Mary Glover

Propranolol for complicated infantile haemangiomas: a case series of 30 infants

of survival in patients with the leukemic phase of cutaneous T cell lymphoma. J Exp Med 2003; 197:1477–88. 8 Capriotti E, Vonderheid EC, Thoburn CF et al. Expression of PLS3, FoxP3 and other tumor-associated markers by leukemic T-cells of cutaneous T-cell lymphoma. Leuk Lymphoma 2008; 49: 1190–201. 9 Nebozhyn M, Loboda A, Kari L et al. Quantitative PCR on 5 genes reliably identifies CTCL patients with 5% to 99% circulating tumor cells with 90% accuracy. Blood 2006; 107:3189–96. 10 Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-DDCt) method. Methods 2001; 25:402–8.

Clinical, Histologic, and Ultrastructural Findings in Two Cases of Infantile Systemic Hyalinosis

Abstract: Two unrelated infants had stiff skin and painful joint eontrac‐tures in the first few months of life. Other features included gingival hy‐perpiasia, small papules on the face and trunk, perianal nodules, and bloody diarrhea. Hyatine material was evident in the papillary dermis and gut mucosa in both patients. Ultrastructural examination revealed a dis‐tinctive fibrillogranuIar appearance. These infants have the same clinical, histologic, and ultrastructural features as four infants we reported previ‐ously with Infantile systemic hyalinosis. One of the patients described here demonstrated some features that overlap with those of juvenile hy‐aline fibromatosis.

Michelin‐Tire Baby Syndrome Resulting from Diffuse Smooth Muscle Hamartoma

Abstract: We cared for an infant who was born with the Michelin‐tire baby syndrome characterized by dermatomegaly and hypertrichosis. Histology revealed a diffuse smooth muscle hamartoma.

Mosaic Activating Mutations in GNA11 and GNAQ Are Associated with Phakomatosis Pigmentovascularis and Extensive Dermal Melanocytosis

Common birthmarks can be an indicator of underlying genetic disease but are often overlooked. Mongolian blue spots (dermal melanocytosis) are usually localized and transient, but they can be extensive, permanent, and associated with extracutaneous abnormalities. Co-occurrence with vascular birthmarks defines a subtype of phakomatosis pigmentovascularis, a group of syndromes associated with neurovascular, ophthalmological, overgrowth, and malignant complications. Here, we discover that extensive dermal melanocytosis and phakomatosis pigmentovascularis are associated with activating mutations in GNA11 and GNAQ, genes that encode Gα subunits of heterotrimeric G proteins. The mutations were detected at very low levels in affected tissues but were undetectable in the blood, indicating that these conditions are postzygotic mosaic disorders. In vitro expression of mutant GNA11R183C and GNA11Q209L in human cell lines demonstrated activation of the downstream p38 MAPK signaling pathway and the p38, JNK, and ERK pathways, respectively. Transgenic mosaic zebrafish models expressing mutant GNA11R183C under promoter mitfa developed extensive dermal melanocytosis recapitulating the human phenotype. Phakomatosis pigmentovascularis and extensive dermal melanocytosis are therefore diagnoses in the group of mosaic heterotrimeric G-protein disorders, joining McCune-Albright and Sturge-Weber syndromes. These findings will allow accurate clinical and molecular diagnosis of this subset of common birthmarks, thereby identifying infants at risk for serious complications, and provide novel therapeutic opportunities.

Propranolol for infantile haemangiomas: single centre experience of 250 cases and proposed therapeutic protocol

Objective To assess the safety and efficacy of systemic propranolol for the treatment of complicated infantile haemangiomas. Design Retrospective review of case notes of paediatric patients treated with propranolol for complicated infantile haemangiomas. Setting Tertiary care childrens hospital. Patients All paediatric patients with complicated infantile haemangiomas who commenced treatment with propranolol from July 2008 to December 2011 and have completed treatment for at least 3 months. Results 250 patients were treated with propranolol; 34.4% were premature and 5.6% postmature. Indications for propranolol included: vision compromise (42.0%), bleeding and/or ulceration (30.4%) airway obstruction (8.8%), feeding difficulty (8.4%), risk of permanent disfigurement (4.4%) and other (6%) (nasal obstruction, auditory canal obstruction, large haemangioma, compression of neck structure and spinal cord). Median age at beginning of treatment was 4.5 months. Median age at end of treatment was 16.7 months. Median length of therapy was 11.8 months. Adverse effects (such as wheezing, worsening of ulceration, sleep disturbance, diarrhoea) occurred in 38 patients (15.2%), leading to modifications in management in 26 patients (10.4%). 240 patients (96%) had good to excellent response to treatment. 20 patients (8%) experienced regrowth of the haemangioma on cessation of propranolol and six patients (2.4%) required propranolol to be restarted. Conclusions In appropriately selected patients, propranolol is a safe and effective treatment for infantile haemangiomas.

The adverse effect profile of oral azathioprine in pediatric atopic dermatitis, and recommendations for monitoring.

Background Azathioprine is efficacious in the treatment of severe childhood atopic dermatitis; however, robust data on adverse effects in this population are lacking. Objective We sought to assess adverse effects of azathioprine treatment in a pediatric atopic dermatitis cohort, and make recommendations for monitoring based on these data. Methods Blood test results for all 82 children prescribed oral azathioprine for atopic dermatitis in our department between 2010 and 2012 were collated prospectively, and clinical notes were reviewed retrospectively. Results Mean age at commencing azathioprine was 8.3 years (SEM 0.4). Mean maximum doses were 2.4 mg/kg (SEM 0.1) and 1.5 mg/kg (SEM 0.1) for normal and reduced serum thiopurine-S-methyltransferase levels, respectively. Adverse effects on blood indices occurred in 34 of 82 patients (41%), with pronounced effects in 18 of 82 (22%) after a median time of 0.4 years. Two patients stopped therapy as a result of abnormal blood indices. Clinical adverse effects occurred in 16 of 82 (20%), two resulting in cessation of therapy. Incidence of adverse effects was unaffected by age, sex, thiopurine-S-methyltransferase level, and drug dose on multivariate regression. Limitations Comparison with other studies is limited by varying definitions of adverse effects. Conclusion Oral azathioprine was associated with few pronounced adverse effects for the duration of use and dosage in this cohort. Recommendations for monitoring are made.

Dermatomyositis pemphigoides: A case with coexistent dermatomyositis and bullous pemphigoid

We describe a patient with coexistent dermatomyositis and bullous pemphigoid; both appeared within a few weeks. Protein blotting showed binding of the patients serum to the classic 220 kd bullous pemphigoid antigen. Because of the close temporal association of the two disorders, we believe that they are almost certainly etiologically linked. One possibility is that exposure of basement membrane antigens by dermatomyositis led to exposure of bullous pemphigoid antigen and subsequent antibody formation.

Lipofibromatosis of the knee in a 19-month-old child

Lipofibromatosis is a rare benign fibrofatty tumor of childhood. The typical presentation of this tumor is as a poorly demarcated and slow-growing mass involving the subcutaneous or deep soft tissues. Lipofibromatosis was first described in 2000, and since then, a small number of cases have been reported in the literature. We report a case of a 19-month-old boy who presented with a swelling of the anterior aspect of the right knee since birth, which had increased in size out of proportion with his growth. Magnetic resonance imaging was extremely useful because it showed the lipomatous nature of the mass, narrowing the differential diagnosis to the pediatric fibrofatty soft tissue tumors. The histologic biopsy revealed the specific diagnosis of lipofibromatosis. We describe the radiologic and pathologic features of this entity and discuss the differential diagnosis in a young child with a fat-containing limb mass.

Atenolol Treatment for Infantile Haemangioma

Since 2008, propranolol has become the first line recommended treatment for infantile haemangiomas (IH) 1,2. Propranolol is a synthetic beta-adrenergic receptor-blocking agent that is non-selective because it blocks both beta 1 and beta 2 adrenergic receptors 3,4. The most commonly reported side effects in infants treated with propranolol for IH are sleep disturbance, cool mottled peripheries and bronchial hyperactivity 3,5 and concerns have been raised about the potential long-term neurodevelopmental or cognitive effects6, 7. A proportion of patients has to stop treatment because of adverse effects, thus treatments with other beta-blockers are considered. This article is protected by copyright. All rights reserved.

Segmental hemangioma of the head and neck: High prevalence of PHACE syndrome

HPV-associated nail unit SCCs (15 patients) were most frequently localized on the fingers, presenting as hyperkeratotic bands with an anteroposterior growth, and as differentiated tumors on histopathologic evaluation (G1). Male patients more frequently had involvement than did female patients, whereas age was equally distributed between the HPVassociated nail unit SCC and HPV-negative nail unit SCCs. HPV-16was the only subtype detected on nail unit SCC in our series, as in most reported studies. The aim of this letter was not to speculate on a possible oncogenic role of HPV-16 in nail unit SCC, but to stimulate future research, because the knowledge of HPV infection in neoplasms of different anatomical locations offers important implications in disease prevention, treatment, and prognosis, thanks to the development of new vaccines. Emi Dika, MD, PhD, Simona Venturoli, MD, Annalisa Patrizi, MD, PhD, Bianca Maria Piraccini, MD, PhD, Pier Alessandro Fanti, MD, Daniela Barbieri, MD, Martina Nocera, MD, Marco Adriano Chessa, MD, Maria Paola Landini, MD, PhD, and Michelangelo La Placa, MD, PhD