trimethoprim--sulfamethoxazole-drug-combination and Hypersensitivity

Topics: Adrenal Cortex Hormones; Antibodies, Monoclonal; Asthma; Drug Hypersensitivity; Food Additives; Food Hypersensitivity; Humans; Humidity; Hypersensitivity; Immunoglobulin E; Latex Hypersensitivity; Rhinitis; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim-sulfamethoxazole (TMP-SMX) hypersensitivity reaction, ranging from circulatory shock to aseptic meningitis and respiratory failure, is a potentially life-threatening condition with dermatologic relevance.. To describe the mucocutaneous findings and clinical features of TMP-SMX hypersensitivity reaction.. This was a retrospective case series study of 7 patients who developed a characteristic rash, hemodynamic changes, and end-organ dysfunction after treatment with TMP-SMX at a large university hospital system during January 2013 to March 2022.. Treatment with TMP-SMX within 2 weeks of the reaction.. Descriptions of the condition, including the demographic information of the affected population, the reaction timeline, and mucocutaneous and clinical features.. The cohort comprised 7 patients (median [range] age, 20 [15-66] years; 4 female and 3 male). The most common mucocutaneous findings were generalized sunburn-like erythema without scale, conjunctivitis, and mild facial and acral edema. Three patients had previous exposure to TMP-SMX and developed symptoms in 1 day or less, while those without prior exposure presented from 4 to 11 days after drug initiation. Among the 7 patients, 6 had fever, 7 had hypotension, and 7 had tachycardia. All patients had lymphopenia and evidence of end-organ dysfunction with either kidney or liver involvement. Median (range) time to resolution was 72 (48-96) hours.. This retrospective case series indicates that SCoRCH (sudden conjunctivitis, lymphopenia, and rash combined with hemodynamic changes) should be considered in the differential diagnosis of patients presenting with acute generalized sunburn-like erythema, conjunctivitis, systemic symptoms, and hemodynamic changes in the setting of recent TMP-SMX use.

Topics: Adult; Exanthema; Female; Humans; Hypersensitivity; Lymphopenia; Male; Multiple Organ Failure; Retrospective Studies; Sunburn; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

This cohort study describes the adaptation of a widely used penicillin allergy clinical decision tool for evaluation of trimethoprim-sulfamethoxazole allergy.

Topics: Anti-Bacterial Agents; Clinical Decision Rules; Drug Hypersensitivity; Humans; Hypersensitivity; Sulfonamides; Trimethoprim, Sulfamethoxazole Drug Combination

The anti-cancer impact of an allergic reaction is strongly linked to immunity enhancement. Trimethoprim-sulfamethoxazole (TMP-SMX), an antibiotic, has potential immunomodulatory effects, but has side effects such as allergies. Thus far, the effects and underlying mechanisms of TMP-SMX in melanoma have not been clarified. This study examined the potential roles of TMP-SMX in melanoma skin cancer using an immunodeficient mouse model. TMP-SMX significantly improved the survival rate and reduced the tumor weight and growth and vascular endothelial growth factor levels in melanoma skin cancer of immunodeficient mice. In the forced swimming test, TMP-SMX significantly reduced immobility time compared to the melanoma skin cancer of immunodeficient mice, indicating improved immunity. TMP-SMX significantly increased infiltration of mast cells and release of allergy-related mediators (IgE, histamine, interleukin (IL)-4, IL-5, IL-13, and IL-33) and immune-enhancing mediators (tumor necrosis factor-α, IL-2, IL-6, and IL-12). In addition, the administration of TMP-SMX significantly increased the caspase-3, 8, and 9 activities. Furthermore, mice given TMP-SMX showed no adverse reactions according to the blood biochemical parameters. TMP-SMX significantly inhibits the growth of melanoma skin cancer by triggering an allergic reaction and promotingimmunity. Hence, we propose that TMP-SMX may be used as an immune booster in cancer chemotherapy.

Topics: Animals; Hypersensitivity; Melanoma; Melanoma, Cutaneous Malignant; Mice; Skin Neoplasms; Trimethoprim, Sulfamethoxazole Drug Combination; Vascular Endothelial Growth Factor A

Sulfamethoxazole (SMX) is a commonly used antibiotic for prevention of infectious diseases associated with HIV/AIDS and immune-compromised states. SMX-induced hypersensitivity is an idiosyncratic cutaneous drug reaction with genetic components. Here, we tested association of candidate genes involved in SMX bioactivation and antioxidant defense with SMX-induced hypersensitivity.. Seventy seven single nucleotide polymorphisms (SNPs) from 14 candidate genes were genotyped and assessed for association with SMX-induced hypersensitivity, in a cohort of 171 HIV/AIDS patients. SNP rs761142 T > G, in glutamate cysteine ligase catalytic subunit (GCLC), was significantly associated with SMX-induced hypersensitivity, with an adjusted p value of 0.045. This result was replicated in a second cohort of 249 patients (p = 0.025). In the combined cohort, heterozygous and homozygous carriers of the minor G allele were at increased risk of developing hypersensitivity (GT vs TT, odds ratio = 2.2, 95% CL 1.4-3.7, p = 0.0014; GG vs TT, odds ratio = 3.3, 95% CL 1.6 - 6.8, p = 0.0010). Each minor allele copy increased risk of developing hypersensitivity 1.9 fold (95% CL 1.4 - 2.6, p = 0.00012). Moreover, in 91 human livers and 84 B-lymphocytes samples, SNP rs761142 homozygous G allele carriers expressed significantly less GCLC mRNA than homozygous TT carriers (p < 0.05).. rs761142 in GCLC was found to be associated with reduced GCLC mRNA expression and with SMX-induced hypersensitivity in HIV/AIDS patients. Catalyzing a critical step in glutathione biosynthesis, GCLC may play a broad role in idiosyncratic drug reactions.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Catalytic Domain; Female; Genotyping Techniques; Glutamate-Cysteine Ligase; Glutathione; HIV Infections; Humans; Hypersensitivity; Inactivation, Metabolic; Male; Polymorphism, Single Nucleotide; Sulfamethoxazole; Trimethoprim, Sulfamethoxazole Drug Combination

The use of co-trimoxazole in HIV-positive patients has been associated with a high frequency (40-80%) of hypersensitivity reactions. This has been attributed to the bioactivation of the sulphonamide component, sulphamethoxazole (SMX), to its toxic hydroxylamine and nitroso metabolites. The aim of this study was to determine whether functionally significant polymorphisms in the genes coding for enzymes involved in SMX metabolism influence susceptibility to SMX hypersensitivity. HIV-positive patients with (n = 56) and without (n = 89) SMX hypersensitivity were genotyped for allelic variants in CYP2C9, GSTM1, GSTT1, GSTP1 and NAT2 using polymerase chain reaction (PCR) and/or PCR-restriction fragment length polymorphism analysis. The CYP2C9*2/*3 genotype and CYP2C9*3 allele frequencies were nine- and 2.5-fold higher in the hypersensitive group compared to non-sensitive patients, respectively, although they were not statistically significant when corrected for multiple testing. There were no differences in the frequencies of the GSTM1 and GSTT1 null genotypes, and the slow acetylator genotype, between hypersensitive and non-sensitive patients, while GSTP1 frequency was lower (although non-significant) in the hypersensitive group [21% versus 32%, odds ratio (OR) = 0.5, Pc = 0.24]. Comparison of the genotype frequencies in HIV-positive and -negative patients showed that the NAT2 slow acetylator genotype frequency in the HIV-positive patients (74%) was significantly (Pc = 0.0003, OR = 2.3) higher than in control subjects (56%). Our results show that genetic polymorphisms in drug metabolizing enzymes are unlikely to be major predisposing factors in determining individual susceptibility to co-trimoxazole hypersensitivity in HIV-positive patients.

Topics: Acetylation; Alleles; Aryl Hydrocarbon Hydroxylases; Arylamine N-Acetyltransferase; Cytochrome P-450 CYP2C9; Cytochrome P-450 Enzyme System; Gene Frequency; Genotype; Glutathione Transferase; HIV Seropositivity; Humans; Hypersensitivity; Inactivation, Metabolic; Odds Ratio; Polymorphism, Restriction Fragment Length; Steroid 16-alpha-Hydroxylase; Steroid Hydroxylases; Sulfamethoxazole; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Age Factors; Aged; Antipsychotic Agents; Astemizole; Comorbidity; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Hypersensitivity; Infant; Risperidone; Schizophrenia; Seizures; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections

Topics: Acquired Immunodeficiency Syndrome; Desensitization, Immunologic; Humans; Hypersensitivity; Trimethoprim, Sulfamethoxazole Drug Combination