Rony Shreberk-Hassidim

Janus kinase inhibitors in dermatology: A systematic review

Background Janus kinase (JAK) inhibitors are emerging as a promising new treatment modality for many inflammatory conditions. Objective Our aim was to systematically review the available data on the use of JAK inhibitors in cutaneous diseases. Methods This is a systematic review of PubMed and ClinicalTrials.gov. Results One hundred thirty‐four articles matched our search terms, of which 78 were original articles and 12 reports on adverse events. Eighteen clinical trials were found. JAK inhibitors have been extensively studied for psoriasis, showing beneficial results that were comparable to the effects achieved by etanercept. Favorable results were also observed for alopecia areata. Promising preliminary results were reported for vitiligo, dermatitis, graft versus host disease, cutaneous T cell lymphoma, and lupus erythematosus. The most common adverse events reported were infections, mostly nasopharyngitis and upper respiratory tract infections. Limitations It was not possible to perform a meta‐analysis of the results. Conclusions This systematic review shows that while JAK inhibitors hold promise for many skin disorders, there are still gaps regarding the correct dosing and safety profile of these medications for dermatologic indications. Additional trials are necessary to address these gaps.

A systematic review of pulse steroid therapy for alopecia areata

To the Editor: Alopecia areata (AA) is an autoimmune disease that causes emotional and social distress. Proper assessment of the efficacy of different therapies is challenging because of the disease’s unpredictable nature and high rates of spontaneous remission. The most frequently used treatments are topical or intralesional corticosteroids, with systemic corticosteroids used in more severe cases. The use of systemic pulse corticosteroid treatment (PCT) was introduced for severe types of AA in 1975, to minimize the side effects associated with prolonged systemic corticosteroid therapy. Since then, many reports on PCT have been published, with conflicting findings.

Atopic Dermatitis in Israeli Adolescents from 1998 to 2013: Trends in Time and Association with Migraine

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.

Kerion celsi of the vulva: An unusual location

Figure 1 A. Erythematous boggy plaque, covered with white scale and pustules, involving the vulva. B. Erythematous plaque covered with several pustules involving the shin. C. Hyphae and arthrospores found within the follicular space, with a dense intrafollicular suppurative inflammation H & E. A. Plaque érythémateuse humide recouverte de squames blanches et de pustules, située sur la vulve. B. Plaque érythémateuse avec des pustules sur la peau. C. Filaments et arthrospores présents dans l’espace folliculaire avec une forte inflammation et suppuration intrafolliculaire. Kerion is the inflammatory extreme of dermatophyte infection, caused by a vigorous T-cell-mediated host response to the dermatophyte infection [1]. It manifests as suppurative and painful plaques or nodules, accompanied by purulent drainage, and with potential folliculitis. It usually affects the scalp, and may result in scarring alopecia if treatment is delayed [2]. Common pathogens to trigger kerion include Trichophyton mentagrophytes, Trichophyton verrucosum, Microsporum canis, Microsporum gypseum, Trichophyton tonsurans, Trichophyton violaceum, and Trichophyton soudanense [2]. We present a rare case of kerion celsi caused by T. mentagrophytes involving the vulva, an unusual site for this disorder. A 19-year-old female patient presented to the department of dermatology in Hadassah — Hebrew University Medical Center with an itchy and painful eruption on her pubis and vulva of 2-month duration. The eruption gradually spread to her chin, right anterior shin, right waist and buttocks. Previous treatments included a combination of local corticosteroids (hydrocortisone acetate and triamcinolone acetonid), antibiotics (gramicidin and neomycin) and antifungals (clotrimazole and nystatin) for two courses of oneweek duration each, and oral amoxicillin/clavulanate 875 mg for 3 days with no improvement. The patient denied owing pets or being in close contact with pets or animals, and mentioned using a personal shaver for pubic hair removal. The patient had one sexual partner who reportedly had no clinical rash. Physical examination demonstrated a boggy, erythematous plaque on the pubis and vulva covered by several pustules and yellow-colored crusts with swelling and alopecia of the labia majora (Fig. 1A). In addition,

Lymphocutaneous nocardiosis caused by Nocardia brasiliensis in an immunocompetent elderly woman.

erythema necroticans. Indian J Lepr 2002; 74: 145–149. 5 Tourlaki A, Marzano AV, Gianotti R, et al. Necrotic erythema nodosum leprosum as the first manifestation of borderline lepromatous leprosy. Arch Dermatol 2008; 144: 818–820. 6 Al Hayki N, Al-Mahmoud B. Erythema necroticans: a presenting manifestation of silent leprosy. J Saudi Soc Dermatol Dermatol Surg 2011; 15: 63–66. 7 Ghorpade AK. Transepidermal elimination of Mycobacterium leprae in histoid leprosy: a case report suggesting possible participation of skin in leprosy transmission. Indian J Dermatol Venereol Leprol 2011; 77: 59–61. 8 Sahu S, Dewan S, Gupta G. De novo histoid leprosy with unique feature of transmigration: a case report. IOSR J Dent Med Sci 2012; 3: 1–4. 9 Namisato M, Kakuta M, Kawatsu K, et al. Transepidermal elimination of lepromatous granuloma: a mechanism for mass transport of viable bacilli. Lepr Rev 1997; 68: 167–172. 10 Ghorpade A. Histoid leprosy with mycobacterial keratinous bullets after possible transepidermalelimination of bacilli. Int J Dermatol 2013; 52: 1530–1532.

Clinical description of skin lesions in pathology requisition forms completed by plastic surgeons is lacking: a retrospective study of 499 lesions

Clinical description of biopsied skin lesions provided on pathology requisition forms (PRFs) has a pivotal role in the pathological examination [1, 2]. However, the literature on which clinical characteristics should be included in the PRFs is sparse. It was previously suggested that the clinical information provided in the PRF will comprise demographic details, morphology, diameter and duration of the lesion, co-morbidities, and differential diagnoses [3, 4]. The ABCDE (asymmetry, border, color, diameter, and evolving) acronym was suggested for melanoma screening [5, 6]. Important clinical data regarding non-melanocytic skin cancer (NMSC) usually consist of characteristics for which we used the acronym BIGLST (size, location, growth rate, bleeding, medical history of immunosuppression, and previous irradiation or liquid nitrogen treatment) [7, 8]. Even though the communication between the clinician and pathologist is of great importance, unfortunately, few studies demonstrate that the clinical description in the PRF is lacking [9]. We aim to evaluate the amount and the quality of information provided by plastic surgeons on the PRF of melanocytic and non-melanocytic skin lesions. We held a retrospective study of 499 consecutive skin lesions which were excised in our plastic surgery clinic between October 2015 and January 2016. The ABCDE criteria were used to evaluate the PRFs of melanocytic skin lesions (ML), while the BIGLST criteria were used for non-melanocytic skin lesions (NML) which were suspected for NMSC. The adjusted score for ML was the amount of criteria filled by the plastic surgeon divided by 5. The adjusted score for NML was the amount of criteria filled by the plastic surgeon divided by 6. Categorical variables were compared using chisquare tests and continuous variables were compared using the independent sample t test. A two-tailed p < 0.05 was considered statistically significant. All analyses were performed with the SPSS 21.0 software (SPSS Inc., Chicago, IL). Yarden Zohar and Rony Shreberk-Hassidim have contributed equally for this research.

Immunopathology of Drug and Toxin-Related Skin Reactions

The skin has an important role as a barrier, protecting the organism from its environment. Therefore, it participates significantly in several immunological processes, and this novel role is gradually revealed in recent studies. We overview the main components of the cutaneous immunological response, divided into contact and systemic antigen exposures. The major players of the immunopathological skin reactions are the keratinocytes, Langerhans cells and dermal dendritic cells. In addition, we discuss the use of animal models for exploring the complexity of these reactions.

Prevalence of Sharing Access Credentials in Electronic Medical Records

Objectives Confidentiality of health information is an important aspect of the physician patient relationship. The use of digital medical records has made data much more accessible. To prevent data leakage, many countries have created regulations regarding medical data accessibility. These regulations require a unique user ID for each medical staff member, and this must be protected by a password, which should be kept undisclosed by all means. Methods We performed a four-question Google Forms-based survey of medical staff. In the survey, each participant was asked if he/she ever obtained the password of another medical staff member. Then, we asked how many times such an episode occurred and the reason for it. Results A total of 299 surveys were gathered. The responses showed that 220 (73.6%) participants reported that they had obtained the password of another medical staff member. Only 171 (57.2%) estimated how many time it happened, with an average estimation of 4.75 episodes. All the residents that took part in the study (45, 15%) had obtained the password of another medical staff member, while only 57.5% (38/66) of the nurses reported this. Conclusions The use of unique user IDs and passwords to defend the privacy of medical data is a common requirement in medical organizations. Unfortunately, the use of passwords is doomed because medical staff members share their passwords with one another. Strict regulations requiring each staff member to have its a unique user ID might lead to password sharing and to a decrease in data safety.

Squamous cell carcinoma in situ in association with HPV 11 in Netherton's syndrome patient: a case report.

crucial role in cancer immune surveillance, promoting antitumour responses. Herein, we report a case of melanoma who responded to nivolumab and whose mRNA levels of granzyme B and IFN-c upregulated in the tumour lesion. A 79-year-old man was referred to our hospital for treatment of metastatic melanoma on his left leg (Fig. 1). He previously underwent a wide resection of the tumour on the left plantar and inguinal lymph nodes (pT4N3M0 stageIIIc). Six months after the operation, the patient noticed small black nodules and spots on the left thigh and lower leg. Physical examination revealed a large number of nodules and black spots with perilesional erythema (Fig. 1a). Skin biopsy from the tumour on his leg revealed metastatic melanoma. We commenced treatment with nivolumab (2 mg/kg). Before the fourth course of nivolumab treatment, we performed another skin biopsy of the leg tumour because the perilesional erythema had expanded rapidly (Fig. 1b). After the fifth course of nivolumab (Fig. 1c), all the perilesional erythema changed to depigmented oval patches surrounding central black nodules and small spots (Fig. 1d). These lesions were proved to be non-neoplastic cells, but melanin-containing macrophages by means of H&E staining (Fig. 1d,e) and Giemsa counterstaining with Melan A and Human melanin black (HMB) 45 (Fig. 1f,g). To understand the mechanism of tumour immunity in a responding lesion, we examined the expression levels of IFN-c, interleukin (IL)-4, granzyme B, perforin, and Fas ligand by means of real-time polymerase chain reaction. The expression levels of IFN-c and granzyme B were upregulated after two treatment courses of nivolumab (Fig. 2). Herein, we report a case of metastatic melanoma following a unique clinical course with nivolumab treatment. The patient had perilesional erythema that spread widely after nivolumab treatment. The perilesional erythema subsequently disappeared and changed to depigmented oval patches at all tumour sites. The mRNA levels of granzyme B and IFN-c upregulated in a responding melanoma lesion after treatment with anti-PD-1 antibody following two courses of nivolumab treatment when the perilesional erythema was spreading rapidly. Consistent with our result, a previous study demonstrated that increased expression of granzyme B – expressing T cells in melanoma biopsies were correlated with a favourable outcome. In addition, another group showed that the number of CD8 and granzyme B T cells increased after treatment with BRAF inhibitor in responding cases. Although it is limited to a single case and further studies are needed in the future, our study suggests that granzyme B and IFN-c may play an essential role in tumour immunity during anti-PD-1 treatment.

Successful treatment of refractory Darier disease with alitretinoin with a follow up of over a year: a case report.

Darier disease is a rare genetic cutaneous disorder (OMIM #124200) of abnormal keratinization (1) manifesting as firm greasy papules with a predilection to seborrheic areas (2). Management is usually unsatisfactory, and includes sun-block creams and emollients, with systemic retinoids saved for more severe or extensive disease (3). Treatment with oral retinoids is challenging in female patients of childbearing age, owing to their teratogenic potential and the long half-life of acitretin. Alitretinoin (9-cis retinoic acid) is a new vitamin A derivate, agonist for both retinoic acid and retinoic X receptors. It was recently approved for the treatment of chronic hand eczema and was shown to have immuno-modulatory, antiproliferative, and anti-inflammatory effects (4). We report a case of a young female with Darier disease unresponsive to isotretinoin therapy, who was treated successfully with oral alitretinoin. Case report