A Systematic Review of Diagnostic Modalities and Strategies for the Assessment of Complications in Adult Patients with Neurofibromatosis Type 1.

BACKGROUND: Neurofibromatosis Type 1 is an autosomal dominant tumour-predisposition condition commonly diagnosed in childhood and fully penetrant by adulthood. Long-term monitoring through imaging is inconsistent and varies between high- and low-income countries. Implementation of a clinical practice guideline through a multidisciplinary clinic is instrumental to the care of adult Neurofibromatosis Type 1 patients. We aim to systematically review international diagnostic modalities and strategies to evaluate any association between a country's socioeconomic status and diagnostic modalities or strategies used for Neurofibromatosis Type 1 patients. METHODS: We searched PubMed, Embase, Web of Science, and Cochrane. Relevant clinical information on the surveillance of adult Neurofibromatosis Type 1 patients worldwide was reviewed, extracted, and synthesised. RESULTS: We identified 51 papers reporting on 7724 individuals. Multiple imaging modalities are actively employed in high-income and upper-middle-income countries for surveying adult Neurofibromatosis Type 1 patients. We did not find any relevant papers from low- and middle-income countries. CONCLUSIONS: This systematic review suggests that there is robust data on diagnostic modalities for adult Neurofibromatosis Type 1 patients in high-income countries, but not for low- and middle-income countries. There is a lack of data on consolidated diagnostic strategies from both high- and low-income countries. Efforts should be made to publish data on usual clinical practice in low- and middle-income countries to develop clinical practice guidelines describing best medical practice to fit a local context.

Cutaneous adenovirus infection in an immunocompromised child.

Adenoviruses are common viral pathogens in childhood; however, cutaneous manifestations are not well-documented. We present a rare case of cutaneous adenovirus infection in a 23-month-old boy with a background of CD40 ligand deficiency, post bone marrow transplant. The clinical morphology of the skin lesions in our patient, described as skin-colored papules with central crusting, has not been previously described and contributes to the growing literature of cutaneous adenovirus cases.

A Sensorised Glove to Detect Scratching for Patients with Atopic Dermatitis.

In this work, a lightweight compliant glove that detects scratching using data from microtubular stretchable sensors on each finger and an inertial measurement unit (IMU) on the palm through a machine learning model is presented: the SensorIsed Glove for Monitoring Atopic Dermatitis (SIGMA). SIGMA provides the user and clinicians with a quantifiable way of assaying scratch as a proxy to itch. With the quantitative information detailing scratching frequency and duration, the clinicians would be able to better classify the severity of itch and scratching caused by atopic dermatitis (AD) more objectively to optimise treatment for the patients, as opposed to the current subjective methods of assessments that are currently in use in hospitals and research settings. The validation data demonstrated an accuracy of 83% of the scratch prediction algorithm, while a separate 30 min validation trial had an accuracy of 99% in a controlled environment. In a pilot study with children (n = 6), SIGMA accurately detected 94.4% of scratching when the glove was donned. We believe that this simple device will empower dermatologists to more effectively measure and quantify itching and scratching in AD, and guide personalised treatment decisions.

Phenotype and genotype correlation of inherited epidermolysis bullosa in Indonesia.

BACKGROUND: Inherited epidermolysis bullosa (EB) is a group of genodermatoses with considerable clinical and genetic heterogeneity. Clinical diagnosis of the EB subtypes is frequently imprecise and requires confirmation with genetic testing. There is still limited study using genetic testing to identify EB subtypes in Indonesia. This study aims to identify the pathogenic variants of inherited EB patients at the Department of Dermatology and Venereology, Universitas Padjadjaran-Dr Hasan Sadikin General Hospital in Bandung, West Java, Indonesia and to describe the correlation between the phenotype and genotype of our patients. METHODS: Twelve patients clinically diagnosed with EB were included in this study. Genetic testing was performed in collaboration with KK Women's and Children's Hospital, Singapore. RESULTS: Pathogenic variants were identified in the COL7A1 gene in seven patients, namely Dominant Dystrophic EB (DDEB) with mutation types c.5945G>T, c.6218G>A, Recessive Dystrophic EB (RDEB) c.2005C>T, c.6081dup, c.1268C>T, c.1784C>T which are all known mutations. Novel mutations were found in the COL7A1 gene in two patients namely DDEB c.6253G>T and RDEB c.6740C>T. Two EB Simplex (EBS) patients showed mutation KRT14 gene as c.356T>C, c.373C>T which are known mutation. In addition, a novel mutation in LAMA3 gene c.2649del was found in one Junctional EB (JEB) patient. CONCLUSION: The molecular diagnoses of 12 Indonesian EB patients were identified, of which three were novel pathogenic variants. Concordance between the initial clinical diagnosis and genetic testing was only 33%. This demonstrated the importance of early genetic testing for accurate diagnosis, prognostication, management and genetic counselling.

Approach to clinically significant vascular anomalies in children.

Vascular anomalies consist of tumours or malformations made up of abnormal growth or collections of blood vessels that can result in functional or cosmetic problems. While many vascular anomalies are present at birth, some do not appear until later in life, making diagnosis more challenging. Although many vascular anomalies are benign, some are associated with serious complications and may involve multiple organ systems. This article highlights the important features of clinically significant vascular anomalies to help physicians promptly identify and refer these cases to a specialised multidisciplinary team for evaluation and management. The discussion includes the various presenting complaints of vascular anomalies in children, namely, rapidly growing birthmarks, painful lesions, seizures/neurological manifestations, bleeding diathesis, cardiac/airway abnormalities and part of an overgrowth syndrome.

Degos disease in a child presenting with acute renal failure.

Degos disease, also termed malignant atrophic papulosis, is a rare systemic vaso-occlusive disorder, seldom reported in the pediatric population. The pathognomonic skin lesion in Degos disease is a papule with an atrophic porcelain-white center with an erythematous, telangiectatic rim. The benign form of the disease remains limited to the skin, whereas, in others, it progresses to thrombotic vasculopathy in multiple organs including the gastrointestinal, cardiorespiratory, and central nervous systems, with a high mortality rate. We present a rare case of Degos disease in an adolescent female, presenting as acute renal failure secondary to thrombotic vasculopathy, with the characteristic skin lesion distinctively seen on dermoscopy.

Cellular neurothekeoma occurring at the site of radiation therapy in a child with medulloblastoma.

Cellular neurothekeoma is a rare, benign cutaneous neoplasm. We report a case of cellular neurothekeoma arising on the mid-back of a 10-year-old boy within the previous radiation therapy field for medulloblastoma. Clinical features of cellular neurothekeoma in children are similar to those in adults, except that there have been no reports of local recurrence in children following surgical excision, and the presence of atypical histological features does not predict clinical behavior. Recognition of this entity in children is important to avoid misdiagnosis and overly aggressive treatments.

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.

Pediatric patch testing in a multi-ethnic Asian population: A retrospective review.

BACKGROUND: Pediatric allergic contact dermatitis (ACD) is increasingly prevalent. Patch testing is the gold-standard diagnostic investigation. The aims of our study were to describe the clinical profile of pediatric patients with ACD in a multi-ethnic Asian population and identify the common contact allergens. METHODS: This was a retrospective study involving children and adolescents aged 16 years or younger with clinically suspected ACD who underwent patch testing between January 2007 and March 2020 at two institutions in Singapore. Information pertaining to their demographics, atopy history, clinical presentation, and patch test results was analyzed. RESULTS: A total of 252 patients were included. The mean age was 10.9 years (1.0-16.7 years). The majority were Chinese (79.8%) and girls (57.5%). Many (66.3%) had atopic dermatitis (AD), which was mild. The most common presentation was an acral eczematous rash. The sensitization rate was 50.0%. The most frequent reactions were to nickel sulfate (49.2%) and fragrance mix (19.1%). The overall rate of relevant positive patch tests was 72.5%. Patients with AD were less likely to have a reaction to fragrance mix (p = .019) and more likely to have a reaction to disperse blue (p = .041). Compared to younger children, adolescents were less likely to have a positive patch test (p = .008). Indians were also less likely to have a positive reaction (p = .004). CONCLUSION: Metals and fragrances were the most common allergens causing childhood ACD in Singapore. Patients with AD were less likely to be sensitized to fragrances and more likely to be sensitized to disperse blue dye.

Juvenile xanthogranulomas in Asian children.

Juvenile xanthogranuloma (JXG) is the most common non-Langerhans cell histiocytic disorder. It can rarely be associated with systemic involvement. There is a paucity of literature on JXG in Asian children. We aim to describe the epidemiology, clinical features, systemic associations, histological features and outcome of a cohort of Asian children with JXG, and review the literature on the condition. We retrospectively reviewed the demographic, clinical and histological data of patients less than 16 years of age, diagnosed with JXG at our tertiary pediatric hospital between January 2002 and April 2019. A total of 147 children with JXG were identified, with a slight male preponderance of 53.1%. The median age of the onset was 15.5 months, with 69.4% presenting before 2 years of age. There was no racial predilection. The most frequently involved site was the head and neck region (44.2%). The majority of patients (76.2%) presented with a solitary lesion. Spontaneous resolution was documented in 57.7% of our patients with mean duration to resolution of 18.8 months. The proportion and speed of resolution did not differ in children with single or multiple lesions. No ophthalmologic complications were detected in our study cohort. JXG in children is generally limited to the skin and is rarely associated with systemic involvement, including the eye. Unless clinically indicated, the results from our study does not support routine screening for juvenile myelomonocytic leukemia, eye or systemic complications, even in the setting of multiple cutaneous JXGs.

Two Histologic Patterns of Lymphomatoid Papulosis Occurring in a Child: A Matter of Timing?

There are several histologic patterns seen in lymphomatoid papulosis, with the possibility of different subtypes occurring in the same patient. We report a case of lymphomatoid papulosis presenting with 2 histologic subtypes (types A and B) occurring concomitantly in a 10-year-old child, and postulate that the different subtypes occur dependent on the age of the lesion biopsied. Incidentally, one of the biopsies also shows a rarely seen pattern of pseudoepitheliomatous hyperplasia in a pediatric lymphomatoid papulosis patient.

Effect of pine-tar bath on disease severity in moderate-to-severe childhood eczema: an investigator-blinded, crossover, randomized clinical trial.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory disease associated with pruritus and sleep loss. Pine-tar has long been used for various chronic skin conditions in which its polycyclic aromatic hydrocarbon (PAH) component is anti-inflammatory and its resin acids antiseptic. The null hypothesis of this trial is that there is no difference in clinical efficacy between a pine-tar product and its vehicle for AD. METHODS: A 3-month, investigator-blinded, crossover, randomized control trial (RCT) was conducted in which each patient was assigned to bathing with pine-tar bath oil for one month and vehicle bath oil for another, with a washout period of 1-month in-between. Acceptability and efficacy of the bath products were measured. Disease severity scores (scoring atopic dermatitis (SCORAD) and patient-oriented eczema measure (POEM), quality of life questionnaires, noninvasive skin biophysiological measurements, blood IgE levels, and Staphylococcus aureus (SA) colonization status were assessed before and following bathing. RESULTS: Significant improvements were found in total SCORAD (p = .030), POEM (p = .004), SA colonization status (p = .002), and log-transformed IgE level (p = .009) among patients who bathed with pine-tar in the overall RCT study using intention-to-treat analysis. For per protocol analysis, significant improvements were found in total SCORAD (p = .024), objective SCORAD (p = .011), extent (p = .014), intensity (p = .032), pruritus (p = .047), POEM (p = .044), SA colonization status (p = .035), and log-transformed IgE level (p = .028). Acceptability to both bath-oils was good, and no product-related serious adverse events were recorded. CONCLUSIONS: Bathing with pine-tar is an efficacious and recommendable adjuvant practice for AD patients. Disease improvement is associated with reduction of SA and IgE.