Sample records for dapsone
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... are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking dapsone, call your doctor.plan to avoid unnecessary or prolonged exposure to sunlight and to wear protective clothing, sunglasses, and sunscreen. Dapsone may make your skin sensitive to sunlight.
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[Dapsone treatment of folliculitis decalvans].
Paquet, P; Piérard, G-E
2004-02-01
Folliculitis decalvans consists of recurrent patchy painful folliculitis of the scalp causing scarring alopecia. The physiopathology of this condition is still unclear, but is likely a manifestation of chronic neutrophilic bacterial folliculitis. Numerous topical and systemic treatments (corticosteroids, antistaphylococcal antibiotics) have been used with variable results. Based on the dapsone antimicrobial activity and its anti-inflammatory action especially directed to the neutrophil metabolism, we treated two patients with severe folliculitis decalvans with this drug. The patients were treated with dapsone at a daily dose of 75 and 100 mg, respectively for 4 to 6 months. After 1 and 2 months, pustular folliculitis progressively cleared, leaving a residual non inflammatory cicatricial alopecia. When maintaining a dapsone dosage at 25 mg/day no relapse occurred during 3 years and 1 year, respectively. No important adverse effect to dapsone was evidenced. After dapsone withdrawal, a moderate relapse of the disease with pruritus and folliculitis occurred after a few weeks in both cases. The disease relapse rapidly cleared after dapsone reintroduction at a daily dose of 25 mg. Dapsone at moderate dosage was well tolerated and rapidly effective in treating the two cases of folliculitis decalvans. A long term and low dose (25 mg daily) maintenance treatment avoided disease relapses.
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... as phenytoin (Dilantin, Phenytek); antimalarial medications such as chloroquine (Aralen), primaquine, and quinine (Qualaquin); dapsone (by mouth); ... and the laboratory.Do not let anyone else use your medication. Ask your pharmacist any questions you ...
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Dapsone 7.5% Gel: A Review in Acne Vulgaris.
Al-Salama, Zaina T; Deeks, Emma D
2017-02-01
Dapsone 7.5% gel (Aczone ® ) is indicated for the once-daily topical treatment of acne vulgaris in patients aged ≥12 years. Dapsone is a sulfone antibacterial with anti-inflammatory actions, which are thought to be largely responsible for its efficacy in treating acne vulgaris. In two phase III trials of 12 weeks' duration in patients aged ≥12 years with moderate acne vulgaris, once-daily dapsone 7.5% gel reduced acne severity (as per the Global Acne Assessment Score) and lesion counts versus vehicle. The benefits of dapsone 7.5% gel over vehicle were seen as early as week 2 for inflammatory lesion counts, and from week 4 or 8 for other outcomes. Dapsone 7.5% gel was well tolerated, with a low incidence of treatment-related adverse events, with the majority of adverse events being administration-site related and mild or moderate in severity. Thus, dapsone 7.5% gel is an effective and well tolerated option for the topical treatment of acne vulgaris in patients aged ≥12 years, with the convenience of once-daily application.
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Dapsone for topical use in extemporaneous preparations.
Wohlrab, Johannes; Michael, Julia
2018-01-01
The sulfone dapsone has an established role in systemic therapy. Its pharmacological and toxicological properties are well known. Topically, dapsone is used in a gel formulation for the treatment of acne vulgaris. In addition, there have been individual case reports on the efficacy of topical dapsone preparations in the treatment of various neutrophilic dermatoses. To date, no finished medicinal product for topical use has been available in Germany. Against this background, we set out to develop extemporaneous preparations containing dapsone (5 %) that meet the quality requirements of the European Pharmacopoeia as well as the manufacturing requirements of the German Ordinance on the Operation of Pharmacies (ApBetrO). These formulations included the incorporation of dapsone in a hydrophobic cream base ("hydrophobe Basiscreme DAC") as well as in methylprednisolone aceponate 0.1 % ointment (alternatively, in the latter's cream base without active ingredient). Tests aimed at investigating the physical, chemical, and microbiological stability of these formulations showed them to meet the aforementioned quality requirements. The extemporaneous formulations presented herein broaden the therapeutic options for topical treatment, in particular for patients with chronic inflammatory dermatoses associated with a neutrophilic pathogenesis. © 2017 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.
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Raman and i.r. studies of the antileprotic drug Dapsone
NASA Astrophysics Data System (ADS)
D'Cunha, Romola; Kartha, V. B.; Gurnani, S.
No information is available on the mode of action of Dapsone in leprosy treatment, the phenomena of drug resistance and toxicity. Information on the interaction of Dapsone with serum proteins can be obtained at the molecular level by spectroscopic investigations on structural changes of the system. As a first step in these investigations, the i.r. and laser Raman spectra of Dapsone and N-deutero Dapsone have been obtained. The characteristic vibrational frequencies of the NH 2 group, the SO 2 group and the aromatic ring have been identified and assigned from isotope shifts and studies in various solvents.
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Dapsone-induced agranulocytosis-possible involvement of low-activity N-acetyltransferase 2.
Potočnjak, Ines; Likić, Robert; Šimić, Iveta; Juričić Nahal, Danica; Čegec, Ivana; Ganoci, Lana; Božina, Nada
2017-10-01
Dapsone-induced agranulocytosis is a rare but potentially fatal adverse drug reaction (ADR). A 45-year-old male Caucasian patient developed agranulocytosis caused by dapsone (diamino-diphenyl sulfone), which he was prescribed for leukocytoclastic vasculitis. Patient's treatment consisted of termination of dapsone, antibiotic therapy, and granulocyte colony-stimulating factor leading to prompt improvement of symptoms and normalization of laboratory blood values. Diagnostic evaluation revealed methemoglobinemia and excluded glucose-6-phosphate dehydrogenase deficiency. Pharmacogenetics testing showed that he was a carrier of NAT2 *5/*6 genotype, predisposing to low activity of the N-acetyltransferase 2 enzyme. This was the first and only ADR to dapsone reported in Croatia. In total, there have been 73 ADR to dapsone recorded worldwide, including only four cases of agranulocytosis. © 2017 Société Française de Pharmacologie et de Thérapeutique.
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Monteiro, Lidiane M; Lione, Viviane F; do Carmo, Flavia A; do Amaral, Lilian H; da Silva, Julianna H; Nasciutti, Luiz E; Rodrigues, Carlos R; Castro, Helena C; de Sousa, Valeria P; Cabral, Lucio M
2012-01-01
Background Dapsone is described as being active against Mycobacterium leprae, hence its role in the treatment of leprosy and related pathologies. Despite its therapeutic potential, the low solubility of dapsone in water results in low bioavailability and high microbial resistance. Nanoemulsions are pharmaceutical delivery systems derived from micellar solutions with a good capacity for improving absorption. The aim of this work was to develop and compare the permeability of a series of dapsone nanoemulsions in Caco-2 cell culture against that of effective permeability in the human body simulated using Gastroplus™ software. Methods and results The release profiles of the dapsone nanoemulsions using different combinations of surfactants and cosolvent showed a higher dissolution rate in simulated gastric and enteric fluid than did the dispersed dapsone powder. The drug release kinetics were consistent with a Higuchi model. Conclusion This comparison of dapsone permeability in Caco-2 cells with effective permeability in the human body simulated by Gastroplus showed a good correlation and indicates potential improvement in the biodisponibility of dapsone using this new system. PMID:23055729
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Monteiro, Lidiane M; Lione, Viviane F; do Carmo, Flavia A; do Amaral, Lilian H; da Silva, Julianna H; Nasciutti, Luiz E; Rodrigues, Carlos R; Castro, Helena C; de Sousa, Valeria P; Cabral, Lucio M
2012-01-01
Dapsone is described as being active against Mycobacterium leprae, hence its role in the treatment of leprosy and related pathologies. Despite its therapeutic potential, the low solubility of dapsone in water results in low bioavailability and high microbial resistance. Nanoemulsions are pharmaceutical delivery systems derived from micellar solutions with a good capacity for improving absorption. The aim of this work was to develop and compare the permeability of a series of dapsone nanoemulsions in Caco-2 cell culture against that of effective permeability in the human body simulated using Gastroplus™ software. The release profiles of the dapsone nanoemulsions using different combinations of surfactants and cosolvent showed a higher dissolution rate in simulated gastric and enteric fluid than did the dispersed dapsone powder. The drug release kinetics were consistent with a Higuchi model. This comparison of dapsone permeability in Caco-2 cells with effective permeability in the human body simulated by Gastroplus showed a good correlation and indicates potential improvement in the biodisponibility of dapsone using this new system.
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Why dapsone stops seizures and may stop neutrophils' delivery of VEGF to glioblastoma.
Kast, R E; Lefranc, F; Karpel-Massler, G; Halatsch, M-E
2012-12-01
Lopez-Gomez et al. recently published remarkable but mechanistically unexplained empirical evidence that the old antibiotic dapsone has antiepileptic activity. We addressed the question "Why should a sulfone antibiotic reduce seizures?". We report here our conclusions based on data from past studies that seizures are associated with elevated interleukin-8 (IL-8) and that dapsone inhibits IL-8 release and function in several different clinical and experimental contexts. Diverse CNS insults cause an increase in CNS IL-8. Thus, the pro-inflammatory environment generated by increase IL-8 leads to a lower seizure threshold. Together this evidence indicates dapsone exerts anti-seizure activity by diminishing IL-8 signalling. Since IL-8 is clearly upregulated in glioblastoma and contributes to the florid angiogenesis of that disease, and since interference with IL-8 function has been shown to inhibit glioblastoma invasion and growth in several experimental models, and dapsone has been repeatedly been shown to clinically inhibit IL-8 function when used to treat human neutrophilic dermatoses, we believe that dapsone thereby reduces seizures by countering IL-8 function and may similarly retard glioblastoma growth by such anti-IL-8 function.
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Chaitanya V, Sundeep; Das, Madhusmita; Bhat, Pritesh; Ebenezer, Mannam
2015-10-01
The molecular basis for determination of resistance to anti-leprosy drugs is the presence of point mutations within the genes of Mycobacterium leprae (M. leprae) that encode active drug targets. The downstream structural and functional implications of these point mutations on drug targets were scarcely studied. In this study, we utilized computational tools to develop native and mutant protein models for 5 point mutations at codon positions 53 and 55 in 6-hydroxymethyl-7, 8-dihydropteroate synthase (DHPS) of M. leprae, an active target for dapsone encoded by folp1 gene, that confer resistance to dapsone. Molecular docking was performed to identify variations in dapsone interaction with mutant DHPS in terms of hydrogen bonding, hydrophobic interactions, and energy changes. Schrodinger Suite 2014-3 was used to build homology models and in performing molecular docking. An increase in volume of the binding cavities of mutant structures was noted when compared to native form indicating a weakening in interaction (60.7 Å(3) in native vs. 233.6 Å(3) in Thr53Ala, 659.9 Å(3) in Thr53Ile, 400 Å(3) for Thr53Val, 385 Å(3) for Pro55Arg, and 210 Å(3) for Pro55Leu). This was also reflected by changes in hydrogen bonds and decrease in hydrophobic interactions in the mutant models. The total binding energy (ΔG) decreased significantly in mutant forms when compared to the native form (-51.92 Kcal/mol for native vs. -35.64, -35.24, -46.47, -47.69, and -41.36 Kcal/mol for mutations Thr53Ala, Thr53Ile, Thr53Val, Pro55Arg, and Pro55Leu, respectively. In brief, this analysis provided structural and mechanistic insights to the degree of dapsone resistance contributed by each of these DHPS mutants in leprosy. © 2015 Wiley Periodicals, Inc.
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Gill, H J; Tingle, M D; Park, B K
1995-01-01
1. The adverse reactions associated with the administration of dapsone are believed to be caused by metabolism to its hydroxylamine. Previous reports suggest that CYP3A4 is responsible for this biotransformation [1]. 2. Data presented in this paper illustrate the involvement of more than one cytochrome P450 enzyme in dapsone hydroxylamine formation using human liver microsomes. Eadie-Hofstee plots demonstrated bi-phasic kinetics in several livers. No correlation could be established between hydroxylamine formation and CYP3A concentrations in six human livers (r = -0.47; P = 0.34). 3. Studies with low molecular weight inhibitors illustrate the importance of CYP2C9 and CYP3A in dapsone N-hydroxylation. 4. Differential sensitivity of dapsone N-hydroxylation to selective CYP inhibitors indicated that the contribution of individual CYP enzymes varies between livers. Selective inhibition ranged from 6.8 to 44.1% by 5 microM ketoconazole, and from 24.0 to 68.4% by 100 microM sulphaphenazole. The extent of inhibition, by either ketoconazole or sulphaphenazole was dependent on the CYP3A content of the liver. 5. The levels of expression of these cytochrome P450 enzymes may be an important determinant of individual susceptibility to the toxic effects of dapsone, and may influence the ability of an enzyme inhibitor to block dapsone toxicity in vivo. Because of the inability to produce complete inhibition, selective CYP inhibitors are unlikely to offer any clinical advantage over cimetidine in decreasing dapsone hydroxylamine formation in vivo. PMID:8703658
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Erlotinib augmentation with dapsone for rash mitigation and increased anti-cancer effectiveness.
Kast, R E
2015-01-01
The epidermal growth factor receptor tyrosine kinase inhibitor erlotinib has failed in many ways to be as potent in the anti-cancer role as pre-clinical studies would have suggested. This paper traces some aspects of this failure to a compensatory erlotinib-mediated increase in interleukin-8. Many other-but not all- cancer chemotherapeutic cytotoxic drugs also provoke a compensatory increase in a malignant clone's interleukin-8 synthesis. Untreated glioblastoma and other cancer cells themselves natively synthesize interleukin-8. Interleukin-8 has tumor growth promoting, mobility and metastasis formation enhancing, effects as well as pro-angiogenesis effects. The old sulfone antibiotic dapsone- one of the very first antibiotics in clinical use- has demonstrated several interleukin-8 system inhibiting actions. Review of these indicates dapsone has potential to augment erlotinib effectiveness. Erlotinib typically gives a rash that has recently been proven to come about via an erlotinib triggered up-regulated keratinocyte interleukin-8 synthesis. The erlotinib rash shares histological features reminiscent of typical neutrophilic dermatoses. Dapsone has an established therapeutic role in current treatment of other neutrophilic dermatoses. Thus, dapsone has potential to both improve the quality of life in erlotinib treated patients by amelioration of rash as well as to short-circuit a growth-enhancing aspect of erlotinib when used in the anti-cancer role.
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Iliev, Yanko T; Zagorov, Marin Y; Grudeva-Popova, Janet G
2015-01-01
Dapsone is a drug commonly used in the treatment of leprosy. In Europe it is rarely prescribed, mostly for the treatment of skin diseases such as dermatitis herpetiformis. Poisoning with dapsone is rare and reports of such cases are of interest for toxicological practice. We describe the only acute dapsone poisoning in a caseload series of 21,000 intoxications treated in the Clinical Toxicology Clinic at St George University Hospital in Plovdiv, Bulgaria between 1999 and 2013. We report on a 36-year-old woman who attempted deliberate self-poisoning with an ingestion of approximately 4.5 g of dapsone and 0.3 g of olanzapine. On admission, the patient was in a state of severe intoxication and comatose. On admission to hospital 9 hours after the ingestion, the methemoglobin level was 51.7%. The patient recovered 8 days later. She received complex treatment including intubation, ventilation, repeated gastric lavage, hemodialysis, blood exchange transfusion and antidote treatment with methylene blue. She was discharged in good clinical condition with minimal organ damage such as mild toxic hepatitis.
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Rim, Min Young; Hong, Junshik; Yo, Inku; Park, Hyeonsu; Chung, Dong Hae; Ahn, Jeong Yeal; Park, Jinny; Kim, Yun Soo; Lee, Jae Hoon
2012-01-01
A 36-year-old woman presented with erythematous confluent macules on her whole body with fever and chills associated with jaundice after 8 months of dapsone therapy. Her symptoms had developed progressively, and a physical examination revealed bilateral cervical lymphadenopathy and splenomegaly. Excisional biopsy of a cervical lymph node showed effacement of the normal architecture with atypical lymphoid hyperplasia and proliferation of high endothelial venules compatible with angioimmunoblastic T-cell lymphoma. However, it was assumed that the cervical lymphadenopathy was a clinical manifestation of a systemic hypersensitivity reaction because her clinical course was reminiscent of dapsone-induced hypersensitivity syndrome. A liver biopsy revealed drug-induced hepatitis with no evidence of lymphomatous involvement. Intravenous glucocorticoid was immediately initiated and her symptoms and clinical disease dramatically improved. The authors present an unusual case of cervical lymphadenopathy mimicking angioimmunoblastic T-cell lymphoma as an adverse reaction to dapsone. PMID:23323115
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Tingle, M D; Coleman, M D; Park, B K
1990-01-01
1. We have utilized a two compartment system in which two teflon chambers are separated by a semi-permeable membrane in order to investigate the role of metabolism in dapsone-induced methaemoglobinaemia. Compartment A contained a drug metabolizing system (microsomes prepared from human liver +/- NADPH), whilst compartment B contained target cells (human red cells). 2. Incubation of dapsone (1-100 microM) with human liver microsomes (2 mg protein) and NADPH (1 mM) in compartment A (final volume 500 microliters) led to a concentration-dependent increase in the methaemoglobinaemia (15.4-18.9% at 100 microM) compared with control (2.3 +/- 0.4%) detected in the red cells within compartment B. In the absence of NADPH dapsone had no effect. 3. Of the putative dapsone metabolites investigated, only dapsone-hydroxylamine caused methaemoglobin formation in the absence of NADPH (40.6 +/- 6.3% with 100 microM). However, methaemoglobin was also detected when monoacetyl-dapsone, 4-amino-4'-nitro-diphenylsulphone and 4-aminoacetyl-4'-nitro-diphenylsulphone were incubated with human liver microsomes in the presence of NADPH. 4 Dapsone-dependent methaemoglobin formation was inhibited by addition of ketoconazole (1-1000 microM) to compartment A, with IC50 values of 285 and 806 microM for the two liver microsomal samples studied. In contrast, methaemoglobin formation was not inhibited by cimetidine or a number of drugs pharmacologically-related to dapsone. The presence of glutathione or ascorbate (500 microM) did not alter the level of methaemoglobin observed. PMID:2288829
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Wang, Na; Parimi, Leela; Liu, Hong; Zhang, Furen
2017-05-01
AbstractDapsone is a bactericidal and bacteriostatic against Mycobacterium leprae , a causative agent of leprosy. Dapsone is also applied in a range of medical fields because of its anti-inflammatory and immunomodulatory effects. Dapsone hypersensitivity syndrome (DHS) is a rare yet serious adverse drug reaction (ADR) caused by dapsone involving multiple organs. We performed a systematic review of published articles describing dapsone-induced hypersensitivity syndrome, including all Chinese articles and the latest literature available in online databases published between October 2009 and October 2015. We determined the prevalence, clinical characteristics, and mortality rate of DHS. Importantly, we also summarized the recent advances in genetic testing allowing prediction of ADRs. In an initial systematic electronic search, we retrieved 191 articles. Subsequently, these articles were further filtered and ultimately 84 articles (60 Chinese case reports, 21 non-Chinese articles, and three epidemiological studies) were selected, which included 877 patients. The prevalence of DHS among Chinese patients was 1.5% with a fatality rate of 9.6%. Early withdrawal of dapsone and appropriate treatment reduced the fatality rate. Most importantly, genetic screening for the HLA-B*13:01 allele among high-risk populations showed a significant utility as a useful genetic marker to DHS. In conclusion, this review discusses the epidemiological and clinical characteristics of DHS among Chinese patients, which may help physicians to understand this syndrome.
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Jing, Zhichun; Zhang, Renbao; Zhou, Doahai; Chen, Jiakeun
2009-06-01
The relentless emergence of dapsone resistance amongst M. leprae threatened leprosy control programmes, and increased the relapse rate of patients cured with dapsone monotherapy. The study aimed to analyse the effect on the relapse rate of dapsone-cured multibacillary (MB) leprosy patients, of re-treatment, using a multidrug therapy (MDT) regimen which differed from the WHO recommended regimen. 794 MB leprosy patients who had been released from treatment after dapsone monotherapy were selected, amongst them 657 were re-treated for 1 year using the modified multidrug therapy regimen (mMDT) including rifampicin, clofazimine and dapsone, and 137 patients were observed as control cases. The regimen was well tolerated with good compliance: 620 patients completed re-treatment with mild side effects and a low incidence of leprosy reactions. There was a statistically significant difference between the relapse rates of re-treated and control groups (chi squaredf = 57.44, P < 0.001). Furthermore, the relapses in the re-treated group were significantly more likely to be later than those in the control group (t = 25.62, P < 0.001). Re-treatment with this modified regimen is acceptable and can reduce the risk of early relapse in dapsone-cured patients. The problem of persisters causing late relapse is likely to remain.
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Faghihi, Gita; Rakhshanpour, Mehrdad; Abtahi-Naeini, Bahareh; Nilforoushzadeh, Mohammad Ali
2014-01-01
Background: Acne vulgaris, a common human skin condition, is an inflammatory disease characterized by comedones, papules, nodules and possibly scarring. This study aimed to evaluate the efficacy of a combination of 5% dapsone gel plus oral isotretinoin in the treatment of acne vulgaris. Materials and Methods: A randomized, placebo-controlled, study was carried out on patients with moderate to severe acne. The patients were randomly divided in two groups: (dapsone gel and vehicle gel). All Patients were administered oral isotretinoin 20 mg daily and topical gel twice a day for 8 weeks. The Global Acne Assessment Score (GAAS), the number lesions and side-effects were documented at base line and weeks 4, 8 and 12. Results: A total of 58 patients (age range: 18-25 years) were included in our study. The number of lesions was significantly lower in the dapsone-treated group at all follow-up visits (P < 0.001). The mean GAAS score in the dapsone-treated group and in the Placebo-treated group decreased, but there was no statistical difference in two groups (P < 0.001). The side-effects on the dapsone-treated group were a mild burning sensation in 7 patients (24.13%), mild erythema of the skin and mild dryness in 4 (13.79%) and 3 (10.34%) cases respectively (P < 0.001). In our study, adverse effects were common but they were minor and tolerable. No clinically significant changes in laboratory parameters were observed (P < 0.001). Conclusions: Dapsone gel was an effective medication for patients who received isotretinoin for acne vulgaris treatment resulting in a significant reduction of the number of lesions. PMID:25250291
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Fleischer, Alan B; Shalita, Alan; Eichenfield, Lawrence F; Abramovits, William; Lucky, Anne; Garrett, Steven
2010-01-01
To evaluate the safety and efficacy of dapsone gel 5% in the treatment of acne when used in combination with adapalene gel 0.1%, benzoyl peroxide gel 4% or moisturizer. This was a twelve-week, randomized, double-blind study. Patients aged 12 years and older (n=301) applied dapsone gel twice daily and were randomly assigned (1:1:1) to one of three additional treatments, applied once daily. By week 12, dapsone gel combined with any of the three additional treatments reduced the mean number of inflammatory lesions. However, the authors did not detect a significant difference in the reduction of inflammatory lesions when dapsone was used in combination with adapalene gel or with benzoyl peroxide gel compared to the dapsone plus moisturizer combination group (P=0.052 for both versus moisturizer combination). Patients treated with dapsone gel combined with adapalene showed a significantly better response in reduction in non-inflammatory and total acne lesion count than those who received the moisturizer combination. Local adverse reactions in all three treatment groups were minimal and generally mild in severity. Dapsone gel in combination with adapalene gel or benzoyl peroxide gel is safe and well tolerated for the treatment of acne vulgaris.
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Alexis, Andrew F; Burgess, Cheryl; Callender, Valerie D; Herzog, Jo L; Roberts, Wendy E; Schweiger, Eric S; Stockton, Toni C; Gallagher, Conor J
2016-02-01
Topical dapsone gel, 5% is approved for treatment of acne vulgaris but has not been studied specifically in women with skin of color (SOC; Fitzpatrick skin types IV, V, or VI). Evaluate safety and efficacy of dapsone gel, 5% applied topically twice daily for 12 weeks in women with SOC. Females with SOC aged 18 years and older with facial acne participated in a multicenter, open-label, single-group, 12-week pilot study of twice-daily monotherapy with dapsone gel, 5%. The investigator-rated 5-point Global Acne Assessment Score (GAAS) was used to assess efficacy. The impact of acne on subjects was assessed using the validated Acne Symptom and Impact Scale (ASIS). The study enrolled and treated 68 women with SOC and facial acne. GAAS decreased significantly from baseline to week 12 (mean, -1.2 [95% CI, -1.4, -1.0]; P<.001), a 39.0% improvement. Overall, 42.9% of subjects were responders based on a GAAS of 0 or 1 at week 12. Subjects also experienced significant reductions in mean total lesions (52% decrease), inflammatory lesions (65%), and comedo counts (41%; all P<.001). Dapsone gel, 5% monotherapy was associated with significant improvement in subject-assessed acne signs (P<.001) and impact on quality of life (QOL; P<.001), based on ASIS. Dapsone gel, 5% used twice daily was well tolerated, with no treatment-related adverse events. The local dermal tolerability scores tended to remain stable or decrease from baseline to week 12. Monotherapy with dapsone gel, 5% administered twice daily was safe and effective for treatment of facial acne in women with SOC. Significant improvement in overall acne severity and both inflammatory lesions and comedones was observed. Further, study subjects reported considerable improvement in both acne signs and impact on QOL.
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Stein Gold, Linda F; Jarratt, Michael T; Bucko, Alicia D; Grekin, Steven K; Berlin, Joshua M; Bukhalo, Michael; Weiss, Jonathan S; Berk, David R; Chang-Lin, Joan-En; Lin, Vince; Kaoukhov, Alexandre
2016-05-01
Treatment of acne vulgaris (acne) with dapsone gel, 5% requires twice-daily dosing, and some patients may not adhere to this regimen.
The objective of this study was to assess the efficacy and safety of a new, once-daily formulation of dapsone gel, 7.5%, with a 50% higher dapsone concentration, versus vehicle over 12 weeks in patients with acne.
This 12-week, randomized, double-blind, vehicle-controlled, multicenter clinical trial enrolled patients with moderate acne aged 12 years and older with 20 to 50 inflammatory lesions and 30 to 100 noninflammatory lesions on the face, and an acne grade of 3 (moderate) on the Global Acne Assessment Score (GAAS). Patients were randomized to receive topical dapsone gel, 7.5% or vehicle once daily for 12 weeks. Investigators assessed GAAS success rate (proportion of patients with GAAS of 0 or 1) and percent change from baseline in inflammatory, noninflammatory, and total lesions.
The intent-to-treat population comprised 2102 patients, 1044 in the dapsone gel, 7.5% group and 1058 in the vehicle group. At week 12, 29.9% of patients in the dapsone gel, 7.5% group and 21.2% in the vehicle group (P<.001) had GAAS success. Mean inflammatory lesions decreased by 55.5% and 49.0%, noninflammatory lesions decreased by 44.4% and 38.4%, and total lesions decreased by 48.7% and 42.4% in the dapsone gel, 7.5% and vehicle groups (all P<.001), respectively, at week 12. The incidence of adverse events was similar in the dapsone gel, 7.5% (19.1%) and vehicle (20.6%) groups. Most events in both groups were mild or moderate in severity. Most patients receiving dapsone gel, 7.5% and vehicle had a severity rating of "none" for stinging/burning, dryness, scaling, and erythema scales at all time points.
Dapsone gel, 7.5% applied topically once daily is an effective, safe, and well-tolerated treatment for acne.
J Drugs Dermatol. 2016;15(5):553-561. -
Eichenfield, Lawrence F; Lain, Ted; Frankel, Ellen H; Jones, Terry M; Chang-Lin, Joan-En; Berk, David R; Ruan, Shiling; Kaoukhov, Alexandre
2016-08-01
Dapsone gel, 5% is administered twice daily for the treatment of acne vulgaris, and some patients may find adherence challenging.
The study objective was to assess the efficacy and safety, compared with vehicle, of acne treatment with a recently FDA-approved, once-daily formulation of dapsone gel, 7.5%, with a 50% greater concentration of dapsone.
This 12-week, randomized, double-blind, vehicle-controlled, multicenter clinical trial enrolled patients aged 12 years and older with 20-50 facial inflammatory lesions, 30-100 facial noninflammatory lesions, and an acne grade of 3 (moderate) on the Global Acne Assessment Score (GAAS). Patients were randomized (1:1 ratio) to topical dapsone gel, 7.5% or vehicle once daily for 12 weeks. Investigators assessed GAAS success rate (proportion of patients with a GAAS of 0 or 1) and percent change from baseline in inflammatory, noninflammatory, and total lesions.
The intent-to-treat population comprised 2238 patients (1118 in the dapsone gel, 7.5% group and 1120 in the vehicle group). The GAAS success rates were 29.8% for the dapsone gel, 7.5% group and 20.9% for the vehicle group (P<0.001) at week 12. At week 12, mean inflammatory lesions decreased from baseline by 53.8% and 47.3%, noninflammatory lesions decreased by 45.9% and 40.4%, and total lesions decreased by 48.9% and 43.2% for the dapsone gel, 7.5% group and the vehicle group, respectively (all, P<0.001). The incidence of treatment-emergent adverse events was similar for dapsone gel, 7.5% (17.6%) and vehicle (17.1%). Most adverse events were mild to moderate in severity. The most frequently reported increase in severity for all of the dermal tolerability scales was from "none" to "mild."
Dapsone gel, 7.5% applied topically once daily is an effective, safe, and well-tolerated treatment for acne vulgaris. Improvements in acne severity and lesions were observed over the 12-week course of treatment.
J Drugs -
Fischer, J H; West, D P; Worobec, S M
1986-12-01
Guidelines for the assessment of patient compliance to dapsone were developed and evaluated. The urinary dapsone-to-creatinine (D/C) ratio following standardization by dose, ideal body weight, and time since last dose was used for assessment of compliance. Compliance standards were established in 12 patients of known compliance and confirmed prospectively in nine inpatients on 14 occasions. Compliance increased significantly among outpatients (N = 30) attending the University of Illinois Hansen's Disease Clinic from 47% at base line to 73% at 6 months and 80% at 18 months after establishing the monitoring program. In a subgroup of 18 patients, a similar increase in compliance was observed from 50% to 80%. A good therapeutic response was seen in the subgroup patients who were compliant. A poor therapeutic response was seen in the consistently noncompliant patients. These results demonstrate that use of a continual compliance monitoring program can improve patient drug compliance in an outpatient Hansen's disease clinic.
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Miyachi, Y; Niwa, Y
1982-08-01
The effects of potassium iodide, colchicine and dapsone on the in vitro generation of polymorphonuclear leukocyte (PMN)-derived oxygen intermediates were investigated. These three drugs have beneficial effects on those conditions in which PMNs play an important pathogenetic role. Three oxygen intermediates, superoxide anion (O2-), hydrogen peroxide (H2O2), hydroxyl radical (OH.) and chemiluminescence were included in assay studies. Dose response studies were performed with therapeutic doses of the drugs (10 microM--mM). We found that both potassium iodide and dapsone significantly suppressed the generation of oxygen intermediates, except for O2-. Colchicine decreased OH. production. Our results show tha these agents to some extent exert their anti-inflammatory effects by interfering with the PMN-dependent production of oxygen intermediates, thus conferring protection from auto-oxidative tissue injury. This may account for their clinical efficacy in many PMN-mediated dermatological diseases.
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Tirado-Sánchez, A; Díaz-Molina, V; Ponce-Olivera, R M
2012-01-01
Bullous pemphigoid is a chronic, blistering and autoimmune disease, common in old age. The treatment usually includes systemic steroids, however, these cause high morbidity rates, and then different products that function as adjuvants have been tried. At present, there are no studies to determine which adjuvant offers a better efficacy and safety profile. We performed a retrospective study which included the records of patients with bullous pemphigoid, treated either with azathioprine or dapsone. We evaluated the time to achieve complete remission, the time to inhibit disease progression, and the control of pruritus. Fifteen records of patients were selected, eight (53%) treated with azathioprine and seven (47%) with dapsone. Complete remission was achieved at week six in both groups. We found no difference in the inhibition of disease progression (p=0.083). Pruritus was controlled at four weeks of treatment in both treatments. Both products are effective as adjuvant in the treatment of bullous pemphigoid, with an acceptable safety profile. Copyright © 2010 SEICAP. Published by Elsevier Espana. All rights reserved.
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Moncrieff, J
1994-03-18
A simple, extractionless method for the determination of dapsone in serum and saliva is described. Reversed-phase high-performance liquid chromatography is used with UV detection at 295 nm or electrochemical detection at 0.7 V. Diazoxide in buffer is the internal standard for UV detection and practolol for electrochemical detection. Sample preparation is minimal with protein precipitation of serum samples whilst saliva samples are simply diluted with addition of an internal standard. Low-level serum and saliva samples are front-cut on-line with a 3 cm laboratory-made precolumn in the loop position on a standard Valco injection valve. Isocratic separation is achieved on a 250 mm x 4.6 mm I.D. stainless-steel Spherisorb S5 ODS-1 column. The mobile phase for high levels of dapsone is acetonitrile-elution buffer (12:88, v/v) at 2 ml/min and a column temperature of 40 degrees C for both serum and saliva separations. For the low-level assays using electrochemical detection and solid-phase clean-up, the mobile phase is acetonitrile-methanol-elution buffer (9:4:87, v/v/v). The UV and electrochemical detection limits are 25 ng/ml and 200 pg/ml, respectively, in both serum and saliva. This simple method is applicable to the routine monitoring of dapsone levels in serum from leprotic patients and electrochemical detection gives a simple, reliable method for the monitoring of trough values in subjects on anti-malarial prophylaxis.
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Clinical Oxidative Stress during Leprosy Multidrug Therapy: Impact of Dapsone Oxidation
Schalcher, Taysa Ribeiro; Borges, Rosivaldo S.; Coleman, Michael D.; Batista Júnior, João; Salgado, Claudio G.; Vieira, Jose Luiz F.; Romão, Pedro R. T.; Oliveira, Fabio R.; Monteiro, Marta Chagas
2014-01-01
This study aims to assess the oxidative stress in leprosy patients under multidrug therapy (MDT; dapsone, clofazimine and rifampicin), evaluating the nitric oxide (NO) concentration, catalase (CAT) and superoxide dismutase (SOD) activities, glutathione (GSH) levels, total antioxidant capacity, lipid peroxidation, and methemoglobin formation. For this, we analyzed 23 leprosy patients and 20 healthy individuals from the Amazon region, Brazil, aged between 20 and 45 years. Blood sampling enabled the evaluation of leprosy patients prior to starting multidrug therapy (called MDT 0) and until the third month of multidrug therapy (MDT 3). With regard to dapsone (DDS) plasma levels, we showed that there was no statistical difference in drug plasma levels between multibacillary (0.518±0.029 µg/mL) and paucibacillary (0.662±0.123 µg/mL) patients. The methemoglobin levels and numbers of Heinz bodies were significantly enhanced after the third MDT-supervised dose, but this treatment did not significantly change the lipid peroxidation and NO levels in these leprosy patients. In addition, CAT activity was significantly reduced in MDT-treated leprosy patients, while GSH content was increased in these patients. However, SOD and Trolox equivalent antioxidant capacity levels were similar in patients with and without treatment. These data suggest that MDT can reduce the activity of some antioxidant enzyme and influence ROS accumulation, which may induce hematological changes, such as methemoglobinemia in patients with leprosy. We also explored some redox mechanisms associated with DDS and its main oxidative metabolite DDS-NHOH and we explored the possible binding of DDS to the active site of CYP2C19 with the aid of molecular modeling software. PMID:24465659
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Fanello, Caterina I; Karema, Corine; Avellino, Pamela; Bancone, Germana; Uwimana, Aline; Lee, Sue J; d'Alessandro, Umberto; Modiano, David
2008-01-01
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common inherited human enzyme defect. This deficiency provides some protection from clinical malaria, but it can also cause haemolysis after administration of drugs with oxidant properties. The safety of chlorproguanil-dapsone+artesunate (CD+A) and amodiaquine+sulphadoxine-pyrimethamine (AQ+SP) for the treatment of uncomplicated P. falciparum malaria was evaluated according to G6PD deficiency in a secondary analysis of an open-label, randomized clinical trial. 702 children, treated with CD+A or AQ+SP and followed for 28 days after treatment were genotyped for G6PD A- deficiency. In the first 4 days following CD+A treatment, mean haematocrit declined on average 1.94% (95% CI 1.54 to 2.33) and 1.05% per day (95% CI 0.95 to 1.15) respectively in patients with G6PD deficiency and normal patients; a mean reduction of 1.3% per day was observed among patients who received AQ+SP regardless of G6PD status (95% CI 1.25 to 1.45). Patients with G6PD deficiency recipients of CD+A had significantly lower haematocrit than the other groups until day 7 (p = 0.04). In total, 10 patients had severe post-treatment haemolysis requiring blood transfusion. Patients with G6PD deficiency showed a higher risk of severe anaemia following treatment with CD+A (RR = 10.2; 95% CI 1.8 to 59.3) or AQ+SP (RR = 5.6; 95% CI 1.0 to 32.7). CD+A showed a poor safety profile in individuals with G6PD deficiency most likely as a result of dapsone induced haemolysis. Screening for G6PD deficiency before drug administration of potentially pro-oxidants drugs, like dapsone-containing combinations, although seldom available, is necessary.
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Previously misdiagnosed linear IgA dermatosis resolved with dapsone.
Tieppo Francio, Vinicius; Towery, Chris; Davani, Saeid; Allen, Travis; Brown, Tony L
2018-04-25
This is the case of a 25-year-old African American woman with a 3-week history of itching with burning, blistering lesions on her torso and extremities. Medical history was unremarkable. Medical treatments included three visits to urgent care, where she was treated with antivirals, oral and topical steroids, antibiotics and antifungals unsuccessfully. We performed a skin biopsy, and immunoflorescent studies revealed a linear deposition of IgA antigen at the basement membrane. The clinical diagnosis of linear IgA dermatosis (LAD) was established, with no eliciting cause, other than potential occupational exposure to Chlamydophila psittaci via her employment in a pet store. This is the first case to our knowledge to report such an association. However, confirmation of the exposure would only establish correlation, not causality. Resolution of symptoms and blisters was achieved with dapsone treatment. Accordingly, we highlight the crucial importance of reviewing exposures, along with the potential aetiology of LAD. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
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Supramolecular Organization of Nonstoichiometric Drug Hydrates: Dapsone
NASA Astrophysics Data System (ADS)
Braun, Doris E.; Griesser, Ulrich J.
2018-02-01
The observed moisture- and temperature dependent transformations of the dapsone (4,4'-diaminodiphenyl sulfone, DDS) 0.33-hydrate were correlated to its structure and the number and strength of the water-DDS intermolecular interactions. A combination of characterization techniques was used, including thermal analysis (hot-stage microscopy, differential scanning calorimetry and thermogravimetric analysis), gravimetric moisture sorption/desorption studies and variable humidity powder X-ray diffraction, along with computational modeling (crystal structure prediction and pair-wise intermolecular energy calculations). Depending on the relative humidity the hydrate contains between 0 and 0.33 molecules of water per molecule DDS. The crystal structure is retained upon dehydration indicating that DDS hydrate shows a non-stoichiometric (de)hydration behavior. Unexpectedly, the water molecules are not located in structural channels but at isolated-sites of the host framework, which is counterintuitively for a hydrate with non-stoichiometric behavior. The water-DDS interactions were estimated to be weaker than water-host interactions that are commonly observed in stoichiometric hydrates and the lattice energies of the isomorphic dehydration product (hydrate structure without water molecules) and a stable anhydrate at room temperature (form III) differ only by approximately 1 kJ mol–1. The computational generation of hypothetical monohydrates confirms that the hydrate with the unusual DDS:water ratio of 3:1 is more stable than a feasible monohydrate structure. Overall, this study addresses the critical class of non-stoichiometric hydrates, highlighting that only a multidisciplinary investigation can unravel hydrate formation at a molecular level, knowledge which is a requirement in modern drug development.
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Supramolecular Organization of Nonstoichiometric Drug Hydrates: Dapsone
Braun, Doris E.; Griesser, Ulrich J.
2018-01-01
The observed moisture- and temperature dependent transformations of the dapsone (4,4′-diaminodiphenyl sulfone, DDS) 0. 33-hydrate were correlated to its structure and the number and strength of the water-DDS intermolecular interactions. A combination of characterization techniques was used, including thermal analysis (hot-stage microscopy, differential scanning calorimetry and thermogravimetric analysis), gravimetric moisture sorption/desorption studies and variable humidity powder X-ray diffraction, along with computational modeling (crystal structure prediction and pair-wise intermolecular energy calculations). Depending on the relative humidity the hydrate contains between 0 and 0.33 molecules of water per molecule DDS. The crystal structure is retained upon dehydration indicating that DDS hydrate shows a non-stoichiometric (de)hydration behavior. Unexpectedly, the water molecules are not located in structural channels but at isolated-sites of the host framework, which is counterintuitively for a hydrate with non-stoichiometric behavior. The water-DDS interactions were estimated to be weaker than water-host interactions that are commonly observed in stoichiometric hydrates and the lattice energies of the isomorphic dehydration product (hydrate structure without water molecules) and (form III) differ only by ~1 kJ mol−1. The computational generation of hypothetical monohydrates confirms that the hydrate with the unusual DDS:water ratio of 3:1 is more stable than a feasible monohydrate structure. Overall, this study highlights that a deeper understanding of the formation of hydrates with non-stoichiometric behavior requires a multidisciplinary approach including suitable experimental and computational methods providing a firm basis for the development and manufacturing of high quality drug products. PMID:29520359
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Supramolecular Organization of Nonstoichiometric Drug Hydrates: Dapsone.
Braun, Doris E; Griesser, Ulrich J
2018-01-01
The observed moisture- and temperature dependent transformations of the dapsone (4,4'-diaminodiphenyl sulfone, DDS) 0. 33-hydrate were correlated to its structure and the number and strength of the water-DDS intermolecular interactions. A combination of characterization techniques was used, including thermal analysis (hot-stage microscopy, differential scanning calorimetry and thermogravimetric analysis), gravimetric moisture sorption/desorption studies and variable humidity powder X-ray diffraction, along with computational modeling (crystal structure prediction and pair-wise intermolecular energy calculations). Depending on the relative humidity the hydrate contains between 0 and 0.33 molecules of water per molecule DDS. The crystal structure is retained upon dehydration indicating that DDS hydrate shows a non-stoichiometric (de)hydration behavior. Unexpectedly, the water molecules are not located in structural channels but at isolated-sites of the host framework, which is counterintuitively for a hydrate with non-stoichiometric behavior. The water-DDS interactions were estimated to be weaker than water-host interactions that are commonly observed in stoichiometric hydrates and the lattice energies of the isomorphic dehydration product (hydrate structure without water molecules) and (form III ) differ only by ~1 kJ mol -1 . The computational generation of hypothetical monohydrates confirms that the hydrate with the unusual DDS:water ratio of 3:1 is more stable than a feasible monohydrate structure. Overall, this study highlights that a deeper understanding of the formation of hydrates with non-stoichiometric behavior requires a multidisciplinary approach including suitable experimental and computational methods providing a firm basis for the development and manufacturing of high quality drug products.
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Boccellino, Mariarosaria; Quagliuolo, Lucio; Alaia, Concetta; Grimaldi, Anna; Addeo, Raffaele; Nicoletti, Giovanni Francesco; Kast, Richard Eric; Caraglia, Michele
2016-11-01
The presence of an aberrantly activated epidermal growth factor receptor (EGFR) in many epithelial tumors, due to its overexpression, activating mutations, gene amplification and/or overexpression of receptor ligands, represent the fundamental basis underlying the use of EGFR tyrosine kinase inhibitors (EGFR-TKIs). Drugs inhibiting the EGFR have different mechanisms of action; while erlotinib and gefitinib inhibit the intracellular tyrosine kinase, monoclonal antibodies like cetuximab and panitumumab bind the extracellular domain of the EGFR both activating immunomediated anti-cancer effect and inhibiting receptor function. On the other hand, interleukin-8 has tumor promoting as well as neo-angiogenesis enhancing effects and several attempts have been made to inhibit its activity. One of these is based on the use of the old sulfone antibiotic dapsone that has demonstrated several interleukin-8 system inhibiting actions. Erlotinib typically gives a rash that has recently been proven to come out via up-regulated keratinocyte interleukin-8 synthesis with histological features reminiscent of typical neutrophilic dermatoses. In this review, we report experimental evidence that shows the use of dapsone to improve quality of life in erlotinib-treated patients by ameliorating rash as well as short-circuiting a growth-enhancing aspect of erlotinib based on increased interleukin-8 secretion.
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Blood-brain barrier dysfunction in mice induced by lipopolysaccharide is attenuated by dapsone.
Zhou, Ting; Zhao, Lei; Zhan, Rui; He, Qihua; Tong, Yawei; Tian, Xiaosheng; Wang, Hecheng; Zhang, Tao; Fu, Yaoyun; Sun, Yang; Xu, Feng; Guo, Xiangyang; Fan, Dongsheng; Han, Hongbin; Chui, Dehua
2014-10-24
Blood-brain barrier (BBB) dysfunction is a key event in the development of many central nervous system (CNS) diseases, such as septic encephalopathy and stroke. 4,4'-Diaminodiphenylsulfone (DDS, Dapsone) has displayed neuroprotective effect, but whether DDS has protective role on BBB integrity is not clear. This study was designed to examine the effect of DDS on lipopolysaccharide (LPS)-induced BBB disruption and oxidative stress in brain vessels. Using in vivo multiphoton imaging, we found that DDS administration significantly restored BBB integrity compromised by LPS. DDS also increased the expression of tight junction proteins occludin, zona occludens-1 (ZO-1) and claudin-5 in brain vessels. Level of reactive oxygen species (ROS) was reduced by DDS treatment, which may due to decreased nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity and NOX2 expression. Our results showed that LPS-induced BBB dysfunction could be attenuated by DDS, indicated that DDS has a therapeutic potential for treating CNS infection and other BBB related diseases. Copyright © 2014 Elsevier Inc. All rights reserved.
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The Neumann Type of Pemphigus Vegetans Treated with Combination of Dapsone and Steroid
Son, Young-Min; Kang, Hong-Kyu; Yun, Jeong-Hwan; Roh, Joo-Young
2011-01-01
Pemphigus vegetans is a rare variant of pemphigus vulgaris and is characterized by vegetating lesions in the inguinal folds and mouth and by the presence of autoantibodies against desmoglein 3. Two clinical subtypes of pemphigus vegetans exist, which are initially characterized by flaccid bullae and erosions (the Neumann subtype) or pustules (the Hallopeau subtype). Both subtypes subsequently develop into hyperpigmented vegetative plaques with pustules and hypertrophic granulation tissue at the periphery of the lesions. Oral administration of corticosteroids alone does not always induce disease remission in patients with pemphigus vegetans. We report here on a 63-year-old woman with pemphigs vegetans. She had a 2-year history of vegetating, papillomatous plaques on the inguinal folds and erosions of the oral mucosa. The enzyme-linked immunosorbent assay was positive for anti-desmoglein 3, but it was negative for anti-desmoglein 1. She was initially treated with systemic steroid, but no improvement was observed. The patient was then successfully treated with a combination of systemic steroid and dapsone with a good clinical response. PMID:22346265
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Omran, Ahmed Ahmed
2005-11-01
A rapid, sensitive and selective spectrophotometric method has been developed for the quantitative determination of dapsone (DAP) and metoclopramide hydrochloride (MCP) in both pure and dosage forms. Individual and simultaneous methods are based on the diazo coupling reaction of these drugs with benzoylacetone (BAC) in alkaline medium. The resulting azo dyes exhibit maximum absorption at 437 and 411 nm with a molar absorptivity of 4.14x10(4) and 2.97x10(4) l mol-1 cm-1 for DAP and MCP, respectively. Simultaneous determination of DAP and MCP was developed utilizing first-order digital derivative spectrophotometry. All variables have been optimized. No interferences were observed from drug excipients and the validity of the methods was tested against reference methods.
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McDonald, Mark; Mannion, Celine; Rafter, Paul
2009-11-13
A rapid confirmatory multi-residue method for the analysis of tetracyclines, sulphonamides, trimethoprim and dapsone by UPLC-MS/MS is described. The method is able to quantify and confirm the following 19 compounds, oxytetracycline, tetracycline, chlortetracycline, doxycycline, sulfadiazine, sulfathiazole, sulfapyridine, trimethoprim, sulfamerazine, sulfamethizole, sulfamethazine, sulfamethoxypyridazine, sulfamonomethoxine, sulfachlorpyridazine, dapsone, sulfamethoxazole, sulfisoxazole, sulfaquinoxaline and sulfadimethoxine. Samples are extracted with 0.1M EDTA and acetonitrile, which is then evaporated under a stream of nitrogen and reconstituted in water. Following centrifugation and filtering, an aliquot is analysed by UPLC-MS/MS using positive electrospray ionisation and multiple reaction monitoring. The method is deemed rapid as all analytes are extracted by a single extraction technique, with no solid-phase extraction clean up required. Validation is according to Commission Decision 2002/657/EC and was carried out for bovine, porcine, ovine and poultry species. Specificity, recovery, repeatability, reproducibility, CCalpha and CCbeta data is presented.
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Varenina, Ivana; Bilandžić, Nina; Kolanović, Božica Solomun; Božić, Đurđica; Sedak, Marija; Đokić, Maja; Varga, Ines
2016-01-01
A quantitative multi-residue method that includes 13 sulfonamides, trimethoprim and dapsone was developed and validated according to Commission Decision 2002/657/EC for muscle, milk egg and honey samples. For all matrices, the same extraction procedure was used. Samples were extracted with an acetone/dichloromethane mixture and cleaned up on aromatic sulfonic acid (SO3H) SPE cartridges. After elution and concentration steps, analytes were identified and quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Data were acquired according to the multiple reaction-monitoring approach (MRM) and analytes were quantified both by the isotope dilution and the matrix-matched approaches calculating the response factors for the scanned product ions. The developed method shows good linearity, specificity, precision (repeatability and within-laboratory reproducibility), and trueness. Estimated CCβ for sulfonamides ranged between 5.6 and 8.2 µg kg(-1) for eggs, between 11.1 and 69.9 µg kg(-1) for milk, between 64.7 and 87.9 µg kg(-1) for muscle, and between 2.7 and 5.3 µg kg(-1) for honey. CCβ values for dapsone were 3.1, 0.6, 0.7 and 1.5 µg kg(-1) and for trimethoprim were 3.1, 6.7, 81.7 and 3.0 µg kg(-1) calculated for eggs, milk, muscle and honey, respectively. Recovery for all matrices was in the range from 89.1% and 109.7%. In matrix effect testing, no significant deviations were found between different samples of muscle and milk; however, a matrix effect was observed when testing different types of honey. The validation results demonstrate that the method is suitable for routine veterinary drug analysis and confirmation of suspect samples.
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Dapsone protects brain microvascular integrity from high-fat diet induced LDL oxidation.
Zhan, Rui; Zhao, Mingming; Zhou, Ting; Chen, Yue; Yu, Weiwei; Zhao, Lei; Zhang, Tao; Wang, Hecheng; Yang, Huan; Jin, Yinglan; He, Qihua; Yang, Xiaoda; Guo, Xiangyang; Willard, Belinda; Pan, Bing; Huang, Yining; Chen, Yingyu; Chui, Dehua; Zheng, Lemin
2018-06-07
Atherosclerosis was considered to induce many vascular-related complications, such as acute myocardial infarction and stroke. Abnormal lipid metabolism and its peroxidation inducing blood-brain barrier (BBB) leakage were associated with the pre-clinical stage of stroke. Dapsone (DDS), an anti-inflammation and anti-oxidation drug, has been found to have protective effects on vascular. However, whether DDS has a protective role on brain microvessels during lipid oxidation had yet to be elucidated. We investigated brain microvascular integrity in a high-fat diet (HFD) mouse model. We designed this study to explore whether DDS had protective effects on brain microvessels under lipid oxidation and tried to explain the underlying mechanism. In our live optical study, we found that DDS significantly attenuated brain microvascular leakage through reducing serum oxidized low-density lipoprotein (oxLDL) in HFD mice (p < 0.001), and DDS significantly inhibited LDL oxidation in vitro (p < 0.001). Our study showed that DDS protected tight junction proteins: ZO-1 (p < 0.001), occludin (p < 0.01), claudin-5 (p < 0.05) of microvascular endothelial cells in vivo and in vitro. DDS reversed LAMP1 aggregation in cytoplasm, and decreased the destruction of tight junction protein: ZO-1 in vitro. We first revealed that DDS had a protective role on cerebral microvessels through preventing tight junction ZO-1 from abnormal degradation by autophagy and reducing lysosome accumulation. Our findings suggested the significance of DDS in protecting brain microvessels under lipid metabolic disorders, which revealed a novel potential therapeutic strategy in brain microvascular-related diseases.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Bhaiya, Payal; Roychowdhury, Sanjoy; Vyas, Piyush M.
2006-09-01
Cutaneous drug reactions (CDRs) associated with sulfonamides are believed to be mediated through the formation of reactive metabolites that result in cellular toxicity and protein haptenation. We evaluated the bioactivation and toxicity of sulfamethoxazole (SMX) and dapsone (DDS) in normal human dermal fibroblasts (NHDF). Incubation of cells with DDS or its metabolite (D-NOH) resulted in protein haptenation readily detected by confocal microscopy and ELISA. While the metabolite of SMX (S-NOH) haptenated intracellular proteins, adducts were not evident in incubations with SMX. Cells expressed abundant N-acetyltransferase-1 (NAT1) mRNA and activity, but little NAT2 mRNA or activity. Neither NAT1 nor NAT2 proteinmore » was detected. Incubation of NHDF with S-NOH or D-NOH increased reactive oxygen species formation and reduced glutathione content. NHDF were less susceptible to the cytotoxic effect of S-NOH and D-NOH than are keratinocytes. Our studies provide the novel observation that NHDF are able to acetylate both arylamine compounds and bioactivate the sulfone DDS, giving rise to haptenated proteins. The reactive metabolites of SMX and DDS also provoke oxidative stress in these cells in a time- and concentration-dependent fashion. Further work is needed to determine the role of the observed toxicity in mediating CDRs observed with these agents.« less
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Kast, Richard E; Hill, Quentin A; Wion, Didier; Mellstedt, Håkan; Focosi, Daniele; Karpel-Massler, Georg; Heiland, Tim; Halatsch, Marc-Eric
2017-05-01
Increased ratio of circulating neutrophils to lymphocytes is a common finding in glioblastoma and other cancers. Data reviewed establish that any damage to brain tissue tends to cause an increase in G-CSF and/or GM-CSF (G(M)-CSF) synthesized by the brain. Glioblastoma cells themselves also synthesize G(M)-CSF. G(M)-CSF synthesized by brain due to damage by a growing tumor and by the tumor itself stimulates bone marrow to shift hematopoiesis toward granulocytic lineages away from lymphocytic lineages. This shift is immunosuppressive and generates the relative lymphopenia characteristic of glioblastoma. Any trauma to brain-be it blunt, sharp, ischemic, infectious, cytotoxic, tumor encroachment, or radiation-increases brain synthesis of G(M)-CSF. G(M)-CSF are growth and motility enhancing factors for glioblastomas. High levels of G(M)-CSF contribute to the characteristic neutrophilia and lymphopenia of glioblastoma. Hematopoietic bone marrow becomes entrained with, directed by, and contributes to glioblastoma pathology. The antibiotic dapsone, the lipid-lowering agent fenofibrate, and the antiviral drug ribavirin are Food and Drug Administration- and European Medicines Agency-approved medicines that have potential to lower synthesis or effects of G(M)-CSF and thus deprive a glioblastoma of some of the growth promoting contributions of bone marrow and G(M)-CSF.
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Lu, Fuguang; Yang, Jinlong; Sun, Min; Fan, Lulu; Qiu, Huamin; Li, Xiangjun; Luo, Chuannan
2012-07-01
This paper reports the preparation of dapsone (DDS) imprinted polymer layer-coated silica submicron particles (SiO(2)) combined with chemiluminescence (CL) toward analysis of tracing DDS in practical samples. To induce the selective occurrence of surface polymerization, the amino groups were first grafted at the surface of SiO(2) by the (3-aminopropyl)triethoxysilane (APTES). The molecularly imprinted polymers (MIP) were coated at the surface of modified SiO(2) by the graft copolymerization. After the removal of templates, recognition sites of DDS were exposed in the polymer layers. The DDS-imprinted products were characterized by FT-IR, SEM, TEM, dynamic adsorption, and static adsorption tests. The proximity between the thickness of MIP layer and the spatial size of DDS indicated that the imprinted sites almost situated at the surface of MIP, leading to rapid adsorption saturation within 90 min. The apparent maximum binding amount of MIP toward DDS was evaluated as 14.98 mg·g(-1), which was much higher than that of non-molecularly imprinted polymers. The CL sensor provided a wide linear range for DDS within 1.0 × 10(-6) to 1.0 × 10(-4) mol·L(-1) with a detection limit of 5.27 × 10(-7) mol·L(-1) and the relative standard deviation of 1.8 % (n = 11) by determinations of 5.0 × 10(-6) mol·L(-1) DDS. This method was applied to determine DDS in urine samples and satisfactory results were obtained.
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Ferreira, Anderson O; Polonini, Hudson C; Silva, Sharlene L; Patrício, Fernando B; Brandão, Marcos Antônio F; Raposo, Nádia R B
2016-01-25
The objective of this study was to evaluate the feasibility of 10 commonly used active pharmaceutical ingredients (APIs) compounded in oral suspensions using an internationally used suspending vehicle (SyrSpend(®) SF PH4 liquid): (i) amlodipine, (as besylate) 1.0mg/mL; (ii) chloroquine phosphate,15.0 mg/mL; (iii) dapsone, 2.0 mg/mL; (iv) phenytoin, 15.0 mg/mL; (v) pyridoxine hydrochloride, 50.0 mg/mL; (vi) sulfadiazine, 100.0 mg/mL; (vii) sulfasalazine, 100.0 mg/mL; (viii) tetracycline hydrochloride, 25.0 mg/mL; (ix) trimethoprim, 10.0 mg/mL; and (x) zonisamide, 10.0 mg/mL. All suspensions were stored both at controlled refrigeration (2-8 °C) and controlled room temperature (20-25 °C). Feasibility was assessed by measuring the percent recovery at varying time points throughout a 90-day period. API quantification was performed by high-performance liquid chromatography (HPLC-UV), via a stability-indicating method. Given the percentage of recovery of the APIs within the suspensions, the expiration date of the final products (API+vehicle) was at least 90 days for all suspensions with regard to both the controlled temperatures. This suggests that the vehicle is stable for compounding APIs from different pharmacological classes. Copyright © 2015 Elsevier B.V. All rights reserved.
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Screening and Evaluation of Experimental Antiparasitic Drugs.
1979-08-01
compounds were tested against one or more of the following lines resistant to chloroquine , cycloguanil, dapsone, mefloquine, pyrimethamine, or quinine...against one or more of the following lines resistant to chloroquine , cycloguanil, dapsone, mefloquine, pyrimeth- amine, or quinine, respectively. Two...four level tests against each drug-resistant line was as follows: mefloquine-resistant line (51); chloroquine -resistant line (67); pyrimethamine
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Molecular detection of multidrug-resistant Mycobacterium leprae from Indian leprosy patients.
Lavania, Mallika; Singh, Itu; Turankar, Ravindra P; Ahuja, Madhvi; Pathak, Vinay; Sengupta, Utpal; Das, Loretta; Kumar, Archana; Darlong, Joydeepa; Nathan, Rajeev; Maseey, Asha
2018-03-01
The emergence of multidrug-resistant (MDR) organisms for any infectious disease is a public health concern. Global efforts to control leprosy by intensive chemotherapy have led to a significant decrease in the number of registered patients. Currently recommended control measures for treating leprosy with multidrug therapy (MDT) were designed to prevent the spread of dapsone-resistant Mycobacterium leprae strains. Here we report the identification of MDR M. leprae from relapse leprosy patients from endemic regions in India. Resistance profiles to rifampicin, dapsone and ofloxacin of the isolated strains were confirmed by identification of mutations in genes previously shown to be associated with resistance to each drug. Between 2009-2016, slit-skin smear samples were collected from 239 relapse and 11 new leprosy cases from hospitals of The Leprosy Mission across India. DNA was extracted from the samples and was analysed by PCR targeting the rpoB, folP and gyrA genes associated with resistance to rifampicin, dapsone and ofloxacin, respectively, in M. leprae. M. leprae Thai-53 (wild-type) and Zensho-4 (MDR) were used as reference strains. Fifteen strains showed representative mutations in at least two resistance genes. Two strains showed mutations in all three genes responsible for drug resistance. Seven, seven and one strain, respectively, showed mutations in genes responsible for rifampicin and dapsone resistance, for dapsone and ofloxacin resistance and for rifampicin and ofloxacin resistance. This study showed the emergence of MDR M. leprae in MDT-treated leprosy patients from endemic regions of India. Copyright © 2017 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.
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Van Malderen, Carine; Van Geertruyden, Jean-Pierre; Machevo, Sonia; González, Raquel; Bassat, Quique; Talisuna, Ambrose; Yeka, Adoke; Nabasumba, Carolyn; Piola, Patrice; Daniel, Atwine; Turyakira, Eleanor; Forret, Pascale; Van Overmeir, Chantal; van Loen, Harry; Robert, Annie; D' Alessandro, Umberto
2012-07-10
Malaria is a leading cause of mortality, particularly in sub-Saharan African children. Prompt and efficacious treatment is important as patients may progress within a few hours to severe and possibly fatal disease. Chlorproguanil-dapsone-artesunate (CDA) was a promising artemisinin-based combination therapy (ACT), but its development was prematurely stopped because of safety concerns secondary to its associated risk of haemolytic anaemia in glucose-6-phosphate dehydrogenase (G6PD)-deficient individuals. The objective of the study was to assess whether CDA treatment and G6PD deficiency are risk factors for a post-treatment haemoglobin drop in African children<5 years of age with uncomplicated malaria. This case-control study was performed in the context of a larger multicentre randomized clinical trial comparing safety and efficacy of four different ACT in children with uncomplicated malaria. Children, who after treatment experienced a haemoglobin drop≥2 g/dl (cases) within the first four days (days 0, 1, 2, and 3), were compared with those without an Hb drop (controls). Cases and controls were matched for study site, sex, age and baseline haemoglobin measurements. Data were analysed using a conditional logistic regression model. G6PD deficiency prevalence, homo- or hemizygous, was 8.5% (10/117) in cases and 6.8% (16/234) in controls (p=0.56). The risk of a Hb drop≥2 g/dl was not associated with either G6PD deficiency (adjusted odds ratio (AOR): 0.81; p=0.76) or CDA treatment (AOR: 1.28; p=0.37) alone. However, patients having both risk factors tended to have higher odds (AOR: 11.13; p=0.25) of experiencing a Hb drop≥2 g/dl within the first four days after treatment, however this finding was not statistically significant, mainly because G6PD deficient patients treated with CDA were very few. In non-G6PD deficient individuals, the proportion of cases was similar between treatment groups while in G6PD-deficient individuals, haemolytic anaemia occurred
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Economou, Anastasios; Petraki, Olympia; Tsipi, Despina; Botitsi, Eleni
2012-08-15
This work reports a sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for identification and quantification of seven sulfonamides, trimethoprim and dapsone in honey. The method is based on a solid-phase extraction (SPE) step of the target analytes with Oasis HLB cartridges after acidic hydrolysis of the honey sample to liberate the sugar-bound sulfonamides. Analysis was performed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) in the positive electro-spray ionization (ESI) mode with two different isotopically labeled internal standards with the view to improve the quantitative performance of the method. The method validation has been performed according to the Commission Decision 2002/657/EC; the average recoveries, measured at three concentration levels (1.5, 2.5 and 5.0 μg kg(-1)), have been estimated in the range 70 to 106% while the respective % relative standard deviations of the within-laboratory reproducibility ranged from 6 to 18%. Mean values of the expanded uncertainties calculated were in the range 22-41% at the 99% confidence level. Decision limit (CCα) and detection capability (CCβ) values were in the ranges 0.4-0.9 and 0.7-1.4 μg kg(-1), respectively. Matrix effects have been investigated demonstrating a moderate signal suppression/enhancement for most of the target compounds. The method described has been successfully applied to the analysis of honey samples; sulfamethoxazole, sulfathiazole and trimethoprim were detected in some cases. Copyright © 2012 Elsevier B.V. All rights reserved.
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Thermoanalytical Investigation of Some Sulfone-Containing Drugs
Salama, Nahla N.; El Ries, Mohammed A.; Toubar, Safaa; Abd El Hamid, Maha; Walash, Mohammed I.
2012-01-01
The thermal behavior of some sulfone-containing drugs, namely, dapsone (DDS), dimethylsulfone (MSM), and topiramate (TOP) in drug substances, and products were investigated using different thermal techniques. These include thermogravimetry (TGA), derivative thermogravimetry (DTG), differential thermal analysis (DTA), and differential scanning calorimetry (DSC). The thermogravimetric data allowed the determination of the kinetic parameters: activation energy (E a), frequency factor (A), and reaction order (n). The thermal degradation of dapsone and topiramate was followed a first-order kinetic behavior. The calculated data evidenced a zero-order kinetic for dimethylsulfone. The relative thermal stabilities of the studied drugs have been evaluated and follow the order DDS > TOP > MSM. The purity was determined using DSC for the studied compounds, in drug substances and products. The results were in agreement with the recommended pharmacopoeia and manufacturer methods. DSC curves obtained from the tablets suggest compatibility between the drugs, excipients and/or coformulated drugs. The fragmentation pathway of dapsone with mass spectrometry was taken as example, to correlate the thermal decomposition with the resulted MS-EI. The decomposition modes were investigated, and the possible fragmentation pathways were suggested by mass spectrometry. PMID:22792516
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Thermoanalytical investigation of some sulfone-containing drugs.
Salama, Nahla N; El Ries, Mohammed A; Toubar, Safaa; Abd El Hamid, Maha; Walash, Mohammed I
2012-01-01
The thermal behavior of some sulfone-containing drugs, namely, dapsone (DDS), dimethylsulfone (MSM), and topiramate (TOP) in drug substances, and products were investigated using different thermal techniques. These include thermogravimetry (TGA), derivative thermogravimetry (DTG), differential thermal analysis (DTA), and differential scanning calorimetry (DSC). The thermogravimetric data allowed the determination of the kinetic parameters: activation energy (E(a)), frequency factor (A), and reaction order (n). The thermal degradation of dapsone and topiramate was followed a first-order kinetic behavior. The calculated data evidenced a zero-order kinetic for dimethylsulfone. The relative thermal stabilities of the studied drugs have been evaluated and follow the order DDS > TOP > MSM. The purity was determined using DSC for the studied compounds, in drug substances and products. The results were in agreement with the recommended pharmacopoeia and manufacturer methods. DSC curves obtained from the tablets suggest compatibility between the drugs, excipients and/or coformulated drugs. The fragmentation pathway of dapsone with mass spectrometry was taken as example, to correlate the thermal decomposition with the resulted MS-EI. The decomposition modes were investigated, and the possible fragmentation pathways were suggested by mass spectrometry.
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Oudrhiri, Lamia; Chiheb, Soumiya; Marnissi, Farida; Zamiati, Soumaya; Benchikhi, Hakima
2012-01-01
We report a case of a 19-year-old girl who presented with 5-year history of swelling of upper lip and fissured tongue treated with dapsone then oral steroids without any improvement. Clinical examination found peripheral facial nerve paralysis and Labial mucosa biopsy showed non-necrotizing giganto-epithelioid granuloma. Diagnosis of Melkersson-Rosenthal syndrome was retaind because of association of cheilitis, lingua plicata and facial paralysis. Given the failure of dapsone and oral steroid we suggested an association of betamethasone injection and doxycycline. Gradual and permanent reduction of the upper lip volume was observed. One year follow up objectified no reactivation of cheilitis. PMID:23397029
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Efficacy of steroidal vs non-steroidal agents in oral lichen planus: a randomised, open-label study.
Singh, A R; Rai, A; Aftab, M; Jain, S; Singh, M
2017-01-01
This study compared the therapeutic efficacy of steroidal and non-steroidal agents for treating oral lichen planus. Forty patients with clinical and/or histologically proven oral lichen planus were randomly placed into four groups and treated with topical triamcinolone, oral dapsone, topical tacrolimus or topical retinoid for three months. Pre- and post-treatment symptoms and signs were scored for each patient. Patients in all treatment groups showed significant clinical improvement after three months (p 0.05) and for topical retinoid vs topical tacrolimus (p > 0.05). Non-steroidal drugs such as dapsone, tacrolimus and retinoid are as efficacious as steroidal drugs for treating oral lichen planus, and avoid the side effects associated with steroids.
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Poirot, Eugenie; Vittinghoff, Eric; Ishengoma, Deus; Alifrangis, Michael; Carneiro, Ilona; Hashim, Ramadhan; Baraka, Vito; Mosha, Jacklin; Gesase, Samwel; Chandramohan, Daniel; Gosling, Roland
2015-01-01
Chlorproguanil-dapsone (CD) has been linked to hemolysis in symptomatic glucose-6-phosphate dehydrogenase deficient (G6PDd) children. Few studies have explored the effects of G6PD status on hemolysis in children treated with Intermittent Preventive Treatment in infants (IPTi) antimalarial regimens. We sought to examine the joint effects of G6PD status and IPTi antimalarial treatment on incidence of hemolysis in asymptomatic children treated with CD, sulfadoxine-pyrimethamine (SP), and mefloquine (MQ). A secondary analysis of data from a double-blind, placebo-controlled trial of IPTi was conducted. Hemoglobin (Hb) measurements were made at IPTi doses, regular follow-up and emergency visits. G6PD genotype was determined at 9 months looking for SNPs for the A- genotype at coding position 202. Multivariable linear and logistic regression models were used to examine hemolysis among children with valid G6PD genotyping results. Hemolysis was defined as the absolute change in Hb or as any post-dose Hb <8 g/dL. These outcomes were assessed using either a single follow-up Hb on day 7 after an IPTi dose or Hb obtained 1 to 14 or 28 days after each IPTi dose. Relative to placebo, CD reduced Hb by approximately 0.5 g/dL at day 7 and within 14 days of an IPTi dose, and by 0.2 g/dL within 28 days. Adjusted declines in the CD group were larger than in the MQ and SP groups. At day 7, homo-/hemizygous genotype was associated with higher odds of Hb <8 g/dL (adjusted odds ratio = 6.7, 95% CI 1.7 to 27.0) and greater absolute reductions in Hb (-0.6 g/dL, 95% CI -1.1 to 0.003). There was no evidence to suggest increased reductions in Hb among homo-/hemizygous children treated with CD compared to placebo, SP or MQ. While treatment with CD demonstrated greater reductions in Hb at 7 and 14 days after an IPTi dose compared to both SP and MQ, there was no evidence that G6PD deficiency exacerbated the adverse effects of CD, despite evidence for higher hemolysis risk among G6PDd infants.
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Topical Acne Treatments and Pregnancy
... are benzoyl peroxide, azelaic acid, glycolic acid, and salicylic acid. Prescription acne medications include tretinoin, adapalene, dapsone, and ... ACOG) recommends topical benzoyl peroxide, azelaic acid, topical salicylic acid and glycolic acid for treatment of acne in ...
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[Congenital hemolytic anemia due to glucose-6-phosphate dehydrogenase deficiency].
Mura, M; Saidi, R; Wolf, A; Moalic, J L; Oliver, M
2009-12-01
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common enzyme defect with a wide range of clinical manifestations that can be severe. A variety of factors including many medications can induce hemolytic episodes. Screening for G6PD deficiency is required before use of some drugs especially primaquine or dapsone.
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Guerrero, Martha Inírida; Colorado, Claudia Lucía; Torres, José Fernando; León, Clara Inés
2014-04-01
There is no information in Colombia on Mycobacterium leprae primary and secondary drug resistance in regards to the WHO-multidrug therapy regime. On the other hand, public health authorities around the world have issued various recommendations, one of which prompts for the immediate organization of resistance surveillance through simple molecular methods. To determine the prevalence of Mycobacterium leprae drug resistance to rifampicin, ofloxacin and dapsone in untreated and previously treated patients at the Centro Dermatológico Federico Lleras Acosta during the 1985-2004 period. We conducted a retrospective study which included multibacillary patient biopsies through elective sampling: 381 of them from new patients and 560 from previously treated patients. Using a microtome, we obtained six slides from each skin biopsy preserved in paraffin, and we extracted M. leprae DNA. We amplified three molecular targets through PCR and obtained the patterns of drug resistance to dapsone, rifampicin and ofloxacin by reverse hybridization. Finally, we collected epidemiological, clinical and demographical data for analyses. From 941 samples under study, 4.14% of them were resistant to one or more drugs, and 5.77 and 3.04% had resistant genotypes in new and previously treated patients, respectively. Total resistance for each drug was 0.43% for dapsone, 3.19% for rifampicin and 1.17% for ofloxacin. We found statistically significant differences for rifampicin and for the total population when comparing the results from untreated versus previously treated patients. Two thirds of the resistant samples were resistant to rifampicin alone or combined. The standard multidrug therapy schemes continue being effective for leprosy cases; however, it is necessary to guarantee adherence and regularity. Surveillance to drug resistance in new and previously treated leprosy cases should be established.
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Lavania, Mallika; Jadhav, Rupendra S; Chaitanya, Vedithi Sundeep; Turankar, Ravindra; Selvasekhar, Abraham; Das, Loretta; Darlong, Famkima; Hambroom, Ujjwal K; Kumar, Sandip; Sengupta, Utpal
2014-09-01
Implementation of multidrug therapy (MDT) in leprosy control programmes has significantly reduced the global prevalence of the disease in the last two decades. After many years of use of MDT, it is expected that drug resistance in Mycobacterium leprae may emerge. This is a major concern, especially during the stage of elimination. In the present study, slit-skin smears were collected from 140 leprosy relapse cases from different Leprosy Mission hospitals across India. DNA extracted from 111 (79%) of these samples was analysed for the genes associated with drug resistance in M. leprae. More than 90% of the patients relapsed as multibacillary (MB) cases. In our study, four (3.6%) of the DNA samples analysed showed mutations associated with rifampicin resistance. We also observed that mutations associated with resistance to dapsone and ofloxacin were observed in 9 (8.1%) of the DNA samples each; two samples had both dapsone and ofloxacin resistance. Further surveillance and appropriate interventions are needed to ensure the continued success of chemotherapy for leprosy.
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Unusual presentation of childhood Systemic Lupus Erythematosus
Kumar, Sathish; Agarwal, Indira
2007-01-01
Bullous systemic lupus erythematosus is a rare blistering condition with a distinctive combination of clinical, histological and immunopathologic features that together constitute a unique bullous disease phenotype. It is often associated with autoimmunity to type VII collagen. Here we report a child who presented with bullous systemic lupus erythematosus. Rapid resolution of the blisters occurred following treatment with dapsone. PMID:18028550
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Tietze, J K; Heppt, M V; von Preußen, A; Wolf, U; Ruzicka, T; Wolff, H; Sattler, E C
2015-09-01
Folliculitis decalvans leads to scarring alopecia through inflammatory destruction of the hair follicle. Currently, antibiotics are most commonly used to treat this disease. However, treatment regimens with antibiotics feature a high relapse rate and encourage the development of resistant bacteria. To evaluate the outcome of different treatment options for folliculitis decalvans. Retrospective study to compare the efficacy of different treatment regimens in 28 patients with folliculitis decalvans. The success of treatment with clindamycin and rifampicin, clarithromycin, dapsone and isotretinoin was analysed. The evaluation of the combination of clindamycin and rifampicin showed the lowest success rate in achieving long-term remission, since 80% of the patients relapsed shortly after end of treatment. Clarithromycin and dapsone were more successful with long-term and stable remission rates of 33% and 43% respectively. Treatment with isotretinoin was the most successful oral treatment in our analysis with 90% of the patients experiencing stable remission during and up to two years after cessation of the treatment. The common use of antibiotics as first-line therapy in folliculitis decalvans needs to be re-evaluated critically and oral isotretinoin should be considered as valid treatment alternative. © 2015 European Academy of Dermatology and Venereology.
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Leprosy Drug Resistance Surveillance in Colombia: The Experience of a Sentinel Country
Beltrán-Alzate, Camilo; López Díaz, Fernando; Romero-Montoya, Marcela; Sakamuri, Rama; Li, Wei; Kimura, Miyako; Brennan, Patrick
2016-01-01
An active search for Mycobacterium leprae drug resistance was carried out, 243 multibacillary patients from endemic regions of Colombia were included from 2004 to 2013 in a surveillance program. This program was a World Health Organization initiative for drug resistance surveillance in leprosy, where Colombia is a sentinel country. M. leprae DNA from slit skin smear and/or skin biopsy samples was amplified and sequenced to identify mutations in the drug resistance determining region (DRDR) in rpoB, folP1, gyrA, and gyrB, the genes responsible for rifampicin, dapsone and ofloxacin drug-resistance, respectively. Three isolates exhibited mutations in the DRDR rpoB gene (Asp441Tyr, Ser456Leu, Ser458Met), two in the DRDR folP1 gene (Thr53Ala, Pro55Leu), and one isolate exhibited mutations in both DRDR rpoB (Ser456Met) and DRDR folP1 (Pro55Leu), suggesting multidrug resistance. One isolate had a double mutation in folP1 (Thr53Ala and Thr88Pro). Also, we detected mutations outside of DRDR that required in vivo evaluation of their association or not with drug resistance: rpoB Arg505Trp, folP1 Asp91His, Arg94Trp, and Thr88Pro, and gyrA Ala107Leu. Seventy percent of M. leprae mutations were related to drug resistance and were isolated from relapsed patients; the likelihood of relapse was significantly associated with the presence of confirmed resistance mutations (OR range 20.1–88.7, p < 0.05). Five of these relapsed patients received dapsone monotherapy as a primary treatment. In summary, the current study calls attention to M. leprae resistance in Colombia, especially the significant association between confirmed resistance mutations and relapse in leprosy patients. A high frequency of DRDR mutations for rifampicin was seen in a region where dapsone monotherapy was used extensively. PMID:27706165
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1975-05-31
Vietnam was resistant to drugs such as chloroquine and quinine, gene-ally r,,conized snce World War II as satisfactory antimalarial agents. Tr,e...Trypanosoma rhodesiense infections in mice. (3) structural analogues of compounds found active in our test system and representing several novel chemical...with chloroquine , dapsone, cycloguanil, or pyrimethamine. Out of the 17 good compounds 7 exhibited quinine equivalent values of greater than 25. These 7
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Fernandes, Iolanda Conde; Sanches, Madalena; Alves, Rosário; Selores, Manuela
2012-01-01
We report a clinical case of a rare variant of pemphigus - pemphigus herpetiformis - which combines the clinical features of dermatitis herpetiformis with the immunological findings of pemphigus. Due to its atypical presentation, it is frequently misdiagnosed as dermatitis herpetiformis. It is basically characterized by the herpetiform pattern of skin lesions, severe pruritus and by the presence of eosinophilic spongiosis confirmed on histopathology. We call attention to the excellent response to dapsone. PMID:23197221
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Avanzi, Charlotte; Busso, Philippe; Benjak, Andrej; Loiseau, Chloé; Fomba, Abdoulaye; Doumbia, Glodia; Camara, Idrissa; Lamou, André; Sock, Gouressy; Drame, Tiguidanké; Kodio, Mamadou; Sakho, Fatoumata; Sow, Samba O; Cole, Stewart T; Johnson, Roch Christian
2016-12-01
Molecular drug susceptibility testing was performed on skin biopsies from 24 leprosy patients from Guinea-Conakry for the first time. We identified primary drug resistance in 4 cases and a dapsone-resistant cluster caused by the same strain. Primary transmission of drug-resistant Mycobacterium leprae, including a rifampicin-resistant strain, is reported. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.
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Drug resistance in Mycobacterium leprae from patients with leprosy in China.
Liu, D; Zhang, Q; Sun, Y; Wang, C; Zhang, Y; Fu, X; Chen, M; Zhou, G; Yu, X; Wang, J; Liu, H; Zhang, F
2015-12-01
Previous studies of drug resistance have shown that mutations in the drug resistance-determining region (DRDR) in the Folp1, RpoB and GyrA genes of Mycobacterium leprae are responsible for resistance to dapsone, rifampin and ofloxacin, respectively. To investigate the prevalence of mutations in genes associated with drug resistance in M. leprae isolates from patients with leprosy in Shandong Province. The DRDR in the FolP1, RpoB and GyrA genes was analysed by direct sequencing of the PCR product from 85 isolates of M. leprae sampled from patients with leprosy in Shandong, China. Sequencing results were obtained for FolP1, RpoB and GyrA in 67, 57 and 81 of the 85 samples, with mutation rates of 1.5% (1/67), 8.8% 5/57 and 25.9% (21/81). Three multidrug-resistant samples were found among the new cases: one had a mutation in both Folp1 and RpoB, while the other two had a mutation in both RpoB and GyrA. Primary resistance appears to be to either single drugs or combinations of two drugs. The resistance rate to dapsone seems to be low. To our knowledge, this is the first case of multidrug-resistant M. leprae from China. © 2015 British Association of Dermatologists.
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Cruz, Rossilene Conceição da Silva; Bührer-Sékula, Samira; Penna, Maria Lúcia F; Penna, Gerson Oliveira; Talhari, Sinésio
2017-01-01
In this review, the most relevant and current epidemiological data, the main clinical, laboratory and therapeutical aspects of leprosy are presented. Detailed discussion of the main drugs used for leprosy treatment, their most relevant adverse effects, evolution of the therapeutic regimen, from dapsone as a monotherapy to the proposed polychemotherapy by World Health Organization (WHO) can be found in this CME. We specifically highlight the drug acceptability, reduction in treatment duration and the most recent proposal of a single therapeutic regimen, with a fixed six months duration, for all clinical presentations, regardless of their classification.
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Scheinfeld, Noah
2013-04-15
Hidradenitis suppurativa (HS), a pathological follicular disease, impacts patients' lives profoundly. HS most commonly involves cutaneous intertriginous areas, such as the axilla, inner thighs, groin and buttocks, and pendulous breasts, but can appear on any follicular skin. Protean, HS manifests with variations of abscesses, folliculitis, pyogenic granulomas, scars (oval honeycombed), comedones, tracts, fistulas, and keloids. The pathophysiology might involve both defects of the innate follicular immunity and overreaction to coagulase negative Staphylococcus. Treatment depends on the morphology, extent, severity, and duration. Topical clindamycin and dapsone are often adequate for treating mild HS. For Stage 1 and 2 HS, first line treatment combines rifampin with either oral clindamycin or minocycline. Other HS treatments include: fluoroquinolones with metronidazole and rifampin, oral dapsone, zinc, acitretin, hormone blockers (oral contraceptive pills, spironolactone, finasteride, and dutasteride), and oral prednisone. For severe HS, cyclosporine, adalimumab, or infliximab (used at double psoriatic doses) and intravenous carbapenems or cephalosporins are often required. Isotretinoin, etanercept, isoniazid, lymecycline, sulfasalazine, methotrexate, metformin, colchicine, clarithromycin, IVIG, and thalidomide are less favored treatments. The role of botulinum toxin is uncertain. The most important life style modification is weight loss. De-roofing fluctuant nodules and injection of intralesional corticosteroids ameliorates the disease and perhaps, if done at regular intervals, improves HS more permanently. Surgical excision and CO2 laser ablation are more definitive treatments. The 1064 nm laser for hair removal aids in the treatment of HS. This article centers on medical therapies and will only passingly mention surgical and laser treatments. This article summarizes my treatment experience with over 350 HS patients.
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[Linear IgA disease with ocular involvement associated with ulcerative colitis].
Klein, A; Wenzel, S M; Messmer, E M; Landthaler, M; Vogt, T
2010-01-01
The association of linear IgA disease (LAD), ulcerative colitis and scarring ocular involvement is very rare and represents a considerable therapeutic challenge. We report a 48-year-old male diagnosed with ulcerative colitis in 1995, who received long-term methylprednisolone therapy. Later, he developed ocular inflammation with conjunctival scarring and synechiae formation as well as episodes of vesicles. Although azathioprine was added to his regimen, the disease was not controlled. After the diagnosis of LAD was established, dapsone was added. With this therapy, the ocular inflammation decreased significantly and the methylprednisolone dose could be successfully tapered slowly without reappearance of vesicles.
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Cruz, Rossilene Conceição da Silva; Bührer-Sékula, Samira; Penna, Maria Lúcia F.; Penna, Gerson Oliveira; Talhari, Sinésio
2017-01-01
In this review, the most relevant and current epidemiological data, the main clinical, laboratory and therapeutical aspects of leprosy are presented. Detailed discussion of the main drugs used for leprosy treatment, their most relevant adverse effects, evolution of the therapeutic regimen, from dapsone as a monotherapy to the proposed polychemotherapy by World Health Organization (WHO) can be found in this CME. We specifically highlight the drug acceptability, reduction in treatment duration and the most recent proposal of a single therapeutic regimen, with a fixed six months duration, for all clinical presentations, regardless of their classification. PMID:29364430
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Laing, A. B. G.
1974-01-01
Potentiating combinations of 4-aminobenzoic acid (PABA) competitors, such as sulfadoxine, sulfalene, or dapsone, and dihydrofolate dehydrogenasea (1.5.1.4) inhibitors, such as pyrimethamine or proguanil, have been subjected to various trials over the last decade. By and large they have proved to be effective agents against drug-resistant strains of malaria parasites, and with the small doses required they have been free of toxic effects. Parasite resistance to such combinations has seldom occurred but may be associated with cross-resistance to other combinations. These combinations should be reserved for the treatment of chloroquine-resistant infections and for use as adjuvants in organized malaria eradication campaigns. PMID:4613505
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Mohanty, Partha Sarathi; Bansal, Avi Kumar; Naaz, Farah; Gupta, Umesh Datta; Dwivedi, Vivek Dhar; Yadava, Umesh
2018-06-01
Leprosy is a chronic infection of skin and nerve caused by Mycobacterium leprae. The treatment is based on standard multi drug therapy consisting of dapsone, rifampicin and clofazamine. The use of rifampicin alone or with dapsone led to the emergence of rifampicin-resistant Mycobacterium leprae strains. The emergence of drug-resistant leprosy put a hurdle in the leprosy eradication programme. The present study aimed to predict the molecular model of ribonucleotide reductase (RNR), the enzyme responsible for biosynthesis of nucleotides, to screen new drugs for treatment of drug-resistant leprosy. The study was conducted by retrieving RNR of M. leprae from GenBank. A molecular 3D model of M. leprae was predicted using homology modelling and validated. A total of 325 characters were included in the analysis. The predicted 3D model of RNR showed that the ϕ and φ angles of 251 (96.9%) residues were positioned in the most favoured regions. It was also conferred that 18 α-helices, 6 β turns, 2 γ turns and 48 helix-helix interactions contributed to the predicted 3D structure. Virtual screening of Food and Drug Administration approved drug molecules recovered 1829 drugs of which three molecules, viz., lincomycin, novobiocin and telithromycin, were taken for the docking study. It was observed that the selected drug molecules had a strong affinity towards the modelled protein RNR. This was evident from the binding energy of the drug molecules towards the modelled protein RNR (-6.10, -6.25 and -7.10). Three FDA-approved drugs, viz., lincomycin, novobiocin and telithromycin, could be taken for further clinical studies to find their efficacy against drug resistant leprosy. Copyright © 2018 Elsevier B.V. All rights reserved.
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Degang, Yang; Akama, Takeshi; Hara, Takeshi; Tanigawa, Kazunari; Ishido, Yuko; Gidoh, Masaichi; Makino, Masahiko; Ishii, Norihisa; Suzuki, Koichi
2012-01-01
Mycobacterium leprae (M. leprae) lives and replicates within macrophages in a foamy, lipid-laden phagosome. The lipids provide essential nutrition for the mycobacteria, and M. leprae infection modulates expression of important host proteins related to lipid metabolism. Thus, M. leprae infection increases the expression of adipophilin/adipose differentiation-related protein (ADRP) and decreases hormone-sensitive lipase (HSL), facilitating the accumulation and maintenance of lipid-rich environments suitable for the intracellular survival of M. leprae. HSL levels are not detectable in skin smear specimens taken from leprosy patients, but re-appear shortly after multidrug therapy (MDT). This study examined the effect of MDT components on host lipid metabolism in vitro, and the outcome of rifampicin, dapsone and clofazimine treatment on ADRP and HSL expression in THP-1 cells. Clofazimine attenuated the mRNA and protein levels of ADRP in M. leprae-infected cells, while those of HSL were increased. Rifampicin and dapsone did not show any significant effects on ADRP and HSL expression levels. A transient increase of interferon (IFN)-β and IFN-γ mRNA was also observed in cells infected with M. leprae and treated with clofazimine. Lipid droplets accumulated by M. leprae-infection were significantly decreased 48 h after clofazimine treatment. Such effects were not evident in cells without M. leprae infection. In clinical samples, ADRP expression was decreased and HSL expression was increased after treatment. These results suggest that clofazimine modulates lipid metabolism in M. leprae-infected macrophages by modulating the expression of ADRP and HSL. It also induces IFN production in M. leprae-infected cells. The resultant decrease in lipid accumulation, increase in lipolysis, and activation of innate immunity may be some of the key actions of clofazimine. PMID:23236531
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Multidrug therapy for leprosy: a game changer on the path to elimination.
Smith, Cairns S; Aerts, Ann; Saunderson, Paul; Kawuma, Joseph; Kita, Etsuko; Virmond, Marcos
2017-09-01
Leprosy is present in more than 100 countries, where it remains a major cause of peripheral neuropathy and disability. Attempts to eliminate the disease have faced various obstacles, including characteristics of the causative bacillus Mycobacterium leprae: the long incubation period, limited knowledge about its mode of transmission, and its poor growth on culture media. Fortunately, the leprosy bacillus is sensitive to several antibiotics. The first antibiotic to be widely used for leprosy treatment was dapsone in the 1950s, which had to be taken over several years and was associated with increasing bacterial resistance. Therefore, in 1981, WHO recommended that all registered patients with leprosy should receive combination therapy with three antibiotics: rifampicin, clofazimine, and dapsone. Global implementation of this highly effective multidrug therapy took about 15 years. In 1985, 5·3 million patients were receiving multidrug therapy; by 1991, this figure had decreased to 3·1 million (a decrease of 42%) and, by 2000, to 597 232 (a decrease of almost 90%). This reduction in the number of patients registered for treatment was due to shortening of the treatment regimen and achievement of 100% coverage with multidrug therapy. This achievement, which owed much to WHO and the donors of the multidrug therapy components, prompted WHO in 1991 to set a global target of less than one case per 10 000 population by 2000 to eliminate the disease as a public health problem. All but 15 countries achieved this target. Since 2000, about 250 000 new cases of leprosy have been detected every year. We believe an all-out campaign by a global leprosy coalition is needed to bring that figure down to zero. Copyright © 2017 Elsevier Ltd. All rights reserved.
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Degang, Yang; Akama, Takeshi; Hara, Takeshi; Tanigawa, Kazunari; Ishido, Yuko; Gidoh, Masaichi; Makino, Masahiko; Ishii, Norihisa; Suzuki, Koichi
2012-01-01
Mycobacterium leprae (M. leprae) lives and replicates within macrophages in a foamy, lipid-laden phagosome. The lipids provide essential nutrition for the mycobacteria, and M. leprae infection modulates expression of important host proteins related to lipid metabolism. Thus, M. leprae infection increases the expression of adipophilin/adipose differentiation-related protein (ADRP) and decreases hormone-sensitive lipase (HSL), facilitating the accumulation and maintenance of lipid-rich environments suitable for the intracellular survival of M. leprae. HSL levels are not detectable in skin smear specimens taken from leprosy patients, but re-appear shortly after multidrug therapy (MDT). This study examined the effect of MDT components on host lipid metabolism in vitro, and the outcome of rifampicin, dapsone and clofazimine treatment on ADRP and HSL expression in THP-1 cells. Clofazimine attenuated the mRNA and protein levels of ADRP in M. leprae-infected cells, while those of HSL were increased. Rifampicin and dapsone did not show any significant effects on ADRP and HSL expression levels. A transient increase of interferon (IFN)-β and IFN-γ mRNA was also observed in cells infected with M. leprae and treated with clofazimine. Lipid droplets accumulated by M. leprae-infection were significantly decreased 48 h after clofazimine treatment. Such effects were not evident in cells without M. leprae infection. In clinical samples, ADRP expression was decreased and HSL expression was increased after treatment. These results suggest that clofazimine modulates lipid metabolism in M. leprae-infected macrophages by modulating the expression of ADRP and HSL. It also induces IFN production in M. leprae-infected cells. The resultant decrease in lipid accumulation, increase in lipolysis, and activation of innate immunity may be some of the key actions of clofazimine.
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Duman, Hatice; Topal, Ilteris Oguz; Kocaturk, Emek; Cure, Kubra; Mansuroglu, Ilknur
2017-01-01
Acute generalized exanthematous pustulosis is a rare drug-induced eruption that is characterized by acute, nonfollicular sterile pustules on an erythematous and edematous base. The most frequently implicated drugs are beta-lactam antibiotics. Hydroxychloroquine has been widely used to treat dermatologic and rheumatologic diseases and has been reported as a rare cause of acute generalized exanthematous pustulosis. A 42-year-old female presented with pustular lesions on the skin surface with erythema, facial edema, and occasional atypical target-like lesions after 21 days of treatment with 200mg/day hydroxychloroquine for rheumatoid arthritis, diagnosed one month previously. We report a case with acute generalized exanthematous pustulosis induced by hydroxychloroquine and treated with dapsone and systemic corticosteroid.
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Methimazole-induced bullous systemic lupus erythematosus: a case report.
Seo, Ji-Yeon; Byun, Hee-Jin; Cho, Kwang-Hyun; Lee, Eun Bong
2012-07-01
Bullous systemic lupus erythematosus (SLE) is a kind of LE-non-specific bullous skin disease that is rarely induced by a medication. We describe the first case of bullous SLE to develop after administration of methimazole. A 31-yr-old woman presented with generalized erythematous patches, multiple bullae, arthralgia, fever, conjunctivitis, and hemolytic anemia. Biopsy of her bulla showed linear deposition of lgG, lgA, C3, fibrinogen, and C1q at dermo-epidermal junction. She was diagnosed as bullous SLE and treated with prednisolone, dapsone, hydroxychloroquine, and methotrexate. Our experience suggests that SLE should be considered as a differential diagnosis when bullous skin lesions develop in patients being treated for hyperthyroidism.
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Linear IgA bullous dermatosis in a neonate.
Hruza, L L; Mallory, S B; Fitzgibbons, J; Mallory, G B
1993-06-01
A newborn black boy had two facial blisters at birth that progressed to bullous lesions over the trunk, genitals, extremities, and oral and tracheal mucosa. A biopsy specimen demonstrated a subepidermal bulla with mixed eosinophilic and neutrophilic, inflammatory infiltrate. Direct immunofluorescence showed linear IgA, IgG, and C3 depositions along the basement membrane zone, consistent with a diagnosis of childhood linear IgA bullous dermatosis (chronic bullous dermatosis of childhood). The skin disease was controlled with combined prednisone and dapsone. This is the youngest reported patient with the disease. Linear IgA bullous dermatosis should be considered in the differential diagnosis of blistering diseases of the newborn, and immunofluorescence should be performed on a skin biopsy specimen.
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Methemoglobinemia in Young Patients With Hematologic Cancer or Aplastic Anemia Treated With Dapsone
2017-04-13
Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Lymphoproliferative Disorder; Methemoglobinemia; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Nonmalignant Neoplasm
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Baunach, Martin; Ding, Ling; Willing, Karsten; Hertweck, Christian
2015-11-02
Sulfa drugs, such as sulfonilamide and dapsone, are classical antibiotics that have been in clinical use worldwide. Despite the relatively simple architectures, practically no natural products are known to feature such aromatic sulfonamide or diarylsulfone substructures. We report the unexpected discovery of three fully unprecedented, sulfonyl-bridged alkaloid dimers (sulfadixiamycins A-C) from recombinant Streptomyces species harboring the entire xiamycin biosynthesis gene cluster. Sulfadixiamycins exhibit moderate antimycobacterial activities and potent antibiotic activities even against multidrug-resistant bacteria. Gene inactivation, complementation, and biotransformation experiments revealed that a flavin-dependent enzyme (XiaH) plays a key role in sulfadixiamycin biosynthesis. XiaH mediates a radical-based, three-component reaction involving two equivalents of xiamycin and sulfur dioxide, which is reminiscent of radical styrene/SO2 copolymerization. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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Pemphigus vulgaris: approach to treatment.
Sinha, Animesh A; Hoffman, Melissa B; Janicke, Elise C
2015-04-01
The therapeutic management of pemphigus vulgaris (PV) is centered around immunosuppression, which can be generalized, as in the use of corticosteroids or steroid sparing agents, or specific, as in therapeutic blockage of autoantibody production, certain cytokines, or signaling pathways. Currently, the backbone of treatment for PV, particularly, first line therapy, remains systemic corticosteroids. Although very effective, the significant side effects of long-term corticosteroid usage are well documented. Adjunctive therapies aim to eliminate, or at least decrease, the necessary dose of corticosteroids. Specifically, azathioprine, cyclophosphamide, methotrexate, cyclosporine, mycophenolate mofetil and dapsone are now widely used in PV. Intravenous immunoglobulin (IVIG), plasmapheresis, immunoadsorption, and most recently, rituximab, are other members of the therapeutic armamentarium. However, despite the widening range of treatment options in PV, well-controlled clinical trials and consensus guidelines are lacking.
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Epidermolysis Bullosa Acquisita: Autoimmunity to Anchoring Fibril Collagen
Chen, Mei; Kim, Gene H.; Prakash, Lori; Woodley, David T.
2012-01-01
Epidermolysis bullosa acquisita (EBA) is a rare and acquired autoimmune subepidermal bullous disease of the skin and mucosa. EBA includes various distinct clinical manifestations resembling Bullous Pemphigus, Brunsting-Perry pemphigoid, or cicatricial pemphigoid. These patients have autoantibodies against type VII collagen, an integral component of anchoring fibrils, which are responsible for attaching the dermis to the epidermis. Destruction or perturbation of the normally functioning anchoring fibrils clinically results in skin fragility, blisters, erosions, scars, milia and nail loss, all features reminiscent of genetic dystrophic epidermolysis bullosa. These anti-type VII collagen antibodies are “pathogenic” because when injected into a mouse, the mouse develops an EBA-like blistering disease. Currently treatment is often unsatisfactory, however some success has been achieved with colchichine, dapsone, photopheresis, plasmaphresis, infliximab, rituximab and IVIG. PMID:21955050
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Sweet's Syndrome: An Evidence-Based Report.
Bhat, Yasmeen J; Hassan, Iffat; Sajad, Peerzada; Akhtar, Saniya; Sheikh, Sheema
2015-07-01
Sweet's syndrome encompasses a variety of neutrophilic dermatosis characterized by acute onset of erythematous, edematous, painful papules, plaques and nodules associated with systemic symptoms, peripheral blood leukocytosis and histological findings of dense neutrophilic infiltrate. Ten patients were diagnosed during a period of one year. The patient population consisted of 7 females and 3 males with mean age of 47.6 years ranging from 32 to 60 years. An associated disorder was observed in 6 patients which were diabetes, hypothyroidism, hypertension and inflammatory bowel disease. Two cases of pregnancy associated disease were observed. Cutaneous lesions consisted of erythematous plaques or nodules. Lesions were located mainly on the face, neck and upper extremities. All biopsy specimens demonstrated a dermal infiltrate composed predominantly of neutrophils. Seven patients were treated by oral corticosteroids and three by oral dapsone, all for a period of 6 weeks.
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Wargo, Jeffrey J; Adams, Megan; Trevino, Julian
2017-01-30
A man aged 56 years with a history of ulcerative colitis (UC) status postsubtotal colectomy was hospitalised with fevers, dry cough, eye redness and a new bloody, mucoid rectal discharge. 2 months prior to admission, the dermatologist had started him on dapsone for subcorneal pustular dermatosis but did not recognise that he had recently self-discontinued mesalamine enemas, inducing a flare of his UC. After a thorough inpatient evaluation, including flexible sigmoidoscopy, active UC involving the rectal stump was determined to be driving his dermatological and ophthalmological findings. By reinstituting mesalamine enemas, control of his UC was achieved and the extraintestinal manifestations of his inflammatory bowel disease (IBD) resolved. This case illustrates the importance of careful history taking and of early recognition of extraintestinal manifestations of IBD in order to appropriately target treatment and prevent unnecessary morbidity. 2017 BMJ Publishing Group Ltd.
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LEPROSY NEPHROPATHY: A REVIEW OF CLINICAL AND HISTOPATHOLOGICAL FEATURES
da Silva, Geraldo Bezerra; Daher, Elizabeth De Francesco; Pires, Roberto da Justa; Pereira, Eanes Delgado Barros; Meneses, Gdayllon Cavalcante; Araújo, Sônia Maria Holanda Almeida; Barros, Elvino José Guardão
2015-01-01
Leprosy is a chronic disease caused by Mycobacterium leprae, highly incapacitating, and with systemic involvement in some cases. Renal involvement has been reported in all forms of the disease, and it is more frequent in multibacillary forms. The clinical presentation is variable and is determined by the host immunologic system reaction to the bacilli. During the course of the disease there are the so called reactional states, in which the immune system reacts against the bacilli, exacerbating the clinical manifestations. Different renal lesions have been described in leprosy, including acute and chronic glomerulonephritis, interstitial nephritis, secondary amyloidosis and pyelonephritis. The exact mechanism that leads to glomerulonephritis in leprosy is not completely understood. Leprosy treatment includes rifampicin, dapsone and clofazimine. Prednisone and non-steroidal anti-inflammatory drugs may be used to control acute immunological episodes. PMID:25651321
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Dermatitis herpetiformis: pathophysiology, clinical presentation, diagnosis and treatment*
Clarindo, Marcos Vinícius; Possebon, Adriana Tomazzoni; Soligo, Emylle Marlene; Uyeda, Hirofumi; Ruaro, Roseli Terezinha; Empinotti, Julio Cesar
2014-01-01
Researches on DH have shown that it is not just a bullous skin disease, but a cutaneous-intestinal disorder caused by hypersensitivity to gluten. Exposure to gluten is the starting point of an inflammatory cascade capable of forming autoantibodies that are brought to the skin, where they are deposited, culminating in the formation of skin lesions. These lesions are vesico-bullous, pruritic, and localized especially on elbows, knees and buttocks, although atypical presentations can occur. Immunofluorescence of perilesional area is considered the gold standard for diagnosis, but serological tests help in cases where it is negative. Patients who follow glutenfree diets have better control of symptoms on the skin and intestine, as well as lower risks of progression to lymphoma. Dapsone remains the main drug for treatment, but it requires monitoring of possible side effects, some potentially lethal. PMID:25387490
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Leprosy. An update: definition, pathogenesis, classification, diagnosis, and treatment.
Eichelmann, K; González González, S E; Salas-Alanis, J C; Ocampo-Candiani, J
2013-09-01
Leprosy is a chronic granulomatous disease caused by the bacillus Mycobacterium leprae. It primarily affects the skin and peripheral nerves and is still endemic in various regions of the world. Clinical presentation depends on the patient's immune status at the time of infection and during the course of the disease. Leprosy is associated with disability and marginalization. Diagnosis is clinical and is made when the patient has at least 1 of the following cardinal signs specified by the World Health Organization: hypopigmented or erythematous macules with sensory loss; thickened peripheral nerves; or positive acid-fast skin smear or skin biopsy with loss of adnexa at affected sites. Leprosy is treated with a multidrug combination of rifampicin, clofazimine, and dapsone. Two main regimens are used depending on whether the patient has paucibacillary or multibacillary disease. Copyright © 2011 Elsevier España, S.L. and AEDV. All rights reserved.
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A clinical trial of pefloxacin and ofloxacin in lepromatous leprosy.
Fajardo, Tranquilino T; Villahermosa, Laarni G; Cruz, Eduardo C Dela; Cellona, Roland V; Balagon, Ma Victoria F; Abalos, Rodolfo M; Gelber, Robert H
2004-12-01
A 2-month clinical trial of pefloxacin and ofloxacin in previously untreated multibacillary patients was conducted at the Leonard Wood Memorial Leprosy Research Center, Cebu, the Philippines. Treatment with either pefloxacin or ofloxacin resulted in rapid clinical improvement, in this regard pefloxacin appearing somewhat superior. Reactions and side effects were minimal. Single doses of either agent did not result in significant killing of Mycobacterium leprae, but significant bactericidal activity was observed for all fluoroquinolone-treated patients by one week of daily therapy (n = 21), and either agent independently by 3 weeks of daily therapy. At the completion of therapy only two of 10 pefloxacin-treated patients and 0 of 11 ofloxacin-treated patients harboured any detectable viable M. leprae from active lesions, confirming previous work that these fluoroquinolones exhibit bactericidal activity in leprosy patients and more than that found previously for dapsone and clofazimine.
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Chronic inflammatory joint disease revealing borderline leprosy.
Miladi, Mohamed Imed; Feki, Imed; Bahloul, Zouhir; Jlidi, Rachid; Mhiri, Chokri
2006-05-01
Musculoskeletal symptoms are not infrequent in leprosy and, when inaugural, may be difficult to differentiate from other conditions, most notably rheumatoid arthritis. We report the case of a 24 year-old man with a 5 year history of intermittent inflammatory arthritis and fever. Physical findings and radiographs were normal initially. Several years later, he had severe wasting of the hand muscles, stocking-glove sensory loss, burn scars on the hands, and plantar ulcers. Electrophysiological test results indicated sensory-motor neuropathy with predominant demyelination. Laboratory tests showed inflammation without immunological abnormalities. A prominent endoneurial inflammatory infiltrate composed of mononuclear cells was seen on a nerve biopsy specimen, suggesting leprosy. A family study then revealed that the patient's aunt had been diagnosed with leprosy. Dapsone, clofazimine, and rifampin were given. The joint manifestations and laboratory tests for inflammation improved. However, no changes were noted in the neurological symptoms.
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Early lesion of palisaded neutrophilic granulomatous dermatitis in ulcerative colitis.
Asahina, Akihiko; Fujita, Hideki; Fukunaga, Yuki; Kenmochi, Yasuko; Ikenaka, Tatsuo; Mitomi, Hiroyuki
2007-01-01
Palisaded neutrophilic granulomatous dermatitis (PNGD) is a rare clinical entity of unknown cause. It often coexists with various autoimmune or immunoreactive systemic diseases, and thus it has been reported under multiple names. We describe a patient with quiescent ulcerative colitis, who presented with recurrent small tender papules, nodules and erythematous plaques, located mainly on her hands, together with finger swelling and polyarthralgia. The histopathologic picture indicated an early stage of PNGD with focal degeneration of collagen fibers but without distinct granuloma formation. The differentiation from neutrophilic dermatoses was necessary because of dense and diffuse infiltration of neutrophils with leukocytoclastic debris throughout the dermis, and the association of ulcerative colitis. Dapsone monotherapy was effective in improving the clinical symptoms. PNGD is only rarely associated with ulcerative colitis, and this case suggests that the concept of PNGD, especially in its early stages, might be considered in the wide spectrum of neutrophilic dermatoses.
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Vargas, Thiago Jeunon de Sousa; Fialho, Mônica; Santos, Luiza Tavares dos; Rodrigues, Palmira Assis de Jesus Barreto; Vargas, Ana Luisa Bittencourt Sampaio Jeunon; Sousa, Maria Auxiliadora Jeunon
2013-01-01
Linear IgA dermatosis has been increasingly associated with inflammatory bowel diseases, particularly ulcerative colitis. A 13-year-old male patient with an 11-month history of ulcerative colitis developed vesicles, pustules and erosions on the skin of the face, trunk and buttocks and in the oral mucosa. The work-up revealed a neutrophil-rich sub-epidermal bullous disease and linear deposition of IgA along the dermoepidermal junction, establishing the diagnosis of linear IgA dermatosis. The patient experienced unsatisfactory partial control of skin and intestinal symptoms despite the use of adalimumab, mesalazine, prednisone and dapsone for some months. After total colectomy, he presented complete remission of skin lesions, with no need of medications during two years of follow-up. A review of previously reported cases of the association is provided here and the role of ulcerative colitis in triggering linear IgA dermatosis is discussed.
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Pyoderma gangrenosum and ulcerative colitis in the tropics.
Alese, Olatunji B; Irabor, David O
2008-01-01
Pyoderma gangrenosum is a rare inflammatory skin condition, characterized by progressive and recurrent skin ulceration. There may be rapidly enlarging, painful ulcers with undermined edges and a necrotic, hemorrhagic base. Disorders classically associated with pyoderma gangrenosum include rheumatoid arthritis, inflammatory bowel disease, paraproteinemia and myeloproliferative disorders. There have been some reports of the occurrence of pyoderma gangrenosum in Africa, and in Nigeria, but only one specifically reported pyoderma gangrenosum in association with ulcerative colitis. We report on a 45-year-old man who presented with pyoderma gangrenosum associated with ulcerative colitis; the second report in Nigeria. The skin lesions were managed with daily honey wound dressings. Oral dapsone and prednisolone were started. The frequency of the bloody diarrhea decreased, and was completely resolved by the second week after admission. The ulcers also showed accelerated healing. The goal of therapy is directed towards the associated systemic disorder, if present.
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Hashimoto, Takashi; Tsuruta, Daisuke; Yasukochi, Atsushi; Imanishi, Hisayoshi; Sekine, Hideharu; Fujita, Teizo; Wanibuchi, Hideki; Gi, Min; Kárpáti, Sarolta; Sitaru, Cassian; Zone, John J; Endo, Daisuke; Abe, Shinichi; Nishino, Tomoya; Koji, Takehiko; Ishii, Norito
2016-08-23
There has been no previous systematic study of bullous skin diseases with granular basement membrane zone deposition exclusively of C3. In this study we collected 20 such patients, none of whom showed cutaneous vasculitis histopathologically. Oral dapsone and topical steroids were effective. Various serological tests detected no autoantibodies or autoantigens. Direct immunofluorescence for various complement components revealed deposition only of C3 and C5-C9, indicating that no known complement pathways were involved. Studies of in situ hybridization and micro-dissection with quantitative RT-PCR revealed a slight reduction in expression of C3 in patient epidermis. These patients may represent a new disease entity, for which we propose the term "granular C3 dermatosis". The mechanism for granular C3 deposition in these patients is unknown, but it is possible that the condition is caused by autoantibodies to skin or aberrant C3 expression in epidermal keratinocytes.
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Chemotherapeutic approaches to protozoa: haemosporina--current level of knowledge and outlook.
Harder, A; Greif, G; Haberkorn, A
2001-09-01
Chloroquine and mefloquine are available for prophylactic treatment in malaria, against a background of the burgeoning problem of resistance developing to chloroquine and related drugs (Mehlhorn and Schrevel 1995). For this reason, highly specific national recommendations are given out regarding prophylaxis. The option of a viable vaccine is currently not available. More new compounds are therefore urgently required, since 2-5 million of the 200 300 million infected people die each year. At the moment, atovaquone and artemisinin derivatives are of great interest, as are drug combinations such as atovaquone/proguanil (since 1997), artemether/ benflumetol (since 1998?; Ciba-Geigy, patent WO9202217) and chlorproguanil/dapsone (since 2000?), as these compounds are also effective against multi-resistant strains of Plasmodium falciparum (Tables 1, 2; Croft 1997; Wang 1997). Pyronaridin (since 2000?) has been discovered in a Chinese academy and is in clinical trials (Trouiller and Olliaro 1998; Pecoul et al. 1999).
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Biomimetic Solid Lipid Nanoparticles of Sophorolipids Designed for Antileprosy Drugs.
Kanwar, Rohini; Gradzielski, Michael; Mehta, S K
2018-06-22
The objective of the present work was to develop solid lipid nanoparticles (SLNs) as drug-encapsulating structures by the solvent injection method. In this report, for the first time the inherent potential of lactonic sophorolipid (glycolipid) was exploited to formulate SLNs. A range of different Pluronic copolymers were screened by dynamic and static light scattering with the aim of obtaining most stable SLNs. To comprehend the structure of the SLNs, techniques such as transmission electron microscopy, differential scanning calorimetry, Fourier transform infrared spectroscopy, and X-ray diffraction were employed. A clear correlation between the type of Pluronic and size and stability of the SLNs could be drawn. The vector properties of the formed SLNs were assessed for both the encapsulated hydrophobic drugs-rifampicin and dapsone. To elucidate the transport mechanism of drug release, kinetic modeling was carried out on the drug release profiles. The promising results of sophorolipid-based SLNs have actually established a new arena beneath the significantly developed field of SLNs.
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Elusive treatment for human rhinosporidiosis.
Janardhanan, Jeshina; Patole, Shalom; Varghese, Lalee; Rupa, V; Tirkey, Amit Jiwan; Varghese, George M
2016-07-01
The aim of this study was to clarify the contentious taxonomic classification of Rhinosporidium seeberi, the cause of human rhinosporidiosis, which may have treatment implications. PCR was used to amplify the internal transcribed spacer (ITS)-2 region from the genomic DNA of the aetiological agent obtained from a sample of human rhinosporidiosis lesions. The amplicon was sequenced and the organism identified using the Basic Local Alignment Search Tools (BLAST). Phylogenetic analysis revealed that the aetiological agent clustered along with the R. seeberi isolated from humans and also with Amphibiocystidium ranae from frogs. This organism is a member of the order Dermocystida in the class Mesomycetozoea. A patient with disseminated rhinosporidiosis did not respond to conventional therapy with dapsone and surgical excision, and treatment with amphotericin B also proved futile. An effective treatment for R. seeberi-a eukaryote belonging to the class Mesomycetozoea-is still elusive. Copyright © 2016. Published by Elsevier Ltd.
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Acute hemorrhagic edema of infancy: a troubling cutaneous presentation with a self-limiting course.
Savino, Francesco; Lupica, Maria M; Tarasco, Valentina; Locatelli, Emanuela; Viola, Serena; di Montezemolo, Luca C; Coppo, Paola
2013-01-01
Acute hemorrhagic edema of infancy (AHEI) is an unusual form of leukocytoclastic vasculitis with dramatic distinguishing skin lesions that occurs in infants ages 4 to 24 months old. The disease presents with skin eruptions that usually start with large (1-5 cm), symmetrically distributed, hemorrhagic lesions in a characteristic cockade pattern. The lesions are typically located on the lower extremities, face (in particular the ears, cheeks, and eyelids), and gluteal area. Fever may accompany skin eruptions. Clinical presentation at onset requires clinical and laboratory examination to distinguish it from more serious diseases and other vasculitis. The main differential diagnosis of AHEI is Henoch-Schönlein purpura. AHEI is generally a self-limiting disease, so a conservative approach should be considered. Topical or systemic corticosteroid therapy has been reported to be beneficial, as well as antihistamines and dapsone, although AHEI usually resolves completely with or without treatment. We report two cases of AHEI and an update of the literature. © 2012 Wiley Periodicals, Inc.
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Updosing of Nonsedating Anti-histamines in Recalcitrant Chronic Urticaria
Godse, Kiran; Bhattar, Prachi; Patil, Sharmila; Nadkarni, Nitin; Gautam, Manjyot
2016-01-01
Chronic urticaria (CU) is a persistent, debiliating condition that causes severe impairment on the quality of life (QoL) of patient by interrupting work productivity. Current guidelines recommend second-generation (nonsedating) anti-histamines for the treatment for all forms of urticaria. In patients who do not respond adequately to conventional doses of anti-histamines, it is recommended to increase the dose to up to four times to obtain control. But there are only few controlled studies that have assessed the efficacy and safety of nonsedating anti-histamines. Though sedating histamines are frequently used as an add-on therapy in severe cases, they have a negative impact on QoL by compromising sleep and performance. The use of other suggested therapeutic options (omalizumab, cyclosporine A, montelukast and dapsone) is also limited by paucity of data on their efficacy and adverse effect profile. Second-generation anti-histamines which are relatively safer require more proven data to support their judicious use to improve disease in patients with CU. PMID:27293247
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Crystal structure of bis[bis(4-azaniumylphenyl) sulfone] tetranitrate monohydrate
Benahsene, Amani Hind; Bendjeddou, Lamia; Merazig, Hocine
2017-01-01
In the title compound, the hydrated tetra(nitrate) salt of dapsone (4,4′-diaminodiphenylsulfone), 2C12H14N2O2S2+·4NO3 −·H2O {alternative name: bis[bis(4,4′-diazaniumylphenyl) sulfone] tetranitrate monohydrate}, the cations are conformationally similar, with comparable dihedral angles between the two benzene rings in each of 70.03 (18) and 69.69 (19)°. In the crystal, mixed cation–anion–water molecule layers lying parallel to the (001) plane are formed through N—H⋯O, O—H⋯O and C—H⋯O hydrogen-bonding interactions and these layers are further extended into an overall three-dimensional supramolecular network structure. Inter-ring π–π interactions are also present [minimum ring centroid separation = 3.693 (3) Å]. PMID:29152359
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Bullous lichen planus - a review.
Liakopoulou, Angeliki; Rallis, Efstathios
2017-03-31
Bullous lichen planus is a rare variant of lichen planus. It is characterized by vesicles or bullae, which usually develop in the context of pre-existing LP lesions. It is often misdiagnosed and should be differentiated from other subepidermal bullous diseases especially lichen planus pemphigoides. The diagnosis is based on clinical suspicion and is confirmed by histopathology and immunofluoresence. The clinical features of bullous lichen planus include typical lichen planus lesions, accompanied by the formation of bullae on the affected or perilesional skin. This is evident on histology, with alteration of the dermo-epidermal junction and intrabasal bullae as a consequence of extensive inflammation. The histologic features in conjunction with the negative immunofluoresence indicate that bullous lichen planus is a form of "hyper-reactive lichen planus" rather than a distinct entity. There is no standard treatment of bullous lichen planus. Topical and systemic corticosteroids, dapsone and acitretin have been described as effective choices.
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Epidermolysis Bullosa Acquitsita
Gupta, Rishu; Woodley, David T.; Chen, Mei
2011-01-01
EBA is a rare, acquired, chronic subepidermal bullous disease of the skin and mucosa characterized by autoantibodies to type VII collagen structures, a major component of anchoring fibrils, that attach the epidermis onto the dermis. EBA patients have tissue-bound as well as circulating anti-type VII collagen autoantibodies that attack type VII collagen and result in a reduction or perturbation of normally functioning anchoring fibrils. Patients with EBA have skin fragility, blisters, erosions, scars, milia, and nail loss: all features reminiscent of genetic dystrophic epidermolysis bullosa. These anti-type VII collagen antibodies are “pathogenic” because when injected into mice, the mice develop an EBA-like blistering disease. In addition to the classical mechanobullous presentation, EBA also has several other distinct clinical syndromes similar to bullous pemphigoid, Brunsting-Perry pemphigoid, or cicatricial pemphigoid. Although treatment for EBA is often unsatisfactory, some therapeutic success has been achieved with colchicine, dapsone, plasmaphoresis, photopheresis, infliximab, and intravenous immunoglobulin. PMID:22137228
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Pyoderma gangrenosum in a patient with chronic granulomatous disease: A case report.
Nanoudis, Sideris; Tsona, Afroditi; Tsachouridou, Olga; Morfesis, Petros; Loli, Georgia; Georgiou, Adamantini; Zebekakis, Pantelis; Metallidis, Symeon
2017-08-01
The simultaneous occurrence of pyoderma gangrenosum (PG) and chronic granulomatous disease (CGD) is uncommon and few cases have been reported worldwide. PG is a rare, chronic, ulcerative, neutrophilic skin disease of unknown etiology that requires immunosuppressive treatment. CGD belongs to Primary Immune Deficiencies in which the main defect lies in an inability of the phagocytic cells to generate superoxide making patients susceptible to serious, potentially life-threatening bacterial and fungal infections. In this manuscript, we present a case of ulcerative pyoderma gangrenosum in a 28-year-old man with recent diagnosis of chronic granulomatous disease during hospitalization for resistant pulmonary tuberculosis complicated with Aspergillus infection. Second-line therapy with dapsone and intravenous immunoglobulin was initially administered but eventually corticosteroids were added to treatment because of disease progression and further ulceration. Patient's ulcers were gradually healed with no side effects. Corticosteroids could be used under close monitoring for the treatment of PG in a patient with CGD, despite the increased risk for infections.
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The use of oral antibiotics in treating acne vulgaris: a new approach.
Farrah, Georgia; Tan, Ernest
2016-09-01
Although acne is not an infectious disease, oral antibiotics have remained a mainstay of treatment over the last 40 years. The anti-inflammatory properties of oral antibiotics, particularly the tetracyclines, are efficacious in treating inflammatory acne lesions. Common prescribing practices in Dermatology exert significant selection pressure on bacteria, contributing to the development of antibiotic resistance. Antibiotic use for acne not only promotes resistance in Propionibacterium acnes, but also affects other host bacteria with pathogenic potential. This review will summarize the commonly used treatments for acne vulgaris, and how they should be combined as rational treatment. The indications for using oral antibiotics in acne will be highlighted. Strategies described in the literature to conserve the utility of oral antibiotics will be summarized. These include limiting the duration of antibiotic therapy, concomitant use of a topical non-antibiotic agent, use of subantimicrobial dose doxycycline, and the introduction of topical dapsone. © 2016 Wiley Periodicals, Inc.
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Familial transmission of leprosy in post-war Britain--discrimination and dissent.
Gill, A L; Gill, G V; Beeching, N J
2008-05-01
A Polish immigrant, who was resident in the United Kingdom (UK), presented with lepromatous leprosy and was detained in two hospitals against his wishes in the late 1940s. The public reaction to his diagnosis was remarkable, with street riots and questions in the Houses of Parliament about 'this leper'. His wife was persecuted and had to change her name. The index patient died of tuberculosis during enforced isolation in hospital, and several years later his daughter (who had never left the UK) presented with a left median nerve palsy and probable lepromatous dactylitis of the left third finger, eventually requiring amputation and prolonged dapsone treatment. Her disease resolved slowly but completely. We believe these two familial cases represent the first documented episode of autochthonous leprosy transmission in the UK since the early 1920s. They also demonstrate the ability of this disease to engender fear, dissent and discrimination amongst the public. Parallels are drawn with reactions to the cholera epidemics in nineteenth century Britain, and to HIV/AIDS, SARS and multi-drug resistant tuberculosis in more recent times.
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Clinical Relevance of Autoantibodies in Patients with Autoimmune Bullous Dermatosis
Mihályi, Lilla; Kiss, Mária; Dobozy, Attila; Kemény, Lajos; Husz, Sándor
2012-01-01
The authors present their experience related to the diagnosis, treatment, and followup of 431 patients with bullous pemphigoid, 14 patients with juvenile bullous pemphigoid, and 273 patients with pemphigus. The detection of autoantibodies plays an outstanding role in the diagnosis and differential diagnosis. Paraneoplastic pemphigoid is suggested to be a distinct entity from the group of bullous pemphigoid in view of the linear C3 deposits along the basement membrane of the perilesional skin and the “ladder” configuration of autoantibodies demonstrated by western blot analysis. It is proposed that IgA pemphigoid should be differentiated from the linear IgA dermatoses. Immunosuppressive therapy is recommended in which the maintenance dose of corticosteroid is administered every second day, thereby reducing the side effects of the corticosteroids. Following the detection of IgA antibodies (IgA pemphigoid, linear IgA bullous dermatosis, and IgA pemphigus), diamino diphenyl sulfone (dapsone) therapy is preferred alone or in combination. The clinical relevance of autoantibodies in patients with autoimmune bullous dermatosis is stressed. PMID:23320017
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A Case of Pemphigus Herpetiformis in a 12-Year-Old Male
Hocar, O.; Ait Sab, I.; Akhdari, N.; Hakkou, M.; Amal, S.
2011-01-01
Pemphigus herpetiformis (PH) is one of the less common forms of pemphigus. PH in children is unreported. We describe a case of a child who developed PH. Observation. A 12-year-old boy was seen at our department with erosive plaques, vesicles, and crusted cutaneous lesions associated with severe itching persisting for six months. Histologic examination showed an intraepidermal bulla containing rare acantholytic epidermal cells with eosinophilic spongiosis. Direct immunofluorescence demonstrated intercellular Ig G and C3 deposit. The serum titer of antibodies against intercellular epidermal was 1/200 UI/l. Diagnosis of PH was made, and treatment with Dapsone 2 mg/kg per day resulted in total clinical remission. However, two months later, new vesicles reappeared and treatment was begun with prednisone at a dose of 2 mg/kg daily. There was a very good response. Discussion. Childhood pemphigus herpetiformis is a rare disease, often initially misdiagnosed. It must not be forgotten that the disease is a possible cause of erosive mucocutaneous disease in children. PMID:22389786
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Pyoderma gangrenosum in a patient with chronic granulomatous disease
Nanoudis, Sideris; Tsona, Afroditi; Tsachouridou, Olga; Morfesis, Petros; Loli, Georgia; Georgiou, Adamantini; Zebekakis, Pantelis; Metallidis, Symeon
2017-01-01
Abstract Rationale: The simultaneous occurrence of pyoderma gangrenosum (PG) and chronic granulomatous disease (CGD) is uncommon and few cases have been reported worldwide. Patient concerns: PG is a rare, chronic, ulcerative, neutrophilic skin disease of unknown etiology that requires immunosuppressive treatment. CGD belongs to Primary Immune Deficiencies in which the main defect lies in an inability of the phagocytic cells to generate superoxide making patients susceptible to serious, potentially life-threatening bacterial and fungal infections. Diagnoses: In this manuscript, we present a case of ulcerative pyoderma gangrenosum in a 28-year-old man with recent diagnosis of chronic granulomatous disease during hospitalization for resistant pulmonary tuberculosis complicated with Aspergillus infection. Interventions: Second-line therapy with dapsone and intravenous immunoglobulin was initially administered but eventually corticosteroids were added to treatment because of disease progression and further ulceration. Outcomes: Patient's ulcers were gradually healed with no side effects. Lessons: Corticosteroids could be used under close monitoring for the treatment of PG in a patient with CGD, despite the increased risk for infections. PMID:28767612
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Primaquine-induced haemolysis in females heterozygous for G6PD deficiency.
Chu, Cindy S; Bancone, Germana; Nosten, François; White, Nicholas J; Luzzatto, Lucio
2018-03-02
Oxidative agents can cause acute haemolytic anaemia in persons with G6PD deficiency. Understanding the relationship between G6PD genotype and the phenotypic expression of the enzyme deficiency is necessary so that severe haemolysis can be avoided. The patterns of oxidative haemolysis have been well described in G6PD deficient hemizygous males and homozygous females; and haemolysis in the proportionally more numerous heterozygous females has been documented mainly following consumption of fava beans and more recently dapsone. It has long been known that 8-aminoquinolines, notably primaquine and tafenoquine, cause acute haemolysis in G6PD deficiency. To support wider use of primaquine in Plasmodium vivax elimination, more data are needed on the haemolytic consequences of 8-aminoquinolines in G6PD heterozygous females. Two recent studies (in 2017) have provided precisely such data; and the need has emerged for the development of point of care quantitative testing of G6PD activity. Another priority is exploring alternative 8-aminoquinoline dosing regimens that are practical and improve safety in G6PD deficient individuals.
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Rochford, Rosemary; Ohrt, Colin; Baresel, Paul C; Campo, Brice; Sampath, Aruna; Magill, Alan J; Tekwani, Babu L; Walker, Larry A
2013-10-22
Individuals with glucose 6-phosphate dehydrogenase (G6PD) deficiency are at risk for the development of hemolytic anemia when given 8-aminoquinolines (8-AQs), an important class of antimalarial/antiinfective therapeutics. However, there is no suitable animal model that can predict the clinical hemolytic potential of drugs. We developed and validated a human (hu)RBC-SCID mouse model by giving nonobese diabetic/SCID mice daily transfusions of huRBCs from G6PD-deficient donors. Treatment of SCID mice engrafted with G6PD-deficient huRBCs with primaquine, an 8-AQ, resulted in a dose-dependent selective loss of huRBCs. To validate the specificity of this model, we tested known nonhemolytic antimalarial drugs: mefloquine, chloroquine, doxycycline, and pyrimethamine. No significant loss of G6PD-deficient huRBCs was observed. Treatment with drugs known to cause hemolytic toxicity (pamaquine, sitamaquine, tafenoquine, and dapsone) resulted in loss of G6PD-deficient huRBCs comparable to primaquine. This mouse model provides an important tool to test drugs for their potential to cause hemolytic toxicity in G6PD-deficient populations.
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Hepatotoxicity due to red bush tea consumption: a case report.
Reddy, Shamantha; Mishra, Pragnyadipta; Qureshi, Sana; Nair, Singh; Straker, Tracey
2016-12-01
Many conventional drugs used today, including isoniazid, dapsone, and acetaminophen, are well recognized culprits of hepatotoxicity. With increasing use of complementary and alternative medical therapies, several herbal medicines, such as Ma-Huang, kava, and chaparral leaf, have been implicated as hepatotoxins. Hepatotoxicity may be the most frequent adverse reaction to these herbal remedies when taken in excessive quantities. A myriad of liver dysfunctions may occur including transient liver enzyme abnormalities due to acute and chronic hepatitis. These herbal products are often overlooked as the causal etiologic agent during the evaluation of a patient with elevated liver function tests. We describe a case of hepatotoxicity due to ingestion of red bush tea diagnosed during preoperative assessment of a patient scheduled for laparoscopic appendectomy. Elevated liver enzymes and thrombocytopenia detected in the patient's laboratory work up confounded the initial diagnosis of acute appendicitis and additional investigations were required to rule out cholecystitis and other causes of hepatitis. Open appendectomy was done uneventfully under spinal anesthesia without any further deterioration of hepatic function. Copyright © 2016. Published by Elsevier Inc.
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[Eosinophilic pustular folliculitis in infancy: an unusual case].
Boudaya, S; Turki, H; Bouassida, S; Khemakhem, M; Marrakchi, S; Zahaf, A
2003-04-01
Eosinophilic pustular folliculitis in children is a follicular inflammatory dermatosis, usually occurring early in life. The disease progresses in flares of prurigenous plaques studded with papules and sterile pustules of the scalp and other areas of the skin. A 7 year-old boy presented with itching papular vesicular and pustular plaques on the scalp and the face. Pigmented plaques with pustular border, located on the trunk, were associated with pustular and erosive lesions of the side of the lower lip and in the nostrils. A specimen taken from the pustules did not show bacterial or fungal infection. Histologic examination of a biopsy specimen showed subcorneal pustules with eosinophilic and neutrophilic infiltrates of follicles. Clinical improvement was obtained only by the combination of steroids and dapsone, but recurrence followed withdrawal of treatment. Eosinophilic pustular folliculitis in children is rare. Our case report combines features of the infancy form (lesions located on the scalp and face) and the adult form (location on the trunk and limbs with annular distribution), expressing the conceptual confusion that remains between both forms. The mucosal involvement seen in our patient has never been reported in the literature neither in the infancy nor in the adult form.
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Rochford, Rosemary; Ohrt, Colin; Baresel, Paul C.; Campo, Brice; Sampath, Aruna; Magill, Alan J.; Tekwani, Babu L.; Walker, Larry A.
2013-01-01
Individuals with glucose 6-phosphate dehydrogenase (G6PD) deficiency are at risk for the development of hemolytic anemia when given 8-aminoquinolines (8-AQs), an important class of antimalarial/antiinfective therapeutics. However, there is no suitable animal model that can predict the clinical hemolytic potential of drugs. We developed and validated a human (hu)RBC-SCID mouse model by giving nonobese diabetic/SCID mice daily transfusions of huRBCs from G6PD-deficient donors. Treatment of SCID mice engrafted with G6PD-deficient huRBCs with primaquine, an 8-AQ, resulted in a dose-dependent selective loss of huRBCs. To validate the specificity of this model, we tested known nonhemolytic antimalarial drugs: mefloquine, chloroquine, doxycycline, and pyrimethamine. No significant loss of G6PD-deficient huRBCs was observed. Treatment with drugs known to cause hemolytic toxicity (pamaquine, sitamaquine, tafenoquine, and dapsone) resulted in loss of G6PD-deficient huRBCs comparable to primaquine. This mouse model provides an important tool to test drugs for their potential to cause hemolytic toxicity in G6PD-deficient populations. PMID:24101478
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2011-01-01
Background Glucose-6-phosphate dehydrogenase (G6PD) deficiency is common in populations living in malaria endemic areas. G6PD genotype and phenotype were determined for malaria patients enrolled in the chlorproguanil-dapsone-artesunate (CDA) phase III clinical trial programme. Methods Study participants, aged > 1 year, with microscopically confirmed uncomplicated Plasmodium falciparum malaria, and haemoglobin ≥ 70 g/L or haematocrit ≥ 25%, were recruited into two clinical trials conducted in six African countries (Burkina Faso, Ghana, Kenya, Nigeria, Tanzania, Mali). G6PD genotype of the three most common African forms, G6PD*B, G6PD*A (A376G), and G6PD*A- (G202A, A542T, G680T and T968C), were determined and used for frequency estimation. G6PD phenotype was assessed qualitatively using the NADPH fluorescence test. Exploratory analyses investigated the effect of G6PD status on baseline haemoglobin concentration, temperature, asexual parasitaemia and anti-malarial efficacy after treatment with CDA 2/2.5/4 mg/kg or chlorproguanil-dapsone 2/2.5 mg/kg (both given once daily for three days) or six-dose artemether-lumefantrine. Results Of 2264 malaria patients enrolled, 2045 had G6PD genotype available and comprised the primary analysis population (1018 males, 1027 females). G6PD deficiency prevalence was 9.0% (184/2045; 7.2% [N = 147] male hemizygous plus 1.8% [N = 37] female homozygous), 13.3% (273/2045) of patients were heterozygous females, 77.7% (1588/2045) were G6PD normal. All deficient G6PD*A- genotypes were A376G/G202A. G6PD phenotype was available for 64.5% (1319/2045) of patients: 10.2% (134/1319) were G6PD deficient, 9.6% (127/1319) intermediate, and 80.2% (1058/1319) normal. Phenotype test specificity in detecting hemizygous males was 70.7% (70/99) and 48.0% (12/25) for homozygous females. Logistic regression found no significant effect of G6PD genotype on adjusted mean baseline haemoglobin (p = 0.154), adjusted mean baseline temperature (p = 0.9617), or
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Carter, Nick; Pamba, Allan; Duparc, Stephan; Waitumbi, John N
2011-08-17
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is common in populations living in malaria endemic areas. G6PD genotype and phenotype were determined for malaria patients enrolled in the chlorproguanil-dapsone-artesunate (CDA) phase III clinical trial programme. Study participants, aged > 1 year, with microscopically confirmed uncomplicated Plasmodium falciparum malaria, and haemoglobin ≥ 70 g/L or haematocrit ≥ 25%, were recruited into two clinical trials conducted in six African countries (Burkina Faso, Ghana, Kenya, Nigeria, Tanzania, Mali). G6PD genotype of the three most common African forms, G6PD*B, G6PD*A (A376G), and G6PD*A- (G202A, A542T, G680T and T968C), were determined and used for frequency estimation. G6PD phenotype was assessed qualitatively using the NADPH fluorescence test. Exploratory analyses investigated the effect of G6PD status on baseline haemoglobin concentration, temperature, asexual parasitaemia and anti-malarial efficacy after treatment with CDA 2/2.5/4 mg/kg or chlorproguanil-dapsone 2/2.5 mg/kg (both given once daily for three days) or six-dose artemether-lumefantrine. Of 2264 malaria patients enrolled, 2045 had G6PD genotype available and comprised the primary analysis population (1018 males, 1027 females). G6PD deficiency prevalence was 9.0% (184/2045; 7.2% [N = 147] male hemizygous plus 1.8% [N = 37] female homozygous), 13.3% (273/2045) of patients were heterozygous females, 77.7% (1588/2045) were G6PD normal. All deficient G6PD*A- genotypes were A376G/G202A. G6PD phenotype was available for 64.5% (1319/2045) of patients: 10.2% (134/1319) were G6PD deficient, 9.6% (127/1319) intermediate, and 80.2% (1058/1319) normal. Phenotype test specificity in detecting hemizygous males was 70.7% (70/99) and 48.0% (12/25) for homozygous females. Logistic regression found no significant effect of G6PD genotype on adjusted mean baseline haemoglobin (p = 0.154), adjusted mean baseline temperature (p = 0.9617), or adjusted log mean baseline
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Phillips-Howard, P. A.; Bjorkman, A. B.
1990-01-01
Serious adverse reactions during malaria chemoprophylaxis are reviewed. Three drugs considered to have caused serious reactions in recent years are pyrimethamine/sulfadoxine (Fansidar), pyrimethamine/dapsone (Maloprim) and amodiaquine. These reactions are principally independent of dose and cannot be determined during screening for optimal doses. However, host factors may precipitate dose-dependent reactions, some of which could be avoided with improvements in drug licensing. Since serious and life-threatening reactions are relatively rare (between 1:1000 and 1:20,000), Phase I to III trials cannot identify them. Reliance must therefore be placed on Phase IV post-marketing studies, including ongoing reviews of national registers, and specially tailored studies to identify the risk using prescription-event monitoring in high-risk populations. Occasionally, medical-record linkage, case-control and cohort studies may provide supportive data. Although large numbers of travellers must, of necessity, be exposed to a drug before relatively rare reactions are identified, the ascertainment of risk using post-marketing surveillance was prevented by the following five deficiencies: lack of awareness of early alerts, inadequate use of national registers, poor attention to epidemiological and statistical rigour, inadequate verification of denominators, and inadequacy of data records. Recommendations are given for minimizing such errors in the future. PMID:2208562
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Pang, Hui; Li, Guilian; Zhao, Xiuqin; Liu, Haican; Wan, Kanglin; Yu, Ping
2015-01-01
Several species of rapidly growing mycobacteria (RGM) are now recognized as human pathogens. However, limited data on effective drug treatments against these organisms exists. Here, we describe the species distribution and drug susceptibility profiles of RGM clinical isolates collected from four southern Chinese provinces from January 2005 to December 2012. Clinical isolates (73) were subjected to in vitro testing with 31 antimicrobial agents using the cation-adjusted Mueller-Hinton broth microdilution method. The isolates included 55 M. abscessus, 11 M. fortuitum, 3 M. chelonae, 2 M. neoaurum, and 2 M. septicum isolates. M. abscessus (75.34%) and M. fortuitum (15.07%), the most common species, exhibited greater antibiotic resistance than the other three species. The isolates had low resistance to amikacin, linezolid, and tigecycline, and high resistance to first-line antituberculous agents, amoxicillin-clavulanic acid, rifapentine, dapsone, thioacetazone, and pasiniazid. M. abscessus and M. fortuitum were highly resistant to ofloxacin and rifabutin, respectively. The isolates showed moderate resistance to the other antimicrobial agents. Our results suggest that tigecycline, linezolid, clofazimine, and cefmetazole are appropriate choices for M. abscessus infections. Capreomycin, sulfamethoxazole, tigecycline, clofazimine, and cefmetazole are potentially good choices for M. fortuitum infections. Our drug susceptibility data should be useful to clinicians.
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Pang, Hui; Li, Guilian; Zhao, Xiuqin; Liu, Haican; Wan, Kanglin; Yu, Ping
2015-01-01
Objectives. Several species of rapidly growing mycobacteria (RGM) are now recognized as human pathogens. However, limited data on effective drug treatments against these organisms exists. Here, we describe the species distribution and drug susceptibility profiles of RGM clinical isolates collected from four southern Chinese provinces from January 2005 to December 2012. Methods. Clinical isolates (73) were subjected to in vitro testing with 31 antimicrobial agents using the cation-adjusted Mueller-Hinton broth microdilution method. The isolates included 55 M. abscessus, 11 M. fortuitum, 3 M. chelonae, 2 M. neoaurum, and 2 M. septicum isolates. Results. M. abscessus (75.34%) and M. fortuitum (15.07%), the most common species, exhibited greater antibiotic resistance than the other three species. The isolates had low resistance to amikacin, linezolid, and tigecycline, and high resistance to first-line antituberculous agents, amoxicillin-clavulanic acid, rifapentine, dapsone, thioacetazone, and pasiniazid. M. abscessus and M. fortuitum were highly resistant to ofloxacin and rifabutin, respectively. The isolates showed moderate resistance to the other antimicrobial agents. Conclusions. Our results suggest that tigecycline, linezolid, clofazimine, and cefmetazole are appropriate choices for M. abscessus infections. Capreomycin, sulfamethoxazole, tigecycline, clofazimine, and cefmetazole are potentially good choices for M. fortuitum infections. Our drug susceptibility data should be useful to clinicians. PMID:26351633
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Drug reaction with eosinophilia and systemic symptoms without skin rash
Sasidharanpillai, Sarita; Binitha, Manikoth P.; Manikath, Neeraj; Janardhanan, Anisha K.
2015-01-01
Drug reaction with eosinophilia and systemic symptoms (DRESS) or drug hypersensitivity syndrome is considered as a severe cutaneous adverse drug reaction which is most commonly precipitated by aromatic anticonvulsants, lamotrigine, dapsone, allopurinol, minocycline, and salazopyrin. Its clinical manifestations are often variable. On rare occasions, it can present with only systemic involvement without any cutaneous features. A complete drug history is of paramount importance in making an early diagnosis. We report the case of a male patient who presented with fever, lymphadenopathy, hepatosplenomegaly, and hepatitis, 2 weeks after starting salazopyrin. The presence of atypical lymphocytes in the peripheral smear was indicative of a viral infection or a hematological dyscrasia. Bone marrow examination revealed a normocellular marrow with an increase in eosinophil precursors. Investigations for the common causes for fever and hepatitis were negative. The presence of eosinophilia, the temporal relationship of the symptoms with the initiation of treatment with salazopyrin, and the marked improvement on withdrawal of the drug along with the administration of systemic corticosteroids, were features consistent with the diagnosis of DRESS. With the incidence of this condition showing a rising trend, it is important for the clinician to be aware of its variable manifestations, as a delay in diagnosis and treatment can be fatal. PMID:26729967
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Drug reaction with eosinophilia and systemic symptoms without skin rash.
Sasidharanpillai, Sarita; Binitha, Manikoth P; Manikath, Neeraj; Janardhanan, Anisha K
2015-01-01
Drug reaction with eosinophilia and systemic symptoms (DRESS) or drug hypersensitivity syndrome is considered as a severe cutaneous adverse drug reaction which is most commonly precipitated by aromatic anticonvulsants, lamotrigine, dapsone, allopurinol, minocycline, and salazopyrin. Its clinical manifestations are often variable. On rare occasions, it can present with only systemic involvement without any cutaneous features. A complete drug history is of paramount importance in making an early diagnosis. We report the case of a male patient who presented with fever, lymphadenopathy, hepatosplenomegaly, and hepatitis, 2 weeks after starting salazopyrin. The presence of atypical lymphocytes in the peripheral smear was indicative of a viral infection or a hematological dyscrasia. Bone marrow examination revealed a normocellular marrow with an increase in eosinophil precursors. Investigations for the common causes for fever and hepatitis were negative. The presence of eosinophilia, the temporal relationship of the symptoms with the initiation of treatment with salazopyrin, and the marked improvement on withdrawal of the drug along with the administration of systemic corticosteroids, were features consistent with the diagnosis of DRESS. With the incidence of this condition showing a rising trend, it is important for the clinician to be aware of its variable manifestations, as a delay in diagnosis and treatment can be fatal.
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Protective effect of 4,4'-diaminodiphenylsulfone against paraquat-induced mouse lung injury
Cho, Sung Chun; Rhim, Ji Heon; Choi, Hae Ri; Son, Young Hoon; Lee, Seok Jin; Song, Kye-Yong
2011-01-01
Although 4,4'-diaminodiphenylsulfone (DDS, dapsone) has been used to treat several dermatologic conditions, including Hansen disease, for the past several decades, its mode of action has remained a topic of debate. We recently reported that DDS treatment significantly extends the lifespan of the nematode C. elegans by decreasing the generation of reactive oxygen species. Additionally, in in vitro experiments using non-phagocytic human fibroblasts, we found that DDS effectively counteracted the toxicity of paraquat (PQ). In the present study, we extended our work to test the protective effect of DDS against PQ in vivo using a mouse lung injury model. Oral administration of DDS to mice significantly attenuated the lung tissue damage caused by subsequent administration of PQ. Moreover, DDS reduced the local expression of mRNA transcripts encoding inflammation-related molecules, including endothelin-1 (ET-1), macrophage inflammatory protein-1α (MIP-1α), and transforming growth factor-β (TGF-β). In addition, DDS decreased the PQ-induced expression of NADPH oxidase mRNA and activation of protein kinase Cµ (PKCµ). DDS treatment also decreased the PQ-induced generation of superoxide anions in mouse lung fibroblasts. Taken together, these data suggest the novel efficacy of DDS as an effective protective agent against oxidative stress-induced tissue damages. PMID:21765237
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[Neuro-neutrophilic Disease and Dementia].
Hisanaga, Kinya
2016-04-01
Neuro-neutrophilic diseases are multisystem inflammatory disorders that include neuro-Behçet and neuro-Sweet disease. These disorders ectopically damage the nervous system due to the abnormal chemotaxis of neutrophils. The neutrophils' chemotaxis is induced by oral muco-cutaneous bacterial infections and the dysregulation of cytokines, including interleukins. The frequencies of human leukocyte antigen (HLA)-B51 in neuro-Behçet disease and HLA-B54 as well as Cw1 in neuro-Sweet disease significantly higher than the levels present in Japanese normal controls. Notably, their frequencies are also higher in patients exhibiting neurological complications than in patients without neurological complications. These HLA types are considered risk factors that are directly related to the etiology of these diseases. Prednisolone and colchicine, which suppress neutrophil activation, are used to treat the acute phase of both diseases. Alternatively, dapsone is prescribed to prednisolone-dependent recurrent cases of neuro-Sweet disease. Dementia is a neurological symptom of these disorders, especially in the chronic progressive subtype of neuro-Behçet disease. Other immunosuppressant drugs, including methotrexate and infliximab, are administered to patients with the chronic progressive type of neuro-Behçet disease. Neuro-neutrophilic diseases are a form of dementia considered treatable.
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[Effect of Environmental Factors on the Ecotoxicity of Pharmaceuticals and Personal Care Products].
Sugihara, Kazumi
2018-01-01
In recent years, pharmaceuticals and personal care products (PPCPs) have emerged as significant pollutants of aquatic environments and have been detected at levels in the range of ng/L to μg/L. The source of PPCPs is humans and livestock that have been administered pharmaceuticals and subsequently excreted them via urine and feces. Unlike agricultural chemicals, the environmental dynamics of PPCPs is not examined and they would undergo structural transformation by environmental factors, e.g., sunlight, microorganisms and treatments in sewage treatment plants (STPs). Processing at STPs can remove various PPCPs; however, they are not removed completely and some persist in the effluents. In this study, we examined the degradation of 9 pharmaceuticals (acetaminophen, amiodarone, dapsone, dexamethasone, indomethacin, raloxifene, phenytoin, naproxen, and sulindac) by sunlight or UV, and investigated the ecotoxicological variation of degradation products. Sunlight (UVA and UVB) degraded most pharmaceuticals, except acetaminophen and phenytoin. Similar results were obtained with UVB and UVA. All the pharmaceuticals were photodegraded by UVC, which is used for sterilization in STPs. Ecotoxicity assay using the luminescent bacteria test (ISO11348) indicated that UVC irradiation increased the toxicity of acetaminophen and phenytoin significantly. The photodegraded product of acetaminophen was identified as 1-(2-amino-5-hydroxyphenyl)ethanone and that of phenytoin as benzophenone, and the authentic compounds showed high toxicity. Photodegraded products of PPCPs are a concern in ecotoxicology.
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Kawabata, Kohei; Sugihara, Kazumi; Sanoh, Seigo; Kitamura, Shigeyuki; Ohta, Shigeru
2013-01-01
In order to investigate the effect of sunlight on the persistence and ecotoxicity of pharmaceuticals contaminating the aquatic environment, we exposed nine pharmaceuticals (acetaminophen (AA), amiodarone (AM), dapsone (DP), dexamethasone (DX), indomethacin (IM), naproxen (NP), phenytoin (PH), raloxifene (RL), and sulindac (SL)) in aqueous media to sunlight and to ultraviolet (UV) irradiation at 254, 302 or 365 nm (UV-C, UV-B or UV-A, respectively). Degradation of the pharmaceuticals was monitored by means of high-performance liquid chromatography (HPLC). Sunlight completely degraded AM, DP and DX within 6 hr, and partly degraded the other pharmaceuticals, except AA and PH, which were not degraded. Similar results were obtained with UV-B, while UV-A was less effective (both UV-A and -B are components of sunlight). All the pharmaceuticals were photodegraded by UV-C, which is used for sterilization in sewage treatment plants. Thus, the photodegradation rates of pharmaceuticals are dependent on both chemical structure and the wavelength of UV exposure. Toxicity assay using the luminescent bacteria test (ISO11348) indicated that UV irradiation reduced the toxicity of some pharmaceuticals to aquatic organisms by decreasing their amount (photodegradation) and increased the toxicity of others by generating toxic photoproduct(s). These results indicate the importance of investigating not only parent compounds, but also photoproducts in the risk assessment of pharmaceuticals in aquatic environments.
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Clinical features and treatment of peristomal pyoderma gangrenosum.
Hughes, A P; Jackson, J M; Callen, J P
2000-09-27
Peristomal pyoderma gangrenosum (PPG), an unusual variant of pyoderma gangrenosum, has been reported almost exclusively in patients with inflammatory bowel disease (IBD) and is frequently misdiagnosed. To better characterize the clinical manifestations, diagnosis, and management of PPG. Retrospective analysis of 7 patients with PPG observed in a university-affiliated community setting between 1988 and December 1999. Clinical and histopathologic features, associated disorders, and microbiologic findings. Two patients had Crohn disease, 2 had ulcerative colitis, and 3 had abdominal cancer. Five patients had at least 1 relapse of PPG after initial healing. Although 3 of 4 patients with IBD had active bowel disease, a parallel course with PPG occurred in only 1 patient. Both patients whose stoma was relocated developed an ulcer at the new site. Effective therapies included topical superpotent corticosteroids; intralesional injection of triamcinolone acetonide at the ulcer margin; topical cromolyn sodium; oral dapsone, prednisone, cyclosporine, mycophenolate mofetil; and intravenous infliximab. Our experiences demonstrate that although PPG has been most often reported in patients with IBD, it may occur in the absence of IBD. Biopsy of the skin lesion is not diagnostic but excludes other causes. Relocation of the stoma may be associated with a new ulceration and should be avoided. Trauma to the skin of a predisposed patient may elicit the pustules or ulcerations associated with pathergy. JAMA. 2000;284:1546-1548.
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Chronic Spontaneous Urticaria: Pathogenesis and Treatment Considerations.
Kaplan, Allen P
2017-11-01
The treatment of chronic spontaneous urticaria begins with antihistamines; however, the dose required typically exceeds that recommended for allergic rhinitis. Second-generation, relatively non-sedating H₁-receptor blockers are typically employed up to 4 times a day. First-generation antihistamines, such as hydroxyzine or diphenhydramine (Atarax or Benadryl), were employed similarly in the past. Should high-dose antihistamines fail to control symptoms (at least 50%), omalizumab at 300 mg/month is the next step. This is effective in 70% of antihistamine-refractory patients. H₂-receptor blockers and leukotriene antagonists are no longer recommended; they add little and the literature does not support significant efficacy. For those patients who are unresponsive to both antihistamines and omalizumab, cyclosporine is recommended next. This is similarly effective in 65%-70% of patients; however, care is needed regarding possible side-effects on blood pressure and renal function. Corticosteroids should not be employed chronically due to cumulative toxicity that is dose and time dependent. Brief courses of steroid e.g., 3-10 days can be employed for severe exacerbations, but should be an infrequent occurrence. Finally, other agents, such as dapsone or sulfasalazine, can be tried for those patients unresponsive to antihistamines, omalizumab, and cyclosporine. Copyright © 2017 The Korean Academy of Asthma, Allergy and Clinical Immunology · The Korean Academy of Pediatric Allergy and Respiratory Disease.
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Brorson, T; Skarping, G; Sandström, J F; Stenberg, M
1990-01-01
1,6-Hexamethylene diamine (HDA), used as raw material in industrial manufacturing operations, was orally administered to six healthy volunteers. After acid hydrolysis of the urine by hydrochloric acid, HDA and the metabolite 6-aminohexanoic acid were quantified. HDA was determined as an ethyl-chloroformate derivative by capillary gas chromatography using thermionic specific detection (TSD), and 6-aminohexanoic acid was quantified by ion chromatography using the ninhydrin reaction. In nonhydrolysed urine, monoacetylated HDA (N-acetyl-1,6-hexamethylene diamine) and HDA, were verified as heptafluorobutyric anhydride derivatives by gas chromatography-mass spectrometry (GC-MS), in a chemical ionization mode using isobutane and ammonia as reagent gases. In hydrolysed urine, a mean of 0.28 mg (range 1-6%) of the administered dose (8.2 mg) was recovered as HDA, and a mean of 0.8 mg (range less than 1-27%) as 6-aminohexanoic acid. The urinary excretion of both the determined compounds was rapid, and the principal part (greater than 90%) of the elimination was completed within 10 h. There was a considerable inter-individual variation in the excreted amounts, but the intra-individual variation in the excretion of HDA was limited. The subjects N-acetylator phenotype was determined by a dapsone test. Three slow acetylators excreted lower amounts (mean 2% of given dose) of HDA than three rapid ones (mean 5%).
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Sontheimer, Richard D
2005-06-01
Subacute cutaneous lupus erythematosus (SCLE) represents a widespread, photosensitive, nonscarring, nonindurated form of lupus erythematosus (LE)-specific skin disease. SCLE lesions are associated with a distinctive immunogenetic background including the production of Ro/SS-A autoantibodies. Individuals who have SCLE skin lesions as a component of their presenting illnesses represent a distinctive subset (subphenotype) of LE that enjoys a good prognosis with respect to life-threatening systemic manifestations of LE. SCLE skin lesions can be triggered by a number of different drugs the majority of which are capable of producing photosensitivity drug reactions in nonlupus patients. Single agent or combination aminoquinoline antimalarial therapy will suffice for 75% of SCLE patients. The remaining 25% will require other forms of systemic antiinflammatory therapy (e.g., diaminodipenylsulfone (Dapsone), thalidomide) or systemic immunosuppressive-immunomodulatory therapy. The etiopathogenesis of SCLE skin lesions is thought to result from four sequential stages: (1) inheritance of susceptibility genes (HLA 8.1 ancestral haplotype [C2, C4 deficiency, TNF-alpha-308A polymorphism], C1q deficiency); (2) loss of tolerance/induction of autoimmunity (ultraviolet light, photosensitizing drugs/chemicals, cigarette smoking, infection, psychological stress); (3) expansion/maturation of autoimmune responses (high levels of autoantibodies (Ro/SS-A), immune complexes, autoreactive T-cells); and (4) tissue injury/disease induction resulting from various autoimmune effector mechanisms (e.g., direct T cell-mediated cytotoxicity, antibody-dependent cell-mediated cytotoxicity).
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Chanprapaph, K; Sawatwarakul, S; Vachiramon, V
2017-10-01
Objective The aim of this study was to investigate the clinical features, laboratory findings, systemic manifestations, treatment and outcome of patients with bullous systemic lupus erythematosus in a tertiary care center in Thailand. Methods We performed a retrospective review from 2002 to 2014 of all patients who fulfilled the diagnostic criteria for bullous systemic lupus erythematosus to evaluate for the clinical characteristics, extracutaneous involvement, histopathologic features, immunofluorescence pattern, serological abnormalities, internal organ involvement, treatments and outcome. Results Among 5149 patients with cutaneous lupus erythematosus and/or systemic lupus erythematosus, 15 developed vesiculobullous lesions. Ten patients had validation of the diagnosis of bullous systemic lupus erythematosus, accounting for 0.19%. Bullous systemic lupus erythematosus occurred after the diagnosis of systemic lupus erythematosus in six patients with a median onset of 2.5 months (0-89). Four out of 10 patients developed bullous systemic lupus erythematosus simultaneously with systemic lupus erythematosus. Hematologic abnormalities and renal involvement were found in 100% and 90%, respectively. Polyarthritis (40%) and serositis (40%) were less frequently seen. Systemic corticosteroids, immunosuppressants, antimalarials and dapsone offered resolution of cutaneous lesions. Conclusion Bullous systemic lupus erythematosus is an uncommon presentation of systemic lupus erythematosus. Blistering can occur following or simultaneously with established systemic lupus erythematosus. We propose that clinicians should carefully search for systemic involvement, especially hematologic and renal impairment, in patients presenting with bullous systemic lupus erythematosus.
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Pires, Carla Andréa Avelar; Viana, Viviane Brito; Araújo, Fernando Costa; Müller, Silvia Ferreira Rodrigues; Oliveira, Miguel Saraty de; Carneiro, Francisca Regina Oliveira
2014-01-01
Pemphigusis a bullous, rare and chronic autoimmune disease. There are two major forms of pemphigus: vulgaris and foliaceus. Epidemiological data and clinical outcome in patients diagnosed in the Brazilian Amazon states are still rare. To study the occurrence of the disease during the study period and analyze the epidemiological profile of patients, the most common subtype of pemphigus, and the clinical evolution of patients. Retrospective analysis of medical records of hospitalized patients with pemphigus foliaceus and pemphigus vulgaris in the period from 2003 to 2010 in Dermatology Service of Hospital Fundação Santa Casa de Misericórdia do Pará, Belém, Northern Brazil. We found a total of 20 cases of pemphigus during the study period, 8 of which were of foliaceus pemphigus and 12 of vulgaris pemphigus. Pemphigus foliaceus had the predominance of male patients (75%), showed satisfactory clinical evolution, and was characterized by absence of pediatric cases. Pemphigus vulgaris affected more women (66.7%), showed mean hospital stay of 1 to 3 months (50%), and there were three cases of death (25%). The prescribed immunosuppressive drugs included prednisone with or without combination of azathioprine and/or dapsone. Sepsis was associated with 100% of the deaths. The occurrence of the disease is rare, there are no familiar/endemic outbreaks in the sample. Evolution is usually favorable, but secondary infection is associated with worse prognosis. The choice of best drugs to treat pemphigus remains controversial.
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Toxoplasmosis in HIV infection: An overview
Basavaraju, Anuradha
2016-01-01
Toxoplasma gondii is an obligate intracellular protozoan parasite presenting as a zoonotic infection distributed worldwide. In HIV-positive individuals, it causes severe opportunistic infections, which is of major public health concern as it results in physical and psychological disabilities. In healthy immunocompetent individuals, it causes asymptomatic chronic persistent infections, but in immunosuppressed patients, there is reactivation of the parasite if the CD4 counts fall below 200 cells/μl. The seroprevalence rates are variable in different geographic areas. The tissue cyst or oocyst is the infective form which enters by ingestion of contaminated meat and transform into tachyzoites and disseminate into blood stream. In immunocompetent persons due to cell-mediated immunity the parasite is transformed into tissue cyst resulting in life long chronic infection. In HIV-infected people opportunistic infection by T. gondii occurs due to depletion of CD4 cells, decreased production of cytokines and interferon gamma and impaired cytotoxic T-lymphocyte activity resulting in reactivation of latent infection. The diagnosis can be done by clinical, serological, radiological, histological or molecular methods, or by the combination of these. There is various treatment regimen including acute treatment, maintenance therapy should be given as the current anti T. gondii therapy cannot eradicate tissue cysts. In HIV patients, CD4 counts <100; cotrimoxazole, alternately dapsone + pyrimethamine can be given for 6 months. Hence, early diagnosis of T. gondii antibodies is important in all HIV-positive individuals to prevent complications of cerebral toxoplasmosis. PMID:27722101
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Alonzo González, M.; Menéndez, C.; Font, F.; Kahigwa, E.; Kimario, J.; Mshinda, H.; Tanner, M.; Bosch-Capblanch, X.; Alonso, P. L.
2000-01-01
Prerequisites for effective interventions against severe anaemia and malaria among infants are economic evaluations to aid the setting of priorities and the making of health policy. In the present study we analysed the cost and effectiveness of three control strategies hypothetically delivered through the Expanded Programme on Immunization (EPI). For the prevention of severe anaemia and from the perspective of the health provider, the cost-effectiveness ratios were, respectively, US$ 8, US$ 9, and US$ 21 per disability-adjusted life year (DALY) for malaria chemoprophylaxis with Deltaprim (a combination of 3.125 mg pyrimethamine and 25 mg dapsone) + iron, Deltaprim alone, or iron supplementation alone. For malaria prevention, Deltaprim + iron cost US$ 9.7 per DALY and Deltaprim alone cost US$ 10.2 per DALY. From a sociocultural perspective the cost-effectiveness ratios ranged from US$ 9 to US$ 26 for severe anaemia prevention and from US$ 11 to US$ 12 for the prevention of clinical malaria. These ratios were highly cost-effective, as defined by the World Bank's proposed threshold of less than US$ 25 per DALY for comparative assessments. Furthermore, all the preventive interventions were less costly than the current malaria and anaemia control strategies that rely on clinical case management. This economic analysis supports the inclusion of both malaria chemoprophylaxis and iron supplementation delivered through EPI as part of the control strategies for these major killers of infants in parts of sub-Saharan Africa. PMID:10686744
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Update on the epidemiology, diagnosis, and treatment of leprosy.
Reibel, F; Cambau, E; Aubry, A
2015-09-01
Leprosy is an infectious disease that has now been reported for more than 2000 years. The leprosy elimination goal set by the World Health Organization (WHO), i.e. a global prevalence rate <1 patient per 10,000 population, was achieved in the year 2000, but more than 200,000 new case patients are still reported each year, particularly in India, Brazil, and Indonesia. Leprosy is a specific infection: (i) it is a chronic infection primarily affecting the skin and peripheral nerves, (ii) Mycobacterium leprae is one of the last bacterial species of medical interest that cannot be cultured in vitro (mainly because of its reductive genome evolution), and (iii) transmission and pathophysiological data is still limited. The various presentations of the disease (Ridley-Jopling and WHO classifications) are correlated with the patient's immune response, bacillary load, and by the delay before diagnosis. Multidrug therapy (dapsone, rifampicin, with or without clofazimine) has been recommended since 1982 as the standard treatment of leprosy; 6 months for patients presenting with paucibacillary leprosy and 12 months for patients presenting with multibacillary leprosy. The worldwide use of leprosy drugs started in the 1980s and their free access since 1995 contributed to the drastic decline in the number of new case patients. Resistant strains are however emerging despite the use of multidrug therapy; identifying and monitoring resistance is still necessary. Copyright © 2015 Elsevier Masson SAS. All rights reserved.
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Treatment of Pneumocystis jirovecii pneumonia in HIV-infected patients: a review.
Huang, Yu-Shan; Yang, Jen-Jia; Lee, Nan-Yao; Chen, Guan-Jhou; Ko, Wen-Chien; Sun, Hsin-Yun; Hung, Chien-Ching
2017-09-01
Pneumocystis pneumonia is a potentially life-threatening pulmonary infection that occurs in immunocompromised individuals and HIV-infected patients with a low CD4 cell count. Trimethoprim-sulfamethoxazole has been used as the first-line agent for treatment, but mutations within dihydropteroate synthase gene render potential resistance to sulfamide. Despite advances of combination antiretroviral therapy (cART), Pneumocystis pneumonia continues to occur in HIV-infected patients with late presentation for cART or virological and immunological failure after receiving cART. Areas covered: This review summarizes the diagnosis and first-line and alternative treatment and prophylaxis for Pneumocystis pneumonia in HIV-infected patients. Articles for this review were identified through searching PubMed. Search terms included: 'Pneumocystis pneumonia', 'Pneumocystis jirovecii pneumonia', 'Pneumocystis carinii pneumonia', 'trimethoprim-sulfamethoxazole', 'primaquine', 'trimetrexate', 'dapsone', 'pentamidine', 'atovaquone', 'echinocandins', 'human immunodeficiency virus infection', 'acquired immunodeficiency syndrome', 'resistance to sulfamide' and combinations of these terms. We limited the search to English language papers that were published between 1981 and March 2017. We screened all identified articles and cross-referenced studies from retrieved articles. Expert commentary: Trimethoprim-sulfamethoxazole will continue to be the first-line agent for Pneumocystis pneumonia given its cost, availability of both oral and parenteral formulations, and effectiveness or efficacy in both treatment and prophylaxis. Whether resistance due to mutations within dihydropteroate synthase gene compromises treatment effectiveness remains controversial. Continued search for effective alternatives with better safety profiles for Pneumocystis pneumonia is warranted.
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Naing, Cho; Aung, Kyan; Win, Daw-Khin; Wah, Mak Joon
2010-11-01
Chloroquine (CQ) is a relatively inexpensive drug for treatment of malaria. If efficacy of CQ is still assumed, then it should be indicated in malaria treatment policies as the drug of choice for uncomplicated Plasmodium vivax malaria in endemic countries with resource constraints. The objective of this review is to summarize the existing evidence on the relative efficacy and safety of CQ in treating patients with uncomplicated P. vivax malaria in endemic countries. We searched online data bases (PUBMED, MEDLINE, EMBASE, The Cochrane Library) and the reference lists of the retrieved articles. Fifteen randomized controlled trials (n=6215) assessing the relative efficacy and safety of CQ for treatment of uncomplicated P. vivax malaria were included. CQ monotherapy was compared to CQ plus primaquine (PQ), artemisinin/artemether, artemisinin based combination therapy, quinine, CQ plus tafenoquine, chlorguanil plus dapsone, azithromycin, or placebo. Treatment efficacy was not significantly different between the CQ monotherapy group and that of the CQ with PQ 14 day group at 28 day follow-up (55/711, 7.7% vs 35/712, 4.9%; P=0.16). Evidence from the trials identified for this review draw a fairly clear conclusion about the relative efficacy and safety of CQ for treating uncomplicated P. vivax malaria infection. However, further research in this field with well powered, randomized, non-inferiority design, using the standardized protocol is needed. Copyright © 2010 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.
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Blisters and Loss of Epidermis in Patients With Lupus Erythematosus
Merklen-Djafri, Carine; Bessis, Didier; Frances, Camille; Poulalhon, Nicolas; Debarbieux, Sébastien; Cordel, Nadège; Lipsker, Dan
2015-01-01
Abstract The nosology of bullous lesions or equivalents (vesicles, erosions, and crusts) in patients with lupus erythematosus (LE) is rarely addressed. The primary aim of this study was to draw up a precise phenotypic inventory of such skin lesions; the secondary objective was to assess a potential relationship between the different types of loss of epidermis and extracutaneous lupus manifestations. We conducted a retrospective multicenter study including 22 patients with definite LE and bullous lesions or equivalents. All biopsies were reviewed. Patients were recruited in the dermatology departments of 6 centers. Patients were included if they met the diagnosis of systemic LE according to American College of Rheumatology and/or Systemic Lupus International Collaborating Clinics criteria or diagnosis of cutaneous LE based on classic clinical criteria and/or histological ascertainment of LE. Patients were recruited through clinician's memory and photographic collections. Three clinico-pathological patterns could be individualized. First, toxic epidermal necrolysis (TEN)-like, sheet-like, skin detachment; sun-exposure, mild mucosal involvement, and dermal mucin deposition allow differential diagnosis with classical Lyell syndrome. Second, vesiculo-bullae and/or crusting occurring on typical lesions of subacute cutaneous lupus erythematosus or chronic cutaneous lupus erythematosus. Third, tense vesicles and/or blisters with an underlying neutrophilic dermatosis and a usual response to dapsone. A careful analysis of 22 LE patients with epidermal detachment reveals 2 main pathomechanisms: a classic LE interface dermatitis, which can be hyperacute and lead to TEN-like skin detachment; and a neutrophilic dermatosis, with tense vesicles and/or blisters, including classic bullous LE. PMID:26579826
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Whole genome sequencing distinguishes between relapse and reinfection in recurrent leprosy cases
Bührer-Sékula, Samira; Benjak, Andrej; Loiseau, Chloé; Singh, Pushpendra; Pontes, Maria A. A.; Gonçalves, Heitor S.; Hungria, Emerith M.; Busso, Philippe; Piton, Jérémie; Silveira, Maria I. S.; Cruz, Rossilene; Schetinni, Antônio; Costa, Maurício B.; Virmond, Marcos C. L.; Diorio, Suzana M.; Dias-Baptista, Ida M. F.; Rosa, Patricia S.; Matsuoka, Masanori; Penna, Maria L. F.; Cole, Stewart T.; Penna, Gerson O.
2017-01-01
Background Since leprosy is both treated and controlled by multidrug therapy (MDT) it is important to monitor recurrent cases for drug resistance and to distinguish between relapse and reinfection as a means of assessing therapeutic efficacy. All three objectives can be reached with single nucleotide resolution using next generation sequencing and bioinformatics analysis of Mycobacterium leprae DNA present in human skin. Methodology DNA was isolated by means of optimized extraction and enrichment methods from samples from three recurrent cases in leprosy patients participating in an open-label, randomized, controlled clinical trial of uniform MDT in Brazil (U-MDT/CT-BR). Genome-wide sequencing of M. leprae was performed and the resultant sequence assemblies analyzed in silico. Principal findings In all three cases, no mutations responsible for resistance to rifampicin, dapsone and ofloxacin were found, thus eliminating drug resistance as a possible cause of disease recurrence. However, sequence differences were detected between the strains from the first and second disease episodes in all three patients. In one case, clear evidence was obtained for reinfection with an unrelated strain whereas in the other two cases, relapse appeared more probable. Conclusions/Significance This is the first report of using M. leprae whole genome sequencing to reveal that treated and cured leprosy patients who remain in endemic areas can be reinfected by another strain. Next generation sequencing can be applied reliably to M. leprae DNA extracted from biopsies to discriminate between cases of relapse and reinfection, thereby providing a powerful tool for evaluating different outcomes of therapeutic regimens and for following disease transmission. PMID:28617800
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NSAIDs and enantiomers of flurbiprofen target γ-secretase and lower Aβ42 in vivo
Eriksen, Jason L.; Sagi, Sarah A.; Smith, Tawnya E.; Weggen, Sascha; Das, Pritam; McLendon, D.C.; Ozols, Victor V.; Jessing, Kevin W.; Zavitz, Kenton H.; Koo, Edward H.; Golde, Todd E.
2003-01-01
Epidemiologic studies demonstrate that long-term use of NSAIDs is associated with a reduced risk for the development of Alzheimer disease (AD). In this study, 20 commonly used NSAIDs, dapsone, and enantiomers of flurbiprofen were analyzed for their ability to lower the level of the 42-amino-acid form of amyloid β protein (Aβ42) in a human H4 cell line. Thirteen of the NSAIDs and the enantiomers of flurbiprofen were then tested in acute dosing studies in amyloid β protein precursor (APP) transgenic mice, and plasma and brain levels of Aβ and the drug were evaluated. These studies show that (a) eight FDA-approved NSAIDs lower Aβ42 in vivo, (b) the ability of an NSAID to lower Aβ42 levels in cell culture is highly predicative of its in vivo activity, (c) in vivo Aβ42 lowering in mice occurs at drug levels achievable in humans, and (d) there is a significant correlation between Aβ42 lowering and levels of ibuprofen. Importantly, flurbiprofen and its enantiomers selectively lower Aβ42 levels in broken cell γ-secretase assays, indicating that these compounds directly target the γ-secretase complex that generates Aβ from APP. Of the compounds tested, meclofenamic acid, racemic flurbiprofen, and the purified R and S enantiomers of flurbiprofen lowered Aβ42 levels to the greatest extent. Because R-flurbiprofen reduces Aβ42 levels by targeting γ-secretase and has reduced side effects related to inhibition of cyclooxygenase (COX), it is an excellent candidate for clinical testing as an Aβ42 lowering agent. PMID:12897211
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Malaria: prevention in travellers.
Croft, Ashley M
2007-11-29
Malaria transmission occurs most frequently in environments with humidity over 60% and ambient temperature of 25-30 degrees C. Risks increase with longer visits and depend on activity. Infection can follow a single mosquito bite. Incubation is usually 10-14 days but can be up to 18 months depending on the strain of parasite. We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of non-drug preventive interventions in adult travellers? What are the effects of drug prophylaxis in adult travellers? What are the effects of antimalaria vaccines in travellers? What are the effects of antimalaria interventions in child travellers, pregnant travellers, and in airline pilots? We searched: Medline, Embase, The Cochrane Library and other important databases up to February 2006 (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). We found 69 systematic reviews, RCTs, or observational studies that met our inclusion criteria. In this systematic review we present information relating to the effectiveness and safety of the following interventions: acoustic buzzers, aerosol insecticides, amodiaquine, air conditioning and electric fans, atovaquone-proguanil, biological control measures, chloroquine (alone or with proguanil), diethyltoluamide (DEET), doxycycline, full-length and light-coloured clothing, insecticide-treated clothing/nets, mefloquine, mosquito coils and vaporising mats, primaquine, pyrimethamine-dapsone, pyrimethamine-sulfadoxine, smoke, topical (skin-applied) insect repellents, and vaccines.
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Peroxidative Metabolism of β2-Agonists Salbutamol and Fenoterol and Their Analogs
Reszka, Krzysztof J.; McGraw, Dennis W.; Britigan, Bradley E.
2009-01-01
Phenolic β2-adrenoreceptor agonists salbutamol, fenoterol and terbutaline relax smooth muscle cells that relieve acute airway bronchospasm associated with asthma. Why their use sometimes fails to relieve bronchospasm, and why the drugs appear to be less effective in patients with severe asthma exacerbations, remains unclear. We show that in the presence of hydrogen peroxide, both myeloperoxidase, secreted by activated neutrophils present in inflamed airways, and lactoperoxidase, which is naturally present in the respiratory system, catalyze oxidation of these β2-agonists. Azide, cyanide, thiocyanate, ascorbate, glutathione, and methimazole inhibited this process, while methionine was without effect. Inhibition by ascorbate and glutathione was associated with their oxidation to corresponding radical species by the agonists’-derived phenoxyl radicals. Using electron paramagnetic resonance (EPR), we detected free radical metabolites from β2-agonists by spin trapping with 2-methyl-2-nitrosopropane (MNP). Formation of these radicals was inhibited by pharmacologically-relevant concentrations of methimazole and dapsone. In alkaline buffers radicals from fenoterol and its structural analog, metaproteronol, were detected by direct EPR. Analysis of these spectra suggests that oxidation of fenoterol and metaproterenol, but not terbutaline, causes their transformation through intramolecular cyclization by addition of their amino nitrogen to the aromatic ring. Together, these results indicate that phenolic β2-agonists function as substrates for airway peroxidases and that the resulting products differ in their structural and functional properties from their parent compounds. They also suggest that these transformations can be modulated by pharmacological approaches using appropriate peroxidase inhibitors or alternative substrates. These processes may affect therapeutic efficacy and also play a role in adverse reactions of the β2-agonists. PMID:19462961
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Peroxidative metabolism of beta2-agonists salbutamol and fenoterol and their analogues.
Reszka, Krzysztof J; McGraw, Dennis W; Britigan, Bradley E
2009-06-01
Phenolic beta(2)-adrenoreceptor agonists salbutamol, fenoterol, and terbutaline relax smooth muscle cells that relieve acute airway bronchospasm associated with asthma. Why their use sometimes fails to relieve bronchospasm and why the drugs appear to be less effective in patients with severe asthma exacerbations remains unclear. We show that in the presence of hydrogen peroxide, both myeloperoxidase, secreted by activated neutrophils present in inflamed airways, and lactoperoxidase, which is naturally present in the respiratory system, catalyze oxidation of these beta(2)-agonists. Azide, cyanide, thiocyanate, ascorbate, glutathione, and methimazole inhibited this process, while methionine was without effect. Inhibition by ascorbate and glutathione was associated with their oxidation to corresponding radical species by the agonists' derived phenoxyl radicals. Using electron paramagnetic resonance (EPR), we detected free radical metabolites from beta(2)-agonists by spin trapping with 2-methyl-2-nitrosopropane (MNP). Formation of these radicals was inhibited by pharmacologically relevant concentrations of methimazole and dapsone. In alkaline buffers, radicals from fenoterol and its structural analogue, metaproteronol, were detected by direct EPR. Analysis of these spectra suggests that oxidation of fenoterol and metaproterenol, but not terbutaline, causes their transformation through intramolecular cyclization by addition of their amino nitrogen to the aromatic ring. Together, these results indicate that phenolic beta(2)-agonists function as substrates for airway peroxidases and that the resulting products differ in their structural and functional properties from their parent compounds. They also suggest that these transformations can be modulated by pharmacological approaches using appropriate peroxidase inhibitors or alternative substrates. These processes may affect therapeutic efficacy and also play a role in adverse reactions of the beta(2)-agonists.
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von dem Borne, P A; Jonkman, M F; van Doorn, R
2017-05-01
Subcorneal pustular dermatosis (SPD), or Sneddon-Wilkinson disease, is a rare pustular skin disease that follows a chronic relapsing course. A well-known association exists between SPD and IgA monoclonal gammopathy of undetermined significance (MGUS), which exists in up to 40% of cases. SPD has also been observed in patients with IgA myeloma. In SPD, direct and indirect immunofluorescence studies do not reveal in vivo bound IgA to the epithelial cell surface, in contrast to IgA pemphigus, which has similar clinicopathological features. Here we describe the case of a male patient with SPD and a concurrent IgA MGUS who had been treated with dapsone for 20 years with frequent relapses. Following development of multiple myeloma, the patient was treated with intensive antimyeloma treatment consisting of high-dose melphalan with autologous stem cell transplantation. This resulted in a complete remission of the myeloma with disappearance of the M-protein. In addition, a sustained remission of SPD was achieved without further treatment. Twenty-eight months after melphalan therapy the M-protein reappeared in the serum, and 2 months later SPD reappeared with histopathologically proven skin lesions at predilection sites. Presence and absence of skin lesions was found to correlate with the presence and absence of the M-protein in the serum. This is the first report of antimyeloma therapy inducing a long-lasting remission in SPD. The findings in this patient strongly suggest a causal role for circulating IgA antibodies in the pathogenesis of SPD. Antimyeloma treatment should be considered in patients with IgA MGUS-associated SPD refractory to other therapies. © 2016 British Association of Dermatologists.
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Treatment of Mycobacterium paratuberculosis infection in ruminants.
St-Jean, G; Jernigan, A D
1991-11-01
Paratuberculosis is a chronic, debilitating, fatal condition that usually is clinically undetectable until the onset of copious diarrhea. Paratuberculosis is caused by an acid-fast organism, M. paratuberculosis. Successful eradication of paratuberculosis depends on the early detection of infected animals, thereby allowing removal of carrier animals from the herd. Treatment for paratuberculosis is therefore rarely indicated or undertaken; however, treatment may be considered for animals of exceptional genetic value or companion animals. Antimicrobials reviewed in this article for the treatment of paratuberculosis include isoniazid, rifampin, streptomycin, amikacin, clofazimine, and dapsone. Treatment of paratuberculosis requires daily medication for extended periods and results in palliation of the disease rather than a definitive cure. The treatment for paratuberculosis recommended by the authors is isoniazid at 20 mg/kg administered orally every 24 hours for the rest of the animal's life. When the animal has acute onset of diarrhea, rifampin at 20 mg/kg every 24 hours is also administered orally. In severe, imminently life-threatening cases, an aminoglycoside should be administered concurrently for 3 to 8 weeks. This protocol (isoniazid, rifampin, and an aminoglycoside) will help ensure that Mycobacteria organisms are sensitive to at least two of the antibiotics. Rifampin treatment can be discontinued if clinical signs of paratuberculosis disappear and the cost of therapy is judged excessive. The combined therapeutic approach has been used in three animals, and the results are presented in this article. Because isoniazid, rifampin, and some aminoglycosides are not approved for use in food animals in the United States of America, the meat or milk from treated animals should not be used for human consumption.
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Diri, R; Anwer, F; Yeager, A; Krishnadasan, R; McBride, A
2016-02-01
Patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) are at risk of numerous opportunistic infections. Pneumocystis jirovecii pneumonia (PJP) is a potentially life-threatening infection that can develop in immunocompromised individuals. Current prophylaxis for PJP includes trimethoprim-sulfamethoxazole (TMP-SMX), dapsone, atovaquone, or inhaled pentamidine (PEN), often with varying breakthrough rates. The use of intravenous (IV) PEN for PJP prophylaxis has been evaluated in pediatric patients. A single-institution retrospective review of electronic medical records was conducted for patients who underwent allo-HSCT between January 2001 and May 2013 and who had received at least 1 dose of IV PEN for PJP prophylaxis. Data collected included patient demographics, diagnosis, previous chemotherapy, pre-transplant conditioning regimen, other medications, microbiology test results, and clinical outcomes. A total of 113 patients were included in the study. The median number of PEN doses administered per patient was 3 (range 1-23). IV PEN was primary PJP prophylaxis in 74 of the patients (65%) and second-line prophylaxis in 39 (35%) post transplant, with the majority switching from oral TMP-SMX. Side effects of IV PEN administration were minimal. No patients who received IV PEN prophylaxis developed PJP infection. No case of PJP was seen in patients who received other agents for PJP prophylaxis. This retrospective study showed that IV PEN is very effective and well-tolerated prophylaxis for PJP; IV PEN can be considered a favorable alternative for PJP in situations where other agents might be contraindicated. Our findings provide strong support for prospective studies of IV PEN for PJP prophylaxis in adult HSCT recipients. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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Review and drug therapy implications of glucose-6-phosphate dehydrogenase deficiency.
Belfield, Kristen D; Tichy, Eric M
2018-02-01
The pathophysiology, diagnosis, and medication-use implications of glucose-6-phosphate dehydrogenase (G6PD) deficiency, the most common enzyme deficiency in humans, are reviewed. Originally identified as favism in patients who experienced hemolysis after ingestion of fava beans, G6PD deficiency results from an X-linked chromosomal mutation that leads to reduced activity of the enzyme responsible for the final step of the pentose phosphate pathway, through which reduced nicotinamide adenine dinucleotide phosphate required for protection of cells from oxidative stress is produced. G6PD deficiency affects about 400 million people worldwide. Diagnosis of G6PD can be made through detection of enzymatic activity (by spectrophotometric testing, fluorescence testing, or formazan-based spot testing) or molecular analysis to detect known mutations of the gene encoding G6PD. Most individuals with G6PD deficiency are asymptomatic throughout life. Symptoms of acute hemolysis associated with G6PD deficiency include anemia, fatigue, back or abdominal pain, jaundice, and hemoglobinuria. The most common precipitators of oxidative stress and hemolysis in G6PD deficiency include medication use and infection. G6PD deficiency should be considered in patients who experience acute hemolysis after exposure to known oxidative medications, infection, or ingestion of fava beans. A diagnosis of G6PD deficiency is most often made through enzymatic activity detection, but molecular analysis may be required in females heterozygous for the disorder. When clinically feasible, rasburicase, primaquine, dapsone, pegloticase, and methylene blue should not be used until a G6PD diagnostic test has been performed. Copyright © 2018 by the American Society of Health-System Pharmacists, Inc. All rights reserved.
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Childhood-onset bullous systemic lupus erythematosus.
Lourenço, D M R; Gomes, R Cunha; Aikawa, N E; Campos, L M A; Romiti, R; Silva, C A
2014-11-01
Bullous systemic lupus erythematosus has rarely been described in pediatric lupus population and the real prevalence of childhood-onset bullous systemic lupus erythematosus has not been reported. From January 1983 to November 2013, 303 childhood-onset SLE (c-SLE) patients were followed at the Pediatric Rheumatology Unit of the Childreńs Institute of Hospital das Clínicas da Faculdade de Medicina Universidade da Universidade de São Paulo, three of them (1%) diagnosed as childhood-onset bullous systemic lupus erythematosus. All three cases presented tense vesiculobullous lesions unassociated with lupus erythematosus lesions, with the median duration of 60 days (30-60). All patients fulfilled bullous systemic lupus erythematosus criteria. Two had nephritis and serositis and presented specific autoantibodies. The histological pattern demonstrated subepidermal blisters with neutrophils-predominant infiltrates within the upper dermis. Direct immunofluorescence (DIF) showed deposits of IgG and complement along the epidermal basement membrane, in the presence or absence of IgA and/or IgM. A positive indirect immunofluorescence on salt-split skin demonstrating dermal binding was observed in two cases. All of them had moderate/severe disease activity at diagnosis with median Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) of 18 (14-24). Two patients received dapsone and one with severe nephritis received immunosuppressive drugs. In conclusion, in the last 30 years the prevalence of bullous lupus in childhood-onset lupus population was low (1%) in our tertiary University Hospital. A diagnosis of SLE should always be considered in children with recurrent tense vesiculobullous lesions with or without systemic manifestations. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.
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Al-Said, Mansour S; Ghorab, Mostafa M; Nissan, Yassin M
2012-07-02
Several new sulfonebiscompounds having a biologically active 1,2-dihydropyridine-2-one 3-19, acrylamide 20, chromene 21, 22 and chromenopyridine 23, 24 moieties were synthesized and evaluated as potential anticancer agents. The structures of the products were confirmed via elemental analyses and spectral data. The screening tests showed that many of the biscompounds obtained exhibited good anticancer activity against human breast cell line (MCF7) comparable to doxorubicin which was used as reference drug. Compounds 11, 17 and 24 showed IC50 values 35.40 μM, 29.86 μM and 30.99 μM, respectively. In order to elucidate the mechanism of action of the synthesized compounds as anticancer agents, docking on the active site of farnesyltransferase and arginine methyltransferase was also performed and good results were obtained.
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Sallans, Larry; Macha, Stephen; Brown, Kari; McGraw, Dennis W.; Kovacic, Melinda Butsch; Britigan, Bradley E.
2011-01-01
β2-Agonists are the most effective bronchodilators for the rapid relief of asthma symptoms, but for unclear reasons, their effectiveness may be decreased during severe exacerbations. Because peroxidase activity and nitrogen oxides are increased in the asthmatic airway, we examined whether salbutamol, a clinically important β2-agonist, is subject to potentially inactivating nitration. When salbutamol was exposed to myeloperoxidase, eosinophil peroxidase or lactoperoxidase in the presence of hydrogen peroxide (H2O2) and nitrite (NO2−), both absorption spectroscopy and mass spectrometry indicated formation of a new metabolite with features expected for the nitrated drug. The new metabolites showed an absorption maximum at 410 nm and pKa of 6.6 of the phenolic hydroxyl group. In addition to nitrosalbutamol (m/z 285.14), a salbutamol-derived nitrophenol, formed by elimination of the formaldehyde group, was detected (m/z 255.13) by mass spectrometry. It is noteworthy that the latter metabolite was detected in exhaled breath condensates of asthma patients receiving salbutamol but not in unexposed control subjects, indicating the potential for β2-agonist nitration to occur in the inflamed airway in vivo. Salbutamol nitration was inhibited in vitro by ascorbate, thiocyanate, and the pharmacological agents methimazole and dapsone. The efficacy of inhibition depended on the nitrating system, with the lactoperoxidase/H2O2/NO2− being the most affected. Functionally, nitrated salbutamol showed decreased affinity for β2-adrenergic receptors and impaired cAMP synthesis in airway smooth muscle cells compared with the native drug. These results suggest that under inflammatory conditions associated with asthma, phenolic β2-agonists may be subject to peroxidase-catalyzed nitration that could potentially diminish their therapeutic efficacy. PMID:20974700
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Bisphenol A and alternatives in thermal paper receipts - a German market analysis from 2015 to 2017.
Eckardt, Martin; Simat, Thomas J
2017-11-01
Bisphenol A (BPA) was commonly used as color developer for thermal paper such as cash register receipts, labels or tickets. Therefore, thermal paper was considered by the European Food Safety Authority (EFSA) as the main source of human exposure to BPA beside epoxy based food contact materials. In this study, a German market analysis on the use of BPA and alternative color developers in thermal paper receipts is provided for the years 2015, 2016 and 2017.114 (2015), 98 (2016) and 99 (2017) samples were randomly collected and analyzed by HPLC-DAD. In summary, BPA was still the most frequently found color developer (48.2% in 2015, 46.9% in 2016 and 52.5% in 2017). The most commonly used alternative was the phenol-free substance Pergafast ® 201 (34.2%, 33.7%, 40.4%). The bisphenol analogs bisphenol S (BPS; 11.4%, 9.2%, 6.1%) and D8 (6.1%, 7.1%, 1.0%) were less common. Another phenol-free substituent, a urea urethane compound (UU), was also detected (3.1% in 2016). Concentrations of color developers in thermal paper ranged from 1.4 to 32.4 mg/g (median values between 2.5 and 15.9 mg/g). Concentrations of BPA were found to be highest followed by BPS, UU, Pergafast ® 201 and D8. In addition, two pharmacologically active substances, dapsone (6.0 mg/g) and tolbutamide (5.5 mg/g), were detected in a non-marketed thermal paper, that was supposed to use ascorbic acid as initial color developer. Different release experiments of the detected color developers were performed. Sensitizers 1,2-diphenoxy-ethane, 1-phenylmethoxy-naphthalene and diphenylsulfone, used frequently in the thermal paper processes, were quantified. Copyright © 2017 Elsevier Ltd. All rights reserved.
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Diagnosis, pathogenesis, and treatment of chronic spontaneous urticaria.
Kaplan, Allen P
2018-05-01
Chronic Spontaneous Urticaria (CSU) is an endogenous disorder that is strongly associated with autoimmunity, particularly with immunoglobulin G (IgG) antibody to the alpha subunit of the IgE receptor seen in 35-40% of patients. Basophils and cutaneous mast cells can be activated and lead to a late-phase-like perivascular infiltration about small venules and hive formation. Review of current literature. Antibody to thyroid antigens are seen in 25% of patients; a small fraction of these may be clinically hypothyroid (Hashimoto's Thyroiditis). Forty percent of patients have angioedema, but not laryngeal edema. Therapy typically begins with second-generation antihistamines (H1 receptor blockers) up to four times a day. The failure rate is substantial, and estimates vary from 25% to 50%. The drug of choice for antihistamine resistant cases is omalizumab, at 300 mg/month, which is effective in 70% of patients. H-2-antagonists and leucotriene antagonists are no longer recommended because the literature does not support additional efficacy beyond blockage of H-1 receptors. For patients unresponsive to antihistamines and omalizumab, cyclosporine is recommended next. This is similarly effective in 65-70% of patients; however, assessment of blood pressure and renal function need to be followed every 4-6 weeks. Corticosteroid should not be employed chronically; however, a brief course of 3-10 days can be used acutely for severe exacerbations. Other agents, such as dapsone, sulfasalazine, or hydroxychloroquin, can be tried when the aforementioned medications fail, but the results are unpredictable because they have not been shown to have efficacy beyond the placebo effect (25-30%), and have not been studied in patients for whom the aforementioned approach i.e. antihistamines, omalizumab, and cyclosporine has failed. High dose antihistamines, omalizumab and cyclosporine (in that order) are effective and recommended for therapy of CUS, an inflammatory skin disorder associated
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Malaria: prevention in travellers.
Croft, Ashley M
2010-07-12
Malaria transmission occurs most frequently in environments with humidity greater than 60% and ambient temperature of 25 °C to 30 °C. Risks increase with longer visits and depend on activity. Infection can follow a single mosquito bite. Incubation is usually 10 to 14 days but can be up to 18 months depending on the strain of parasite. We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of non-drug preventive interventions in non-pregnant adult travellers? What are the effects of drug prophylaxis in non-pregnant adult travellers? What are the effects of antimalaria vaccines in adult and child travellers? What are the effects of antimalaria interventions in child travellers, pregnant travellers, and in airline pilots? We searched: Medline, Embase, The Cochrane Library, and other important databases up to November 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). We found 79 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. In this systematic review we present information relating to the effectiveness and safety of the following interventions: aerosol insecticides, amodiaquine, air conditioning and electric fans, atovaquone-proguanil, biological control measures, chloroquine (alone or with proguanil), diethyltoluamide (DEET), dietary supplementation, doxycycline, electronic mosquito repellents, full-length and light-coloured clothing, insecticide-treated clothing/nets, mefloquine, mosquito coils and vapourising mats, primaquine, pyrimethamine-dapsone, pyrimethamine-sulfadoxine, smoke, topical (skin-applied) insect repellents, and vaccines.
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Borderline tuberculoid leprosy in childhood onset systemic lupus erythematosus patient.
Lopes, V A P; Lourenço, D M R; Guariento, A; Trindade, M A; Avancini, J; Silva, C A
2015-11-01
Leprosy is a contagious and chronic systemic granulomatous disease caused by the bacillus Mycobacterium leprae. To our knowledge, no case of leprosy in a childhood-onset systemic lupus erythematosus (c-SLE) patient has been reported. For a period of 31 years, 312 c-SLE patients were followed at the Pediatric Rheumatology Unit of our University Hospital. One of them (0.3%) had tuberculoid leprosy skin lesions during the disease course and is here reported. A 10-year-old boy from Northwest of Brazil was diagnosed with c-SLE based on malar rash, photosensitivity, oral ulcers, lymphopenia, proteinuria, positive antinuclear antibodies, anti-double-stranded DNA, anti-Sm and anti-Ro/SSA autoantibodies. He was treated with prednisone, hydroxychloroquine and intravenous cyclophosphamide, followed by mycophenolate mofetil. At 12-years-old, he presented asymmetric skin lesions characterized by erythematous plaques with elevated external borders and hypochromic center with sensory loss. Peripheral nerve involvement was not evidenced. No history of familial cases of leprosy was reported, although the region where the patient resides is considered to be endemic for leprosy. Skin biopsy revealed a well-defined tuberculoid form. A marked thickening of nerves was observed, often destroyed by granulomas, without evidence of Mycobacterium leprae bacilli. At that time, the SLEDAI-2K score was 4 and he had been receiving prednisone 15 mg/day, hydroxychloroquine 200 mg/day and mycophenolate mofetil 3 g/day. Paucibacillary treatment for leprosy with dapsone and rifampicine was also introduced. In conclusion, we have reported a rare case of leprosy in the course of c-SLE. Leprosy should always be considered in children and adolescents with lupus who present skin abnormalities, particularly with hypoesthesic or anesthesic cutaneous lesions. © The Author(s) 2015.
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2012-01-01
Background Pneumocystis jiroveci pneumonia (PCP) prophylaxis is recommended for patients with CD4 counts of less than 200 cells/mm3. This study examines the proportion of patients in the TREAT Asia HIV Observational Database (TAHOD) receiving PCP prophylaxis, and its effect on PCP and mortality. Methods TAHOD patients with prospective follow up had data extracted for prophylaxis using co-trimoxazole, dapsone or pentamidine. The proportion of patients on prophylaxis was calculated for each calendar year since 2003 among patients with CD4 counts of less than 200 cells/mm3. The effect of prophylaxis on PCP and survival were assessed using random-effect Poisson regression models. Results There were a total of 4050 patients on prospective follow up, and 90% of them were receiving combination antiretroviral therapy. Of those with CD4 counts of less than 200 cells/mm3, 58% to 72% in any given year received PCP prophylaxis, predominantly co-trimoxazole. During follow up, 62 patients developed PCP (0.5 per 100 person-years) and 169 died from all causes (1.36/100 person-years). After stratifying by site and adjusting for age, CD4 count, CDC stage and antiretroviral treatment, those without prophylaxis had no higher risk of PCP, but had a significantly higher risk of death (incident rate ratio 10.8, p < 0.001). PCP prophylaxis had greatest absolute benefit in patients with CD4 counts of less than 50 cells/mm3, lowering mortality rates from 33.5 to 6.3 per 100 person-years. Conclusions Approximately two-thirds of TAHOD patients with CD4 counts of less than 200 cells/mm3 received PCP prophylaxis. Patients without prophylaxis had significantly higher mortality, even in the era of combination ART. Although PCP may be under-diagnosed, these data suggest that prophylaxis is associated with important survival benefits. PMID:22281054
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Vieira, Ana Paula; Trindade, Maria Angela Bianconcini; de Paula, Flávio Jota; Sakai-Valente, Neusa Yurico; Duarte, Alberto José da Silva; Lemos, Francine Brambate Carvalhinho; Benard, Gil
2017-04-24
Due to its chronic subclinical course and large spectrum of manifestations, leprosy often represents a diagnostic challenge. Even with proper anti-mycobacteria treatment, leprosy follow up remains challenging: almost half of leprosy patients may develop reaction episodes. Leprosy is an infrequent complication of solid organ transplant recipients. This case report illustrates the challenges in diagnosing and managing leprosy and its reactional states in a transplant recipient. A 53-year-old man presented 34 months after a successful renal transplantation a borderline-tuberculoid leprosy with signs of mild type 1 upgrading reaction (T1R). Cutaneous manifestations were atypical, and diagnosis was only made when granulomatous neuritis was found in a cutaneous biopsy. He was successfully treated with the WHO recommended multidrug therapy (MDT: rifampicin, dapsone and clofazimine). However he developed a severe T1R immediately after completion of the MDT but no signs of allograft rejection. T1R results from flare-ups of the host T-helper-1 cell-mediated immune response against Mycobacterium leprae antigens in patients with immunologically unstable, borderline forms of leprosy and has been considered an inflammatory syndrome in many aspects similar to the immune reconstitution inflammatory syndromes (IRS). The T1R was successfully treated by increasing the prednisone dose without modifying the other immunosuppressive drugs used for preventing allograft rejection. Immunological study revealed that the patient had a profound depletion of both in situ and circulating regulatory T-cells and lack of expansion of the Tregs upon M. leprae stimulation compared to T1R leprosy patients without iatrogenic immunosuppression. Our case report highlights that leprosy, especially in the transplant setting, requires a high degree of clinical suspicion and the contribution of histopathology. It also suggests that the development of upgrading inflammatory syndromes such as T1R can occur
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Resistance of M. leprae to quinolones: a question of relativity?
Veziris, Nicolas; Chauffour, Aurélie; Escolano, Sylvie; Henquet, Sarah; Matsuoka, Masanori; Jarlier, Vincent; Aubry, Alexandra
2013-11-01
Multidrug resistant leprosy, defined as resistance to rifampin, dapsone and fluoroquinolones (FQ), has been described in Mycobacterium leprae. However, the in vivo impact of fluoroquinolone resistance, mainly mediated by mutations in DNA gyrase (GyrA2GyrB2), has not been precisely assessed. Our objective was to measure the impact of a DNA gyrase mutation whose implication in fluoroquinolone resistance has been previously demonstrated through biochemical studies, on the in vivo activity of 3 fluoroquinolones: ofloxacin, moxifloxacin and garenoxacin. We used the proportional bactericidal method. 210 four-week-old immunodeficient female Nude mice (NMRI-Foxn1(nu) /Foxn1(nu) ) were inoculated in the left hind footpad with 0.03 ml of bacterial suspension containing 5 × 10(3), 5 × 10(2), 5 × 10(1), and 5 × 10(0) M. leprae AFB organisms of strain Hoshizuka-4 which is a multidrug resistant strain harboring a GyrA A91V substitution. An additional subgroup of 10 mice was inoculated with 5 × 10(-1) bacilli in the untreated control group. The day after inoculation, subgroups of mice were treated with a single dose of ofloxacin, moxifloxacin, garenoxacin or clarithromycin at 150 mg/kg dosing. 12 months later mice were sacrificed and M. leprae bacilli were numbered in the footpad. The results from the untreated control group indicated that the infective inoculum contained 23% of viable M. leprae. The results from the moxifloxacin and garenoxacin groups indicated that a single dose of these drugs reduced the percentage of viable M. leprae by 90%, similarly to the reduction observed after a single dose of the positive control drug clarithromycin. Conversely, ofloxacin was less active than clarithromycin. DNA gyrase mutation is not always synonymous of lack of in vivo fluoroquinolone activity in M. leprae. As for M. tuberculosis, in vivo studies allow to measure residual antibiotic activity in case of target mutations in M. leprae.
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Ghorab, Mostafa Mohammed; Al-Said, Mansour Sulaiman; Nissan, Yassin Mohammed
2012-01-01
N,N'-(4,4'-Sulfonylbis(4,1-phenylene))bis(2-cyanoacetamid) 2 was utilized as a key intermediate for the synthesis of novel dihydropyridines 3, 4, 8, dihydroisoquinolines 5-7, dithiolan 10, dithian 11, acrylamide 12, benzochromenes 17 and 18 and chromenopyridones 19 and 20. Compound 2 was the starting material in the synthesis of the acrylamide derivative 14, the pyrazole derivative 15 and the pyrazolopyrimidine derivative 16. All the synthesized compounds were evaluated for their in vitro anticancer activity against human breast cancer cell line (MCF7). Compound 19 showed the best cytotoxic activity with IC(50) value 19.36 µM. In addition, molecular docking study of the synthesized compounds on the active sites of farnesyltransferase and arginine methyltransferase was performed in order to give a suggestion about the mechanism of action of their cytotoxic activity.
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Acute arthropod envenomation. Incidence, clinical features and management.
Binder, L S
1989-01-01
Black widow spider (Latrodectus mactans) envenomation is found throughout both the temperate and tropical latitudes, and is one of the leading causes of death from arthropod envenomations worldwide. The venom is highly neurotoxic, affecting the presynaptic motor endplate to allow massive noradrenaline (norepinephrine) and acetylcholine release into synapses causing excessive stimulation and fatigue of the motor end plate and muscle. Clinically, patients develop a bite site lesion and pain, abdominal pain and tenderness, and lower extremity pain and weakness within minutes to hours of envenomation. Symptoms progress over several hours, then subside over 2 to 3 days. The recommended treatment of 'common' envenomation is calcium gluconate 10% intravenously, titrated to relief of symptoms; antivenin, although effective, may cause hypersensitivity and serum sickness reactions, and should be restricted to life-threatening envenomations only. Brown recluse spider (Loxosceles reclusa) envenomations are seen in the Americas and in Europe, and are endemic to the south and central United States. The venom contains at least 8 enzymes, consisting of various lysins (facilitating venom spread) and sphingomyelinase D, which causes cell membrane injury and lysis, thrombosis, local ischaemia, and chemotaxis. Local envenomations begin as pain and itching that progresses to vesiculation with violaceous necrosis and surrounding erythema, and ultimately ulcer formation. Systemic envenomations may be life threatening, and present with fever, constitutional symptoms, petechial eruptions, thrombocytopenia, and haemolysis with haemoglobinuric renal failure. Treatment of local envenomations is conservative (local wound care, cryotherapy, elevation, tetanus prophylaxis, and close follow-up); systemic envenomation requires supportive care and treatment of arising complications, corticosteroids to stabilise red blood cell membranes, and support of renal function. Dapsone 100mg daily has emerged
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2011-01-01
appreciably alter the pharmacokinetics of atovaquone/proguanil, chlorproguanil/dapsone, or sulphadoxine/pyrimethamine, and mefloquine and pyronaridine do not alter the pharmacokinetics of DHA. Finally, there is evidence suggesting that the pharmacokinetics of AS and/or DHA following AS administration may be altered by pregnancy and by acute malaria infection, but further investigation would be required to define those alterations precisely. PMID:21914160
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Munyazesa, Elisaphane; Emile, Ivan; Mutimura, Eugene; Hoover, Donald R; Shi, Qiuhu; McGinn, Aileen P; Musiime, Stephenson; Muhairwe, Fred; Rutagengwa, Alfred; Dusingize, Jean Claude; Anastos, Kathryn
2012-01-01
Objectives Although haematological abnormalities are common manifestations of HIV infection, few studies on haematological parameters in HIV-infected persons have been undertaken in sub-Saharan Africa. The authors assessed factors associated with haematological parameters in HIV-infected antiretroviral-naïve and HIV-uninfected Rwandan women. Study design Cross-sectional analysis of a longitudinal cohort. Setting Community-based women's associations. Participants 710 HIV-infected (HIV+) antiretroviral-naïve and 226 HIV-uninfected (HIV−) women from the Rwanda Women's Interassociation Study Assessment. Haematological parameters categorised as (abnormal vs normal) were compared by HIV status and among HIV+ women by CD4 count category using proportions. Multivariate logistic regression models using forward selection were fit. Results Prevalence of anaemia (haemoglobin (Hb) <12.0 g/dl) was higher in the HIV+ group (20.5% vs 6.3%; p<0.001), and increased with lower CD4 counts: ≥350 (7.6%), 200–349 (16%) and <200 cells/mm3 (32.2%). Marked anaemia (Hb <10.0 g/dl) was found in 4.2% of HIV+ and none of the HIV− women (p<0.001), and was highest in HIV+ women with CD4 <200 cells/mm3 (8.4%). The HIV+ were more likely than HIV− women (4.2 vs 0.5%, respectively, p=0.002) to have moderate neutropenia with white blood cells <2.0×103 cells/mm3 and 8.4% of HIV+ women with CD4 <200 cells/mm3 had moderate neutropenia. In multivariate logistic regression analysis, BMI (OR 0.87/kg/m2, 95% CI 0.82 to 0.93; p<0.001), CD4 200–350 vs HIV− (OR 3.59, 95% CI 1.89 to 6.83; p<0.001) and CD4 <200 cells/mm3 vs HIV− (OR 8.09, 95% CI 4.37 to 14.97; <0.001) had large independent associations with anaemia. There were large independent associations of CD4 <200 cells/mm3 vs HIV− (OR 7.18, 95% CI 0.78 to 65.82; p=0.081) and co-trimoxazole and/or dapsone use (OR 5.69, 95% CI 0.63 to 51.45; p=0.122) with moderate neutropenia. Conclusions Anaemia was more common than neutropenia or
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Hughes, Michael A.; Parisi, Michele; Grossman, Stuart
Purpose: Patients with primary brain tumors are often treated with high doses of corticosteroids for prolonged periods to reduce intracranial swelling and alleviate symptoms such as headaches. This treatment may lead to immunosuppression, placing the patient at risk of life-threatening opportunistic infections, such as Pneumocystis carinii pneumonia. The risk of contracting some types of infection may be reduced with prophylactic antibiotics. The purpose of this study was to determine the occurrence of low CD4 counts and whether monitoring CD4 counts during and after radiotherapy (RT) is warranted. Methods and Materials: CD4 counts were measured during RT in 70 of 76more » consecutive patients with newly diagnosed Grade III and IV astrocytoma and anaplastic oligodendroglioma treated with corticosteroids and seen at the Johns Hopkins Hospital. Weekly CD4 measurements were taken in the most recent 25 patients. Prophylactic trimethoprim-sulfamethoxazole (160 mg/800 mg p.o. every Monday, Wednesday, and Friday) or dapsone (100 mg p.o. daily) in those with sulfa allergy was prescribed only if patients developed a low CD4 count. Carmustine chemotherapy wafers were placed at surgery in 23% of patients, evenly distributed between the groups. No patient received any other chemotherapy concurrent with RT. Results: CD4 counts decreased to <200/mm{sup 3} in 17 (24%) of 70 patients. For the 25 patients with weekly CD4 counts, all CD4 counts were >450/mm{sup 3} before RT, but 6 (24%) of 25 fell to <200/mm{sup 3} during RT. Patients with counts <200/mm{sup 3} were significantly more likely to be hospitalized (41% vs. 9%, p <0.01) and be hospitalized for infection (23% vs. 4%, p <0.05) during RT. Overall survival was not significantly different between the groups. All patients with low CD4 counts were treated with prophylactic antibiotics, and no patient developed Pneumocystis carinii pneumonia. No patients developed a serious adverse reaction to antibiotic therapy. The mean dose
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Araujo, Sergio; Goulart, Luiz Ricardo; Truman, Richard W; Goulart, Isabela Maria B; Vissa, Varalakshmi; Li, Wei; Matsuoka, Masanori; Suffys, Philip; Fontes, Amanda B; Rosa, Patricia S; Scollard, David M; Williams, Diana L
2017-06-01
Real-Time PCR-High Resolution Melting (qPCR-HRM) analysis has been recently described for rapid drug susceptibility testing (DST) of Mycobacterium leprae. The purpose of the current study was to further evaluate the validity, reliability, and accuracy of this assay for M. leprae DST in clinical specimens. The specificity and sensitivity for determining the presence and susceptibility of M. leprae to dapsone based on the folP1 drug resistance determining region (DRDR), rifampin (rpoB DRDR) and ofloxacin (gyrA DRDR) was evaluated using 211 clinical specimens from leprosy patients, including 156 multibacillary (MB) and 55 paucibacillary (PB) cases. When comparing the results of qPCR-HRM DST and PCR/direct DNA sequencing, 100% concordance was obtained. The effects of in-house phenol/chloroform extraction versus column-based DNA purification protocols, and that of storage and fixation protocols of specimens for qPCR-HRM DST, were also evaluated. qPCR-HRM results for all DRDR gene assays (folP1, rpoB, and gyrA) were obtained from both MB (154/156; 98.7%) and PB (35/55; 63.3%) patients. All PCR negative specimens were from patients with low numbers of bacilli enumerated by an M. leprae-specific qPCR. We observed that frozen and formalin-fixed paraffin embedded (FFPE) tissues or archival Fite's stained slides were suitable for HRM analysis. Among 20 mycobacterial and other skin bacterial species tested, only M. lepromatosis, highly related to M. leprae, generated amplicons in the qPCR-HRM DST assay for folP1 and rpoB DRDR targets. Both DNA purification protocols tested were efficient in recovering DNA suitable for HRM analysis. However, 3% of clinical specimens purified using the phenol/chloroform DNA purification protocol gave false drug resistant data. DNA obtained from freshly frozen (n = 172), formalin-fixed paraffin embedded (FFPE) tissues (n = 36) or archival Fite's stained slides (n = 3) were suitable for qPCR-HRM DST analysis. The HRM-based assay was also able to
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Leishmaniasis: recognition and management with a focus on the immunocompromised patient.
Choi, Christine M; Lerner, Ethan A
2002-01-01
lesions on the face or other cosmetically important areas are treated to reduce the size of the resultant scar. In addition, the species of parasite should be identified so that infection with Leishmania braziliensis and Leishmania panamensis can be treated to reduce the risk of development of mucocutaneous disease. Treating patients with Leishmania and HIV co-infection requires close monitoring for effectiveness of treatment, especially because of the high relapse rates. Proven treatments include: antimonials, pentamidine, amphotericin B, interferon with antimony. Treatments where current clinical experience is too limited include: allopurinol, ketoconazole, itraconazole, immunotherapy, rifampin, dapsone, localized heat, paromomycin ointment and cryotherapy. Investigational treatments include: WR6026, liposomal amphotericin and miltefosine. In addition, vaccines for leishmaniasis are being investigated in clinical trials.
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Historical Overview of Leprosy Control in Cuba.
Beldarraín-Chaple, Enrique
2017-01-01
INTRODUCTION Leprosy, an infectious disease caused by Mycobacterium leprae, affects the nervous system, skin, internal organs, extremities and mucous membranes. Biological, social and environmental factors influence its occurrence and transmission. The first effective treatments appeared in 1930 with the development of dapsone, a sulfone. The main components of a control and elimination strategy are early case detection and timely administration of multidrug therapy. OBJECTIVES Review the history of leprosy control in Cuba, emphasizing particularly results of the National Leprosy Control Program, its modifications and influence on leprosy control. EVIDENCE ACQUISITION The historiological method was applied using document review, complemented by interviews with experts on leprosy and its control. Archived documents, medical records, disease prevalence censuses conducted since 1942, and incidence and prevalence statistics for 1960-2015 from the Ministry of Public Health's National Statistics Division were reviewed. Reports and scientific literature published on the Program and the history of leprosy in Cuba were also reviewed. DEVELOPMENT Leprosy has been documented in Cuba since 1613. In 1938, the Leprosy Foundation was created with ten dispensaries nationwide for diagnosis and treatment. The first National Leprosy Control Program was established in 1962, implemented in 1963 and revised five times. In 1972, leper colonies were closed and treatment became ambulatory. In 1977, rifampicin was introduced. In 1988, the Program instituted controlled, decentralized, community-based multidrug treatment and established the criteria for considering a patient cured. In 2003, it included actions aimed at early diagnosis and prophylactic treatment of contacts. Since 2008, it prioritizes actions directed toward the population at risk, maintaining five-year followup with dermatological and neurological examination. Primary health care carries out diagnostic and treatment
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Goulart, Luiz Ricardo; Truman, Richard W.; Goulart, Isabela Maria B.; Vissa, Varalakshmi; Li, Wei; Matsuoka, Masanori; Suffys, Philip; Fontes, Amanda B.; Rosa, Patricia S.; Scollard, David M.; Williams, Diana L.
2017-01-01
Background Real-Time PCR-High Resolution Melting (qPCR-HRM) analysis has been recently described for rapid drug susceptibility testing (DST) of Mycobacterium leprae. The purpose of the current study was to further evaluate the validity, reliability, and accuracy of this assay for M. leprae DST in clinical specimens. Methodology/Principal findings The specificity and sensitivity for determining the presence and susceptibility of M. leprae to dapsone based on the folP1 drug resistance determining region (DRDR), rifampin (rpoB DRDR) and ofloxacin (gyrA DRDR) was evaluated using 211 clinical specimens from leprosy patients, including 156 multibacillary (MB) and 55 paucibacillary (PB) cases. When comparing the results of qPCR-HRM DST and PCR/direct DNA sequencing, 100% concordance was obtained. The effects of in-house phenol/chloroform extraction versus column-based DNA purification protocols, and that of storage and fixation protocols of specimens for qPCR-HRM DST, were also evaluated. qPCR-HRM results for all DRDR gene assays (folP1, rpoB, and gyrA) were obtained from both MB (154/156; 98.7%) and PB (35/55; 63.3%) patients. All PCR negative specimens were from patients with low numbers of bacilli enumerated by an M. leprae-specific qPCR. We observed that frozen and formalin-fixed paraffin embedded (FFPE) tissues or archival Fite’s stained slides were suitable for HRM analysis. Among 20 mycobacterial and other skin bacterial species tested, only M. lepromatosis, highly related to M. leprae, generated amplicons in the qPCR-HRM DST assay for folP1 and rpoB DRDR targets. Both DNA purification protocols tested were efficient in recovering DNA suitable for HRM analysis. However, 3% of clinical specimens purified using the phenol/chloroform DNA purification protocol gave false drug resistant data. DNA obtained from freshly frozen (n = 172), formalin-fixed paraffin embedded (FFPE) tissues (n = 36) or archival Fite’s stained slides (n = 3) were suitable for qPCR-HRM DST
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Lockwood, Diana N J; Darlong, Joydeepa; Govindharaj, Pitchaimani; Kurian, Royce; Sundarrao, Pamidipani; John, Annamma S
2017-03-01
Leprosy Type 1 reactions are difficult to treat and only 70% of patients respond to steroid treatment. Azathioprine has been used as an immune-suppressant and we tested its efficacy in treating leprosy T1R. Randomised controlled trial adding azathioprine to steroid treatment for leprosy reactions. This trial was conducted in four leprosy hospitals in India. Patients with a new leprosy Type 1 reaction affecting either skin or nerve were recruited. They were given a 20 week course of oral prednisolone either with placebo or azathioprine 50mg for 24, 36 or 48 weeks. Outcomes were measured using a verified combined clinical reaction severity score (CCS) and the score difference between baseline and end of study calculated. An intention to treat analysis was done on the 279 patients who had an outcome. 345 patients were recruited, 145 were lost due to adverse events, loss to follow up or death. 36% needed extra steroids due to a recurrence of their skin and/or nerve reaction. 76% of patients had improvements in their CCS the end of the study, 22% had no change and 1.1% deteriorated. Adding azathioprine to steroid treatment did not improve CCS. So the improvements were attributable to treatment with steroids. We analysed the skin, sensory and motor scores separately and found that skin improvement contributed most with 78.9% of patients having skin improvement, azathioprine treatment for 48 weeks improved sensory scores it also improved motor scores but so did treatment with prednisolone alone. We identified significant adverse effects attributable to steroid treatment. When azathioprine and Dapsone were given together significant numbers of patients developed significant anaemia. Azathioprine is not recommended for the treatment of leprosy reactions and does not improve steroid treatment. Recurrent reactions are a major challenge. We have also identified that 65% of patients with sensory and 50% with motor nerve damage do not improve. Future studies should test giving
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Darlong, Joydeepa; Govindharaj, Pitchaimani; Kurian, Royce; Sundarrao, Pamidipani; John, Annamma S.
2017-01-01
Background Leprosy Type 1 reactions are difficult to treat and only 70% of patients respond to steroid treatment. Azathioprine has been used as an immune-suppressant and we tested its efficacy in treating leprosy T1R. Methodology Randomised controlled trial adding azathioprine to steroid treatment for leprosy reactions. This trial was conducted in four leprosy hospitals in India. Patients with a new leprosy Type 1 reaction affecting either skin or nerve were recruited. They were given a 20 week course of oral prednisolone either with placebo or azathioprine 50mg for 24, 36 or 48 weeks. Outcomes were measured using a verified combined clinical reaction severity score (CCS) and the score difference between baseline and end of study calculated. An intention to treat analysis was done on the 279 patients who had an outcome. Principal findings 345 patients were recruited, 145 were lost due to adverse events, loss to follow up or death. 36% needed extra steroids due to a recurrence of their skin and/or nerve reaction. 76% of patients had improvements in their CCS the end of the study, 22% had no change and 1.1% deteriorated. Adding azathioprine to steroid treatment did not improve CCS. So the improvements were attributable to treatment with steroids. We analysed the skin, sensory and motor scores separately and found that skin improvement contributed most with 78.9% of patients having skin improvement, azathioprine treatment for 48 weeks improved sensory scores it also improved motor scores but so did treatment with prednisolone alone. We identified significant adverse effects attributable to steroid treatment. When azathioprine and Dapsone were given together significant numbers of patients developed significant anaemia. Conclusions Azathioprine is not recommended for the treatment of leprosy reactions and does not improve steroid treatment. Recurrent reactions are a major challenge. We have also identified that 65% of patients with sensory and 50% with motor nerve
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Radeva-Petrova, Denitsa; Kayentao, Kassoum; ter Kuile, Feiko O; Sinclair, David; Garner, Paul
2014-10-10
,481 pregnant women met our inclusion criteria. These trials were conducted between 1957 and 2008, in Nigeria (three trials), The Gambia (three trials), Kenya (three trials), Mozambique (two trials), Uganda (two trials), Cameroon (one trial), Burkina Faso (one trial), and Thailand (two trials). Six different antimalarials were evaluated against placebo or no intervention; chloroquine (given weekly), pyrimethamine (weekly or monthly), proguanil (daily), pyrimethamine-dapsone (weekly or fortnightly), and mefloquine (weekly), or intermittent preventive therapy with SP (given twice, three times or monthly). Trials recruited women in their first or second pregnancy (eight trials); only multigravid women (one trial); or all women (eight trials). Only six trials had adequate allocation concealment.For women in their first or second pregnancy, malaria chemoprevention reduces the risk of moderate to severe anaemia by around 40% (RR 0.60, 95% CI 0.47 to 0.75; three trials, 2503 participants, high quality evidence), and the risk of any anaemia by around 17% (RR 0.83, 95% CI 0.74 to 0.93; five trials,, 3662 participants, high quality evidence). Malaria chemoprevention reduces the risk of antenatal parasitaemia by around 61% (RR 0.39, 95% CI 0.26 to 0.58; seven trials, 3663 participants, high quality evidence), and two trials reported a reduction in febrile illness (low quality evidence). There were only 16 maternal deaths and these trials were underpowered to detect an effect on maternal mortality (very low quality evidence).For infants of women in their first and second pregnancies, malaria chemoprevention probably increases mean birthweight by around 93 g (MD 92.72 g, 95% CI 62.05 to 123.39; nine trials, 3936 participants, moderate quality evidence), reduces low birthweight by around 27% (RR 0.73, 95% CI 0.61 to 0.87; eight trials, 3619 participants, moderate quality evidence), and reduces placental parasitaemia by around 46% (RR 0.54, 95% CI 0.43 to 0.69; seven trials, 2830 participants
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Radeva-Petrova, Denitsa; Kayentao, Kassoum; ter Kuile, Feiko O; Sinclair, David; Garner, Paul
2014-01-01
assessed the quality of evidence using the GRADE approach. Main results Seventeen trials enrolling 14,481 pregnant women met our inclusion criteria. These trials were conducted between 1957 and 2008, in Nigeria (three trials), The Gambia (three trials), Kenya (three trials), Mozambique (two trials), Uganda (two trials), Cameroon (one trial), Burkina Faso (one trial), and Thailand (two trials). Six different antimalarials were evaluated against placebo or no intervention; chloroquine (given weekly), pyrimethamine (weekly or monthly), proguanil (daily), pyrimethamine-dapsone (weekly or fortnightly), and mefloquine (weekly), or intermittent preventive therapy with SP (given twice, three times or monthly). Trials recruited women in their first or second pregnancy (eight trials); only multigravid women (one trial); or all women (eight trials). Only six trials had adequate allocation concealment. For women in their first or second pregnancy, malaria chemoprevention reduces the risk of moderate to severe anaemia by around 40% (RR 0.60, 95% CI 0.47 to 0.75; three trials, 2503 participants, high quality evidence), and the risk of any anaemia by around 17% (RR 0.83, 95% CI 0.74 to 0.93; five trials,, 3662 participants, high quality evidence). Malaria chemoprevention reduces the risk of antenatal parasitaemia by around 61% (RR 0.39, 95% CI 0.26 to 0.58; seven trials, 3663 participants, high quality evidence), and two trials reported a reduction in febrile illness (low quality evidence). There were only 16 maternal deaths and these trials were underpowered to detect an effect on maternal mortality (very low quality evidence). For infants of women in their first and second pregnancies, malaria chemoprevention probably increases mean birthweight by around 93 g (MD 92.72 g, 95% CI 62.05 to 123.39; nine trials, 3936 participants, moderate quality evidence), reduces low birthweight by around 27% (RR 0.73, 95% CI 0.61 to 0.87; eight trials, 3619 participants, moderate quality evidence), and