A 48-year-old man who recently immigrated to the United States comes to the physician with multiple skin lesions. Physical examination shows a few well-defined, hypopigmented lesions on the skin of his lower extremities that have diminished sensation. After confirming the diagnosis of leprosy, the patient undergoes further testing to help classify the severity of his disease. Intradermal injection of heat-killed Mycobacterium leprae causes the development of a large indurated nodule. The patient is most likely to demonstrate which of the following additional findings?

Question

A 48-year-old man who recently immigrated to the United States comes to the physician with multiple skin lesions.  Physical examination shows a few well-defined, hypopigmented lesions on the skin of his lower extremities that have diminished sensation.  After confirming the diagnosis of leprosy, the patient undergoes further testing to help classify the severity of his disease.  Intradermal injection of heat-killed Mycobacterium leprae causes the development of a large indurated nodule.  The patient is most likely to demonstrate which of the following additional findings?

Quizplus · Accepted Answer

11ec160b_38fa_e24c_9249_e983208eb3cb_MD0001_00 Leprosy is a chronic, slowly progressive, communicable disease caused by Mycobacterium leprae that typically involves the skin and peripheral nerves. Clinical manifestations are widely variable depending on the strength of the T_H1 cell-mediated immune response to the organism. Disease is classified along a spectrum between tuberculoid (mild) to lepromatous (severe) forms. Patients with tuberculoid leprosy develop a strong T_H1-mediated response (interleukin [IL]-2, IFN-γ, and IL-12) in affected tissues, leading to the activation of macrophages that kill M leprae organisms, thereby limiting disease extent. However, this localized inflammation damages the skin and cutaneous nerves, leading to the development of a small number of hypopigmented, well-demarcated plaques with decreased sensation. Lepromatous leprosy is a more disseminated form of the disease characterized by an innate inability to recognize and mount a cellular immune response against M leprae antigens. Affected tissues show extensive accumulation of acid-fast bacilli within macrophages and often a T_H2 cytokine profile (IL-4, IL-5, and IL-10). Patients with lepromatous leprosy develop more numerous, poorly demarcated plaques that are widespread across the body. Over time, the bacterial load increases and the nodular lesions coalesce, causing the development of leonine facies and degeneration and loss of the nose and digits. The lepromin skin test (in which M leprae antigens are injected intradermally) can be used to distinguish between tuberculoid and lepromatous leprosy. Patients with tuberculoid leprosy will develop an indurated nodule at the site of the injection (much like a positive PPD test for M tuberculosis). In contrast, the test is usually nonreactive in patients with lepromatous leprosy due to their weak T_H1 cell-mediated immune response. (Choice A) Patients with lepromatous leprosy have a high bacterial load with widespread involvement throughout the peripheral (cooler) tissues of the body. As a result, intermittent bacteremia often occurs in the later stages of the disease. However, this patient's few lesions and positive lepromin skin test are more indicative of tuberculoid leprosy, which has a very low bacterial load with limited tissue involvement. (Choice B) High serum antimycobacterial antibody levels are more frequently seen in lepromatous leprosy than tuberculous leprosy. Because M leprae resides mostly within macrophages, circulating immunoglobulins have little access to the organism and are unable to bind, opsonize, or fix complement. Humoral immunity does not influence the positivity of the lepromin skin test. (Choice C) In lepromatous leprosy, macrophages remain inactivated due to the inability of T_H1 cells to recognize M leprae antigens. This form of leprosy is characterized by a poor cell-mediated response and diffuse spread of the organism. This patient is presenting with the tuberculoid form, in which activated macrophages actively kill M leprae organisms. (Choice E) Acid-fast bacteria typically do not accumulate in the skin lesions of tuberculoid leprosy due to the strong cell-mediated response that is effective at eradicating M leprae. In some instances, this immune response is so effective that tuberculoid leprosy can be self-limited and heal completely without treatment. Educational objective: The lepromin skin test will be positive in patients with tuberculoid leprosy as they exhibit a strong CD4+ T_H1 cell-mediated immune response to Mycobacterium leprae. Patients with lepromatous leprosy will test negative due to their weak T_H1 cell-mediated immune response.

A 48-Year-Old Man Who Recently Immigrated to the United States