Autosomal recessive congenital ichthyosis due to novel CYP4F22 mutation presenting with a collodion membrane and ocular manifestations.

Autosomal recessive congenital ichthyoses (ARCI) are a range of genetic disorders of keratinization. The rare CYP4F22 gene mutation can present with or without collodion membrane at birth and leads to the development of mild ichthyosis phenotype. We report a case of a novel pathogenic CYP4F22 genetic mutation presenting with collodion membrane and ocular manifestations. Ocular manifestations have recently been reported in a patient with ARCI with known CYP4F22 mutation, which further supports a possible correlation between the CYP4F22 mutation and this distinct phenotype.

Atopic dermatitis-like graft-versus-host disease treated with dupilumab.

The mainstay of treatment for atopic dermatitis (AD)-like graft-versus-host disease (GVHD) in both pediatric and adult patients includes oral corticosteroids with or without other systemic immunosuppressive therapies. To our knowledge, we report the first case series of dupilumab in the treatment of AD-like GVHD in a pediatric cohort of four patients, where we observed clinical improvement of GVHD as well as a reduction in itch in 3/4 (75%) patients. Our findings suggest that dupilumab is not only effective in treating AD-like GVHD, but also reduces systemic immunosuppression in the pediatric transplant population. The ability to reduce the length and amount of immunosuppression as well as improve quality of life suggest that dupilumab may serve as a safe and effective therapeutic option in our transplant population with GVHD.

Multifocal Kaposiform Hemangioendothelioma in a Newborn With Confirmatory Histopathology.

Kaposiform hemangioendothelioma is classified as a locally aggressive vascular tumor of childhood resulting from abnormal angiogenesis and lymphangiogenesis. Most commonly, KHE presents as a single tissue mass, ranging from an erythematous papule to a violaceous indurated tumor. Definitive diagnosis requires tissue sampling with the demonstration of ill-defined nodules and fascicles of spindle-shaped D2-40 positive endothelial cells, forming slit-like vascular channels. This newborn presented with multifocal cutaneous Kaposiform hemangioendothelioma associated with Kasabach-Merritt phenomenon confirmed on histopathology with immunostaining.

Severe recalcitrant hidradenitis suppurativa in a 2-year-old boy with partial trisomy 13.

We report the case of a 2-year-old boy with mosaic trisomy 13 and immunodeficiency who developed severe hidradenitis suppurativa beginning at the age of 18 months. Unresponsive to standard therapies, he exhibited a partial response to immunoglobulin replacement therapy.

Cutaneous mastocytosis in a child with a de novo GNB1 mutation.

In the last few years, de novo mutations in the GNB1 gene have been found to cause a neurodevelopmental disorder typically characterized by global developmental delay and hypotonia. Only 4 cases of maculopapular cutaneous mastocytosis in children with GNB1 mutations have been reported to date. Here, we describe another case of the condition with concomitant cutaneous mastocytosis.

Toxic erythema of chemotherapy affecting the ears of an infant: A case report.

A 15-month-old boy presented with new onset symmetric erythema of the conchal bowls bilaterally in the setting of treatment with cytarabine. Findings were consistent with a diagnosis of toxic erythema of chemotherapy, an adverse effect of chemotherapy. In this report, we detail this uncommon manifestation in a young child along with a brief literature review of the background, pathophysiology, and treatment strategies of toxic erythema of chemotherapy to increase awareness of this presentation in pediatric populations.

Prevalence and Types of Genital Lesions in Organ Transplant Recipients.

Importance: Squamous cell carcinoma (SCC) is the most common skin cancer diagnosed in solid organ transplant recipients (OTRs) and confers significant mortality. The development of SCC in the genital region is elevated in nonwhite OTRs. Viral induction, specifically human papillomavirus (HPV), is hypothesized to play a role in the pathophysiology of these lesions. Objective: To assess the prevalence and types of genital lesions observed in OTRs. Design, Setting, and Participants: This retrospective review included 496 OTRs who underwent full skin examination from November 1, 2011, to April 28, 2017, at an academic referral center. The review was divided into 2 distinct periods before a change in clinical management that took effect on February 1, 2016 (era 1) and after that change (era 2). Patient awareness of genital lesions was assessed. All lesions clinically suggestive of malignant tumors were biopsied and underwent HPV polymerase chain reaction typing. Main Outcomes and Measures: Number and types of genital lesions, proportion of malignant tumors positive for HPV, and patients cognizant of genital lesions. Results: Of the total 496 OTRs, 376 OTRs were evaluated during era 1 (mean [SD] age, 60 years; age range, 32-94 years; 45 [65.2%] male; 164 [43.6%] white) and 120 OTRs were evaluated during era 2 of the study (mean age, 56 years; age range, 22-79 years; 76 [63.3%] male; 30 [25.0%] white). Overall, 111 of the 120 OTRs (92.5%) denied the presence of genital lesions during the history-taking portion of the medical examination. Genital lesions were found in 53 OTRs (44.2%), cutaneous malignant tumors (basal cell carcinoma and SCC in situ) in 6 (5.0%), genital SCC in situ in 3 (4.2%), and condyloma in 29 (24.2%). Eight of the 12 SCC in situ lesions (66.7%) were positive for high-risk HPV. Seven tested positive for HPV-16 and HPV-18, and 1 tested positive for high-risk HPV DNA but could not be further specified. Conclusions and Relevance: Genital lesions in OTRs are common, but awareness is low. All OTRs should undergo thorough inspection of genital skin as a part of routine posttransplant skin examinations. Patients with darker skin types are disproportionately affected by cutaneous genital malignant tumors and should undergo a targeted program of early detection, prevention, and awareness focused on the risk of genital skin cancer after transplant. High-risk HPV subtypes are associated with genital SCC in OTRs. Additional studies are warranted to identify significant risk factors for HPV infection and to assess the utility of pretransplant HPV vaccination in the prevention of cutaneous genital malignant tumors.

Ladarixin, a dual CXCR1/2 inhibitor, attenuates experimental melanomas harboring different molecular defects by affecting malignant cells and tumor microenvironment.

CXCR1 and CXCR2 chemokine receptors and their ligands (CXCL1/2/3/7/8) play an important role in tumor progression. Tested to date CXCR1/2 antagonists and chemokine-targeted antibodies were reported to affect malignant cells in vitro and in animal models. Yet, redundancy of chemotactic signals and toxicity hinder further clinical development of these approaches. In this pre-clinical study we investigated the capacity of a novel small molecule dual CXCR1/2 inhibitor, Ladarixin (LDX), to attenuate progression of experimental human melanomas. Our data showed that LDX-mediated inhibition of CXCR1/2 abrogated motility and induced apoptosis in cultured cutaneous and uveal melanoma cells and xenografts independently of the molecular defects associated with the malignant phenotype. These effects were mediated by the inhibition of AKT and NF-kB signaling pathways. Moreover, systemic treatment of melanoma-bearing mice with LDX also polarized intratumoral macrophages to M1 phenotype, abrogated intratumoral de novo angiogenesis and inhibited melanoma self-renewal. Collectively, these studies outlined the pre-requisites of the successful CXCR1/2 inhibition on malignant cells and demonstrated multifactorial effects of Ladarixin on cutaneous and uveal melanomas, suggesting therapeutic utility of LDX in treatment of various melanoma types.

Detection of low level histamine H3 receptor occupancy by autoradiography.

Histamine H(3) receptor antagonists have been proposed as a novel approach to the treatment of cognitive, attentional, and sleep disorders. It is apparent that H(3) receptor antagonists produce in vivo effects in preclinical animal models of central diseases across a wide dose range. In order to characterize the relationship between efficacy in the preclinical models and H(3) receptor occupancy, a brain slice receptor autoradiography method was used. Brain slice receptor autoradiography requires less in vitro tissue processing, preserves brain structure, and provides anatomical localization of compound in the brain. Consistent with H(3) receptor distribution, in vitro autoradiography experiments demonstrated specific binding of [(3)H]NAMH (N-alpha-methylhistamine) in rat cortex, and other brain regions, but not in cerebellum. Ex vivo H(3)R brain slice autoradiography was able to detect H(3) receptor occupancy by reference antagonists at doses lower than previously found using a homogenate assay format. The method is relatively quick with image acquisition on a beta-imager and is capable of detecting receptor occupancy in different brain regions simultaneously. Furthermore, the increased sensitivity should be useful in providing dosing guidelines for H(3) antagonists in both preclinical and clinical settings.