Long-term follow-up of patients with extensive segmental infantile hemangioma of the cervical or facial region: A French single-center prospective study.

BACKGROUND: Infantile hemangiomas (IHs) can be part of PHACE (posterior fossa anomalies, hemangioma, arterial anomalies, cardiac anomalies, eye anomalies) syndrome when they are segmental, extensive, and located on the face or neck. The initial assessment is codified and well known, but there are no recommendations for the follow-up of these patients. The aim of this study was to assess the long-term prevalence of different associated abnormalities. METHODS: Patients with a history of large segmental IHs of the face or neck. diagnosed between 2011 and 2016 were included in the study. Each patient underwent an ophthalmological, dental, ENT (ear, nose, and throat), dermatological, neuro-pediatric, and radiological assessment at inclusion. Eight patients including five with PHACE syndrome were prospectively evaluated. RESULTS: After a mean follow-up of 8.5 years, three patients presented with an angiomatous aspect of the oral mucosa, two with hearing loss, and two with otoscopic abnormalities. No patients developed ophthalmological abnormalities. The neurological examination was altered in three cases. Brain magnetic resonance imaging follow-up was unchanged in three out four patients and revealed atrophy of the cerebellar vermis in 1 patient. Neurodevelopmental disorders were found in five of the patients and learning difficulties were observed in five patients. The S1 location appears to be associated with a higher risk of neurodevelopmental disorders and cerebellar malformations, while the S3 location was associated with more progressive complications, including neurovascular, cardiovascular, and ENT abnormalities. CONCLUSION: Our study reported late complications in patients with a large segmental IH of the face or neck, whether associated with PHACE syndrome or not, and we proposed an algorithm to optimize the long-term follow-up.

Effectiveness and safety of dupilumab in the treatment of atopic dermatitis in children (6-11 years): data from a French multicentre retrospective cohort in daily practice.

BACKGROUND: Dupilumab is the first biotherapy available for the treatment of moderate-to-severe childhood atopic dermatitis (AD). OBJECTIVE: The aim of this study was to evaluate the effectiveness and safety of dupilumab in daily practice. METHODS: Patients aged 6-11, who had received a first dose of dupilumab, were included in this multicentre retrospective cohort study. The primary endpoint was change in SCORAD after 3 months of treatment. Secondary endpoints were change in IGA score at 3 months, proportion of patients with SCORAD50 and SCORAD75, description of adverse events and proportion of children in our cohort who would be excluded from pivotal phase 3 clinical trial. RESULTS: Eighty patients were included. After 3 months of treatment, there was a significant decrease in SCORAD (mean: 21.8 ± 13.8 vs 53.9 ± 18.5; P < 0.0001) and IGA (1.3 ± 0.8 vs 3.5 ± 0.7; P < 0.0001). Conjunctivitis was observed in 11.3% (n = 9/80); three patients experienced dupilumab facial redness (DFR); 17.5% (n = 14/80) reported injection site reactions; 6.3% (n = 5/80) discontinued treatment. 61.2% (n = 49/80) children were ineligible in the phase 3 trial. LIMITATIONS: There is no control group. Because it was a real life study based on information from patient medical records in a French multicentre cohort, we cannot rule out the presence of reporting bias generated by the use of patient reported characteristics and missing information. CONCLUSION: These real-life data confirm the efficacy and safety of dupilumab in children with moderate to severe AD extended to dyshidrosis and atopic prurigo, but it also revealed a lower frequency of DFR and conjunctivitis. However, administration in injectable form may be a barrier in this age group.

Long-term outcome in patients with juvenile dermatomyositis: A case series.

BACKGROUND: Follow-up of juvenile dermatomyositis (JDM) patients has demonstrated the impact of the disease on several organs in the long term. OBJECTIVE: As there is little information on the long-term outcome of JDM, we aimed to assess long-term outcomes in a series of JDM patients. METHODS: After selection of JDM patients, a consultation with a dermatologist and a rheumatologist was held for each patient. Cutaneous, muscle, and disease damage was assessed using different validated scores including the abbreviated Cutaneous Assessment Tool (aCAT), 8-muscle Manual Muscle Testing (MMT8), Childhood Myositis Assessment Scale (CMAS), Myositis Damage Index (MDI), Childhood Health Assessment Questionnaire (CHAQ), and Health Assessment Questionnaire (HAQ). Long-term disease outcomes were recorded including growth and pubertal development, educational and vocational achievement, and development of comorbidities. RESULTS: Seven patients were included in the study. After a mean follow-up of 14.9±8.8 years, the mean aCAT score was 0.57±1.4 and only one patient had a positive aCAT activity score. The mean aCAT damage score was 1.4±1.3 and five (71%) patients had a score of ≥1. Five (71.4%) patients had normal muscle strength with an MMT8 score of >72, and none had severe muscle weakness (MMT8 ≤32, and CMAS<35). The mean total extent of damage according to the MDI was ≥1 in five (71%) patients and mainly involved the skin. Two (29%) patients had mild disability according to the CHAQ/HAQ disability index. In terms of quality of life, no patient had a score of<40 (1 SD below the mean for healthy controls). CONCLUSIONS: Based on validated cutaneous and musculoskeletal scores, our study demonstrated the good functional outcomes of JDM at long-term follow-up.

[Resistant and progressive cutaneous lupus erythematosus treated with belimumab: A retrospective monocentric study]. / Lupus érythémateux cutanés réfractaires traités par bélimumab : étude descriptive monocentrique.

BACKGROUND: Belimumab is currently approved for the treatment of active systemic lupus erythematosus (SLE). The aim of our study was to evaluate the efficacy of belimumab in the treatment of cutaneous lupus erythematosus (CLE), resistant to conventional therapy. PATIENTS AND METHODS: Seven patients with resistant and progressive LEC and treated with belimumab were retrospectively analyzed. The efficacy and safety of belimumab were evaluated with the CLASI, RCLASI and DLQI scores, after 6 to 12 months of treatment. RESULTS: Eighty-three percent of patients demonstrated a significant clinical improvement based on the CLASI and RCLASI activity scores, including 1 complete and 4 partial responses, without worsening of CLASI and RCLASI damage scores. Eighty percent of patients also showed an improvement of their quality of life (DLQI). Oral corticosteroids were discontinued in all patients. Tolerance was acceptable with only one serious adverse event (bacteriema). CONCLUSION: Our study suggests the clinical efficiency of belimumab in a series of 7 patients presenting a resistant and progressive CLE.

Incontinentia pigmenti in boys: Causes and consequences.

INTRODUCTION: Incontinentia pigmenti (IP) is an X-linked genodermatosis caused by mutation of the NEMO/IKBKG gene. While lethal in male foetuses, heterozygous females survive because of X-inactivation mosaicism. Herein we discuss 9 male patients with IP. MATERIALS AND METHODS: This is an observational, descriptive, retrospective, multicentre, French study carried out with the help of the SFDP research group. Statistical analysis was performed both on our own patients and on those reported in the literature. RESULTS: Nine boys with no family history of IP but with typical neonatal skin reactions were included. Genetic analysis of blood (n=8) and skin biopsy (n=3) confirmed the diagnosis of IP by identification of common deletion of the IKBKG/NEMO gene (exons 4 to 10) in the state of somatic mosaic in 6 and 2 cases respectively. Where analysed, the karyotype was normal (n=6). Over a median follow-up period of 48 months (3 months to 10 years), 3 patients had neurological abnormalities, 2 had severe ophthalmologic abnormalities, and 1 had dental abnormalities. Extensive skin involvement is a systemic risk factor, unlike cutaneous scarring. CONCLUSION: IP in boys is often due to a mosaic mutation that should be sought in blood and skin. Long-term neurological and ophthalmological monitoring is essential, especially in cases of extensive skin involvement.

[Pseudoxanthoma elasticum-like papillary dermal elastolysis: A case report]. / Élastolyse du derme papillaire « pseudoxanthome élastique-like ¼ : un cas.

BACKGROUND: Pseudoxanthoma elasticum-like papillary dermal elastolysis (PXE-PDE) is a rare disease clinically resembling pseudoxanthoma elasticum (PXE). Herein we report a typical case. PATIENTS AND METHODS: A 77-year-old woman consulted for an acquired papular eruption present for 4 years. Her history included breast cancer, which was considered to be in remission. The eruption had begun on the right armpit before extending to the right side of the chest, left armpit, neck and right inguinal fold. It was completely asymptomatic. It consisted of non-follicular flabby, skin-colored papules, without anetoderma. Histological examination with hematoxylin-eosin and orcein staining revealed papillary and mid-dermal elastolysis without elastorrhexis. Based on the clinical aspect of PXE as well as histologically demonstrated elastolysis, a diagnosis of PXE-PDE was made. DISCUSSION: PXE-PDE is a rare acquired entity that affects only women, usually after the age of 60 years. Although it is clinically similar to PXE, PXE-PDE may be differentiated through its late onset, the absence of systemic symptoms, and the attendant histological features. Dermoscopy may also contribute to differential diagnosis. Histological examination allows confirmation of the diagnosis and shows normal elastic fibers that may be either missing or present in vastly reduced quantities in the papillary and mid-dermis. The physiopathology continues to be unclear, but may involve skin aging, elastogenesis abnormalities and UV exposure. To date, no treatment has demonstrated its efficiency. CONCLUSION: PXE-PDE is a rare condition, but it displays typical histological and clinical features. Knowledge of this entity avoids unnecessary explorations and enables rapid reassurance of patients.

Biological treatments for paediatric psoriasis : a retrospective observational study on biological drug survival in daily practice in childhood psoriasis.

BACKGROUND: Three biotherapies - etanercept, adalimumab and ustekinumab - are licensed in childhood psoriasis. The few data available on their efficacy and tolerance are mainly derived from industry trials. However, biological drug survival impacts long-term performance in real-life settings. OBJECTIVE: The objective of this study was to evaluate the survival rates of biological therapies in children with psoriasis in real-life conditions. Secondary objectives were to evaluate the factors associated with the choice of the biological therapy and to report severe adverse events. MATERIALS AND METHODS: This study was an observational retrospective study. Data were extracted from the clinical records of 134 children. Kaplan-Meier estimates were used to analyse drug survival overall and in subgroups of plaque psoriasis, bio-naïve and non-naïve patients. RESULTS: We analysed 184 treatment courses: 70 with etanercept, 68 with adalimumab and 46 with ustekinumab. Factors associated with the choice of first-line biological agent were age at initiation (younger for adalimumab, P < 0.0001), age at onset of psoriasis (younger for adalimumab and etanercept, P = 0.03) and baseline Psoriasis Assessment Severity Index and Physician global assessment (both higher for adalimumab, P < 0.001). Drug survival rates were higher for ustekinumab than for adalimumab and etanercept (P < 0.0001) for all treatment and all psoriasis types, plaque-type psoriasis (P = 0.0003), patients naïve for biological agents (P = 0.0007) and non-naïve patients (P = 0.007). We reported eight serious adverse events (SAEs): severe infections (n = 3), significant weight gain (n = 2), psoriasis flare (n = 1) and malaise (n = 1). Biological therapy was discontinued in three children (one with psoriasis flare and two with weight gain). Only the two cases of weight gain resulted in an unfavourable outcome. CONCLUSIONS: Our real-life comparative study found that ustekinumab had the best drug survival outcome. The profile of SAEs in children was comparable to that in adults. These results will assist dermatologists in the decision-making process when choosing treatment options for children with psoriasis in daily practice.

Tongue psoriasis: Clinical aspects and analysis of epidemiological associations in 313 children, with a systematic literature review.

BACKGROUND: Little information is available on the prevalence and clinical aspects of tongue involvement in children with psoriasis. The aim was to evaluate the prevalence, clinical aspects and risk factors concerning tongue involvement in children with psoriasis. PATIENTS AND METHODS: This study was carried out in two stages. We performed a multicentre, cross-sectional study in 23 French dermatology centers. All children seen for psoriasis during the one-year study were systematically included. The clinical features of the tongue and of psoriasis were recorded. Association with clinical aspects of psoriasis and comorbidities was evaluated. We then carried out a literature review to evaluate the prevalence of tongue involvement in children with psoriasis and its positive predictive value for psoriasis. A search was conducted in the PUBMED database using the following keywords: "child" and "psoriasis" and ("tongue" or "glossitis" or "migratory glossitis" or "benign migratory glossitis" or "geographic tongue" or "fissured tongue"). RESULTS: 7.7% of the 313 children with psoriasis had tongue involvement. The clinical aspects were geographic tongue (4.2%), fissured tongue (2.8%) and both (0.64%). There was no association between tongue involvement and the clinical characteristics of the children. Two hundred and ninety-five articles were referenced and 3 were analysed. Psoriasis is very rare in cases of tongue abnormalities. CONCLUSION: The prevalence of tongue involvement was 7.7% in children with psoriasis. No clinical or epidemiological association was shown. Tongue involvement does not modify the management of psoriasis. In the literature review it was not possible to evaluate either the prevalence of tongue involvement in psoriasis or the positive predictive value thereof.

[Two cases of granuloma annulare under anti-PD1 therapy]. / Deux observations de granulome annulaire sous anti-PD1.

BACKGROUND: Granuloma annulare as a granulomatous cutaneous reaction may be drug-induced. Immune checkpoint inhibitors including programmed death-1 (PD-1) inhibitors show remarkable antitumor activity and are approved for melanoma and other cancers. Different immune-related adverse effects have been described. We report herein a rare adverse effect of anti-PD1 therapy given for metastatic melanoma : granuloma annulare. PATIENTS AND METHODS: Two women receiving pembrolizumab metastatic melanoma presented with granuloma annulare. The therapy was continued in both cases. In the first patient, granuloma annulare appeared and then subsided; in the second patient, the lesion resolved completely with topical corticosteroids. DISCUSSION: While there have been reported cases of sarcoidosis induced by immunotherapies, immunotherapy-induced granuloma annulare has not been described. The pathogenesis of drug-induced granulomatous reactions is thought to involve autoimmune dysregulation affecting T cells, especially Th1 cells, which lead to granuloma formation. Granuloma annulare should thus be considered a cutaneous adverse effect of anti-PD1 immunotherapy.

[Congenital hemangiomas: Report on ten patients]. / Hémangiomes congénitaux : à propos de dix cas.

INTRODUCTION: Congenital hemangiomas (CHs) are rare congenital vascular tumors seldom mentioned in the literature. MATERIALS AND METHODS: We carried out a retrospective study of all the cases of CH diagnosed and treated at Besançon Hospital from 2008 to 2014. The clinical, radiological, and histological data of each case were collected. All the children were seen again in 2014. RESULTS: Ten CHs (seven rapidly involuting CHs, RICH and three non-involuting CH, NICH), predominantly full-term eutrophic male infants, were enrolled. RICHs were located on the head (n=2), trunk (n=2), and lower limbs (n=3), and NICHs were found on the hands. Diagnosis was clinical for all ten infants. All CHs resembled "tumor" congenital lesions: single, oval-shaped, nonpulsatile, and well delimited, and their size did not increase after birth. Two RICHs were warm, one had phlebolites, and two had draining veins at the first visit. The mean age of the RICH involution onset was 1.7 months and the mean time to complete involution was 10.4 months. One CH was classified as a PICH (partially involuting CH) due to partial regression, two RICHs were still in the involution process at the age of 10 and 15 months, and one regressed very quickly within 7 days. No complications were observed in the NICH. Two RICHs presented benign complications (ulcerations and bleeding). Two RICHs regressed entirely, and five regressed with sequelae: lipoatrophy (n=3), cutaneous excess (n=2), dysplastic veins (n=3), a pigmented area (n=1), and an anemic halo (n=2). DISCUSSION: The small number of patients in our cohort, in spite of the length of the study, confirms the rarity of CH. The sex-ratio in favor of male infants and the location of NICH on the hands have not been reported. The most discriminating element remained the follow-up over 1 year. The initial clinical aspect of the NICH and the progression of one RICH into a NICH suggested possible overlapping forms between RICH and NICH. Some CHs, including one PICH, presented clinical and radiological criteria similar to those of vascular malformations (warm lesion, dysplastic veins, and echo-Doppler results in favor of vascular malformation). RICH regressed with sequelae in most cases. CONCLUSION: This study reveals a polymorphous clinical presentation of CH and provides a thorough description of their progression. It underlines the existence of overlapping phenomena between RICH and NICH, and between CH and vascular malformations, thus suggesting a possible link between proliferation and malformation phenomena at the origin of these lesions.

[Recessive epidermolysis bullosa due to composite heterozygote mutations in the COL7A1 gene]. / Épidermolyse bulleuse héréditaire dystrophique par hétérozygotie composite COL7A1.

BACKGROUND: Dystrophic epidermolysis bullosa (DEB) is a genodermatosis characterized by various abnormalities of anchoring fibrils, composed mainly of type VII collagen, at the dermal-epidermal junction. These changes are induced by mutations in the type VII collagen gene (COL7A1). PATIENTS AND METHODS: A new-born boy was diagnosed with recessive DEB on the basis of typical skin lesions composed of multiple blisters with erosions on trauma-exposed body sites, including the hands and feet and the navel. Diagnosis was confirmed by pathology examination and irregular immunofluorescence staining of type VII collagen. Genomic DNA from the patient and parents were subjected to direct sequencing for the COL7A1 gene. Two heterozygous mutations were detected in the affected child. Each parent was a carrier of one heterozygous mutation. DISCUSSION: Over 730 mutations of the COL7A1 gene have been identified as responsible for phenotypic polymorphism of EBD. The relatively mild phenotype seen in our patient, known as "non-Hallopeau-Siemens" or "mitis" EBD, is due to residual synthesis of collagen VII. The mutation present on the maternal allele that prevents synthesis of collagen VII is compensated by the mutation on the paternal allele, which enables more or less functional collagen VII synthesis.