122 research outputs found
Phenotypic variation in familial chilblain lupus (FCL) and Aicardi-Goutières syndrome (AGS) associated with TREX1 mutation in 4 family members
Keratoacanthoma management: results of a survey of UK dermatologists and surgeons.
Distinction of keratoacanthoma (KA) from squamous cell carcinoma (SCC) is challenging. Management is controversial, with some advocating prompt surgical excision and others monitoring to allow for spontaneous resolution(1) . The controversy is compounded by rare reports of metastasis(2) . And yet the benign natural history of KA is supported by various studies, including a systematic review of 455 cases with no cases of metastasis or death(1) , and observational studies confirming spontaneous resolution(1)
Identifying the best predictive diagnostic criteria for psoriasis in children (< 18 years): a UK multicentre case-control diagnostic accuracy study (DIPSOC study).
BACKGROUND: In children, psoriasis can be challenging to diagnose. Difficulties arise from differences in the clinical presentation compared with adults. OBJECTIVES: To test the diagnostic accuracy of previously agreed consensus criteria and to develop a shortlist of the best predictive diagnostic criteria for childhood psoriasis. METHODS: A case-control diagnostic accuracy study in 12 UK dermatology departments (2017-2019) assessed 18 clinical criteria using blinded trained investigators. Children (< 18 years) with dermatologist-diagnosed psoriasis (cases, N = 170) or a different scaly inflammatory rash (controls, N = 160) were recruited. The best predictive criteria were identified using backward logistic regression, and internal validation was conducted using bootstrapping. RESULTS: The sensitivity of the consensus-agreed criteria and consensus scoring algorithm was 84·6%, the specificity was 65·1% and the area under the curve (AUC) was 0·75. The seven diagnostic criteria that performed best were: (i) scale and erythema in the scalp involving the hairline, (ii) scaly erythema inside the external auditory meatus, (iii) persistent well-demarcated erythematous rash anywhere on the body, (iv) persistent erythema in the umbilicus, (v) scaly erythematous plaques on the extensor surfaces of the elbows and/or knees, (vi) well-demarcated erythematous rash in the napkin area involving the crural fold and (vii) family history of psoriasis. The sensitivity of the best predictive model was 76·8%, with specificity 72·7% and AUC 0·84. The c-statistic optimism-adjusted shrinkage factor was 0·012. CONCLUSIONS: This study provides examination- and history-based data on the clinical features of psoriasis in children and proposes seven diagnostic criteria with good discriminatory ability in secondary-care patients. External validation is now needed
Therapeutic targeting of cathepsin C::from pathophysiology to treatment
Cathepsin C (CatC) is a highly conserved tetrameric lysosomal cysteine dipeptidyl aminopeptidase. The best characterized physiological function of CatC is the activation of pro-inflammatory granule-associated serine proteases. These proteases are synthesized as inactive zymogens containing an N-terminal pro-dipeptide, which maintains the zymogen in its inactive conformation and prevents premature activation, which is potentially toxic to the cell. The activation of serine protease zymogens occurs through cleavage of the N-terminal dipeptide by CatC during cell maturation in the bone marrow. In vivo data suggest that pharmacological inhibition of pro-inflammatory serine proteases would suppress or attenuate deleterious effects of inflammatory/auto-immune disorders mediated by these proteases. The pathological deficiency in CatC is associated with Papillon-Lefèvre syndrome. The patients however do not present marked immunodeficiency despite the absence of active serine proteases in immune defense cells. Hence, the transitory pharmacological blockade of CatC activity in the precursor cells of the bone marrow may represent an attractive therapeutic strategy to regulate activity of serine proteases in inflammatory and immunologic conditions. A variety of CatC inhibitors have been developed both by pharmaceutical companies and academic investigators, some of which are currently being employed and evaluated in preclinical/clinical trials
Abnormal pigmentation in hypomelanosis of Ito and pigmentary mosaicism: the role of pigmentary genes
Pigmentary mosaicism with hyperpigmented streaks on the palmoplantar lesion associated with balanced X; autosome translocations t(X; 9)(p11.21; q34.1)
Familial BAP1 mutation presenting in a child with innocuous-looking skin lesions demonstrating a histologically distinct subtype of an atypical spitzoid tumour, and fatal paraganglioma in the father
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