[show abstract][hide abstract] ABSTRACT: Infantile myofibromatosis (IM) is the most common benign fibrous tumor of soft tissues affecting young children. By using whole-exome sequencing, RNA sequencing, and targeted sequencing, we investigated germline and tumor DNA in individuals from four distinct families with the familial form of IM and in five simplex IM cases with no previous family history of this disease. We identified a germline mutation c.1681C>T (p.Arg561Cys) in platelet-derived growth factor receptor ? (PDGFRB) in all 11 affected individuals with familial IM, although none of the five individuals with nonfamilial IM had mutations in this gene. We further identified a second heterozygous mutation in PDGFRB in two myofibromas from one of the affected familial cases, indicative of a potential second hit in this gene in the tumor. PDGFR-? promotes growth of mesenchymal cells, including blood vessels and smooth muscles, which are affected in IM. Our findings indicate p.Arg561Cys substitution in PDGFR-? as a cause of the dominant form of this disease. They provide a rationale for further investigations of this specific mutation and gene to assess the benefits of targeted therapies against PDGFR-? in aggressive life-threatening familial forms of the disease.
The American Journal of Human Genetics 05/2013; · 11.20 Impact Factor
[show abstract][hide abstract] ABSTRACT: Haemophagocytic lymphohistiocytosis complicating Epstein-Barr virus positive T-cell lymphoproliferative disease of childhood is a rare and life-threatening entity. We report a child with this condition presenting with a toxic epidermal necrolysis-like eruption.
Australasian Journal of Dermatology 04/2013; · 0.97 Impact Factor
[show abstract][hide abstract] ABSTRACT: We present a case series of childhood lymphomatoid papulosis (LyP), an entity which is commonly misdiagnosed and poorly described in the paediatric dermatology literature. Clinically and histologically, the features of LyP in children can mimic insect bite reactions, with prominent dermal neutrophils and eosinophils. However, CD30 immunohistochemical staining of atypical lymphocytes within a mixed inflammatory infiltrate should point to the diagnosis of LyP. There is no consensus to guide management of childhood LyP due to its rarity and largely unknown natural course. We discuss our experience with LyP in five children and the use of methotrexate to induce rapid resolution of persistent lesions and to reduce recurrences in two children. Although none of our cases have experienced malignant transformation to date, life-long monitoring is advocated.
Australasian Journal of Dermatology 11/2011; 52(4):279-83. · 0.97 Impact Factor
[show abstract][hide abstract] ABSTRACT: We present two families in whom infantile myofibromatosis affects two generations. The disease expression in these families suggests an autosomal dominant mode of inheritance. Clinical diagnosis and establishment of the inheritance pattern have important prognostic implications for the affected individual and family members and serves to guide subsequent genetic counselling.
Australasian Journal of Dermatology 08/2011; 52(3):214-7. · 0.97 Impact Factor
[show abstract][hide abstract] ABSTRACT: We present seven cases of a targetoid eruption, clinically mimicking erythema multiforme, occurring in paediatric patients aged 12 months to 14 years. All patients presented with a pruritic targetoid eruption on body and acral sites which spared mucosal areas. All patients demonstrated a spongiotic reaction pattern on histology without lichenoid change and demonstrated excellent responses to either oral prednisolone or topical corticosteroids. We propose the term 'targetoid spongiotic reaction pattern (TSRP)' for our subset of paediatric patients. We review the literature regarding targetoid eruptions in the paediatric population.
Australasian Journal of Dermatology 05/2011; 52(2):117-22. · 0.97 Impact Factor
[show abstract][hide abstract] ABSTRACT: We present the case of a boy with a clinical diagnosis of Goltz (focal dermal hypoplasia) syndrome. This is a rare genodermatosis characterized by widespread dysplasia of mesodermal and ectodermal tissues. It is inherited in an X-linked dominant fashion and is normally lethal in male patients. Mutations in the PORCN gene (Xp11.23), the proteins of which are key regulators in embryonic development, have been found to be responsible for the syndrome. Sequencing of the PORCN gene was negative in our patient. This case highlights some of the challenges of obtaining a molecular diagnosis in male patients with suspected Goltz syndrome in the clinical setting.
Australasian Journal of Dermatology 02/2011; 52(1):48-51. · 0.97 Impact Factor
[show abstract][hide abstract] ABSTRACT: We present a case series of 25 paediatric patients with refractory discoid eczema treated with methotrexate. Patients were commenced on either 5 mg or 10 mg of methotrexate per week. Sixteen patients (64%) completely cleared their eczema after an average of 10.5 months of methotrexate therapy. A further three patients (12%) have responded well and are almost clear at the time of writing. Methotrexate was well tolerated by the majority of patients and no serious adverse events were observed. Methotrexate should be considered in moderate to severe paediatric discoid eczema that has failed to respond to conventional therapies.
Australasian Journal of Dermatology 05/2010; 51(2):128-30. · 0.97 Impact Factor
[show abstract][hide abstract] ABSTRACT: We present seven cases of orofacial granulomatosis occurring in paediatric patients aged 6-16 years. All patients were investigated for Crohn's disease and a strong association was found. All patients were treated with intralesional corticosteroid injections with excellent clinical responses. We review the literature and discuss the epidemiological association between childhood orofacial granulomatosis and Crohn's disease, as well as various treatment options, and propose a treatment protocol that was efficacious and well tolerated in all our patients.
Australasian Journal of Dermatology 05/2010; 51(2):124-7. · 0.97 Impact Factor
[show abstract][hide abstract] ABSTRACT: A severe cutaneous eruption in an unwell patient can be a major cause of physician anxiety. With numerous differential diagnoses, an early accurate diagnosis can be challenging. infectious causes are the most important to exclude in a timely manner and drug rash and eosinophilia with systemic symptoms (DRESS) is another differential diagnosis that should be considered in children. This hypersensitivity reaction is associated with multisystem involvement. Children with underlying chronic diseases may have impairment of normal metabolic pathways and are also often on multiple medications. Therefore, drugs should always be considered in the aetiopathology of any new symptoms and signs. This case report informs readers of the association of sulfasalazine and DRESS in an 11-year-old with inflammatory bowel disease and discusses its pathogenesis and treatment. Increased awareness of this disorder will hopefully lead to increased reporting and consequently illuminate the syndrome more clearly and help guide its prevention and treatment.
Journal of Paediatrics and Child Health 04/2010; 46(4):193-6. · 1.25 Impact Factor
[show abstract][hide abstract] ABSTRACT: We describe a patient with a solitary mastocytoma arising at a site of trauma. The patient was born with the umbilical cord wrapped around her right thigh and subsequently developed a solitary mastocytoma in the exact site and distribution of this injury. The pathogenesis of mast cell proliferation in solitary mastocytoma is not completely understood. Cytokines released after injury, such as stem cell factor, may stimulate the proliferation of mast cells, as well as fibroblasts and melanocytes to form a mastocytoma. Mast cells in a newborn may be more sensitive to stem cell factor in the presence of cytokines released after injury due to an increased density of c-kit receptors. We present our patient and review the literature to support a hypothesis that this condition represents a reactive, and not neoplastic, process.
Australasian Journal of Dermatology 06/2009; 50(2):133-5. · 0.97 Impact Factor
[show abstract][hide abstract] ABSTRACT: Topical therapies are the mainstay in the treatment of atopic dermatitis, and are effective in the majority of patients with mild and localized disease. In patients with widespread or recalcitrant moderate to severe dermatitis, systemic therapies may be required. The frequently used systemic therapies are immunosuppressants, immune response modifiers, anti-inflammatories, antihistamines, and antibiotics. In this article, the indications and scientific support for the use of these medications is reviewed.