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.

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.

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.

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.

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.

Late rebound of infantile hemangioma after cessation of oral propranolol.

Propranolol has become the first line of treatment for infantile hemangiomas (IHs), with a high response rate, but rebound growth after cessation of propranolol has been reported, primarily in the first year of life. We sought to determine the frequency and associated factors leading to late regrowth after successful treatment at an age when the proliferative phase has usually ceased. We retrospectively reviewed the clinical charts, serial photographs, and radiologic images of children with rebound IH occurring after the age of 15 months after a successful course of oral propranolol averaging 2.6 mg/kg/day (range 2-3 mg/kg/day). Thirteen (10 female, 3 male) of 212 patients (6%) treated with oral propranolol since 2008 were evaluated. The mean age at the start of treatment was 5.3 months (range 1.8-13 months), and an average of 10.3 months (range 4.5-16 months) of treatment was given. It took an average of 5.3 months (range 1-13.8 months) for a significant rebound to appear. Late rebound after successful propranolol indicates a prolonged proliferation phase of IH even after 15 months of age. This is compared with previous reports of rebound, which occurred primarily in infants younger than 1 year old. Late proliferation can occur in localized, small, mixed, and deep IH, even after several months of a positive response to propranolol. A second course of propranolol readily controlled the recurrence.

Targetoid hemosiderotic hemangiomas (hobnail hemangiomas) are vascular lymphatic malformations: a study of 12 pediatric cases.

BACKGROUND: Targetoid hemosiderotic hemangioma (THH), also called hobnail hemangioma, is a benign vascular lesion and thought to be of lymphatic origin. OBJECTIVE: We sought to perform a clinicopathologic analysis of cases diagnosed as THH in a tertiary care children's hospital. METHODS: Clinical and histopathologic data were obtained from a chart review of 12 confirmed pediatric cases of THH. To determine the presence or absence of lymphatic vessels in lesional biopsy specimens, we evaluated the expression of the lymphatic endothelial cell marker podoplanin using the D2-40 antibody. Wilms tumor-1 gene immunostaining and Ki-67 proliferation index were also performed to evaluate the proliferative nature of these lesions. RESULTS: Three children had a lesion since birth and 4 had a history of trauma before appearance of the THH. D2-40 immunostaining was positive in every case. Wilms tumor-1 gene immunostaining was negative in 9 cases, focally positive in two cases, and not performed in one case. The Ki-67 proliferation index was very low in all cases studied. LIMITATIONS: The small number of cases and restriction to a pediatric population were limitations. CONCLUSION: Our findings suggest that THH should be classified as a lymphatic vascular malformation.

Connective tissue nevi in children: institutional experience and review.

BACKGROUND: Connective tissue nevi (CTN) are circumscribed hamartomas of the skin in which there is an abnormal mixture of normal components of the dermis that may be sporadic or associated with syndromes such as Buschke-Ollendorff, tuberous sclerosis, and Proteus. OBJECTIVE: We sought to specify the clinical and histologic features of CTN in childhood and to propose a diagnostic approach and updated classification. METHODS: This was a retrospective study in a tertiary pediatric outpatient population, accessing clinical and histopathological records. RESULTS: We classified 114 cases of CTN from 1980 to 2008. LIMITATIONS: The majority of cases were confirmed by histopathological examination. Therefore, our series excludes many CTN that were not biopsied. In addition, follow-up was variable. CONCLUSION: Our series demonstrates the usefulness of a modified classification for CTN. Biopsy should be done when clinical diagnosis is uncertain, or in multiple lesions. When biopsy is performed it should include normal-appearing skin for comparison and, in Buschke-Ollendorff syndrome, limited anterior-posterior x-rays of the hands, wrists, feet, ankles, knees, and pelvis instead of a full skeletal survey.

Treatment of periocular infantile hemangiomas with propranolol: case series of 18 children.

PURPOSE: To study the efficacy of propranolol in the treatment of periocular infantile hemangiomas (IHs). DESIGN: Retrospective interventional case series. PARTICIPANTS: Eighteen children presenting periocular IH with occlusion of the pupil, anisometropic astigmatism, proliferating eyelid IH, or cosmetically disfiguring periocular IH. METHODS: All patients received treatment with propranolol started at 0.5 mg/kg/day with an incremental increase by 0.5 mg/kg/day every 4 days, up to a maximum of 2 to 3 mg/kg/day. Complete eye examinations and serial photographs were obtained before, during, and after treatment. Doppler ultrasound and magnetic resonance imaging performed pre- and post-treatment were compared when available. MAIN OUTCOME MEASURES: Evolution of the treated IH was evaluated with respect to astigmatism, amblyopia, and size of the lesion. RESULTS: The IH size decreased in 17 of 18 patients. We noted a greater reduction when treatment was administered during the proliferative phase of growth of IHs. At the conclusion of treatment, none of our patients had amblyopia. The mean value of amblyogenic astigmatism (n = 7) decreased from 2.71 diopters (D) pretreatment to 1.03 D post-treatment. On radiology, 8 patients had significant regression of the lesion size of their IH and 1 patient had a limited progression. Propranolol had to be temporarily discontinued in only 1 patient because of symptomatic hypotension. CONCLUSIONS: Propranolol seems to be an effective modality of treatment for periocular IH. It seems to be most efficacious when initiated in the proliferative phase of IH but may be beneficial even in the later stage. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Propranolol versus prednisone in the treatment of infantile hemangiomas: a retrospective comparative study.

The goal of the current study was to compare the clinical effectiveness of oral propranolol with that of oral prednisone in the treatment of infantile hemangiomas (IH). Patients treated for IH with oral propranolol were retrospectively matched with patients treated with oral prednisone according to type, location, and size of the IH and age at start of treatment. Response to treatment was evaluated by rating serial medical photographs taken 1, 2, and 6 months after initiation of treatment. Degree of clinical improvement in overall appearance (including color and size) was rated as follows: worse or stable (0), slight (<25%), moderate (25-50%), good (50-75%), or excellent (>75%). A second assessment was done using a 100-mm visual analog scale to rate improvement at 6 months. Pre and post-treatment imaging was available for several patients. Twelve pairs of infants with IH were analyzed. At 1 month, clinical improvement in the propranolol group was moderate to good in all patients. In the prednisone group, only one patient had moderate improvement, with others showing slight (7/12) or no improvement or stabilization (3/12) from baseline and one case worsening. At 6 months, the propranolol group showed good to excellent response in all cases, whereas nine in the prednisone group showed slight to moderate response. Doppler ultrasound and magnetic resonance imaging correlated with the clinical improvement in the cases in which it was performed. No major side effects were observed in either group. Propranolol appears superior to oral prednisone in inducing more-rapid and greater clinical improvement in this study. A larger prospective study comparing these two treatment modalities is warranted.

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.

Large congenital melanocytic nevi and neurocutaneous melanocytosis: one pediatric center's experience.

BACKGROUND: Large congenital melanocytic nevi (LCMN) predispose to neurocutaneous melanocytosis (NCM), which is associated with significant morbidity and mortality. OBJECTIVE: To identify risk factors for NCM in patients with LCMN and suggest guidelines for their management. METHODS: Medical records of patients with LCMN were reviewed at Sainte-Justine Hospital between 1980 and 2006. Presence of multiple satellite nevi and posterior midline location were evaluated as risk factors for NCM using chi-square test. Magnetic resonance imaging scans were reviewed by a neuroradiologist. RESULTS: Twenty-six of 52 patients underwent radiologic investigation. Six of 26 (23%) had NCM. Patients with this condition are more likely to have multiple satellite nevi (100% vs 50%, P = .03) and have a trend to posterior midline location of their LCMN (100% vs 60%, P = .08). Patients with NCM are more likely to have both multiple satellite nevi and posterior midline location (100% vs 25%, P = .002). Radiologic findings are also presented. LIMITATIONS: This was a retrospective case series with imprecise chart data in 38% of cases. CONCLUSION: The presence of multiple satellite nevi alone or with associated posterior midline location of LCMN is associated with a higher risk of NCM. We recommend magnetic resonance imaging testing before 4 months of age in patients with these features.