Anakinra for palmoplantar pustulosis: results from a randomized, double-blind, multicentre, two-staged, adaptive placebo-controlled trial (APRICOT).

BACKGROUND: Palmoplantar pustulosis (PPP) is a rare, debilitating, chronic inflammatory skin disease that affects the hands and feet. Clinical, immunological and genetic findings suggest a pathogenic role for interleukin (IL)-1. OBJECTIVES: To determine whether anakinra (an IL-1 receptor antagonist) delivers therapeutic benefit in PPP. METHODS: This was a randomized (1 : 1), double-blind, two-staged, adaptive, UK multicentre, placebo-controlled trial [ISCRTN13127147 (registered 1 August 2016); EudraCT number: 2015-003600-23 (registered 1 April 2016)]. Participants had a diagnosis of PPP (> 6 months) requiring systemic therapy. Treatment was 8 weeks of anakinra or placebo via daily, self-administered subcutaneous injections. Primary outcome was the Palmoplantar Pustulosis Psoriasis Area and Severity Index (PPPASI) at 8 weeks. RESULTS: A total of 374 patients were screened; 64 were enrolled (31 in the anakinra arm and 33 in the placebo arm) with a mean (SD) baseline PPPASI of 17·8 (10·5) and a PPP investigator's global assessment of severe (50%) or moderate (50%). The baseline adjusted mean difference in PPPASI favoured anakinra but did not demonstrate superiority in the intention-to-treat analysis [-1·65, 95% confidence interval (CI) -4·77 to 1·47; P = 0·30]. Similarly, secondary objective measures, including fresh pustule count (2·94, 95% CI -26·44 to 32·33; favouring anakinra), total pustule count (-30·08, 95% CI -83·20 to 23·05; favouring placebo) and patient-reported outcomes, did not show superiority of anakinra. When modelling the impact of adherence, the PPPASI complier average causal effect for an individual who received ≥ 90% of the total treatment (48% in the anakinra group) was -3·80 (95% CI -10·76 to 3·16; P = 0·285). No serious adverse events occurred. CONCLUSIONS: No evidence for the superiority of anakinra was found. IL-1 blockade is not a useful intervention for the treatment of PPP.

An economic evaluation of the randomized controlled trial of topical corticosteroid and home-based narrowband ultraviolet B for active and limited vitiligo (the HI-Light Vitiligo Trial).

BACKGROUND: Economic evidence for vitiligo treatments is absent. OBJECTIVES: To determine the cost-effectiveness of (i) handheld narrowband ultraviolet B (NB-UVB) and (ii) a combination of topical corticosteroid (TCS) and NB-UVB compared with TCS alone for localized vitiligo. METHODS: Cost-effectiveness analysis alongside a pragmatic, three-arm, placebo-controlled randomized controlled trial with 9 months' treatment. In total 517 adults and children (aged ≥ 5 years) with active vitiligo affecting < 10% of skin were recruited from secondary care and the community and were randomized 1: 1: 1 to receive TCS, NB-UVB or both. Cost per successful treatment (measured on the Vitiligo Noticeability Scale) was estimated. Secondary cost-utility analyses measured quality-adjusted life-years using the EuroQol 5 Dimensions 5 Levels for those aged ≥ 11 years and the Child Health Utility 9D for those aged 5 to < 18 years. The trial was registered with number ISRCTN17160087 on 8 January 2015. RESULTS: The mean ± SD cost per participant was £775 ± 83·7 for NB-UVB, £813 ± 111.4 for combination treatment and £600 ± 96·2 for TCS. In analyses adjusted for age and target patch location, the incremental difference in cost for combination treatment compared with TCS was £211 (95% confidence interval 188-235), corresponding to a risk difference of 10·9% (number needed to treat = 9). The incremental cost was £1932 per successful treatment. The incremental difference in cost for NB-UVB compared with TCS was £173 (95% confidence interval 151-196), with a risk difference of 5·2% (number needed to treat = 19). The incremental cost was £3336 per successful treatment. CONCLUSIONS: Combination treatment, compared with TCS alone, has a lower incremental cost per additional successful treatment than NB-UVB only. Combination treatment would be considered cost-effective if decision makers are willing to pay £1932 per additional treatment success.

Randomized controlled trial of topical corticosteroid and home-based narrowband ultraviolet B for active and limited vitiligo: results of the HI-Light Vitiligo Trial.

BACKGROUND: Evidence for the effectiveness of vitiligo treatments is limited. OBJECTIVES: To determine the effectiveness of (i) handheld narrowband UVB (NB-UVB) and (ii) a combination of potent topical corticosteroid (TCS) and NB-UVB, compared with TCS alone, for localized vitiligo. METHODS: A pragmatic, three-arm, placebo-controlled randomized controlled trial (9-month treatment, 12-month follow-up). Adults and children, recruited from secondary care and the community, aged ≥ 5 years and with active vitiligo affecting < 10% of skin, were randomized 1 : 1 : 1 to receive TCS (mometasone furoate 0·1% ointment + dummy NB-UVB), NB-UVB (NB-UVB + placebo TCS) or a combination (TCS + NB-UVB). TCS was applied once daily on alternating weeks; NB-UVB was administered on alternate days in escalating doses, adjusted for erythema. The primary outcome was treatment success at 9 months at a target patch assessed using the participant-reported Vitiligo Noticeability Scale, with multiple imputation for missing data. The trial was registered with number ISRCTN17160087 on 8 January 2015. RESULTS: In total 517 participants were randomized to TCS (n = 173), NB-UVB (n = 169) and combination (n = 175). Primary outcome data were available for 370 (72%) participants. The proportions with target patch treatment success were 17% (TCS), 22% (NB-UVB) and 27% (combination). Combination treatment was superior to TCS: adjusted between-group difference 10·9% (95% confidence interval 1·0%-20·9%; P = 0·032; number needed to treat = 10). NB-UVB alone was not superior to TCS: adjusted between-group difference 5·2% (95% CI - 4·4% to 14·9%; P = 0·29; number needed to treat = 19). Participants using interventions with ≥ 75% expected adherence were more likely to achieve treatment success, but the effects were lost once treatment stopped. Localized grade 3 or 4 erythema was reported in 62 (12%) participants (including three with dummy light). Skin thinning was reported in 13 (2·5%) participants (including one with placebo ointment). CONCLUSIONS: Combination treatment with home-based handheld NB-UVB plus TCS is likely to be superior to TCS alone for treatment of localized vitiligo. Combination treatment was relatively safe and well tolerated but was successful in only around one-quarter of participants.

Management of nail psoriasis.

Nail involvement is estimated to affect 80-90% of patients with psoriasis at some point in their lives and is often associated with severe disease. Patients with nail involvement experience pain, functional impairment and social stigma, with significant restriction of daily activities and quality of life. Nail psoriasis is also considered a risk factor for the development of psoriatic arthritis (PsA). Management of nail psoriasis is deemed challenging and as a result, it is often left untreated by physicians. Assessing the severity of nail disease can also be difficult in clinical practice. While the Nail Psoriasis Severity Index is used widely in trials, it is time-consuming and rarely used in the clinic, highlighting the need to develop a simplified disease severity score for nail psoriasis. All patients should be advised to keep their nails short, wear gloves for wet and dirty work, and regularly apply emollient to the nail folds and nail surface. Patients with mild nail psoriasis, without signs of severe cutaneous psoriasis or PsA, may benefit from topical treatment, while systemic treatment is indicated in patients with severe nail involvement. Evidence suggests that all anti-tumour necrosis factor (TNF)-α, anti-interleukin (IL)-17, and anti-IL-12/23 antibodies available for plaque psoriasis and PsA are highly effective treatments for nail psoriasis. This article aims to provide an up-to-date review of the therapeutic options currently available for the management of nail psoriasis in patients with or without skin psoriasis. Therapeutic options for the management of nail psoriasis in children will also be discussed.

New mutation identified in two sisters with adult-onset erythropoietic protoporphyria.

BACKGROUND: Erythropoietic protoporphyria (EPP; OMIM #177000) is a rare disease that usually presents in infancy or early childhood. The uncommon adult-onset EPP is often associated with acquired somatic mutations of the FECH gene, secondary to blood dyscracias. METHODS: We investigated two sisters with adult-onset EPP. RESULTS: We found a novel germline mutation in the FECH gene, in trans with the common hypomorphic IVS3-48C allele. CONCLUSIONS: The adult presentation and identical genotypes of the two sisters suggests that the late development of the condition is to an extent a function of the mutation. The exact mechanism for this delayed penetrance is not clear, although these atypical cases raise the possibility of other genetic or nongenetic disease-modifying factors.

Cephalothoracopagus janiceps asymmetros twins: antenatal sonographic diagnosis.

Conjoined twins have been the subject of myth and legend since antiquity because of the rarity and peculiarity of their juxtaposition. Fortunately, modern medical technology and concurrent advancements in surgical techniques provide an opportunity for successful separation and hope of a normal independent existence for these unique children. Antenatal sonography allows timely detection of this condition so that further management may be planned.

Myocardial protection by Salvia miltiorrhiza Injection in streptozotocin-induced diabetic rats through attenuation of expression of thrombospondin-1 and transforming growth factor-ß1.

OBJECTIVES: To investigate the myocardially protective effects of Salvia miltiorrhiza injection in streptozotocin-induced diabetic rats and the possible mechanisms involved. METHODS: Adult male Sprague-Dawley rats were randomized into three groups (n = 10 per group): diabetes, no treatment (Sm-); diabetes, S. miltiorrhiza injection (Sm+); control (no diabetes; saline treatment). After model induction and 4 weeks' treatment, heart function of five rats from each group was tested by Langendorff isolated in vivo heart perfusion. In the remaining rats, pathological changes of the myocardium were observed by haematoxylin and eosin staining, and protein levels of thrombospondin-1 (TSP-1) and transforming growth factor-ß1 (TGF-ß1) were assessed by immunohistochemistry. RESULTS: Left ventricular systolic end pressure and left ventricular developed pressure were significantly improved in the Sm+ group compared with the Sm- group. Pathological changes were ameliorated through significantly reduced TSP-1 and TGF-ß1 protein levels. CONCLUSIONS: S. miltiorrhiza injection may improve the heart function of diabetic rats and protect against cardiomyopathy by downregulating TSP-1 and TGF-ß1 in myocardial tissue.

Simultaneous determination of one nonionic and two anionic surfactants using Fourier transform infrared spectrometry and multivariate analysis.

A direct and reagent free procedure for simultaneous determination of sodium lauryl ether sulfate (SLES), coconut diethanol amide (CDEA) and linear alkylbenzene sulfonate (LABS) in undiluted samples of hand dishwashing liquids has been developed. This determination was carried out by using attenuated total reflectance Fourier transform infrared spectrometry (ATR-FTIR) and multivariate analysis. An implementation of the PLS statistical approach to quantitative analysis of one nonionic and two anionic surfactants was applied to a set of mid-infrared spectra (1305-990 cm(-1)) recorded for commercial detergent samples and ternary standard solutions. An orthogonal calibration design for three components and five levels for standards were employed. Number of factors and scans and also the resolution were optimized. The statistical parameters such as the root mean square error of calibration (RMSEC), root mean square error of cross-validation (RMSECV), standard error of prediction (SEP) and relative standard deviation (R.S.D.) were evaluated. These parameters were obtained as: RMSEC 0.13, 0.20 and 0.14, RMSEV 0.09, 0.17 and 0.04 and SEP 0.12, 0.39 and 0.18 (g per 100 g) for SLES, CDEA and LABS, respectively. R.S.D. for five independent analyses were 1.69 for SLES, 3.76 for CDEA and 1.76 for LABS. The component linear correlation coefficients comparing actual and predicted concentrations of SLES, CDEA and LABS in some real samples were 0.9995, 0.9915 and 0.9974, respectively.

Does solitary morphoea profunda progress?

Solitary morphoea profunda (SMP) is an unusual form of scleroderma and is rarely mentioned in the literature. The back of the trunk is described as the commonest site of involvement by SMP. This disease has been recognized as a nonprogressive condition. We report three cases of SMP seen at our department within a 1-year period. Interestingly, all three patients were females and the lesions were situated on the right upper buttock. In one patient the lesion extended despite using topical tacrolimus but subsequently the lesion was kept under control with topical clobetasol propionate.