Diagnostic Challenges of Lepromatous Leprosy in a Non‐Endemic Setting: A Case of Atypical Primary Hyperpigmentation

Leprosy is a chronic granulomatous infection caused by Mycobacterium leprae, with a diverse clinical spectrum determined by host immunity [1]. In non-endemic regions, leprosy remains a diagnostic challenge as migration leads to sporadic cases [1]. Here, we report a case of lepromatous leprosy (LL) presenting with diffuse hyperpigmentation in a Myanmarese migrant in South Korea, initially misdiagnosed as an acquired pigmentary dermatosis. A 25-year-old Myanmarese male presented with a 16-month history of progressive, asymptomatic, dark-brown patches. The lesions initially appeared on the face, and then on the extremities. The patient had immigrated to Korea 2 years prior and had a history of agricultural and painting work with potential chemical exposure in Korea. Riehl's melanosis and erythema dyschromicum perstans were initially considered. Physical examination revealed diffuse hyperpigmented patches on the face and extremities, accompanied by facial nodules, lateral eyebrow loss (madarosis), and mild non-pitting edema of the extremities (Figure 1). No definite anesthesia or paresthesia was observed. A punch biopsy from the right thigh revealed increased basal melanin pigmentation. The superficial and deep dermis demonstrated granulomatous inflammation without necrosis, composed of foamy histiocytes (Figure 2A,B). Notably, abundant periodic acid-Schiff (PAS)-positive globi within the infiltrates (Figure 2C) were subsequently identified as numerous rod-shaped acid-fast bacilli by Ziehl-Neelsen staining (Figure 2D). Although polymerase chain reaction (PCR) showed amplification of nontuberculous mycobacteria, cross-reactivity with M. leprae was suspected, leading to a referral to the Korea Hansen Welfare Association (KHWA). At KHWA, slit-skin smears demonstrated high bacterial load with a bacterial index (BI) of 6+ and a morphological index (MI) of 80%. Mycobacterium leprae was confirmed via PCR, establishing the diagnosis of LL. The patient was started on a 12-month multidrug therapy (MDT) regimen, consisting of daily dapsone and clofazimine with monthly rifampicin. After 1 month of therapy, hyperpigmentation persisted, but the edema showed rapid improvement. A repeat slit-skin smear demonstrated fragmentation of previously solid-stained bacilli, suggesting loss of infectivity. The patient was maintained on outpatient follow-up without drug-related adverse effects. Hyperpigmentation in leprosy is usually secondary to MDT, and primary hyperpigmentation is considered an uncommon presentation. Only a few cases have been described in the literature, predominantly within the tuberculoid or borderline spectrum [2, 3]. In those reports, the hyperpigmented lesions were relatively localized, occurring on the lower extremities [2] and trunk [3]. Histopathological findings revealed increased melanin pigmentation confined to the epidermal layer [2]. The mechanism of hyperpigmentation remains unclear; it is thought to result from melanocytic stimulation driven by the inflammatory responses with Mycobacterium leprae. This case is notable for diffuse hyperpigmentation in lepromatous leprosy. Together with an indistinct Grenz zone, it may be related to inflammation extending toward the dermoepidermal junction (Figure 2B), facilitating melanocytic activation. This may explain why hyperpigmentation is more often reported in tuberculoid or borderline forms, where the Grenz zone is less developed. Predominance in sun-exposed areas also suggests a possible contributory role of ultraviolet exposure. Delays in the diagnosis of leprosy frequently culminate in irreversible nerve damage and disability, posing a significant clinical and public health burden. Misdiagnosis is considered the primary driver of these delays, particularly in non-endemic countries [4]. While diffuse hyperpigmentation in this case contributed to the initial diagnostic delay, accompanying clinical signs such as facial nodules, madarosis, and characteristic truncal lesions should have served as critical clues to suspect leprosy earlier. Although leprosy is uncommon in many non-endemic settings, sporadic cases continue to be reported. This case underscores the necessity of maintaining a high index of clinical suspicion for leprosy, even when faced with atypical pigmentary presentations. Clinicians should recognize the diverse clinical spectrum of leprosy to facilitate early diagnosis and treatment. This work was supported by the Ministry of Health and Welfare (RS-2023-KH141731) and a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: RS-2025-25460246). The authors declare no conflicts of interest. The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.