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We report a case of pemphigus vulgaris in which a recalcitrant area of erosion on the cheek cleared only when topical tacrolimus was used in addition to a regime of systemic therapy consisting of cyclophosphamide and prednisolone. Clinical improvement occurred within 10 days of applying topical tacrolimus with healing of erosions and reduction in pain and burning sensations. Topical tacrolimus may inhibit local activation of T lymphocytes through altered expression of cytokines such as interleukin- 1, -4 and -5, tumour necrosis factor-α and interferon-γ. Some of these cytokines may also contribute directly to increasing keratinocyte fragility in the aetiology of pemphigus vulgaris erosions. This case illustrates that topical tacrolimus may be a useful adjunct in the management of patients with pemphigus vulgaris. [ABSTRACT FROM AUTHOR]

This article presents information about the research paper entitled "Stimulation of phospholipase A2 in epidermal extracts by a phosphatase inhibitor," presented by P. H. Cartwright, H. J. Yardley, and others at the British Society for Investigative Dermatology Annual Meeting, Cambridge, September 1987. Phospholipase A2 is present in normal epidermis and its activity is raised in psoriasis. Phospholipase A2 activity is controlled by the protein lipocortin, the inhibitory activity of which is determined by its degree of phosphorylation: the more it is phosphorylated, the less it inhibits.

This series is your opportunity to seek an expert answer to a puzzling question -- clinical, professional or otherwise. [ABSTRACT FROM AUTHOR]

Simple Summary: Large granular lymphocyte leukaemia associated with severe neutropaenia is extremely rare in dogs. A search of the veterinary literature identified only two case reports. The present study included six dogs with this condition. All patients presented with pyrexia and lethargy and had severe neutropaenia on haematology (median neutrophil count 0.07 × 109/L) with no peripheral lymphocytosis. In all dogs, bone marrow cytology revealed infiltration of granular T lymphocytes. All patients received systemic chemotherapy (five received chlorambucil and prednisolone, one received vincristine, cyclophosphamide, and prednisolone); resolution of the neutropaenia was observed within 19 weeks. Two dogs were euthanised 133 and 322 days after diagnosis due to progressive disease, two were lost to follow-up after 224 and 357 days, and two were alive and disease free at 679 and 721 days. The aim of this retrospective study was to describe the clinical characteristics, treatments, and outcomes of dogs with chronic LGL leukaemia with suspected immune-mediated cytopaenia(s) upon presentation. This condition should be considered in the differential diagnosis of patients presenting with severe neutropaenia. Canine chronic large granular lymphocyte (LGL) leukaemia is commonly characterised by moderate to marked lymphocytosis but not neutropaenia. In humans, LGL leukaemia is often associated with autoimmune disorders, including immune-mediated cytopaenias (mainly neutropaenia). This presentation is rare in dogs. The aim of this retrospective study was to describe the clinical characteristics, treatments, and outcomes of dogs with chronic LGL leukaemia with suspected immune-mediated cytopaenia. Six dogs with a median age of 4.5 years (range 2–8 years) were included in the study. The most common presenting signs were pyrexia and lethargy. All dogs had severe neutropaenia (median neutrophil count 0.07 × 109/L), three had thrombocytopaenia (median platelet count 66 × 109/L), and one had anaemia (HCT 0.32 L/L). In all dogs, bone marrow cytology revealed infiltration of granular T lymphocytes; PARR analysis confirmed clonality in four, and bone marrow flow cytometry identified CD3+ CD8+ neoplastic cells in two cases. All patients received systemic chemotherapy, and the cytopaenias resolved after 1–19 weeks. Two dogs were euthanised 133 and 322 days after diagnosis, two were lost to follow-up after 224 and 357 days, and two were alive at 546 and 721 days. A subset of LGL leukaemia in dogs is associated with immune-mediated cytopaenia and has a unique clinical presentation. [ABSTRACT FROM AUTHOR]

Erythropoietic protoporphyria is an inherited disorder of porphyrin metabolism, in which reduced activity of the enzyme ferrochelatase leads to accumulation of protoporphyrins in erythrocytes. Protoporphyrins are photoactivated by ultra-violet light causing tissue damage by release of free oxygen radicals, which manifests as photosensitivity. The majority of cases of erythropoietic protoporphyria present in childhood although sometimes symptoms are delayed until the second decade. We report here a case presenting in adulthood and discuss the risk of liver disease in the condition. [ABSTRACT FROM AUTHOR]

Data normalization is a data preprocessing task and one of the first to be performed during intellectual analysis, particularly in the case of tabular data. The importance of its implementation is determined by the need to reduce the sensitivity of the artificial intelligence model to the values of the features in the dataset to increase the studied model's adequacy. This paper focuses on the problem of effectively preprocessing data to improve the accuracy of intellectual analysis in the case of performing medical diagnostic tasks. We developed a new two-step method for data normalization of numerical medical datasets. It is based on the possibility of considering both the interdependencies between the features of each observation from the dataset and their absolute values to improve the accuracy when performing medical data mining tasks. We describe and substantiate each step of the algorithmic implementation of the method. We also visualize the results of the proposed method. The proposed method was modeled using six different machine learning methods based on decision trees when performing binary and multiclass classification tasks. We used six real-world, freely available medical datasets with different numbers of vectors, attributes, and classes to conduct experiments. A comparison between the effectiveness of the developed method and that of five existing data normalization methods was carried out. It was experimentally established that the developed method increases the accuracy of the Decision Tree and Extra Trees Classifier by 1–5% in the case of performing the binary classification task and the accuracy of the Bagging, Decision Tree, and Extra Trees Classifier by 1–6% in the case of performing the multiclass classification task. Increasing the accuracy of these classifiers only by using the new data normalization method satisfies all the prerequisites for its application in practice when performing various medical data mining tasks. [ABSTRACT FROM AUTHOR]

Summary: Erythroderma (exfoliative dermatitis) is associated with important metabolic changes that include an enhancement in energy expenditure. The key components to total energy expenditure (TEE) include basal metabolic rate (~68% of TEE), physical activity (~22% of TEE) and thermic effect of food (~10% of TEE). In the erythrodermic state, there are likely multiple contributors to the increase in basal metabolic rate, such as 'caloric drain' resulting from increased evaporation of water from enhanced transepidermal water loss, increased activity of the cardiovascular system (including high‐output cardiac failure), increased nonshivering thermogenesis and hormonal changes such as hypercortisolaemia. A change in the patient's level of physical activity and appetite as a result of ill health status may further impact on their TEE and energy consumption. In Part 2 of this two‐part concise review, we explore the key constituents of energy homeostasis and the potential mechanisms influencing energy homeostasis in erythroderma, and suggest much‐needed dietetic management strategies for this important condition. Click here for the corresponding questions to this CME article. [ABSTRACT FROM AUTHOR]

Summary: Erythroderma (exfoliative dermatitis), first described by Von Hebra in 1868, manifests as a cutaneous inflammatory state, with associated skin barrier and metabolic dysfunctions. The annual incidence of erythroderma is estimated to be 1–2 per 100 000 population in Europe with a male preponderance. Erythroderma may present at birth, or may develop acutely or insidiously (due to progression of an underlying primary pathology, including malignancy). Although there is a broad range of diseases that associate with erythroderma, the vast majority of cases result from pre‐existing and chronic dermatoses. In the first part of this two‐part concise review, we explore the underlying causes, clinical presentation, pathogenesis and investigation of erythroderma, and suggest potential treatment targets for erythroderma with unknown causes. Click here for the corresponding questions to this CME article. [ABSTRACT FROM AUTHOR]

Harlequin ichthyosis (HI) is the most severe and frequently lethal form of recessive congenital ichthyosis. Although defects in lipid transport, protein phosphatase activity, and differentiation have been described, the genetic basis underlying the clinical and cellular phenotypes of HI has yet to be determined. By use of single-nucleotide-polymorphism chip technology and homozygosity mapping, a common region of homozygosity was observed in five patients with HI in the chromosomal region 2q35. Sequencing of the ABCA12 gene, which maps within the minimal region defined by homozygosity mapping, revealed disease-associated mutations, including large intragenic deletions and frameshift deletions in 11 of the 12 screened individuals with HI. Since HI epidermis displays abnormal lamellar granule formation, ABCA12 may play a critical role in the formation of lamellar granules and the discharge of lipids into the intercellular spaces, which would explain the epidermal barrier defect seen in this disorder. This finding paves the way for early prenatal diagnosis. In addition, functional studies of ABCA12 will lead to a better understanding of epidermal differentiation and barrier formation. [ABSTRACT FROM AUTHOR]

Broomcorn millet is one of the most important plants species in pre-history. It was first domesticated in China and subsequently spread across Eurasia becoming a significant staple crop. For a long time, the arrival of millet into Europe was assumed to have taken place in the Neolithic. However, this has recently been challenged, with new direct radiocarbon measurements on reportedly Neolithic charred millet grains in fact dating to the Middle Bronze Age. To aid in understanding the timing of millet's spread across East-Central Europe in the Bronze Age we present the results of over 120 new paired radiocarbon dates and stable isotope (δ 13C and δ 15N) measurements on human bone collagen from individuals across 33 archaeological sites in Poland and western Ukraine. In doing so we directly assess millet's role in the Bronze Age diets. Our results show a clear increase in bone collagen δ 13C values from the middle 15th century BC onwards. This increase is rapid across the whole study area, occurring almost simultaneously with respect to the precision of our radiocarbon dates. Pilot stable isotope data for contemporary animals suggests that they were not foddered with millet and hence it was probably eaten directly by humans. Interestingly, individuals consuming millet appear to be exclusive to geographically upland regions compared to lowland ones. However, not all individuals from upland zone have δ 13C values consistent with millet consumption. Based on the stable isotope evidence for upland millet consumption and the well documented evidence for connections between these people and those in the northern Carpathian Basin at this time, we posit that it is through this route, across the Carpathians, that millet was introduced into the region. An increase of its economic importance in Lesser Poland was plausibly caused by a significant growth in human populations. • Introduction of millet to diet of East-Central Europeans took place in 15th c. BC. • The peak of millet consumption occurred in mid-13th c. BC. • The rise of millet as a staple crop is linked to a demographic growth. [ABSTRACT FROM AUTHOR]

Background: Recessive forms of congenital ichthyosis encompass a group of rare inherited disorders of keratinization leading to dry, scaly skin. So far, 13 genes have been implicated, but there is a paucity of data on genotype-phenotype correlation in some populations., Objectives: We compiled an English cohort of 146 individuals with recessive ichthyosis and assessed genotype-phenotype correlation., Methods: Deep phenotyping was undertaken by history-taking and clinical examination. DNA was screened for mutations using a next-generation sequencing ichthyosis gene panel and Sanger sequencing., Results: Cases were recruited from 13 National Health Service sites in England, with 65% of patients aged < 16 years at enrolment. Pathogenic biallelic mutations were found in 83% of cases, with the candidate gene spread as follows: TGM1 29%, NIPAL4 12%, ABCA12 12%, ALOX12B 9%, ALOXE3 7%, SLC27A4 5%, CERS3 3%, CYP4F22 3%, PNPLA1 2%, SDR9C7 1%. Clinically, a new sign, an anteriorly overfolded ear at birth, was noted in 43% of patients with ALOX12B mutations. The need for intensive care stay (P = 0·004), and hand deformities (P < 0·001), were associated with ABCA12 mutations. Self-improving collodion ichthyosis occurred in 8% of the cases (mostly TGM1 and ALOX12B mutations) but could not be predicted precisely from neonatal phenotype or genotype., Conclusions: These data refine genotype-phenotype correlation for recessive forms of ichthyosis in England, demonstrating the spectrum of disease features and comorbidities, as well as the gene pathologies therein. Collectively, the data from these patients provide a valuable resource for further clinical assessment, improving clinical care and the possibility of future stratified management. What's already known about this topic? Recessive forms of ichthyosis are rare but often difficult to diagnose. Mutations in 13 genes are known to cause recessive forms of ichthyosis: ABCA12, ALOX12B, ALOXE3, CERS3, CYP4F22, LIPN, NIPAL4, PNPLA1, SDR9C7, SLC27A4, SULT2B1, ST14 and TGM1. Some phenotypic features may associate with certain gene mutations, but paradigms for genotype-phenotype correlation need refining. What does this study add? The genotypic spectrum of recessive ichthyosis in England (based on 146 cases) comprises TGM1 (29%), NIPAL4 (12%), ABCA12 (12%), ALOX12B (9%), ALOXE3 (7%), SLC27A4 (5%), CERS3 (3%), CYP4F22 (3%), PNPLA1 (2%) and SDR9C7 (1%). New or particular phenotypic clues were defined for mutations in ALOX12B, ABCA12, CYP4F22, NIPAL4, SDR9C7 and TGM1, either in neonates or in later life, which allow for greater diagnostic precision. In around 17% of cases, the molecular basis of recessive ichthyosis remains unknown., (© 2019 British Association of Dermatologists.)

Objective: To assess the clinical outcomes of 45 cases of harlequin ichthyosis and review the underlying ABCA12 gene mutations in these patients., Design: Multicenter, retrospective, questionnaire-based survey., Setting: Dermatology research institute., Participants: Patients with harlequin ichthyosis for whom we had performed ABCA12 mutation analysis., Main Outcome Measures: Referring physicians were asked to complete a questionnaire using the patients' notes, detailing the clinical outcome of the affected child. In each case, the causative ABCA12 mutation was identified using standard polymerase chain reaction and sequencing techniques., Results: Of the 45 cases, the ages of the survivors ranged from 10 months to 25 years, with an overall survival rate of 56%. Death usually occurred in the first 3 months and was attributed to sepsis and/or respiratory failure in 75% of cases. The early introduction of oral retinoids may improve survival, since 83% of those treated survived, whereas 76% who were not given retinoids died. Recurrent skin infections in infancy affected one-third of patients. Problems maintaining weight affected 44%. Three children developed an inflammatory arthritis, and developmental delay was reported in 32%. Mutation analysis revealed that 52% of survivors had compound heterozygous mutations, whereas all deaths were associated with homozygous mutations., Conclusions: Harlequin ichthyosis should be regarded as a severe chronic disease that is not invariably fatal. With improved neonatal care and probably the early introduction of oral retinoids, the number of survivors is increasing. Compound heterozygotes appear to have a survival advantage.

Epidermal phospholipase A2 (PLA2) in RA patients was significantly higher than in normals (p less than 0.0001) but lower than in psoriatic patients (p less than 0.05). No relationship was observed between PLA2 activity and commonly used measures of rheumatoid disease activity in a cross-sectional study. However, in a longitudinal study change in PLA2 activity correlated strongly with changes in disease activity.