A curious case of a spontaneous infective native pseudoaneurysm of the internal carotid artery.

We present a case of a 77-year-old patient who presented with a stroke. She subsequently became unwell and was found to have a spontaneous infective native carotid artery pseudoaneurysm. The patient was managed conservatively as per her wishes. Despite the rarity of this clinical diagnosis, clinicians should be aware of the pathophysiology of this entity and the available literature on management.

Treatment outcomes of patients with Atopic Dermatitis (AD) treated with dupilumab through the Early Access to Medicines Scheme (EAMS) in the UK.

BACKGROUND: Dupilumab, a monoclonal antibody against interleukin (IL)-4 receptor alpha that inhibits IL-4/IL-13 signalling is indicated in dermatology for the treatment of moderate-to-severe atopic dermatitis (AD) in adult and adolescent patients 12 years and older and severe AD in children 6-11 years, who are candidates for systemic therapy. Dupilumab received Early Access to Medicines Scheme (EAMS) approval for adults in March 2017. OBJECTIVES: The purpose of this study was to assess the efficacy outcomes of treatment with dupilumab in EAMS. METHODS: A retrospective analysis of adult patients enrolled in the dupilumab EAMS in the UK. Scores were assessed at baseline and follow up, including the Eczema Area and Severity Index (EASI), Investigator's Global Assessment Score (IGA) and Dermatology Life Quality Index (DLQI). RESULTS: Data were available for 57 adult patients treated with dupilumab for at least 12 weeks; 73.6% of patients had received prior treatment with 3 or 4 immunosuppressants. Baseline scores for the EASI and DLQI were 27.93 (standard deviation, SD 13.09) and 18.26 (SD 6.18) respectively. AD severity scores showed statistically significant improvement at week 16±4 weeks (p <0.001 for all). The mean change in EASI was 14.13 points with 66.7% and 36.7% achieving a 50% (EASI-50) and 75% (EASI-75) improvement in EASI, respectively at 16+/- 4 weeks. IGA scores improved by at least two categories for 75% patients. DLQI scores decreased by a mean of 9.0 points, with 80% patients demonstrating a MCID 4-point improvement. For 85% patients, clinicians rated the treatment response as being either 'better' (19%) or 'much better' (65%). CONCLUSIONS: Dupilumab is associated with a significant and clinically relevant improvements in AD as measured by patient- and physician-reported outcome measures. Importantly, the clinical efficacy, despite the refractory disease of this EAMS cohort, is comparable to that previously reported in clinical trials.

Genetic interaction between placental growth factor and vascular endothelial growth factor A in psoriasis.

BACKGROUND: Expression of vascular endothelial growth factor A (VEGFA) is increased in chronic inflammatory skin diseases, including psoriasis, and loci for two VEGFA single nucleotide polymorphisms are associated with early-onset psoriasis (presenting before the age of 40 years). Studies have suggested that expression of placenta growth factor (PGF) is also upregulated in cutaneous inflammation and that VEGFA-mediated angiogenesis may be dependent on the simultaneous presence of PGF within the skin. AIM: To elucidate the biological importance of PGF in psoriasis. METHODS: We investigated whether two commonly occurring PGF polymorphisms were associated with early-onset psoriasis and the genetic interaction between VEGFA and PGF in psoriasis. RESULTS: We observed a significant (P = 0.04) association between rs2268614 TT and rs2268615 AA genotypes of PGF and early-onset psoriasis. In addition, genetic complement, comprising the PGF rs2268615 AA genotype and the VEGFA -460 (rs833061) T allele, was significantly associated with the development of early-onset psoriasis (P < 0.03). We identified that the VEGFA genotype influences PGF expression (P = 0.001) and that mean plasma levels of PGF are lower in patients with severe psoriasis compared with those with mild-moderate disease (P = 0.04). CONCLUSION: Our observed genetic interaction between PGF and VEGFA appears relevant to psoriasis, a disease with an angiogenic basis, and may influence development of an antiangiogenic approach to treatment.

Validity and sensitivity to change of laser Doppler imaging as a novel objective outcome measure for cutaneous lupus erythematosus.

OBJECTIVES: The objectives of this study were to assess the reliability of a novel objective outcome measure, laser Doppler imaging (LDI), its validity against skin biopsy histology and other clinical instruments, including localized cutaneous lupus disease area and severity index (L-CLASI) and visual analogue scale (VAS) score of photographs, and its responsiveness to clinical change with therapy. METHODS: A prospective observational cohort study was conducted in 30 patients with active cutaneous lupus erythematosus (CLE). At baseline and 3 months, disease activity was assessed using L-CLASI and a high resolution LDI system by two assessors. Skin biopsy was scored as 0 = non-active, 1 = mild activity and 2 = active. Photographs were assessed by two clinicians using 100 mm VAS. Inter-rater reliability was analyzed using Bland-Altman limits of agreement. Correlation between histology and LDI, L-CLASI and VAS and sensitivity to change of LDI with physician subjective assessment of change (PSAC) at 3 months were analyzed using Kendall's tau-a. RESULTS: Of 30 patients with CLE, 28 (93%) were female, mean (SD) age 48.4 (11.5) y, 25 (83%) were Caucasians, 25 (83%) had concurrent systemic lupus erythematosus and 16 (53%) were smokers. CLE subtypes were acute = 9, subacute = 8 and chronic = 13. Inter-rater agreement for LDI was fair but for VAS score of photographs was poor. In 20 patients with biopsy, correlation with histology was better for LDI (tau-a = 0.53) than L-CLASI (tau-a = 0.26) (difference = 0.27; 90% CI 0.05-0.49) or VAS score of photographs (tau-a = 0.17) (difference = 0.36; 90% CI 0.04-0.68). There was a moderate correlation between PSAC score and change in LDI (tau-a = 0.56; 90% CI 0.38-0.74; p < 0.001, n = 15). CONCLUSION: LDI provides a reliable, valid and responsive quantitative measure of inflammation in CLE. It has a better correlation with histology compared to clinical instruments. LDI provides an objective outcome measure for clinical trials.

Assessment of two screening tools to identify psoriatic arthritis in patients with psoriasis.

BACKGROUND: Many patients with psoriasis have undiagnosed psoriatic arthritis. Low specificity is found with many PsA screening tools. A new instrument, the CONTEST questionnaire, was developed utilizing the most discriminative items from existing instruments. OBJECTIVE: The aim of this study was to compare the CONTEST and PEST screening tools. METHODS: People attending secondary care clinics with psoriasis, but not PsA, completed the questionnaires, were assessed for function and quality of life, and had a physical examination. Patients thought to have PsA were compared to those without. The performance of CONTEST and PEST was compared using area under the receiver operating curve (AUC), and sensitivity and specificity at the previously published cut-offs. RESULTS: A total of 451 dermatology patients were approached, 35% were reviewed and 27 (17%, 95% CI 12.3-21.7) had unidentified psoriatic arthritis. The sensitivity and specificity (95% CI) of PEST were 0.60 (0.42-0.78)/0.76 (0.69-0.83) and for CONTEST 0.53 (0.34-0.72)/0.71 (0.63-0.79). The confidence limits for the AUC overlapped (AUC for PEST 0.72 (0.61-0.84), for CONTEST 0.66 (0.54-0.77). CONCLUSIONS: PEST and CONTEST questionnaires performed equally well, with no superiority of the new CONTEST tool.

Inflammatory bowel disease meta-evidence and its challenges: is it time to restructure surgical research?

AIM: The aim of this study was to compare the methodological quality and input paper characteristics of systematic reviews and meta-analyses reported in the medical and surgical literature by performing a systematic 'overview of reviews'. Ulcerative colitis (UC) and Crohn's disease (CD) were used as the framework for this comparison as they are relatively common serious conditions, with both medical and surgical options for therapy. METHOD: Medline, Embase, CINHAL and the Cochrane Database were searched to November 2013. Eligible papers were systematic reviews or meta-analyses that considered a question of therapy in CD or UC. Two independent reviewers selected the papers, extracted the data and scored their methodology using the AMSTAR scoring system. The papers were categorized into medical therapy (M), surgical therapy (S) or medical and surgical therapy (MS) groups. Following retrieval of the sample of meta-evidence papers, the original input studies used in their creation were identified and a search of Medline, Embase, CINHAL and the Cochrane Database was performed. A team of researchers then examined the collection of papers for bibliographic and financial information. RESULTS: Five hundred papers were identified in the meta-evidence search, of which 118 were deemed eligible. There was a difference in the AMSTAR-rated average quality of the papers between the S and M group (S 7.36 vs M 8.75, P = 0.01). On average S papers were published in journals with a lower impact factor (S 3.26, M 5.04, MS 5.30, P < 0.001). S papers also showed more heterogeneity (I(2) ; S 37%, M 24%, MS 10%, P < 0.001). Some 25% of S meta-analyses used data-sets with significant heterogeneity (I(2) > 75%), compared with 8% of M meta-analyses and 3% of the MS meta-analyses. Some 5% of S papers were done on data sets that had I(2) values > 90%. There was no difference in the average number of papers assessed in each group, the average number of patients per meta-paper, the average time covered by the reviews, the average number of papers considered within each meta-analysis, or the average number of patients considered within each meta-analysis. Considering the conclusions of each meta-analysis, S meta-evidence was 50% more likely than M meta-evidence to be unable to make recommendations for practice. A total of 1499 original input papers were identified, of which 283 were used in more than one review. Within the non-repeated papers (n = 1023) the average impact factor within the S group was lower than that of the M and the MS groups (3.720 vs 11.230 vs 7.563, respectively; ANOVAP < 0.001). M papers had higher rates of pharmaceutical sponsorship than S papers (M 56% vs S 1%) and twice the level of government support (M 16% vs S 8%). Of note, 21% of M papers had corporate sponsorship but did not list any conflict of interest. CONCLUSION: Compared with M meta-analyses, S meta-analyses in the UC and CD domain are more likely to be of poorer methodological quality, are of a greater degree of heterogeneity and less often offer a positive conclusion. The papers used to generate meta-evidence in M papers have a greater degree of corporate and government sponsorship, and are more likely to come from journals with higher impact factors.

Acute generalised exanthematous pustulosis induced by Pneumocystis jirovecii pneumonia prophylaxis with dapsone.

We describe the case of HIV-1 infected patient presenting to hospital with a severe cutaneous adverse drug reaction shortly after commencing dapsone therapy as Pneumocystis jirovecii pneumonia prophylaxis. To the best of our knowledge, acute generalised exanthematous pustulosis has not been reported as a reaction to dapsone in the setting of HIV.

Outcomes of infected abdominal aortic grafts managed with antimicrobial therapy and graft retention in an unselected cohort.

OBJECTIVE: To document the treatment of all patients with infected aortic grafts at Christchurch Hospital between 1999 and 2010, focussing on the mortality and morbidity of those treated without graft explantation. METHODS: Cases of infected aortic grafts were reviewed. Cases required a compatible clinical syndrome, CT imaging and tissue/blood culture results. RESULTS: Eighteen patients were identified. Organisms isolated at diagnosis from blood or graft site were Staphylococcus aureus 6 (MRSA 1), beta haemolytic streptococci 2, enteric organisms 9.There was no isolate from 2. One case had graft explantation and brief antimicrobial therapy. Seventeen patients had the graft retained. Of these, 14 received intravenous antimicrobial therapy for 6 weeks and 14 lifelong oral therapy. None died during their initial admission or within 30 days. During a mean follow-up of 57 months, 10 (59%) relapsed (median time 31 months, range 0--98), 4 (24%) underwent graft explantation and 10 (59%) died (median 40 months, range 1e 198). Four of 10 who relapsed had organisms isolated (all enteric). CONCLUSION: Patients treated with lifelong antimicrobial therapy and graft retention survived a median of 41 months, with low early mortality although over half relapsed. Empiric therapy should cover skin organisms and enteric organisms, even for those outside the post-operative period.

Practical experience of ustekinumab in the treatment of psoriasis: experience from a multicentre, retrospective case cohort study across the U.K. and Ireland.

BACKGROUND: There are limited data on the use of ustekinumab outside of clinical trials. OBJECTIVES: To assess the efficacy and safety of ustekinumab in patients with severe psoriasis attending 10 dermatology centres in the U.K. and Ireland. METHODS: A retrospective case-note review of 129 patients with psoriasis treated with ustekinumab. RESULTS: Baseline Psoriasis Area and Severity Index (PASI) was 22·9±10·1 (mean±SD). After 16weeks of treatment with ustekinumab PASI 75 (75% reduction in PASI) was observed in 63·0% (n=80/127) of patients, although four patients required concomitant therapy at the 16-week time point. Previous biologic use did show a small, non-significant trend towards treatment failure. A PASI 75 response was seen in 29·4% (n=5/17) of individuals weighing 90-100kg and treated with the standard 45mg ustekinumab dose compared with PASI 75 of 70·3%, 71·4%, 75·0% and 55·6% for weight groups <80, 80-90, 100-110 and >110kg, respectively (P=0·024). Ustekinumab therapy was well tolerated; serious adverse events were observed in 2·3% (n=3/129) of patients. CONCLUSIONS: Ustekinumab is a novel biologic agent for psoriasis. When used in everyday clinical practice it demonstrates high levels of short-term therapeutic efficacy with an acceptable short-term safety profile.

Psoriatic arthritis--what the dermatologist needs to know.

Psoriasis is commonly associated with a co-existent arthritis known as psoriatic arthritis (PsA). Although there is some treatment overlap for psoriasis and psoriatic arthritis, it is possible that dermatologists may not diagnose or treat appropriately patients who are developing psoriatic arthritis at an early stage of the disease process when joint damage may be preventable. In this article we review the criteria for diagnosis of this sero-negative arthritis, look at the clinical indications for referral to a rheumatologist and discuss evolving treatment options relevant to both conditions.

Simvastatin plus nitric oxide synthase inhibition modulates remote organ damage following skeletal muscle ischemia-reperfusion injury.

UNLABELLED: Ischemia-reperfusion injury (IRI) to the lower extremities causes both local damage and serious dysfunction to remote organs, including lungs and kidneys. However, effective therapies are not available. This study aims to determine if simvastatin reduced the severity of remote damage following IRI. METHODS: Rats were given simvastatin before hind limb IRI. Lung and kidney tissues were assessed for neutrophil infiltration using myeloperoxidase assays and basement membrane damage by quantitative immunohistochemical measurement of collagen IV. The effect of nitric oxide synthase (NOS) inhibition on remote damage after IRI and simvastatin was assessed using the NOS inhibitor, L-NIO. RESULTS: Simvastatin (2 mg/kg) protected kidneys against IRI-induced neutrophil infiltration. Simvastatin also inhibited the IRI-induced activation of MMP-9 in the lungs. However, paradoxically, simvastatin exacerbated IRI-induced neutrophil infiltration into the lungs. IRI induced collagen IV degradation in the lungs but not in the kidneys. The degree of collagen breakdown in the lungs was significantly ameliorated by 2 mg/kg simvastatin. NOS inhibition markedly protected both the lungs and the kidneys against IRI-induced neutrophil infiltration but did not alter collagen IV degradation. Administration of simvastatin to L-Nio-treated animals enhanced the degree of protection against IRI-induced neutrophil infiltration in the kidneys but not in the lungs. CONCLUSIONS: Simvastatin protects against remote IRI-induced damage in the lungs and kidneys, suggesting statins may reduce the severity of IRI during major vascular surgery.