193 results on '"Abraham, Zlotogorski"'
Search Results
2. The efficacy of off-label IL-5-modulating treatment in rare eosinophil-mediated diseases
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Oded Shamriz, Alon Y. Hershko, Aviv Talmon, Yaarit Ribak, Anat Scheiman Elazary, Liran Horev, Adeeb NaserEddin, Tzahi Neuman, Sheer Shabat, Abraham Zlotogorski, and Yuval Tal
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Immunologic diseases. Allergy ,RC581-607 - Published
- 2021
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3. Exacerbation of Hailey-Hailey Disease Following SARS-CoV-2 Vaccination
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Gil Armoni-Weiss, Sivan Sheffer-Levi, Liran Horev, Laurent Klapholz, Emily Avitan-Hersh, Abraham Zlotogorski, and Yuval Ramot
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hailey-hailey ,sars-cov-2 ,covid-19 ,mrna vaccine ,vaccination ,genodermatosis ,Dermatology ,RL1-803 - Abstract
Abstract is missing (Short communication)
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- 2021
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4. Multiple Nasal Papules in a 12-year-old Boy: A Quiz
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Dania Abu Assab, Alexander Maly, Abraham Zlotogorski, and Vered Molho-Pessach
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nasal papules ,eccrine hidrocystoma ,pediatric ,Dermatology ,RL1-803 - Published
- 2020
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5. Integrated safety analysis of baricitinib in adults with severe alopecia areata from two randomized clinical trials
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Brett King, Arash Mostaghimi, Yutaka Shimomura, Abraham Zlotogorski, Gwang-Seong Choi, Ulrike Blume-Peytavi, Thierry Passeron, Katrin Holzwarth, Yves Dutronc, Jill McCollam, Fan Emily Yang, Sarah Stanley, Wen-Shuo Wu, and Rodney Sinclair
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Dermatology - Abstract
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.
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- 2022
6. Efficacy of ultraviolet <scp>A</scp> 1 phototherapy for inflammatory, sclerotic and neoplastic dermatological diseases: A 10‐year tertiary referral center experience
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Shachar Ronen, Yuval Ramot, Abraham Zlotogorski, and Rony Shreberk‐Hassidim
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Immunology ,Immunology and Allergy ,Radiology, Nuclear Medicine and imaging ,Dermatology ,General Medicine - Abstract
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.To assess the efficacy of UVA1 phototherapy and identify correlation between different indications and treatment protocols to response rates.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.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/cmUVA1 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.
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- 2022
7. The role of immune checkpoint receptors in the malignant phenotype of cutaneous T cell lymphoma
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Rony Shreberk-Hassidim, Anat Geiger-Maor, Galit Eisenberg, Sharon Merims, Emma Hajaj, Jonathan E. Cohen, Shiri Klein, Shoshana Frankenburg, Lilach Moyal, Emilia Hodak, Abraham Zlotogorski, and Michal Lotem
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Phenotype ,Programmed Cell Death 1 Receptor ,Immunology ,Humans ,Antibodies, Monoclonal ,Immunotherapy ,Ligands ,B7-H1 Antigen ,Lymphoma, T-Cell, Cutaneous - Abstract
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.
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- 2022
8. Subcutaneous Levodopa Infusion for Parkinson's Disease: 1 <scp>‐Year</scp> Data from the <scp>Open‐Label BeyoND</scp> Study
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Nissim Sasson, Shir Fuchs Orenbach, Nir Giladi, Sheila Oren, David Arkadir, Tanya Simuni, Peter A. LeWitt, Abraham Zlotogorski, Alberto J. Espay, Werner Poewe, Astrid Thomas, Karl Kieburtz, Stuart Isaacson, Georg Ebersbach, Tami Yardeni, C Warren Olanow, Liat Adar, Ryan Case, Olivia Rosenfeld, Fabrizio Stocchi, and Aaron Ellenbogen
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Levodopa ,Movement disorders ,Parkinson's disease ,business.industry ,Carbidopa ,Parkinson Disease ,medicine.disease ,Discontinuation ,Antiparkinson Agents ,Drug Combinations ,Hematoma ,Neurology ,Anesthesia ,medicine ,Humans ,Neurology (clinical) ,Dosing ,medicine.symptom ,Adverse effect ,business ,Gels ,medicine.drug - Abstract
Background Continuous, subcutaneous (SC) levodopa/carbidopa infusion with ND0612 is under development as a treatment for patients with Parkinson's disease (PD) and motor fluctuations. Objective Evaluate 1-year safety data. Methods BeyoND is an open-label study evaluating the long-term safety of two ND0612 dosing regimens. Results Of 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. Conclusions Subcutaneous 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.
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- 2021
9. Guidelines for clinical trials of frontal fibrosing alopecia: consensus recommendations from the International FFA Cooperative Group (IFFACG)*
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Wilma F. Bergfeld, Maria K. Hordinsky, S. Papanikou, Giselle Martins Pinto, Isabella Doche, Satoshi Itami, S. Malakar, K. Khobzei, Elise A. Olsen, Paradi Mirmirani, T. Silyuk, V. Chasapi, Rod Sinclair, Valerie D. Callender, Amy J. McMichael, Kenneth Washenik, Matthew Harries, R. O. Soares, Rodrigo Pirmez, N. Enechukwu, Lidia Rudnicka, Ulrike Blume-Peytavi, Won Soo Lee, Abraham Zlotogorski, Pascal Reygagne, David Saceda-Corralo, Yuliya Ovcharenko, Jerry Shapiro, A. Souissi, George Cotsarelis, Ramon Grimalt, O. Correia, Antonella Tosti, Douglas Canfield, Ncoza C. Dlova, Sergio Vano-Galvan, Annika Vogt, Rachita Dhurat, Andrew G. Messenger, Bianca Maria Piraccini, Janet L. Roberts, Olsen E.A., Harries M., Tosti A., Bergfeld W., Blume-Peytavi U., Callender V., Chasapi V., Correia O., Cotsarelis G., Dhurat R., Dlova N., Doche I., Enechukwu N., Grimalt R., Itami S., Hordinsky M., Khobzei K., Lee W.S., Malakar S., Messenger A., McMichael A., Mirmirani P., Ovcharenko Y., Papanikou S., Pinto G.M., Piraccini B.M., Pirmez R., Reygagne P., Roberts J., Rudnicka L., Saceda-Corralo D., Shapiro J., Silyuk T., Sinclair R., Soares R.O., Souissi A., Vogt A., Washenik K., Zlotogorski A., Canfield D., and Vano-Galvan S.
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Frontal fibrosing alopecia, group of experts in hair loss, consensus recommendations for clinical trials ,Clinical Trials as Topic ,medicine.medical_specialty ,Consensus ,Scalp ,business.industry ,Frontal fibrosing alopecia ,Lichen Planus ,MEDLINE ,Alopecia ,Guidelines as Topic ,Dermatology ,Scarring alopecia ,Patient assessment ,medicine.disease ,Clinical trial ,Cicatrix ,Hair loss ,medicine ,Etiology ,Humans ,Cooperative group ,business ,Intensive care medicine - Abstract
Background Frontal fibrosing alopecia (FFA) has become one of the most common causes of cicatricial alopecia worldwide. However, there is a lack of clear aetiology and robust clinical trial evidence for the efficacy and safety of agents currently used for treatment. Objectives To enable data to be collected worldwide on FFA using common criteria and assessment methods. Methods A multicentre, international group of experts in hair loss was convened by email to create consensus recommendations for clinical trials. Consensus was defined at > 90% agreement on each recommended part of these guidelines. Results Standardized diagnostic criteria, severity rating, staging, and investigator and patient assessment of scalp hair loss and other clinical features of FFA were created. Conclusions These guidelines should allow the collection of reliable aggregate data on FFA and advance efforts in both clinical and basic research to close knowledge gaps in this condition.
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- 2021
10. Reversal of Alopecia Areata Following Treatment With the JAK1/2 Inhibitor Baricitinib
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Ali Jabbari, Zhenpeng Dai, Luzhou Xing, Jane E. Cerise, Yuval Ramot, Yackov Berkun, Gina A. Montealegre Sanchez, Raphaela Goldbach-Mansky, Angela M. Christiano, Raphael Clynes, and Abraham Zlotogorski
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Alopecia areata ,Interferon gamma ,JAK inhibitor ,CANDLE syndrome ,Autoimmune disease ,Baricitinib ,Gene expression profiling ,Autoinflammatory ,Medicine ,Medicine (General) ,R5-920 - Abstract
Background: Alopecia areata (AA) is an autoimmune disease resulting in hair loss with devastating psychosocial consequences. Despite its high prevalence, there are no FDA-approved treatments for AA. Prior studies have identified a prominent interferon signature in AA, which signals through JAK molecules. Methods: A patient with AA was enrolled in a clinical trial to examine the efficacy of baricitinib, a JAK1/2 inhibitor, to treat concomitant CANDLE syndrome. In vivo, preclinical studies were conducted using the C3H/HeJ AA mouse model to assess the mechanism of clinical improvement by baricitinib. Findings: The patient exhibited a striking improvement of his AA on baricitinib over several months. In vivo studies using the C3H/HeJ mouse model demonstrated a strong correlation between resolution of the interferon signature and clinical improvement during baricitinib treatment. Interpretation: Baricitinib may be an effective treatment for AA and warrants further investigation in clinical trials.
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- 2015
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11. Sechs Fälle von Pityriasis rosea nach SARS-CoV-2-Impfung mit BNT162b2
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Yuval Ramot, Krassimira Nanova, Sofia‐Maria Faitatziadou, Dania Abu Assab, Yackov Berkun, and Abraham Zlotogorski
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Pityriasis Rosea ,SARS-CoV-2 ,COVID-19 ,Humans ,Dermatology ,BNT162 Vaccine - Published
- 2022
12. Dermatological adverse events under programmed cell death‐1 inhibitors as a prognostic marker in metastatic melanoma
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Rony Shreberk‐Hassidim, Lilach Aizenbud, Shalev Lussheimer, Elena Thomaidou, Tali Bdolah‐Abram, Sharon Merims, Aron Popovtzer, Alex Maly, Michal Lotem, and Abraham Zlotogorski
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Pruritus ,Programmed Cell Death 1 Receptor ,Humans ,Apoptosis ,Neoplasms, Second Primary ,Dermatology ,General Medicine ,Exanthema ,Prognosis ,Immune Checkpoint Inhibitors ,Melanoma ,Retrospective Studies - Abstract
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.
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- 2022
13. The Alopecia Areata Consensus of Experts (ACE) study part II: Results of an international expert opinion on diagnosis and laboratory evaluation for alopecia areata
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Samantha Eisman, Won Soo Lee, V. Jolliffe, Laita Bokhari, George Cotsarelis, Matthew Harries, Pascal Reygagne, Pooja Sharma, Paradi Mirmirani, Rodney Sinclair, Paul Farrant, Nekma Meah, Annika Vogt, Ulrike Blume-Peytavi, Jeff C. Donovan, Janet L. Roberts, Valerie D. Callender, Dmitri Wall, Maria K. Hordinsky, Brittany G. Craiglow, Bevin Bhoyrul, Adriana Rakowska, Elise A. Olsen, Leona Yip, Seth J. Orlow, Bianca Maria Piraccini, Katherine York, Brett A. King, Ramon Grimalt, Antonella Tosti, Martin S Wade, Vijaya Chitreddy, Alan D. Irvine, Andrew G. Messenger, Andrea Combalia, Jack Green, Abraham Zlotogorski, Jerry Shapiro, Satoshi Itami, Amy J. McMichael, Daniel Asz-Sigall, Wilma F. Bergfeld, Lidia Rudnicka, and Regina C. Betz
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medicine.medical_specialty ,Consensus ,Alopecia Areata ,Delphi Technique ,International Cooperation ,Delphi method ,Dermoscopy ,Comorbidity ,Dermatology ,Severity of Illness Index ,Global Burden of Disease ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,Quality of life ,Risk Factors ,Epidemiology ,medicine ,Humans ,business.industry ,Expert consensus ,Guideline ,Dermatology Life Quality Index ,Alopecia areata ,Prognosis ,medicine.disease ,030220 oncology & carcinogenesis ,Family medicine ,Expert opinion ,Practice Guidelines as Topic ,business ,Hair Follicle - Abstract
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.
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- 2021
14. Six cases of pityriasis rosea following SARS-CoV-2 vaccination with BNT162b2
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Yuval Ramot, Krassimira Nanova, Sofia‐Maria Faitatziadou, Dania Abu Assab, Yackov Berkun, and Abraham Zlotogorski
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Pityriasis Rosea ,COVID-19 Vaccines ,SARS-CoV-2 ,Vaccination ,COVID-19 ,Humans ,Dermatology ,BNT162 Vaccine - Published
- 2022
15. Acral peeling skin syndrome resulting from a novel homozygous mutation in the CSTA gene—A report of two cases
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Abraham Zlotogorski, Georgina-Maria Sarika, Ruba Ibrahim, and Vered Molho-Pessach
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medicine.medical_specialty ,genetic structures ,integumentary system ,business.industry ,Ichthyosis ,Genodermatosis ,Dermatology ,medicine.disease ,Asymptomatic ,Cystatin A ,Pediatrics, Perinatology and Child Health ,Mutation (genetic algorithm) ,Medicine ,medicine.symptom ,business ,Gene ,Acral peeling skin syndrome - Abstract
Acral peeling skin syndrome is a rare genodermatosis characterized by asymptomatic peeling of the acral skin. It is usually caused by biallelic mutations in the gene TGM5. However, biallelic mutations in the CSTA gene have also been described to cause APSS with exfoliative ichthyosis, so far in only five pedigrees. Here, we report two new pedigrees, each with one patient having APSS, due to a novel CSTA mutation.
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- 2021
16. Two Phase 3 Trials of Baricitinib for Alopecia Areata
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Brett, King, Manabu, Ohyama, Ohsang, Kwon, Abraham, Zlotogorski, Justin, Ko, Natasha A, Mesinkovska, Maria, Hordinsky, Yves, Dutronc, Wen-Shuo, Wu, Jill, McCollam, Chiara, Chiasserini, Guanglei, Yu, Sarah, Stanley, Katrin, Holzwarth, Amy M, DeLozier, Rodney, Sinclair, and Matthew, Zirwas
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Adult ,Sulfonamides ,Alopecia Areata ,Purines ,Azetidines ,Humans ,Janus Kinase Inhibitors ,Pyrazoles ,General Medicine - Abstract
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.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.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) (P0.001 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) (P0.001 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.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.).
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- 2022
17. Endocrine Focus on H Syndrome
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Vered Molho-Pessach, MD and Abraham Zlotogorski, MD
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Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Published
- 2016
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18. Retraction Notice to 'Generalized verrucosis and abnormal T cell activation due to homozygous TAOK2 mutation'
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Vered Molho-Pessach, Yuval Ramot, Maxim Mogilevsky, Leonor Cohen-Daniel, Eli M. Eisenstein, Abdulsalam Abu-Libdeh, Ihab Siam, Michael Berger, Rotem Karni, and Abraham Zlotogorski
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Dermatology ,Molecular Biology ,Biochemistry - Published
- 2022
19. Exacerbation of Hailey-Hailey Disease Following SARS-CoV-2 Vaccination
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Liran Horev, Gil Armoni-Weiss, Yuval Ramot, Sivan Sheffer-Levi, Laurent Klapholz, Emily Avitan-Hersh, and Abraham Zlotogorski
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mrna vaccine ,2019-20 coronavirus outbreak ,Hardware_MEMORYSTRUCTURES ,COVID-19 Vaccines ,Exacerbation ,Coronavirus disease 2019 (COVID-19) ,Pemphigus, Benign Familial ,business.industry ,SARS-CoV-2 ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Vaccination ,Genodermatosis ,COVID-19 ,Dermatology ,General Medicine ,medicine.disease ,Virology ,Hailey–Hailey disease ,RL1-803 ,medicine ,Humans ,hailey-hailey ,business ,genodermatosis - Abstract
is missing (Short communication)
- Published
- 2021
20. 33966 Integrated safety analysis of baricitinib in adults with severe alopecia areata from 2 randomized clinical trials
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Brett King, Arash Mostaghimi, Yutaka Shimomura, Abraham Zlotogorski, Katrin Holzwarth, Maher Issa, Yves Dutronc, Sarah Stanley, Wen-Shuo Wu, and Rodney Sinclair
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Dermatology - Published
- 2022
21. Chronic demodicosis in patients with immune dysregulation: An unexpected infectious manifestation of Signal transducer and activator of transcription (STAT)1 gain-of-function
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Abraham Zlotogorski, Sigal Matza-Porges, Zev Davidovics, Oded Shamriz, Vered Molho-Pessach, Ori Toker, Raz Somech, Amos J. Simon, Ortal Barel, Yuval Tal, Elisheva Javasky, Atar Lev, and Adir Shaulov
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Adult ,Male ,Mite Infestations ,Adolescent ,Immunology ,medicine.disease_cause ,Immunophenotyping ,Immune system ,Demodicosis ,Immunology and Allergy ,Medicine ,Animals ,Humans ,STAT1 ,Skin Diseases, Parasitic ,Chronic mucocutaneous candidiasis ,Child ,Retrospective Studies ,Mites ,biology ,business.industry ,Genetic Diseases, Inborn ,Infant ,Original Articles ,Immune dysregulation ,Middle Aged ,medicine.disease ,biology.organism_classification ,STAT1 Transcription Factor ,Immune System Diseases ,Gain of Function Mutation ,Chronic Disease ,biology.protein ,STAT protein ,Female ,business ,Demodex - Abstract
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.
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- 2021
22. Wax Stripping and Isotretinoin Treatment: A Warning Not to Be Missed
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Abraham Zlotogorski and Yuval Ramot
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Wax ,medicine.medical_specialty ,business.industry ,Stripping (fiber) ,Dermatology ,visual_art ,Acne Vulgaris ,visual_art.visual_art_medium ,medicine ,Humans ,business ,Isotretinoin ,medicine.drug ,Skin - Published
- 2021
23. Recurrent varicella following SARS‐CoV‐2 vaccination with BNT162b2
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Abraham Zlotogorski, Yuval Ramot, and Krassimira Nanova
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2019-20 coronavirus outbreak ,COVID-19 Vaccines ,Coronavirus disease 2019 (COVID-19) ,business.industry ,SARS-CoV-2 ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Vaccination ,COVID-19 ,Dermatology ,Virology ,Chickenpox ,Correspondence ,Medicine ,Humans ,business ,BNT162 Vaccine - Published
- 2021
24. Zosteriform cutaneous leishmaniasis diagnosed with the help of dermoscopy
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Yuval Ramot, Krassimira Nanova, Ruslana Alper-Pinus, and Abraham Zlotogorski
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Dermatology ,RL1-803 - Abstract
Cutaneous leishmaniasis is usually easy to recognize; however, several atypical features exist, which may pose a diagnostic challenge. Here we report a 55-year-old female patient, who presented with an itchy and painful eruption localized in a dermatomal distribution along the right upper chest. Although the clinical appearance of the lesions suggested the diagnosis of herpes zoster, dermoscopic evaluation revealed erythema, hyperkeratosis, burst star whitish appearance and hairpin vessels, compatible with the diagnosis of cutaneous leishmaniasis. Indeed, leishmania amastigotes were detected by smear from the lesions. Zosteriform presentation of cutaneous leishmaniasis, as exemplified by our patient, is especially rare. In our case dermoscopy has proven to be an accessible and easy tool to diagnose such atypical presentation of cutaneous leishmaniasis, and dermatologists in endemic areas should be familiar with its typical dermoscopic features.
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- 2014
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25. An Update on the Cutaneous Manifestations of Darier Disease
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Morad Khayat, Abraham Zlotogorski, Algit Yeshurun, Michael Ziv, Olga Polyakov, Muhammad Sah, Shiraz Vered, Boaz Amichai, D. Rozenman, Stavit A. Shalev, Eran Cohen-Barak, and Roni P. Dodiuk-Gad
- Subjects
Adult ,Male ,medicine.medical_specialty ,Dermatology ,Cohort Studies ,030207 dermatology & venereal diseases ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Darier Disease ,Surveys and Questionnaires ,medicine ,Humans ,Aged ,Aged, 80 and over ,Mucous Membrane ,business.industry ,Genetic disorder ,Middle Aged ,medicine.disease ,030220 oncology & carcinogenesis ,Surgery ,Female ,business - Abstract
Background Knowledge about the clinical features of Darier disease, an orphan autosomal-dominant genetic disorder, is sparse and has been evaluated only in few studies. Objectives To investigate the clinical features of a large group of patients with Darier disease, and to explore for associations between disease characteristics and severity of the disease. Methods Seventy-six individuals with Darier disease were evaluated utilizing a structured questionnaire-based interview, a physical examination, and a retrospective assessment of their medical records. Results The most frequent locations of lesions were hands (99%) and fingernails (93%). Wart-like lesions on the hands were more visible after soaking them in water for 5 minutes, we therefore named this phenomenon the “wet hand sign”. Oral involvement was found in 43% of patients, while 48% of women and 16% of men showed genital lesions. Patients with severe Darier disease had a tenfold greater risk of developing genital lesions than those with mild disease ( P = .01). Most patients (88%) in our study exhibited a combination of the four types of the disease patterns of distribution (flexural, seborrheic, nevoid, and acral). Conclusions Documentation of disease on the hands and fingernails provides a highly sensitive means to aid in the diagnosis of Darier disease. It is important to evaluate mucosal lesions including genital and oral mucosa.
- Published
- 2021
26. A Global eDelphi Exercise to Identify Core Domains and Domain Items for the Development of a Global Registry of Alopecia Areata Disease Severity and Treatment Safety (GRASS)
- Author
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Jeff C. Donovan, Cheng Zhou, Valerie D. Callender, Dmitri Wall, Ncoza C. Dlova, Leonardo Spagnol Abraham, Laita Bokhari, Martin S Wade, Sergio Vano-Galvan, Bruna Duque-Estrada, Alan D. Irvine, Wilma F. Bergfeld, Antonella Tosti, Abby Ellison, David Saceda Corralo, Jen Chambers, Pooja Sharma, Seth J. Orlow, Andrew G. Messenger, Bianca Maria Piraccini, Ulrike Blume-Peytavi, Spartak Kaiumov, Brett A. King, Roisin Adams, Rodney Sinclair, Annika Vogt, Melissa Riley, Katherine York, Rachita Dhurat, Won Soo Lee, Brittany G. Craiglow, Bevin Bhoyrul, Aida Gadzhigoroeva, Leslie Jones, Chel Campbell, V. Jolliffe, Juan Ferrando Barberá, Gang Chen, Regina C. Betz, Adriana Rakowska, Elise A. Olsen, Amy J. McMichael, Samantha Eisman, Abraham Zlotogorski, Matthew Harries, George Cotsarelis, Jerry Shapiro, Paul Farrant, Vijaya Chitreddy, Paradi Mirmirani, Leona Yip, Lidia Rudnicka, Nino Lortkipanidze, Yuliya Ovcharenko, Ramon Grimalt, Pascal Reygagne, Maria K. Hordinsky, Tatiana Silyuk, Rodrigo Pirmez, Desmond J. Tobin, Nekma Meah, Wall D., Meah N., York K., Bhoyrul B., Bokhari L., Abraham L.S., Adams R., Bergfeld W., Betz R.C., Blume-Peytavi U., Callender V., Campbell C., Chambers J., Chen G., Chitreddy V., Cotsarelis G., Craiglow B., Dhurat R., Dlova N., Donovan J., Duque-Estrada B., Eisman S., Ellison A., Farrant P., Barbera J.F., Gadzhigoroeva A., Grimalt R., Harries M., Hordinsky M., Irvine A.D., Jolliffe V., Jones L., King B., Lee W.-S., Lortkipanidze N., McMichael A., Messenger A., Mirmirani P., Olsen E., Orlow S.J., Ovcharenko Y., Piraccini B.M., Pirmez R., Rakowska A., Reygagne P., Riley M., Rudnicka L., Saceda Corralo D., Shapiro J., Sharma P., Silyuk T., Kaiumov S., Tobin D.J., Tosti A., Vano-Galvan S., Vogt A., Wade M., Yip L., Zlotogorski A., Zhou C., and Sinclair R.
- Subjects
medicine.medical_specialty ,Consensus ,Internationality ,Alopecia Areata ,Delphi Technique ,Delphi method ,MEDLINE ,Redress ,Consensu ,Dermatology ,Disease ,Subspecialty ,Severity of Illness Index ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,Surveys and Questionnaires ,Global network ,medicine ,Humans ,Surveys and Questionnaire ,Registries ,skin and connective tissue diseases ,Pharmaceutical industry ,integumentary system ,business.industry ,Alopecia areata ,medicine.disease ,030220 oncology & carcinogenesis ,Family medicine ,business ,Human - Abstract
Importance A recent expert consensus exercise emphasized the importance of developing a global network of patient registries for alopecia areata to redress the paucity of comparable, real-world data regarding the effectiveness and safety of existing and emerging therapies for alopecia areata. Objective To generate core domains and domain items for a global network of alopecia areata patient registries. Evidence Review Sixty-six participants, representing physicians, patient organizations, scientists, the pharmaceutical industry, and pharmacoeconomic experts, participated in a 3-round eDelphi process, culminating in a face-to-face meeting at the World Congress of Dermatology, Milan, Italy, June 14, 2019. Findings Ninety-two core data items, across 25 domains, achieved consensus agreement. Twenty further noncore items were retained to facilitate data harmonization in centers that wish to record them. Broad representation across multiple stakeholder groups was sought; however, the opinion of physicians was overrepresented. Conclusions and Relevance This study identifies the domains and domain items required to develop a global network of alopecia areata registries. These domains will facilitate a standardized approach that will enable the recording of a comprehensive, comparable data set required to oversee the introduction of new therapies and harness real-world evidence from existing therapies at a time when the alopecia areata treatment paradigm is being radically and positively disrupted. Reuse of similar, existing frameworks in atopic dermatitis, produced by the Treatment of Atopic Eczema (TREAT) Registry Taskforce, increases the potential to reuse existing resources, creates opportunities for comparison of data across dermatology subspecialty disease areas, and supports the concept of data harmonization.
- Published
- 2021
27. Can Tofacitinib Offer Protection against COVID-19 Infection?
- Author
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Tal Goldberger and Abraham Zlotogorski
- Subjects
2019-20 coronavirus outbreak ,Letter ,Tofacitinib ,Coronavirus disease 2019 (COVID-19) ,business.industry ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Medicine ,Dermatology ,business ,Virology - Published
- 2020
28. Multiple Nasal Papules in a 12-year-old Boy: A Quiz
- Author
-
Abraham Zlotogorski, Dania Abu Assab, Alexander Maly, and Vered Molho-Pessach
- Subjects
Male ,Eccrine hidrocystoma ,medicine.medical_specialty ,business.industry ,Hidrocystoma ,General Medicine ,Dermatology ,Eccrine Glands ,Nose ,Sweat Gland Neoplasms ,pediatric ,RL1-803 ,nasal papules ,Skin Abnormalities ,Medicine ,Humans ,eccrine hidrocystoma ,business ,Child - Published
- 2020
29. The efficacy of off-label IL-5-modulating treatment in rare eosinophil-mediated diseases
- Author
-
Alon Y. Hershko, Yuval Tal, Aviv Talmon, Yaarit Ribak, Tzahi Neuman, Oded Shamriz, Abraham Zlotogorski, Liran Horev, Adeeb NaserEddin, Sheer Shabat, and Anat Scheiman Elazary
- Subjects
lcsh:Immunologic diseases. Allergy ,Adult ,Male ,business.industry ,General Medicine ,Off-Label Use ,Eosinophil ,Middle Aged ,Antibodies, Monoclonal, Humanized ,Eosinophils ,Text mining ,medicine.anatomical_structure ,Immune System Diseases ,Interleukin-5 Receptor alpha Subunit ,Immunology ,medicine ,Immunology and Allergy ,Humans ,Female ,Interleukin-5 ,lcsh:RC581-607 ,business ,Interleukin 5 ,Aged - Published
- 2020
30. [EFFECTIVE TREATMENT FOR BULLOUS PEMPHIGOID WITH OMALIZUMAB]
- Author
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Michal, Neumark, Yuval, Tal, Abraham, Zlotogorski, and Vered, Molho-Pessach
- Subjects
Male ,Anti-Allergic Agents ,Pemphigoid, Bullous ,Antibodies, Monoclonal ,Humans ,Prednisone ,Omalizumab ,Aged ,Autoimmune Diseases - Abstract
Bullous pemphigoid is a common autoimmune blistering disorder, characterized by sub-epidermal bullae formation, that tends to affect older patients. We report on a 78 -year-old male patient suffering from bullous pemphigoid, whose disease persisted despite treatment with potent topical corticosteroids, systemic tetracyclines, prednisone and azathioprine. Recently, omalizumab was reported to be effective in several patients with resistant bullous pemphigoid. Omalizumab is a monoclonal antibody against IgE, approved for the treatment of asthma and chronic urticaria and known for its excellent safety profile. The patient was treated accordingly with omalizumab for his bullous pemphigoid with dramatic and rapid regression of his disease.
- Published
- 2020
31. [JAK INHIBITORS FOR THE TREATMENT OF ALOPECIA AREATA]
- Author
-
Yuval, Ramot and Abraham, Zlotogorski
- Subjects
Arthritis, Rheumatoid ,Alopecia Areata ,Arthritis, Psoriatic ,Animals ,Humans ,Janus Kinase Inhibitors ,Psoriasis - Abstract
JAK inhibitors are small molecules that are capable of blocking T-cell-mediated inflammation. They have been shown to be beneficial in several inflammatory conditions, such as rheumatoid arthritis, psoriasis and psoriatic arthritis. Treatment with three JAK inhibitors, ruxolitinib, baricitinib and tofacitinib, led to hair regrowth in alopecia areata patients, and similar effects have also been demonstrated in animal models for alopecia areata. Based on these data, JAK inhibitors have gained widespread popularity for the treatment of moderate-to-severe alopecia areata patients. Nevertheless, treatment with JAK inhibitors can lead to adverse events, with infections being the most worrisome. Furthermore, the durability of JAK inhibitors for alopecia areata is still unknown. Clinical trials with topical and systemic JAK inhibitors for alopecia areata are ongoing, and hopefully will provide us with better understanding of the safety and efficacy of these medications. If indeed these treatments will prove to be effective and safe, they might become the first FDA-approved treatment for alopecia areata. Disclosures: Prof. Ramot received lecture fees from Novartis and Lilly.
- Published
- 2020
32. The Alopecia Areata Consensus of Experts (ACE) study: Results of an international expert opinion on treatments for alopecia areata
- Author
-
Wilma F. Bergfeld, Valerie D. Callender, A.D. Irvine, Abraham Zlotogorski, Maria K. Hordinsky, Victoria Jolliffe, Daniel Asz Sigall, Jerry Shapiro, Jack Green, Lidia Rudnicka, Nekma Meah, Elise A. Olsen, Jeff C. Donovan, Adriana Rakowska, Dmitri Wall, Won Soo Lee, Ulrike Blume-Peytavi, Katherine York, Samantha Eisman, George Cotsarelis, Seth J. Orlow, Antonella Tosti, Satoshi Itami, Ramon Grimalt, Matthew Harries, Vijaya Chitreddy, Pooja Sharma, Pascal Reygagne, Leona Yip, Annika Vogt, Amy J. McMichael, Brittany G. Craiglow, Bevin Bhoyrul, Martin S Wade, Brett A. King, Paul Farrant, Laita Bokhari, Regina C. Betz, Paradi Mirmirani, Andrew G. Messenger, Andrea Combalia, Bianca Maria Piraccini, Janet L. Roberts, Rodney Sinclair, and Meah N, Wall D, York K, Bhoyrul B, Bokhari L, Sigall DA, Bergfeld WF, Betz RC, Blume-Peytavi U, Callender V, Chitreddy V, Combalia A, Cotsarelis G, Craiglow B, Donovan J, Eisman S, Farrant P, Green J, Grimalt R, Harries M, Hordinsky M, Irvine AD, Itami S, Jolliffe V, King B, Lee WS, McMichael A, Messenger A, Mirmirani P, Olsen E, Orlow SJ, Piraccini BM, Rakowska A, Reygagne P, Roberts JL, Rudnicka L, Shapiro J, Sharma P, Tosti A, Vogt A, Wade M, Yip L, Zlotogorski A, Sinclair R.
- Subjects
Complementary Therapies ,medicine.medical_specialty ,Alopecia Areata ,Delphi Technique ,Administration, Topical ,Delphi method ,Administration, Oral ,Topical treatment ,Dermatology ,Injections, Intralesional ,Severity of Illness Index ,Systemic therapy ,law.invention ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,Adrenal Cortex Hormones ,law ,Humans ,Medicine ,Expert Testimony ,Patient registry ,business.industry ,Alopecia areata, Treatments for alopecia areata ,Age Factors ,alopecia areata, steroid, methotrexate, cyclosporin ,Expert consensus ,Phototherapy ,Alopecia areata ,medicine.disease ,Combined Modality Therapy ,Treatment Outcome ,030220 oncology & carcinogenesis ,Expert opinion ,Family medicine ,Dermatologic Agents ,business - Abstract
Background A systematic review failed to identify any systemic therapy used in alopecia areata (AA) where use is supported by robust evidence from high-quality randomized controlled trials. Objective To produce an international consensus statement on the use and utility of various treatments for AA. Methods Fifty hair experts from 5 continents were invited to participate in a 3-round Delphi process. Agreement of 66% or greater was considered consensus. Results In the first round, consensus was achieved in 22 of 423 (5%) questions. After a face-to-face meeting in round 3, overall, consensus was achieved for only 130 (33%) treatment-specific questions. There was greater consensus for intralesional treatment of AA (19 [68%]) followed by topical treatment (25 [43%]). Consensus was achieved in 45 (36%) questions pertaining to systemic therapies in AA. The categories with the least consensus were phototherapy and nonprescription therapies. Limitations The study included a comprehensive list of systemic treatments for AA but not all treatments used. Conclusion Despite divergent opinions among experts, consensus was achieved on a number of pertinent questions. The concluding statement also highlights areas where expert consensus is lacking and where an international patient registry could enable further research.
- Published
- 2020
33. STAT1 gain‐of‐function and chronic demodicosis
- Author
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Vered Molho-Pessach, Abraham Zlotogorski, Adaia Kamshov, Yuval Ramot, and Arnon Meltser
- Subjects
Mutation ,medicine.medical_specialty ,business.industry ,Dermatology ,Immune dysregulation ,medicine.disease ,medicine.disease_cause ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,Papulopustular ,030220 oncology & carcinogenesis ,Chalazion ,Pediatrics, Perinatology and Child Health ,medicine ,Demodicosis ,Chronic mucocutaneous candidiasis ,Blepharitis ,business ,Immunodeficiency - Abstract
Heterozygous STAT1 gain-of-function (GOF) mutations result in a combined form of immunodeficiency which is the most common genetic cause of chronic mucocutaneous candidiasis (CMC). We present a pedigree with a GOF mutation in STAT1, manifesting with chronic demodicosis in the form of a facial papulopustular eruption, blepharitis, and chalazion. So far, demodicosis has been described in only one family with STAT1-GOF mutation. We suggest that chronic demodicosis is an under-recognized feature of the immune dysregulation disorder caused by STAT1 gain-of-function mutations.
- Published
- 2019
34. RETRACTED: Generalized verrucosis and abnormal T cell activation due to homozygous TAOK2 mutation
- Author
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Ihab Siam, Abdulsalam Abu-Libdeh, Eli M. Eisenstein, Rotem Karni, Michael Berger, Maxim Mogilevsky, Vered Molho-Pessach, Yuval Ramot, Abraham Zlotogorski, and Leonor Cohen-Daniel
- Subjects
0301 basic medicine ,Mutation ,MAP kinase kinase kinase ,T cell ,Dermatology ,Biology ,Mitogen-activated protein kinase kinase ,medicine.disease_cause ,Biochemistry ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Immune system ,Immunophenotyping ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Cancer research ,medicine ,Missense mutation ,Kinase activity ,Molecular Biology - Abstract
Background Generalized verrucosis (GV) is a chronic and progressive cutaneous human papillomavirus (HPV) infection resulting in multiple warts and associated with acquired or genetic immune defects. We identified a consanguineous Arab family manifesting GV and recurrent bacterial and viral infections, in association with inflammatory bowel disease (IBD). Objective To identify the mutated gene responsible for GV, recurrent infections and IBD, in this family. Methods Flow cytometry of peripheral blood mononuclear cells was performed, as well as proliferation and cell cycle assays of T cells. Whole exome sequencing was utilized to detect candidate mutated genes, assuming an autosomal recessive mode of inheritance. Skin fibroblasts from a patient, the mother and control were incubated with sorbitol to detect the phosphorylation ability of TAOK2, and a clonogenic assay was performed to assess the survival and proliferative capacity of fibroblasts’ colonies. Results Despite normal immunophenotyping of T and B cells, T cell proliferation upon activation was impaired in a patient compared to a heterozygous family member and a control. Genetic analyses identified a rare homozygous missense variant, c.2098C>T (p.R700C) in the TAOK2 gene, segregating with the disease phenotype in the family. TAOK2 encodes the TAO2 kinase, a mitogen activated protein kinase kinase kinase (MAP3K) in the p38-MAPK cascade. The mutation is predicted to disrupt its normal folding and molecular interaction; however, no impairment was observed in TAOK2 kinase activity toward its downstream target, MEK3/6, in patient's fibroblasts. Despite this normal kinase activity, a noticeably higher survival/proliferation of patient's skin fibroblasts was found. Conclusions A mutation in TAOK2 appears to cause a novel form of primary immunodeficiency, characterized by an impaired T cell proliferation upon activation. This novel cause of GV gives further support to the importance of the p38-MAPK pathway in the immune response against HPV, and possibly also in the pathogenesis of IBD.
- Published
- 2017
35. Re-evaluation of epidermodysplasia verruciformis: Reconciling more than 90 years of debate
- Author
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Abraham Zlotogorski, Joanna Przybyszewska, and Yuval Ramot
- Subjects
medicine.medical_specialty ,business.industry ,TMC6 ,Papillomavirus Infections ,Genodermatosis ,Dermatology ,Epidermodysplasia verruciformis ,Clinical manifestation ,Pityriasis ,medicine.disease ,Phenotype ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Epidermodysplasia Verruciformis ,Mutation ,medicine ,Humans ,TMC8 ,business ,Immunodeficiency - Abstract
Epidermodysplasia verruciformis (EV) is a rare genodermatosis characterized by abnormal susceptibility to cutaneous human beta-papillomavirus infections causing persistent flat warts or pityriasis versicolor–like lesions. This generalized verrucous skin disorder resembles generalized verrucosis, but these 2 conditions are distinguished by differences in clinical manifestation and the human papillomavirus types involved. A breakthrough in our understanding of EV was the discovery that homozygous inactivating mutations in TMC6 ( EVER1 ) and TMC8 ( EVER2 ) determine susceptibility to this disorder; however, they have not solved all EV cases fully. These deficiencies account for 75% of affected individuals, leaving a substantial number of patients without an underlying genetic cause. Recently, it has been revealed that mutations in additional genes ( RHOH , MST-1 , CORO1A , and IL-7 ) result in extensive human beta-papillomavirus replication and therefore manifest with an EV-like phenotype. The term "acquired EV" is used to describe an EV-like phenotype that develops in immunocompromised hosts, and the introduction of this entity further aggravates the confusion. Reevaluation of these entities is warranted. Here, we review the available data on this issue, provide up to date information on the major characteristics that differentiate between these seemingly clinically similar disorders, and highlight the different mechanisms involved in each disorder.
- Published
- 2017
36. Tocilizumab Promotes Regulatory T-cell Alleviation in STAT3 Gain-of-function−associated Multi-organ Autoimmune Syndrome
- Author
-
Orly Elpeleg, Abu Rmeileh Ayman, Vered Molho-Pessach, Abraham Zlotogorski, Yaron Ilan, Tawfik Khoury, Neville Berkman, and Yuval Ramot
- Subjects
Adult ,Male ,0301 basic medicine ,Regulatory T cell ,Antibodies, Monoclonal, Humanized ,medicine.disease_cause ,T-Lymphocytes, Regulatory ,Autoimmune Diseases ,Autoimmunity ,03 medical and health sciences ,chemistry.chemical_compound ,Tocilizumab ,medicine ,Humans ,Pharmacology (medical) ,IL-2 receptor ,STAT3 ,Pharmacology ,biology ,Interleukin-6 ,business.industry ,Interleukin-2 Receptor alpha Subunit ,FOXP3 ,Syndrome ,Flow Cytometry ,Receptors, Interleukin-6 ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,Immunology ,Cancer research ,STAT protein ,biology.protein ,business ,CD8 - Abstract
Purpose Signal transducer and activator of transcription 3 is a member of a family of proteins involved in the regulation of inflammation, differentiation, proliferation, and survival of cells. Here we describe a 38-year-old male who has experienced gastrointestinal, dermatologic, pulmonary, and malignant manifestations. Methods Whole-exome sequencing, validated by Sanger sequencing, was performed after extensive investigations. Findings Whole-exome sequencing revealed a heterozygous missense mutation in the signal transducer and activator of transcription 3 gene, c.1261G>A (p.G421R). Fluorescence-activated cell sorting analysis of peripheral T lymphocytes revealed low levels of CD4 + CD25 + FoxP3 and CD8 + CD25 + FoxP3 regulatory T cells. After treatment with 2 cycles of tocilizumab, an interleukin-6 receptor antibody, a significant increase in the level of regulatory T cells was observed, accompanied by clinical improvement. Implications This case sheds light on the emerging role of signal transducer and activator of transcription 3 gain-of-function mutation in the pathogenesis of autoimmune diseases, and further addresses the therapeutic role of interleukin-6 blocker treatment in this syndrome.
- Published
- 2017
37. Spontaneous Quick Resolution of Uncombable Hair Syndrome-Like Disease
- Author
-
Abraham Zlotogorski, Vered Molho-Pessach, and Yuval Ramot
- Subjects
medicine.medical_specialty ,integumentary system ,Uncombable hair syndrome ,business.industry ,Hair shaft ,Trichohyalin ,Dermatology ,Disease ,medicine.disease ,Novel Insights from Clinical Practice ,Medicine ,sense organs ,business - Abstract
Uncombable hair syndrome (UHS) is a unique hair shaft disease characterized by frizzy, straw-colored hair, which is resistant to combing and brushing. Familial cases have been described, and recently mutations in genes related to trichohyalin production have been reported as the cause for this condition. UHS usually manifests during early childhood, and gradually resolves at puberty. Herein, we report on a 2-year-old boy whose hair changed to a UHS-like phenotype “overnight” with no apparent trigger. The condition resolved abruptly after 9 months. Genetic analysis revealed a heterozygous variant in the PLCD1 gene, which has been connected to hair development. This case raises the possibility that a genetic cause can lead to a temporary change in hair shaft appearance, possibly after exposure to a yet unknown external trigger.
- Published
- 2018
38. Hirsutism Induced by Facial Autologous Fat Grafting
- Author
-
Yuval Ramot, Abraham Zlotogorski, Tatiana Silyuk, and Sari Murad
- Subjects
medicine.medical_specialty ,Side effect ,business.industry ,Mesenchymal stem cell ,Dermatology ,Hair follicle ,medicine.disease ,Surgery ,chemistry.chemical_compound ,medicine.anatomical_structure ,chemistry ,Novel Insights from Clinical Practice ,Adipocyte ,medicine ,Endocrine system ,Autologous fat grafting ,Stem cell ,business ,hirsutism - Abstract
Autologous fat grafting (AFG) is a common procedure, which gains popularity for a large number of indications, mainly for reshaping and filling of contour defects. It is considered a safe procedure, with only uncommon and mild complications. Here we report on a 60-year-old female patient who developed excess hair growth on both cheeks 1 month following facial AFG done in conjunction with a facelift. Complete endocrine evaluation was within normal levels. Previous reports have suggested that adipocyte mesenchymal stem cells can secrete a number of growth factors, which in turn can lead to activation of stem cells in the hair follicle, affecting their growth. However, to the best of our knowledge, this is the first report on hirsutism as a side effect of AFG.
- Published
- 2019
39. Phototherapy decreases red blood cell deformability in patients with psoriasis
- Author
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Saul Yedgar, Yuval Ramot, Roni Biran, Abraham Zlotogorski, Noa Hadayer, and Gregory Barshtein
- Subjects
Goeckerman regimen ,Adult ,Male ,medicine.medical_specialty ,Physiology ,Population ,030204 cardiovascular system & hematology ,Gastroenterology ,030218 nuclear medicine & medical imaging ,Microcirculation ,03 medical and health sciences ,0302 clinical medicine ,Physiology (medical) ,Internal medicine ,Psoriasis ,Erythrocyte Deformability ,medicine ,Erythrocyte deformability ,Humans ,In patient ,education ,education.field_of_study ,business.industry ,Hematology ,Phototherapy ,medicine.disease ,Red blood cell ,medicine.anatomical_structure ,Treatment Outcome ,Female ,Cardiology and Cardiovascular Medicine ,business ,Psoriasis treatment - Abstract
Background Alternations in erythrocyte deformability (ED), namley, the ability of erythrocytes to change shape under flow in the microcirculation, can contribute to cardiovascular diseases. Psoriasis, a systemic inflammatory skin disorder, is associated with an increased cardiovascular risk. The effect of psoriasis and psoriasis treatment on ED was only scarcely evaluated. Objective To evaluate ED changes in psoriasis patients following narrow band-ultraviolet B (NB-UVB) treatment. Methods Erythrocyte deformability was determined using a computerized cell flow properties analyzer in 9 patients with psoriasis before and after a course of Goeckerman regimen. ED was quantified using two parameters: average elongation ratio (AER) in the cell population, and the fraction of low deformable cells (% LDFC). Results All 9 patients showed decreased ED (i.e. impaired deformability) following NB-UVB treatment. There was a significant (p = 0.003) decrease in AER after treatment (AER±SD; 1.58±0.06) compared to the starting values (1.69±0.1). Additionally, there was a significant (p = 0.002) increase in the fraction of low deformable cells (% LDFC±SD; 60.00±9.05) compared to their fraction before treatment (34.86±11.44). Conclusions The decreased ED observed following phototherapy could have clinical influences on psoriasis patients, and may partially explain why phototherapy does not decrease the cardiovascular risk in psoriasis compared to other treatments.
- Published
- 2019
40. Darier disease in Israel: combined evaluation of genetic and neuropsychiatric aspects
- Author
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D. Rozenman, Abraham Zlotogorski, A. Shani-Adir, H. Milo, N. Danial-Faran, B. Amichai, Z. Borochowitz, M. Khayat, L. Amariglio-Diskin, Stavit A. Shalev, Roni P. Dodiuk-Gad, M. Ziv, Eran Cohen-Barak, and M. Sah
- Subjects
Adult ,Male ,0301 basic medicine ,Heterozygote ,medicine.medical_specialty ,Dermatology ,Sarcoplasmic Reticulum Calcium-Transporting ATPases ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,Darier Disease ,Internal medicine ,ATP2A2 ,medicine ,Humans ,Israel ,Family history ,Psychiatry ,Neurologic Examination ,business.industry ,Genetic heterogeneity ,Mental Disorders ,Genodermatosis ,Exons ,medicine.disease ,Phenotype ,030104 developmental biology ,Mood disorders ,Mutation ,Cohort ,Mutation (genetic algorithm) ,Female ,business - Abstract
Summary Background Darier disease (DD) is a rare genodermatosis caused by heterozygous mutations in the ATP2A2 gene. It has been associated with neuropsychiatric manifestations. Objectives To investigate the genetic basis of Israeli patients with DD, and its association with the neuropsychiatric phenotype. Methods A cohort of 32 families comprising 74 affected individuals and 13 unaffected family members was recruited from the Haemek Dermatology Department and other dermatology clinics in Israel. The individuals were evaluated by detailed questionnaires, physical examination and genetic analysis. The main outcome measures were genetic mutations, psychiatric profile and their association. Results Twenty-three mutations in ATP2A2 were scattered over the entire gene, 14 of them novel. Two families shared the same mutation. Twenty-one patients (28%) had a history of psychiatric disorders, most of them mood disorders. Another seven patients (9%) were highly suspected of having a psychiatric disorder; 21 (28%) reported suicidal thoughts and five (7%) had attempted suicide. The psychiatric phenotype demonstrated inter- and intrafamilial variability, and was not associated with disease severity, family history of psychiatric disease or mutation location. Conclusions The cohort demonstrated genetic heterogeneity with no mutation cluster along the gene, and a high prevalence of psychiatric disorders. Although no clear genotype–phenotype correlation was found, the results point to a major effect of genetic background on psychiatric phenotype, together with other modifiers.
- Published
- 2016
41. Complete Regrowth of Beard Hair with Ruxolitinib in an Alopecia Universalis Patient
- Author
-
Abraham Zlotogorski and Yuval Ramot
- Subjects
medicine.medical_specialty ,Ruxolitinib ,integumentary system ,business.industry ,Alopecia totalis ,Dermatology ,Alopecia areata ,medicine.disease ,Body hair ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,Novel Insights from Clinical Practice ,030220 oncology & carcinogenesis ,Scalp ,Alopecia universalis ,medicine ,Effective treatment ,Janus kinase ,business ,medicine.drug - Abstract
While most alopecia areata (AA) cases resolve spontaneously, the more severe types of AA, alopecia totalis (AT) and alopecia universalis (AU), can be highly resistant to therapy. We report on a 33-year-old ultraorthodox Jewish man with an 11-year history of AA that resulted in complete loss of the scalp and body hair 7 years ago. Previous treatments with intralesional and systemic corticosteroids had only partial and temporary effects. The patient was treated with ruxolitinib, 20 mg twice daily, resulting in complete growth of the beard after 4 months of treatment. The beard has a special significance for ultraorthodox Jews, and loss of the beard hair can have marked social and psychological consequences in AA patients. The Janus kinase (JAK) inhibitors have recently emerged as an effective treatment modality in AA, including the more severe forms, such as AT or AU. This report highlights the beneficial effects of the JAK inhibitors, especially in populations where the hair has a special importance due to cultural and religious backgrounds.
- Published
- 2017
42. Dermatology today and tomorrow: from symptom control to targeted therapy
- Author
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Ulrike Blume-Peytavi, Eggert Stockfleth, Brigitte Dréno, M. Saint Aroman, H.W. Lim, Dominique Tennstedt, Victor Georgescu, Carle Paul, Valérie Mengeaud, T. Nocera, Abraham Zlotogorski, Martine Bagot, Anne-Marie Schmitt, UCL - SSS/IREC/PNEU - Pôle de Pneumologie, ORL et Dermatologie, and UCL - (SLuc) Service de dermatologie
- Subjects
medicine.medical_specialty ,Skin Neoplasms ,Ultraviolet Rays ,medicine.medical_treatment ,Population ,Disease ,Dermatology ,Targeted therapy ,Dermatitis, Atopic ,Medication Adherence ,030207 dermatology & venereal diseases ,03 medical and health sciences ,Cicatrix ,0302 clinical medicine ,Acne Vulgaris ,medicine ,Humans ,Molecular Targeted Therapy ,Precision Medicine ,education ,Acne ,education.field_of_study ,business.industry ,Alopecia ,Atopic dermatitis ,medicine.disease ,Precision medicine ,Skin Aging ,Hair loss ,Infectious Diseases ,030220 oncology & carcinogenesis ,Personalized medicine ,Immunotherapy ,business ,Sunscreening Agents - Abstract
For many decades and until recently, medical approach to dermatologic diseases has been based on the physician’s ability to recognize and treat symptoms. Nowadays, advances in the understanding of the biology of diseases and in technologies for intervening against them have allowed physicians to diagnose and treat underlying disease pro- cesses rather than simply addressing the symptoms. This means that rather than addressing ‘the disease in humans’, physicians can now address the particular pathologic (biologic, molecular) disturbance as it presents in the individual patient, i.e., physicians now can practice something much closer to ‘personalized medicine’, leading to greater benefits for the patients and the health of society in general. The deeper understanding of ultraviolet radiation, the importance of photo- protection and increased knowledge about signalling pathways of melanoma and carcinoma have led to more complete care for the dermatologic patient. The current popularity for excessive exposure to the sun, without adequate application of the appropriate photoprotection remedies, is the origin of melanoma, but also for the weakening of the structure and func- tions of the skin. Indeed, fragility of the skin can affect humans around the world. In the senior population, this skin fragility is accompanied by pruritus, whereas atopic dermatitis is an inflammatory disease with highest prevalence in children and adolescents. Acne, the number one reason for dermatologic consultations worldwide, increases its prevalence in adoles- cents and in females. Senescent alopecia affects humans after menopause and andropause. The articles in this publication present an overview of the current advanced understanding of the diagnosis and therapeutic approaches in 6 fields of der- matology – dermatopaediatry and gerontodermatology, oncodermatology, hair loss, atopic dermatitis, photoprotection and acne – and thereby serve as a useful compendium of updated information and references for all healthcare professionals who see patients with presentations of the symptoms of these diseases.
- Published
- 2018
43. Solitary angiokeratoma of the vulva mimicking malignant melanoma
- Author
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Yuval, Ramot, Tamar, Tetro, Leonidas, Soteriou, Victoria, Doviner, Alexander, Maly, and Abraham, Zlotogorski
- Subjects
Diagnosis, Differential ,Skin Neoplasms ,Vulvar Neoplasms ,Humans ,Dermoscopy ,Female ,Melanoma ,Aged ,Angiokeratoma - Published
- 2018
44. Additive loss-of-function proteasome subunit mutations in CANDLE/PRAAS patients promote type I IFN production
- Author
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Kristina I. Rother, Wanxia L. Tsai, Qing Zhou, Elaine F. Remmers, Rhina D. Castillo, Yan Huang, Anja Brehm, Raphaela Goldbach-Mansky, Franziska Sotzny, Yin Liu, Robert Wesley, Bernadette Marrero, Peter W. Hildebrand, Helen J. Lachmann, Deborah L. Stone, André Mégarbané, Ebun Omoyinmi, Adriana Almeida de Jesus, Massimo Gadina, Paul A. Brogan, Antonio Torrelo, Adam L Reinhardt, Angel Vera Casano, Dawn Chapelle, G Montealegre, Phil McCoy, Jae Jin Chae, Lela Kardava, Martin Pelletier, Susan Moir, Suvimol Hill, Elke Krüger, Diane E. Brown, Ling Gao, Abraham Zlotogorski, Angelique Biancotto, Jilian Brady, Hanna Kim, Ivona Aksentijevich, Afzal Sheikh, Daniel L. Kastner, Chyi-Chia Richard Lee, Yongqing Chen, [Brehm,A, Sotzny,F, Krüger,E] Charité-Universitätsmedizin Berlin, Institute of Biochemistry, Berlin, Germany. [Liu,Y, Sheikh,A, Marrero,B, Montealegre,G, Almeida de Jesus,A, Kim,H, Chapelle,D, Huang,Y, Chen,Y, Goldbach-Mansky,R] Translational Autoinflammatory Disease Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), Bethesda, Maryland, USA. [Sheikh,A, Zhou,Q, Remmers,EF, Chae,JJ, Brady,J, Stone,D, Kastner,DL, Aksentijevich,I] Inflammatory Disease Section, National Human Genome Research Institute, NIH, Bethesda, Maryland, USA. [Omoyinmi,E, Brogan,P] University College London Institute of Child Health and Great Ormond Street Hospital, NHS Foundation Trust, London, United Kingdom. [Biancotto,A, McCoy,P] Center of Human Immunology, National Heart, Lung, and Blood Institute, NIH, Bethesda, Maryland, USA. [Reinhardt,A] Children’s Hospital and Medical Center and University of Nebraska Medical Center, Omaha, Nebraska, USA. [Pelletier,M] Autoimmunity Branch. [Tsai,WL, Gadina,M] Office of Science and Technology, NIAMS. [Kardava,L, Moir,S] Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases. [Hill,S] Clinical Center, NIH, Bethesda, Maryland, USA. [Lachmann,HJ] National Amyloidosis Centre, University College Medical School, London, United Kingdom. [Megarbane,A] Medical Genetics Unit, Saint Joseph University, Beirut, Lebanon. Institut Jerome Lejeune, Paris, France. [Castillo,RD, Brown,D] Children’s Hospital Los Angeles and University of Southern California, Los Angeles, California, USA. [Vera Castillo,A] Hospital Carlos Haya, Malaga, Andalusia, Spain. [Gao,L] College of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA. [Lee,CR] Laboratory of Pathology, National Cancer Institute, NIH, Bethesda, Maryland, USA. [Torrelo,A] Pediatric Dermatology, Hospital Niño Jesús, Madrid, Spain. [Zlotogorski,A] Hadassah-Hebrew University Medical Center, Jerusalem, Israel. [Wesley,R] Reproductive Biology and Medicine Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development. [Rother,KR] Section on Pediatric Diabetes and Metabolism, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NIH, Bethesda, Maryland, USA. [Hildebrand,PW] Charité-Universitätsmedizin Berlin, Institute of Medical Physics and Biophysics, Berlin, Germany., and This research was supported by the Intramural Research Program of NIAMS at the NIH, by the Berlin Institute of Health, and by the Deutsche Forschungsgemeinschaft (SFB TR 43 to E. Krüger, SFB740 to E. Krüger and P.W. Hildebrand).
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Phenomena and Processes::Genetic Phenomena::Phenotype [Medical Subject Headings] ,Lipodystrophy ,Transcription, Genetic ,PSMA3 ,Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings] ,Células cultivadas ,Subunidades de proteínas ,0302 clinical medicine ,Clinical investigation ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Models, Theoretical::Models, Molecular [Medical Subject Headings] ,Medicine ,Chemicals and Drugs::Biological Factors::Intercellular Signaling Peptides and Proteins::Interferons::Interferon Type I [Medical Subject Headings] ,Interferón de tipo I ,Chaperonas moleculares ,Cells, Cultured ,Alineación de secuencias ,General Medicine ,Pedigree ,Enfermedades autoinflamatorias hereditarias ,Deleción de secuencias ,Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease::Syndrome [Medical Subject Headings] ,Interferon Type I ,RNA Interference ,Phenomena and Processes::Genetic Phenomena::Genotype [Medical Subject Headings] ,Erratum ,Fenotipo ,Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Molecular Chaperones [Medical Subject Headings] ,Phenomena and Processes::Genetic Phenomena::Genetic Variation::Mutation [Medical Subject Headings] ,Genotype ,Molecular Sequence Data ,Síndrome ,Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Protein Subunits [Medical Subject Headings] ,03 medical and health sciences ,Mutación de sentido erróneo ,Diseases::Congenital, Hereditary, and Neonatal Diseases and Abnormalities::Genetic Diseases, Inborn::Hereditary Autoinflammatory Diseases [Medical Subject Headings] ,Humans ,Secuencia de aminoácidos ,Amino Acid Sequence ,Loss function ,Hereditary Autoinflammatory Diseases ,Phenomena and Processes::Genetic Phenomena::Genetic Variation::Mutation::Sequence Deletion [Medical Subject Headings] ,Fibroblasts ,Conformación de proteínas ,Transcripción genética ,Protein Subunits ,Regulación de la expresión génica ,030104 developmental biology ,Information Science::Information Science::Information Services::Documentation::Molecular Sequence Data [Medical Subject Headings] ,Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression Regulation::Epigenesis, Genetic::Gene Silencing::RNA Interference [Medical Subject Headings] ,Proteasome ,Complejo de endopeptidasas de los proteasomas ,Anatomy::Cells::Cells, Cultured [Medical Subject Headings] ,Immunology ,Mutation ,Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Molecular Structure::Amino Acid Sequence [Medical Subject Headings] ,Genotipo ,Molecular Chaperones ,0301 basic medicine ,Models, Molecular ,Protein Conformation ,Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression Regulation [Medical Subject Headings] ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Pedigree [Medical Subject Headings] ,Modelos moleculares ,Chemicals and Drugs::Macromolecular Substances::Multiprotein Complexes::Multienzyme Complexes::Proteasome Endopeptidase Complex [Medical Subject Headings] ,Missense mutation ,Homología de secuencias de aminoácidos ,RNA, Small Interfering ,Anatomy::Cells::Connective Tissue Cells::Fibroblasts::Myofibroblasts [Medical Subject Headings] ,Sequence Deletion ,Genetics ,Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::RNA::RNA, Untranslated::RNA, Small Untranslated::RNA, Small Interfering [Medical Subject Headings] ,Type I IFN production ,Syndrome ,Interferencia por ARN ,Phenomena and Processes::Genetic Phenomena::Genetic Variation::Mutation::Mutation, Missense [Medical Subject Headings] ,Phenotype ,Research Article ,Datos de Secuencia Molecular ,Proteasome Endopeptidase Complex ,Protein subunit ,Mutation, Missense ,Biology ,Linaje ,Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression::Transcription, Genetic [Medical Subject Headings] ,Mutación ,Sequence Homology, Amino Acid ,business.industry ,PSMB8 ,Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Molecular Structure::Molecular Conformation::Protein Conformation [Medical Subject Headings] ,PSMB9 ,PSMB4 ,Molecular biology ,Fibroblastos ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Sequence Alignment [Medical Subject Headings] ,Gene Expression Regulation ,Proteasome assembly ,Proteasome maturation protein ,business ,Sequence Alignment ,Phenomena and Processes::Genetic Phenomena::Sequence Homology::Sequence Homology, Amino Acid [Medical Subject Headings] ,030215 immunology - Abstract
Journal Article; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't;Erratium en J Clin Invest. 2016 Feb 1;126(2):795. doi: 10.1172/JCI86020: https://www.jci.org/articles/view/86020 Autosomal recessive mutations in proteasome subunit β 8 (PSMB8), which encodes the inducible proteasome subunit β5i, cause the immune-dysregulatory disease chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE), which is classified as a proteasome-associated autoinflammatory syndrome (PRAAS). Here, we identified 8 mutations in 4 proteasome genes, PSMA3 (encodes α7), PSMB4 (encodes β7), PSMB9 (encodes β1i), and proteasome maturation protein (POMP), that have not been previously associated with disease and 1 mutation in PSMB8 that has not been previously reported. One patient was compound heterozygous for PSMB4 mutations, 6 patients from 4 families were heterozygous for a missense mutation in 1 inducible proteasome subunit and a mutation in a constitutive proteasome subunit, and 1 patient was heterozygous for a POMP mutation, thus establishing a digenic and autosomal dominant inheritance pattern of PRAAS. Function evaluation revealed that these mutations variably affect transcription, protein expression, protein folding, proteasome assembly, and, ultimately, proteasome activity. Moreover, defects in proteasome formation and function were recapitulated by siRNA-mediated knockdown of the respective subunits in primary fibroblasts from healthy individuals. Patient-isolated hematopoietic and nonhematopoietic cells exhibited a strong IFN gene-expression signature, irrespective of genotype. Additionally, chemical proteasome inhibition or progressive depletion of proteasome subunit gene transcription with siRNA induced transcription of type I IFN genes in healthy control cells. Our results provide further insight into CANDLE genetics and link global proteasome dysfunction to increased type I IFN production. Yes
- Published
- 2015
45. The twisting tale of woolly hair: a trait with many causes
- Author
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Abraham Zlotogorski and Yuval Ramot
- Subjects
Isolated finding ,Cardiomyopathy ,Woolly hair ,Treatment options ,Biology ,medicine.disease ,Bioinformatics ,Heart disorder ,Phenotype ,Palmoplantar keratoderma ,Keratoderma, Palmoplantar ,otorhinolaryngologic diseases ,Genetics ,Trait ,medicine ,Humans ,Cardiomyopathies ,Hair Diseases ,Genetics (clinical) - Abstract
Woolly hair is an uncommon condition among non-black people, which may be an isolated finding or associated with additional clinical symptoms. When woolly hair is accompanied by palmoplantar keratoderma, it may herald a deadly cardiomyopathy, and therefore this condition should alert the physician for a heart disorder. Until recently, the underlying causes for this rare phenotype were obscure, and only three genes were associated with this condition. However, in recent years, many more genes were found to underlie this disorder, uncovering new molecular pathways. Better knowledge of the different mechanisms that control the curliness of hair may offer new treatment options for this condition, and may also make it possible to affect hair texture in general.
- Published
- 2015
46. Squamous cell carcinoma in situ in association with HPV 11 in Netherton's syndrome patient: a case report
- Author
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Alexander Maly, Abraham Zlotogorski, Liran Horev, Ayal Hassidim, N. Adler, Rony Shreberk-Hassidim, and Yuval Ramot
- Subjects
0301 basic medicine ,Oncology ,medicine.medical_specialty ,S syndrome ,business.industry ,MEDLINE ,Dermatology ,medicine.disease ,Bioinformatics ,030207 dermatology & venereal diseases ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Infectious Diseases ,Internal medicine ,Carcinoma ,Medicine ,Basal cell ,business - Published
- 2016
47. Ausgedehnte Papeln und hyperkeratotische Knoten
- Author
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Alexander Maly, Yuval Ramot, Mariana Zamir, and Abraham Zlotogorski
- Subjects
Dermatology - Published
- 2015
48. Atopic Dermatitis in Israeli Adolescents from 1998 to 2013: Trends in Time and Association with Migraine
- Author
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Yoav Gronovich, Abraham Zlotogorski, Adam Dalal, Vered Molho-Pessach, Ayal Hassidim, and Rony Shreberk-Hassidim
- Subjects
Male ,medicine.medical_specialty ,Pediatrics ,Adolescent ,Cross-sectional study ,Migraine Disorders ,Population ,Dermatology ,Comorbidity ,Risk Assessment ,Body Mass Index ,Dermatitis, Atopic ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Confidence Intervals ,Odds Ratio ,Prevalence ,Humans ,Israel ,Sex Distribution ,education ,Conjunctivitis, Allergic ,Retrospective Studies ,education.field_of_study ,Anthropometry ,business.industry ,Retrospective cohort study ,Odds ratio ,Atopic dermatitis ,medicine.disease ,Rhinitis, Allergic ,Asthma ,Cross-Sectional Studies ,Socioeconomic Factors ,Pediatrics, Perinatology and Child Health ,Population study ,Female ,business ,Body mass index ,030217 neurology & neurosurgery - Abstract
Background Recent data have shown an increasing occurrence of atopic dermatitis (AD) in children and adolescents, as well as in adults. Most of the epidemiologic research on AD is limited to pediatric and youth populations and is based on self-reported questionnaires. Methods A nationwide, population-based, cross-sectional retrospective study of adolescents with AD was performed to estimate its prevalence, trends, and association with demographic factors and comorbidities. The study included all Israeli teens going through medical evaluation as part of the assessment before being conscripted into the military from 1998 to 2013. Results A total of 1,187,757 adolescents were included in the study population, with an overall prevalence of AD of 0.64% in boys and 0.9% in girls. Over the study period, the prevalence of AD steadily increased, especially in the mild disease group. A greater risk of AD was found in subjects with high predicted socioeconomic status (male: odds ratio [OR] 1.14 [95% confidence interval {CI} 1.11, 1.16]; female: OR 1.08, [95% CI 1.05, 1.10]) and Israeli-born subjects (male: OR 1.34 [95% CI 1.21, 1.48]; female: OR 1.12 [95% CI 1.01, 1.23]). Allergic conditions such as asthma, conjunctivitis, and contact dermatitis were more prevalent in subjects with AD. There was a significantly higher prevalence of migraine in patients with AD (male: OR 1.35 [95% CI 1.18, 1.54]; female: OR 1.51 [95% CI 1.30, 1.74]). Conclusion This large cross-sectional study demonstrates the increasing prevalence of AD in adolescents and its relation to other allergic diseases and migraine. It is hoped that greater awareness of the distinctive epidemiologic characteristics of this population will lead to better recognition and management of the disease and its comorbidities.
- Published
- 2017
49. Secukinumab for the Treatment of Deficiency of Interleukin 36 Receptor Antagonist in an Adolescent
- Author
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Danielle Gordon, Vered Molho-Pessach, Rinad Alyan, Abraham Zlotogorski, and Hussein Jaradat
- Subjects
Male ,Adolescent ,Injections, Subcutaneous ,Dermatology ,Pharmacology ,Antibodies, Monoclonal, Humanized ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,Psoriasis ,medicine ,Humans ,Skin pathology ,Skin ,030203 arthritis & rheumatology ,biology ,Dose-Response Relationship, Drug ,business.industry ,Interleukins ,Interleukin ,Antibodies, Monoclonal ,medicine.disease ,Interleukin 1 receptor antagonist ,Interleukin 36 receptor antagonist ,Monoclonal ,biology.protein ,Secukinumab ,Antibody ,business - Published
- 2017
50. Fleckförmiger Haarausfall am Hinterkopf
- Author
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Abraham Zlotogorski, Alexander Maly, Yael Renert-Yuval, and Yuval Ramot
- Subjects
Dermatology - Published
- 2014
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