Title:There is pseudoepitheliomatous hyperplasia of the epidermis overlying a diffuse dermal infiltrate of histiocytes with sparse lymphocytes and plasma cells. Histiocytes have abundant clear and granular cytoplasm. Acid-fast bacillus and Fite stains highlight numerous bacilli within histiocytes.
Citation:Dermatology Online Journal 14 (5): 21
Authors:Christine Liang MD, Anthony C. Soldano MD,,  William Levis MD
Affiliations:Department of Dermatology, New York University
Abstract:
A 47-year-old man from Ecuador presented with a 2-year history of asymptomatic, erythematous plaques and nodules on the thighs, knees, and elbows. Histopathologic examination showed elongated collections of macrophages that contained numerous acid-fast bacilli and Fite-positive bacteria in the dermis. The clinical and histopathologic findings were consistent with a diagnosis of multibacillary or lepromatous leprosy. Leprosy is a chronic, granulomatous infectious disease caused by Mycobacterium leprae. Multi-drug treatment with dapsone, rifampin, and clofazamine has appreciably reduced the worldwide prevalence of leprosy but has not decreased the incidence in countries with high endemic rates.

Body:

	A:Clinical synopsis
A 47-year-old man presented to the Dermatology Clinic at Bellevue Hospital Center in January, 2006, with a 2-year history of asymptomatic, erythematous plaques and nodules on the thighs, knees, and elbows. The first lesion appeared on the left knee 2 years ago and gradually spread to the thighs, trunk, and upper extremities. They were not pruritic or painful. The patient had not received previous treatment. He denied fevers, chills, or any loss of sensation. He took no medications. There was no history of sexually transmitted disease, hepatitis, or drug use. Review of systems disclosed a 15 pound weight loss over six months and chronic nasal congestion. Family history of skin disease was negative. He was born in Ecuador and immigrated to the United States in 1998, where he has remained. The patient was treated with dapsone 50 mg daily and minocycline 100 mg daily.

A punch biopsy was obtained from a left inner thigh nodule, and shave biopsy was taken from a thin plaque on the right back.

	A:Physical Examination
Multiple, symmetric, erythematous plaques and nodules were located on the thighs, knees, and elbows. On the anterior trunk were numerous light pink, thin plaques with accentuated skin markings. On the back were multiple, skin-colored, finely wrinkled patches and thin pink plaques. Also noted was thickening of facial skin, madarosis of the lateral eyebrows, and pendulous earlobes. An enlarged left ulnar nerve was palpable. Sensation remained intact in all 4 extremities.

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A complete blood count, basic metabolic panel, liver function tests, and C-reactive protein were normal. Erythrocyte sedimentation rate was elevated to 25 mm/hr. A human immunodeficiency virus test was negative, and T-cell subsets were normal. A rapid plasma reagin test was non-reactive. Antinuclear antibody, rheumatoid factor, and hepatitis B antigen and antibody tests were negative.

	A:Histopathology
There is pseudoepitheliomatous hyperplasia of the epidermis overlying a diffuse dermal infiltrate of histiocytes with sparse lymphocytes and plasma cells. Histiocytes have abundant clear and granular cytoplasm. Acid-fast bacillus and Fite stains highlight numerous bacilli within histiocytes.

	A:Comment
Leprosy or Hansen disease is a chronic, granulomatous infection that primarily affects the skin, peripheral nerves, and mucous membranes. It is caused by the acid-fast bacillus Mycobacterium leprae. The introduction of multi-drug treatment has appreciably decreased the worldwide prevalence of leprosy [1]. However, leprosy incidence has remained stable in countries with high endemic rates despite the advent of multi-drug therapy [2, 3]. Brazil, India, Madagascar, Mozambique, and Nepal have the highest endemic rates. [1] According to the World Health Organization (WHO), 166 new cases were reported in the United States in 2005 [4].

Mycobacterium leprae is an obligate, intracellular parasite that multiplies very slowly and optimally at 27 to 33°C. This fact correlates clinically with its predilection for affecting cooler areas of the body. The organism cannot be cultured in vitro but can multiply in animals, such as the armadillo, which has a cooler body temperature. The route of transmission is uncertain but is probably spread via respiratory droplets [5]. Predisposing risk factors for the acquisition of leprosy include close contact [6] and impaired cell-mediated immunity [7]. The large majority of people exposed to leprosy will not develop the disease, and those that do may develop only a single lesion that resolves. Those that develop multibacillary leprosy typically have an impaired cell-mediated immune response, which can be measured utilizing the lepromin skin test. 

The two principal classification schemes are the WHO and Ridley-Jopling systems. WHO system is based on the number of skin lesions present and the whether bacilli are detected on skin smears. Those individuals with negative smears are described as paucibacillary (tuberculoid) leprosy and those with positive smears as multibacillary (lepromatous) leprosy [8]. The Ridley-Jopling system is based on an immunologic status, as a high resistance tuberculoid response (TT), borderline tuberculoid (BT), mid-borderline (BB), borderline lepromatous (BL), and a low resistance response lepromatous leprosy (LL). Clinically, tuberculoid leprosy has hypopigmented or annular hypoesthetic patches. Lepromatous leprosy is characterized by plaques, nodules, and a diffuse dermal infiltrate. Extracutaneous manifestations include sensory neuropathy, chronic nasal congestion, hypogonadism, corneal damage, and uveitis. 

Histolopathologic findings in lepromatous leprosy consist of a dermal infiltrate of foamy macrophages underneath a Grenz zone. Acid-fast bacilli are highlighted with a Fite stain. Tuberculoid leprosy shows epithelioid-cell granulomas that may reach the epidermis and tend to be linear along nerves. Acid-fast bacilli are rare or not present with Fite stain in tuberculoid leprosy [9].

Leprosy is a curable disease and multidrug therapy is standard treatment. In multibacillary disease most patients are treated with dapsone, rifampin, and clofazamine [10]. In the United States, paucibacillary disease is treated for 12 months and multibacillary disease for 24 months. Ofloxacin, levofloxacin, minocycline, and clarithromycin also are being used for treatment [11, 12]. Patients are considered non-infectious after the first dose of multi-drug therapy. The widespread use of multi-drug therapy has reduced the worldwide prevalence of leprosy.

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1. Global Leprosy Situation, 2006. Weekly Epidemiological Record 2006; 31:309
2. Lockwood DN. Leprosy: too complex a disease for a simple elimination paradigm. Bull World Health Organ 2005;83:230
3. Scollard DM, et al. The continuing challenges of leprosy. Clin Microbiol Rev 2006;19:338
4. American Region: Leprosy situation at the end of 2005. World Health Organization
5. Britton WK, et al. Leprosy. Lancet 2004;363:1209
6. Moet FJ, et al. Physical distance, genetic relationship, age, and leprosy classification are independent risk factors for leprosy in contacts of patients with lepros. J Infect Dis 2006;193:346
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8. WHO Expert Committee on Leprosy. Seventh Report. WHO Tech Rep Ser No 874, Geneva, WHO, 1998
9. Rapini RP. Bacterial diseases. In: Rapini, RP ed. Practical Dermatopathology. 1st edition. Philadelphia: Mosby, 2005:163
10. Lockwood DN, et al. Treatment of leprosy. Br Med J 2004;328:1447
11. Gelber RH, et al. A clinical trial of minocycline in lepromatous leprosy. Br Med J 2993;304:91
12. Ji B, et al. Powerful bactericidal activities of clarithromycin and minocycline against Mycobacterium leprae in lepromatous leprosy. J Infect Dis 1993;168:188