Background . Psoralen plus ultraviolet A (PUVA) is the preferred phototherapeutic modality for early-stage folliculotropic mycosis fungoides (FMF), and for early-stage non-FMF refractory to narrow-band ultraviolet B (NBUVB). However, PUVA has a problematic safety profile. Literature on the treatment with the combination of UVA and NBUVB for MF is sparse. Objective . To evaluate the effectiveness of UVA combined with NBUVB for early-stage MF, specifically for FMF and NBUVB-refractory non-FMF, in adult and pediatric patients. Methods . A retrospective analysis was conducted for patients treated with UVA combined with NBUVB at our center, during 1/2008–8/2022. Results . The cohort included 51 patients: 35 adults and 16 pediatric patients. The overall response rate (ORR) of 39 patients with early-FMF (25 adults and 14 children) was 95%, and the complete response (CR) was 62%. No significant differences in ORR/CR rates were noted between adult and pediatric patients. Of 12 patients with non-FMF (10 adults and 2 children), the ORR was 83% and the CR was 50%. In 17 patients (8 FMF and 9 non-FMF), prior NBUVB therapy resulted in partial response/stable disease; yet, UVA + NBUVB led to CR in 9 patients (4 FMF and 5 non-FMF). Side effects were minimal. Conclusion . Combined UVA and NBUVB is a good alternative to PUVA for adult or pediatric patients with early-stage MF , with FMF or non-FMF refractory to NBUVB.

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.

Background: The clinical diagnosis of papular eruptions is common but poorly characterized in the literature and the etiology is often unknown. Objective: To characterize the entity of idiopathic papular dermatitis in the spectrum of chronic papular eruptions. Methods: The cohort consisted of patients who presented at a tertiary medical center in 2005–2014 with a papular eruption of at least 4 months’ duration. Findings on histological analysis and thorough clinical investigation, performed in all cases, were collected. The patients completed a questionnaire on disease course and outcome. Results: Sixty-five patients were included. Sixteen patients showed morphological changes over time and were excluded. Investigations in the remaining 49 patients with a consistent papular morphology yielded a well-defined diagnosis in 23 (46%). Twenty-six patients (54%; 14 male) were diagnosed with idiopathic papular dermatitis. Their mean age at onset was 61.6 ± 14.4 years and the mean duration of disease 3.11 ± 2.726 years. In 60%, the rash resolved with conservative treatment during follow-up (mean 4.35 ± 2.53 years). Conclusions: Chronic papular eruptions encompass a wide range of skin diseases. In more than half of the cases, the etiopathogenesis remains unclear. On the basis of our results, we propose a diagnostic algorithm for idiopathic papular dermatitis.

10092 Background: Epidermal growth factor receptor inhibitors (EGFR-I), which are indicated for various tumor types, are associated with acneiform rash on the face/torso in approximately 90% of patients. This rash adversely impact patients' quality-of-life and may result in dose reductions/delays and treatment discontinuation. Methods: This randomized double blind trial investigated chloramphenicol 3% + prednisolone 0.5% (Threolone) vs chloramphenicol 3% vs aqua cream as prophylactic treatment for acneiform rash caused by EGFR-I. Adult cancer patients treated with EGFR-I (cetuximab, panitumumab, erlotinib, or gefitinib) were randomized to treatment with the 3 above mentioned options and were instructed to administer the assigned topical treatment to their face daily for 3 weeks and every 2 days for another week. The severity of the rash was assessed using the Common Terminology Criteria for Adverse Events (CTCAE) v4.0 as well as the number of facial lesions. Severe rash was defined as grade≥3 by the CTCAE criteria or ≥10 facial lesions. The rash was assessed on Days 0, 14, and 28. Results: Overall, 69 patients were randomized (21 chloramphenicol 3% + prednisolone 0.5%, 23 chloramphenicol 3%, and 25 aqua cream). The arms were similar with respect to demographics and tumor types. Number of facial lesions and CTCAE grade were highly correlated (r = 0.9). According to the number of facial lesions, chloramphenicol + prednisolone but not chloramphenicol alone was significantly more effective than aqua cream (Table). Conclusions: Topical chloramphenicol 3% + prednisolone 0.5% may be an effective prophylactic treatment for EGFR-I-associated acneiform rash. Clinical trial information: NCT01256437. Proportion of patients with protocol specified severe acneiform rash. Study arm N Day 14 Day 28 Day 14 or 28 Severity by CTCAE, % Severity by NOL, % Severity by CTCAE, % Severity by NOL, % Severity by CTCAE, % Severity by NOL, % Chloramphenicol 3% + prednisolone 0.5% 21 0 14a 0 6a 0 19a Chloramphenicol 3% 23 5 40 5 16 5 39 Aqua cream 25 20 48 5 43 20 52 aP< 0.05 vs aqua cream treatment. All other 2-way comparisons were non-significant. NOL: number of lesions

SummaryThe gold‐standard method for dermatophyte identification involves direct microscopy and culture, which have inherent shortcomings. Only few molecular methods have been standardised for routine clinical work. This study aimed to develop and test a platform for identifying the most common dermatophytes in Israel using multiplex real‐time polymerase chain reaction (RT‐PCR). Specific primers were designed for the multiplex system (LightCycler 480) according to known cultures and validated by reference isolates. The dermatophyte detection rate was compared to smear and culture in 223 clinical samples obtained from a tertiary medical centre. Inconsistencies between methods were evaluated by sequencing. The RT‐PCR was further evaluated in 200 community‐based samples obtained from a health maintenance organisation and 103 military‐personnel‐based samples analysed at a central laboratory. In hospital‐based clinical samples, complete concordance between methods was observed in 190 samples (85%; Kappa = 0.69). In most cases of non‐concordance, sequencing was consistent with RT‐PCR results. RT‐PCR correctly identified all smear‐ and culture‐positive cases in community and military‐personnel samples. The results were available within 4 hours. The multiplex RT‐PCR platform is a rapid and efficient method for identifying dermatophyte species in clinical samples and may serve as a first step in the diagnostic algorithm of superficial fungal infections.

BACKGROUND:CF101, an adenosine A3 receptor agonist, is an orally bioavailable small molecule drug presenting an anti-psoriatic effect demonstrated in a Phase 2 clinical trial in psoriasis patients.OBJECTIVE:To evaluate the safety and efficacy of CF101 treatment in a Phase 2/3 study in patients with moderate to severe plaque-type psoriasis.METHODS:This multicenter, double-blind, 2-segment, placebo-controlled study randomized subjects with moderate to severe plaque psoriasis to CF101 1 or 2 mg, or placebo twice daily. At either week 12 (Segment 1) or 16 (Segment 2), the placebo group crossed over to CF101 BID through week 32 in an open-label fashion. At week 12, following an interim analysis, the CF101 1mg group was discontinued due to futility. The primary endpoint was proportion of patients achieving ≥75% improvement in Psoriasis Area Severity Index (PASI 75). Efficacy testing was performed using the Cochran-Mantel Haenszel test, the primary analysis of PASI 75 was performed at the 0.035 significance level.RESULTS:CF101 had an excellent safety profile at all tested dosages with a profile similar to the placebo group. The most common adverse events were infections and gastrointestinal events, and there was no cumulative intolerance over the 32-week dosing period. The study did not meet the primary endpoint of PASI 75 at week 12 (2 mg: 8.5% vs. placebo: 6.9%, P=0.621). However, at week 32, PASI mean percent improvement with CF101 2 mg was 57% (P<0.001) compared to baseline, with linear improvement in PASI 50 (63.5%), 75 (35.5%), 90 (24.7%), and 100 (10.6%).CONCLUSIONS:Oral CF101 was found to be safe and very well tolerated, demonstrating evidence of efficacy in patients with moderate to severe plaque psoriasis through 32 weeks of treatment.J Drugs Dermatol. 2016;15(8):931-938.

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.

Psoriasis is a multifactorial chronic inflammatory disease. Monogenic psoriasis has been described recently, including dominantly inherited plaque and generalized pustular types, related to activating mutations in the CARD14 gene. We describe here a family with CARD14-related psoriasis, exhibiting an extreme variability of clinical presentation (from mild plaque-type to generalized pustular psoriasis) and early disease onset. The affected family members harboured the c.349G>A [p.Gly117Ser] mutation in CARD14, which has not previously been linked to pustular psoriatic phenotype. Furthermore, most severely affected individuals carried 3 additional CARD14 coding region polymorphisms (rs2066964, rs34367357 and rs11652075), suggesting their possible effect on disease expression. Early-onset psoriasis co-segregated with the HLA-C*0602, indicating that HLA-C*0602 could potentially modulate the time of disease onset. In summary, this paper describes a family with CARD14-related psoriasis and discusses the possible influence of the specific haplotypes on intra-familial variation in the clinical phenotype of the disease.

There are no studies of the possible association of the human leukocyte antigen (HLA) system with lichen planopilaris (LPP). To determine whether the HLA system is associated with LPP, 40 consecutive Jewish Israeli patients with LPP (study group) and 252 volunteers (controls) were typed for DRB1*and DQB1* loci by molecular methods. Compared with controls, the study group had a significantly higher frequency of the DRB1*11 allele (62% vs. 21%, corrected p-value (pc)=0.001) owing to increased frequencies of DRB1*11: 01 and DRB1*11: 04. The DQB1*03 allele was also expressed at a significantly higher frequency in the study group (70% vs. 33%, pc=0.0005); specifically, the frequency of DQB1*03: 01 was increased. The majority (82.5%) of the patients were of non-Ashkenazi origin. We conclude that LPP appears to be over-represented in non-Ashkenazi Jewish patients and is associated with an increased frequency of HLA DRB1*11 and DQB1*03 alleles. These findings suggest that immunogenetic factors play a role in LPP.

Rituximab has recently been reported in retrospective studies to be effective in pemphigus at the dosing schedule used for treating rheumatoid arthritis (RA) of two 1,000 mg infusions 2 weeks apart. While the effect of rituximab on B cells has been well described, its effect on global T cell function has not been assessed. Ten patients who received RA dosage rituximab were prospectively assessed for clinical response. Immunological response including autoantibody titers, CD20+ B cell, and CD4+ T cell counts was assessed pre- and post-treatment. The CD4+ T cell function was determined by a novel assay measuring intracellular ATP levels in response to mitogenic stimulus. At 6 months, 90 % of patients achieved remission. Disease control and remission were achieved at median times of 1 and 3.7 months, respectively. There was a 67 % relapse rate during an average follow-up of 22 months. Global CD4+ T cell numbers and function were preserved 3 months after rituximab. A single cycle of RA dosage rituximab with concomitant immunosuppression is effective in pemphigus. We did not find an effect on total CD4+ T cell numbers or function 3 months after treatment.

Selective IgE deficiency (IgED) is currently defined as a significant decrease in serum levels of IgE (<2 kIU/L) in a patient whose other immunoglobulin levels are normal. There are no published large-scale epidemiological studies regarding the prevalence of and clinical features of IgED. In the population-based case-control study, we investigated clinical and laboratory characteristics of patients with IgED. Case samples were drawn from all subjects (n = 18487), with serum total IgE measurement during 2012 at Leumit Health Care Services (Israel) and had serum total IgE of <2 kIU/L. The control group was randomly sampled from the remaining 18,261 subjects with a case-control ratio of four controls for each case (1:4). Comorbid diseases were identified by specific International Classification of Diseases, Ninth Revision, Clinical Modification diagnostic codes given by the corresponding board-certificated physicians. Two hundred twenty-six subjects showed serum total IgE levels of <2 kIU/L; 68 (30.9%) were between the ages of 4 and 12 years (children) and 250 (69.1%) were ≥12 years old (adults). Matched control groups were selected for each age group. The children group was characterized by higher prevalence of asthma and hyperreactive airways disease; and both children and adult groups had significantly higher prevalence of chronic sinusitis, otitis media, autoimmune, and oncological diseases than their respective controls. Undetectable serum total IgE may serve as a marker of immune dysregulation and autoimmunity.

BACKGROUND:Opportunistic infections (OIs) can be defined as infections in immunosuppressed patients that are more frequent or severe because of immunosuppression. The literature on OIs in pemphigus is sparse.OBJECTIVE:We assessed the incidence, risk factors, and characteristics of OIs in patients with pemphigus.METHODS:This was a historical prospective study following a cohort of 172 patients with newly diagnosed pemphigus for the development of OIs.RESULTS:Fourteen patients developed OIs at a mean of 4 months from the time of diagnosis while taking a mean dose of 0.8 mg/kg/day of prednisone, 5 in conjunction with azathioprine. The risk of developing an OI in the first year after the diagnosis of pemphigus was 9.3%, subsequently dropping to 0. Advanced age and possibly diabetes were found to be risk factors for OI development. Infectious agents included Nocardia, cytomegalovirus, Legionella, and Listeria. Two patients died within 2 months of OI diagnosis, and 2 more had neurologic impairment.LIMITATIONS:Limitations include the extraction of historical data and the cohort originating from a single geographic region.CONCLUSION:OIs present in a significant number of patients with pemphigus during the first year after the diagnosis of pemphigus, with potential deleterious effects. Older and possibly diabetic patients are at increased risk. Physician vigilance and patient education on limiting pathogen exposure is recommended.

BACKGROUND:The literature on mycosis fungoides (MF) in children/adolescents is sparse.OBJECTIVE:We sought to evaluate the characteristics of juvenile MF in a large cohort.METHODS:Data were collected on all patients with MF, aged 18 years or younger at the time of clinicopathologic diagnosis, who attended the Rabin Medical Center Dermatology Department, Petach Tikva, Israel, between 1994 and 2012 and were followed up prospectively.RESULTS:There were 50 patients (30 male; mean age 11.4 years at diagnosis); 18 (36%) had Fitzpatrick skin type IV or higher. All were given a diagnosis of early-stage disease (IA-IIA) except 1 (tumor stage, IIB). Eight had classic MF lesions only and 42 had other variants, alone or in combination; these were mainly hypopigmented MF (n = 29) and cases with subtle but clear clinicopathologic features of folliculotropic MF (FMF) (n = 18). Among the various skin-targeted therapies, psoralen plus ultraviolet A (systemic/bath) proved beneficial for FMF. During a follow-up period of 0.25 to 15 years (mean 4.5), 2 patients progressed from stage IA to IB or IIA.LIMITATIONS:Relatively short follow-up is a limitation.CONCLUSIONS:This case series shows that FMF is not uncommon in children and adolescents. It is characterized by more superficial clinical features and less heavy perifollicular lymphocytic infiltrates than adult FMF, and responds well to psoralen plus ultraviolet A. The prognosis of childhood FMF remains unclear.

In a recently published issue of the journal, Bracke et al. demonstrate an impressive improvement in psoriasiform features in allogeneic human skin grafts transplanted onto immune-deficient mice. This improvement was achieved using a novel nanosome (SECosome) as a vehicle for delivering topically applied siRNA to human epidermis. Targeting the gene DFB4 with this delivery system, they prevented translation of the antimicrobial peptide, human β defensin-2(hBD2), thus normalizing the psoriasiform epidermal phenotype of siRNA/SECosome-treated human skin grafts. This study encourages the exploration of topical gene silencing strategies in dermatology and refocuses our attention on both, the role of hBD2 in psoriasis pathogenesis and the thorny question which animal model reflects human psoriasis most faithfully.

Background: Rituximab is increasingly being appreciated as a remarkably effective treatment for pemphigus, mostly concomitantly with other immunosuppressive medications. The majority of studies have used a single cycle of rituximab with the same dosage as approved for the treatment of lymphomas, ie, 375 mg/m(2) weekly x 4 weeks. Rituximab is also approved for the treatment of rheumatoid arthritis, with a different dosing regimen: 1000 mg x 2, days 1 and 15.Objective: We aimed to assess the clinical response of patients with pemphigus to a single cycle of rituximab at the dosage used in rheumatoid arthritis. We also evaluated the response to repeated cycles of rituximab.Methods: A total of 47 patients with pemphigus who were treated with rituximab at a dosage of 1000 mg x 2, days 1 and 15, most with concurrent immunosuppressive medications, were retrospectively studied.Results: Remission rates after the first treatment cycle reached 76%. Repeating the treatment further increased the remission rates to 91%. There was a 22% relapse rate at a median time of 8 months, but 75% of relapsing patients achieved remission again with additional cycles. The side-effect profile was similar to previous reports, except for an immediate postinfusion pemphigus exacerbation in 4 patients.Limitations: This was a retrospective study with a limited follow-up period.Conclusion: The rheumatoid arthritis dosage of rituximab was efficacious and well tolerated in patients with pemphigus. Patients who fail to achieve remission after 1 cycle or patients who relapse seem to benefit from repeated rituximab cycles. (J Am Acad Dermatol 2013;68:404-11.)