Possible Association of Interleukin-31/-31RA Signalling and Basophils with Itch in Porokeratosis.

is missing (Short communication).

Efficacy of aluminum chloride in severe regorafenib-associated hand-foot skin reactions: a single-arm trial.

BACKGROUND: Regorafenib, a multikinase inhibitor, causes a high frequency of hand-foot skin reactions (HFSRs). The present study evaluated the efficacy of topical aluminum chloride, a perspiration suppressant, in reducing the severity of hand-foot skin reactions (HFSRs) caused by regorafenib. METHODS: The present single-arm study included patients with metastatic colorectal cancer receiving regorafenib. Aluminum chloride ointment was applied topically one week prior to the start of regorafenib treatment, and the observation period was 12 weeks. The primary endpoint was the incidence of regorafenib-related grade 3 HFSR. Secondary endpoints were the incidence of all grades of HFSR, time to any grade of HFSR, time to improvement from grade 2 or higher to grade 1 or lower, treatment discontinuation rate, treatment interruption rate or dosage reduction due to HFSR, and incidence of adverse effects of aluminum chloride. RESULTS: In total 28 patients were enrolled, and 27 patients were analyzed. The incidence of grade 3 HFSR was 7.4%, meeting the primary endpoint. The incidence of all grades of HFSR was 66.7%, and the median time to the occurrence of any grade of HFSR was 15 days. No patients discontinued or reduced the regorafenib dosage because of HFSR. The most common reason for the interruption of regorafenib therapy was liver dysfunction in nine patients (33%) and HFSR in three patients (11%). No serious adverse events related to aluminum chloride were observed. CONCLUSIONS: Aluminum chloride ointment, a drug commonly used in routine practice to treat hyperhidrosis, is safe to use, has no serious side effects, and may be effective in reducing the occurrence of severe, regorafenib-related HFSR. TRAIL REGISTRATION: ClinicalTrials.gov. identifier: jRCTs031180096, Registered on 25/01/2019.

Improvement in the elution performance of an N,N,N',N-tetraoctyl diglycolamide impregnated extraction chromatography adsorbent using neodymium via micro-particle-induced X-ray emission analysis.

An adsorbent used for the recovery of trivalent minor actinides (MA(III); Am and Cm) from high level liquid waste generated from reprocessing of spent nuclear fuel was subjected to micro-particle induced X-ray emission (micro-PIXE) analysis to improve its elution performance. The experimental adsorbent comprised SiO2 particles, a polymer coating, and an N,N,N',N'-tetraoctyl diglycolamide (TODGA). The particles to be analyzed were subjected to Nd adsorption and an elution operation, but Nd in the adsorbent was found to be uniformly distributed. This might have been caused by individual differences in the amount of impregnated TODGA. The remaining Nd species were not localized to a specific part of the adsorbent after the adsorption operation. Some Nd elements were retained in the adsorbent after elution, probably because of the poor diffusion of the mobile phase inside the adsorbent. An adsorbent having a different microstructure from the first was then evaluated, and rapid elution was observed on new adsorbent along micro-PIXE analysis.

IL-31 and IL-31 receptor alpha in pemphigus: Contributors to more than just itch?

Pemphigus is an autoimmune blistering disorder with four major subtypes: pemphigus vulgaris (PV), pemphigus vegetans (PVe), pemphigus foliaceus (PF), and pemphigus herpetiformis (PH). Among them, PF and PH present itching as a clinical feature; however, the mechanisms behind the pruritus are still unclear. In this report, we sought to investigate the expression of a type 2 inflammation-related pruritogenic cytokine IL-31 and its receptor subunit IL-31RA through immunofluorescence staining analysis. The number of eosinophils, basophils, and mast cells, and the expression levels of thymic stromal lymphopoietin (TSLP) and periostin were also investigated. Evaluation showed an increase in the number of dermal IL-31+ cells and IL-31RA+ cells in PH and PVe. Epidermal expression of IL-31RA increased in PV, PF, and PVe, but not in PH, compared to healthy individuals. The number of dermal eosinophils and basophils was also increased in PVe and PH. The number of dermal mast cells and expression levels of TSLP and periostin did not change among pemphigus subtypes and healthy controls. Collectively, enhanced IL-31/IL-31RA signaling and the increased numbers of dermal eosinophils and basophils may participate in itching in PH. On the other hand, IL-31/IL-31RA signaling seemed unable to provoke itching in PVe, a non-pruritic subtype of pemphigus, although it might contribute to epidermal thickening and dermal fibrosis.

IL-31-generating network in atopic dermatitis comprising macrophages, basophils, thymic stromal lymphopoietin, and periostin.

BACKGROUND: IL-31 is a type 2 cytokine involved in the itch sensation in atopic dermatitis (AD). The cellular origins of IL-31 are generally considered to be TH2 cells. Macrophages have also been implicated as cellular sources of IL-31. OBJECTIVE: We sought to determine the expression of IL-31 by macrophages and to elucidate the productive mechanisms and contributions to itch in AD skin lesions. METHODS: Expression of IL-31 by macrophages, expressions of thymic stromal lymphopoietin (TSLP) and periostin, and presence of infiltrating basophils in human AD lesions were examined through immunofluorescent staining, and correlations were assessed. Furthermore, mechanisms of inducing IL-31-expressing macrophages were analyzed in an MC903-induced murine model for AD in vivo and in mouse peritoneal macrophages ex vivo. RESULTS: A significant population of IL-31+ cells in human AD lesions was that of CD68+ cells expressing CD163, an M2 macrophage marker. The number of IL-31+/CD68+ cells correlated with epidermal TSLP, dermal periostin, and the number of dermal-infiltrating basophils. In the MC903-induced murine AD model, significant scratching behaviors with enhanced expressions of TSLP and periostin were observed, accompanied by massive infiltration of basophils and IL-31+/MOMA-2+/Arg-1+ cells. Blockade of IL-31 signaling with anti-IL-31RA antibody or direct depletion of macrophages by clodronate resulted in attenuation of scratching behaviors. To effectively reduce lesional IL-31+ macrophages and itch, basophil depletion was essential in combination with TSLP- and periostin-signal blocking. Murine peritoneal macrophages produced IL-31 when stimulated with TSLP, periostin, and basophils. CONCLUSIONS: A network comprising IL-31-expressing macrophages, TSLP, periostin, and basophils plays a significant role in AD itch.

Increased touch-evoked itch (punctate hyperknesis) in postherpetic itch: Implications of reduced intraepidermal nerve fibers representing small fiber neuropathy.

Chronic itch conditions are often accompanied by neural itch sensitization, known as hyperknesis (excessive itch induced by stimuli that would normally induce only mild itching or pain) and alloknesis (considerable itch evoked by light tactile stimuli). Herpes zoster (shingles) can cause neuropathic itch (postherpetic itch), although it is unknown whether hyperknesis accompanies postherpetic itch. The authors report five patients with postherpetic itch who showed increased touch-evoked itch (punctate hyperknesis) in the affected skin areas compared with the contralateral site. Collected skin biopsy specimens from two patients showed histopathologically detected reduced intraepidermal nerve fibers in the affected skin areas, reflective of small C/Aδ fiber neuropathy. In one case, improvement in itching and comparable levels of touch-evoked itch on the affected and contralateral sites were noted after 6 months without any medication, accompanied by restored intraepidermal nerve fibers proven through rebiopsy of the affected site. Reduced intraepidermal nerve fibers could be one of the precipitating factors for postherpetic itch and its associated punctate hyperknesis.

Summary of the current status of clinically diagnosed cases of Schnitzler syndrome in Japan.

BACKGROUND: Schnitzler syndrome is a rare disorder with chronic urticaria, and there is no report summarizing the current status in Japan. METHODS: A nationwide survey of major dermatology departments in Japan was conducted in 2019. We further performed a systematic search of PubMed and Ichushi-Web, using the keywords "Schnitzler syndrome" and "Japan" then contacted the corresponding authors or physicians for further information. RESULTS: Excluding duplicates, a total of 36 clinically diagnosed cases were identified from 1994 through the spring of 2022, with a male to female ratio of 1:1. The median age of onset was 56.5 years. It took 3.3 years from the first symptom, mostly urticaria, to reach the final diagnosis. The current status of 30 cases was ascertained; two patients developed B-cell lymphoma. SchS treatment was generally effective with high doses of corticosteroids, but symptoms sometimes recurred after tapering. Colchicine was administered in 17 cases and was effective in 8, but showed no effect in the others. Tocilizumab, used in six cases, improved laboratory abnormalities and symptoms, but lost its efficacy after several years. Rituximab, used in five cases, was effective in reducing serum IgM levels or lymphoma mass, but not in inflammatory symptoms. Four cases were treated with IL-1 targeting therapy, either anakinra or canakinumab, and achieved complete remission, except one case with diffuse large B-cell lymphoma. CONCLUSIONS: Since Schnitzler syndrome is a rare disease, the continuous collection and long-term follow-up of clinical information is essential for its appropriate treatment and further understanding of its pathophysiology.

Proinflammatory role of basophils in oxazolone-induced chronic intestinal inflammation.

BACKGROUND AND AIM: The functions of basophils have not been elucidated until recently because of their rarity. However, with recent developments in basophil-specific antibodies and basophil-deficient animals, the roles of basophils in various diseases related to chronic inflammation have been clarified. In this study, we aimed to investigate the roles of basophils in human ulcerative colitis (UC) and oxazolone (OXA) colitis using genetically engineered Mcpt8DTR mice. METHODS: Immunohistochemical staining of human colon specimens was performed to examine the involvement of basophils in the pathogenesis of UC. We examined the correlation between the number of infiltrating basophils and the UC endoscopic index of severity (UCEIS), Mayo score, and Matts score. We also examined the correlation between eosinophil count and basophil infiltration. In murine experiments, we examined whether basophil infiltration was involved in OXA-induced colitis and whether basophil depletion improved inflammation in Mcpt8DTR mice. RESULTS: Colonic basophil infiltration was significantly increased in patients with UC. There were significant correlations between UCEIS, Mayo score, Matts score, and the number of infiltrating basophils. In murine OXA-induced colitis, a significant increase in basophil infiltration was observed. When basophils were depleted by diphtheria toxin in Mcpt8DTR mice, inflammation improved significantly and mRNA expression of some proinflammatory cytokines, including Tnf-α and Ifn-γ decreased significantly. CONCLUSION: Basophil infiltration correlated with endoscopic, clinical, and pathological scores in human UC independently of eosinophil infiltration, and depletion of basophils ameliorated mucosal inflammation in murine OXA-induced colitis, collectively suggesting that basophils exert a proinflammatory role in chronic intestinal inflammation such as UC.