DIAGNOSIS of Leprosy

Leprosy most commonly presents with both characteristic skin lesions and skin histopathology. Thus the disease should be suspected when a patient from an endemic area has suggestive skin lesions or peripheral neuropathy; the diagnosis should be confirmed by histopathology. In tuberculoid leprosy, lesional areas—preferably the advancing edge—must be biopsied because normal-appearing skin does not have pathologic features. In lepromatous leprosy, nodules, plaques, and indurated areas are optimal biopsy sites, but biopsies of normalappearing skin are also generally diagnostic. Lepromatous leprosy is associated with diffuse hyperglobulinemia, which may result in falsepositive serologic tests (e.g., VDRL, RA, ANA) and therefore may cause diagnostic confusion. On occasion, tuberculoid lesions may not (1) appear typical, (2) be hypesthetic, and (3) contain granulomas but only nonspecific lymphocytic infiltrates. In such instances, two of these three characteristics are considered sufficient for a diagnosis. It is preferable to overdiagnose leprosy rather than to allow a patient to remain untreated.

IgM antibodies to PGL-1are found in 95% of untreated lepromatous leprosy patients; the titer decreases with effective therapy. However, in tuberculoid leprosy—the form of disease most often associated with diagnostic uncertainty owing to the absence or paucity of AFB—patients have significant antibodies to PGL-1 only 60% of the time; moreover, in endemic locales, exposed individuals without clinical leprosy may harbor antibodies to PGL-1. Thus PGL-1 serology is of little diagnostic utility in tuberculoid leprosy. Heat-killed M. leprae (lepromin) has been used as a skin test reagent. It generally elicits a reaction in tuberculoid leprosy patients, may do so in individuals without leprosy, and gives negative results in lepromatous leprosy patients; consequently, it is likewise of little diagnostic value. Unfortunately, PCR of the skin for M. leprae, although positive in LL and BL leprosy, yields negative results in 50% of tuberculoid leprosy cases, again offering little diagnostic assistance.

Included in the differential diagnosis of lesions that resemble leprosy are sarcoidosis, leishmaniasis, lupus vulgaris, lymphoma, syphilis, yaws, granuloma annulare, and various other disorders causing hypopigmentation. Sarcoidosis may result in perineural inflammation, but actual granuloma formation within dermal nerves is pathognomonic for leprosy. In lepromatous leprosy, sputum specimens may be loaded with AFB—a finding that can be inappropriately interpreted as representing pulmonary tuberculosis.

Source: Harrison_s_Principles_of_Internal_Medicine_16th_Edition