Pimecrolimus for the Treatment of Atopic Dermatitis in Infants: An Asian Perspective.

Atopic dermatitis (AD) is a common chronic, multisystem inflammatory skin disease in pediatric patients. There has been an increase in the incidence of AD in the pediatric population of the Asia-Pacific region. Studies have shown that genetic, epigenetic, environmental and cultural factors may lead to differences in the clinical manifestation and prevalence of AD between races. Early treatment of AD is necessary to prevent the atopic march leading to comorbidities such as asthma and allergic rhinitis. Topical corticosteroids (TCS) are used as first-line therapy for the treatment of AD, but their long-term usage poses a risk to the patient's health. Pimecrolimus (1%) is a topical calcineurin inhibitor (TCI) that is indicated for the treatment of mild to moderate AD. Pimecrolimus has no apparent increase in adverse events compared to TCS, and it causes less of a burning sensation than tacrolimus. The safety and efficacy of pimecrolimus has been established through various clinical trials; yet, in many Asian countries, the use of pimecrolimus in infants is still restricted due to safety concerns. Based on the available evidence, the expert panel recommends pimecrolimus in infants between 3 months and 2 years of age in the Asian population.

Pimecrolimus 1% cream for mild-to-moderate atopic dermatitis: a systematic review and meta-analysis with a focus on children and sensitive skin areas.

This systematic literature review (SLR) and meta-analysis assessed the efficacy and safety of pimecrolimus vs other topical treatments in patients with mild-to-moderate atopic dermatitis (AD), focusing on children and sensitive skin areas. An SLR was conducted in MEDLINE, Embase and Cochrane Library databases on January 15th, 2020, to identify randomized controlled trials (RCTs) with pimecrolimus as a study arm. Another SLR performed on October 5th, 2020 identified RCTs with a crisaborole study arm. Direct pair-wise meta-analysis was used to compare pimecrolimus with vehicle, tacrolimus or topical corticosteroids (TCS; n = 27 studies). Outcomes included Investigator's Global Assessment (IGA) score 0/1 up to week 6 and adverse events. Pimecrolimus was more efficacious than vehicle in achieving IGA 0/1 up to week 6 in children, and similar safety profiles were observed with pimecrolimus and vehicle in children and the mixed population, including on sensitive skin. No significant differences in efficacy and safety were observed between pimecrolimus and tacrolimus 0.03%. Efficacy and safety were similar for pimecrolimus and mild medium potency TCS; mildly potent steroids caused transient epidermal thinning in sensitive skin areas (not seen with pimecrolimus). Pimecrolimus can be considered as a first-line option for mild-to-moderate AD, particularly in children and sensitive skin areas.

Bringing the Treatment of Atopic Eczema Into a New Era with Janus Kinase Inhibitors: A Position Statement By the Persatuan Dermatologi Malaysia

Abstract@#Atopic eczema (AE) is a complex, chronic and recurrent inflammatory pruritic skin condition that impacts the quality of life and exerts an economic toll on patients and their families. One of the factors contributing to AE is the immune dysregulation of the Janus kinase-signal transducers and activators of transcription (JAK-STAT) inflammatory pathway. This has prompted the conduct of various large clinical trial programs to evaluate the efficacy and safety of Janus kinase inhibitors (JAK-i) for AE. The overall and significant benefit of these drugs from clinical studies resulted in regulatory approvals for JAK-i to treat moderate-to-severe atopic eczema. The objective of this position paper was to evaluate the safety, efficacy and role of upadacitinib, baricitinib and abrocitinib in managing AE and update the current recommended treatment algorithm within the 2018 Malaysian Clinical Practice Guidelines for the Management of Atopic Eczema. The Persatuan Dermatologi Malaysia recommends that these JAK-i can be considered as an option for systemic therapy in severe AE.

Food restriction, nutrition status, and growth in toddlers with atopic dermatitis.

BACKGROUND: Multiple factors affect growth in children with atopic dermatitis (AD). We investigated food restriction practice, nutrition, and growth in children with AD. Food restriction is defined as restriction ≥3 types of food due to AD or food allergy. METHODS: A cross-sectional study was performed in 150 children aged 12-36 months. EXCLUSION CRITERIA: recurrent infections, moderate to severe asthma, recent systemic steroid, other diseases affecting growth/nutrition. Growth parameters, SCORing Atopic Dermatitis (SCORAD), hemoglobin, hematocrit, sodium, potassium, albumin, protein, calcium, phosphate, B12, iron, and folate values were determined. Parents completed a 3-day food diary. RESULTS: The prevalence of food restriction was 60.7%. Commonly restricted foods were shellfish 62.7%, nuts 53.3%, egg 50%, dairy 29.3%, and cow's milk 28.7%. Food-restricted children have significantly lower calorie, protein, fat, riboflavin, vitamin B12, calcium, phosphorus and iron intakes and lower serum iron, protein and albumin values. Z scores of weight-for-age (-1.38 ± 1.02 vs -0.59 ± 0.96, P = .00), height-for-age (-1.34 ± 1.36 vs -0.51 ± 1.22, P = .00), head circumference-for-age (-1.37 ± 0.90 vs -0.90 ± 0.81, P = .00), mid-upper arm circumference (MUAC)-for-age (-0.71 ± 0.90 vs -0.22 ± 0.88, P = .00), and BMI-for-age (-0.79 ± 1.15 vs -0.42 ± 0.99, P = .04) were significantly lower in food-restricted compared to non-food-restricted children. More food-restricted children were stunted, underweight with lower head circumference and MUAC. Severe disease was an independent risk factor for food restriction with OR 5.352; 95% CI, 2.26-12.68. CONCLUSION: Food restriction is common in children with AD. It is associated with lower Z scores for weight, height, head circumference, MUAC, and BMI. Severe disease is an independent risk factor for food restriction.

Management of Atopic Eczema in primary care

@#Introduction: Atopic eczema (AE) is a common infammatory skin dermatosis that is increasing in prevalence. However, it can present in various clinical presentations, which leads to challenges in the diagnosis and treatment of the condition, especially in a primary care setting. Te Clinical Practice Guidelines on the Management of Atopic Eczema was developed by a multidisciplinary development group and approved by the Ministry of Health Malaysia in 2018. It covers the aspects of diagnosis, severity assessment, treatment, and referral.

Patch Testing in Children and Adolescents: 7 Years’ Experience in Hospital Kuala Lumpur

Introduction:Allergic contact dermatitis (ACD) was thought to be infrequent in children. However, there isincreasing number of case reports and cross-sectional studies that indicate ACD is not as rare aspreviously thought. This study aims to explore the pattern of allergic contact dermatitis in childrenand adolescent patients.Methods:This is a retrospective study of children and adolescent patients between 5 and 19-years-old whounderwent patch test in the Department of Dermatology, Hospital Kuala Lumpur, Malaysia fromJanuary 2010 to December 2016. Patch tests were performed with European Baseline Series andother additional commercial series. Readings were recorded according to the International ContactDermatitis Research Group recommendation.Results:There were 116 children and adolescent patients who underwent patch test. The median age of patientswas 14 years (range: 5-19) with a male to female ratio of 1: 2.7. Seventy patients had dermatitisinvolving the upper limbs (60.3%), followed by 61(52.6%) patients with dermatitis involving thelower limbs, 36(31.0%) patients with face and ears involvement and 31(26.7%) patients with truncalinvolvement. Of the 116 patients, 74(63.8%) had at least one positive patch test reaction. The 5most common allergens were nickel sulfate (39.2%), fragrance mix (17.6%), potassium dichromate(14.9%), cobalt chloride (12.2%), methylcholoroisothiozolinone and methylisothiozolinone (KathonCG) (8.1%) and thimerosal (8.1%).Conclusion:Around 64% of our children and adolescents had a positive patch test reaction. Patch testing shouldbe recommended for children and adolescents suspected to have allergic contact dermatitis.

Food and Aeroallergens Sensitisation Pattern amongst Atopic Dermatitis Children in Hospital Kuala Lumpur

Introduction:Various foods and aeroallergens are commonly attributed as the cause and exacerbating factors ofatopic dermatitis (AD) in children. This study aim to describe the common food and aeroallergensImmunoglobulin E (IgE) sensitisation pattern and the association between atopic dermatitis (AD)children of varying eczema severities and age groups.Methods:Patients who fulfil the criteria of AD were recruited and their eczema severities were assessed usingEczema Area and Severity Index (EASI) score. Skin prick test (SPT) was performed and serum totalIgE and specific IgE taken for 6 common foods (cow’s milk, soya, egg white, peanut, wheat andchicken) and 4 aeroallergens [cat dander (Felix domesticus) and house dust mites (Dermatophagoidespteronyssinus, Dermatophagoides farinae and Blomia tropicalis)]. IgE sensitisation was diagnosedpositive when the SPT yield a wheal of ≥3mm compared with the negative control and/or serumspecific IgE level of >0.35ku/L. Data was analysed using SPSS®v20.Results:Overall IgE sensitisation to at least one food and/or aeroallergen was 95%. The most prevalentfood allergen in Group A [≤1 year old] (n=10) was egg white in which both tests showed statisticalsignificant results when compared with Group B [>1 year old] (n=50). Other common food allergensincluded cow’s milk and peanut. D. pteronyssinus was the commonest aeroallergen. Aeroallergenswere significantly more prevalent in Group B when comparing both groups.Conclusion:Food and aeroallergen sensitisations were very common among AD children. Food allergens weremore common in infants and aeroallergens in older children. Bigger sample size may provide morerepresentative results.

Rhabdomyosarcoma Arising in A Giant Congenital Melanocytic Nevus

A variety of malignancies have been documented to arise within congenital melanocytic nevi (CMNs).Although the most frequent malignancy arising within a CMN is melanoma, the association betweenrhabdomyosarcoma and CMN has rarely been documented. We report a 4-month-old girl presentedwith ulcerated nodule overlying a giant CMN at the posterior back that exhibited rapid growth.Biopsy of the nodule revealed embryonal rhabdomyosarcoma in association with CMN. She receivedchemotherapy with vincristine and actinomycin D. This the first case of rhabdomyosarcoma associatedwith giant CMN reported in our local setting. Clinicians must consider rhabdomyosarcoma as one ofthe differential diagnosis in patients presenting with ulcerated nodules on giant CMN.

Vascular Anomalies: A 3-Year Review in the Paediatric Institute Hospital Kuala Lumpur Between 2013 And 2015

Introduction:Vascular anomalies, regardless of tumour or malformation, may result in significant morbidity. Thediagnosis of vascular anomalies in the paediatric group is always challenging. We aim to describe thepattern of vascular anomalies referred to the Paediatric Institute Kuala Lumpur Hospital (PIKLH).Methods:This is a 3-year retrospective review on vascular anomalies among children referred to PIKLH between2013 and 2015.Results:There were 289 children; male to female ratio of 1:2.1; aged from birth to 14 years with median age of5 months recruited. The referring diagnoses included haemangioma (71.3%), capillary malformation(13.8%), lymphatic malformation (1.7%), kaposiform hemangioendothelioma (1.0%) and others. Ahundred and sixty-one (55.7%) had lesions located at the head and neck region, followed by trunk(14.2%), lower limbs (9.3%), upper limbs (7.6%), perineum (3.8%) and multiple sites (6.9%). In 197patients (68.2%), there were no further investigations performed, 13.5% had ultrasonography, 7.3%had MRI, 4.8% had both ultrasonography and MRI; 4.1% had skin biopsy, 0.3% had angiogram.The final diagnoses were haemangioma (72.3%) of which 10 were ulcerated; capillary malformations(17.6%), combined vascular malformations (2.4%), kaposiform hemangioendothelioma (2.8%),lymphatic malformations (2.1%); venous malformations (1.4%); tufted angioma (1.0%) andarteriovenous malformations (0.3%). One hundred and nine patients (37.7%) received beta-blockers;71(24.6%) underwent laser, 16(5.5%) received sirolimus, 9(3.1%) received systemic corticosteroidswith vincristine, 4(1.4%) had systemic corticosteroids, 3(1.0%) had excision and 2(0.7%) hadsclerotherapy. The remaining patients were put under observation.Conclusion:Three-quarters of the vascular anomalies referred were hemangioma followed by vascularmalformations. Vascular anomalies have a large variation in clinical presentation. Expertise inthe diagnosis and management modalities are essential to achieve optimum outcomes. Thereforevascular anomalies are best managed in a multidisciplinary setting.

Molecular characterization of two Malaysian patients with Wiskott-Aldrich syndrome.

The Wiskott-Aldrich Syndrome (WAS) is an X-linked immunodeficiency condition characterized by microthrombocytopenia, eczema and recurrent infections. It is caused by mutations in the Wiskott-Aldrich Syndrome protein (WASP) gene. We investigated two Malay boys who presented with congenital thrombocytopenia, eczema and recurrent infections. Here we report two cases of WASP mutation in Malaysia from two unrelated families. One had a novel missense mutation in exon 1 while the other had a nonsense mutation in exon 2. Both patients succumbed to diseaserelated complications. A differential diagnosis of WAS should be considered in any male child who present with early onset thrombocytopenia, especially when this is associated with eczema and recurrent infections.

Molecular characterization of two Malaysian patients with Wiskott-Aldrich syndrome

The Wiskott-Aldrich Syndrome (WAS) is an X-linked immunodeficiency condition characterized by microthrombocytopenia, eczema and recurrent infections. It is caused by mutations in the Wiskott-Aldrich Syndrome protein (WASP) gene. We investigated two Malay boys who presented with congenital thrombocytopenia, eczema and recurrent infections. Here we report two cases of WASP mutation in Malaysia from two unrelated families. One had a novel missense mutation in exon 1 while the other had a nonsense mutation in exon 2. Both patients succumbed to diseaserelated complications. A differential diagnosis of WAS should be considered in any male child who present with early onset thrombocytopenia, especially when this is associated with eczema and recurrent infections.

A retrospective observational study of propanolol use in the treatment of infantile haemangioma: A single centre experience

Introduction: Infantile haemangioma (IH) is a common benign vascular tumour which is characterised by rapid proliferation in early infancy period followed by slow involution for years. The initial rapid growth and the location of haemangioma may result in significant morbidity. The introduction of oral Propranolol for the treatment of IH in recent years has seen many promising results though with potential risks. Objective: To review the demography, clinical pattern, management and outcome of patients with IH treated with propranolol in a paediatric dermatology referral centre. Methodology: A retrospective observational study of medical records of patients with IH treated with oral propranolol (maximum dose 2mg/kg/day) from May 2009 to May 2011 in Paediatric Institute, Kuala Lumpur Hospital. Results: A total of 17 patients (14 girls, 3 boys) were studied. They were 12 Malays (70.6%), 2 Chinese(11.8%), 2 Indians(11.8%) and 1 Indonesian (5.9%). Mostly term babies (88%). The age of presentation is from birth to 2 months old. The location of haemangiomas involve periocular (35.3%), perioral (17.6%), facial segmental (17.6%), nasal (5.9%), multiple (17.6%) and spinal (5.9%). They were started on Propranolol at a mean age of 5 months old except one at 2 years old. Five patients had concurrent adjunctive therapies. 70.6% had significant reduction of the size and colour of haemangiomas, 11.8% not significant, 11.8% unclear, and one patient defaulted follow up. Some patients developed wheezing episodes (29.4%), diarrhoea (17.6%), regurgitation (5.9%); but no serious consequences. Conclusion: Low dose oral propranolol is a safe and effective treatment with minor side effects from our experience.