Severe cutaneous adverse drug reactions: diagnostic approach and genetic study in a Brazilian case series.

Summary: Background. Severe cutaneous adverse reactions (SCAR) are potentially fatal reactions. Genetic predisposition is involved in their pathogenesis related to drugs and ethnicities, however in a mixed population these relationships are still unknown. The aim of this study was to describe phenotypes, suspect drugs and HLA-alleles related to SCAR, identified by a systematized approach in a Brazilian case series. Methods. Patients who were diagnosed with SCAR between March 2011 and July 2019 at our university hospital were included. European Network for Drug Allergy (ENDA) questionnaire was used to collect clinical and laboratory data and algorithms for assessment of drug causality were applied. Socio-demographic variables included age, gender and skin color/ethnicity. Drug patch tests (DPT) and HLA-A, -B, -DRB1 typing were carried out. Results. A total of 74 patients were included: 36 (48.64%) with SJS/TEN, 32 (43.24%) DRESS/DIHS, 3 (4.05%) AGEP, 2 (2.70%) overlap(DRESS/SJS and DRESS/AGEP) and 1 (1.35%) GBFDE. The median age was31.5 years (IQR = 14-52.25), most were female (n = 44/59.46%) and brown (n = 38/51.35%). Anticonvulsants (n = 32/43.24%) were the largest group involved and antibiotics (n = 26/35.13%) were the second most common. Two patients with DRESS died during the acute phase. Positive DPT were shown only in anticonvulsant associated DRESS. HLA related to abacavir, allopurinol and carbamazepine were identified. Conclusions. A systematized approach allowed the phenotypic characterization of SCAR. The HLA-A*31:01, B*57:01 and B*58:01 alleles were identified, reinforcing the causality in SCAR by CBZ, ABC and ALLO in the Brazilian population.

Clinical experience of a chronic urticaria referral university center.

Summary: Objective. Describing routine procedures, clinical profile and evolution of patients treated in a chronic urticaria CU reference center of a university hospital. Methods. Retrospective analysis of clinical records and database of CU patients registered between March 2011 and February 2016 in a reference center. Besides demographic characteristics, disease duration, comorbidities, angioedema, thyroid lab tests, urticaria subtypes, provocation tests, UAS and CUQ2oL scores were recorded. Patients with 3 or more visits were included in analysis regarding the first and last visits, to evaluate pharmacological treatment and differences of UAS/CUQ2oL scores, antihistamines anti H1 dosages and need of other medications, according urticaria subtypes. Results.During the study, 252 patients were attended, 200 with CU, including 162 women, median age 45 years, perc 25 - 75 = 27 - 58, and median duration of symptoms before diagnosis 24 months, perc 25 - 75 = 9 - 60. Regarding the etiology, 166 (83%) patients had chronic spontaneous urticaria (CSU), 34 (17%) had isolated chronic inducible urticaria (CIndU) and 66 (33%), CSU with CIndU. Among the 123 patients followed up for 3 or more visits, first prescription to 106 (86.2%) patients was monotherapy with anti-H1, and associations with other medications were prescribed to 17 (13.8%). At the last visit, 94 (76.5%) received antihistamines, and 29 (23.5%) used associations. Patients with CSU + CIndU + ASST positive need more association of anti-H1 with other medications than patients with CSU + CIndU and only CIndU (÷2 = 7.998; p 0.01). Between first and last visits, CUQ2oL mean scores changed from 35.7 (± 21.9) to 22.6 (± 21.0) (Z = -4.833 p less than 0.000). Conclusions.Most of the patients presented CSU, frequently associated with CIndU. There was an improvement in the patients' quality of life during the follow-up period. All patients were treated with antihistamines and there was a great need for doses above the standardized and also for combination with other medications, especially in patients with concomitance of urticaria subtypes.