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.

Genotype-phenotype correlation in a large English cohort of patients with autosomal recessive ichthyosis.

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.

Propranolol in the treatment of infantile haemangiomas: lessons from the European Propranolol In the Treatment of Complicated Haemangiomas (PITCH) Taskforce survey.

BACKGROUND: Oral propranolol is widely prescribed as first-line treatment for infantile haemangiomas (IHs). Anecdotally, prescribing practice differs widely between centres. OBJECTIVES: The Propranolol In the Treatment of Complicated Haemangiomas (PITCH) Taskforce was founded to establish patterns of use of propranolol in IHs. METHODS: Participating centres entered data on all of their patients who had completed treatment with oral propranolol for IHs, using an online data capture tool. RESULTS: The study cohort comprised 1097 children from 39 centres in eight European countries. 76·1% were female and 92·8% had a focal IH, with the remainder showing a segmental, multifocal or indeterminate pattern. The main indications for treatment were periocular location (29·3%), risk of cosmetic disfigurement (21·1%) and ulceration and bleeding (20·6%). In total 69·2% of patients were titrated up to a maintenance regimen, which consisted of 2 mg kg(-1) per day (85·8%) in the majority of cases. 91·4% of patients had an excellent or good response to treatment. Rebound growth occurred in 14·1% upon stopping, of whom 53·9% were restarted and treatment response was recaptured in 91·6% of cases. While there was no significant difference in the treatment response, comparing a daily maintenance dose of < 2 mg kg(-1) vs. 2 mg kg(-1) vs. > 2 mg kg(-1) , the risk of adverse events was significantly higher: odds ratio (OR) 1 vs. adjusted OR 0·70, 95% confidence interval (CI) 0·33-1·50, P = 0·36 vs. OR 2·38, 95% CI 1·04-5·46, P = 0·04, Ptrend < 0·001. CONCLUSIONS: The PITCH survey summarizes the use of oral propranolol across 39 European centres, in a variety of IH phases, and could be used to inform treatment guidelines and the design of an interventional study.

Investigation of cutaneous photoadaptation to narrowband ultraviolet B.

BACKGROUND: Photoadaptation describes the skin's ability to withstand an increased dose of ultraviolet (UV) radiation with repeated exposure, and this is the reason for exposure doses being increased during a course of phototherapy. However, directly measured data on photoadaptation are available only for broadband (BB) and not narrowband (NB)-UVB. OBJECTIVES: To measure photoadaptation to narrowband UVB. METHODS: We measured the degree of photoadaptation in patients with psoriasis during a standard course of NB-UVB phototherapy. The minimal erythemal dose (MED) was measured before and towards the end of a course of phototherapy. An adaptation factor (AF) was calculated for each patient using the ratio of final MED to initial MED. Sigmoid dose-response curves were also constructed. RESULTS: MED results were available for 50 patients (mean age 44 years, 28 female). The mean AF was 2·7 (95% confidence interval 2·4-3·0). There was no significant correlation between AF and skin type or initial MED. Dose-response curves were right shifted and parallel after phototherapy, and there was no significant difference in the maximum slope (P = 0·73). CONCLUSIONS: The photoadaptation caused by NB-UVB is considerably less than that reported for BB-UVB. The variation in photoadaptation between patients was not explained by skin type or baseline MED. Physical factors (such as tanning and epidermal thickening) are probably sufficient to account for photoadaptation, rather than downregulation of the inflammatory response. These data should help in the design of phototherapy protocols for NB-UVB to achieve optimal clearance of psoriasis.

Narrowband ultraviolet B phototherapy in children with moderate-to-severe eczema: a comparative cohort study.

BACKGROUND: There is only retrospective evidence for the efficacy of narrowband ultraviolet B (NB-UVB) in children with eczema. OBJECTIVES: To measure the difference in means for objective scores [Six Area Six Sign Atopic Dermatitis score (SASSAD), percentage surface area] and quality-of-life scores, between patients treated with NB-UVB and unexposed cohorts at the end of treatment, and 3 and 6 months post-treatment. METHODS: Twenty-nine children aged 3-16 years for whom NB-UVB was indicated, were scored prospectively using SASSAD and percentage surface area involvement at baseline, at 12 weeks (end of treatment) and 3 and 6 months post-NB-UVB. Their scores were compared with those of unexposed children (n = 26) for whom NB-UVB phototherapy was indicated and offered, but who chose not to undertake treatment. RESULTS: There was a 61% reduction in mean SASSAD score in the NB-UVB cohort compared with an increase of 6% in the unexposed cohort. Mean SASSAD score for the NB-UVB cohort at the end of treatment was 11.6 vs. 24.8 for the unexposed; difference in means -13.2 [95% confidence interval (CI) -18.7 to -7.7, P < 0.0001]. Mean surface area involvement at the end of treatment was 11% for the NB-UVB cohort vs. 36% for the unexposed cohort; difference in means -25% (95% CI -34% to -16%, P < 0.0001). Subjective and quality-of-life scores showed significant difference between cohorts at the end of treatment (P < 0.05). Objective scores remained significantly lower than in the unexposed cohort 3 and 6 months after treatment. CONCLUSION: NB-UVB is clinically effective and improves quality of life in children with moderate-to-severe eczema. The effect is maintained for 6 months after treatment.

Evaluation of the clinical efficacy of the 1,450 nm laser in acne vulgaris: a randomized split-face, investigator-blinded clinical trial.

BACKGROUND: The 1450 nm laser shrinks sebaceous glands histologically, reduces seborrhoea and has been shown in numerous small uncontrolled studies to improve inflammatory acne. OBJECTIVES: To assess objectively the clinical efficacy and long-term outcome of the 1450 nm laser for inflammatory acne vulgaris. METHODS: Participants over 16 years of age with moderate to severe acne vulgaris were recruited from a secondary care dermatology department. A split-face format was used: the side of the face to be treated was randomized with the other side serving as a within-patient control. Treatment was delivered with the Candela 1450 nm Smoothbeam laser (Candela, Cwmbran, U.K.) using a double-pass technique, 6 mm spot size, 210 ms pulse duration and fluence of 8 or 9 J cm(-2) . Three treatments were performed monthly. The primary outcome was the change in inflammatory lesion count and grading (using the Leeds Revised Acne Grading Scale) between baseline and 4 weeks after the third treatment on the treated side as compared with the change in the control side. Participants were followed up every 3 months for 12 months after the last treatment. The single assessor was blinded as to the side treated. RESULTS: Thirty-eight participants entered the study and 32 completed the study at the primary outcome measure. Within participants, on average, the lesion count reduced by the same amount on both sides of the face [median 0, 95% confidence interval (CI) -4 to 2]. On average, acne grade reduced by the same amount on both sides (median 0, 95% CI -1 to 0). Twelve months after the last treatment (n = 23) the change in lesion count and grade between the treated and control sides of the face remained similar. Treatment was well tolerated. CONCLUSIONS: Treatment with the 1450 nm laser does not reduce inflammatory lesion count or acne grade when compared with a control side, using a split-face format in participants recruited from secondary care. Both sides of the face improved and a systemic effect of the laser is possible.

Do antineutrophil cytoplasmic antibodies (ANCA) play a key role in neutrophilic dermatoses? A case of propylthiouracil-induced neutrophilic dermatosis with positive perinuclear ANCA.

We report a case of neutrophilic dermatosis caused by propylthiouracil (PTU), with positive perinuclear antineutrophil cytoplasmic antibodies (p-ANCA). PTU is well known to cause vasculitis associated with positive ANCA titres, and this typically occurs late in the treatment (after months to years). PTU rarely causes neutrophilic dermatoses (three case reports). In the three cases described, ANCA was positive at the outset. Our patient's initial ANCA testing was negative and her positive p-ANCA evolved. This may be because PTU binds to myeloperoxidase (MPO) inside neutrophils, altering its configuration and thus causing antibody formation to this abnormal MPO-PTU configuration, which would not be detected by standard laboratory techniques. ANCA has been implicated in spreading neutrophil activation and thus its pathogenic effect and clinical significance may extend beyond the realm of vasculitis alone.

Modulating effects of oatmeal extracts in the sodium lauryl sulfate skin irritancy model.

The aim of the present study was to assess the anti-inflammatory activity of two topically applied oatmeal extracts, i.e. Avena sativa and Avena Rhealba, using the sodium lauryl sulfate (SLS) irritation model. At baseline, test areas on the volar surface of the upper arms of 12 healthy individuals were pretreated with the two extracts and their vehicle (petrolatum ointment) under occlusion for 2 h, and one site was left untreated. Then a patch with a 1% SLS solution was applied to the test sites for 24 h. Irritation was determined at each period by measuring by chromametry and laser-Doppler. In a dose-ranging study with the Avena Rhealba extract alone, the 20 and 30% concentrations exerted a slight inhibition of the a* parameter increase and a marked reduction of the blood flow increase (p < 0.05, compared to vehicle). Then, the effects of the two extracts at the concentration of 20% were compared. All extracts displayed a statistically significant counteracting effect on both parameters (p < 0.05), but no statistically significant difference between treatment groups could be demonstrated. In conclusion, this study demonstrates the preventive effects of oatmeal extracts on skin irritation in the SLS model.