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Background: 2‐Hydroxyethyl methacrylate (HEMA) was added into the European baseline series (EBS) in 2019. There is limited data regarding the frequency, relevance, and sources of exposure to HEMA. Objectives: To investigate the frequency and clinical relevance of positive reactions to HEMA in the EBS in Israel, and explore sources of exposure. Methods: Retrospective cohort study that included all patients who underwent patch testing with the EBS in a tertiary center in Israel between 2020 and 2023. Positive reactions to HEMA were stratified by sex, six age groups, and year of study. Sources of exposure to HEMA as well as occupational data were recorded. Results: A total of 1671 consecutive patients underwent HEMA patch testing, with 135 (8.1%) showing positive reactions to HEMA (130 females, 5 males). The prevalence in women (11.0%) was significantly higher compared to men (1.0%) (p < 0.001). Stratification by age and sex revealed the highest frequency of HEMA sensitivity of 16.7% among women younger than 30 years of age, with odds ratio of 2.3 (95%CI: 1.6–3.3, p < 0.001) compared to older women. There was an increase in frequency among women between the years 2022 and 2023 when compared to 2020–2021 (OR 1.7, 95%CI: 1.5–2.1, p < 0.01) attributable to COVID‐19 pandemic and social restrictions. Among men the frequency fluctuations over the study period and age categories were nonsignificant. 111 (84%) were judged to be of clinical relevance and nail cosmetics was responsible for 95% of them. Of 111 patients with relevant reaction (110 females, 1 males), 20 (18%) had occupational contact dermatitis (18 nails stylists, 2 dentists). Other culprit products included sanitary pads (n = 4), medical adhesives (n = 3), and paints (n = 2). Conclusion: We report the highest frequency of HEMA sensitivity to date of 8.1%, that was most common among young women and in vast majority of cases was attributable to nail cosmetics. Our findings reflect the popularity of nail cosmetics in Israel as well as the global trend of increasing sensitivity to (meth)acrylates. [ABSTRACT FROM AUTHOR]

Background: From a dermatologist's perspective, there are four major types of cutaneous porphyrias (CPs): porphyria cutanea tarda (PCT), erythropoietic protoporphyria (EPP), variegate porphyria (VP) and hereditary coproporphyria (HCP). Scarce data are available regarding the epidemiology of CPs. Objectives: To describe the epidemiology of CPs in Israel, including distribution, incidence and prevalence rates of major types. Methods: This retrospective study includes all patients who were diagnosed with CPs between the years 1988–2018. It is based on data from Israel's National Service for the Biochemical Diagnoses of Porphyrias, and Israeli patients' nationwide electronic medical charts. Incidence and prevalence rates were calculated. Results: Of 173 patients with CPs diagnosed during a 30‐year period, 65 (38%) had VP, 62 (36%) had PCT, 31 (18%) had HCP and 15 (9%) had EPP; with incidence rates of 0.29, 0.30, 0.17, 0.07, and prevalence rates of 6.3, 4.8, 2.9, 1.6, respectively, per million population. Characteristics of patients with PCT differed from those with other CPs with regard to lack of family history, older mean age at diagnosis [51 vs. 36 (VP), 35 (HCP) and 25 (EPP) years] and male predominance (81% vs. similar distribution). All patients with PCT were diagnosed at adulthood, while 20%, 19% and 15% of patients with VP, HCP and EPP, respectively, were diagnosed during childhood or adolescence. Conclusions: Variegate porphyria and PCT were found to be the most prevalent in Israel; however, CPs might be underdiagnosed, thus dermatologists' awareness of these rare disorders is highly important. [ABSTRACT FROM AUTHOR]

Background: Tefillin are a religious article worn by Jewish men during daily prayer. Tefillin dermatitis secondary to potassium dichromate sensitivity is recognised, but data remain sparse., Objective: To investigate the prevalence and clinical characteristics of tefillin dermatitis., Methods: Patients who underwent patch testing with the European baseline series in a tertiary dermatology clinic in 2009-2023 and were diagnosed with tefillin dermatitis were identified by file review and their clinical data recorded., Results: Of 1679 consecutive male patients tested, 25 (1.49%) were diagnosed with tefillin dermatitis, accounting for 15.34% of all potassium-dichromate-positive patients (163/1679). Mean pre-symptomatic duration of tefillin use was 38 ± 16.9 years, and mean follow-up time, 3.1 ± 2.9 years. Patients presented with an eczematous rash on body areas in direct contact with the leather box or straps of the tefillin. An id reaction was noted in 32%, and sensitivity to other leather accessories, in 44%. Fourteen patients (56%) switched to chromate-free tefillin: symptoms resolved completely in 11 (79%) and partially in 2., Limitations: Retrospective cohort design., Conclusion: This is the largest study to date of tefillin dermatitis caused by sensitivity to potassium dichromate used in leather production. Prognosis after switching to chromate-free tefillin was good-to-excellent. Tefillin dermatitis may be more prevalent than previously thought., (© 2024 The Author(s). Contact Dermatitis published by John Wiley & Sons Ltd.)

Background: Pincer nail deformity (PND) is a common toenail disorder characterized by transverse over-curvature of the nail plate. It can cause severe pain, chronic inflammation, and recurrent infections. Both conservative and surgical treatment options carry different disadvantages of limited efficacy, high recurrence rate, and poor cosmetic outcome. The study aimed to evaluate the safety and effectiveness of carbon dioxide (CO2) laser matricectomy for the treatment of PND., Methods: The database of the laser unit of a tertiary medical center was retrospectively searched for all patients who were diagnosed with PND in 2016-2022 and treated with lateral and/or medial matricectomy using CO2 laser. Clinical and follow-up data were collected from the medical files.&nbsp; Results: The cohort included 19 patients (5 male, 14 female) who underwent 25 partial matricectomies during the study period (some patients had more than one diseased nail). All procedures were successful, with no intraoperative or postoperative complications. There was one documented recurrence at 7 months after treatment., Conclusion: Partial CO2 laser matricectomy is safe and effective for the treatment of PND. J Drugs Dermatol. 2023;22(11):1099-1102&nbsp; &nbsp;&nbsp; doi:10.36849/JDD.7574.

Hair removal with lasers and intense pulsed light (IPL) is considered safe. However, data on the efficacy and safety of these procedures specifically in the pediatric population remain sparse. To determine the efficacy and safety of lasers and IPL for hair reduction in children and adolescents, a systematic review was conducted of original studies evaluating hair removal with lasers or IPL in patients aged less than 18 years. Primary outcome measures were efficacy and safety of treatment. The literature review yielded 2 retrospective cohort studies and 11 case reports/case series including a total of 71 patients aged 9 months to 17 years. Diagnoses ranged from localized lumbosacral to generalized hypertrichosis. Six treatment modalities were evaluated: alexandrite, Nd:YAG, Q-switched Nd:YAG, ruby, and diode lasers and IPL. Only one of the cohort studies (n = 28), using the ruby laser, provided efficacy data. The results showed a 63% hair loss in 89% of patients after completion of treatment, although partial regrowth was evident during 6 to 32 weeks of follow-up. Most of the case reports and case series (10/11) reported significant hair reduction following laser and IPL treatments. None of the patients experienced scarring or dyspigmentation. Some kind of pain management was necessary in 65% of patients; 25% required general anesthesia. On the basis of the limited available data which consisted primary of case reports and case series, lasers and IPL might be effective for pediatric hair reduction. Recurrence following treatment may be higher in children than adults, and pain control may be a limiting factor., (© 2023. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Objective: In patients with acute hepatic porphyria (AHP), prolonged fasting is a known trigger of AHP attacks. Despite this, some Jewish AHP patients-mainly hereditary coproporphyria (HCP) and variegate porphyria (VP) patients-fast for 25 consecutive hours during the traditional Jewish holy day known as Yom Kippur. In this study, we evaluated the effect of the fast on these patients., Methods: A retrospective study and survey of AHP patients in Israel was carried out. Patients were asked whether they have fasted and whether any symptoms were induced by this fast. Patients' medical records were reviewed for an emergency department (ED) visit following Yom Kippur between 2007 and 2019. Only 3 acute intermittent porphyria (AIP) patients reported fasting; they were excluded from analysis., Results: A total of 21 HCP patients and 40 VP patients completed the survey; 30 quiescent patients reported they fast, while 31 did not fast. The majority of fasting patients (96.67%) reported no symptoms following a fast. We found no statistically significant association between ED visits 1 week (0.26% in both fasting and non-fasting patients) or 1 month (2.1% visits in non-fasting versus 0.78% in fasting patients) following Yom Kippur. Of the symptomatic ED visits following a fast, none were defined as severe attacks., Conclusion: A 25-hour fast in stable HCP and VP patients did not increase the risk of an acute attack and can probably be regarded as safe.

Actinic keratoses are common cutaneous lesions with a potential to progress to invasive squamous cell carcinoma. Therefore, treatment is crucial. The Tixel® is a noninvasive thermomechanical device designed to transfer heat to the upper dermis in a controlled manner according to a predetermined setting. This study aimed to evaluate the safety and efficacy of a thermomechanical fractional skin resurfacing technology for the treatment of facial and scalp actinic keratoses. A prospective, open-label, before-after study was conducted in a tertiary medical centre from May 2020 to April 2021. Patients presenting with facial/scalp actinic keratoses of mild-to-moderate thickness underwent 2 or 3 Tixel treatments (depending on clinical improvement), 3-4 weeks apart. The reduction in lesion count and overall improvement in appearance were assessed by clinical examination and digital photography. Findings were compared between baseline and follow-up at 3 months after the last treatment session. Patient satisfaction was evaluated by questionnaire, and adverse effects were documented. A total of 20 patients participated in the study. All completed 2-3 treatments and follow-up visits. Assessment of digital photographs was performed by 2 assessors blinded to the timepoint at which each photo was taken (before or after treatment). The average number of lesions at baseline was 9.8 (± 4.8) and the mean reduction in lesion count was 7.9 (± 4.4) (80.6%). Complete clearance was observed in 31.6% of patients. No adverse effects were noted during treatment and follow-up. Most patients reported being "very satisfied" or "satisfied" with the treatment results (85%) and experience (95%). Treating facial and scalp actinic keratoses with the Tixel device was found to be effective and safe., (© 2022. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Background: There is a paucity of data regarding demodicidosis-associated facial hyperpigmentation., Objective: To delineate the clinical, dermoscopic, and histopathologic features of demodicidosis-associated facial hyperpigmentation., Methods: Clinical and diagnostic data were collected from the medical files of patients who were referred to our outpatient dermatology clinic in 2006-2019 for evaluation of facial hyperpigmentation and were diagnosed with demodicidosis., Results: The cohort included 19 patients (13 male) aged 42-76 years, all with Fitzpatrick skin type 3-4. All presented with mostly asymptomatic dusky, brown-gray, facial pigmentation, localized or diffuse with background erythema in 36.8% of cases, and skin roughness in 26.3%. Dermoscopy yielded characteristic findings of white gelatinous or opaque protrusions from hair follicles or infiltration of follicular openings with an amorphic material. A specific finding was perifollicular and reticulated pigmentation of the affected areas. Findings were confirmed on microscopic (n = 7) and histopathologic (n = 5) studies. Anti-demodectic treatment led to complete (73.6%) or partial (23.4%) resolution of pigmentation within 2 years., Conclusion: We describe unique clinicopathological and dermoscopic findings associated with an under-recognized type of facial hyperpigmentation caused by demodex for which we propose the term "pigmented demodicidosis." Demodicidosis should be added to the list of causes of facial hyperpigmentation., (© 2021 the International Society of Dermatology.)

The sequential application of fractional ablative/10,600 nm/CO 2 followed by 1570 nm non-ablative laser treatment might produce better results than applying either laser treatment alone. However, histological data regarding the safety of this combination is lacking. This study aimed to assess and compare clinical effects, histological tissue damage, and wound healing after monochromatic and sequential fractional laser treatments. In this prospective porcine model study, three adult female pigs were each irradiated using three different wavelengths: (a) monochromatic fractional ablative CO 2 laser; (b) monochromatic fractional non-ablative 1570 nm laser; (c) sequential fractional 10,600 nm/CO 2 followed by 1570 nm laser treatment. There were six power levels in the monochromatic 1570 nm laser, five in the 10,600 nm/CO 2 , and five in the sequential treatment. The immediate skin reaction (ISR), crusting and adverse effects, was evaluated across different time points throughout the healing process. Wound biopsies were taken at immediately after (0) and at 3, 7, and 14 days after irradiation. Depth and width of craters, and width of coagulation zone were measured and compared. Similar ISR and crusting score values were obtained following the monochromatic and sequential irradiation in a similar dose-response manner. During 14 days of follow-up, the skin looked intact and non-infected with no signs of necrosis. The mean depth and width of craters were comparable only at the maximal energy level (240 mJ) of CO 2 laser, with the coagulation size greater after the sequential treatment. In histology, a similar wound healing was evident. On day 3, crusts were observed above all lesions as was epithelial regeneration. The sequential irradiation with 10,600 nm/CO 2 and 1570 nm lasers did not pose any additional risk compared to the risk of each laser alone., (© 2021. The Author(s).)

The pulsed dye laser (PDL) is the standard treatment for port-wine stains (PWS). Maximal improvement occurs after multiple treatment sessions; however, the optimal treatment interval has yet to be determined. The aim of this study was to review whether there is an association between PDL treatment interval and outcome of PWS. Six databases were searched by three reviewers for publications investigating treatment of PWS with PDL. The 75% improvement rates (75IR) were extracted for quantitative analysis. Meta-regression was used to investigate the association between treatment intervals and 75IR. The systematic review included 1 RCT and 33 cohort studies (7 prospective cohorts and 26 retrospective cohorts), with a total of 3777 patients. The pooled 75IR was 37% (95% CI 29-45%; I 2 = 95%). Light Fitzpatrick skin type (p = 0.04), facial anatomic location (p = 0.01), and young age (p = 0.008) were associated with 75IR. In an unadjusted (p = 0.42) and multivariable adjusted (p = 0.98) meta-regression, no association was found between time interval between treatments and 75IR. These results persisted in a sensitivity analysis of studies with a mean patient age of ≤ 1. The majority of included studies were heterogeneous and retrospective. Based on cohort studies of low-to-moderate quality, time intervals between PDL treatments are not associated with PWS outcome., (© 2021. The Author(s), under exclusive licence to Springer-Verlag London Ltd. part of Springer Nature.)

Solar urticaria is a well-recognized photodermatosis, sometimes accompanied by angioedema. However, isolated solar angioedema (ISA) is a rare and unrecognized entity. The purpose of our work was to systematically review the available data on ISA. Therefore, a systematic review of studies evaluating ISA was performed. Additionally, a case of a 21-years-old patient from our photodermatosis service is presented. The search yielded 421 publications, with 3 eligible for review. Together with our case, 5 cases were included overall. All patients were female. Four out of 5 patients first experienced ISA at childhood or early adulthood (age range 6-22 years). UVA photoprovocation was positive in the 3 out of the 4 patients who were tested. Improvement was noted following NB-UVB hardening (2 out of 5 patients) or a short course of oral prednisone (3 out of 5 patients) combined with regular sunscreen application. To conclude, ISA is an extremely rare entity, although it may be underdiagnosed due to lack of awareness. The clinician must consider ISA in the differential diagnosis of angioedema since it can have a detrimental effect on quality of life. Besides sun avoidance, there is no consensus regarding treatment., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Inherited genetic erythropoietic protoporphyria (EPP) is characterized by a photosensitive rash that emerges during infancy or early childhood. Acquired EPP can erupt at any age, even during adulthood, and is associated with hematological disorders. A third, less-studied type of EPP is also inherited but appears later in life (during adulthood)., Purpose: To evaluate the characteristics of inherited genetic late-onset (IGLO) EPP., Methods: A systematic comprehensive search of the literature was conducted using PubMed, Google Scholar, ScienceDirect, and clinicaltrials.gov databases. Studies describing patients with IGLO EPP were included. Additionally, we present an index case of a patient, treated at our clinic in whom inherited genetic EPP was diagnosed at age 21 years., Results: The search yielded 1514 citations. Five publications were eligible for review. Along with our case, 7 patients (4 males) were included in the analysis. Mean age at disease onset was 34.2 years (range 18-69, median 30). Most patients presented with mild pruritus and rash in a photosensitive distribution. Mean level of free erythrocyte protoporphyrin IX (FEP) was 8.6 μmol/L. A mutant ferrochelatase gene (FECH) in trans to a hypomorphic FECH allele was found in 3 of the 4 patients who underwent genetic testing., Conclusion: We describe the distinct features of IGLO EPP. This work emphasizes that a diagnosis of inherited genetic EPP should not be ruled out in adults with new-onset photosensitive manifestations., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Paradoxical hypertrichosis (PH) is an uncommon, poorly understood adverse effect associated with laser or intense pulsed light treatment for hair removal., Objective: The objective of this study was to conduct a systematic review and meta-analysis to determine PH prevalence and associated risk factors., Methods: We conducted a systematic review and meta-analysis of studies evaluating hair removal with lasers or intense pulsed light. Primary outcome was PH prevalence. Meta-regression and subgroup analysis were used to investigate associations among treatment modality, patients' characteristics, and PH., Results: Included were 9733 patients in two randomized controlled trials and 20 cohort studies (three prospective and 17 retrospective). Pooled PH prevalence was 3% (95% confidence interval 1-6; I 2 = 97%). Paradoxical hypertrichosis was associated with a face or neck anatomic location, and occurred in only 0.08% of non-facial/neck cases. Treatment modality and interval between treatments had no effect on the PH rate. There were insufficient data to determine the association between sex and skin type to PH. In three out of four studies, PH gradually improved with continued therapy., Conclusions: Based primarily on cohort studies, PH occurs in 3% of patients undergoing hair removal with lasers or intense pulsed light, yet rarely outside the facial/neck areas. Treatment modality does not seem to be a contributing factor. Continuation of treatment in areas with PH may be the most appropriate treatment., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: There are three major types of genetic cutaneous porphyrias (GCP): erythropoietic protoporphyria (EPP), variegate porphyria (VP), and hereditary coproporphyria (HCP). Scarce data are available regarding their impact on patients' quality of life in the Mediterranean region., Purpose: To describe the cutaneous features of GCP in Israel., Methods: An established nationwide cohort of patients with GCP diagnosed during 1988-2019 was surveyed by telephone for cutaneous features of GCP. Impact on quality of life was assessed using the Dermatology Life Quality Index., Results: Of the 95 patients with GCP, 71 (75%) completed the survey (21 HCP; 40 VP; 10 EPP). All EPP patients reported cutaneous symptoms compared with 58% of VP and 5% of HCP (P < .001). Mean age at symptom onset was 7 ± 6 years in EPP and 25 ± 15 years in VP (P < .001). Photosensitivity was the most common symptom in EPP (90%). In VP photosensitivity (52%), blistering (52%) and scarring (74%) were all common symptoms. In both VP and EPP, the dorsal hands/forearms were the most affected regions (≥96%), and in ≥ 78%, symptoms occurred on an almost daily basis. All EPP patients changed their lifestyle due to cutaneous symptoms vs 57% in VP. Major effect on quality of life was observed among EPP patients compared with a moderate effect in VP. No treatment was effective in EPP, while phototherapy and moisturizers were effective in 5 of 7 (71%) VP patients., Conclusion: This study sheds light on the cutaneous features of the GCP, which have a substantial effect on patients' quality of life., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Hereditary coproporphyria (HCP) and variegate porphyria (VP) are referred to as neurocutaneous porphyrias (NCP). Data concerning their systemic presentation are limited and no direct attempt of comparison of the two has ever been made. Our aim was to describe the type and frequency of systemic manifestations of NCPs in Israeli patients. A cross-sectional survey was conducted. The study population included all patients with NCP diagnosed at the Israeli National Service for Biochemical Diagnoses of Porphyrias (INSP) between 1988 and 2019. Of the 83 patients with NCP who were alive in 2019, 61 (73%) completed the survey, 40 with VP and 21 with HCP. Systemic symptoms were reported by 63% of the VP group and 62% of the HCP group ( p  = .96); corresponding rates of cutaneous symptoms were 58% and 5% ( p  < .001). We found no association between the occurrence of systemic and cutaneous symptoms. Among patients with systemic involvement, abdominal pain was the predominant systemic symptom, found in 64% of the VP group and 69% of the HCP group; Analysis of symptom frequency showed that in 68% of the VP group, systemic symptoms (either abdominal, musculoskeletal or neuropsychiatric) occurred on a daily/weekly basis, whereas the HCP group experienced less than one symptom per week ( p  < .001). This nationwide study depicts a significantly heavier disease burden in VP patients compared to HCP owing to its more frequent neurovisceral and cutaneous manifestations., Competing Interests: The authors declare they have no conflict of interest., (© 2021 The Authors. Published by Elsevier Inc.)

Cutaneous viral warts (CVW), caused by human papillomavirus, often have a self-limited course. However, some patients experience a recalcitrant disease despite treatment. Retinoids are considered the mainstay of therapy in many dermatologic diseases. Data on their use for viral warts are limited. To systematically review the published evidence on the efficacy and safety of retinoids for the treatment of CVW. A systematic review and meta-analysis of topical or systemic retinoid treatment for CVW was performed in accordance with the PRISMA statement. The primary outcome was clinical response; secondary outcomes were recurrence rate and adverse events. Fourteen publications including 399 patients treated exclusively with retinoids (65% topical, 35% systemic) were evaluated. The complete response rate was 64% (95% CI, 46-78%; I 2 =80%) for topical treatment and 61% (95% CI, 44-76%; I 2 =69%) for systemic treatment. The most common side effects were irritant contact dermatitis and cheilitis, respectively. Relapse rates were 6% and 17%, respectively. The reviewed studies were considerably heterogenous and most lacked a control group. Both topical and systemic retinoids are effective and safe as monotherapy for CVW. Further studies are required to determine their exact role in this setting., (© 2020 Wiley Periodicals LLC.)

Background: Genital warts, caused by the human papillomavirus, are a common sexually transmitted disease. The warts can regress spontaneously or exhibit a persistent clinical course. Various therapeutic modalities are available, yet none is curative, and there may be recurrences. Retinoids are considered the mainstay of therapy in many dermatologic diseases. Data on their use for genital warts are limited., Objective: To systematically review the published evidence on the efficacy and safety of retinoids for the treatment of genital warts., Methods: A systematic review and meta-analysis of all publications evaluating topical or systemic retinoids for the treatment of genital warts was performed. The primary outcome was complete response (CR); the secondary outcomes were recurrence rate and adverse events., Results: Six publications were evaluated, three randomized controlled trials and three prospective cohort studies, including a total of 141 patients with genital warts treated exclusively with retinoids (90% with isotretinoin). CR rates were 100% for systemic etretinate (3 out of 3 patients, 95% CI 28-81%) and 56% for isotretinoin (95% CI 28-81%; I2 = 84%). Topical etretinate did not induce CR. The most common side effect of topical agents was irritant contact dermatitis (36%) and that of systemic agents mucocutaneous disorders (80%). The relapse rate was 12% for oral isotretinoin and was unavailable for the other modalities., Conclusions: Current data suggest that unlike topical retinoids, systemic retinoids are an effective and safe treatment for genital warts. Further studies are required to determine their specific role and the most effective regimen for each derivative., (© 2020 S. Karger AG, Basel.)

Introduction: In a randomized prospective trial, adjuvant rituximab was more efficacious than corticosteroids alone in the treatment of pemphigus; however, real-life data are limited. Rituximab treatment for pemphigus has only recently been introduced to the Israeli health basket. Previously, patients received rituximab if they paid out of pocket or through private insurance, separating patients into 2 treatment groups, mostly based on economic capability., Methods: A retrospective cohort study of the 12-month clinical response of pemphigus vulgaris/foliaceus patients. We compared patients after a single cycle (1,000 mg on days 0 and 15 or weekly 375 mg/m2 for 4 weeks) of adjuvant rituximab with systemic corticosteroids ± steroid-sparing agents, to patients who were prescribed rituximab, could not obtain it, and received systemic corticosteroids ± steroid-sparing agents., Results: Forty-five patients were included (adjuvant rituximab, n = 29; immunosuppression alone, n = 16). At baseline, rituximab patients had a higher mean pemphigus disease area index (PDAI) (p = 0.07) and higher mean daily dosages of prednisone (1.51 vs. 1.16 mg/kg, p = 0.39). All patients but 1 in the rituximab group continued systemic steroids, and 31% in the rituximab group versus 50% in the immunosuppression-alone group received systemic adjuvants. At 12 months, partial or complete remission rates (on or off maximum 40 mg/day prednisone equivalent) were nonsignificantly higher in the rituximab group (62 vs. 50%, p = 0.53); however, patients on rituximab showed faster remissions (3.4 ± 1.9 vs. 5.9 ± 3.6 months; p = 0.03) with a trend for a greater PDAI reduction (p = 0.051). Adverse events were comparable., Conclusions: In this real-life study, a single cycle of rituximab achieved more remissions and sooner compared to conventional immunosuppression, but the differences were not significant, probably due to a small sample size and severe baseline disease in the rituximab group. Future real-life studies on larger groups are needed., (© 2020 S. Karger AG, Basel.)

Background: The incidence of epidermal growth factor receptor inhibitor (EGFRI)-induced papulopustular rash is 60-85%., Objective: To investigate prophylactic topical treatment for EGFRI-induced rash., Methods: A single-center, randomized, double-blind, placebo-controlled trial. Adult cancer patients initiating treatment with EGFRIs were randomized to receive facial topical treatment with chloramphenicol 3% + prednisolone 0.5% (CHL-PRED) ointment, chloramphenicol 3% (CHL) ointment, or aqua cream (AQUA). The primary end points were the incidence of ≥grade 3 rash using the Common Terminology Criteria for Adverse Events (CTCAE), on days 14 and 30. A subanalysis was conducted for incidence of a protocol-specified significant rash, defined as ≥10 facial papulopustular lesions., Results: The per-protocol analysis on day 14 included 69 patients, who received CHL-PRED (21), CHL (23), or AQUA (25). The incidence of CTCAE ≥grade 3 rash was not statistically significant between arms; however, the incidence of the protocol-specified significant rash was: CHL-PRED 14%, CHL 39%, and AQUA 48% (p = 0.03, CHL-PRED vs. AQUA). At 30 days, the CTCAE ≥grade 3 incidence was similar, but the incidences of protocol-specified significant rash were 6%, 16%, and 43% (p = 0.03, CHL-PRED vs. AQUA). No significant differences were found between CHL and CHL-PRED and between CHL and AQUA., Conclusions: Prophylactic topical CHL-PRED was efficacious when compared to AQUA, in the treatment of EGFRI-induced facial papulopustular rash., (© 2020 S. Karger AG, Basel.)

High levels of efficacy were demonstrated in randomized controlled trials assessing the efficacy of guselkumab; however, real-life data are lacking. In this retrospective cohort study, we assessed the efficacy and safety of guselkumab in a cohort of psoriasis patients heavily pretreated with biologic agents. Primary efficacy endpoint was the percentage of patients achieving ≥psoriasis area and severity index (PASI) 90 response at week 24. The cohort included 33 patients of mean age 60 ± 13 years. Guselkumab was initiated after a mean of 4.0 ± 1.0 prior biologics failed over a mean period of 7. 4 ± 3.8 years. The mean duration of guselkumab treatment was 9.5 ± 3.7 months; 29 patients completed at least 24 weeks of treatment. At week 24, 22 patients (76%) achieved response of PASI 75 or higher, 18 (62%) achieved PASI 90 or higher, five (17%) PASI 100, and seven (24%) ≤PASI 50. No adverse effects were observed. This study confirms the efficacy and safety of guselkumab in real-world clinical practice, although for a lesser degree compared with clinical trials., (© 2020 Wiley Periodicals LLC.)

Background: Erythropoietic protoporphyria (EPP) is a semi-dominantly inherited porphyria presenting with photosensitivity during early childhood. Acquired EPP has been reported; however, data regarding this rare disorder are scarce., Purpose: To evaluate the characteristics of acquired EPP., Methods: A comprehensive search of PubMed, Google Scholar, ScienceDirect, and clinicaltrials.gov databases was performed by three reviewers. Studies describing patients with acquired EPP were included. Additionally, we present an index case of a 26-year-old patient who acquired clinically and biochemically typical EPP in association with myelodysplastic syndrome (MDS)., Results: We included 20 case reports describing 20 patients. Most (80%) patients were male of mean age 58 ± 13 years. In all patients, acquired EPP was associated with hematological disease, most commonly MDS (85%) followed by myeloproliferative disease (10%). In 86% of cases, hematological disease led to abnormality or somatic mutation in chromosome 18q (the locus of the ferrochelatase gene). The mean erythrocyte protoporphyrin IX concentration was very high (4286 μg/dL). Most (90%) patients presented with photosensitivity, 20% experienced blistering, and 25% presented with hepatic insufficiency, both uncommon in EPP. In 55% of patients, hematological disease was diagnosed after occurrence of cutaneous symptoms. Beta-carotene led to partial control of symptoms in 5 patients and resolution in another patient. Azacitidine treatment of MDS led to resolution of cutaneous symptoms in three patients., Conclusion: We present the distinct features of acquired EPP and highlight that any patient presenting with new-onset photosensitivity, irrespective of age should be evaluated for porphyria., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Disorders of the umbilicus are commonly seen in infancy, including hernias, infections, anomalies, granulomas, and malignancies. Meticulous inspection of the umbilicus at birth might reveal a persisting embryonic remnant, such as an omphalomesenteric duct (OMD), manifested by a variety of cutaneous signs, such as an umbilical mass, granulation tissue, or discharge., Objective: To systematically review the available data regarding the presence and management of OMD remnant with cutaneous involvement to suggest a practical approach for diagnosis and treatment., Methods: A systematic review of the literature evaluating OMD anomalies presenting with cutaneous symptoms was performed. In addition, an index case of an 11-month-old patient is presented., Results: We included 59 publications reporting 536 cases; 97% of the patients whose age was noted were infants (mean age 11 months). In 7.5% of the cases, diagnosis was established only after treatment failure. In 6.4% of patients, nonlethal complications were reported, and in 10.3%, the outcome was death, partly due to delayed diagnosis or mismanagement., Limitations: Limited quality of the collected data, reporting bias., Conclusion: OMD is relatively rare; however, the clinician must consider this remnant while examining patients with umbilical abnormalities because mismanagement could cause severe morbidity and mortality., (Copyright © 2019 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Whole-body integrated positron emission tomography / contrast-enhanced computed tomography (PET/CT) scan is increasingly used in cutaneous lymphomas. However, the value of PET/CT in the detection of cutaneous lesions in primary cutaneous B-cell lymphoma (PCBCL) has barely been investigated., Objectives: To investigate the diagnostic accuracy of PET/CT in tracking cutaneous involvement in PCBCL., Methods: A retrospective study was conducted on 35 consecutive patients diagnosed with cutaneous B-cell lymphoma according to the World Health Organization classification who were evaluated with PET/CT as the initial staging procedure before treatment., Results: Thirty-five patients met the study criteria. In two patients extracutaneous disease was detected by PET/CT and CT and confirmed by biopsy. Of the 33 patients with PCBCL, 26 (79%) had small cell PCBCL (18 marginal-zone, 8 follicle-center lymphoma) and 7 (21%) had large cell PCBCL (3 follicle-center, 3 leg-type, 1 indeterminate). PET/CT detected skin lesions in 3 of 26 patients (12%) with small-cell PCBCL as compared to 6 of 7 patients with large-cell PCBLC (86%), a 7.4-fold detection risk (95% confidence interval, 2.4-22, P = 0.004). The PET-positive subgroup was characterized by larger lesion size (P < 0.001) and a higher Ki-67 proliferation index (P < 0.001)., Conclusions: The sensitivity of PET/CT for detecting cutaneous involvement of lymphomas is low for small-cell PCBCL but high for large-cell types, and thus may facilitate therapeutic strategies.

Background: The association between body mass index (BMI) and acne is unclear., Objective: To determine the association between BMI and acne in youths., Methods: A nationwide, population-based, cross-sectional study was conducted in 2002-2015 by using medical data on 600,404 youths during compulsory military service. BMI was measured at age 17 years. Acne was diagnosed by dermatologists. Unadjusted and adjusted odds ratios (aORs) of acne in relation to BMI (stratified into 8 groups) were calculated, with the low-normal group (18.5≤ BMI ≤21.99 kg/m 2 ) serving as the reference., Results: The study included 299,163 males (49.9%) and 301,241 females (50.1%) with a mean age of 18.9 years (standard deviation, 0.6) and 18.7 years (standard deviation, 0.5), respectively, at recruitment. Acne was diagnosed in 55,842 males (18.7%) and 48,969 females (16.3%). The proportion of participants with acne decreased gradually from the underweight to the severely obese group (males, from 19.9% to 13.9%; females, from 16.9% to 11.3%). The findings on multivariable analysis were similar to the unadjusted analysis results, showing the lowest odds of acne in severely obese participants (aOR for males, 0.53; 95% confidence interval, 0.42-0.64; aOR for females, 0.5; 95% confidence interval, 0.37-0.62). The findings persisted in the sensitivity analyses., Limitations: Information was lacking on potential confounders and acne severity., Conclusion: In youths, overweight and obesity are inversely associated with acne in a dose-dependent manner., (Copyright © 2019 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Biologic therapies pose a risk for opportunistic infections, especially for reactivating latent tuberculosis infection (LTBI)., Objective: The aim was to describe the clinical features and mortality rate of active Mycobacterium tuberculosis (TB) in psoriasis patients receiving biologic therapies., Methods: A systematic review of PubMed, Google Scholar, ScienceDirect, Cochrane Library, and ClinicalTrials.gov databases was performed. Studies describing active TB in patients with psoriasis receiving biologic therapy from inception to May 31, 2018 were included. Clinical data as well as mortality rates were recorded., Results: Fifty-one studies were included, evaluating 78 patients with active TB: 11 prospective studies, 13 retrospective, and 27 case reports/series. Most patients (73%) with active TB were male, the mean age was 48 ± 13 years, and 85% were of European or Asian origin. Pre-treatment LTBI screening was negative for 63% of patients. Disease presented in 33% of patients within the first 3 months of treatment, and in 51% within the first 6 months. Most patients (72%) presented with extra-pulmonary TB, and 49% had disseminated disease. The mortality rate was 7%., Limitations: Limitations of this review are its small sample size and inclusion of case reports., Conclusions: Some patients develop active TB despite LTBI screening. Clinicians initiating biologic therapy in patients with psoriasis should be aware of the clinical features of active TB in this scenario.

Background: Bullous pemphigoid (BP) is the most common autoimmune blistering skin disease worldwide. Systemic corticosteroids are considered the mainstay of therapy; however, they may cause significant adverse effects and treatment failures, so additional therapeutic modalities with better safety profiles are required. Rituximab and omalizumab are novel biologic agents administered in recent years for the treatment of BP, yet data regarding their use in the disease are limited., Objective: Our objective was to systematically review the current literature regarding the use of rituximab and omalizumab for the treatment of BP to evaluate their safety and efficacy., Methods: A systematic review of all publications evaluating patients with BP treated with rituximab or omalizumab was performed. The primary outcome was clinical response; secondary outcomes were adverse events and recurrence rate., Results: The systematic review included 35 publications (84 patients: 62 receiving rituximab and 22 receiving omalizumab). In total, 61 of 63 patients had not experienced disease control with systemic corticosteroids before receiving the biologic treatment. Complete response rates were 85% and 84% for rituximab and omalizumab, respectively. The recurrence rate was considerably lower with rituximab (29%) than with omalizumab (80%). Mean time to recurrence was 10.2 and 3.4 months, and adverse effects occurred in 24% and 20% of the patients, respectively., Conclusions: Available data, although potentially limited because of publication bias, suggest that rituximab and omalizumab have similar safety profiles and provide clinical benefit for patients with BP. The reviewed data indicated that rituximab resulted in lower recurrence rates and a longer time until recurrence than omalizumab.

Background: Actinic cheilitis (AC) is a common, chronic premalignant condition resulting from protracted sun exposure affecting the vermilion border of the lower lip. Treatment of AC aims at terminating the progression to squamous cell carcinoma by obliterating the primary lesion, and includes ablative methods; nonablative modalities such as cryotherapy, electrodessication, chemical peeling, topical imiquimod and 5-fluorouracil; and photodynamic therapy (PDT). Daylight-activated PDT, in which natural daylight serves as the light source, showed promising results in the treatment of actinic keratoses with substantially less pain than conventional PDT., Purpose: To determine the safety and efficacy of daylight PDT in a series of patients with AC., Methods: Eleven patients with AC were treated with daylight PDT. All patients underwent repeated treatment sessions until clinical and histological remission were achieved., Results: Cure rate was 91% (10 of 11 patients, three females/eight males; mean age 59.2 ± 14.4 years). Mean number of treatments to attain cure was 2.7. Patients experienced mild erythema and minimal to no pain during treatment., Conclusions: Daylight PDT is a promising modality for the treatment of AC, with impressive cosmetic results and few side effects., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: Acne vulgaris is a common skin disorder with a significant impact on patients' quality of life. There is currently no treatment designated to treat acne lesions and scars concurrently. However, mid-infrared lasers may promote neocollagenesis within atrophic scars, while exerting a beneficial effect on acne lesions. Objectives: To determine the safety and efficacy of an integrated cooling-vacuum-assisted non-fractional 1540-nm Erbium:Glass laser for the treatment of acne lesions and scars. Patients and Methods: Twenty-two patients (8 male, 14 female) with mild-to-moderate acne and moderate-to-severe acne scars were included. Patients were treated using a non-fractional 1540-nm Er:Glass laser (Harmony XL™, Alma Lasers Ltd.). Acne lesions and scars were exposed to 3-4 stacked pulses emitted at a rate of 3Hz for up to two passes per treatment session (spot size, 4 mm; fluence, 400-600 mJ/pulse), receiving overall 3-7 treatments with 2-3-week intervals. Patients were followed-up one and three months following their last treatment. Clinical evaluation including (i) overall aesthetic appearance, (ii) acne lesions, and (iii) acne scars, assessed independently by two dermatologists and graded on a scale of 0 (exacerbation) to 4 (76-100 percent improvement); and (iv) pain perception, adverse effects and patients’ satisfaction. Results: All but one patient completed treatment and follow-up and had moderate-to-significant improvement in all outcomes (overall aesthetic appearance, mean 3.9 [1 month] and 3.75 [3 month] improvement; acne lesions, 3.5 [1 month] and 2.3 [3 month] improvement; scarring 4 [1 month] and 4.2 [3 month] improvement). Pain and adverse effects were mild and transient. Patients' mean satisfaction was 4.2. Conclusion: Cooling-vacuum-assisted 1540 nm laser is a safe and effective modality for the simultaneous treatment of acne lesions and scars.

Background: Solar urticaria (SU) is a rare photodermatosis causing a significant impact on patients' quality of life. Although the condition can be controlled with phototherapy and/or a combination therapy of antihistamines and leukotriene antagonist in most patients, a subset of patients require additional therapy with omalizumab; however, efficacy data are sparse., Objective: The objective of this study was to determine the efficacy and safety of omalizumab for treating SU., Methods: A case series of 5 patients with SU refractory to antihistamine and leukotriene antagonist combination who were treated with omalizumab is described. In addition, a systematic review of studies evaluating patients with SU treated with omalizumab was conducted. The primary outcome was partial/complete clinical response. Secondary outcomes were 10-fold decreases in the baseline minimal urticarial dose and adverse events., Results: Our case series included 5 patients with SU. Monthly omalizumab doses of 150 to 600 mg resulted in clinical improvement in all patients and complete remission in 4. No adverse effects were reported. The systematic review included 22 studies (48 patients). All patients failed to control disease with antihistamines before omalizumab treatment. Patients received omalizumab at monthly doses of 150 to 750 mg over a follow-up period of 4 to 200 weeks. Thirty-eight patients (79%) experienced clinical improvement. Four patients (11%) had mild adverse effects., Conclusions: Omalizumab provided clinical benefits in approximately 80% of patients with SU. Patients failing to improve on standard omalizumab doses may benefit from higher monthly dosages., (Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Current systemic treatments for atopic dermatitis (AD) offer limited efficacy and are often restricted by safety concerns. Biologics may address the unmet need for improved AD therapeutics., Objective: The aim of this study was to evaluate the efficacy and safety of biologic agents in AD., Methods: A systematic review and meta-analysis of studies evaluating AD patients treated with biologics was performed. The primary outcome was the Eczema Area and Severity Index (EASI)-75 response, while secondary outcomes were SCOring Atopic Dermatitis (SCORAD)-75, EASI-50, SCORAD-50, Investigator Global Assessment 0/1 responses, change in responses from baseline, and adverse events., Results: We included 13 randomized controlled trials (RCTs) and 10 observational studies evaluating nine biologics. High-quality evidence was available for dupilumab, nemolizumab and ustekinumab. Pooling five studies, at weeks 12-16 dupilumab 300 mg every week to every 2 weeks achieved EASI-75 responses of 55%, superior to placebo [relative risk (RR) 3.3, 95% confidence interval (CI) 2.9-3.6]. Nemolizumab had similar EASI-75 responses as placebo, but significantly improved pruritus. In online reports, lebrikizumab demonstrated superior EASI-50 responses versus placebo (RR 1.3, 95% CI 1.04-1.7), while tralokinumab had superior SCORAD-50 responses versus placebo, with borderline significance (RR 1.7, 95% CI 0.97-3.1). In two RCTs each, omalizumab and ustekinumab were comparable with placebo, while antithymic stromal lymphopoietin receptor, infliximab, and rituximab lacked adequate evidence of efficacy. All medications had a comparable safety profile to placebo., Limitations: Lack of RCTs and the use of variable outcome measures limited conclusions., Conclusion: Dupilumab is currently the only biologic with robust evidence of efficacy in AD. Nemolizumab, lebrikizumab, and tralokinumab show promise but further data are needed. Longer follow-up and larger studies will establish their safety profile.

Background: Patients with psoriasis on biologic therapies and a history of viral hepatitis carry a risk for reactivation., Objective: We evaluated safety of biologic therapies in psoriasis patients seropositive for hepatitis B or C viruses (HBV, HCV)., Methods: A retrospective cohort study design was used. Clinical and laboratory data for 30 patients undergoing biologic therapy who were seropositive for HBV or HCV were evaluated. Next, a systematic review was performed. Primary outcomes were hepatitis and viral reactivation during therapy. Treatment duration and antiviral prophylaxis were also recorded., Results: Serology indicated HCV infection in 4 patients, past HBV infection in 17 patients, isolated core antibody in 8 patients, and chronic HBV infection in 1 patient. During follow-up (mean 4.85 ± 3.1 years), no patients experienced hepatitis or viral reactivation. The systematic review of the literature included 49 studies comprising 312 patients followed for a mean of 30.9 months. Viral reactivation occurred in 2/175 patients who were seropositive for core antibody and 3/97 with HCV infection (yearly rates, 0.32% and 2.42%, respectively) compared with 8/40 patients with chronic HBV infection (yearly rate, 13.92%). Three of these 8 patients with reactivated HBV infection received antiviral prophylaxis., Limitations: We pooled heterogeneous studies evaluating different biologic therapies., Conclusion: Biologic therapies pose minimal risk for viral reactivation in low-risk patients without hepatitis seropositive for HCV or HBV core antibody but are a considerable risk in patients with chronic HBV infection, highlighting the necessity of antiviral prophylaxis., (Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Opportunistic infections (OIs) are a dreaded adverse effect of immunosuppressive therapy, leading to the use of opportunistic infection prophylaxis (OIP) in many immunosuppressed conditions. However, guidelines for OIP in pemphigus are lacking., Objective: Our objective was to evaluate the approach of leading pemphigus experts towards OIP., Methods: We conducted an online survey of OIP trends., Results: The survey was completed by 33 experts. Prior to initiation of immunosuppressive therapy, 75% routinely screened for hepatitis viruses, and at least half screened for HIV or tuberculosis. Most experts (76%) prescribed OIP but to <10% of their patients, and the most frequent drugs of choice were sulfamethoxazole/trimethoprim and acyclovir. Most experts agreed that treatment with three or more immunosuppressive agents or a previous history of OIs would lead to the use of OIP that was then discontinued with cessation of immunosuppression. The arguments against OIP were the lack of evidence for its necessity and concern about side effects or emergence of resistant pathogens. The surveyed experts treated patients with severe disease in a tertiary care setting, which may have led to an overestimation of the use of OIP. Infectious disease specialists were not included., Conclusion: Substantial disparities exist in approaches to OIP for patients with pemphigus, including the decision to treat, type of treatment, and risk stratification among pemphigus experts.

Background: Allergic contact dermatitis (ACD) is associated with increased production of cytokines. The patch test is the "gold-standard" diagnostic method, but it poses a risk of false results., Objective: To evaluate a novel laboratory technique, the Luminex LiquiChip, which simultaneously measures blood levels of multiple cytokines, as a diagnostic tool in patients with chrome-induced ACD., Methods: The study group included 20 patients with ACD and relevant patch test results for potassium dichromate and 19 patients with ACD for nickel or fragrance as control. Peripheral blood mononuclear cells (PBMCs) were cultured in the presence and absence of potassium dichromate. The Luminex LiquiChip was used to measure levels of the following cytokines: granulocyte-macrophage colony-stimulating factor, interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, interferon-γ, and tumor necrosis factor (TNF)-α., Results: Potassium dichromate-stimulated PBMCs secreted significantly higher amounts of all cytokines except TNF-α than nonstimulated PBMCs. PBMCs from patients with ACD to chromium secreted significantly higher amounts of all cytokines tested, except IL-4, compared to PBMCs from patients with ACD to nickel or fragrance., Conclusions: Potassium dichromate stimulates the production of both Th1- and Th2-type cytokines in patients with chrome allergy. The Luminex LiquiChip is a promising in vitro method and may serve as a diagnostic tool for ACD., (© 2017 S. Karger AG, Basel.)