Immune response to SARS-CoV-2 mRNA vaccine in patients with psoriasis treated with biologics.

The effect of psoriasis treatment with biologics on the efficacy of COVID-19 vaccines is largely unknown. Our study aimed to evaluate antibody response against SARS-CoV-2 following two doses of BNT162b2 (Pfizer/BioNTech vaccine) in patients with psoriasis receiving biologic monotherapy, and compare it with that of healthy controls.

Polymorphism in Gene for ABCC2 Transporter Predicts Methotrexate Drug Survival in Patients with Psoriasis.

Background and Objectives: Methotrexate is widely prescribed for the treatment of moderate-to-severe psoriasis. As drug survival encompasses efficacy, safety, and treatment satisfaction, such studies provide insights into successful drug treatments in the real-life scenario. The objective was to define methotrexate drug survival and reasons for discontinuation, along with factors associated with drug survival, in a cohort of adult patients with moderate-to-severe plaque psoriasis. Materials and Methods: Data on methotrexate treatment were extracted from our institutional registry. Drug survival was estimated by Kaplan-Meier analysis, and predictors of drug survival were analyzed by Cox proportional hazards regression. Results: We included 133 patients treated with methotrexate. Due to significant effects of the year of treatment initiation, drug survival analysis was performed for 117 patients who started methotrexate in 2010 or later. Median methotrexate drug survival was 11.0 months. Overall, 89% of patients discontinued treatment, with over half of these (51%) due to lack of efficacy. Significantly longer drug survival was seen for patients who discontinued treatment due to lack of efficacy versus drug safety (p = 0.049); when stratified by sex, this remained significant only for women (p = 0.002). The patient ABCC2 rs717620 genotype was significantly associated with drug survival in both univariate log-rank and multivariate Cox regression analyses, with variant T allele associated with longer drug survival (hazard ratio, 0.606; 95% confidence interval, 0.380-0.967; p = 0.036). Conclusions: We have identified the novel association of patient ABCC2 rs717620 genotype with methotrexate drug survival. This pharmacogenetic marker might thus help in the management of psoriasis patients in daily practice.

Apremilast monotherapy for palmoplantar pustulosis: Report of three cases.

Palmoplantar pustulosis or palmoplantar pustular psoriasis is chronic skin conditions, characterised by eruptions of sterile pustules on an erythematosquamous background. High-quality data on the treatment of palmoplantar pustulosis are limited, and none is accepted as being effective in general. Apremilast is a small molecule inhibitor of phosphodiesterase 4 approved for the treatment of plaque psoriasis and psoriatic arthritis. We report three cases of palmoplantar pustulosis treated with apremilast monotherapy. Our three cases, as well as previous reports, demonstrate the potential for apremilast to be beneficial for a subset of patients with palmoplantar pustulosis or palmoplantar pustular psoriasis.

Polymorphisms in GNMT and DNMT3b are associated with methotrexate treatment outcome in plaque psoriasis.

Methotrexate is used as first-line treatment of moderate to severe psoriasis. Despite the marked variability in treatment outcomes, no pharmacogenetic markers are currently used for personalised management of therapy. In this retrospective study, we investigated the effects of genetic predisposition on efficacy and toxicity of low-dose methotrexate in a cohort of 137 patients with moderate to severe plaque psoriasis. We genotyped 16 polymorphisms in genes for enzymes involved in the folate-methionine pathway and in methotrexate transport, and analysed their association with treatment efficacy and toxicity using classification and regression tree analysis and logistic regression. The most pronounced effect observed in this study was for GNMT rs10948059, which was identified as a risk factor for inadequate efficacy leading to treatment discontinuation. Patients carrying at least one variant allele had ~7-fold increased risk of treatment failure compared to patients with the wild-type genotype, as shown by the classification and regression tree analysis and logistic regression (odds ratio [OR], 6.94; p = 0.0004). Another risk factor associated with insufficient treatment responses was DNMT3b rs2424913, where patients carrying at least one variant allele had a 4-fold increased risk of treatment failure compared to patients with the wild-type genotype (OR, 4.10; p = 0.005). Using classification and regression tree analysis, we show that DNMT3b rs2424913 has a more pronounced role in patients with the variant GNMT genotype, and hence we suggest an interaction between these two genes. Further, we show that patients with the BHMT rs3733890 variant allele had increased risk of hepatotoxicity (OR, 3.17; p = 0.022), which is the most prominent reason for methotrexate discontinuation. We also show that variants in the genes for methotrexate transporters OATP1B1 (rs2306283/rs4149056 SLCO1B1 haplotypes) and ABCC2 (rs717620) are associated with increased risk of treatment failure. The associations identified have not been reported previously. These data suggest that polymorphisms in genes for enzymes of the methionine cycle (which affect cell methylation potential) might have significant roles in treatment responses to methotrexate of patients with psoriasis. Further studies are warranted to validate the potential of the pharmacogenetic markers identified.

Drug survival of biological therapy is showing class effect: updated results from Slovenian National Registry of psoriasis.

BACKGROUND: Drug survival is an important measure of successful treatment of patients with chronic diseases such as psoriasis. Therefore, the objective was to calculate drug survival and examine safety profile of biologics and immunomodulators (adalimumab, apremilast, etanercept, ixekizumab, infliximab, secukinumab, and ustekinumab) from the Slovenian National Registry of patients with moderate-to-severe psoriasis. METHODS: Data about the patients with moderate-to-severe plaque psoriasis treated with biologics were collected from 2005 until July 2018. Kaplan-Meier survival curves and Cox regression were used to calculate drug survival, where ustekinumab was selected as a reference. RESULTS: Overall, 1,606 patients were analyzed within 2,241 treatment episodes; adalimumab N = 831, apremilast N = 94, etanercept N = 101, ixekizumab N = 98, infliximab N = 164, secukinumab N = 340, and ustekinumab N = 613, respectively. Loss of efficacy was the most frequent reason for treatment discontinuation (contributing to 66.1% of all discontinuations). Ustekinumab was associated with the highest drug survival, meanwhile apremilast was the drug with the lowest survival rate compared to all others. Both IL-17 inhibitors, secukinumab and ixekizumab, showed similar survival rate. CONCLUSIONS: Ustekinumab was associated with the highest drug survival and most favorable safety profile compared to other biologics. Drug survival rates can be associated with the class effect of biological targets. Highest survival rate was observed for IL-12/23 inhibitor, followed by IL-17 and TNF-α inhibitors, and last by an immunomodulator such as apremilast. Adverse events occurred most frequently with TNF-α inhibitors.

Sporotrichoid presentation of Mycobacterium marinum infection of the upper extremity. A case report.

BACKGROUND: Mycobacterium marinum is a human opportunistic pathogen that is known to inhabit swimming pools, home aquariums, and natural bodies of salt and fresh water. Epidemic cases involving swimming pools are easily recognized, but sporadic cases are frequently misdiagnosed. OBJECTIVE: A 42-year-old male presented with a 2-month history of the appearance of livid, verrucous, painless nodules on his right upper extremity. He had cleaned an aquarium with tropical fish for the past 2 years. METHODS: A histopathological examination suggested a granulomatous inflammation. After incubation on Löwenstein-Jensen medium, Mycobacterium marinum was identified using biochemical methods and the PCR technique. RESULTS: Systemic therapy with rifampicin, ethambutol, and clarithromycin over a period of 6 months led to complete resolution of the skin lesions with some residual scars. CONCLUSION: Knowledge of this condition is very important to avoid unnecessary diagnostic procedures and improper treatment.

Idiopathic eruptive macular pigmentation.

We present the case of a 10-year-old girl with a six months history of disseminated asymptomatic, brown pigmented macules on the trunk and proximal parts of the extremities. The clinical picture, histological findings, and the course of disease were similar to those of idiopathic eruptive macular pigmentation. The cutaneous lesions gradually disappeared over the next two years without any treatment, and no relapse occurred. The knowledge of this disease is important in order to avoid unnecessary treatment as spontaneous resolution of the lesions may be expected within months or a few years. The spontaneous regression without any treatment is an additional diagnostic criterion.