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International Journal of Dermatology May 2017Pyoderma gangrenosum (PG) is a sterile neutrophilic disorder that rarely affects children. Clinical, epidemiological, and therapeutic data on pediatric PG is poor as... (Review)
Review
Pyoderma gangrenosum (PG) is a sterile neutrophilic disorder that rarely affects children. Clinical, epidemiological, and therapeutic data on pediatric PG is poor as there are many newly reported associated diseases and drugs. This paper aims to review all recent available data on pediatric PG. A systematic review of the literature was conducted using Embase, Medline, and Cochrane databases. A total of 132 articles were included in the review. The most commonly reported underlying diseases in pediatric PG are inflammatory bowel diseases followed by hematologic disorders, vasculitis, immune deficiencies and Pyogenic Arthritis, Pyoderma gangrenosum and Acne (PAPA) syndrome. More than half of the cases occur with no underlying disease. The most frequently reported clinical presentation is multiple disseminated ulcers. Treatment should be tailored according to the underlying etiology. It includes systemic steroids, corticosteroid sparing agents such as dapsone and cyclosporine, and TNF-alpha inhibitors such as adalimumab and infliximab. Response to treatment is high with cure rates reaching 90%. A high index of suspicion and a thorough workup are mandatory in the management of pediatric PG.
Topics: Acne Vulgaris; Adolescent; Arthritis, Infectious; Child; Child, Preschool; Hematologic Diseases; Humans; Immunologic Deficiency Syndromes; Infant; Infant, Newborn; Inflammatory Bowel Diseases; Pyoderma Gangrenosum; Vasculitis
PubMed: 28233293
DOI: 10.1111/ijd.13584 -
The American Journal of Tropical... May 2017AbstractDapsone is a bactericidal and bacteriostatic against , a causative agent of leprosy. Dapsone is also applied in a range of medical fields because of its... (Review)
Review
AbstractDapsone is a bactericidal and bacteriostatic against , 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.
Topics: Adolescent; Adult; Aged; Alleles; Child; China; Dapsone; Drug Hypersensitivity; Drug Substitution; Female; Genetic Testing; HLA-B13 Antigen; Humans; Leprostatic Agents; Leprosy; Male; Middle Aged; Mycobacterium leprae; Prevalence; Primary Prevention; Survival Analysis; Syndrome
PubMed: 28167593
DOI: 10.4269/ajtmh.16-0628 -
The Cochrane Database of Systematic... Jul 2016There have been a number of studies with conflicting results which have examined the effect of anti-tuberculous therapy in Crohn's disease. A meta-analysis was performed... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
There have been a number of studies with conflicting results which have examined the effect of anti-tuberculous therapy in Crohn's disease. A meta-analysis was performed to evaluate the use of anti-tuberculous therapy for the maintenance of remission in Crohn's disease.
OBJECTIVES
To evaluate the effects of anti-tuberculous therapy for the maintenance of remission in patients with Crohn's disease.
SEARCH METHODS
We searched MEDLINE, EMBASE, the Cochrane LIbrary, and the Cochrane IBD Group Specialized Register from inception to June 22, 2015.
SELECTION CRITERIA
Randomized controlled trials (RCTs) of anti-tuberculous therapy compared to placebo or another active therapy in patients with quiescent Crohn's disease were considered for inclusion.
DATA COLLECTION AND ANALYSIS
At least two authors independently extracted data and assessed the quality of included studies using the Cochrane risk of bias tool. We calculated the risk ratio (RR) and corresponding 95% confidence interval (CI) for dichotomous outcomes.. The primary outcome was relapse. Secondary outcomes included adverse events, withdrawals due to adverse events and serious adverse events. All data were analyzed on an intention-to-treat basis. The overall quality of the evidence supporting the primary and secondary outcomes was evaluated using the GRADE criteria.
MAIN RESULTS
Four placebo-controlled RCTs including 206 participants were included. Three trials included an 8 to 16 week induction phase with tapering corticosteroids (prednisone, prednisolone or methylprednisolone) as induction therapy. Anti-tuberculous therapy included monotherapy with clofazimine, combination therapy with clofazimine, rifampin, ethambutol, and dapsone or combination therapy with clarithromycin, rifabutin and clofazimine. All of the studies were rated as unclear risk of bias for allocation concealment, three were rated as unclear risk of bias for random sequence generation and two were rated as unclear risk of bias for blinding or participants and personnel. There was a statistically significant difference in relapse rates favoring anti-tuberculous therapy over placebo. Thirty-nine per cent (44/112) of patients in the anti-tuberculous therapy group relapsed at 9 months to 2 years compared to 67% (63/94) of placebo patients (RR 0.58, 95% CI 0.45 to 0.75, I(2) = 47%). A GRADE analysis indicates that the overall quality of the evidence supporting this outcome was very low due to unknown risk of bias and sparse data. Adverse events occurred more frequently in the anti-tuberculous therapy group (37/159) compared to the placebo group (14/163) with a pooled RR of 2.57 (95% CI 1.45 to 4.55; N=322; studies=4, I(2)=64%). A GRADE analysis indicates that the overall quality of the evidence supporting this outcome was very low due to unknown risk of bias, unexplained heterogeneity and sparse data. There was no difference in withdrawals due to adverse events. Nine per cent (14/159) of anti-tuberculous therapy patients withdrew due to adverse events compared to 7% (11/163) of placebo patients (RR 1.29, 95% CI 0.60 to 2.77, I(2) = 0%). Common adverse events included increased skin pigmentation and rashes. No serious adverse events were reported in any of the included studies.
AUTHORS' CONCLUSIONS
Anti-tuberculous therapy may provide a benefit over placebo for the prevention of relapse in participants with Crohn's disease in remission. However, this result is very uncertain due to unclear study quality and the small numbers of patients assessed. Further studies are needed to provide better quality evidence for the use of anti-tuberculous therapy for maintaining remission in people with quiescent Crohn's disease.
Topics: Antitubercular Agents; Clarithromycin; Clofazimine; Crohn Disease; Ethambutol; Glucocorticoids; Humans; Maintenance Chemotherapy; Methylprednisolone; Prednisone; Randomized Controlled Trials as Topic; Recurrence; Remission Induction; Rifabutin; Rifampin; Secondary Prevention
PubMed: 27444319
DOI: 10.1002/14651858.CD000299.pub3 -
Journal of the European Academy of... Sep 2016Eosinophilic cellulitis (Wells syndrome) is a rare inflammatory skin disease defined by erythematous, tender, sometimes urticarial plaques, possibly with vesicles and... (Review)
Review
Eosinophilic cellulitis (Wells syndrome) is a rare inflammatory skin disease defined by erythematous, tender, sometimes urticarial plaques, possibly with vesicles and bullae, and granulomatous eosinophilic infiltrates in the dermis. Usually the disease has a benign course with spontaneous remission within a few weeks. Nevertheless, recurrences are quite frequent and may occur for several years. The objective of this study was to review the so far reported treatment options for Wells syndrome in a systematic manner. This systematic review is based on a search on Medline, Embase and Cochrane Central Register for English and German articles from 1970 to 2015. Advices on the treatment of Wells syndrome are limited predominately to case reports or to small case series. There are no randomized controlled trials, and control groups are missing. A variety of treatment options for Wells syndrome were reported including topical and systemic corticosteroids, antihistamines, cyclosporine, dapsone, azathioprine, griseofulvin, doxycycline, minocycline, antimalarial medications, oral tacrolimus/topical tacrolimus, sulfasalazine, interferon alpha and gamma, TNF alpha inhibitors, colchicine and PUVA therapy. As well-designed, randomized controlled trials are missing, no guidelines for the treatment of this disease can be given. Due to the small number of patients and the frequent misdiagnosis of this clinical entity, the aim of this systematic overview is to call attention to this rare condition and to help clinicians to diagnose and treat Wells syndrome effectively. Due to the good prognosis and tendency to resolve, systemic treatment should be limited to cases resistant to local therapy or with widespread lesions.
Topics: Cellulitis; Dermatologic Agents; Eosinophilia; Humans
PubMed: 27357601
DOI: 10.1111/jdv.13706 -
The British Journal of Dermatology Dec 2018Clinically amyopathic dermatomyositis (CADM) affects a subset of 5-20% of patients with dermatomyositis and is defined as the presence of cutaneous features of...
Clinically amyopathic dermatomyositis (CADM) affects a subset of 5-20% of patients with dermatomyositis and is defined as the presence of cutaneous features of dermatomyositis without clinical muscle weakness for ≥ 6 months. There is no consensus on first-line treatment for CADM and whether treatment should differ from treatment of classic dermatomyositis with muscle weakness. We carried out a systematic review of published literature about treatment of adult patients with CADM, via the Embase, Medline, CINAHL and ClinicalTrials.gov databases on 17 February 2015. The aim was to establish which treatments have been used for adult-onset CADM and what evidence is available regarding the efficacy of these treatments including topical treatments, dapsone, antimalarials, intravenous immunoglobulin (IVIG), nonsteroidal oral immunosuppressants and biological therapies. Eighteen cases series and 42 case reports were found. These provided data on 153 adult patients who met the inclusion criteria. No randomized controlled trials or robust observational studies were found. The majority of patients (60%) had tried more than one treatment due to side-effects or lack of efficacy. Antimalarial agents were the most commonly used treatment type. In the majority of patients (55%), antimalarial treatments were discontinued due to lack of improvement or inability to wean concomitant steroids. IVIG was the treatment that led to improvement or remission in the greatest proportion of patients. Further robust, high-quality studies are needed to assess treatment efficacy in CADM without bias.
Topics: Adult; Antimalarials; Dermatomyositis; Humans; Immunoglobulins, Intravenous; Treatment Outcome
PubMed: 27167896
DOI: 10.1111/bjd.14726 -
Oral Surgery, Oral Medicine, Oral... Aug 2015To determine the efficacy and safety of interventions for mucous membrane pemphigoid (MMP). (Review)
Review
OBJECTIVE
To determine the efficacy and safety of interventions for mucous membrane pemphigoid (MMP).
STUDY DESIGN
We conducted a systematic review from 2003 to 2013 according to the Cochrane Collaboration methodology. Randomized controlled trials (RCTs) or controlled clinical trials and observational studies were included, with diagnosis confirmed by clinical, histopathologic, and immunofluorescence criteria. The primary outcome was lesion remission or healing; several relevant secondary outcomes were also included.
RESULTS
In the final analysis, 1 RCT and 32 observational studies were included. The one included RCT with a high risk of bias in multiple domains found limited evidence that pentoxifylline, combined with corticosteroid and cyclophosphamide, was more effective than standard therapy (corticosteroid + cyclophosphamide alone) for ocular MMP. We summarize here the outcomes from 32 observational studies examining 242 patients across 19 unique treatments. Interventions that show promise include rituximab and intravenous immunoglobulin.
CONCLUSIONS
This systematic review is the most recent since 2003-2009. There is still lack of high-quality research providing evidence-based MMP treatments.
Topics: Anti-Infective Agents; Cyclophosphamide; Dapsone; Glucocorticoids; Humans; Immunoglobulins, Intravenous; Immunosuppressive Agents; Pemphigoid, Benign Mucous Membrane; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 25953640
DOI: 10.1016/j.oooo.2015.01.024 -
The Cochrane Database of Systematic... Apr 2015Pneumocystis jiroveci pneumonia (PCP) remains the most common opportunistic infection in patients infected with the human immunodeficiency virus (HIV). Among patients... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pneumocystis jiroveci pneumonia (PCP) remains the most common opportunistic infection in patients infected with the human immunodeficiency virus (HIV). Among patients with HIV infection and PCP the mortality rate is 10% to 20% during the initial infection and this increases substantially with the need for mechanical ventilation. It has been suggested that corticosteroids adjunctive to standard treatment for PCP could prevent the need for mechanical ventilation and decrease mortality in these patients.
OBJECTIVES
To assess the effects of adjunctive corticosteroids on overall mortality and the need for mechanical ventilation in HIV-infected patients with PCP and substantial hypoxaemia (arterial oxygen partial pressure < 70 mmHg or alveolar-arterial gradient > 35 mmHg on room air).
SEARCH METHODS
For the original review we searched The Cochrane Library (2004, Issue 4), MEDLINE (January 1980 to December 2004) and EMBASE (January 1985 to December 2004) without language restrictions. We further reviewed the reference lists from previously published overviews, searched UptoDate version 2005 and Clinical Evidence Concise (Issue 12, 2004), contacted experts in the field and searched the reference lists of identified publications for citations of additional relevant articles.In this update of our review, we searched the above-mentioned databases in September 2010 and April 2014 for trials published since our original review. We also searched for ongoing trials in ClinicalTrials.gov and the World Health Organization International Clinical Trial Registry Platform (ICTRP). We searched for conference abstracts via AEGIS.
SELECTION CRITERIA
Randomised controlled trials that compared corticosteroids to placebo or usual care in HIV-infected patients with PCP in addition to baseline treatment with trimethoprim-sulfamethoxazole, pentamidine or dapsone-trimethoprim, and reported mortality data. We excluded trials in patients with no or mild hypoxaemia (arterial oxygen partial pressure > 70 mmHg or an alveolar-arterial gradient < 35 mmHg on room air) and trials with a follow-up of less than 30 days.
DATA COLLECTION AND ANALYSIS
Two teams of review authors independently evaluated the methodology and extracted data from each primary study. We pooled treatment effects across studies and calculated a weighted average risk ratio of overall mortality in the treatment and control groups using a random-effects model.In this update of our review, we used the GRADE methodology to assess evidence quality.
MAIN RESULTS
Of 2029 screened records, we included seven studies in the review and six in the meta-analysis. Risk of bias varied: the randomisation and allocation process was often not clearly described, five of seven studies were double-blind and there was almost no missing data. The quality of the evidence for mortality was high. Risk ratios for overall mortality for adjunctive corticosteroids were 0.56 (95% confidence interval (CI) 0.32 to 0.98) at one month and 0.59 (95% CI 0.41 to 0.85) at three to four months of follow-up. In adults, to prevent one death, numbers needed to treat are nine patients in a setting without highly active antiretroviral therapy (HAART) available, and 23 patients with HAART available. The three largest trials provided moderate quality data on the need for mechanical ventilation, with a risk ratio of 0.38 (95% CI 0.20 to 0.73) in favour of adjunctive corticosteroids. One study was conducted in infants, suggesting a risk ratio for death in hospital of 0.81 (95% CI 0.51 to 1.29; moderate quality evidence).
AUTHORS' CONCLUSIONS
The number and size of trials investigating adjunctive corticosteroids for HIV-infected patients with PCP is small, but the evidence from this review suggests a beneficial effect for adult patients with substantial hypoxaemia. There is insufficient evidence on the effect of adjunctive corticosteroids on survival in infants.
Topics: AIDS-Related Opportunistic Infections; Adrenal Cortex Hormones; Adult; Chemotherapy, Adjuvant; Humans; Hypoxia; Pneumocystis carinii; Pneumonia, Pneumocystis; Randomized Controlled Trials as Topic; Respiration, Artificial
PubMed: 25835432
DOI: 10.1002/14651858.CD006150.pub2 -
Drugs Feb 2015While a variety of intervention options have been described for pemphigus vulgaris, the optimal treatment strategy has not been established. (Review)
Review
BACKGROUND
While a variety of intervention options have been described for pemphigus vulgaris, the optimal treatment strategy has not been established.
OBJECTIVES
The objective of this systematic review is to assess the literature on the efficacy and safety of interventions for the treatment of pemphigus vulgaris.
DATA SOURCES
Five electronic databases were searched, including The Cochrane Skin Group's Specialized Register, The Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, MEDLINE and Latin American and Caribbean Health science Information database (LILACS). Five trial registers as well as reference lists of included RCTs were also searched.
STUDY ELIGIBILITY CRITERIA
Any published randomised controlled trial (RCT) on intervention for pemphigus vulgaris was included, provided the diagnosis of pemphigus vulgaris was confirmed with appropriate clinical features, histopathology and immunofluorescence studies. Studies which included forms of pemphigus other than pemphigus vulgaris were excluded.
INTERVENTIONS
Altogether 18 RCTs were identified including 16 distinct interventions.
STUDY APPRAISAL AND SYNTHESIS METHODS
Included studies were assessed for patient selection, methods of randomisation, blinding, follow-up and selective reporting.
RESULTS
Current evidence is incomplete and inconclusive. The interventions which appear promising, but will require further evaluation include adjuvant mycophenolate mofetil (MMF), azathioprine, intravenous immunoglobulins (IVIG), sulfasalazine and pentoxifylline, infliximab, epidermal growth factor and pimecrolimus. Interventions with inconclusive evidence include high (120-180 mg) versus low (45-60 mg) prednisone dosage, pulsed dexamethasone, cyclophosphamide, dexamethasone-cyclophosphamide pulse therapy (DCP), cyclosporine, dapsone, etanercept, acyclovir and tacrolimus.
LIMITATIONS
Our review is limited by the small number of high-quality RCTs and variety of outcome measures, precluding the performing of a meta-analysis.
CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS
The optimal treatment strategy for pemphigus vulgaris remains unclear. Higher quality RCTs are required in the future to re-evaluate many interventions and to explore other unstudied interventions.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Dose-Response Relationship, Drug; Glucocorticoids; Humans; Immunologic Factors; Pemphigus; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 25655250
DOI: 10.1007/s40265-015-0353-6 -
Journal of the European Academy of... Aug 2015Granuloma annulare (GA) is a benign inflammatory skin disease. Localized GA is likely to resolve spontaneously, while generalized GA (GGA) is rare and may persist for... (Review)
Review
Granuloma annulare (GA) is a benign inflammatory skin disease. Localized GA is likely to resolve spontaneously, while generalized GA (GGA) is rare and may persist for decades. GGA usually is resistant to a variety of therapeutic modalities and takes a chronic course. The objective of this study was to summarize all reported treatments of generalized granuloma annulare. This is a systematic review based on MEDLINE, Embase and Cochrane Central Register search of articles in English and German and a manual search, between 1980 and 2013, to summarize the treatment of generalized granuloma annulare. Most medical literature on treatment of GGA is limited to individual case reports and small series of patients treated without a control group. Randomized controlled clinical studies are missing. Multiple treatment modalities for GGA were reported including topical and systemic steroids, PUVA, isotretinoin, dapsone, pentoxifylline, hydroxychloroquine, cyclosporine, IFN-γ, potassium iodide, nicotinamide, niacinamide, salicylic acid, dipyridamole, PDT, fumaric acid ester, etanercept, infliximab, adalimumab. While there are numerous case reports of successful treatments in the literature including surgical, medical and phototherapy options, well-designed, randomized, controlled clinical trials are required for an evidence-based treatment of GGA.
Topics: Granuloma Annulare; Humans
PubMed: 25651003
DOI: 10.1111/jdv.12976 -
International Journal of Dermatology Sep 2015Patients with chronic spontaneous urticaria (CSU) are sometimes unresponsive to nonsedating, second-generation, H1 antihistamines; this study summarizes published... (Review)
Review
BACKGROUND
Patients with chronic spontaneous urticaria (CSU) are sometimes unresponsive to nonsedating, second-generation, H1 antihistamines; this study summarizes published clinical evidence for patients who remain symptomatic despite treatment.
OBJECTIVE
To evaluate, via a systematic literature review, clinical evidence of management strategies for patients with CSU who remain symptomatic despite approved use of nonsedating H1 antihistamines.
METHODS
Using a prespecified protocol, we searched MEDLINE, Embase, the Cochrane Library (1 January 1960-20 December 2011), and published conference abstracts (2010-2012). Rigorous criteria identified trials in patients with CSU who had a history of inadequate response to previous treatment or had used combination treatments. Trials evaluating treatment-naïve patients or first-line therapies were excluded.
RESULTS
Qualitative data synthesized from 26 randomized, controlled trials, four prospective studies, and one retrospective study showed cyclosporine, desloratadine plus dapsone or dipyridamole, montelukast, and omalizumab reduced urticaria activity scores, weals, and pruritus, versus placebo. Optimal treatment doses and durations were unclear due to varying trial durations, outcome measurement scales, and assessment timings. No safety concerns were reported.
CONCLUSIONS
This review confirms that available evidence to guide treatment choice for patients with CSU with inadequate response to H1 antihistamines varies in quality. Further research is warranted due to low-quality trials with methodological and reporting limitations.
Topics: Cholinergic Antagonists; Chronic Disease; Drug Therapy, Combination; Female; Histamine H1 Antagonists, Non-Sedating; Humans; Male; Prospective Studies; Randomized Controlled Trials as Topic; Retrospective Studies; Risk Assessment; Severity of Illness Index; Treatment Failure; Urticaria
PubMed: 25515967
DOI: 10.1111/ijd.12727