Concept: Pruritus ani
Abstract Background: Pruritus ani (PA) is defined as intense chronic itching affecting perianal skin. Objective: We aimed to determine the efficacy of topical tacrolimus treatment in atopic dermatitis (AD) patients who have PA. Methods: The study included 32 patients with AD who were suffering PA. Patients were randomized into two groups. In total, 16 patients used 0.03% tacrolimus ointment and 16 patients used Vaseline® as placebo. All groups applied topical treatments to their perianal area twice daily for 4 weeks. The treatments were then reversed for 4 weeks after a 2 weeks wash out period. Results: In total, 32 patients with AD who had refractory anal itching were enrolled in the present study. None of the patients had obtained successful results with previous treatments. There was a statistically significant decrease in the recorded EASI, DLQI and itching scores for the tacrolimus group compared to the placebo groupat weeks 4 and 6 of treatment (p < 0.05). Conclusion: Topical tacrolimus treatment was well tolerated and effective in controlling persistent PA in AD patients.
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Itch is a common side-effect of treatment with anti-EGFR antibodies and tyrosine-kinase inhibitors. We designed a pilot single-centre study to assess the effects of aprepitant-a neurokinin receptor inhibitor-for management of severe pruritus induced by biological drugs.
Benign anorectal conditions produce anal pain, rectal bleeding, or discharge from the perianal region, which are highly prevalent symptoms in the general population. Hemorrhoidal disease, anal fissure, perianal abscess, proctalgia syndromes and pruritus anii are the most common clinical disorders. Well-trained physicians irrespective of their specialty can treat most of these disorders and refer them to a specialist in proctology only when necessary. The aim of this review is to provide a practical guide to the management of benign anorectal disorders in terms of their initial management and the criteria for specialist referral.
Interleukin-31 (IL-31) is implicated in pruritus associated with pruritic skin diseases like atopic dermatitis. Although pruritus is a prominent feature in dermatomyositis (DM), few studies have evaluated the pathogenesis of DM-associated itch.
Veterinarians and pet owners have limited ability to assess pruritic behaviors in dogs. This pilot study assessed the capacity of the Vetrax® triaxial accelerometer to measure these behaviors in six dogs with pruritus likely due to environmental allergens. Dogs wore the activity monitor for two weeks while consuming their usual pet food (baseline), then for eight weeks while consuming a veterinary-exclusive pet food for dogs with suspected non-food-related skin conditions (Hill’s Prescription Diet® Derm DefenseTM Canine dry food). Veterinarians and owners completed questionnaires during baseline, phase 1 (days 1-28) and phase 2 (days 29-56) without knowledge of the activity data. Continuous 3-axis accelerometer data was processed using proprietary behavior recognition algorithms and analyzed using general linear mixed models with false discovery rate-adjusted p values. Veterinarian-assessed overall clinical signs of pruritus were significantly predicted by scratching (β 0.176, p = 0.008), head shaking (β 0.197, p < 0.001) and sleep quality (β -0.154, p < 0.001), while owner-assessed quality of life was significantly predicted by scratching (β -0.103, p = 0.013) and head shaking (β -0.146, p < 0.001). Among dogs exhibiting pruritus signs eating the veterinary-exclusive food, the Vetrax® sensor provided an objective assessment of clinically relevant pruritic behaviors that agreed with owner and veterinarian reports.
Pruritus is the most frequently reported complaint or symptom for psoriasis patients. Despite the morbidity associated with pruritus in psoriasis few studies have evaluated the prevalence of itch in psoriasis with the current use of biological agents.
Opioids in skin function during stress response, regeneration, ageing and, particularly in regulating sensation. In chronic pruritus, topical treatment with Naltrexone changes μ-opioid receptor (μ-OR) localization to relieve itch. The molecular mechanisms behind the effects of Naltrexone on μ-OR function in reduction of itching behavior has not been studied. There is an immediate need to understand the endogenous complexity of μ-OR dynamics in normal and pathological skin conditions. Here we evaluate real-time behavior of μ-OR-Endomorphine complexes in the presence of agonist and antagonists. The μ-OR ligand Endomorphine-1 (EM) was conjugated to the fluorescent dye Tetramethylrhodamine (TAMRA) to investigate the effects of agonist and antagonists in N/TERT-1 keratinocytes. The cellular localization of the EM-TAMRA was followed through time resolved confocal microscopy and population analysis was performed by flow cytometry. The in vitro analyses demonstrate fast internalization and trafficking of the endogenous EM-TAMRA-μ-OR interactions in a qualitative manner. Competition with Endomorphine-1, Naltrexone and CTOP show both canonical and non-canonical effects in basal and differentiated keratinocytes. Acute and chronic treatment with Naltrexone and Endomorphine-1 increases EM-TAMRA binding to skin cells. Although Naltrexone is clinically effective in relieving itch, the mechanisms behind re-distribution of μ-ORs during clinical treatments are not known. Our study has given insight into cellular mechanisms of μ-OR ligand-receptor interactions after opioid agonist and antagonist treatments in vitro. These findings potentially offer opportunities in using novel treatment strategies for skin and peripheral sensory disorders.
Tofacitinib is an oral Janus kinase inhibitor. This post-hoc analysis aimed to investigate the psychometric properties of the Itch Severity Item (ISI), a numeric rating scale from 0 (no itching) to 10 (worst possible itching) for pruritus in psoriasis, and review the effect of tofacitinib on pruritus in patients with psoriasis participating in Phase 3 studies (n = 3,641). The ISI showed high test-retest reliability (intra-class correlation coefficient: 0.84). The clinically important difference was defined as a 1.48 point change, using Patient Global Assessment as an anchor. Mean changes from baseline in ISI scores with tofacitinib were significantly greater than placebo by Day 2 and exceeded the clinically important difference by Week 4 and Week 2 for tofacitinib 5 and 10 mg twice daily, respectively. The sound psychometric properties of the ISI as an assessment tool for pruritus in psoriasis were confirmed. Tofacitinib provided clinically meaningful improvements in psoriatic pruritus versus placebo.
Itching is an intricate, common symptom of dermatologic and systemic diseases, and both TRPV3 and TRPA1 channels have been suggested to function as downstream effector targets. But the relative contributions of TRPV3 and TRPA1 to itch sensation in vivo remain unclear. To dissect the role of TRPA1 or TRPV3 in the cutaneous sensation of itching, we took the advantage of a natural compound carvacrol from oregano, and examined its effect on the induction of scratching behavior in mice. We showed that the intradermal injection of carvacrol (0.01%, 0.1% and 1%, 50 μL) induced scratching in a concentration-dependent manner. But in TRPV3-knockout mice, the scratching induced by carvacrol (1%, 50 μL) was markedly decreased by approximately 64% (from 275 scratching bouts down to 90) within 60 min. Further analysis revealed that TRPV3-knockout caused a reduction of scratching bouts for approximately 40% in the first 20 min (the initial phase), whereas the scratching bouts were reduced by approximately 90% in the last 40 min (the sustained phase). These results were in consistence with those in our whole-cell recordings in HEK-293T cells expressing either TRPA1 or TRPV3: carvacrol exhibited similar potencies in activating either TRPA1 or TRPV3, but carvacrol-activated TRPA1 current showed a rapid desensitization, which was reduced by approximately 90% within 5 min before a complete washout, whereas carvacrol-induced TRPV3 current showed a slow desensitization that caused less than 30% of current reduction in 10 min and left a significant residual TRPV3 current after washout. Our results demonstrate that carvacrol from plant oregano is a skin sensitizer or allergen; TRPV3 is involved in the initial phase and the sustained phase of pruritus, whereas TRPA1 likely contributes to the initial phase.