Apparent exacerbation of Hansen's disease despite appropriate antimicrobial therapy

Military Medicine,  Nov 2003  by Zapor, Michael,  Kaplan, Keith,  Hawkes, Clifton

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In 1991, the World Health Organization and its member states resolved to reduce the global prevalence of Hansen's disease (leprosy) by at least 90%. Despite its waning prevalence, however, the disease remains endemic in parts of Africa, Asia, and Latin America. Moreover, imported cases are occasionally encountered in nonendemic areas. This fact, coupled with the current tempo of overseas deployments, makes it imperative that military physicians familiarize themselves with both the presentation and potential complications of Hansen's disease. Here, we present the case of a soldier referred to Walter Reed Army Medical Center for apparent worsening of his disease despite appropriate antibiotic therapy. On evaluation, the patient was diagnosed with reversal reaction, an immune-mediated phenomenon resembling disease exacerbation and requiring prompt intervention to avert lasting sequelae. Following the case presentation, we discuss the clinical manifestations, pathophysiology, and management of reversal reactions as well as the related entity erythema nodosum leprosum.

Introduction

Although Hansen's disease (leprosy) persists in endemic regions, its global prevalence is declining, and in most countries, it is no longer considered to be a public health problem (as defined by prevalence greater than 1/10,000 in a population above one million). In the United States, the diagnosis is exceedingly uncommon. In 1996, for example, there were 112 reported cases, the majority of which were clustered within Texas, California, and Hawaii.1 Despite its waning prevalence, Hansen's disease remains problematic in parts of Africa, Asia, and Latin America. This fact, coupled with the current tempo of overseas deployments by U.S. armed forces, increases the likelihood that Medical Corps officers will eventually encounter the diagnosis. Consequently, a military physician deploying from a low prevalence area may not only miss the diagnosis but may be unfamiliar with the presentation and management of potential complications. One such complication is the reactional episode, a collective term for two immune-mediated reactions (reversal reaction [RR], erythema nodosum leprosum [ENL]) resembling disease exacerbation. The following is an illustrative case report and brief discussion about the clinical presentation and management of patients undergoing these reactions.

Case Report

A 26-year-old Micronesian man, living in Germany, was diagnosed with borderline tuberculoid Hansen's disease after presenting with progressive skin lesions and paresthesia of 3 months' duration. Biopsy demonstrated acid-fast bacilli and granulomas, and therapy with dapsone and rifampin was initiated. Following an initial response to therapy, there was an abrupt flare in the intensity of the lesions and allodynia developed. The patient was subsequently transferred to our institution for further evaluation and management. Examination revealed a stocky male with numerous erythematous, scaling, annular plaques on the face, trunk, and extremities (Fig. 1). Some were hypoesthetic and others dysesthetic. The patient also had edema of the face and hands with clawing of the latter (Fig. 2). Neurological examination was notable for diminished sensation to light touch and temperature along the distribution of the maxillary and mandibular branches of the fifth cranial nerve on the right, the lateral aspect of the left upper extremity, and both lower extremities below the knees. There were no grossly enlarged nerves, but palpation along the ulnar nerves was painful. Aside from ichthyotic skin changes on the dorsum of both feet (Fig. 3), examination was otherwise unremarkable. Several lesions were biopsied, and histopathology was notable for both the presence of perivascular and perineural granulomas as well as the absence of acid-fast bacilli (Fig. 4).

Antibiotic therapy with dapsone and rifampin was continued, and the patient was treated symptomatically for his neuralgia with nonsteroidal anti-inflammatory drugs and gabapentin. The patient's clinical presentation and histopathology were suggestive of reaction, and aggressive therapy was instituted with gradual clinical improvement.

Discussion

During the course of the disease, both treated and untreated patients may suffer from a reactional episode. The particular reaction corresponds to the type of disease. Generally, patients with borderline disease undergo RR, whereas those with lepromatous disease are at risk for ENL. Roughly one-half of the patients being treated for (borderline) lepromatous disease will develop ENL.2 This is a humoral-mediated phenomenon resembling an arthus reaction and probably results from the formation of complexes consisting of circulating antibodies and antigens released from disintegrating Mycobacterium leprae bacteria.3 Clinical features may include: fever, iridocyclitis, synovitis, adenopathy, hepatosplenomegaly, orchitis, neuralgia, glomerulonephritis (secondary to the deposition of immune complexes in the kidneys), and the formation of tender erythematous cutaneous and subcutaneous nodules, which are prone to ulceration and necrosis. Histology may show cutaneous, neural, and vascular infiltration by neutrophils, edema, and in severe cases, destruction of the dermis.