Hansen's Disease (Leprosy): Current and Future Pharmacotherapy and Treatment of Disease‐Related Immunologic Reactions

Abstract

Hansen's disease, also known as leprosy, remains an important public health problem throughout the world, including North America. The causative microbe in Hansen's disease is Mycobacterium leprae, an acid-fast organism that is difficult to grow in vitro. The nine-banded armadillo is the major animal reservoir in the United States. Manifestations of disease vary based on host immune response and can range from tuberculoid to lepromatous leprosy (paucibacillary to multibacillary disease). Hansen's disease typically affects the skin, nerves, and eyes, and patients may present with skin lesions, weakness, numbness, eye pain, or loss of vision. Definitive diagnosis is based on a combination of physical examination findings and skin biopsy and/or smear. Modern antibacterial therapy typically consists of combinations of dapsone and rifampin with or without clofazimine. Clofazimine is available only as an investigational drug through the National Hansen's Disease Program. Other options include moxifloxacin, ofloxacin, minocycline, and clarithromycin. Hansen's disease is associated with type 1 (reversal) and type 2 (erythema nodosum leprosum) immunologic reactions, during which the disease process appears to worsen dramatically. These reactions may occur at any time before, during, or after treatment. Antibacterial therapy should usually be continued during these reactions. Treatment options for these reactions differ based on clinical manifestations and include corticosteroids, thalidomide, pentoxiphylline, tumor necrosis factor inhibitors, and T cell inhibitors. Prompt diagnosis, antimicrobial therapy, and treatment of reactions dramatically reduce complications of the disease.

Complex Type 2 Reactions in Three Patients with Hansen's Disease from a Southern United States Clinic

“…7 Type 2 reactions (T2Rs), also known as erythema nodosum leprosum (ENL), are systemic events that occur in borderline lepromatous and lepromatous cases and can cause damage to the nerves, eyes, and skin. 8 Typical symptoms included fever, arthralgias, neuritis, nerve trunk inflammation, and classic painful erythematous skin nodules, hence the name ENL. These reactions can vary greatly from patient to patient, with several reports of unique clinical manifestations.…”

Development and characterization of a new oral dapsone nanoemulsion system: permeability and in silico bioavailability studies

“…1 During this process, this disease can worsen dramatically, and antibacterial therapy should continue during these periods. 1,2 Since 1947, dapsone (4,4-diaminodiphenyl sulfone) has been known to be a useful drug in the treatment of leprosy. 2 Its mechanism of action is via competitive inhibition of M. leprae dihydropteroate synthase, thus inhibiting the synthesis of folic acid.…”

“…The treatment options differ according to the clinical manifestations. 1 Leprosy can be associated with type 1 (reversal) and type 2 (erythema nodosum leprosum) immunologic reactions that may occur at any time before, during, or after the start of treatment. 1 During this process, this disease can worsen dramatically, and antibacterial therapy should continue during these periods.…”

“…1 Leprosy can be associated with type 1 (reversal) and type 2 (erythema nodosum leprosum) immunologic reactions that may occur at any time before, during, or after the start of treatment. 1 During this process, this disease can worsen dramatically, and antibacterial therapy should continue during these periods. 1,2 Since 1947, dapsone (4,4-diaminodiphenyl sulfone) has been known to be a useful drug in the treatment of leprosy.…”

“…It is caused by Mycobacterium leprae, and affects the skin, eyes, and nerves, leading to skin lesions, eye pain, loss of vision, weakness, and numbness. 1 The final diagnosis is based on a combination of findings on skin biopsy, smear, and physical examination. The treatment options differ according to the clinical manifestations.…”