Proposal for a 6-step approach for differential diagnosis of neonatal erythroderma

The broad differential diagnosis of neonatal erythroderma often poses a diagnostic challenge. Mortality of neonatal erythroderma is high due to complications of the erythroderma itself and the occasionally severe and life-threatening underlying disease. Early correct recognition of the underlying cause leads to better treatment and prognosis. Currently, neonatal erythroderma is approached on a case-by-case basis. The purpose of this scoping review was to develop a diagnostic approach in neonatal erythroderma. After a systematic literature search in Embase (January 1990 - May 2020, 74 cases of neonatal erythroderma were identified, and 50+ diagnoses could be extracted. Main causes were the ichthyoses (40%) and primary immunodeficiencies (35%). Congenital erythroderma was present in 64% (47/74) of the cases, predominantly with congenital ichthyosis (11/11; 100%), Netherton syndrome (12/14, 86%) and Omenn syndrome (11/23, 48%). Time until diagnosis ranged from 102 days to 116 days for cases of non-congenital erythroderma and congenital erythroderma respectively. Among the 74 identified cases a total of 17 patients (23%) died within a mean of 158 days and were related to Omenn syndrome (35%), graft-versus-host disease (67%) and Netherton syndrome (18%). Disease history and physical examination are summarized in this paper. Age of onset and a collodion membrane can help to narrow the differential diagnoses. Investigations of blood, histology, hair analysis, genetic analysis and clinical imaging are summarized and discussed. A standard blood investigation is proposed, and the need for skin biopsies with lympho-epithelial Kazal-type related Inhibitor staining is highlighted. Overall, this review shows that diagnostic procedures narrow the differential diagnosis in neonatal erythroderma. A 6-step flowchart for the diagnostic approach for neonatal erythroderma during the first month of life is proposed. The approach was made with the support of expert leaders from international multidisciplinary collaborations in the European Reference Network Skin-subthematic group Ichthyosis.Peer reviewe

Stroke severity, its correlates and impact on thrombolysis in a population-based study

OBJECTIVE: Data about the distribution of stroke severity and its correlates are sparse. In a population-based approach, we determined the NIH Stroke Scale Score (NIHSSS) and studied associations with demographic variables, stroke unit care, etiology, the onset assessment interval (OAI), and the rate of thrombolysis. METHODS: We performed a databank-based post-hoc analysis of data ascertained during the prospective, population-based stroke study among the 188,015 permanent residents of Basel City, Switzerland. RESULTS: In 246/269 (91.4%) patients, NIHSSS was available. The median NIHSSS was 5.0 +/- 6.0. NIHSSS 0-6, 7-15, and 0.001), shorter OAI (p = 0.009), and thrombolytic therapy (p > 0.001). In multivariate regression analyses, age, OAI, and thrombolysis correlated independently with higher NIHSSS. Stroke unit patients differed from non-stroke unit patients in shorter OAI, younger age, and higher NIHSSS. CONCLUSION: In a geographically defined stroke population, 1/3 patients had moderate-to-severe stroke. Patients with less severe strokes were younger, sought medical attention later and were less likely to receive thrombolysis. Thus, public stroke awareness programs might consider targeting also younger individuals and stress that also mild-to-moderate strokes benefit from emergency medical care

Analysis of the relationship between total cholesterol, age, body mass index among males and females in the WHO MONICA Project

OBJECTIVE: To explore the relationship between hypercholesterolaemia, age and BMI among females and males. DESIGN: Population-based cross-sectional survey. SUBJECTS: The data came from the initial surveys of the WHO MONICA Project. In all, 27 populations with 48 283 subjects (24 017 males and 24 266 females) aged 25-64 y were used for the analysis. MEASUREMENTS: Total cholesterol, weight, height, BMI, prevalence of hypercholesterolaemia (PHC) defined as cholesterol >/=6.5 mmol/l, and the prevalence of obesity (POB) defined as BMI >/=30 kg/m(2). RESULTS: PHC increased with age, with PHC in males being significantly higher than in females at age range 25-49 y and significantly lower than in females at age range 50-64 y. Age-related increase in hypercholesterolaemia was steeper in females than in males. There was a statistically significant positive association between hypercholesterolaemia and BMI. Multiple logistic regression analysis revealed a negative statistically significant (P<0.001) effect modification involving age and BMI on the risk of having hypercholesterolaemia both in females and males. The relation between PHC and BMI became weaker in higher age groups, with no statistically significant association in females aged 50-64 y. CONCLUSION: Public health measures should be directed at the prevention of obesity in young adults since the strongest effect of obesity on the risk of hypercholesterolaemia has been found in subjects aged 25-39 y

Cutaneous lesions in COVID-19 patients

Aside from the typical respiratory symptoms resulting from an infection with SARS-CoV-2, there are reports of cutaneous lesions in patients diagnosed with a SARS-CoV-2 infection. There are reports of multiple groups of skin lesions presenting in different stages of this diagnosis. The most common reported groups are chilblains, vesicular eruptions, morbilliformexanthems, acute urticaria and livedo. It is unlikely that all these groups of skin lesions are distinctive of an infection with SARS-CoV-2. Chilblains of new onset, however, could possibly be a distinctive symptom of a mild/asymptomatic infection with SARS-CoV-2. It is recommended to consider an infection with SARS-CoV-2 in the differential diagnosis in patients presenting with these groups of skin lesions. Consider testing for SARS-CoV-2 and consult the dermatologist if needed, especially in case of chilblains, to ensure histopathological evaluation of the skin lesions to increase knowledge of the underlying pathophysiology

Cutaneous lesions in COVID-19 patients

Aside from the typical respiratory symptoms resulting from an infection with SARS-CoV-2, there are reports of cutaneous lesions in patients diagnosed with a SARS-CoV-2 infection. There are reports of multiple groups of skin lesions presenting in different stages of this diagnosis. The most common reported groups are chilblains, vesicular eruptions, morbilliformexanthems, acute urticaria and livedo. It is unlikely that all these groups of skin lesions are distinctive of an infection with SARS-CoV-2. Chilblains of new onset, however, could possibly be a distinctive symptom of a mild/asymptomatic infection with SARS-CoV-2. It is recommended to consider an infection with SARS-CoV-2 in the differential diagnosis in patients presenting with these groups of skin lesions. Consider testing for SARS-CoV-2 and consult the dermatologist if needed, especially in case of chilblains, to ensure histopathological evaluation of the skin lesions to increase knowledge of the underlying pathophysiology

Adhesive stripping to remove epidermis in junctional epidermolysis bullosa for revertant cell therapy

Background Replacing mutant skin in epidermolysis bullosa (EB) by epithelial sheets of transduced autologous keratinocytes is the essential surgical step of ex vivo gene therapy. The same applies for revertant cell therapy in which epithelial sheets of revertant autologous keratinocytes are used. Revertant cells can be found in patches of normal skin in patients with junctional EB (JEB) due to revertant mosaicism caused by in vivo reversions. Objectives To develop a technique of adhesive tape stripping as a method for epidermis removal to prepare the acceptor site for revertant cell therapy in a patient with revertant mosaic JEB. Methods We performed revertant cell therapy on a patient with mosaic type XVII collagen-deficient non-Herlitz JEB. Skin biopsies were taken from revertant skin on the wrist. Graft production took place on a 3T3-J2 feeder layer resulting in two 6 x 7 cm grafts. An innovative method that uses the pathological plane of least resistance of JEB skin was developed to prepare the acceptor site. A polyacrylate adhesive plaster was placed on the skin and then pulled off with the epidermis. Results The epidermis was easily removed with the plaster. The skin separated at the level of the lamina lucida, leaving a bloodless wound bed of naked lamina densa. Transplantation was successful; the acceptor site healed without scarring. However, blistering could be provoked. The functional repair was not achieved due to the low percentage of revertant cells in the graft. Conclusions We conclude that adhesive stripping is a simple, effective and almost painless procedure for removing epidermis for ex vivo cell therapy in EB