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European Journal of Internal Medicine Jun 2021To assess the efficacy and safety of adjuvant therapies in newly diagnosed or relapsing giant cell arteritis (GCA) in terms of relapse rate at week 52 (primary outcome)... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To assess the efficacy and safety of adjuvant therapies in newly diagnosed or relapsing giant cell arteritis (GCA) in terms of relapse rate at week 52 (primary outcome) and to assess the impact of GC tapering regimen on adjuvant effectiveness.
METHODS
For this systematic review and meta-analysis, we searched PubMed, EMBASE, CENTRAL, trial registries, from inception to November 2020. We included all randomized controlled trials (RCTs) and controlled prospective studies evaluating adjuvant treatments in GCA, without date or language restriction. Two reviewers independently selected studies, extracted data and assessed risk of bias. Quality of evidence was summarised with GRADE.
RESULTS
Of the 680 records identified, 16 studies were included (1,068 participants) evaluating various adjuvant therapies compared to GC only. No study compared adjuvants with each other. Risk of bias was high in 5/7 trials evaluating our primary outcome. Risk of relapse at week 52 was reduced for only the anti-IL6 and IL6-receptor drug class versus the control (RR=0.45, 95%CI 0.30-0.66, I2=38%), particularly tocilizumab (RR=0.38, 95%CI 0.23-0.63, I2=42%) with a moderate quality of evidence. We found no significant interaction according to GC tapering regimen. Our meta-analysis did not show a significant benefit for methotrexate. Except for dapsone, ciclosporine and hydroxychloroquine, other adjuvants did not seem to show increased risk of adverse events.
CONCLUSIONS
Tocilizumab seems to reduce the relapse rate in GCA at week 52 but the quality of evidence was moderate. No other molecule has shown efficacy. No significant interaction on relapse rate by GC tapering regimen was found.
STUDY REGISTRATION
PROSPERO CRD42020172011.
Topics: Drug Therapy, Combination; Giant Cell Arteritis; Glucocorticoids; Humans; Methotrexate; Steroids
PubMed: 33879385
DOI: 10.1016/j.ejim.2021.03.040 -
Antibiotics (Basel, Switzerland) Feb 2021Chronic spontaneous urticaria (CSU) is a disease with wheals and/or angioedema. Some drugs, especially antibiotics for () eradication and the sulfone antibiotic... (Review)
Review
BACKGROUND
Chronic spontaneous urticaria (CSU) is a disease with wheals and/or angioedema. Some drugs, especially antibiotics for () eradication and the sulfone antibiotic dapsone, may be candidates for treating CSU. The present study assessed the efficacy of these antibiotic therapies for CSU.
METHODS
Databases (MEDLINE, the Cochrane Central Register of Controlled Trials, EMBASE, the World Health Organization International Clinical Trials Platform Search Portal and ClinicalTrials.gov) were searched until October 2020. Study selection, data abstraction and quality assessments were independently performed using the Grading of Recommendations Assessment, Development and Evaluation approach. The outcomes were the remission of CSU-related symptoms, activities and adverse events due to antibiotics for eradication or dapsone.
RESULTS
Nine randomized controlled trials (RCTs; 361 patients) were included. The antibiotics for eradication increased the remission rate (risk ratio (RR) = 3.99, 95% confidence interval (CI) = 1.31 to 12.14; I = 0%), but dapsone did not (RR = 1.15, 95% CI = 0.74 to 1.78). Antibiotics for eradication (standard mean difference (SMD) = 1.49, 95% CI = 0.80 to 2.18; I = 69%) and dapsone (SMD = 7.00, 95% CI = 6.92 to 7.08; I = 0%) improved symptoms. The evidence of certainty was moderate. Dapsone was associated with mild adverse events, whereas eradication was not.
CONCLUSION
Antibiotics, especially those for eradication, improved the remission rate and symptoms of CSU with few adverse events. Further studies are needed.
PubMed: 33557074
DOI: 10.3390/antibiotics10020156 -
Journal of Oral Pathology & Medicine :... Sep 2020In oral medicine, colchicine is a therapeutic alternative for idiopathic recurrent aphthous stomatitis (RAS), Behçet disease (BD), periodic fever, aphthous stomatitis,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
In oral medicine, colchicine is a therapeutic alternative for idiopathic recurrent aphthous stomatitis (RAS), Behçet disease (BD), periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome, and mouth and genitals ulcers with inflamed cartilage (MAGIC) syndrome. The present review aims to evaluate reliability of colchicine against recurrent oral ulcers.
METHODS
A systematic review was conducted, with the following PICO (Patient, Intervention, Control, Outcome) question: "In populations with idiopathic or secondary recurrent oral ulcers, is colchicine more effective in improving pain and accelerating healing, compared to other intervention or placebo?"
RESULTS
Seven RCTs and 3 OCTs were considered eligible. Four RCTs focused on BD, two RCTs and three OCTs on RAS, and one RCT on PFAPA syndrome. Heterogeneity between RCTs prevented from meta-analysis. Regarding BD, no significant difference between colchicine and placebo was found in two of three placebo-controlled RCTs, whereas the third RCT showed benefit. A comparative RCT found ciclosporin more effective than colchicine for oral lesions of BD. One open-label RCT showed promising but partial results on colchicine in reducing PFAPA attacks, when compared to corticosteroids. Concerning RAS, colchicine appeared less effective than clofazimine, thalidomide and dapsone, and with outcomes similar to low-dosage corticosteroids but higher gastric discomfort than prednisolone. One OCT reported positive results compared with no treatment but a RCT found no difference with placebo.
CONCLUSION
Role of colchicine as treatment for idiopathic or secondary recurrent oral ulcers is still controversial. Further standardized RCTs and crossover trials are needed.
Topics: Colchicine; Humans; Lymphadenitis; Oral Ulcer; Reproducibility of Results; Stomatitis, Aphthous
PubMed: 32281694
DOI: 10.1111/jop.13020 -
Clinical and Experimental Pediatrics May 2020IgA vasculitis, formerly known as Henoch-Schönlein purpura, is a systemic IgA-mediated vasculitis of the small vessels commonly seen in children. The natural history of...
IgA vasculitis, formerly known as Henoch-Schönlein purpura, is a systemic IgA-mediated vasculitis of the small vessels commonly seen in children. The natural history of IgA vasculitis is generally self-limiting; however, one-third of patients experience symptom recurrence and a refractory course. This systematic review examined the use of dapsone in refractory IgA vasculitis cases. A literature search of PubMed databases retrieved 13 articles published until June 14, 2018. The most common clinical feature was a palpable rash (100% of patients), followed by joint pain (69.2%). Treatment response within 1-2 days was observed in 6 of 26 patients (23.1%) versus within 3-7 days in 17 patients (65.4%). Relapse after treatment discontinuation was reported in 17 patients (65.4%) but not in 3 patients (11.5 %). Four of the 26 patients (15.4%) reported adverse effects of dapsone including arthralgia (7.7%), rash (7.7%), and dapsone hypersensitivity syndrome (3.8%). Our findings suggest that dapsone may affect refractory IgA vasculitis. Multicenter randomized placebo-controlled trials are necessary to determine the standard dosage of dapsone at initial or tapering of treatment in IgA vasculitis patients and evaluate whether dapsone has a significant benefit versus steroids or other medications.
PubMed: 32024340
DOI: 10.3345/kjp.2019.00514 -
Allergy May 2020Drug hypersensitivity reactions (DHRs) are associated with high global morbidity and mortality. Cutaneous T cell-mediated reactions classically occur more than 6 hours...
Drug hypersensitivity reactions (DHRs) are associated with high global morbidity and mortality. Cutaneous T cell-mediated reactions classically occur more than 6 hours after drug administration and include life-threatening conditions such as toxic epidermal necrolysis, Stevens-Johnson syndrome, and hypersensitivity syndrome. Over the last 20 years, significant advances have been made in our understanding of the pathogenesis of DHRs with the identification of human leukocyte antigens as predisposing factors. This has led to the development of pharmacogenetic screening tests, such as HLA-B*57:01 in abacavir therapy, which has successfully reduced the incidence of abacavir hypersensitivity reactions. We have completed a PRISMA-compliant systematic review to identify genetic associations that have been reported in DHRs. In total, 105 studies (5554 cases and 123 548 controls) have been included in the review reporting genetic associations with carbamazepine (n = 31), other aromatic antiepileptic drugs (n = 24), abacavir (n = 11), nevirapine (n = 14), trimethoprim-sulfamethoxazole (n = 11), dapsone (n = 4), allopurinol (n = 10), and other drugs (n = 5). The most commonly reported genetic variants associated with DHRs are located in human leukocyte antigen genes and genes involved in drug metabolism pathways. Increasing our understanding of genetic variants that contribute to DHRs will allow us to improve diagnosis, develop new treatments, and predict and prevent DHRs in the future.
Topics: Carbamazepine; Drug Hypersensitivity; Drug Hypersensitivity Syndrome; HLA-B Antigens; Humans; Pharmaceutical Preparations; Stevens-Johnson Syndrome; T-Lymphocytes
PubMed: 31899808
DOI: 10.1111/all.14174 -
Anais Brasileiros de Dermatologia 2019Pyoderma gangrenosum is a neutrophilic dermatosis characterized by chronic ulcers due to an abnormal immune response. Despite the existence of diagnostic criteria, there...
Pyoderma gangrenosum is a neutrophilic dermatosis characterized by chronic ulcers due to an abnormal immune response. Despite the existence of diagnostic criteria, there is no gold standard for diagnosis or treatment. In Latin America, recognizing and treating pyoderma gangrenosum is even more challenging since skin and soft tissue bacterial and non-bacterial infections are common mimickers. Therefore, this review aims to characterize reported cases of pyoderma gangrenosum in this region in order to assist in the assessment and management of this condition. Brazil, Mexico, Argentina, and Chile are the countries in Latin America that have reported the largest cohort of patients with this disease. The most frequent clinical presentation is the ulcerative form and the most frequently associated conditions are inflammatory bowel diseases, inflammatory arthropaties, and hematologic malignancies. The most common treatment modalities include systemic corticosteroids and cyclosporine. Other reported treatments are methotrexate, dapsone, and cyclophosphamide. Finally, the use of biological therapy is still limited in this region.
Topics: Diagnosis, Differential; Humans; Latin America; Prevalence; Pyoderma Gangrenosum
PubMed: 31789268
DOI: 10.1016/j.abd.2019.06.001 -
International Journal of Women's... Dec 2018Erythema dyschromicum perstans (EDP) can be difficult to diagnose and treat; therefore, we reviewed the literature to assess whether histology can be used to... (Review)
Review
OBJECTIVE
Erythema dyschromicum perstans (EDP) can be difficult to diagnose and treat; therefore, we reviewed the literature to assess whether histology can be used to differentiate lichen planus pigmentosus (LPP) from EDP and determine which treatments are the most effective for EDP. We also present a case of a patient who was treated successfully with narrow-band ultraviolet B (NB-UVB).
METHODS
A systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses was conducted up to July 2017 using four databases.
RESULTS
Histologic analyses from the literature reveal a significant percentage of melanophages, lymphocytic infiltrates, and basal vacuolar degeneration in EDP, and a significant histologic overlap with LPP. The review of the literature on treatment outcomes showed that NB-UVB and tacrolimus were effective with minimal side effects. Clofazimine was effective, but demonstrated significant-to-intolerable side effects. Griseofulvin, isotretinoin, and dapsone provided unsatisfactory results as lesions recurred after discontinuation. Lasers were largely ineffective and may cause postinflammatory hyperpigmentation and fibrosis.
CONCLUSION
A diagnosis of EDP should not be based on histologic findings alone. Clinical history, morphology, and distribution should be used to differentiate EDP and LPP. NB-UVB and tacrolimus are promising treatments for EDP with minimal side effects. This is the first report to our knowledge of sustained resolution of EDP after treatment with NB-UVB at long-term follow-up of 4 years. Larger studies are needed to confirm these findings.
PubMed: 30627620
DOI: 10.1016/j.ijwd.2018.08.003 -
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 -
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