ABSTRACT
Susceptibility to Pemphigus, an autoimmune disease of the skin, has been previously linked to DRB1*0402, 1401/04 and DQB1*0503 in pemphigus vulgaris (PV), to DRB1*0102, 0404, 1402/06 in endemic pemphigus foliaceus in Brazil and to DRB1*04 in Italian patients suffering from pemphigus foliaceus (PF). The disease is caused by autoantibodies against desmoglein (Dsg1 in PF, Dsg3 in PV). Molecular typing of 57 French patients suffering from PV (37) and from PF (20) confirmed previous results concerning PV and showed that DRB1*0102 and 0404 are susceptible molecules to PF in France. We have analysed the characteristics of the 'pockets' of the susceptibility-associated molecules to PV and PF and we showed that (i) in PV, two kinds of Dsg3 derived peptides may be presented by HLA-DR according to HLA polymorphism (DRB1*0402 or DRB1*14/0406), (ii) the same Dsg1 peptides may be presented by DRB1*0102, DQB1*0404 or DRB1*14 in PF, (iii) the DRB1*14/0406 PV-related molecules may be able to present Dsg1 and Dsg3 peptides thereby providing an explanation for the cases of PV with combined responses to Dsg1 and to Dsg3 which are typified by a muco-cutaneous clinical phenotype.
Subject(s)
Cytoskeletal Proteins/genetics , Genes, MHC Class II , Pemphigus/genetics , Pemphigus/immunology , Peptides/genetics , Peptides/immunology , Polymorphism, Genetic/immunology , Alleles , Amino Acid Sequence , Autoantigens/genetics , Cadherins/genetics , Desmoglein 1 , Desmogleins , Desmoplakins , Desmosomes/genetics , Female , Genetic Predisposition to Disease , HLA-DQ Antigens/classification , HLA-DQ Antigens/genetics , HLA-DQ beta-Chains , HLA-DR Antigens/classification , HLA-DR Antigens/genetics , HLA-DRB1 Chains , Humans , Male , Middle Aged , Molecular Sequence Data , Peptides/classification , Prospective Studies , Protein Binding/geneticsABSTRACT
BACKGROUND: Withdrawal of the drug(s) that cause severe cutaneous adverse reactions is usually recommended without proof that it alters the course of those reactions. OBJECTIVE: To determine whether the timing of causative drug withdrawal is related to the prognosis of patients with toxic epidermal necrolysis (TEN) or Stevens-Johnson syndrome (SJS). DESIGN: A 10-year observational study (January 1, 1987, through October 30, 1997) of patients admitted to a dermatological intensive care unit, using binary logistic regression analysis. SETTING: A single referral unit in a university hospital. PATIENTS: Consecutive sample of 203 patients with TEN or SJS. Exclusion criteria included causative drug undetermined, lack of information on disease evolution, the date of causative drug(s) withdrawal, or the date when the first definite sign of TEN or SJS appeared. MAIN OUTCOME MEASURE: Death before hospital discharge. RESULTS: One hundred thirteen patients were included; 74 had TEN and 39 had SJS; 20 died. The drug causing TEN or SJS was withdrawn early in 64 patients and late (after the first definite sign of TEN or SJS) in 49 patients. After adjustment for confounding variables (age, maximum extent of detachment, admission year, human immunodeficiency virus status), our model showed that the earlier the causative drug was withdrawn, the better the prognosis (odds ratio, 0.69 for each day; 95% confidence interval, 0.53-0.89). Patients exposed to causative drugs with long half-lives had an increased risk of dying (odds ratio, 4.9; 95% confidence interval, 1.3-18.9). The variables did not interact. CONCLUSIONS: Prompt withdrawal of drug(s) that are suspected to cause SJS or TEN may decrease mortality. Prompt withdrawal of causative drugs should be a priority when blisters or erosions appear in the course of a drug eruption.
