Genotype-Phenotype Correlation in Junctional Epidermolysis Bullosa: Signposts to Severity.

Junctional epidermolysis bullosa (JEB) is a rare autosomal recessive genodermatosis with a broad spectrum of phenotypes. Current genotype-phenotype paradigms are insufficient to accurately predict JEB subtype and characteristics from genotype, particularly for splice site variants, which account for over a fifth of disease-causing variants in JEB. This study evaluated the genetic and clinical findings from a JEB cohort, investigating genotype-phenotype correlations through bioinformatic analyses and comparison with previously reported variants. Eighteen unique variants in LAMB3, LAMA3, LAMC2, or COL17A1 were identified from 17 individuals. Seven had severe JEB, 9 had intermediate JEB, and 1 had laryngo-onycho-cutaneous syndrome. Seven variants were previously unreported. Deep phenotyping was completed for all intermediate JEB cases and demonstrated substantial variation between individuals. Splice site variants underwent analysis with SpliceAI, a state-of-the-art artificial intelligence tool, to predict resultant transcripts. Predicted functional effects included exon skipping and cryptic splice site activation, which provided potential explanations for disease severity and in most cases correlated with laminin-332 immunofluorescence. RT-PCR was performed for 1 case to investigate resultant transcripts produced from the splice site variant. This study expands the JEB genomic and phenotypic landscape. Artificial intelligence tools show potential for predicting the functional effects of splice site variants and may identify candidates for confirmatory laboratory investigation. Investigation of RNA transcripts will help to further elucidate genotype-phenotype correlations for novel variants.

IgA nephropathy in adults with epidermolysis bullosa.

Epidermolysis bullosa (EB) is a devastating genetic condition caused by mutations in genes that give rise to aberrant proteins. There are 16 different such proteins implicated in EB that are important in maintaining the integrity of the dermoepidermal junction. It is classified into four major subtypes: (i) EB simplex; (ii) junctional EB (JEB); (iii) dystrophic EB (DEB); and (iv) Kindler EB. Renal disease is a recognized complication of EB and the aetiology is complex. We describe our experience of managing five patients with EB and IgA nephropathy. We recommend that patients with recessive DEB and JEB routinely have the following monitored: renal function, urinary albumin/creatinine ratio, urine analysis, serum albumin levels and immunoglobulins; specifically serum IgA. Management of IgA nephropathy in the context of EB should be tailored to the individual and be carried out within a specialist multidisciplinary team. Our case series provides important insights into the treatment of IgA nephropathy in patients with EB and will help inform treatment in this rare genetic disease. Case series and reports like ours are key in gaining real-life data to quantify the actual risk of morbidity and mortality from each of the treatment modalities discussed.

Paediatric dermatology teleconsultations: a survey of healthcare professionals in the UK.

The COVID-19 pandemic catapulted dermatology services into a digital era, with the rapid introduction of teleconsultations. The UK National Health Service operational planning guidance recommends ≥ 25% of consultations are delivered remotely. There is a lack of data regarding the acceptability and effectiveness of paediatric dermatology teleconsultations. We surveyed UK healthcare professionals (HCPs) to explore their experiences of teleconsultations in paediatric dermatology, with a focus on follow-up consultations for paediatric eczema (PE), to inform a future clinical trial. There were 119 responses. Pre-pandemic, 37% provided some form of teleconsultation service, rising to 92% post-pandemic. In total, 41% (n = 49) now carry out > 25% of consultations remotely. We found 55% felt teleconsultations were less effective than face-to-face ones for PE follow-up. Eighty HCPs offered teleconsultations for PE. Among the HPCs who offered teleconsultations for PE, the most effective format for follow-up consultations was felt to be telephone with photographs (52/80, 65%). Our results demonstrate varying opinion on the effectiveness and optimal format of paediatric teleconsultations, supporting the need for further research.

Successful use of rituximab, an anti-CD20 monoclonal antibody, to treat IgA nephropathy in a patient with recessive dystrophic epidermolysis bullosa.

We describe the successful use of rituximab for the treatment of IgA nephropathy in a patient with recessive dystrophic epidermolysis bullosa. To our knowledge, this is the first reported case in the literature.

Treatment of paediatric eczema with narrowband ultraviolet light B therapy.

BACKGROUND: Narrowband ultraviolet B phototherapy (nbUVB) is a well-established, well-tolerated and efficacious treatment for eczema. There is a distinct lack of literature surrounding the therapeutic use of nbUVB in eczema in children and especially in children with higher skin phototypes (III to VI). METHODS: We undertook a retrospective review of children aged 18 years and under with eczema who had undergone nbUVB in our department between 1 January 2011 and 31 December 2017. Abstracted data included sex, age, skin phototype, severity as graded by a paediatric dermatologist, cumulative dose, response to treatment and subsequent remission. RESULTS: In total, 60 children had nbUVB. Of those, 56 had more than 10 nbUVB exposures. Complete or near-complete clearance was achieved in 31 children (52%). Of those, 24 (77%) had a skin phototype of III or greater. Clinical remission rates of these patients were 100%, 87%, 57% and 52% at 0, 3, 6 and 12 months, respectively. Seventeen patients (28%) suffered side effects. Most commonly these were mild side effects such as erythema and xerosis. CONCLUSION: We have demonstrated that nbUVB is a safe, well-tolerated and efficacious form of treatment for children with atopic eczema. We have shown it to be effective in those with skin phototypes greater than III and shown that they are a group that may derive greater long-term efficacy. In clinical practice, preference for nbUVB as second-line treatment, over oral systemics, should always be considered.

Primary cutaneous osteosarcoma of the scalp in an immunosuppressed individual: A case report and review of the literature.

We report a case of a 76-year-old man presenting with a 12-month history of a solitary lesion on his scalp. The histopathology was consistent with a grade 2/3 osteosarcoma extending to the subcutis. Full-body imaging excluded any involvement of the underlying bony tissue or solid organ malignancy, thus a diagnosis of primary cutaneous osteosarcoma (PCO) was made. Given the exceedingly rare nature of PCO, we discuss the clinico-pathological features of this case and those previously reported in the literature.

Chemotherapy-induced skin toxicity and capillary leak syndrome.

BACKGROUND: The occurrence of chemotherapy-related adverse cutaneous reactions in the setting of capillary leak syndrome (CLS) is quite rare. Our objective was to identify the type of skin reactions associated with CLS. METHODS: Leukemia or hematopoietic stem cell transplant patients between January 2010 and December 2017 were identified, and medical records were reviewed for a dermatology consultation occurring concomitantly with CLS. RESULTS: Five patients were identified, two with a diagnosis of toxic erythema of chemotherapy (TEC) and three others with a skin diagnosis of toxic epidermal necrolysis (TEN). Pathology of all patients was available for clinical-pathologic confirmation. CONCLUSIONS: Although TEC is generally self-limited, both TEC and TEN can present with severe adverse skin manifestations during CLS secondary to toxicity from chemotherapy.

Clinical and histopathological spectrum of toxic erythema of chemotherapy in patients who have undergone allogeneic hematopoietic cell transplantation.

OBJECTIVE/BACKGROUND: Toxic erythema of chemotherapy (TEC) is a well-recognized adverse cutaneous reaction to chemotherapy. Similar to many skin diseases, the clinical presentations may vary. Our objective is to expand on the typical and atypical clinical and histopathological presentations of TEC. METHODS: Forty patients with a diagnosis of TEC were included from 500 patients who had undergone an allogeneic hematopoietic stem cell transplant. Relevant information and demonstrative photos and pathology were selected. RESULTS: Classic clinical presentations included hand and foot erythema and dysesthesias; atypical presentations included facial involvement, hyperpigmentation, dermatomyositis-like, and erythroderma associated with capillary leak syndrome. CONCLUSION: The diagnosis of TEC should be considered after a correlation of clinical and histological findings in conjunction with a timeline of chemotherapy administration. Suggested criteria for the diagnosis of TEC may be helpful to dermatologists and clinicians when caring for these patients.

Temporal trends in prenatal risk factors for the development of infantile hemangiomas.

BACKGROUND/OBJECTIVES: Specific maternal risk factors have recently been identified in the development of infantile hemangiomas (IH), including gestational diabetes (GDM), maternal antihypertensive medication use or gestational hypertension (GHTN), maternal progesterone use, and artificial reproductive technologies (ART). We sought to explore the change in incidence of these risk factors over time and determine their association with the increased incidence of hemangiomas over 35 years, as previously reported. METHODS: The charts of 869 mother and infant pairs (infants previously diagnosed with IH between January 1, 1976, and December 31, 2010) were reviewed for prenatal complications. Rates of the prenatal complications over the 35-year period in birth mothers of infants diagnosed with IH were determined and evaluated by year of diagnosis (1976-1990, 1991-2000, and 2001-2010). RESULTS: Over the 35-year period in which the incidence of IH was previously examined, maternal age at delivery, prepregnancy body mass index (BMI), use of ART, maternal progesterone use, placental abnormalities, and GDM also increased. CONCLUSIONS: GDM, ART, and maternal progesterone use increased over the past 35 years, mirroring the previously reported trend of increasing incidence of IH. Maternal age and BMI also increased in mothers of infants with IH. Further exploration of this association may direct future research in the pathogenesis of infantile hemangiomas.

Association between obesity and pediatric psoriasis.

Obese children are at higher risk of developing psoriasis, and obesity severity is correlated with psoriasis severity. The relationship between obesity and pediatric psoriasis was explored in a well-defined population. Obesity and psoriasis coexist at diagnosis, but it is likely that obesity commonly precedes psoriasis in children.

The in-hospital burden of hidradenitis suppurativa in patients with inflammatory bowel disease: a decade nationwide analysis from 2004 to 2014.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory disease that significantly affects the patient's quality of life. Multiple studies have shown a strong association between HS and inflammatory bowel disease (IBD). Our primary goal was to explore the in-hospital burden of HS on patients with IBD. Our secondary goal was to establish unique baseline characteristics and comorbidities of IBD patients with HS. METHODS: This was a retrospective cohort study using the National Inpatient Sample (NIS) database for the years 2004 through 2014. All patients with ICD-9 CM codes for any diagnosis of IBD and HS were included. The primary outcome was the medical and financial burden of HS on patients with IBD. Medical burden was measured by in-hospital morbidity and mortality, and financial burden was measured by resource utilization. RESULTS: A total of 3,079,332 admissions with IBD were recorded, of which 4369 had a concomitant diagnosis of HS. IBD-HS patients were significantly younger and mostly African-American females; they were more likely to be smokers, obese, and have diabetes mellitus, depression, and anemia. There was no mortality difference between the IBD-HS and IBD-only groups; nevertheless, there was a higher likelihood of developing sepsis in the IBD-HS cohort (4.9% vs. 2.6%; P < 0.001). Patients with IBD-HS had an increased hospital length of stay (5 vs. 4 days; P < 0.001) and higher total hospitalization costs ($13,272 vs. $12,237; P = 0.013). CONCLUSIONS: This large-scale study strengthens the evidence that these two inflammatory conditions are truly associated and establishes their joint effect on overall morbidity, mortality, and resource utilization.

Agminated segmental plaque-type blue nevus associated with hypertrichosis and soft tissue hypertrophy: Report of a case and review of the literature.

Blue nevi are common skin neoplasms that typically present as asymptomatic solitary papules, although they may rarely occur in an agminated configuration. We describe a case of agminated blue nevus in a segmental facial distribution associated with soft tissue hypertrophy and hypertrichosis in a 16-year-old boy and present a review of the literature. Although they are generally considered to be benign, concurrent soft tissue changes occurring within an agminated blue nevus should be investigated thoroughly to exclude alternate diagnoses.