BACKGROUND:As the incidence of frontal fibrosing alopecia (FFA) continues to rise, there is a need for an optimal treatment algorithm for FFA. OBJECTIVES:To produce an international consensus statement on the treatment modalities and prognostic indicators of FFA. METHODS:Sixty-nine hair experts from six continents were invited to participate in a three-round Delphi process. The final stage was held as a virtual meeting facilitated via Zoom. The consensus threshold was set at ≥66%. RESULTS:Of 365 questions, expert consensus was achieved in 204 (56%) questions following completion of the three rounds. Three additional questions were included at the final meeting. The category with the strongest consensus agreement was disease monitoring (9; 100%). Questions pertaining to physical therapies achieved the least category consensus (15; 40%), followed by systemic therapy (45; 43%). LIMITATIONS:The study lacked sufficient representation from Africa and South America. CONCLUSIONS:SOFFIA highlights areas of agreement and disagreement among experts. Robust research is warranted to provide evidence-based treatment recommendations.

BACKGROUND:Ectodermal dysplasia-syndactyly syndrome (EDSS) is a rare form of ectodermal dysplasia caused by biallelic mutations in NECTIN4 (PVRL4) gene. OBJECTIVES:To identify new and rare mutations of the NECTIN4 gene in two unrelated families with EDSS. METHODS:Six patients from two unrelated families were diagnosed with EDSS. Next generation sequencing and Sanger sequencing were performed on DNA extracted from peripheral blood from affected and unaffected individuals from the families. We performed a literature search to identify previously reported cases of EDSS. RESULTS:A homozygous c.680A>G p.His227Arg mutation in NECTIN4 was found in five affected members of both families. One patient was found to be compound heterozygous for the latter mutation and for another novel missense mutation in NECTIN4 (c.79+1G>A). Both mutations affect the extracellular domain of nectin-4. A literature search identified only 13 reported families affected by this rare disorder. CONCLUSIONS:We described two families with six affected members presenting with EDSS caused by two novel NECTIN4 mutations. We also reviewed the current available data on EDSS in the medical literature.

OBJECTIVE:The familial type of oral lichen planus (OLP) is rare, with a paucity of data regarding its clinical significance. Our objective was to characterize patients with familial OLP. METHODS:Families with at least two members diagnosed with OLP were included. Clinical and demographic data and medical history were recorded. RESULTS:Twenty families, 19 Jewish and 1 Arab, were identified. Of the Jewish families, 57.8% were non-Ashkenazi, originating mainly from central Asia. Of those with OLP there were 14 males and 23 females with an average age of 49.1. Dyslipidemia, cardiovascular, and thyroid disorders (27.7%, 22.2%, and 16.6%, respectively) were the most common comorbidities. Five patients from five distinct families had oral cancer, two with second primary. CONCLUSIONS:To the best of our knowledge, this is the largest study describing familial OLP. The predominant and common ethnicity of the families with multiple members diagnosed with OLP may imply an ethnic tendency. The higher tendency of hypothyroidism and the high percentage of OSCC among familial OLP patients might be connected to familial OLP and the latter suggests that this population is predisposed to malignant transformation. Thus, this group should be considered as a high-risk group.

Abstract Background Alopecia areata (AA) is an auto‐immune disorder characterized by non‐scarring hair loss. With the emergence of effective therapies for severe AA, there is a need to better understand the prognosis of untreated AA, specifically the potential for spontaneous hair regrowth. Objectives To describe hair regrowth occurring on placebo during the first 36 weeks of the BRAVE‐AA trials. Methods This analysis pools the data of 345 placebo‐treated patients from BRAVE‐AA1 and BRAVE‐AA2, two Phase 3 clinical trials of baricitinib, an oral selective Janus kinase inhibitor, approved for the treatment of adults with severe AA. Scalp hair regrowth was assessed by the mean change from baseline in Severity of Alopecia Tool (SALT), the proportion of patients achieving a SALT score ≤20 (less than 20% hair loss); and SALT50 (50% improvement from baseline in SALT score), between Weeks 0 and 36. Patients achieving Clinician Reported Outcome (ClinRO) measures for eyebrow and eyelash hair loss™ scores of 0 or 1 (full coverage or minimal gaps) with a ≥2‐point improvement from baseline were also assessed. Results At Week 36, the mean [SD] change from baseline in SALT score was −5.5 [20.9], with 14 (4.1%) and 32 (9.3%) of the 345 placebo‐treated patients achieving a SALT score ≤20 and SALT50, respectively. A total of 9 (3.8%) and 8 (4.3%) patients achieved a ClinRO score of 0 or 1 with a ≥2‐point improvement from baseline for eyebrow (n = 236) and eyelash (n = 186), respectively. Patients achieving a SALT score ≤20 tended to have a lower mean SALT score at baseline and a shorter duration since the onset of AA. Conclusions The low likelihood of spontaneous hair regrowth observed in the BRAVE‐AA trials is consistent with other published literature. These results can aid in understanding the prognosis of severe AA when left untreated and, in turn, inform treatment‐related decisions.

The caspase activation and recruitment domain 11 (CARD11) gene encodes a scaffold protein required for lymphocyte antigen receptor signaling. Dominant-negative, loss-of-function (LOF) pathogenic variants in CARD11 result in CARD11-associated atopy with dominant interference of NF-κB signaling (CADINS) disease. Patients with CADINS suffer with severe atopic manifestations including atopic dermatitis, food allergy, and chronic spontaneous urticaria in addition to recurrent infections and autoimmunity. We assessed the response of dupilumab in five patients and omalizumab in one patient with CADINS for the treatment of severe atopic symptoms. CARD11 mutations were validated for pathogenicity using a T cell transfection assay to assess the impact on activation-induced signaling to NF-κB. Three children and three adults with dominant-negative CARD11 LOF mutations were included. All developed atopic disease in infancy or early childhood. In five patients, atopic dermatitis was severe and recalcitrant to standard topical and systemic medications; one adult suffered from chronic spontaneous urticaria. Subcutaneous dupilumab was initiated to treat atopic dermatitis and omalizumab to treat chronic spontaneous urticaria. All six patients had rapid and sustained improvement in atopic symptoms with no complications during the follow-up period. Previous medications used to treat atopy were able to be decreased or discontinued. In conclusion, treatment with dupilumab and omalizumab for severe, refractory atopic disease in patients with CADINS appears to be effective and well tolerated in patients with CADINS with severe atopy.

BACKGROUND Baricitinib, an oral, selective, reversible Janus kinase (JAK)1/JAK2 inhibitor, is an approved treatment for adults with severe alopecia areata (AA) in the USA, European Union and Japan. OBJECTIVES To report safety data for baricitinib in patients with severe AA from two clinical trials including long-term extension periods. METHODS This analysis includes pooled patient-level safety data from two trials, an adaptive phase II/III trial (BRAVE-AA1) and a phase III trial (BRAVE-AA2) (ClinicalTrials.gov, NCT03570749 and NCT03899259). Data are reported in three datasets: (i) the placebo-controlled dataset (up to week 36): baricitinib 2 mg and 4 mg vs. placebo; (ii) the extended dataset (up to the data cutoff): patients remaining on continuous treatment with baricitinib 2 mg or 4 mg from baseline; and (iii) the all-baricitinib dataset (all-BARI, up to the data cutoff): all patients receiving any dose of baricitinib at any time during the trials. Safety outcomes include treatment-emergent adverse events (TEAEs), adverse events of special interest and abnormal laboratory changes. Proportions of patients with events and incidence rates (IR) were calculated. RESULTS Data were collected for 1303 patients who were given baricitinib, reflecting 1868 patient-years of exposure (median 532 days). The most frequently reported TEAEs during the placebo-controlled period (based on the baricitinib 4-mg group) were upper respiratory tract infection, nasopharyngitis, headache, acne and elevated blood creatine phosphokinase (CPK). During the placebo-controlled period, the frequency of acne was higher with baricitinib than placebo, and elevated CPK was higher with baricitinib 4 mg than placebo and baricitinib 2 mg. In all-BARI, the IR of serious infections was low (n = 16, IR 0.8). There was one opportunistic infection (IR 0.1), and 34 cases of herpes zoster (IR 1.8). There was one positively adjudicated major adverse cardiovascular event (myocardial infarction) (IR 0.1), one pulmonary embolism (IR 0.1), three malignancies other than nonmelanoma skin cancer (IR 0.2) and one gastrointestinal perforation (IR 0.1). No deaths were reported. CONCLUSIONS This integrated safety analysis in patients with severe AA is consistent with the overall safety profile of baricitinib. Some differences with atopic dermatitis were noted that may be attributable to the disease characteristics of AA.

Melanoma is widely treated with programmed cell death-1 (PD-1) inhibitors. As part of their anti-tumor immunity effect, they increase the susceptibility to cutaneous immune-related adverse events (cIRAE) among other autoimmune effects. To characterize the manifestations of cIRAE in melanoma patients treated with PD-1 inhibitors, and evaluate the correlation with tumor response. A retrospective study of 95 metastatic malignant melanoma patients treated with PD-1 inhibitors at the Hadassah Medical Center during 2013-2016. The most common cIRAE was pruritus reported by 39 (41%) patients. All other cIRAE were noted in 34 patients (35.8%), of which the most common cutaneous manifestation was vitiligo, demonstrated in 17 patients (17.9%) followed by various rashes (7.4%, including erythema multiforme, oral lichen planus, photosensitive rash, insect bite-like reaction, and urticaria), psoriasiform rash (3.2%), bullous pemphigoid (3.2%), and eczema (1%). Interestingly, higher response rates to immunotherapy were demonstrated in patients who developed pruritus (85%) and cIRAE (88%), with lower mortality rates in the cIRAE group (38.2%) versus the non-cIRAE group (70.5%, p = 0.002). cIRAE are common among malignant melanoma patients treated with PD-1 inhibitors and may be a marker for favorable prognosis.

Immune checkpoint receptors (ICR) modulate the immune response and are critical hubs for immunotherapy. However, data on their role in T lymphoid malignancies, such as cutaneous T cell lymphoma (CTCL), is sparse. We aimed to explore the role of ICR in the malignant features of transformed T lymphocytes and evaluate the effect of ICR-targeting monoclonal antibodies, often used as immunotherapy for solid tumors. We used the CTCL cell line HH and the Sézary cell line Hut78 to examine ICR expression and the effects of ICR inhibition on cell viability and proliferation. Despite their shared T cell progeny, the different CTCL cell lines exhibit markedly different ICR expression profiles. Programmed cell death-ligand 1 (PD-L1) was expressed by both cell lines, while programmed death-1 (PD-1) was expressed only by the HH cell line. Common to all malignant T cells was an autonomous hyper-proliferative state that did not require T cell receptor stimulation. A monoclonal antibody blocking PD-1 had a small but statistically significant augmenting effect on T cell proliferation. Of note, when the cells were exposed to ionizing radiation, healthy lymphocytes and those derived from the HH cell line were salvaged by anti-PD-L1. We show a regulatory role of ICR, mainly PD-1 and its ligand PD-L1, on cutaneous T cell malignancy.

BACKGROUND:Alopecia areata is an autoimmune condition characterized by rapid hair loss in the scalp, eyebrows, and eyelashes, for which treatments are limited. Baricitinib, an oral, selective, reversible inhibitor of Janus kinases 1 and 2, may interrupt cytokine signaling implicated in the pathogenesis of alopecia areata.METHODS:We conducted two randomized, placebo-controlled, phase 3 trials (BRAVE-AA1 and BRAVE-AA2) involving adults with severe alopecia areata with a Severity of Alopecia Tool (SALT) score of 50 or higher (range, 0 [no scalp hair loss] to 100 [complete scalp hair loss]). Patients were randomly assigned in a 3:2:2 ratio to receive once-daily baricitinib at a dose of 4 mg, baricitinib at a dose of 2 mg, or placebo. The primary outcome was a SALT score of 20 or less at week 36.RESULTS:We enrolled 654 patients in the BRAVE-AA1 trial and 546 in the BRAVE-AA2 trial. The estimated percentage of patients with a SALT score of 20 or less at week 36 was 38.8% with 4-mg baricitinib, 22.8% with 2-mg baricitinib, and 6.2% with placebo in BRAVE-AA1 and 35.9%, 19.4%, and 3.3%, respectively, in BRAVE-AA2. In BRAVE-AA1, the difference between 4-mg baricitinib and placebo was 32.6 percentage points (95% confidence interval [CI], 25.6 to 39.5), and the difference between 2-mg baricitinib and placebo was 16.6 percentage points (95% CI, 9.5 to 23.8) (P<0.001 for each dose vs. placebo). In BRAVE-AA2, the corresponding values were 32.6 percentage points (95% CI, 25.6 to 39.6) and 16.1 percentage points (95% CI, 9.1 to 23.2) (P<0.001 for each dose vs. placebo). Secondary outcomes for baricitinib at a dose of 4 mg but not at a dose of 2 mg generally favored baricitinib over placebo. Acne, elevated levels of creatine kinase, and increased levels of low- and high-density lipoprotein cholesterol were more common with baricitinib than with placebo.CONCLUSIONS:In two phase 3 trials involving patients with severe alopecia areata, oral baricitinib was superior to placebo with respect to hair regrowth at 36 weeks. Longer trials are required to assess the efficacy and safety of baricitinib for alopecia areata. (Funded by Eli Lilly under license from Incyte; BRAVE-AA1 and BRAVE-AA2 ClinicalTrials.gov numbers, NCT03570749 and NCT03899259.).

JDDG: Journal der Deutschen Dermatologischen GesellschaftVolume 20, Issue 8 p. 1123-1124 Clinical LetterFree Access Six cases of pityriasis rosea following SARS-CoV-2 vaccination with BNT162b2 Yuval Ramot, Yuval Ramot Department of Dermatology, Hadassah Medical Center, Hebrew University of Jerusalem, Faculty of Medicine, Jerusalem, IsraelSearch for more papers by this authorKrassimira Nanova, Krassimira Nanova Clalit Health Services, Jerusalem, IsraelSearch for more papers by this authorSofia-Maria Faitatziadou, Sofia-Maria Faitatziadou Department of Dermatology, Hadassah Medical Center, Hebrew University of Jerusalem, Faculty of Medicine, Jerusalem, IsraelSearch for more papers by this authorDania Abu Assab, Dania Abu Assab Department of Dermatology, Hadassah Medical Center, Hebrew University of Jerusalem, Faculty of Medicine, Jerusalem, IsraelSearch for more papers by this authorYackov Berkun, Yackov Berkun Department of Pediatrics, Hadassah Mount Scopus Medical Center, Hebrew University of Jerusalem, Faculty of Medicine, Jerusalem, IsraelSearch for more papers by this authorAbraham Zlotogorski, Corresponding Author Abraham Zlotogorski zloto@cc.huji.ac.il Department of Dermatology, Hadassah Medical Center, Hebrew University of Jerusalem, Faculty of Medicine, Jerusalem, Israel Correspondence to Abraham Zlotogorski, MD Department of Dermatology Hadassah Medical Center Hebrew University of Jerusalem, The Faculty of Medicine Jerusalem, 9112001, Israel E-mail: zloto@cc.huji.ac.ilSearch for more papers by this author Yuval Ramot, Yuval Ramot Department of Dermatology, Hadassah Medical Center, Hebrew University of Jerusalem, Faculty of Medicine, Jerusalem, IsraelSearch for more papers by this authorKrassimira Nanova, Krassimira Nanova Clalit Health Services, Jerusalem, IsraelSearch for more papers by this authorSofia-Maria Faitatziadou, Sofia-Maria Faitatziadou Department of Dermatology, Hadassah Medical Center, Hebrew University of Jerusalem, Faculty of Medicine, Jerusalem, IsraelSearch for more papers by this authorDania Abu Assab, Dania Abu Assab Department of Dermatology, Hadassah Medical Center, Hebrew University of Jerusalem, Faculty of Medicine, Jerusalem, IsraelSearch for more papers by this authorYackov Berkun, Yackov Berkun Department of Pediatrics, Hadassah Mount Scopus Medical Center, Hebrew University of Jerusalem, Faculty of Medicine, Jerusalem, IsraelSearch for more papers by this authorAbraham Zlotogorski, Corresponding Author Abraham Zlotogorski zloto@cc.huji.ac.il Department of Dermatology, Hadassah Medical Center, Hebrew University of Jerusalem, Faculty of Medicine, Jerusalem, Israel Correspondence to Abraham Zlotogorski, MD Department of Dermatology Hadassah Medical Center Hebrew University of Jerusalem, The Faculty of Medicine Jerusalem, 9112001, Israel E-mail: zloto@cc.huji.ac.ilSearch for more papers by this author First published: 14 June 2022 https://doi.org/10.1111/ddg.14784AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume20, Issue8August 2022Pages 1123-1124 RelatedInformation

BACKGROUND:Ultraviolet (UV) A1 phototherapy is considered a beneficial treatment for various inflammatory, sclerotic, malignant, and other skin conditions. However, the available data regarding its efficacy for different indications, the potential side effects, and the recommended treatment protocols are sparse. OBJECTIVES:To assess the efficacy of UVA1 phototherapy and identify correlation between different indications and treatment protocols to response rates. METHODS:We performed a retrospective study of a cohort of 335 patients treated with UVA1 phototherapy at the Department of Dermatology at Hadassah Medical Center, Jerusalem, Israel, between 2008 and 2018. RESULTS:The study population included 163 patients with inflammatory diseases (mainly atopic dermatitis and other types of eczema), 67 patients with sclerotic diseases (morphea and graft versus host disease), nine patients with neoplastic diseases (cutaneous T cell lymphoma), and 188 patients with other cutaneous disorders. Response rates ranged between 85% and 89% across indications, without differences in response rates among the indication groups (p = .941). In a multivariant logistic regression model, increased number of treatments and higher maximal dosages were associated with response to treatment (p < .001). Using ROC analysis, a cut-off of 8 UVA1 phototherapy treatments was chosen as predictive for beneficial response (86.4% sensitivity, 78% specificity). A cut-off of 40 J/cm2 was chosen as an optimal maximal dosage for differentiating between responders and non-responders (51.1% sensitivity, 83.1% specificity). CONCLUSIONS:UVA1 phototherapy is an effective treatment for a variety of skin conditions. In most patients, at least eight treatments of a medium-high dosage are required for clinical response.

ABSTRACTBackgroundContinuous, subcutaneous (SC) levodopa/carbidopa infusion with ND0612 is under development as a treatment for patients with Parkinson's disease (PD) and motor fluctuations.ObjectiveEvaluate 1‐year safety data.MethodsBeyoND is an open‐label study evaluating the long‐term safety of two ND0612 dosing regimens.ResultsOf the 214 enrolled patients (24‐hour SC infusion: n = 90; 16‐hour SC infusion: n = 124), 120 (56%) completed 12 months of treatment. Leading causes for study discontinuation were consent withdrawal (19.6%) and adverse events (17.3%). Rates of discontinuation were reduced from 49% to 29% after a protocol revision and retraining. Systemic safety was typical for PD patients treated with levodopa/carbidopa. Most patients experienced infusion site reactions, particularly nodules (30.8%) and hematoma (25.2%), which were judged mostly mild to moderate and led to discontinuation in only 10.3% of the participants.ConclusionsSubcutaneous levodopa/carbidopa continuous infusion with ND0612 is generally safe, with typical infusion site reactions for SC delivery as the main adverse event. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Abstract is missing (Short communication)

Signal transducer and activator of transcription (STAT)1 heterozygous gain‐of‐function (GOF) mutations are known to induce immune dysregulation and chronic mucocutaneous candidiasis (CMCC). Previous reports suggest an association between demodicosis and STAT1 GOF. However, immune characterization of these patients is lacking. Here, we present a retrospective analysis of patients with immune dysregulation and STAT1 GOF who presented with facial and ocular demodicosis. In‐depth immune phenotyping and functional studies were used to characterize the patients. We identified five patients (three males) from two non‐consanguineous Jewish families. The mean age at presentation was 11.11 (range = 0.58–24) years. Clinical presentation included CMCC, chronic demodicosis and immune dysregulation in all patients. Whole‐exome and Sanger sequencing revealed a novel heterozygous c.1386C>A; p.S462R STAT1 GOF mutation in four of the five patients. Immunophenotyping demonstrated increased phosphorylated signal transducer and activator of transcription in response to interferon‐α stimuli in all patients. The patients also exhibited decreased T cell proliferation capacity and low counts of interleukin‐17‐producing T cells, as well as low forkhead box protein 3+ regulatory T cells. Specific antibody deficiency was noted in one patient. Treatment for demodicosis included topical ivermectin and metronidazole. Demodicosis may indicate an underlying primary immune deficiency and can be found in patients with STAT1 GOF. Thus, the management of patients with chronic demodicosis should include an immunogenetic evaluation.

Background: We previously reported the Alopecia Areata Consensus of Experts study, which presented results of an international expert opinion on treatments for alopecia areata. Objective: To report the results of the Alopecia Areata Consensus of Experts international expert opinion on diagnosis and laboratory evaluation for alopecia areata. Methods: Fifty hair experts from 5 continents were invited to participate in a 3-round Delphi process. Consensus threshold was set at greater than or equal to 66%. Results: Of 148 questions, expert consensus was achieved in 82 (55%). Round 1 consensus was achieved in 10 of 148 questions (7%). Round 2 achieved consensus in 47 of 77 questions (61%). The final face-to-face achieved consensus in 25 of 32 questions (78%). Consensus was greatest for laboratory evaluation (12 of 14 questions [86%]), followed by diagnosis (11 of 14 questions [79%]) of alopecia areata. Overall, etiopathogenesis achieved the least category consensus (31 of 68 questions [46%]). Limitations: The study had low representation from Africa, South America, and Asia. Conclusion: There is expert consensus on aspects of epidemiology, etiopathogenesis, clinical features, diagnosis, laboratory evaluation, and prognostic indicators of alopecia areata. The study also highlights areas where future clinical research could be directed to address unresolved hypotheses in alopecia areata patient care.