Anne Halbert

Trichodysplasia spinulosa associated with chemotherapy for acute lymphocytic leukaemia

We report two boys with trichodysplasia spinulosa associated with chemotherapy for acute lymphocytic leukaemia. Trichodysplasia spinulosa is a cutaneous viral infection of immunosuppressed patients that causes abnormal hair follicle maturation. Our patients presented with widespread papules, some extruding a central keratin spicule, which were most prominent on the face. Histopathology demonstrated hair follicles dilated by a proliferation of large eosinophilic cells containing numerous abnormal trichohyaline granules. Electron microscopy in case 1 revealed 30‐nm viral particles in the stratum corneum consistent with a papovavirus. In case 1, the eruption persisted despite topical salicyclic acid 4%, ammonium lactate 17.5%, tretinoin 0.05% and oral acitretin. However, it resolved once the patients immune function returned to normal (total duration of 2 years). In case 2, the eruption spontaneously resolved after 9 months. This case report discusses the characteristic clinicopathological features of trichodysplasia spinulosa and, for the first time, follows the conditions natural history.

Topical 0.1% rapamycin for angiofibromas in paediatric patients with tuberous sclerosis: A pilot study of four patients

Tuberous sclerosis complex (TSC) is an autosomal dominant genodermatosis characterised by the development of hamartomatous tumours in multiple organs including the brain, skin, kidneys, heart and lungs. Facial angiofibromas are the most visible and unsightly of the cutaneous manifestations of TSC, often resulting in stigmatisation for both the affected individuals and their families. Current treatments include vascular laser, ablative lasers and other destructive techniques such as shave excision and electrodessication. For the best outcome these treatments have to be repeated throughout childhood and teenage years, necessitating multiple general anaesthetics. We report a pilot study of topical rapamycin in four children with TSC and facial angiofibromas. Two patients were trialled on 0.1% rapamycin in petrolatum and the other two patients with 0.1% rapamycin solution (Rapamune) applied topically. Both preparations were rapidly and equally effective, however the 0.1% in petrolatum was much better tolerated. Younger patients with smaller angiofibromas had the best response with near complete clearance. Both preparations were more cost effective than pulsed dye laser under general anaesthesia. Although larger studies are needed, this treatment shows a potential to be a first‐line management for facial angiofibromas in TSC and appears safe to start in early childhood.

Mutations in STAMBP, encoding a deubiquitinating enzyme, cause microcephaly-capillary malformation syndrome

Microcephaly–capillary malformation (MIC-CAP) syndrome is characterized by severe microcephaly with progressive cortical atrophy, intractable epilepsy, profound developmental delay and multiple small capillary malformations on the skin. We used whole-exome sequencing of five patients with MIC-CAP syndrome and identified recessive mutations in STAMBP, a gene encoding the deubiquitinating (DUB) isopeptidase STAMBP (STAM-binding protein, also known as AMSH, associated molecule with the SH3 domain of STAM) that has a key role in cell surface receptor–mediated endocytosis and sorting. Patient cell lines showed reduced STAMBP expression associated with accumulation of ubiquitin-conjugated protein aggregates, elevated apoptosis and insensitive activation of the RAS-MAPK and PI3K-AKT-mTOR pathways. The latter cellular phenotype is notable considering the established connection between these pathways and their association with vascular and capillary malformations. Furthermore, our findings of a congenital human disorder caused by a defective DUB protein that functions in endocytosis implicates ubiquitin-conjugate aggregation and elevated apoptosis as factors potentially influencing the progressive neuronal loss underlying MIC-CAP syndrome.

Adverse effects of topical corticosteroids in paediatric eczema: Australasian consensus statement

Atopic eczema is a chronic inflammatory disease affecting about 30% of Australian and New Zealand children. Severe eczema costs over AUD 6000/year per child in direct medical, hospital and treatment costs as well as time off work for caregivers and untold distress for the family unit. In addition, it has a negative impact on a childs sleep, education, development and self‐esteem. The treatment of atopic eczema is complex and multifaceted but a core component of therapy is to manage the inflammation with topical corticosteroids (TCS). Despite this, TCS are often underutilised by many parents due to corticosteroid phobia and unfounded concerns about their adverse effects. This has led to extended and unnecessary exacerbations of eczema for children. Contrary to popular perceptions, (TCS) use in paediatric eczema does not cause atrophy, hypopigmentation, hypertrichosis, osteoporosis, purpura or telangiectasia when used appropriately as per guidelines. In rare cases, prolonged and excessive use of potent TCS has contributed to striae, short‐term hypothalamic‐pituitary‐adrenal axis alteration and ophthalmological disease. TCS use can also exacerbate periorificial rosacea. TCS are very effective treatments for eczema. When they are used to treat active eczema and stopped once the active inflammation has resolved, adverse effects are minimal. TCS should be the cornerstone treatment of atopic eczema in children.

Topical rapamycin for angiofibromas in paediatric patients with tuberous sclerosis: Follow up of a pilot study and promising future directions

One of the most visible and potentially disfiguring cutaneous manifestations of tuberous sclerosis complex is the development of multiple facial angiofibromas, present in over 80% of patients. Topical rapamycin has been shown in many reports to be a safe and effective treatment for facial angiofibromas. In February 2012 we reported the results of a pilot study of four patients undertaken at a paediatric tertiary hospital in Australia. Since then, we have continued to refine the optimal formulation and concentration of topical rapamycin and expanded our selection of patients. We present an update on our current cohort of treated patients, discuss the optimal formulation of topical rapamycin and include a literature review on all published cases to date. Although topical rapamycin is not a curative treatment, we have demonstrated that its early institution significantly reduces both the vascularity and palpability of angiofibromas and prevents their progression with age. It is well tolerated and now a cost effective option.

Blau syndrome presenting with ichthyosis

A 12‐year‐old girl presented with uveitis, joint disease and ichthyosis resembling ichthyosis vulgaris. A biopsy taken from the affected lower leg demonstrated sarcoidal‐type granulomas. Synovial biopsy from the knee also showed granulomas. There was a family history of similar clinical features in the patients younger sister. There were no other systemic features present to suggest a diagnosis of sarcoidosis or other granulomatous disease such as Crohns disease or tuberculosis. The familial nature of the condition also made these diagnoses less likely. A clinical diagnosis of Blau syndrome was made. Blau syndrome is an uncommon sarcoidosis‐like multisystem autosomal‐dominant granulomatous disorder caused by mutations in the CARD15 gene. This gene has also recently been found to be a factor in the development of psoriatic arthritis and Crohns disease. Although many forms of skin involvement have been described in Blau syndrome, this is the first case described of ichthyosis as the primary skin manifestation.

Anogenital and buttock ulceration in infancy

Rashes in the anogenital and buttock region are some of the commonest dermatological problems occurring in infancy. The most frequent causes seen in clinical practice are ulcerating haemangiomas, bullous impetigo and severe irritant contact dermatitis. Other causes include nutritional deficiencies, bullous diseases, trauma, Langerhans cell histiocytoses and inflammatory disorders such as pyoderma gangrenosum and Crohn’s disease. This review presents a brief overview of these causes and outlines the recommended management strategies.

Objective Monitoring of mTOR Inhibitor Therapy by Three-Dimensional Facial Analysis

With advances in therapeutics for rare, genetic and syndromic diseases, there is an increasing need for objective assessments of phenotypic endpoints. These assessments will preferentially be high precision, non-invasive, non-irradiating, and relatively inexpensive and portable. We report a case of a child with an extensive lymphatic vascular malformation of the head and neck, treated with an mammalian target of Rapamycin (mTOR) inhibitor that was assessed using 3D facial analysis. This case illustrates that this technology is prospectively a cost-effective modality for treatment monitoring, and it supports that it may also be used for novel explorations of disease biology for conditions associated with disturbances in the mTOR, and interrelated, pathways.

Dermatology outpatient population profiling: Indigenous and non-indigenous dermatoepidemiology

Background:  Little is known about the population using Australian dermatology outpatient services, in particular, Indigenous patients. This information is important to direct the strategic planning of dermatology services.

Paediatric atopic dermatitis in Perth general practice

Ninety‐seven Perth general practitioners completed a self‐administered postal questionnaire that aimed to examine their caseload and management practices for childhood atopic dermatitis (AD). General practitioners saw a median of two new cases and three follow‐up consultations per month for childhood AD, and referred a median of 10% of cases to a specialist, usually a dermatologist. Most (77%) recommended emollients for all patients, but only 21% specifically reported advising their use immediately after bathing. Sixty‐one percent would use topical corticosteroids in all or most patients, but cream preparations were more commonly used (58%) than ointments (40%). Atrophy was rated as a common or very common side‐effect of topical corticosteroid therapy by 23% of general practitioners. Twenty‐six percent reported using oral corticosteroids in children with AD. Dietary changes would be recommended in at least a few AD patients by 79% of general practitioners, and 31% would recommend a change from cows milk to soy in the absence of a history of dietary triggers. We conclude that general practitioners appeared generally well informed about AD management. However, dermatologists, through targeted education, may be in a position to help general practitioners further improve outcomes for these patients.