Scurvy presenting as difficulty in walking in a child.

Scurvy, a disease caused by ascorbic acid (vitamin C) deficiency, is a rare disease in the modern world. We report a case of a boy in middle childhood, with a background of autism, presenting bed-bound due to progressive bilateral lower limb pain, with concomitant rashes, bleeding gums and worsening lethargy. Detailed dietary history revealed a severely restricted diet. Physical examination showed bilateral lower limb ecchymoses, perifollicular hemorrhages, perifollicular hyperkeratosis and cockscrew hairs which are pathognomonic features of scurvy. A low serum ascorbic acid level confirmed the diagnosis. Therapy with oral vitamin C supplement and rehabilitation with multidisciplinary care was successful, with complete resolution of symptoms. This case emphasises the importance of thorough dietary evaluation in children with autism and food selectivity presenting with non-specific symptoms. Physician awareness of nutritional deficiencies avoids unnecessary extensive investigations and sub-specialty referrals and translates to savings in medical expenses.

Monozygotic twins with identical premature timing of acne onset: A Case report.

Acne vulgaris, a common dermatological condition that affects most adolescents and young adults, can indicate an underlying pathology if present prematurely in mid-childhood. Premature acne can be caused by premature adrenarche secondary to non-classical congenital adrenal hyperplasia (NC-CAH), a condition arising from 21-hydroxylase deficiency. This report describes a pair of monozygotic twin brothers with identical premature onset of acne, who were found to have an identical homozygous mutation in the promoter region of the CYP21A2 gene. While it is widely known that NCCAH is associated with genetic changes, the drive behind onset of adrenarche are widely unknown. As such, this report provokes thoughts on whether adrenarche could be influenced by adrenal genetic polymorphisms.

A novel NSDHL variant in CHILD syndrome with gastrointestinal manifestations and localized skin involvement.

BACKGROUND: CHILD syndrome is an X-linked dominant disorder associated with pathogenic mutations in the NSDHL gene. The condition is predominantly found in females as it is lethal in males. Most cases present at birth with extensive unilateral ichthyosiform erythroderma involving the trunk and limbs. Milder and less extensive presentations have been reported, leading to misdiagnosis especially during early childhood. METHODS AND RESULTS: We report an adult female of Malay ancestry who presented with minimal skin and limb involvement. She was only diagnosed in adulthood when she presented with gastrointestinal symptoms and worsening of skin manifestations. The clinical diagnosis was suspected after a combination of clinical, pathological and immunohistochemistry correlation, and molecularly confirmed with the discovery of a frameshift variant in NSDHL. The novel variant was inherited from her mother who had some linear hypopigmented patches over the medial aspects of both her arms and right forearm. CONCLUSION: We uncovered a novel frameshift variant associated with presentations that cast a new light on the clinical features of CHILD syndrome.

Epidermolytic ichthyosis in a child and systematized epidermolytic nevi in the mosaic parent associated with a KRT1 variant.

Epidermolytic ichthyosis and epidermolytic nevi share the same histopathological features of epidermolytic hyperkeratosis, characterized by distinctive vacuolar degeneration and hypergranulosis of the superficial epidermis. Both are caused by pathogenic variants in either of two keratin genes KRT1or KRT10, with epidermolytic ichthyosis presenting as a generalized phenotype and epidermolytic nevi presenting as a mosaic phenotype. We report a boy who presented as epidermolytic ichthyosis, with diffuse erythema, superficial erosions and flaccid blisters at birth progressing to generalized ichthyosis. He was found to have inherited a novel KRT1 variant from his mother who presented with extensive epidermolytic nevi or mosaic form of epidermolytic ichthyosis, with extensive, linear and Blaschkoid verrucous, hyperkeratotic plaques over the trunk and limbs. This case highlights the importance of recognising post-zygotic mosaicism which might be transmitted to a child, and the different presentations for germline and mosaic carriers.

CARD14-associated papulosquamous eruption (CAPE) in a toddler responding to treatment with acitretin.

CARD14-associated papulosquamous eruption (CAPE) is a rare autosomal dominant dermatosis that presents classically in early childhood with clinical features of both psoriasis and pityriasis rubra pilaris (PRP). The disease is known to be refractory to topical and systemic therapies classically used for psoriasis, with the majority of reported cases requiring treatment with biologics, such as ustekinumab and secukinumab. We present a toddler with a clinical presentation consistent with CAPE and found to have a novel heterozygous variant of the CARD14 gene. She was refractory to treatment with topical emollients and topical corticosteroids, but responsive to oral acitretin.

Dupilumab for children and adolescents with atopic dermatitis: An Asian perspective.

Atopic dermatitis (AD) is a common, chronic, recurrent inflammatory skin disease. Poorly controlled AD can lead to reduced quality of life (QoL) and psychosocial impairment. Dupilumab is the first approved monoclonal antibody targeting type 2 inflammation, for adolescent and adult patients with moderate-to-severe AD. We performed a retrospective analysis of the efficacy and safety of dupilumab in a cohort of Asian children and adolescents with moderate-to-severe AD. Clinical response was documented with investigator global assessment (IGA) and eczema area and severity index (EASI) scores. Improvement in QoL was assessed using child dermatology life quality index (CDLQI) or Teenager's quality of life (T-QoL), and caregivers' QoL was assessed using dermatitis family impact (DFI) questionnaire. Twelve patients were recruited, aged between 6 to 18 years of age (mean 13.3 years), with mean duration of AD of 9.8 years. At baseline, the mean IGA score was four and the mean EASI was 48.2. The mean T-QoL and DFI scores at baseline were 18.7 and 19.6, respectively. After 12 to 16 weeks of treatment, the mean IGA score decreased to 2.2. The mean EASI decreased to 19.3 with mean reduction of 28.9. The mean T-QoL decreased to 7.5 with mean reduction of 11.2, and the mean DFI decreased to 8.6 with mean reduction of 11. Adverse events included mild conjunctivitis in two patients and paradoxical head and neck erythema in one patient. Our study supports dupilumab as an effective and safe treatment option for Asian children and adolescents with moderate-to-severe AD.

Utility of mammaglobin and gross cystic disease fluid protein-15 (GCDFP-15) in confirming a breast origin for recurrent tumors.

There are limited data that compare the utility of immunohistochemical detection of mammaglobin with Gross Cystic Disease Fluid Protein-15 (GCDFP-15) in locally recurrent and metastatic breast cancers. Forty-three local and 72 distant recurrences of breast cancer, 8 metastatic lesions to the breast from other organs, and 30 metastases from non-breast primaries were immunohistochemically stained with mammaglobin and GCDFP-15 antibodies. Mammaglobin was expressed in 55 (47.8%) and GCDFP-15 detected in 13 (11.3%) locally and distantly recurrent breast cancers. A higher percentage of tumor cells was stained with mammaglobin at greater staining intensity than GCDFP-15, for both metastatic and locally recurrent breast cancers. The difference in staining intensity as well as mean percentage of tumor cells stained for both markers was statistically significant (p < 0.005). Metastases to the breast from other organs and metastatic lesions from non-breast primaries were uniformly negative for both mammaglobin and GCDFP-15. Our study demonstrates that immunohistochemical analysis of mammaglobin is superior to GCDFP-15 in detecting a tumor of breast origin, and can be incorporated into immunohistochemical panels evaluating tumors from unknown primary sites.