Switching between JAK Inhibitors in Patients with Atopic Dermatitis: Unanswered Questions in Daily Clinical Practice.

Data on switching between agents in patients with atopic dermatitis (AD) are scarce (1-3). We report the case of a patient with severe AD and inadequate response to upadacitinib who showed a complete response after switching to abrocitinib. A 23-year-old male patient with severe AD was enrolled in the Measure Up double-blind, placebo-controlled, phase 3 randomized clinical trial. At baseline, the Eczema Area Severity Index (EASI) was 50.6, the Investigator's Global Assessment (IGA) was 4, the affected Body Surface Area (BSA) was 80%, and the Worst Pruritus-Numeric Rating Scale (WP-NRS) was 10/10 (Figure 1). At week 124, the patient discontinued participation in the trial, while EASI was 9.2, IGA 3, BSA 20%, and WP-NRS 5/10 at the time. After one month off treatment, and while expecting unblinding, the patient again presented with exacerbation of AD, since EASI was 45.6, IGA 4, BSA 80%, and WP-NRS 10/10. At that point of time, access to both dupilumab and tralokinumab was not available in Greece, while upadacitinib was avoided due to inadequate patient satisfaction, partly due to recurrent ocular herpes simplex infections during the previous upadacitinib treatment. The patient was prescribed abrocitinib 200 mg daily. One month after initiation of therapy, the patient achieved complete control of the disease (EASI 0.0, IGA 0, BSA 0%, and WP-NRS 0/10) (Figure 2). This has been maintained with no reported adverse events after 12 months of continuous treatment. After unblinding, the patient was confirmed to have received 15 mg of upadacitinib daily during his participation in the clinical trial. When to switch agents in the treatment of patients with severe AD if the response is not adequate, and what agent to switch to, is an issue that is not clearly defined. Data available from the JADE EXTEND study concluded that patients failing to achieve efficacy outcomes with dupilumab can benefit from switching to both doses of abrocitinib (1). However, a number of patients in this study did not achieve efficacy outcomes even after treatment with 200 mg of abrocitinib. Furthermore, sub-population analysis of the JADE EXTEND study, evaluating difficult-to-achieve patient-oriented outcomes such as Patient Oriented Eczema Measure (POEM) ≤2 and Dermatology Life Quality Index (DLQI) ≤1, further emphasized that switching might be beneficial for a significant number of patients, but unmet need was still evident for some of them (4). The literature lacks data on switching between Janus kinase (JAK) inhibitors in AD. Treat-to-target might be different for early control of the disease, as baricitinib and upadacitinib were assessed at 16 weeks, while abrocitinib was assessed at 12 weeks in the pivotal studies. Regarding the present case, the different clinical response obtained cannot be clearly defined since abrocitinib and upadacitinib are both selective JAK1 inhibitors. Consequently, the targeted inflammatory pathways and the expected regulation of immune functionality could be similar. We may assume that the high dose of abrocitinib vs. the low dose of upadacitinib could have accounted for the improved response. However, it is impossible to assess whether clinical outcomes would have been comparable with the administration of the full dose of upadacitinib 30 mg daily or whether usage of a half-dose of abrocitinib 100 mg daily would have also resulted in inadequate response in the same patient. Switching within the same class of treatment agents has also been a heavily-debated issue for psoriasis for many years; however, recent data suggest that switching between interleukin (IL)-17A antagonists may be of benefit to some patients, although the underlying mechanism of action is still under investigation (5,6). Treatment modification in inadequate response could include: up-dosing, adding classical treatments like methotrexate to the JAK inhibitor, switching to monoclonals, or switching to another JAK inhibitor, taking into account published metanalyses of the efficacy of novel agents. Consequently, there is an unmet need to determine an algorithmic step-by-step approach of treat-to-target and switching or adding treatment in the current landscape of AD therapy. Different policies of reimbursement in different countries, along with a lack of comparative studies, may complicate adding such recommendations to existing treatment guidelines.

Atopic Dermatitis: Striving for Reliable Biomarkers.

Atopic dermatitis (AD) is a highly heterogeneous inflammatory disease regarding both its pathophysiology and clinical manifestations. However, it is treated according to the "one-size-fits-all" approach, which may restrict response to treatment. Thus, there is an unmet need for the stratification of patients with AD into distinct endotypes and clinical phenotypes based on biomarkers that will contribute to the development of precision medicine in AD. The development of reliable biomarkers that may distinguish which patients with AD are most likely to benefit from specific targeted therapies is a complex procedure and to date none of the identified candidate biomarkers for AD has been validated for use in routine clinical practice. Reliable biomarkers in AD are expected to improve diagnosis, evaluate disease severity, predict the course of disease, the development of comorbidities, or the therapeutic response, resulting in effective and personalized treatment of AD. Among the studied AD potential biomarkers, thymus and activation-regulated chemokine/C-C motif ligand 17 (TARC/CCL17) has the greatest evidence-based support for becoming a reliable biomarker in AD correlated with disease severity in both children and adults. In this review, we present the most prominent candidate biomarkers in AD and their suggested use.

Occupational contact allergy of construction workers in Greece: Trends during 2009-2018.

BACKGROUND: Recent trends in the sensitization of construction workers show a decrease in potassium dichromate and an increase in epoxy resin sensitization. OBJECTIVES: To present the trends of occupational contact allergy of construction workers in Greece from 2009 to 2018. METHODS: We retrospectively reviewed the files of patients with eczema patch tested in our Contact Dermatitis Clinic who were construction workers. RESULTS: A total of 191 construction workers initially reported contact dermatitis. Of these, 138 had occupation-relevant allergic contact dermatitis (ACD) or irritant contact dermatitis (ICD). All patients were men. After being patch tested, 98 (71.0%) were diagnosed with ACD and 40 with ICD. Median duration of occupation till onset of ACD was 2 years (interquartile range [IQR] 0.8-7). The hands were the most common location for ACD (73.5%), followed by the trunk (39.8%), the legs (38.8%), and the face (11.2%). Of the patients, 74.6% had lesions affecting multiple body sites. Potassium dichromate (67%) was the most frequent allergen, followed by thiuram mix (37.4%) and cobalt chloride (31.8%). Sensitization to epoxy resins was lower (12.1%). CONCLUSION: The sensitization pattern of Greek construction workers does not follow the trends in Central or Northern Europe, rather sharing attributes with less industrialized countries.

Heterologous Type I Collagen as an Add-on Therapy to Narrowband Ultraviolet B for the Treatment of Vitiligo: A Pilot Study.

BACKGROUND: There is still an unsatisfied need for new treatments for vitiligo with more rapid onset and long-term sustainability of repigmentation. OBJECTIVE: We sought to evaluate the possible efficacy of heterologous type I collagen as an add-on therapy to narrowband ultraviolet B (NB-UVB) for the treatment of vitiligo. METHODS: Five patients with non-segmental vitiligo older than 18 years with bilateral and approximately symmetrical vitiligo lesions that did not evolve in size for at least six months were included. All vitiligo lesions were treated with NB-UVB therapy according to the Vitiligo Working Group recommendations. Two selected nonfacial lesions of each patient were also treated with intradermal injections of heterologous type I collagen (HTIC) every two weeks. Repigmentation of HTIC plus NB-UVB-treated lesions and their symmetrical counterparts treated just with NB-UVB was evaluated at baseline and Week 12. RESULTS: Repigmentation of the HTIC-injected lesions started after the first treatment session in three cases and after the second session in two cases. After six sessions (Week 12), the mean repigmentation rate was 70.5 percent (95% confidence interval:0.569-0.841) in the NB-UVB plus HTIC treatment group versus 16.5 percent (95% confidence interval: 0.137-0.192) in NB-UVB treatment group (p=0.0006, paired t-test). CONCLUSION: Although the number of patients treated with the combination treatment was limited in our study, our results suggest that the addition of HTIC to NB-UVB therapy might offer a more rapid onset of repigmentation in patients with vitiligo.

Incidence of anogenital warts: epidemiological risk factors and real-life impact of human papillomavirus vaccination.

Anogenital warts (AGWs) rank among the most frequent sexually transmitted infections in young adults. They are benign lesions, but they pose a significant economic cost to health care systems and a substantial psychological burden on patients, who need evidence-based counselling. Human papillomavirus (HPV) vaccination has shown very high protection rates against AGWs in clinical trials and real-world settings but vaccination coverage remains low in many countries. The aim of this review is to summarize the current evidence on the risk factors for AGW development and to present the available real-life data on the impact of HPV vaccination on AGW incidence. An increased number of lifetime sexual partners, a new sexual partner in the last 12 months, smoking, and immunosuppression have been associated with increased risk for AGWs. HPV vaccination has led to a dramatic decline in AGW incidence in populations that have achieved high vaccination rates. These conclusions can contribute to primary prevention of AGWs and evidence-based counselling of AGW patients.

Impact of vitamin D receptor gene polymorphisms on vitiligo susceptibility and clinical features in a Southeastern European Caucasian population.

An association of vitamin D receptor (VDR) polymorphisms and vitiligo has been suggested. However, previous studies have reported contradictory results while including limited data among Caucasians. The aim of this single­center study was to evaluate the effect of three common VDR gene polymorphisms (FokI, TaqI and BsmI) on susceptibility and clinical aspects of vitiligo in a Southeastern European Caucasian population. A total of 110 unrelated vitiligo cases and 509 general population controls were enrolled from October 2018 to November 2019. Genomic DNA was extracted from whole blood after de­identification and anonymization of the samples and genotyped for the selected VDR polymorphisms by the qPCR (melting curve analysis). Subgroup analysis by clinical features among subsets of patients indicated that, compared to subjects with the FokI TT genotype or T allele, carriers of the FokI CC genotype or C allele exhibited significantly decreased risk of developing vitiligo before the age of 30 [TT vs. CC: odds ratio (OR)=0.286, 95% confidence interval (CI): 0.083­0.984, P=0.041; T vs. C: OR=0.545, 95% CI: 0.313­0.948, P=0.031]. Intra­patient analysis also revealed that, compared to T allele, the presence of TaqI C allele was adversely associated with the incidence of concurrent leukotrichia (T vs. C: OR=1.874, 95% CI: 1.018­3.451, P=0.042). Comparisons between the case and control groups showed no evidence to support an association between susceptibility to vitiligo and the VDR BsmI, TaqI, and FokI polymorphisms in this cohort. Thus, the studied VDR polymorphisms might indirectly impact the clinical course and treatment decision­making despite their lack of association with vitiligo per se. Further research with larger sample sizes, especially across Caucasian individuals, should be performed to confirm these findings.

Occupational and non-occupational allergic contact dermatitis to hair dyes in Greece. A 10-year retrospective study.

BACKGROUND: Oxidative hair dyes are an important source of chemical exposure and a major risk factor for the development of occupational and non-occupational allergic contact dermatitis (ACD) worldwide. OBJECTIVE: To identify the frequency of common allergens associated with occupational and non-occupational ACD to hair dyes during the last 10 years, in Greece. METHODS: We retrospectively reviewed the medical records of patients with suspected ACD to hair dyes from 2010-2019. All patients with patch-test-confirmed ACD to hair dyes were evaluated. RESULTS: Out of 501 patients with suspected ACD to hair dyes, 362 had at least one positive reaction to hair dye allergens (62.4% were customers and 37.6% were hairdressers). The mean age of customers and hairdressers was 43.8 years and 30.8 years, respectively. Of the customers, 58.9% were exposed to dyes for >10 years and 61% of hairdressers for <5 years. The most common site of ACD among customers was the scalp (85%) and among hairdressers the hands (90%). p-Phenylenediamine (PPD) was the most common contact allergen (52.2%), followed by toluene-2,5-diamine, p-aminophenol, m-aminophenol, and ammonium persulfate. CONCLUSIONS: Sensitization prevalences for PPD and cross-reacting allergens have increased in Greece during the last decade, regardless of occupational or non-occupational exposure to hair dyes.

Childhood Vitiligo.

Vitiligo is a common acquired depigmenting skin disease characterized by a progressive loss of functional melanocytes. It may appear from the first years of life to late adulthood. Childhood vitiligo (CV), defined as vitiligo that begins before the age of 12 years, is common and may differ from post-CV in terms of epidemiology, clinical presentation, comorbidities, and treatment options. Taking into consideration the potential significant psychosocial impact of the disease on both children and their parents, all available therapeutic options must be offered to patients who desire treatment. According to the most recent guidelines, topical corticosteroids, topical calcineurin inhibitors, and narrowband ultraviolet B phototherapy are the most commonly used treatment modalities for vitiligo in children. This review presents recent data regarding the whole spectrum of CV. Differences between CV and post-CV are also discussed.