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.

Novel and recurrent mutations in keratin 1 cause epidermolytic ichthyosis and palmoplantar keratoderma.

Mutations in keratin genes underlie a variety of epidermal and nonepidermal cell-fragility disorders, and are the genetic basis of many inherited palmoplantar keratodermas (PPKs). Epidermolytic PPK (EPPK) is an autosomal dominant disorder that can be due to mutations in the keratin 1 gene, KRT1. Epidermolytic ichthyosis (EI), the major keratinopathic ichthyosis, is characterized by congenital erythroderma, blistering and erosions of the skin. Causative mutations in KRT1 and KRT10 have been described, with PPK being present primarily in association with the former. We report four unrelated cases (one with sporadic EI and three with autosomal dominant PPK), due to two novel and two recurrent KRT1 mutations. Mutations in KRT1 are not only scattered throughout the keratin 1 protein, as opposed to being clustered, but can result in a range of phenotypes as further confirmed by these mutations, giving a complex genotype/phenotype pattern.

Reactivity to autologous serum skin test and relationship with complement levels in chronic idiopathic urticaria and angio-oedema.

BACKGROUND: A role for complement in autoantibody-mediated histamine release in urticaria has been suggested but not proven in vivo. Aim. To study serum complement levels in patients with chronic idiopathic urticaria (CIU) and to determine whether there was a relationship with autologous serum skin test (ASST) reactivity. METHODS: We recruited 35 patients with CIU. Complement (C3, C4) levels and ASST were measured in all patients; additional investigations were undertaken dependent on history and examination. RESULTS: Complement concentrations were outside the population reference intervals in 19/35 patients, with low C3 noted in 3/35 and low C4 in 18/35. Of 12 patients with a positive ASST, 7 had low complement levels, and 12/23 with a negative ASST had low complement levels. Patients with a positive ASST had a median C3 of 1.24 g/L (range 0.35-1.51) compared with a median of 1.25 g/L in those with a negative ASST (P = 0.36), and a median C4 of 0.20 g/L (range 0.185-0.452) in those with a positive ASST compared with 0.18 g/L in those with a negative ASST (P = 0.88). CONCLUSIONS: We conclude that both a reduction in C4 and positive ASST are common in CIU and although these immunological abnormalities often coexist, there is no clear relationship between them. Other components of the complement system may be worth exploring.

Narrowband ultraviolet B (UVB) phototherapy in children.

BACKGROUND: While narrowband ultraviolet B (UVB) phototherapy is a well-established treatment for a range of skin conditions in adults, there is little in the literature about its use in children and data regarding its long-term carcinogenic potential are lacking. AIM: We undertook a retrospective review of the use of narrowband UVB phototherapy in a paediatric population attending two Glasgow Hospitals. METHODS: Phototherapy case notes for all children aged 16 years and under at time of treatment were reviewed at two hospital sites between 1996 and 2002. RESULTS: In total, 77 children had been treated (median age 12 years, range 4-16). The conditions treated most frequently were psoriasis (45%) and atopic eczema (32%). Other dermatoses treated included alopecia areata, acne, hydroa vacciniforme and polymorphic light eruption. Treatment courses for atopic conditions were longer than those required for psoriatic conditions: median number of treatments 24 for atopic eczema (range 3-46), and 17.5 for psoriasis (range 9-35). By the end of treatment, 68% of the atopic patients and 63% of the patients with psoriasis had cleared. The adverse event profile was similar to that in adults, with erythema, herpes simplex reactivation and PLE all recorded. Anxiety was a problem for five patients. CONCLUSION: We conclude that narrowband UVB phototherapy is a useful and well-tolerated treatment for children with severe or intractable inflammatory skin disease, but concerns remain regarding long-term side-effects.

A randomized trial of topical 5% 5-fluorouracil (Efudix cream) in the treatment of actinic keratoses comparing daily with weekly treatment.

BACKGROUND: Topical 5-fluorouracil (5-FU) cream is widely used in the treatment of actinic keratoses (AKs) but the optimum treatment regimen that provides efficacy while minimizing side-effects remains unclear. OBJECTIVES: A randomized trial to compare the efficacy and side-effects of daily vs. weekly application of 5% 5-FU in the treatment of AKs of the scalp and face. PATIENTS/METHODS: Twenty patients were recruited and randomized to two groups. Group 1 (13 patients) applied 5% 5-FU twice daily for 3 weeks, group 2 (seven patients) applied 5% 5-FU twice daily for 1 day per week for 12 weeks. Patients were reviewed at weeks 3, 12, 24 and 52. At each review a lesion count and lesion map were completed and patients were asked to score efficacy and inflammation. RESULTS: At week 0 the median lesion count was the same in both groups, 17.5 lesions. At 12 weeks the median lesion count in group 1 had fallen to 0 where it remained for the duration of follow-up. In group 2 the median lesion count fell to 6 at 12 weeks, 5.5 at 24 weeks and was 3 at 52 weeks. The difference in the lesion count was significant at all time points after week 0: P < 0.05 at weeks 12 and 52, and P < 0.01 at week 24. The mean inflammation score was higher in patients clear of AKs at 12 weeks compared with those who had not cleared, 3.8 compared with 1.9. This difference was statistically significant (P < 0.05) suggesting that inflammation is necessary for efficacy. CONCLUSIONS: We conclude that daily application of 5% 5-FU cream is more effective than weekly application at clearing AKs from the scalp and face. Our results also suggest that inflammation is likely to be required to achieve a therapeutic effect.

The clinical photography of Herbert Brown: a perspective on early 20th Century dermatology.

Herbert Brown was Consultant Dermatologist to the Victoria Infirmary, Glasgow during the first half of the 20th Century. He was a keen amateur photographer, and his large archive of photographs illustrates comprehensively the work of a clinical dermatologist in that era.

Rising levels of serum S100 protein precede other evidence of disease progression in patients with malignant melanoma.

BACKGROUND: Several serum markers may be useful in the detection of metastatic melanoma, but none is in routine clinical use. OBJECTIVE: To assess the validity of S100 protein as a serum marker of melanoma progression. METHODS: Serum S100 protein levels were measured in 496 serum samples from 214 melanoma patients, using the Sangtec luminescence immunoassay. There were 75 patients with stage 1 melanoma, 66 initially with stage 2 melanoma, 49 initially with stage 3 melanoma and 24 with stage 4 melanoma. RESULTS: Serum S100 protein levels were < 0.2 microg L-1 in 71 of 75 (95%) stage 1 patients. One patient who had a normal level developed local recurrence. Fifty-eight of 66 (88%) stage 2 patients also had normal serum S100 protein levels. One with elevated levels progressed to stage 3 melanoma and five with elevated levels progressed to stage 4 disease. The remaining two with elevated serum S100 protein remained well. Thirty-five of 49 (71%) stage 3 patients had normal levels and, of these, two have progressed to stage 4 disease. Three patients with stage 3 disease had an elevated serum S100 protein level on one occasion but remained well. Eleven of 13 patients who developed stage 4 melanoma during the study had rising levels of serum S100 protein > 0.2 microg L-1 5-23 weeks before detection of melanoma progression by conventional means. Twenty-two of 24 patients with stage 4 disease throughout the study had consistently elevated serum S100 protein levels, and the two patients with normal levels were clinically disease free after surgery and chemotherapy. None of 14 control subjects with atypical naevi had elevated S100 protein levels, and only one of 11 healthy normal controls had an elevated level. CONCLUSIONS: Thus, rising levels of serum S100 protein are a specific and sensitive clinically relevant marker of tumour progression in melanoma patients, which precedes other evidence of melanoma recurrence.

Identification of novel mutations in basic hair keratins hHb1 and hHb6 in monilethrix: implications for protein structure and clinical phenotype.

Monilethrix is an hereditary hair dystrophy recently shown to be due to mutations in the helix termination motif of two type II (basic) human hair keratin genes, hHb1 and hHb6. It has been suggested that mutation in hHb1 produces a less severe phenotype. We have studied hair keratin genes and clinical features in 18 unrelated pedigrees of monilethrix from Germany, Scotland, Northern Ireland, and Portugal, in 13 of which mutations have not previously been identified. By examining the rod domains of hHb1, hHb3 and hHb6, we have identified mutations in nine of the new pedigrees. We again found the glutamine-lysine substitution (E413K) in the helix termination motif of hHb6 in two families, and in another, the corresponding E413K substitution in the hHb1 gene. In four families a similar substitution E402K was present in a nearby residue. In addition two novel mutations within the helix initiation motif of hHb6 were found in Scottish and Portuguese cases, in whom the same highly conserved asparagine residue N114 was mutated to histidine (N114H) or aspartic acid (N114D) residues, respectively. In four other monilethrix pedigrees mutations in these domains of hHb1, hHb3, and hHb6 were not found. The mutations identified predict a variety of possible structural consequences for the keratin molecule. A comparison of clinical features and severity between cases with hHb1 and hHb6 mutations does not suggest distinct effects on phenotype, with the possible exception of nail dystrophy, commoner with hHb1 defects. Other factors are required to explain the marked variation in clinical severity within and between cases.