Lymphomatoid papulosis in children: a series of 25 cases.

BACKGROUND: Lymphomatoid papulosis (LyP) is an uncommon cutaneous T-cell lymphoproliferative disorder (CTLPD) rarely encountered in children. OBJECTIVES: To specify characteristics of paediatric LyP and to describe both diagnostic difficulties and the course of the disease with the experience of 10 years' follow-up. METHODS: This was a retrospective, single-centre study of 25 children diagnosed with LyP according to the 2008 World Health Organization guidelines, and a clinical and pathological correlation by two experts. RESULTS: The mean age at onset was 7·5 years. The lesions were mostly papulonodular with frequent pruritus (40%). Mucosal involvement was sometimes observed. A single ulcerative nodule was initially suggestive of a primary cutaneous anaplastic large-cell lymphoma (C-ALCL). Pityriasis lichenoides was associated in 36% of cases, atopic dermatitis in 28% and nonspecific infections in 28%. Complete remission was observed in 44% of cases. Through the mean follow-up of 10 years, none of our patients have experienced lymphoma occurrence. Histopathological subtype A clearly predominated (82%). A marked eosinophilic infiltrate was present in 44% of cases and a cutaneous T-gamma clone in 40%. No correlation was observed between histopathological subtype, cutaneous clone or LyP clinical course. CONCLUSIONS: Paediatric LyP belongs to the group of CD30-positive CTLPDs including C-ALCL. Children have to be carefully followed up lifelong, even if the prognosis appears good. The high frequencies of an associated viral infection, atopic dermatitis, marked eosinophilic infiltrate and a good outcome suggest that paediatric LyP could be considered a reactional disease rather than a malignant disorder.

Nutritional outcome in children with severe generalized recessive dystrophic epidermolysis bullosa: a short- and long-term evaluation of gastrostomy and enteral feeding.

BACKGROUND: Generalized recessive dystrophic epidermolysis bullosa (RDEB) is often complicated by high nutritional difficulties with risks of malnutrition. OBJECTIVES: To provide information regarding the benefits of enteral feeding by gastrostomy (GTF), energy and protein requirements, tolerance, growth and pubertal development in children with RDEB. METHODS: Twenty-four patients were referred over a 7-year period in a retrospective study. Gastrostomy placement was decided in patients unable to feed orally and/or presenting loss in weight and height of at least 1 SD compared with their best growth level, despite regular nutritional advice. Weight and height were expressed as Z-scores. Catch-up growth following GTF onset was studied. RESULTS: Gastrostomies were performed in 11 children (aged 9·0±5·8years), and one young man aged 18years. The body weight Z-score was -2·3±1·0, height Z-score 1·1±1·1, weight-for-height was 81±11% and height-for-age 95± 4%. At onset, GTF provided 74±21% and 180±81% of the recommended dietary allowance (RDA) for energy and proteins, respectively. At study update (53±20months), GTF provided 91±29% and 205±100% of RDA for energy and proteins, respectively. Weight-for-height reached 92±15% and height-for-age 98±5%. A normal puberty was obtained when GT was performed before the age of 10years. Skin was not improved. CONCLUSION: Malnutrition was observed in 50% of the children with generalized RDEB. Protein and energy needs are particularly high. GTF is well tolerated and helps with catch-up growth and puberty. It must be considered before malnutrition onset, and, if necessary, before puberty.

Germline mosaicism in keratitis-ichthyosis-deafness syndrome: pre-natal diagnosis in a familial lethal form.

Keratitis-ichthyosis-deafness (KID) syndrome is an autosomal dominant congenital ectodermal defect characterized by the association of skin lesions, hearing loss and keratitis. Most of the cases appear to be sporadic. KID syndrome is mostly related to mutations of GJB2 gene encoding connexin-26. Recently, a lethal form of the disease during the first year of life has been reported in two unrelated Caucasian patients. This rare lethal form is caused by the G45E mutation of GJB2 gene. We here report the first pre-natal molecular genetic diagnosis of the lethal form of KID syndrome relating to a G45E mutation. In the same family, the occurrence of this condition in three other siblings born to African non-consanguineous healthy parents lead to perform pre-natal diagnosis for this last pregnancy. Molecular analysis confirms the diagnosis of the lethal form of KID for the fetus. These results establish the role of germline mosaicism in KID syndrome and warrant careful genetic counseling. Furthermore, analysis of our cases and the literature allowed us to define a characteristic severe neonatal phenotype including facial dysmorphy, severe cornification with massive focal hyperkeratosis of the skin with erythroderma, dystrophic nails, complete atrichia and absence of foreskin.

Efficacy of tacrolimus 0.03% ointment as second-line treatment for children with moderate-to-severe atopic dermatitis: evidence from a randomized, double-blind non-inferiority trial vs. fluticasone 0.005% ointment.

Tacrolimus 0.03% ointment is licensed for second-line treatment of children with atopic dermatitis (AD). Although data are available from clinical trials, no study has enrolled only second-line patients. This double-blind, non-inferiority study compared tacrolimus 0.03% and fluticasone 0.005% ointments in children with moderate-to-severe AD, who had responded insufficiently to conventional therapies. Children (aged 2-15 yr) were randomized to tacrolimus ointment (n = 240) or fluticasone ointment (n = 239), twice daily until clearance or for a maximum of 3 wk and, if lesions remained, once daily for up to 3 wk further. Primary end-point was week 3 response rate (improvement of >or=60% in modified Eczema Area and Severity Index and not withdrawn for lack of efficacy). Secondary end-points included pruritus and sleep quality, global assessment of clinical response, incidence of new flares and safety. Response rates were 86.3% with tacrolimus ointment and 91.5% with fluticasone. Lower limit of the 95% confidence interval was -11.8%, exceeding the non-inferiority limit of -15% and meeting the primary end-point. Moderate or better improvement on the physicians' global assessment occurred in 93.6% and 92.4% of patients in the tacrolimus ointment and fluticasone arms, respectively, while median pruritus scores improved by 84.0% and 91.5%. Sleep quality improved by approximately 92% in both treatment arms. After day 21, new flare-up occurred in 5.5% and 11.3% of patients receiving tacrolimus ointment and fluticasone, respectively; mean times to new flares were 6.5 +/- 5.0 and 8.6 +/- 5.2 days. Adverse events were similar between the two arms, with the exception of application-site skin burning sensation in the tacrolimus ointment group. In conclusion, efficacy of tacrolimus 0.03% ointment as second-line treatment was not inferior to that of fluticasone 0.005% ointment, with similar benefits on global disease improvement and quality of sleep.

Cutaneous manifestations of immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome.

BACKGROUND: Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a rare disorder characterized by neonatal autoimmune enteropathy, diabetes and thyroiditis, food allergies and skin rash. IPEX syndrome is caused by mutations in FOXP3, a master control gene of regulatory T cells (Tregs), resulting in absent or dysfunctional Tregs. Data in the literature are scarce and the cutaneous manifestations are rarely depicted. OBJECTIVES: To evaluate the frequency and characteristics of cutaneous manifestations found in IPEX. METHODS: Retrospective single-centre study of a case series of IPEX. Patients' data were retrieved from medical files and numerous parameters concerning general and cutaneous characteristics of the disease were recorded. RESULTS: Ten children with IPEX were studied. Cutaneous involvement was present in seven of 10 children; age at onset was 0-4 months, median 1.5. All patients presented with atopic dermatitis (AD). Three presented more psoriasiform lesions. Eczema was severe; most affected areas were lower limbs, trunk and face. Pruritus was present in four of seven, and painful fissurary cheilitis in four of seven. Hyper-IgE was found in seven of 10 and hypereosinophilia in five of 10. Skin biopsies showed eczematiform or psoriasiform features. Affected patients were improved by dermocorticoids; no clear improvement was obtained with immunosuppressive regimens. Other features were urticaria secondary to food allergies and staphylococcal sepsis, mostly Staphylococcus aureus and catheter related. CONCLUSIONS: AD seems to be a frequent finding in IPEX syndrome, which is characterized by Treg anomalies. This hints to a possible role of Tregs in AD, which is then discussed in this study.

Subcutaneous fat necrosis of the newborn: a systematic evaluation of risk factors, clinical manifestations, complications and outcome of 16 children.

BACKGROUND: Subcutaneous fat necrosis (SFN) of the newborn is a rare acute transient hypodermatitis that develops within the first weeks of life in term infants. It often follows a difficult delivery. Prognosis is generally good except for the development of hypercalcaemia in severe cases. Only several case reports or small patients series have been published. OBJECTIVES: To evaluate risk factors, complications and outcomes of SFN in 16 consecutive patients seen from 1996 to 2002 in our Department of Paediatric Dermatology. METHODS: On a case-report form created for the study, we recorded putative risk factors concerning the mother, pregnancy and delivery, clinical aspects of SFN, and early and late outcomes. The study was conducted in two stages: the first was a retrospective analysis of the observations and the second analysed data collected on children and their parents during a new consultation (n=10). RESULTS: All the children were born at term. Lesions appeared a mean of 4 days after delivery. Three-quarters of the children had diffuse SFN. Risk factors identified were newborn failure to thrive (12/16), forceps delivery (7/16), maternal high blood pressure (3/10) and/or diabetes (2/10), and newborn cardiac surgery (1/16). Putative novel risk factors were macrosomia (7/16), exposure to active (4/10) or passive (3/10) smoking during pregnancy, putative or known maternal, paternal or newborn risk factors for thrombosis (5/10), and dyslipidaemia (2/10). Complications were hypercalcaemia (9/16), pain (4/16), dyslipidaemia (1/16), renal insufficiency (1/16) and late subcutaneous atrophy (6/6). CONCLUSIONS: This study on 16 newborns with SFN provides new information. Familial or newborn risk factors for thrombosis are frequent. Macrosomia, familial dyslipidaemia and smoking should be evaluated. The main complications identified were severe pain, hypercalcaemia and subcutaneous atrophy.

[Sirolimus-induced onychopathy in renal transplant recipients]. / Onychopathie associée au sirolimus chez les transplantés rénaux.

INTRODUCTION: A large number of drugs may be responsible for the development of nail changes. Sirolimus is an immunosuppressive drug recently developed in organ transplantation. Herein, we evaluate sirolimus-induced nail abnormalities in renal transplant recipients. PATIENTS AND METHODS: The nails of 80 consecutive renal transplant recipients receiving sirolimus have been evaluated in a systematic dermatological study in 2003. The patients were mainly men (60%) with a mean age of 48 years. The mean duration of the graft was 6 years and of sirolimus treatment 18 months. Mycophenolate mofetil and steroids were combined with sirolimus in 86% of patients. RESULTS: Fifty-seven patients (74%) complained for nail alterations. The most frequent anomalies (88%) were matrix alterations including slow growth, onychomalacia, onychorrexis, and leukonychia. Nail bed alterations (onycholysis), vascular phenomenon (erythema, splinter hemorrhages), and periungual anomalies (mainly pyogenic granulomas) were observed in 42, 42 and 19% of cases respectively. One observation of type 1 photo-onycholysis was described. DISCUSSION: This study reports a new drug-induced onychopathy. Responsibility of sirolimus is highly suggested. The main pathogenesis hypothesis to explain these nail alterations is inhibition of EGF (epidermal growth factor) pathway by sirolimus.

Treatment of paediatric atopic dermatitis with pimecrolimus (Elidel, SDZ ASM 981): impact on quality of life and health-related quality of life.

AIM: To report on quality of life (QoL) and health-related quality of life (HRQL) impacts of pimecrolimus (Elidel, Novartis A.G., Basel, Switzerland, SDZ ASM 981) 1% cream in the long-term treatment of paediatric atopic dermatitis. METHODS: QoL and HRQL data are presented from two 12-month international clinical trials evaluating the efficacy and safety of pimecrolimus 1% cream. Both trials were randomized and double blinded and compared two treatment strategies, one involving the use of emollients, pimecrolimus and topical corticosteroids, the other is 'usual care' (emollients plus topical corticosteroids) with a vehicle cream to maintain study blinding. The first trial (the infant trial) involved patients between ages 3 months and 2 years, whereas the children trial included patients aged 2-17 years. In both trials, QoL of the affected child's parent was evaluated with the parent's index of quality of life in atopic dermatitis (PIQoL-AD). HRQL was assessed in the children trial only with the children's dermatology life quality index (CDLQI). QoL and HRQL assessments were conducted at baseline, 6 weeks, 6 months and 12 months. RESULTS: Generalized linear modelling of PIQoL-AD scores at each post-baseline visit showed a greater impact on parent's QoL for pimecrolimus compared with control at all time-points in both trials. HRQL scores showed a greater improvement from baseline for children in the pimecrolimus group compared with those in the control group at all time-points. CONCLUSIONS: The results show a beneficial impact of pimecrolimus on parents' QoL in paediatric atopic dermatitis, confirming findings from earlier shorter term trials. There was also a clear benefit to the HRQL of the children treated.

[The value of topical immunosuppressors in the treatment of atopic dermatitis in children]. / Place des immunosuppresseurs topiques dans le traitement de la dermatite atopique de l'enfant.

The use of topical immunosuppressors during treatment of atopic dermatitis is an important innovation that reinforces the therapeutic arsenal in this chronic disease in children. Two products have been studied in depth: tacrolimus, which exists in pomade form at a concentration of 0.1 and 0.03% under the trademark Protopic. It is the 0.03% concentration that has been studied in children and obtained official indication in children aged over 2. Pimecrolimus marketed under the trademark Elidel in the form of a 1% cream has also been studied in depth and obtained European marketing authorisation for prescription in children aged over 2. Unfortunately it is not yet available in France, although it is marketed in nearly all countries worldwide. These products decrease the production of cytokines by the T-cell lymphocytes when stimulated by the antigen. This effect is produced by the inhibition of calcineurine. The clinical efficacy of these two products has been demonstrated in many studies in the United States and in Europe. Short term efficacy has been demonstrated in comparisons versus a placebo or versus grade 2 or 3 corticosteroids. Longer term studies (6 months to one year) have confirmed the efficacy. Short-term tolerance to these new treatments has been shown, although, as with any new product, the long-term results are unknown. Nevertheless, tolerance studies after more than 4 years' use exist. The side effects most often reported are local, erythema-like at the start of treatment with burning and pruritus. There has been no significant increase in the number of bacterial and viral infections compared with control groups. Doubt remains regarding viral infections of herpetic origin, notably Kaposi-Juliusberg's disease, although no significant difference has been observed compared with the placebo-treated. No systemic impact has been reported with these two products or inhibition of the effect of vaccinations made in infants or children. However, care should be taken: not to use the products in patients with a history of Kaposi-Juliusberg's disease and any contact with a patient exhibiting herpes should be avoided; the photoprotection measures should be respected as instructed in the patient insert for the use of tacrolimus.

Validation of the Eczema Area and Severity Index for atopic dermatitis in a cohort of 1550 patients from the pimecrolimus cream 1% randomized controlled clinical trials programme.

OBJECTIVE: To validate the Eczema Area and Severity Index (EASI) by assessing its internal consistency, reliability and sensitivity to change and by correlating it to other efficacy parameters. DESIGN: Three short-term and two long-term double-blind, randomized, controlled trials, performed in 138 study centres in Europe, South Africa, Australia, New Zealand, and North and South America. PATIENTS AND METHODS: In total, 1550 paediatric patients with atopic dermatitis were studied. Pimecrolimus cream 1% was used twice daily to treat atopic dermatitis. The three short-term studies were placebo controlled. The two long-term studies evaluated the efficacy and safety of early intervention with pimecrolimus to prevent progression to disease flare requiring topical corticosteroid treatment, compared with reactive treatment with topical corticosteroids to treat flares of atopic dermatitis. MAIN OUTCOME MEASURES: Five parameters were measured: (i) the EASI (range of score 0-72); (ii) Investigators' Global Assessment (IGA), using a six-point (0-5) scale; (iii) patients' assessment, using a four-point (0-3) scale; (iv) severity of pruritus assessment, using a four-point (0-3) scale; and (v) a quality-of-life evaluation. RESULTS: The EASI score varied in parallel and in correlation with the IGA, pruritus and patients' assessment. All correlation coefficients were statistically different from 0 (P < 0.05). The EASI correlated well with each of its components, and all paired comparisons were within agreed limits. The EASI showed good sensitivity to changes in severity. CONCLUSION: In a large, multinational patient population with atopic dermatitis, the EASI showed good validity, reliability and sensitivity to change and correlated well with other measures of severity. It therefore qualifies as a valid method of assessment in clinical studies of atopic dermatitis.