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Psoriasis is a common cutaneous disorder. For a third of patients, it has a childhood onset. Management of children with psoriasis is difficult. It is necessary to explain to the children and their parents, what is the disease and its evolution. Child alteration of quality of life have to be evaluate to propose the adequate treatment, from local to general therapies. [Copyright &y& Elsevier]

Topical treatments for psoriasis have been used for a very long time. They were designed to reduce epidermal proliferation and hyperkeratosis. Recent pathophysiological data have led to the use of many immunological therapies, initially systemically in severe forms and, in recent years, topically. Calcineurin inhibitors are now a well-established treatment for atopic dermatitis and have also been evaluated in psoriasis. The first trials of tacrolimus (Protopic®, Astellas) and pimecrolimus (Elidel®, Novartis) failed to demonstrate any positive results on plaque-type psoriasis, but several studies showed a definite efficacy on facial and intertriginous psoriasis. Calcineurin inhibitors do not induce skin atrophy and are therefore particularly useful in sites in which the skin is thinner (face, intertriginous areas). A third substance, sirolimus (Rapamune®, Wyeth), has recently been tested topically in psoriasis. A recent study demonstrated that topical sirolimus crosses the cutaneous barrier and is effective on psoriasis lesions. These studies therefore show an indisputable efficacy of calcineurin inhibitors and sirolimus in the treatment of localized psoriasis. The major advantage is the absence of skin atrophy. However, large-scale efficacy and safety studies must be conducted in this indication. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Summary 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 ± 5·8 years), and one young man aged 18 years. 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 ± 20 months), 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 10 years. 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. [ABSTRACT FROM AUTHOR]

Sbidian E, Feldmann D, Bengoa J, Fraitag S, Abadie V, de Prost Y, Bodemer C, Hadj-Rabia S. 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. [ABSTRACT FROM AUTHOR]

Doss N, Kamoun M-R, Dubertret L, Cambazard F, Remitz A, Lahfa M, de Prost Y. 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. Pediatr Allergy Immunol 2010: 21: 321–329. © 2009 John Wiley & Sons A/S 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 ≥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. [ABSTRACT FROM AUTHOR]

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 chidren; 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background It is not clear whether bullous pemphigoid (BP) of infancy is linked to maternal transmission of pathogenic autoantibodies. Objectives To search for anti-BP180 antibodies in the sera of infants with BP and their mothers, using sensitive and specific methods. Methods Four infants (< 6 months) with BP and their mothers were tested for anti-BP180 antibodies by indirect immunofluorescence, immunoblotting and enzyme-linked immunosorbent assay (ELISA). Results We found anti-BP180 antibodies in the sera of the four infants with all methods. These antibodies reacted with the extracellular domain NC16A. In the serum of their mothers we found 180 and 160 kDa proteins, each in one case, but indirect immunofluorescence and ELISA were negative, suggesting the absence of anti-BP180 autoantibodies reacting with the extracellular domain NC16A. Conclusions BP of infants is not due to maternofetal transmission of pathogenic autoantibodies. Other hypotheses for the pathophysiology of BP are discussed. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

Psoriasis is a T-cell-mediated immunological disease characterized by epidermal proliferation. The nature of the antigen(s) responsible for T-cell activation is still unknown. It has been suggested that the human papillomaviruses (HPVs) associated with epidermodysplasia verruciformis (EV), including the oncogenic HPV5, may contribute to the pathogenesis of psoriasis. To determine whether EV-HPVs may play a role early in the disease, we searched for these viruses in children with psoriasis. The influence of clinical data on EV-HPV infection was investigated. We studied scrapings of involved skin from 26 children aged 1·5–13 years with psoriasis. As controls, we analysed scrapings from 28 adults with psoriasis and 15 children with atopic dermatitis, as well as scrapings from normal skin of 28 adults with no known history of HPV infection. We searched for EV-HPV DNA sequences with a nested polymerase chain reaction method using degenerate primers specific for EV-HPVs and primers specific for HPV5 and HPV36, two EV-HPVs frequently detected in adults with psoriasis. Similar high prevalences were observed in children and adults with psoriasis for EV-HPVs (38·5% vs. 35·7%), HPV5 (46·2% vs. 46·4%) and HPV36 (15·4% vs. 25·0%). As in adults, we found several EV-HPV genotypes and HPV5 and HPV36 variants. A novel HPV36 subtype, HPV36b, was identified. Lower prevalences were observed in children with atopic dermatitis and in adults from the general population (6·7–10·1%). No correlation was observed between frequency of detection of HPVs and clinical data. It is noteworthy that HPV5 was identified in an 18-month-old girl and in a boy with psoriasis developing for only 1 week. The early detection of several EV-HPV genotypes in children further supports the link between psoriasis and EV-HPVs and suggests a putative role for these viruses in the pathogenesis of psoriasis. [ABSTRACT FROM AUTHOR]

Discusses the treatment of atopic dermatitis. Management of the disease; Limitations of treatment for the disease; Therapeutic objectives for the disease; Safety aspects of treatment for the disease.

Examines the occurrence of cervicofacial hemangioma and a minor sternal malformation in a female child born by normal vaginal delivery. Characteristics of the disease; Distinction between hemangiomas and vascular malformations; Diagnosis of the disease.

A letter to the editor is presented in response to an article about the study which examines the relationship between infantile myofibromatosis and maternal stem cells in pregnant women that appeared in previous issue.

A letter to the editor is presented which describes the first case of fixed drug eruption (FDE) associated with teicoplanin in a 10-year-old girl.

Pimecrolimus is a calcineurin inhibitor developed for the topical treatment of atopic dermatitis. During the clinical development of 1% pimecrolimus cream, 1133 patients 3 to 23 months of age with mild to severe atopic dermatitis were treated for up to 2 years. The objective of this review is to discuss the safety and tolerability of 1% pimecrolimus cream among infants, on the basis of the combined results from all studies (4 pharmacokinetic studies and 6 clinical trials) conducted among these patients. Pimecrolimus blood concentrations measured for 35 patients were consistently low (< or =1 ng/mL in >80% of samples), irrespective of the disease severity and extent, and remained low during intermittent treatment for up to 1 year. The level of systemic exposure to pimecrolimus among infants was comparable to that observed for older pediatric patients enrolled in the same studies and treated in the same way with 1% pimecrolimus cream, which indicated that young pediatric patients are not at higher risk of significant percutaneous absorption of topically applied pimecrolimus, despite their large skin surface area/body mass ratio. The 6 clinical trials included a total of 1098 infants, who were treated for periods ranging from 4 weeks to 2 years. Most of these patients (60%) had moderate to severe disease at baseline. The most frequently reported adverse events were common childhood disorders such as nasopharyngitis, pyrexia, upper respiratory tract infections, ear infections, and bronchitis. During the double-blind (DB) studies or DB phases of studies, the incidence rates for the most frequently reported adverse events were similar for patients who received 1% pimecrolimus cream and patients who received the vehicle, except for the incidence of teething, which was higher among the pimecrolimus-treated infants (relative risk: 2.02; 95% confidence interval: 1.32-3.27). Treatment with 1% pimecrolimus cream was not associated with an increase in the overall incidence of nonskin infections, compared with the vehicle (relative risk: 1.015; 95% confidence interval: 0.88-1.18). The incidence density (ID) rates for total bacterial, fungal, parasitic, and viral skin infections during the DB studies or DB phases of studies were comparable for patients treated with 1% pimecrolimus cream and patients who received the vehicle. The ID rate of herpes simplex virus infections was 0.8 cases per 1000 patient-months of follow-up monitoring among patients treated with 1% pimecrolimus cream and 1.7 cases per 1000 patient-months of follow-up monitoring among patients who received the vehicle. Considering all 1098 infants treated with 1% pimecrolimus cream in DB trials and open-label studies, the ID rate of clinically diagnosed eczema herpeticum was 1.3 cases per 1000 patient-months of follow-up monitoring. Burning and erythema were the most frequently reported application site reactions, with ID rates of 2.0 and 1.2 cases per 1000 patient-months of follow-up monitoring, respectively. No sign of immunosuppression was found among infants treated intermittently with 1% pimecrolimus cream for up to 2 years; they demonstrated normal immune responses to vaccinations and did not show increases in the incidence of systemic infections or skin infections over time. [ABSTRACT FROM AUTHOR]

Objective. Pimecrolimus cream (SDZ ASM 981), a nonsteroid inhibitor of inflammatory cytokines, is effective in atopic dermatitis (AD). We assessed whether early treatment of AD signs/symptoms with pimecrolimus could influence long-term outcome by preventing disease flares.Methods. Early intervention with pimecrolimus was compared with a conventional AD treatment strategy (ie, emollients and topical corticosteroids). In this 1-year, controlled, double-blind study, 713 AD patients (2-17 years) were randomized 2:1 to a pimecrolimus-based or conventional regimen. Both groups used emollients for dry skin. Early AD signs/symptoms were treated with pimecrolimus cream or, in the conventional treatment group, vehicle to prevent progression to flares. If flares occurred, moderately potent topical corticosteroids were mandated. The primary efficacy endpoint was ranked flares at 6 months. Safety was monitored clinically, and a skin recall-antigen test was performed at study completion.Results. Baseline Characteristics of the Patients. The mean age for both groups was approximately 8 years, and the majority of patients had moderate disease at baseline.Patient Follow-up and Exposure to Study Medication. The mean duration of follow-up (+/-standard error) was 303.7 (+/-5.30) days in the pimecrolimus group and 235.2 (+/-9.40) days in the control group. The discontinuation rate was significantly higher in the control group than in the pimecrolimus group (51.5% vs 31.6% at 12 months), and proportionately more patients with severe or very severe disease discontinued in the control group. The main reason for the higher discontinuation rate in the control group was unsatisfactory therapeutic effect (30.4% vs 12.4%). This resulted in a substantially higher mean number of study medication treatment days in the pimecrolimus group compared with the control group: 211.9 (69.8% of study days) versus 156.0 (66.3% of study days). Of those patients who completed 12 months on study, 14.2% and 7.0% of patients in the pimecrolimus and vehicle groups, respectively, used study medication continuously.Efficacy. Patients in the pimecrolimus group experienced significantly fewer AD flares than those in the control group, according to the primary efficacy analysis on ranked flares of AD (Van Elteren test). The proportion of patients who completed 6 or 12 months with no flares was approximately twice as high in the pimecrolimus group compared with control (61.0% vs 34.2% at 6 months; 50.8% vs 28.3% at 12 months). Fewer flares were observed in the pimecrolimus group regardless of baseline disease severity, so even severe patients derived benefit from the treatment. The analysis of time to first flare showed that treatment with pimecrolimus was associated with a significantly longer flare-free period (log- rank test). Covariate analysis indicated a statistically significant effect on time to first flare of baseline Eczema Area and Severity Index score, and whether patients had 'severe' or 'very severe' disease at baseline according to the Investigators' Global Assessment, although patients in all baseline disease severity subgroups benefited from treatment. Age had no significant effect.Fewer patients in the pimecrolimus group required topical corticosteroid therapy compared with control (35.0% vs 62.9% at 6 months; 42.6% vs 68.4% at 12 months), and patients in the pimecrolimus group spent fewer days on topical corticosteroid therapy (57.4% vs 31.6% [pimecrolimus vs control, respectively] spent 0 days on topical corticosteroid therapy, 17.1% vs 27.5% 1-14 days, and 25.5% vs 41.0% >14 days over the 12 months of the study). This steroid-sparing effect of pimecrolimus was evident despite pimecrolimus-treated patients being on study longer than patients in the control group. The average proportion of study days spent on second-line corticosteroids was 4.08% in the pimecrolimus group and 9.10% in the control group. Analysis of Eczema Area and Severity Index over time showed significantly lower median scores, thus indicating better disease control in the pimecrolimus group compared with the control group. Similar results were obtained from analysis of the Investigators' Global Assessment (not shown). The treatment groups were well balanced with respect to the number of patients using antihistamines during the study (57.2% vs 62.9%, pimecrolimus vs control, respectively).Safety. There were no appreciable differences between treatment groups in the overall incidence of adverse events. The most frequent adverse events were common childhood infections and ailments, including nasopharyngitis, headache, and cough. The incidence of suspected drug-related adverse events was not significantly different in the pimecrolimus group (24.7% vs 18.7%--pimecrolimus vs control), and the incidence of serious adverse events was low (8.3% vs 5.2%-pimecrolimus vs control). Life-table analysis of incidence of adverse events revealed no significant differences between the treatment groups, except for cough.Local tolerability was good in both treatment groups. The most common application site reaction reported was sensation of burning (10.5% vs 9.3%-pimecrolimus vs control). There were no major differences between treatment groups in the duration or severity of application site reactions, most of which were mild-to-moderate and transient, occurring within the first week of treatment.Skin infections were reported in both groups. There were no between-group differences in the life-table analysis of time to first occurrence of bacterial skin infections nor in the adjusted incidence of bacterial skin infections. Although there were no significant differences between treatment groups in the incidence of individual viral skin infections, the incidence of grouped viral skin infections (12.4% vs 6.3%-pimecrolimus vs control) showed a slightly higher incidence in the pimecrolimus group.Laboratory values and vital signs showed no significant between-group differences.There were no significant differences between treatment groups in response to recall antigens in those patients who remained on study for 12 months.Conclusions. Treatment of early AD signs/symptoms with pimecrolimus was effective in preventing progression to flares in more than half the patients, reducing or eliminating the need for topical corticosteroids. The benefits were consistently seen at 6 months across important disease severity subgroups and with respect to the various predefined efficacy endpoints. Furthermore, these benefits were sustained for 12 months, providing evidence that long-term treatment with pimecrolimus leads to better control of AD. Treatment with pimecrolimus was well tolerated and was not associated with clinically relevant adverse events compared with the conventional treatment group. The results reported here offer the prospect of effective long-term management of AD with reduced need for topical corticosteroids. [Abstract for this article also available on page 158 of printed version. Full article available at http://www.pediatrics.org/cgi/content/full/110/1/e2] [ABSTRACT FROM AUTHOR]