Search

Abstract Introduction Ixekizumab, a monoclonal antibody against interleukin-17A, demonstrated effectiveness in the treatment of psoriasis in a Chinese real-world study that was consistent with previous randomized controlled trials. Here, we report further analyses from this study to explore the effectiveness of ixekizumab for treating patients with psoriasis and the involvement of special body areas (scalp, nail, joint, palmoplantar, or genital areas). Methods A multicenter, prospective, observational, single-arm, post-marketing surveillance study was conducted in patients aged ≥ 18 years with moderate-to-severe plaque psoriasis and prescribed with ixekizumab in 26 Chinese hospitals. Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) scores were compared between patients with versus without psoriasis in special body areas in the overall study population and across subgroups by body area. Results In total, 612 patients were included. At baseline, most patients (93.6%) had psoriasis involvement in at least one special body area. Overall, patients with psoriasis in special body areas reported a worse quality of life (QoL) than those without. Patients with versus without psoriasis in special body areas achieved a comparable mean reduction from baseline in PASI score (10.9 vs. 9.2 at week 2, and 16.9 vs. 14.7 at week 12, respectively) and DLQI score (6.0 vs. 4.4 at week 2, and 9.9 vs. 7.5 at week 12, respectively); a similar proportion of patients also achieved PASI 50 at week 2, and PASI 75 and PASI 90 at week 12, and a DLQI (0/1) at weeks 2 and 12. Several significantly different results were reported between subgroups, the majority of which favored patients with special body area involvement. Conclusion Most patients had psoriasis involvement in a special body area which was associated with worse QoL. Ixekizumab is similarly effective in reducing disease severity and improving QoL in patients with plaque psoriasis across different special body areas.

Objective To report a case of hemophagocytic lymphohistiocytosis syndrome (HLH) secondary to systemic hydroa vacciniforme lymphoproliferative disorder (systemic HVLPD) and review relevant literature, in order to improve understanding of the disease. Methods Clinical data of the case, laboratory examination, histopathology, immunohistochemistry, TCR gene rearrangement, and whole exon gene sequencing were collected for analyses. Results A 19 years old man was admitted to the hospital due to generalized papules, blisters, necrotic scabs and fever for 7 months. The clinical manifestations included hydroa vacciniforme-like rashes, lymphadenopathy, splenomegaly, pancytopenia, hypertriglyceridemia, decreased NK cell activity, high levels of sIL-2r, positive for VCA-IgA and EA-IgA, and elevated EBV DNA load. The whole exon sequencing did not show pathogenic gene mutations. Histopathological changes in the skin lesions included liquefaction degeneration of epidermal and follicular basal cells, pigmentary incontinence, lymphocytic infiltrates of the epidermis and follicular epithelium, perivascular and perifollicular infiltrates of lymphocytes and eosinophils in the dermis, extravasation of erythrocytes, as well as focal infiltrates of atypical lymphoid cells around appendages and small blood vessels. Pathologic mitosis was visible. Immunohistochemistry showed CD3 (+), CD5 (+), CD20 (individual+), CD30 (small patch+), CD79a (individual+), CD4 (+), CD7 (+), CD8 (+), TIA-1 (+), CD56 (scattered lymphocyte+), ≈50% of Ki-67(+), and in situ hybridization EBER (+). TCRβ gene monoclonal rearrangements were detected. According to the results of clinical and auxiliary examination, patient was diagnosed with HLH secondary to systemic HVLPD. After 8 months of follow-up, the patient passed away while waiting for transplantation of allogeneic hematopoietic stem cells. Conclusions Systemic HVLPD is rare and requires vigilance for the development of secondary hemophagocytic syndrome. The awareness of hemophagocytic syndrome should be improved to avoid possible misdiagnosis and delayed treatment.

Objective To report a case of hereditary skin disease mainly characterized by burning pain of the lower legs and feet, accompanied by flush and elevated skin temperature, and to identify the pathogenic genes and mutation sites in order to explore effective treatment methods. Methods The clinical data of the case were collected and peripheral blood was taken from the patient and relatives to extract genomic DNA. Next-generation sequencing of hereditary skin disease genes was performed, and suspected pathogenic mutations were verified with Sanger sequencing. The patient was treated with aspirin for anti-inflammation, rizatriptan benzoate tablet, mexiletine hydrochloride, carbamazepine, local injection of botulinum toxin analgesia, topical compound polymyxin B ointment and cooling therapy. Results A heterozygous mutation of SCN9A:NM_002977.3:c.688+142G>A or SCN9A:ENST00000375387.4:c.626G>A was detected in the patient's peripheral blood genomic DNA. The same mutation was found in the patient's sister, an uncle and a cousin. Based on the pathogenic gene and clinical manifestations, the patient was diagnosed with primary erythromelalgia (PEM). After the treatment, the pain was significantly alleviated. Conclusions The intron mutation of NM_002977.3:c.688+142G>A or missense mutation c.626G>A(p.Gly209Asp) of the SCN9A gene is the cause of PEM in this case. Combination therapy of aspirin, rizatriptan benzoate, mexiletine hydrochloride, carbamazepine and local treatment can effectively control the symptoms of PEM, reduce the frequency of acute attacks and improve the prognosis.

The pathogenesis of AD has not been fully elucidated, and it is currently recognized that it is related to genetic and environmental factors, skin barrier dysfunction and immune dysregulation dominated by type 2 inflammation. In recent years, with the in-depth study of intestinal microbiota, microbe therapy may make up for the shortage of topical glucocorticoids and other treatments. This article focuses on the relationship of the changes in microecology with the pathogenesis of AD, elaborates the important role of intestinal microbiota, cutaneous microbiota and their metabolites in AD, and reviews the research progress in microbe therapy, so as to provide new enlightenment for the treatment of AD.

A case of Wolf's isotopic response is reported. A 68-year-old-female presented with vesicles and bullae on the scars of the left chest and the back for 2 months. Dermatological examination revealed five vesicles and bullae of various sizes on the edge of a 10 cm×5 cm scar, with a deep central ulcer sized 5 cm×5 cm, under the left armpit. Ulcer was with little discharge and dark crusts. The vesicles were with clear fluid and negative for Nikolsky's sign. Two bullae were seen on a 3 cm×2 cm hypertrophic scar at T2 to T4 of the left anterior chest. One hypertrophic scar with a bulla sized 1.5 cm and another one with 1 cm erosion and pustular secretion were on the left back. Patient had no mucosal involvement. Histology of skin lesion showed subepidermal blister and perivascular infiltrates of a few lymphohistiocytes, neutrophils and plasma cells in the superficial dermis. Direct immunofluorescence showed linear deposition of C3 in the basement membrane zone. The diagnosis was isotopic response: bullous pemphigoid secondary to herpes zoster. After the treatment with oral prednisone acetate, the blisters resolved in 2 weeks. No recurrence was observed during 15-months follow-up. The follow-up is still ongoing.

Objective To explore the effect of 6-hydroxydopamine blockade of sympathetic nerves on systemic inflammation in an imiquimod(IMQ)-induced psoriasis-like mouse model. Methods Twenty-four SPF C57BL/6J mice were randomly divided into psoriasis-like dermatitis model group (model group), Candida albicans infected group, blank control group, psoriasis-like dermatitis model with vehicle treatment group (vehicle model group), 6-hydroxydopamine (6-OHDA) treated group, vehicle control group, with 4 mice in each group. The changes of lesion in each group were observed every day. Local inflammation in the dorsal and ear lesions of mice was detected by HE staining, q-PCR and Western blotting of interleukin 17A(IL-17A). Spleens of mice were taken to detect inflammatory cells by flow cytometry, and the level of interleukin 6(IL-6) and interleukin 1β(IL-1β) were detected by q-PCR and Western blotting for the systemic inflammation. Results Epidermal thickening, hypokeratosis, basal keratinocyte proliferation, inflammatory cell infiltration and IL-17A increasing were observed on the dorsal lesions of mice in the Candida albicans infection group and the psoriasis-like model group. Compared with the Candida albicans infected group, there were a large number of skin scale production and spleen enlargement, and splenic inflammatory cells increased, the level of IL-6, IL-1β increased in the psoriasis-like model group. Compared with the solvent model group, the spleen in the 6-OHDA treated group was smaller, the number of macrophages derived from neutrophils and monocytes in the spleen was significantly decrease, and the levels of IL-6 and IL-1β in the spleen were significantly lower. Conclusions IMQ-induced psoriasis-like mouse model lead to systemic inflammation, which can be caused by excessive sympathetic activation.

A case of plantar basal cell carcinoma is reported. The patient was a 70-year-old male with a black patch on the sole of his right foot for 2 years. Dermatological examination showed a demarcated 2 cm*3 cm black patch on the sole of the right foot. There was a superficial ulcer on the surface of the skin lesion, without redness, swelling, exudation, bleeding, pus, or tenderness. Dermoscopy showed yellow-white structure with a little blue-gray structure, and a few atypical ulcers with a few punctate blood vessels. Histopathological examination of the skin lesion showed tumor mass of basal cell carcinoma in the superficial dermis, and retraction spaces. It was diagnosed as basal cell carcinoma (superficial phenotype). Patient was treated with carbon dioxide fractional laser combined with 5-aminolevulinic acid photodynamic therapy once a week for 4 weeks, followed by imiquimod cream, once every other day. After 2 months of treatment, the skin lesions resolved and the skin color became normal. No recurrence was found after 15 months of follow-up. The follow-up is still ongoing.

Background: Omalizumab is an effective treatment for chronic spontaneous urticaria (CSU) patients aged ≥12 years, but its efficacy in patients aged

B7-H3 is over-expressed in multiple types of solid tumors, making it an ideal target for chimeric antigen receptor (CAR)-T therapy. Here, we first report a case of multiple basal cell carcinoma (BCC) patient treated with humanized monoclonal anti-B7-H3 CAR-T cells through direct intratumoral injection. After three dose-escalated injections, the lesion in the abdomen decreased by 40% in volume, shrank from bulging to flat, but was not eradicated completely. The large lesion in the forehead became dry from original ulcer and bleeding. The adverse events observed were itching, myalgia, and redness. Immunohistochemistry analysis demonstrated that B7-H3-positive tumor cells and B7-H3 expression intensity were reduced after injections of CAR-T cells. The number of infiltrating CD3 T cells increased significantly but mainly located outside the tumor region. Subsequently, high levels of TGF-β in the tumor area were observed, suggesting that solid tumor microenvironment may hinder the infiltration and effect of CAR-T cells. In summary, in this particular case report, intratumoral injection of B7-H3 CAR-T cells partially controls tumor growth in the BCC patient with minor adverse events. The efficacy and safety of B7-H3 CAR-T therapy need to be further investigated with a larger cohort of patients. Although only one clinical case is reported here, the anti-B7-H3 CAR-T cell therapy should be considered as a treatment option for solid tumors in the future. This clinical trial was registered at the Chinese Clinical Trial Registry (www.chictr.org.cn) with registration number ChiCTR2100044386.

BackgroundSystemic sclerosis (SSc) is a rare disabling connective tissue disease with few available treatment options. Diffuse cutaneous systemic sclerosis (dcSSc) is associated with high mortality. A previous experiment has shown that JAK2 inhibitor can significantly improve skin fibrosis in bleomycin (BLM)-induced murine model, including reducing dermal thickening and collagen accumulation. We aimed to describe the efficacy of oral JAK1/2 inhibitor baricitinib in SSc patients, especially focusing on skin fibrosis and microvascular manifestations.MethodsWe described the different effects of oral selective JAK1, JAK2, or JAK3 inhibitor treatment in a BLM-induced skin fibrosis mouse model. Furthermore, 10 adult patients with dcSSc were treated with baricitinib. We assessed the changes in modified rodman skin score (mRSS) and digital ulcer net burden at week 12 and 24 from baseline. We also compared the absolute changes in scores on the Scleroderma Health Assessment Questionnaire (SHAQ) and a total score on the St. George's Respiratory Questionnaire (SGRQ) over a 24-week period.ResultsIn the experimental mouse model of skin fibrosis, a JAK1 and JAK2 inhibitor ameliorated skin fibrosis, and a JAK2 inhibitor had the most obvious effect. Treatment with the JAK2 inhibitor also blunted the capillary rarefaction. We demonstrated that skin fibrosis and digital ulcers were significantly relieved in 10 SSc patients treated with baricitinib. The mRSS significantly improved at week 12 from baseline, with a mean change in mRSS of −8.3 [95% confidence interval (CI), −12.03 to −4.574; p = 0.0007] and improved greater at week 24 to −11.67 (95% CI, −16.84 to −6.496; p = 0.0008). Among the four patients with digital ulcers (DU), three were completely healed at week 24, the number of ulcers in another patient was significantly reduced, and there was no patient with new ulcers. Only one adverse event (AE) of herpes zoster was observed.ConclusionsOur results indicate that selective JAK1 and JAK2 inhibitor alleviates skin fibrosis, and oral JAK1/2 inhibitor baricitinib is a potentially effective treatment for dcSSc patients with skin fibrosis and DU. Baricitinib was well-tolerated by most patients in this study. Additional large clinical trials are needed to confirm our pilot findings.Chinese Clinical Trial Registry NumberChiCTR2000030995.

Chronic urticaria (CU) is a debilitating skin disease that lasts for more than 6 weeks with wheals and/or angioedema, including chronic spontaneous urticaria (CSU) and chronic inducible urticaria (CIndU). In China, the prevalence of this disease is high, more than 1%, and on the rise. CU has a major impact on the quality of life (QoL) of patients who frequently experience sleep disturbance, depression, and anxiety. Nearly one-third of patients with CSU, in China, are resistant to second-generation H1-antihistamines (sgAHs), even at a fourfold dose (second line; off-label). Omalizumab is approved for the treatment of CSU treatment in Europe and shows remarkable efficacy and safety. In China, regulatory approval for the use of omalizumab is pending, and its use in clinical practice varies widely. Consensus on omalizumab CU treatment in China is urgently needed. The aim of this article is to propose a practical omalizumab treatment algorithm for the management of antihistamine-resistant CSU and CIndU in adults and special population including children and adolescents, and pregnant or breast feeding women, to guide daily clinical practice in China. In the development of this consensus, an expert group including mainly dermatologists, allergists, but also pulmonologists, ENTs, immunologists, and pediatricians in Allergic Disease Prevention and Control Committee, Chinese Preventive Medicine Association, reviewed the existing evidence and developed consensus on the use of omalizumab in CU patients from China. The goal of this consensus is to assist clinicians in making rational decisions in the management of refractory CU with omalizumab. The key clinical questions covered by the treatment algorithm are: 1) Omalizumab treatment routine strategy in both CSU and CIndU patients; 2) Recommended dose and treatment duration for different age stratification; 3) Treatment duration for CU patients with other allergic comorbidities; 4) Recommendation on omalizumab stopping strategy.

Interleukin- (IL-)10 and IL-13 play important roles in Th2 cell differentiation and production of autoantibodies in patients with (SLE). However, the mechanisms leading to IL10 and IL13 overexpression in SLE patients are not well understood. In this study, we confirm that the levels of both IL10 and IL13 mRNA in CD4+ T cells and of serum IL10 and IL13 proteins are increased in SLE patients. We show that the DNA methylation levels within IL10 and IL13 gene regulatory domains are reduced in SLE CD4+ T cells relative to healthy controls and negatively correlate with IL10 and IL13 mRNA expression. Moreover, treating healthy CD4+ T cells with the demethylating agent 5-azacytidine (5-azaC) increased IL10 and IL13 mRNA transcription. Together, our results show that promoter methylation is a determinant of IL10 and IL13 expression in CD4+ T cells, and we propose that DNA hypomethylation leads to IL10 and IL13 overexpression in SLE patients. [ABSTRACT FROM AUTHOR]