CYP2C19*2 status in patients with Stevens-Johnson syndrome and toxic epidermal necrolysis.

PURPOSE: Genetic polymorphisms have been linked to an increased predisposition to developing certain diseases. For example, patients of Han-Chinese descent carrying the HLA-B*1502 allele are at an increased risk of developing Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) if given carbamazepine. Given the complexity of in vivo drug metabolism, it is plausible that the activity of enzyme systems unrelated to specific drug metabolism may be important. Although multiple biomarkers have been identified in unique ethnic groups, there has yet to be a study investigating the presence of the slow metabolizing allele of CYP2C19, denoted CYP2C19*2, in diverse groups and the risk of developing SJS/TEN. PATIENTS AND METHODS: This study looked into the carrier status of CYP2C19*2, a poor metabolizing variant of CYP2C19, in patients diagnosed with SJS/TEN. We looked at its status in our series as a whole and when patients were divided by ethnicity. Genomic DNA was extracted from formalin-fixed paraffin-embedded tissue of patients with biopsy-proven SJS/TEN and real-time polymerase chain reaction was used to assess for the presence of CYP2C19*2. RESULTS: CYP2C19*2 status was determined in 47 patients. Twenty-nine of these 47 patients had a single medication implicated as causing their disease, and eight of these patients were heterozygous or homozygous for CYP2C19*2. There was insufficient evidence to conclude that the presence of CYP2C19*2 is an independent predictor of risk for developing SJS/TEN in our series as a whole. This analysis also confirmed that the frequency of the CYP2C19*2 polymorphism within the different ethnicities in our series did not vary statistically from reported ethnic rates. CONCLUSION: Our study was unable to show a relationship between CYP2C19*2 status and predisposition toward SJS/TEN. We had a heterogeneous population, making it difficult to control for possible confounding factors.

Polydactyly in neurofibromatosis type I: a potential clue to diagnosis.

Neurofibromatosis type 1 is a genetic disorder characterized by variable phenotypic manifestations. The diagnostic criteria, 25 established in 1987, are broad to encompass these pleiotropic findings. Included are the specific osseous manifestations of 26 sphenoid dysplasia and dysplasia or thinning of the cortex of long bones. This review highlights recent evidence on the role of 27 neurofibromin in bone development and suggests consideration for additional diagnostic criteria.

Visiting consultant clinics to study prevalence rates of juvenile rheumatoid arthritis and childhood systemic lupus erythematosus across dispersed geographic areas.

OBJECTIVE: Visiting consultant clinics (VCC) may provide pediatric rheumatologic care to children in rural populations, but the clinical demands have not been studied. We studied whether these clinics could be effective in determining prevalence rates of rheumatic illness like juvenile rheumatoid arthritis (JRA) and childhood systemic lupus erythematosus (SLE) across large dispersed geographic areas. METHODS: The study population included children diagnosed with JRA or SLE at the only civilian pediatric rheumatology center in the State of Hawaii. Prevalence rates of these illnesses were then calculated for the urban and more rural neighbor island areas. VCC and prevalence data were calculated over a 10-year period. RESULTS: We found a lower prevalence of JRA in the urban area (38.3 per 100,000) when compared to the rural neighbor islands (63.2 per 100,000). However, an equivalent prevalence of SLE was found in the urban (24.0 per 100,000) and neighboring islands (21.8 per 100,000). Clinical demands increased significantly with the success of the VCC, and with an increase in pediatric rheumatologic staffing. CONCLUSION: We found an increased prevalence of JRA in rural areas when compared to urban areas. Similar prevalence rates of SLE suggested the finding was not due to referral bias alone. VCC are useful to estimate disease prevalence over large areas, and therefore make it possible to identify areas at greater risk. Further investigations are needed to elucidate the possible environmental and genetic factors that may explain the regional differences in JRA prevalence.