Management of Melasma: Laser and Other Therapies-Review Study.

Melasma is a commonly occurring pigmented skin condition that can significantly affect one's appearance, described as symmetric hyperpigmentation that presents as irregular brown to gray-brown macules on various facial areas, such as the cheeks, forehead, nasal bridge, and upper lip, along with the mandible and upper arms. Due to its complex pathogenesis and recurrent nature, melasma management is challenging and the outcomes following treatment are not always deemed satisfactory. Solely treating hyperpigmentation may prove ineffective unless paired with regenerative techniques and photoprotection, since one of the main reasons for recurrence is sun exposure. Hence, the treatment protocol starts with addressing risk factors, implementing stringent UV protection, and then treatment using different strategies, like applying topical treatments, employing chemical peels, laser and light therapies, microneedling, and systemic therapy. This review aims to provide a summary of the effectiveness and safety of the frequently employed laser and light therapies for treating melasma, focusing on laser therapy as a treatment for melasma.

Paediatric Mycosis Fungoides: Clinical Variants, Treatment Modalities and Response to Therapy.

Mycosis fungoides is a rare cutaneous lymphoma in the paediatric population. The aim of this study was to examine the epidemiological, clinical, and histological characteristics, as well as the treatment modalities and response to therapy of paediatric patients with mycosis fungoides. This retrospective cohort study reviewed the records of 37 paediatric patients treated at Rambam Medical Center, Israel, between 2013 and 2021. Extracted data included epidemiology, clinical presentation, histological reports, infiltrate clonality status, treatment modalities and response to therapy. The mean follow-up period was 60 months. All patients were diagnosed with stage IA or IB disease. Folliculotropic mycosis fungoides was the most prevalent variant (49%). Most patients were treated with phototherapy (90%), with a response rate of 85%, and a complete response rate of 55% after the first course. There were no significant differences in response to phototherapy between the folliculotropic or other variants (p = 0.072). Similarly, delayed diagnosis, atopic diathesis, clonality, phototherapy type or number of treatments, were not associated with response to therapy, while protracted phototherapy was associated with prolonged remission. In conclusion, mycosis fungoides in the paediatric population is an indolent disease with a favourable prognosis and potentially prolonged response to phototherapy.

Clinical-Epidemiological Characteristics of Hidradenitis Suppurativa: A Retrospective Cohort Study from a Tertiary Care Centre in Northern Israel.

BACKGROUND: Hidradenitis suppurativa (HS) is characterised by inflamed lesions that typically appear in apocrine-rich flexural areas. Although studies have reported clinical and epidemiological data from western countries, data from the Middle East are scarce. The aim of this study is to characterise the differences in the clinical characteristics of patients with HS of Arab and Jewish ancestry and review the clinical characteristics, the course of the disease, the comorbidities, and the response to treatment. METHODS: This is a retrospective study. We collected clinical and demographic data from patient files between 2015-2018 at the Rambam Healthcare Campus dermatology clinic-a tertiary hospital located in the north of Israel. Our results were compared to those of a previously published Israeli control group registered in Clalit Health Services. RESULTS: Of the 164 patients with HS, 96 (58.5%) were men and 68 (41.5%) were women. The average age at diagnosis was 27.5 years and the average latency between the onset and diagnosis of the disease was 4 years. We found a higher adjusted prevalence of HS in Arab patients (56%) than in their Jewish counterparts (44%). Gender, smoking, and obesity, as well as axilla and buttock lesions, were risk factors for severe HS, with no differences between ethnicities. No differences were documented in comorbidities and in response to adalimumab, with a high overall response rate of 83%. CONCLUSIONS: Our findings revealed differences between Arab and Jewish patients with HS in terms of incidence and gender predominance, while no differences were documented in comorbidities and response to adalimumab.

Propranolol for infantile hemangioma: Evaluating efficacy and predictors of response and rebound growth.

Propranolol emerged as the first-line therapy for infantile hemangioma (IH). Determinants of interindividual variation in drug response and predictors of rebound growth after drug discontinuation are yet to be firmly established. We aimed to evaluate the outcomes of a relatively large cohort of patients with IH treated by propranolol and to determine predictors of (a) an excellent response to treatment (≥90 improvement) and (b) of rebound growth after drug cessation. A retrospective cohort study was conducted to follow all patients with IH receiving systemic propranolol in a referral center-based specialized clinic. Multivariate logistic regression analysis was performed to identify predictors of excellent response and rebound growth. The study included 206 patients who completed oral propranolol treatment. The mean (SD) age in which the drug was initiated was 4.8 (3.1) months. The average improvement rate was estimated at 85.5 (13.8)%. Initiation of propranolol at the age of 0 to 3 (adjusted odds ratio [OR], 3.43; 95% confidence interval [CI], 1.25-9.40; P = .016) and 3 to 6 (adjusted OR, 3.71; 95% CI, 1.50-9.19; P = .005) months was associated with an increased likelihood of excellent response. Twenty-four (11.7%) patients developed rebound growth following cessation of propranolol. No significant predictors of rebound were identified in the multivariate analysis. Eleven (5.3%) patients experienced mild adverse events, which necessitated drug discontinuation in only two (1.0%) patients. Propranolol is highly effective and safe based on the real-life experience of a referral center for IH. The current study supports early initiation of propranolol.

Nonprescription acne vulgaris treatments: Their role in our treatment armamentarium-An international panel discussion.

BACKGROUND: Acne vulgaris (acne), a common inflammatory skin disorder, has its peak incidence between 14 and 19 years of age, with girls frequently developing acne earlier than boys. Over recent years, persistent acne is becoming more prevalent in adult women. OBJECTIVES: This review and panel discussion addresses challenges in acne management, particularly in adult women. The role which nonprescription acne treatment can play is explored when used as monotherapy or as an adjunctive treatment for acne of all severity. METHODS: The best available evidence on nonprescription acne treatment was coupled with the opinion of an international expert panel of dermatologists to adopt statements and recommendations discussed in this review. RESULTS: All severity of acne has a significant burden on patients. Addressing environmental factors that are important for the individual with acne may help to educate, prevent, effectively manage, and maintain acne, as per the panel. They agreed that the adult female acne population has unique needs because of their aging skin and social environment. Nonprescription acne treatment products may help to balance the efficacy and tolerability of prescription acne treatment. Currently, there are no specific guidelines for how to use nonprescription acne treatment products in these patients. CONCLUSION: The panel agreed that guidelines including nonprescription acne treatment either as monotherapy for mild acne or in combination with prescription treatments for more severe acne would address a significant unmet need.

Oral propranolol administration is effective for infantile hemangioma in late infancy: A retrospective cohort study.

The highest efficacy of oral propranolol is for infantile hemangioma (IH) in the proliferative phase. Evaluation of the effectiveness of oral propranolol is less established when it is administered in late infancy following the proliferative phase. We aimed to assess the clinical outcomes of pediatric patients managed by oral propranolol beyond the proliferative phase of IH. A retrospective cohort study in a tertiary health care referral center was conducted to track all patients with IH receiving systemic propranolol following the proliferative phase. Twenty-eight eligible patients were managed by 2 to 3 mg/kg per day of oral propranolol for IH beyond the proliferative phase, defined at 9 months of age. The mean age at the initiation of propranolol was estimated at 11.25 (SD 2.24) months. All eligible patients experienced some degree of clinical resolution, with the average improvement rate being estimated at 77.1% (SD 16.1). Comparable results were achieved among patients who were placed on propranolol at an age older than 12 months and those managed between the age of 9 and 12 months. No serious adverse events were observed during the follow-up duration. In conclusion, oral propranolol is a safe and effective treatment for patients with IH initiating this agent beyond the proliferative phase.

[DERMATOLOGIC CONDITIONS IN MONOZYGOTIC TWINS].

INTRODUCTION: Genetic twin studies may shed light on the genetic basis as well as environmental and epigenetic factors in disease pathogenesis. Herein, we present four pairs of monozygotic twins sharing similar phenotypes in three dermatologic conditions, and a literature review regarding twin studies in these diseases.

[AT THE BOTTOM OF THE ULCER - THE IMPORTANCE OF A BIOPSY IN DIAGNOSING HARD TO TREAT ULCERS].

INTRODUCTION: We report a case of a patient who presented with bilateral chronic painful necrotic leg ulcers. A skin biopsy revealed histopathological findings compatible with calciphylaxis, a rare phenomenon accompanied by high morbidity and mortality. Treatment options are limited and are based mainly on case reports and small series, so further research is needed in this area. This case highlights the importance of a skin biopsy in the diagnosis of chronic ulcers.

Hydroxychloroquine sulphate therapy of erosive oral lichen planus.

BACKGROUND/OBJECTIVES: Erosive oral lichen planus (LP) may be painful and debilitating. Symptomatic oral LP has been treated with a wide spectrum of topical and systemic therapies, but few have been evaluated in large series. Hydroxychloroquine is suggested to be effective in oral LP. METHODS: Twenty-one consecutive patients with erosive, biopsy-confirmed oral LP were prescribed. hydroxychloroquine sulphate 400 mg/day. Symptomatic improvement was evaluated by means of a visual analogue scale into three groups: no change, moderate to marked improvement and complete remission. RESULTS: Five (24%) patients obtained complete remission, 12 (57%) patients showed moderate to marked improvement, 3 (14%) patients did not improve at all and in one patient therapy was terminated after 1 month due to side effects. Response to therapy was observed after 2-4 months. Side effects which ultimately led to termination of therapy in three patients were elevated creatinine serum levels (after 1 month), visual field defects (after 8 months) and hyperpigmentation (after 24 months). Among six patients who responded to therapy, three flared on stopping. CONCLUSIONS: Hydroxychloroquine sulphate may be effective and relatively safe treatment for erosive oral LP.

Acne during adolescence did not predict skin rash reaction to cetuximab.

Cetuximab, a monoclonal antibody, is a part of the treatment for metastatic colorectal cancer. The most common side effect of cetuximab is skin rash, which has a similar distribution to acne vulgaris and some overlapping pathophysiological mechanisms. The aim of the current study was to determine whether acne vulgaris in adolescence (AinA) is predictive of a cetuximab-related rash to better understand the pathogenesis of this side effect and explore potential preventive actions. From July 2013 to June 2015, patients with metastatic colorectal cancer planned for treatment with cetuximab were enrolled in the study. Before initiating treatment, patients completed a questionnaire evaluating endocrine disorders, other chronic diseases, smoking, chronic medications, allergies, and dermatologic history of AinA and its severity. Patients were followed for 6 months. Data were collected from 32 participants (16 women, 16 men). Twenty-three (69%) patients experienced a cetuximab-associated skin reaction. Nine (28%) patients had a history of AinA. Of these, seven developed a cetuximab-associated skin reaction. Three of the five (60%) patients who used proton pump inhibitors (PPIs) developed severe (grades 3-4) skin toxicity versus 4/27 (15%) patients who were not on PPIs (P=0.057). The degree of skin toxicity correlated to the median time-to-tumor-progression: 2 months for patients with grades 0-1 compared with 5.5 months for grades 2-4 skin toxicity (P=0.047, 95% confidence interval 1.06-4.95). No significant correlation was found between AinA and cetuximab-associated skin reactions. The correlation between PPI treatment and severe skin toxicity related to cetuximab should be examined further.

Clinical and imaging findings in patients with neurosyphilis: a study of a cohort and review of the literature.

BACKGROUND: Most patients with neurosyphilis are considered asymptomatic. The diagnosis is challenging and the role of neuroimaging is not yet well established. The present study was conducted to focus on the clinical findings and further characterize the imaging features of the disease, along with a review of the pertinent literature. METHODS: Six male patients with neurosyphilis based on abnormal cerebrospinal fluid findings, five of whom were asymptomatic at presentation, underwent cranial computerized tomography (CT) and magnetic resonance imaging (MRI). They also underwent a complete physical, neurological, and ophthalmological examination, with special attention paid to atherosclerotic vascular risk factors. In addition, all were examined for cardiac involvement using electrocardiography and cardiac ultrasound. RESULTS: The meticulous neurological and ophthalmological examination revealed abnormalities in five patients, most commonly cranial nerve involvement (three patients) and hemiparesis (two patients). The CT and MRI studies revealed abnormalities in five of the six patients, and in all six patients, respectively. The most common findings were brain infarcts, which were demonstrated in four of the six patients. MRI was found to be more sensitive than CT in detecting these brain infarcts, as expected. CONCLUSIONS: Vascular insult was the most common neuroimaging finding in our patients with neurosyphilis, probably due to meningovascular endarteritis. Neurosyphilis should always be considered in young patients with unexplained brain infarcts.

A study of histologic and immunophenotypical staining patterns in cutaneous lymphoid hyperplasia.

BACKGROUND: Cutaneous lymphoid hyperplasia (CLH) is generally classified according to clinicopathologic entities or put into broad spectrums of B-cell or T-cell predominance or co-dominance. OBJECTIVE: We sought to discern histologic features and immunohistochemical staining patterns in CLH that may form a basis for a histologic classification system. METHODS: We studied the clinical, histologic, immunophenotypical, and molecular characteristics of 24 consecutive patients with CLH. RESULTS: The 24 cases were classified according to characteristic histologic features and immunophenotypical staining patterns as follows: presence of germinal center (GC) cell clusters forming well-defined lymphoid follicles (n = 10); presence of clusters of GC cell clusters not forming well-defined lymphoid follicles (n = 6); persistent arthropod assault type CLH (n = 1); CLH with a prominent histiocytic component (n = 4); and CLH without specific histologic and immunophenotypical features, that is, nonspecific mixed T-cell and B-cell CLH (n = 3). Most of the CLH cases did not demonstrate clonal T-cell receptor and/or immunoglobulin heavy chain gene rearrangements except for 3 cases in which the long-term follow-up was uneventful. LIMITATIONS: There were a limited number of cases in our study. CONCLUSIONS: A classification based on characteristic histologic features and immunophenotypical staining patterns, along with pertinent clinical and molecular data, may enhance the diagnosis of CLH.

Contact hypersensitivity in patients with primary cutaneous lymphoproliferative disorders.

BACKGROUND: One of the suggested causes of primary cutaneous lymphoproliferative disorders is persistent antigenic stimulation. OBJECTIVE: To study the prevalence of contact hypersensitivity in patients with primary cutaneous lymphoproliferative disorders other than mycosis fungoides (MF). MATERIALS AND METHODS: Thirty consecutive patients with primary cutaneous lymphoproliferative disorders other than MF were patch tested to a European Standard & partial metal series. The results were compared with those of 792 consecutive patients with other skin diseases referred to our clinic and a large published series of 9760 healthy individuals from North America. RESULTS: Twenty-two patients with primary cutaneous lymphoma other than MF and eight patients with pseudolymphomas were included in the study. Altogether there were 23 positive patch tests in 13 patients. Only the prevalence of positive patch tests to cobalt (5/30 patients = 17%) was found to be significantly higher in the studied group than in the two control groups (P<0.01 and P=0.05, respectively). The contact hypersensitivity to cobalt and the other allergens, however, could not be related causally to the pathogenesis of the lesions. CONCLUSIONS: The relative prevalence of contact hypersensitivity to cobalt only was found to be increased in a group of primary cutaneous lymphoproliferative disorders, but a causal relationship to the lymphoproliferative disorders could not be established.

Multifocal congenital lymphangioendotheliomatosis without gastrointestinal bleeding and/or thrombocytopenia.

A 5-month-old male infant presented with an increasing number of widespread asymptomatic violaceous cutaneous macules, papules, and nodules since birth. He is 1 of the 2 identical twins born to unrelated healthy parents. Histology revealed proliferation of dilated thin-walled vascular channels lined by bland endothelial cells in the dermis and subcutis. In some of the vascular channels, there were formations of intravascular papillae surrounded by hobnail endothelial cells. Immunohistochemistry demonstrated positive staining for CD31, CD34 factor VIII and vascular endothelial growth factor-3 (VEGFR-3) and negative staining for D2-40 and latencyassociated nuclear antigen-1 (LANA-1). The clinical and histologic findings were compatible with multifocal congenital lymphangioendothelionmatosis with thrombocytopenia, except that a year of follow-up was uneventful and no gastrointestinal bleeding or thrombocytopenia was recorded.

Topical erythropoietin promotes wound repair in diabetic rats.

Wound healing in diabetic patients is slower than in healthy individuals. Erythropoietin (EPO) has non-hemopoietic targets in the skin, and systemically administered EPO promotes wound healing in experimental animals. This study investigated the effect of topical EPO treatment on defective wound repair in the skin of diabetic rats. Full-thickness excisional skin wounds were made in 38 rats, of which 30 had diabetes. The wounds were then treated topically with a cream that contained either vehicle, 600 IU ml(-1) EPO (low dose), or 3,000 IU ml(-1) (high dose) EPO. We assessed the rate of wound closure during the 12-day treatment period, and microvascular density (MVD), vascular endothelial growth factor (VEGF), and hydroxyproline (HP) contents, and the extent of apoptosis in wound tissues at the end of the 12-day treatment period. Topical EPO treatment significantly reduced the time to final wound closure. This increased rate of closure of the two EPO-treated wounds in diabetic rats was associated with increased MVD, VEGF, and HP contents, and a reduced extent of apoptosis. In light of our finding that topical EPO treatment promotes skin wound repair in diabetic rats, we propose that topical EPO treatment is a therapeutically beneficial method of treating chronic diabetic wounds.

A unique pattern of dyskeratosis characterizes epidermolytic hyperkeratosis and epidermolytic palmoplantar keratoderma.

Hereditary skin diseases that are characterized ultrastructurally by intracellular clumpings of keratin tonofilaments, such as Darier disease and Ichthyosis Hystrix of Curth-Macklin, display epidermal dyskeratosis also histologically. Epidermolytic hyperkeratosis (EHK) and epidermolytic palmoplantar keratoderma (Voerner type) (EPPK) are 2 types of autosomal dominant keratodermas, which are also characterized ultrastructurally by intracellular clumpings of tonofilaments but usually without a clear description of histological dyskeratosis. The main aim of the present study was to characterize the histologic signs of keratin aggregation and clumping in the involved epidermis of EHK and EPPK. Two cases of EHK caused by KRT1 mutations and 4 cases of EPPK caused by KRT9 mutations were studied. The biopsies were obtained mostly from the involved skin of the palm. All 6 biopsies were studied histologically, and 4 biopsies (2 EHKs and 2 EPPKs) were also studied ultrastructurally. All 6 cases displayed the characteristic histological epidermolytic changes. In addition, intracytoplasmic and perinuclear eosinophilic homogenizations and round to oval eosinophilic inclusions were identified with varying frequencies in the involved epidermis of all 6 cases. These findings, which were more prominent in the EHK cases, corresponded most likely to the intracytoplasmic aggregates of tonofilaments and to the large round to oval dense clumps of tonofilaments, which were observed ultrastructurally. In conclusion, varying degrees of dyskeratosis are frequently present in EHK and EPPK and should be considered to be a histological characteristic of these disorders.

The applicability of the new WHO-EORTC classification of primary cutaneous lymphomas to a single referral center.

Recent years have witnessed differences between the World Health Organization (WHO) and the European Organization for Research and Treatment of Cancer (EORTC) classification systems of primary cutaneous lymphomas (PCLs). Recently, a joint WHO-EORTC classification system for PCLs has been reached. This study was performed to assess the applicability of this new classification to a single referral center. All new PCL cases, excluding mycosis fungoides and Sezary syndrome, who were referred from 1999 to 2005 were included. The histological, immunohistochemical stainings and molecular studies were reviewed, and additional stains were performed as needed. The cases were then reclassified according to the WHO-EORTC classifications. The clinical files were also studied, and the patients were followed up clinically. There were 43 new non-mycosis fungoides/Sezary syndrome PCLs, including 29 B-cell lymphomas of which 14 were follicle center lymphoma, 10 marginal zone lymphoma, 4 diffuse large-B-cell lymphoma, leg type, and 1 diffuse large-B-cell lymphoma, other. The 14 T-cell lymphomas included 5 cases of lymphomatoid papulosis, 2 CD30+ anaplastic large-cell lymphomas, 1 NK/T-cell lymphoma, and 6 peripheral T-cell lymphomas, unspecified. Of the 6 "unspecified" T-cell lymphomas, 3 were CD4+ small/medium-sized pleomorphic T-cell lymphoma, which is considered currently a provisional entity under the unspecified T-cell category. The remaining 3 cases could not be classified beyond the unspecified T-cell category, of which 2 cases had an aggressive course. The new WHO-EORTC classification is applicable to most non-mycosis fungoides/Sezary syndrome PCL cases, especially the B-cell lymphomas. However, there is still a substantial subset of T-cell PCLs which cannot be classified beyond the unspecified peripheral T-cell category, some of which may have an aggressive course.

Rapid detection of homozygous mutations in congenital recessive ichthyosis.

Congenital recessive ichthyoses (CRI) form a remarkably heterogeneous group of diseases, resulting from mutations in at least eight distinct genes, six of which have been identified so far. In the present study we ascertained two CRI families of Iranian and Druze origins. Exploiting the high degree of consanguinity characterizing these populations, we typed all family members for microsatellite markers spanning the major CRI chromosomal loci and used homozygosity mapping to identify candidate genes for subsequent mutational analysis. This strategy led to the rapid identification of two novel homozygous CRI-causing mutations in TGM1 (c.2058delC) and FLJ39501 (p.W521X). The present data demonstrate that the molecular analyses of CRI in consanguineous families can be readily completed in less than 96 h at relatively low costs.

Cutaneous lymphoid hyperplasia presenting as a solitary facial nodule: clinical, histopathological, immunophenotypical, and molecular studies.

OBJECTIVE: To elucidate the clinicopathological, immunophenotypical, and molecular characteristics of cutaneous lymphoid hyperplasia presenting as a solitary facial nodule. DESIGN: Retrospective study. SETTING: University dermatology department. PATIENTS: Three patients with a solitary facial nodule were studied clinically, histologically, immunophenotypically, and molecularly for T-cell receptor and immunoglobulin heavy chain gene rearrangements. MAIN OUTCOME MEASURES: Histological, immunophenotypical, and molecular characteristics in relation to the clinical outcome. RESULTS: Histologically, dense diffuse lymphocytic infiltrates were present throughout the dermis, occasionally extending into the subcutaneous fat and the epidermis and hair follicles. Small lymphocytes predominated, but in 2 cases there were also medium to large atypical lymphocytes, with some blastlike lymphocytes. The lymphocytic population was mixed with more CD3(+) T cells than CD20(+) B cells, without germinal centers. There were more CD4(+) than CD8(+) cells, and some of the T cells stained for the memory T-cell marker CD45RO. Numerous CD68(+) histiocytes were scattered or formed small aggregates, and in 1 case small granulomas and many scattered S100 protein-positive and CD1a(+)dendritic cells were present. In addition, several polytypic plasma cells, eosinophils, and extravasated erythrocytes were found. Immunostaining for CD10, CD21, CD30, CD56, and BCL6 was negative. The Ki-67 proliferation index was relatively low (5%-10%). Results of the T-cell receptor gene rearrangement studies were positive in 2 cases, 1 of which also harbored clonal B cells. Serologic test results for Borrelia burgdorferi, Borrelia afzelii, and Borrelia garinii were negative in all 3 cases. Two lesions regressed spontaneously after an incisional biopsy, and none of the cases showed recurrence or extracutaneous spread during a follow-up period of 5.0 to 5.5 years. CONCLUSIONS: Cutaneous lymphoid hyperplasia that presents as a solitary facial nodule may share clinical, cytological, immunophenotypical, and molecular features with both benign reactive lymphocytic infiltrates and cutaneous lymphomas, and therefore a careful clinical and therapeutic approach is warranted.

Positive patch test reactions to allergens of the dental series and the relation to the clinical presentations.

The clinical manifestations of contact allergic dermatitis to dental materials are not uniform. This study was performed to detect the frequent allergens in the dental series associated with contact dermatitis and to define the causal relationship between the different allergens and the relevant clinical presentations. Between the years 2000 and 2004, 134 patients, aged 20-80 years, were patch tested. 121 patients were included in the study. The most frequent oral manifestations were cheilitis and perioral dermatitis (25.6%), burning mouth (15.7%), lichenoid reaction (14.0%), and orofacial granulomatosis (10.7%). 18 (14.9%) patients were dental personnel, all of whom suffered from hand dermatitis. The common allergens detected included goldsodiumthiosulphate (14.0%), nickel sulfate (13.2%), mercury (9.9%), palladium chloride (7.4%), cobalt chloride (5.0%), and 2-hydroxyethyl methacrylate (5.8%). Positive reactions to metals were frequent in all the different clinical variants, and no specific association between a specific clinical presentation and a particular allergen was found. Allergy to mercury was not a significant factor contributing to the pathogenesis of oral lichenoid reactions. However, a strong association with contact allergy to mercury in dental fillings was found in 2 patients with orofacial granulomatosis.