thioacetazone and Stevens-Johnson-Syndrome

Prospective randomised clinical trial comparing the safety and efficacy of rifampicin- and thiacetazone-containing regimens in human immunodeficiency virus (HIV)-infected adults with pulmonary tuberculosis (TB) at the National Tuberculosis Treatment Centre, Kampala, Uganda.. To assess demographic, clinical and laboratory risk factors associated with toxicity during treatment with streptomycin, thiacetazone and isoniazid (STH) of HIV-1 infected adults with pulmonary TB.. Nested case-control study of all subjects randomized to the STH treatment arm. Baseline demographic, clinical, microbiological, hematological and radiographic characteristics were compared between subjects who developed and those who did not develop adverse drug reactions (ADR).. Of the 90 subjects randomized to STH, 13 developed ADR yielding an incidence rate of 19.6 events per 100 person years of observation (PYO). Eleven of the 13 ADR were cutaneous hypersensitivity reactions, including one fatal case of Stevens-Johnson syndrome. Eight of 13 patients who developed ADR were tuberculin anergic, compared to 12 of 77 patients who did not develop ADR (P < 0.001). An absolute lymphocyte count below 2000 cells/mm3 was also associated with ADR (P = 0.02).. Initial anergy to tuberculin and lymphocytopenia, markers of advanced HIV infection and immunosuppression, were associated with increased risk for adverse drug reactions during STH chemotherapy.

Topics: Adolescent; Adult; AIDS-Related Opportunistic Infections; Antitubercular Agents; Case-Control Studies; Clonal Anergy; Confidence Intervals; Developing Countries; Drug Eruptions; Drug Therapy, Combination; Female; HIV-1; Humans; Incidence; Jaundice; Lymphopenia; Male; Middle Aged; Odds Ratio; Prospective Studies; Rifampin; Risk Factors; Stevens-Johnson Syndrome; Survival Rate; Thioacetazone; Tuberculosis, Pulmonary; Uganda

Toxic epidermal necrolysis is a severe disease often leading to death or to mucosal, particularly ocular, after effects. The principle drugs responsible are antibacterial sulfonamides, anti-epileptics, non-steroid anti-inflammatories, allopurinol and chlormezanone. We report a series of 38 cases of toxic epidermal necrolysis, observed in Dakar, imputable to thiacetazone and lethal in 60 percent of cases.. Our study was retrospective. Diagnosis of toxic epidermal necrolysis was made in patients presenting more than 30 p. 100 of the epidermis of their total body surface stripped off, multi-orificial mucosal damage and epidermal necrosis revealed on histological examination. Drug imputability was established on classical criteria. Treatment was composed of reanimation and antibiotics.. Among the 38 cases of toxic epidermal necrolysis counted, 24 were imputable to thiacetazone. All the patients presented typical clinical features, confirmed histologically. Evolution was lethal in 60 p. 100 of cases. The causes of death were frequently hypovolemic shock during the first week and septic shock during the second. The deceased were generally aged over 50, had more than 50 p. 100 of total epidermis stripped off, presented evolving tuberculosis at the time of the accident and HIV infection at the AIDS stage. After effects were vaginal synechia and 2 cases of blindness.. Our series is exceptional in that a) the drug responsible: thiacetazone, an economic tuberculostatic of minor efficacy, was systematically introduced after 2 months of intensive treatment with 4 major anti-tuberculosis agents; b) the 60 percent mortality rate, two-fold greater that that usually observed. Other than the known elements of poor prognosis in our patients, the treatment conditions of this dermatological emergency explain this high rate of mortality.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antitubercular Agents; Cause of Death; Child; Developing Countries; Female; Humans; Male; Middle Aged; Retrospective Studies; Senegal; Stevens-Johnson Syndrome; Survival Rate; Thioacetazone

Topics: AIDS-Related Opportunistic Infections; Antitubercular Agents; Cost Savings; Developing Countries; Humans; Malawi; Stevens-Johnson Syndrome; Thioacetazone; Tuberculosis, Pulmonary

Because thiacetazone has been linked with serious adverse cutaneous reactions, we undertook 1 year of systematic surveillance for cutaneous thiacetazone-associated adverse reactions within the national tuberculosis programme of Tanzania. For individual cases, we collected information on age, sex, interval between commencing thiacetazone-containing treatment and occurrence of adverse reaction, most severe clinical presentation (toxic epidermal necrolysis, rash without necrolysis, itching without rash), and outcome (dead or alive) within 2 weeks of onset. Univariate and multivariate analyses were done of variables relevant to outcome. 1273 patients with adverse reactions were reported. The frequency of fatal outcome from any cutaneous reaction was 3.1 per 1000 among all tuberculosis patients, and 19.1% among patients with toxic epidermal necrolysis. About 60% of all adverse reactions and deaths occurred within 20 days of starting thiacetazone. Case fatality from adverse cutaneous reactions was considerably less frequent than reported previously, suggesting that improved management might allow retention of thiacetazone in the armamentarium of national tuberculosis programmes even where infection with HIV is prevalent.. Thiacetazone is a useful and inexpensive companion drug in the treatment of tuberculosis (TB). Its main contribution is its ability to prevent failure and relapse in patients with initially isoniazid-resistant strains. Early toxicity studies showed that the drug was generally better tolerated in East Africa than in many other countries. Thiacetazone is an essential drug in the Tanzania National Tuberculosis/Leprosy Program. Under trial conditions in Tanzania, before the HIV epidemic, adverse reactions associated with thiacetazone were uncommon. Serious, and occasionally fatal, toxic cutaneous reactions to sulphur-containing drugs in HIV-infected patients have been recognized for several years. Recently, the use of thiacetazone in HIV-infected patients has been linked with serious adverse cutaneous reactions, including toxic epidermal necrolysis. Most reports, however, concerned only patients admitted to referral hospitals, so the Tanzania National Tuberculosis Program began a nationwide one-year systematic surveillance study to determine the frequency and severity of adverse cutaneous reactions. Individual-level data were collected on each case's age, sex, interval between commencing thiacetazone-containing treatment and occurrence of adverse reaction, most severe clinical presentation, and outcome within two weeks of onset. The study identified 1273 patients with adverse reactions. The frequency of fatal outcome from any cutaneous reaction was 3.1 per 1000 among all tuberculosis patients and 19.1% among patients with toxic epidermal necrolysis. Approximately 60% of all adverse reactions and deaths occurred within twenty days of starting thiacetazone. Case fatality from adverse cutaneous reactions was considerably less frequent than previously reported, suggesting that improved management may allow the retention of thiacetazone as a weapon against TB even where infection with HIV is prevalent.

Topics: Adult; Drug Eruptions; Female; Humans; Male; Middle Aged; Multivariate Analysis; Risk Factors; Stevens-Johnson Syndrome; Tanzania; Thioacetazone; Tuberculosis

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are potentially life-threatening illnesses that have often been linked to drug exposure.. We looked retrospectively for all cases of SJS and TEN that were admitted to Siriraj Hospital between 1981 and 1990 to determine the drug etiology.. Fifty-eight cases of SJS and 20 cases of TEN were identified. Eight patients initially had an SJS-like aspect, which subsequently evolved into TEN. A culpable drug was determined in 60 patients (77%). The mean time from first drug administration to onset of SJS or TEN was 6.8 +/- 6.5 days (range, 1 to 28 days). A longer incubation period was observed with thiacetazone (10.5 +/- 5.6 days), phenytoin (12 +/- 8.5 days), and carbamazepine (11.3 +/- 3.4 days).. The culprit drugs included the following: antibiotics, 32 cases (penicillin, sulfonamides, tetracycline, erythromycin); anticonvulsants, nine (phenytoin, carbamazepine, barbiturates); antitubercular drugs, eight (thiacetazone); analgesics, four (acetylsalicylic acid, fenbufen); sulfonylurea, two; allopurinol, one; and others, four. The most frequent underlying diseases justifying the ingestion of one or more drugs in our patients were infections (52.7%), followed by pulmonary tuberculosis (10.8%), and by seizures (8.1%). The total mortality rate was 14%; 5% for SJS, and 40% for TEN. Mortality was not affected by the type of drug responsible.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticonvulsants; Cause of Death; Child; Child, Preschool; Disease; Female; Humans; Male; Middle Aged; Penicillins; Retrospective Studies; Sepsis; Skin Diseases, Infectious; Stevens-Johnson Syndrome; Sulfonamides; Thailand; Thioacetazone; Time Factors

Tuberculosis is one of the most common infections in Zambian adults and children infected with HIV. In Africa, cutaneous hypersensitivity reactions attributed to thiacetazone during treatment of tuberculosis in adults infected with HIV-I have been well documented. This study monitored adverse drug reactions during treatment for tuberculosis over an 18 month period (1 April 1990 to 31 October 1991) in 237 children with a clinical diagnosis of tuberculosis (125 boys and 112 girls; 88/237 (37%) infected with HIV-I) and 242 control children (149 boys and 93 girls; 26/242 (11%) infected with HIV-I). Twenty two (9%) of the 237 children with tuberculosis developed hypersensitivity skin reactions during the course of treatment. Adverse skin reactions were seen more often in children infected with HIV than in those who were not (odds ratio 11.65, 95% confidence interval 3.07 to 34.88). These represented 19 (21%) of 88 children infected with HIV and three (2%) of 149 children not infected with HIV. These skin reactions occurred after a period of treatment ranging between two and four weeks among 14 children receiving the HST (isoniazid, streptomycin, thiacetazone) regimen and eight children receiving the HSTR (isoniazid, streptomycin, thiacetazone, rifampicin) regimen. Twelve (55%) of the 22 children who reacted adversely to treatment developed the Stevens-Johnson syndrome. All 12 of these children with the Stevens-Johnson syndrome were infected with HIV. The mortality among these children who developed the Stevens-Johnson syndrome was 91% (11 of 12 died within three days of the onset of the reaction). No further reactions were observed in the 11 children who recovered from the cutaneous hypersensitivity reactions after thiacetazone was discontinued over a period of six months of further treatment of tuberculosis. The results of this study were in part responsible for the recommendations put forward by the World Health Organization to avoid the use of thiacetazone in the treatment of tuberculosis in children infected with HIV.

Topics: Adolescent; AIDS-Related Opportunistic Infections; Child; Child, Preschool; Drug Eruptions; Female; HIV Seropositivity; HIV-1; Humans; Incidence; Infant; Male; Prospective Studies; Stevens-Johnson Syndrome; Thioacetazone; Time Factors; Tuberculosis; Zambia

Concurrent infection with HIV-1 and Mycobacterium tuberculosis is increasingly common in East Africa. In the past, a drug regimen consisting of 2 months of intramuscular streptomycin plus 12 months of isoniazid and thiacetazone has been used in tuberculosis control programs with acceptable efficacy and low incidence of adverse reactions. Anecdotal reports of increasing cases of Stevens-Johnson syndrome prompted a 2 month prospective search for cases of severe cutaneous hypersensitivity reactions at Muhimbili Medical Centre in Dar es Salaam, Tanzania. Five such patients were admitted to a single ward during this time, 4 of whom were HIV-seropositive and all of whom were being treated with isoniazid and thiacetazone. These findings have implications for the management of tuberculosis in East Africa and perhaps other countries with high prevalence of both HIV-1 and tuberculosis.. Concurrent infection with HIV-1 and Mycobacterium tuberculosis (TB) is increasingly common in East Africa. In HIV-infected individuals, pulmonary TB tends to occur before the onset of opportunistic infections. A common treatment regimen in developing countries is two months of intramuscular streptomycin combined with twelve months of isoniazid and thiacetazone. TB control programs have found this approach to be of acceptable efficacy with a low incidence of adverse reactions. Anecdotal reports of increasing cases of Stevens-Johnson syndrome, however, prompted a two-month prospective search for cases of severe cutaneous hypersensitivity reactions at Muhimbili Medical Center in Dar es Salaam, Tanzania. Five such patients were admitted to an hospital ward over the two-month period, four of whom were HIV-seropositive and all of whom were being treated with isoniazid and thiacetazone. Two were also receiving streptomycin. Four had extensive mucosal involvement of the eyelids, lips, and mouth, consistent with Stevens-Johnson syndrome. The remaining patient had bullous skin lesions, without mucosal involvement, consistent with an exfoliative dermatitis. On admission, medications were discontinued and patients underwent routine management, including the administration of steroids. Four patients were discharged from the hospital 3-7 weeks after admission with improved conditions. One patient died suddenly after five weeks of hospitalization due to unknown causes. These patients give extra support to observations that thiacetazone is associated with the increased incidence of severe cutaneous hypersensitivity syndrome in people infected with HIV-1. Further studies are needed to quantify the excess morbidity and mortality resulting from this treatment regimen.

Topics: Acquired Immunodeficiency Syndrome; Adult; Comorbidity; Drug Combinations; Drug Eruptions; Drug Therapy, Combination; Female; HIV-1; Hospitals, University; Humans; Incidence; Isoniazid; Male; Population Surveillance; Prospective Studies; Stevens-Johnson Syndrome; Streptomycin; Tanzania; Thioacetazone; Tuberculosis, Pulmonary

Topics: Dermatitis, Exfoliative; Humans; Stevens-Johnson Syndrome; Thioacetazone; Tuberculosis

The effects of the human immunodeficiency virus (HIV) on tuberculosis management was investigated in 227 patients initially treated with a regimen containing streptomycin, isoniazid, and thiacetazone (STH). 93 of these 227 were HIV-seropositive. 60 patients, of whom 18 were HIV-seropositive, received a regimen consisting of streptomycin, isoniazid, rifampicin, and pyrazinamide (SHRZ) in the initial phase, and thiacetazone and isoniazid (TH) in the continuation phase. Cutaneous hypersensitivity reactions occurred in 22 of 111 (20%) HIV-seropositive patients, and in 2 of 176 (1%) HIV-seronegative patients (RR = 18, 95% CI 4.4-76, p less than 10(-7]. During the first 8 weeks of treatment 18 reactions occurred among the 93 HIV-seropositive patients on STH, whereas no reaction occurred in 17 HIV-seropositive patients during the initial phase of SHRZ/TH (p = 0.04). None of the 18 HIV-seropositive patients with cutaneous reactions who were subsequently challenged with isoniazid reacted, nor did any of the 10 tested with streptomycin, but 6 of the 7 challenged with thiacetazone reacted. 3 patients (all HIV-positive and with toxic epidermal necrolysis) died as a result of the cutaneous reaction. These results have major implications for tuberculosis control programmes in Africa.

Topics: Adult; Antitubercular Agents; Drug Administration Schedule; Drug Eruptions; Erythema Multiforme; Evaluation Studies as Topic; Follow-Up Studies; HIV Seropositivity; Humans; Prospective Studies; Risk Factors; Skin Tests; Stevens-Johnson Syndrome; Thioacetazone; Time Factors; Tuberculosis, Pulmonary

Topics: Drug Eruptions; Erythema Multiforme; Humans; Stevens-Johnson Syndrome; Terminology as Topic; Thioacetazone

Topics: Adult; Drug Hypersensitivity; Female; Humans; Middle Aged; Stevens-Johnson Syndrome; Thioacetazone; Tuberculosis, Pulmonary

Topics: Adult; Female; Humans; Male; Nepal; Stevens-Johnson Syndrome; Thioacetazone; Tuberculosis, Pulmonary

Topics: Adult; Dermatitis, Exfoliative; Drug Hypersensitivity; Humans; Male; Stevens-Johnson Syndrome; Thioacetazone; Time Factors

Topics: Dapsone; Drug Combinations; Humans; Isoniazid; Male; Middle Aged; Stevens-Johnson Syndrome; Thioacetazone

Topics: Adult; Drug Combinations; Humans; Isoniazid; Male; Middle Aged; Penicillin G Procaine; Prednisolone; Stevens-Johnson Syndrome; Thioacetazone

In Lyell's syndrome a toxic skin erythema is concerned which leads to the epidermal necrolysis and desquamation. An infantile and an adult form are differed; the latter is usually induced by medicaments. Two patients with apparently medicamentously induced Lyell's syndrome are presented. The evoking medicaments were penicillin and thioacetazone. The two patients showed a severe course with an extensive affection of the body surface. The therapy with glucocorticosteroids, electrolyte substitution and local treatment of the skin lesions was successful in the two cases.

Topics: Adult; Glucocorticoids; Humans; Male; Middle Aged; Penicillins; Stevens-Johnson Syndrome; Thioacetazone

Topics: Adult; Drug Eruptions; Female; Humans; Male; Middle Aged; Stevens-Johnson Syndrome; Thioacetazone

Topics: Adult; Child, Preschool; Drug Eruptions; Humans; Male; Stevens-Johnson Syndrome; Thioacetazone

Topics: Chemical and Drug Induced Liver Injury; Drug Eruptions; Female; Humans; Male; Middle Aged; Stevens-Johnson Syndrome; Thioacetazone

Topics: Adult; Chloroquine; Humans; Male; Middle Aged; Stevens-Johnson Syndrome; Thioacetazone

Topics: Adolescent; Adult; Female; Humans; Male; Middle Aged; Prognosis; Stevens-Johnson Syndrome; Thioacetazone

Topics: Female; Humans; Male; Middle Aged; Stevens-Johnson Syndrome; Thioacetazone

Topics: Adult; Aged; Autopsy; Humans; Male; Stevens-Johnson Syndrome; Thioacetazone; Tuberculosis, Pulmonary

Topics: Adult; Humans; Isoniazid; Male; Stevens-Johnson Syndrome; Streptomycin; Thioacetazone; Tuberculosis, Pulmonary

Topics: Adult; Humans; Male; Stevens-Johnson Syndrome; Thioacetazone; Tuberculosis, Pulmonary; Vision Disorders

Topics: Adolescent; Adult; Aged; Blindness; Child; Corneal Ulcer; Female; Humans; Male; Middle Aged; Stevens-Johnson Syndrome; Sulfonamides; Thioacetazone

Topics: Child; Humans; Isoniazid; Male; Stevens-Johnson Syndrome; Thioacetazone; Thiosemicarbazones

Topics: Erythema Multiforme; Humans; Skin; Stevens-Johnson Syndrome; Thioacetazone; Thiosemicarbazones; Tuberculosis, Pulmonary