The overlap syndrome of urticaria and gastroesophageal reflux disease.

BACKGROUND: One-quarter of systemic symptoms associated with chronic spontaneous urticaria (CSU) are related to gastrointestinal complaints (GICs). OBJECTIVES: To investigate the prevalence and features of urticaria-overlapping GICs. METHODS: In this retrospective cross-sectional survey, 1426 consecutive outpatients were observed at our University Department. Only patients suffering from urticaria or GICs with a complete diagnostic work-up including serum total IgE level (Tot-IgE), differential blood count and urticaria activity score (UAS), were evaluated. RESULTS: Among different GICs, gastroesophageal reflux disease (GERD) was the most frequent syndrome observed (15.4%; 95%CI: 13.6-17.3). The prevalence of overlap syndrome for urticaria and GERD was 5.9% (95%CI: 4.7-7.2). In urticaria-patients, the prevalence of GERD was four-fold higher than in patients without hives (44% vs. 11%, p<0.001). UAS was significantly higher in urticaria and GERD overlap syndromes vs. isolated urticarias. In patients with GERD or acute/chronic urticaria or overlap syndrome, Tot-IgE and eosinophil blood count (EBC) differed significantly, with a stepwise increase in their values; from the subgroup of patients with GERD only, to that with overlap of CSU to GERD. Prevalence values for urticaria overlapping with GERD were three- and two-fold higher in CSU and in long-duration GERD cases respectively compared to acute urticaria or short-duration GERD cases. Similar to Th2 pathology models, CSU and GERD overlap syndrome was significantly and independently associated with Total-IgE ≥100IU/ml or EBC ≥250/mmc compared to CSU or GERD. Endoscopic/bioptic findings of non-erosive reflux disease (NERD) or Barrett's esophagus (BE) were more frequent in chronic overlap syndrome than in GERD-patients. CONCLUSIONS: GERD was the most frequent GIC in patients with urticaria. Overlap syndrome was more frequent among patients with CSU, where this syndrome was associated with higher values of UAS, Tot-IgE, EBC and frequencies of NERD and BE. These results suggest that overlap syndrome is frequently a chronic syndrome with a Th2-like profile.

Telaprevir may induce adverse cutaneous reactions by a T cell immune-mediated mechanism.

The HCV protease inhibitor telaprevir associated with peginterferon-alpha and ribavirin, was widely used in the recent past as standard treatment in HCV genotype-1 infected patients. Telaprevir improves the sustained virology response rates, but at the same time increases the frequency of adverse cutaneous reactions. However, mechanisms through which telaprevir induces cutaneous lesions are not yet defined. A 50-year-old woman, affected by HCV genotype 1b, was admitted to our Department for a telaprevir-related severe cutaneous eruptions, eight weeks after starting a triple therapy (telaprevir associated with Peginterferon-alpha and ribavirin). Mechanisms of cutaneous reactions were investigated by skin tests with non-irritating concentrations of telaprevir and by activating in vitro T lymphocyte with different concentrations. Immediate and delayed responses to skin testing were negative, but the drug-induced lymphocytes activation was significantly higher as compared to patient's baseline values and to parallel results obtained in three healthy subjects (p < 0.05). In conclusion, adverse cutaneous reactions of our patient were caused by a telaprevir-induced T-cell dependent immune mechanism.

Omalizumab for difficult-to-treat dermatological conditions: clinical and immunological features from a retrospective real-life experience.

BACKGROUND: Omalizumab, a therapeutic monoclonal antibody specific for human IgE, has thus far been used as add-on therapy for moderate-to-severe allergic asthma in adults and children. OBJECTIVE: The objective of this study was to test omalizumab efficacy in other conditions in which the IgE-mast cell axis is supposed to play a role. METHODS: Nine patients with dermatological manifestations possibly related to activation of the IgE-mast cell axis (six chronic spontaneous urticaria and three atopic dermatitis patients) were administered off-label omalizumab because of refractoriness to standard therapy. All patients were subjected to strict clinical, laboratoristic, and imaging follow-up to monitor for possible adverse effects. In addition, to further assess the role of omalizumab on T cells, mast cells, and eosinophils, T-cell immune polarisation as well as eosinophil cationic protein and tryptase serum levels were determined before and during omalizumab administration. RESULTS: Therapy was effective in seven out of nine patients (six complete responses, one partial response, and two no responses). Interestingly, omalizumab appeared to induce lymphocyte polarisation toward a type 2 immune response and to be able to quench eosinophil-mediated inflammation, particularly in atopic dermatitis patients. Tryptase serum levels were generally low and remained unchanged during omalizumab treatment. Despite treatment spanning over several years in most of the patients, no adverse effects nor new ensuing medical conditions have thus far been observed (median follow-up: 42 months). CONCLUSIONS: Off-label omalizumab was safe and effective in our patients. The novel immunologic features recorded in our patients add further complexity to the mechanism of action of omalizumab.