Clinical Indicators Suggesting Dapsone-Induced Methemoglobinemia in Dermatology Outpatients: A Pilot Retrospective...

Background Dapsone is used widely in dermatology as an anti-inflammatory agent for diseases including lichen planus, dermatitis herpetiformis, bullous pemphigoid, and sub-corneal pustular dermatosis (SCPD). Anemia and methemoglobinemia are known hematologic adverse effects of dapsone. These occur through distinct mechanisms and therefore develop independently of each other. Mild-to-moderate methemoglobinemia produces non-specific symptoms such as fatigue, exertional dyspnea, headache, and postural syncope that may affect daily functioning, impair treatment compliance, and lead to unnecessary evaluation when dapsone is not recognized as the cause. Biochemical confirmation requires arterial blood gas (ABG) measurement with co-oximetry, not routinely performed in dermatology outpatient settings. Objectives In this pilot retrospective cohort study, we aimed to estimate the prevalence and describe the clinical pattern of findings consistent with dapsone-induced methemoglobinemia in a dermatology outpatient clinic, evaluate the feasibility of a simple symptom- and pulse-oximetry-based screening strategy, and generate hypotheses for a prospective study with systematic methemoglobin (MetHb) measurement. Methods This study was conducted at a tertiary care dermatology outpatient clinic in central Kerala, India, over an 18-month period. Of a total of 41 patients prescribed dapsone during the study period, 28 had at least one follow-up visit while on dapsone and were included in the study. Clinical findings consistent with methemoglobinemia were defined as new-onset symptoms (fatigue, exertional dyspnea, headache, or postural syncope) or peripheral oxygen saturation (SpO2) at or below 94% on pulse oximetry, temporally correlated with dapsone initiation and not attributable to anemia or other comorbid illness. ABG MetHb levels were available in four patients only. Non-parametric tests were used for all comparisons due to the small sample size. All analyses were considered exploratory and hypothesis-generating given the pilot design. Results Of 28 patients followed up, 12 (43%) had clinical findings consistent with dapsone-induced methemoglobinemia, nine did not have any of the findings, and seven had insufficient data to be assessed against the clinical definition. Elevated MetHb levels were confirmed on ABG in four patients, all of whom had been classified as consistent with methemoglobinemia on clinical grounds, providing preliminary support for the feasibility of symptom and pulse-oximetry-based screening. No evaluated risk factor reached statistical significance. No patient required treatment beyond dapsone discontinuation. Conclusion This pilot study identifies a substantial burden of clinical findings consistent with dapsone-induced methemoglobinemia in a dermatology outpatient setting, comparable to rates in immunocompromised cohorts. Mild-to-moderate symptoms, easily misattributed to other causes, were the dominant presentation and carry real implications for symptom burden and treatment compliance. The four ABG-confirmed cases suggest, but do not confirm, the validity of clinical screening. Prospective studies are needed to evaluate the diagnostic performance and clinical utility of systematic screening strategies in dermatology outpatients receiving dapsone.