trimethoprim--sulfamethoxazole-drug-combination and Stevens-Johnson-Syndrome

Topics: Acute Generalized Exanthematous Pustulosis; Aged; Diagnosis, Differential; Dose-Response Relationship, Drug; Drug Eruptions; Drug Hypersensitivity Syndrome; Drug Interactions; Eosinophilia; Humans; Male; Methylprednisolone; Prescription Drugs; Prognosis; Stevens-Johnson Syndrome; Trimethoprim, Sulfamethoxazole Drug Combination

Adverse cutaneous reactions frequently occur during the treatment of AIDS associated pneumocystosis by trimethoprime-sulfamethoxazole. The most common form is a maculous rash. Treating throughout the duration of hypersensitivity may lead to potentially lethal Stevens-Johnson and Lyell syndromes. Slow acetylator phenotype, a glutathion deficiency and a history of adverse cutaneous reactions have been identified as risk factors of cutaneous reactions. An adjuvant corticosteroid therapy decreases the frequency of adverse cutaneous reactions during the treatment of hypoxaemic pneumocystosis by trimethoprim-sulfamethoxazole.

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Drug Eruptions; Humans; Incidence; Pneumonia, Pneumocystis; Risk Factors; Stevens-Johnson Syndrome; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Drug-induced Stevens-Johnson syndrome (SJS) is a rare but life-threatening hypersensitivity reaction. Drug desensitization might be considered in drug-allergic patients with no therapeutic alternative. A 29-year-old man with a recent diagnosis of HIV and HBV (CD4 count: 4 cells/mm3) who has been receiving Trimethoprim/sulfamethoxazole (TMP/SMX) for Pneumocystis pneumonia (PCP) prophylaxis was admitted at Imam Khomeini hospital complex affiliated to Tehran University of Medical Sciences, with the diagnosis of SJS due to TMP/SMX. After 45 days of supportive care, the patient was a candidate for TMP/SMX desensitization due to our region's unavailability of alternative agents. A 9-day desensitization protocol was used, but the patient complained about diarrhea with severe pain in the rectal mucosa, and macules developed over his lips again on the third day. As a result, the desensitization process immediately stopped, and after the signs and symptoms were resolved, the patient was discharged with Clindamycin tablet 600 mg TDS. Unfortunately, two weeks after discharge, the patient experienced acute kidney injury (AKI) and expired after two dialysis sessions.

Topics: Adult; Anti-Infective Agents; HIV Infections; Humans; Iran; Male; Retrospective Studies; Stevens-Johnson Syndrome; Trimethoprim, Sulfamethoxazole Drug Combination

Evidence is lacking on the association between antibiotic use and risk of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in Asians.. We assessed the risk of SJS/TEN associated with different antibiotic classes in Japanese.. We conducted a case-crossover study using a claims database. Firth conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of SJS/TEN associated with antibiotic use in a 56-day hazard period versus 3 control periods. We created 18 cohorts for each antibiotic class and calculated 56-day cumulative incidence per 100,000 new users. The association between antibiotic class and SJS/TEN was also evaluated in each case using the ALgorithm of Drug causality for Epidermal Necrolysis (ALDEN).. Our case-crossover study included 170 SJS/TEN cases. Increased ORs were observed for lincomycins (OR, 33.00 [95% CI, 3.74-4332.05]), trimethoprim-sulfamethoxazole (21.20 [6.73-105.98]), penicillins (14.39 [6.95-34.21]), glycopeptides (14.37 [3.17-136.10]), cephalosporins (7.06 [4.25-12.21]), aminoglycosides (6.55 [1.97-26.84]), quinolones (5.98 [3.34-11.20]), fosfomycin (5.40 [1.20-30.97]), carbapenems (5.09 [1.85-15.64]), tetracyclines (4.95 [1.78-15.27]), and macrolides (3.78 [2.13-6.83]). Cumulative incidence of SJS/TEN was 67.4 for trimethoprim-sulfamethoxazole, 86.2 for glycopeptides, and below 10.0 for the others. Despite the high incidence, only 2 cases had a probable causal relationship with glycopeptides.. Some antibiotic classes, including lincomycins, glycopeptides, aminoglycosides, fosfomycin, and carbapenems, were newly suggested to be associated with risk of SJS/TEN; considered together with the high incidence for trimethoprim-sulfamethoxazole and glycopeptides, these findings warrant caution in clinical practice.

Topics: Aminoglycosides; Anti-Bacterial Agents; Carbapenems; Cross-Over Studies; Fosfomycin; Glycopeptides; Humans; Stevens-Johnson Syndrome; Trimethoprim, Sulfamethoxazole Drug Combination

Co-trimoxazole has been reported as a common culprit drug for various cutaneous adverse drug reactions (CADRs). However, information on genotypic and phenotypic characteristics is still limited. We aimed to study clinical characteristics, genetic suitability, laboratory findings, and treatment outcomes in patients with co-trimoxazole-induced CADR and determine variables associated with severe cutaneous adverse reactions (SCARs).. The medical records of all patients diagnosed with co-trimoxazole-induced CADR during October 2015 and October 2021 were reviewed. Clinical characteristics and laboratory investigation with an emphasis on human leukocyte antigen (HLA) class I and HLA-DRB1 results linked to subtypes of cutaneous adverse reactions were evaluated.. Seventy-two patients diagnosed with co-trimoxazole-induced CADR were included in the study. Mean age at diagnosis was 38.0 ± 14.6 years old, and 72% were female. Subtypes of reactions included maculopapular eruption (MPE; 56.9%), drug reaction with eosinophilia and systemic symptoms (DRESS; 23.6%), Stevens-Johnson syndrome (SJS; 12.5%), fixed drug eruption (4.2%), and urticaria (2.8%). Characteristics that were significantly associated with SCARs included male gender (OR = 3.01, 95% CI: 1.04-8.75), HIV infection (OR = 3.48, 95% CI: 1.13-10.75), prophylactic use of co-trimoxazole (OR = 4.89, 95% CI: 1.54-15.57), and co-trimoxazole administration longer than 10 days (OR = 7.65, 95% CI: 2.57-22.78). HLA-B*38:02 was associated with co-trimoxazole-induced SJS, while HLA-A*11:01, HLA-B*13:01, and HLA-DRB1*12:01 were associated with co-trimoxazole-induced DRESS. HLA-B*52:01 was associated with co-trimoxazole-induced MPE.. Co-trimoxazole could induce various phenotypes of CADRs. Genotypic and phenotypic factors that may potentially predict co-trimoxazole-induced SCARs include male gender, HIV infection, prophylactic and prolonged drug use, as well as the presence of HLA-A*11:01, HLA-B*13:01, HLA-B*38:02, or HLA-DRB1*12:01 alleles.

Topics: Adult; Cicatrix; Female; HIV Infections; HLA-A Antigens; HLA-B Antigens; HLA-DRB1 Chains; Humans; Male; Middle Aged; Phenotype; Stevens-Johnson Syndrome; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis Syndrome (TENS) are severe and potentially lethal adverse drug reactions characterized by acute inflammation of the skin, mucous membranes, and ocular surface that typically occurs within weeks of a culprit drug ingestion. The purpose of this study is to report a retrospective trend analysis of SJS spectrum diagnoses and associated culprit drugs in patients admitted to the Loyola University Medical Center (LUMC) Burn Unit, the major referral center in the Chicagoland region for patients with SJS disease spectrum.. The electronic medical records (EMR) of 163 patients with a diagnosis of SJS/TENS admitted to the LUMC Burn Unit from 2000 to 2019 were reviewed. Clinical data in addition to the well-established algorithm of drug causality for epidermal necrolysis (ALDEN) allowed us to identify the single most probable culprit drug in 131 cases.. From 2000 to 2019, the most common spectrum classification was TENS (48.1%), followed by SJS (33.6%) and SJS-TEN Overlap Syndrome (18.3%). Anticonvulsants were found to be the most probable culprit class in 30% of cases followed by Trimethoprim-Sulfamethoxazole in 19% of cases. Beta-lactams were the most probable culprit class in 11% of cases while NSAIDs and allopurinol were each the most probable culprit class/drug in 8.4% of cases.. This is one of the largest single center series of SJS/TENS cases in the United States. Further study into culprit drug distribution by region as well as continuous monitoring of trends is crucial in order to advise prescribing practices.

Topics: Allopurinol; Anti-Inflammatory Agents, Non-Steroidal; Anticonvulsants; beta-Lactams; Burn Units; Burns; Humans; Retrospective Studies; Stevens-Johnson Syndrome; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Emollients; Humans; Q Fever; Stevens-Johnson Syndrome; Trimethoprim, Sulfamethoxazole Drug Combination

Stevens-Johnson syndrome is a rare but consequential and often life-threatening disorder that is most often drug-induced.. An 81-year-old Black man presented with 5 days of dysphagia, odynophagia, and rash. He said he had begun a course of trimethoprim-sulfamethoxazole 6 days prior for a presumed urinary tract infection. Owing to the cutaneous lesions and punch biopsy findings, he was diagnosed with drug-induced Stevens-Johnson syndrome.. Stevens-Johnson syndrome is associated with a relatively high mortality rate. It is most commonly drug-induced and presents with extensive erythema, erosions, and blisters throughout the body.. Stevens-Johnson syndrome is a rare and often life-threatening disease. Early diagnosis and management is important for delivering high-quality patient care.

Topics: Aged, 80 and over; Humans; Male; Stevens-Johnson Syndrome; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Humans; Stevens-Johnson Syndrome; Sulfonylurea Compounds; Trimethoprim, Sulfamethoxazole Drug Combination

Toxic epidermal necrolysis (TEN) is a severe cutaneous reaction that can be life-threatening. In the United States, there are no established guidelines for the treatment of TEN. Supportive care including fluids and supportive therapies are the current recommendations. Research surrounding TEN involves mostly case studies or small, uncontrolled studies. Recent literature describes the use of tumor necrosis factor blockers in the treatment of TEN with positive results. These case reports describe decreased time to reepithelization, hospital length of stay, and minimal side effects. Conversely, we present three fatalities after the administration of etanercept.

Topics: Adult; Aged; Etanercept; Fatal Outcome; Female; Humans; Immunosuppressive Agents; Lamotrigine; Stevens-Johnson Syndrome; Trimethoprim, Sulfamethoxazole Drug Combination

The purpose of this study is to compare the severity of chronic ocular complications of Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) induced by lamotrigine (LT) vs. trimethoprim-sulfamethoxazole (TS).. This retrospective cross-sectional study evaluated all SJS/TEN patients treated within our hospital network from 2008 to 2018. Inclusion criteria included patients with reactions identified as caused by either LT or TS, and patients with at least one ophthalmology follow up in the chronic phase (≥3 months from disease onset). Primary outcome measures included LogMAR best-corrected VA at most recent visit and the presence or absence of severe ocular complications (SOC). Secondary outcome measures included chronic ocular complication severity scores using a modified Sotozono scoring system.. Forty-eight eyes of 24 patients were included in the study. The mean duration of follow-up was 39.50 ± 35.62 vs. 48.17 ± 33.09 months, respectively (p = 0.482). The LT group had worse average VA at the most recent visit (LogMAR VA; 0.508 vs. 0.041, p < 0.0001) and had a higher prevalence of SOCs (66.7% vs. 8.3%, p = 0.0038). The LT group scored worse on Sotozono chronic complications scores for the cornea (1.875 vs. 0.5, p = 0.0018), eyelid margin (5.583 vs.3.083, p = 0.0010), and overall condition (8.500 vs. 4.833, p = 0.0015). Sub-analyses showed that a moderate or severe acute ocular severity score was a significant predictor of chronic outcomes.. Compared to patients with TS-induced SJS/TEN, patients with LT-induced SJS/TEN developed worse chronic ocular complications on several parameters. Future prospective studies are warranted to provide additional insight into the drug type as a predictor of chronic ocular complications.

Topics: Cross-Sectional Studies; Humans; Lamotrigine; Retrospective Studies; Stevens-Johnson Syndrome; Trimethoprim, Sulfamethoxazole Drug Combination

Co-trimoxazole (CTX) causes various forms of severe cutaneous adverse reactions (SCARs). This case-control study was conducted to investigate the involvement between genetic variants of human leukocyte antigen (HLA) and CYP2C9 in CTX-induced SCARs, including Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS) in Thai patients. Thirty cases of CTX-induced SCARs were enrolled and compared with 91 CTX-tolerant controls and 150 people from the general Thai population. Cases comprised 18 SJS/TEN and 12 DRESS patients. This study demonstrated that genetic association of CTX-induced SCARs was phenotype-specific. HLA-B*15:02 and HLA-C*08:01 alleles were significantly associated with CTX-induced SJS/TEN, whereas the HLA-B*13:01 allele was significantly associated with CTX-induced DRESS. In addition, a significant higher frequency of HLA-A*11:01-B*15:02 and HLA-B*13:01-C*03:04 haplotypes were detected in the group of CTX-induced Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and DRESS cases, respectively. Genetic association of CTX-induced SCARs is phenotype-specific. Interestingly, these association was observed only in HIV-infected patients but not in non-HIV-infected patients.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Case-Control Studies; Drug Hypersensitivity Syndrome; Female; Genetic Association Studies; Genetic Predisposition to Disease; Haplotypes; HIV Infections; HLA Antigens; Humans; Male; Middle Aged; Phenotype; Prospective Studies; Risk Assessment; Risk Factors; Severity of Illness Index; Stevens-Johnson Syndrome; Thailand; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Topics: Crystalloid Solutions; Cyclosporine; Electrolytes; Hospitalization; Humans; Interdisciplinary Communication; Male; Middle Aged; Pain Management; Patient Care Team; Resuscitation; Stevens-Johnson Syndrome; Trimethoprim, Sulfamethoxazole Drug Combination

Steven Johnson syndrome and toxic epidermal necrolysis are severe and rare adverse drug reactions usually caused by drugs like antiepileptics, penicillin and allopurinol and sometimes also due to infections, malignancy or idiopathic in some cases. Here we are reporting a case of a 50 years female who came with complaint of a burning sensation on the upper half of the body with atypical flat target lesion that later coalesced involving her face, chest and bilateral upper limbs. On examination, positive nikolsky sign and tenderness with <10% body surface area involvement was noticed. The diagnosis of cotrimoxazole induced Steven Johnson syndrome was made. Patient was shifted to ICU and given supportive care along with prophylactic teicoplanin, itraconazole and dexamethasone. The mechanism of eruptions in our patient was due to cotrimoxazole. Cotrimoxazole induced Steven Johnson syndrome is rare and the supportive management with broad spectrum antibiotic and the corticosteroid was enough to beat this life-threatening condition. Keywords: cotrimoxazole; pneumonia; Steven Johnson syndrome.

Topics: Allopurinol; Anti-Bacterial Agents; Anticonvulsants; Female; Humans; Middle Aged; Stevens-Johnson Syndrome; Trimethoprim, Sulfamethoxazole Drug Combination

BACKGROUND Stevens Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are causes of rare but life-threatening emergencies characterized by desquamation of the skin and mucosa. As SJS most commonly presents with skin rash followed by mucosal involvement, we present a case of vulvovaginal lesions as the initial presentation with progression to SJS after re-exposure to the culprit drug. CASE REPORT A 27-year-old female with acute cystitis was given trimethoprim-sulfamethoxazole. After 2 days, she reported vaginal pain. Three days later, she was hospitalized with vulvovaginal ulcerations and restarted on trimethoprim-sulfamethoxazole, leading to worsening vaginal lesions with rapid desquamation of conjunctival and oropharyngeal involvement. Biopsies of arm lesions revealed SJS. CONCLUSIONS It is important to recognize SJS as a rare but life-threatening cause of vulvovaginal ulceration, as early diagnosis is vital for successful treatment.

Topics: Adult; Anti-Infective Agents, Urinary; Female; Humans; Pain; Skin Ulcer; Stevens-Johnson Syndrome; Trimethoprim, Sulfamethoxazole Drug Combination; Vulvar Diseases

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening hypersensitivity reactions mainly caused by drugs. Data on incubation period, hospital stay, and outcome for HIV-positive patients are sparse. Role of corticosteroids in their management is still controversial.. Indoor cases of SJS, SJS-TEN overlap, and TEN were analyzed for causative drugs, incubation period, a severity-of-illness score for toxic epidermal necrolysis (SCORTEN) score, HIV status, treatment, and outcome. Comparison of parameters between HIV and non-HIV cases was done. Utilization pattern of corticosteroids and their role in outcome were evaluated.. Four SJS, 15 SJS-TEN overlap, and 21 TEN cases were evaluated. Antimicrobials (27.1%), antiviral (23%), antiseizure drugs (8.4%), and analgesics (8.4%) were commonly associated drugs. Among 12 (30%) HIV-reactive cases, nevirapine (97.6%) and cotrimoxazole (41.6%) were common causative drugs. Males (75%) were affected more than females (25%) among HIV-positive individuals. Incubation period was significantly higher in HIV-reactive patients. Total 30 (75%) patients were treated with corticosteroids. Dexamethasone (90%) and prednisolone (26.6%) were most commonly used. No significant difference was found among cases treated with or without corticosteroids.. Antimicrobial drugs are common to cause SJS/TEN. Among HIV-reactive patients, male have more risk, incubation period is more and severity of reaction is less. Effectiveness of corticosteroids for treatment of SJS/TEN is inconclusive.

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Aged; Analgesics; Anti-Bacterial Agents; Anticonvulsants; Antiviral Agents; Asian People; Child; Female; HIV Seropositivity; Humans; India; Length of Stay; Male; Middle Aged; Nevirapine; Retrospective Studies; Severity of Illness Index; Stevens-Johnson Syndrome; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Linear IgA bullous dermatosis (LABD) is an autoimmune blistering skin disorder characterized by linear IgA deposits along the dermoepidermal junction. Usually idiopathic, LABD can be drug-induced.. To report the atypical characteristics of a case of trimethoprim-sulfamethoxazole-induced LABD presenting as toxic epidermal necrolysis (TEN).. A 63-year-old woman treated with trimethoprim-sulfamethoxazole for Pneumocystis jirovecii infection developed a generalized maculopapular rash with herpetiform lesions, rosette-like lesions, and tense bullae with Nikolsky sign.. Anti-basement membrane zone antibodies were negative, but immunoblot revealed a 160 kDa band corresponding to subepidermal class IgA desmoglein 1. Skin biopsy specimens revealed a subepidermal bulla and direct immunofluorescence showed linear IgA deposition along the basement membrane zone. A diagnosis of toxic epidermal necrolysis was excluded and replaced by trimethoprim-sulfamethoxazole-induced LABD.. We report a case of trimethoprim-sulfamethoxazole-induced LABD with a 160 kDa IgA desmoglein 1 found by immunoblotting analysis, probably by epitope spreading.

Topics: Anti-Bacterial Agents; Basement Membrane; Biopsy; Diagnosis, Differential; Female; Humans; Immunoglobulin A; Linear IgA Bullous Dermatosis; Middle Aged; Skin; Stevens-Johnson Syndrome; Trimethoprim, Sulfamethoxazole Drug Combination

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but severe cutaneous adverse drug reactions. We assessed incidence, drug exposure and mortality, analysing data obtained from the Lombardy Registry of Severe Cutaneous Reactions (REACT).. Data were collected from hospitals in the Italian Lombardy region (9,502,272 people). A trained monitor was sent to the reporting hospital to collect data on drug exposure and clinical features. The algorithm for drug causality for epidermal necrolysis algorithm was applied to assess drug causality. Defined Daily Dose (DDD) was used to express drug consumption.. From April 2009 to November 2014, 17 cases of TEN and 59 cases of SJS were collected. The overall incidence rate was 1.40 cases (95%CI, 1.12-1.76) per million people per year. A total of 15 cases died during hospitalization with a mortality rate of 16.9% for SJS and 29.4% for TEN. Overall, 55.4% of cases had a probable or very probable relation with drug exposure. In a total of five patients (6.6%), no causative drug for the reaction was identifiable. Allopurinol contributed to the highest number of cases (23 cases), while the highest incidence based on more than one case reported was observed for cotrimoxazole and lamotrigine, with 5.37 cases (95%CI, 2.09-13.80) and 3.54 (95%CI, 1.21-10.42) per 10 million DDD/year, respectively.. We confirmed that SJS and TEN are rare adverse cutaneous reactions. As expected, mortality was influenced by the degree of skin detachment. The profile of drugs associated with the reactions was in agreement with data from other surveillance systems.

Topics: Adolescent; Adult; Adverse Drug Reaction Reporting Systems; Aged; Aged, 80 and over; Allopurinol; Child; Child, Preschool; Female; Humans; Incidence; Italy; Lamotrigine; Male; Middle Aged; Mortality; Registries; Stevens-Johnson Syndrome; Triazines; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Topics: Anti-Bacterial Agents; Diagnosis, Differential; Factitious Disorders; Humans; Male; Malingering; Middle Aged; Psychological Techniques; Stevens-Johnson Syndrome; Trimethoprim, Sulfamethoxazole Drug Combination

Fixed drug eruptions (FDE) are peculiar drug rashes that tend to be violaceous, hyperpigmented, and round to oval-shaped plaques with dusky gray centers. The lesions tend to recur in a similar dermatologic distribution upon re-exposure to the offending medication, leading to intensified inflammation and sometimes the formation of blisters, bullae, and erosions. This bullous form of FDE can be mistaken clinically for Stevens Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN).. We report two cases of patients presenting to the emergency department (ED) with characteristic blistering skin lesions and reports of similar prior episodes; both patients were initially diagnosed in the ED as "recurrent SJS" and admitted to the burn intensive care unit. Each patient was evaluated emergently by dermatology consultants, identified as cases of FDE rather than SJS, and transferred to the general medical ward with an uncomplicated hospital course and complete re-epithelialization within 7 days after removal of the inciting agent. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: We discuss distinguishing features of bullous FDE and SJS/TEN in order to highlight this entity and aid in diagnostic accuracy and appropriate management by emergency physicians. In cases identified as classic or suspected SJS/TEN, the patient warrants aggressive resuscitation and admission to a burn unit, while cases identified as obvious bullous FDE can be managed much more conservatively. Although the clinical clues outlined here may help distinguish classic cases of FDE from SJS/TEN, it is always advisable to admit to a higher level of care or obtain an urgent dermatology consult when diagnostic uncertainty remains.

Topics: Adult; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Blister; Diagnosis, Differential; Drug Eruptions; Female; Humans; Ibuprofen; Male; Recurrence; Stevens-Johnson Syndrome; Trimethoprim, Sulfamethoxazole Drug Combination

Co-trimoxazole is a sulfonamide-containing antibiotic that is effective in the treatment of several infections and for prophylaxis of Pneumocystis jiroveci pneumonia. This drug has been reported as a common culprit drug for the Stevens-Johnson syndrome (SJS) and for toxic epidermal necrolysis (TEN). Human leukocyte antigens (HLAs) play a key role in the immunopathogenesis of severe cutaneous reactions induced by several drugs. This study investigated the association between the HLA class I and HLA-DRB1 polymorphisms and co-trimoxazole-induced SJS/TEN in a Thai population.. Forty-three patients with co-trimoxazole-induced SJS/TEN and 91 co-trimoxazole-tolerant patients were enrolled in the study. HLA class I and HLA-DRB1 were genotyped using the reverse sequence-specific oligonucleotide probe method.. The frequencies of three alleles of HLA, namely HLA-B*15:02, HLA-C*06:02, and HLA-C*08:01, were significantly higher in the co-trimoxazole-induced SJS/TEN group compared with controls. The risks for co-trimoxazole-induced SJS/TEN in patients with the HLA-B*15:02, HLA-C*06:02, or HLA-C*08:01 allele were about 3-11-fold higher when compared with those who did not carry one of these alleles. Individuals who carried the HLA-B*15:02-C*08:01 haplotype had a 14-fold higher risk for co-trimoxazole-induced SJS/TEN.. Evidence of associations between co-trimoxazole-induced SJS/TEN and HLA alleles including HLA-B*15:02, HLA-C*06:02, and HLA-C*08:01 were found in the study population. These findings may suggest that apart from the HLA molecules, other molecules involved in the molecular pathogenesis of these severe cutaneous adverse drug reactions may play an important role in the susceptibility of individuals to SJS/TEN caused by co-trimoxazole.

Topics: Adult; Alleles; Demography; Female; Genetic Association Studies; Genetic Predisposition to Disease; HLA Antigens; Humans; Male; Middle Aged; Stevens-Johnson Syndrome; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Administration, Cutaneous; Dermatologic Agents; Drug Eruptions; Female; Follow-Up Studies; Humans; Hydroxides; Middle Aged; Potassium Compounds; Stevens-Johnson Syndrome; Trimethoprim, Sulfamethoxazole Drug Combination

Toxic epidermal necrolysis (TEN) is a rare but serious dermatological emergency characterised by diffuse exfoliation of the skin and mucous membranes due to immune mediated destruction of the epidermis which can lead to sepsis and respiratory distress. Trimethoprim-sulfamethoxazole is a widely used antibiotic which can rarely lead to TEN. Early diagnosis and aggressive medical care is essential for the reduction of high morbidity and mortality associated with this disease. We present a case of successfully recovered TEN due to trimethoprim-sulfamethoxazole in a 62-year-old woman.

Topics: Anti-Bacterial Agents; Antibiotic Prophylaxis; Dose-Response Relationship, Drug; Early Diagnosis; Female; Fluid Therapy; Follow-Up Studies; Humans; Middle Aged; Stevens-Johnson Syndrome; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections; Wound Healing

A 46 years old HIV reactive patient developed Stevens Johnson syndrome (SJS) probably due to nevirapine and/or co-trimoxazole. Patient was on zidovudine + lamivudine + nevirapine along with Co-trimoxazole since last two months. After 15 days, zidovudine was replaced with stavudine due to development of anemia. All these drugs were stopped after development of reaction. Temporal association was found between stavudine, lamivudine, nevirapine, cotrimoxazole and development of the reaction. Nevirapine and Co-trimoxazole were suspected to cause this reaction most probably due to associated hepatotoxicity and their common potential to cause SJS. In our case, patient died despite stopping of all medications.

Topics: Anti-HIV Agents; Anti-Infective Agents; Fatal Outcome; HIV Infections; Humans; Male; Middle Aged; Nevirapine; Stevens-Johnson Syndrome; Trimethoprim, Sulfamethoxazole Drug Combination

Stevens-Johnson syndrome (SJS) can be a severe and life-threatening reaction with many potential causes, including multiple medications used in HIV care and treatment. Specific risk factors, especially in children, are not currently well-understood.. We describe a series of cases of SJS that occurred from 2006 to 2010 in an HIV-focused clinic in Mbabane, Swaziland. The electronic medical and pharmacy records of all pediatric patients <20 years old were reviewed to identify cases of SJS. Patient demographic, immunosuppression and outcome data were also collected.. A total of 19 cases of SJS were documented. Eighty-four percent of cases were attributed to nevirapine (NVP) exposure whereas the remaining cases were caused by cotrimoxazole (11%) and efavirenz (5%). Median symptom onset was 22 days after initiation of the offending medication (interquartile range = 14-25 days). At time of SJS, 84% had advanced or severe immunosuppression. Forty-two percent of patients required hospitalization, and no SJS-associated deaths were known to occur. Use of efavirenz was attempted in 8 NVP-associated cases after SJS resolution and was successful in all except 1.. SJS occurrence was rare in this population, with the majority of cases being associated with NVP. All occurred within 32 days of medication initiation, providing a target window for intensified monitoring and anticipatory guidance. SJS can occur in children at any age, with any level of immunosuppression, and can occur during the lead-in dosing period of NVP.

Topics: Adolescent; Alkynes; Anti-HIV Agents; Benzoxazines; CD4 Lymphocyte Count; Child; Child, Preschool; Cyclopropanes; Eswatini; Female; HIV Infections; Hospitalization; Humans; Infant; Male; Nevirapine; Retrospective Studies; Stevens-Johnson Syndrome; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Stevens-Johnson syndrome and toxic epidermal necrolysis are uncommon acute dermatologic disorders. The purpose of this study was to examine the frequency, aetiology and outcome of cases of Stevens-Johnson syndrome and toxic epidermal necrolysis admitted to the dermatology ward at the University Hospital of the West Indies.. This was a retrospective study looking at all patients who were admitted with a diagnosis of Stevens-Johnson syndrome, Stevens-Johnson syndrome/toxic epidermal necrolysis overlap syndrome and toxic epidermal necrolysis over a nine-year period.. The results showed almost equal numbers of males and females. The drugs most commonly implicated were phenytoin and cotrimoxazole. The most common complications were hepatic impairment and ophthalmic complications.. Stevens-Johnson syndrome and toxic epidermal necrolysis contribute significantly to morbidity and mortality of patients on the dermatology ward although mortality was low compared to other studies.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Infective Agents; Anticonvulsants; Female; Hospitals, University; Humans; Jamaica; Male; Middle Aged; Phenytoin; Retrospective Studies; Stevens-Johnson Syndrome; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Reactivation of certain latent viruses has been linked with a more severe course of drug-induced hypersensitivity reaction (HSR). For example, reactivation of human herpes virus (HHV)-6 is associated with severe organ involvement and a prolonged course of disease. The present study discusses an HSR developed in a previously healthy male exposed to ceftriaxone, doxycycline, vancomycin, and trimethoprim/sulfamethoxazole (co-trimoxazole; TMP/SMX). Initially, the patient presented clinical manifestations of HSR, as well as clinical and laboratory measurements compatible with liver and renal failure. Moreover, the patient presented skin desquamation compatible with Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis. During the reaction, it was observed HHV-6 reactivation. The severity of clinical symptoms is correlated with HHV-6 titer, as well as with results of the in vitro lymphocyte toxicity assay (LTA). Serum levels of a large panel of cytokines are compared between the patient, a large population of SJS patients, and a cohort of healthy controls, using data collected by our laboratory over the years. HHV-6 was measured in the cell culture media from lymphocytes incubated with each of the 4 drugs. Moreover, we describe a new assay using cytokines released by patient lymphocytes following in vitro exposure to the incriminated drugs as biomarkers of HSR. Based on LTA results, HHV-6 reactivation and cytokine measurements, we establish that only doxycycline and TMP/SMX were involved in the HSR. As result of this analysis, the patient could continue to use the other 2 antibiotics safely.

Topics: Anti-Bacterial Agents; Chemical and Drug Induced Liver Injury; Cytokines; Doxycycline; Drug Eruptions; Drug Hypersensitivity; Herpesvirus 6, Human; Humans; Lymphocytes; Male; Roseolovirus Infections; Stevens-Johnson Syndrome; Translational Research, Biomedical; Trimethoprim, Sulfamethoxazole Drug Combination; Virus Activation; Young Adult

Topics: Anti-Bacterial Agents; Diagnosis, Differential; Exanthema; Face; Facial Dermatoses; Female; Fever; Humans; Stevens-Johnson Syndrome; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Topics: Anti-Infective Agents; Conjunctivitis; Corneal Diseases; Eyelids; Female; Humans; Middle Aged; Stevens-Johnson Syndrome; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Infective Agents; Humans; Seasons; Stevens-Johnson Syndrome; Trimethoprim, Sulfamethoxazole Drug Combination

With an incidence of 1.5-1.8/1 million inhabitants per year, toxic epidermal necrolysis is a rare but life threatening disease. It is almost always drug-induced and its lethality is pronounced with up to 50 %. Several therapeutic options are described in literature; however, there is still lack of a universally accepted and specific therapy of toxic epidermal necrolysis.. This survey considers 8 cases of toxic epidermal necrolysis diagnosed and treated in our clinic from 2003 to 2007. The epidermal sloughing was > 30 % of the body surface in each case.. After immediately discontinuing the drug suspected of being responsible for toxic epidermal necrolysis, we treated with systemic corticosteroids in an initial dose of up to 1.5 mg/kg. Moreover, special emphasis was put on basic measures such as control of vital parameters. With this treatment we reached good results; none of the patients died. conclusions: Immediate beginning of therapy is essential for a successful treatment of toxic epidermal necrolysis. Besides systemic therapy with corticosteroids, certain basic measures such as isolation of patients at adequate room temperature to prevent hypothermia, strict control of circulation, temperature and laboratory parameters, daily smears of skin and mucous membranes and a diet rich in calories due to the catabolic metabolic status are very important for successful outcome.

Topics: Adult; Aged; Aged, 80 and over; Allopurinol; Anti-Bacterial Agents; Anti-Inflammatory Agents; Anticonvulsants; Bacterial Infections; Ciprofloxacin; Drug Combinations; Female; Folic Acid; Gout Suppressants; Humans; Hydroxocobalamin; Lidocaine; Male; Middle Aged; Phenytoin; Prednisone; Pyridoxine; Stevens-Johnson Syndrome; Superinfection; Survival Rate; Trimethoprim, Sulfamethoxazole Drug Combination

The causative factors and ocular complications of Stevens-Johnson syndrome and toxic epidermal necrolysis are reported here. Six out of seven patients developed the syndrome secondary to ingestion of sulphadoxine/pyrimethamine while one developed it as a complication of HAART (highly active antiretroviral therapy). The ocular complications were ankyloblepharon, symblepharon, chronic conjunctivitis, corneal vascularization and conjunctivalization, and blindness. One patient died. A shift to the WHO-recommened artemisin-based combination therapy for the treatment of malaria is advised. Early referral to the ophthalmologist will help to reduce the complications.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Antiretroviral Therapy, Highly Active; Child, Preschool; Eye Diseases; Female; Hospitals, University; Humans; Male; Nigeria; Ophthalmic Solutions; Stevens-Johnson Syndrome; Trimethoprim, Sulfamethoxazole Drug Combination

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare and severe cutaneous adverse reactions to medications and infections.. We sought to determine whether a seasonal variation to SJS and TEN exists and to define the characteristics in our tertiary referral hospital.. A retrospective chart review of 50 patients from 1995 through 2007 was performed and statistically analyzed.. The most common medication implicated as a cause of SJS/TEN was trimethoprim-sulfamethoxazole (TMX) (26%). A seasonal trend, favoring springtime, was observed for the total number of cases of SJS and TEN (P = .34). There was a significant increase in cases due to TMX (53%) occurring in spring compared to other seasons (P = .002). These patients were significantly younger (37.8 +/- 13.7) than other patients with SJS and TEN (53.7 +/- 16.4) (P = .003). Their overall mortality (1 death) and average SCORTEN value (1.62 +/- 1.6) was also significantly lower (P = .04 and 0.03, respectively). Based on outpatient pharmacy records, there was no increase in TMX prescriptions filled during the spring.. The study was limited by reliance on chart data, the use of inpatient records, and number of patients.. A seasonal variation in SJS and TEN caused by TMX affecting younger patients may exist.

Topics: Adult; Aged; Aged, 80 and over; Anti-Infective Agents; Female; Humans; Male; Middle Aged; Retrospective Studies; Seasons; Stevens-Johnson Syndrome; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

1) Lyell syndrome is characterised by toxic epidermal necrolysis in which epidermal detachment affects more than 30% of the body surface area. Stevens-Johnson syndrome is a minor form affecting less than 10% of the body surface area; 2) Patients who present with these cutaneous symptoms, along with throat pain, red eyes and a damaged or detached oral mucosa must be hospitalised immediately; 3) Lyell syndrome is exclusively caused by drugs while Stevens-Johnson syndrome can also be caused by bacteria and viruses. Rapid withdrawal of the drug improves prognosis.

Topics: Allopurinol; Anti-Infective Agents; Anti-Inflammatory Agents; Anticonvulsants; Erythema Multiforme; Humans; Stevens-Johnson Syndrome; Sulfonamides; Trimethoprim, Sulfamethoxazole Drug Combination

We report a case of Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) secondary to trimethoprim-sulfamethoxazole (TMP-Sx) therapy for presumed community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infection. Although the association between SJS/TEN and the sulfonamide class of antibiotics is well established, the increasing prevalence of CA-MRSA has left practitioners with limited regimens to effectively treat skin and soft tissue infections (SSTIs) in the outpatient setting. In the case of SSTIs, alternative treatment of these infections should be considered, especially when the bacterial pathogen is unknown. Future investigations evaluating the efficacy of adjunctive antibiotics for purulent SSTIs and monitoring the incidence of SJS/TEN in the era of CA-MRSA are necessary to reduce unnecessary use of sulfonamide drugs. The potential development of SJS/TEN, a severe life-threatening illness, emphasizes the need for judicious use of TMP-Sx and close monitoring and follow-up for patients who were given TMP-Sx for SSTIs.

Topics: Adolescent; Anti-Bacterial Agents; Cellulitis; Communicable Diseases, Emerging; Community-Acquired Infections; Diagnostic Errors; Humans; Immunoglobulins, Intravenous; Male; Methicillin-Resistant Staphylococcus aureus; Pneumonia; Recurrence; Scarlet Fever; Sepsis; Soft Tissue Infections; Staphylococcal Infections; Staphylococcal Skin Infections; Stevens-Johnson Syndrome; Trimethoprim, Sulfamethoxazole Drug Combination

Toxic epidermal necrolysis (TEN) is a rare, potentially life-threatening bullous drug reaction. Rapid diagnosis of TEN can lower the mortality rate when the offending drug is withdrawn immediately. Simple diagnostic tools such as cytology of skin blisters may be useful if rapid diagnosis is needed, in particular if standard histopathology service fails. An even faster bedside test for TEN in patients with black skin is color evaluation of skin blister fluid.

Topics: Adult; Anti-Bacterial Agents; Black or African American; Body Fluids; Bronchitis; Color; Early Diagnosis; Female; Humans; Keratinocytes; Melanins; Mucositis; Point-of-Care Systems; Stevens-Johnson Syndrome; Stomatitis; Trimethoprim, Sulfamethoxazole Drug Combination

A retrospective study of the presentation, etiology, and prognosis of non-burn epidermal loss managed at the Lagos University Teaching Hospital Nigeria over a 12-year period.. Admission records of patients managed for non-burn skin loss were retrieved from the medical records. Demographic details of the patients, the initial diagnosis, final diagnosis, treatment and outcome of treatment was noted.. A total of 23 patients were identified, 17 (74%) had idiosyncratic drug reactions. Of this 17, 6 (26%) had Steven Johnson Syndrome, 6 (26%) had Steven Johnson Syndrome/toxic epidermal necrolysis while 5 (22%) presented with toxic epidermal necrolysis. Three of the five patients with toxic epidermal necrolysis died. The age range of patients with idiosyncratic adverse drug reactions was 2-28 years, mean, 10.18+/-1.44 years and male to female ratio of 1:1.83. The body surface area involved ranged from 8 to 78%; mean 26.65+/-6.08%. The agents suspected for the reactions were Co-trimoxazole (41.2%) and combination of Co-trimoxazole, and Fansidar (17.6%). Other conditions seen were two (9%) Staphylococcal Scalded Skin Syndrome, three (13%) had Necrotizing Faciitis, one of whom was HIV positive and died. One (4%) patient presented with pemphigus vulgaris. The presentation and management of the patients was discussed.

Topics: Adolescent; Adult; Anti-Infective Agents; Bandages; Burn Units; Child; Child, Preschool; Developing Countries; Drug Combinations; Female; Humans; Male; Nigeria; Prognosis; Pyrimethamine; Retrospective Studies; Staphylococcal Scalded Skin Syndrome; Stevens-Johnson Syndrome; Sulfadoxine; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; Anti-Bacterial Agents; Anti-Infective Agents; Emergency Service, Hospital; Erythromycin; Exanthema; Female; Fluid Therapy; Humans; Saudi Arabia; Stevens-Johnson Syndrome; Trimethoprim, Sulfamethoxazole Drug Combination

A two-year-old, male English springer spaniel developed severe mucocutaneous ulceration following treatment with trimethoprim-potentiated sulphadiazine. The clinical signs were consistent with Stevens-Johnson syndrome (SJS): there were no target or arciform lesions typical of erythema multiforme minor and major; more than one mucosal surface was affected; epidermal detachment affected less than 10 per cent of the body surface area; and there was a clear history of drug exposure. Systemic signs included a severe hepatopathy, dyspnoea, pyrexia and cachexia. Glucocorticoid therapy was associated with secondary infection by Pseudomonas aeruginosa. The clinical signs rapidly resolved following a single intravenous infusion of 0.51 g/kg human immunoglobulin (ivHIG) as a 5 per cent solution. By blocking FAS/FAS ligand (CD95/CD95L) interactions, ivHIG is thought to prevent keratinocyte apoptosis. It also binds to immunoglobulin G Fc receptors, inhibiting cell activation and cytokine synthesis, neutralises autoantibodies and immune complexes, blocks complement activity, is antimicrobial and increases colloid osmotic pressure. To the authors' knowledge, this is the first report of successful treatment of canine SJS using ivHIG, although it has been used to treat erythema multiforme in a cat and toxic epidermal necrolysis in a dog.

Topics: Animals; Anti-Infective Agents; Diagnosis, Differential; Dog Diseases; Dogs; Immunoglobulins, Intravenous; Male; Stevens-Johnson Syndrome; Surgical Wound Infection; Trimethoprim, Sulfamethoxazole Drug Combination

Toxic epidermal necrolysis (TEN) is a very rare but extremely severe drug reaction characterized by widespread apoptosis of epidermis with extensive blisters. We previously found drug-specific cytotoxic CD8 T lymphocytes in the blisters of a single patient.. To confirm the role of drug specific cytotoxic lymphocytes in a larger series, to test the cytotoxicity on keratinocytes, and to look for cross-reactivity between chemically related drugs.. The phenotype of lymphocytes present in the blister fluids of 6 patients with TEN was analyzed by flow cytometry. Cytotoxic functions were tested by chromium release assay on a variety of target cells (autologous or MHC class I-matched EBV-transformed lymphocytes, autologous keratinocytes) after nonspecific (CD3 monoclonal antibody) or specific (suspected and potentially cross-reactive drugs) activation.. Blister lymphocytes were CD8 + HLA-DR + CLA + CD56 + . In all 6 cases, they were cytotoxic after nonspecific activation. A drug-specific cytotoxicity was observed in 4 cases (3 related to cotrimoxazole and 1 to carbamazepine) toward lymphocytes. Blister cells also killed IFN-gamma-activated autologous keratinocytes in the presence of drug in the 2 patients tested. Blister cells showed a strong immunoreactivity for granzyme B, and cytotoxicity was abolished by EGTA, but not by anti-Fas/CD95, suggesting perforin/granzyme-mediated killing. By using several sulfonamides for testing the specificity of the drug T-cell receptor interaction, we observed cross-reactivity only between 4 structurally closely related medications.. These results strongly suggest that drug-specific, MHC class I-restricted, perforin/granzyme-mediated cytotoxicity probably has a primary role in TEN.

Topics: B-Lymphocytes; Blister; Cell Line; Cross Reactions; Granzymes; Humans; Immunophenotyping; Keratinocytes; Membrane Glycoproteins; Perforin; Pore Forming Cytotoxic Proteins; Serine Endopeptidases; Stevens-Johnson Syndrome; T-Lymphocytes, Cytotoxic; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Aerospace Medicine; Aircraft; Anti-Infective Agents; Humans; Military Personnel; Stevens-Johnson Syndrome; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Infective Agents, Urinary; Diagnosis, Differential; Drug Eruptions; Exanthema; Humans; Kidney Transplantation; Male; Middle Aged; Serum Sickness; Stevens-Johnson Syndrome; Trimethoprim, Sulfamethoxazole Drug Combination; Urticaria

Topics: Adult; Aerospace Medicine; Aircraft; Anti-Infective Agents; Female; Humans; Military Personnel; Stevens-Johnson Syndrome; Transportation of Patients; Trimethoprim, Sulfamethoxazole Drug Combination

To report a new surgical technique to manage severe acute toxic epidermal necrolysis.. Two interventional case reports.. Two patients. Case 1: A 6-year-old boy had severe toxic epidermal necrolysis develop after being treated with trimethoprim and sulfamethoxazole for chronic otitis media. Both eyes and eyelids were affected. He underwent bilateral lysis of symblepharon and all adhesions and bilateral amniotic membrane transplantation to the entire ocular surface except the cornea. Loss of eyelid skin required transplantation of amniotic membrane to all four eyelids and strips of amniotic membrane at the eyelid margins. Case 2: An 8-year-old girl with severe toxic epidermal necrolysis associated with mycoplasma pneumonia had bilateral, diffuse keratoconjunctivitis, diffuse corneal epithelial defects, and bilateral symblepharon. Amniotic membrane transplantation was performed bilaterally, using a symblepharon ring in the left eye.. Amniotic membrane transplantation.. Preservation of normal ocular and eyelid surfaces and prevention of blindness.. Case 1: Thirty-six months after bilateral ocular surgery, there is no symblepharon, good ocular surface wetting, and an uncorrected bilateral vision of 20/20. Case 2: Amniotic membrane transplantation protected both ocular surfaces and prevented conjunctival contracture without adhesion of the eyelids to the ocular surface. The central vision was preserved. There was minimal peripheral corneal vascularization and mild conjunctival scarring of the tarsal conjunctival surface 34 months postoperatively.. These are the first cases of acute toxic epidermal necrolysis treated with amniotic membrane transplantation and the first use of the procedure on external eyelid surfaces with good healing of the eyelids. This new treatment for acute toxic epidermal necrolysis preserves normal ocular and eyelid surfaces and may prevent blindness.

Topics: Acute Disease; Amnion; Child; Eyelid Diseases; Female; Humans; Keratoconjunctivitis; Male; Ophthalmologic Surgical Procedures; Pneumonia, Mycoplasma; Stevens-Johnson Syndrome; Trimethoprim, Sulfamethoxazole Drug Combination; Visual Acuity

Toxic epidermal necrolysis is an extremely severe drug reaction, manifesting itself by widespread apoptosis of keratinocytes, generally considered to result from Fas/CD95-FasLigand interaction, but of unknown primary mechanism. We looked at the role of cells present in the skin blisters as probable effectors of this immune reaction. In a patient suffering from cotrimoxazole-induced toxic epidermal necrolysis, blister fluid cells were phenotyped by FACS and tested without prior restimulation for cytotoxicity on autologous and allogeneic cells in the presence of the drug. Blister fluid lymphocytes were predominantly CD8+, DR+, CLA+, CD56+ T lymphocytes, perforin positive and expressing preferentially two Vbeta chains of the T cell receptor repertoire. These lymphocytes were cytotoxic only in the presence of the drug towards autologous EBV transformed lymphocytes and towards allogeneic cells sharing HLA-Cw4. Cytotoxicity occurred in the presence of either cotrimoxazole, sulfamethoxazole, or the nitroso metabolite of sulfamethoxazole, but not with the hydroxylamine metabolite of sulfamethoxazole. The lysis was blocked by an anti-MHC class I monoclonal antibody. It was abolished by EGTA and CMA, but neither by anti-fas, brefeldin A, nor by anti-TRAIL receptor monoclonal antibodies, strongly suggesting perforin/granzyme-mediated cytotoxicity, without implication of Fas or TRAIL at this stage. This is direct evidence that T lymphocytes present within the lesions of toxic epidermal necrolysis may exhibit, without any re-stimulation, a drug-specific cytotoxicity against autologous cells. Harboring the markers of classical CTL and MHC class I restriction these lymphocytes reacted against the parent drug and one of its reactive metabolites. These results challenge several current concepts and could support new therapeutic approaches.

Topics: Anti-Infective Agents; Blister; CD8 Antigens; Histocompatibility Antigens Class I; Humans; Immunophenotyping; Male; Middle Aged; Receptors, Antigen, T-Cell, alpha-beta; Stevens-Johnson Syndrome; T-Lymphocytes, Cytotoxic; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Aged; Aged, 80 and over; Anti-Infective Agents, Urinary; Biopsy, Needle; Drug Therapy, Combination; Follow-Up Studies; Humans; Male; Risk Assessment; Severity of Illness Index; Stevens-Johnson Syndrome; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections

Toxic epidermal necrolysis (TEN) is a rare drug-induced life-threatening disease. Currently, the disease is only treated by supportive and antiseptic measures. Quite recently intravenous immunoglobulins (IG) were shown to be a promising TEN treatment. The rationale for their use is based on the fact that keratinocyte apoptosis in TEN involves the CD95 (APO-1/Fas) cell surface receptor-ligand system. We successfully treated a TEN patient with high dose of intravenous IG. The clinical recovery appeared exceptionally rapid. Immunohistochemistry showed that the IG action probably developed on the CD95 receptor-ligand system at the keratinocytes surface.

Topics: Aged; Anti-Infective Agents; fas Receptor; Humans; Immunoglobulins, Intravenous; Male; Stevens-Johnson Syndrome; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adolescent; Female; Humans; Stevens-Johnson Syndrome; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections

Topics: Adolescent; Anti-Infective Agents; Female; Humans; Immunoglobulins, Intravenous; Sinusitis; Stevens-Johnson Syndrome; Trimethoprim, Sulfamethoxazole Drug Combination

A 15-year-old boy with T-cell acute lymphoblastic leukemia (ALL) (FAB L1), diagnosed in 1995, received combination chemotherapy consisting of 6 weeks of induction (vincristine, epirubicin, L-asparaginase, prednisolone) and 2 weeks of consolidation (cytosine arabinosides, etoposide). After achieving remission, for further maintenance of remission, he was treated with 14 cycles of intensive chemotherapy consisting of 6-MP, 10 mg/kg orally on the first 4 days, and cyclophosphamide, 1200 mg/m2, vincristine, 1.5 mg/m2, epirubicin, 15 mg/m2, and cytosine arabinoside, 40 mg/m2, intravenously on days 4, 11, 39, and 40, respectively. On day 18 of each cycle, he received intravenous methotrexate (MTX) infusion in a total dose of 150 mg/m2 plus oral leucovorin (30 mg/m2 ) rescue 36 h after starting MTX therapy. In addition, oral trimethoprim-sulfamethoxazole was given regularly to prevent Pneumocystis carinii infection. The patient achieved remission during the first course of treatment, but 8 months later the disease relapsed. He then received four doses of MTX (800 mg intravenously) plus leucovorin rescue in the following 4 months. During the last MTX therapy, small hemorrhagic bullae were found on the lateral side of the right ankle, but subsided after a few days. Due to partial remission of the disease, he was admitted again in January 1999 for high-dose MTX therapy. An initial hemogram on admission revealed hemoglobin 7.2 g/dL, white cell count 15,200/mm3, platelet count 153/mm3, blood creatinine 0.5 mg/dL, and alanine leucine aminotransferase (ALT) 20 U/L. He received 8500 mg of MTX (5000 mg/m2 ) as a continuous intravenous infusion for 24 h. Thirty-six hours after the start of MTX infusion, leucovorin (30 mg, intravenous) rescue was initiated every 6 h for 3 days. Another preventive measure to cover MTX toxicity included aggressive intravenous fluid replacement (4 L/m2 /day) and the addition of 25 meq/L sodium bicarbonate to the intravenous fluid to alkalinize the urine. Concurrent medication included 6-MP (50 mg) once daily and trimethoprim-sulfamethoxazole (120 mg, 600 mg) twice daily every other day. Plasma MTX levels were 52.36 micromol/L 24 h after MTX infusion, 1.87 micromol/L after 48 h, 0.57 micromol/L after 72 h, and 0.41 micromol/L after 96 h. These indicated delayed MTX plasma clearance. The blood creatinine level was mildly elevated from 0.5 mg/dL to 0.7 mg/dL. Thirty-six hours after the administration of MTX, the patient developed an erythematous

Topics: Adolescent; Anti-Infective Agents; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Fatal Outcome; Humans; Male; Methotrexate; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Stevens-Johnson Syndrome; Trimethoprim, Sulfamethoxazole Drug Combination

Cutaneous adverse drug reactions in HIV-positive patients with their wide spectrum of manifestations remain a diagnostic and therapeutic challenge. Skin diseases as erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis belong to this group. The typical primary lesions are erythematous macules and papules, which rapidly extend to the entire body and may be accompanied by a extensive epidermal detachment. Diagnosis and immediate therapy is indispensable because of the possible fulminant course of the disease. We report a HIV-positive patient with a cutaneous adverse drug reaction showing predominantly hemorrhagic lesions.

Topics: AIDS-Related Opportunistic Infections; Diagnosis, Differential; Drug Eruptions; Drug Therapy, Combination; Fatal Outcome; HIV Infections; Humans; Male; Middle Aged; Stevens-Johnson Syndrome; Trimethoprim, Sulfamethoxazole Drug Combination

Toxic epidermal necrolysis (TEN) is a severe, progressive disease characterized by the sudden onset of skin necrosis. It is frequently associated with systemic involvement and has a high rate of morbidity and mortality. Standard therapy includes meticulous wound care, fluid replacement, and nutritional support in an intensive care setting.. We evaluated the outcomes of patients treated in a burn unit for TEN over a 9-year period and compared the outcomes of a subset of patients treated with plasmapheresis with those managed by conventional means.. The records of 16 patients with a diagnosis of TEN obtained from a computerized database were reviewed. Parameters recorded included extent of body surface area involvement and number of mucous membranes involved at admission, complications such as sepsis or need for mechanical ventilation, length of stay, and disposition.. Sixteen patients were included in this study. Ten were treated with conventional support measures alone. Six were treated with plasmapheresis. The average age was 42.4 years; the male/female ratio was 1:2.2. Sulfamethoxazole/trimethoprim was implicated in causation in 6 patients. The average extent of involvement on admission in all patients was 51.5% total body surface area. The average length of stay in all patients was 14.8 days. Eight patients (50%) were discharged home, 4 (25%) were discharged to a rehabilitation facility, and 4 (25%) died (2 of sepsis, 2 of cardiopulmonary arrest). None of the plasmapheresis-treated patients died.. Plasmapheresis is a safe intervention in extremely ill TEN patients and may reduce the mortality in this severe disease. Prospective studies are needed to further define its usefulness.

Topics: Adolescent; Adult; Aged; Child, Preschool; Female; Humans; Male; Middle Aged; Phenytoin; Plasmapheresis; Stevens-Johnson Syndrome; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

The objective of this study was to quantify the risk of serious blood and skin disorders associated with co-trimoxazole.. We conducted a population-based cohort study of serious blood and skin disorders requiring hospitalization among otherwise healthy users of co-trimoxazole at Group Health Cooperative and Puget Sound (GHC).. During the years 1987 to 1993 we found six cases of co-trimoxazole-associated blood disorders and three cases of co-trimoxazole-associated skin disorders yielding risks of 5.6/100,000 (95% CI 2.6-12.2) and 2.8/100,000 (95% CI 0.9-8.2) respectively. In all cases found there was prompt recovery after discontinuation of co-trimoxazole. We found no cases of toxic epidermal necrolysis.. We conclude that the risk of blood and skin disorders associated with the use of co-trimoxazole leading to hospitalization is low.

Topics: Adult; Aged; Anti-Infective Agents; Child, Preschool; Cohort Studies; Erythema Multiforme; Female; Hematologic Diseases; Hospitalization; Humans; Leukopenia; Longitudinal Studies; Male; Middle Aged; Neutropenia; Pancytopenia; Risk Assessment; Skin Diseases; Stevens-Johnson Syndrome; Thrombocytopenia; Trimethoprim, Sulfamethoxazole Drug Combination

To quantify the risk of serious blood and skin disorders requiring hospitalization among otherwise healthy users of co-trimoxazole.. We conducted a population-based cohort study at Group Health Cooperative of Puget Sound (GHC).. During the years 1987 to 1993 we found six cases of co-trimoxazole-associated blood disorders and three cases of co-trimoxazole-associated skin disorders yielding risks of 5.6/100,000 (95% CI 2.6-12.2) and 2.8/100,000 (95% CI 0.9-8.2) respectively. In all cases found there was prompt recovery after discontinuation of co-trimoxazole. We found no cases of toxic epidermal necrolysis.. We conclude that the risk of blood and skin disorders associated with the use of co-trimoxazole leading to hospitalization is low.

Topics: Adult; Aged; Anti-Infective Agents; Child, Preschool; Cohort Studies; Erythema Multiforme; Female; Hematologic Diseases; Hospitalization; Humans; Leukopenia; Longitudinal Studies; Male; Middle Aged; Neutropenia; Pancytopenia; Product Surveillance, Postmarketing; Risk Assessment; Skin Diseases; Stevens-Johnson Syndrome; Thrombocytopenia; Trimethoprim, Sulfamethoxazole Drug Combination

The development of heterotopic ossification (HO) as a complication of toxic epidermal necrolysis (TEN) has not been previously reported. TEN, also known as Lyell's syndrome, is a rare but serious skin disorder that typically occurs after the administration of drugs, especially sulfonamides, barbiturates, phenytoin, and nonsteroidal anti-inflammatory agents. TEN is characterized by the development of large fluid-filled bullae with separation of large sheets of skin. Complications of TEN can include extensive denudation of skin with dehydration and electrolyte abnormalities, gastrointestinal hemorrhage, acute tubular necrosis, secondary infection of denuded skin, pneumonia, bacterial conjunctivitis, keratitis, and septic infarcts of internal organs. We report a case of HO in a patient with TEN after treatment with trimethoprim-sulfamethoxazole. A 49-year-old man developed an erythematous rash, bullae, fever, and extensive skin loss consistent with a diagnosis of TEN. He was intubated for complications of TEN (pneumonia) and maintained on bed rest for several weeks. In addition, he developed HO that resulted in multiple joint contractures. He was treated with aggressive range of motion by physical therapy, surgical resection of the HO followed by radiation to both elbows, right hip, and right knee. Postoperative outpatient rehabilitation enabled improved function in his mobility and activities of daily living. HO is known to occur after spinal cord and brain injuries and burns. It has not been reported to occur after TEN. Our experience with this case suggests that HO may merit inclusion into the list of complications of TEN.

Topics: Anti-Infective Agents; Contracture; Humans; Joint Diseases; Male; Middle Aged; Ossification, Heterotopic; Radiography; Radiotherapy, Adjuvant; Stevens-Johnson Syndrome; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acetazolamide; Aged; Aged, 80 and over; Anti-Infective Agents; Anti-Infective Agents, Urinary; Diuretics; Furosemide; Humans; Macrophage Migration-Inhibitory Factors; Macrophages; Male; Middle Aged; Nitrofurantoin; Stevens-Johnson Syndrome; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Desensitization, Immunologic; Drug Eruptions; Humans; Male; Pneumonia, Pneumocystis; Stevens-Johnson Syndrome; Trimethoprim, Sulfamethoxazole Drug Combination

The treatment of two cases of toxic epidermal necrolysis (Lyell's syndrome) is described. Although some features were common for both ones (young men practically of the same age, reaction after using the same drug) the clinical course of illness was very different. Spontaneous epithelisation of partial-thickness lesions and definitive healing under the xenografts in one patient and full-thickness skin-loss on 12% of body surface with severe septic complications requiring application of cultured keratinocytes and/or skin autografting in the other patient were the main differences. The interdisciplinary approach using a burns treatment protocol in non-burned patient including the close co-operation with the tissue bank in preparing different types of biological covers has been applied.

Topics: Adolescent; Anti-Infective Agents; Histamine H1 Antagonists; Histamine H2 Antagonists; Humans; Immunization, Passive; Male; Skin Transplantation; Stevens-Johnson Syndrome; Transplantation, Heterologous; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Calculi

Topics: Drug Costs; Humans; Risk; Stevens-Johnson Syndrome; Trimethoprim, Sulfamethoxazole Drug Combination

To report a case of erythema multiforme (EM) major treated with cyclophosphamide and prednisone.. General medicine and dermatology consult services, Department of Veterans Affairs Medical Center.. A 44-year-old man with C4-C5 quadriplegia developed a skin reaction characterized by a painful, generalized maculopapular rash, bullae, ulceronecrotic lesions, and mucosal and epidermal sloughing after taking trimethoprim/sulfamethoxazole. The patient was treated with intravenous cyclophosphamide 150 mg infused over 1 hour every 24 hours and oral prednisone 15 mg every 6 hours. After two doses of cyclophosphamide, formation of bullae and epidermal sloughing had ceased, and the erythema was markedly diminished. Cyclophosphamide was discontinued before the third dose because of evolving leukopenia. Prednisone therapy was continued until the patient was discharged on hospital day 5, at which time the dosage was tapered.. Cyclophosphamide has been used extensively for other dermatologic reactions. Relief of pain and regression of the lesions in our patient occurred more quickly than anticipated.. Treatment of EM major with cyclophosphamide combined with prednisone appeared to be highly successful in this patient. Cyclophosphamide may be an effective, empiric initial treatment in reversing EM major.

Topics: Adult; Alkylating Agents; Anti-Infective Agents, Urinary; Anti-Inflammatory Agents; Cyclophosphamide; Drug Therapy, Combination; Humans; Injections, Intravenous; Male; Prednisone; Quadriplegia; Spinal Cord Injuries; Stevens-Johnson Syndrome; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Aged; Aged, 80 and over; Anti-Infective Agents; Anti-Infective Agents, Urinary; Humans; Male; Patch Tests; Stevens-Johnson Syndrome; Sulfamethoxazole; Trimethoprim, Sulfamethoxazole Drug Combination

Various types of cutaneous drug eruptions and the incriminating drugs were analyzed in 50 children and adolescents up to 18 years of age (34 or 65% boys, 16 or 32% girls). Thirteen (26%) patients had a maculopapular rash, 11 (22%) a fixed drug eruption (FDE), 10 erythema multiforme (EM), 6 (12%) toxic epidermal necrolysis (TEN), 5 (10%) Stevens-Johnson syndrome (SJS), 3 (6%) urticaria, and 2 (4%) erythroderma. The incubation period for maculopapular rashes, SJS and TEN due to commonly used antibiotics and sulfonamides was short, a few hours to two to three days, reflecting reexposure, and for drugs used sparingly such as antiepileptics and antituberculosis agents, was approximately one week or more, suggesting a first exposure. Antibiotics were responsible for cutaneous eruptions in 27 patients, followed by antiepileptics in 17, analgin in 4, and metronidazole and albendazole in 1 each. Cotrimoxazole, a combination of sulfamethoxazole and trimethoprim, was the most common antibacterial responsible for eruptions (11 patients), followed by penicillin and its semisynthetic derivatives (8 patients), sulfonamide alone (3 patients), and other antibiotics (4 patients). Antiepileptics were the most frequently incriminated drugs in EM, TEN, and SJS. The role of systemic corticosteroids in the management of SJS and TEN is controversial. We administered prednisolone or an equivalent corticosteroid 2 mg/kg/day for 7 to 14 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Anti-Bacterial Agents; Anticonvulsants; Antitubercular Agents; Case-Control Studies; Child; Child, Preschool; Dermatitis, Exfoliative; Dipyrone; Drug Eruptions; Erythema Multiforme; Female; Humans; India; Infant; Male; Penicillins; Prednisolone; Prospective Studies; Stevens-Johnson Syndrome; Sulfonamides; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination; Urticaria

Topics: Administration, Oral; Fatal Outcome; Female; Humans; Middle Aged; Nasal Obstruction; Stevens-Johnson Syndrome; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acetylation; Adolescent; Adult; Aged; Aged, 80 and over; Anticonvulsants; Arylamine N-Acetyltransferase; Female; Genetic Predisposition to Disease; Genotype; Humans; Male; Middle Aged; Risk Factors; Stevens-Johnson Syndrome; Sulfonamides; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Aged; Aged, 80 and over; Anti-Infective Agents, Urinary; Diagnosis, Differential; Humans; Male; Patch Tests; Stevens-Johnson Syndrome; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Dapsone is used in prophylaxis for and treatment of Pneumocystis carinii pneumonia. We present a case of Stevens-Johnson syndrome that was likely induced by administration of dapsone. A review of charts at the HIV Treatment Center of Northwestern University (Chicago) revealed that 40.3% of patients treated with trimethoprim-sulfamethoxazole could not tolerate the medication, while 25.2% of those treated with dapsone were intolerant of the drug. We also found a higher rate of adverse reactions to dapsone among patients with prior intolerance to trimethoprim-sulfamethoxazole than among patients without such a history; however, the difference was not significant.

Topics: Acquired Immunodeficiency Syndrome; Adult; Dapsone; Drug Tolerance; Humans; Male; Pneumonia, Pneumocystis; Stevens-Johnson Syndrome; Trimethoprim, Sulfamethoxazole Drug Combination

An attempt was made to estimate the risk of severe cutaneous adverse reactions (SCARs) to Fansidar (sulfadoxine plus pyrimethamine). Cases were identified through a spontaneous reporting system. Persons exposed were estimated using sales data of 27 countries reporting one SCAR case for either Fansidar or a related product, Bactrim (cotrimoxazole; sulfamethoxazole plus trimethoprim). Between 1974 and 1989, 126 cases were notified for Fansidar: 87 cases of erythema multiforme or Stevens-Johnson syndrome, and 39 cases of toxic epidermic necrolysis. 86% of cases were reported in Europe or North America. In 116 cases with use known, prophylaxis was the reason in 103, and treatment in 13. Toxic epidermolysis and erythema multiforme/Stevens-Johnson syndrome had case fatalities of 36 (95% confidence intervals 21 to 53%) and 9% (4 to 18%), respectively. Fansidar users were estimated at 117 million, and the overall SCAR risk to be 1.1 (0.9 to 1.3) per million. For developing countries with mainly single dose use, the risk was estimated to 0.1 (0.0 to 0.1) per million. For Europe and North America with mainly prophylactic use, the risk was 10 (8 to 12) and 36 (23 to 48) per million, respectively. Prophylactic use had a 40 times higher risk than single dose therapeutic use. The aggregated risk peaked in 1984-1985, with global and North American SCAR frequencies of 3.4 (2.4 to 4.3) and 72 (41 to 102) per million, respectively. After 1985, North America reported only one further case despite continued use by an estimated 0.3 million persons.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adverse Drug Reaction Reporting Systems; Antimalarials; Drug Combinations; Drug Eruptions; Drug Utilization; Erythema Multiforme; Humans; Malaria; Pyrimethamine; Risk Factors; Stevens-Johnson Syndrome; Sulfadoxine; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acquired Immunodeficiency Syndrome; Adult; Humans; Male; Methylprednisolone; Pneumonia, Pneumocystis; Stevens-Johnson Syndrome; Trimethoprim, Sulfamethoxazole Drug Combination

Recent reports suggest that acquired immunodeficiency syndrome (AIDS) patients are at higher risk of developing mucocutaneous reactions such as toxic epidermal necrolysis and Stevens-Johnson syndrome (SJS). Resultant dry eye may be further exacerbated by human immunodeficiency virus (HIV) related lacrimal gland dysfunction and lead to a chronic keratoconjunctivitis. We report one patient with AIDS and toxic epidermal necrolysis and two patients with AIDS and SJS who developed severe dry eye misdiagnosed as infectious keratoconjunctivitis. Cicatrizing mucocutaneous reactions should be suspected in AIDS patients and the dry eye treated to control symptoms and prevent complications.

Topics: Acquired Immunodeficiency Syndrome; Adult; Dry Eye Syndromes; Humans; Keratoconjunctivitis; Lacrimal Apparatus Diseases; Male; Stevens-Johnson Syndrome; Trimethoprim, Sulfamethoxazole Drug Combination

Six cases of drug-induced toxic epidermal necrolysis treated in a burns unit are presented. The mean skin loss was 67.3 per cent of the total body surface area. Two patients developed renal failure and two had ocular symptoms. The mortality rate was 50 per cent, with two patients dying from septicaemia and one from respiratory and renal failure. The diagnosis of toxic epidermal necrolysis can be confirmed by skin biopsy. We recommend that this disease is treated in a burns unit so that both adequate wound care and essential intensive supportive treatment can be given. Antibiotics are indicated only for specific infections such as septicaemia or pneumonia. Steroids have been shown to increase greatly the mortality from septic complications and are not recommended. The mortality ranges from 10 per cent to 70 per cent and bad prognostic factors include increasing age, greater than 50 per cent of body surface skin loss and neutropenia.

Topics: Adolescent; Adult; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Antimalarials; Chlorpromazine; Clavulanic Acids; Diagnosis, Differential; Drug Combinations; Female; Humans; Hypoglycemic Agents; Male; Middle Aged; Pyrimethamine; Retrospective Studies; Stevens-Johnson Syndrome; Sulfadoxine; Trimethoprim, Sulfamethoxazole Drug Combination; Zimeldine

Topics: Aged; Aged, 80 and over; Anti-Infective Agents; Bronchitis; Drug Combinations; Humans; Male; Postoperative Complications; Stevens-Johnson Syndrome; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections

Topics: Aged; Drug Combinations; Humans; Stevens-Johnson Syndrome; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acquired Immunodeficiency Syndrome; Adult; Coccidiosis; Drug Combinations; Enteritis; Humans; Male; Stevens-Johnson Syndrome; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

This paper is written to heighten awareness of the presence of the most severe form of fixed drug eruption. Two patients with a widespread bullous form of fixed drug eruption (FDE) were initially given the diagnosis of toxic epidermal necrolysis (TEN). Both gave a history of a previous widespread eruption from the responsible drug, each had biopsies consistent with fixed drug eruption, and most importantly, both had an uncomplicated course, with complete cutaneous reepithelialization within 10 days. These observations suggest that widespread bullous fixed drug eruption may portend a more favorable prognosis than TEN, thus stressing the potential importance of distinguishing the two diseases. A review of fixed drug eruption and possible means of differentiating the widespread bullous form from TEN are discussed.

Topics: Adult; Anti-Infective Agents; Diagnosis, Differential; Drug Combinations; Female; Humans; Male; Phenytoin; Skin Diseases, Vesiculobullous; Stevens-Johnson Syndrome; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Like many other drugs co-trimoxazole can induce a large number of different skin reactions, mainly of allergic pathogenesis. The majority of these reactions, such as urticarial, purpuric, maculo-papular, and pustular exanthemas as well as photallergic reactions, generally do not endanger the life of the patient. Apart from very rare cases of anaphylactic shock, there is a risk of lethality associated with Stevens-Johnson syndrome and Lyell's syndrome of approximately 1% and 30%, respectively. Between 1981 and 1985, an extensive epidemiological survey was carried out in Germany which enabled approximation of drug induced severe skin reactions (Lyell's syndrome, Stevens-Johnson syndrome). Preliminary evaluation of the survey allowed the identification of 217 Lyell's syndromes and 296 Stevens-Johnson syndromes. The total registration rate resulting from an almost complete survey of all applicable medical units (dermatology, burns, intensive care) was 92%. The basic risk amongst the population of acquiring Lyell's syndrome and Stevens-Johnson syndrome, as calculated from the data gathered between 1981 and 1985, is 0.8 and 1.0 per year, and per one million inhabitants respectively, in the drug-related incidence calculation. Co-trimoxazole is in the upper third of the table of drugs which certainly, probably, or possibly induced a Lyell's syndrome and in the middle of the table of those that induced Stevens-Johnson syndrome.

Topics: Anti-Infective Agents; Drug Combinations; Drug Eruptions; Humans; Skin; Stevens-Johnson Syndrome; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Lymphocyte transformation tests (LTT) to drugs remain widely used in drug reactions, despite controversies about their real usefulness. We tested the lymphocytes of 12 patients recovering from a drug-induced Toxic epidermal necrolysis (TEN). There was no difference between the amounts of thymidine incorporated when patients' lymphocytes were cultivated with culprit or innocent drugs. In both situations the lymphocytes from patients reacted like the lymphocytes from controls cultivated with the same panel of drugs. These negative results do not exclude that a hypersensitivity reaction may play a role in the physiopathology of TEN. Anyhow, they clearly indicate that testing lymphocyte transformation to drugs has no practical value in the diagnosis of TEN.

Topics: Adolescent; Adult; Aged; Carbamazepine; Child; Dipyrone; Drug Combinations; Female; Flurbiprofen; Humans; Lymphocyte Activation; Lymphocytes; Male; Middle Aged; Oxyphenbutazone; Phenylbutyrates; Piroxicam; Propionates; Pyrazolones; Stevens-Johnson Syndrome; Sulfadiazine; Sulfamethoxazole; Thiazines; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Aspirin; Drug Combinations; Drug Eruptions; Female; Humans; Middle Aged; Respiratory Tract Infections; Stevens-Johnson Syndrome; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; Allopurinol; Burns; Critical Care; Drug Combinations; Emergencies; Female; Humans; Middle Aged; Phenylbutazone; Stevens-Johnson Syndrome; Sulfamethoxazole; Trauma Centers; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Infective Agents, Urinary; Drug Combinations; Humans; Male; Middle Aged; Stevens-Johnson Syndrome; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adolescent; Adult; Aged; Bacterial Infections; Child; Child, Preschool; Drug Combinations; Erythema Multiforme; Female; HLA Antigens; Humans; Infant; Male; Middle Aged; Mucocutaneous Lymph Node Syndrome; Mycoplasma Infections; Stevens-Johnson Syndrome; Sulfamethoxazole; Sulfonamides; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Virus Diseases