Safety profile during initiation of propranolol for treatment of infantile haemangiomas in an ambulatory day-care hospitalization setting.

BACKGROUND: Propranolol is the mainstay of treatment for infantile haemangioma. Despite its good safety profile, it is not risk-free. Guidelines for propranolol initiation and monitoring have been suggested, but protocols vary among practitioners. OBJECTIVE: This study sought to assess the prevalence of adverse events and clinically significant fluctuations in haemodynamic parameters in children with infantile haemangioma during initiation of treatment with propranolol in a day-hospitalization setting. METHODS: Children with infantile haemangioma treated with propranolol in a day-hospitalization department of a tertiary paediatric medical centre in 2008-2014 were identified retrospectively. The pretreatment evaluation included clinical examination by a paediatric dermatologist and electrocardiography, echocardiography and clinical examination by a paediatric cardiologist. The propranolol dosage was escalated from 0.5 mg/kg/day to 2 mg/kg/day, divided into three doses/day, over 3 days. Heart rate, blood pressure and blood glucose level were measured before treatment onset and 60 min after the first two doses each day. The third dose was given at home. RESULTS: The cohort included 220 children aged 1 month to 5 years. No severe treatment-related adverse events were documented; 27 patients had minor side-effects. There was a significant decrease in heart rate each day after the first two doses (P < 0.001), and in systolic blood pressure, on day 2 (1 mg/kg/day) after the first dose (P = 0.01). Blood glucose level remained stable. The haemodynamic changes were clinically asymptomatic and did not require intervention. CONCLUSIONS: Propranolol treatment (2 mg/kg/day in three doses) for infantile haemangioma is well tolerated and safe and may be administered and monitored in an ambulatory setting.

Barrier-restoring therapies in atopic dermatitis: current approaches and future perspectives.

Atopic dermatitis is a multifactorial, chronic relapsing, inflammatory disease, characterized by xerosis, eczematous lesions, and pruritus. The latter usually leads to an "itch-scratch" cycle that may compromise the epidermal barrier. Skin barrier abnormalities in atopic dermatitis may result from mutations in the gene encoding for filaggrin, which plays an important role in the formation of cornified cytosol. Barrier abnormalities render the skin more permeable to irritants, allergens, and microorganisms. Treatment of atopic dermatitis must be directed to control the itching, suppress the inflammation, and restore the skin barrier. Emollients, both creams and ointments, improve the barrier function of stratum corneum by providing it with water and lipids. Studies on atopic dermatitis and barrier repair treatment show that adequate lipid replacement therapy reduces the inflammation and restores epidermal function. Efforts directed to develop immunomodulators that interfere with cytokine-induced skin barrier dysfunction, provide a promising strategy for treatment of atopic dermatitis. Moreover, an impressive proliferation of more than 80 clinical studies focusing on topical treatments in atopic dermatitis led to growing expectations for better therapies.

Refractive and structural changes in infantile periocular capillary haemangioma treated with propranolol.

PURPOSE: To evaluate the optical and anatomical effects of oral propranolol treatment for infantile periocular capillary haemangioma. METHODS: All children diagnosed with infantile capillary haemangioma in 2008-2010 at a tertiary paediatric medical centre underwent comprehensive evaluation, including imaging, by a multidisciplinary team followed by oral propranolol treatment. Clinical follow-up was performed regularly until the lesions disappeared. Main outcome measures included changes in anatomical extraocular extension, refractive sphere and cylindrical power, and spherical equivalent in the involved eye before and after treatment and between the two eyes. RESULTS: A total of 30 patients (8 male; mean age at diagnosis, 1.6±2.8 months) participated. The lesions affected the left eye in 53.3% and were located preseptally in 83.3%. Four patients (13.3%) received steroids before propranolol. A treatment dosage of 2 mg/kg per day was started at mean age 5.0±4.5 months, 3.3±4.3 months from disease onset. Side effects occurred in 11 patients and warranted a dose reduction (to 1 mg/kg per day) in 3 and treatment termination in 1. Findings were significant for mean reduction in involved extraocular area (P<0.0001), post-treatment reduction in mean cylindrical power in involved eyes (P=0.02), pre- and post-treatment differences in mean cylindrical power between involved and uninvolved eyes (P=0.02 and P=0.01, respectively), and post-treatment change in absolute values of mean spherical power between involved and uninvolved eyes (P=0.025). CONCLUSIONS: Early diagnosis of infantile periocular capillary haemangioma and prompt treatment with propranolol lead to a significant reduction in the involved ocular area, in astigmatism, and prevent ocular/facial disfiguration/deformation, without rebound. Propranolol is recommended as the preferred treatment compared with other accepted therapies.

An autosomal recessive exfoliative ichthyosis with linkage to chromosome 12q13.

A new variant of congenital exfoliative ichthyosis in two related Bedouin families is reported. The ichthyosis appeared shortly after birth as a fine peeling of nonerythematous skin on the palms and soles. The prominent well-demarcated areas of denuded skin in moist and traumatized regions resembled the 'mauserung' phenomenon of ichthyosis bullosa of Siemens (IBS). Unlike in IBS, epidermolysis is absent on histological examination. Electron microscopy revealed a prominent intercellular oedema and numerous aggregates of keratin filaments in basal keratinocytes. Abnormal keratin (K) 1 expression was seen in the affected epidermis; however, all other keratins, including K2e, had a distribution comparable to that seen in normal controls. A maximum two-point LOD score of 2.53 and multipoint LOD score of 3.76 were obtained for marker D12S390, suggesting linkage to the type II keratin cluster on chromosome 12q13. Sequencing of both the K1 gene, the promotor and the 3' calcium regulatory region did not reveal a mutation. K2e and K5 genes, as well as the genes harboured within the minimal region, such as retinoic acid receptor gamma, sterol O-acyltransferase 2, integrin beta7 and insulin-like growth factor binding protein-6, were also excluded. This combination of clinical, histological, ultrastructural and genetic features has not been previously reported in other congenital exfoliative ichthyoses. We therefore suggest that it represents a new form of exfoliative ichthyosis.

Development of psoriatic lesions during acute and convalescent phases of Kawasaki disease.

A 7-month-old infant developed a discrete pustular rash confined to both soles during the acute phase of Kawasaki disease. Histological examination of a pustular lesion from the sole of a foot showed subcorneal neutrophilic microabscesses, psoriasiform acanthosis with a thin granular layer and mononuclear perivascular infiltrates in the upper dermis, consistent with psoriasis. Following the standard treatment with intravenous gamma globulin, the initial symptoms and signs of Kawasaki disease resolved completely. Eight weeks later, psoriasiform plaques appeared on both cheeks and on the extensor surfaces of the forearms and legs. Skin biopsy from one of these lesions revealed psoriasiform epidermal hyperplasia, focal parakeratosis and dilated papillary capillaries. The patient was treated with mild-potency topical steroids that resulted in rapid and complete resolution of the skin lesions. Concurrent association of psoriatic skin lesions and Kawasaki disease might not be incidental and could stem from a common pathogenetic mechanism induced by superantigens.

A new variant of autosomal recessive exfoliative ichthyosis.

We report unusual congenital ichthyosiform dermatosis in 5 of 12 children in two related families of unaffected, consanguineous Bedouin parents. It appeared shortly after birth as a fine peeling of nonerythematous skin on palms and soles. Gradually it evolved into prominent, well-demarcated areas of peeling skin in moist and traumatized regions. The cutaneous manifestations share features of ichthyosis bullosa of Siemens (IBS) and peeling skin syndrome (PSS). Histologic examination revealed orthokeratosis, a thickened granular cell layer, and spongiosis without epidermolytic hyperkeratosis. On electron microscopy there was prominent intercellular edema and numerous aggregates of keratin filaments in basal keratinocytes. This combination of clinical, histologic, and ultrastructural features has not been previously reported in the heterogeneous group of congenital ichthyoses. We suggest that it represents a new variant of exfoliative ichthyosis.

Penetrating neck trauma: hidden injuries-oesophagospinal traumatic fistula.

Injuries to the eosophagus are notoriously difficult to diagnose pre-operatively. Patients with such injuries usually will not have pre-operative signs and symptoms to suggest the presence of this type of injury. These injuries require a high index of suspicion, appreciation of the presence of injuries to adjacent structures, and an understanding that the clinical and radiological findings may evolve over a period of time. We describe a child with a rare presentation of an acute traumatic esophageal spinal fistula due to a bullet wound. This complicated injury required a variety of diagnostic modalities, including contrast radiography, multiple computerised tomography (CT) scans and operative assessments to make the definitive diagnosis.

Association of Ureaplasma urealyticum colonization in male urethra and Condyloma acuminatum.

BACKGROUND: The frequent coexistence of two or more sexually transmitted diseases in one patient has been reported in non-dermatological literature, mostly in languages other than English. Identification of Ureaplasma urealyticum, Chlamydia trachomatis and Mycoplasma hominis in men with other STDs is important, since these bacteria have been implicated in a variety of diseases such as non-gonococcal urethritis, premature rupture of fetal membranes, and infertility in female sexual partners of these patients. OBJECTIVE: To assess the frequency of concomitant STD, particularly urethral colonization of U. urealyticum, C. trachomatis and M. hominis, in men consulting for suspected STD-related symptoms. METHODS: All patients attending our dermatology clinic for STD-related symptoms during a 12 month period in 1996-97 underwent systematic clinical and laboratory screening for syphilis, gonorrhea, NGU, prostatitis, genital herpes simplex infection, Condyloma acuminatum, urethral carriage of U. urealyticum, C. trachomatis and M. hominis, as well as serological screening for HIV, and hepatitis B and C infections. RESULTS: A total of 169 men with STD-related symptoms were enrolled in the study. The following clinical diagnoses were established: NGU in 109 men, C. acuminatum in 40, genital herpes simplex in 10, prostatitis in 7, latent syphilis in 6, primary syphilis in 1, and Behcet's disease in 1. No clinical evidence of STD was found in 13 patients. Of the 169 patients, 39 (23%) had two or more concomitant STDs, of whom 27 (69%) had C. acuminatum associated with one or more of the urethral pathogens. A positive U. urealyticum culture was found in 67.5% (27/40) of the men with C. acuminatum as compared to 42% (40/96) among the patients with NGU who did not have C. acuminatum (P = 0.004, chi 2 test). Conversely, the prevalence of C. acuminatum among patients positive for U. urealyticum was significantly higher than the prevalence among those who were negative--27/75 (36%) vs. 13/94 (14%), P < 0.0009, chi 2 test. About half of the U. urealyticum-positive patients with C. acuminatum had no clinical signs or symptoms of urethritis. CONCLUSION: Our findings suggest that patients with C. acuminatum should be assessed for U. urealyticum carriage and, when identified, their sexual contacts should be actively sought and treated.

Plantar hidradenitis in children induced by exposure to wet footwear.

Painful erythematous papules and nodules involving either the palms of the hands, or, more commonly, the soles of the feet, characterize palmoplantar eccrine hidradenitis or palmoplantar hidradenitis (PH). The younger pediatric population is predominately affected. Histologically, the eccrine gland apparatus is the target of inflammatory neutrophilic infiltrates. This entity has been reported under a variety of names, including traumatic plantar urticaria, neutrophilic eccrine hidradenitis, plantar erythema nodosum, and idiopathic recurrent palmoplantar hidradenitis. All are essentially the same process, described in different forms. Despite the growing number of reported cases, the pathogenesis remains obscure. We present four children with PH of the soles of the feet, who shared a common recent history of exposure to cold, damp, footwear. The temporal relationship between exposure to dampness and cold and the appearance of the skin lesions suggest a possible pathogenetic mechanism.

Deletion patterns of the STS gene and flanking sequences in Israeli X-linked ichthyosis patients and carriers: analysis by polymerase chain reaction and fluorescence in situ hybridization techniques.

BACKGROUND: Deletion of the entire steroid sulfatase (STS) gene is the most common molecular defect in X-linked ichthyosis (XLI) patients. Usually, additional flanking sequences are also missing. The aim of this study was to estimate the extent of deletions in an ethnically heterogeneous population of Israeli XLI patients. METHODS: Multiplex polymerase chain reaction (PCR) and fluorescence in situ hybridization (FISH) techniques were applied in the analysis of blood samples of 24 patients and amniotic cells of seven affected fetuses from 22 unrelated families. RESULTS: In 19 families, a large deletion of the 2-3 megabase was found. It included the whole STS gene and spanned adjacent areas up- and downstream between the loci DXS 1139 and DXS 1132. Two unrelated families of Iraqi ancestry had a partial deletion of the gene and its centromeric adjacent sequence. In another family, the telomeric end of the extragenic segment was only partially missing. Application of FISH on metaphase blood cells and interphase amniotic cells confirmed the diagnosis of XLI in all patients, except the three with partial intragenic deletion. In those cases, the remaining fraction of the gene was sufficient to provide a false negative result. Diagnosis of carriers and prenatal diagnosis in uncultured cells was applicable only by FISH. CONCLUSIONS: Our study revealed a remarkable heterogeneity in the deletion pattern among Israeli patients with XLI. This heterogeneity could not be attributed to specific ethnic groups because of the small size of the study group. More studies involving patients of various ancestries should be carried out. In addition, this study demonstrated the usefulness of the FISH technique in the prenatal diagnosis of fetuses with suspected XLI.

Relapse of cutaneous leishmaniasis in a patient with an infected subcutaneous rheumatoid nodule.

Cutaneous leishmaniasis is a protozoal infection generally considered to be limited to the skin. In Israel, the disease is common in geographically defined areas and is caused predominantly by Leishmania major. Sporotrichoid subcutaneous spread has been reported but is uncommon. We describe a patient with rheumatoid arthritis, treated with methotrexate and prednisone, in whom numerous rheumatoid nodules concomitant with cutaneous leishmaniasis were found, mimicking sporotrichoid spread of the disease. In a rheumatoid nodule that was examined by electron microscopy, Leishmania parasites were found at intracellular and extracellular locations. This observation supports the hypothesis that cutaneous leishmaniasis parasites persist after clinical cure of the disease and may re-emerge as a result of immunosuppression.

Pigmented purpuric dermatosis (Schamberg's purpura) in an infant.

Purpura in an infant is usually an alarming sign of a systemic (infectious, hematologic-oncologic or immunologic) disease. Chronic purpuric dermatoses have not been reported in infants and, therefore, are not considered in the differential diagnosis of purpuras in this age. We report on a female infant with progressive purpura who underwent extensive laboratory investigations to rule out a systemic disease. Based on the laboratory findings and clinical course, the diagnosis of Schamberg's purpura was established.

Influence of genetic and environmental factors on melanocytic naevi: a lesson from Turner's syndrome.

Females with Turner syndrome (TS) are alleged to have increased numbers of melanocytic naevi. Although a high count of acquired melanocytic naevi (AMN) is one of the major risk factors for melanoma, this malignancy has been reported only rarely in patients with TS. The purpose of this study was to explore the effects of environmental and genetic factors on AMN count and density in TS. AMN count and density in 24 patients with TS treated with growth hormone (GH). 24 GH-treated females with GH deficiency (GHD) and 24 normal females were compared in a cross-sectional study. The average AMN density in TS was 50 naevi/m2 as compared with 18 naevi/m2 in the GHD group and 24 naevi/m2 in normal controls (P = 0.001 and P = 0.004, respectively). Duration of GH therapy did not correlate with AMN count (P = 0.44) or AMN density (P = 0.81). The pattern of distribution of naevi between constantly exposed, intermittently exposed and unexposed skin was similar in all groups. Sun exposure was the major factor that affected the regional AMN densities in the control groups, but not in the TS group. The findings of our study indicate that the effects of environmental factors on AMN count and density may vary among genetically different populations. A review of the literature suggested that melanoma is no more prevalent in TS than in the general population.

Reticulolinear aplasia cutis congenita of the face and neck: a distinctive cutaneous manifestation in several syndromes linked to Xp22.

A distinct form of aplasia cutis congenita presenting as linear facial skin defects has been described under a variety of names as Xp deletion syndrome. MIDAS (microphthalmia, dermal aplasia and sclerocornea) syndrome, MLS (microphthalmia and linear skin defects) and Gazali-Temple syndrome. The syndrome is lethal in males, and its severity in females varies from a relatively mild residual facial scarring with short stature to lethal developmental organ malformations. A new case with peculiar ultrastructural findings is presented. A review of the literature suggests that these associations represent a series of contiguous-gene syndromes.

Cutaneous bronchogenic cyst: delineation of a poorly recognized lesion.

Bronchogenic cyst is a benign congenital developmental abnormality of the embryonic foregut. The most common extrapulmonary location of these lesions is the mediastinum. Over 50 cases of cutaneous bronchogenic cyst were reported in the English literature. Nevertheless, it is poorly recognized by clinicians and is sometimes confused with branchial cyst. In almost all cases the diagnosis is established by histopathologic examination. We report an unusual clinical presentation of bronchogenic cyst in a 4-year-old girl and review the literature. This lesion is four times more common in males than in females. The most common location is the suprasternal notch, followed by the presternal area, neck, and scapula. The characteristic histologic findings are a ciliated pseudostratified epithelial lining with the presence of smooth muscle cells, goblet cells and, less frequently, cartilage. Our review of the clinical and histologic features of all reported cases further delineates this entity and may facilitate its clinical diagnosis. Bronchogenic cyst should be included in the differential diagnosis of congenital cystic and nodular skin lesions on the upper chest, upper back, and neck.