Dermatologic Manifestations of Leprosy Workup

Updated: May 14, 2018
  • Author: Felisa S Lewis, MD; Chief Editor: Dirk M Elston, MD  more...
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Workup

Laboratory Studies

Skin biopsy

The presence of an inflamed nerve in a skin biopsy specimen is considered the criterion standard for diagnosis.

The skin biopsy sample should be examined for morphologic features and for the presence of acid-fast bacilli. Biopsy is useful for determining the morphologic index, which is used in the evaluation and treatment of patients. The morphologic index is the number of viable bacilli per 100 bacilli in the leprous tissue. The bacterial index of granuloma (BIG) does not differentiate between viable and nonviable bacilli. [73]

In pure neural leprosy, a biopsy of skin near the affected nerve is recommended before attempting a nerve biopsy, as it is less invasive. If a nerve biopsy is deemed necessary, sensory nerves should be sampled. The sural nerve is often a logical place to start. [50]

See Histologic Findings below.

Lepromin testing

This test indicates host resistance to Mycobacterium leprae. Its results do not confirm the diagnosis, but they are useful in determining the type of leprosy.

A positive finding indicates cell-mediated immunity, which is observed in tuberculoid leprosy. A negative finding suggests a lack of resistance to disease and is observed in patients with lepromatous leprosy. A negative result also indicates a worsened prognosis.

To perform this test, bacillary suspension is injected into the forearm. An assessment of the reaction at 48 hours is called the Fernandez reaction, and a positive result indicates delayed hypersensitivity to antigens of M leprae or mycobacteria that cross-react with M leprae. When the reaction is read at 3-4 weeks, it is called the Mitsuda reaction, and a positive result indicates that the immune system is capable of mounting an efficient cell-mediated response.

Serology and polymerase chain reaction (PCR) testing

These are most useful in detecting multibacillary disease. However, serological tests to detect early or subclinical leprosy as a supplement or alternative to histopathology has become more important in the quest to reduce the number of new cases.

The most common serologic test detects antibodies to M leprae–specific phenolic glycolipid-I (PGL-I). This test is useful primarily in patients with untreated lepromatous leprosy, because 90% of patients have antibodies. However, antibodies are present in only 40-50% of patients with paucibacillary disease. PGL-I antibody levels decline significantly during MDT; therefore, these levels may be monitored for chemotherapy effectiveness. [74]

Lateral flow assays can detect PGL-I antibodies within 10 minutes with a sensitivity of 90-97.4% in multibacillary leprosy patients. It has the added advantages of using whole blood (versus serum), the technique is easily taught, the results are easily interpreted, and it requires no special equipment. [75] The immunogold OnSite Leprosy Ab Rapid test [Gold-LFA] and the luminescent up-converting phosphor anti-PGL-I test [UCPLFA] may be especially useful in detecting multibacillary patients with low bacillary indices. [76]

The use of the anti–45-kd and modified anti-PGL-I antibody assays in combination may be more sensitive in detecting cases of paucibacillary leprosy than either assay individually. [77]

A combination of the MDO-LID test and the Smart-Reader system (a cellphone-based test reader platform) has demonstrated 87% sensitivity on multibacillary patients and 32.3% on paucibacillary patients, with a specificity of 97.4%. [78]

PCR analysis targeting 16s ribosomal RNA can be used to detect and identify M leprae. The technique is used most often when acid-fast bacilli are detected but clinical or histopathologic features are atypical. Specimens for PCR should be fixed in alcohol or should be rapidly processed because prolonged formalin fixation decreases the sensitivity. [79]

In-situ PCR directed against the 36-kd antigen of M leprae has shown promise in detecting 60% of suspect and 70% of early leprosy. [80]

The development of a one-step reverse transcriptase PCR assay may be more sensitive in detecting bacilli in slit smears and skin biopsy specimens. This RNA-based assay is also effective for monitoring bacteria clearance during therapy. [81]

Rapid diagnostic tests and enzyme-linked immunosorbent assay (ELISA) systems continue to evolve and be highly sensitive and specific. [82] One study in Brazil found an increase of IgM and IgG (specifically IgG1 and IgG) antibodies against NDO-HSA, LID-1, and NDO-LID detected by ELISA in multibacillary patients. [83]

Cytology

Fine-needle aspirate (FNA) cytology with Ziehl-Neelsen staining and multiplex PCR was successful in diagnosing pure neural leprosy in the field. [84]

Diagnosis of erythema nodosum leprosum has been made using H&E staining with modified Ziehl-Neelsen stain on FNA material. [85]

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Imaging Studies

Radiographs

Plain radiographs may be useful to detect and monitor leprosy-induced bone changes. [86]

Resorption, fragmentation, and maligned fractures are common signs of leprosy-induced bone changes. Medullary sclerosis or wavy diaphyseal borders indicate diaphyseal whittling.

Ultrasound

Sonographic measurement of peripheral nerves to calculate cross-sectional areas to determine nerve enlargement and entrapment is increasingly useful in the diagnosis of pure neural leprosy. [87] Well-established as a method of nerve evaluation, it also offers the advantages of being low-cost, widely available, and noninvasive. [88]

Color Doppler can also be applied to evaluate for normal hypovascularization and increased vascularity with inflammation. [42]

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Procedures

Nerve conduction studies (NCS), either at the muscle or at the nerve itself, are most useful in diagnosing nerve impairment, especially in pure neural leprosy, in which the neuropathy may be silent. At the least, NCS can help in determining the nerve from which to obtain a biopsy specimen from for histology studies. [50]

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Histologic Findings

In the indeterminate form, findings are nonspecific. Histiocytes and lymphocytes are scattered, with some concentration around dermal appendages and nerves. At times, an acid-fast bacillus can be observed in a nerve bundle. The number of dermal mast cells may be increased.

In the tuberculoid form of leprosy, well-developed epithelioid granulomas are observed in the papillary dermis, often around neurovascular structures. The granulomas are surrounded by lymphocytes, which extend into the epidermis. Langhans giant cells are common. Dermal nerves are destroyed or swollen because of the granulomas. Acid-fast bacilli are not observed. S-100 is useful in identifying nerve fragmentation and differentiating it from other granulomatous disease. [89] Fite-Faraco staining combined with PCR was shown to be more sensitive than H&E and Ziehl-Neelsen staining. [90]

In the borderline tuberculoid form, well-developed epithelioid cell granulomas are apparent and diffuse, but few or no Langhans giant cells are observed. Few lymphocytes are present in the epidermis in this form, compared with tuberculoid leprosy. Bacilli are absent or rare, but they can be found in dermal nerves and in the arrector pilorum. Nerves are moderately swollen.

In the borderline borderline form of leprosy, diffuse epithelioid granulomas that lack giant cells are observed in the dermis below the subepidermal zone of uninvolved papillary dermis (ie, grenz zone). Nerves are slightly swollen, and acid-fast bacilli are present in moderate numbers.

In the borderline lepromatous form, smaller granulomas with some foamy changes and numerous lymphocytes are observed. Nerves often have an onionskin appearance as a result of invasion of the perineurium. A few epithelioid cells may be observed.

In the lepromatous form of leprosy, a diffuse infiltrate of foamy macrophages is present in the dermis below a subepidermal grenz zone. An enormous number of acid-fast bacilli develop within the foamy macrophages, singly or in clumps, called globi. Lymphocytes are scant, and giant cells are typically absent. Numerous bacilli invade the nerves, but these are fairly well preserved with little infiltrate. Nodular, or dermatofibroma-like lesions in lepromatous leprosy, referred to as histoid leprosy, result in a diffuse fascicular arrangement of spindled cells in the dermis admixed with foamy macrophages that contain numerous bacilli.

The histoid form has spindle-shaped clusters of histiocytes in a whorled or parallel pattern. In paucibacillary histoid leprosy, these clusters are in the papillary and mid dermis. Multibacillary histoid leprosy has a grenz zone with the histiocytes located in the mid and deep dermis. [91] Globus formation is usually absent. They also tend to grow in an expansive, rather than infiltrative, manner. Bacilli are notably longer than ordinary lepra bacilli.

Compared to primary leprosy, the histology of reversal reactions are more edematous, with a greater number of lymphocytes and macrophages with epithelioid characteristics. Foci of necrosis and epidermal involvement are also seen. [63]

In pure neural leprosy, biopsies of the nerve may show similar histology to that of an affected cutaneous lesion. If unaffected skin near an affected nerve was taken, a clue may be an inflammatory infiltrate around cutaneous nerve filaments. [50]

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