RESUMO
INTRODUCTION: Acne vulgaris is a common skin disease prevalent in skin of color patients. Studies have demonstrated that dapsone gel, 7.5% (Aczone) used once daily is effective, safe, and well-tolerated for the treatment of acne in both men and women. However, minimal data are available in skin of color populations. This single-center, open-label clinical study investigated the efficacy and safety of dapsone gel, 7.5% in the treatment of moderate to severe acne vulgaris in patients with Fitzpatrick skin types IV-VI. METHODS: Twenty (20) adult subjects with moderate to severe acne and Fitzpatrick skin types IV-VI were enrolled in this study and treated with dapsone gel, 7.5% once daily for 24 weeks. RESULTS: Dapsone gel, 7.5% applied daily for 24 weeks reduced acne severity, post-inflammatory hyperpigmentation, and decreased new inflammatory and noninflammatory acne lesions in skin of color patients with moderate to severe acne vulgaris. Treatment resulted in improved acne health-related quality of life and patient symptoms related to acne, including patient-reported post-inflammatory hyperpigmentation, especially with a treatment duration of 18 weeks or longer. Limitations: The sample size was small and underpowered to detect statistically significant changes in some endpoints. CONCLUSION: Dapsone gel 7.5% was safe, well-tolerated, and efficacious in treating acne vulgaris and post-inflammatory hyperpigmentation in skin-of-color patients. Larger studies involving skin-of-color populations with acne vulgaris are warranted. J Drugs Dermatol. 2024;23(6):410-417. doi:10.36849/JDD.7897.
Assuntos
Acne Vulgar , Administração Cutânea , Dapsona , Índice de Gravidade de Doença , Adolescente , Adulto , Feminino , Humanos , Masculino , Adulto Jovem , Acne Vulgar/tratamento farmacológico , Dapsona/administração & dosagem , Dapsona/efeitos adversos , Géis , Hiperpigmentação/induzido quimicamente , Hiperpigmentação/tratamento farmacológico , Qualidade de Vida , Pigmentação da Pele , Resultado do Tratamento , Minorias Étnicas e RaciaisRESUMO
BACKGROUND: Pneumocystis jirovecii pneumonia (PCP) is a common opportunistic infection among people living with HIV (PWH), particularly among new and untreated cases. Several regimens are available for the prophylaxis of PCP, including trimethoprim-sulfamethoxazole (TMP-SMX), dapsone-based regimens (DBRs), aerosolized pentamidine (AP), and atovaquone. OBJECTIVES: To compare the efficacy and safety of PCP prophylaxis regimens in PWH by network meta-analysis. METHODS: DATA SOURCES: Embase, MEDLINE, and CENTRAL from inception to June 21, 2023. STUDY ELIGIBILITY CRITERIA: Comparative randomized controlled trials (RCTs). PARTICIPANTS: PWH. INTERVENTIONS: Regimens for PCP prophylaxis either compared head-to-head or versus no treatment/placebo. ASSESSMENT OF RISK OF BIAS: Cochrane risk-of-bias tool for RCTs 2. METHODS OF DATA SYNTHESIS: Title or abstract and full-text screening and data extraction were performed in duplicate by two independent reviewers. Data on PCP incidence, all-cause mortality, and discontinuation due to toxicity were pooled and ranked by network meta-analysis. Subgroup analyses of primary versus secondary prophylaxis, by year, and by dosage were performed. RESULTS: A total of 26 RCTs, comprising 55 treatment arms involving 7516 PWH were included. For the prevention of PCP, TMP-SMX was ranked the most favourable agent and was superior to DBRs (risk ratio [RR] = 0.54; 95% CI, 0.36-0.83) and AP (RR = 0.53; 95% CI, 0.36-0.77). TMP-SMX was also the only agent with a mortality benefit compared with no treatment/placebo (RR = 0.79; 95% CI, 0.64-0.98). However, TMP-SMX was also ranked as the most toxic agent with a greater risk of discontinuation than DBRs (RR = 1.25; 95% CI, 1.01-1.54) and AP (7.20; 95% CI, 5.37-9.66). No significant differences in PCP prevention or mortality were detected among the other regimens. The findings remained consistent within subgroups. CONCLUSIONS: TMP-SMX is the most effective agent for PCP prophylaxis in PWH and the only agent to confer a mortality benefit; consequently, it should continue to be recommended as the first-line agent. Further studies are necessary to determine the optimal dosing of TMP-SMX to maximize efficacy and minimize toxicity.
Assuntos
Infecções por HIV , Metanálise em Rede , Pneumocystis carinii , Pneumonia por Pneumocystis , Ensaios Clínicos Controlados Aleatórios como Assunto , Combinação Trimetoprima e Sulfametoxazol , Humanos , Pneumonia por Pneumocystis/prevenção & controle , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Combinação Trimetoprima e Sulfametoxazol/administração & dosagem , Combinação Trimetoprima e Sulfametoxazol/efeitos adversos , Pneumocystis carinii/efeitos dos fármacos , Infecções por HIV/complicações , Infecções Oportunistas Relacionadas com a AIDS/prevenção & controle , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Dapsona/uso terapêutico , Dapsona/efeitos adversos , Dapsona/administração & dosagem , Pentamidina/uso terapêutico , Pentamidina/administração & dosagem , Pentamidina/efeitos adversos , Atovaquona/uso terapêutico , Atovaquona/efeitos adversos , Antifúngicos/uso terapêutico , Antifúngicos/administração & dosagem , Antifúngicos/efeitos adversos , Resultado do TratamentoRESUMO
Methaemoglobinaemia occurs when iron in haemoglobin is oxidised into a form that cannot transport oxygen. At low levels, it is asymptomatic, though at rising levels symptoms arise from impaired oxygenation, and it can ultimately be fatal. While uncommon, it is important to consider in hypoxaemic COVID-19 patients, especially if they are not clinically improving on standard treatments and workup for other causes does not explain the ongoing hypoxaemia. It is often diagnosed through a mismatch in peripheral and arterial oxygen, with the former typically less than the latter. We present the case of a COVID-19 patient who was found to have methaemoglobinaemia due to dapsone use for Pneumocystic jirovecii pneumonia (PJP) prophylaxis while on chemotherapy. Dapsone was stopped and supplemental high-flow nasal cannula was provided, and methaemoglobin levels improved over a 5-day period. She was discharged to follow-up with her haematologist in the clinic.
Assuntos
COVID-19 , Metemoglobinemia , Feminino , Humanos , Metemoglobinemia/induzido quimicamente , Metemoglobinemia/diagnóstico , Metemoglobina , Dapsona/efeitos adversos , OxigênioRESUMO
BACKGROUND: The occurrence of adverse drug events (ADEs) during dapsone (DDS) treatment in patients with leprosy can constitute a significant barrier to the successful completion of the standardized therapeutic regimen for this disease. Well-known DDS-ADEs are hemolytic anemia, methemoglobinemia, hepatotoxicity, agranulocytosis, and hypersensitivity reactions. Identifying risk factors for ADEs before starting World Health Organization recommended standard multidrug therapy (WHO/MDT) can guide therapeutic planning for the patient. The objective of this study was to develop a predictive model for DDS-ADEs in patients with leprosy receiving standard WHO/MDT. METHODOLOGY: This is a case-control study that involved the review of medical records of adult (≥18 years) patients registered at a Leprosy Reference Center in Rio de Janeiro, Brazil. The cohort included individuals that received standard WHO/MDT between January 2000 to December 2021. A prediction nomogram was developed by means of multivariable logistic regression (LR) using variables. The Hosmer-Lemeshow test was used to determine the model fit. Odds ratios (ORs) and their respective 95% confidence intervals (CIs) were estimated. The predictive ability of the LRM was assessed by the area under the receiver operating characteristic curve (AUC). RESULTS: A total of 329 medical records were assessed, comprising 120 cases and 209 controls. Based on the final LRM analysis, female sex (OR = 3.61; 95% CI: 2.03-6.59), multibacillary classification (OR = 2.5; 95% CI: 1.39-4.66), and higher education level (completed primary education) (OR = 1.97; 95% CI: 1.14-3.47) were considered factors to predict ADEs that caused standard WHO/MDT discontinuation. The prediction model developed had an AUC of 0.7208, that is 72% capable of predicting DDS-ADEs. CONCLUSION: We propose a clinical model that could become a helpful tool for physicians in predicting ADEs in DDS-treated leprosy patients.
Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Hanseníase , Adulto , Humanos , Feminino , Dapsona/efeitos adversos , Hansenostáticos/efeitos adversos , Rifampina/uso terapêutico , Quimioterapia Combinada , Estudos de Casos e Controles , Clofazimina/uso terapêutico , Brasil/epidemiologia , Hanseníase/tratamento farmacológico , Organização Mundial da SaúdeRESUMO
Leprosy is a global health issue, causing long-term functional morbidity and stigma. Rapid diagnosis and appropriate treatment are important; however, early diagnosis is often challenging, especially in nonendemic areas. Here, we report a case of borderline lepromatous leprosy accompanied by dapsone-induced (neutropenia, anemia, and methemoglobinemia) and clofazimine-induced (skin discoloration and ichthyosis) side effects and type 1 leprosy reactions during administration of the multidrug therapy. The patient completely recovered without developing any deformities or visual impairment. To ensure early diagnosis and a favorable outcome, clinicians should be aware of the diminished sensation of skin lesions as a key physical finding and manage the drug toxicities and leprosy reactions appropriately in patients on multidrug therapy.
Assuntos
Hipersensibilidade , Hanseníase Dimorfa , Hanseníase Virchowiana , Hanseníase Multibacilar , Hanseníase , Doenças do Sistema Nervoso Periférico , Dermatopatias Bacterianas , Humanos , Clofazimina/efeitos adversos , Dapsona/efeitos adversos , Quimioterapia Combinada , Hansenostáticos/efeitos adversos , Hanseníase/patologia , Hanseníase Dimorfa/diagnóstico , Hanseníase Dimorfa/tratamento farmacológico , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Hanseníase Multibacilar/tratamento farmacológico , Hanseníase Virchowiana/diagnóstico , Hanseníase Virchowiana/tratamento farmacológico , Hanseníase Virchowiana/patologiaRESUMO
Since the introduction of multidrug therapy (MDT), various disabilities/morbidities due to leprosy have been prevented. However, there is a subset of patients in whom the skin lesions do not resolve completely or remain unchanged despite a full course of MDT, which is a great source of anxiety to the patient and their family members. Hence, we tried to ascertain the putative causes and risk factors of persistent skin lesions (PSLs) by analyzing the clinical, histopathological, bacteriological, and drug resistance patterns. This is a retrospective, cohort study wherein 35 patients who had PSLs after completion of MDT were included. The majority of the patients were 18 to 30 years of age, with males predominating. Borderline tuberculoid leprosy was the most common clinical spectrum observed (71.4%). The majority had PSLs distributed predominantly over photo-exposed sites (upper limbs > trunk > face). Eight patients (22.8%) had a history of contact with leprosy patients in their family, and six patients (17.1%) had associated comorbidities. Improvement in histopathological parameters such as a decrease in granuloma fraction was observed in 22 patients (62.8%) with PSLs after release from treatment in comparison with baseline. Four patients (11.4%) were noted to have drug resistance (three to rifampicin and one to dapsone). Thus, our study emphasizes that leprosy patients with PSLs after completion of MDT should undergo histopathological evaluation and drug resistance studies.
Assuntos
Hanseníase , Dermatopatias , Masculino , Humanos , Hansenostáticos , Estudos Retrospectivos , Quimioterapia Combinada , Estudos de Coortes , Hanseníase/complicações , Hanseníase/tratamento farmacológico , Hanseníase/epidemiologia , Dapsona/uso terapêutico , Dapsona/efeitos adversos , Dermatopatias/tratamento farmacológicoRESUMO
BACKGROUND: Management of hidradenitis suppurativa (HS) is challenging since no single treatment provides consistently effective results, leaving patients with frequent relapses. Dapsone combines anti-microbial and anti-inflammatory properties that address aspects of HS pathogenesis. Few studies have evaluated the efficacy of oral dapsone on HS, especially in severe disease. OBJECTIVE: This study aims to evaluate the clinical outcomes of patients with moderate-to-severe HS treated with dapsone. METHODS: This retrospective chart review evaluated HS patients treated with oral dapsone over the past 10 years at one center. Treatment outcomes were classified based on Hurley staging, physician exam, and symptom progression. Adverse effects and concomitant treatment with dapsone were reviewed. RESULTS: Nineteen (19) patients with moderate-to-severe (Hurley Stage II-III) HS treated with oral dapsone were identified. Within 1-3 months, on dosages of dapsone varying from 25-100 mg/day, 3 patients (15.8%) had a clinically significant improvement in symptoms, 10 patients (52.6%) had a slight improvement, and 6 patients (31.6%) had no change in disease state; no patients deteriorated. The majority who improved were also on other medications, most commonly adalimumab. 4 patients experienced adverse effects, with nausea being most common; otherwise, dapsone was well-tolerated. CONCLUSIONS: Dapsone may have some efficacy for moderate-to-severe HS and seems well-tolerated. J Drugs Dermatol. 2023;22(11):e12-e16 doi:10.36849/JDD.4936e.
Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Hidradenite Supurativa , Humanos , Hidradenite Supurativa/diagnóstico , Hidradenite Supurativa/tratamento farmacológico , Estudos Retrospectivos , Adalimumab , Dapsona/efeitos adversosRESUMO
PURPOSE OF REVIEW: As a sulfone antibacterial agent, dapsone has been widely used to treat leprosy. Moreover, dapsone is also used in many immune diseases such as herpetic dermatitis because of its anti-inflammatory and immunomodulatory effects. However, dapsone can cause several adverse effects, the most serious being dapsone hypersensitivity syndrome. Dapsone hypersensitivity syndrome is characterized by a triad of eruptions, fever, and organ involvement, which limits the application of dapsone to some extent. RECENT FINDINGS: In this article, we review current research about the interaction model between HLA-B*13:01, dapsone, and specific TCR in dapsone-induced drug hypersensitivity. In addition to the proposed mechanisms, we also discussed clinical features, treatment progress, prevalence, and prevention of dapsone hypersensitivity syndrome. These studies reveal the pathogenesis, clinical features, and prevalence from the perspectives of genetic susceptibility and innate and adaptive immunity in dapsone hypersensitivity syndrome, thereby guiding clinicians on how to diagnose, prevent, and treat dapsone hypersensitivity syndrome.
Assuntos
Hipersensibilidade a Drogas , Hipersensibilidade , Hanseníase , Humanos , Dapsona/efeitos adversos , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/genética , Hipersensibilidade a Drogas/terapia , Hipersensibilidade/complicações , Síndrome , Hanseníase/induzido quimicamente , Hanseníase/complicações , Hanseníase/tratamento farmacológicoRESUMO
Dapsone hypersensitivity syndrome (DHS) is restricted to HLA-B∗13:01. However, the positive predictive value for HLA-B∗13:01 is only 7.8%. To explore the potential coexisting factors involved in the occurrence of DHS, we carried out a GWAS and a genome-wide DNA methylation profile analysis comparing patients with DHS with dapsone-tolerant control subjects (all carrying HLA-B∗13:01). No non-HLA SNPs associated with DHS were identified at the genome-wide level. However, the pathway of antigen processing and presentation was enriched in patients with DHS, and the gene TAP2 was identified. Expression of TAP2 and its molecular chaperone, TAP1, were validated by quantitative PCR, and in vitro functional experiments were performed. The results showed that patients with DHS have higher mRNA levels of TAP1 and TAP2 and an enhanced capacity for antigen-presenting cells activating dapsone-specific T cells compared with dapsone-tolerant controls. Activation of dapsone-specific T cells was inhibited when TAP function of antigen-presenting cells was impaired. This study shows that epigenetic regulation of TAP1 and TAP2 affects the function of antigen-presenting cells and is a critical factor that mediates the development of DHS.
Assuntos
Síndrome de Hipersensibilidade a Medicamentos , Hipersensibilidade , Humanos , Epigênese Genética , Dapsona/efeitos adversos , Antígenos HLA-B/genética , Membro 3 da Subfamília B de Transportadores de Cassetes de Ligação de ATPRESUMO
OBJECTIVE: The World Health Organization (WHO) recommends multidrug therapy (MDT) with rifampicin, dapsone, and clofazimine for treating leprosy, which is based on very low-quality evidence. Here, we performed a network meta-analysis (NMA) to produce quantitative evidence to strengthen current WHO recommendations. METHOD: All studies were obtained from Embase and PubMed from the date of establishment to October 9, 2021. Data were synthesized with frequentist random-effects network meta-analyses. Outcomes were assessed using odds ratios (ORs), 95% confidence intervals (95% CIs), and P score. RESULTS: Sixty controlled clinical trials and 9256 patients were included. MDT was effective (range of OR: 1.06-1255584.25) for treating leprosy and multibacillary leprosy. Six treatments (Range of OR: 1.199-4.50) were more effective than MDT. Clofazimine (P score=0.9141) and dapsone+rifampicin (P score=0.8785) were effective for treating type 2 leprosy reaction. There were no significant differences in the safety of any of the tested drug regimens. CONCLUSIONS: The WHO MDT is effective for treating leprosy and multibacillary leprosy, but it may not be effective enough. Pefloxacin and ofloxacin may be good adjunct drugs for increasing MDT efficacy. Clofazimine and dapsone+rifampicin can be used in the treatment of a type 2 leprosy reaction. Single-drug regimens are not efficient enough to treat leprosy, multibacillary leprosy, or a type 2 leprosy reaction. AVAILABILITY OF DATA AND MATERIALS: All data generated or analyzed during this study are included in this published article [and its supplementary information files].
Assuntos
Hanseníase Multibacilar , Hanseníase , Humanos , Hansenostáticos/efeitos adversos , Rifampina/efeitos adversos , Clofazimina/efeitos adversos , Metanálise em Rede , Quimioterapia Combinada , Hanseníase/tratamento farmacológico , Dapsona/efeitos adversos , Hanseníase Multibacilar/tratamento farmacológicoRESUMO
BACKGROUND: The appearance of bite cells associated with methemoglobinemia can be caused by oxidizing drugs such as dapsone in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency or high drug serum levels. Bite cells are often pathognomonic for oxidant injury in patients with G6PD deficiency and suggest active hemolysis. CASE PRESENTATION: We report a case of a woman with no prior history of G6PD deficiency who presented with anemia, methemoglobinemia and bite cells on peripheral blood smear after dapsone therapy for new onset idiopathic urticaria. Laboratory tests for G6PD, blood count and liver function were within normal limits prior to initiation of therapy. During the patient's hospital course, moderate methemoglobinemia and anemia were identified despite mildly increased serum G6PD level. These pathologies were reversed upon stopping dapsone therapy. CONCLUSION: This case highlights the potential for therapeutic levels of dapsone to induce side effects in patients without G6PD deficiency and highlights the importance of routine blood monitoring for anemia and hemolysis during the course of drug therapy.
Assuntos
Deficiência de Glucosefosfato Desidrogenase , Metemoglobinemia , Urticária , Feminino , Humanos , Deficiência de Glucosefosfato Desidrogenase/complicações , Deficiência de Glucosefosfato Desidrogenase/diagnóstico , Metemoglobinemia/induzido quimicamente , Metemoglobinemia/diagnóstico , Metemoglobinemia/tratamento farmacológico , Dapsona/efeitos adversos , HemóliseRESUMO
BACKGROUND: Peripheral neuropathy is a dose-limiting adverse effect of vincristine (VCR) in cancer chemotherapies. Dapsone is commonly used for the prevention of opportunistic infections following cancer therapies. Therefore, a high rate of VCR and dapsone co-administration has occurred in leukemias. Recently neuroprotective effects of dapsone have been reported in various diseases. OBJECTIVES: Regarding the physiopathology of VCR-induced peripheral neuropathy (VIPN) and dapsone neuroprotection, this study evaluated the effect of dapsone on VIPN. METHODS: VIPN was induced by VCR injection (0.5 mg/kg IP, every other day, 1 week) in male Wistar rats. In the treatment group, dapsone(12.5 mg/kg IP, 1 week) was injected 30 min before VCR. Hot plate, Von Frey, motor neuron conduction velocity (MNCV), and histopathological tests were applied. The levels of TNF-α and NF-kB in the sciatic nerve and caspase-3 activity in dorsal root ganglion were measured by the ELISA method. The levels of malondialdehyde (MDA) and Glutathione (GSH) in the sciatic nerve were measured by spectrophotometry and colorimetric assays. RESULTS: VIPN was observed as araised thermal and mechanical threshold, reduced MNCV, and sciatic nerve demyelination. However, dapsone reduced the mechanical and thermal threshold and improved the MNCV. Also, dapsone reduced TNF-α, NF-kB, MDA, and Caspase-3 activity, and increased the GSH level in the sciatic nerve. Moreover, dapsone prevented VCR-induced demyelination in the sciatic nerve. CONCLUSION: This research demonstrated that dapsone could be used as a protective drug against VIPN. It improves the impaired thermal and mechanical sensations by reducing inflammatory, oxidant, and apoptosis factors and preventing demyelination in the sciatic nerve.
Assuntos
Antineoplásicos Fitogênicos , Doenças Desmielinizantes , Neoplasias , Fármacos Neuroprotetores , Doenças do Sistema Nervoso Periférico , Ratos , Animais , Masculino , Vincristina/efeitos adversos , Nociceptividade , Fator de Necrose Tumoral alfa , Dapsona/efeitos adversos , NF-kappa B , Caspase 3 , Doenças Neuroinflamatórias , Ratos Wistar , Antineoplásicos Fitogênicos/farmacologia , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Estresse Oxidativo , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Glutationa/metabolismo , Neoplasias/tratamento farmacológico , Doenças Desmielinizantes/induzido quimicamente , Doenças Desmielinizantes/tratamento farmacológicoRESUMO
A woman in her 30s presented to our emergency department with vomiting and lethargy after an intentional ingestion of unknown antimicrobial pills which was later found to be dapsone. The patient developed cyanosis, hypoxia and tachycardia due to acute methaemoglobinaemia (level of 30.9% on venous blood gas analysis). As dapsone is notorious for prolonged and rebound methaemoglobinaemia, she was managed with repeated doses of intravenous methylene blue and oral multidose activated charcoal which warranted elective intubation and intensive care unit admission. Subsequent drug-induced hepatitis and delayed dapsone-induced haemolysis were managed conservatively. She was discharged in a stable condition with outpatient follow-ups. Physician familiarity with the nuances of this rare condition and its complications contributes to better patient care.