ABSTRACT
OBJECTIVE: We aimed to identify the clinical and genetic [IL23 receptor (IL23R) single nucleotide polymorphisms (SNPs)] predictors of response to therapy in patients with ulcerative colitis. PATIENTS AND METHODS: A total of 174 patients with ulcerative colitis, 99 women and 75 men, were included. The mean age of the patients was 47±15 years and the mean disease duration was 11±9 years. The number of patients classified as responders (R) or nonresponders (NR) to several therapies was as follows: 110 R and 53 NR to mesalazine (5-ASA), 28 R and 20 NR to azathioprine (AZT), 18 R and 7 NR to infliximab. Clinical and demographic variables were recorded. A total of four SNPs were studied: IL23R G1142A, C2370A, G43045A, and G9T. Genotyping was performed by real-time PCR using Taqman probes. RESULTS: Older patients were more prone to respond to 5-ASA (P=0.004), whereas those with pancolitis were less likely to respond to such therapies (P=0.002). Patients with extraintestinal manifestations (EIMs) were less likely to respond to 5-ASA (P=0.001), AZT (P=0.03), and corticosteroids (P=0.06). Carriers of the mutant allele for IL23R SNPs had a significantly higher probability of developing EIMs (P<0.05), a higher probability of being refractory to 5-ASA (P<0.03), but a higher likelihood of responding to AZT (P=0.05). A significant synergism was observed between IL23R C2370A and EIMs with respect to nonresponse to 5-ASA (P=0.03). CONCLUSION: Besides extent of disease and age at disease onset, the presence of EIMs may be a marker of refractoriness to 5-ASA, corticosteroids, and AZT. IL23R SNPs are associated both with EIMs and with nonresponse to 5-ASA and corticosteroids.
Subject(s)
Anti-Inflammatory Agents/therapeutic use , Colitis, Ulcerative/genetics , Colitis, Ulcerative/therapy , Gastrointestinal Agents/therapeutic use , Polymorphism, Single Nucleotide , Receptors, Interleukin/genetics , Adrenal Cortex Hormones/therapeutic use , Adult , Age Factors , Antibodies, Monoclonal/therapeutic use , Azathioprine/therapeutic use , Colitis, Ulcerative/immunology , Female , Genetic Predisposition to Disease , Humans , Infliximab , Male , Mesalamine/therapeutic use , Middle Aged , Phenotype , Portugal , Retrospective Studies , Risk Factors , Severity of Illness Index , Treatment OutcomeABSTRACT
BACKGROUND: A 62-year-old white woman was admitted to hospital with a 2-month history of progressive, painless, left supraclavicular and axillary lymph node enlargement. The patient's history was significant for chronic HCV infection, for which she had just completed a 48-week course of treatment with pegylated interferon alpha (180 microg once weekly) plus ribavirin (1,000 mg daily). She attained an end-of-treatment response and subsequent qualitative measurement of HCV RNA confirmed a sustained virological response. The onset of progressive painless lymph node enlargement had been noted by the patient during the last 2 weeks of her treatment for HCV. INVESTIGATIONS: Physical examination, otorhinolaryngological examination, laboratory investigations (including complete blood counts, liver function tests and serological tests), mammography, thyroid and abdominal ultrasound, CT scans, abdominal MRI, upper gastrointestinal endoscopy, colonoscopy, supraclavicular lymph node biopsy, (67)Ga scintigraphy and bronchoalveolar lavage. DIAGNOSIS: Granulomatous lymphadenitis of uncertain etiology with sarcoid-type and tuberculoid-type granulomas. MANAGEMENT: Standard antituberculosis treatment with isoniazid, rifampicin, pyrazinamide and ethambutol for 2 months, followed by isoniazid and rifampicin for 7 months.
