 27 patients presented with respiratory symptoms, including cough, breathless, chest pain, and asthma. Compared with patients without intrathoracic disease, IgG4-related intrathoracic disease had higher IgG4 and C-reactive protein level, and higher incidence of allergy, fever, and multi-organ involvement. Most of lung interstitial disease, mediastinal mass, and bronchial thickening were sensitive to corticosteroid and immunosuppressant therapy, while 36.3% (8/22) of solitary nodular lesions were unresponsive to treatment. Eight patients were on no treatment, with 5 cases remained stable, 2 patients improved spontaneously, and 1 patient was lost follow-up. Intrathoracic lesions are not rare in patients with IgG4-RD, involving bronchial thickening, nodules, ground glass opacity, pleural thickening/effusion, lymphadenopathy, etc. Efficacy of corticosteroid and immunosuppressant therapy were noted in most of patients with lung interstitial disease, mediastinal mass, and bronchial thickening.
Wang, Si-Yun; Yin, Ling; Guan, Xiao-Ming; Xiao, Bing-Bing; Zhang, Yan; Delgado, Amanda
Background: Single port laparoscopic surgery (SPLS) is an innovative approach that is rapidly gaining recognition worldwide. The aim of this study was to determine the feasibility and safety of SPLS compared to conventional laparoscopic surgery for the treatment of benign adnexal masses. Methods: In total, 99 patients who underwent SPLS for benign adnexal masses between December 2013 and March 2015 were compared to a nonrandomized control group comprising 104 conventional laparoscopic adnexal surgeries that were performed during the same period. We retrospectively analyzed multiple clinical characteristics and operative outcomes of all the patients, including age, body mass index, size and pathological type of ovarian mass, operative time, estimated blood loss (EBL), duration of postoperative hospital stay, etc. Results: No significant difference was observed between the two groups regarding preoperative baseline characteristics. However, the pathological results between the two groups were found to be slightly different. The most common pathological type in the SPLS group was mature cystic teratoma, whereas endometrioma was more commonly seen in the control group. Otherwise, the two groups had comparable surgical outcomes, including the median operation time (51 min vs. 52 min, P = 0.909), the median decreased level of hemoglobin from preoperation to postoperation day 3 (10 g/L vs. 10 g/L, P = 0.795), and the median duration of postoperative hospital stay (3 days vs. 3 days, P = 0.168). In SPLS groups, the median EBL and the anal exsufflation time were significantly less than those of the conventional group (5 ml vs. 10 ml, P < 0.001; 10 h vs. 22 h, P < 0.001). Conclusions: SPLS is a feasible and safe approach for the treatment of benign adnexal masses. Further study is required to better determine whether SPLS has significant benefits compared to conventional techniques. PMID:27231167
Jedrych, Jaroslaw; McNiff, Jennifer M
The histological discrimination between desmoplastic trichoepithelioma, infiltrative basal cell carcinoma, and microcystic adnexal carcinoma encountered in small biopsies is challenging when only morphological criteria are applied. The objective of this study is to test the use of p75 neurotrophin receptor (p75NTR) as an adjunct aid in classification of these tumors. Immunohistochemistry for p75NTR antigen was performed on routinely processed biopsies of 37 desmoplastic trichoepitheliomas, 11 infiltrative basal cell carcinomas, and 9 microcystic adnexal carcinomas diagnosed by morphological criteria in conjunction with results of CK20 immunostains. Cases were analyzed for the extent and intensity of p75NTR expression. Diffuse immunoreactivity was defined as involving >90% of tumor cells. Of the 37 desmoplastic trichoepitheliomas, 35 (94%) displayed strong diffuse immunoreactivity of tumor cells, proving high sensitivity of the marker to detect this tumor. However, despite the fact that diffuse p75NTR expression reached statistical significance in differentiating desmoplastic trichoepithelioma from infiltrative basal cell carcinoma (Fisher exact test P < 0.0001) and microcystic adnexal carcinoma (P < 0.0016), specificity of the stain is unsatisfactory because strong diffuse expression of p75NTR by neoplastic cells was observed in 4 (36%) cases of infiltrative basal cell carcinomas and 4 (44%) cases of microcystic adnexal carcinoma. This study demonstrates a significant difference in p75NTR expression in selected sclerosing neoplasms of the skin. Nevertheless, the practical value of p75NTR as an adjunct marker in the differential diagnosis of these tumors seems to be limited because of significant overlap in amount of p75NTR immunoreactivity.
Nakamura, Yuichi; Kayano, Hidekazu; Kakegawa, Emi; Uchida, Yumiko; Shimada, Tsuneyuki; Wakimoto, Naoki; Ito, Yoshihiro; Bessho, Masami
We report a patient with hairy cell leukemia Japanese variant (HCL-Jv) that developed after radiotherapy for orbital adnexal MALT lymphoma. A 78-year-old man was diagnosed as having MALT lymphoma in the left conjunctiva in December 2003. The patient was treated by local radiotherapy and the tumor disappeared. Thereafter, he gradually developed leukocytosis and mild splenomegaly. In May 2009, the leukocyte count was 34,300 with 80% lymphoid cells. A diagnosis of HCL-Jv was made since the lymphoid cells showed a hairy morphology with round nuclei and indistinct nucleoli. These cells expressed CD11c, CD19, CD20, CD103 and showed weak reaction for tartrate-resistant acid phosphatase (TRAP). Bone marrow was infiltrated by atypical cells with an intrasinusoidal pattern. No treatment was needed as the patient was asymptomatic without anemia, thrombocytopenia or lymphadenopathy. Results of the immunoglobulin light chain expression and the heavy chain rearrangement in the tumor cells indicated that the two mature B-lymphoid neoplasms, MALT lymphoma and HCL-Jv, in this patient were derived from independent clones. This appears to be the first reported case of HCL-Jv associated with other lymphoid tumor. Further analysis is needed to clarify the risk of secondary malignancy in HCL-Jv.
Chukus, Anjeza; Tirada, Nikki; Restrepo, Ricardo; Reddy, Neelima I
Ectopic pregnancy occurs when implantation of the blastocyst takes place in a site other than the endometrium of the uterine cavity. Uncommon implantation sites of ectopic pregnancy include the cervix, interstitial segment of the fallopian tube, scar from a prior cesarean delivery, uterine myometrium, ovary, and peritoneal cavity. Heterotopic and twin ectopic pregnancies are other rare manifestations. Ultrasonography (US) plays a central role in diagnosis of uncommon ectopic pregnancies. US features of an interstitial ectopic pregnancy include an echogenic interstitial line and abnormal bulging of the myometrial contour. A gestational sac that is located below the internal os of the cervix and that contains an embryo with a fetal heartbeat is indicative of a cervical ectopic pregnancy. In a cesarean scar ectopic pregnancy, the gestational sac is implanted in the anterior lower uterine segment at the site of the cesarean scar, with thinning of the myometrium seen anterior to the gestational sac. An intramural gestational sac implants in the uterine myometrium, separate from the uterine cavity and fallopian tubes. In an ovarian ectopic pregnancy, a gestational sac with a thick hyperechoic circumferential rim is located in or on the ovarian parenchyma. An intraperitoneal gestational sac is present in an abdominal ectopic pregnancy. Intra- and extrauterine gestational sacs are seen in a heterotopic pregnancy. Two adnexal heartbeats suggest a live twin ectopic pregnancy. Recognition of the specific US features will help radiologists diagnose these uncommon types of ectopic pregnancy.
Tenorio-Guadalupe, María Del Rosario; Arsentales-Montalva, Valeria; Yonz-Buendía, Yessabell Sonia; Fiestas-Saldarriaga, Fabián; Pimentel-Álvarez, Patricia
Germ cell carcinoma during pregnancy is rare. However, its detection has increased due to the use of ultrasound fetal monitoring in the antenatal care program. In this article, we present the case of a Germ cell carcinoma during pregnancy is rare. However, its detection has increased due to the use of ultrasound fetal monitoring in the antenatal care program. In this article, we present the case of a pregnant 27-year-old diagnosed with an adnexal germ cell carcinoma at six weeks of gestation, whose initial approach was local resection (suboptimal cytoreduction). Four weeks after surgery, the patient presented with grade IV peripheral neuropathy in the lower limbs; magnetic resonance imaging scan indicated an infiltrative lesion at D5. The local medical board decided on chemotherapy starting on the 19th week of gestation. The rest of the pregnancy period was uneventful and the patient had a cesarean section at 34 weeks of gestation and a live newborn with no complications. Unfortunately, four days after caesarean section, the patient died of a septic shock with respiratory focus.
Johansson, Patricia; Klein-Hitpass, Ludger; Grabellus, Florian; Arnold, Georg; Klapper, Wolfram; Pförtner, Roman; Dührsen, Ulrich; Eckstein, Anja; Dürig, Jan; Küppers, Ralf
The pathogenesis of ocular adnexal marginal zone lymphomas of mucosa-associated lymphatic tissue-type (OAML) is still poorly understood. We analyzed 63 cases of such lymphomas for non-synonymous mutations in 24 candidate genes by amplicon sequencing. We validated frequent mutations in the NF-κB regulators MYD88, TNFAIP3 and TNIP1 in OAML, but also identified recurrent mutations in several additional components of the NF-κB pathway, including BCL10 and NFKBIA. Overall, 60% of cases had mutations in at least one component of NF-κB signaling, pointing to a central role of its genetic deregulation in OAML pathogenesis. Mutations in NOTCH1 and NOTCH2 were each found in 8% of cases, indicating a pathogenetic function of these factors in OAML. KMT2D was identified as the first epigenetic regulator with mutations in OAML, being mutated in 22% of cases. Mutations in MYD88 were associated with an inferior disease-free survival. Overall, we identified here highly recurrent genetic lesions in components of the NF-κB pathway, of NOTCH1 and NOTCH2 as well as KMT2D in OAML and thereby provide major novel insights into the pathogenesis of this B cell malignancy. PMID:27566587
Mertens, Richard B; de Peralta-Venturina, Mariza N; Balzer, Bonnie L; Frishberg, David P
Initial investigations reported GATA3 to be a sensitive and relatively specific marker for mammary and urothelial carcinomas. Recently, GATA3 expression has been described in several other epithelial tumors. However, there has been only limited investigation of GATA3 expression in cutaneous epithelial tumors. The objective of this study was to examine the immunohistochemical expression of GATA3 in a wide variety of cutaneous epithelial neoplasms. GATA3 expression was evaluated in 99 benign and 63 malignant cutaneous epithelial tumors. GATA3 was consistently and usually strongly expressed in clear cell acanthoma, trichofolliculoma, trichoepithelioma, trichilemmoma, sebaceous adenoma, sebaceoma, apocrine hidrocystoma, apocrine tubular papillary adenoma, hidradenoma papilliferum, and syringocystadenoma papilliferum. Hidradenomas exhibited variable positive staining. Most poromas, syringomas, chondroid syringomas, cylindromas, and spiradenomas were negative or only focally and weakly positive. Focal staining was present in all pilomatrixomas. Thirteen of 14 basal cell carcinomas, 21 of 24 squamous carcinomas, and all 6 sebaceous carcinomas exhibited positive staining. The 1 apocrine carcinoma, both mucinous carcinomas, and 2 of 3 microcystic adnexal carcinomas also exhibited positive staining, whereas the 1 eccrine porocarcinoma and the 1 adenoid cystic carcinoma were negative. One of 11 Merkel cell carcinomas exhibited focal weak staining. Our findings demonstrate that GATA3 is expressed in a wide variety of benign and malignant cutaneous epithelial neoplasms. In addition to carcinomas of breast and urothelial origin and other more recently described GATA3-positive tumors, the differential diagnosis of a metastatic tumor of unknown primary origin that expresses GATA3 should also include a carcinoma of cutaneous epithelial origin.
Shah, Mamta; Lee, Grace; Lefebvre, Daniel R; Kronberg, Benjamin; Loomis, Stephanie; Brauner, Stacey C; Turalba, Angela; Rhee, Douglas J; Freitag, Suzanne K; Pasquale, Louis R
We studied the relation between prostaglandin analogue use and ocular adnexal features. We used a prospective, cross-sectional study involving 157 current, 15 past, and 171 never users of prostaglandin analogues. Patients 50 years of age or older and without conditions affecting ocular adnexal anatomy underwent glaucoma medication use history, external digital photography and systematic external adnexal exam. Two masked readers assessed the digital photos for upper lid dermatochalasis and lower lid steatoblepharon using a validated grading scheme. Another masked clinical examiner also assessed upper lid ptosis, levator muscle function, and inferior scleral show. We performed ordinal logistic regression analysis accounting for multiple covariates to assess the relation between prostaglandin analogue use and adnexal features. Multivariable analyses indicated there was a 230-fold increased risk of incremental involution of dermatochalasis (odds ratio (OR) = 2.30; 95% confidence interval (CI) 1.43-3.69; p = 5.44E-04) and a 249-fold increased risk of incremental loss of lower lid steatoblepharon (OR = 2.49; 95% CI, 1.54-4.03; p= 1.98E-04) associated with current prostaglandin analogue use (bimatoprost 0.03%, travoprost 0.005%, or latanoprost 0.004%) versus prostaglandin analogue never or past users. Upper lid ptosis (OR = 4.04; 95% CI, 2.43-6.72; p = 7.37E-08), levator dysfunction (OR = 7.51; 95% CI, 3.39-16.65; p = 6.74E-07) and lower lid retraction (OR = 2.60; 95% CI, 1.58-4.28; p = 1.72E-04) were highly associated with current prostaglandin analogue use versus prostaglandin analogue never or past users. The associations between prostaglandin analogue use and deepening of the upper lid sulci and between prostaglandin analogue use and loss of inferior periorbital fat are confirmed in this multivariable analysis. The associations between prostaglandin analogue use and levator muscle dysfunction and between prostaglandin analogue use and upper lid ptosis represent
Tranchina, Michelle M; Scott, Danny W; McDonough, Sean P
A small population of resident T-lymphocytes is present in the normal epidermis of humans, mice, and rats. However, resident epidermal lymphocytes have not been reported in the normal skin of the cat. Skin-biopsy specimens from the normal skin of the dorsolateral trunk from 30 cats were examined histologically and immunohistochemically for the presence of lymphocytes, CD3+ cells, and BLA.36+ cells in epidermis and adnexal epithelia. All examinations were negative. It appears that lymphocytes occur rarely, if at all, in the epidermis and adnexal epithelial of normal cat skin. Hence, the presence of lymphocytes in these structures should be considered abnormal.
Cho, Yeon Jean; Kim, Mi-La; Lee, Soo Yoon; Lee, Hee Suk; Kim, Joo Myoung; Joo, Kwan Young
Objective To compare the operative outcomes, postoperative pain, and subsequent convalescence after laparoendoscopic single-site surgery (LESS) or conventional laparoscopic surgery for adnexal preservation. Study design From December 2009 to September 2010, 63 patients underwent LESS (n = 33) or a conventional laparoscopic surgery (n = 30) for cyst enucleation. The overall operative outcomes including postoperative pain measurement using the visual analog scale (VAS) were evaluated (time points 6, 24, and 24 hours). The convalescence data included data obtained from questionnaires on the need for analgesics and on patient-reported time to recovery end points. Results The preoperative characteristics did not significantly differ between the two groups. The postoperative hemoglobin drop was higher in the LESS group than in the conventional laparoscopic surgery group (P = 0.048). Postoperative pain at each VAS time point, oral analgesic requirement, intramuscular analgesic requirement, and the number of days until return to work were similar in both groups. Conclusion In adnexa-preserving surgery performed in reproductive-age women, the operative outcomes, including satisfaction of the patients and convalescence after surgery, are comparable for LESS and conventional laparoscopy. LESS may be a feasible and a promising alternative method for scarless abdominal surgery in the treatment of young women with adnexal cysts PMID:22448110
Saito, Shigeko; Kajiyama, Hiroaki; Miwa, Yoko; Mizuno, Mika; Kikkawa, Fumitaka; Tanaka, Shiho; Okamoto, Tomomitsu
Laparoscopy has become the standard surgery for the treatment of benign ovarian tumors. The aim of this study was to evaluate the appropriateness of laparoscopy for ovarian tumors, including those with malignant potential. A total of 487 patients with adnexal masses underwent laparoscopic surgery in Social Insurance Chukyo Hospital from January 2000 to December 2012. We reviewed 471 cases that fulfilled the criteria set for this study, and examined 10 cases with unexpected ovarian malignancy to analyze their preoperative diagnosis, second surgery, postoperative chemotherapy, and prognosis. The ages of the 471 patients ranged from 13 to 50 years, with a median of 31. Nulliparous patients numbered 321(68.1%). Of all, 436 patients mostly consisted of those with endometrioma, benign ovarian neoplasm or functional cyst. In all, we histologically identified 10 women with malignancy: 6 with borderline ovarian tumors (BOT), 2 with ovarian cancer, and 2 with histologically rare tumors (immature teratoma and granulosa cell tumor). All patients with BOT were diagnosed with a mucinous histology. Two patients underwent both second radical surgery (hysterectomy and contra- or bilateral salpingo-oophorectomy) and chemotherapies that consisted of CBDCA and PTX or DTX. Thus, 2 patients underwent staging procedures, but the remaining 8 cases did not. None of them had evidence of recurrences. With accurate staging and careful postoperative follow-up, laparoscopic surgery could be a feasible initial operation for patients with adnexal masses including early-stage ovarian malignancy.
Harada, Ken; Murakami, Naoya; Kitaguchi, Mayuka; Sekii, Shuhei; Takahashi, Kana; Yoshio, Kotaro; Inaba, Koji; Morota, Madoka; Ito, Yoshinori; Sumi, Minako; Suzuki, Shigenobu; Tobinai, Kensei; Uno, Takashi; Itami, Jun
Purpose: To evaluate the natural history, behavior of progression, prognostic factors, and treatment-related adverse effects of primary ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphoma (POAML). Methods and Materials: Eighty-six patients with histologically proven stage I POAML treated with radiation therapy at National Cancer Center Hospital, Tokyo between 1990 and 2010 were retrospectively reviewed. The median age was 56 years (range, 18-85 years). The median dose administered was 30 Gy (range, 30-46 Gy). Seventy-seven patients (90%) were treated by radiation therapy alone. Results: The median follow-up duration was 9 years (range, 0.9-22 years). The 5- and 10-year overall survival (OS) rates were 97.6% and 93.5%, respectively, and no patients died of lymphoma. Patients with tumor sizes ≥4 cm showed a greater risk of contralateral relapse (P=.012). Six patients with contralateral relapse were seen and treated by radiation therapy alone, and all the lesions were controlled well, with follow-up times of 3 to 12 years. There was 1 case of local relapse after radiation therapy alone, and 3 cases of relapse occurred in a distant site. Cataracts developed in 36 of the 65 eyes treated without lens shielding and in 12 of the 39 patients with lens shielding (P=.037). Conclusions: The majority of patients with POAML showed behavior consistent with that of localized, indolent diseases. Thirty gray of local irradiation seems to be quite effective. The initial bilateral involvement and contralateral orbital relapses can be also controlled with radiation therapy alone. Lens shielding reduces the risk of cataract.
Hashimoto, Naoki; Sasaki, Ryohei; Nishimura, Hideki; Yoshida, Kenji; Miyawaki, Daisuke; Nakayama, Masao; Uehara, Kazuyuki; Okamoto, Yoshiaki; Ejima, Yasuo; Azumi, Atsushi; Matsui, Toshimitsu; Sugimura, Kazuro
Purpose: To evaluate the long-term treatment outcome and disease behavior of primary ocular adnexal MALT (mucosa-associated lymphoid tissue) lymphoma (POAML) after treatment with radiotherapy. Methods and Materials: Seventy-eight patients (42 male, 36 female) diagnosed with stage I POAML between 1991 and 2010 at Kobe University Hospital were included. The median age was 60 years (range, 22-85 years). The median radiation dose administered was 30.6 Gy. Rituximab-based targeted therapy and/or chemotherapy was performed in 20 patients (25.6%). Local control (LC), recurrence-free survival (RFS), and overall survival (OS) rates were calculated using the Kaplan-Meier method. Results: The median follow-up duration was 66 months. Major tumor sites were conjunctiva in 37 patients (47.4%), orbita in 29 (37.2%), and lacrimal glands in 12 (15.4%). The 5- and 10-year OS rates were 98.1% and 95.3%, respectively. The 5- and 10-year LC rates were both 100%, and the 5- and 10-year RFS rates were 88.5% and 75.9%, respectively. Patients treated with a combination of radiotherapy and targeted therapy and/or chemotherapy had a trend for a better RFS compared with those treated with radiotherapy alone (p = 0.114). None developed greater than Grade 2 acute morbidity. There were 14 patients who experienced Grade 2 morbidities (cataract: 14; retinal disorders: 7; dry eye: 3), 23 patients who had Grade 3 morbidities (cataract: 23; dry eye: 1), and 1 patient who had Grade 4 glaucoma. Conclusions: Radiotherapy for POAML was shown to be highly effective and safe for LC and OS on the basis of long-term observation. The absence of systemic relapse in patients with combined-modality treatment suggests that lower doses of radiation combined with targeted therapy may be worth further study.
Han, Jae Joon; Kim, Tae Min; Jeon, Yoon Kyung; Kim, Mee Kum; Khwarg, Sang In; Kim, Chul-Woo; Kim, Il Han; Heo, Dae Seog
Ocular adnexal lymphoma (OAL) has been associated with Chlamydophila psittaci infection, for which doxycycline has been suggested as a treatment option. We conducted this study to evaluate the long-term results of first-line doxycycline treatment in patients with OAL. Ninety patients with histologically confirmed OAL with marginal zone B cell lymphoma were enrolled. Each patient received one or two cycles of doxycycline (100 mg bid) for 3 weeks. After a median follow-up period of 40.5 months (8-85), the 5-year progression-free survival (PFS) rate was 60.9 %. All patients were alive at the last follow-up date. Thirty-one patients (34 %) showed local treatment failure without systemic spread. However, PFS rate in these patients was 100 % after salvage chemotherapy and/or radiotherapy. PFS was independently predicted in multivariate analysis by the tumor-node-metastasis (TNM) staging (hazard ratio [HR], 4.35; 95 % confidence interval [CI], 2.03-9.32; P < 0.001) and number of cycles of doxycycline (HR, 0.31; 95 % CI, 0.14-0.69; P = 0.004). No serious adverse event was reported during doxycycline therapy. In conclusion, first-line doxycycline therapy was effective and safe. Patients who failed to respond to doxycycline therapy were successfully salvaged with chemotherapy and/or radiotherapy without compromising long-term outcomes. Patients with T1N0M0 disease could be considered good candidates for first-line doxycycline.
Prayson, Richard A
This report documents a 47-year-old man who presented with back pain, uveitis and an elevated Westergren sedimentation rate. On biopsy, a paraspinal lesion showed a nonspecific chronic inflammatory cell infiltrate. The eye symptoms, after initially responding to immunosuppressive therapy, worsened and progressed to pain, resulting in an extirpation of the right eye. The histopathology of the excised eye showed an inflammatory pseudotumor marked by a lymphoplasmacytic infiltrate, areas of fibrosis, rare evidence of obliterative phlebitis and, focally, over 20 Immunoglobulin G4 (IgG4)-positive staining cells per high power microscopic field. IgG4-related ophthalmic disease is a relatively rare inflammatory lesion involving the eye and periorbital region. It is defined by a marked lymphoplasmacytic cell infiltrate, fibrosis obliterative phlebitis and increased IgG4 immunostaining (at least 10 cells per high power microscopic field in excised tissue). The entity is not unique to the eye, and has been described in other organs including the brain, endocrine organs, liver and kidney. The clinical presentation is often related to the location of the inflammatory infiltrates, and treatment involves the use of corticosteroids and other immunosuppressive agents. It is important to recognize IgG4-related ophthalmic disease because the condition appears to put patients at increased risk of developing lymphoma.
Stagner, Anna M; Jakobiec, Frederick A
Ophthalmic pathologic studies of retinoblastoma first definitively elucidated a genetic etiology for cancer three decades ago. Advances in DNA sequencing, protein expression profiling, and the exploration of epigenetics have since led to categorization of tumors and clinical prognostication based on genetic aberrancy. There are now many neoplasms that are defined by a characteristic genetic signature. In the past several years alone, much has been discovered in regard to the original tumor-suppressor gene initially defined in retinoblastoma as well as in other intraocular tumors such as medulloepithelioma. Our further understanding of ocular adnexal tumors that result in substantial morbidity and mortality, such as sebaceous carcinoma, has also benefited from a genetic approach. In this article, we review the clinicopathologic features of the foregoing three entities--retinoblastoma, medulloepithelioma, and sebaceous carcinoma--in order to highlight discoveries in their underlying abnormal molecular genetic functioning.
Nakanuma, Yasuni; Harada, Kenichi; Sasaki, Motoko; Sato, Yasunori
The biliary tract and pancreas are located closely anatomically, and both develop from the endoderm foregut almost at the same time. Interestingly, the lining epithelia of the bile duct and main pancreatic duct show similar morphologies and phenotypes, and both are accompanied by periductal glands. Furthermore, the exocrine pancreatic acini are remnantly found in the peribiliary glands. Based on these findings, it seems plausible that the biliary tract has features of pancreatic elements in addition to the duct system, which is specialized for the drainage of bile secreted by hepatic parenchyma, particularly, hepatocytes. Interestingly, some pancreatic and biliary diseases show similar pathological features and even biological behaviors. For example, extrahepatic cholangiocarcinoma and ductal adenocarcinoma of the pancreas share many clinicopathological features. Both of them are hypothesized to arise from similar preneoplastic and early neoplastic intraepithelial lesions. Intraductal papillary tumors, with frequent mucin hyperproduction, develop in the pancreas (intraductal papillary mucinous neoplasm) and also in the biliary tract (intraductal papillary neoplasm of the bile duct). IgG4-related disease affects the biliary tract (IgG4-related sclerosing cholangitis) and the pancreas (autoimmune pancreatitis) in the same patients, with both showing similar morphologies. Herein, we propose that these non-neoplastic and neoplastic biliary diseases showing similarities to corresponding pancreatic diseases could be included in a new disease concept "biliary diseases with pancreatic counterparts". Based on this new concept, information obtained in biliary tract diseases could be applied to the analysis of pancreatic disease and vice versa, and also novel therapeutical strategies and molecular and genetic studies on pancreatic and biliary diseases may be developed with a unified approach.
Aspects of autoimmune thyroid disease updated in this review include: immunoglobulin G4 (IgG4)-related thyroid disease (Riedel's thyroiditis, fibrosing variant of Hashimoto's thyroiditis, IgG4-related Hashimoto's thyroiditis, and Graves' disease with elevated IgG4 levels); recent epidemiological studies from China and Denmark indicating that excess iodine increases the incidence of Hashimoto's thyroiditis and hypothyroidism; immunomodulatory agents (ipilimumab, pembrolizumab, nivolumab) activate immune response by inhibiting T-cell surface receptors which down-regulate immune response, i.e., cytotoxic T-lymphocyte antigen 4 and programmed cell death protein 1 pathways; alemtuzumab is a humanised monoclonal antibody to CD52 which causes immune depletion and thyroid autoimmune disease especially Graves' hyperthyroidism; small molecule ligand (SML) agonists which activate receptors, SML neutral antagonists, which inhibit receptor activation by agonists, and SML inverse agonists which inhibit receptor activation by agonists and inhibit constitutive agonist independent signaling have been identified. SML antagonism of thyroid-stimulating hormone-receptor stimulatory antibody could treat Graves' hyperthyroidism and Graves' ophthalmopathy; and thyroxine treatment of subclinical hypothyroidism can produce iatrogenic subclinical hyperthyroidism with the risk of atrial fibrillation and osteoporosis. The increased risk of harm from subclinical hyperthyroidism may be stronger than the potential benefit from treatment of subclinical hypothyroidism. PMID:28029020
Andrew, Nicholas; Kearney, Daniel; Sladden, Nicole; Goss, Alastair; Selva, Dinesh
A 71-year-old woman presented with erythematous, nontender, bilateral hard palate nodules of 6-month duration. Biopsy showed collagenous sclerosis and a follicular lymphoplasmacytic infiltrate among the minor salivary glands. Immunoglobulin G (IgG) and IgG4 staining showed 280 IgG4(+) cells per high-power field and a ratio of IgG4(+) to IgG(+) cells of 0.8. The patient subsequently developed bilateral lacrimal gland and parotid gland enlargement associated with an increased serum IgG4 level of 3,031 mg/dL (≤ 135 mg/dL). Left lacrimal gland biopsy confirmed IgG4-related dacryoadenitis. The patient declined corticosteroid treatment for IgG4-related disease (IgG4-RD) and remained stable at 15 months after the first presentation. Spontaneous, partial resolution of the palatal lesion was observed during follow-up. IgG4-RD should be considered in the differential diagnosis of lymphoplasmacytic lesions of the hard palate.
Lee, In Ok; Yoon, Jung Won; Chung, Dawn; Yim, Ga Won; Nam, Eun Ji; Kim, Sunghoon; Kim, Sang Wun
Objective The purpose of this study was to compare clinical and surgical outcomes between laparo-endoscopic single-site (LESS) surgery and traditional multiport laparoscopic (TML) surgery for treatment of adnexal tumors. Methods Medical records were reviewed for patients undergoing surgery for benign adnexal tumors between January 2008 and April 2012 at our institution. All procedures were performed by the same surgeon. Clinical and surgical outcomes for patients undergoing LESS surgery using Glove port were compared with those patients undergoing TML surgery. Results A review of 129 patient cases undergoing LESS surgery using Glove port and 100 patient cases undergoing TML surgery revealed no significant differences in the baseline characteristics of the two groups. The median operative time was shorter in the LESS group using Glove port at 44 minutes (range, 19-126 minutes) than the TML group at 49 minutes (range, 20-196 minutes) (P=0.0007). There were no significant differences between in the duration of postoperative hospital stay, change in hemoglobin levels, pain score or the rate of complications between the LESS and TML groups. Conclusion LESS surgery showed comparable clinical and surgical outcomes to TML surgery, and required less operative time. Future prospective trials are warranted to further define the benefits of LESS surgery for adnexal tumor treatment. PMID:25264529
Abbas, A.M.; Zahran, K.M.; Nasr, A.; Kamel, H.S.
Objective: To determine the most discriminating two-dimensional gray-scale and colour Doppler sonographic features that allow differentiation between malignant and benign adnexal masses, and to develop a scoring model that would enable more accurate diagnosis with those features. Methods: A cross sectional prospective study was conducted on patients scheduled for surgery due to presence of adnexal masses at Woman’s Health Center, Assiut University, Egypt between October 2012 and October 2013. All patients were evaluated by 2D ultrasound for morphological features of the masses combined with colour Doppler examination of their vessels. The final diagnosis, based on histopathological analysis, was used as a gold standard. Results: One hundred forty-six patients were recruited, 104 with benign masses, 42 with malignant masses. Features that allowed statistically significant discrimination of benignity from malignancy were; volume of mass, type of mass, presence and thickness of septae, presence and length of papillary projections, location of vessels at colour Doppler and colour score. A scoring model was formulated combining these features together; Assiut Scoring Model (ASM). The cut-off level with the highest accuracy in detection of malignancy, was ≥6, had a sensitivity of 93.5% and specificity of 92.2%. Conclusion: Our Scoring Model; a multiparameter scoring using four gray-scale ultrasound and two colour Doppler features, had shown a high sensitivity and specificity for prediction of malignancy in adnexal masses compared with previous scoring systems. PMID:25009729
Cameselle-Teijeiro, José; Ladra, María Jesús; Abdulkader, Ihab; Eloy, Catarina; Soares, Paula; Barreiro, Francisco; Sobrinho-Simões, Manuel; Beiras-Iglesias, Andrés
The present study describes in depth a case of Riedel thyroiditis (RT) to clarify its pathogenesis and its putative inclusion in the spectrum of IgG4-related disease. We report the clinicopathological, immunohistochemical, and ultrastructural features of a case of RT in a 39-year-old white Spanish woman, admitted with a hard goiter and cold nodule in the left thyroid lobe. This case represents 0.05 % of a series of 1,973 consecutive thyroidectomies performed in our hospital. More than 80 % of the left thyroid lobe was effaced by fibrosis and inflammation (lymphocytes, 57 IgG4+ plasma cells per 1 high-power field, an IgG4/IgG ratio of 0.67, and eosinophils) with extension into the surrounding tissues and occlusive phlebitis. Immunostaining for podoplanin (D2-40) detected signs of increased lymphangiogenesis in the fibroinflammatory areas that were confirmed by electron microscopy. A strong, diffuse stain for podoplanin and transforming growth factor ß1 was also detected in the same areas. The increased number of lymphatic vessels in RT is reported for the first time. Our findings support the inclusion of RT within the spectrum of IgG4-related thyroid disease (IgG4-RTD). Although the etiology and physiopathology of IgG4-RTD still remain elusive, the results obtained in the present case suggest the participation of lymphatic vessels in the pathogenesis of RT.
Topçu, Hasan Onur; İskender, Can Tekin; Ceran, Ufuk; Kaymak, Oktay; Timur, Hakan; Uygur, Dilek; Danışman, Nuri
We aimed to evaluate the diagnostic accuracy of serum D-dimer levels in pregnant women with adnexal torsion (AT). The pregnant women with ovarian cysts who suffered from pelvic pain were divided into two groups; the first group consisted of the cases with surgically proven as AT (n = 17) and the second group consisted of the cases whose pain were resolved in the course of follow-up period without required surgery (n = 34). The clinical characteristics and serum D-dimer levels were compared between the groups. Patients with AT had a higher rate of elevated serum white blood cell (WBC) count (57% vs. 16%, p = 0.04) and serum D-dimer levels (77% vs. 21%, p < 0.01) on admission in the study group than in the control group. Elevated D-dimer and cyst diameter larger than 5 cm yielded highest sensitivity (82% for each); whereas the presence of nausea and vomiting and elevated CRP had the highest specificity (85% and 88%, respectively). This is the first study that evaluates the serum D-dimer levels in humans in the diagnosis of AT, and our findings supported the use of D-dimer for the early diagnosis of AT in pregnant women.
Sundberg, J P; Beamer, W G; Shultz, L D; Dunstan, R W
Nearly 100 mouse mutations have been described as causing some type of abnormality of the skin or hair. As only a few of these mutations have been studied in detail, they remain an untapped resource for furthering knowledge of basic cutaneous physiology and understanding the pathophysiology of analogous diseases in humans. Several diverse murine mutations are discussed. These include "asebia," a mildly hyperkeratotic disorder with sebaceous gland hypoplasia; "ichthyosis," an example of abnormal hair growth associated with hyperkeratosis; "rhino" and "hairless," two related examples of congenital follicular malformations; and "flaky skin", a potential animal model of eruptive psoriasis.
Mora-Horna, Eduardo R; Rojas-Padilla, Rubí; López, Vianhi G; Guzmán, Martín J; Ceriotto, Ariel; Salcedo, Guillermo
The purpose of the study was to describe the main clinical and epidemiologic characteristics, treatment options, and outcome in a large series of patients with periocular and orbital amyloidosis. This is a retrospective, descriptive, observational study of a case series of 14 patients with periocular and orbital amyloidosis and is a review of previously published cases with this diagnosis between September 2004 and January 2015. In this study, we analyzed our 14 patients in conjunction with 69 well-documented cases of orbital and/or periocular amyloidosis previously reported, with a total of 83. Of these, 54 were female (65.1 %), 28 male (33.7 %), and one with unspecified gender. The mean age at diagnosis was 54.9 years (range, 18-87). The localization of the amyloidosis was classified as superficial, deep and combined, with involvement of 53 (63.9 %), 26 (31.3 %), and four cases (4.8 %) in each group, respectively. The main findings in superficial amyloidosis were mass or tissue infiltration (84.9 %) and ptosis (30.2 %) and, in the cases with deep involvement, mass (65.4 %), proptosis (57.7 %), limited ocular movements (34.6 %), ocular displacement (30.8 %), and ptosis (26.9 %). The cases with combined involvement presented with signs and symptoms of the two groups. Regarding the outcome, 43 patients were reported stable after the diagnosis and 21 had recurrence or required new surgical procedures. Periocular and orbital amyloidosis is a rare disease that can present with a variety of symptoms and signs depending on the localization and extension of involvement. Its prompt recognition is important in order to investigate systemic disease, which will affect the prognosis of each case.
Yajima, Hidetaka; Yamamoto, Motohisa; Shimizu, Yui; Sakurai, Nodoka; Suzuki, Chisako; Naishiro, Yasuyoshi; Imai, Kohzoh; Shinomura, Yasuhisa; Takahashi, Hiroki
Both multicentric Castleman's disease (MCD) and immunoglobulin (Ig)G4-related disease (IgG4-RD) are systemic diseases, presenting with hypergammaglobulinemia and elevated serum levels of IgG4. However, with regard to histopathological findings, MCD shows atrophic germinal centers. On the other hand, expanded germinal centers are detected in IgG4-RD. We extracted germinal centers from specimens of each disorder by microdissection and analyzed the expression of mRNAs by real-time polymerase chain reaction to clarify the mechanisms underlying atrophied germinal centers in MCD. This analysis disclosed loss of interleukin (IL)-21 and B cell lymphoma (Bcl)-6 in the germinal centers of MCD. Loss of IL-21 is considered to be involved in the disappearance of Bcl-6 and leads to atrophied germinal centers in MCD.
Dagklis, A; Ponzoni, M; Govi, S; Cangi, M G; Pasini, E; Charlotte, F; Vino, A; Doglioni, C; Davì, F; Lossos, I S; Ntountas, I; Papadaki, T; Dolcetti, R; Ferreri, A J M; Stamatopoulos, K; Ghia, P
Evidence from certain geographical areas links lymphomas of the ocular adnexa marginal zone B-cell lymphomas (OAMZL) with Chlamydophila psittaci (Cp) infection, suggesting that lymphoma development is dependent upon chronic stimulation by persistent infections. Notwithstanding that, the actual immunopathogenetical mechanisms have not yet been elucidated. As in other B-cell lymphomas, insight into this issue, especially with regard to potential selecting ligands, could be provided by analysis of the immunoglobulin (IG) receptors of the malignant clones. To this end, we studied the molecular features of IGs in 44 patients with OAMZL (40% Cp-positive), identifying features suggestive of a pathogenic mechanism of autoreactivity. Herein, we show that lymphoma cells express a distinctive IG repertoire, with electropositive antigen (Ag)-binding sites, reminiscent of autoantibodies (auto-Abs) recognizing DNA. Additionally, five (11%) cases of OAMZL expressed IGs homologous with autoreactive Abs or IGs of patients with chronic lymphocytic leukemia, a disease known for the expression of autoreactive IGs by neoplastic cells. In contrast, no similarity with known anti-Chlamydophila Abs was found. Taken together, these results strongly indicate that OAMZL may originate from B cells selected for their capability to bind Ags and, in particular, auto-Ags. In OAMZL associated with Cp infection, the pathogen likely acts indirectly on the malignant B cells, promoting the development of an inflammatory milieu, where auto-Ags could be exposed and presented, driving proliferation and expansion of self-reactive B cells.
Cani, Andi K.; Soliman, Moaaz; Hovelson, Daniel H.; Liu, Chia-Jen; McDaniel, Andrew S.; Haller, Michaela J.; Bratley, Jarred; Rahrig, Samantha; Li, Qiang; Briceño, César A.; Tomlins, Scott A.; Rao, Rajesh C.
Non-Hodgkin lymphoma of the orbit and ocular adnexa is the most common primary orbital malignancy. Treatments for low- (extra-nodal marginal zone and follicular lymphomas) and high-grade (diffuse large B-cell lymphoma) are associated with local and vision-threatening toxicities. High-grade lymphomas relapse frequently and exhibit poor survival rates. Despite advances in genomic profiling and precision-medicine, orbital and ocular adnexal lymphomas remain poorly characterized molecularly. We performed targeted next-generation sequencing profiling of 38 formalin-fixed, paraffin-embedded, orbital and ocular adnexal lymphomas obtained from a single-center using a panel targeting near-term, clinically-relevant genes. Potentially actionable mutations and copy-number alterations were prioritized based on gain- and loss-of function analyses, catalogued approved and investigational therapies. Of 36 informative samples, including marginal zone lymphomas (n=20), follicular lymphomas (n=9), and diffuse large B-cell lymphomas (n=7), 53% harbored a prioritized alteration (median=1, range 0–5/sample). MYD88 was the most frequently altered gene in our cohort, with potentially clinically-relevant hot-spot gain-of-function mutations identified in 71% of diffuse large B-cell and 25% of marginal zone lymphomas. Prioritized alterations in epigenetic modulators were common and included gain-of-function EZH2 and loss-of-function ARID1A mutations (14% of diffuse large B-cell lymphomas and 22% of follicular lymphomas contained alterations in each of these two genes). Single prioritized alterations were also identified in the histone methyltransferases KMT2B (follicular lymphoma) and KMT3B (diffuse large B-cell lymphoma). Loss-of-function mutations and copy-number alterations in the tumor suppressors TP53 (diffuse large B-cell and follicular lymphoma), CDKN2A (all subtypes), PTEN (diffuse large B-cell lymphoma), ATM (diffuse large B-cell lymphoma) and NF1 (diffuse large B-cell lymphoma
ZHOU, RONG-RONG; ZHAO, QI-MING; ZHANG, XU-DONG; GAN, JING-BING
Microcystic adnexal carcinoma (MAC) is a rare and locally aggressive adenocarcinoma with low-grade malignancy. The present study describes the first reported case and treatment of a Chinese male with a MAC located on the nasal dorsum and nosewing. A 44-year-old man presented with a nasal deformity caused by local repeated infections following an accidental injury to the nose 20 years previously. The nose had been injured by a brick, and treatment at a local hospital 12 years previously had resulted in a nasal scar and a gradually enlarging mass. A physical examination revealed a hypertrophic deformity of the nose and an indurated scar plaque, measuring 2.0×2.0 cm, on the nasal dorsum and nosewing. Microscopic examination revealed a tumor consisting of solid cell nests and a cystic structure with a capsular space. In addition, ductal cells of an adnexal cell origin were visible in the outer epithelium. The medial portion exhibited a microductal structure and invasion of deeper tissues without evident atypia. The tumor cells presented normal nuclear to cytoplasmic ratios and minimal mitotic activity. Pathological examination verified that the tumor was a MAC of low-grade malignancy. A complete surgical resection was performed via Mohs micrographic surgery (MMS), and reconstruction was achieved using an expanded rotational forehead skin flap. No tumor recurrence was detected after a three-year follow-up period. Therefore, for effective treatment of similar MAC cases, complete surgical resection using MMS is recommended, and successful reconstruction may be achieved using an expanded skin flap. PMID:26622465
Şen, Serhat; Kuru, Oğuzhan; Akbayır, Özgür; Oğuz, Hilal; Yasasever, Vildan; Berkman, Sinan
Objective Investigation of serum markers which could be used in the malignancy prediction of adnexal masses. Material and Methods Vascular endothelial growth factor (VEGF), interleukin 6 (IL-6), leptin, C-reactive protein (CRP), creatine-kinase-MB (CK-MB) and cancer antigen 15-3 (CA 15-3) levels were determined prospectively in serum samples that were obtained from patients who underwent surgery for an adnexal mass and who were referred to Istanbul University, Faculty of Medicine, Department of Obstetrics and Gynecology, between 2009 and 2011, and then were compared with the serum samples of completely healthy outpatient patients as a control group. Based onto the ovarian cancer status, cases were divided into four groups: 13 patients were included in the early-stage malignant group, 12 patients were included in the advanced-stage malignant group, 25 in the benign group and 19 in the healthy control group. Patients with only epithelial ovarian cancer were included into the cancer group. Ethics Commitee approval was obtained for this study. The budget was supported by the Istanbul University Scientific Research Projects Unit. Results Results related with sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and odds ratio (OR), respectively, and the following values were calculated: 48%, 95%, 92%, 59% and +OR 9.6 −OR 0.5 for CA; 15-3; 52%, 75%, 72%, 55%, +OR 2.08 −OR 0.64 for leptin; 72%, 70%, 75%, 66% 2.4-0.5 for IL-6; 24%, 80%, 60%, 45%, 1.2-0.92 for VEGF; 68%, 30%, 55%, 43%, 0.97–1.06 for CRP; and 8%, 70%, 25%, 38%, 026–1.31 for CK-MB. Conclusion CA 15-3, IL-6, Leptin, VEGF and CRP were effective in the prediction of benign and malignant masses; however they may be more suitable in selected cases as they have a limited use because of their inadequate potential regarding sensitivity and specificity. PMID:24591997
Vasconcelos, Luiza; Vieira, Érica Cristina; Minicucci, Eliana Maria; Salvio, Ana Gabriela; de Souza, Mair Pedro; Marques, Mariangela Esther Alencar; Marques, Silvio Alencar
Graft-versus-host disease is observed mainly in recipients of hematopoietic cell transplantation and is expressed by cutaneous or systemic signals and symptoms. Graft-versus-host disease is clinically classified as acute or chronic. Chronic Graft-versus-host disease occurs in up to 70% of hematopoietic cell transplanted patients and its clinical manifestations have important impact on morbidity and quality of life. The authors report an expressive cutaneous, oral and adnexal involvement in a patient with chronic Graft-versus-host disease with multiple lesions of lichenoid and atrophic pattern. PMID:24173188
We discuss the histological and immunohistochemical features of 6 cases of urothelial carcinomas of lipid cell variant and 4 cases with shadow cell differentiation, one of which showed additionally sebaceous differentiation, one of which shows additional sebaceous differentiation, from our archive cases from the last 15 years. Conventional urothelial carcinoma (UC) was seen in all lipid cell variant cases, and micropapillary carcinoma was seen in 3. The ratio of the lipid cell component was between 10% and 40% in these 6 cases. Typical histologic features of the lipid cell variant include lipoblast-like cells with a notched nuclear appearance, abundant vacuoles, an eccentric nucleus, and pagetoid spread in some areas. GATA3 and pancytokeratin AE1/AE3 immunohistochemical staining were positive in all cases. Adipophilin was positive in various degrees in 5 of the 6 lipid cell variant cases but was also positive in the case with sebaceous differentiation. α-methylacyl-CoA racemase was positive in the lipid cell areas and negative or focal weakly positive in the conventional UC areas in 4 of the 6 cases. Vimentin, S-100 protein, and PAX8 were negative in the lipid cell component. Follow-up information was available for all cases with follow-up ranging from 6 to 84 months (mean, 34 months). Four patients died of the disease. One pT4 patient who had been followed up for 6 months lives with the disease, whereas another is disease free. In conclusion, the lipid cell variant is a rare UC variant that usually presents at an advanced stage, and tumor cells are histologically similar to lipoblasts, resemble sebaceous differentiation, and show positive immunohistochemical staining with adipophilin.
Jun, Heungman; Jung, Cheol Woong
Immunoglobulin (Ig) G4-related disease is reportedly among the various causes of inflammatory abdominal aortic aneurysm (IAAA). Many IgG4-related diseases are closely related to allergic constitution and autoimmune disease. We report a case of a 72-year-old man with IgG4-related IAAA associated with myasthenia gravis, with contained rupture.
Zhang, Haoze; Li, Ping; Wu, Di; Xu, Dong; Hou, Yong; Wang, Qian; Li, Mengtao; Li, Yongzhe; Zeng, Xiaofeng; Zhang, Fengchun; Shi, Qun
To characterize serum IgG subclass levels in several autoimmune diseases, including primary Sjogren syndrome (pSS), systemic sclerosis (SSc), systemic lupus erythematosus (SLE), and primary biliary cirrhosis (PBC). We aimed to analyze serum IgG subclass distribution and to test whether serum IgG4 levels are elevated in these diseases. Serum IgG subclass levels from 102 pSS, 102 SSc, 100 SLE, and 59 PBC patients, as well as 40 healthy controls (HCs), were measured using the immunonephelometric assay. The distribution of IgG subclasses among these autoimmune diseases was analyzed. In this cross-sectional study, serum IgG1 (IgG1/IgG) and/or IgG3 (IgG3/IgG) were significantly increased, compared with those in HCs. Only 6.34% of patients had levels of serum IgG4 >135 mg/dL. There were no significant differences in the frequency of elevated serum IgG4 levels between patients and HC. In pSS, serum IgG1 levels were much higher than those in other disease groups, whereas serum IgG2 and IgG3 levels were most prominently increased in PBC. A strikingly different serum IgG subclass distribution was detected in patients with autoimmune diseases compared with HCs. Serum IgG subclass levels also showed distinct characteristics among different autoimmune diseases. Serum IgG4 levels in these patients were lower or not much higher than those in HCs, which differed from IgG4-related diseases.
Faria, Ricardo Jacaranda; Clemente, Cintia Mendes; Carneiro, Fabiana P.; Santos-Neto, Leopoldo
Background Pancreatitis and exocrine pancreatic insufficiency may occur as extraintestinal manifestations of inflammatory bowel disease. Recently, autoimmune pancreatitis and colitis have been described as presentations of IgG4-related disease. IgG4+ plasma cells have been identified in colon tissue from patients with refractory forms of inflammatory bowel disease. The presence of elevated serum/tissue levels of IgG4 and the frequency of exocrine pancreatic insufficiency in inflammatory bowel disease are still a source of controversy. Our aim was to investigate the meaning of elevated IgG4 levels in patients with inflammatory bowel disease. Methods A cross-sectional study analyzed 56 patients with a diagnosis of inflammatory bowel disease recruited by convenience sampling from two tertiary centers in Midwestern Brazil. All patients underwent fecal pancreatic elastase testing for detection of exocrine pancreatic insufficiency and serum IgG4 measurement. Findings were correlated with clinical and epidemiological data and disease activity. Results Elevated serum IgG4 levels were found in 10 patients, and were most frequent in ulcerative colitis (nine cases), with a prevalence ratio of 16.42 (95% CI: 3.32 - 79.58). Ten patients (10 of 56, 17.8%) were diagnosed with exocrine pancreatic insufficiency, which did not correlate with disease activity, and serum IgG4 levels. Conclusion Exocrine pancreatic insufficiency is prevalent in patients with inflammatory bowel disease, but it is not associated with elevated serum IgG4 levels. The high prevalence of elevated serum IgG4 in ulcerative colitis suggests that this parameter has potential for use as a diagnostic biomarker. PMID:27785293
Mulay, Kaustubh; Wick, Mark R
IgG4-related disease (IgG4-RD) is a distinct entity that frequently occurs in an ophthalmic location. As such, IgG4-RD is not limited to the orbit but may also involve other anatomical structures in and around the eye. Hence, the term 'ophthalmic IgG4-RD' is preferred over 'orbital IgG4-RD.' A high level of suspicion for the diagnosis can be derived from careful clinicoradiologic examination; the use of immunohistochemical staining for IgG4 in the context of characteristic histopathologic features is needed to reach a correct diagnosis. Recently described diagnostic criteria for ophthalmic IgG4-RD address subtle, yet significant, differences from IgG4-RD as seen in other systemic sites. Serum IgG4 titers are neither sensitive nor specific for the diagnosis of IgG4-RD and should not relied upon solely. Although most cases respond well to therapy with glucocorticoids, refractoriness to treatment and relapses are common. They necessitate the use of additional immunotherapy in such patients.
Humphreys, Ian M.
Objective: Immunoglobulin G4 (IgG4) related sclerosing disease (RSD) of the paranasal sinuses is a rare lesion of dense lymphoplasmacytic tissue, with a high proportion of IgG4+ plasma cells. We presented a rare case of IgG4-RSD with isolated involvement of the paranasal sinuses in the absence of multiorgan involvement. Methods: A case report and comprehensive literature review. Results: To our knowledge, only 11 cases of IgG4-RSD with paranasal sinus involvement have been reported. Patients with IgG4-RSD commonly present with epistaxis and symptoms that mimic chronic rhinosinusitis, e.g., rhinorrhea, nasal obstruction, and facial pressure. On imaging, an expansive and erosive process is described. Surgery provides tissue for immunohistologic evaluation; however, there is a paucity of evidence about the direct extent of surgical resection or medical therapies. Postoperative steroids were typically started, although the regimen was not standardized. Conclusion: Few cases of paranasal sinus IgG4-RSD have been reported in the literature. Evidence-based recommendations regarding treatment and surveillance of paranasal sinus IgG4-RSD are lacking; however, most reports describe systemic steroids as the mainstay of treatment. This single subject analysis, with a review of previously reported cases adds to the expanding body of data related to this rare disorder. PMID:27658185
... 1 link) Retroperitoneal fibrosis Educational Resources (3 links) Disease InfoSearch: Retroperitoneal fibrosis MalaCards: retroperitoneal fibrosis Orphanet: IgG4-related retroperitoneal fibrosis Patient Support and Advocacy Resources (2 ...
Andrew, Nicholas H; Coupland, Sarah E; Pirbhai, Adnan; Selva, Dinesh
Lymphoid hyperplasia (LH) is a benign lymphoproliferative disorder that, in a minority of cases, may be associated with concurrent or metachronous non-Hodgkin lymphoma. LH cases are further subdivided into "reactive" and "atypical" categories based on the presence or absence of unequivocal malignant features. With improving molecular diagnostic technologies, "reactive" LH is by far the most common category of LH, with atypical LH accounting for only a small minority of specimens. Similarly, lesions previously diagnosed as LH are now being revised as low-grade B-cell non-Hodgkin lymphoma or diagnosed as newly described benign conditions such as IgG4-related disease. Additional differential diagnoses include specific and nonspecific orbital inflammations, infiltrative processes, and depositions. Hence, there are emerging changes in the patterns and proportions of entities that fall within the spectrum of lymphoproliferative disorders of the orbit and ocular adnexa. Reactive LH and low-grade malignant lymphoproliferative disorders in the orbit and ocular adnexa are clinically and radiologically indistinguishable from each other, requiring tissue biopsy in all cases. The prognosis of ocular adnexal LH is generally favorable, but the small risk of non-Hodgkin lymphoma mandates follow-up for at least 5 years. We summarize the current state of knowledge on LH occurring in the orbit and ocular adnexa.
Usui, Yoshihiko; Rao, Narsing A.; Takase, Hiroshi; Tsubota, Kinya; Umazume, Kazuhiko; Diaz-Aguilar, Daniel; Kezuka, Takeshi; Mochizuki, Manabu; Goto, Hiroshi; Sugita, Sunao
Infectious agents have been identified as a major cause of specific types of human cancers worldwide. Several microorganisms have been identified as potential aggravators of ocular adnexal neoplasms; however, given the rarity of these neoplasms, large epidemiological studies are difficult to coordinate. This study aimed to conduct an exhaustive search for pathogenic DNA in lymphoproliferative disorders (LPD) of the ocular adnexa in a total of 70 patients who were diagnosed with LPD of the ocular adnexa between 2008 and 2013. Specimens were screened for bacterial, viral, fungal, and parasitic DNA by multiplex polymerase chain reaction (PCR) and quantitative real-time PCR. Among cases of conjunctival mucosa-associated lymphoid tissue lymphoma, human herpes virus (HHV)-6, HHV-7, chlamydia, Epstein-Barr virus (EBV) and bacterial 16S ribosomal DNA were detected. In cases of IgG4-related ocular disease, similar pathogens were detected but in a larger number of patients. Our PCR assays detected DNAs of various infectious agents in tumor specimens, especially HHV6, HHV7, and EBV, with different positive rates in various types of LPD. Chronic inflammatory stimulation or activation of oncogenes from these infectious agents might be involved in the pathogenesis of LPD of the ocular adnexa. PMID:27830722
Iwata, Yohei; Mizoguchi, Yoshikazu; Takahashi, Masayuki; Tanaka, Beni; Kuroda, Makoto; Yagami, Akiko; Matsunaga, Kayoko
Immunoglobulin G4-related disease (IgG4-RD) is a newly recognized disease characterized by elevated serum IgG4 levels, tissue infiltration rich in IgG4(+) plasma cells. We report on a case which was first considered as pseudolymphoma from the histopathological analysis, but finally diagnosed as IgG4-related skin lesions. As the morphological features of cutaneous involvement of IgG4-RD are consistent with those of cutaneous pseudolymphoma, we tried immunostaining past potential cases of IgG4-RD. Thirty-two skin specimens (15 men and 17 women; mean age, 53 years) diagnosed as having pseudolymphoma were retrieved from the archives to conduct hematoxylin-eosin, IgG and IgG4 staining. Out of the 32 cases of cutaneous pseudolymphoma, germinal center formation was seen in 22 cases, and moderate-severe fibrosis was seen in seven cases. Eleven cases showed more than 10 IgG4(+) plasma cell infiltration/high-power field, and among these 11 cases, seven cases (22%) showed A ratio of IgG4(+)/IgG(+) cells of more than 40%. Thus, out of the 32 cases of cutaneous pseudolymphomas, two cases (6.3%) satisfied IgG4-RD histopathological diagnostic criteria. As clinical presentations and histopathological features of skin involvement of IgG4-RD are analogous to cutaneous B-cell pseudolymphoma, careful identification is required through systemic examination, serum IgG4 measurement and other means.
Cornell, Lynn D; Chicano, Sonia L; Deshpande, Vikram; Collins, A Bernard; Selig, Martin K; Lauwers, Gregory Y; Barisoni, Laura; Colvin, Robert B
Autoimmune pancreatitis (AIP) is a mass-forming chronic fibroinflammatory condition centered on the pancreatobiliary system and characterized by predominant immunoglobulin G4 (IgG4)-positive plasma cells. Recent reports have brought to light the multiorgan involvement of this disease. We describe a series of 5 cases of tubulointerstitial nephritis (TIN) associated with AIP and characterize the clinical, pathologic, ultrastructural, and immunopathologic features of TIN. The specimens consisted of 4 biopsies and 1 nephrectomy. The average patient age was 64 years (range 45 to 78) and the male to female ratio was 4:1. All had histologic and/or clinical and radiographic evidence of AIP, mass-forming sclerosing cholangitis, or both. The clinical impression in 4 patients was a renal mass or vasculitis. Two patients had renal insufficiency. Histologic preparations revealed a dense tubulointerstitial lymphoplasmacytic infiltrate. Eosinophils were often numerous. Tubulitis and tubular injury were present, along with tubular atrophy with focally thickened tubular basement membranes (TBMs). The histologic appearance ranged from a cellular, inflammatory pattern without tubular atrophy to a striking expansive interstitial fibrosis with tubular destruction. The nephrectomy specimen demonstrated a masslike nodular pattern of inflammation with normal renal tissue elsewhere. Glomeruli were uninvolved. By immunohistochemistry or immunofluorescence, numerous plasma cells in the infiltrate were positive for IgG4. TBM granular IgG deposits, predominantly of the IgG4 subclass, were detected in 4 of 5 cases by either immunofluorescence or immunohistochemistry. By electron microscopy, corresponding amorphous electron-dense deposits were present in the TBM in these cases. This type of TIN, typically characterized by a masslike lesion consisting of a lymphoplasmacytic infiltrate with eosinophils and prominent IgG4-positive plasma cells and immune-complex deposits in the TBM, may be part of
Borrelli, Maria; Geerling, Gerd
Ophthalmic Plastic and Reconstructive Surgery is a specialized area of ophthalmology that deals with the management of deformities and abnormalities of the eyelids, lacrimal system and the orbit. An ophthalmoplastic surgeon is able to identify and correct abnormalities of the ocular adnexae such as ectropion, lid retraction, conjunctival scarring with severe entropion, that can cause secondary ocular surface disorders; manage patients with watering eye, and when needed intervene with a dacryocystorhinostomy by external or endonasal approach and moreover minimize disfigurement following enucleation or evisceration and prevent further corneal damage, alleviate complains of tearing and grittiness, but also cosmetic complaints in patients with Graves’ orbitopathy. Aim of this manuscript was to review current established and recently evolving surgical procedures. PMID:26504698
Benkiran, L; Gamra, L; Lamalmi, N; Essouyeh, M; Regragui, A; Amrani, M; Souadka, A; Melabbas, M A
The purpose of this report is to describe the case of a 35-year-old patient admitted to the National Oncology Institute in Rabat, Morocco for pelvic pain and deteriorating general status ongoing for 8 months. Clinical and ultrasonographic examination showed a heterogenous mass measuring 7 cm in maximum width located inferior and lateral to the inferior aspect of the right side of the uterus. These findings were suggestive of a malignant tumor of the right ovary. Ovariectomy and omentectomy were performed. Histological examination of surgical specimens demonstrated right tubo-ovarian actinomycosis associated with peritonitis. Genital tract actinomycosis is an uncommon finding in women of childbearing age. It is due to colonization by a pyogenic bacteria (Actinomyces) usually secondary to a gastrointestinal infection, e.g. ileocecum, and sometimes in association with the presence of an intrauterine device or foreign body. Based on this case report, the authors discuss abdominopelvic actinomyocosis with emphasis on tumor-like findings that can lead to misdiagnosis by clinicians and radiologists.
Shaco-Levy, Ruthy; Bean, Sarah M; Vollmer, Robin T; Papalas, John A; Bentley, Rex C; Selim, Maria Angelica; Robboy, Stanley J
The Duke experience with 56 vulvar Paget disease patients was analyzed emphasizing pathologic features and controversial issues. Nearly all patients were Caucasian, and their mean age was 69 years. The average length of follow-up was 5.6 years. For each case, the following histologic features were evaluated and their association with disease course was examined: pseudo-invasion, adnexal involvement, signet-ring cells, cytologic atypia, glands formation, epidermal acantholysis, parakeratosis, hyperkeratosis, and chronic inflammation. The recurrence rate after surgical management was 32%, with epidermal acantholysis being the only statistically significant risk factor. Stromal invasion occurred in 10 patients (18%), and was not a statistically significant adverse prognostic indicator, although the single patient who died of the disease had the deepest stromal invasion. Recurrence was more common after resections with positive surgical margins, but this correlation was not statistically significant. Intraoperative frozen section analysis of the margins did not reduce recurrence rate, nor was it useful in attaining permanent free margins. The Paget cells were consistently reactive with cytokeratin-7 and carcinoembryonic antigen and unreactive with S-100 protein, HMB-45, and Mart-1. In addition, the tumor cells were usually positive for mucin stains. This profile helps distinguish vulvar Paget disease from its mimics, Pagetoid squamous cell carcinoma and malignant melanoma.
Lokdarshi, Gautam; Pushker, Neelam; Bajaj, Mandeep S
Orbital sclerosing inflammation is a distinct group of pathologies characterized by indolent growth with minimal or no signs of inflammation. However, contrary to earlier classifications, it should not be considered a chronic stage of acute inflammation. Although rare, orbital IgG4-related disease has been associated with systemic sclerosing pseudotumor-like lesions. Possible mechanisms include autoimmune and IgG4 related defective clonal proliferation. Currently, there is no specific treatment protocol for IgG4-related disease although the response to low dose steroid provides a good response as compared to non-IgG4 sclerosing pseudotumor. Specific sclerosing inflammations (e.g. Wegener's disease, sarcoidosis, Sjogren's syndrome) and neoplasms (lymphoma, metastatic breast carcinoma) should be ruled out before considering idiopathic sclerosing inflammation as a diagnosis.
Calvo, Jessica; Carbonell, Nicolas; Scatton, Olivier; Marzac, Christophe; Ganne-Carrie, Nathalie; Wendum, Dominique
The nodular lymphoid lesion of the liver known as reactive lymphoid hyperplasia or pseudolymphoma is rare and its pathogenesis is unknown. We report two cases of nodular lymphoid lesions of the liver with numerous IgG4-positive plasma cells in patients with primary biliary cirrhosis. Histologically, in both cases, the lesion showed a dense lymphoplasmacytic infiltrate with lymphoid follicles and granulomas. Fibrous tissue was scarce and without a storiform pattern. Obliterative phlebitis was not identified. The IgG4+ plasma cell counts were 82 and 76 per high power field, with an IgG4/IgG ratio of 75 and 64 %, respectively, which qualifies the lesions according to the diagnostic criteria for IgG4-related disease as « probable histological feature of IgG4-related disease ». There were no rearrangements of immunoglobulin heavy-chain genes and plasma cells had a polytypic pattern of kappa and lambda light-chain expression. The non-tumor liver showed primary biliary cirrhosis with destructive cholangitis without IgG4 plasma cells. In both cases, IgG4-related disease was not found in other organs neither at the time of diagnosis nor 3 years later. Serum IgG4 levels normalized after local ablation of the lesions. It seems unlikely that these lesions are a manifestation of IgG4-related disease. However, because the pathogenesis of both nodular lymphoid lesions and IgG4-related disease remains unclear, further studies are needed to elucidate a potential link between nodular lymphoid lesions of the liver and an increased number of IgG4 plasma cells. More definite conclusions will be possible when the pathogenesis of IgG4-related disease has been clarified.
Introduction Extramammary Paget’s disease is an uncommon intraepithelial neoplasm that arises in areas rich in apocrine glands. Treatment includes wide surgical excision and nonsurgical modalities. We present the case of a patient with perianal Paget’s disease with no recurrent disease after wide surgical resection. Case presentation Our patient was a 46-year-old man of Macedonian ethnicity who presented with a pruritic perianal lesion measuring up to 6cm without pain or bleeding. Two biopsies and a perianal wide surgical excision were performed. The tissue specimens were formalin-fixed and the paraffin-embedded samples analyzed according to standard histochemical and immunohistochemical procedures. Surgical perianal skin excision revealed diffuse eczematoid, whitish plaques. Pathohistology showed Paget cells infiltrating his epidermis and adnexal epithelium, with ulceration. Immunohistochemical analysis revealed positive Paget cell expression for cytokeratin 7, epithelial membrane antigen, carcinoembryonic antigen, androgen receptor and human epidermal growth factor receptor 2, and negative expression for cytokeratin 20 and melan-A. Conclusion Paget’s disease is a rare disorder that should be considered in the differential diagnosis of perianal lesions. Reporting cases of extramammary Paget’s disease is crucial for diagnostic guidelines and different therapeutic options. PMID:23786719
... History Research Resources Research at NIDDK Meetings & Events Technology Advancement & Transfer Health Information Diabetes Digestive Diseases Kidney Disease Weight Management Liver Disease Urologic Diseases Endocrine Diseases Diet & Nutrition ...
... History Research Resources Research at NIDDK Meetings & Events Technology Advancement & Transfer Health Information Diabetes Digestive Diseases Kidney Disease Weight Management Liver Disease Urologic Diseases Endocrine Diseases Diet & Nutrition ...
Gaitán, Hernando; Angel, Edith; Diaz, Rodrigo; Parada, Arturo; Sanchez, Lilia; Vargas, Cara
OBJECTIVE: To evaluate the clinical diagnosis of pelvic inflammatory disease (PID) compared with the diagnosis of PID made by laparoscopy, endometrial biopsy, transvaginal ultrasound, and cervical and endometrial cultures. Study design: A diagnostic performance test study was carried out by cross-sectional analysis in 61 women. A group presenting PID (n = 31) was compared with a group (n = 30) presenting another cause for non-specific lower abdominal pain (NSLAP). Diagnosis provided by an evaluated method was compared with a standard diagnosis (by surgical findings, histopathology, and microbiology). The pathologist was unaware of the visual findings and presumptive diagnoses given by other methods. RESULTS: All clinical and laboratory PID criteria showed low discrimination capacity. Adnexal tenderness showed the greatest sensitivity. Clinical diagnosis had 87% sensitivity, while laparoscopy had 81% sensitivity and 100% specificity; transvaginal ultrasound had 30% sensitivity and 67% specificity; and endometrial culture had 83% sensitivity and 26% specificity. CONCLUSIONS: Clinical criteria represent the best diagnostic method for discriminating PID. Laparoscopy showed the best specificity and is thus useful in those cases having an atypical clinical course for discarding abdominal pain when caused by another factor. The other diagnostic methods might have limited use. PMID:12648310
Ito, Kotaro; Imafuku, Shinichi; Hamaguchi, Yasuhito; Fujimoto, Manabu; Nakayama, Juichiro
Dermatomyositis is a rare connective tissue disease often associated with internal malignancy and interstitial pneumonitis. Serologically, various auto-antibodies (Ab) are associated with dermatomyositis. Anti-transcription intermediary factor-1-γ/α (TIF-1-γ/α) Ab was recently identified as an auto-Ab and was observed mostly in cancer-associated dermatomyositis. IgG4-related disease is a newly described entity characterized by increased serum IgG4 levels and IgG4-positive plasma cell infiltration with fibrosis in organs such as the pancreas and parotid gland. IgG4-related disease also includes inflammatory pseudotumors in various organs. We report herein a 59-year-old Japanese man who had dermatomyositis complicated with a gastric cancer and an IgG4-related pulmonary inflammatory pseudotumor. He manifested typical classical Gottron's papules on the fingers, V-sign erythema on the chest, flagellate erythema on the back, nail fold bleeding and facial erythema. Serum levels of anti-TIF-1-γ/α Ab were positive as assessed by immunoprecipitation assay. He also had bilateral swelling of the parotid gland, and an excised specimen of the lung showed inflammatory pseudotumor with IgG4-positive plasma cells. As far as we know, this case is the first to report the association of IgG4-related disease and TIF-1-γ/α-positive dermatomyositis. Further accumulation of such cases is required to elucidate the mechanism of this association.
Butman, John A.; Linehan, W. Marston; Lonser, Russell R.
von Hippel-Lindau disease (VHL) is an autosomal dominant neoplasia syndrome that is the result of a germline mutation of the VHL tumor suppressor gene on the short arm of chromosome 3. VHL patients are predisposed to develop lesions of the central nervous system (CNS) and viscera. CNS lesions include hemangioblastomas (the most common tumor in VHL) and endolymphatic sac tumors (ELSTs). Visceral manifestations include renal carcinomas and cysts, pancreatic neuroendocrine tumors and cysts, pheochromocytomas and cystadenomas of the reproductive adnexal organs. Despite their benign pathology, hemangioblastomas and ELSTs are a frequent cause of morbidity and mortality in VHL patients. Recent molecular biologic investigations into these VHL-associated CNS lesions provide new insight into their origin and development. Emerging data from serial imaging and clinical surveillance protocols provide insight into the natural history of these lesions. Because of the dissimilar pathobiology and clinical course between hemangioblastomas and ELSTs, the optimal management strategies for these neurologic manifestations of VHL are very different. PMID:18799446
... sheet Hashimoto's disease fact sheet Illnesses and disabilities Lupus fact sheet What is Graves' disease? What are the symptoms of Graves' disease? Who gets Graves' disease? What causes Graves' disease? How do I find out if ...
... Diseases Small Text Medium Text Large Text Periodontal Diseases Periodontal diseases are disorders of the gums, or gingiva, and other tissues around the teeth. Periodontal diseases vary in severity, from the reversible, recurring mild ...
... Emergency Room? What Happens in the Operating Room? Parkinson's Disease KidsHealth > For Kids > Parkinson's Disease A A ... symptoms of something called Parkinson's disease. What Is Parkinson's Disease? You may have seen the actor Michael ...
... Loss Surgery? A Week of Healthy Breakfasts Shyness Lyme Disease KidsHealth > For Teens > Lyme Disease A A A ... Northwest, and the northern midwestern states. What Is Lyme Disease? People get Lyme disease through tick bites. The ...
... disease and improve diagnosis) to effectively evaluate brain biochemistry and disease progression, and expanding the use of ... disease and improve diagnosis) to effectively evaluate brain biochemistry and disease progression, and expanding the use of ...
... Gum Disease Risk Factors Gum Disease Symptoms Gum Disease Prevention Gum Disease and Other Diseases Gum Disease and ... Gum Disease Risk Factors Gum Disease Symptoms Gum Disease Prevention Gum Disease and Other Diseases Gum Disease and ...
... Gum Disease Risk Factors Gum Disease Symptoms Gum Disease Prevention Gum Disease and Other Diseases Gum Disease and ... Gum Disease Risk Factors Gum Disease Symptoms Gum Disease Prevention Gum Disease and Other Diseases Gum Disease and ...
Crohn's disease causes inflammation of the digestive system. It is one of a group of diseases called inflammatory ... small intestine called the ileum. The cause of Crohn's disease is unknown. It may be due to an ...
... Newsroom Blogs Image Library News Conferences Press Releases Radio Public Service Announcements Real Stories, Real People Share ... National Foundation for Infectious Diseases (NFID) Pneumococcal Disease Radio Public Service Announcement National Foundation for Infectious Diseases ( ...
... this page: //medlineplus.gov/ency/article/000760.htm Alzheimer disease To use the sharing features on this page, ... of brain function that occurs with certain diseases. Alzheimer disease is one form of dementia. It affects memory, ...
... they can't breathe deeply. Pulmonary fibrosis and sarcoidosis are examples of lung tissue disease. Lung circulation ... tuberculosis Pulmonary veno-occlusive disease Rheumatoid lung disease Sarcoidosis Simple pulmonary eosinophilia Patient Instructions Chronic obstructive pulmonary ...
Huntington's disease (HD) is an inherited disease that causes certain nerve cells in the brain to waste away. ... express emotions. If one of your parents has Huntington's disease, you have a 50 percent chance of getting ...
... page from the NHLBI on Twitter. What Is Kawasaki Disease? Kawasaki (KAH-wah-SAH-ke) disease is a ... condition involves inflammation of the blood vessels. In Kawasaki disease, the walls of the blood vessels throughout the ...
... frequent, urgent urination Bladder cancer Doctors diagnose bladder diseases using different tests. These include urine tests, x- ... National Institute of Diabetes and Digestive and Kidney Diseases
... you're like most people, you think that heart disease is a problem for others. But heart disease is the number one killer in the ... of disability. There are many different forms of heart disease. The most common cause of heart disease ...
Columnaris disease is caused by the Gram-negative bacterium, Flavobacterium columnare. The disease was first described in 1917-1919 in the United States and the bacterium was not successfully isolated and grown in the laboratory until 1944. Columnaris disease continues to be a prevalent disease of...
Rossi, Giovanni M; Emmi, Giacomo; Corradi, Domenico; Urban, Maria L; Maritati, Federica; Landini, Federica; Galli, Paola; Palmisano, Alessandra; Vaglio, Augusto
Mediastinal fibrosis is a rare disease characterised by fibrous proliferation in the mediastinum. It can be idiopathic or secondary to several conditions such as infections and malignancies. Anecdotal reports have described idiopathic mediastinal fibrosis (IMF) in association with other fibro-inflammatory or autoimmune diseases. We report nine new IMF cases recently seen at our Fibro-Inflammatory Disease Clinic and reviewed the IMF cases reported in the English language literature throughout 2006-2016. The purposes of our literature search were to assess the frequency of the association between IMF and other immune-mediated disorders and to analyse which disorders most often coexist with IMF. Of our nine IMF cases, one was associated with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, one with large-vessel arteritis, three with idiopathic retroperitoneal fibrosis (one of which was IgG4-related), one with pancreatitis and one with IgG4-related seminal vesicle involvement. The remaining two cases, in which IMF was not associated with any other disease, were both classifiable as IgG4-related. The literature review showed that, of the 84 IMF cases identified, 27 (32 %) were associated with other idiopathic autoimmune or fibro-inflammatory disorders, particularly small-vessel vasculitis, Behçet disease, retroperitoneal fibrosis and other conditions belonging to the IgG4-related disease spectrum. Based on our own data and the literature review, we conclude that IMF is often associated with other autoimmune or fibro-inflammatory diseases; therefore, its clinical management requires an accurate screening of associated conditions. Immune-mediated mechanisms may be shared by these disorders.
AlGhamdi, Fares E.; Al-Khatib, Talal A.; Marzouki, Hani Z.; AlGarni, Mohammed A
Kimura disease is a chronic inflammatory disease that mainly manifests as a lump in the cervical region. Although the underlying pathophysiology is not clear yet, the diagnosis can be established based on specific histopathological characteristics. The first case of this disease was described in China, as well as the majority of subsequent cases that were also described in the Far East countries made Kimura disease traditionally a disease of adult patients of Asian descent. This report describes the occurrence of Kimura disease in pediatric non-Asian patient with a similar clinicopathologic presentation. PMID:26905356
Wilson disease is a rare inherited disorder that prevents your body from getting rid of extra copper. You need ... copper into bile, a digestive fluid. With Wilson disease, the copper builds up in your liver, and ...
Raynaud's disease is a rare disorder of the blood vessels, usually in the fingers and toes. It causes the ... secondary Raynaud's, which is caused by injuries, other diseases, or certain medicines. People in colder climates are ...
Fifth disease is a viral infection caused by parvovirus B19. The virus only infects humans; it's not the same parvovirus that dogs and cats can get. Fifth disease mostly affects children. Symptoms can include a low ...
... blood pressure and water and salt balance. Addison disease happens if the adrenal glands don't make ... problem with your immune system usually causes Addison disease. The immune system mistakenly attacks your own tissues, ...
Chagas disease is caused by a parasite. It is common in Latin America but not in the United States. ... nose, the bite wound or a cut. The disease can also spread through contaminated food, a blood ...
Parkinson's disease (PD) is a type of movement disorder. It happens when nerve cells in the brain don't ... coordination As symptoms get worse, people with the disease may have trouble walking, talking, or doing simple ...
Legionnaires' disease is a type of pneumonia caused by bacteria. You usually get it by breathing in mist from ... spread from person to person. Symptoms of Legionnaires' disease include high fever, chills, a cough, and sometimes ...
... low, you may have a hormone disorder. Hormone diseases also occur if your body does not respond ... In the United States, the most common endocrine disease is diabetes. There are many others. They are ...
... the back of the eye Macular degeneration - a disease that destroys sharp, central vision Diabetic eye problems ... defense is to have regular checkups, because eye diseases do not always have symptoms. Early detection and ...
... Infections Your doctor can do blood and urine tests to check if you have kidney disease. If your kidneys fail, you will need dialysis or a kidney transplant. NIH: National Institute of Diabetes and Digestive and Kidney Diseases
... small intestine. People with celiac disease cannot eat gluten, a protein found in wheat, barley, and rye. ... Treatment Doctors treat celiac disease by prescribing a gluten-free diet. Symptoms significantly improve for most people ...
... immune disease in which people can't eat gluten because it will damage their small intestine. If you have celiac disease and eat foods with gluten, your immune system responds by damaging the small ...
... Versions PDF Version (198 KB) Additional Links Hyperthyroidism Pregnancy and Thyroid Disease Thyroid Tests This content is provided as a service of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), part of the National Institutes of Health. ...
... disease often leads to reduced thyroid function, or hypothyroidism. Hypothyroidism is a disorder that occurs when the thyroid ... Hashimoto’s disease is the most common cause of hypothyroidism in the United States. 1 Read more in ...
... examining the genetic origins of Menkes disease and studying the effectiveness of early copper injections and gene-replacement therapies for treating the disease. Research also includes work on a universal newborn screening test for newborns. ...
... for tickborne diseases ranges from studying the basic biology of the microbes that cause these diseases to ... Nucleotide Polymorphism Phylogenetics & Ontology Proteomics & Protein Analysis Systems Biology Data Portals Software Applications BCBB Mobyle Interface Designer ( ...
... interfere with your blood's ability to clot. An enzyme that breaks down these fatty substances doesn't ... people who have Gaucher's disease. Treatment often includes enzyme replacement therapy. An inherited disorder, Gaucher's disease is ...
Parvovirus B19; Erythema infectiosum; Slapped cheek rash ... Fifth disease is caused by human parvovirus B19. It often affects preschoolers or school-age children during the spring. The disease spreads through the fluids in the nose and ...
... Loss Surgery? A Week of Healthy Breakfasts Shyness Kidney Disease KidsHealth > For Teens > Kidney Disease Print A ... Syndrome Coping With Kidney Conditions What Do the Kidneys Do? You might never think much about some ...
... up the bacteria when they bite mice or deer that are infected with B burgdorferi . You can ... syndrome Images Lyme disease organism, Borrelia burgdorferi Tick, deer engorged on the skin Lyme disease - Borrelia burgdorferi ...
... night blindness due to degeneration of the retina (retinitis pigmentosa). If the disease progresses, other symptoms may include ... night blindness due to degeneration of the retina (retinitis pigmentosa). If the disease progresses, other symptoms may include ...
... neurological disorders such as Behcet's disease. The National Human Genome Research Institute, another Institute of the National ... neurological disorders such as Behcet's disease. The National Human Genome Research Institute, another Institute of the National ...
... approximately one in 5,000 newborns. Children with Down syndrome and other medical problems, such as congenital heart ... For example, about one in 100 children with Down syndrome also has Hirschsprung disease. Hirschsprung disease is congenital, ...
... The disease occurs when both parents carry and pass on the defective gene that regulates the protein ... The disease occurs when both parents carry and pass on the defective gene that regulates the protein ...
... if your child has any symptoms of Canavan disease. Prevention Genetic counseling is recommended for people who want to have children and have a family history of Canavan disease. Counseling should be considered if both parents are ...
... Loss Surgery? A Week of Healthy Breakfasts Shyness Kidney Disease KidsHealth > For Teens > Kidney Disease A A ... Syndrome Coping With Kidney Conditions What Do the Kidneys Do? You might never think much about some ...
... amounts of some or all of its hormones ( hypopituitarism ) Autoimmune disorder that affects the nerves and the ... disease) Dermatitis herpetiformis Diabetes Graves disease Hyperthyroidism Hypoparathyroidism Hypopituitarism Immune response Myasthenia gravis Ovarian hypofunction Pernicious anemia ...
Capriotti, Teri; Terzakis, Kristina
Parkinson disease (PD) is a progressive neurodegenerative disease that affects one million people in the United States. This article reviews the etiology and pathophysiology of PD, risk factors, clinical manifestations, diagnostic criteria, and treatment of this common disease. Implications for home care clinicians are included.
Schessel, David A.
Meniere's disease is characterized by unpredictable spells of severe vertigo and fluctuations in hearing and tinnitus. This article discusses the incidence of Meniere's disease, the present status of our understanding of this disease, controversies in its diagnosis, and the multiple therapeutic modalities recruited in its treatment. (Contains…
Short history of Kawasaki disease, clinical features (principal symptoms and other significant symptoms or findings), diagnosis, cardiovascular involvement, epidemiology. Pathological features (lesion of vessels and lesion of organs exclusive of vessels), comparison between infantile periarteritis nodosa (IPN)/Kawasaki disease and classic periarteritis nodosa (CPN), etiology, treatment and management of Kawasaki disease are described. PMID:25792773
... disease is caused by a bacterium known as legionella. You can't catch legionnaires' disease from person-to-person contact. Instead, most people ... with weakened immune systems are particularly susceptible to legionnaires' disease. The legionella bacterium also causes Pontiac fever, a milder illness ...
Short history of Kawasaki disease, clinical features (principal symptoms and other significant symptoms or findings), diagnosis, cardiovascular involvement, epidemiology. Pathological features (lesion of vessels and lesion of organs exclusive of vessels), comparison between infantile periarteritis nodosa (IPN)/Kawasaki disease and classic periarteritis nodosa (CPN), etiology, treatment and management of Kawasaki disease are described.
Taylor, George C.
This overview of the public health significance of Lyme disease includes the microbiological specifics of the infectious spirochete, the entomology and ecology of the ticks which are the primary disease carrier, the clinical aspects and treatment stages, the known epidemiological patterns, and strategies for disease control and for expanded public…
Odaka, Makoto; Mori, Shohei; Asano, Hisatoshi; Yamashita, Makoto; Kamiya, Noriki; Morikawa, Toshiaki
This report describes a rare case of IgG4-related lung disease that was difficult to distinguish from lung cancer. CT revealed a well-demarcated round tumor in S10 of the right lung of a 56-year-old man suspected of having lung cancer. PET revealed high fluorodeoxyglucose uptake with a maximum standardized uptake value of 14.0. Because primary lung cancer was strongly suspected, lower lobectomy was performed via the thoracoscopic approach without mini-thoracotomy. Histopathology showed lymphoplasmacytic infiltration. Immunostaining revealed numerous IgG4-positive plasma cells diffusely infiltrating the tumor. Serum IgG4 levels increased, thereby confirming the diagnosis of IgG4-related lung disease.
Geschwind, Michael D.
Purpose of Review This article presents an update on the clinical aspects of human prion disease, including the wide spectrum of their presentations. Recent Findings Prion diseases, a group of disorders caused by abnormally shaped proteins called prions, occur in sporadic (Jakob-Creutzfeldt disease), genetic (genetic Jakob-Creutzfeldt disease, Gerstmann-Sträussler-Scheinker syndrome, and fatal familial insomnia), and acquired (kuru, variant Jakob-Creutzfeldt disease, and iatrogenic Jakob-Creutzfeldt disease) forms. This article presents updated information on the clinical features and diagnostic methods for human prion diseases. New antemortem potential diagnostic tests based on amplifying prions in order to detect them are showing very high specificity. Understanding of the diversity of possible presentations of human prion diseases continues to evolve, with some genetic forms progressing slowly over decades, beginning with dysautonomia and neuropathy and progressing to a frontal-executive dementia with pathology of combined prionopathy and tauopathy. Unfortunately, to date, all human prion disease clinical trials have failed to show survival benefit. A very rare polymorphism in the prion protein gene recently has been identified that appears to protect against prion disease; this finding, in addition to providing greater understanding of the prionlike mechanisms of neurodegenerative disorders, might lead to potential treatments. Summary Sporadic Jakob-Creutzfeldt disease is the most common form of human prion disease. Genetic prion diseases, resulting from mutations in the prion-related protein gene (PRNP), are classified based on the mutation, clinical phenotype, and neuropathologic features and can be difficult to diagnose because of their varied presentations. Perhaps most relevant to this Continuum issue on neuroinfectious diseases, acquired prion diseases are caused by accidental transmission to humans, but fortunately, they are the least common form and
Gaucher disease is the commonest lysosomal storage disease seen in India and worldwide. It should be considered in any child or adult with an unexplained splenohepatomegaly and cytopenia which are seen in the three types of Gaucher disease. Type 1 is the non-neuronopathic form and type 2 and 3 are the neuronopathic forms. Type 2 is a more severe neuronopathic form leading to mortality by 2 years of age. Definitive diagnosis is made by a blood test–the glucocerebrosidase assay. There is no role for histological examination of the bone marrow, liver or spleen for diagnosis of the disease. Molecular studies for mutations are useful for confirming diagnosis, screening family members and prognosticating the disease. A splenectomy should not be performed except for palliation or when there is no response to enzyme replacement treatment or no possibility of getting any definitive treatment. Splenectomy may worsen skeletal and lung manifestations in Gaucher disease. Enzyme replacement therapy (ERT) has completely revolutionized the prognosis and is now the standard of care for patients with this disease. Best results are seen in type 1 disease with good resolution of splenohepatomegaly, cytopenia and bone symptoms. Neurological symptoms in type 3 disease need supportive care. ERT is of no benefit in type 2 disease. Monitoring of patients on ERT involves evaluation of growth, blood counts, liver and spleen size and biomarkers such as chitotriosidase which reflect the disease burden. Therapy with ERT is very expensive and though patients in India have so far got the drug through a charitable access programme, there is a need for the government to facilitate access to treatment for this potentially curable disease. Bone marrow transplantation is an inferior option but may be considered when access to expensive ERT is not possible. PMID:25755533
Pierson, Duane L.
This is a collection of viewgraphs on the Johnson Space Center's work on infectious disease. It addresses their major concern over outbreaks of infectious disease that could jeopardize the health, safety and/or performance of crew members engaged in long duration space missions. The Antarctic environment is seen as an analogous location on Earth and a good place to carry out such infectious disease studies and methods for proposed studies as suggested.
... have any type of breathing problem. Alternative Names Legionella pneumonia; Pontiac fever; Legionellosis Images Legionnaires' disease organism, legionella References Edelstein PH, Roy CR. Legionnaires' ...
Sun, Li; Zhou, Qiang; Brigstock, David R; Yan, Su; Xiu, Ming; Piao, Rong-Li; Gao, Yan-Hang; Gao, Run-Ping
Type 1 autoimmune pancreatitis (AIP) or chronic sclerosing sialadenitis (Küttner's tumour) is an uncommon disorder that has recently been confirmed as an IgG4-related disease. Here, we describe a rare case of a 53-year-old male patient who primarily presented with pancreatic body mass, left neck mass and several lumps in his lower lip mimicking pancreatic cancer (PC) and neck metastasis. The patient underwent pancreatic body mass and labial gland lumps resection as well as an ultrasound-guided biopsy of the left neck mass. He was diagnosed with IgG4-related focal type of AIP (f-AIP) and Küttner's tumour by immunohistochemistry. The patient responded well to corticosteroid therapy and remains healthy with no signs of recurrence at one year follow-up. The differentiation of f-AIP from PC is very important to avoid unnecessary pancreatic resection.
... Gum Disease Risk Factors Gum Disease Symptoms Gum Disease Prevention Gum Disease and Other Diseases Gum Disease and ... Gum Disease Risk Factors Gum Disease Symptoms Gum Disease Prevention Gum Disease and Other Diseases Gum Disease and ...
... Contact Us Vascular Disease What is Vascular Disease? Education and Awareness Vascular Diseases Abdominal Aortic Aneurysm Aortic Dissection Arteriovenous Malformation Atherosclerosis Buerger's Disease Carotid Artery Disease ...
... Contact Us Vascular Disease What is Vascular Disease? Education and Awareness Vascular Diseases Abdominal Aortic Aneurysm Aortic Dissection Arteriovenous Malformation Atherosclerosis Buerger's Disease Carotid Artery Disease ...
... Women - particularly African-American, Hispanic-American, and Native-American women - have a higher risk for some autoimmune diseases. There are more than 80 types of autoimmune diseases, and some have similar symptoms. This makes it hard for your health care provider to know if ...
Cardiovascular disease (CVD), particularly CHD (coronary heart disease) and stroke, remain the leading causes of death of women in America and most developed countries. In recent years the rate of CVD has declined in men but not in women. This is contributed to by an under-recognition of women’s C...
Pradhan, D J; Ikins, P M
Aspiration disease, a term used to define both an acute and chronic form of a disease entity, is described. Etiological factors, pathophysiology and therapy are discussed with emphasis on aspiration of gastric juice. A brief mention of a small clinical experience is included.
Prion diseases comprise a set of rare fatal neurological diseases found in humans and other mammals. A prion is a protein capable of converting a normal cellular protein (PrPC) into a prion and thereby propagating an infection. A prion and PrPC differ solely in their conformation. There are differen...
Stephan, F; Haber, R
Fabry disease, also known as Anderson-Fabry disease or angiokeratoma corporis diffusum universale, is an X-linked recessive form of sphingolipidosis caused by total or partial deficiency of the lysosomal hydrolase, alpha-galactosidase A. From the youngest age, it results in a gradual ubiquitous build-up of glycosphingolipids that are not degraded by the missing enzyme. Cutaneous, neurological, nephrologic, cardiac, gastrointestinal, ophthalmological, respiratory, cochleovestibular and haematological involvement are responsible for increased mortality and significant impairment of quality of life in subjects affected by the disease. Angiokeratomas are the most common cutaneous sign of this disease, although they are not specific to it and must be distinguished from angiokeratomas either occurring in isolation or associated with systemic diseases. Other cutaneous signs encountered in this disease include hyperhidrosis, oral lesions, lower limb oedemas, etc. The diagnosis is mainly clinical and should be considered in the presence of a personal and/or familial history; it is confirmed by assay of enzyme activity within leucocytes or by molecular studies. Management is multidisciplinary and involves symptomatic treatment as well as specific treatment, resulting in improved survival and enhanced quality of life for patients presenting the disease. Enzyme replacement therapy with alpha-galactosidase A forms the cornerstone of specific treatment and may be associated with other types of treatments such as galactose and molecular chaperones. Gene therapy is now also used extensively. At present, these marked therapeutic advances, which closely involve dermatologists, could help transform the prognosis for patients presenting Fabry disease.
... provider if you think you may have Chagas disease. Prevention Insect control with insecticides and houses that are less likely to have high insect populations will help control the spread of the disease. Blood banks in Central and South America screen ...
... cerebrospinal fluid (CSF) Genetic testing MRI of the head Nerve conduction velocity Testing for the GALC gene defect Treatment There is no specific treatment for Krabbe disease. Some people have had a bone marrow transplant in the early stages of the disease, but ...
Rizk, Tamer M.; Ariganjoye, Rafiu O.; Alsaeed, Gihad I.
We aim to describe an 8-year-old boy with an unusual clinical presentation of Gaucher disease (GD). Gaucher disease is a progressive lysosomal storage disorder due to deficiency of the specific enzyme glucocerebrosidase with varying clinical features, but often involving the monocytes-macrophages systems. This child ran a progressive course with a devastating outcome. Three distinct GD subtypes have been described with varying clinical features based on the presence or absence of neurologic involvement. Gaucher disease diagnosis is obtained via: enzyme activity assay, gene mutation study, bone marrow aspiration in addition to multiple other tests that have been successfully used in diagnosis of cases of GD. Treatment modalities include enzyme replacement treatment, substrate reduction therapy, bone marrow transplantation, blood transfusion, and surgery are available management modalities for GD. Gaucher disease is a chronic disease requiring a multidisciplinary team approach with regular follow up with multiple subspecialties. PMID:26166597
Scheltens, Philip; Blennow, Kaj; Breteler, Monique M B; de Strooper, Bart; Frisoni, Giovanni B; Salloway, Stephen; Van der Flier, Wiesje Maria
Although the prevalence of dementia continues to increase worldwide, incidence in the western world might have decreased as a result of better vascular care and improved brain health. Alzheimer's disease, the most prevalent cause of dementia, is still defined by the combined presence of amyloid and tau, but researchers are gradually moving away from the simple assumption of linear causality as proposed in the original amyloid hypothesis. Age-related, protective, and disease-promoting factors probably interact with the core mechanisms of the disease. Amyloid β42, and tau proteins are established core cerebrospinal biomarkers; novel candidate biomarkers include amyloid β oligomers and synaptic markers. MRI and fluorodeoxyglucose PET are established imaging techniques for diagnosis of Alzheimer's disease. Amyloid PET is gaining traction in the clinical arena, but validity and cost-effectiveness remain to be established. Tau PET might offer new insights and be of great help in differential diagnosis and selection of patients for trials. In the search for understanding the disease mechanism and keys to treatment, research is moving increasingly into the earliest phase of disease. Preclinical Alzheimer's disease is defined as biomarker evidence of Alzheimer's pathological changes in cognitively healthy individuals. Patients with subjective cognitive decline have been identified as a useful population in whom to look for preclinical Alzheimer's disease. Moderately positive results for interventions targeting several lifestyle factors in non-demented elderly patients and moderately positive interim results for lowering amyloid in pre-dementia Alzheimer's disease suggest that, ultimately, there will be a future in which specific anti-Alzheimer's therapy will be combined with lifestyle interventions targeting general brain health to jointly combat the disease. In this Seminar, we discuss the main developments in Alzheimer's research.
Playfer, J. R.
Parkinson's disease is a common disabling disease of old age. The diagnosis of idiopathic Parkinson's disease is based on clinical signs and has poor sensitivity, with about 25% of patients confidently diagnosed as having the disease actually having other conditions such as multi-system atrophy and other parkinsonism-plus syndromes. Benign essential tremor and arteriosclerotic pseudo-parkinsonism can easily be confused with Parkinson's disease. The cause of Parkinson's disease remains unknown. Speculative research highlights the role of oxidative stress and free radical mediated damage to dopaminergic cells. Parkinson's disease is the one neurodegenerative disorder in which drugs have been demonstrated to be of value. There is now a wide variety of drugs and formulations available, including anticholinergics, amantidine, L-dopa, dopamine agonists including apomorphine, selegiline and soon to be available catechol-O-methyltransferase inhibitors. Disabling side-effects of treatment, fluctuations, dyskinesias and psychiatric problems require strategic use of the drugs available. There is an increasing potential for neurosurgical intervention. PMID:9196696
Ohn, Jungyoon; Park, Seon Yong; Moon, Jungyoon; Choe, Yun Seon
Morgellons disease is a rare disease with unknown etiology. Herein, we report the first case of Morgellons disease in Korea. A 30-year-old woman presented with a 2-month history of pruritic erythematous patches and erosions on the arms, hands, and chin. She insisted that she had fiber-like materials under her skin, which she had observed through a magnifying device. We performed skin biopsy, and observed a fiber extruding from the dermal side of the specimen. Histopathological examination showed only mild lymphocytic infiltration, and failed to reveal evidence of any microorganism. The polymerase chain reaction for Borrelia burgdorferi was negative in her serum. PMID:28392653
Aruna, Chintaginjala; Ramamurthy, D. V. S. B.; Neelima, T.; Bandaru, Haritha
Keratosis lichenoides chronica also known as Nekam's disease is a rare mucocutaneous disorder, characterized clinically by asymptomatic violaceous keratotic papules arranged in linear, reticular, or plaque form usually on the trunk and extremities and histologically by interface dermatitis. The disease is considered rare with only 128 cases being reported in the literature till date and very few from India. We report a case of a 40-year-old man who presented with constellation of features of lichen planus, seborrheic dermatitis, and apthous ulcers, which upon workup was found to be Nekam's disease. PMID:27990390
Schucany, William G.; Opatowsky, Michael J.
Kummell disease, or avascular necrosis of a vertebral body, presents as vertebral osteonecrosis typically affecting a thoracic vertebra with compression deformity, intravertebral vacuum cleft, and exaggerated kyphosis weeks to months after a minor traumatic injury. This rare disease is increasing in prevalence secondary to an aging population and the associated rise in osteoporosis. Treatment with vertebroplasty or surgical decompression and fusion is often required. We present a classic case of Kummell disease to illustrate the salient features of the condition, with associated imaging findings on computed tomography and magnetic resonance imaging. PMID:23814399
... Blogs Image Library News Conferences Press Releases Radio Public Service Announcements Real Stories, Real People Share Your Story Additional ... Centers for Disease Control and Prevention (CDC) #NoRegrets Public service announcement on the importance of getting vaccinated against both ...
... autoimmune thyroid disease. This includes radiation from the atomic bomb in Japan, the nuclear accident at Chernobyl, ... symptoms as normal pregnancy , such as fatigue and weight gain. Yet untreated underactive thyroid during pregnancy may ...
... good flexibility while your child is growing. The stretching exercises pictured in the treatment section can lower ... your child has already recovered from Sever's disease, stretching and putting ice on the heel after activity ...
... measles, mumps, rubella) and the Varicella (chicken pox) vaccines . Children over 6 months of age should receive the inactivated influenza (flu) vaccine injection. Long-term follow-up: Children treated for Kawasaki Disease who do not develop ...
... Digestive Diseases in the United States Healthy Moments Radio Listen to health tips from Dr. Rodgers in ... la salud en español Health Statistics Healthy Moments Radio Broadcast Clinical Trials For Health Care Professionals Community ...
... retina provide vision by conveying information from the visual field to the brain. The macula is responsible ... progression of symptoms in Stargardt disease is variable. Visual acuity (the ability to distinguish details and shape) ...
... is called hyperthyroidism . (An underactive thyroid leads to hypothyroidism .) Graves disease is the most common cause of ... radioactive iodine often will cause an underactive thyroid (hypothyroidism). Without getting the correct dosage of thyroid hormone ...
... cells make and use a brain chemical called dopamine (say: DOH-puh-meen) to send messages to ... coordinate body movements. When someone has Parkinson's disease, dopamine levels are low. So, the body doesn't ...
Vaginal problems are some of the most common reasons women go to the doctor. They may have ... that affect the vagina include sexually transmitted diseases, vaginal cancer, and vulvar cancer. Treatment of vaginal problems ...
... or gained weight very quickly. It's also more common in people of African heritage, kids who started ... worse and can't be traced to an injury — your doctor may consider Blount disease as a ...
... nerve cells use for communicating with adjacent cells. Biology & Genetics Scientists are examining how abnormal prion protein ... the abnormal form. Read more about prion diseases biology and genetics Therapeutic Approaches Although there are no ...
... away from the teeth. This is known as periodontitis (pronounced: pair-ee-oh-don-TY-tus), a more advanced form of gum disease. With periodontitis, gums become weakened and form pockets around the ...
Alzheimer's disease (AD) is the most common form of dementia among older people. Dementia is a brain disorder that seriously affects a person's ability to carry out daily activities. AD begins slowly. It first involves the parts of ...
... have surgery are fully cured and able to pass bowel movements normally. About Hirschsprung Disease Hirschsprung (HERSH- ... The condition — which prevents bowel movements (stool) to pass through the intestines due to missing nerve cells ...
... that may be associated with this disease: Anxiety, stress, and tension Difficulty swallowing Speech impairment Symptoms in children: Rigidity Slow movements Tremor Exams and Tests The doctor will perform a physical ...
... with this type may live into adulthood. Symptoms Bleeding because of low platelet count is the most common symptom seen in Gaucher disease. Other symptoms may include: Bone pain and fractures Cognitive impairment (decreased thinking ability) Easy bruising Enlarged ...
... Rigor & Reproducibility Scientific Resources Animal Models Cell/Tissue/DNA Clinical and Translational Resources Gene Expression Research Reagents ... Definition Alpers' disease is a progressive, neurodevelopmental, mitochondrial DNA depletion syndrome characterized by three co-occurring clinical ...
Portillo, Aránzazu; Santibáñez, Sonia; Oteo, José A
Lyme disease (LD) is a worldwide-distributed multisystemic process caused by Borrelia burgdorferi sensu lato (s.l.) and transmitted by hard ticks. In fact, it is the most common tick-borne infectious disease in the northern hemisphere. In Spain it is transmitted by Ixodes ricinus ticks and Borrelia garinii is the genoespecies of B. burgdorferi s.l. mostly involved in our area. LD is known as "the last great imitator" due to the broad clinical spectrum that may cause. Except in the case of erythema migrans (pathognomonic feature of the disease), the remaining clinical manifestations should be confirmed using microbiological tests. This review is intended to provide readers a current vision of the etiology, epidemiology, clinical manifestations, laboratory diagnosis and treatment of Lyme disease in our environment. Controversial aspects arising from the use of non-validated microbiological tests that are being used without scientific rigor are highlighted.
... large bowel ( colon ). Crohn's disease may lead to deep ulcers in the intestinal tract, giving a "cobblestone" ... understanding of the possible charges you will incur. Web page review process: This Web page is reviewed ...
Your liver is the largest organ inside your body. It helps your body digest food, store energy, and remove poisons. There are many kinds of liver diseases. Viruses cause some of them, like hepatitis ...
... your menstrual period. Your thyroid helps control your menstrual cycle. Too much or too little thyroid hormone can ... Problems getting pregnant. When thyroid disease affects the menstrual cycle, it also affects ovulation. This can make it ...
... of CAM are herbal products, chiropractic , acupuncture , and hypnosis . If you have an autoimmune disease, you might ... help you to feel your best. Meditation, self-hypnosis, and guided imagery, are simple relaxation techniques that ...
Nair, Jagdish R; Moots, Robert J
Behçet's disease (BD) is a chronic relapsing and remitting vasculitis of unknown aetiology. It has the capacity to affect almost all organ systems because of its potential to involve both arteries and veins of all sizes, resulting in significant organ-threatening morbidity and mortality. Traditionally known as the 'silk road' disease, it has a worldwide occurrence. The aetiopathological mechanisms of disease development in BD remain poorly understood, but genome wide studies show human leukocyte antigen and non-human leukocyte antigen associations. Environmental influences and genetic factors may have a role in the aetiopathogenetic mechanisms that lead to development of the disease, indicating the autoimmune and auto-inflammatory nature of BD. The evidence base for treatment is limited but new knowledge is emerging and current treatment options range from symptomatic treatment, through to non-biological and biological immunosuppressive drugs, to cover the spectrum of clinical manifestations.
... passed down through families. It affects the way bilirubin is processed by the liver, and causes the ... eat. Exams and Tests A blood test for bilirubin shows changes that occur with Gilbert disease. The ...
Huster, D; Kühn, H-J; Mössner, J; Caca, K
Wilson disease is an autosomal recessive inherited disorder of human copper metabolism that leads to neurological symptoms and hepatic damage of variable degree. The affected gene ATP7B encodes a hepatic copper transport protein, which plays a key role in human copper metabolism. Clinical symptoms are complex with neurologic symptoms such as tremor, dysarthria, psychiatric disorders etc., predominant hepatic disease or mixed forms. Copper deposition in the liver results in acute liver failure, chronic hepatitis or liver cirrhosis. Early recognition by means of clinical, biochemical or genetic examination and early initiation of therapy with chelators or zinc-salts are essential for outcome and prognosis. Liver transplantation is an alternative in cases with acute and chronic liver failure and cures the hepatic disease. Frequent monitoring of drug therapy, adverse effects, and compliance is critical for the prognosis of the disease.
... relatively simple tests in the office to judge: Motor symptoms Reflexes Muscle strength Muscle tone Coordination Balance ... drinking utensils adapted for people with limited fine motor skills Managing Huntington's disease is demanding on the ...
Burdge, David R.; O'Hanlon, David
Lyme borreliosis is an infectious disease caused by the tick-transmitted spirochete Borrelia burgdorferi. To date, the only known endemic focus of Lyme disease in Canada is Long Point, Ont. A national case definition for surveillance purposes, consensus statement regarding laboratory diagnosis, and treatment guidelines have recently been developed in an attempt to standardize the approach to surveillance, diagnosis, and management of Lyme borreliosis in Canada. PMID:21221399
Bardelli, M; D'Arienzo, M; Veneziani, C
The authors describe the clinical appearance of Ledderhose disease and emphasize the association with Dupuytren disease. They report on a series of patients treated at the 2nd Orthopedic Unit of University of Florence and describe the operating technique used. They believe that the procedure of removal of nodules must always be performed in association with careful exeresis of normal tissue, employing total aponeurectomy only in revision surgery.
Fabry disease, an X-linked disorder of glycosphingolipids that is caused by mutations of the GLA gene that codes for α-galactosidase A, leads to dysfunction of many cell types and includes a systemic vasculopathy. As a result, patients have a markedly increased risk of developing ischemic stroke, small-fiber peripheral neuropathy, cardiac dysfunction and chronic kidney disease. Virtually all complications of Fabry disease are non-specific in nature and clinically indistinguishable from similar abnormalities that occur in the context of more common disorders in the general population. Recent studies suggested a much higher incidence of mutations of the GLA gene, suggesting that this disorder is under-diagnosed. However, some of the gene variants may be benign. Although the etiology of Fabry disease has been known for many years, the mechanism by which the accumulating α-D-galactosyl moieties cause this multi organ disorder has only recently been studied and is yet to be completely elucidated. Specific therapy for Fabry disease has been developed in the last few years but its role in the management of the disorder is still being investigated. Fortunately, standard 'non-specific' medical and surgical therapy is effective in slowing deterioration or compensating for organ failure in patients with Fabry disease.
Bates, Gillian P; Dorsey, Ray; Gusella, James F; Hayden, Michael R; Kay, Chris; Leavitt, Blair R; Nance, Martha; Ross, Christopher A; Scahill, Rachael I; Wetzel, Ronald; Wild, Edward J; Tabrizi, Sarah J
Huntington disease is devastating to patients and their families - with autosomal dominant inheritance, onset typically in the prime of adult life, progressive course, and a combination of motor, cognitive and behavioural features. The disease is caused by an expanded CAG trinucleotide repeat (of variable length) in HTT, the gene that encodes the protein huntingtin. In mutation carriers, huntingtin is produced with abnormally long polyglutamine sequences that confer toxic gains of function and predispose the protein to fragmentation, resulting in neuronal dysfunction and death. In this Primer, we review the epidemiology of Huntington disease, noting that prevalence is higher than previously thought, geographically variable and increasing. We describe the relationship between CAG repeat length and clinical phenotype, as well as the concept of genetic modifiers of the disease. We discuss normal huntingtin protein function, evidence for differential toxicity of mutant huntingtin variants, theories of huntingtin aggregation and the many different mechanisms of Huntington disease pathogenesis. We describe the genetic and clinical diagnosis of the condition, its clinical assessment and the multidisciplinary management of symptoms, given the absence of effective disease-modifying therapies. We review past and present clinical trials and therapeutic strategies under investigation, including impending trials of targeted huntingtin-lowering drugs and the progress in development of biomarkers that will support the next generation of trials. For an illustrated summary of this Primer, visit: http://go.nature.com/hPMENh.
Cunha, Burke A; Burillo, Almudena; Bouza, Emilio
Since first identified in early 1977, bacteria of the genus Legionella are recognised as a common cause of community-acquired pneumonia and a rare cause of hospital-acquired pneumonia. Legionella bacteria multisystem manifestations mainly affect susceptible patients as a result of age, underlying debilitating conditions, or immunosuppression. Water is the major natural reservoir for Legionella, and the pathogen is found in many different natural and artificial aquatic environments such as cooling towers or water systems in buildings, including hospitals. The term given to the severe pneumonia and systemic infection caused by Legionella bacteria is Legionnaires' disease. Over time, the prevalence of legionellosis or Legionnaires' disease has risen, which might indicate a greater awareness and reporting of the disease. Advances in microbiology have led to a better understanding of the ecological niches and pathogenesis of the condition. Legionnaires' disease is not always suspected because of its non-specific symptoms, and the diagnostic tests routinely available do not offer the desired sensitivity. However, effective antibiotics are available. Disease notification systems provide the basis for initiating investigations and limiting the scale and recurrence of outbreaks. This report reviews our current understanding of this disease.
Čeović, Romana; Desnica, Lana; Pulanić, Dražen; Serventi Seiwerth, Ranka; Ilić, Ivana; Grce, Magdalena; Mravak Stipetić, Marinka; Klepac Pulanić, Tajana; Bilić, Ervina; Bilić, Ernest; Milošević, Milan; Vrhovac, Radovan; Nemet, Damir; Pavletic, Steven Z
Aim To determine the frequency and the characteristics of cutaneous manifestations, especially vitiligo and alopecia areata, in patients with chronic graft-vs-host disease (cGVHD). Methods 50 patients with cGVHD were prospectively enrolled in the observational study protocol and evaluated by an experienced dermatologist. The evaluation was focused on the clinical spectrum of skin and adnexal involvement, and the cutaneous GVHD score was determined according to National Institutes of Health (NIH) Consensus criteria. The presence of vitiligo, alopecia, xerosis, nail changes, and dyspigmentation was also assessed. Results Out of 50 cGVHD patients, 28 (56%) had skin involvement, and 27 of them (96%) had hypo and/or hyperpigmentations. 11 patients (39%) had a mild cutaneous NIH cGVHD score, 22% moderate, and 39% severe. 15 (30%) patients had nail changes and 10 (20%) had vitiligo or alopecia areata. Univariate analysis showed that patients with vitiligo/alopecia areata received more lines of prior systemic immunosuppressive therapy (P = 0.043), had lower Karnofsky performance status (P = 0.028), and had a higher B-cell number (P = 0.005), platelet count (P = 0.022), and total protein (P = 0.024). Vitiligo and alopecia areata were associated with higher NIH skin score (P = 0.001), higher intensity of immunosuppressive treatment (P = 0.020), and total body irradiation conditioning (P = 0.040). Multivariate regression model showed that patients with higher NIH skin scoring were 3.67 times more likely to have alopecia and/or vitiligo (odds ratio 3.67; 95% confidence interval 1.26-10.73), controlled for all other factors in the model (age at study entry, number of B-cells, platelet count, and global NIH score). Conclusion These data indicate that vitiligo and alopecia areata occur more frequently in cGVHD than previously reported. PMID:27374824
Cardiovascular Diseases; Coronary Disease; Cerebrovascular Accident; Heart Diseases; Myocardial Infarction; Infection; Chlamydia Infections; Cytomegalovirus Infections; Helicobacter Infections; Atherosclerosis
Wolters, E C; Calne, D B
In Parkinson's disease there is degeneration of neurons in the substantia nigra, with consequent depletion of the neurotransmitter dopamine. The triad of tremor, rigidity and bradykinesia is the clinical hallmark. Drugs currently used for palliative therapy fall into three categories: anticholinergic agents, dopamine precursors (levodopa combined with extracerebral decarboxylase inhibitors) and artificial dopamine agonists. It has been argued, on theoretical grounds, that some drugs slow the progress of Parkinson's disease, although no firm evidence has supported this. Treatment must be individualized, and more than one type of drug can be given concurrently after a careful build-up in dosage. We review the adverse effects of various drugs and consider new developments such as slow-release preparations, selective D-1 and D-2 agonists and transplants of dopaminergic cells into the brain. The treatment of Parkinson's disease can be demanding, rewarding and sometimes frustrating, but it remains a most challenging exercise in pharmacotherapy. Images Fig. 1 Fig. 2 Fig. 3 PMID:2563667
Introduction Crohn's disease is a chronic condition of the gastrointestinal tract. It is characterised by transmural, granulomatous inflammation that occurs in a discontinuous pattern, with a tendency to form fistulae. The cause is unknown but may depend on interactions between genetic predisposition, environmental triggers, and mucosal immunity. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of medical treatments to induce remission in adults with Crohn's disease? What are the effects of surgical interventions to induce and maintain remission in adults with small-bowel Crohn's disease? What are the effects of surgical interventions to induce remission in adults with colonic Crohn's disease? What are the effects of medical interventions to maintain remission in adults with Crohn's disease; and to maintain remission following surgery? What are the effects of lifestyle interventions to maintain remission in adults with Crohn's disease? We searched: Medline, Embase, The Cochrane Library, and other important databases up to December 2009 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 93 systematic reviews, RCTs, or observational studies that met our inclusion criteria. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: aminosalicylates, antibiotics, azathioprine/mercaptopurine, ciclosporin, corticosteroids (oral), enteral nutrition, fish oil, infliximab, methotrexate, probiotics, resection, segmental colectomy, smoking cessation, and strictureplasty. PMID:21524318
Celiac disease is a genetically determined, permanent intolerance to gluten, a protein complex found in wheat, rye and barley. As many as 1:163 people are affected by it, but only a small percentage are aware of the condition, which begins either in infancy, with gastrointestinal symptoms, or in childhood and later years with non-Gl signs and symptoms, such as fatigue, depression, anxiety, anemia, stunted growth, and delayed puberty. A strong association with Type 1 diabetes and Down syndrome is also found, thus making screening mandatory for these subjects. Celiac disease is often entirely clinically silent, yet it must be detected in order to prevent long-term complications.
Whipple's disease is a rare infectious disorder affecting mostly middle aged men. The causative organism, Tropheryma whipplei, recently has been cultivated and phylogenetically identified as an actinomycete. The rareness of the disease despite the ubiquitous occurence of T. whipplei presumably is related to a predisposing defect in cellular immunity. The diagnosis usually can be established by small bowel biopsy, but is frequently delayed due to protean clinical manifestations. The initiation of antibiotic treatment in most cases results in clinical remission, however, a significant number of patients is refractory to antimicrobial therapy or has a relapsing course.
... and inflammation in the central nervous system and digestive organs. Vascular System Some people with Behçet’s disease have blood clots ... colon that causes diarrhea, cramps, and weight loss. Digestive tract. The body system that breaks down food. The digestive tract includes ...
Green, Peter H R; Lebwohl, Benjamin; Greywoode, Ruby
This review will focus on the pathogenesis, clinical manifestations, diagnosis, and management of celiac disease (CD). Given an increasing awareness of gluten-related disorders, medical professionals of all varieties are encountering patients with a diagnosis of CD or who are thought to have food intolerance to gluten. The prevalence of CD among the general population is estimated to be 1% in Western nations, and there is growing evidence for underdiagnosis of the disease, especially in non-Western nations that were traditionally believed to be unaffected. The development of serologic markers specific to CD has revolutionized the ability both to diagnose and monitor patients with the disease. Additionally, understanding of the clinical presentations of CD has undergone a major shift over the past half century. Although it is well understood that CD develops in genetically predisposed subjects exposed to gluten, the extent of other environmental factors in the pathogenesis of the disease is an area of continued research. Currently, the main therapeutic intervention for CD is a gluten-free diet; however, novel nondietary agents are under active investigation. Future areas of research should also help us understand the relationship of CD to other gluten-related disorders.
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Mohammadi, Ladan; Miller, Anthony; Ashurst, John V.
Marijuana smoke can cause thermal injury, and since legalization and increased use of marijuana in our society, differentiating, diagnosing, and managing this condition have become mandatory. A case of a 28-year-old male with Quincke's disease secondary to marijuana inhalation is presented. PMID:28217604
Burns, E C; Dunger, D B; Dillon, M J
We report five children who presented with Raynaud's disease in whom we could find no clinical, haematological, or immunological evidence of a collagen disorder. Oral phenoxybenzamine proved useful for maintenance treatment in most, with infusions of prostacyclin, nitroprusside, and ketanserin during acute attacks. PMID:3160308
Fabry disease results from deficient activity of the enzyme α-galactosidase A and progressive lysosomal deposition of globotriaosylceramide (GL-3) in cells throughout the body. The main neurological presentations of Fabry disease patients are painful neuropathy, hypohidrosis, and stroke. Fabry neuropathy is characterized as a length-dependent peripheral neuropathy affecting mainly the small myelinated (Aδ) fibers and unmyelinated (C) fibers. Enzyme replacement therapy (ERT) has been shown to have some positive effects on the reduction of neuropathic pain, the improvement of detection threshold for thermal sensation, and sweat function. On the contrary, the effect of ERT on the central nervous system has not been established. Early initiation of ERT before irreversible organ failure is extremely important, and alternative therapeutic approaches are currently being explored. Heterozygotes suffer from peripheral neuropathy at a higher rate than previously shown, significant multisystemic disease, and severely decreased quality of life. As well as being carriers, heterozygotes also display symptoms of Fabry disease, and should be carefully monitored and given adequate therapy.
... after radioiodine therapy as a supplemental treatment. Side effects of both drugs include rash, joint pain, liver failure or a decrease in disease-fighting white blood cells. Methimazole isn't used to treat pregnant women in the first trimester because of the slight ...
... that contain genetic material, and use your own cells to multiply Fungi - primitive plants, like mushrooms or mildew Protozoa - one-celled animals that use other living things for food and a place to live NIH: National Institute of Allergy and Infectious Diseases
... Behçet’s Disease Progress and Promise Key Words The Immune System When your body is attacked – perhaps by a virus or other germs – your immune system defends you. It “sees” and kills the germs ...
was of importance in arresting the disease. On the other hand, tuberculous patients may develop a sarcoidosis -like hypersensitivity to vitamin D; if...action of vitamin D and become hypercalcemic, as in sarcoidosis . Normal quantities of vitamins and other nutrients help to maintain host resistance at
... are defective, the cells do not have enough energy. The unused oxygen and fuel molecules build up in the cells and cause damage. The symptoms of mitochondrial disease can vary. It depends on how ... high energy needs, so muscular and neurological problems are common. ...
The sunflower disease chapter is part of the Sunflower Oilseeds Monograph, which will be a new publication in the AOCS Oilseeds Monograph series. The monograph contains an overview and history of sunflower crop development, how the oilseed is cultivated, how the oilseed is produced, how the seed is...
... You can get them from contaminated food or water, a bug bite, or sexual contact. Some parasitic diseases are easily treated and some are not. Parasites range in size from tiny, ... Contaminated water supplies can lead to Giardia infections. Cats can ...
When you breathe, your lungs take in oxygen from the air and deliver it to the bloodstream. The cells in your body need oxygen to ... you breathe nearly 25,000 times. People with lung disease have difficulty breathing. Millions of people in ...
Lyme disease is among the most frequently diagnosed zoonotic tick-borne diseases worldwide. The number of human cases has been on the increase since the first recognition of its aetiological agent. Lyme disease is caused by spirochete bacteria belonging to the genus Borrelia, with B. burgdorferi sensu stricto (s.s.) found in the Americas, and B. afzelii and B. garinii, in addition to B. burgdorferi s.s., in Europe and Asia. Environmental factors, such as human encroachment onto habitats favourable to ticks and their hosts, reduced deforestation, increased human outdoor activities, and climatic factors favouring a wider distribution of tick vectors, have enhanced the impact of the disease on both humans and animals. Clinical manifestations in humans include, in the early phases, erythema migrans, followed several weeks later by neuro-borreliosis (meningo-radiculitis, meningitis or meningo-encephalitis), Lyme arthritis and/or Borrelia lymphocytoma. In dogs, acute signs include fever, general malaise, lameness, lymph node enlargement and polyarthritis, as well as neuro-borreliosis in the chronic form. Diagnosis is mainly serological in both humans and animals, based on either a two-tier approach (an immunoenzymatic test followed by a Western blot confirmatory test) in humans or C(6) peptide, only in dogs. Early treatment with antibiotics, such as doxycycline or amoxicillin, for three weeks usually reduces the risk of chronic disease. Tick control, including the use of tick repellents for both humans and animals, particularly dogs, is highly reliable in preventing transmission. Vaccines are not available to prevent human infection, whereas several vaccines are available to reduce transmission and the clinical manifestations of infection in dogs.
Celiac disease (CD) is a common autoimmune disorder, induced by the intake of gluten proteins present in wheat, barley and rye. Contrary to common belief, this disorder is a protean systemic disease, rather than merely a pure digestive alteration. CD is closely associated with genes that code HLA-II antigens, mainly of DQ2 and DQ8 classes. Previously, it was considered to be a rare childhood disorder, but is actually considered a frequent condition, present at any age, which may have multiple complications. Tissue transglutaminase-2 (tTG), appears to be an important component of this disease, both, in its pathogenesis and diagnosis. Active CD is characterized by intestinal and/or extra-intestinal symptoms, villous atrophy and crypt hyperplasia, and strongly positive tTG auto-antibodies. The duodenal biopsy is considered to be the “gold standard” for diagnosis, but its practice has significant limitations in its interpretation, especially in adults. Occasionally, it results in a false-negative because of patchy mucosal changes and the presence of mucosal villous atrophy is often more severe in the proximal jejunum, usually not reached by endoscopic biopsies. CD is associated with increased rates of several diseases, such as iron deficiency anemia, osteoporosis, dermatitis herpetiformis, several neurologic and endocrine diseases, persistent chronic hypertransami-nasemia of unknown origin, various types of cancer and other autoimmune disorders. Treatment of CD dictates a strict, life-long gluten-free diet, which results in remission for most individuals, although its effect on some associated extraintestinal manifestations remains to be established.
Vasconcelos, Carlos; Kallenberg, Cees; Shoenfeld, Yehuda
Refractory disease (RD) definition has different meanings but it is dynamic, according to knowledge and the availability of new drugs. It should be differentiated from severe disease and damage definitions and it must take into account duration of adequate therapy and compliance of the patient. It can be related to inadequate or inefficacious treatment or to pathogenesis. RD definition has multiple implications to clinical guidelines and to the use of off-label drugs. It should not be regarded as lost cases and prospective studies, registries and clinical trials should be planned.
Fabry disease (FD) is a progressive, X-linked inherited disorder of glycosphingolipid metabolism due to deficient or absent lysosomal α-galactosidase A activity. FD is pan-ethnic and the reported annual incidence of 1 in 100,000 may underestimate the true prevalence of the disease. Classically affected hemizygous males, with no residual α-galactosidase A activity may display all the characteristic neurological (pain), cutaneous (angiokeratoma), renal (proteinuria, kidney failure), cardiovascular (cardiomyopathy, arrhythmia), cochleo-vestibular and cerebrovascular (transient ischemic attacks, strokes) signs of the disease while heterozygous females have symptoms ranging from very mild to severe. Deficient activity of lysosomal α-galactosidase A results in progressive accumulation of globotriaosylceramide within lysosomes, believed to trigger a cascade of cellular events. Demonstration of marked α-galactosidase A deficiency is the definitive method for the diagnosis of hemizygous males. Enzyme analysis may occasionnally help to detect heterozygotes but is often inconclusive due to random X-chromosomal inactivation so that molecular testing (genotyping) of females is mandatory. In childhood, other possible causes of pain such as rheumatoid arthritis and 'growing pains' must be ruled out. In adulthood, multiple sclerosis is sometimes considered. Prenatal diagnosis, available by determination of enzyme activity or DNA testing in chorionic villi or cultured amniotic cells is, for ethical reasons, only considered in male fetuses. Pre-implantation diagnosis is possible. The existence of atypical variants and the availability of a specific therapy singularly complicate genetic counseling. A disease-specific therapeutic option - enzyme replacement therapy using recombinant human α-galactosidase A - has been recently introduced and its long term outcome is currently still being investigated. Conventional management consists of pain relief with analgesic drugs
Tümer, Zeynep; Møller, Lisbeth B
Menkes disease (MD) is a lethal multisystemic disorder of copper metabolism. Progressive neurodegeneration and connective tissue disturbances, together with the peculiar 'kinky' hair are the main manifestations. MD is inherited as an X-linked recessive trait, and as expected the vast majority of patients are males. MD occurs due to mutations in the ATP7A gene and the vast majority of ATP7A mutations are intragenic mutations or partial gene deletions. ATP7A is an energy dependent transmembrane protein, which is involved in the delivery of copper to the secreted copper enzymes and in the export of surplus copper from cells. Severely affected MD patients die usually before the third year of life. A cure for the disease does not exist, but very early copper-histidine treatment may correct some of the neurological symptoms.
Minamata disease (methylmercury poisoning) was first discovered in 1956 around Minamata Bay, Kumamoto Prefecture, Japan. A second epidemic in Japan occurred in 1965 along the Agano River, Niigata Prefecture. This paper presents a brief review of Minamata disease with an emphasis on the cases found in Kumamoto Prefecture. At autopsy, the most conspicuous destructive lesion in the cerebrum was found in the anterior portions of the calcarine cortex. Less severe but similar lesions may be found in the post-central, pre-central and temporal transverse cortices. Secondary degeneration from primary lesions may be seen in cases with long survival. In the cerebellum, pathological changes occur deep in the hemisphere. The granule cell population was more affected, compared with Purkinje cells. Among peripheral nerves, sensory nerves were more affected than motor nerves. Our recent experimental studies that reveal knowledge of the pathogenesis of methylmercury poisoning will be discussed.
Tümer, Zeynep; Møller, Lisbeth B
Menkes disease (MD) is a lethal multisystemic disorder of copper metabolism. Progressive neurodegeneration and connective tissue disturbances, together with the peculiar ‘kinky' hair are the main manifestations. MD is inherited as an X-linked recessive trait, and as expected the vast majority of patients are males. MD occurs due to mutations in the ATP7A gene and the vast majority of ATP7A mutations are intragenic mutations or partial gene deletions. ATP7A is an energy dependent transmembrane protein, which is involved in the delivery of copper to the secreted copper enzymes and in the export of surplus copper from cells. Severely affected MD patients die usually before the third year of life. A cure for the disease does not exist, but very early copper-histidine treatment may correct some of the neurological symptoms. PMID:19888294
Accordino, Robert E; Engler, Danielle; Ginsburg, Iona H; Koo, John
Morgellons disease, a pattern of dermatologic symptoms very similar, if not identical, to those of delusions of parasitosis, was first described many centuries ago, but has recently been given much attention on the internet and in the mass media. The present authors present a history of Morgellons disease, in addition to which they discuss the potential benefit of using this diagnostic term as a means of building trust and rapport with patients to maximize treatment benefit. The present authors also suggest "meeting the patient halfway" and creating a therapeutic alliance when providing dermatologic treatment by taking their cutaneous symptoms seriously enough to provide both topical ointments as well as antipsychotic medications, which can be therapeutic in these patients.
... Physician Resources Professions Site Index A-Z Peripheral Artery Disease (PAD) Peripheral artery disease (PAD) refers to ... is peripheral artery disease treated? What is peripheral artery disease (PAD)? Peripheral artery disease, or PAD, refers ...
Fausto de Souza, Dominique; Micaelo, Lilian; Cuzzi, Tullia
Plantar fibromatosis, or Ledderhose disease, is a rare hyperproliferative disorder of the plantar aponeurosis. It may occur at any age with the greatest prevalence at middle age and beyond. This disorder is more common in men than woman and it is sometimes associated with other forms of fibromatosis. A 28-year-old Brazilian woman with a six-year history of painless bilateral plantar nodules is described in this article. PMID:20877526
Hu, Linden T
This issue provides a clinical overview of Lyme disease, focusing on prevention, diagnosis, treatment, and practice improvement. The content of In the Clinic is drawn from the clinical information and education resources of the American College of Physicians (ACP), including MKSAP (Medical Knowledge and Self-Assessment Program). Annals of Internal Medicine editors develop In the Clinic in collaboration with the ACP's Medical Education and Publishing divisions and with the assistance of additional science writers and physician writers.
In recent years, it has become apparent that Tropheryma whipplei not only causes a chronic multisystemic infection which is often preceded by arthropathies for many years, well known as 'classical' Whipple's disease, but also clinically becomes manifest with localized organ affections and acute (transient) infections in children. T. whipplei is found ubiquitously in the environment and colonizes in some healthy carriers. In this review, we highlight new aspects of this enigmatic infectious disorder.
After two workers at the nuclear weapons plant at Oak Ridge National Laboratory in Tennessee were diagnosed earlier this year with chronic beryllium disease (CBD), a rare and sometimes fatal scarring of the lungs, the Department of Energy ordered up a 4-year probe. Now, part of that probe has begun - tests conducted by the Oak Ridge Associated Universities' Center for Epidemiological Research measuring beryllium sensitivity in 3,000 people who've been exposed to the metal's dust since Manhattan Project managers opened the Y-12 plant at Oak Ridge in 1943. Currently, 119 Y-12 employees process beryllium, which has a number of industrial uses, including rocket heat shields and nuclear weapon and electrical components. The disease often takes 20 to 25 years to develop, and the stricken employees haven't worked with beryllium for years. There is no cure for CBD, estimated to strike 2% of people exposed to the metal. Anti-inflammatory steroids alleviate such symptoms as a dry cough, weight loss, and fatigue. Like other lung-fibrosis diseases that are linked to lung cancer, some people suspect CBD might cause some lung cancer. While difficult to diagnose, about 900 cases of CBD have been reported since a Beryllium Case Registry was established in 1952. The Department of Energy (DOE) estimates that about 10,000 DOE employees and 800,000 people in private industry have worked with beryllium.
Scherer, John R
Celiac disease is an autoimmune disorder caused by the continued ingestion of gluten, a protein found in wheat, barley and rye, by predisposed individuals. With the development of highly sensitive serologic tests, this has become an increasingly recognized disease with prevalence as high as 1% in certain patient populations, such as Caucasian females. Almost all celiac patients carry the human leukocyte antigen DQ2/DQ8 gene. Much has recently been discovered about the role of the innate immune system in exposing genetically vulnerable patients to the pathogenic gliadin fraction of gluten. The "classical" presentation of chronic diarrhea and malabsorption is now a rarity. Due to earlier detection and increased awareness, celiac disease now presents with a myriad of "atypical" signs and symptoms such as iron-deficiency anemia and osteoporosis. Associated conditions include T-cell lymphoma, dermatitis herpetiformis, autoimmune thyroiditis and type 1 diabetes. Diagnosis requires serologic confirmation with either antiendomysial or antitransglutaminase antibodies as well as histologic confirmation from endoscopic small bowel biopsy. The only effective treatment necessitates a lifelong, continual adherence to a gluten-free diet.
Madigan, J E; Pusterla, N
Equine granulocytic and monocytic ehrlichiosis caused by Ehrlichia equi and E. risticii, respectively, are seasonal diseases in horses that occur throughout the United States E. equi is transmitted by lxodes ticks and causes high fever, depression, anorexia, limb edema, petechiation, icterus, ataxia, and stiffness in gait. E. risticii, also known as the agent of Potomac horse fever, causes a febrile illness with a colitis of variable severity. Its occurrence is associated with aquatic habitats. The natural route of transmission is oral, through the ingestion of E. risticii infected trematode stages either free in water or in an intermediate host, such as aquatic animals.
Uebelhart, Brigitte; Rizzoli, René
Calcium intake shows a small impact on bone mineral density and fracture risk. Denosumab is a more potent inhibitor of bone resorption than zoledronate. Abaloparatide, PTHrP analog, increases bone mineral density and decreases fracture incidence. Teriparatide could be delivered via a transdermic device. Romosozumab and odanacatib improve calculated bone strength. Sequential or combined treatments with denosumab and teriparatide could be of interest, but not denosumab followed by teriparatide. Fibrous dysplasia, Paget disease and hypophosphatasia are updated, as well as atypical femoral fracture and osteonecrosis of the jaw.
Celiac disease is an immunologically mediated enteropathy of the small intestine, characterized by lifelong intolerance to the gliadin and related prolamines from wheat and other cereals, that occurs in genetically predisposed individuals. Symptoms result from structural damage to the mucosa of the small intestine, which may cause malabsorption with positive autoantibodies in the sera. Normal mucosal architecture is restored after the use of a gluten-free diet and the normalization of the autoantibodies. Villous atrophy and high levels of autoantibodies reappear when gluten is reintroduced into the diet (gluten challenge).
Henchcliffe, Claire; Severt, W Lawrence
Parkinson's disease (PD) is an age-related, progressive, multisystem neurodegenerative disorder resulting in significant morbidity and mortality, as well as a growing social and financial burden in an aging population. The hallmark of PD is loss of dopaminergic neurons of the substantia nigra pars compacta, leading to bradykinesia, rigidity and tremor. Current pharmacological treatment is therefore centred upon dopamine replacement to alleviate symptoms. However, two major problems complicate this approach: (i) motor symptoms continue to progress, requiring increasing doses of medication, which result in both short-term adverse effects and intermediate- to long-term motor complications; (ii) dopamine replacement does little to treat non-dopaminergic motor and non-motor symptoms, which are an important source of morbidity, including dementia, sleep disturbances, depression, orthostatic hypotension, and postural instability leading to falls. It is critical, therefore, to develop a broader and more fundamental therapeutic approach to PD, and major research efforts have focused upon developing neuroprotective interventions. Despite many encouraging preclinical data suggesting the possibility of addressing the underlying pathophysiology by slowing cell loss, efforts to translate this into the clinical realm have largely proved disappointing in the past. Barriers to finding neuroprotective or disease-modifying drugs in PD include a lack of validated biomarkers of progression, which hampers clinical trial design and interpretation; difficulties separating symptomatic and neuroprotective effects of candidate neuroprotective therapies; and possibly fundamental flaws in some of the basic preclinical models and testing. However, three recent clinical trials have used a novel delayed-start design in an attempt to overcome some of these roadblocks. While not examining markers of cell loss and function, which would determine neuroprotective effects, this trial design
Tanowitz, H B; Kirchhoff, L V; Simon, D; Morris, S A; Weiss, L M; Wittner, M
Chagas' disease, caused by Trypanosoma cruzi, is an important cause of morbidity in many countries in Latin America. The important modes of transmission are by the bite of the reduviid bug and blood transfusion. The organism exists in three morphological forms: trypomastigotes, amastigotes, and epimastigotes. The mechanism of transformation and differentiation is currently being explored, and signal transduction pathways of the parasites may be involved in this process. Parasite adherence to and invasion of host cells is a complex process involving complement, phospholipase, penetrin, neuraminidase, and hemolysin. Two clinical forms of the disease are recognized, acute and chronic. During the acute stage pathological damage is related to the presence of the parasite, whereas in the chronic stage few parasites are found. In recent years the roles of tumor necrosis factor, gamma interferon, and the interleukins in the pathogenesis of this infection have been reported. The common manifestations of chronic cardiomyopathy are arrhythmias and thromboembolic events. Autoimmune, neurogenic, and microvascular factors may be important in the pathogenesis of the cardiomyopathy. The gastrointestinal tract is another important target, and "mega syndromes" are common manifestations. The diagnosis and treatment of this infection are active areas of investigation. New serological and molecular biological techniques have improved the diagnosis of chronic infection. Exacerbations of T. cruzi infection have been reported for patients receiving immuno-suppressive therapy and for those with AIDS. Images PMID:1423218
Inflammatory bowel disease in children - Crohn disease; IBD in children - Crohn disease; Regional enteritis - children; Ileitis - children; Granulomatous ileocolitis - children; Colitis in children; CD - children
Roca Espiau, Mercedes
The exposition aims, is to review the pathophysiological mechanisms of bone marrow involvement and the patterns of marrow infiltration by Gaucher cells. We have reviewed the different methods of assessment of bone marrow infiltration and its temporal development. Qualitative methods include simple radiography, magnetic resonance imaging (MRI), computed tomography (CT) and radioisotope. The simple radiography is the basic element, but its sensitivity is limited and only allows for assessing changes and trabecular bone remodeling MRI allows us to appreciate the bone marrow infiltration, detection of complications and response to therapy. Radioisotopes can contribute to the differential diagnosis of osteomyelitis and bone crises. Among the quantitative methods are the QCSI (quantitative chemical shift imaging) and the dual-energy X-ray absorptiometry (DEXA), as well as new quantitative techniques of CT, MRI and ultrasound densitometry. The QCSI performed an assessment of fat content of bone marrow in the spine. DEXA quantifies bone density by measuring the attenuation coefficient. The semiquantitative methods have various "scores" to establish criteria for generalized bone disease endpoints of disease progression and response to therapy.
... Disease Venous Thromboembolism Aortic Aneurysm More Inflammation and Heart Disease Updated:Oct 12,2016 Understand the risks of ... inflammation causes cardiovascular disease, inflammation is common for heart disease and stroke patients and is thought to be ...
Diet - heart disease; CAD - diet; Coronary artery disease - diet; Coronary heart disease - diet ... diet and lifestyle can reduce your risk of: Heart disease, heart attacks, and stroke Conditions that lead ...
Heart disease, Coronary heart disease, Coronary artery disease; Arteriosclerotic heart disease; CHD; CAD ... buildup of plaque in the arteries to your heart. This may also be called hardening of the ...
Heart disease - prevention; CVD - risk factors; Cardiovascular disease - risk factors; Coronary artery disease - risk factors; CAD - risk ... a certain health condition. Some risk factors for heart disease you cannot change, but some you can. ...
... Old Feeding Your 1- to 2-Year-Old Lyme Disease KidsHealth > For Parents > Lyme Disease A A A ... Pacific Northwest, and the northern Midwest states. About Lyme Disease Lyme disease is caused by the bacterium Borrelia ...
... Home Conditions Undifferentiated Connective Tissue Disease (UCTD) Undifferentiated Connective Tissue Disease (UCTD) Make an Appointment Find a Doctor ... L. Goldstein, MD, MMSc (February 01, 2016) Undifferentiated connective tissue disease (UCTD) is a systemic autoimmune disease. This ...
... Well with Rheumatic Disease Genetics and Rheumatic Disease Genetics and Rheumatic Disease Fast Facts Studying twins has ... 70%, and for non-identical pairs, even lower. Genetics and ankylosing spondylitis Each rheumatic disease has its ...
Briese, V; Seyfarth, M; Brock, J
Secretory IgA (S-IgA) was measured in serum samples from pregnant women by means of radial immunodiffusion according to Mancini with an antiserum against the secretory component and an S-IgA standard. The results neglect the differentiation in SC, S-IgA, and S-IgM. The study includes S-IgA serum levels during pregnancy and post partum as well as in patients with cervical carcinoma and inflammation of the genital tract. The S-IgA serum levels of pregnant women (2nd and 3rd trimester) and after delivery were increased significantly in comparison to nonpregnant women (p less than 0.01). The S-IgA levels in genital inflammation diseases and cervical carcinoma were only sometimes elevated. Pregnant women, 1st trimester: means = 40.0 mg/l (s = 12.2); pregnant women, 2nd trimester: means = 60.13 mg/l (s = 18.9); pregnant women, 3 rd trimester: means = 73.5 mg/l (s = 17.4); post partum: means = 77.5 mg/l (s = 29.52); cervical carcinoma: means = 41.9 mg/l (s = 17.3); adnexitis: means = 46.46 mg/l (s = 16.8); controls: means = 38.61 mg/l (s = 10.5). In a second part S-IgA could be estimated in serum samples of pregnant women by means of an enzyme-linked immunosorbent assay (ELISA). The levels ranged from 7.1 mg/l to 19.3 mg/l in the 1st trimenon and from 16.8 mg/l to 82 mg/l in the 3rd trimenon (means = 11.72 mg/l; s = 4.419; n = 21 and means = 40.01 mg/l; s = 15.117; n = 60). This increasing was significant too (p less than 0.01).
Orlicka, Katarzyna; Barnes, Eleanor
Immunosuppressive therapy is frequently used to treat gastrointestinal diseases such as inflammatory bowel disease, autoimmune hepatitis, IgG4-related disease (autoimmune pancreatitis and sclerosing cholangitis) and in the post-transplantation setting. These drugs interfere with the immune system. The main safety concern with their use is the risk of infections. Certain infections can be prevented or their impact minimized. Physicians must adopt preventative strategies and should have a high degree of suspicion to recognize infections early and treat appropriately. This article reviews the risk factors for infections, the mechanism of action of immunosuppressive therapy and proposes preventive strategies. PMID:23819020
... They Work Kidney Disease A-Z Acquired Cystic Kidney Disease What is acquired cystic kidney disease? Acquired cystic kidney disease happens when a ... cysts. What are the differences between acquired cystic kidney disease and polycystic kidney disease? Acquired cystic kidney ...
Bratton, Laura; Salloum, Rabih; Cao, Wenqing
Solitary fibrous tumor is a rare, benign spindle cell neoplasm that was first described in the thoracic pleura. This tumor is now known to occur at many extrapleural sites. There are established criteria for the diagnosis of malignant solitary fibrous tumor including ≥4 mitotic figures per 10 high-power fields, increased cellularity, cytologic atypia, infiltrative margins, and/or necrosis. Although all solitary fibrous tumors have the potential to recur or metastasize, those with malignant histologic features tend to behave more aggressively. We report a case of solitary fibrous tumor, with malignant histologic features, in a 21-year-old woman which arose from the serosal surface of the sigmoid colon. PMID:27672467
Hayashi, Takuo; Kumasaka, Toshio; Mitani, Keiko; Terao, Yasuhisa; Watanabe, Masao; Oide, Takashi; Nakatani, Yukio; Hebisawa, Akira; Konno, Ryo; Takahashi, Kazuhisa; Yao, Takashi; Seyama, Kuniaki
Lymphangioleiomyomatosis (LAM), a systemic disorder affecting almost exclusively young women, is characterized by the abnormal proliferation of smooth muscle-like cells (LAM cells). LAM can occur either in association with the tuberous sclerosis complex (TSC) (TSC-LAM) or without TSC (sporadic LAM). Recent studies have demonstrated that LAM is a neoplasm arising from constitutive activation of the mammalian target of rapamycin signaling pathway dysregulated by a functional loss of TSC genes, but the primary organ of origin remains unclear. Therefore, we performed histologic and immunohistologic analyses of gynecologic organs in 20 patients, half with and the other half without pulmonary LAM, to determine how often LAM involves the uterus. The results showed that 9 of 10 (90%) patients with pulmonary LAM had uterine LAM lesions. In contrast, no patients without pulmonary LAM had so. All uterine LAM lesions were accompanied by LAM lesions in retroperitoneal or pelvic lymph nodes and LAM cell clusters, each enveloped by a monolayer of vascular endothelial growth factor receptor-3-positive lymphatic endothelial cells. Furthermore, when we compared uterine lesions of TSC-LAM with those of sporadic LAM, proliferation of HMB45-positive epithelioid-shaped LAM cells and infiltrates with a tongue-like growth pattern was more prominent in the former, whereas the extent of lymphangiogenesis within the myometrium was greater in the latter. These results indicate that uterine involvement is a common manifestation of LAM, and, possibly, that the uterus or an adjacent locale in the retroperitoneum or pelvic cavity is the primary site of origin of LAM.
... HUMAN SERVICES Food and Drug Administration 21 CFR Part 866 Medical Devices; Immunology and Microbiology... for the filing and review of a petition for reclassification of such class III devices. In order to... effectiveness of the device for its intended use. After review of the information submitted in the petition,...
... screening or diagnostic test for ovarian cancer. Off-label use of the test (e.g., in patients who are not... gynecological oncologist, despite negative results from other clinical and radiographic tests for ovarian cancer... labeling provisions of this final rule are not subject to review by the Office of Management and...
... test for ovarian cancer. Off-label use of the test (e.g., in patients who are not already ] identified... gynecological oncologist, despite negative results from other clinical and radiographic tests for ovarian cancer...? FDA concludes that labeling provisions of this proposed rule are not subject to review by the...
Pérez-Martínez, Ignacio Jaime; Mantilla-Morales, Alejandra; Cruz-Esquivel, Iván; Gallegos-Hernández, José Francisco
Antecedente: el carcinoma triquilemal es una neoplasia maligna poco frecuente originada en los anexos de la piel. Debido a su escasa prevalencia suele confundirse con otros tumores dérmicos, su presentación clínica no favorece el diagnóstico diferencial y generalmente éste se hace por exclusión. En teoría, su comportamiento es lento, con poca tendencia a enviar metástasis regionales ganglionares y sistémicas. Debido al escaso número de casos no existe consenso en relación con el pronóstico, aunque generalmente se estima bueno. El objetivo de este reporte es mostrar un caso que, contrario a lo informado, es de manifestación agresiva en un paciente sin factores de riesgo para cáncer de piel, con gran infiltración tumoral de los tejidos blandos alrededor del sitio de origen. Caso clínico: paciente masculino de 65 años de edad que acudió con diagnóstico citológico de carcinoma en un tumor facial preparotídeo; al momento del diagnóstico motraba infiltración de la piel de la cara, del pabellón auricular y de la glándula parótida. Se efectuó resección completa de la neoplasia en bloque con isla de piel facial, parotidectomía total y disección radical del cuello; el defecto de partes blandas fue cubierto con un colgajo pediculado. La evolución ha sido satisfactoria; sin embargo, el seguimiento es corto. Se evalúa la experiencia asentada en la bibliografía en relación con el pronóstico y tratamiento de estos pacientes. Conclusión: el carcinoma triquilemal puede tener comportamiento localmente invasor lo que hace difícil determinar el pronóstico, que quizá dependa de la etapa clínica al momento del diagnóstico.
Lee, Yvonne Y; Tucker, Simon C; Prow, Natalie A; Setoh, Yin Xiang; Banney, Leith A
Trichodysplasia spinulosa is a rare polyomavirus-associated cutaneous eruption occurring in the setting of immunosuppression. Clinically it is characterised by multiple centrofacial folliculocentric papules with spinous protuberances. The histopathology is distinct and treatment with antiviral agents appears to be the most effective.
Nisanci, Mustafa; Sahin, Ismail; Guzey, Serbulent
Although striking improvements have been achieved in overall management of burn injury, postburn contractures are still an ongoing challenge to burn surgeons. Axillary adduction contracture is one of the most common types of these disabling postburn complications that usually result from suboptimal treatment after acute burns. An unusual and complicated case of axillary contracture in which the unburned, healthy axillary dome skin was trapped as a cystic mass under the scarred area was reconstructed by transfer of a big (17×13-cm) thoracodorsal artery perforator flap after contracture release. The result was satisfactory in terms of function and acceptable cosmetically. The underlying reasons for the inadequate treatment the patient received after surviving a severe electrical injury were discussed.
H'ng, M W C; Wanigasiri, U I D K; Ong, C L
Perineural (Tarlov) cysts are usually incidental findings during magnetic resonance imaging (MRI) performed for low back pain. However, in a tertiary women's hospital, they may present as incidental findings on gynecological ultrasound imaging. Approximately 40,000 pelvic scans are performed annually in our department. Tarlov cysts were identified in three women between August 2007 and September 2008. In two patients (Cases 1 and 3), these cysts were initially misdiagnosed as hydrosalpinges on ultrasound examination, the latter having a differential diagnosis of an ovarian cyst. Two patients (Cases 1 and 2) were symptomatic, although Case 2 had symptoms that could not entirely be accounted for by the location of the cyst. Although asymptomatic, Case 3 underwent laparoscopy with a view to salpingectomy/cystectomy. In these patients, confirmation of Tarlov cysts was subsequently made on either computed tomography (CT) or MRI. All three patients were managed conservatively. Here we describe their clinical presentation, the appearance of the cysts on ultrasound imaging and on CT or MRI, and their eventual outcomes.
Oliver Perez, M Reyes; Magriñá, Javier; García, Alvaro Tejerizo; Jiménez Lopez, Jesus Salvador
At present, there is no effective screening of ovarian cancer. Primary prevention may be the only strategy to decrease the mortality from ovarian cancer, not only in women at high risk but also at low risk. Several recent studies have identified the distal fimbriae end of the fallopian tubes as primary precursor of High-grade serous carcinoma. Serous tubal intraepithelial carcinomas and occult invasive serous carcinomas have been identified in 2-17% of the fallopian tubes of BRCA1/2 positive women undergoing risk-reducing salpingo-oophorectomy. Removal of the fallopian tubes with ovarian preservation has been suggested as a reasonable strategy that could reduce the risk of developing ovarian carcinoma in both low and high-risk women. It has been proposed after childbearing in women at high risk to be followed by bilateral oophorectomy at a later date. Bilateral salpingectomy is also suggested for low risk women, at the time of other benign gynaecologic surgery as a primary preventive strategy. Some studies have shown a risk reduction of ovarian cancer in women with bilateral prophylactic salpingectomy. Current research regarding bilateral salpingoophorectomy as primary prevention approach of ovarian cancer is reviewed here. In addition, the potential use of bilateral salpingectomy as prevention approach of ovarian cancer is discussed.
... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Tumor Associated Antigen... surgery is planned, is malignant. The test is for adjunctive use, in the context of a negative primary clinical and radiological evaluation, to augment the identification of patients whose gynecologic...
Belletti, Gerardo A; Savio, Verónica; Minoldo, Daniel; Caminos, Susana; Yorio, Marcelo A
A 66 years female, who was since last year under astenia, arthralgias, pimply lesions in spread plates and tests showing eritrosedimentation over 100 mm, anemi, leucocitosis with neutrofilia, policlonal hypergammaglobulinemia, slight proteinuria and IgE on 900. This patient was sporadically treated with corticoids. When made the medical consult had lost 34lb., was under anorexy, as well as dyspepsia. Hemoglobyn 6.9 gr/dl, leucocytes 20000/mm3, neutrofils at 90%, proteinogram the same as former, with hypoalbuminemia. She was taking prednisona, 16 mg/day. When examined showed depress of conscience, astenia, and dermic lesions already quoted. 4 cm nonpainful right axillary adenopaty adhered to deep planes. Medulogram with increased iron, hyperegenerative. Ganglionar biopsia: linfoid hyperplasic process linked to inmune response. Toracoabdominal tomography with adenomegalia in torax and retroperitoneo. Skin biopsia: neutrofilic vasculitis. The patient suspends the 16 mg of prednisona and fever as well as generalized adenopatias come up. After laying aside other ethiologies, and understanding as Castleman Multicentric disease, it is started to supply prednisona 1 mg/kg of weight with a clinical and biochemical fast and outstanding response. After 7 months it was progressively suspended the esteroids and 60 days later, the process fall back; for that, corticoids are restarted, with a good evolution. The illness of Castleman although it is not very frequent, it should be considered as differential diagnosis in those clinical cases that are accompanied with important general commitment, linphadenopaties and respons to steroid therapy.
Benninger, David H
In advanced Parkinson's disease (PD), the emergence of symptoms refractory to conventional therapy poses therapeutic challenges. The success of deep brain stimulation (DBS) and advances in the understanding of the pathophysiology of PD have raised interest in noninvasive brain stimulation as an alternative therapeutic tool. The rationale for its use draws from the concept that reversing abnormalities in brain activity and physiology thought to cause the clinical deficits may restore normal functioning. Currently the best evidence in support of this concept comes from DBS, which improves motor deficits, and modulates brain activity and motor cortex physiology, although whether a causal interaction exists remains largely undetermined. Most trials of noninvasive brain stimulation in PD have applied repetitive transcranial magnetic stimulation (rTMS), targeting the motor cortex. Current studies suggest a possible therapeutic potential for rTMS and transcranial direct current stimulation (tDCS), but clinical effects so far have been small and negligible with regard to functional independence and quality of life. Approaches to potentiate the efficacy of rTMS include increasing stimulation intensity and novel stimulation parameters that derive their rationale from studies on brain physiology. These novel parameters are intended to simulate normal firing patterns or to act on the hypothesized role of oscillatory activity in the motor cortex and basal ganglia with regard to motor control and its contribution to the pathogenesis of motor disorders. Noninvasive brain stimulation studies will enhance our understanding of PD pathophysiology and might provide further evidence for potential therapeutic applications.
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Siroky, Brian J.; Yin, Hong
Glomerulocystic disease is a rare renal cystic disease with a long descriptive history. Findings from recent studies have significantly advanced the pathophysiological understanding of the disease processes leading to this peculiar phenotype. Many genetic syndromes associated with glomerulocystic disease have had their respective proteins localized to primary cilia or centrosomes. Transcriptional control of renal developmental pathways is dysregulated in obstructive diseases that also lead to glomerulocystic disease, emphasizing the importance of transcriptional choreography between renal development and renal cystic disease. PMID:20091054
Skip Navigation Bar Home Current Issue Past Issues Skin Diseases Skin Health and Skin Diseases Past Issues / Fall 2008 Table of Contents ... acne to wrinkles Did you know that your skin is the largest organ of your body? It ...
Fujioka, Shinsuke; Curry, Sadie E; Kennelly, Kathleen D; Tacik, Pawel; Heckman, Michael G; Tsuboi, Yoshio; Strongosky, Audrey J; van Gerpen, Jay A; Uitti, Ryan J; Ross, Owen A; Ikezu, Tsuneya; Wszolek, Zbigniew K
We retrospectively investigated the co-occurrence of Crohn's disease in a cohort of 876 patients with Parkinson's disease, based on the observation that LRRK2 is a shared genetic risk factor. We identified 2 patients with Crohn's disease; this number was consistent with the number of cases expected in the general population.
McBroom, Lynn W.
Alzheimer's disease, a form of dementia in middle-age and older adults is becoming more evident because of growing numbers of older people and better diagnosis and detection methods. Describes the behavioral and physical symptoms of the disease as well as specific suggestions for care of patients with Alzheimer's disease, including dealing with…
Tay-Sachs disease is a rare, inherited disease. It is a type of lipid metabolism disorder. It causes too ... cells, causing mental and physical problems. . Infants with Tay-Sachs disease appear to develop normally for the first few ...
... disease Long-term infections, such as bacterial endocarditis, osteomyelitis (bone infection), HIV/AIDS , hepatitis B or hepatitis ... disease Crohn disease Erythropoietin test Juvenile idiopathic arthritis Osteomyelitis Rheumatic fever Ulcerative colitis Review Date 2/1/ ...
... Instagram Email Menu Understanding Mitochondrial Disease What is Mito? What is Mitochondrial Disease? Types of Mitochondrial Disease ... Program Frequently Asked Questions Newly Diagnosed Treatments & Therapies Mito 101 MitoFIRST Handbook Current Clinical Trials & Studies Community ...
... system. Some people are born with an arrhythmia. Heart valve diseases occur when one of the four valves in ... heart attack, heart disease, or infection, can cause heart valve diseases. Some people are born with heart valve problems. ...
... of Pediatric Gastroenterology and Nutrition Nurses Print Share Celiac Disease Many kids have sensitivities to certain foods, ... protein found in wheat, rye, and barley. Pediatric Celiac Disease If your child has celiac disease, consuming ...
... Disease How do doctors treat celiac disease? A gluten-free diet Doctors treat celiac disease with a ... absorb nutrients from food into the bloodstream normally. Gluten-free diet and dermatitis herpetiformis If you have ...
... work? How does inflammatory bowel disease interfere with digestion? Who gets inflammatory bowel disease? How is inflammatory ... top How does inflammatory bowel disease interfere with digestion? When the small intestine becomes inflamed, as in ...
... Disease Venous Thromboembolism Aortic Aneurysm More Cardiovascular Disease & Diabetes Updated:Nov 4,2016 The following statistics speak ... disease. This content was last reviewed August 2015. Diabetes • Home • About Diabetes • Why Diabetes Matters Introduction Cardiovascular ...
Your doctor has told you that you have Parkinson disease . This disease affects the brain and leads ... have you take different medicines to treat your Parkinson disease and many of the problems that may ...
... What Happens in the Operating Room? What's Mad Cow Disease? KidsHealth > For Kids > What's Mad Cow Disease? A A A You might have heard news reports about mad cow disease and wondered: What the heck is that? ...
... Fact files Questions & answers Features Multimedia Contacts Ebola virus disease Fact sheet Updated January 2016 Key facts ... survivors of Ebola virus disease Symptoms of Ebola virus disease The incubation period, that is, the time ...
... autoimmune diseases associated with Peyronie’s disease affect connective tissues. Connective tissue is specialized tissue that supports, joins, or ... penis are more likely to develop Peyronie’s disease. Connective Tissue and Autoimmune Disorders Men who have certain connective ...
Lyme disease is an acute inflammatory disease characterized by skin changes, joint inflammation and symptoms similar to the ... that is caused by the bacterium Borrelia burgdorferi . Lyme disease is transmitted by the bite of a deer ...
... What are Crohn's & Colitis? > What is Crohn’s Disease? Crohn’s Disease is a Chronic Condition By understanding your ... live a full and rewarding life What is Crohn’s Disease? Email Print + Share Named after Dr. Burrill ...
... from the NHLBI on Twitter. What Is Von Willebrand Disease? Von Willebrand disease (VWD) is a bleeding disorder. ... while hemophilia mainly affects males. Types of von Willebrand Disease The three major types of VWD are called ...
Still's disease - adult; AOSD ... than 1 out of 100,000 people develop adult-onset Still's disease each year. It affects women more often than men. The cause of adult Still's disease is unknown. No risk factors for ...
... be coronary heart disease (CHD), heart failure, and diabetic cardiomyopathy. Diabetes by itself puts you at risk for heart disease. Other risk factors include Family history of heart disease Carrying extra ...
... Heart Disease Diseases of the arteries, valves, and aorta, as well as cardiac rhythm disturbances Aortic Valve ... are two main types of mitral valve disease: Stenosis – the valve does not open enough to allow ...
... in girls, and muscle weakness. Graves disease , an autoimmune disease, is the most common cause of hyperthyroidism. The ... toes thy-roy-DYE-tiss) is also an autoimmune disease and is the most common cause of hypothyroidism ...
... Home > Resources > Liver Disease and IBD Go Back Liver Disease and IBD Email Print + Share Several complications ... be necessary to make the definitive diagnosis. FATTY LIVER DISEASE (HEPATCI STEATOSIS) This is the most common ...
Liver disease test panel - autoimmune ... Autoimmune disorders are a possible cause of liver disease. The most common of these diseases are autoimmune hepatitis and primary biliary cirrhosis. This group of tests helps your health care provider ...
Resources - heart disease ... The following organizations are good resources for information on heart disease: American Heart Association -- www.heart.org Centers for Disease Control and Prevention -- www.cdc.gov/heartdisease
Resources - kidney disease ... The following organizations are good resources for information on kidney disease: National Kidney Disease Education Program -- www.nkdep.nih.gov National Kidney Foundation -- www.kidney.org National ...
... diseases Autoimmune diseases Degenerative diseases such as amyotrophic lateral sclerosis and spinal muscular atrophy Symptoms vary but might include pain, numbness, loss of sensation and muscle weakness. These symptoms can occur around the spinal ...
... Pollutants Natural Disasters Drinking Water Waterborne Diseases & Illnesses Water Cycle Water Treatment Videos Games Experiments For Teachers Home ... Pollutants Natural Disasters Drinking Water Waterborne Diseases & Illnesses Water Cycle Water Treatment Waterborne Diseases & Illnesses The Basics Would ...
Annibali, Ombretta; Chiodi, Francesca; Sarlo, Chiara; Cortes, Magdalena; Quaranta-Leoni, Francesco M; Quattrocchi, Carlo; Bianchi, Antonella; Bonini, Stefano; Avvisati, Giuseppe
Ocular Adnexal Lymphomas are the first cause of primary ocular malignancies, and among them the most common are MALT Ocular Adnexal Lymphomas. Recently systemic immunotherapy with anti-CD20 monoclonal antibody has been investigated as first-line treatment; however, the optimal management for MALT Ocular Adnexal Lymphomas is still unknown. The present study evaluated retrospectively the outcome of seven consecutive patients with primary MALT Ocular Adnexal Lymphomas, of whom six were treated with single agent Rituximab. All patients received 6 cycles of Rituximab 375 mg/mq every 3 weeks intravenously. The overall response rate was 100%; four patients (67%) achieved a Complete Remission, and two (33%) achieved a partial response. In four patients an additional Rituximab maintenance every 2-3 months was given for two years. After a median follow-up of 29 months (range 8-34), no recurrences were observed, without of therapy- or disease-related severe adverse events. None of the patients needed additional radiotherapy or other treatments. Rituximab as a single agent is highly effective and tolerable in first-line treatment of primary MALT Ocular adnexal Lymphomas. Furthermore, durable responses are achievable with the same-agent maintenance. Rituximab can be considered the agent of choice in the management of an indolent disease in whom the "quality of life" matter is of primary importance.
Annibali, Ombretta; Chiodi, Francesca; Sarlo, Chiara; Cortes, Magdalena; Quaranta-Leoni, Francesco M.; Quattrocchi, Carlo; Bianchi, Antonella; Bonini, Stefano; Avvisati, Giuseppe
Ocular Adnexal Lymphomas are the first cause of primary ocular malignancies, and among them the most common are MALT Ocular Adnexal Lymphomas. Recently systemic immunotherapy with anti-CD20 monoclonal antibody has been investigated as first-line treatment; however, the optimal management for MALT Ocular Adnexal Lymphomas is still unknown. The present study evaluated retrospectively the outcome of seven consecutive patients with primary MALT Ocular Adnexal Lymphomas, of whom six were treated with single agent Rituximab. All patients received 6 cycles of Rituximab 375 mg/mq every 3 weeks intravenously. The overall response rate was 100%; four patients (67%) achieved a Complete Remission, and two (33%) achieved a partial response. In four patients an additional Rituximab maintenance every 2-3 months was given for two years. After a median follow-up of 29 months (range 8–34), no recurrences were observed, without of therapy- or disease-related severe adverse events. None of the patients needed additional radiotherapy or other treatments. Rituximab as a single agent is highly effective and tolerable in first-line treatment of primary MALT Ocular adnexal Lymphomas. Furthermore, durable responses are achievable with the same-agent maintenance. Rituximab can be considered the agent of choice in the management of an indolent disease in whom the “quality of life” matter is of primary importance. PMID:26425558
Fructose Metabolism, Inborn Errors; Glycogen Storage Disease; Glycogen Storage Disease Type I; Glycogen Storage Disease Type II; Glycogen Storage Disease Type III; Glycogen Storage Disease Type IV; Glycogen Storage Disease Type V; Glycogen Storage Disease Type VI; Glycogen Storage Disease Type VII; Glycogen Storage Disease Type VIII
Berg, Aaron N; Soma, Lorinda; Clark, Beth Z; Swerdlow, Steven H; Roth, Christine G
Lymphoplasmacytic infiltrates in the breast, a modified skin appendage, include lymphocytic lobulitis, other nonspecific benign proliferations, and mucosa-associated lymphoid tissue (MALT)-type lymphoma. Distinguishing these entities, all of which may be B-cell rich and may have associated sclerosis, can be difficult. In addition, the proportion that represents IgG4-related disease is unknown, and the similarity of MALT lymphomas to primary cutaneous marginal zone lymphoma is uncertain. To address these questions, the clinical, histologic, and immunohistochemical features of 50 benign and malignant breast lymphoplasmacytic infiltrates (10 lymphocytic lobulitis, 1 granulomatous, 19 not otherwise specified, 20 MALT lymphomas) were evaluated. Compared with the MALT lymphomas, benign cases had a less dense infiltrate (P < .001), fewer but more histologically apparent germinal centers (P < .001), and more marked fibrosis (P < .0001). Greater than 60% B cells were present in 23% (7/30) benign cases versus 75% (15/20) MALT lymphomas (P = .0003). Plasma cells were predominantly IgG+ in 83% (24/29) benign cases and predominantly IgM+ in 73% (14/19) MALT lymphomas (P < .0001). None of the benign cases had greater than 50 IgG4+ plasma cells/high-power field, and only 1 lymphocytic lobulitis case had an IgG4/IgG ratio exceeding 40% and no clinical evidence for extramammary IgG4-related disease. Although there may be some overlapping features, routine histopathology together with limited immunohistochemical stains can distinguish benign from neoplastic lymphoplasmacytic infiltrates in the breast. Despite frequent sclerosis, the breast is not a common site of unrecognized IgG4-related sclerosing disease. Although there are similarities, breast MALT lymphomas can be separated from cutaneous marginal zone lymphoma.
Sun, Kai; Buchan, Natalie; Larminie, Chris; Pržulj, Nataša
The growing body of transcriptomic, proteomic, metabolomic and genomic data generated from disease states provides a great opportunity to improve our current understanding of the molecular mechanisms driving diseases and shared between diseases. The use of both clinical and molecular phenotypes will lead to better disease understanding and classification. In this study, we set out to gain novel insights into diseases and their relationships by utilising knowledge gained from system-level molecular data. We integrated different types of biological data including genome-wide association studies data, disease-chemical associations, biological pathways and Gene Ontology annotations into an Integrated Disease Network (IDN), a heterogeneous network where nodes are bio-entities and edges between nodes represent their associations. We also introduced a novel disease similarity measure to infer disease-disease associations from the IDN. Our predicted associations were systemically evaluated against the Medical Subject Heading classification and a statistical measure of disease co-occurrence in PubMed. The strong correlation between our predictions and co-occurrence associations indicated the ability of our approach to recover known disease associations. Furthermore, we presented a case study of Crohn's disease. We demonstrated that our approach not only identified well-established connections between Crohn's disease and other diseases, but also revealed new, interesting connections consistent with emerging literature. Our approach also enabled ready access to the knowledge supporting these new connections, making this a powerful approach for exploring connections between diseases.
Sanan, Akshay; Cognetti, David M
The differential diagnosis for "rare" parotid gland diseases is broad and encompasses infectious, neoplastic, autoimmune, metabolic, and iatrogenic etiologies. The body of knowledge of parotid gland diseases has grown owing to advances in imaging and pathologic analysis and molecular technology. This article reviews rare parotid diseases, discussing the respective disease's clinical presentation, diagnosis, imaging, pathogenesis, treatment, and prognosis.
... Disease Chronic Kidney Disease (CKD) What Is Chronic Kidney Disease? Causes of CKD Tests & Diagnosis Managing CKD Eating Right Preventing CKD What If My Kidneys Fail? Clinical Trials Anemia High Blood Pressure Heart ... Nephropathy Kidney Disease in Children Childhood Nephrotic Syndrome Hemolytic ...
... in families). It causes a type of abnormal hemoglobin (a protein found in red blood cells). Hemoglobin carries oxygen in the blood. Normal red blood ... betathalassemia, chronic hemolytic anemia, drepanocytic anemia, Hb S disease, ... disease, hemoglobin SC disease, hemoglobin SS disease, hemoglobin synthesis, ...
Interstitial lung disease is the name for a large group of diseases that inflame or scar the lungs. The inflammation and scarring make it hard to ... air is responsible for some types of interstitial lung diseases. Specific types include Black lung disease among ...
Ahearn, Joseph; Shields, Kelly J; Liu, Chau-Ching; Manzi, Susan
Cardiovascular disease is increasingly recognized as a major cause of premature mortality among those with autoimmune disorders. There is an urgent need to identify those patients with autoimmune disease who are at risk for CVD so as to optimize therapeutic intervention and ultimately prevention. Accurate identification, monitoring and stratification of such patients will depend upon a panel of biomarkers of cardiovascular disease. This review will discuss some of the most recent biomarkers of cardiovascular diseases in autoimmune disease, including lipid oxidation, imaging biomarkers to characterize coronary calcium, plaque, and intima media thickness, biomarkers of inflammation and activated complement, genetic markers, endothelial biomarkers, and antiphospholipid antibodies. Clinical implementation of these biomarkers will not only enhance patient care but also likely accelerate the pharmaceutical pipeline for targeted intervention to reduce or eliminate cardiovascular disease in the setting of autoimmunity.
Wanner, Nicola; Bechtel-Walz, Wibke
DNA methylation and histone modifications determine renal programming and the development and progression of renal disease. The identification of the way in which the renal cell epigenome is altered by environmental modifiers driving the onset and progression of renal diseases has extended our understanding of the pathophysiology of kidney disease progression. In this review, we focus on current knowledge concerning the implications of epigenetic modifications during renal disease from early development to chronic kidney disease progression including renal fibrosis, diabetic nephropathy and the translational potential of identifying new biomarkers and treatments for the prevention and therapy of chronic kidney disease and end-stage kidney disease.
Fabri, Gisele M C; Savioli, Cynthia; Siqueira, José T; Campos, Lucia M; Bonfá, Eloisa; Silva, Clovis A
Gingivitis and periodontitis are immunoinflammatory periodontal diseases characterized by chronic localized infections usually associated with insidious inflammation This narrative review discusses periodontal diseases and mechanisms influencing the immune response and autoimmunity in pediatric rheumatic diseases (PRD), particularly juvenile idiopathic arthritis (JIA), childhood-onset systemic lupus erythematosus (C-SLE) and juvenile dermatomyositis (JDM). Gingivitis was more frequently observed in these diseases compared to health controls, whereas periodontitis was a rare finding. In JIA patients, gingivitis and periodontitis were related to mechanical factors, chronic arthritis with functional disability, dysregulation of the immunoinflammatory response, diet and drugs, mainly corticosteroids and cyclosporine. In C-SLE, gingivitis was associated with longer disease period, high doses of corticosteroids, B-cell hyperactivation and immunoglobulin G elevation. There are scarce data on periodontal diseases in JDM population, and a unique gingival pattern, characterized by gingival erythema, capillary dilation and bush-loop formation, was observed in active patients. In conclusion, gingivitis was the most common periodontal disease in PRD. The observed association with disease activity reinforces the need for future studies to determine if resolution of this complication will influence disease course or severity.
Kolettis, Peter N
Genetic diseases that do not primarily affect the genitourinary tract may have urologic manifestations. These urologic manifestations range from benign and malignant renal disease to infertility. Thus, the practicing urologist may be involved in the care of these patients and should have knowledge of these diseases. Continued improvements in the diagnosis and treatment of these genetic diseases will likely result in improved survival and will increase the number of patients who may develop urologic manifestations of these diseases.
Gouras, Gunnar K
Immunotherapy approaches for Alzheimer disease currently are among the leading therapeutic directions for the disease. Active and passive immunotherapy against the beta-amyloid peptides that aggregate and accumulate in the brain of those afflicted by the disease have been shown by numerous groups to reduce plaque pathology and improve behavior in transgenic mouse models of the disease. Several ongoing immunotherapy clinical trials for Alzheimer disease are in progress. The background and ongoing challenges for these immunological approaches for the treatment of Alzheimer disease are discussed.
... borne diseases such as ehrlichiosis, babesiosis, Lyme disease , Rocky Mountain Spotted Fever and others. People can also become infected with ... borne diseases such as ehrlichiosis, babesiosis, Lyme disease , Rocky Mountain Spotted Fever and others. The symptoms caused by these diseases ...
Liver Disease Pulmonary & PH Hypertension Did you know that if you have liver disease, you are at risk for pulmonary hypertension? ... tissue diseases (scleroderma and lupus for example), chronic liver disease, congenital heart disease, or HIV infec- tion. ...
Jia, Lin; Yuan, Zeng; Wang, Yiying; Cragun, Janiel M; Kong, Beihua; Zheng, Wenxin
Serous endometrial intraepithelial carcinoma is often associated with extrauterine disease. It is currently unclear where does the extrauterine disease come from. This study addressed this issue. A total of 135 samples from 21 serous endometrial intraepithelial carcinoma patients were studied. Cellular lineage relationships between intrauterine and extrauterine serous carcinomas were determined by TP53-mutation analysis and correlated to the clinicopathologic features. There were three conditions contributing the extrauterine disease: metastasis from serous endometrial intraepithelial carcinoma (n=10) showed identical TP53 mutation between intrauterine lesions and extrauterine disease, cases of adnexal origin (n=5) had discordant TP53 mutations, and the mixed cellular origin cases (n=6) with both identical and discordant mutation status. Patients with extrauterine disease from serous endometrial intraepithelial carcinoma metastasis typically had small tumor masses (<2 cm) in extrauterine sites and without finding of serous tubal intraepithelial carcinoma, while extrauterine disease with adnexal or tubal origin commonly had larger tumor masses in extrauterine sites including ovary and omentum and serous tubal intraepithelial carcinoma. The majority of extrauterine diseases associated with serous endometrial intraepithelial carcinoma are metastasized from the endometrium. Serous endometrial intraepithelial carcinoma is frequently associated with serous cancers of adnexal or tubal origin, indicating that endometrial and adnexal or tubal serous cancers may share similar etiologies. TP53-mutation analysis provides a strong linkage for cellular lineage analysis. Tumor size in extrauterine disease and presence of serous tubal intraepithelial carcinoma or not are useful clinicopathologic features to determine primary cancer site, which helps in clinical management.
Mikolasevic, Ivana; Milic, Sandra; Turk Wensveen, Tamara; Grgic, Ivana; Jakopcic, Ivan; Stimac, Davor; Wensveen, Felix; Orlic, Lidija
Non-alcoholic fatty liver disease (NAFLD) is one of the most common comorbidities associated with overweight and metabolic syndrome (MetS). Importantly, NAFLD is one of its most dangerous complications because it can lead to severe liver pathologies, including fibrosis, cirrhosis and hepatic cellular carcinoma. Given the increasing worldwide prevalence of obesity, NAFLD has become the most common cause of chronic liver disease and therefore is a major global health problem. Currently, NAFLD is predominantly regarded as a hepatic manifestation of MetS. However, accumulating evidence indicates that the effects of NAFLD extend beyond the liver and are negatively associated with a range of chronic diseases, most notably cardiovascular disease (CVD), diabetes mellitus type 2 (T2DM) and chronic kidney disease (CKD). It is becoming increasingly clear that these diseases are the result of the same underlying pathophysiological processes associated with MetS, such as insulin resistance, chronic systemic inflammation and dyslipidemia. As a result, they have been shown to be independent reciprocal risk factors. In addition, recent data have shown that NAFLD actively contributes to aggravation of the pathophysiology of CVD, T2DM, and CKD, as well as several other pathologies. Thus, NAFLD is a direct cause of many chronic diseases associated with MetS, and better detection and treatment of fatty liver disease is therefore urgently needed. As non-invasive screening methods for liver disease become increasingly available, detection and treatment of NAFLD in patients with MetS should therefore be considered by both (sub-) specialists and primary care physicians. PMID:27920470
Lung disease - rheumatoid arthritis; Rheumatoid nodules; Rheumatoid lung ... Lung problems are common in rheumatoid arthritis. They often cause no symptoms. The cause of lung disease associated with rheumatoid arthritis is unknown. Sometimes, the medicines used to ...
... Kawasaki Disease Long Q-T Syndrome Marfan Syndrome Metabolic Syndrome Mitral Valve Prolapse Myocardial Bridge Myocarditis Obstructive Sleep Apnea Pericarditis Peripheral Vascular Disease Rheumatic Fever Sick Sinus Syndrome Silent Ischemia Stroke Sudden ...
Lewy body disease is one of the most common causes of dementia in the elderly. Dementia is the loss of mental ... to affect normal activities and relationships. Lewy body disease happens when abnormal structures, called Lewy bodies, build ...
Pelvic inflammatory disease (PID) is an infection and inflammation of the uterus, ovaries, and other female reproductive organs. It causes scarring ... United States. Gonorrhea and chlamydia, two sexually transmitted diseases, are the most common causes of PID. Other ...
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... brain with blood. If you have carotid artery disease, the arteries become narrow, usually because of atherosclerosis. ... one of the causes of stroke. Carotid artery disease often does not cause symptoms, but there are ...
NPD; Sphingomyelinase deficiency; Lipid storage disorder - Niemann-Pick disease; Lysosomal storage disease - Niemann-Pick ... cannot properly break down cholesterol and other fats (lipids). This leads to too much cholesterol in the ...
... Education » Fact Sheets Machado-Joseph Disease 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 ...