An alternative multidrug regimen for multibacillary Hansen’s disease: a case report

Abstract

Background

Leprosy (Hansen’s disease) is an infectious disease most common in resource-limited countries caused by the acid-fast bacilli Mycobacterium leprae and Mycobacterium lepromatosis that frequently affects the skin and peripheral nerves. Prompt diagnosis and treatment with multidrug therapy is crucial to reduce disease transmission and sequelae, which include nerve function impairment, ocular injury, and stigmatizing physical deformities. Traditional treatment of multibacillary leprosy consists of 12–24 months of multidrug therapy with dapsone, rifampin, and clofazimine. However, this regimen is associated with high pill burden and side effects that limit adherence.

Case presentation

We report a case of multibacillary leprosy in a previously healthy 30-year-old Hispanic man who recently immigrated to the USA from South America and presented with progressive nodular skin lesions on his face and extremities. He was treated with a monthly regimen of rifampin, moxifloxacin, and minocycline. At follow-up there was significant improvement of his cutaneous lesions without signs of reversal reaction or erythema nodosum leprosum.

Conclusions

This case report adds to the growing repertoire of literature supporting the use of rifampin, moxifloxacin, and minocycline. Further studies are needed to assess the efficacy of this antimycobacterial regimen and monitor rates of relapse and delayed immunologic reactions, which may occur 5–10 years after completion of treatment.

Background

Leprosy, also called Hansen’s disease, is an infectious disease most common in resource-limited countries caused by the acid-fast bacilli Mycobacterium leprae and Mycobacterium lepromatosis [1,2,3]. It frequently affects the skin and peripheral nerves, with clinical manifestations due to the host’s cellular immune response that include hypopigmented or erythematous cutaneous lesions, peripheral nerve enlargement, and sensory loss [1, 4]. Leprosy is classified on a spectrum, from paucibacillary (tuberculoid) to multibacillary (lepromatous), on the basis of the Ridley–Jopling system that combines clinical, bacteriologic, and histologic features [5].

Despite public health efforts to eliminate the disease, approximately 200,000 new cases are reported annually to the World Health Organization (WHO), primarily from Africa and Southeast Asia [6]. According to the National Hansen’s Disease Program (NHDP), 159 new cases were reported in the USA in 2020, mostly imported from endemic areas [7]. While it is difficult to identify source of infection given its prolonged incubation period, risk factors include close contact with leprosy patients, zoonotic exposure (specifically, the nine-banded armadillo in the southern USA and red squirrel in the British Isles), advanced age, and immunosuppression [2, 8, 9].

Prompt diagnosis and treatment with multidrug therapy consisting of dapsone, rifampin, and clofazimine is crucial to reduce disease transmission and sequelae, which include nerve function impairment, ocular injury, and stigmatizing physical deformities [3, 4]. However, this regimen is associated with significant side effects that impact both quality of life and clinical outcomes. Thus, alternative regimens with reduced toxicity are needed.

Case presentation

A 30-year-old Hispanic male with no past medical history presented to the emergency department with 8 months of progressive nodular skin lesions on his face and extremities, nasal obstruction, epistaxis, and facial numbness. Review of systems was also positive for testicular pain, tactile fevers, malaise, abdominal pain, and nausea. The patient recently immigrated to the USA from Peru, traveling through Ecuador, Colombia, Panama, Nicaragua, El Salvador, Guatemala, and Mexico. He denied known sick contacts. He lived in an apartment with multiple roommates and was sexually active with one female partner.

Physical exam was notable for numerous nontender, erythematous papules and nodules involving the bilateral earlobes, face, extensor surfaces of the forearms, and lower extremities (Fig. 1A). Additionally, there was left facial hypoesthesia in the V1/V2 distribution, mild soft tissue edema of the external nose, a small right testicular nodule, and a 2 cm ulcerated papule on the dorsal aspect of his right hand. No hypopigmentation, peripheral nerve enlargement, hair loss, or ophthalmic involvement were noted. Fiber-optic flexible laryngoscopy performed by an otolaryngologist revealed hyposensate bilateral anterior nasal cavities with erythematous crusting.

Fig. 1

Ulcerated papule on the dorsal aspect of the right hand and numerous erythematous nodules on the bilateral earlobes and face before (A), after 2 months (B), and after 12 months (C) of treatment with rifampin, moxifloxacin, and minocycline

Laboratory studies, including complete blood count with differential, basic metabolic panel, liver function tests, urinalysis, and blood cultures were unremarkable. Infectious work-up, including human immunodeficiency virus (HIV), tuberculosis quantiferon gold, syphilis, urine test for gonorrhea/chlamydia, and viral hepatitis panel were also negative. Erythrocyte sedimentation rate was mildly elevated at 47 mm per hour and C-reactive protein was normal. Testicular ultrasound revealed hypoechoic testicular lesions with central internal vascularity within both testes and prominent bilateral inguinal lymph nodes. Chest X-ray, abdominal ultrasound, and magnetic resonance imaging (MRI) of the face and orbits were unremarkable. Due to initial concern for mucocutaneous leishmaniasis given his presentation and report of multiple insect bites sustained during travel, he received a 6-day course of intravenous liposomal amphotericin B while awaiting biopsy results, although serologic tests later returned negative.

Biopsy samples of the nasal mucosa and right dorsal hand were obtained and demonstrated a dense dermal infiltrate of vacuolated histiocytes with numerous organisms on Fite stain compatible with Mycobacterium lepromatosis. After discussion with the NHDP, the patient was started on a once monthly regimen of rifampin 600 mg, moxifloxacin 400 mg, and minocycline 100 mg (RMM) for an anticipated 12–24 months. On his 12-month follow-up, there was significant improvement of his cutaneous lesions (Fig. 1B and C).

Discussion

Traditional treatment of multibacillary leprosy, as recommended by the WHO and NHDP, consists of 12–24 months of multidrug therapy with dapsone, rifampin, and clofazimine [10, 11]. Their guidelines differ in that the NHDP recommends longer duration of treatment, increased frequency of rifampin administration, and excludes the use of clofazimine for paucibacillary leprosy. However, these regimens are associated with high pill burden and side effects that limit adherence. Severe side effects include skin discoloration, dose-dependent hemolytic anemia in glucose-6-phosphate dehydrogenase deficiency, agranulocytosis, and hepatotoxicity [12]. Alternative agents include minocycline, clarithromycin, and ofloxacin, which are typically reserved for patients with resistance or contraindications.

A single dose of rifapentine, moxifloxacin, and minocycline was previously shown to kill 99.9% of viable M. leprae in mouse footpad infection [13]. A recently published case series of ten patients with multibacillary or pure neural leprosy treated with an alternative regimen of rifampin, moxifloxacin, and minocycline (RMM) for 12–24 months demonstrated rapid clinical response, minimal side effect profile, and improved adherence [14]. We report a case of multibacillary leprosy with mucosal and testicular involvement in a patient who recently immigrated from South America treated with RMM. As shown in Fig. 1, the patient had improvement of his skin lesions at 12 months. There were no significant side effects. He adhered to and tolerated the regimen well without signs of reversal reaction (type 1 reaction) or erythema nodosum leprosum (type 2 reaction). Since the medications were covered by the NHDP at no cost to the patient, there were no financial barriers to treatment.

Conclusions

This case report adds to the growing repertoire of literature supporting the use of RMM. Further studies are needed to assess the efficacy of this antimycobacterial regimen and monitor rates of relapse and delayed immunologic reactions, which may occur 5–10 years after completion of treatment [15].