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FREE COMMUNICATIONS 1 O1 Development and organization of human Stratum Corneum after birth: Identification of new specific markers for epidermal maturation in infancy

O2 Nail changes in very low birth weight babies: reflection of systemic abnormalities in child and mother

C. de Belilovsky1; J. Fluhr2; N. Lachmann3; M. Haftek4; C. Baudouin3; R. Darlenski5; P. Msika3 1 Institut Alfred Fournier, Paris, France, 2Charite
- University Clinic, Berlin, Germany, 3Laboratoires Expanscience, Epernon, France, 4Universite
Lyon 1, Lyon, France, 5Tokuda Hospital, Sofia, Bulgaria

S. Pradhan1; T. Padhi1; B.P. Nayak2 1 Veer Surendra Sai Medical College and Hospital, Dermatology Venerology and Leprosy, Sambalpur, India, 2 Veer Surendra Sai Medical College and Hospital, Paediatric, Sambalpur, India

Introduction: The postnatal period is a time of active functional maturation and cutaneous adaptation to the dry extra-uterine environment. Recent investigative and imaging methods opened new fields to skin barrier function studies. We summarized here 10 years of research on infant Stratum Corneum organization, antioxidant and antibacterial epidermal functions and on epidermal construction via Stem Cells (SC) analysis. Data were collected from birth and longitudinally followed till adulthood in order to precisely determine their maturation age. Methods: - Physical skin barrier function evolution and maturation were investigated on different age groups of young children including newborns. Corneocytes attached to non-invasively removed D-squames were analyzed by Scanning Electron Microscopy (SEM) and a maturation score (E.M.I.: Electron Microscopy Isotropy) was developed. Corneocytes samples were also labeled with antibody to corneodesmosin revealed with silver-enhanced immunogold particles. - We have modeled the epidermis of infants and children of different ages in vitro and measured the differential expression of genes by full transcriptome microarray, confirmed by quantitative RT-PCR. Genes of barrier function, cell protection, innate immunity and interfollicular Stem Cells were analyzed. Then, we have UV-irradiated children reconstructed epidermis of 2-4 months and 11-12 years and analyzed Stem Cells parameters. Results: Physical skin barrier function is immature till 1-2 years. SEM study showed a clear correlation between age and the E.M.I. score with a high maturation rate from birth to the age of 2 years. Corneodesomes from the youngest age group showed weakness in the central immunolabelling, indicating a poorly controlled desquamation process. Genes of epidermal differentiation and barrier function (involucrin, claudin 1, keratin 1. . .) studied on reconstructed epidermis were less expressed in younger infants and their expression increased with age. Response to oxidative stress (gluthatione peroxidase) tends to increase with age. Innate immunity (beta defensins 1 and 4) is less expressed during the first months of life than in adults. Stem Cells may be involved in skin barrier construction: indeed, SC markers expression (specific of SC proliferation, regulation and interaction with the niche) was the highest in the samples from younger infants and it quickly decreased with age. Then, markers (niche and protection) like alpha 6 and beta 1 integrin, survivin and TP63 (at gene and protein levels), were decreased after UV irradiation, with a more pronounced decrease in the 2-4 months-aged reconstructed epidermis than in the older ones. Conclusion: This integrated research program on epidermal development from birth gives new light to very fine physical and biological maturation steps. Several months to few years are necessary to set a global skin defense system. For the first time, the active role of Stems Cells has been observed during this process.

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Introduction: Nail changes in neonates can be a sign of systemic disorders. It can reflect developmental defects as well as metabolic alteration. Aims and objective: To study nail changes among very low birth weight babies so as to detect systemic disorders and developmental defects at the earliest. Materials and methods: 100 patients admitted in neonatal unit for very low birth weight were included in the study. A detailed history regarding demographic details of mother and child, obstetric course and presence of cutaneous and systemic disorders was taken.Nails were examined clinically and digital photographs were taken.Correlation was made between nail abnormalities and systemic disorders in both child and mother. Results: 36 patients had nail abnormalities.Ingrowing toe nail with hypertrophy of lateral nail fold of big toes in 15patients (41.67%), hyperpigmentation of proximal nail folds 6 (16.67%) patients, half and half nail in 6 (16.67), anonychia (2.8%), beau’s line, proximal nail fold erythema and longitudinal pigmented band, koilonychia were found in 3 patients (8.3%) each. While correlating nail findings with systemic disorders, beau’s line was found in neonates suffering from severe intrauterine distress and mother having preeclampsia, half and half nail in neonates with respiratory distress and mother having chronic kidney disease, koilonychia in neonates suffering severe anemia and mother with severe malnutrition. Conclusion: Nail abnormalities are seen commonly among neonates who belong to the very low birth weight category. A routine examination of the nail apparatus in all such cases should be to diagnose presence of developmental and systemic abnormalities early.

O3 Panniculitis as presenting sign of hereditary alpha-1antitrypsin-deficiency in a 13 year old boy B. Kunz; A. Boer-Auer; B. Loegering; E. Lentz; K. Reich Dermatologikum, Hamburg, Germany Panniculitis is a heterogenous group of diseases. In children, erythema nodosum and cold panniculitis are among common forms. Very rarely, it may be a complication of severe alpha-1-antitrypsin deficiency. Here we present a boy with severe relapsing panniculitis as first and so far single presentation of hereditary alpha-1-antitrypsin deficiency. History: A 13 years old boy presented with a ten months history of recurrent subcutaneous indurated nodules, initially induced by trauma, in changing locations on trunk and extremities. Some lesions had been incised, discharging an oily orange liquid. They did not respond to systemic steroid treatment and only temporarily to Doxycycline. Healed lesions left atrophic areas. The boy was otherwise healthy, in good overall condition and apyretic. He lived on a farm with contact to animals. Clinical presentation: The child presented with tender erythematous subcutaneous nodules of 10 cm diameter on the abdomen and right arm. He had several areas of lipoatrophy and striae.

2 FREE COMMUNICATIONS Histopathology: Suppurative-granulomatous panniculitis with formation of abscesses. Special stains, PCR and tissue cultures were negative for diverse bacterial and fungal organisms. Additional investigations: Complete blood cell count, metabolic panel, lipase, amylase, c-reactive protein, ANA, complement, vaccination titers, serologies/ PCR for multiple infectious agents as well as review of internal organs were unremarkable. Alpha- 1-antitrypsin (A1AT) serum level: 0.25 g/l (normal: 0.9-2.0 g/l); Phenotyping revealed a homozygous Pi ZZ A1AT type, confirming hereditary alpha-1-antitrypsin deficiency. Treatment: Dapsone 50 mg/d was started and resulted in good control of the disease. Discussion: Alpha -1-antitrypsin (A1AT) is an important serine protease inhibitor, antagonizing proteolytic enzymes including trypsin, collagenase, elastase and others. Deficiency results from mutation of the SERPINA 1 gene (chr.14 q31-32.3) and mostly manifests as emphysema and liver cirrhosis in adulthood. Panniculitis is a very rare complication with less than 100 cases described to date. More than 60% of these are related to the Pi-ZZ phenotype, associated with the lowest A1AT serum levels. Recently, co-accumulation of neutrophils and polymers of Z-type A1AT have been demonstrated in biopsies of affected skin by murine monoclonal antibodies, suggesting a pathogenetic role in panniculitis. Dapson is the recommended first line treatment, effective in about 90% of patients. In severe affection, replacement therapy with A1AT concentrate has been shown to be very helpful. Although A1AT deficiency is an extremely rare cause of childhood panniculitis, it should be considered in the differential diagnosis with respect to the lifelong implications of this genetic disease.

O4 Amelanotic melanoma in a child. Case report R. Filippetti Ospedale S.Camillo-Forlanini, Dermatologia, Rome, Italy Introduction: According to the data of the literature the occurrence of an amelanotic melanoma is excedeeing rare. Diagnosis is difficult due to its uncommon occurrence as well as similarities to common skin pathologies. Case report: A 10 year-old boy presented with a history of a cherry red 7 mm nodule with a speck of blue-gray in the peripheral on his upper arm. Dermoscopy revealed an irregular, reddish, diffuse pigmentation an focal brown-gray bodies (corresponding to the bluegray pigmented area). Dermoscopic data were typicalfor a melanocitic nature of the lesion and the nodule was widely excised. Hystology confirmed the diagnosis of an amelanotic melanoma, Breslow thickness mm 1,7. A biopsy of the sentinel node was megative for metastasis. A strict surveillance program was scheduled. Conclusions: Amelanotic melanoma may appear similar to many common benign skin lesions (pyogenic granuloma, angioma and dermal nevi) and often erroneously removed with non surgical procedures. Careful differential diagnosis of red nodules is warranted and further histological investigation should be performed if cancer is suspected.

O5 A congenital case of Degos disease with systemic involvement I. Thanopoulou1; V. Hill2; P. Brogan3; D. Atherton1; A. Martinez1; M. Glover1; V. Kinsler1 1 Great Ormond Street Hospital for Children, Paediatric Dermatology, London, United Kingdom, 2Barnet Hospital, Dermatology, London, United Kingdom, 3Great Ormond Street Hospital for Children, Paediatric Rheumatology, London, United Kingdom Background: Degos disease with systemic involvement is an extremely rare small to medium sized vessel vasculopathy of unknown aetiology, which targets mainly the skin, the gastrointestinal tract

and central nervous system. There are various theories regarding the underlying pathophysiologic mechanisms, including coagulation or complement pathway defects, abnormalities of the vascular endothelium or a combination of all the above. Congenital disease has not previously been described. Methods: A female infant was noted at birth to have three skin lesions but was otherwise well. On Day 10 of life she developed bilious vomiting and was commenced on i.v antibiotics and antivirals for suspected sepsis. More skin lesions had developed since birth. At 2 weeks she was transferred to surgery at Great Ormond Street Hospital (GOSH) where intestinal obstruction was excluded. Clinically and biochemically she appeared to respond to antimicrobials, although the skin lesions did not resolve. Over the next six weeks skin lesions increased in number, she developed rectal bleeding and feeding intolerance. At eight weeks she had an acute onset of ophthalmoplegia and was referred to GOSH Dermatology. At this time she had approximately 20 cutaneous lesions. These were round, 0.5-1.0 cm in diameter, with newer lesions porcelain white centrally with peripheral telangiectasia, and a minority of these showing central atrophy. More evolved lesions showed central necrosis and scabbing, with two frankly ulcerated lesions on the buttocks. A clinical diagnosis of Degos disease with systemic involvement was made. She was admitted for further investigation. Results: MRI/MRA of the head revealed multiple anterior and posterior cerebral arterial infarcts. Clotting indices were abnormal and platelets were low. ECHO revealed a pericardial effusion, and there were biochemical signs of pancreatitis and transaminitis. Skin biopsy showed thinning of the epidermis overlying a wedge of necrotic dermis and a small vessel with occluded lumen without associated inflammatory infiltrate, compatible with the diagnosis of Degos disease. Over the next week she deteriorated rapidly, with a DIC picture and multi-organ failure. A multidisciplinary meeting agreed a trial of pulsed methylprednisolone 10 mg/kg/day followed by oral prednisolone 2 mg/kg once a day. However, in despite this she developed tachypnoea, hypotension and abdominal distension. Oral steroids were discontinued after discussion with the family and the palliative care team. The patient passed away within 24 hours. Conclusion: Degos disease with systemic involvement is not only an extremely rare condition but to our knowledge it has not been described at birth. Onset in infancy has rarely been seen. Systemic involvement in children usually implies serious and untreatable disease with a fatal outcome. Only when the exact pathogenesis is revealed will targeted therapies be developed.

O6 Idiopathic facial aseptic granuloma case report G. Rainer; B. Volc-Platzer SMZ Ost Donauspital Vienna, Dermatology, Vienna, Austria A three year old girl presented in our outpatient department with a non-inflammatory and also otherwise symptomless nodule, approximately 1,5 cm in diameter, on her left cheek. A scar was noted close to the lesion, and a second scar was noted on the left side of the neck. Patient history revealed that upon first appearance of a granulomatous nodular lesion on the neck the patient had been treated with different broad spectrum antibiotics aiming at a possible infectious cause of the granuloma. The lesion, however, was refractory to various antibiotics. Ultrasound examination pointed to abscess formation. Therefore, the lesion was surgically removed by pediatric surgeons. Bacterial cultures yielded negative results. Additional PCR screening for bacteria and mycobacteria also remained negative.No other causal infectious agents including broad virologic examination could be detected. Histopathology revealed a granulomatous raction of the foreign body type with giant cells. During follow up a new lesion developed on the cheek and was surgically removed, with identical histolopathologic results.

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FREE COMMUNICATIONS 3 When the third lesion appeared on the left cheek, in close proximity to the first one we decided for “watchful waiting” with frequent clinical controls. Neither systemic symptoms nor pathologic laboratory results developed. Finally, the lesion regressed within 11 months, and neither relapse nor regrowth could be observed. Based on history, clinical appearance and histopathology of a noninfectious granuloma of foreign body granuloma type with spontaneous regression and self-healing the diagnosis of an “Idiopathic facial aseptic granuloma” (IFAG) was made. This aseptic granuloma occurs in early childhood. It is a rarely seen entity in outpatient pediatric dermatology clinic. However, it is important to recognize this entity because of the predelection sites central face and neck. A French multicenter retrospective analysis by C. Leaute ́ -Labreze et al. (Arch Dermatol 2001; 137:1253-5.; British Journal of Dermatology 2007 156, pp705-708; Pediatric Dermatology Vol. 30 No. 4 429-432, 2013) was the basis for further disease management decisions, in order to avoid overtreatment and unnecessary surgery in the central face of infants and children.

O7 A pilot study on the efficacy and safety of shortcontact adapalene 0.1% gel in the surface area reduction of neuropathic ulcer among leprosy patients M.C.M. Rescober1; L.L. Villafuerte2 1 Jose R. Reyes Memorial Medical Center, Dermatology, Manila, Philippines, 2Jose R. Reyes Memorial Medical Center, Dermatology, Quezon City, Philippines Background: Neuropathic ulcer is the single most common cause of disability and dehabilitation of patients with leprosy. Short-contact tretinoin has been found to have positive effects on wound healing. However, side effects such as erythema and pain have been reported. Adapalene, known to behave similarly to tretinoin but with less adverse effects, may also be efficacious in the closure of ulcer among leprosy patients. Objective: To determine the efficacy and safety of short-contact adapalene 0.1% gel in the surface area reduction of neuropathic ulcer among leprosy patients after 16 weeks of usage Methods: Pilot study of 12 leprosy patients with neuropathic ulcer. Patients applied adapalene 0.1% gel on ulcer once at night for 4 weeks. Surface area was assessed every 2 weeks until 16 weeks by manual planimetry and photography. Primary endpoint was determined as 50% or greater reduction in the percent change in ulcer surface area from baseline until the end of the study. Secondary endpoint was the number of weeks at which reduction in ulcer surface was observed. Results: Eleven (92%) of 12 ulcers demonstrated 50% or greater reduction in size by the end of the study period. Two (17%) ulcers closed completely by the 8th week. There was significant change seen at the size of the ulcer as early as the 6th week (P = 0.009). Optimal effect of adapalene 0.1% gel was seen at the 10th week (P = 0.0001). There were no reported adverse effects such as erythema, pain, nor edema during the treatment period. Conclusion: Short-contact adapalene 0.1% gel is effective and generally safe to use in the reduction of surface area of neuropathic ulcer among leprosy patients. This study suggests that adapalene may be a novel treatment option for treating neuropathic ulcers. Larger randomized, controlled trials are needed to further establish its efficacy and safety in ulcer closure.

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O8 Corneocyte membrane undulation and intercellular lipid membranes as an indicator for severity in netherton syndrome, ichtyosis vulgaris and atopic dermatitis? Comparison of SC ultrastructures and barrier lipids in a pilot study using electron microscopy and Lipbarvis

€hnhardt-Pfeiffer1; D. Da €hnhardt1; C. Schmetz1; S. Da 2 € lster-Holst2 M. Buchner ; R. Fo 1 € hnhardt GmbH, Flintbek, Germany, Microscopy Services Da 2 University Kiel, Department for Dermatology, Kiel, Germany Netherton syndrom (NTS) is a rare autosomal recessive disorder of cornification, characterized by the triad of ichthyosis, hair shaft anomalies and atopy. The syndrome is present at birth or soon after with generalized exfoliative erythroderma, with or without an atopic diathesis. The stratum corneum (SC) often shows persistent nuclei in the cytoplasm of the corneocytes without granular layers detached from the underlying epidermis. The lamellar bodies prematurely secrete into the intercellular spaces and their content remains unprocessed. The lipid lamellae in the upper SC show various disorganization depending on the severity as well as on different composition. To investigate the shape of the corneocytes in the upper SC and to analyse the barrier function we use the non-invasive skin sampling technique Lipbarvis. In a pilot study we compare skin samples from patients with i) netherton syndrome (NTS), ii) ichthyosis vulgaris (IV), iii) atopic dermatitis (AD) and, iv) healthy skin (HS). Skin samples were taken and prepared for analysis with transmission electron microscopy (TEM). The shape of the corneocytes were investigated in the TEM and documented. For the analysis of the lipid lamellae in the intercellular space, the lipid lamellae length in the intercellular space were analysed as nICLL as described previously. We found that the undulation of the corneocyte membranes differs between the investigated skin types (i-vi). Highly undulated corneocyte membranes were visible in NTS, little less undulation of the corneocytes in skin samples with IV, and a lesser extent undulation as in NTS and IV show skin samples of AD. To quantify these undulations more precise as a visual scoring, we measured the membrane length between two selected points (A and B) at the corneocyte membrane. The ratio - further named as “ratio of undulation” (RoU) - between the distance from A to B and the measured membrane length correlate with the investigated skin types. NTS skin shows highly undulated membranes with a RoU 0.4, whereas in IV the RoU is in average 0.6 and in AD 0.9. HS shows a RoU of 0.95. The intercellular lipid membranes were semiquantitative analysed and showed also a variation in the investigated skin types. HS shows normal values for the normalized intercellular lipid length, nICLL, (~200 nm lipid lamellae/1000 nm2 intercellular space), in AD the nICLL is around 50 nm/1000 nm2, in IV around 40-50 nm/ 1000 nm2. In NTS we found areas with high amounts of intercellular lipid membranes and in neighbourhood regions with no detectable intercellular lipid membranes The measurement of the undulation and the estimation of the RoU should be proofed in further studies. Nevertheless, the analysis of the “ratio of undulation” of corneocyte membranes in the SC, in combination with the Lipbarvis skin sampling technique, could be used as a helpful tool for distinction between different skin diseases, especially in pediatric dermatology.

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FREE COMMUNICATIONS 2 O9 Extending the phenotypic spectrum associated with loss of desmoglein 1 C. Has; T. Jakob; Y. He; D. Kiritsi; L. Bruckner-Tuderman Medical Center - University of Freiburg, Freiburg, Germany The integrity of the epidermal barrier plays an essential role in cutaneous homeostasis and also in the pathogenesis of allergic skin disorders. This concept is strongly supported by several Mendelian disorders of cornification associated with severe atopy, in which the expression of essential components of epidermal barrier formation, e.g. filaggrin, corneodesmosin or LEKTI, is altered. Recently, homozygous loss-of-function mutations in the gene for desmoglein 1 (DSG1) were associated with a new disorder with severe dermatitis, multiple allergies and metabolic wasting in two families (SAM syndrome). We describe the natural history and the complex phenotype of a 17-year-old female with a homozygous nonsense DSG1 mutation. The mutation p.R887* led to DSG1 mRNA decay and loss of desmoglein 1 in the skin and manifested with severe palmoplantar keratoderma, wooly hair and chronic dermatitis, with episodes of aggravation. We did not find evidence for malabsorbtion, hypoalbuminemia, developmental delay or severe recurrent infections, as in the previously reported cases. In the skin, absence of desmoglein 1 led to loss of intercellular adhesion and skin cleavage within the granular layer, resulting in compromised epidermal barrier. This correlated with high IgE levels and sensitization to multiple environmental allergens. Additional studies are required to unravel the full phenotypic complexity and the pathomechanisms of this disorder. It is likely that multiple environmental factors and presumably genetic modifiers may account for the phenotypic variability in cases with DSG1 mutations.

O10 An exceptional presentation of dyskeratosis congenita (DKC) diagnosed by WES M.-A.C. Morren1; C. Wouters2; B. Verhamme1; L. Mestach1; K. Staats3; L.Van Eyck3; I. Meyts2; A. Liston3 1 Katholieke Universiteit Leuven, Dermatology, Leuven, Belgium, 2Katholieke Universiteit Leuven, Pediatrics, Leuven, Belgium, 3Katholieke Universiteit Leuven VIB, Autoimmune Genetics Laboratory, Leuven, Belgium A 8 yr old boy with autism and psychomotor retardation was referred because of extremely painful progressive onychodystrophy of the toe- and to a lesser extent fingernails. Family history revealed mild autism in his sister. This sister is also moderately retarded. Parents are not related. Previous antifungal and antiHPV treatments had no result. Moreover at the age of 3 years (2005) he was diagnosed with IgG deficiency treated with immunoglobulin substitution.On clinical examination bilateral hyperkeratotic dystrophy of the nails of all 10 toes and of fingers 4 and 5, some with koilonychia was seen. There was hyperkeratosis of the nailbed and surrounding skin. Clinical examination of skin and mucosae were uneventful. A wedge biopsy of the nail apparatus in october 2011 was compatible with the diagnosis of psoriasis. However, the child had no other signs of psoriasis. X-ray of the handswas normal. MRI did not show synovitis or bone oedema. A treatment with acitretin 10 mg daily was associated with painful paronychia and was interrupted. A second wedge biopsy in july 2012 showed apoptotic keratinocytes, numerous intraepidermal eosinophils below the stratum granulosum and orthohyperkeratosis: no arguments for psoriasis. Nailcultures were repeatedly negative for fungae. Actually the boy is treated with acitretin 10 mg every two days in association with azithromycin 500 mg 3 days every 2 weeks and monthly IV Ig (Privigen) with some improvement of the thickening and without exacerbation of paronychia. During 2013 intermittent

neutropenia was diagnosed as well which became persistent with time, and responded to treatment with Neupogen. Later findings included mild proteinuria (normal renal function) and hypertension. On WES a heterozygous variant in RTEL1 gene (rs41297642) was found, also in the patient’s father, not in his mother nor sister. This variant was described before in DKC in compound heterozygous patients. Sanger sequencing confirmed this finding and moreover a deletion on chromosome 20 spanning the RTEL1 gene on the other chromosome was found, which was shared with his mother and sister. Autosomal recessive mutations in RTEL1 are responsible for the most severe form (HH type) of the disease. Conclusion: Painful hypertrophy of nails can be the presenting sign of Dyskeratosis congenita.

O11 Computer-aided facial recognition of individuals with X-linked hypohidrotic ectodermal dysplasia S. Hadj-Rabia; Ectodermal dysplasia group Sorbonne Paris Cite
, site Descartes, Dermatology, Paris, France X-linked hypohidrotic ectodermal dysplasia (XLHED) is a genetic disorder characterized by hypohidrosis, hypotrichosis and hypodontia. Early diagnosis of XLHED is a key factor in reducing the risk for severe hyperthermia and pulmonary infections. Patients display a distinct craniofacial phenotype characterized by retruded appearance of the midface with maxillary hypoplasia and mandibular prognathism. In this study, a novel facial dysmorphology analysis system based on 2D photographs (FDNA) was used to identify XLHEDaffected individuals. Following photograph acquisition from male patients with clinically and/or genetically-confirmed XLHED (n = 27 newborns, n = 64 age 1-10 yrs, n = 42 age 11 + yrs, plus controls), 130 facial fiducial points were localized per photograph and their geometrical relationships determined. The final classification was based on these measurements as well as on a global “gestalt” detector. Cross validation of the recognition capability involved 20 rounds of analysis with the data split randomly to training and testing data. In this proof-of-concept study, the statistical power of the test in identifying XLHED patients using average area under the ROC curve was 96% for individuals >11 years; 97% for children 110 years, and 98%-99% for newborns. Overall, the system had a high level of specificity (97-100%) at 90% sensitivity across all age groups. These results demonstrate the strength and utility of computer-based facial analysis utilizing ordinary photographs in the identification of XLHED-affected patients. With further refinement, a universal newborn screening platform is plausible that will alert families to this clinical condition. Early diagnosis may also be critical for successful ectodysplasin therapy in this disorder (NCT01775462).

O12 Vitamin D status in different forms of ichthyosis in Germany: differences depending on the severity of hyperkeratosis and/or erythema and high prevalence of 25OHD deficiency and hyperparathyreoidism M.R. Egbert1; J. Fischer2; N.A. Schlipf2; H.C. Hennies3; I. Hausser-Siller4; H. Traupe1; V. Oji1 1 € nster, Department of Dermatology, Mu € nster, University of Mu Germany, 2University Medical Center Freiburg, Institute of Human Genetics, Freiburg, Germany, 3University of Cologne, Cologne Center for Genomics, Cologne, Germany, 4University Hospital of Heidelberg, Department of Dermatology, Heidelberg, Germany Introduction: Vitamin D is essential in calcium metabolism and bone health. Several reports pointed out that 25OHD deficiency is present in skin diseases, among others in ichthyosis. This heterogeneous

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FREE COMMUNICATIONS 5 group of Mendelian Disorders of Cornification (MeDOC) is characterized by hyperkeratosis and/or scaling affecting the entire skin. Hypothesis. Patients with ichthyosis living in Germany could be prone to vitamin D deficiency as inflammation and hyperkeratosis may influence the vitamin D synthesis in the skin depending on UV exposure. Methods: The 25OH-vitamin D (25OHD) and parathormone (PTH) levels of patients with lamellar ichthyosis (n = 14), congential ichthyosiform erythroderma (n = 14), Netherton syndrome/peeling skin diseases (n = 9), epidermolytic ichthyoses (n = 8), X-linked recessive ichthyosis (n = 7), and ichthyosis vulgaris (n = 9) were investigated in a prospective study in a North Rhine-Westphalian University Hospital in Germany. The diagnoses were confirmed clinically, by ultrastructure and/or mutation analysis. Moreover we determined the Scaling and Cornification Score in Ichthyosis (SCSI, range: 0-4), the degree of erythema (range: 0-3), and excluded concomitant diseases such as malnutrition that could be of influence on vitamin D status. Results: Our preliminary data show a high prevalence of 25OHD deficiency of around 90% for all ichthyosis forms: 1/3 of the patients demonstrated a clear deficiency as defined by 25OHD < 10 ng/ml, 2/3 had an insufficiency between 10 and 30 ng/ml. 15% of the patients showed a secondary hyperparathyroidism (PTH >65 pg/ml). Interestingly, the 25OHD values showed a linear correlation with the degree of erythema as well as with the SCSI. The highest incidence of 25OHD deficiency has been found in the group of lamellar ichthyosis due to transglutaminase-1 deficiency (62,5%), in which 50% of the affected individuals showed a moderate hyperparathyroidism. Interestingly, also 50% of patients with epidermolytic ichthyosis, who show a high degree of erythema, had clear 25OHD deficiency with a prevalence of hyperparathyreoidism of 28,6%. Conclusion: This is the first study on patients with specifically defined forms of ichthyosis, which herewith confirms a high prevalence of 25OHD deficiency and hyperparathyreoidism in German patients. Especially individuals with lamellar and keratinopathic ichthyosis seem to be prone to have low 25OHD levels. Vitamin D supplementation should be considered to prevent deficiency-related symptoms.

O13 Cutaneous manifestations of primary immunodeficiency diseases in Libyan children S.S. Elfaituri1; I. Matoug2; K. Bujlawi2; A. Elteer2; H. Elsalheen2; Y. Belrasali2 1 Benghazi University, Dermatology, Benghazi, Libyan Arab Jamahiriya, 2Benghazi University, Pediatric, Benghazi, Libyan Arab Jamahiriya Primary immunodeficiency diseases (PIDs) comprise a number of serious and rare genetically determined disorders characteristically observed in children. Early diagnosis of PIDs is important because it can lead to lifesaving treatment, prevention of complications, and significant improvement in the quality of life. The skin may be involved in PIDs and the dermatologist may be the first to diagnose an immune defect. Only a few studies describing the spectrum of skin disorders in PIDs are available and no similar studies have been reported from Libya. The objective of this study was to determine the frequency and nature of cutaneous changes in children with PIDs. Sixty pediatric patients with a diagnosis of PID were studied at the immunology department of pediatric hospital in Benghazi, Libya between 2007 and 2013. Fifty five percent was males and 45% females, 90% had onset of their disease before the first year of life. Sixty percent of the patients had positive family history resembling PIDs and 58% of their parents were relatives. PIDs were classified as phagocytic (72%), cellular (11%), humeral (8%) and combined (9%). Phagocytic PIDs included chonic granulomatous disease(CGD) (67%), neutropenia (3%) and leukocyte adhesion defect (2%). ª 2014 The Authors | JDDG ª Blackwell Verlag GmbH | JDDG | 1610-0379/2014/12s2

Cellular defects included hyper I g E syndrome (8%) and Di George syndrome (3%). Agammaglobulinemia (8%) constituted humoral whereas ataxia telangectasia (7%) and common variable immune deficiency (2%) constituted combined PIDs. Eighty seven percent had developed skin disease, and the cutaneous alterations were the presenting problem in 47% of the patients. Cutaneous infections were the most prevalent manifestations, seen in 80% followed by eczematous dermatitis (12%), non infectious granuloma (8%), erythroderma (3%) and autoimmune diseases (2%). Among skin infections; bacterial were the commonest, they were seen in all patients with hyper Ig E syndrome, in 93% of CGD and in 60% of agammaglobulinemia. Eczematous dermatitis was a predominant feature in hyper Ig E (100%), it was seen in ataxia telangectasia and CGD (2%). Non infectious granuloma was observed in 13% of CGD . In conclusion; most PIDs have cutaneous manifestations which may be the presenting signs. Skin infections as well as eczema and cutaneous granulomas characterize many PIDs. The knowledge of the skin findings associated with PIDs is important for early diagnosis. and mangement of these serious life-threatening immunological defects.

O14 Child syndrome: Successful treatment of the skin lesions with topical lovastatin/cholesterol cream. A case report A. Alexopoulos; T. Kakourou Aghia Sofia Children’s Hospital, 1st Department of Pediatrics, Athens University, Athens, Greece Presentation: A 10-year old Greek girl presented in our clinic with the diagnosis of CHILD syndrome. She had a severely malformed upper right extremity, including a markedly underdeveloped arm and forearm and the existence of only three distorted fingers on the affected limb with significant onychodystrophy. In addition to the skeletal malformations she had ichthyosiform erythrodermic plaques on the dorsal surface of her rudimentary right hand, over the surface of her right axilla, over her right inguinal area extending to both the inner thigh and the genital area sharply demarcated in the midline and over her right popliteal fossa. All the skin lesions showed an unusual right lateralization. Earlier molecular screening analysis had detected in the coding region of the NSDHL gene a missence mutation confirming the diagnosis of a CHILD syndrome (congenital hemidysplasia with ichthyosiform erythroderma and limb defects). Treatment/outcome: There was no improvement of her extremely itchy ichthyosiform skin lesions with any of the topical applications of emollients, keratolytics, retinoids or calcineurin inhibitors used before. Our patient responded surprisingly fast with the topical application of lovastatin/cholesterol products twice daily as suggested in the recent literature for only another two older patients with a similar condition worldwide. The scales of her skin lesions cleared completely and the dryness on the skin significantly improved within a very short period of topical treatment (3 weeks), with postinfllammatory hypopigmentation remaining. Conclusion: This pathogenesis based therapy, which was successfully applied to our patient, targets the cutaneous abnormalities of distal cholesterol metabolism disorders such as seen in the CHILD syndrome, therefore encompasses a very promising and effective therapeutic approach for some syndromic lipid metabolic disorders.

6 FREE COMMUNICATIONS O15 National survey and genetic background of ectodermal dysplasias and ectodermal dysplasia syndromes among pediatric patients in Hungary Z.Z. Szalai
l Children’s Hospital, Dermatology, Budapest, Heim Pa Hungary Objective: The ectodermal dysplasias create a complex group of disorders. In this group of conditions there is abnormal development of the skin, hair, nails, teeth, or sweat glands. Lamartine and co-workers created 4 functional groups based on pathophysiology, Priolo and Lagan a reclassified in two groups: (1)defects in developmental regulation/ epithelial-mesenchymal interaction, (2) defects in cytoskeleton maintenance and cell stability. With the leading clinical signs the pure Ectodermal Dysplasia forms and Ectodermal Dysplasia syndromes should be differentiated. There are two main groups. Group I: developmental regulation (Ectodermal - mesenchymal signalling) Group II. epithelial structural proteins (cytokeratins); and adhesive molecules (desmosomal components). In each group there are some syndromes which have the main features of these groups. Methods: By screening the population, two main groups had been created I: epithelial-mesenchymal transition group: which plays an important role in cancer development, fibrosis, and different types of diseases and syndromes. In group II: the major clinical sign is hyperkeratosis (desmocollin, desmoglein, placoglobin, desmoplakin, KIF, etc.) There are different keratin genes in this group: K1, K2, K10, K6a, K6b, K16, K17, K9, K81, K83, K86, K85. The further clinical signs are deafness, cleft lip/palate (CLP), and retinal degeneration. The pathways controlled by p63 influences the cancer progression and epithelial differentiation. TAp63 prevents premature tissue aging. Results: At a large number of patients genetic results had been performed, the ectodermal dysplasia syndromes had been diagnosed. For future therapy fibroblasts from healthy donors and EEC patients for induced pluripotent stem cell lines has the potential of hope.

O16 Treatment of xeroderma pigmentosum with imiquimod
ndez-Mart
ın A. Torrelo; L. Noguera; A. Herna ~ o Jesu
s, Dermatology, Madrid, Spain Hospital del Nin

Case report: A 5-year-old boy was diagnosed of xeroderma pigmentosum (XP) on clinical grounds of dry, scaly skin on sun-exposed areas, lentigines, and pigmented basal cell carcinomas (BCCs). These lesions affected mainly the face. Treatment with imiquimod 5% cream was started for a small area containing 3 BCCs, and a complete clearing of BCCs and pigmented lesions was achieved. Hence, further areas of face involvement were treated with imiquimod 5% cream, that permitted clearing of all areas treated. Discussion: In children with early lesions of XP, a complete clearing of lesions could induce a favorable course and prognosis of the disease. We propose sequential treatment with imiquimod cream 5% before severe carcinomas related with XP may develop.

FREE COMMUNICATIONS 3 O17 Idiopathic urticaria or food allergy to an allergen underrepresented in routine diagnostic tests, a gap in clinical urticaria diagnostic? W. Anemueller1; U. Jappe2 1 University Hospital Luebeck, Dermatology, Luebeck, Germany, 2Research Center Borstel, Borstel, Germany A 7-year-old boy with no history of atopy and/or allergy presented with recurrent urticaria for 4 years, sometimes combined with diarrhea, vomiting, fever, dizziness and loss of consciousness.

Urticaria diagnostic screening tests were negative, mastocytosis was excluded. Routine prick testing for atopy was negative. Because of the history of diarrhea and vomiting sometimes accompanying urticaria, diagnostic measures included prick to prick tests with food, which was consumed in connection with the episodes of urticaria, but were negative. Additional in vitro screening tests for specific IgEantibodies to food including pork, beef and the wheat component Tri a 19 were negative as well. Subsequently, the patient0 s serum was investigated in an immunoblot with Cetuximab and Galactosea-1,3-Galactose (aGal) as target antigens and showed a positive reaction for anti-a-Gal-IgE. The boy was advised to avoid red meat completely, and as a consequence urticaria and dizziness resolved. Due to the fact that the symptoms of a-Gal-associated meat allergy mostly develop after 3 to more than 6 hours it can be difficult to detect, since routine diagnostic tests for IgE to meat (pork and beef) as in our case often remain negative. a-Gal-sensitization is generally missed in routine allergy tests.

O18 Attentiveness and IgE-levels are altered in children with atopic dermatitis and children with attention deficit hyperactivity disorder: Similarities and differences

€ lfer1; K. Krauel2; B. Bonnekoh1; H.-H. Flechtner2; W. Wo H. Gollnick1; A. Ambach1 1 Otto-von-Guericke-University, Clinic for Dermatology and Venereology, Magdeburg, Germany, 2Otto-von-GuerickeUniversity, Clinic for Child and Adolescent Psychiatry, Magdeburg, Germany

Atopic dermatitis (AD) is supposed to be an independent risk factor for attention deficit hyperactivity disorder (ADHD). The molecular basis of this connection remains to be elucidated. Among other phenomena, AD-pathophysiology is characterized by a reduction of intracellular storage organelles and disturbed granule release mechanisms in several cell systems. This results in an often adequate but not sustained reaction to stimulation. We hypothesized that CNSreactions requiring sustained granule release (from neurons) may be impaired in AD-patients as well. Therefore, we compared the reaction of children with AD in several neuropsychological tests to ADHD-patients which are known to be unable to keep up an enduring CNS-response. 14 ADHD-inpatients with confirmed diagnosis (13 m, 1f), 11 ADchildren (8 m, 3f) and 8 healthy individuals (HI; 6 m, 2f) without any atopic/psychiatric background were studied in three modules: A) child psychiatry, B) dermato-allergology, C) laboratory. In A, using a neuropsychological computer-based test battery [Psytest 2.2, Herzogenrath, Germany], short term (120 signals / 4 min, “sprint”) and long term (900 signals / 30 min, “endurance”) attentiveness towards visual and acoustic stimuli was tested. ADHD symptoms, emotional/ behavioural difficulties and personality traits (e.g. novelty seeking) were assessed employing questionnaires (CBCL, DISYPS II-ADHD, JTCI). In B, Erlanger Atopie Score (EAS), SCORAD and a prick test with common aero allergens were performed. In C, total serum IgE, eosinophilic cationic protein (ECP) and differential blood count were determined. A) 2 AD-children were omitted from analysis since parents reported a significant number of ADHD symptoms. In the short term attentiveness test, AD-children reacted comparable to the ADHD-group: significantly slower with more mistakes than HI. this was most pronounced in AD-children with exacerbated disease. In the long term attentiveness test, AD-children showed again prolonged reaction times which slowed down even more over time as compared to HI, but did not make as many errors as ADHD-patients. B) 12/14 ADHD-children did not have any AD-symptoms nor any history of atopy, 13/14 showed a white dermographism, EAS was 9  3 (atopic skin diathesis unclear). 5/11 AD-patients showed exac-

ª 2014 The Authors | JDDG ª Blackwell Verlag GmbH | JDDG | 1610-0379/2014/12s2

FREE COMMUNICATIONS 7 erbated disease at the timepoint of the study (SCORAD > 10, mean EAS 12  3). C) ADHD- and AD-patients had elevated IgE levels (500  420 kU/l and 653  950 kU/l), eosinophila (8.7  9% and 7  6%) and high ECP-levels (31  30 and 39  33 lg/l). Our results confirm the hypothesis that CNS-reactions requiring sustained granule release are impaired in AD. Thus, having in mind the well known granule defects in epidermis and immune system of AD, granule alterations seem to be a general cell biologic AD-phenomenon. Similarities in neurophysiological tests were mirrored by similar ECP- and IgE-levels among AD-/ ADHS-children. This may suggest a common cell biological basis for these phenomena.

O19 Contact allergy in children with and without atopic dermatitis; which are the frequent allergens? S. Lubbes1; T. Rustemeyer2; M.L.A. Schuttelaar3; J.H. Sillevis Smitt1; M.A. Middelkamp-Hup1 1 Academic Medical Center, University of Amsterdam, Dermatology, Amsterdam, Netherlands, 2VU University Medical Center, Dermatology, Amsterdam, Netherlands, 3 University Medical Center Groningen, Dermatology, Groningen, Netherlands Background: Data on contact allergies in children are conflicting. This study aims to identify frequent contact allergens and their relevance in children with and without atopic dermatitis (AD). This will allow better identification of potential sensitizers and improve patients’ care in children. Methods: We conducted a retrospective study of 1083 patient records of children aged 0-18 years suspected of having contact dermatitis. Children were patch tested between 1996-2013 in 3 University Hospitals in the Netherlands. Patch testing was performed using the Chamber technique and the TRUE test. Patients were excluded (n = 71) when not tested with at minimum the European Baseline Series. Results of additional patch tested series, tested “on indication” according to the patient history, were also evaluated. The primary analysis was performed on routinely tested allergens, while the secondary analysis was performed on the combined data from routinely tested allergens plus allergens tested “on indication”. Provided relevance scores are the current “certain” and “probable” relevance scores combined. Statistical analysis was performed with Chi-square or Fisher’s exact test. Results: 1012 children (female 63%, mean age 13 years) were included, and 469 (46%) of children developed ≥1 positive reaction. The most frequent reactions were to nickel (16,4%: 164/998), cocamidopropyl betaine (CAPB) (15,9%: 54/339), fragrance mix I (9,9%: 100/1008), Amerchol L-101 (8,8%: 30/339) and wool alcohols (6,2%: 63/1009). 52% of children had AD, 39% did not have AD and in 9% had an unknown atopic status. Sensitization rates for children with and without AD were similar (48% vs. 47%). In children with AD, CAPB was the most frequent allergen (19%; 33/174). Compared to children without AD, the primary analysis showed no significant difference. However, when analyzing all reactions to CAPB found in the routinely tested series plus the “on indication” tested series together, a significant difference between children with and without AD was seen for CAPB (17% vs. 9%; p < 0.02). Reactions to CAPB were considered relevant in the majority of cases (56%). Reactions to wool alcohols (p < 0.04) and fragrances (p < 0.05) were found significantly more often in children with AD vs. children without AD, with relevance scores of at least 59% and 63%, respectively. Surprisingly, less positive reactions to wool alcohols and fragrances were found with the TRUE test as compared to the Chamber technique. Conclusion: Sensitisation rates in children with and without AD were similar, but significant differences were found in the reacting allergens between these 2 groups. Reactions to CAPB, fragrances and wool alcohols are more common in children with AD, and these should be tested when a contact dermatitis is suspected in this popuª 2014 The Authors | JDDG ª Blackwell Verlag GmbH | JDDG | 1610-0379/2014/12s2

lation. The difference in positive reactions to wool alcohols and fragrances between TRUE test and Chamber technique is striking and needs further investigation.

O20 Lobar neutrophilic panniculitis of children with lipoatrophy


ndez-Mart
ın A. Torrelo; L. Noguera; A. Herna ~ o Jesu
s, Dermatology, Madrid, Spain Hospital del Nin Introduction: The terms ‘lipophagic panniculitis’, ‘idiopathic lobar panniculitis of children’, ‘lipoatrophic panniculitis of the ankles’ or ‘Weber-Christian panniculitis’ have been used to describe a peculiar type of childhood panniculitis characterized by recurrent attacks of fevers and inflammatory subcutaneous nodules followed by permanent fatty tissue atrophy. Case reports: We present 4 cases of children with recurrent attacks of lobar panniculitis with subsequent lipoatrophy. They coursed along with fever, malaise and abdominal pain. Histopathology showed lobar panniculitis with mixed inflammatory infiltrates, prominent in neutrophils. Late lesions show macrophages with fat phagocytosis and fatty tissue atrophy. Lab studies ruled out other known causes of panniculitis. Elevation of ESR and CRP were the only consistent anomalies. Autoimmunity markers were negative. Conclusion: We propose the term lobar neutrophilic panniculitis of children with lipoatrophy to name this disease. The clinical and analytical picture of the patients suggests some kind of autoinflammatory syndrome.

O21 Childhood lichen sclerosus et atrophicus - differential diagnoses and therapy A. Bygum Odense University Hospital, Department of Dermatology and Allergy Centre, Odense, Denmark Lichen sclerosus et atrophicus is a chronic skin disorder with a predilection for the anogenital area. The disease is mostly seen in prepubertal and postmenopausal females. The prevalence of vulvar lichen sclerosus has been reported to be one in 900 girls. The lesions present as sharply demarcated white plaques encircling the vagina and anus. The atrophic form can lead to scarring of the affected area. Most patients have itching, some have soreness and sometimes also local bleeding may occur. Some children have dysuria or constipation as their main complaint, which may be related to painful fissuring in the anogenital area. Although the clinical features are quite obvious, a diagnostic delay is often a reality. It is not unusual that patients have been treated for suspected eczema, fungal or bacterial infection before beeing diagnosed with lichen sclerosus et atrophicus. Also a suspicion of sexual abuse may have been raised. In atypical cases a skin biopsy may be necessary to confirm the diagnosis. Potent/ultrapotent corticosteroids are the treatment of choice. In selected cases calcineurin inhibitors may be used. The purpose of this session is to draw attention to lichen sclerosus et atrophicus in children as a highly symptomatic and treatable disorder.

8 FREE COMMUNICATIONS O22 Psoriasis and obesity in childhood. A cross-sectional, multicentre, case-control study (c-Psocar study)


1; A. Beauchet2; C. Bodemer3; A. Phan4; E. Mahe A.-C. Bursztejn5; F. Boralevi6; A.-L. Souillet4; C. Chiaverini7; E. Bourrat8; J. Miquel9; P. Vabres10; S. Barbarot11; D. Bessis12; C. Eschard13; M.-L. Sigal14;
te
S. Hadj-Rabia3; Groupe de Recherche de la Socie
diatrique Franc ß aise de Dermatologie Pe 1 Hospital Victor Dupouy, Dermatology, Argenteuil, France, 2 Hospital Ambroise Pare
, Boulogne-Billancourt, France, 3 Hospital Necker-Enfants Malades, Paris, France, 4Hospital, Lyon, France, 5Hospital, Vandoeuvre les Nancy, France, 6 Hospital, Bordeaux, France, 7Hospital, Nice, France, 8 Hospital Robert Debre
, Paris, France, 9Hospital, Rennes, France, 10Hospital, Dijon, France, 11Hospital, Nantes, France, 12 Hospital, Montpellier, France, 13Hospital, Reims, France, 14 Hospital Victor Dupouy, Argenteuil, France

Introduction: Obesity is more frequent in patients with psoriasis than in the general population. Few data are available in children but this link seems to be confirmed in children with plaque psoriasis. The objective of this study was to evaluate the prevalence of overweight (including obesity) in children with psoriasis, regardless of the type of psoriasis, in French population. Materials and methods: Cross-sectional, multicenter, case-control study performed from April 2012 to March 2013, in 23 French dermatologic centers. All children (> 2 y, < 18 y) with psoriasis were consecutively included. Metabolic and cardiovascular comorbidities in children and parents were systematically reported. Controls were children seen in the department of dermatology, matched for age and sex, without chronic or genetic inflammatory disease. The definitions of overweight, abdominal obesity and obesity were those used by the French Health Authority (HAS, Recommendations 2011). Results: 261 children with psoriasis, and 261 controls were included. Mean age was 9.8  3.8 years, G / F: 126/135. 84 children were considered to have severe psoriasis (use of systemic therapy). Only 42% of psoriasis were plaque psoriasis. Among psoriatic children, 10.7% were overweight (¾ of them with abdominal obesity) and 10.0% were obese. If we include all children with overweight (obesity included), there was no significant difference from the control group. Overweight with abdominal obesity, and obesity were more common in psoriasis group (p = 0.009 and p = 0.0001 respectively). These differences have not been found for severe psoriasis, or plaque psoriasis. We also evaluated if known determinants of obesity in children (i.e. sport, weight at birth, parents comorbidities) had influence on this difference. None of these determinants explain the difference. Discussion: This study shows that in psoriatic children with abdominal obesity overweight and obesity are more common than in pediatric control population. This is shown if we include all types of psoriasis. The severity is not however associated with overweight and obesity in our study.

O23 Effect of narrow band UVB (NB-UVB) on TLR7 and TLR9 in psoriasis vulgaris D.M. Mahgoub Cairo University, Dermatology, Cairo, Egypt Background and Objective: Psoriasis is a common chronic inflammatory, recurrent, immune mediated disease of the skin and joints. Toll-like receptors are pattern recognition receptors for conserved molecular patterns of pathogenic microorganisms.Under certain circumstances, self nucleic acids can trigger TLR 7 and TLR 9, which can lead to autoimmune diseases such as psoriasis.

Patients and methods: The study included 15 psoriatic patients (plaque type) and 15 controls, patients received 36 sessions of phototherapy (NB-UVB). Skin biopsies were taken from all the patients (before & after NB-UVB) and controls and were assessed for TLR 7 & TLR 9 by PCR. Results: Showed significant difference between patients and controls as regards TLR 7 & TLR 9. In addition a significant decrease in thier levels in patients after phototherapy with NB-UVB. Conclusion: TLR 7 and TLR 9 may play a role in the pathogenesis of poriasis. Decrease in their levels after NB-UVB may be one of the therapeutic mechanisms of NB-UVB in psoriasis.

O24 Neurological abnormalities in children with congenital melanocytic naevi: a prospective 25 year study R. Waelchli1; S. Aylett2; K. Chong3; V. Kinsler4 1 Great Ormond Street Hospital for Children, Paediatric Dermatology, London, United Kingdom, 2Great Ormond Street Hospital for Children, Paediatric Neurology, London, United Kingdom, 3Great Ormond Street Hospital for Children, Paediatric Neuroradiology, London, United Kingdom, 4Great Ormond Street Hospital for Children, London, United Kingdom Background: Congenital melanocytic naevi (CMN) can be associated with abnormalities of the central nervous system (CNS). The spectrum of these abnormalities is very broad, including congenital and acquired pathologies with widely varying clinical outcomes. This study aims to classify the abnormalities on the basis of radiological appearence, to produce clinically-useful prospective follow-up data for the different categories, and to review existing published guidelines(1) on imaging. Methods: 630 children with CMN were seen in the Paediatric Dermatology department at Great Ormond Street Hospital between 1988-2013. 377 were followed prospectively with sufficiently detailed clinical phenotyping for inclusion in this study. An MRI of the CNS was performed if pre-defined criteria were fulfilled. All MRIs were reported by a Paediatric Neuroradiologist, and categorized. Variables were radiological (MRI result) and clinical (largest CMN projected adult size, total number of naevi at presentation). Outcome measures were seizures, neurodevelopmental delay, neurosurgery required, primary CNS malignant melanoma, and death. Statistical modeling of outcome measures was by multivariate logistic regression. Results: 5 children were neurologically symptomatic at the time of referral to GOSH. 290 children fulfilled the criteria for MR imaging of the whole CNS, of which 272 were performed successfully. 47/ 272 were abnormal, and were classified as group 1 “intraparenchymal melanosis only” (n = 28), and group 2 “other” (n = 20). Any radiological abnormality was a stronger predictor than clinical phenotyping for all outcome measures: seizures (OR 7.833 (95% CI 2.556-24.003)), neurodevelopmental abnormalities (OR 4.272 (2.075 - 8.794)), and requirement for neurosurgery (OR 85.265 (10.805-672.816). Furthermore, a significant difference was found between groups 1 and 2, as no patient from group 1 required neurosurgery (0/28 vs 13/20, p < 0.001) or died (all from primary CNS melanoma) (0/28 vs 5/20 p < 0.001). Published guidelines were found to have reduced the numbers of MRI performed, while still maintaining the same detection rate of abnormalities. Conclusions: 20% of children with two or more CMN at birth have radiological evidence of neurological abnormalities. Radiological classification is a stronger predictor of all clinical outcome measures than clinical phenotyping. Patients with intraparenchymal melanosis alone are not at increased risk of death, even if clinically symptomatic. Guidelines for imaging from 2008 are appropriate. MRI in the first six months therefore dictates the direction of multi-discliplinary clinical management, as well as giving accurate prognostic information to families.

ª 2014 The Authors | JDDG ª Blackwell Verlag GmbH | JDDG | 1610-0379/2014/12s2