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Leprosy is caused by infection by the acid-fast bacteria Mycobacterium leprae Leprosy is the most common cause of peripheral neuropathy in Southeast Asia, Africa, and South America There is a spectrum of clinical manifestations ranging from tuberculoid leprosy at one end to lepromatous leprosy on the other end of the spectrum, with borderline leprosy in between (Table 15 2)1 3 The clinical manifestations of the disease are determined by the immunological response of the host to the infection In tuberculoid leprosy, the cell-mediated immune response is intact1,2,4 Thus, there are focal, circumscribed in ammatory responses to the bacteria within the affected areas of skin and nerves The resulting skin lesions appear as well-de ned, scattered hypopigmented patches and plaques with raised, erythematous borders (Figs 15 1 and 15 2) Cutaneous nerves are often affected, resulting in a loss of sensation in the center of these skin lesions Cooler regions of the body (eg, face and limbs) are more susceptible than warmer regions such as the groin or axilla In addition, the ulnar nerve at the medial epicondyle, the median nerve at the distal forearm, the peroneal nerve at the bular head, the sural nerve, the greater auricular nerve, and the super cial radial nerve at the wrist are common sites of involvement and become encased with granulomas, leading to mononeuropathy or mononeuropathy multiplex These nerves are thickened and often palpable In lepromatous leprosy, cell-mediated immunity is severely impaired, leading to extensive in ltration of the bacilli and hematogenous dissemination, producing con uent and symmetrical areas of rash, anesthesia, and anhidrosis1,2,4 The clinical manifestations tend to be more severe in the lepromatous subtype
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Sensory nerve conduction studies (NCS) are usually absent in the lower limb and are reduced in amplitude in arms1,6,7 Motor NCS may demonstrate reduced amplitudes in affected nerves7,8 Motor NCS are normal or slightly reduced; however, a few patients may demonstrate values less than 20 m/s in both the upper and the lower limb Electromyography (EMG) reveals mild-tomoderate degrees of active denervation The pattern of involvement on the EMG and NCS can be generalized
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TABLE 15 1 INFECTIOUS AGENTS ASSOCIATED WITH NEUROPATHIES
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Bacterial: Mycobacterium leprae (Leprosy) Borrelia burdorferi (Lyme disease) Corynebacterium diphtheriae (Diphtheria) Viral: Human immunode ciency virus (HIV) Distal symmetric polyneuropathy Acute in ammatory demyelinating polyradiculoneuropathy Chronic in ammatory demyelinating polyradiculoneuropathy Other polyradiculoneuropathy Mononeuropathy multiplex Autonomic neuropathy Sensory ganglionopathy Human T-lymphocytic type 1 (HTLV-1) Cytomegalovirus (CMV) Hepatitis B and C Herpes varicella zoster (HVZ)
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as symmetric or re ective of a mononeuropathy or multiple mononeuropathies, as apparent from the clinical features
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HISTOPATHOLOGY
Leprosy is usually diagnosed with skin lesion biopsy and using the Fite method to stain the acid-fast bacilli red2 Nerve biopsies can also be diagnostic, particularly when there are no apparent skin lesions The host s immune response to the bacilli determines the histopathology (Table 15 2)2,3,6 The tuberculoid form is characterized by granulomas formed by macrophages and Th1 cells, which are surrounded by Th2 cells Caseation may or may not be present, and typical lesions extend throughout the dermis Importantly, bacilli are not seen In contrast with lepromatous leprosy, large number of in ltrating bacilli, Th2 lymphocytes,
TABLE 15 2 CLINICAL, LABORATORY, IMMUNOLOGICAL, AND HISTOPATHOLOGICAL FEATURES OF LEPROSY
Tuberculous Leprosy (TT)
Lepromin test Bacterial index Morphological index (MI) Immunology Positive (>5 mm induration) 0 Low (down to zero) Cell-mediated immunity: intact; Th 1 > Th2 lymphocytes; cytokines expressed: IL-2 and -IF Few localized and welldemarcated large skin lesions; erythematous macules and plaques with raised borders; centers of lesions may be hypopigmented Localized granulomas and giant cells encompassed by dense lymphocytic in ltrate extending to epidermis; Fite stain: negative for bacteria
Mid-Borderline Leprosy (BB)
+/ (2 5 mm induration) 2 4 Moderate Cell-mediated immunity: unstable (can range and switch from intact to absent) Size, number, and appearance of the skin lesions are intermediate between that seen in the TT and LL poles
Lepromatous Leprosy (LL)
Negative (0 2 mm induration) 5 6 High (up to 10) Cell-mediated immunity: absent; Th 2 > Th1 lymphocytes; cytokines expressed: IL-4, IL-5, and IL-10 Multiple, symmetrical small macules and papules; older lesions form plaques and nodules
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