Analysis of clinical factors as possible predictors of response to omalizumab and relapse after treatment discontinuation in chronic spontaneous urticaria.

Omalizumab is a monoclonal anti-IgE antibody which is effective in chronic spontaneous urticaria (CSU), although clinical response appears to be variable in the real-life setting. The aim of this study was to evaluate whether the response of CSU to omalizumab and disease relapse are associated with individual and/or clinical characteristics of patients. We retrospectively evaluated the clinical records of 124 patients treated with omalizumab for moderate to severe CSU refractory to antihistamines. Disease activity was assessed using the urticaria activity score over the last 7 days (UAS7). After 24 weeks of treatment, 91% of patients showed complete remission (UAS7 = 0) or good control (UAS7 < 7) of CSU. Omalizumab was re-administered in 45 patients because of recurrence of moderate to severe symptoms at week 8 after treatment discontinuation or later, and clinical results achieved with retreatment were similar to those observed in the first course. Among the parameters included in our analysis (age and sex of patients, documented history of atopy or autoimmune thyroid disease, CSU duration and baseline severity, concurrent angioedema, and association with chronic inducible urticaria), none was associated with response to omalizumab in our study population. Similarly, these parameters did not significantly differ between patients who experienced CSU relapse and those without relapse. Predictors of response to omalizumab treatment in CSU patients are still unclear, and further studies are needed to evaluate the presence of baseline factors that can influence treatment outcome.

Outcome of cutaneous psoriasis in hepatitis C virus-infected patients treated with Direct-Acting Antiviral therapy.

Apart from chronic liver disease, hepatitis C virus (HCV) may be responsible for several extra-hepatic manifestations. Its involvement in psoriasis development is still controversial. The aim of this study was to evaluate the possible effect of anti-HCV direct-acting antiviral (DAA) treatment on cutaneous psoriasis. Thirty-seven consecutive HCV patients with cutaneous psoriasis underwent efficacious DAA treatment, and all of them were efficiently cured as shown by HCV RNA negativity 24 weeks after stopping therapy (PT24W). An expert dermatologist evaluated the skin lesions at baseline, end of treatment (EOT) and PT24W using the psoriasis area severity index (PASI) scoring system. The impact on quality of life was measured with the Dermatologic Quality of Life Index (DLQI). Six patients had a stable disease throughout the study period, whereas 31/37 patients (83.8%) showed a significant improvement of the skin lesions at EOT (P < .0001). However, 24 of these 31 patients (77.4%) had a dramatic worsening of the psoriatic lesions at PT24W compared with EOT (P < .001), with lesion severity comparable to baseline. The outcome of psoriasis during and after treatment was independent of baseline PASI score, age, sex, HCV genotype, liver disease stage and of the presence of arterial hypertension, diabetes and autoimmune diseases. In conclusion, DAA-based HCV cure has only a transient effect on skin lesions of patients with concomitant cutaneous psoriasis.

From regulatory limitations to new opportunities: Real-life experience on the effectiveness of short courses of omalizumab in the treatment of chronic idiopatic urticaria.

Economic sustainability of long-term continuous treatment of antihistamine refractory chronic urticaria with omalizumab may be an issue. We assessed the efficacy of relatively short courses (5-6 months) of omalizumab in patients with chronic idiopathic urticaria (CIU). We retrospectively studied 40 patients (observed between June 2015 and January 2019) affected by moderate-to-severe CIU refractory to anti-H1 antihistamines (up to fourfold doses). Omalizumab was administered every 4 weeks for 24 weeks, then for 20 weeks in case of a relapse of moderate-to-severe degree, then again for 24 weeks in case of a second relapse. Monthly clinical evaluations were performed. Mean disease severity significantly dropped after 1 month and further decreased thereafter, with 30 complete remissions after the first course of treatment. In 2-4 months, 18 patients had a relapse of moderate-to-severe degree. The profile of response to the second course of omalizumab was similar to the first. A third course was necessary for seven patients. No adverse effects were recorded. Courses of 5-6 months of omalizumab may induce rapid significant improvement of urticaria and many prolonged complete remissions. In case of relapse, further courses show a similar profile of response and may induce additional long-term complete remissions.

Possible Roles of IL-33 in the Innate-Adaptive Immune Crosstalk of Psoriasis Pathogenesis.

BACKGROUND: IL-33 belongs to the IL-1 family, playing a role in several biologic processes as well as in the pathogenesis of different diseases, including skin pathologies. It acts as an alarmin, released by damaged cells. Binding to a ST2 receptor, it stimulates many immune cells such as ILC2 and Th2 cells. IL-33/ST2 axis seems to be involved in Th17 response. According to this, a review was performed to analyze if IL-33 even interplay in the onset of psoriasis, a Th1/Th17 inflammatory disease. METHODS: Data obtained from the included articles are study author name, publication date, group studied, clinical and biological variables, laboratory tests, and outcome of interest of the study. RESULTS: Data are obtained from the 19 studies identified, which assessed the association between IL-33 and psoriasis. DISCUSSION: It seems to promote the innate-adaptive immune crosstalk: it could induce mast cells and neutrophil response after being released by injured keratinocytes and after stimulation by some cytokines, in particular TNFα, INFγ, and IL-17A. In addition, it seems to be involved from the onset of disease to the development of comorbidities, as psoriatic arthritis. CONCLUSION: The core of the future research on psoriasis could be to fully understand the role of this complex cytokine, in order also to find a new therapeutic approach.

Auditory System Involvement in Psoriasis.

Psoriasis is a systemic inflammatory disorder associated with many other chronic and progressive diseases. There are few studies on the association of psoriasis with alterations in auditory function. A clinical and instrumental pilot study of auditory function was performed with 77 psoriatic patients and 77 age- and sex-matched healthy controls. The main results were: (i) hearing loss, mostly of sensorineural type, was significantly more frequent in patients than in controls; (ii) conductive and mixed hearing loss were more frequent in arthropathic than in non-arthropathic psoriatic patients; (iii) duration of psoriasis > 10 years or smoking were associated with higher frequency of hearing loss; (iv) psoriasis was more severe in patients with hearing loss than in those without hearing loss. Tympanogram abnormalities were found in patients more often than in controls. These data expand the list of extracutaneous conditions associated with psoriasis, and support the need for further basic and clinical research in this field.

Involvement of RAGE and Oxidative Stress in Inflammatory and Infectious Skin Diseases.

The surface receptor for advanced glycosylation end-products (RAGE) and its soluble (sRAGE) and endogenous secretory (EN-RAGE) forms belong to the superfamily of toll-like receptors and play important roles in inflammation and autoimmunity, directly or through binding with advanced glycosylation end-products (AGE) and advanced oxidation protein products (AOPP). We reviewed the literature on the role of RAGE in skin diseases. Research in this field is still rather limited (28 articles) but suggests the involvement of RAGE and RAGE-related pathways in chronic inflammatory diseases (lupus, psoriasis, atopic dermatitis, and lichen planus), infectious diseases (leprosy, Staphylococcus aureus-induced skin lesions), alterations of the repairing processes in diabetic skin, systemic sclerosis, and ulcers. These data prompt further research in this field, which not only will be useful to better understand the pathogenetic mechanisms of diseases, but is also likely to have intriguing clinical implications. Indeed, when their role in the complex and multifactorial inflammatory balance will be adequately defined, RAGE and related molecules could be used as markers of disease severity and/or response to treatment. Moreover, future promising therapeutic perspectives could be topical administration of some of these molecules (e.g., sRAGE) to modulate local inflammatory response and/or the development of anti-RAGE antibodies for systemic treatment.

Secukinumab for plaque psoriasis with ocular comorbidity: a clinical experience.

Psoriasis is a systemic inflammatory disorder associated with many other chronic and progressive diseases. Ocular comorbidity has been reported in 10-15% of patients with plaque psoriasis, but the real incidence is still underestimated. This paper reports successful treatment with secukinumab of a patient with plaque psoriasis and dry eye syndrome. Secukinumab treatment was rapidly effective on skin psoriasis and this result was in agreement with observations reported in the literature. Interestingly, both the skin condition and the ocular disease improved after treatment. Our experience suggests that this drug should be used in patients with plaque psoriasis and ophthalmologic manifestations.

Glutathione S-transferase M1/T1 genotype and melanoma in a Southern Italian population: a case-control study.

BACKGROUND: The aim of this study was to assess the frequency of GSTM1 and GSTT1 null genotype in melanoma patients and controls from Sicily and Calabria, two regions of Southern Italy never investigated on this issue before, that present a peculiar gene pool because of their geographical and historical characteristics. METHODS: One hundred and twelve Caucasian melanoma patients and 150 age- and sex-matched healthy controls were examined; their GSTM1/GSTT1 genotype was defined by polymerase chain reaction on a sample of oral mucosa cells obtained by buccal swabs. RESULTS: Odds ratio for melanoma was increased not significantly in case of fair hair/eye color, presence of many naevi or solar lentigines, or history of actinic keratosis, skin cancer or sunburns; frequencies of GSTM1 null, GSTT1 null and all their possible combinations were not significantly different between patients and controls. CONCLUSIONS: Our results, in agreement with worldwide literature, show that melanoma is apparently independent from genetic lack of GSTM1/GSTT1. However, melanoma is notoriously linked to a history of sunburns, and GSTM1/GSTT1 null are a significant risk factor for sunburns. We describe a possible explanation of this apparent contradiction, taking into account the different roles of the multiple components of human skin in photoprotection, and their variable importance in different conditions of exposure to UV radiations. Simultaneous evaluation of a larger number of components of the antioxidant system, to assess their individual contribution to protection against melanoma, is advisable and should be considered in future studies. This could allow to better define risks for each patient and possibly to tailor preventive measures.