"Indian" strains of Trichophyton mentagrophytes with reduced itraconazole susceptibility in Germany.

We use published reports and three of our own tinea cases as an opportunity to report on "Indian" strains of Trichophyton (T.) mentagrophytes with ITS genotype VIII and reduced susceptibility to itraconazole due to the mutation c.1342G>A in the SQLE gene in Germany. In vitro measurements of resistance revealed normal susceptibility to terbinafine, but markedly reduced susceptibility to itraconazole - although no valid breakpoints are currently defined and minimum inhibitory concentrations (MICs) depend on the methods used. Problems related to the determination and interpretation of MICs are outlined. Our cases show that azole-resistant "Indian" strains of T. mentagrophytes with ITS genotype VIII occurred in Germany as early as 2011, which is earlier than was previously assumed. This variant of the pathogen cannot be phenotypically distinguished from customary strains of T. mentagrophytes; its identification is based on genetics. The taxonomic classification is still under debate. This variant is anthropophilic and causes only mildly inflammatory tinea lesions with many fungal elements. Its further dissemination must therefore be expected. Prerequisites for rapid and valid antimycotic testing against dermatophytes need to be developed.

Association of Clinical and Demographic Factors With the Severity of Palmoplantar Pustulosis.

Importance: Although palmoplantar pustulosis (PPP) can significantly impact quality of life, the factors underlying disease severity have not been studied. Objective: To examine the factors associated with PPP severity. Design, Setting, and Participants: An observational, cross-sectional study of 2 cohorts was conducted. A UK data set including 203 patients was obtained through the Anakinra in Pustular Psoriasis, Response in a Controlled Trial (2016-2019) and its sister research study Pustular Psoriasis, Elucidating Underlying Mechanisms (2016-2020). A Northern European cohort including 193 patients was independently ascertained by the European Rare and Severe Psoriasis Expert Network (2014-2017). Patients had been recruited in secondary or tertiary dermatology referral centers. All patients were of European descent. The PPP diagnosis was established by dermatologists, based on clinical examination and/or published consensus criteria. The present study was conducted from October 1, 2014, to March 15, 2020. Main Outcomes and Measures: Demographic characteristics, comorbidities, smoking status, Palmoplantar Pustulosis Psoriasis Area Severity Index (PPPASI), measuring severity from 0 (no sign of disease) to 72 (very severe disease), or Physician Global Assessment (PGA), measuring severity as 0 (clear), 1 (almost clear), 2 (mild), 3 (moderate), and 4 (severe). Results: Among the 203 UK patients (43 men [21%], 160 women [79%]; median age at onset, 48 [interquartile range (IQR), 38-59] years), the PPPASI was inversely correlated with age of onset (r = -0.18, P = .01). Similarly, in the 159 Northern European patients who were eligible for inclusion in this analysis (25 men [16%], 134 women [84%]; median age at onset, 45 [IQR, 34-53.3] years), the median age at onset was lower in individuals with a moderate to severe PGA score (41 years [IQR, 30.5-52 years]) compared with those with a clear to mild PGA score (46.5 years [IQR, 35-55 years]) (P = .04). In the UK sample, the median PPPASI score was higher in women (9.6 [IQR, 3.0-16.2]) vs men (4.0 [IQR, 1.0-11.7]) (P = .01). Likewise, moderate to severe PPP was more prevalent among Northern European women (57 of 134 [43%]) compared with men (5 of 25 [20%]) (P = .03). In the UK cohort, the median PPPASI score was increased in current smokers (10.7 [IQR, 4.2-17.5]) compared with former smokers (7 [IQR, 2.0-14.4]) and nonsmokers (2.2 [IQR, 1-6]) (P = .003). Comparable differences were observed in the Northern European data set, as the prevalence of moderate to severe PPP was higher in former and current smokers (51 of 130 [39%]) compared with nonsmokers (6 of 24 [25%]) (P = .14). Conclusions and Relevance: The findings of this study suggest that PPP severity is associated with early-onset disease, female sex, and smoking status. Thus, smoking cessation intervention might be beneficial.

Successful intra-class switching among IL-17 antagonists: a multicentre, multinational, retrospective study.

IL-17 blockers are among the newer anti-psoriatic treatment options and little is known about the interclass switching. We have thus initiated a multi-center, multi-national, retrospective study to assess the treatment response of patients who were switched from one IL-17 blocker to another. Analysis consisted of data from patients with moderate-to-severe psoriasis who did not respond satisfactorily to one of the available IL-17 blockers (secukinumab, ixekizumab, brodalumab) and were subsequently switched to another drug of this class. After 12 weeks of treatment, patients' PASIs were evaluated. Treatment success was defined as reaching PASI 75 after 12 weeks. Topical treatment was allowed and used in all patients. 26 patients were included (13 male, 13 female) and 29 switches were evaluated. Overall, 29 switches in 21 patients were evaluated. 18 patients changed their therapy from secukinumab to ixekizumab, or in 7 cases to brodalumab. Brodalumab was used in 3 cases after failure of treatment with ixekizumab. Only in one case, non-response of brodalumab resulted in a therapy switch to secukinumab. In 15 (52%) cases, PASI 75 was reached. In 6 (20%) patients, the switch led to a PASI 50 response. No success of treatment was seen among 8 (28%) participants. When patients fail to respond or do not tolerate an IL-17 blocker, switching to another anti-IL-17A/RA is a promising viable option. Larger studies are needed to confirm our results.

Clinical and genetic differences between pustular psoriasis subtypes.

BACKGROUND: The term pustular psoriasis indicates a group of severe skin disorders characterized by eruptions of neutrophil-filled pustules. The disease, which often manifests with concurrent psoriasis vulgaris, can have an acute systemic (generalized pustular psoriasis [GPP]) or chronic localized (palmoplantar pustulosis [PPP] and acrodermatitis continua of Hallopeau [ACH]) presentation. Although mutations have been uncovered in IL36RN and AP1S3, the rarity of the disease has hindered the study of genotype-phenotype correlations. OBJECTIVE: We sought to characterize the clinical and genetic features of pustular psoriasis through the analysis of an extended patient cohort. METHODS: We ascertained a data set of unprecedented size, including 863 unrelated patients (251 with GPP, 560 with PPP, 28 with ACH, and 24 with multiple diagnoses). We undertook mutation screening in 473 cases. RESULTS: Psoriasis vulgaris concurrence was lowest in PPP (15.8% vs 54.4% in GPP and 46.2% in ACH, P < .0005 for both), whereas the mean age of onset was earliest in GPP (31.0 vs 43.7 years in PPP and 51.8 years in ACH, P < .0001 for both). The percentage of female patients was greater in PPP (77.0%) than in GPP (62.5%; P = 5.8 × 10-5). The same applied to the prevalence of smokers (79.8% vs 28.3%, P < 10-15). Although AP1S3 alleles had similar frequency (0.03-0.05) across disease subtypes, IL36RN mutations were less common in patients with PPP (0.03) than in those with GPP (0.19) and ACH (0.16; P = 1.9 × 10-14 and .002, respectively). Importantly, IL36RN disease alleles had a dose-dependent effect on age of onset in all forms of pustular psoriasis (P = .003). CONCLUSIONS: The analysis of an unparalleled resource revealed key clinical and genetic differences between patients with PPP and those with GPP.

An experimental study on antitumoral effects of KI-21-3, a synthetic fragment of antimicrobial peptide LL-37, on oral squamous cell carcinoma.

PURPOSE: The aim of this study was to investigate the oncolytic properties of KI-21-3, a shortened fragment of LL-37, against oral squamous cell carcinoma (OSCC) in an animal model. MATERIALS AND METHODS: Twelve athymic nude mice were divided into a therapy and a control group of six animals each. In both groups, SCC-4 cells were administered extraorally into the floor of the mouth in order to create an OSCC model. In the study group, KI-21-3 was applied intravenously during the 8th and 9th weeks. The subjects in the control group were injected with phosphate buffered saline solution in the same manner. During an examination period of 12 weeks, weight control was performed twice a week. Tumor growth was further controlled volumetrically via ultrasonography once a week with regular intervals. Following sacrifice, ablated tumoral tissues were immunohistochemically evaluated in order to determine the proliferation and apoptotic properties. RESULTS: The mean tumor weight in the AMP group was 0.0236 ± 0.023 g, which was 30% lower than the control group with the mean value of 0.01651 ± 0.012 g. In the control group, the approximate number of the proliferating cells per visualized field was fourfold higher compared to the therapy group. Moreover, in the control group, the number of apoptotic cells per visualized field was significantly lower compared to the therapy group. CONCLUSION: KI-21-3 showed considerable oncolytic properties on SCC-4 carcinoma cells via antiproliferative and caspase-3 apoptotic pathway. Further investigations are necessary to clarify the dose-dependent effects of this agent.