Intralesional human papillomavirus vaccine for the treatment of recalcitrant cutaneous warts.

Human papillomavirus (HPV) is ubiquitously distributed in the population worldwide and its most frequent clinical presentation is cutaneous warts. Despite various treatment options currently available, many patients experience persistent and refractory disease. We sought to evaluate the clinical effectiveness and safety profile of intralesional HPV 9-valent vaccine for the treatment of recalcitrant warts. A retrospective study was performed for all cases of cutaneous warts treated with intralesional 9-valent HPV vaccine between January 2017 and March 2021. Epidemiologic, clinical, and treatment data, including safety and effectiveness scores, were reviewed. Our cohort was composed of 20 patients: 13 adults and seven children. Twelve patients (60%) displayed a complete response whereas 8 patients (40%) showed a partial response. Older age was associated with a better response to treatment, while a history of laser therapy was associated with a worse prognosis. Adverse events were local, transient, and negligible. No systemic adverse effects were reported. Intralesional 9-valent HPV vaccine may be considered for the treatment of recalcitrant cutaneous warts. Controlled studies are required to confirm these results.

Data From a One-Stop-Shop Comprehensive Cancer Screening Center.

PURPOSE: Cancer is the second leading cause of death globally. However, by implementing evidence-based prevention strategies, 30%-50% of cancers can be detected early with improved outcomes. At the integrated cancer prevention center (ICPC), we aimed to increase early detection by screening for multiple cancers during one visit. METHODS: Self-referred asymptomatic individuals, age 20-80 years, were included prospectively. Clinical, laboratory, and epidemiological data were obtained by multiple specialists, and further testing was obtained based on symptoms, family history, individual risk factors, and abnormalities identified during the visit. Follow-up recommendations and diagnoses were given as appropriate. RESULTS: Between January 1, 2006, and December 31, 2019, 8,618 men and 8,486 women, average age 47.11 ± 11.71 years, were screened. Of 259 cancers detected through the ICPC, 49 (19.8%) were stage 0, 113 (45.6%) stage I, 30 (12.1%) stage II, 25 (10.1%) stage III, and 31(12.5%) stage IV. Seventeen cancers were missed, six of which were within the scope of the ICPC. Compared with the Israeli registry, at the ICPC, less cancers were diagnosed at a metastatic stage for breast (none v 3.7%), lung (6.7% v 11.4%), colon (20.0% v 46.2%), prostate (5.6% v 10.5%), and cervical/uterine (none v 8.5%) cancers. When compared with the average stage of detection in the United States, detection was earlier for breast, lung, prostate, and female reproductive cancers. Patient satisfaction rate was 8.35 ± 1.85 (scale 1-10). CONCLUSION: We present a proof of concept study for a one-stop-shop approach to cancer screening in a multidisciplinary outpatient clinic. We successfully detected cancers at an early stage, which has the potential to reduce morbidity and mortality as well as offer substantial cost savings.[Media: see text].

Monitoring oral propranolol for infantile hemangiomata.

Treating infantile hemangiomas with oral propranolol may be initiated in accordance with various protocols some require hospitalization. However, different adverse events have been reported during treatment, thus it is of special importance to find a protocol which is both safe and feasible. We performed a retrospective cohort study of all cases of infantile hemangiomas treated with oral propranolol at our institute between January 2010 and February 2020. Pretreatment evaluation consisted of pediatric cardiologist evaluation including electrocardiography and echocardiography. The propranolol starting dosage was 0.5 mg/kg bid; 2 weeks later the dosage was escalated to 1 mg/kg bid. During the initiation and escalation visits, heart rate and blood pressure were measured before and every hour for a total of 3 h, and blood glucose level was measured within the first hour of treatment. A total of 131 children were treated during the study period. Scalp, facial and genital region infantile hemangiomas were more prevalent in regard to their relative body surface area. No symptomatic bradycardia, hypotension, hypoglycemia, or any other adverse events were documented; few patients had asymptomatic bradycardia and hypotension, which were more common in infants below 6-months of age. Only one patient had asymptomatic hypoglycemia, not requiring any intervention. Initiation and escalation of propranolol treatment for infantile hemangiomas proved to be safe, and without symptomatic adverse effects. However, considering the young age of the patients and the possible asymptomatic adverse reactions, we recommend the following simple protocol as presented, for pretreatment evaluation and short monitoring during treatment initiation and dose escalation.

A review of combined treatments for melasma involving energy-based devices and proposed pathogenesis-oriented combinations.

BACKGROUND: Melasma is an acquired disorder of hyperpigmentation, affecting a million individuals worldwide. Energy-based devices (EBDs) employed to treat melasma include various types of lasers, intense pulsed light (IPL), and radiofrequency (RF). Recent studies have attempted to address recalcitrant and recurring melasma by combining energy-based devices with topical or oral medications. OBJECTIVE: This article reviews EBDs-based augmented treatment for melasma and suggests practical pathogenesis-oriented treatment regimens. Treatment algorithms are proposed to address various components of melasma. METHODS: A systematic PubMed search was conducted acquiring information from various studies on combination treatments of melasma involving EBDs. RESULTS: The 286 retrieved articles were filtered by title to contain at least one type of energy-based modality such as laser, IPL, or RF along with at least one other treatment method. Based on their subject matter, combinations were further categorized into the subheadings: laser plus medication, laser plus laser, and IPL- and RF-containing treatment methods. CONCLUSION: There are many energy-based combination treatments that have been explored for mitigation of melasma including laser therapy with medication, multi-laser therapies, IPL, RF, and microneedling devices. Melasma is an exceedingly difficult condition to treat, however, choosing the appropriate tailor-made treatment combination can improve the final outcome.

Predictors of the CD24/CD11b Biomarker among Healthy Subjects.

The CD24 gene has raised considerable interest in tumor biology as a new prognostic factor and a biomarker for the early detection of cancer. There are currently no studies that assess predictors of CD24 in blood tests among healthy individuals. Our aims were (1) to evaluate predictors of the CD24/CD11b biomarker among healthy subjects and (2) to assess CD24/CD11b levels of participants with and without benign tumors. Our cohort included 1640 healthy subjects, aged 20-85, recruited at the Health Promotion and Integrated Cancer Prevention Center (ICPC) in the Tel Aviv Medical Center. Eligible subjects completed a detailed questionnaire on medical history and other epidemiologic information. CD24/CD11b expression in peripheral blood leukocytes (PBLs) obtained from blood samples of participants was analyzed by flow cytometry. Our results showed that the average levels of CD24/CD11b in healthy patients (22.8 ± 9.3) was statistically significant lower compared to subjects with benign cancers (26.1 ± 10.5, p < 0.001). Our multivariable analysis demonstrated that elevated levels of CRP (coefficient ß: 1.98, p = 0.011) were significantly associated with high levels of CD24/CD11b expression among healthy participants. Other risk factors of cancer were not associated with elevated CD24 levels among healthy subjects. In conclusion, our findings may assist in further development and optimization of the CD24/CD11b biomarker to serve as a cancer screening test for early detection of cancer among the healthy population.

Feasibly of CD24/CD11b as a Screening Test for Hematological Malignancies.

An estimated 1.24 million blood cancer cases occur annually worldwide, accounting for approximately 6% of all cancer cases. Currently, there are no standardized hematology cancer screening tests that are recommended for the general population. CD24 is a mucin-like cell surface molecule and P-selectin ligand, which plays a significant role in the maturation of B-lymphocytes and was found to be overexpressed in a number of hematological malignancies. Our primary aim was to assess the sensitivity and specificity of the CD24/CD11b-based blood test for the detection of hematological malignancies. Our cohort included 488 subjects with positive hematological cancer diagnosis (n = 122) and healthy subjects (n = 366). CD24/CD11b expression in peripheral blood leukocytes (PBLs) obtained from blood samples of participants was analyzed by flow cytometry. Our results demonstrated that the average levels of CD24/CD11b in healthy patients (21.7 ± 9.0) were statistically significantly lower compared to levels of CD24/CD11b in cancer patients (29.5 ± 18.7, p < 0.001). The highest levels of CD24/CD11b were found in multiple myeloma (39.1 ± 23.6), followed by chronic myeloid leukemia (33.0 ± 13.7) and non-Hodgkin lymphoma (32.3 ± 13.3). The test had an overall sensitivity for hematologic cancers of 78.5% (95% CI, 70.7-86.3%) and specificity of 80.2% (95% CI, 76.1-84.3%). In conclusion, our findings indicate the feasibility of a CD24/CD11b-based blood test as a screening test of hematological malignancies.

Treatment options for DOCK8 deficiency-related severe dermatitis.

BACKGROUND: Cutaneous manifestations of dedicator of cytokinesis 8 gene (DOCK8) deficiency, a combined type of T and B cell immunodeficiency, previously designated as autosomal recessive hyper IgE syndrome, includes dermatitis and skin infections. There are limited treatment options for dermatitis related to the syndrome. OBJECTIVE: To describe a cohort of patients with DOCK8 deficiency with a focus on the treatment of their cutaneous manifestations. METHODS: A retrospective study on all children with the genetic diagnosis of DOCK8 deficiency treated at the Sheba Medical Center between 1/1/2003 and 1/1/2021 was preformed. Collected data included: demographic features, family history, laboratory, genetic testing, skin manifestations, treatment, and disease course. Description of two cases of severe recalcitrant dermatitis treated with dupilumab is detailed. RESULTS: Nine children with a genetic diagnosis of DOCK8 deficiency were included, of whom six were girls (66%) with a median age of 8.5 (±2.2 SD) years. The median age at diagnosis was 2.8 (±2.6 SD) years. Six patients were born to consanguineous parents. Five out of six patients who received hematopoietic stem cell transplantation (HSCT) had a complete response, and one was recently transplanted. Of note, two patients, while awaiting HSCT, were treated with dupilumab for their severe dermatitis resulting in a marked improvement of the cutaneous manifestations and pruritus. CONCLUSIONS: Hematopoietic stem cell transplantation is the gold standard and most effective therapy for patients with DOCK8 deficiency. Dupilumab, a biological therapy indicated for atopic dermatitis and other Th2 derived dermatoses, is an excellent option for dermatitis in patients with DOCK8 deficiency and can be used as a bridge before HSCT. Larger studies are needed to confirm this observation.

Enhanced Percutaneous Delivery of Beta-Blockers Using Thermal Resurfacing Drug Delivery System for Topical Treatment of Infantile Hemangiomas.

BACKGROUND: Infantile hemangiomas (IHs) are the most common vascular tumors in children. In the past few years, topical beta-blockers (bBs) have been reported to be an effective treatment of superficial IHs. OBJECTIVE: We sought to evaluate the clinical effectiveness and safety profile of enhanced percutaneous delivery of bBs for the treatment of IH. METHODS: A retrospective study of all cases of IHs treated with enhanced percutaneous delivery of bBs between 2018 and 2019 was performed. Epidemiologic, clinical, and treatment data, including effectiveness score and safety, were reviewed. RESULTS: The study included 11 patients with a total of 11 IHs. Of the total number of IHs, 7 (63.7%) showed a good response to treatment and 4 (36.3%) had a partial response; thus all patients (100%) had good or partial response to treatment. No systemic or local adverse effects were reported. LIMITATIONS: This is an uncontrolled retrospective study. CONCLUSION: Enhanced percutaneous delivery of bBs is a safe and efficient topical therapy for IH.

Treatment of port wine stain with Tixel-induced rapamycin delivery following pulsed dye laser application.

Although pulsed dye laser (PDL) is considered the gold standard treatment for port wine stains (PWS), post PDL revascularization is one of the main causes of incomplete regression and recurrence. Recently, topical sirolimus have been shown to improve treatment outcome probably through minimizing post-laser revascularization. We sought to evaluate the added value of the Tixel drug delivery system (DDS) to the PDL and topical rapamycin treatment for PWS. This case series includes three teenager patients with previously treated PWS with PDL. Upon enrollment, every stain was divided into A and B halves for treatment assignments to the following regimens: (A) PDL + DDS + rapamycin; (B) PDL + rapamycin. Subjects were instructed to apply rapamycin topically over the PWS twice daily for the entire treatment period. Assessment of the treatment and adverse reactions as well as photographs was performed at baseline and before every PDL treatment. There were clinically significant differences in blanching responses favoring PWS receiving PDL + DDS + rapamycin as compared to PDL + rapamycin alone. Transient hyperpigmentation was noted in one patient. Two patients developed mild transient irritation and dermatitis following the treatment on both halves. The use of drug delivery system combined with topical rapamycin has no remarkable adverse effects, improves the results of PDL treatment for port wine stains, and can reduce the total number of required PDL sessions.

Effectiveness of topical propranolol 4% gel in the treatment of pyogenic granuloma in children.

Pyogenic granuloma is a benign acquired vascular tumor that affects the skin and mucous membranes, occurring more often in children and young adults. Treatment is often required due to the associated risk of ulceration and bleeding. There are several publications reporting the use of beta-blockers for the treatment of pyogenic granuloma. The aim of the present study was to evaluate the clinical effectiveness and safety profile of topical propranolol 4% gel for the treatment of pyogenic granuloma. A retrospective study of all cases of pyogenic granuloma treated with topical propranolol 4% gel between 2014 and 2015 was performed. Epidemiological, clinical and treatment data, including effectiveness score and safety, were reviewed. Of a total of 18 patients with pyogenic granuloma, 11 (61.1%) showed complete resolution of the lesion while two (11.1%) had an almost complete response. In three cases (16.6%), the treatment was discontinued due to bleeding, and the lesions were removed by curettage. Local irritation and lack of compliance led to treatment discontinuation in two cases. Altogether, 13 out of 18 patients (72%) had complete or almost complete response to treatment. There was a correlation between treatment duration and response to treatment. One patient only reported local side-effects including irritation, redness and scaling of the treated area leading to discontinuation of the treatment and curettage of the pyogenic granuloma. No systemic adverse effects were reported. This is an uncontrolled retrospective study. Propranolol 4% gel may be considered as a safe and efficient topical therapy for pyogenic granuloma.

Predicting neurofibromatosis type 1 risk among children with isolated café-au-lait macules.

BACKGROUND: Although isolated cafe-au-lait macules (CALMs) are a common skin finding, they are an early feature of neurofibromatosis type 1 (NF1). OBJECTIVE: We sought to develop an algorithm determining the risk of children with CALMs to have constitutional NF1. METHODS: We conducted a retrospective study of patients with isolated CALMs. Diagnosis of NF1 was based on detecting NF1 mutation in blood or fulfilling clinical criteria. RESULTS: In all, 170 of 419 (41%) and 21 of 86 (24%) children with isolated CALMs who underwent molecular testing and clinical follow-up, respectively, were given a diagnosis of NF1. Presence of fewer than 6 CALMs at presentation or atypical CALMs was associated with not having NF1 (P < .001). An algorithm based on age, CALMs number, and presence of atypical macules predicted NF1 in both cohorts. According to the algorithm, children older than 29 months with at least 1 atypical CALM or less than 6 CALMs have a 0.9% (95% confidence interval 0%-2.6%) risk for constitutional NF1 whereas children younger than 29 months with 6 or more CALMs have a high risk (80.4%, 95% confidence interval 74.6%-86.2%). LIMITATIONS: The study was designed to detect constitutional NF1 and not NF1 in mosaic form. CONCLUSIONS: A simple algorithm enables categorization of children with isolated CALMs as being at low or high risk for having NF1.

Assessment of the effectiveness of topical propranolol 4% gel for infantile hemangiomas.

BACKGROUND: Infantile hemangiomas (IHs) are the most common vascular tumors in children. Because of their benign character and natural involution, the vast majority of IHs do not require any treatment. In the past few years, topical beta blockers have been reported to be an effective treatment of superficial IHs. OBJECTIVE: We sought to evaluate the clinical effectiveness and safety profile of topical propranolol 4% gel for the treatment of IHs. METHODS: A retrospective study of all cases of IHs treated with topical propranolol 4% gel between 2013 and 2015 was performed. All patients were evaluated in a pediatric dermatology unit of a tertiary medical center. Epidemiologic, clinical, and treatment data, including effectiveness score and safety, were reviewed. RESULTS: The study included 63 patients with a total of 75 IHs. Of the total number of IHs, 43 (57.3%) showed a good response to treatment, 19 (25.3%) a partial response, and 13 (17.33%) poor or no response, thus 62 (82.6%) had good or partial response to treatment. Age at treatment initiation, treatment time, thickness of the superficial component, and size of the lesions were shown to predict response to therapy. Out of the entire examined group, only two patients reported minor local side effects manifested by irritation, redness, and scaling of the treated area. No systemic adverse effects were reported. LIMITATIONS: This is an uncontrolled retrospective study. CONCLUSION: Propranolol 4% gel is a safe and efficient topical therapy for IH.

Childhood Pemphigus Foliaceus with Exclusive Immunoglobulin G Autoantibodies to Desmocollins.

Pemphigus refers to a group of potentially fatal blistering skin diseases that are often due to the deleterious effects of autoantibodies directed against desmosomal antigens. Although desmogleins have been mainly implicated as autoantigens in pemphigus, a steadily growing body of evidence suggests that other desmosomal proteins may be causally involved as well. Antibodies directed against desmocollin-3 have been shown to play a direct role in the pathogenesis of several types of pemphigus. Here we describe the case of a child with localized pemphigus foliaceus and immunoglobulin G (IgG) reactivity exclusively directed to desmocollins. The present report suggests that autoantibodies against nondesmoglein antigens may play a role in the pathogenesis of superficial pemphigus, in addition to pemphigus vulgaris, paraneoplastic pemphigus, and IgA pemphigus.

Pemphigus and depression comorbidity: a case control study.

BACKGROUND: While quality of life can be significantly affected in pemphigus patients, few studies have systematically investigated the co-morbidity of psychiatric disorders in these patients. OBJECTIVE: To assess the association between pemphigus and depression comorbidity, using the computerized medical database of Israel's largest health maintenance organization. METHODS: In a case-control study, co-morbidities of adult pemphigus patients retrieved from the database of a large healthcare organization from 1998 to 2010 were compared with age- and gender-matched controls from the same database. The main outcome measure was the prevalence of co-morbid psychiatric disorders (anxiety, psychosis, schizophrenia and depression) in pemphigus patients and controls. The study included 255 pemphigus patients (157 women (62%) and 98 (38%) men) and 509 controls (313 women (62%) and 196 (38%) men) aged 20 years and older (a ratio of 3:2 in both groups). Mean age was 63.5 ± 15.7 years in the pemphigus group and 63.2 ± 15.7 years in the control group. RESULTS: Depression was the only psychiatric disorder significantly increased among pemphigus patients compared with controls. Alcohol abuse and smoking did not differ between groups. Depression was over-represented in a large population of pemphigus patients, indicating the disorder as a possible significant co-morbidity. After controlling for confounders including age, gender, and duration of corticosteroid therapy, the association with depression persisted (OR = 1.19, 95% CI: 1.12-1.27), p<0.001). CONCLUSION: The increased prevalence of depressive morbidity, especially in the presence of commonly prescribed corticosteroid treatment, emphasizes the need for psychiatric assessment and intervention in these patients.

Cognitive profile of school-age children and teenagers with hypohidrotic ectodermal dysplasia (HED).

Anhidrotic/hypohidrotic ectodermal dysplasia (HED) is the most common of the ectodermal dysplasias characterized by a triad of absent or reduced sweat, hypodontia and misshapen teeth, and missing or sparse hair. As the central nervous system is primarily ectodermal in origin, it has long been a concern that HED may be associated with developmental delay and/or intellectual disabilities. While published reviews report abnormalities in mental or motor development in 15-25% of HED-affected patients, there is no report in the literature including a systematic assessment of intellectual abilities in a cohort of patients with this rare disorder. During yearly health care updates, many of our clinic families report attention difficulties in young HED patients without evidence of a significant impact on school performance. In an exploratory study to identify and quantify intellectual abnormalities that may be associated with HED, we performed a psychological examination of 23 HED patients by means of the Wechsler Intelligence Scales, WPPSI-III, and WISC-IV. The interpretation of the tests shows no significant impairment in the achievements of the sample group compared with normative values (full scale scores, and index scale scores of the WISC-IV). At an individual level, the HED-affected patients were characterised by higher scores on the Verbal Comprehension Index, on Perceptual Reasoning and Working Memory Indices, and lower scores on the Processing Speed Index. As all of the Indices were within normal limits for the study population, in the absence of major mental/motor disabilities these findings support the mainstream education of HED-affected children.

Infantile myofibromatosis: a series of 28 cases.

BACKGROUND: Infantile myofibromatosis (IM) is a rare disorder of fibroblastic/myofibroblastic proliferation in children. OBJECTIVES: We sought to document common and unusual characteristics of patients with IM. METHODS: This was a retrospective study of 28 children diagnosed with histopathologically confirmed IM between 1992 and 2012. Epidemiologic, clinical, and treatment data were reviewed. RESULTS: IM was more frequent in boys (60.8%). Skin lesions were congenital in 64.3% of cases. The solitary form accounted for 50% of cases. Most nodules were painless, arising in cutaneous or subcutaneous tissue. The multicentric form accounted for 39% of cases; the skin, subcutaneous tissue, or muscle was involved in 97.8% of cases, and the bones in 50% of cases. The generalized form had a mortality rate of 33% (one-third of cases). Multicentric and generalized forms regressed spontaneously; severe local complications were observed, and late recurrent nodules developed in a few cases. LIMITATIONS: The retrospective review and the ascertainment of patients (from the departments of obstetrics and pediatrics) may have introduced bias in the analysis of severity of the different forms of IM. CONCLUSION: The diagnosis of IM must be confirmed histopathologically because the clinical presentation can be misleading. The prognosis is usually good, although local morbidity can occur. The generalized and multicentric forms merit long-term follow-up.

Congenital erosive and vesicular dermatosis: a new case and review of the literature.

Congenital erosive and vesicular dermatosis is a rare syndrome first described by Cohen et al in 1985. Most of the 18 cases published have been reported in premature newborns. Affected babies typically present with erosions and vesicles that tend to heal shortly after birth with reticulated scaring. We report an additional case, followed up for 5 years, in which we excluded a pathogenic mutation in the TP63 gene.