Factors Related to Omalizumab Drug Survival and Treatment Responses in Chronic Urticaria.

INTRODUCTION: This study aimed to evaluate factors affecting drug survival and treatment response in patients with chronic urticaria treated with omalizumab in clinical practice. METHODS: This study included 386 patients with chronic urticaria. Demographic characteristics, clinical features, laboratory parameters, and omalizumab treatment data were analyzed retrospectively. The 7-day urticaria activity score (UAS7) and urticaria control test (UCT) were used to assess disease severity and treatment responses. RESULTS: Well-controlled disease (UAS7 ≤6) was achieved in 59.3% of patients at a median of 2 months. Complete response was significantly higher in patients treated with omalizumab for ≥12 months (p < 0.001). Family history of asthma (p = 0.01) was less frequent, and disease duration (p = 0.041) was shorter in patients with well-controlled disease. Total treatment duration was longer in patients with relapse (p < 0.001) and serum Helicobacter pylori IgA positivity (p = 0.029). DISCUSSION/CONCLUSION: Treatment response is better in patients treated with omalizumab for ≥12 months. However, prolonged treatment does not prevent relapse. Our findings suggest that continuous or intermittent therapy is an appropriate alternative treatment option in patients with severe chronic urticaria; however, continuous therapy can be preferred to maintain the patient's quality of life.

Omalizumab versus cyclosporin-A for the treatment of chronic spontaneous urticaria: can we define better-responding endotypes?

BACKGROUND: Chronic Spontaneous Urticaria (CSU) is characterized by recurrent wheals and/or angioedema for longer than 6-weeks. Guidelines recommend Omalizumab (Oma) as first-line and Cyclosporine-A (Cs-A) as second-line treatment in antihistamine resistant CSU. This step-wise algorithm might be time-consuming and costly. OBJECTIVE: To determine indicators of response to Oma or Cs-A in CSU patients. METHODS: We retrospectively analyzed data from seven centers in Turkey; the inclusion criteria for patients were to receive both Oma and Cs-A treatment (not concurrently) at some point in time during their follow-up. Clinical and laboratory features were compared between groups. RESULTS: Among 110 CSU patients; 47 (42.7%) were Oma-responders, 15 (13.6%) were Cs-A-responders, and 24 (21.8%) were both Oma and Cs-A responders and 24 (21.8%) were non-responders to either drug. High CRP levels were more frequent in Cs-A-responders (72.7% vs. 40.3%; p = 0.055). Oma-responders had higher baseline UCT (Urticaria Control Test) scores (6 vs. 4.5; p = 0.045). Responders to both drugs had less angioedema and higher baseline UCT scores compared to other groups (33.3% vs. 62.8%; p = 0.01 and 8 vs. 5; p = 0.017). Non-responders to both drugs had an increased frequency in the female gender and lower baseline UCT scores compared to other groups (87.5% vs. 61.6%; p = 0.017 and 5 vs. 7; p = 0.06). STUDY LIMITATIONS: Retrospective nature, limited number of patients, no control group, the lack of the basophil activation (BAT) or BHRA (basophil histamine release assay) tests. CONCLUSIONS: Baseline disease activity assessment, which considers the presence of angioedema and disease activity scores, gender, and CRP levels might be helpful to predict treatment outcomes in CSU patients and to choose the right treatment for each patient. Categorizing patients into particular endotypes could provide treatment optimization and increase treatment success.

Birt-Hogg-Dubé Syndrome: Diagnostic Journey of Three Cases from Skin to Gene.

Birt-Hogg-Dube syndrome (BHDS) is a rare disorder characterized by the triad of cutaneous lesions, renal tumors, lung cysts and inactivation of the gene folliculin (FLCN). Here, we present three female patients diagnosed with BHDS. First case a 55-year-old female had flesh moles histopathology compatible with angiofibroma, multiple cysts in the lung and kidneys, FLCN gene mutations ('c.1285dupC [p.His429Profs*]' 11th exon and 'c.653G>A [p.Arg258His]' 7th exon). The second case a 76-year-old female had trichodiscoma on her skin, multiple cysts in the lung, spontaneous pneumothorax, FLCN gene mutation 'c.1285dupC (p.His429Profs*27) 11th exon' and, her son had renal carcinoma history under 50 years of age. Our third case, also the daughter of case 2, had dermal papules histopathology compatible with trichodiscoma, spontaneous pneumothorax, FLCN gene mutation 'c.1285dupC (p.His429Profs*27) 11th exon' and, parotid oncocytoma. Through our cases, we document the first case of two mutations ('c.1285dupC [p.His429Profs*]' 11th exon and 'c.653G>A [p.Arg258His]' 7th exon) in the same FLCN gene and the 11th known case of parotid oncocytoma associated with BHDS in the light of the literature.

Assessment of disease activity and quality of life in patients with recurrent bradykinin-mediated versus mast cell-mediated angioedema.

OBJECTIVE: Recurrent Angioedema (RAE) is characterized by sudden swelling of mucosal surfaces or deep dermis and is either mast cell-(MMAE) or bradykinin-mediated (BMAE). How patients with BMAE and MMAE differ in terms of disease activity and impact remains largely unknown. Here, we determined validity, reliability, and sensitivity to change of Turkish versions of angioedema activity score (AAS) and quality of life questionnaire (AE-QoL) and used both instruments to investigate and compare patients with BMAE and MMAE. METHODS: Turkish versions of AAS28 and AE-QoL were applied to 94 patients with RAE (18-72 years). Patients' global self-assessment of QoL (PGA-QoL), disease activity (PGA-DA-VRS, PatGA-DA-VAS), and 12-Item-Short Form Survey were used at week 4 (visit 2), and week 8 (visit 3). Demographic characteristics, clinical features, and AAS28 and AE-QoL values were compared between 31 patients with BMAE and 63 patients with MMAE. RESULTS: Turkish AAS28 and AE-QoL showed excellent internal consistency, high reproducibility and known-groups validity. Compared to patients with MMAE, BMAE patients were younger (34.6 ± 10.7 vs. 40.7 ± 13.3 years), had longer disease duration (236 ± 178 vs. 51 ± 78 months), high prevalence of family history (63% vs 14%), longer duration of attacks (65 ± 20 vs. 40 ± 25 h), and they were more commonly affected by upper airway angioedema (70% vs 23%). Disease activity (AAS28) was lower (29.3 ± 24.6 vs 55.2 ± 52.9), but AE-QoL was higher (44.2 ± 16.1 vs 34.5 ± 22.5) in BMAE patients as compared to MMAE patients. CONCLUSIONS: Patients with BMAE and MMAE have distinct disease characteristics. Recurrent bradykinin-mediated angioedema impacts quality of life more than mast cell-mediated angioedema. The discriminating characteristics of patients with BMAE and MMAE may help to improve the diagnosis and management of patients with RAE.