Leprosy mimicking lymphoproliferative disorders: a case report and structured literature search

Leprosy is a chronic infectious disease caused by Mycobacterium leprae that remains endemic in several regions, including Brazil. The disease predominantly affects the skin and peripheral nerves, but atypical presentations dominated by systemic symptoms such as fever and lymphadenopathy, particularly when accompanied by nonclassical cutaneous findings, are rare and may be mistaken for lymphoproliferative disorders. This study aim to raise clinical suspicion for atypical leprosy among health care providers in endemic areas, complemented by a structured literature search of comparable published cases to better characterize this diagnostic pitfall.

This study was conducted in two steps. First, we reported an index case of multibacillary borderline leprosy in accordance with the CAse REport (CARE) guidelines. Second, we performed a structured literature search across MEDLINE, Embase, and the Cochrane Library to identify published case reports and case series describing leprosy presenting as, or mimicking, lymphoma or another lymphoproliferative disorder.

We describe a 44-year-old woman from southern Brazil with a 1-year history of progressive, initially painful, generalized lymphadenopathy (inguinal, cervical, and axillary), a diffuse pruritic erythematous eruption, and systemic B symptoms (fever, night sweats, and 9 kg of unintentional weight loss). An outside skin biopsy had been read as psoriasiform dermatitis, and the patient had been treated unsuccessfully with methotrexate. One year later, skin and lymph node biopsies subsequently demonstrated acid-fast bacilli on Ziehl-Neelsen staining and histopathology consistent with Hansen's disease, establishing a diagnosis of multibacillary borderline leprosy. The patient was started on multidrug therapy (rifampicin, clofazimine, dapsone). Skin lesions progressively improved and constitutional symptoms resolved with treatment, although residual neuropathic symptoms persisted. Household contact investigation identified a sister with compatible skin lesions.

Of 785 records screened, 20 underwent full-text assessment; 13 case reports described a comparable diagnostic pitfall. The closest parallels involved generalized lymphadenopathy with a full constitutional syndrome misattributed to tuberculosis or lymphoma (Bagla, Mahajan, Singh, Herekar, Kiran, and especially Reis et al., a Brazilian case with an almost identical systemic symptom profile); a second group mimicked lymphoma cutaneously (Gunawan, Nawalerspanya, Rodríguez et al.). Taken together, our structured literature search identified relatively few reports combining, as our patient did, disseminated multi-chain lymphadenopathy and a full constitutional syndrome. This combination underscores both the rarity of such a comprehensive presentation and the persistent risk of diagnostic delay when leprosy is not considered in patients from endemic regions presenting with lymphadenopathy and systemic symptoms, reinforcing the educational aim of this case report and structured literature search.

This case and accompanying structured literature search highlight leprosy as an important, underrecognized mimicker of lymphoproliferative disorders when it presents with systemic symptoms and lymphadenopathy. Increased clinical awareness, particularly in primary care and endemic settings, along with systematic contact tracing, is essential to reduce diagnostic delay and interrupt transmission.