Lepromatous leprosy presenting with chronic painless ulcers and inflammatory arthropathy: a case report from a non-endemic setting

Abstract

Background

Hansen’s disease is a chronic infectious disease caused commonly by Mycobacterium leprae. Although it is rare in Europe, sporadic cases occur due to migration from endemic areas. In Portugal there are 4 cases reported in 2023 and 4 cases reported in 2024. Lepromatous leprosy represents the anergic pole of the disease spectrum, characterized by diffuse bacillary proliferation and multisystem involvement, often mimicking autoimmune conditions.

Case presentation

A 36-year-old Brazilian male from Rio de Janeiro living in Portugal presented with recurrent painless leg ulcers and violaceous halos for one year, accompanied by non-tender granulomatous lesions on the ears, eyelids, and nasal alas. He developed inflammatory polyarthralgias involving small and medium joints. Subsequent serologic and autoimmune studies revealed mild inflammatory activity, positive antinuclear antibodies and rheumatoid factor, elevated angiotensin-converting enzyme, and polyclonal hypergammaglobulinemia. Imaging demonstrated hepatomegaly and mild axillary and inguinal lymphadenopathy. Sarcoidosis was considered as the main differential diagnosis. Skin biopsy of an ulcer revealed foamy histiocytes and numerous acid-fast bacilli on Fite-Faraco staining, consistent with M. leprae. He was treated with multidrug therapy (rifampicin, clofazimine, and dapsone), leading to rapid resolution of lesions and arthralgias.

Conclusions

In an increasingly globalised world, even in non-endemic regions, leprosy should be considered in the differential diagnosis of chronic ulcers and inflammatory arthropathy, especially when patients come from endemic areas. An enhanced awareness among clinicians is needed. Early recognition, histopathologic confirmation, and multidrug therapy are essential to prevent irreversible complications and reduce transmission.

Background

Hansen’s disease, caused by Mycobacterium leprae or Mycobacterium lepromatosis [1], is one of the oldest known infectious diseases, yet remains a public health concern in several developing countries [2] and still carries a heavy burden of stigma [3]. Despite significant global control efforts, the World Health Organization (WHO) reported over 174 000 new cases in 2022, with the majority of cases occurring in India, Brazil, Indonesia and Bangladesh [4]. Transmission is thought to occur through prolonged respiratory exposure to droplets containing M. leprae, although percutaneous and zoonotic routes have been postulated [5–7]. In Portugal, the available data on Hansen’s disease is from Instituto Nacional de Saúde Dr. Ricardo Jorge, that reported 4 cases in 2023 and 4 cases in 2024, in patients with travel history, origin from endemic regions or cohabitation with patients with leprosy [8].

The clinical manifestations of leprosy represent a spectrum of immune responses [9, 10]. At one extreme, tuberculoid leprosy shows strong cell-mediated immunity, resulting in localized skin lesions and nerve involvement with few or no bacilli (paucibacillary) [9, 10]. At the opposite pole, lepromatous leprosy reflects defective cell-mediated immunity, leading to disseminated lesions, numerous bacilli (multibacillary), and frequent systemic involvement [9, 10]. Between the tuberculoid and lepromatous poles, borderline forms reflect immunologically unstable states, and patients may develop reactional episodes (type 1 reactions or reversal reactions) linked to shifts in cell-mediated immunity and type 2 reactions (erythema nodosum leprosum) driven by immune complex deposition.

The disease primarily affects the skin, peripheral nerves, upper respiratory mucosa, and eyes [11]. However, systemic features including lymphadenopathy [12], hepatomegaly [13], testicular atrophy [14], and rheumatologic manifestations [15, 16] are well described. Musculoskeletal involvement may occur and often mimics autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, or vasculitis [17].

We present a clinical case of leprosy to raise the awareness to this diagnosis, since in non-endemic countries clinicians may not consider Hansen’s disease in the differential diagnosis of chronic ulcers or granulomatous skin lesions, leading to significant diagnostic delay with misdiagnosis as vasculitis, pyoderma gangrenosum, or sarcoidosis being frequent [1, 4, 11]. Histopathological and microbiological confirmation remain the gold standard for diagnosis [11].

Case presentation

A 36-year-old Brazilian male from Rio de Janeiro, resident in northern Portugal in Viana do Castelo for 3 years, presented to his primary care clinic in June 2024 with a painful lesion on his right leg that evolved over 1 month into a painless ulcer, leaving a hyperpigmented scar with a violaceous halo. He noted non-tender nodular lesions on the auricles, nasal alas, and eyelids. Weight loss, anorexia, neuropathic symptoms and unprotected sex were denied. The patient works in the restaurant industry, practises martial arts and travels to Brazil every 6 months. He had no significant past medical history, did not smoke, and denied alcohol or drugs use and lived alone in good sanitary conditions.

In June 2024, serologic testing for sexually transmitted infections showed a positive venereal disease research laboratory (VDRL) test (1:2). Primary syphilis was diagnosed, and he received intramuscular benzathine penicillin G (2.4 million IU, single dose). However, it is important to note that no treponemal test was performed. New ulcers appeared on the left lower limb, upper limbs and abdomen, while older ones healed leaving hyperpigmented macules with violaceous halos. By August 2024, rapid plasma reagin (RPR) test was negative. In February 2025, he developed inflammatory arthralgias in hands, wrists, ankles, and feet, with morning stiffness and mild swelling. Naproxen 500 mg twice daily led to partial relief with no complete resolution of pain. Laboratory results showed mild microcytic anemia, high erythrocyte sedimentation rate (ESR) and C reactive protein (CRP), positive antinuclear antibodies (ANA; 1:160; homogeneous), elevated rheumatoid factor (RF; 37IU/mL), and normal complement levels. Computed tomography of the thorax and the upper and lower endoscopies were unremarkable.

In May 2025, he presented to the emergency department, referred by his attending physician, with worsening ulcers and new-onset low-grade fever (~ 38–38.5 °C). On examination, he was hemodynamically stable, afebrile, without respiratory and cardiac symptoms, or neurological deficits. Skin examination revealed multiple painless ulcers on both legs, some with fibrinous or purulent exudate, surrounded by violaceous halos (Fig. 1). Non-tender granulomatous lesions were seen on the auricles, nasal alas, and eyelids (Fig. 2). There was atrophy of both lower limbs (calf circumference inferior to 27 cm) but no palpable lymphadenopathy. Routine laboratory tests revealed microcytic anemia (haemoglobin of 12.4 g/dL with mean corpuscular volume of 78.6fL) without iron deficiency, normal leucocytes and platelet count, normal kidney and liver parameters (creatinine, transaminases and bilirubin), high ESR (37 mm/h), mildly elevated CRP (0.95 mg/dL, reference ranges < 0.51), and normal procalcitonin. Viral serologies (human immunodeficiency virus, B hepatitis virus, C hepatitis virus, cytomegalovirus, Epstein-Barr virus) and blood cultures were negative. Urinalysis was normal. Chest radiograph was unremarkable (Fig. 3). Computed tomography of the thorax, abdomen, and pelvis demonstrated hepatomegaly (~ 20 cm) and small, non-specific, bilateral axillary and inguinal lymphadenopathy (Fig. 4). Patient was admitted in the Internal Medicine ward for further study.

Fig. 1.

Painless ulcers of the patient, left leg

Fig. 2.

Non-tender granulomatous plaques of the patient, right auricle (A) and right nasal ala (B)

Fig. 3.

Chest radiograph of the patient

Fig. 4.

Computed tomography of the patient with hepatomegaly (A) and inguinal lymphadenopathy (B)

Initial differential diagnosis included tropical infectious diseases (nocardiosis, leishmaniasis, mycobacteriosis), vasculitis (namely, polyarteritis nodosa), sarcoidosis, and pyoderma gangrenosum. Dermatology consultation determined findings being highly suggestive of lupus pernio, accompanied with granulomatous lesions and systemic features, with sarcoidosis being initially favoured, although histologic confirmation was needed to confirm and rule out other differential diagnosis. Further analytical study showed polyclonal hypergammaglobulinemia (A immunoglobulin 529 mg/dL, reference rages 60 to 400; G immunoglobulin 2240 mg/dL, reference ranges 700 to 1600; M immunoglobulin 270 mg/dL, reference ranges 40 to 230), elevated levels of angiotensin-converting enzyme (ACE; ~166IU/L, reference rages 20 to 70), positive ANA (1:320; homogeneous) and normal levels of RF (8IU/mL).

Biopsies from an active left leg ulcer (including the edge of the ulcer) were performed on May 22, 2025. Histologic examination was available 3 weeks after. Figures 5, 6, 7 and 8 shows the complete histologic examination. The examination shows an atrophic epidermis with a narrow grenz zone and a dense dermal infiltrate of foamy histiocytes (Figs. 5 and 6). The presence of some macrophages and collagen bands in the Hematoxylin & Eosin staining could be attributed to the previous antibiotic use. Fite-Faraco (Fig. 7) and Ziehl–Neelsen (Fig. 8) stains revealed numerous acid-fast bacilli within histiocytes. The bacilloscopic index [18] was 5+. Although Ziehl-Neelsen staining is not the most sensitive method for diagnosing leprosy compared to Fite-Faraco staining, it can still demonstrate acid-fast bacilli, particularly in multibacillary forms of the disease where the bacterial load is high [11, 19]. Periodic acid–Schiff stain was negative for fungi. The findings were diagnostic of Hansen’s disease on lepromatous pole.

Fig. 5.

Photomicrograph showing diffuse dermal infiltration by histiocytes with a vaguely granulomatous pattern (Hematoxylin & Eosin, ×10)

Fig. 6.

Photomicrograph showing the dermis with foamy cells with central nuclei of the histiocytic type (Hematoxylin & Eosin, ×40)

Fig. 7.

(A) Photomicrograph showing positivity for Fite-Faraco staining with several bacilli isolated and grouped, solid and fragmented (Fite-Faraco, ×40). (B) Photomicrograph showing positivity for Fite-Faraco staining with several bacilli isolated and grouped, solid and fragmented (Fite-Faraco, ×100)

Fig. 8.

(A) Photomicrograph showing positive Ziehl-Neelsen with several bacilli stained with fuchsin, acquiring a pinkish-red color (they are isolated and grouped, solid and fragmented) (Ziehl-Neelsen, ×40). (B) Photomicrograph showing positive Ziehl-Neelsen with several bacilli stained with fuchsin, acquiring a pinkish-red color (they are isolated and grouped, solid and fragmented) (Ziehl-Neelsen, ×100)

After obtaining the medication through importation and the results of normal glucose-6-phosphate dehydrogenase levels quantification, WHO-recommended multidrug therapy (MDT) for multibacillary leprosy was prescribed on July 29, 2025, with rifampicin 600 mg monthly, clofazimine 300 mg monthly plus 50 mg daily and dapsone 100 mg daily, through an estimated period of 12 months. A sightly alternative regimen was administered with clofazimine 100 mg every 2 days, since 50 mg pills were unavailable. Notification was made to the Portuguese National Epidemiological Surveillance System (SINAVE). Isolation was suspended and patient returned to work the day after starting treatment.

After 1 month of treatment, the patient showed remarkable improvement: all ulcers had re-epithelialized (Fig. 9), granulomatous lesions had regressed (Fig. 10), and arthralgias had completely resolved.

Fig. 9.

Ulcers of the patient, left leg, 1 month after treatment

Fig. 10.

Non-tender granulomatous plaques of the patient, right auricle (A) and right nasal ala (B), 1 month after treatment

Follow-up laboratory results in September 2025 showed normalization of inflammatory parameters, stable haemoglobin, normalization of ACE and maintaining positivity for ANA. No drug-related adverse effects occurred. The patient continues MDT with clinical remission (Figs. 11 and 12).

Fig. 11.

Ulcers of the patient, left leg, 5 months after treatment

Fig. 12.

Non-tender granulomatous plaques of the patient, right auricle (A) and right nasal ala (B), 5 months after treatment

Discussion

Hansens’ disease remains an important but underrecognized cause of chronic dermatologic and rheumatologic symptoms [2]. Although eradicated from most industrialized countries, globalization and migration have reintroduced sporadic cases into Europe [20]. In Portugal, like other southern European countries, is done the diagnoses of imported cases from endemic regions such as Brazil [8]. In 2021 Quentin Beauvillain [21] report one autochthonous case of borderline lepromatous leprosy in a 71-year-old Portuguese woman that only had been in European countries, namely Portugal and France, with the origin of the infection non identified, which may raise the possibility of transmission within non-endemic regions. The disease is transmitted by droplets (nasal and/or oral) after close and prolonged contact with an infected individual [11]. The incubation period can range from a few months to 50 years [11].

The polymorphic presentation of leprosy explains frequent misdiagnosis [1, 4, 11]. In our case, the presence of painless ulcers, granulomatous lesions, lupus pernio, ANA positivity, and elevated ACE suggested sarcoidosis. Indeed, leprosy can mimic different diseases [11], being a great imitator [22], and the diagnosis may only become clear after histopathology reveals acid-fast bacilli or with a slit-skin smear determining the bacterial index and the morphological index, as stated in WHO diagnostic criteria [11]. However, the slit-skin smear appears to be less sensitive [23].

Arthralgia and arthritis are common in leprosy, often preceding cutaneous manifestations [24, 25]. The spectrum includes acute polyarthritis resembling rheumatoid arthritis, chronic erosive arthritis, and reactive arthritis during immune reactions (Type 1 or Type 2 reactions) [25, 26]. The mechanisms involve immune complex deposition, direct infection of synovium, and inflammatory cytokine release [27, 28]. In our patient, inflammatory arthralgias without arthritis likely represented a subclinical leprous rheumatism, resolving rapidly after MDT initiation. Also, in our patient the mechanism associated with type 2 reaction could explain the ulcers [9, 10], since there was no trauma.

Laboratory findings such as elevated immunoglobulins, positive RF and positive ANA reflect polyclonal B-cell activation rather than true autoimmunity [28–30]. These false-positive autoantibodies have been reported in ~ 25% of leprosy cases [27, 29]. Also, the VDRL positive test could be interpreted as a false positive result, since this could occur with non-treponemal tests in the M. leprae infection.

Lepromatous leprosy represents the failure of Th1 cellular immunity against M. leprae, with a predominant Th2 cytokine profile [31–33]. This impaired cell-mediated response allows uncontrolled bacillary multiplication within macrophages, forming foamy histiocytes laden with bacilli [31, 34]. The grenz zone separating epidermis from the infiltrate is a hallmark feature [31, 35], as seen in the histology of our patient. Because of this mechanisms the disease may affect multiple organs, including the liver [13] and lymph nodes [12], consistent with our patient’s hepatomegaly and mild lymphadenopathy. At the time of writing this article, the patient has not shown any thyroid or testicular alterations.

In endemic countries, particularly Brazil, PCR (polymerase chain reaction) and ELISA (enzyme-linked immunosorbent assay) tests are available and have high positive predictive value, in opposition to non-endemic countries. These tests facilitate diagnosis when used on patients presenting with typical symptoms, namely skin lesions and paraesthesia and/or hypoesthesia [36, 37]. In fact, conventional PCR have a sensitivity of ~ 75% and a specificity of ~ 95% [36].

Multidrug therapy remains the cornerstone of management, combining rifampicin, dapsone, and clofazimine for 12 months in multibacillary forms [11]. Treatment success exceeds 90%, though relapse may occur in inadequately treated cases [11, 38, 39]. Early therapy prevents nerve damage and disability [11, 39]. Our patient demonstrated a rapid clinical response, despite the unconventional approach, as previously justified, suggesting that lesions were active but reversible. The patient’s family members and close contacts (namely work colleagues) showed no signs of illness. Adherence to therapy and a follow-up for potential immune reactions, namely erythema nodosum leprosum or reversal reactions are essential [11], since these complications are serious. Because of this, our patient will be followed up in consultation for years.

Leprosy continues to carry social stigma in many societies. Early diagnosis and notification are critical to interrupt transmission. Clinicians in non-endemic regions should maintain awareness when evaluating chronic ulcers or granulomatous skin lesions associated with paraesthesia and/or hypoesthesia, especially in migrants from endemic areas. In fact, in an increasingly globalised world, doctors need to be alert to endemic infections from tropical regions that have been imported. Correct diagnosis allows for appropriate treatment and, consequently, increases the likelihood of a good prognosis, without sequelae for the patient.

Conclusions

This case illustrates how Hansen’s disease in lepromatous pole can masquerade as other diseases in non-endemic settings. In an increasing globalised world, the combination of chronic painless ulcers, granulomatous lesions, and inflammatory arthropathy should prompt consideration of Hansen’s disease, particularly in individuals from endemic regions.

Histopathological confirmation remains essential for diagnosis, and multidrug therapy is highly effective. Increased clinician awareness is key to early recognition, reducing transmission, and preventing long-term sequelae.

Author contributions

B.D.C. collected clinical data, management the case and drafted the manuscript. A.F. and C.R. supervised clinical data and case management and critically revised the manuscript. P.T.A., D.S.F. and N.G. helped in case management and critically revised the manuscript. J.C.C. analysed the histological preparations. All authors read and approved the final version of the manuscript.

Funding

This work received no funding.

Data availability

No datasets were generated or analysed during the current study.

Declarations

Ethical approval

Not applicable.

Consent for publication

Written informed consent for publication of this case report and any accompanying figures was obtained from the patient. A copy of the written consent is available for review by the Editor-in-Chief of BMC Infectious Diseases and was sent along with the manuscript as supplementary material.

Competing interests

The authors declare no competing interests.