Borderline lepromatous leprosy mimicking prurigo nodularis

Dear Editors, Leprosy caused by Mycobacterium leprae is a major global public health issue,1 with approximately 200,000 new cases annually, most of which occur in India, Brazil, and Indonesia.2 The transmission mechanisms of leprosy remain incompletely understood, with prolonged close interpersonal contact via respiratory droplets being the most widely recognized route. Approximately 5%–10% of cases present with atypical skin lesions that can be easily misdiagnosed as other dermatological disorders, including sarcoidosis or histiocytosis.3 According to the Ridley-Jopling classification system, borderline lepromatous (BL) leprosy manifests as an intermediate immunocompromised state, exhibiting clinical features between those of tuberculous leprosy type (TT) and lepromatous leprosy type (LL).4 This case report documents a challenging diagnosis combining features of BL leprosy and prurigo nodularis (PN). The case highlights the diagnostic complexity of leprosy, particularly in cases with atypical presentations. Early accurate diagnosis is crucial for improving patient outcomes and reducing complications. A 43-year-old Han Chinese male patient (Fitzpatrick skin phototype IV) was admitted with recurrent pruritic rashes that had manifested on both lower limbs for four months. There was no personal or family history of previous skin disorders. A clinical diagnosis of PN had been made previously, and the patient was given clobetasol ointment. However, his skin condition failed to improve. On physical examination, scattered dark red papules (3–10 mm in diameter) and hemispherical nodules were identified on both lower extremities. Some of these lesions showed ulceration and exudation. Neurological examination showed reduced temperature sensation and diminished tactile sensitivity over the lateral aspect of the left calf and dorsum of the left foot, while other areas were normal (Figure 1). Motor strength and reflexes were preserved in all extremities. Although the patient reported persistent pruritus, the affected lesions exhibited relative hypoesthesia rather than complete anesthesia. Laboratory findings indicated rheumatoid factor (RF) level of 341 U/mL (normal < 20 U/mL), decreased complement C4 of 0.46 g/L (normal 0.5–1.2 g/L), and erythrocyte sedimentation rate (ESR) of 66 mm/hour (normal < 20 mm/hour). Skin exudate for a skin smear was obtained by incision of the leg lesion and was examined under an oil immersion lens. The skin smear showed numerous acid-fast bacilli, with a bacteriological index of 4+ (Figure 2). Histopathological examination revealed diffuse infiltration of histiocytes in the dermis, predominantly foamy cells, with inflammatory cell infiltration surrounding the nerve bundles (Figure 3a). Mycobacterium leprae were observed in the acid-fast staining (Figure 3b). The patient was diagnosed with BL leprosy. He was treated with WHO-recommended multidrug combination therapy (MDT) for multibacillary leprosy, including rifampin 600 mg once monthly, clofazimine 300 mg once monthly and 50 mg daily, and dapsone 100 mg daily, for a total duration of twelve months.4 Currently, after four months of therapy, the patient is tolerating the treatment well with gradual resolution of his lesions. Contact tracing of family members and close contacts revealed no additional cases, and no clear source of infection could be identified. Leprosy presents a broad clinical spectrum, and atypical cutaneous manifestations remain a significant cause of misdiagnosis, particularly in non-endemic areas. In this case, BL leprosy manifested with lesions mimicking PN, which is an uncommon presentation and can easily mislead clinicians into diagnoses such as hypertrophic lichen simplex chronicus, nodular scabies, or subacute prurigo, rather than infectious etiologies like leprosy. Previous reports have described leprosy mimicking granuloma annulare, sarcoidosis, and histiocytosis, as well as PN-like lesions in lepromatous leprosy,5 and multibacillary leprosy mimicking PN;6 however, such presentations remain rarely documented, particularly in borderline lepromatous forms, highlighting the ongoing diagnostic challenge. Additionally, the clinical findings may resemble histoid leprosy, a variant characterized by nodular lesions; however, the histopathological absence of spindle-shaped histiocytes excludes this diagnosis. In our patient the presence of hypoesthesia, abundant acid-fast bacilli with a high bacteriological index, and dermal infiltration by foamy histiocytes with perineural inflammation were pivotal in establishing the diagnosis. These features are consistent with BL leprosy within the Ridley-Jopling classification, representing an intermediate immune response between the tuberculoid and lepromatous poles. The coexistence of pruritus and partial sensory impairment in our patient highlights the complex neuroimmune interactions in leprosy and may contribute to clinical misdiagnosis as PN. This paradoxical coexistence is characteristic of early neural involvement in leprosy. Although PN is not a distinct disease entity but a clinical reaction pattern secondary to chronic itch from various causes, it shares certain immune signaling pathways with leprosy. In both conditions, prominent Th2/Th17 immune polarization and neuroimmune crosstalk exist: in leprosy, lepromatous (LL) and BL forms exhibit Th2 dominance (with elevated IL-4, IL-10, TGF-β), which impairs control of Mycobacterium leprae,7 while PN features Th2-driven inflammation (IL-4, IL-13, IL-31) and Th17/Th22 responses (IL-17, IL-22) promoting epidermal hyperplasia, fibrosis, and itch.8 Both involve bidirectional nervous-immune system interactions, with leprosy showing nerve damage linked to reduced nerve growth factor (NGF) and anti-NGF autoantibodies,9 and PN involving sensory neuron release of substance P (SP) and calcitonin gene-related peptide (CGRP) to trigger further inflammation,8 while chronic inflammation in both lowers itch thresholds via neuronal sensitization to pruritogens or altered pain/itch signaling.8, 9 Therefore, the coexistence of pruritic nodules and partial sensory impairment in our patient may reflect overlapping immune and neural dysregulation rather than identical pathogenic mechanisms. This case emphasizes the importance of maintaining a high index of suspicion in patients with chronic and refractory pruritic skin diseases, especially when neurological symptoms coexist. This case study will enhance clinicians’ understanding of atypical leprosy. Prompt recognition and initiation of standardized MDT can lead to rapid clinical improvement and reduce the long-term burden of the disease. This work was supported by National Natural Science Foundation of China [No. 82303998]. None.