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The Journal of Allergy and Clinical... Feb 2019Urticarial vasculitis (UV) is a difficult-to-treat condition characterized by long-lasting urticarial rashes and histopathologic findings of leukocytoclastic vasculitis....
Urticarial vasculitis (UV) is a difficult-to-treat condition characterized by long-lasting urticarial rashes and histopathologic findings of leukocytoclastic vasculitis. Treatment is dictated by the severity of skin and systemic involvement and the underlying systemic disease. This is a comprehensive systematic review of the efficacy of current UV treatment options. We searched for relevant studies in 7 databases, including MEDLINE, Scopus, and Web of Science. In total, 261 eligible studies and 789 unique patients with UV were included in the systematic review. Most patients with UV are adult women with chronic (≥6 weeks) and systemic disease. UV is mostly idiopathic but can be associated with drugs, malignancy, autoimmunity, and infections. It usually resolves with their withdrawal or cure. Corticosteroids are effective for the treatment of skin symptoms in more than 80% of patients with UV. However, their long-term administration can lead to potentially serious adverse effects. The addition of immunomodulatory or immunosuppressive agents often allows corticosteroid tapering and improves the efficacy of therapy. Biologicals, including omalizumab, as well as corticosteroids, cyclophosphamide, dapsone, mycophenolate mofetil, plasmapheresis, colchicine, hydroxychloroquine, intravenous immunoglobulin, nonsteroidal anti-inflammatory drugs, and cyclosporine, can be effective for both skin and systemic symptoms in patients with UV. H-antihistamines, montelukast, danazol, H-antihistamines, pentoxifylline, doxepin, and tranexamic acid are not effective in most patients with UV. As of yet, no drugs have been approved for UV, and management recommendations are based mostly on case reports and retrospective studies. Prospective studies investigating the effects of treatment on the signs and symptoms of UV are needed.
Topics: Adrenal Cortex Hormones; Adult; Animals; Biological Therapy; Female; Humans; Immunosuppressive Agents; Male; Omalizumab; Skin; Urticaria; Vasculitis
PubMed: 30268388
DOI: 10.1016/j.jaci.2018.09.007 -
JBI Database of Systematic Reviews and... Jul 2018The objective of this review was to determine the best available evidence on the most effective treatment of Madura foot.
REVIEW QUESTION/OBJECTIVE
The objective of this review was to determine the best available evidence on the most effective treatment of Madura foot.
INTRODUCTION
Madura foot or mycetoma is a chronic granulomatous soft-tissue infection that is endemic to several regions of Africa and Asia. It may be of fungal (eumycetoma) or bacterial (actinomycetoma) origin, warranting therapy with either antifungal or antibacterial medication as well as surgery. Without timely intervention, it often results in lifelong disability. However, it is unclear what regimes are most effective for treatment.
INCLUSION CRITERIA
This review considered studies that included individuals of all ages with Madura foot (actinomycetoma or eumycetoma) as confirmed by microbiological or histological studies. Studies that evaluated antibiotic and antifungal regimens (any drug, dosage, frequency, duration) as well as surgical interventions (wound debridement, advanced excision or limb amputation) for Madura foot were included. Outcomes of interest were disease resolution (as determined by complete healing of mycetoma lesion after treatment), recurrence (return of mycetoma lesion after successful treatment) and mortality. Although this review considered both experimental and epidemiological study designs for inclusion, only case series and individual case reports were identified and were therefore included in the review.
METHODS
A three-step search strategy, involving an initial search, a second more comprehensive search using identified keywords and a third search involving the reference lists of included articles, was utilized. Ten databases were searched. An additional 13 sources were searched for gray and/or unpublished literature. Included studies were assessed by two independent reviewers for methodological validity prior to inclusion in the review using standardized critical appraisal instruments from the Joanna Briggs Institute. Disagreements were resolved through discussion or with a third reviewer. A data extraction tool was used to extract data on interventions, populations, study designs and outcomes of significance to the review question. Statistical pooling was not possible, therefore a narrative synthesis was performed.
RESULTS
Thirty-one studies were included in the review (27 case reports and four case series). A total of 47 patients with Madura foot were analyzed. Twenty-five had eumycetoma, 21 actinomycetoma and one had both. Therapy involved varying dosages of sulfa drugs (co-trimoxazole and dapsone), amikacin and tetracyclines administered for the therapy of actinomycetoma with resolution of disease in all affected patients. The azole derivatives (itraconazole, ketoconazole, voriconazole, fluconazole and miconazole) as well as co-trimoxazole were the most commonly employed drugs for eumycetoma, with resolution of disease in 88% of included patients. Surgery was performed in a total of 21 patients with resolution of disease in all cases. The overall resolution rate following therapy was 95.7%.
CONCLUSION
Therapy for Madura foot is informed by case series and case reports which provide low level evidence for practice. Antimicrobials in conjunction with surgery lead to resolution of disease.
Topics: Adult; Africa; Amputation, Surgical; Anti-Bacterial Agents; Antifungal Agents; Humans; Mycetoma; Treatment Outcome
PubMed: 29995713
DOI: 10.11124/JBISRIR-2017-003433 -
Journal of Cutaneous Medicine and... 2018Generalized pustular psoriasis (GPP) is a rare but serious and difficult to treat cutaneous disease, with high morbidity and mortality rates. Despite the numerous...
Generalized pustular psoriasis (GPP) is a rare but serious and difficult to treat cutaneous disease, with high morbidity and mortality rates. Despite the numerous treatment regimens available, the overall quality of evidence-based research is limited with a lack of an algorithmic approach available. In this review, we aim to evaluate the current level of evidence regarding the efficacy and safety/tolerability of systemic monotherapies available in the treatment of GPP. A comprehensive MEDLINE, EMBASE, and PubMed search of clinical studies examining systemic monotherapy treatment options for GPP was conducted. In total, 31 studies met eligibility criteria. Described treatment modalities included retinoids, cyclosporine, biologics, and dapsone. Despite the lack of high-quality evidence or a well-accepted treatment algorithm for GPP, systemic retinoids, cyclosporine, biologics, and dapsone are all possible first-line agents, with retinoids being one of the best-supported treatment options and biologics as an emerging therapeutic field with great potential requiring additional data. However, the final choice of treatment should be considered within the unique context of each patient.
Topics: Adult; Female; Humans; Male; Middle Aged; Psoriasis
PubMed: 29707979
DOI: 10.1177/1203475418773358 -
JAMA Dermatology Apr 2018Dapsone-induced hypersensitivity syndrome (DHS) is a life-threatening adverse drug reaction. Based on available epidemiologic studies, HLA genotypes may play an... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Dapsone-induced hypersensitivity syndrome (DHS) is a life-threatening adverse drug reaction. Based on available epidemiologic studies, HLA genotypes may play an important role in DHS.
OBJECTIVE
To assess the association between HLA-B*1301 and dapsone-induced cutaneous adverse drug reactions (cADRs).
DATA SOURCES
Human studies investigating associations between HLA-B*1301 and dapsone-induced cADRs were systematically searched without language restriction from the inception of each database until September 12, 2017, in PubMed, the Human Genome Epidemiology Network), and the Cochrane Library. Combinations of HLA genotypes, dapsone, and synonymous terms were used; reference lists were searched in selected articles.
STUDY SELECTION
Two reviewers identified studies investigating the associations between HLA-B*1301 and dapsone-induced cADRs that reported sufficient data for calculating the frequency of HLA-B*1301 carriers among case and control patients, in which all patients received dapsone before HLA-B*1301 screening. An initial search of the databases identified 391 articles, of which 3 studies (2 in Chinese populations and 1 in a Thai population) met the inclusion criteria.
DATA EXTRACTION AND SYNTHESIS
Overall odds ratios (ORs) with 95% CIs were calculated using a random-effects model to determine the association between HLA-B*1301 and dapsone-induced cADRs. Subgroup analyses by type of cADR were also performed. PRISMA guidelines were used to abstract and assess data.
MAIN OUTCOMES AND MEASURES
Primary outcomes were associations between HLA-B*1301 and dapsone-induced cADRs in dapsone-tolerant controls. The outcomes are reported as overall OR. Statistical heterogeneity was assessed using the Q statistic and I2 tests.
RESULTS
From the 3 included studies, there were 111 unique patients with dapsone-induced cADRs (subsequently used in the meta-analysis), 1165 dapsone-tolerant patients, and 3026 healthy controls. The cases included 64 men and 49 women (2 patients were missing from the meta-analysis; 1 each from 2 of the 3 studies); mean age was 39.7 years. An association between HLA-B*1301 and dapsone-induced cADRs was identified (summary OR, 43.0; 95% CI, 24.0-77.2). Subgroup analyses among types of cADRs produced similar findings in DHS (OR, 51.7; 95% CI, 16.9-158.5), dapsone-induced severe cADRs (Stevens-Johnson syndrome and toxic epidermal necrolysis [SJS/TEN] plus drug rash [adverse skin reaction to a drug] along with eosinophilia and systemic symptoms [DRESS]) (OR, 54.0; 95% Cl, 8.0-366.2), dapsone-induced SJS/TEN (OR, 40.5; 95% CI, 2.8-591.0), and dapsone-induced DRESS (OR, 60.8; 95% CI, 7.4-496.2). There was no heterogeneity (I2 = 0%, P = .38).
CONCLUSIONS AND RELEVANCE
Associations between HLA-B*1301 and dapsone-induced cADRs were found in dapsone-tolerant and healthy control groups. For patient safety, genetic screening for HLA-B*1301 in Asian populations before dapsone therapy is warranted.
Topics: Anti-Infective Agents; Dapsone; Drug Eruptions; Drug Hypersensitivity Syndrome; Genotype; HLA-B13 Antigen; Humans
PubMed: 29541744
DOI: 10.1001/jamadermatol.2017.6484 -
The British Journal of Dermatology Aug 2018Pyoderma gangrenosum (PG) is a neutrophilic dermatosis with substantial morbidity. There is no consensus on gold-standard treatments.
BACKGROUND
Pyoderma gangrenosum (PG) is a neutrophilic dermatosis with substantial morbidity. There is no consensus on gold-standard treatments.
OBJECTIVES
To review the effectiveness of systemic therapy for PG.
METHODS
We searched six databases for 24 systemic therapies for PG. Primary outcomes were complete healing and clinical improvement; secondary outcomes were time to healing and adverse effects.
RESULTS
We found 3326 citations and 375 articles underwent full-text review; 41 studies met the inclusion criteria. There were 704 participants in 26 retrospective cohort studies, three prospective cohort studies, seven case series, one case-control study, two open-label trials and two randomized controlled trials (RCTs). Systemic corticosteroids were the most studied (32 studies), followed by ciclosporin (21 studies), biologics (16 studies) and oral dapsone (11 studies). One RCT (STOP-GAP, n = 121) showed that prednisolone and ciclosporin were similar: 15-20% of patients showed complete healing at 6 weeks and 47% at 6 months. Another RCT (n = 30) found that infliximab was superior to placebo at 2 weeks (46% vs. 6% response), with a 21% complete healing rate at 6 weeks. Two uncontrolled trials showed 60% and 37% healing within 4 months for canakinumab and infliximab, respectively; other data suggest that patients with concurrent inflammatory bowel disease may benefit from biologics. The remaining studies were poor quality and had small sample sizes but supported the use of corticosteroids, ciclosporin and biologics.
CONCLUSIONS
Systemic corticosteroids, ciclosporin, infliximab and canakinumab had the most evidence in treating PG. However, current literature is limited to small and lower-quality studies with substantial heterogeneity.
Topics: Administration, Oral; Biological Products; Clinical Trials as Topic; Cyclosporine; Dapsone; Dose-Response Relationship, Drug; Glucocorticoids; Humans; Injections, Intralesional; Injections, Intravenous; Observational Studies as Topic; Pyoderma Gangrenosum; Treatment Outcome
PubMed: 29478243
DOI: 10.1111/bjd.16485 -
Medicine Sep 2017Corticosteroid sparing is required in 15% to 40% of adults with persistent or chronic primary immune thrombocytopenic purpura (ITP). Herein, the efficacy of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Corticosteroid sparing is required in 15% to 40% of adults with persistent or chronic primary immune thrombocytopenic purpura (ITP). Herein, the efficacy of immunomodulatory drugs (dapsone, interferon alpha, danazol, and hydroxychloroquine as second-third-line therapies in ITP is investigated.
METHODS
MEDLINE was searched for studies that included patients with persistent or chronic primary ITP and published before the end of December 2014. Two investigators independently extracted data regarding study design, patient characteristics, dosage schedule, time to response, and occurrence of adverse events. The pooled overall response rate (ORR; platelet count >30 × 10 L) and the complete response rate (CRR; platelet count >100 × 10 L) were evaluated to determine drug efficacy by calculating weighted mean proportion using a fixed or random-effects model according to heterogeneity (I > 50%). The study was performed following the MOOSE and PRISMA guidelines.
RESULTS
A total of 28 studies (415 patients) were included (dapsone: k = 7 studies, n = 80; danazol: k = 12, n = 224; interferon alpha: k = 8, n = 83; hydroxychloroquine: k = 1, n = 28). The mean patient age was 50 years (female sex 70%, splenectomy 47%). The ORR and CRR were 55% (95% CI: 44%-66%, I = 0%) and 21% (95% CI: 13%-31%, I = 0%), respectively, for dapsone; 42% (95% CI: 22%-65%, I = 63%) and 18% (95% CI: 10%-29%, I = 9%), respectively, for interferon alpha; and 58% (95% CI: 42%-72%, I = 67%) and 29% (95% CI: 19%-42%, I = 63%), respectively, for danazol. The ORR was 50% (95% CI: 32%-67%) for hydroxychloroquine (data not available for CRR). Meta-regression analysis found a correlation between the ORR for interferon alpha and the splenectomized status of the patient (P = .02) and between the CRR for danazol and disease duration (P < .001). In total, 73%, 51%, 30%, and 0% of patients who received danazol, dapsone, interferon alpha, and hydroxychloroquine experienced side effects, respectively.
CONCLUSION
The ORR was equivalent for hydroxychloroquine, danazol, and dapsone in ITP. Regarding their low CRR, patients at high risk of infection or at low risk of bleeding should benefit from these treatments. Thanks to their best efficacy and safety profiles, dapsone and hydroxychloroquine in patients with antinuclear antibodies should be preferred over danazol and interferon alpha.
Topics: Humans; Immunomodulation; Purpura, Thrombocytopenic, Idiopathic
PubMed: 28906353
DOI: 10.1097/MD.0000000000007534 -
Acta Dermato-venereologica Jan 2018Granuloma faciale is an uncommon benign chronic dermatosis characterized by reddish-brown to violaceous asymptomatic plaques appearing predominantly on the face. The... (Review)
Review
Granuloma faciale is an uncommon benign chronic dermatosis characterized by reddish-brown to violaceous asymptomatic plaques appearing predominantly on the face. The pathogenesis of granuloma faciale remains unclear, and it is frequently unresponsive to therapy. This systematic review aims to summarize all recent publications on the management of granuloma faciale. The publications are mainly individual case reports, small case series and a few retrospective studies. Treatment options included topical, intralesional and systemic corticosteroids, topical pimecrolimus and tacrolimus, topical and systemic dapsone, systemic hydroxychloroquine, clofazimine, and tumour necrosis factor-alpha inhibitors. More invasive therapies using lasers as well as cryosurgery and surgery were also reported. Topical glucocorticosteroids and tacrolimus remain treatments of first choice, possibly supplemented by topical dapsone.
Topics: Adrenal Cortex Hormones; Calcineurin Inhibitors; Cryosurgery; Dapsone; Facial Dermatoses; Granuloma; Humans; Laser Therapy
PubMed: 28880343
DOI: 10.2340/00015555-2784 -
Wellcome Open Research 2017Antimalarial drugs affect the central nervous system, but it is difficult to differentiate the effect of these drugs from that of the malaria illness. We conducted a...
Antimalarial drugs affect the central nervous system, but it is difficult to differentiate the effect of these drugs from that of the malaria illness. We conducted a systematic review to determine the association between anti-malarial drugs and mental and neurological impairment in humans. We systematically searched online databases, including Medline/PubMed, PsychoInfo, and Embase, for articles published up to 14th July 2016. Pooled prevalence, heterogeneity and factors associated with prevalence of mental and neurological manifestations were determined using meta-analytic techniques. Of the 2,349 records identified in the initial search, 51 human studies met the eligibility criteria. The median pooled prevalence range of mental and neurological manifestations associated with antimalarial drugs ranged from 0.7% (dapsone) to 48.3% (minocycline) across all studies, while it ranged from 0.6% (pyrimethamine) to 42.7% (amodiaquine) during treatment of acute malaria, and 0.7% (primaquine/dapsone) to 55.0% (sulfadoxine) during prophylaxis. Pooled prevalence of mental and neurological manifestations across all studies was associated with an increased number of antimalarial drugs (prevalence ratio= 5.51 (95%CI, 1.05-29.04); P=0.045) in a meta-regression analysis. Headaches (15%) and dizziness (14%) were the most common mental and neurological manifestations across all studies. Of individual antimalarial drugs still on the market, mental and neurological manifestations were most common with the use of sulphadoxine (55%) for prophylaxis studies and amodiaquine (42.7%) for acute malaria studies. Mefloquine affected more domains of mental and neurological manifestations than any other antimalarial drug. Antimalarial drugs, particularly those used for prophylaxis, may be associated with mental and neurological manifestations, and the number of antimalarial drugs taken determines the association. Mental and neurological manifestations should be assessed following the use of antimalarial drugs.
PubMed: 28630942
DOI: 10.12688/wellcomeopenres.10658.2 -
Clinical Gastroenterology and... Nov 2017
Topics: Adult; Anti-Infective Agents; Dapsone; Drug Hypersensitivity; Female; Humans; Immunosuppressive Agents; Liver Failure, Acute; Male; Middle Aged; Prospective Studies; Retrospective Studies; Steroids; Treatment Outcome
PubMed: 28552804
DOI: 10.1016/j.cgh.2017.05.031 -
The Journal of Dermatological Treatment Feb 2018Knowledge of effectiveness and safety of the nonbiologic, nonantihistamine treatments used for chronic urticaria is important as in some cases the principal... (Review)
Review
BACKGROUND
Knowledge of effectiveness and safety of the nonbiologic, nonantihistamine treatments used for chronic urticaria is important as in some cases the principal guideline-recommended drug; omalizumab, has limited effect, side effects or is too expensive or unavailable. Herein, we systematically review the evidence for the use of the nonbiologic treatments in antihistamine-refractory chronic urticaria.
METHODS
We performed a systematic review of the literature using PubMed and Webofscience and identified studies that reported use of one or more of the nonbiological, nonantihistamine treatment options for chronic urticaria. The studies were evaluated based on study design, number of patients, effect of treatment and safety.
RESULTS
We identified 118 studies or case series with 13 different treatments (azathioprine, chloroquine, colchicine, cyclosporine, dapsone, intravenous immunoglobulin (IVIG), methotrexate, montelukast, mycophenolate mofetil, plasmapheresis, sulfasalazine, tranexamic acid and ultraviolet light (UV) A, UVB) totaling 1682 patients. There was a paucity of controlled trials for most of the treatments reviewed albeit the strongest evidence in favor of a beneficial effect in chronic urticaria was, apart from montelukast and cyclosporine, seen for UV therapy and dapsone followed by IVIG.
CONCLUSION
The treatment options reviewed should be seen as potential alternatives in treatment-resistant chronic urticaria where guideline-based selections have failed. However, larger controlled trials are warranted to advance the level of evidence, possibly supporting some treatments' future recommendation in selected patients.
Topics: Anti-Allergic Agents; Chronic Disease; Cyclosporine; Dapsone; Databases, Factual; Drug Resistance; Histamine Antagonists; Humans; Immunoglobulins, Intravenous; Plasmapheresis; Ultraviolet Therapy; Urticaria
PubMed: 28513247
DOI: 10.1080/09546634.2017.1329505