Lepromatous leprosy

Cytokines, eg, interferons, interleukins, tumor necrosis factor (TNF), and certain growth factors, could have antitumor activity directiy, or may modulate cellular mechanisms of antitumor activity (2). Cytokines may be used to influence the proliferation and differentiation of T-ceUs, B-ceUs, macrophage—monocyte, myeloid, or other hematopoietic cells. Alternatively, the induction of interferon release may represent an important approach for synthetic—medicinal chemistry, to search for effective antiinflammatory and antifibrotic agents. Inducers of interferon release may also be useful for lepromatous leprosy and chronic granulomatous disease. The potential cytokine and cytokine-related therapeutic approaches to treatment of disease are summarized in Table 4. A combination of cytokines is a feasible modaUty for treatment of immunologically related diseases however, there are dangers inherent in such an approach, as shown by the induction of lethal disserninated intravascular coagulation in mice adrninistered TNF-a and IFN-y. 

Additional studies illustrate that IFN-y stimulates phagocytic activity in humans suffering from various cancers, AIDS and lepromatous leprosy (leprosy is caused by the bacterium Mycobacterium leprae. Lepromatous leprosy is a severe contagious form of the disease leading to disfigurement). IFN-y may thus prove useful in treating such conditions. 

R. L. Barnhill, A. C. Mcdougall, Thalidomide Use and Possible Mode of Action in Reactional Lepromateous Leprosy and in Various Other Conditions ,./. Am. Acad. Dermatol. 1982, 7, 317-323. 

One description of a clinical picture that results from tuberculoid leprosy is characterized by intact cell-mediated immunity, a positive lepromin skin reaction, granuloma formation, and a relative paucity of bacilli. At the other extreme, lepromatous leprosy is characterized by depressed cell-mediated immunity, numerous bacilli within the tissues, no granulomas, and a negative skin test for lepromin. Within these two extremes are the patients with an intermediate or borderline form of leprosy who show a variable lepromin reaction and few bacilli they may progress to either tuberculoid or lepromatous leprosy. 

A 68-year-old white South African man receiving treatment for lepromatous leprosy has increasing red-brown pigmentation. Which of the following antileprosy drugs is responsible for the patient s skin pigmentation ... 

PABA) incorporation into folic acid (inhibition of folate synthesis). In large proportion of Mycobacterium leprae infections e.g. in lepromatous leprosy, resistance can develop, so combination of dapsone, rifampicin and clofazimine is used in initial therapy. 

Recently, thalidomide (50-100 mg capsule form, approved by FDA), an immunomodulatory agent is used in erythema nodosum leprosum (ENL) which is a complication of leprosy occurring in approximately one half of borderline lepromatous and lepromatous leprosy patients. 

Several drugs closely related to the sulfonamides have been used effectively in the long-term treatment of leprosy. The most widely used is dapsone (diaminodiphenylsulfone). Like the sulfonamides, it inhibits folate synthesis. Resistance can emerge in large populations of M leprae, eg, in lepromatous leprosy, if very low doses are given. Therefore, the combination of dapsone, rifampin, and clofazimine is recommended for initial therapy. Dapsone may also be used to prevent and treat Pneumocystis jiroveci pneumonia in AIDS patients. 

Rifampin (see earlier discussion) in a dosage of 600 mg daily is highly effective in lepromatous leprosy. Because of the probable risk of emergence of rifampin-resistant M leprae, the drug is given in combination with dapsone or another antileprosy drug. A single monthly dose of 600 mg may be beneficial in combination therapy. 

The clinical effectiveness of deoxyfructoserotonin in leprosy has been tested in the Institute Marchoux in Bamako (Rep. of Mali). Seven patients suffering from leprosy were treated during 6 months with deoxyfructoserotonin at a daily rate of 5 - 20 mg/kg body weight. Considerable improvement was observed in a few weeks in cases classified "borderline" and in a few months in cases of lepromatous leprosy (23). 

Lepromatous leprosy occurs in people who exhibit an efficient antibody response to M. leprae but an inefficient cellular immune response. The antibody arm of the immune system is not useful in neutralizing intracellular pathogens such as M. leprae therefore, people who initially react to invasion by M. leprae by making antibodies may be at risk for developing more severe forms of leprosy. Researchers are not sure what determines whether a person will react with a cellular response or an antibody response current evidence suggests that the cellular immune response may be controlled by a special gene. If a person has this gene, he or she will probably develop the less severe tuberculoid leprosy if exposed to M. leprae. 

Cellular immune response—The part of the immune system that destroys infected cells. Lepromatous leprosy—The most severe form of leprosy, characterized by numerous lesions and extensive nerve damage. 

Thalidomide has anti-inflammatory and immimo-suppressant actions and retains a limited specialist use in, for example, lepromatous leprosy, and oral ulceration in AIDS (some cases). 

Intraneural deposition of a ceroid-like pigment has been seen after treatment of lepromatous leprosy with clofazimine (6). This pigment does not affect the healing process. Treatment can be continued, provided that the dose is not too high. 

Clofazimine can inhibit the liver damage that is associated with lepromatous leprosy and the leprosy reaction it has only minimal or no deleterious effects on Uver function (11). 

McDougall AC, Jones RL. Intra-neural ceroid-like pigment following the treatment of lepromatous leprosy with clofazimine (B663 Lamprene). J Neurol Neurosurg Psychiatry 1981 44(2) 116-20. 

A French woman with chronic urticaria (12) and an Indian man with lepromatous leprosy (13) developed fever, wheezing, and breathlessness. Both had peripheral eosinophilia and chest X-rays showed infiltrates. The woman s symptoms began 2 weeks after she started to take dapsone but recurred a few hours after a subsequent rechallenge. The man s symptoms occurred a few hours after each daily dose. Symptoms in both cases resolved within a few days of stopping dapsone. 

In 28 patients with lepromatous leprosy, clofazimine did not influence the urinary excretion of dapsone, except in one case (46). 

Single or multiple lesions of erythema nodosum lepro-sum occurred in 60% of patients given intradermal interferon gamma for lepromatous leprosy, and severe systemic symptoms required thalidomide treatment in two patients (18). 

Sampaio EP, Moreira AL, Sarno EN, Malta AM, Kaplan G. Prolonged treatment with recombinant interferon gamma induces erythema nodosum leprosum in lepromatous leprosy patients. J Exp Med 1992 175(6) 1729-37. 

Jonquieres ED, Mosto SJ, Brusco CM. Tahdomida y reac-cion leprosa lepromatosa. [Thahdomide and lepromatous leprosy reaction.) Arch Argent Dermatol 1967 17(3) 279-86. 

Clofazimine is used in the treatment of lepromatous leprosy. including dap.sone-resistant forms of the di.sca.se. In sidition to its antibacterial action, the drug appears to possess anti-inflammatory and immune-modulating effects that are of value in controlling neuritic complications and in suppressing erythema nodosum leprosum reactions associated with lepromatous leprosy. It is frequently used in combina-iion with other drugs, such as dapsone or rifampin. 

Protection from mbercnlosis is characterized by effective Mycobacterium-specific Thl responses and it has been hypothesized that co-infections with helminths will prevent the necessary Thl response by either disturbing the Thl/Th2 balance, or by driving the immune response towards a more anti-inflammatory status. Early observations showed that the incidence of lepromatous leprosy was twice as high in areas where onchocerciasis was endemic (Prost et al. 1979). 

Clarithromycin or azithromycin is recommended as first-line therapy for prophylaxis and treatment of disseminated infection caused by M. avium-intracellulare in AIDS patients and for treatment of pulmonary disease in non-HIV-infected patients. Azithromycin (1.2 g once weekly) or clarithromycin (500 mg twice daily) is recommended for primary prevention for AIDS patients with fewer than 50 CD cells per mm. Single-agent therapy should not be used for treatment of active disease or for secondary prevention in AIDS patients. Clarithromycin (500 mg twice daily) plus ethambutol (15 mg/kg once daily) with or without rifabutin is an effective combination regimen. Azithromycin (500 mg once daily) may be used instead of clarithromycin, but clarithromycin appears to be slightly more efficacious. Clarithromycin also has been used with minocychne for the treatment of Mycobacterium leprae in lepromatous leprosy. 

Flairy-cell and chronic lymphocytic leukemias non-Flodgkin s lymphoma chronic multiple sclerosis Pneumocystis carinii pneumonia associated with AIDS Lepromatous leprosy Treahng pain in cancer Hemophiha B Multiple sclerosis Hyahne membrane disease Mulhple sclerosis... 

Ji, B., Jamet, R, Perani, E. G., Bobin, R, and Grosset, J. H. (1993). Powerful bactericidal activities of clarithromycin and minocycline against Mycobacterium leprae in lepromatous leprosy. 

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