Novel approaches in the treatment of Hansen's disease (Leprosy): a case series of multidrug therapy of monthly rifampin, moxifloxacin, and minocycline (RMM) in the United States.

The World Health Organization (WHO) recommends multidrug therapy (MDT) for the treatment of paucibacillary and multibacillary forms of leprosy, also known as Hansen's disease (HD). MDT combinations of dapsone, rifampin, and clofazimine have reduced the prevalence of the disease but are not without adverse effects impacting regimen adherence. Hence, an urgent need exists to consider alternative MDT regimens with an improved safety profile that promotes treatment adherence. Herein, we described a case series of 10 patients with HD (nine patients with multibacillary leprosy and one with pure neural leprosy) treated with monthly rifampin, moxifloxacin, and minocycline (RMM). The United States National Hansen's Disease Program (NHDP) diagnosed and treated patients across US institutions. All patients received a regimen of 12-24 months of RMM. We reviewed the clinical outcomes, adherence, rate of completion, and adverse events of patients treated with monthly RMM from January 2019 to August 2022. Nine patients had multibacillary leprosy, with some having type-2 reactions. One patient had pure neural leprosy with a reversal reaction. In this case series, we identified that all patients completed the RMM regimen without treatment interruptions. None of the patients experienced any skin hyperpigmentation or any significant side effects. All patients tolerated the monthly RMM regimen with rapid improvement of skin lesions and without logistic hurdles. Based on previous clinical evidence and the results of this case series, the NHDP and other programs should consider the RMM regimen as first-line therapy.

A Hand-Held Ultrasound Device for the Assessment of Peripheral Nerves in Leprosy.

BACKGROUND AND PURPOSE: Mycobacterium leprae complex affects peripheral nerves, causing nerve enlargement. This proof-of-concept pilot study was conducted to determine if a small hand-held ultrasound device can accurately identify nerve involvement in individuals with leprosy. METHODS: Peripheral nerve ultrasound was conducted of the bilateral median (wrist, forearm, elbow, and mid-humerus), ulnar (wrist, forearm, elbow, 4 cm proximal to the elbow, and mid-humerus), C5 root, and greater auricular nerves with a standard ultrasound device (15 Mhz) and a hand-held ultrasound device (5 MHz). Nerve cross-sectional areas were compared using the two devices. RESULTS: Eight individuals with leprosy were examined. Strong correlation was found between the standard and hand-held ultrasound devices (r = .76, P < .001). A certain amount of variability between ultrasound devices may occur for multiple reasons. CONCLUSION: A hand-held ultrasound device can readily identify nerve enlargement in individuals with leprosy. This type of device may assist in the diagnosis of leprosy in areas with limited healthcare resources because of the portability and low-cost nature of such devices.

Persistent Infection Versus Type 2 Immunological Reaction in Lepromatous Leprosy.

The distinction between persistent infection and immunologic reactions in leprosy is often difficult but critically important since their management is different. We present the case of a 51-year-old Vietnamese female who presented in 2015 with areas of erythema and skin infiltration on face and chest, as well as edema on her hands and feet. Skin biopsy was consistent with lepromatous leprosy. She was treated with rifampin, clarithromycin, and levofloxacin for 2 years. Her lower extremity edema was attributed to type 2 immunological reaction for which she was started on prednisone and methotrexate, but she was lost to follow-up for 19 months. She presented with new skin lesions and pain on her extremities. New biopsies revealed an intense neutrophilic infiltrate in the dermis and acid-fast bacilli focally within cutaneous nerve twigs. As compared with the initial biopsy, the inflammatory infiltrates were diminished and the bacilli had a degenerating appearance. These findings were consistent with type 2 immunological reaction. The patient was treated with thalidomide with improvement in the appearance of the skin lesions. A follow-up biopsy showed lack of neutrophilic infiltrates and decreased number of bacilli. This case illustrates the importance of differentiating between persistent infection and immunologic reactions in leprosy. Clinicians should be aware of these complications. A high index of suspicion and accurate interpretation of skin biopsy results are essential for appropriate diagnosis.

Leprosy: Treatment and management of complications.

In the second article in this continuing medical education series, we review the treatment of leprosy, its immunologic reactions, and important concepts, including disease relapse and drug resistance. A fundamental understanding of the treatment options and management of neuropathic sequelae are essential to reduce disease burden and improve patients' quality of life.

Leprosy: Clinical aspects and diagnostic techniques.

Leprosy, also known as Hansen's disease, is a curable infectious disease that remains endemic in >140 countries around the world. Despite being declared "eliminated" as a global public health problem by the World Health Organization in the year 2000, approximately 200,000 new cases were reported worldwide in 2017. Widespread migration may bring leprosy to nonendemic areas, such as North America. In addition, there are areas in the United States where autochthonous (person-to-person) transmission of leprosy is being reported among Americans without a history of foreign exposure. In the first article in this continuing medical education series, we review leprosy epidemiology, transmission, classification, clinical features, and diagnostic challenges.

Isolation of Mycobacterium lepromatosis and Development of Molecular Diagnostic Assays to Distinguish Mycobacterium leprae and M. lepromatosis.

BACKGROUND: Mycobacterium leprae was thought to be the exclusive causative agent of leprosy until Mycobacterium lepromatosis was identified in a rare form of leprosy known as diffuse lepromatous leprosy (DLL). METHODS: We isolated M. lepromatosis from a patient with DLL and propagated it in athymic nude mouse footpads. Genomic analysis of this strain (NHDP-385) identified a unique repetitive element, RLPM, on which a specific real-time quantitative polymerase chain reaction assay was developed. The RLPM assay, and a previously developed RLEP quantitative polymerase chain reaction assay for M. leprae, were validated as clinical diagnostic assays according to Clinical Laboratory Improvement Amendments guidelines. We tested DNA from archived histological sections, patient specimens from the United States, Philippines, and Mexico, and US wild armadillos. RESULTS: The limit of detection for the RLEP and RLPM assays is 30 M. leprae per specimen (0.76 bacilli per reaction; coefficient of variation, 0.65%-2.44%) and 122 M. lepromatosis per specimen (3.05 bacilli per reaction; 0.84%-2.9%), respectively. In histological sections (n = 10), 1 lepromatous leprosy (LL), 1 DLL, and 3 Lucio reactions contained M. lepromatosis; 2 LL and 2 Lucio reactions contained M. leprae; and 1 LL reaction contained both species. M. lepromatosis was detected in 3 of 218 US biopsy specimens (1.38%). All Philippines specimens (n = 180) were M. lepromatosis negative and M. leprae positive. Conversely, 15 of 47 Mexican specimens (31.91%) were positive for M. lepromatosis, 19 of 47 (40.43%) were positive for M. leprae, and 2 of 47 (4.26%) contained both organisms. All armadillos were M. lepromatosis negative. CONCLUSIONS: The RLPM and RLEP assays will aid healthcare providers in the clinical diagnosis and surveillance of leprosy.

Case report: Hansen's disease in an active duty soldier presenting with type 1 reversal reaction.

Leprosy, or Hansen's disease (HD), is caused by the bacterium Mycobacterium leprae and is a significant cause of morbidity worldwide. Clinical manifestations range from isolated skin rash to severe peripheral neuropathy. Treatment involves a prolonged course of multiple antimicrobials. Although rare in the U.S., with only 168 new cases reported in 2016, HD remains a prevalent disease throughout the world, with 214,783 new cases worldwide that same year.1 It remains clinically relevant for service members born in and deployed to endemic regions. This report describes a case of HD diagnosed in an active duty soldier born and raised in Micronesia, a highly endemic region.

Trends of leprosy and multibacillary infection in the state of Georgia since the early 1900s.

Few investigations to date have analyzed the epidemiology of Hansen's disease (leprosy) in the United States, and in particular, if birth location is related to multibacillary versus paucibacillary leprosy. We collected data on 123 patients diagnosed with leprosy in Georgia from the National Hansen's Disease Program from 1923-January 2018. A logistic regression model was built to examine the relationship between country of origin (U.S.-born or immigrant) and the type of leprosy. While the model showed no significant relationship between country of origin and type of leprosy, being Asian or Pacific Islander was associated with a higher odds of multibacillary disease (aOR = 5.71; 95% CI: 1.25-26.29). Furthermore, since the early 1900s, we found an increasing trend of leprosy reports in Georgia among both domestic born and immigrant residents, despite the overall decrease in cases in the United States during the same time period. More research is therefore necessary to further evaluate risk for multibacillary leprosy in certain populations and to create targeted interventions and prevention strategies.

Dapsone Resistance in Leprosy Patients Originally from American Samoa, United States, 2010-2012.

Skin biopsies from US leprosy patients were tested for mutations associated with drug resistance. Dapsone resistance was found in 4 of 6 biopsies from American Samoa patients. No resistance was observed in patients from other origins. The high rate of dapsone resistance in patients from American Samoa warrants further investigation.

Tuberculosis and Leprosy Coinfection: A Perspective on Diagnosis and Treatment.

Both leprosy and tuberculosis (TB) are known to have similar geographic endemicity. In the setting of coinfection, interferon-gamma release assays (IGRAs) to detect latent TB can be falsely positive. We report a case of leprosy with a positive IGRA and asymptomatic active pulmonary TB. Minocycline and dapsone therapy was initiated during the workup for TB and changed to rifampin (Rif), isoniazid, pyrazinamide, and ethambutol, with the addition of dapsone once coinfection was confirmed. Our review of the literature revealed a preponderance of coinfection reported with borderline and lepromatous disease. Ten patients were diagnosed with leprosy as the first infection; 7 of these patients (70%) were treated with Rif before TB diagnosis, and 70% (7/10) of coinfected patients were on steroids. If treatment for leprosy is a consideration before ruling out active TB, then minocycline may temporarily replace the Rif. The dire implications of Rif monotherapy in undiagnosed coinfection may warrant chest radiography with or without sputum microbiology as routine initial workup for all leprosy cases.

Hansen's Disease and Rheumatoid Arthritis Crossover of Clinical Symptoms: A Case Series of 18 Patients in the United States.

Hansen's Disease (HD) is a rare, chronic granulomatous infection of the skin and peripheral nerves caused by the noncultivable organism Mycobacterium leprae. Arthritis is the third most common symptom of HD. Subjects with both confirmed HD on skin biopsy and chronic arthritis were identified at the National Hansen's Disease Program (NHDP). We conducted a series of medical chart reviews and extracted and logged personally deidentified data into a database and carried out descriptive analyses. Eighteen of 261 subjects presented to the NDHP with both HD and chronic arthritis between 2001 and 2015. Among these, 16 were male, 16 were white, and 15 were residents of Louisiana. The median age at diagnosis of HD was 67 years. Ten of these subjects were diagnosed with borderline lepromatous leprosy, seven were diagnosed with lepromatous, and one was diagnosed with borderline tuberculoid leprosy. Patients were symptomatic with arthritis for a median of 5.3 years before HD diagnosis. Sixty-two percent of patients (11) were diagnosed with rheumatoid arthritis (RA) before HD diagnosis, and 10 of which were seronegative RA. Hands, feet, wrists, and elbows were most commonly reported as affected joints. Over half of the patients (61%) had completed HD multidrug therapy at the time of review, and 73% of these subjects had persistent joint pain requiring steroids or methotrexate for symptomatic control. Chronic arthritis in HD patients is present in a series of US-acquired cases of HD. Arthritis did not resolve with successful treatment of HD in most cases.

Mycobacterium lepromatosis Lepromatous Leprosy in US Citizen Who Traveled to Disease-Endemic Areas.

We report Mycobacterium lepromatosis infection in a US-born person with an extensive international travel history. Clinical symptoms, histopathology, and management are similar to those of infections caused by M. leprae. Clinicians should consider this pathogen in the diagnosis of patients with symptoms of leprosy who have traveled to endemic areas.

Two Cases of Leprosy in Siblings Caused by Mycobacterium lepromatosis and Review of the Literature.

We describe two leprosy cases in Mexican siblings caused by a new species Mycobacterium lepromatosis This is likely the first report of family clustering of this infection. The patients showed severe prolonged leprosy reactions after antimicrobial treatment, raising a challenge for clinical management. The current status of M. lepromatosis infection is reviewed.

Indigenous Cases of Leprosy (Hansen's Disease) in Southern Mississippi.

Hansen's disease or leprosy is a chronic infection of the skin and peripheral nerves caused by Mycobacterium leprae. In the U.S., leprosy is mainly reported in immigrants, but indigenous leprosy cases have been also reported in this country, especially in semitropical southern states (i.e., Texas, Louisiana). The objective of this series of cases is to describe indigenous leprosy cases reported in southern Mississippi (MS) during the period 2012-2014. Information was collected from medical records at Hattiesburg Clinic and the MS Department of Health. Four cases were reported during the period of study (3 Caucasian males, 1 African-American woman). Non of visited endemic leprosy country. The age ranged from 60 to 83 years (median: 75.5 years). Of the four cases, three presented with a slowly progressive erythematous rash disseminated mainly on the thorax and abdomen, with a lesser degree on the extremities. The time between onset of rash until the diagnosis ranged from 5 to 16 months (median: 7 months). Only one case had direct contact with armadillos (blood exposure). Non of these patients had a history of immunosuppression. The most common symptoms were neuropathic pain (n=2), generalized pruritus (n=2) and loss of sensation in extremities (n=2). One case had severe peripheral neuropathy with muscle weakness, atrophy in left arm, and wasting on left hand. Skin biopsies showed diffuse granulomatous infiltrate with foamy histiocytes along with acid fast bacilli by Fite stain. By Ridley-Jopling classification system, three cases were diagnosis as lepromatous leprosy, and one, borderline lepromatous. Treatment included clofazimine, dapsone and rifampin that was offered free of charge by the National Hansen's Diseases Program, Baton Rouge, L.A. One patient did not tolerate therapy. In conclusion, a slowly progressive disseminated erythematous skin rash on the trunk should raise suspicion for leprosy in the elderly population in south MS.