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Phalangeal microgeodic syndrome (PMS) is a rare condition typically affecting children and is characterised by painful digits precipitated by cold temperatures. In medical literature, cases appear to be clustered in Japan. Adult-onset PMS is particularly rare and although imaging features are characteristic, it may go undiagnosed, as it is not commonly encountered. We present, to our knowledge, the fifth reported case in the literature of adult PMS, the second to affect the feet rather than hands, and the first in a Caucasian adult patient. This case report aims to raise awareness of this likely underdiagnosed condition to allow optimal management and avoidance of unnecessary diagnostic procedures.

OBJECTIVES To examine concurrent validity and discrimination of modified minimal disease activity (mMDA) criteria in peripheral spondyloarthritis (pSpA) following OMERACT filter principles and determine predictors of mMDA response. METHODS Four mMDA versions were derived in the ABILITY-2 study using the SPondyloArthritis Research Consortium of Canada (SPARCC) or Leeds Enthesitis Index (LEI) but excluding psoriasis. To assess concurrent validity, mMDA versions were correlated with Peripheral SpondyloArthritis Response Criteria (PSpARC) remission, Ankylosing Spondylitis Disease Activity Score for inactive disease (ASDAS ID), and physician global. Treatment discrimination was assessed between adalimumab and placebo at week 12. Multiple logistic regression was used to determine baseline predictors of long-term mMDA responses and sustained mMDA. RESULTS The four mMDA versions showed a stronger positive correlation with PSpARC remission (rtet >0.95) versus ASDAS ID (rtet >0.75) at week 12 and years 1-3 and were able to show discrimination (p

The implications of COVID-19 are wide-ranging for specialties such as rheumatology in which immunomodulatory therapies are prescribed. There has been much trepidation among many healthcare professionals regarding the best course of management during this time.

Community organisations have a crucial role in involving under-represented population groups

The outbreak of SARS-CoV-2 has resulted in wide-ranging turmoil at an international level. During the peak of the pandemic, healthcare services in countries worst hit by COVID-19 were required to drastically reconfigure models of care delivery in order to optimise access to both resources and a

Summary Background Chlamydia is the most common sexually transmitted bacterial infection worldwide. National screening programmes and antibiotic treatment have failed to decrease incidence, and to date no vaccines against genital chlamydia have been tested in clinical trials. We aimed to assess the safety and immunogenicity, in humans, of a novel chlamydia vaccine based on a recombinant protein subunit (CTH522) in a prime–boost immunisation schedule. Methods This phase 1, first-in-human, double-blind, parallel, randomised, placebo-controlled trial was done at Hammersmith Hospital in London, UK, in healthy women aged 19–45 years. Participants were randomly assigned (3:3:1) to three groups: CTH522 adjuvanted with CAF01 liposomes (CTH522:CAF01), CTH522 adjuvanted with aluminium hydroxide (CTH522:AH), or placebo (saline). Participants received three intramuscular injections of 85 μg vaccine (with adjuvant) or placebo to the deltoid region of the arm at 0, 1, and 4 months, followed by two intranasal administrations of 30 μg unadjuvanted vaccine or placebo (one in each nostril) at months 4·5 and 5·0. The primary outcome was safety and the secondary outcome was humoral immunogenicity (anti-CTH522 IgG seroconversion). This study is registered with Clinicaltrials.gov, number NCT02787109. Findings Between Aug 15, 2016, and Feb 13, 2017, 35 women were randomly assigned (15 to CTH522:CAF01, 15 to CTH522:AH, and five to placebo). 32 (91%) received all five vaccinations and all participants were included in the intention-to-treat analyses. No related serious adverse reactions were reported, and the most frequent adverse events were mild local injection-site reactions, which were reported in all (15 [100%] of 15) participants in the two vaccine groups and in three (60%) of five participants in the placebo group (p=0·0526 for both comparisons). Intranasal vaccination was not associated with a higher frequency of related local reactions (reported in seven [47%] of 15 participants in the active treatment groups vs three [60%] of five in the placebo group; p=1·000). Both CTH522:CAF01 and CTH522:AH induced anti-CTH522 IgG seroconversion in 15 (100%) of 15 participants after five immunisations, whereas no participants in the placebo group seroconverted. CTH522:CAF01 showed accelerated seroconversion, increased IgG titres, an enhanced mucosal antibody profile, and a more consistent cell-mediated immune response profile compared with CTH522:AH. Interpretation CTH522 adjuvanted with either CAF01 or aluminium hydroxide appears to be safe and well tolerated. Both vaccines were immunogenic, although CTH522:CAF01 had a better immunogenicity profile, holding promise for further clinical development. Funding European Commission and The Innovation Fund Denmark.

Trial design We present a study protocol for a multi-centre, randomised, double-blind, parallel-group, placebo-controlled trial that seeks to test the feasibility, acceptability and effectiveness of a 52-week period of treatment with the first-in-class co-stimulatory blocker abatacept for preventing or delaying the onset of inflammatory arthritis. Methods The study aimed to recruit 206 male or female subjects from the secondary care hospital setting across the UK and the Netherlands. Participants who were at least 18 years old, who reported inflammatory sounding joint pain (clinically suspicious arthralgia) and who were found to be positive for serum autoantibodies associated with rheumatoid arthritis (RA) were eligible for enrolment. All study subjects were randomly assigned to receive weekly injections of investigational medicinal product, either abatacept or placebo treatment over the course of a 52-week period. Participants were followed up for a further 52 weeks. The primary endpoint was defined as the time to development of at least three swollen joints or to the fulfilment of the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria for RA using swollen but not tender joints, whichever endpoint was met first. In either case, swollen joints were confirmed by ultrasonography. Participants, care givers, and those assessing the outcomes were all blinded to group assignment. Clinical assessors and ultrasonographers were also blinded to each other’s assessments for the duration of the study. Conclusions There is limited experience of the design and implementation of trials for the prevention of inflammatory joint diseases. We discuss the rationale behind choice and duration of treatment and the challenges associated with defining the “at risk” state and offer pragmatic solutions in the protocol to enrolling subjects at risk of RA. Trial registration Current Controlled Trials, ID: ISRCTN46017566. Registered on 4 July 2014. Electronic supplementary material The online version of this article (10.1186/s13063-019-3403-7) contains supplementary material, which is available to authorized users.

The term ‘inflammatory arthritis’ (IA) encompasses a spectrum of diseases, of which the most common forms are rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS). Over the past decade, the advent of immunomodulatory biological therapies has dramatically changed the management of such diseases, and offers alternatives for patients with a poor response to the more conventional disease-modifying anti-rheumatic drugs (DMARDs). Over recent years, more emphasis has been placed on the concept of shared care between specialist and primary care physicians for many chronic conditions once on a stable treatment regime, in order to improve hospital workload and enable more flexibility for patients. This brief review highlights the key points relevant to primary care physicians involved in the care of patients with IA on biologic agents. Immunomodulatory biologic agents (Table 1) are proteins derived from human genes that are genetically engineered to inhibit precise components of the immune system.1 By doing so, they suppress specific pathways that play a pivotal role in IA pathogenesis and, hence, differ from the more commonly used DMARDs, which have broader targets.1 If tolerated, biologic agents are used in combination with methotrexate, or an alternative DMARD, in view of enhanced efficacy. View this table: Table 1. Summary of biologic agents licensed for …

Summary The mechanisms underlying the exaggerated inflammatory response in Behçet's syndrome (BS) remain poorly understood. We investigated the response of CD14+ blood monocytes to interferon (IFN)-γ, focusing on the chemokine CXCL10. Chemokine synthesis and release were analysed at a protein and mRNA level following stimulation with IFN-γ. Findings in BS patients were compared with 25 healthy controls (HC), 15 rheumatoid arthritis (RA) and 15 systemic lupus erythematosus (SLE) disease control patients. BS monocytes produced significantly more CXCL10 protein than HC monocytes from 2 h following IFN-γ stimulation, despite equivalent quantities of mRNA, suggesting more efficient translation. This was significantly more pronounced in BS with high disease activity and in those with ocular and neurological clinical manifestations. The imbalance between CXCL10 protein and mRNA expression was not observed in either RA or SLE patients, and was not seen with other chemokines studied (CXCL9, CXCL11 and CCL2). Furthermore, BS monocytes treated with an alternative stimulant (LPS) did not show abnormal tumour necrosis factor (TNF)-α release. Sucrose density gradients to segregate monocyte CXCL10 mRNA into free RNA or polysome-associated RNA showed equal proportions in BS and HC samples, suggesting that the difference between BS and HC may be due to reduced negative control of CXCL10 translation in BS at a post-initiation level. We conclude that BS monocytes have dysfunctional post-transcriptional regulation of CXCL10 mRNA, resulting in over-expression of CXCL10 protein upon IFN-γ stimulation. As CXCL10 is a chemokine that recruits mononuclear cells, this abnormality may contribute to the exaggerated inflammatory responses that characterizes BS.

International audience; Intradermal (i.d.) and intramuscular (i.m.) injections when administered with or without electroporation (EP) have the potential to tailor the immune response to DNA vaccination. This Phase I randomized controlled clinical trial in human immunodeficiency virus type 1-negative volunteers investigated whether the site and mode of DNA vaccination influences the quality of induced cellular and humoral immune responses following the DNA priming phase and subsequent protein boost with recombinant clade C CN54 gp140. A strategy of concurrent i.d. and i.m. DNA immunizations administered with or without EP was adopted. Subtle differences were observed in the shaping of vaccine-induced virus-specific CD4+ and CD8+ T cell-mediated immune responses between groups receiving: i.d.EP + i.m., i.d. + i.m.EP, and i.d.EP + i.m.EP regimens. The DNA priming phase induced 100% seroconversion in all of the groups. A single, non-adjuvanted protein boost induced a rapid and profound increase in binding antibodies in all groups, with a trend for higher responses in i.d.EP + i.m.EP. The magnitude of antigen-specific binding immunoglobulin G correlated with neutralization of closely matched clade C 93MW965 virus and Fc-dimer receptor binding (FcγRIIa and FcγRIIIa). These results offer new perspectives on the use of combined skin and muscle DNA immunization in priming humoral and cellular responses to recombinant protein.

Psoriatic arthritis (PsA) causes inflammation in and around the joints and usually affects people who already have psoriasis. However, some patients develop the joint problems before the psoriasis. Currently, there are five anti-TNF-α agents licensed for use in patients with PsA: adalimumab, certolizumab pegol, etanercept, golimumab and infliximab. Golimumab, a human monoclonal antibody, has been approved by the US FDA for the treatment of PsA and is targeted against the pro-inflammatory molecule TNF-α. The Phase III GO-REVEAL study confirmed this drug was well tolerated and showed significant improvement in disease activity compared with placebo.

To the Editor: Psoriatic arthritis (PsA) is a chronic inflammatory disease involving the skin and joints. It requires detection in primary care, subsequent referral, and initiation of management in secondary care and ongoing joint management. PsA has been associated with greater cardiovascular (CV) disease mortality, morbidity, and atherosclerosis1. The increased CV mortality risk has been shown to be comparable with that of rheumatoid arthritis (RA) and diabetes (risk ratio 1.74, 95% CI 1.32–2.30)2. In addition, risk factors for CV disease, such as hypercholesterolemia, impaired glucose tolerance, and obesity, have all been associated with PsA1,2,3. We sought to establish the current knowledgebase and lifestyle choices of patients with PsA managed in secondary care. This data could then guide changes to services to assist patients in reducing their risk of CV morbidity and mortality. A hundred patients diagnosed with PsA sequentially attending a rheumatology outpatient clinic completed an anonymous electronic questionnaire. Patients were asked to … Address correspondence to Dr. Anna Timmis, Imperial GP Specialty Training, Department of Primary Care and Public Health, Imperial College London, Charing Cross Campus, Reynolds Building, London W6 8RP, UK. E-mail: anna.timmis{at}doctors.org.uk

Aim To assess the efficacy of microvascular imaging in detecting low-grade inflammation in arthritis compared with Power Doppler ultrasound (PDUS). Method and materials Patients presenting for ultrasound with arthralgia were assessed with grey-scale, PDUS and Superb Microvascular Imaging (SMI). Videoclips were stored for analysis at a later date. Three musculoskeletal radiologists scored grey-scale changes, signal on PDUS and/or SMI within these joints. If a signal was detected on both PDUS and SMI, the readers graded the conspicuity of vascular signal from the two Doppler techniques using a visual analogue scale. Results Eighty-three patients were recruited with 134 small joints assessed. Eighty-nine of these demonstrated vascular flow with both PD and SMI, whilst in five no flow was detected. In 40 joints, vascularity was detected with SMI but not with PDUS (p = 0.007). Out of the 89 joints with vascularity on both SMI and PDUS, 23 were rated as being equal; while SMI scored moderately or markedly better in 45 cases (p

Objectives To establish if changes in Th1/Th17 cell populations previously reported in experimental arthritis occur in patients with rheumatoid arthritis (RA) treated with anti-tumour necrosis factor α (TNFα) agents, and whether the therapeutic response to anti-TNFα is compromised in patients and mice because of elevated Th17/IL-17 levels. Finally, to assess the efficacy of combined blockade of anti-TNFα and anti-IL-17 in experimental arthritis. Methods A longitudinal study of two independent cohorts (cohort 1, n=24; cohort 2, n=19) of patients with RA treated with anti-TNFα biological agents was carried out to assess their Th17/IL-17 levels before and after the start of anti-TNFα therapy. IL-12/23p40 production was assessed in plasma Peripheral blood lymphocytes (PBLs) and monocytes. Mice with collagen-induced arthritis (CIA) were treated with anti-TNFα alone, anti-IL17 alone or a combination of the two. Efficacy of treatment and response was assessed from changes in Disease Activity Score 28–erythrocyte sedimentation rate scores in patients, and in clinical scores and histological analysis in CIA. Results Significant increases in circulating Th17 cells were observed in patients after anti-TNFα therapy and this was accompanied by increased production of IL-12/23p40. There was an inverse relationship between baseline Th17 levels and the subsequent response of patients with RA to anti-TNFα therapy. In addition, PBLs from non-responder patients showed evidence of increased IL-17 production. Similarly, in anti-TNFα-treated mice, there was a strong correlation between IL-17 production and clinical score. Finally combined blockade of TNFα and IL-17 in CIA was more effective than monotherapy, particularly with respect to the duration of the therapeutic effect. Conclusions These findings, which need to be confirmed in a larger cohort, suggest that a Th17-targeted therapeutic approach may be useful for anti-TNFα non-responder patients or as an adjunct to anti-TNFα therapy, provided that safety concerns can be addressed.

Secretory phospholipase A2 group IIA (sPLA2-IIA) was examined as a point of care marker for determining disease activity in rheumatoid (RA) and psoriatic (PsA) arthritis. Serum concentration and activity of sPLA2-IIA were measured using in-house antibodies and a novel point of care lateral flow device assay in patients diagnosed with varying severities of RA (n = 30) and PsA (n = 25) and found to correlate strongly with C-reactive protein (CRP). Levels of all markers were elevated in patients with active RA over those with inactive RA as well as both active and inactive PsA, indicating that sPLA2-IIA can be used as an analogue to CRP for RA diagnosis at point of care.

The human body consists of millions of commensal bacteria (the microbiome), with the intestinal tract being the most prevalent site of colonization. This colonization process begins at birth, and despite numerous factors such as ageing, diet and drug use affecting the microbiome make-up, by adulthood the composition of the gut bacteria is relatively consistent across local populations. The recent advent of new scientific techniques has enabled us to explore how the microbiome affects health and, in particular, has shed light on the involvement of the microbiome in the pathogenesis of inflammatory disease. In this review we highlight the current evidence for microbiome manipulation in inflammatory arthritis in animal and human models and discuss potential therapeutics targeting the microbiome as treatment for these diseases.

Clinical Question How should we manage disease-modifying antirheumatic drugs (DMARDs) in primary care when used as part of a shared-care arrangement in inflammatory arthritis? Inflammatory arthritis such as rheumatoid and psoriatic arthritis are chronic diseases requiring long-term management. The overall goal of treatment is to achieve remission or sustained low disease activity.1 The majority of patients are managed effectively using disease-modifying antirheumatic drugs (DMARDs). Traditionally, patients have been managed in secondary care by planned consultation with a rheumatologist every 3–6 months. This system of follow-up accounts for >75% of a rheumatologist’s workload2 and evidence has shown that up to 45% of routine consultations are undertaken without demonstrated patient need.3 Projected future shortages of specialist physicians including rheumatologists mean this arrangement may be untenable in the near future.3 Greater emphasis has therefore been placed on managing patients with stable inflammatory arthritis within the community using shared-care arrangements. Innovations within primary care have developed the role of specialist nurse practitioners and interface teams responsible for the continued monitoring of DMARDs. Shared care is defined as: ‘… the joint participation of GPs and specialists in the planned delivery of care for patients with a chronic condition, informed by an enhanced information exchange, over and above the routine discharge/referral letters.’ 4 This model has been used successfully for >10 years in chronic conditions including asthma and diabetes. Studies have consistently demonstrated that versions of shared care are not inferior to traditional follow-up in controlling disease activity in patients with inflammatory arthritis.3,5,6 Furthermore, symptom control facilitated by shared care is likely to be more cost-effective than treatment delivered in secondary care in 60–90% of cases.7 In the UK it is becoming common to manage patients with stable inflammatory arthritis within primary care using a shared-care arrangement, once …

Summary We investigated changes in circulating T helper type 17 (Th17) cells following anti-tumour necrosis factor (TNF) in rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) patients. Peripheral blood mononuclear cells (PBMC) were isolated from 25 RA, 15 AS and eight PsA patients at baseline 4 and 12 weeks after treatment, and Th17 cell frequencies were analysed using interleukin (IL)-17 enzyme-linked immunospot (ELISPOT) and flow cytometry. A significant increase in IL-17-producing cells was observed by ELISPOT in RA and AS patients at 12 weeks. Flow cytometry confirmed significant increases in CD4+IL-17+ cells at 12 weeks in RA and AS and 4 weeks in PsA patients. Anti-TNF treatment increases circulating Th17 cells in three different diseases.

Innate immune responses are critically dependent on MAPK (mitogen-activated protein kinase) signalling pathways, in particular JNK (c-Jun N-terminal kinase) and p38 MAPK. Both of these kinases are negatively regulated via their dephosphorylation by DUSP1 (dual­-specificity phosphatase 1). Several pro- and anti-inflammatory stimuli converge to regulate the DUSP1 gene and to modulate the time course of its expression. In turn, the pattern of expression of DUSP1 dictates the kinetics of activation of JNK and p38 MAPK, and this influences the expression of several mediators of innate immunity. DUSP1 is therefore a central regulator of innate immunity, and its expression can profoundly affect the outcome of inflammatory challenges. We discuss possible implications for immune-mediated inflammatory diseases and their treatment.

The stress-activated protein kinase p38 stabilizes a number of mRNAs encoding inflammatory mediators, such as cyclooxygenase 2 (Cox-2). In HeLa cells the anti-inflammatory glucocorticoid dexamethasone destabilizes Cox-2 mRNA by inhibiting p38 function. Here we demonstrate that this effect is phosphatase dependent. Furthermore, in HeLa cells dexamethasone induced the sustained expression of mitogen-activated protein kinase phosphatase 1 (MKP-1), a potent inhibitor of p38 function. The inhibition of p38 and the induction of MKP-1 by dexamethasone occurred with similar dose dependence and kinetics. No other known p38 phosphatases were induced by dexamethasone, and other cell types which failed to express MKP-1 also failed to inhibit p38 in response to dexamethasone. The proinflammatory cytokine interleukin 1 (IL-1) induced MKP-1 expression in a p38-dependent manner and acted synergistically with dexamethasone to induce MKP-1 expression. In HeLa cells treated with IL-1 or IL-1 and dexamethasone, the dynamics of p38 activation mirrored the expression of MKP-1. These observations suggest that MKP-1 participates in a negative-feedback loop which regulates p38 function and that dexamethasone may inhibit proinflammatory gene expression in part by inducing MKP-1 expression.

Mycobaterium tuberculosis (MTB) accounts for significant morbidity and mortality worldwide. Non-tuberculous mycobacteria (NTM) species, usually considered benign contaminants, are increasingly recognized to be associated with pulmonary disease in immuno-compromised hosts. The tuberculin skin test (TST) is of limited benefit in immuno-supressed individuals who often fail to mount a delayed type hypersensitivity reaction. In such patients, the ELISpot assay is considered a more robust method of diagnosing tuberculosis. We present a case which illustrates that ELISpot can be negative in mycobacterial disease. A 51 year old Jamaican housekeeper, living in the UK for the past 45 years, presented with a 5-month history of a productive cough, shortness of breath and fatigue. She had a 10 year history of sero-positive rheumatoid arthritis which was well controlled with methotrexate and etanercept, an anti-tumour necrosis factor (TNF) biologic. She had …

Psoriasis arthritis (PsA) is a chronic, inflammatory disease, affecting predominantly skin and joints (Figure 1). Skin psoriasis develops before arthritis in the majority of cases, with a typical time lag of 5 to 10 years. However, around 20% of PsA patients never develop psoriasis.1 The prevalence of psoriasis in the UK is approximately 2% of the adult population.2 Figure 1. Typical clinical presentation of psoriasis arthritis. The white arrow denotes dactylitis and the black arrows denote psoriasis. Epidemiological studies indicate that between 10% and 30% of people with psoriasis will go on to develop PsA, giving a population prevalence for PsA of 0.4%. Out of 40 million adults in England, around 160 000 would be expected to have PsA. According to the National Institute for Health and Care Excellence (NICE), only 6200 people in England are currently registered to receive biological therapies for PsA, representing 4% of this population. Of the 350 000 people in the UK who have rheumatoid arthritis (RA), 35 000 (10%) are on biological therapies. PsA appears to be underdiagnosed not only in the UK but also abroad. According to the American Psoriasis Foundation, there are over 7 million adults in the US who have psoriasis but only 520 000 (7.4%) of these patients have …

Seasonal flu affects 5–15% of the population.[1][1] In the UK, the influenza vaccine is offered annually to those considered to be at risk and belonging to particular target groups which include people aged 65 and over, and those suffering from chronic diseases.[2][2] Influenza immunisation has

A 76 year old man was seen in the rheumatology clinic with a rash (fig 1⇓), monoarthritis of the right wrist, and fatigue. He also had bilateral painful ears (fig 2⇓), an intermittent hoarse voice, and hearing loss. He had a history of gout and was a non-smoker. Six months before presentation, the patient had an episode of anterior uveitis. One year before presentation, he had a prolonged episode of central pleuritic chest pain and an associated dry cough. At this time he was diagnosed with severe atypical pneumonia or possible early interstitial lung disease. He did not respond to three courses of antibiotics, but his symptoms spontaneously improved within six months. At presentation his erythrocyte sedimentation rate was 110 mm (normal range 0-10 mm) in the first hour, C reactive protein was 154 mg/l (0-10 mg/l), haemoglobin was 86 g/l (125-170 g/l), and albumin was 23 g/l (33-34 g/l). Audiometry showed right sided sensorineural hearing loss. Atypical pneumonia, viral serology, and autoimmune serology were negative. High resolution computed tomography of the chest showed mild non-specific fissural nodularity, with minor basal reticulation. Transbronchial biopsy had shown a mild chronic inflammatory interstitial infiltrate and mild fibrosis, but no granulomas or vasculitis. Pulmonary function tests were normal. ### Short answers Fig 3 Purpuric vasculitic rash on the legs (arrow) Fig 4 Auricular chondritis (arrow)

To the Editor: We thank Bachmeyer, et al 1 for their interest in our article “Extraarticular Manifestations of Rheumatoid Arthritis Develop in Patients Receiving Anti-tumor Necrosis Factor-α Treatment: A Retrospective Chart Review from a UK Center”2. Our study assessed the development of extraarticular manifestations of rheumatoid arthritis (RA) — lung disease, renal disease, nodules, and vasculitis — in patients receiving anti-tumor necrosis factor-α (TNF-α) treatment. There were 152 patients (86.7% women) with an established diagnosis of RA being followed up in the rheumatology department at the time of the study, and who had received anti-TNF-α therapy [infliximab, etanercept (ETN), adalimumab (ADA)] initiated between 2000 and 2011. We acknowledge that a wide range of lung … Address correspondence to Dr. A. Negoescu, Rheumatology Research Unit, Addenbrooke’s Hospital, Rheumatology, Box 194, Hills Road, Cambridge, Cambridgeshire CB2 0QQ, UK. E-mail: andra_negoesc08{at}yahoo.com

The topic of smoking seems to be quite controversial of late, with the health hazards being advertised across the board, from smoking cartons to billboards. Despite the increased publicity and warnings, people at large continue to smoke. This is of significant concern considering the health risks of

A 67-year-old lady with known seropositive Rheumatoid Arthritis (RA) was investigated for persistent unexplained positive urine dipstick test for bilirubin, despite normal liver function tests (LFTs). She had originally presented, aged 45 years, with painful feet, minimally responsive to a non-steroidal anti-inflammatory (NSAID), indomethacin. She was found to be strongly rheumatoid factor positive (1:1280) and a diagnosis of RA was made. Initial treatment was with the disease modifying antirheuamtic drug (DMARD), sulphasalazine. Over the following years, her synovitis and erosive arthropathy became refractory to sulphasalazine and she required another DMARD, weekly intramuscular methotrexate 12.5 mg (with folic acid), corticosteroid (deflazocort 3 mg daily) and (etodolac 300 mg) to control her disease. While on these DMARDs she was monitored with 6–8 weekly monitoring of her liver, renal and bone marrow function. At a routine blood and urine monitoring visit she was found to have a positive urinary dipstick for bilirubin.

A 40-year-old woman presented to the emergency department in August, 2013, with a 6 week history of gradual onset pain and swelling over the anteromedial aspect of her left thigh. She had a 10 year history of type II diabetes and was taking oral hypoglycaemic agents, had no history of trauma, and no constitutional symptoms. Physical examination revealed pronounced generalised swelling of the left thigh. The overlying skin was hot and the underlying soft tissue was tender to palpation, with no fl uctuance, erythema or rash. She was unable to weight bear or straight leg raise. Sensation and pulses were intact throughout. She had no diabetic macrovascular complications, but did have bilateral nonproliferative retinopathy. Blood tests showed C-reactive protein 38·1 mg/L (normal: 0–5 mg/L) and erythrocyte sedimentation rate of 95 mm/h (normal: 0–12 mm/h). Glycosylated haemoglobin was 149 mmol/mol (normal: 20–42 mmol/mol). Urine protein/creatinine ratio was 28 units (reference range 0–25). Autoantibody screen, creatinine kinase, and all other blood tests remained normal throughout admission. Doppler ultrasound of the left thigh revealed subcutaneous oedema, but no evidence of deep vein thrombosis or discrete collection. MRI showed extensive soft tissue oedema and diff use swelling of the vastus medialis and intermedius in the left distal thigh. Both muscles heterogeneously enhanced after contrast administration, suggesting necrosis (fi gure). Ultrasound-guided biopsy of the left vastus medialis and lateralis showed widespread fi bre necrosis with endomysial oedema and mild, focal chronic infl ammation (fi gure). Features were consistent with diabetic myonecrosis, also known as diabetic muscle infarction. The patient was treated conservatively with bed rest, non-steroidal anti-infl ammatory medication (naproxen), and physiotherapy. She was started on insulin to improve her glycaemic control. She recovered well and was discharged after 4 weeks. At follow-up in October, 2013, the pain and swelling had improved signifi cantly, and her glycaemic control was better. A systematic review showed that diabetic muscle infarction was more common in women (61·5%), with a mean age at presentation of 42·6 years. Almost 60% of cases had type I diabetes, and the mean duration of disease was 14·3 years. The cause is not fully understood. Several hypotheses have been proposed, including atherosclerosis, hypoxia-reperfusion injury, vasculitis, thrombosis, and a hyper coagulable state. The short-term outlook is generally good, with spontaneous resolution over weeks to months. However, long-term prognosis is poor, and recurrence has been reported in up to 48% of patients, in most cases aff ecting other muscle groups. This case emphasises the need for a high index of suspicion of diabetic muscle infarction when a patient with poorly controlled diabetes presents with nontraumatic limb pain. Clinical history, MRI features, and histology are important to confi rm the correct diagnosis. Muscle biopsy is especially important, to exclude other causes such as pyomyositis, necrotising fasciitis, and neoplasm.

Dear Sir, It is well recognised that patients with autoimmune disease have an increased risk of infection both through virtue of their underlying disease and through concomitant drug use. Following the heavily publicised announcement of the H1N1 or ‘swine flu’ pandemic, there has been much concern expressed by patients taking immunosuppressive therapy. The risk of influenza in these patient groups has not been defined. Extrapolation from data in transplant recipients suggests that prevalence of influenza is low (0–2%).1 However, such patients are …

The renal papilla has a double blood supply - from both the vasa recta and the calyceal arteries. The importance of the latter supply is not established. A case of polyarteritis associated with papillary necrosis is reported, in which the calyceal vessels, supplying the area, show acute necrotizing arteritis and occlusion. The pathophysiological and clinical implications are discussed.

A 70 year old Nigerian man presented to an emergency department in west London with a two day history of progressive drowsiness, lethargy, and reduced appetite. He had no history of fever, cough, urinary symptoms, gastrointestinal symptoms, headaches, or focal neurology. He had a history of type 2 diabetes treated with metformin and glibenclamide, no known allergies, and was fully independent with his activities of daily living. Although he lived in the United Kingdom, he travelled to Nigeria two to three times a year. His last visit to Nigeria had been two months earlier. He had never smoked and rarely drank alcohol. On examination, he did not have a fever (36.7°C), his blood pressure was 113/70 mm Hg, and heart rate was 100 beats/min. He was drowsy but could be roused and had a Glasgow coma scale score of 14. Systems examinations were normal. The bedside blood glucose concentration was 20.6 mmol/L (reference range 3.9-7.8). His urine dipstick was positive for blood and protein. His venous blood gases showed a pH of 7.38 kPa (7.35-7.45), bicarbonate 22 mmol/l (22-26), base deficit −3.3 (−2 to +2), and lactate 2.7 mmol/L (0.5-2). Blood tests showed white cell count 7.2×109/L (4-11), haemoglobin 125 g/L (125-170), platelet count 21×109/L (120-400), activated partial thromboplastin time 28.5 s (24-32), prothrombin time 10.9 s (9.6-11.6), and international normalised ratio 1.2. The C reactive protein was 214 mg/L (0-10), urea 13.8 mmol/L (2.5-8), creatinine 107 mmol/L (60-125), sodium 129 mmol/L (135-145), potassium 4.4 mmol/L (3.5-5.3), total bilirubin 48 μmol/L (0-17), alanine aminotransferase 28 IU/L (0-40), alkaline phosphatase 77 IU/L (30-130), and albumin 27 g/L (33-47). Electrocardiography showed sinus tachycardia. Chest radiography showed clear lung fields. In view of the thrombocytopenia a blood film was requested (figs 1⇓ and …