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.

A management algorithm for congenital erythropoietic porphyria derived from a study of 29 cases.

BACKGROUND: Congenital erythropoietic porphyria (CEP) is an autosomal recessive photomutilating porphyria with onset usually in childhood, where haematological complications determine prognosis. Due to its extreme rarity and clinical heterogeneity, management decisions in CEP are often difficult. OBJECTIVES: To develop a management algorithm for patients with CEP based on data from carefully characterized historical cases. METHODS: A single investigator collated data related to treatments and their outcomes in 29 patients with CEP from the U.K., France, Germany and Switzerland. RESULTS: Six children were treated with bone marrow transplantation (BMT); five have remained symptomatically cured up to 11.5 years post-transplantation. Treatments such as oral charcoal, splenectomy and chronic hypertransfusion were either of no benefit or were associated with complications and negative impact on health-related quality of life. Lack of consistent genotype-phenotype correlation meant that this could not be used to predict disease prognosis. The main poor prognostic factors were early age of disease onset and severity of haematological manifestations. CONCLUSIONS: A management algorithm is proposed where every patient, irrespective of disease severity at presentation, should receive a comprehensive, multidisciplinary clinical assessment and should then be reviewed at intervals based on their predicted prognosis, and the rate of onset of complications. A BMT should be considered in those with progressive, symptomatic haemolytic anaemia and/or thrombocytopenia. Uroporphyrinogen III synthase genotypes associated with poor prognosis would additionally justify consideration for a BMT. Rigorous photoprotection of the skin and eyes from visible light is essential in all patients.

Congenital erythropoietic porphyria: a single-observer clinical study of 29 cases.

BACKGROUND: Congenital erythropoietic porphyria (CEP) is an autosomal recessive cutaneous porphyria caused by decreased activity of uroporphyrinogen III synthase (UROS). Its predominant characteristics include bullous cutaneous photosensitivity to visible light from early infancy, progressive photomutilation and chronic haemolytic anaemia. Due to its rarity and genetic heterogeneity, clinical phenotypes are unclear and its impact on health-related quality of life (HRQoL) has not been previously assessed. OBJECTIVES: To define comprehensively CEP phenotypes and assess their impact on HRQoL, and to correlate these factors with laboratory parameters. METHODS: A single observer assessed patients with CEP from four European countries. RESULTS: Twenty-seven unrelated patients with CEP, aged between 7.6 and 65 years, participated in the study. The patients came from the U.K. (17), France (4), Switzerland (4) and Germany (2). Additional data were obtained for two deceased patients. Newly characterized features of CEP include acute-onset cutaneous and noncutaneous symptoms immediately following sunlight exposure, and pink erythematous facial papules. There was a lack of consistent genotype-phenotype correlation in CEP. The main poor prognostic factors in CEP are the early age of disease onset and haematological complications. CONCLUSIONS: CEP is a multisystem disease; cutaneous, ocular, oral and skeletal manifestations also contribute to disease severity and impact on HRQoL, in addition to the haematological complications. The rarity of the disease can lead to delayed diagnosis. The lack of consistent genotype-phenotype correlation in CEP suggests a contribution to phenotype from other factors, such as environment, patients' photoprotective behaviour and genes other than UROS. There is currently an unmet need for multidisciplinary management of patients with CEP.

Omenn's syndrome: lessons from a red baby.

Exfoliative dermatitis and erythroderma in infancy are rare. Clinicians need to be alert to the possible diagnosis of Omenn's syndrome (OS), a rare form of combined immunodeficiency in infants presenting with exfoliative dermatitis, erythroderma, recurrent infections, eosinophilia and raised IgE. OS is fatal unless treated by bone-marrow transplantation (BMT). We describe a 3-week-old girl who presented with a widespread scaly erythematous rash and stomatitis, and was initially treated for presumed atopic eczema and primary herpes stomatitis. Aged 3 months, she developed erythroderma, diarrhoea and hepatosplenomegaly associated with eosinophilia, raised serum IgE and low IgG, IgA and IgM levels, abnormal lymphocyte populations and skin histology, consistent with a diagnosis of OS. She remains well 16 months after a human leucocyte antigen-matched bone-marrow transplant from an unrelated donor.

The Dermatology Life Quality Index: assessing the efficacy of biological therapies for psoriasis.

BACKGROUND: Clinical trials show improvement in physical and health-related quality of life (HRQoL) measures in patients with psoriasis treated with biologics compared with placebo. However, these reports only give limited interpretation of the meaning of Dermatology Life Quality Index (DLQI) scores and provide limited comparison data. OBJECTIVES: The aim of this paper is to identify which biological therapy provides the greatest improvement in HRQoL following treatment of patients with chronic plaque psoriasis, as assessed by the DLQI. METHODS: We reviewed all data published up to August 2006 of randomized placebo-controlled trials (RCTs) of the four biologics currently licensed in some countries for clinical use in chronic plaque psoriasis (alefacept, efalizumab, etanercept and infliximab) which have used the DLQI as an outcome measure. The DLQI data were assessed based on overall improvement according to the DLQI descriptor bands and on clinically meaningful improvement of > or = 5. RESULTS: Fifteen peer-reviewed articles and 59 abstracts describing 11 multicentre, double-blind RCTs were reviewed. Treatment with any one of the four biologics led to a clinically meaningful improvement in the DLQI of > or = 5. However, when applying the DLQI banding concept, infliximab and etanercept provided the greatest improvement in the overall HRQoL from a 'very large effect on overall HRQoL' at baseline to 'a small effect on overall HRQoL' following treatment. CONCLUSIONS: The DLQI banding concept provides a further tool to assess the impact of biologics on HRQoL of patients with psoriasis. Based on retrospective application of DLQI bands to published RCT data, infliximab, followed by etanercept, showed the greatest improvement in the overall HRQoL paralleled by a 75% improvement in the Psoriasis Area and Severity Index. However, some publications did not provide absolute baseline DLQI values, making interpretation of data and comparison between the agents difficult. Side-to-side comparative studies between biologics and between biologics and nonbiological psoriasis treatments will aid evidence-based psoriasis management decisions in the future.

Oral retinoid therapy for disorders of keratinization: single-centre retrospective 25 years' experience on 23 patients.

BACKGROUND: Over the last three decades, the oral retinoids etretinate and acitretin have revolutionized the treatment of disorders of keratinization (DOK). Many patients with DOK require life-long treatment with oral retinoids. However, the longest follow-up data of patients with DOK on oral retinoid therapy is 10 years for adults and up to 11 years for children. OBJECTIVES: The aim of our study was to collect long-term retrospective data including disease response, side-effects and pregnancy outcome in a cohort of patients with DOK who were among the first in the world to commence oral retinoids 25 years ago. METHODS: Between 1979 and 1981, 30 patients with DOK were commenced on oral etretinate in our department. Case notes of these patients were reviewed retrospectively, and patients interviewed where possible to obtain the following information: diagnosis, age when treatment commenced, duration of treatment, reason for discontinuation of therapy, side-effects, abnormal investigation results and pregnancy outcomes. RESULTS: Case notes of 23 of the 30 patients were available for review; of these, two patients were deceased and 14 were interviewed. In the 23 patients, the mean age of commencing treatment was 33.5 years (range 4.2-61) and the mean duration of etretinate therapy was 5.2 years (range 1 month to 14 years). Reasons for discontinuing treatment were an overall improvement in the skin disease (six of 23), no benefit +/- side-effects (11 of 23) and noncompliance (one of 23). Two patients died of causes unrelated to their skin disease or treatment, 12 and 4 years after stopping etretinate. Five patients (one female, four males) subsequently changed to acitretin and are currently continuing therapy. The mean total duration of retinoid therapy (etretinate and acitretin) for the four males was 23.7 years (range 20.6-25.1). The female patient continued intermittent courses (due to planned pregnancies) of oral retinoids for a total of 10.1 years over the last 25 years. Abnormal investigation results included elevated serum triglycerides and cholesterol (two of 23), isolated high triglycerides (three of 23), isolated high cholesterol (three of 23), worsening of liver enzymes in a patient with alcohol dependence, and elevated serum alkaline phosphatase (ALP) in healthy adults (three of 23). In two children, the elevated pretreatment ALP levels increased further after commencing etretinate but returned to normal in adulthood while treatment continued. One patient developed diffuse idiopathic skeletal hyperostosis after 21 years of retinoid therapy. One female patient had two early spontaneous abortions 2.75 and 3.2 years after discontinuing etretinate; she subsequently had two normal children. Two other females had normal children 1, 3 and 5 years after stopping etretinate. Two male patients fathered a total of three healthy children while on etretinate. CONCLUSIONS: This study provides the longest available follow-up data of children and adults with DOK on oral retinoid therapy. Such information is essential for clinicians and their patients with DOK embarking on life-long treatment with retinoids.

Primary cutaneous CD30+ T-cell lymphoproliferative disorder following cardiac transplantation in a 15-year-old boy with Netherton's syndrome.

Primary cutaneous T-cell lymphoproliferative disorders (PCTCLDs) are uncommon in organ transplant recipients. CD30+ PCTCLDs are rare in children and have not previously been reported following organ transplantation. We report a 15-year-old boy with Netherton's syndrome who developed CD30+ PCTCLD 6 years following a cardiac transplantation.

Clinical management decisions are related to the impact of psoriasis on patient-rated quality of life.

BACKGROUND: Clinical decisions over psoriasis are based on many factors. Patients' quality of life (QOL) is not directly related to disease severity alone as judged by physical signs, so decisions should not be based on physical assessments alone. This is increasingly important as new potent biological therapies become available. OBJECTIVES: This study aimed to determine whether clinicians' routine decisions in psoriasis correlate with patient-rated QOL. PATIENTS AND METHODS: Over 35 weeks all 687 outpatient psoriasis consultations by 13 clinicians were included. Each patient received a Dermatology Life Quality Index (DLQI) questionnaire following their consultation. Case notes were analysed to assign management decisions taken by clinicians to one of 11 categories. Patient-rated DLQI was correlated with the type of management decision. RESULTS: Three hundred and eighty-three completed DLQI questionnaires were analysed. Within the 'no change to main type of therapy' group the mean DLQI for patients not changing the potency, dose or frequency of main treatment was 8.9. For patients in whom the potency, dose or frequency of main treatment was increased, the mean DLQI was 11.9. For patients in whom the potency, dose or frequency of main treatment was decreased, the mean DLQI was 6.2. Major management decisions were associated with a high mean DLQI such as change of topical therapy (11.2), topical to systemic therapy (14.8), change of systemic therapy (16.7), starting photo(chemo)therapy (13) and requiring hospital admission (14.4). By contrast, patients discharged reported low DLQI values (mean 4.0). The cohort of patients in whom a decision was taken to start day treatment had a surprisingly low mean DLQI of 8.6. Significant differences in mean DLQI were seen in the cohorts classified by type of management decision. For example, when the mean DLQI values in each cohort were compared (Mann-Whitney U-test), significant differences were seen between the cohorts in whom treatment was increased in potency, dose or frequency, compared with the cohorts whose treatment was unchanged (P < 0.05) or decreased (P < 0.01) or who were discharged from clinic (P < 0.01). CONCLUSIONS: In psoriasis there is a relationship between the type of management decision and the patient-rated QOL. However, there is a very wide score scatter for each management decision, challenging the appropriateness of some clinical decisions.

Intestinal bypass syndrome presenting as erythema nodosum.

Intestinal bypass was a popular surgical procedure for morbid obesity resulting, on average, in a 50 kg weight loss. We describe a 66-year-old woman who underwent the procedure 12 years earlier and subsequently presented with recurrent episodes of erythema nodosum-like lesions. Further investigations revealed hyperoxaluria, renal failure, deficiency of fat-soluble vitamins (causing night blindness, osteomalacia and easy bruising) and anaemia. Antibiotics led to only temporary remission and, as with 24-30% of similar cases, she underwent surgical reversal to prevent the complications from worsening.

The neurogenic vasodilator response to endothelin-1: a study in human skin in vivo.

We have investigated the mediators and mechanisms underlying the vasodilator effects of the potent vasoactive peptide, endothelin-1 (ET-1) and its isomers ET-2 and ET-3 in human skin, in vivo, using cutaneous microdialysis to quantify the release of mediators within the dermal response and scanning laser Doppler imaging to measure changes in blood flux. The effects of local anaesthesia, inhibition of nitric oxide synthase (NOS) by L-NAME and ET receptor blockade on the ET-induced vascular response were also investigated. ET-1, -2 and -3 all caused a dose-dependent area of pallor surrounded by a long-lasting flare which was accompanied by a short-lived burning pruritus. The concentration of nitric oxide (NO) in dialysate collected within the pallor response to 5 microM ET-1 (1.43 +/- 0.64 microM, n = 5) was not significantly different from baseline levels collected prior to injection (0.86 +/- 0.38 microM) whilst that in the flare increased to reach a peak value of 2.28 +/- 0.61 microM at between 4 and 10 min after intradermal injection (P < 0.004). Pretreatment with local anaesthetic slowed the development of the flare and significantly reduced its size by up to 52% at 20 min after injection (P < 0.05) but had no significant effect on the central pallor. L-NAME, delivered by dialysis also caused a significant reduction in the ET-1-induced flare (P < 0.005). Bosentan, the non-selective ET(A)/ET(B) antagonist, when given by dialysis at the site of injection, reduced the area of both the ET-1-induced pallor and surrounding flare by 41 and 26%, respectively. No significant increase in tissue histamine was measured within either the pallor or flare response to ET-1, -2 or -3. Together these data confirm that the vasodilator response to endothelin-1 in human skin is neurogenic in origin and that it is in part mediated by the local release of nitric oxide. There appears to be little evidence for the involvement of mast cell-derived histamine in the initiation or modulation of ET-induced vasodilatation, in vivo.