Hansen's Disease (Leprosy)

Current and Future Pharmacotherapy and Treatment of Disease-related Immunologic Reactions

Davey P. Legendre, Pharm.D.; Christina A. Muzny, M.D.; Edwin Swiatlo, M.D., Ph.D.

Disclosures

Pharmacotherapy. 2012;32(1):27-37. 

In This Article

Immunologic Reactions

Immunologic reactions to M. leprae antigens are generally classified as either type 1 (reversal) or type 2 (erythema nodosum leprosum [ENL]) and reflect the predominant immunologic response locally in either nerves or skin. An example of a type 1 (reversal) reaction is shown in Figure 2. Approximately one third of patients with borderline leprosy are at risk for type 1 reactions, whereas type 2 reactions affect 50% of patients with the lepromatous form and 10% of those with the borderline lepromatous form of leprosy. These reactions may be a presenting feature of the disease or occur during or after multidrug therapy.[23] These reactions have also been described in patients with human immunodeficiency virus as part of the immune reconstitution inflammatory syndrome.[24] Prompt recognition and treatment of inflammatory reactions are necessary to minimize progressive nerve damage that can occur with sustained inflammatory responses.

Figure 2.

Example of a type 1 (reversal) reaction to therapy for Hansen's disease (leprosy) appearing as skin lesions on the patient's back.

Type 1 reactions are characterized by a shift to Th1-type immune responses in the host and are associated with locally elevated levels of interferon-γ, tumor necrosis factor-α (TNF-α), interleukin-12, and inducible nitric oxide synthase.[25] This type of reaction can be seen in any type of leprosy but is uncommon in the tuberculoid form of the disease as an appropriate Th1-type immune response already exists. The diagnosis of type 1 reactions is generally made clinically; however, skin biopsy is often useful. Histologic criteria for type 1 reactions are not standardized, but common findings include dermal edema, large epithelioid granulomas, and plasma cells.[26] Skin lesions may become larger and more erythematous and may ulcerate. New or worsening symptoms of neuritis may appear and can include both motor and sensory nerve dysfunction.[23] Generalized edema may occur, but systemic symptoms are not common.

Type 2 reactions, also known as ENL, are distinguished clinically by fever, malaise, and the rapid appearance of new subcutaneous nodules that are erythematous and quite painful.[17] These lesions are typically found on the face and extensor surfaces of the limbs, but any site of the body can be affected.[23] Painful neuritis is a common complication. Erythema nodosum leprosum is thought to be an immune complex disease with consequent activation of complement. Circulating levels of TNF-α and interferon-γ are elevated.[27] Widespread immune complex deposition can occur and cause polyarthritis, iridocyclitis, orchitis, lymphadenitis, and glumerulonephritis.[17] Peripheral leukocytosis with neutrophils is a common laboratory finding. Patients with borderline or the lepromatous form of leprosy are at highest risk for ENL because they have a higher bacteriologic index.[23]

A rare but potentially life-threatening reaction to M. leprae is erythema necroticans or Lucio's phenomenon.[28] This reaction is distinct from type 1 and 2 reactions and is characterized by necrotizing vasculitis that has been ascribed to invasion of vascular endothelium with M. leprae. Clinical manifestations include bluish or violaceous and hemorrhagic plaques, followed by necrotic ulcerations. These symptoms typically occur in the absence of systemic complaints or leukocytosis. The precise role of dysregulated immune responses in this reaction has not been fully studied.

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