A novel pathogenic RHOA variant in a patient with patterned cutaneous hypopigmentation associated with extracutaneous findings.

RHOA-related neuroectodermal syndrome is characterised by linear skin hypopigmentation along Blaschko's lines associated with alopecia, leukoencephalopathy, facial and limb hypoplasia, and ocular, dental, and acral anomalies. Herein, we report a patient with patterned cutaneous hypopigmentation with a similar phenotype due to a novel postzygotic RHOA variant (c.210G>T; p.Arg70Ser). This illustrates that the complexity of the orchestration of morphogenesis and organogenesis can be affected by different variants in the same gene.

Pediatric Cutaneous Hematologic Disorders: Cutaneous Lymphoma and Leukemia Cutis-Experience of a Tertiary-Care Pediatric Institution and Review of the Literature.

BACKGROUND: Cutaneous hematologic malignancies are rare in children, and the literature about them is still sparse. OBJECTIVE: The purpose of our study was to report our experience with pediatric cases of cutaneous hematologic disorders and describe their clinical and histological features. METHODS: Data were retrospectively collected from the histopathologic database of the CHU Sainte-Justine, University of Montreal, Montreal, Canada. All patients up to 18 years of age with a diagnosis of a primary cutaneous lymphoma (including lymphomatoid papulosis), secondary cutaneous lymphoma or cutaneous manifestations of leukemia, followed from 1980 to 2019 at our center were reviewed. RESULTS: Thirty-six patients were included. Age at presentation ranged from birth to 18 years of age (mean 7.83 ± 5.16; median 7.0). Ten different hematologic disorders were identified according to the WHO-EORTC classifications: lymphomatoid papulosis (10 cases), mycosis fungoides (6 cases), anaplastic large cell lymphoma (4 cases), pre-B acute lymphoid leukemia (5 cases), primary cutaneous marginal zone B-cell lymphoma (4 cases), primary cutaneous CD4+medium T-cell lymphoproliferative disorder (1 case), extranodal NK/T-cell lymphoma (1 case), hydroa vacciniforme-like lymphoproliferative disorder (1 case), B-cell lymphoblastic lymphoma (1 case) and acute myeloid leukemia (3 cases). CONCLUSION: The most common subtype of cutaneous hematologic disease in our single institution study was lymphomatoid papulosis (type A and type C), followed by mycosis fungoides. Recognition of this large clinical and histological spectrum by dermatologists is important because diagnosis is often established by biopsy of skin lesions, even in secondary cutaneous cases. Moreover, the clinicopathological correlation is of utmost importance for the final diagnosis of those pathologies.

Linear cutaneous lupus erythematosus in children-report of two cases and review of the literature: A case report.

Linear cutaneous lupus erythematosus is an unusual presentation of cutaneous lupus following Blaschko's lines. It is described mostly in children and young adults and is usually not associated with systemic involvement. We report two cases of linear cutaneous lupus erythematosus in children who significantly improved after treatment with hydroxychloroquine in combination with topical corticosteroids and tacrolimus. These rare cases underline the importance of including linear cutaneous lupus erythematosus in the differential diagnosis of blaschkoid inflammatory lesions.

Kaposiform hemangioendothelioma with overlapping features of rapidly involuting congenital hemangioma and a delayed complication of necrotizing fasciitis.

We report the case of a male infant born at term with kaposiform hemangioendothelioma (KHE) of the right forearm and coagulopathy. Our case was unusual as it involuted leaving subcutaneous atrophy and prominent veins, which are more commonly observed in rapidly involuting congenital hemangioma. At 3 years of age, the child developed recurrent superficial thrombophlebitis localized to the area where the KHE had regressed. Subsequently, he developed necrotizing fasciitis and thrombotic veins in the same location and group A streptococcal septic shock.

Skin Manifestations in Pediatric Patients Treated With a TNF-Alpha Inhibitor for Inflammatory Bowel Disease: A Retrospective Study [Formula: see text].

BACKGROUND: Tumor necrosis factor (TNF) alpha inhibitors (anti-TNF) are effective in the treatment of inflammatory bowel disease (IBD) as well as psoriasis. Their increasing use has raised the identification of cutaneous side effects (CSEs). Evidence in children is limited. OBJECTIVES: The objective of this study is to describe CSEs of anti-TNF treatment in a pediatric population with IBD. METHODS: This is a retrospective single-center study of children with IBD under anti-TNF treatment between 2013 and 2016. A total of 40 patients with CSEs related to anti-TNF were referred to our pediatric dermatology clinic. A control group was randomly selected from patients receiving anti-TNF for IBD, who were referred to the dermatology clinic for other conditions unrelated to anti-TNF. RESULTS: Of 343 patients with IBD, 40 (11.3%) presented CSEs potentially related to the treatment. No differences in sex, age, and underlying disease were found between those with and without CSEs. The most frequent CSEs were psoriasiform eruptions (41%) which were more exudative than usual, located especially in skin folds and on the scalp; skin infections (20%); and eczematous eruptions (10%). Only 5% of patients changed or discontinued the current anti-TNF because of CSEs. CONCLUSION: This is one of the largest pediatric cohorts of IBD patients with CSEs. Psoriasiform eruptions were the most common CSEs, with predilection for skin folds and scalp, and frequent superimposed bacterial infection. Topical and/or systemic antibiotics were required in addition to topical corticosteroids in 25% of patients. The rate of discontinuation of anti-TNF therapy due to CSEs was low.

Patterned cutaneous hypopigmentation phenotype characterization: A retrospective study in 106 children.

BACKGROUND: Cutaneous patterned hypopigmentation's phenotype is highly variable and may be associated with extracutaneous anomalies. OBJECTIVE: We evaluated the phenotypic and clinical characteristics of patients with cutaneous patterned hypopigmentation to determine whether certain patterns were more likely to be associated with underlying anomalies. METHODS: The charts of 106 children with cutaneous patterned hypopigmentation were reviewed retrospectively (2007-2018) at Sainte-Justine University Hospital Centre, in Montreal, Canada. Retrieved information included sex, age at diagnosis, phototype, pattern, and distribution of the cutaneous lesions and the presence of extracutaneous findings. Data were recorded on a software tool which collects and analyzes phenotypic information. RESULTS: The predominant types of cutaneous patterned hypopigmentation were along Blaschko's lines in narrow (38.7%) and broad bands (53.8%). Mixed patterns were observed in 22.5% of children. The anterior trunk and posterior trunk were most frequently affected (69% and 56%, respectively). Extracutaneous involvement, especially neurological and developmental, was present in 28.3% of patients and was significantly associated with ≥ 4 involved body sites. CONCLUSION: Distribution and types of cutaneous patterned hypopigmentation were not predictive of extracutaneous findings, with the exception of multiple sites involvement and possibly centrofacial location and blocklike lesions. Follow-up until school entry should help identify subtler associated extracutaneous anomalies.

Silver-coated textiles in hidradenitis suppurativa: A case report.

Hidradenitis suppurativa is a chronic and debilitating skin disease of apocrine gland-bearing areas. The mainstay of treatment usually includes topical and systemic antibiotics. These agents can be used as monotherapy or combination therapy. The therapeutic role of functional textiles with antimicrobial activity has been recently emerging in the treatment of other skin diseases such as atopic dermatitis and epidermolysis bullosa. The pathologic processes involved in the development of atopic dermatitis and hidradenitis suppurativa are still incompletely understood, but these two diseases share some similarities including bacterial proliferation and chronic inflammation. We report the case of a 14-year-old boy with hidradenitis suppurativa that has been successfully treated with silver-coated textiles. To the best of our knowledge, this article is the first to report the benefits of silver-coated textiles in the treatment of hidradenitis suppurativa.

Non-involuting congenital hemangiomas (NICH) with postnatal atypical growth: A case series.

BACKGROUND: Non-involuting congenital hemangiomas (NICH) are fully formed vascular tumors at birth, with a distinctive clinical, radiologic, and histopathological profile, and classically lack expansion or involution over time. We describe a series of NICH cases with atypical postnatal growth. METHODS: The authors retrospectively analyzed all NICH cases diagnosed from 2007 to 2017. We reviewed charts and photographic databases from our Vascular Anomalies Clinic. We included in the study all NICH with an atypical postnatal growth. Clinical data, imaging, and histopathology were analyzed. RESULTS: Eighty cases of NICH were identified. Nine presented with atypical postnatal growth after a stable period, at ages from 2 to 10 years (mean: 5.3 years). Two patients had associated pain; 5 patients showed new red papules on the surface of the lesion; 2 reported bleeding from the papules; and 1 developed a pyogenic granuloma. All patients had Doppler ultrasound and/or MRI compatible with NICH, and a confirmatory biopsy was performed in 4 cases. In treatment, 2 patients received endovascular embolization, and one required further surgery. CONCLUSIONS: Non-involuting congenital hemangiomas (NICH) may develop significant postnatal growth over time (10% in our series), requiring closer follow-up for longer periods. The development of red papules, pyogenic granulomas, and superficial bleeding may be observed. Since this is a small series, we were not able to establish risk factors for NICH with postnatal growth.

Multiple superficial oral mucoceles after Mycoplasma-induced mucositis.

Oral mucoceles are lesions arising mainly from the minor salivary glands and are thought to occur after excretory duct trauma. We report a case of multiple superficial oral mucoceles on a child's labial mucosa after Mycoplasma pneumoniae mucositis. Mucoceles can mimic persistent or recurrent stomatitis and lead to potential errors in management.

Emergence of African species of dermatophytes in tinea capitis: A 17-year experience in a Montreal pediatric hospital.

BACKGROUND/OBJECTIVES: An increase in dermatophyte infections caused by African species is reported in countries receiving African immigrants. Our goal was to determine the epidemiologic and clinical characteristics of tinea capitis in children infected with African species of dermatophytes in Montreal, Canada. METHODS: Demographic and clinical data from medical records of children infected with African species of dermatophytes were retrieved retrospectively (2000-2016) at Sainte-Justine University Hospital Center. RESULTS: In Montreal, the number of tinea capitis cases caused by African species of dermatophytes increased sixfold over 17 years. African immigrant children (84%), men and boys (61%), and preschoolers (2-5 years old) (51%) were the most frequently affected in our 315 cases. Family contamination was frequent (45%). Referring physicians prescribed systemic antifungal treatment in 39% of cases and pediatric dermatologist consultants in 90%. Treatment failure to oral terbinafine occurred in 39% of Microsporum audouinii infections. CONCLUSION: In Montreal, there was a significant increase in tinea capitis caused by African species of dermatophytes. Microsporum audouinii is highly transmissible and often resistant to oral terbinafine. Recognizing tinea capitis trends in a given environment will improve patient care.

Pilomatricoma Associated with Kabuki Syndrome.

We report three cases of pilomatricomas associated with Kabuki syndrome (KS), supporting the hypothesis proposed of an association between pilomatricomas and KS and suggesting a noncoincidental association, because the Wnt pathway mutations involved could affect both morphogenesis and tumorigenesis in these patients.

Aortic Dilatation Associated With a De Novo Mutation in the SOX18 Gene: Expanding the Clinical Spectrum of Hypotrichosis-Lymphedema-Telangiectasia Syndrome.

BACKGROUND: We report a 13-year-old female patient followed since birth for multiple rare congenital defects, including hypotrichosis, telangiectasia, and severe dilatation of the ascending aorta. METHODS: Comprehensive phenotype assessment throughout childhood included repeated echocardiographic measurements, evaluation of renal function, and immunohistochemical analysis of skin biopsy samples. Whole-exome sequencing was performed for the patient and both unaffected parents. RESULTS: We identified a novel de novo mutation in the transcription factor SOX18 (c.481C>T:p.Gln161*) in the patient, which was absent in all unaffected family members. Echocardiography revealed early onset and progressive dilatation of the ascending aorta. Skin biopsy results confirmed the defects of the blood vasculature in the presence of intact lymphatic vessels. Assessment of renal function did not show any signs of renal problems or renal failure in the patient. CONCLUSIONS: The genetic finding of a pathogenic SOX18 mutation enabled the diagnosis of the rare hypotrichosis-lymphedema-telangiectasia syndrome in our patient. The identification of a novel stop gain mutation in the SOX18 gene in association with dilatation of the aorta highlights the importance of this gene during the development of the circulatory system. Our study highlights the importance of whole-exome sequencing in the rapid identification of genes and gene mutations involved in rare conditions and thus expanding the knowledge and spectrum of clinical manifestations associated with them.

Diseases of abnormal sensitivity to cold in children on psychostimulant drugs.

BACKGROUND: Oral psychostimulant (PS) drugs, the pharmacologic treatment of choice for attention-deficit/hyperactivity disorder (ADHD), have been associated with diseases of abnormal sensitivity to cold (DASC) such as Raynaud phenomenon and acrocyanosis. OBJECTIVES: In a cohort of pediatric patients with DASC, we sought to identify prevalence and clinical features of patients on PS drugs. METHODS: A 6-year retrospective chart review (2005-2011) of Ste-Justine University Hospital Center DASC patients with and without exposure to PS drugs was performed. Clinical data were analyzed with descriptive statistical methods. RESULTS: Of 43 patients with DASC, 11 (25%) were exposed to PS drugs. In this group males were overrepresented, there was no evidence of collagen vascular diseases, serologic findings were not significant and the mean duration of PS intake was of 2.5 years. DASC age of onset was similar in both exposed and nonexposed patients. The incidence of more than one DASC type was greater in teenager patients with a positive family history of autoimmune and/or collagen vascular diseases. LIMITATIONS: This study is limited by its small population size, short follow-up period and its retrospective nature. CONCLUSION: Physicians should be aware of PS drugs as possible triggers for DASC.

Pigmented purpuric dermatosis: clinicopathologic characterization in a pediatric series.

Pigmentary purpuras (PPs) are a group of chronic disorders of unknown origin seldom described in children. With this study we sought to better characterize PP eruptions, including clinical evolution and management. A retrospective chart review from 2003 to 2013 querying characteristics of children with a biopsy-proven diagnosis of PP in the Centre Hospitalier Universitaire Ste-Justine dermatology clinic (Montreal, Quebec, Canada) was performed. Follow-up was obtained through telephone interviews. Descriptive statistical analysis was used. Of the 17 subjects, 8 were male and the mean age of onset was 9 years. PP was asymptomatic in 11 patients, pruritic in 3, and of cosmetic concern in 3. Schamberg's disease was the most frequent subtype in 12 cases. Resolution of PP was found in 13 cases with a median duration of less than 1 year (range 6 months-9 years). Five patients experienced spontaneous clearing without treatment, and improvement was observed in 75% of cases treated with topical corticosteroids and 100% with narrowband ultraviolet B (nbUVB). No associated disease, significant drug exposure, or contact allergens were found. Those findings support that PPs in children are idiopathic, chronic eruptions that can benefit from watchful waiting, although topical corticosteroids or nbUVB are may be useful if the patient or family desires faster resolution. This study was limited by its small size, its retrospective nature, and selection and recall bias.

Diseases of abnormal sensitivity to cold in children on psychostimulant drugs.

BACKGROUND: Oral psychostimulant (PS) drugs, the pharmacologic treatment of choice for attention-deficit/hyperactivity disorder (ADHD), have been associated with diseases of abnormal sensitivity to cold (DASC) such as Raynaud phenomenon and acrocyanosis. OBJECTIVES: In a cohort of pediatric patients with DASC, we sought to identify prevalence and clinical features of patients on PS drugs. METHODS: A 6-year retrospective chart review (2005-2011) of Ste-Justine University Hospital Center DASC patients with and without exposure to PS drugs was performed. Clinical data were analyzed with descriptive statistical methods. RESULTS: Of 43 patients with DASC, 11 (25%) were exposed to PS drugs. In this group males were overrepresented, there was no evidence of collagen vascular diseases, serologic findings were not significant and the mean duration of PS intake was of 2.5 years. DASC age of onset was similar in both exposed and nonexposed patients. The incidence of more than one DASC type was greater in teenager patients with a positive family history of autoimmune and/or collagen vascular diseases. LIMITATIONS: This study is limited by its small population size, short follow-up period and its retrospective nature. CONCLUSION: Physicians should be aware of PS drugs as possible triggers for DASC.

Quality of life in pediatric patients before and after cosmetic camouflage of visible skin conditions.

BACKGROUND: Visible vascular and pigmentary conditions have a negative impact on children's and adolescents' quality of life (QoL). We sought to quantitate the effect of visible skin anomalies and their camouflage on QoL. METHODS: In all, 41 patients, 5 years of age and older, were taught to use cosmetic camouflage. QoL was assessed using the Children's Dermatology Life Quality Index (CDLQI) before and 6 months after the intervention. Satisfaction and use were evaluated after 1 and 6 months. RESULTS: Baseline QoL scores revealed a small impact of vascular anomalies (CDLQI score 4.2) and a small to moderate effect of pigmentary anomalies (CDLQI score 6.1). Six months after the intervention, QoL improved in the study population as a whole (CDLQI score 5.1 vs 2.1, P<.001), with significant improvements documented for facial lesions and vascular malformations. Cosmetic camouflage was well tolerated and patients with pigmentary anomalies were more likely to continue using the products. LIMITATIONS: Limitations include small study population, few male patients, cultural influences not addressed, and limited range of conditions. CONCLUSIONS: Children and teenagers with visible vascular and pigmentary anomalies experience an impairment of QoL that is abrogated by introduction to use of cosmetic camouflage.

Expression of the senescence marker p16INK4a in skin biopsies of acute lymphoblastic leukemia survivors: a pilot study.

BACKGROUND: Most childhood cancer survivors will develop ionizing radiation treatment-related health conditions that, in many instances, resemble age-associated pathologies. Treatment-induced premature senescence could be an underlying mechanism. FINDINGS: Here we wanted to know whether the expression of p16INK4a, a senescence/aging biomarker, is increased in skin biopsies of acute lymphoblastic leukemia survivors (ALL), previously exposed to chemotherapy and radiation therapy. Several years post-treatments, we found p16INK4a mRNA levels are 5.8 times higher in scalp skin biopsies (targeted by cranial irradiation therapy) compared to buttocks skin biopsies (n = 10, p = 0.01). CONCLUSIONS: These results demonstrate for the first time that premature senescence is induced in pediatric cancer survivors and that p16INK4a expression could be used as a potential biomarker in this population.