Characteristics of Café-au-lait Macules and their Association with the Neurofibromatosis type I Genotype in a Cohort of Greek Children.

Cafe-au-lait macules are the most distinctive clinical finding in neurofibromatosis type I. The aim of this prospective study of Greek children diagnosed with neurofibromatosis type I was to describe the dermatological phenotype and to analyse the characteristics of cafe-au-lait macules and their association with genotype. Pigment intensity and melatonin content of cafe-au-lait macules were measured with a narrowband spectrophotometer. A total of 63 children aged 6 months to 16 years old were studied. Mean melanin content varied, both among patients, and within each patient (p < 0.001). Females had a higher number of cafe-au-lait macules than did males (p = 0.025), and the melanin content of cafe-au-lait macules was lower in females than males (p < 0.001). Patients with protein-truncating variants in the neurofibromatosis type I gene had higher melanin content of cafe-au-lait macules than other types of genetic variants t (55) = 2.196, p = 0.032. Plexiform neurofibromas were also detected in the majority of patients with protein- truncating variants, while juvenile xanthogranulomas were detected equally in patients with protein-truncating and non-protein-truncating variants. In conclusion, cafe-au-lait macules with high melatonin content are associated with patients carrying non-protein-truncating variants. Therefore, measurement of cafe-au-lait macule pigment intensity might provide useful information for initial assessment of patients with neurofibromatosis type I and the severity of their future phenotype.

Sensitivity to treatment and score bands of the Infants and Toddlers Dermatology Quality of Life questionnaire.

Background: The Infants and Toddlers Dermatology Quality of Life (InToDermQoL) questionnaire is the first dermatology-specific proxy health related QoL instrument for children from birth to 4 years. Score meaning bands and the sensitivity to successful therapeutic intervention are important to interpret the clinical meaning of an instrument. Objective: The aim of the present study was to check the sensitivity to successful therapeutic intervention and establish score bands of the InToDermQoL questionnaire. Methods: Parents or grandparents of 424 children with skin diseases from Spain, Malta, Croatia, Romania, Greece, and Ukraine filled in national language versions of the InToDermQoL questionnaire. Disease severity of children with atopic dermatitis was assessed by SCORAD (Scoring atopic dermatitis). Cohen's d was used to assess the responsiveness of the instrument. Results: The mean total InToDermQoL scores significantly decreased after treatment. Severity grading of the SCORAD scores gave stratification of the InToDermQoL severity grades based on 95% confidence intervals. Scores below a calculated minimal important difference of 2 corresponded to no effect on patient's health related QoL. Limitations: Score banding may be slightly different across patient population and study context. Conclusion: All 3 age-specific versions of the InToDermQoL questionnaire showed sensitivity to treatment. Score bands for the InToDermQoL questionnaire have been established.

A randomized, observer-blind, vehicle-control, multi-center clinical investigation for assessing the efficacy and tolerability of a 1% ectoine and hyaluronic acid 0.1%-containing medical device in pediatric patients with mild-to-moderate atopic dermatitis.

BACKGROUND: Ectoine is a widespread osmolyte enabling halophilic bacteria to withstand high osmotic stress that has many potential applications ranging from cosmetics to its use as a therapeutic agent. OBJECTIVE: The aim of this study was to compare the efficacy and tolerability of ectoine 1% and hyaluronic acid 0.1% containing (EHA) cream with a vehicle cream in children with mild-to-moderate atopic dermatitis (AD). METHODS: A randomized, controlled, observer-blind, multicenter clinical trial was conducted in children aged 2-18 years, diagnosed with mild-to-moderate AD (SCORAD ≤20). Patients were randomized to either receiving EHA cream or vehicle cream twice daily for 4 weeks. The primary outcome measure was the mean change in objective SCORAD from baseline to the final visit. The secondary outcome measures included the mean change in Investigator's Global Assessment score, patient's judgment of efficacy and patient's assessment of pruritus. Safety of EHA cream was also assessed. RESULTS: A total of 70 patients (35 in each group) were randomized and 57 were included in the final analysis set. Based on SCORAD measurements, patients using EHA cream achieved superior clinical improvement compared to the control group at 28 days (p < .001). EHA cream was also superior to the vehicle cream regarding all secondary outcome measures. Eight (23.5%) patients receiving EHA cream and two (5.7%) patients receiving vehicle cream experienced mild cutaneous adverse events (AEs). CONCLUSIONS: In children 2-18 years old with mild-to-moderate AD, EHA cream was superior to vehicle cream, with minor AEs.

Initial validation of the epidermolysis bullosa-specific module of the Infants and Toddlers Dermatology Quality of Life questionnaire.

Children with epidermolysis bullosa (EB) experienced the highest quality of life impact among several skin conditions and have problems which had not been reported by parents of children with other skin diseases. The EB-specific module of the Infants and Toddlers Dermatology Quality of Life (InToDermQoL) questionnaire was recently developed to measure the impact of disease-specific aspects in children from birth to the age of 4 years. The aim of this study was initial validation of the InToDermQoL-EB questionnaire. Parents of 44 children with EB from seven countries completed the InToDermQoL-EB questionnaire. Cronbach's alpha was .86, .89 and .91 for three age-specific versions. Differences between severity levels were all significant except for that between moderate and severe level in the version for 3- to 4-year-old children. All items of the three versions of the InToDermQoL-EB showed very high levels of relevance except "problems with defecation" in children younger than 1 year and "rejection by other children" in 3- to 4-year-old children. The three versions of the InToDermQoL-EB instrument showed good internal consistency and discriminated well between different severity levels. All InToDermQoL-EB items were confirmed as being of high relevance and the questionnaire may be used in practice and clinical trials.

Pediatric vasculitis: a single center experience.

BACKGROUND: Existing studies of children with vasculitis are limited. The aim of this study was to assess the epidemiology, clinical manifestations, laboratory findings, course, and outcome of Greek children presenting with vasculitic rash. METHODS: The relevant data included in the study were collected retrospectively using a standardized form from children who were admitted into our department between 2003 and 2013, with the provisional diagnosis of vasculitis of the skin. RESULTS: The study sample consisted of 95 children (58 boys, 37 girls) with a mean age of 5.9 years. In total, 76 out of 95 (80%) of the children were diagnosed with Henoch-Schönlein purpura, 10/95 (10.5%) with hypersensitivity vasculitis, 6/95 (6.3%) with urticarial vasculitis, and 3/95 (3.1%) with acute hemorrhagic edema of infancy. The mean age of the children was 5.7 years for Henoch-Schönlein purpura, 9 years for hypersensitivity vasculitis, 5.1 years for urticarial vasculitis, and 0.5 years for acute hemorrhagic edema of infancy. CONCLUSIONS: (i) The most common vasculitis presenting with skin rash in children is Henoch-Schönlein purpura; (ii) hypersensitivity vasculitis occurs in older children more often when compared to other types of vasculitis; (iii) urticarial vasculitis lesions may be a sign of severe underlying disease; therefore a thorough examination of these patients is warranted; (iv) Despite relapses, the overall prognosis of patients with pediatric skin vasculitides is good, with the exception of those with the urticarial vasculitis type.

Mycoplasma pneumoniae as a cause of vulvar ulcers in a non-sexually active girl: a case report.

BACKGROUND: Non-sexually active young females very rarely develop genital ulcers. Such ulcers pose a diagnostic challenge as well as physical and emotional distress for patients and family; therefore, the search for their etiology requires exhaustive investigation. Several viruses such as Epstein-Barr virus have been associated with this entity; however, Mycoplasma pneumoniae has rarely been linked to such ulcers in the literature. We present a case of vulvar ulcers in a non-sexually active young girl during the course of pneumonia caused by Mycoplasma pneumoniae. CASE PRESENTATION: A 10-year-old non-sexually active girl of cypriot origin presented at a hospital with fever, dry cough, and acute vulvar ulcers. Laboratory investigations as well as imaging studies revealed Mycoplasma pneumoniae as the cause of her pneumonia and acute vulvar ulcers. CONCLUSIONS: Although a rare cause of vulvar ulcers, Mycoplasma pneumoniae should be considered in the differential diagnosis of acute vulvar ulcers coexisting with respiratory symptoms.

CHILD Syndrome: Successful Treatment of Skin Lesions with Topical Simvastatin/Cholesterol Ointment--A Case Report.

CHILD syndrome is a rare X-linked dominant condition that presents with congenital hemidysplasia, Ichthyosiform erythroderma, and limb defects in affected patients. We report the case of a 10-year-old girl treated with topical simvastatin and cholesterol ointment, after which her skin lesions significantly improved within the first 30 days of treatment.

Childhood and adolescent psoriasis in Greece: a retrospective analysis of 842 patients.

BACKGROUND: Childhood and adolescent psoriasis is not an uncommon disease, but epidemiological information from a large series of studies is still lacking. OBJECTIVE: Our purpose was to present the demographics, clinical features, and outcome of psoriasis appearing in Greek patients from infants up to adolescents. METHODS: We conducted a retrospective analysis of 842 children and adolescents who diagnosed with psoriasis over a period of twenty years. RESULTS: The mean age of psoriasis onset was 7.33 years, and the sex distribution was equal between boys and girls. Plaque-type psoriasis was the most frequent type (82.1%), followed by perianal, inverse, and guttate. The limbs and the scalp were the main body areas affected. The affected body surface area (BSA) was more than 10% in only 1.7% of patients, and the overall disease manifestations were considered to be mild. Psoriatic nails were detected in 11.8% of patients, while psoriatic arthritis in only six (0.7%) patients. An additional autoimmune disease was present in 3.8% of patients, and 16.7% had a positive family history for first-degree relatives. The main choice of therapy was topical treatment. CONCLUSION: Gender distribution, type of psoriasis, and body area affection is almost the same as in adults. Most of the patients presented with mild disease of little extent, possibly indicating the favorable effect of sun in a Mediterranean country. The most often prescribed treatment for the majority of patients was topical.

Retrospective analysis of the relationship between infantile seborrheic dermatitis and atopic dermatitis.

A growing number of dermatologists dispute the existence of infantile seborrheic dermatitis (ISD) as an independent clinical entity. Therefore the aim of the present study was to estimate the epidemiologic features of ISD in a defined population of Greek children, assess its course, and identify associations, if any, with other common dermatoses of childhood. Children from the region of Athens who were examined and diagnosed with typical clinical features of ISD between 1997 and 2011 were included in the study. The relevant data were collected retrospectively from their medical records using a standardized form. Eighty-seven children were enrolled (50 boys, 37 girls; mean age 3.1 mos at the time of ISD diagnosis). The main body areas affected were the scalp and face for the majority of the children (78/87), whereas the trunk and limbs were less frequently involved (9/87). In all cases, erythema and scaling of affected patients were mild to moderate. Forty-nine of the 87 children were followed up over a period of 5 years. Thirty children in this group developed features of atopic dermatitis (AD) at a later stage, according to the UK diagnostic criteria of AD, and 23 of these children were diagnosed with AD, at an average time interval of 6.4 months from ISD onset, and seven presented with clinical features of AD at the time of ISD diagnosis. The remaining 19 children in the follow-up group progressed without developing any other chronic skin disease, and all recovered within 6 months of its onset. Thirty-eight had no further follow-up after their initial ISD diagnosis. In spite of the lack of information on the disease course for the last group, assuming they all recovered, the prevalence of AD (34.4%) in our ISD sample was significantly higher than the prevalence of AD (10.7%) in the general population for the same age group, as shown in a previous study performed in the municipality of Athens (p < 0.001). A significant number of children were found to develop AD shortly after their ISD diagnosis. This finding demonstrates a strong association in the clinical course between the two diseases or indicates that the two diseases may be in the same clinical spectrum. Further epidemiologic studies must be conducted to assess the significance of this finding.

Recommendations for pimecrolimus 1% cream in the treatment of mild-to-moderate atopic dermatitis: from medical needs to a new treatment algorithm.

Pimecrolimus 1% cream is an effective, non-corticosteroid, topical anti-inflammatory treatment for atopic dermatitis (AD). The aim of this article was to review published clinical data that have examined how pimecrolimus can address the medical needs of AD patients. Clinical studies have demonstrated that early treatment with pimecrolimus decreases the progression to disease flares, rapidly improves pruritus and significantly enhances quality of life. Patients find the formulation easy to apply, which may result in improved adherence with the treatment regimen. Pimecrolimus, in contrast to topical corticosteroids (TCSs), does not induce skin atrophy or epidermal barrier dysfunction and is highly effective for the treatment of AD in sensitive skin areas. Furthermore, pimecrolimus reduces the incidence of skin infections compared with TCSs and is not associated with other TCS-related side effects such as striae, telangiectasia and hypothalamic-pituitary-adrenal axis suppression. An additional benefit of pimecrolimus is its substantial steroid sparing effect. On the basis of these data, a new treatment algorithm for patients with mild-to-moderate AD is proposed in which pimecrolimus is recommended as a first line therapy for patients with established mild AD at the first signs and symptoms of disease. Pimecrolimus is also recommended for mild-to-moderate AD after initial treatment with a TCS. After resolution of lesions, maintenance treatment with pimecrolimus may effectively prevent subsequent disease flares. In conclusion, the clinical profile of pimecrolimus suggests that it may be considered the drug of choice for the treatment of mild-to-moderate AD in children as well as adults and particularly in sensitive skin areas.

Human papillomavirus (HPV) genotyping of cutaneous warts in Greek children.

The human papillomavirus (HPV) infects the squamous epithelium of the skin and produces common warts, plantar warts, and flat warts, which occur commonly on the hands, face, and feet. The objective of this study was to determine the presence of HPV in warts in children in order to associate the virus with the disease. Sixty-eight children with clinically diagnosed cutaneous warts were recruited. Skin biopsy samples were examined and DNA was extracted using a commercially available kit. To distinguish between the HPV types, we used a specific pair of primers to amplify the HPV DNA. Polymerase chain reaction amplification of the L1 region was followed by restriction fragment length polymorphism analysis and Luminex xMAP technology. HPV 57 was the predominant type in our study, although the detection of the high-risk HPV type 16 in 33% of our positive samples indicates the presence of mucosal high-risk HPV types in the skin of children. It seems that the newly introduced Luminex assay maximized the discrimination of genotypes even in the case of multiple HPV infections. Or findings also suggest the presence of high-risk HPV types in cutaneous warts.

Propranolol treatment for severe infantile hemangiomas: a single-centre 3-year experience.

AIM: To evaluate the effectiveness, safety and tolerability of propranolol as single-agent treatment in patients with problematic, proliferative-phase, infantile hemangiomas (IHs). METHODS: Oral propranolol was administered at a dose of 2 mg/kg/day to 28 children. Cardiologic evaluation was performed before treatment initiation. Hemodynamic variables and blood glucose levels were monitored during the first 24 h of treatment, while the children were hospitalized. Clinical response and tolerance were assessed every month, along with photographic documentation. Macroscopic regression was considered the reduction >90% in the size of the IHs. RESULTS: Effects on colour and growth were observed within the first month in all cases. Twenty-four patients completed treatment after a mean duration of 7.56 months, and their hemangiomas were successfully regressed. Propranolol was administered again, with satisfactory results, in three patients (12.5%) because of hemangioma regrowth. Satisfactory response is noticeable in ongoing cases. Episodes of hypotension were noted in four patients. There were no treatment interruptions because of side effects. CONCLUSIONS: Propranolol, as first-line treatment, yielded excellent results with very good clinical tolerance and also seems to be effective in relapses. The optimal duration of the treatment remains to be defined by long-term observation.

Cases of Tinea capitis due to pale isolates of Trichophyton violaceum (Trichophyton glabrum) in South-East Europe. A challenge to the clinical laboratory.

Two recent indigenous cases of tinea capitis in children due to pale isolates of Trichophyton violaceum are reported herein for the first time from South-East Europe (Greece). Pale isolates of Trichophyton violaceum, reported in the past as Trichophyton glabrum, are thus far sporadically reported only from African or Asian countries. The cases reported herein raise the awareness of its existence in the community, assigning special importance to its accurate identification in the clinical laboratory.

Actinic varicella vaccine rash.

The case of an 18-month-old girl with vesicular rash confined to a sunburned area after significant ultraviolet radiation exposure is reported. The child had been vaccinated 32 days before presentation, and a high viral load of Oka strain virus was detected in vesicular fluid. Possible pathogenesis is discussed.

Incontinentia pigmenti revisited. A novel nonsense mutation of the IKBKG gene.

AIM: To describe and evaluate the clinical and molecular findings of patients with incontinentia pigmenti (IP) in Greece. METHODS: We examined 12 female patients, initially aged 2 weeks to 7 months with clinical diagnosis of IP. Standard tests were performed including skin biopsies and ocular, dental and neurologic examinations. Molecular analysis was carried out on 8 out of 12 cases. RESULTS: The initial clinical examination was stage 1 (vesicular lesions), stage 2 (verrucous lesions) or stage 3 (hyperpigmented linear lesions of the trunk/limbs). At the final clinical examination, 10 of our patients had typical vesicular, verrucous or mixed hyper-hypopigmented skin lesions which had persisted from the neonatal period; seven had delayed dentition or conical teeth; two had developmental delay; one had microcephaly and strabismus and two had scarring alopecia. In seven patients, deletion of exons 4-10 of the IKBKG gene was found. In one patient, skewed X-inactivation was demonstrated and a novel mutation p.Gln332X was found. The mothers' DNA analyses were all normal. CONCLUSION: In our sample, all the cases were sporadic and the diagnosis of IP was based mainly on clinical features and confirmed with skin histology. Molecular analysis was used to find the mutations, in some cases to confirm diagnosis and to identify the carriers, which are crucial for prenatal and preimplantation diagnosis.

Guidelines for the management of tinea capitis in children.

Practice guidelines for the treatment of tinea capitis (TC) from the European Society for Pediatric Dermatology are presented. Tinea capitis always requires systemic treatment because topical antifungal agents do not penetrate the hair follicle. Topical treatment is only used as adjuvant therapy to systemic antifungals. The newer oral antifungal agents including terbinafine, itraconazole, and fluconazole appear to have efficacy rates and potential adverse effects similar to those of griseofulvin in children with TC caused by Trichophyton species, while requiring a much shorter duration of treatment. They may be, however, more expensive (Grading of recommendation A; strength of evidence 1a). Griseofulvin is still the treatment of choice for cases caused by Microsporum species. Its efficacy is superior to that of terbinafine (Grading of recommendation A; strength of evidence 1b), and although its efficacy and treatment duration is matched by fluconazole (Grading of recommendation A; strength of evidence 1b) and itraconazole (Grading of recommendation A; strength of evidence 1b), griseofulvin is cheaper. It must be noted, however, that griseofulvin is nowadays not available in certain European countries (e.g., Belgium, Greece, Portugal, and Turkey).

Febrile seizures and primary human herpesvirus 6 infection.

Primary human herpesvirus 6 infection is acquired mainly during the first two years of life and is often associated with febrile seizures. The aim of the present study was to investigate in Greece the frequency and clinical characteristics of primary human herpesvirus 6 (HHV-6) infection in hospitalized children with febrile seizures. Children aged from 6 months to 5 years without known neurologic disease were examined for primary HHV-6 infection, by real-time polymerase chain reaction in acute-phase plasma and by indirect immunofluorescent assay for antibody titers in acute and convalescent serum. Of 65 children included in the analysis, 55 experienced the first febrile episode of seizures and 10 the second. Primary HHV-6 infection was verified in 10 of 55 children with a first febrile episode (18%), whereas none of the 10 children with a second episode of seizures had primary HHV-6 infection. Eight children were infected with HHV-6 type B and two with type A. None of the 85 control subjects had primary HHV-6 infection, but 49% had immunoglobulin G antibodies against the virus. These findings suggest that primary HHV-6 infection is frequently associated with febrile seizures in children in this geographic region and should be considered, especially for a first episode of febrile seizures.

Vitiligo in children.

BACKGROUND: Vitiligo is an acquired depigmentary disorder affecting around 1% of the world's population. In 25% of cases it has its onset prior to the age of 14 years. DATA SOURCES: Articles on vitiligo in children published after 1995 were retrieved from PubMed. The prevalence, etiology, clinical presentation, differential diagnosis, treatment and management of vitiligo in children were summarized. RESULTS: Vitiligo is characterized by acquired, sharply demarcated depigmented macules or patches on the skin, the mucous membranes and/or white hair and it is mainly differentiated from congenital achromic skin lesions. It is frequently associated with various autoimmune diseases. Hashimoto's thyroiditis is the most common association in children. Information on the nature, possible causes and course of the disease leads to acceptance of the disorder and higher compliance with the treatment. The choice of medical treatment depends on the type, location and duration of lesions as well as the eagerness of the child and his/her parents to pursue therapy. CONCLUSION: The management of childhood vitiligo includes information and reassurance of young patients and their parents on the disease, thyroid investigation, avoidance of trigger factors, topical treatment and proper follow-up.

Clinical aspects of diffuse cutaneous mastocytosis in children: two variants.

OBJECTIVE: This paper describes two different clinical presentations of diffuse cutaneous mastocytosis (DCM), based on the largest series published to date. As far as we are aware, these two variants of clinical presentations have not yet been reported. DESIGN: We undertook a case controlled analysis of 8 children with DCM. Results of laboratory testing including mast cell mediator levels, and clinical symptoms on presentation and during follow-up were analyzed. RESULTS: The levels of relevant mast cell mediators were initially high in all cases but declined sharply later on. There was a reduction of 20% in 2 of the 7 cases, whereas there was a reduction of 80% in the remaining 5. No reduction occurred in 1 case. Clinical improvement followed the same pattern. CONCLUSIONS: DCM is a rare variant of cutaneous childhood onset mastocytosis. Various forms show the same or overlapping features at various times. It appears to follow a course similar to that in other types of childhood onset mastocytosis, taking into account the decreased symptoms and the levels of mast cell mediators during follow-up. Obtaining a bone marrow biopsy should be considered only in those cases where there is no improvement or even worsening of signs or symptoms and persistent elevated levels of mast cell mediators.

Histological and immunohistochemical study of granuloma annulare and subcutaneous granuloma annulare in children.

BACKGROUND: The aim of this study was to investigate the histological and immunohistochemical features of granuloma annulare (GA) in comparison to deep granuloma annulare (DGA) and granulomatous dermatoses (GDs). METHODS: Our material comprised 13 GA, 8 DGA and 1 atypical granuloma annulare (AGA) in a child with primary immunodeficiency, 10 cases of nonspecific GDs and 1 case of sarcoidosis with cutaneous involvement. The immunohistochemical streptavidin-biotin-Horseradish peroxidase (HRP) analysis was performed on paraffin sections for the detection of CD68/KP-1, CD68/anti-human CD68 clone PGM1 (PGM1), lysozyme, S-100 protein, CD1a, CD3, CD20/L-26, CD4 and CD8. RESULTS: All 13 GA were characterized by typical palisading and interstitial granulomas. In 6 cases, the lesion extended to the subcutaneous fat, while a considerable perivascular lymphocytic infiltrate without any signs of vasculitis was observed in 10 cases. The DGA were located to the deep dermis and subcutaneous fat, showing palisading granulomas with central necrobiosis. Immunohistochemistry revealed a broad intense expression of CD68/PGM1 in the histiocytic population in all cases, a constant but fainter detection of CD68/KP-1 and a variable one of lysozyme. T-cell markers (CD3, CD4 and CD8) were mainly detected in the perivascular lymphocytic infiltrate of GA and DGA, with CD4+ T lymphocytes predominating over CD8+ in GA and DGA, while CD8+ T lymphocytes was the predominant population in AGA. CONCLUSIONS: CD68/PGM1 is a sensitive and reliable histiocytic marker in confirming the histiocytic nature of equivocal GA and DGA, but the histiocytic immunoprofile is of no particular usefulness in differentiating GA from other GD.