Esther Burden-Teh

Antagonism of the interleukin-1 receptor following traumatic brain injury in the mouse reduces the number of nitric oxide synthase-2-positive cells and improves anatomical and functional outcomes

Interleukin (IL)‐1β plays an important role in the inflammatory response that results from traumatic brain injury and antagonism of the actions of this cytokine can affect outcome. We subjected male mice to aseptic cryogenic injury and assessed recovery through anatomical, histological and functional measures following treatment with recombinant mouse IL‐1 receptor antagonist (IL‐1ra). A single dose (1 µg, i.c.v.) at the time of injury reduced lesion volume 3 days later, as assessed by Nissl staining, and also the number (30%) of FluoroJade‐positive degenerating neurones. Mice treated with IL‐1ra performed better on the beam balance and in the grid test as compared with vehicle‐treated animals. Furthermore, IL‐1ra‐treated animals showed fewer (40%) nitric oxide synthase‐2‐positive cells in and around the lesion. These data suggest that activation of the IL‐1 receptor following trauma contributes to the pathology and that antagonism can reduce both anatomical and functional consequences of neuroinflammation.

The epidemiology of childhood psoriasis: a scoping review

Psoriasis is an inflammatory noncommunicable skin disease that affects both adults and children. At present, the epidemiology and natural history of psoriasis are not widely understood. This scoping review aimed to map the existing literature on the epidemiology of childhood psoriasis, identify research gaps for future studies and provide a comprehensive, clinically useful review. Search strategies were developed for Ovid Medline, Ovid Embase, Google Scholar and hand searching. In total, 131 articles met the inclusion criteria and were mapped; 107 articles were included for data extraction. Over the last 25 years there has been a dramatic increase in the volume of published observational epidemiological studies on childhood psoriasis. The majority were case series or cross‐sectional studies, concentrated in Europe, Asia and North America. The prevalence of childhood psoriasis was found to be higher in European countries, older children and girls. Up to 48·8% of children had a family history of psoriasis in a first‐degree relative. The most frequent subtype was plaque psoriasis and the most common initial sites of presentation were the scalp, limbs and trunk. Specific genetic differences have been found between child‐onset and adult‐onset populations. Case–control and cohort studies investigating risk factors for psoriasis onset, comorbidities and long‐term health outcomes were extremely limited. The choice of study design and heterogeneity in methodology limit the validity and generalizability of the information, consistency of the results, and comparability of the studies. Well‐designed epidemiological studies are needed to provide precise and consistent information about the frequency and clinical presentation, risk factors, associated diseases and long‐term outcomes in childhood psoriasis.

Development and testing of new candidate psoriatic arthritis screening questionnaires combining optimal questions from existing tools

Several questionnaires have been developed to screen for psoriatic arthritis (PsA), but head‐to‐head studies have found limitations. This study aimed to develop new questionnaires encompassing the most discriminative questions from existing instruments.

What Is a Pragmatic Clinical Trial

Pragmatic trials Pragmatic clinical trials seek to determine the effectiveness of an intervention in a real-world setting to inform clinical decision making (Roland and Torgerson, 1998). Researchers designing pragmatic trials take particular care to ensure that the study population is as similar as possible to the population on which the intervention is meant to be used (external validity), reflecting the normal range of diversity in disease severity, comorbidities, age, sex, and social and ethnic groups seen in everyday clinical practice. Pragmatic trials also ensure that the sorts of interventions tested can be plausibly rolled out in clinical practice and that the outcomes used to assess effectiveness are valid and easily understood by a range of users, including clinicians, patients, policy makers, and health commissioners. Pragmatic clinical trial patients may also be used to test “strategies” or treatment policies rather than one specific drug at a time. For example, the BLISTER (Bullous Pemphigoid Steroids and Tetracyclines Study) randomized controlled trial tests the policy of starting treatment for bullous pemphigoid patients with either doxycycline or prednisolone (Chalmers et al., 2015). The policy evaluates the trade-off between the shortterm smaller benefit for blister control, as might be anticipated for doxycycline, and the long-term safety concerns that may disadvantage patients randomized to prednisolone. It does not matter whether the dose of prednisolone is altered during the study as would normally occur in clinical practice, nor does it matter if some of the patients initially randomized to the strat-

Psoriasis and uveitis--should we be asking about eye symptoms?

G. V INCENZA C . CATR I CA L A M. ARD IG O Department of Dermatology, San Gallicano Dermatological Institute, Via Chianesi, 53, Rome 00144, Italy Employees’ State Insurance Hospital & Post Graduate Institute of Medical Sciences and Research, New Delhi, India UOC of Dermatology, University of Rome Tor Vergata, Rome, Italy Department of Mental Health, Section of Pathology, Second University of Naples, Naples, Italy Correspondence: Marco Ardig o. E-mail: ardigo@ifo.it

Can a simple outpatient‐based treatment be used to treat cutaneous leishmaniasis in young children? A Critically Appraised Topic

A 5‐year‐old boy from rural Afghanistan presented with a 1‐year history of a skin lesion on his left knee, confirmed by polymerase chain reaction to be cutaneous leishmaniasis (Leishmania tropica). Conventional treatment of cutaneous leishmaniasis involves intravenous or intralesional pentavalent antimonials. The aim of this Critically Appraised Topic (CAT) is therefore to determine what alternative effective but less painful treatments (such as oral or topical therapies) can be used to treat cutaneous leishmaniasis in children. Embase and PubMed were searched for ‘cutaneous leishmania*’ AND ‘treatment’ AND ‘children’ in August 2014. All abstracts from April 2008 to August 2014 were reviewed. This search period was chosen to follow on from the Cochrane reviews on Old World and American leishmaniasis. Five randomized controlled trials met our inclusion criteria and have been included in this CAT. The study design and reporting quality in most of the trials included in both Cochrane reviews was found to be poor, and neither Cochrane review investigated the effect of patient age on response to treatment. This CAT identified two nonpainful treatments, topical paromomycin and oral miltefosine, whose effective use in children is supported in the literature. However, both of these treatments are currently unlicensed in the U.K. Our patient was successfully treated with miltefosine 20 mg twice daily for 4 weeks, leading to good resolution of the leishmaniasis plaque but with residual scarring.

How are we using systemic drugs to treat psoriasis in children? An insight into current clinical U.K. practice.

there was no sign of recurrence at 12 months. Until recently, memory T-cell populations have been categorized as central memory T (TCM) cells, which coexpress CCR7 and CD62L, and effector memory T (TEM) cells, which do not express these molecules. TCM cells are restricted to secondary lymphoid organs and blood, whereas TEM cells circulate between peripheral tissues, blood and the spleen. Recent studies have identified that a third subset of memory T cells, TRM cells, permanently reside in peripheral tissues. The best characterized are CD8 TRM cells that express CD103 and CD69 but stain negative for CCR7 and CD62L, and may provide sitespecific protection against pathogen re-exposure. These cells are sequestered in the skin epidermis and do not recirculate. In contrast, memory CD4 T cells that presumably belong to TEM cells are found within the dermis and at least a proportion of these cells are capable of recirculating. A recent study showed that mycosis fungoides arises from skin-resident CD4 TEM cells, whereas S ezary syndrome arises from CD4 TCM cells. 6 Most CTCLs derive from CD4 T cells, and CD8 CTCLs occur infrequently. With respect to PTCL-NOS, Bekkenk et al. demonstrated that four of 19 cases originated from CD8 T cells. Although PTCL-NOS is considered to have a poor prognosis, several CD8 PTCL-NOS cases exhibiting indolent clinical behaviour without systemic disease have been reported, including a case of CD8 PTCL-NOS in an 18-year-old woman, which we previously reported. No detailed analysis was performed in the cases reported by Khamaysi et al. and Kempf et al., whereas the tumour cells reported by Rosmaninho et al. exhibited abCD3CD8CD27 phenotype, and our case exhibited abCD3CD8CD45RO memory phenotype. As a detailed analysis using the markers for TRM cells was not performed in these cases, it is uncertain whether they are identical to those in the case of CD8 PTCL-NOS in the 96-year-old man reported above. Whether this case should be considered a specific entity of CTCL is currently unknown. However, a distinct set of markers specific for CD8 TRM cells expressed by the tumour cells in this case suggest that there may be a distinct entity of CD8 peripheral T-cell lymphoma, presumably of TRM origin, which may be limited to skin without extracutaneous involvement. Further cases with detailed analyses are needed to confirm this hypothesis.

A U.K. multicentre audit of the assessment and management of psoriasis in children

DEAR EDITOR, To ascertain the current management of psoriasis in children in the U.K., we conducted the first multicentre national audit comparing the practice of paediatric dermatologists with the published National Institute for Health and Care Excellence (NICE) guidelines for the management of chronic plaque psoriasis (Table 1). Participating centres were identified through the British Society of Paediatric Dermatology. Over a 12-week period, all consecutive new and follow-up outpatients with psoriasis, aged ≤ 18 years, were included. Completed proformas (n = 285) were audited against NICE guidance for the assessment of disease severity and impact, therapeutic interventions and screening for associated comorbidities. The data showed a slight female preponderance (n = 174; 61 0%) and the age of the patients ranged from 8 months to 18 years (median 11 years 7 months), which is broadly similar to previously published demographic data. The majority of children (n = 236; 82 0%) were white. The age of onset of psoriasis varied from the neonatal period to 16 years and 7 months (median 7 years). Psoriasis had initially been diagnosed as eczema in 63 (22 0%) patients. The majority of these diagnoses were made in primary care (48 of 63; 76 0%) rather than secondary care (nine of 63; 14 0%). Other initial diagnoses included fungal infection (n = 16; 6 0%) and seborrhoeic dermatitis (n = 4; 1 5%). NICE guidance recommends that disease severity and impact be objectively assessed at diagnosis and therapeutic efficacy be determined. Overall compliance with this standard was poor; Table 1 shows that formal assessment of disease severity and impact was only documented in approximately one-third of patients and there was no difference in meeting this standard between new and follow-up appointments. Adherence to recommended assessment standards improved as therapy escalated from topical agents to biological therapies (Table 2). NICE guidance recommends annual screening for psoriatic arthritis in adult patients with psoriasis, using a validated screening tool such as the Psoriatic Arthritis Epidemiology Assessment Tool. In almost half (n = 128; 45 0%), screening for psoriatic arthritis was documented, performed most frequently (n = 107) as direct questions by a dermatologist (Table 1). At present, the relationship between psoriasis and juvenile psoriatic arthritis is not fully defined, and the role of screening for joint disease in children is unclear. The screening questions asked for other comorbidities are shown in Table 1. NICE guidelines recommend offering topical therapies as first-line treatment for psoriasis, with concomitant use of secondand third-line agents in cases where topical treatment alone is unlikely to control the disease. Selection of drugs appropriate to specific anatomical sites was generally in accordance with NICE guidance, although clear documentation of frequency and duration of topical treatments was often missing. Of children with scalp psoriasis, 39 0% (56 of 145) were treated in line with guidelines recommending a potent topical steroid, often prescribed in a combination product such as Diprosalic (n = 10; MSD, Hoddesdon, U.K.) or Dovobet (n = 18; LEO Laboratories, Dublin, Ireland). Two-thirds of patients (67 of 107) with facial psoriasis and nearly all children with flexural (27 of 28; 96 0%) and genital (25 of 28; 89 0%) psoriasis were treated in line with guidelines recommending a mild-to-moderate topical steroid. In 61 0% (124 of 202) of patients a vitamin D analogue, potent topical steroid or combination of both was used on the trunk and limbs, most frequently Dovobet (76/202; 38%). Topical treatments were not infrequently prescribed outside of licensed indications, such as pimecrolimus (Elidel; Meda Pharma, Somerset, NJ, U.S.A.) or tacrolimus (Protopic; Astellas, Northbrook, IL, U.S.A.), prescribed for facial psoriasis in 34 0% (37 of 107) of patients, and Dovobet, prescribed for children younger than 12 years, in 16 0% of patients (32 of 202). In the majority of children there was a clear indication for treatment with phototherapy, and systemic and biologic therapy (Table 2). Overall, this audit indicates considerable variation in the U.K. management of children with psoriasis when compared with the NICE guidelines. Generally, the choice of topical agent appears appropriate, and the clinical indications for initiating secondand third-line treatment are clearly documented. However, formal assessment of disease severity and impact does not form part of regular clinical practice with the exception of those patients with more severe disease in which biological therapies are being considered. The limitations of our audit include the potential for missing data if clinical assessments were not recorded in the case notes. Performance bias may also have arisen from self-selection of participating centres and the prospective nature of the audit. The paucity of studies establishing the safety and efficacy of therapeutic interventions in childhood psoriasis has

Quality of life in people with vitiligo: a systematic review and meta-analysis

Vitiligo is cosmetically disfiguring and has profound psychosocial effects due to stigmatization, problems in sexual function, anxiety, self-esteem and difficulty finding employment. Previous studies suggest a reduction in quality of life (QoL) due to vitiligo, but to date no systematic review has quantified this in comparison to people without vitiligo. Therefore, the aim of this review was to compare QoL in people with and without vitiligo.

Early recognition and detection of juvenile psoriatic arthritis: a call for a standardized approach to screening

National Institute for Health and Care Excellence (NICE) guidelines recommend annual screening for psoriatic arthritis (PsA) in all patients with psoriasis. Currently, no validated assessment tools have been recommended for screening for juvenile PsA (JPsA).