Mucormycosis and chromoblastomycosis occurring in a patient with leprosy type 2 reaction under prolonged corticosteroid and thalidomide therapy.

Mucormycosis is an uncommon fungal infection caused by Mucorales. It frequently occurs in patients with neutropenia, diabetes, malignancy and on corticoid therapy. However, it is rare in patients with AIDS. Clinical disease can be manifested in several forms. The case reported illustrates the rare occurrence of chromoblastomycosis and mucormycosis in an immunosuppressed patient with multibacillary leprosy, under prolonged corticosteroid and thalidomide therapy to control leprosy type 2 reaction. Neutrophil dysfunction, thalidomide therapy and work activities are some of the risk factors in this case. Chromoblastomycosis was treated by surgical excision and mucormycosis with amphotericin B. Although the prognosis of mucormycosis is generally poor, in the reported case the patient recovered successfully. This case should alert dermatologists to possible opportunistic infections in immunosuppressed patients.

Mucormycosis and chromoblastomycosis occurring in a patient with leprosy type 2 reaction under prolonged corticosteroid and thalidomide therapy / Mucormicose e cromoblastomicose em um paciente com reação hansênica tipo II sob terapia prolongada com corticosteróide e talidomida

Mucormycosis is an uncommon fungal infection caused by Mucorales. It frequently occurs in patients with neutropenia, diabetes, malignancy and on corticoid therapy. However, it is rare in patients with AIDS. Clinical disease can be manifested in several forms. The case reported illustrates the rare occurrence of chromoblastomycosis and mucormycosis in an immunosuppressed patient with multibacillary leprosy, under prolonged corticosteroid and thalidomide therapy to control leprosy type 2 reaction. Neutrophil dysfunction, thalidomide therapy and work activities are some of the risk factors in this case. Chromoblastomycosis was treated by surgical excision and mucormycosis with amphotericin B. Although the prognosis of mucormycosis is generally poor, in the reported case the patient recovered successfully. This case should alert dermatologists to possible opportunistic infections in immunosuppressed patients.

Mucormicose é uma infecção fúngica incomum causada por Mucorales. Ocorre frequentemente em pacientes com neutropenia, diabetes, corticoterapia e condições malignas. Porém, é rara em pacientes com AIDS. A doença pode apresentar-se em diferentes formas. Este caso ilustra a rara ocorrência de mucormicose e cromoblastomicose em um paciente com hanseníase multibacilar, que estava sendo tratado com prednisona e talidomida devido a eritema nodoso (reação hansênica tipo II). Disfunção de neutrófilos, uso de talidomida e atividades profissionais são alguns fatores de risco neste caso. A cromoblastomicose foi tratada por excisão cirúrgica e a mucormicose com anfotericina B. Embora o prognóstico da mucormicose seja ruim, neste caso o tratamento foi bem sucedido. Este caso alerta dermatologistas para a possibilidade de infecções oportunistas em pacientes imunossuprimidos.

Immediate hypersensitivity to rifampicin in 3 patients: diagnostic procedures and induction of clinical tolerance.

BACKGROUND: Desensitization with drugs may be indicated in some clinical situations. Apart from large experiences with beta-lactam antibiotics and cotrimoxazole in HIV infection, experience with other drugs is limited. Rifampicin may elicit exanthema and urticaria, and their pathomechanisms are not known in detail. Since therapy with rifampicin may be indispensable in mycobacterial infections or against multiresistant Staphylococcus aureus, desensitization may be indicated in some patients. OBJECTIVE: Report of immediate hypersensitivity to rifampicin and description of diagnostic and desensitization procedures. METHODS: We report 3 patients with immediate urticarial reactions to rifampicin. Diagnostic procedures included skin and in vitro tests (specific IgE, lymphocyte transformation test, LTT, and CAST). The non-irritant cutoff concentration was evaluated in 24 volunteers. A 7-day desensitization procedure was used. RESULTS: Only intradermal tests at a dilution of at least 1:10,000 (concentration of rifampicin approximately 0.006 mg/ml) were true positive, whereas in vitro tests (IgE, LTT and CAST) did not correctly identify hypersensitive patients. Two patients had positive accidental reexposure. All patients were successfully desensitized with rifampicin according to a slow 7-day protocol. CONCLUSIONS: Rifampicin rarely elicits immediate hypersensitivity symptoms which may be diagnosed by intradermal skin tests. In vitro tests did not contribute to the diagnosis. Therefore, an IgE-mediated mechanism remains to be proven. Desensitization with rifampicin using different protocols has been reported. In our 3 cases, clinical tolerance to rifampicin was achieved using a 7-day protocol.

Thalidomide: current and potential clinical applications.

More than three decades after its withdrawal from the world marketplace, thalidomide is attracting growing interest because of its reported immunomodulatory and anti-inflammatory properties. Current evidence indicates that thalidomide reduces the activity of the inflammatory cytokine tumor necrosis factor (TNF)-alpha by accelerating the degradation of its messenger RNA. Thalidomide also inhibits angiogenesis. Recently, the drug was approved for sale in the United States for the treatment of erythema nodosum leprosum, an inflammatory complication of Hansen's disease. However, it has long been used successfully in several other dermatologic disorders, including aphthous stomatitis, Behçet's syndrome, chronic cutaneous systemic lupus erythematosus, and graft-versus-host disease, the apparent shared characteristic of which is immune dysregulation. Many recent studies have evaluated thalidomide in patients with human immunodeficiency virus (HIV) infection; the drug is efficacious against oral aphthous ulcers, HIV-associated wasting syndrome, HIV-related diarrhea, and Kaposi's sarcoma. To prevent teratogenicity, a comprehensive program has been established to control access to the drug, including registration of prescribing physicians, dispensing pharmacies, and patients; mandatory informed consent and education procedures; and limitation of the quantity of drug dispensed. Clinical and, in some patients, electrophysiologic monitoring for peripheral neuropathy is indicated with thalidomide therapy. Other adverse effects include sedation and constipation. With appropriate safeguards, thalidomide may benefit patients with a broad variety of disorders for which existing treatments are inadequate.

Induction of lepromin positivity following immuno-chemotherapy with Mycobacterium w vaccine and multidrug therapy and its impact on bacteriological clearance in multibacillary leprosy: report on a hospital-based clinical trial with the candidate antileprosy vaccine.

A vaccine based on autoclaved Mycobacterium w was administered, in addition to standard multidrug therapy (MDT), to 157 bacteriologically positive, lepromin-negative, multibacillary (LL, BL and BB) leprosy patients. The vaccinees were supported by a well-matched control group of 147 patients with similar type of disease who received a placebo injection in addition to MDT. The MDT was given for a minimum period of 2 years and continued until skin-smear negativity, while the vaccine was given at 3-month intervals up to a maximum of 8 doses. The lepromin response evaluated in terms of percentage of subjects converting to positivity status, measurement in millimeters, and duration of lepromin positivity sustained, reflected a statistically significant better outcome in the vaccine group patients (especially LL and BL leprosy) in comparison to those in the placebo group. The data indicate that lepromin-positivity status seems to have an impact on accelerating the bacteriological clearance, as is evident by the statistically significant accelerated decline in the BI of those patients who converted to lepromin positivity as compared to those remaining lepromin negative throughout therapy and post-therapy follow up. To conclude, the addition of the Mycobacterium w vaccine to standard MDT induces a lepromin response of a statistically significant higher magnitude than that observed with MDT alone.

Crescentic glomerulonephritis due to rifampin treatment in a patient with pulmonary atypical mycobacteriosis.

A 64-year-old male was treated continuously with rifampin, isoniazid and streptomycin for pulmonary atypical mycobacteriosis, Mycobacterium kansasii. Five weeks after beginning the treatment, the patient suddenly developed acute renal failure. A renal biopsy showed crescentic lesions characteristic of rapidly progressive glomerulonephritis with moderate interstitial changes. Serum antirifampin antibody was detected, and the cessation of rifampin treatment was followed by a rapid spontaneous recovery of the patient's renal function. This is, to our knowledge, the first case of rapidly progressive crescentic glomerulonephritis associated with rifampin treatment where circulating antirifampin antibody is demonstrated and the renal function spontaneously improved after discontinuing rifampin treatment.

Post-vaccination sensitization with ICRC vaccine.

ICRC vaccine is one of the candidate anti-leprosy vaccines under test in a large scale comparative vaccine in trial. The objectives of the present study was to study the sensitization potential, as measured by Rees' MLSA and lepromin, and reactogenicity of this vaccine preparation in the local population. The study included 368 'healthy' individuals aged 1-70 years. Each individual received either ICRC vaccine or normal saline (control) by random allocation. They were also tested with Rees' MLSA and lepromin-A, 12 weeks after vaccination. Reactions to Rees' MLSA were measured after 48 hours and those to lepromin-A after 48 hours and three weeks. Character and size of local response, at the vaccination site, were recorded at 3rd, 8th and 15th week after vaccination. The results of the study showed that healing of vaccination lesion was uneventful, the mean size of the lesion being 10.3 mm. The mean sizes of post-vaccination reactions, to Rees' MLSA and lepromin (both early and late reactions), were significantly higher in the vaccine group compared to that in the normal saline group; the sensitizing effect attributable to the vaccine was of the order of 3.5 mm, 1.7 mm and 2.2 mm respectively. In conclusion, the study has demonstrated that ICRC vaccine was 'safe' and produced significant sensitizing effect as measured by post-vaccination sensitization to Rees' MLSA and lepromin, in the local population.

Immune status of subsided cases of tuberculoid (TT) and borderline tuberculoid (BT) leprosy.

A comparative study of lepromin reactions (early and late), M. leprae induced lymphocyte blastogenesis, per cent T Cell number in peripheral blood and immunoglobulin (IgG, IgA and IgM) levels have been made in TT-active, TT-subsided, BT-active and BT-subsided leprosy cases. No significant difference has been noted amongst these groups in the above mentioned investigations except in subsided BT cases where 9 out of 11 cases failed to evoke any late skin reaction to Dharmendra antigen. In addition, BT subsided cases also showed significantly raised levels of IgG. The significance of these findings with respect to their immunity and reinfection has been discussed.