Clinical and haemodynamic risk factors associated with discrepancies in lower limb length with capillary malformations: data from the national paediatric French cohort CONAPE.

BACKGROUND: Genetics discoveries have allowed for a better understanding of capillary malformations (CMs) associated with overgrowth syndrome. However, molecular analyses are still not easy to perform or interpret. Other analytical methods are needed. OBJECTIVES: To identify clinical and haemodynamic factors associated with leg length discrepancy (LLD) in children with CMs of the lower limbs. METHODS: Data were obtained from the multicentre French national cohort CONAPE (COhorte Nationale d'enfants atteints d'Angiome Plan de membrE inférieur), from children aged 2-12 years old with CMs of the lower limbs. Clinical characteristics were prospectively collected. Haemodynamic factors were measured by an sonographer who calculated the arterial blood flow (ABF) in both lower limbs. An ABF difference ≥ 50% between the two lower limbs was considered relevant. LLD ≥ 2% was determined by the same radiologist on centralized radiographs. RESULTS: We analysed data at baseline for 96 children. The mean ± SD age was 5·6 ± 3·1 years; 49 (51%) were male; and 14 (15%) showed LLD. In total, 32 patients (33%) had venous anomalies, 13 (14%) lymphatic anomalies and in one child a diagnosis of Parkes Weber syndrome was made. Only an increased circumference above the knee was more frequent with than without LLD (43% vs. 13%, P = 0·02). In all, 10/79 patients (13%) showed a difference in ABF ≥ 50%: four had LLD. The frequency of differences in ABF ≥ 50% was greater with than without LLD [33% (n = 4/12) vs. 9% (n = 6/67), P = 0·04]. CONCLUSIONS: ABF measured by Duplex ultrasonography is a simple, low-cost and noninvasive complementary examination for help in detecting LLD, with a difference of ≥ 50% possibly associated.

Nail features in healthy term newborns: a single-centre observational study of 52 cases.

INTRODUCTION: The anatomy and embryology of the nail are well known, and nail abnormalities are a feature of many genodermatoses. However, the physiological aspect is not well described. We aimed to analyse the physiological features of nails in healthy newborns. METHODS: We performed an observational, prospective study at University Hospital Center of Tours between July and October 2015. Newborns were included by a dermatologist assistant during the systematic examination on release of the mother from the hospital. The medical history of the mother and infant were recorded by using a standardized questionnaire. Finger- and toenails were systematically photographed for a second interpretation by a dermatologist with blinding to the first photograph. RESULTS: Fifty-eight patients were eligible, and 52 were included. Half of the newborns were males, and the mean age at inclusion was 3.6 ± 1.2 days. Fingernails had an oval shape (71.1%) or a flat curvature (63.5%), and half had a lunula. Toenails showed an apparent hypertrophy of the proximal nail fold (38.4%) and lateral nail fold (73.1%). The shape of the nails was triangular (50.0%) or round (21.1%). We noted koilonychia in 32.7% of infants and lunula in 7.7%. Distal parts showed onychoschizia (28.8%) and onycholysis (26.9%). CONCLUSION: Koilonychia, onychoschizia of toenails or absence of lunula are physiological features of nails in newborns.

Prognostic value of antibodies to Merkel cell polyomavirus T antigens and VP1 protein in patients with Merkel cell carcinoma.

BACKGROUND: Merkel cell polyomavirus (MCPyV) is the main aetiological agent of Merkel cell carcinoma (MCC). Serum antibodies against the major MCPyV capsid protein (VP1) are detected in the general population, whereas antibodies against MCPyV oncoproteins (T antigens) have been reported specifically in patients with MCC. OBJECTIVES: The primary aim was to assess whether detection of serum antibodies against MCPyV proteins at baseline was associated with disease outcome in patients with MCC. The secondary aim was to establish whether evolution of these antibodies during follow-up was associated with the course of the disease. METHODS: Serum T-antigen and VP1 antibodies were assessed by enzyme-linked immunosorbent assay using recombinant proteins in a cohort of 143 patients with MCC, including 84 patients with serum samples available at baseline. RESULTS: Low titres of VP1 antibodies at baseline (< 10 000) were significantly and independently associated with increased risk of recurrence [hazard ratio (HR) 2·71, 95% confidence interval (CI) 1·13-6·53, P = 0·026] and death (HR 3·74, 95% CI 1·53-9·18, P = 0·004), whereas T-antigen antibodies were not found to be associated with outcome. VP1 antibodies did not differ between patients in remission and those with recurrence or progression during follow-up. However, T-antigen antibodies were more frequently detected in patients with recurrence or progression at 12 months (P = 0·020) and 24 months (P = 0·016) after diagnosis. CONCLUSIONS: VP1 antibodies constitute a prognostic marker at baseline, whereas T-antigen antibodies constitute a marker of disease recurrence or progression if detected > 12 months after diagnosis.

Vitamin D deficiency is associated with greater tumor size and poorer outcome in Merkel cell carcinoma patients.

BACKGROUND: Merkel cell polyomavirus has been recognized to be associated with Merkel cell carcinoma (MCC), but the evolution of this cancer probably depends on various factors. Vitamin D deficiency, defined by serum 25-hydroxyvitamin D levels <50 nmol/L, seems to influence cancer behavior and progression, but has never been assessed in MCC patients. OBJECTIVES: First, to evaluate whether vitamin D deficiency was associated with tumor characteristics and prognosis in a cohort of MCC patients. Second, to assess expression of the vitamin D receptor (VDR) in MCC tumors. METHODS: Clinical findings, Merkel cell polyomavirus markers and vitamin D status were assessed in a cohort of French MCC patients. The study was limited to the 89 patients for whom the serum sample had been collected within 3 years after the diagnosis of MCC. Correlation between vitamin D deficiency and MCC characteristics and outcome were determined in regression analyses. VDR expression in MCC tumours was assessed by immunohistochemistry. RESULTS: Vitamin D deficiency was noted in 65.1% of the patients and was independently associated with greater tumor size at diagnosis (P = 0.006) and with metastasis recurrence (HR, 2.89; 95% CI, 1.03 to 8.13; P = 0.043), but not with death from MCC, although there was a trend (HR, 5.28; 95% CI, 0.75 to 36.96; P = 0.093). VDR was found to be strongly expressed in all 28 MCC tumor specimens investigated. CONCLUSION: The association between vitamin D deficiency and MCC characteristics and outcome, together with detection of the VDR in MCC cells, suggest that vitamin D could influence the biology of MCC.

Serial lymphoscintigraphic findings in a patient with Gorham's disease with lymphedema.

Gorham's disease is a rare disorder characterized by vascular, "lymphangio- matous" and/or "hemangiomatous" lesions in bone and surrounding soft tissues. Associated lymphedema has not been reported and clinical evolution is unpredictable. Plain radiographs, CT, MRI, and occasionally bone scintigraphy, are used to detect the bone and soft tissues changes. Biopsy is a major component of the diagnostic process. We report the findings of serial lymphoscintigraphy in a young boy with a polyostotic Gorham's disease associated with lymphangioma of the thigh and lower limb lymphedema. In this patient, lymphoscintigraphy was useful for diagnosis and follow-up of primary lymphedema. It provided valuable information concerning the occurrence, location, and progression of lymphatic lesions in both bone and soft tissues.

[Frequency of lymphoscintigraphic anomalies in the contralateral limb and progression of unilateral primary lymphedema in children]. / Fréquence des anomalies lymphoscintigraphiques infracliniques controlatérales et évolution des lymphœdèmes primaires unilatéraux de l'enfant.

BACKGROUND: Primary lymphoedema (LE) is the consequence of lymphatic insufficiency, usually associated with hypoplasia of the lymph vessels and/or nodes. Lymphoscintigraphy allows early diagnosis. OBJECTIVES: To assess the frequency of contralateral LE by lymphoscintigraphy in children with unilateral primary LE of one limb; to assess facets of clinical bilateralization of LE. METHODS: This retrospective single-centre study included children with unilateral LE followed up at the Tours university hospital centre between 2004 and 2014. Parents were contacted by phone to obtain follow-up data. RESULTS: Of the 13 children included, 6 (46%) displayed bilateral lymphatic anomalies on lymphoscintigraphy. Within a median follow-up period of 6 years, clinical bilateralization was observed in one girl after progression of her LE for 7 years; in her case, bilateral lymphatic insufficiency was detected at the initial lymphoscintigraphy. CONCLUSION: While contralateral subclinical lymphatic insufficiency is frequent in children with unilateral primary LE of the limbs, clinical bilateralization appears only rarely.

[Thigh root reconstruction with a pedicled DIEP flap]. / Reconstruction d'une perte de substance de racine de cuisse sur membre lymphœdèmateux par un lambeau DIEP pédiculé

Root thigh extensive loss of substance requires surgical coverage. The presence of chronic lymphedema (LC) makes random with the postoperative healing time longer. We report an original case of reconstruction of extensive loss of substance from the root of the thigh using a pedicled deep inferior epigastric flap perforator (DIEP) flap. A 22-year-old woman with angiosarcoma occurring in hemi-body lymphedema. The defect generated by the oncologic resection was 16×24cm. She was reconstructed by a pedicled DIEP flap. Skin wound healing was obtained within 30 days. Donor site healing was obtained within 15 days. The pedicled DIEP flap seems to be effective for root thigh reconstruction.

Patients' acceptance of medical photography in a French adult and paediatric dermatology department: a questionnaire survey.

BACKGROUND: Despite the increasing use of medical photography by dermatologists, no study on patients' perceptions of photography in dermatology has been performed to date. OBJECTIVES: Firstly, to evaluate patients' perceptions of medical photography. Secondly, to assess whether perceptions differed between patients in our adult department and parents accompanying a child in our paediatric department. METHODS: An opinion survey was conducted at the Hospital of Tours (France) among adult patients (adult department) and accompanying parents (paediatric department) by completion of a questionnaire after any medical photography had been performed. RESULTS: We collected 272 questionnaires regarding 158 adults and 114 children. A camera used only in the department, and storage of the images in the department's records were the most accepted modalities (> 90%), especially in the paediatric survey. Respondents agreed with the sharing of the images with other practitioners and in medical meetings (> 85%) rather than distribution via publications (58·3%), e-mails (45·5%), health magazines (44·3%) and websites (32·0%). Most (78·8%) considered that the consent form should list all the possible uses of the images. Need for renewed consent for each use of the images was significantly more often expressed in the paediatric than the adult survey (44·5% vs. 24·5%, P = 0·001). More than 95% of respondents considered medical photography to be useful for improving diagnosis, monitoring of skin disease and aiding teaching. CONCLUSIONS: These findings could be used to improve practice, to increase the acceptability of medical photography and for devising a standardized consent form for medical practitioners performing medical photography.

Contributions of SPECT/CT imaging to the lymphoscintigraphic investigations of the lower limb lymphedema.

Lymphoscintigraphy is a safe and reliable technique for investigating lymphedema. However, interpretation of delayed planar conventional imaging may be questionable due to the superimposition of soft tissues. Therefore, the aim of this retrospective study was to evaluate the contribution of single photon emission computed tomography/computed tomography (SPECT/CT) to lymphoscintigraphic investigation in a selected population with abnormal interstitial activity. Forty one patients with lower limb lymphedema either primary (n=17) or secondary (n=5), or associated with chronic venous insufficiency (n=19) underwent lymphoscintigraphy according to a standard protocol. SPECT/CT imaging that started immediately after planar imaging covered the part of the lower limbs with the most significant interstitial activity. The CT images were also analyzed separately to identify the typical honeycomb pattern of lymphedema. SPECT/CT identified additional abnormalities in vessels and soft tissues in 19 patients (46%). The additional information, primarily related to dermal collateralization of flow, dermal backflow, lymphangioma, and lymphorrhea, aided in understanding the physiopathology of edema and may have influenced management in 35 patients (85%). The honeycomb appearance of the soft tissues was noted on CT in most patients (90%). This study suggests that SPECT/CT is a promising addition to planar imaging in lymphoscintigraphic investigations of lymphedema.

[The CONSORT statement (CONsolidated Standards Of Reporting Trials)]. / Les recommandations CONSORT (CONsolidated Standards Of Reporting Trials).

The CONSORT group, made up in particular of methodologists and journal editors, has created a tool in the form of a list. This tool, known as the "CONSORT statement", sets out all items that must be reported when preparing for publication in medical journals with regard to methods, results and discussion of randomised controlled trials (RCT). The aim of this group and of the CONSORT statement is to help authors prepare a standard presentation of the methodology and results of their studies. The desired effect is to ensure greater transparency and optimal rigor in such presentations, and thus in study design. This will make it easier for readers to verify such studies and to assess any potential sources of study bias.

Visceral and mucosal involvement in neonatal haemangiomatosis.

BACKGROUND: Two types of neonatal haemangiomatosis (NH) are distinguished: diffuse which is associated with a high rate of mortality linked to mucosal/visceral involvement, and benign. OBJECTIVES: First, this study aimed to examine the frequency of mucosal and visceral (especially hepatic) involvement in NH, according to skin extension, and second, it aimed to examine clinical, pathological (with glucose transporter 1 (GLUT-1) immunostaining), and imaging features of NH, including follow-up data. METHODS: This was a descriptive retrospective study carried out in the University Hospital Center of Tours, France. RESULTS: The study included 19 patients with cutaneous NH (number of skin haemangiomas ranging from 5 to >100). Mucosal involvement was observed in 32% of all cases (100% and 19% in diffuse and other cutaneous cases respectively) and hepatic involvement in 42% (67% and 38% respectively). The number of hepatic haemangiomas ranged from 1 to >10. Half of the hepatic haemangiomas cases exhibited increased hepatic arterial blood flow. CONCLUSIONS: Mucosal and hepatic involvement was frequent in cases with a high number of cutaneous haemangiomas (>100), but only frequency of mucosal involvement was statistically significant (P = 0.021).

Changes in the nail unit in patients with secondary lymphoedema identified using clinical, dermoscopic and ultrasound examination.

BACKGROUND: Secondary lymphoedema is characterized by lymphatic stasis that is often the result of a lymph node lesion. At advanced stages it may cause trophic changes in the skin. However, the presence of changes in the nail unit has not been reported to date. OBJECTIVES: The aim of this study was to determine the presence of nail abnormalities in cases of secondary lymphoedema. METHODS: This was a prospective study, conducted on patients with unilateral secondary lymphoedema. A comparative clinical and dermoscopic examination and 20-MHz high-resolution ultrasound imaging of the affected limb and the contralateral limb were performed. RESULTS: Thirty-three patients were included. On physical examination, hyperkeratosis of the lateral nail folds, friability of the nail surface, 'ragged' proximal nail folds and cuticle and apparent leuconychia were observed more frequently on the lymphoedematous limb. The ultrasound study of the nails of the thumb and the big toe did not reveal any differences in thickness of the different structures of the nail between the lymphoedema side and the opposite side. The nail matrix was longer on the lymphoedema side. CONCLUSIONS: Our study showed mild changes in the nail unit compatible with the xerosis often associated with severe lymphoedema. However, the study also showed frequent evidence of 'ragged' cuticles, which in these patients at high risk of erysipelas are entry points for bacteria. This should be taken into account when counselling patients with limb lymphoedema in order to prevent erysipelas.

[Original treatment of constitutional painful callosities by surgical excision, collagen/elastin matrix (MatriDerm(®)) and split thickness skin graft secured by negative wound therapy]. / Traitement original des callosités plantaires douloureuses constitutionnelles par exérèse, matrice de collagène et d'élastine (MatriDerm(®)) et greffe de peau mince en un temps, associée à une thérapie par pression négative.

Constitutional painful callosities is an unusual pathology, integrated in the frame of "palmoplantar keratodermia" (PPK). Lesions are located at areas of support of the sole. These lesions are painful and disable the normal walking. Treatments are suspensive and painkillers. We report our experience of a single surgical treatment: surgical excision, split thickness skin graft applied on a dermal substitute and secured by negative wound therapy. A 28-year-old patient, affected by this disease, has a desire of pregnancy but her treatment is highly teratogen. A year post-op, wounds were healed. The walk was possible with a relief of the pain, without any ulcerations. The surgical treatment by excision and graft or flaps was previously reported for PPK. The use of dermal substitute was never described for this indication. Dermal substitute compensate the thickness of the soft tissue defect and give an accurate quality of elasticity in this localisation .The negative wound therapy enhances the quality and shortens the length of graft taking, and the adhesion of the dermal substitute on his bed.

Successful treatment of ulcerated haemangioma with propranolol.

BACKGROUND: Ulceration is a frequent complication of proliferating haemangioma. METHODS: Four patients with ulcerated hemangioma aged 2, 4, 5 months and 5 weeks were treated with 2 mg/kg KG propranolol. RESULTS: Efficacy and safety of propranolol were excellent in all four cases. CONCLUSIONS: Propranolol may be the first-choice therapy for ulcerated haemangioma.

[Assessment of the usefulness of autologous serum skin testing in chronic urticaria: a retrospective single-centre study of 74 patients]. / Evaluation de l'utilité du test au sérum autologue dans l'urticaire chronique idiopathique: étude rétrospective chez 74 patients.

BACKGROUND: Chronic urticaria (CU) is a debilitating disease, and patients and their physicians often seek an aetiological explanation. Studies have suggested that idiopathic CU is associated with the presence of serum auto-antibodies that may be detected by autologous serum skin test (ASST). AIM: To confirm the frequency of positivity of ASST and to evaluate its usefulness and possible correlation with the severity of urticaria (greater resistance to AH1, greater activity score or longer duration). PATIENTS AND METHODS: Patients referred for CU between 1 October 2001 and 31 March 2005 were submitted to standardized explorations including clinical examination, physical tests, CBC, ESR, CRP and anti-thyroperoxidase antibodies, and an ASST was ordered. Inclusion criteria included no discernible cause of CU, acceptance of the protocol, including blood sampling and injection of ASST 3 weeks later, serological tests for HBV, HCV and HIV, and discontinuation of anti-H1 agents and corticosteroids. Exclusion criteria comprised the presence of dermographism, physical urticaria, urticarial vasculitis, and failure to discontinue anti-H1 drugs or corticosteroids. In April 2006, we contacted patients by mail to assess their current treatment, their CU activity score or its resolution. RESULTS: Seventy-four patients (67 women, seven men) of mean age 43 years were included. ASST was positive in 43 patients (58 %) and negative in 31 (42 %). The only noticeable difference, although not statistically significant (p=0.23), was a positive anti-thyroperoxidase antibody result in 12 % of patients with negative ASST versus 24 % of patients with positive ASST. The occurrence of angioedema, the duration of CU, the severity score, the relative inefficiency of AH1 and the use of corticosteroids or cyclosporine were similar between the two groups. DISCUSSION: ASST was positive in more than half of the patients with idiopathic CU both in our study and in the literature, with sensitivity of around 70 % and specificity approaching 80 %. However, while this test can help patients understand their disease better and avoid both a fruitless search for other causes and unnecessary proscription of food allergens, our study shows that positive or negative ASST results have no bearing on treatment and are not associated with greater severity of urticaria or greater resistance to treatment. Consequently, we do not recommend routine use of ASST in patients presenting idiopathic CU.

[Efficacy and risks of topical 5-fluorouracil in Darier's disease]. / Traitement de la maladie de Darier par 5-fluorouracile topique: quelle efficacité, quels risques?

BACKGROUND: Darier's disease, an autosomal dominant disorder, is often resistant to therapy. There have been few encouraging reports in recent years of treatment using topical 5-fluorouracil (5FU) in this indication. We describe three cases of Darier's disease treated with Efudix: though it initially proved very effective, after several months this treatment became inefficacious. PATIENTS AND METHODS: Case 1: a 16-year-old girl with Darier's disease refractory to conventional treatments. Treatment with topical 5FU was initiated. After 3 weeks, her cutaneous lesions had practically disappeared, leaving only pigmented scars. At 6 months, worsening of the disease was controlled by increasing 5FU. At 11 months, the disease worsened and 5FU, which proved inefficient, was stopped. Case 2: a 59-year-old woman presenting treatment-resistant Darier's disease was given 5FU. After 1 week, improvement began and was evident at 4 months. However, after 13 months of treatment, the disease progressed, and increased 5FU proved completely ineffective. Case 3: a 29-year-old woman was hospitalized for inflammatory Darier's disease. Topical 5FU was applied to the left half of the body and a short course of oral corticosteroids was prescribed. After 10 days of treatment, there was a clear improvement. After 6 weeks, the patient showed episodes of healthy skin. However after 3 months, the patient stopped taking her treatment due to inefficacy. DISCUSSION: While topical 5FU seems to be effective initially in treating Darier's disease, this efficacy subsides over time. Although no adverse effects were noted in our patients, use of 5FU can result in serious adverse reactions. Because of the loss of efficacy of this treatment following initial success, coupled with its poorly evaluated safety, caution must be exercised when prescribing it, particularly in patients with dihydropyriminidine dehydrogenase (DPD) deficiency or for use on damaged skin.