David Orchard

A Recurrent PDGFRB Mutation Causes Familial Infantile Myofibromatosis

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 β (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-β promotes growth of mesenchymal cells, including blood vessels and smooth muscles, which are affected in IM. Our findings indicate p.Arg561Cys substitution in PDGFR-β 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-β in aggressive life-threatening familial forms of the disease.

Epidemiology of Epidermolysis Bullosa in the Antipodes: The Australasian Epidermolysis Bullosa Registry With a Focus on Herlitz Junctional Epidermolysis Bullosa

OBJECTIVE To present epidemiologic and clinical data from the Australasian Epidermolysis Bullosa (EB) Registry, the first orphan disease registry in Australia. DESIGN Observational study (cross-sectional and longitudinal). SETTING Australian private dermatology practice, inpatient ward, and outpatient clinic. PATIENTS Systematic case finding of patients with EB simplex, junctional EB (JEB), and dystrophic EB and data collection were performed throughout Australia and New Zealand from January 1, 2006, through December 31, 2008. Patients were consecutively enrolled in the study after clinical assessment and laboratory diagnosis. Medical records were retrospectively examined, and physicians involved in EB care were contacted to obtain patient history. A Herlitz JEB case series was prepared from registry data. MAIN OUTCOME MEASURES Demographics and prognosis of patients with Herlitz JEB. RESULTS A total of 259 patients were enrolled in the study: 139 with EBS, 91 with dystrophic EB, 28 with JEB, and 1 with Kindler syndrome. Most enrollees were Australian citizens (n = 243), with an Australian prevalence rate of 10.3 cases per million. The age range in the registry was birth to 99 years, with a mean and median age of 24.1 and 18.0 years, respectively. Ages were similar in patients with EBS and dominant dystrophic EB but were markedly lower in patients with JEB. Patients with Herlitz JEB (n = 10) had the highest morbidity and mortality rates, with a mean age at death of 6.8 months. Sepsis, failure to thrive, and tracheolaryngeal complications were the leading causes of death. CONCLUSIONS The Australasian EB registry is the first registry in Australia and New Zealand to provide original data on age, sex, ethnicity, and geographical and disease subtype distribution. The Australasian Herlitz JEB cohort witnessed a high infant mortality rate and poor prognosis overall.

Clinical heterogeneity in recessive epidermolysis bullosa due to mutations in the keratin 14 gene, KRT14

Background.  Epidermolysis bullosa simplex (EBS), the most common subtype of EB, is usually inherited as an autosomal dominant trait caused by mutations in either the keratin 5 (KRT5) or keratin 14 (KRT14) genes. Recessive EBS (R‐EBS) is extremely rare.

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.

Methotrexate is a safe and effective treatment for paediatric discoid (nummular) eczema: A case series of 25 children

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.

Spitz naevi misdiagnosed histologically as melanoma: Prevalence and clinical profile

A Spitz naevus is a benign melanocytic tumour that may histologically resemble a malignant melanoma. Data was retrospectively gathered from patients who attended the Victorian Melanoma Service to determine the prevalence of Spitz naevi pathologically misdiagnosed as melanoma. Assessment of the clinical characteristics of these patients was also performed and compared to those with correctly diagnosed melanoma. It was found that 6.5% of all melanomas referred were in fact Spitz naevi and that Spitz naevi represented the majority of pathologically misdiagnosed melanomas. The Spitz naevi were more likely to be on the lower extremities and were on average, considerably smaller than the melanomas. Patients with Spitz naevi were more likely to be younger, female, have fewer dysplastic naevi and have brown eyes. One hundred per cent of the Spitz naevi were brought to the attention of the initial doctor by the patient compared to 72% of the melanomas. This study concludes that Spitz naevi that are pathologically misdiagnosed as melanomas retain the clinical characteristics of other Spitz naevi and mat greater clinicopathological communication may reduce the frequency of diagnostic error.

Skin prick testing to food allergens in breast-fed young infants with moderate to severe atopic dermatitis

The role of food allergy in atopic dermatitis is controversial. This study presents results of skin prick tests to 31 different food allergens in a selected population of predominantly breast‐fed young infants who had moderate to severe generalized atopic dermatitis. Of the 59 infants (22 female, mean age 26.5 weeks) tested, 54 infants (91.5%) had positive responses to one or more foods, 53 infants (90%) were positive to one or more of the five common food allergens (egg white, cows milk, peanuts, wheat or soy) and 80% were positive to egg white, which was by far the most common positive test. A total of 37 infants had strongly positive responses to one or more foods, with 33 of these 37 having strongly positive responses to egg white. The significance of these responses is discussed. It is concluded that positive skin prick tests to foods, particularly to egg white, are very common in this selected population of breast‐fed infants with moderate to severe atopic dermatitis.

Combination topical treatment of molluscum contagiosum with cantharidin and imiquimod 5% in children: A case series of 16 patients

The objective of this study was to assess the efficacy and tolerability of combination therapy for molluscum contagiosum (MC) with topical cantharidin and imiquimod 5%. A prospective case series of 16 paediatric patients with a mean age of 4.8 years had cantharidin applied to lesions by a dermatologist, followed by home treatment with imiquimod 5% cream nightly for an average of 5 weeks. This regimen resulted in >90% of lesions clearing in 12 patients, with half of these being totally clear. Two patients had 80–90% of lesions resolve. Two patients had 30–50% clearance of lesions at the end of the treatment period. One patient found the cantharidin reaction too strong. The mean number of imiquimod 250 mg sachets used was 4.25. In conclusion, this study suggests that combination therapy using cantharidin and imiquimod for treatment of MC in children is effective and well tolerated.

Systemic therapy of paediatric atopic dermatitis: An update

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.

Fixed drug eruption to tartrazine

An 11‐year‐old girl with a recurrent fixed drug eruption to tartrazine on the dorsum of the left hand is presented. Oral provocation tests to both the suspected food, an artificially coloured cheese crisp, and to tartrazine were positive. This case highlights the need to consider artificial flavours, colours and preservatives as potential culprits in classic‘drug eruptions’.