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1) Delays between the onset of symptoms and first rheumatology consultation in patients with rheumatoid arthritis: a national survey
Rebecca J Stack, Christian Mallen, Clare Jinks, Peter Nightingale, Karen Shaw, Sandy Herron-Marx,
Rob Horne, Patrick Kiely, Chris Deighton and Karim Raza
Introduction: The first three months following the onset of rheumatoid arthritis (RA) symptoms represents a therapeutic window during which treatment is particularly effective at limiting subsequent joint damage. Therefore, it is vital that patients are seen quickly following the onset of RA symptoms.
Previous research has identified that delays exists at multiple levels including patient delay in seeking help and primary care delays in making timely referrals to a rheumatologist, however, little is known about national patterns of delay. This study investigates the extent and causes of delay in assessment of patients with RA across the UK.
Methods: Ethical approval was obtained from South Birmingham Research Ethics Committee. A national cross-sectional survey of the length of time between the onset of symptoms, first seeing a
GP, being referred to a rheumatologist and being seen by a rheumatologist was undertaken. Newly presenting adults with synovitis (either RA or unclassified arthritis) were recruited from secondary care rheumatology clinics from across 34 NHS Trusts in England and Scotland. Data were collected on levels of delay, as well as demographic characteristics and RA related features (rheumatoid factor and
ACPA status and disease activity).
Results: 815 patients were recruited (548 female, mean age 55 years). The median time between the onset of symptoms and the patient first seeking help from a healthcare professional was 5.4 weeks;
IQR 1.4 - 26.3 weeks). The median time between first seeing a healthcare professional and being referred to a rheumatologist was 6.9 weeks (IQR 2.3 – 20.3 weeks) with patients making a mean of 4 visits before being referred. The median time between being referred to secondary care and seeing a rheumatologist was 4.7 weeks (IQR 2.9 – 7.5 weeks). Overall the median time between symptom onset and seeing a rheumatologist was 26.9 weeks (IQR 14 – 66 weeks); only20% of patients were seen within the first 3 months following symptom onset. Significant differences were found between
NHS Trusts for patient delay (p=0.002), primary care delay (p<0.001) and secondary care delay
(p<0.001).
Conclusions: National guidelines advise that patients should be treated within the first 3 months following symptom onset, however, this research has identified that these guidelines are being achieved in only 20% of patients. In addition, significant variations in patient delay, primary care delay, and secondary care delay were found across NHS Trusts surveyed. Further research is needed to understand barriers to accessing rheumatology services across the UK, and interventions are needed to promote rapid help seeking on the part of the patient and prompt early rheumatology referrals from primary care.
This study has been funded by the National Institute for Health Research’s Research for Patient
Benefit (RfPB) Programme.
2) Prevalence and associations of posterior heel pain in the general population: an epidemiological study
Benjamin D Chatterton 1 , Sara Muller 1 , Edward Roddy 1
1 Arthritis Research UK Primary Care Centre, Research Institute for Primary Care and Health
Sciences, Keele University, Staffordshire, ST5 5BG, United Kingdom. b.chatterton@keele.ac.uk
Objectives
Foot pain is a common complaint in the general population, affecting 17 to 24% of adults. In clinical practice, pain in specific regions of the foot is commonly attributed to specific disorders. Posterior heel pain (PHP) is related largely to disorders of the Achilles’ tendon and associated structures, and causes significant disability. This study aimed to identify the prevalence of PHP and related disability in the general population, and to identify factors associated with PHP.

Methods
A postal questionnaire was mailed to all adults aged 50 years and older registered with four general practices, irrespective of consultation for foot pain. Ethical approval was obtained from the Coventry
Research Ethics Committee (10/H1210/5). Participants reporting foot pain in the last month were asked to indicate the location of foot pain by shading on a foot manikin (© The University of
Manchester 2000. All rights reserved). The presence of disabling foot pain was assessed using the
Manchester Foot Pain and Disability Index. The prevalence of PHP was calculated. Odds ratios (OR) and 95% confidence intervals (95%CI) were calculated for the associations of PHP and disabling PHP with age, sex, neighbourhood deprivation quartile (NDQ), occupational class, body mass index (BMI) and diabetes mellitus using logistic regression.
Results
Out of 9194 mailed participants, there were 5109 responders to the study (56%). 675 (13%) reported
PHP in either heel, of whom 382 reported bilateral symptoms. Disabling PHP was reported by 398
(8%). Having any PHP was significantly associated with a higher BMI, manual occupations (OR 1.89,
95%CI 1.45, 2.47), and diabetes mellitus (OR 1.32, 95%CI 1.03, 1.69), but not age, gender or neighbourhood deprivation. Bilateral PHP was additionally associated with older age and NDQ.
Disabling PHP was significantly associated with age >75 years (OR 12.39, 95%CI 3.71, 41.33), BMI
≥35.0 (OR 2.35, 95%CI 1.01, 5.47), lowest NDQ (OR 3.08, 95% CI 1.47, 6.46), and diabetes mellitus
(OR 2.22, 95%CI 1.00, 4.90).
Conclusions
PHP and related disability are common in adults aged 50 years and older, and are associated with obesity, diabetes mellitus, and neighbourhood deprivation. Bilateral and disabling PHP are also strongly associated with age. This study raises the possibility that weight loss may be a possible treatment for PHP, although prospective studies are needed to identify whether obesity is a causal factor for PHP.
3) Anti TNF therapy in Ankylosing spondylitis
Is there any influence of ethnicity and smoking in treatment outcome?
Das P, Samanta A, Moorthy A, University Hospitals of Leicester NHS Trust, Leicester
Introduction
Ankylosing spondylitis (AS) is a chronic inflammatory condition, which can cause significant disability.
Anti TNF treatment revolutionised the disease outcome in AS. However disease activity, functional impairment, and efficacy of treatment are affected by various environmental, genetic factors e.g. smoking 1 ,ethnicity 2 .Previous comparative studies have looked at the influence of ethnicity on RA 3 ,
SLE 4 . Studies also highlighted a significant delay in initial presentation, initiation of therapy and poor adherence to medications among South Asian patients 5 , however similar studies are sparse in AS.
Smoking is independently associated with earlier onset of Inflammatory back pain, higher disease activity, poorer functional status, quality of life and treatment responses 1 , no previous studies looked into the influence of smoking among South Asians patients with Rheumatic diseases. We attempt to assess the influence of ethnicity and smoking in the disease outcome and treatment responses in our cohort of AS patients on anti-TNF therapy.
Aims:
1.To assess anti-TNF therapy response in South Asian patients.
2.To compare the antiTNF therapy response among South Asians and white British patients.
3.To study the impact of smoking on the disease outcome and treatment responses in AS patients on antiTNF therapy
Methodology:
This is a retrospective observational study. We selected two groups of AS patients on antiTNF therapy
(25 white British and 25 South Asians). Clinical, demographic, investigational parameters and disease outcome measures were collected from the clinical notes and biologics database at University
Hospitals of Leicester NHS Trust. We looked into the impact of Ethnicity and smoking on the disease activity (BASDAI), functional ability (BASFI), systemic inflammatory responses (CRP) and treatment

outcomes comparing South Asian and White British patients. Data collected on an excel sheet and analysed through online statistics software.
Results
Total number of cases included in the study was 50(n=50) 25 South Asian (SA) and 25 white British patients. Demographic details are as shown in Table 1.and clinical parameters are in Table 2.
Table 1. Demographics Table 2. Clinical parameters
South
Asian
White
British
Age (years)
Age of onset of disease (years)
40.7
27.6
41.3
23.2
Average disease duration (years)
GP review and referral to rheumatology service (months)
Rheumatology r/v and start of antiTNF therapy (yrs)
Gender (Male) 88% 68%
HLAB27 - positive
South Asian White
British
9.1
9.6
7.2
7.8
6.4
25%
4.8
66%
Table 3. Treatment outcome
South Asian White British
P value
CRP
BASDAI
Pre antiTNF
14.6
7.01
Post antiTNF
8.4
4.59
Pre antiTNF
12.1
6.6
Post antiTNF
6.2
3.7
P=0.821 p= 0.032
BASFI 6.5
Spinal VAS 7.5
4.8
4.6
6.9
7.2
3.6
4.0 p=0.025 p=0.123
Discussion: South Asian patients got late onset of disease, delay in initial presentation and initiation of anti TNF therapy. Amongst these two groups South Asians patient demonstrated comparatively poorer response to Anti TNFtreatment. There was no statistically significant difference in inflammatory response between these two ethnic groups. The negative impact of smoking on AS disease parameters have been reported in previous studies, which has been confirmed in our group. Smokers from both ethnic groups have showed poorer treatment response, however sub analysis demonstrated
South Asian smokers got comparatively poorer response to anti TNF therapy BASDAI (p=0.003),
BASFI (p=0.026) and Spinal VAS (0.031).
Conclusion:
1. Compared to white British patient, south Asian patient group shown poor treatment response to
Anti-TNF therapy
2. In South Asian patient group there is a delay in referral to secondary care and initiation of anti
TNF therapy.
3. Both ethnic group smokers showed poor clinical outcome and treatment responses to antiTNF therapy.
References
1 Cigarette smoking has a dose dependent impact on progression of structural damage in the spine in patients with axial spondyloarthritis: Results from the German Spondyloarthritis Inception Cohort (GESPIC)Citation:
Annals of the Rheumatic Diseases, August 2013;1468-2060
.2 Kim T. -J.; Kim T. -H.Features of undifferential spondyloarthropathy and juvenile spondyloarthropathy among
Asian populations. Current Rheumatology Reviews, May 2008, vol./is. 4/2(105-110), 1573-3971
3 Panchal S, Moorthy A, Hayat S et al (2012) A national audit of patients with rheumatoid arthritis of black and minority ethnic origin. Annals of the Rheumatic Diseases 71(Suppl. 3):465.
4 Samanta A, Feehally J, Roy S et al (1991) High prevalence of systemic disease and mortality in Asian subjects with systemic lupus erythematosus. Annals of the Rheumatic Diseases 50:490 –2.
5. Kumar K, Daly E, Khattak F et al. The influence of ethnicity on the extent of, and reasons underlying, delay in general practitioner consultation in patients with RA. Rheumatology 2010, 49:1005 –12.

4) Thrombotic Thrombocytopenic Purpura in Systemic Lupus Erythrmatosus: A life thretening complication requiring prompt recognition and treatment.
Adam P. Croft 1,2 , Vijya Rao 1,2 and Caroline Gordon 1,2
1. Rheumatology Research Group, Centre for Translational Inflammation Research, University of
Birmingham, Birmingham, UK. 2. Lupus UK Centre for Excellence Sandwell and West Birmingham
Hospitals NHS trust, West Midlands UK.
Thrombotic Thrombocytopenic Purpura (TTP) is a life-threatening complication of SLE characterised by microangiopathic haemolytic anaemia and thrombocytopenia. Other complications include neurological abnormalities, renal insufficiency and fever (1). It is commonly associated with infection, drugs, malignancy and underlying autoimmune diseases. In patients with SLE the prevalence of TTP is 1-2% (2) and whilst the overall mortality from TTP has fallen from 90% to 25% with institution of plasma exchange transfusion therapy (3), TTP in the context of SLE continues to have a much higher mortality at 50% (4). Early recognition of TTP in patients with SLE and prompt initiation of plasma exchange transfusion is the most important determinant of outcome in these patients (5). TTP must be considered in the differential diagnosis of thrombocytopenia in patients with SLE and SLE must be considered in all patients who develop TTP.
We will present our experience in the recognition and management of TTP in several patients with established SLE and discuss the multi-disciplinary approach to acute management and the importance of early institution of plasma exchange therapy and the role of cytotoxic agents including more recently Rituximab in severe and refractory cases of TTP in patients with SLE.
References
1. Ridolfi RL, Bell WR. Thrombotic thrombocytopenic purpura. Reports of 25 cases and review of the literature. Medicine 1981:60:413-28.
2 S. K. Kwok, J. H. Ju, C. S. Cho, H. Y. Kim, and S. H. Park, “Thrombotic thrombocytopenic purpura in systemic l upus erythematosus: risk factors and clinical outcome: a single centre study,” Lupus.
2009:18:1: 16 –21.
3. G. A. Rock, K. H. Shumak, N. A. Buskard et al., “Comparison of plasma exchange with plasma infusion in the treatment of thrombotic thrombocytopenic p urpura,” The New England Journal of
Medicine. 1991:325:6:393 –397.
4. A. A. Shah, J. P. Higgins, and E. F. Chakravarty, “Thrombotic microangiopathic hemolytic anemia in a patient with SLE: diagnostic difficulties,” Nature Clinical Practice Rheumatology, 2007:3:6:357–362.
5. Musio F et al. Review of thrombotic thrombocytopenic purpura in the setting of systemic lupus erythematosus. Semin Arthritis Rheum 1998:28: 1 –19
5) Does intra-articular corticosteroid injection in the pre-operative period increase the risk of joint infection following hip or knee arthroplasty? A systematic review and meta-analysis
Authors: Nicolas Ellerby, Edward Roddy, Samantha Hider, John Belcher and Christian Mallen
Overview; Intra-articular corticosteroid injections are often used to treat osteoarthritis. There is concern that their use prior to joint replacement surgery increases the risk of joint infection postoperatively
Aims of study: To determine whether prior intra-articular corticosteroid injection increases the risk of post-operative joint infection following primary hip or knee arthroplasty
Methods: A systematic literature search was undertaken in MEDLINE, EMBASE, CINHAL, AMED,
Cochrane library, and Web of Science databases using terms pertaining to corticosteroids, intraarticular injection and joint replacement. Duplicates were removed. Titles, abstracts and full-text papers were screened by 2 reviewers, with disagreement resolved by consensus. Data were extracted using pre-set criteria and methodological quality was assessed using Newcastle-Ottawa quality appraisal tools. Risk estimates from each study were compared, with pooled estimates (95%CI) of the risk of post-operative infection calculated using a random effects model. Heterogeneity was assessed visually with Fores t plots and numerically with Cochran’s Q test and I 2 test.
Results: 61 papers were identified after duplicates were removed. After screening of title and abstract
8 papers met the eligibility criteria with an additional 4 identified through citation search. 12 papers underwent full text review. The studies were separated into hip and knee replacement, with 3 studies from each category included in the meta-analysis. For hip replacement patients the pooled odds ratio was 1.72 (95% CI 0.54-4.59), relative risk 1.61 (95% CI 0.94-2.76) and difference in infection rate

between study and control groups 0.04 (95% CI -0.04-0.11). Of the knee replacement group pooled odds ratio was 1.57 (95% CI 0.49-5.03), relative risk 1.58 (95% CI 0.61-4.08) and difference in infection rate between study and control group was 0.026 (95% CI -0.059-0.111).
Conclusion: Although the methodological quality of studies was generally poor, post-operative infection rate does not appear to increase with prior intra-articular steroid injection.
6) To what extent are we following NICE Guidance on the switching of Biologic drugs In
Rheumatoid arthritis? A regional audit of the midlands
A multi-centre regional audit across 18 Rheumatology units within East and West Midlands was conducted in order to assess NICE compliance of biologic drug switches for RA.
Methods
Data was collected via an online tool on RA patients who had undergone at least one switch of a biologic drug during 2011. The standards specified in NICE TA195 and TA198 were used to assess compliance to NICE guidance on biologic drug therapy in RA. Simple statistical analysis was performed.
Results
There were 335 biologic drug switches in 317 patients. 143 (45%) patients were in the age range of 51 to 65 (mode). 238 (75%) patients were female, 212 (67%) were seropositive (rheumatoid factor and/or anti-CCP). In 299 (94%) switches there was only one switch of biologic drug. 130 (39%) switches were from Etanercept. 173 (52%) switched from a biologic drug to Rituximab. The most common reason given for switching to a drug was NICE guidelines (242, 72%). Physician choice came second (122,
36%). Lack of effect was the most common reason for discontinuing a drug (224, 67%). For patients on Rituximab, Methotrexate was used in 134 switches (77% of the time). Overall NICE compliance for all units was 65% (range 50 to 100%), with anti-tnf to anti-tnf switches for inefficacy making up the majority of non-compliant switches. It would appear that Etanercept is the most discontinued anti-tnf
(90, 40%). Etanercept was also the biologic that led to the most adverse drug reactions (28, 37%).
There was also geographical variation in restrictions on prescribing biologic drugs.
Conclusions
Overall, 219 (65%) switches across 18 units met NICE compliance for switching of biologic drugs.
There are still a number of switches happening due to physician’s choice. Using Rituximab without
Methotrexate and anti-tnf to anti-tnf switching due to inefficacy were the main reasons for noncompliance. Individual units need to look at how well NICE guidance has been implemented and adhered to at a local level to assess the cost impact. Use of commissioning tools and a local common biologic pathway may facilitate smoother and more consistent funding for these drugs in the future.

1) Zoledronate monitoring and adverse events: the Haywood experience
Paul Arkell, Vas Lostarkos, Zoe Paskins Stoke on Trent
Background
Zoledronate is an intravenous bisphosphonate used for treatment of post-menopausal and steroidinduced osteoporosis. Current local guidance is to measure Vitamin D (Vit D), Magnesium (Mg), corrected Calcium (Ca) and Estimated Glomerular Filtration Rate (eGFR) 8 weeks prior to infusion and measurement of Ca and eGFR 4 weeks post infusion. This guidance is informed by the BNF, recent
MHRA alerts regarding zoledronate, and recent national guidance on Vitamin D testing and replacement. The aim of this work was to audit local pre- and post- infusion blood monitoring. In addition, we took the opportunity to evaluate the nature and number of adverse events associated with zoledronate infusion.
Methods
Zoledronate infusions occurring between September 2010 and August 2012 were identified from pharmacy dispensing records, and systematic retrospective case-note review was undertaken for the first 100 unit numbers alphabetically. Clinic letters, discharge summaries and other correspondence were searched for reports of possible adverse events for the whole duration of zoledronate therapy, and biochemistry reports surrounding patients’ most recent infusion date were reviewed. Ca and eGFR pre and post infusion were compared using paired t-tests. In patients with eGFR<45mL/min/1.73m
2 , creatinine clearance (CrCl) was calculated using the Cockcroft-Gault (CG) equation due to concerns about inaccuracy of eGFR.
Results
97 patients with a diagnosis of osteoporosis were included with median (IQR) age 77 (69-83) and 85% being female. Pre-infusion Vit D, Mg, Ca and eGFR were performed within the target 8 weeks in 34%,
60%, 82% and 85% of cases respectively. Post infusion Ca and eGFR were performed in 57% of cases. In one patient with eGFR 44mL/min/1.73m
2 , calculated creatinine clearance using CG was 29 ml/min. During 170 patient years of therapy there were 5 serious adverse events (AEs) including two suspected anterior uveitis, one acute kidney injury, one allergy and one incidence of AF. Other commonly reported AEs were flu-like symptoms following first infusions (13), hypocalcaemia (6) and pyrophosphate arthropathy (2). 6 patients dropped one CKD stage post treatment.
Discussion
This audit shows that the majority of patients receiving zoledronate in our unit are monitored according to our locally agreed guidance. Vitamin D testing pre infusion has only recently been recommended which may explain the lower adherence for this test. eGfR may be an inaccurate test in elderly patients with low body weight and counter checking creatinine clearance in patients with low eGFR, using CG is recommended. The audit has resulted in changing the process of monitoring osteoporosis patients by instituting monitor clinics; this is hoped to both improve adherence and also reduce time nurses spend in administrative duties chasing results allowing them more time for face to face patient care. The frequency of AEs is in line with national figures, however the potential seriousness of these underline the need for timely and appropriate monitoring pre and post treatment.
2) The association between gout and radiographic osteoarthritis: a cross-sectional study
Authors: Megan Bevis, Michelle Marshall, Trishna Rathod, Edward Roddy
Introduction:
Gout is the most common type of inflammatory arthritis and is largely managed in primary care. It classically affects the first metatarsophalangeal joint and distal peripheral joints, whereas the axial joints are typically spared. The reason for this particular distribution is not well understood, however, it has been suggested that osteoarthritis (OA) may be the key factor.

One hypothesis is that there is an association between the disease states of gout and OA as the conditions share common risk factors. The main aim of this study was to determine whether there is an association between gout and (1) radiographic nodal OA at the level of the person and (2) radiographic OA at individual joint sites.
Methods:
A cross-sectional study was performed using participants from three observational cohorts of people aged 50 years and over with knee, hand and foot pain; Clinical Assessment Study of the Knee
(CASK), Hand (CASHA) and Foot (CASF) respectively. Ethical approval was obtained from North
Staffordshire Local Research Ethics Committee (project reference number: 1430) and Coventry
Research Ethics Committee (REC reference number: 10/H1210/5).
Participants with gout were identified through primary care medical records and matched by age and gender to four individuals without gout. The presence and severity of radiographic OA were scored using validated atlases. Crude odd ratios (ORs) and 95% confidence intervals (CI) were calculated between gout and the presence and severity of radiographic OA in the hand, knee and foot. ORs were then adjusted (aOR) for body mass index, diuretic use and hand and knee pain using a conditional logistic regression model.
Results:
Analysis was carried out between gout participants (n=53) and matched subjected without gout
(n=211). No statistically significant associations were observed between gout and radiographic hand, foot or knee OA; however, individuals with gout were more likely to have hand OA including nodal OA
(aOR 1.46; 95% CI 0.61, 3.50) and eight or more hand joints affected with moderate to severe OA
(aOR 3.57; 95% CI 0.62, 20.45), and foot OA including at least one foot joint affected (aOR 2.16; 95%
CI 0.66, 7.06), three of more foot joints affected (aOR 4.00; 95% CI 0.99, 16.10) and severe talonavicular joint OA (aOR 3.69; 95% CI 0.87, 15.77).
Conclusions:
Although these analyses were under-powered, this study does not provide evidence of an association between gout and nodal OA at the level of the person. However, although not statistically significant, hand and foot OA appeared to be more common in people with gout at the level of the individually affected
3) Haemophagocytic Lymphohistiocytosis (HLH)-a devastating consequence of autoimmune disease.
Nehal Narayan, Christopher Marguerie, Rheumatology Dept ,Warwick Hospital
HLH, often referred to as haemophagocytic syndrome, is a rare syndrome of pathologic immune activation, characterized by clinical signs and symptoms of extreme inflammation and haemophagocytosis histologically. Primary HLH is associated with autosomal recessive genetic mutations, and there may be a strong family history on questioning. Secondary HLH, has a wide variety of triggers, including viral infection, malignancy and autoimmune disease. It is thought to be extremely rare-to date, there is no published data on its incidence. It is often referred to as
Macrophage Activation Syndrome when associated with autoimmune disease. Many autoimmune conditions have been linked to HLH in adults, including SLE, vasculitides and Adult onset Still’s disease. In 2004, the histiocyte society published updated diagnostic criteria for HLH (see table).
Diagnosis is often late in the illness and prognosis is poor if treatment is not initiated early in the course of the disease, with death in over 85% of cases. There is little standardised management for
HLH presenting in adulthood, but treatment options include intravenous immunoglobulin, anti-tumour necrosis factor therapy and cyclosporin. More recently, the IL-1 receptor antagonist anakinra has been reported to be effective in controlling HLH in adults.
Here, we describe 2 cases to highlight the importance of early recognition of HLH in those with autoinflammatory disease. In one case, HLH was recognised early, resulting in quick control of

inflammatory disease. In the second case, we demonstrate the consequences of uncontrolled inflammation leading to HLH, and fatal bone marrow failure.
Our first patient is a 51 year old male, diagnosed with psoriatic arthritis 10 years ago. His disease had been in remission on oral methotrexate. He complained of a 4 month history of 4 kg weight loss and night sweats. Examination was unremarkable. Bloods demonstrated raised CRP at 81 and raised ferritin at 887 (ref range 15350 µg/l). Virology unremarkable, full body CT was clear. A bone marrow trephine demonstrated haemophagocytosis. He received an infusion of intravenous immunoglobulins, and symptoms rapidly settled, CRP and ferritin normalised. He is now maintained on 3 monthly immunoglobulin infusions, with no signs of disease recurrence.
Our second patient is a 79 year old male, presenting with a 6 month history of episodic joint swelling, abdominal pain and testicular inflammation. CRP was 418. CT thorax/abdomen/pelvis did not demonstrate any malignancy. A diagnosis of likely polyarteritis nodosa was made, and he received intravenous methylprednisolone. Cyclophosphamide initiation was delayed due to E.Coli urosepsis, and the patient took his own discharge before cyclophosphamide was commenced. He returned 4 weeks later, with widespread joint swelling and drenching sweats. He had splenomegaly on examination. Serum ferritin was 1489, with grossly elevated CRP, haemoglobin of 6.6 and platelets of
98 only. A blood film demonstrated a leukoerythroblastic picture, indicative of bone marrow failure, and bone marrow trephine demonstrated haemophagocytosis. The patient received high dose methylprednisolone and intravenous immunoglobulins, and initially, CRP declined, haemoglobin and platelet count rose, and symptoms began to settle. Two weeks later, the patient deteriorated, with falling platelet count and haemoglobin. A further course of high dose steroid and immunoglobulins did not help, and platelet count fell to 19. The patient developed pneumonia and sadly died.
These cases demonstrate the importance of being aware of HLH in those with autoimmune disease.
Both of these cases highlight the fact that prompt recognition of HLH has important implications for the patient-in the first case we were able to diagnose HLH prior to the onset of cytopenias, with obvious prognostic benefits for the patient.
4) A case of Interstitial Granulomatous Dermatitis with Arthritis (IGDA).
Nehal Narayan, Christopher Marguerie, Rheumatology Dept Warwick Hospital
Here, we describe a patient presenting with skin lesions, iritis and synovitis. Histology was characteristic of interstitial granulomatous dermatitis with arthritis (IGDA). Our case highlights the clinical features of this rare entity. In addition, our case highlights the association of IGDA with iritis, a previously unreported phenomenon.
Our patient, a 56 year old previously fit and well Caucasian postman, attended the medical assessment unit with painful eyes for several weeks. He mentioned a 3 month history of illness, starting with dry cough and nasal congestion, followed by red, painful eyes. Antimicrobial eyes drops from his GP were of little help. 4 week later, he noticed a rash. This consisted of painful lesions starting on the forehead, spreading into the nose, ears, hands, feet and lower limbs. His GP had treated these with a combination of antiseptic cream and low dose oral aciclovir with no effect. At the same time, his ankles and knees became painful and swollen. On examination, he was afebrile. There was an erythematous nodulopapular rash over the cheeks, hands and feet, and several similar lesions over the patellae. There were overlying vesicles over the rash on the forehead, and inside the nose.
Examination of the eyes revealed a serous discharge, with grossly injected conjunctiva bilaterally.
There was florid synovitis of both ankles and knees.
Investigations revealed a normocytic anaemia, normal white cell count. CRP was 330, with plasma viscosity of 2.47mPa.s (ref range 1.50-1.72mPa.s). The patient was commenced on intravenous aciclovir, and further investigations were arranged. Chest X ray was clear, and 3 sets of bloods were unremarkable. Viral swabs were clear. Autoimmune profile demonstrated negative ANCA, ANA, rheumatoid factor. HIV and hepatitis serology negative. Serum ACE was normal. Ophthalmology review confirmed iritis. A diagnosis of likely granulomatous inflammatory disease, with superimposed viral infection of skin lesions, was made. A skin biopsy was taken. The patient received 2 intravenous infusions of 500mg of methylprednisolone, with dramatic improvement in eye, skin and joint symptoms. CRP declined to 100, and he was discharged on oral steroid at 30mg daily.

Skin biopsy demonstrated interstitial granulomatous dermatitis with focally prominent neutrophils and palisading histiocytes (see figure 1). These findings are characteristic of interstitial granulomatous dermatitis with arthritis (IGDA).
At 4 weeks from discharge, the patient’s symptoms had improved, with no new skin lesions but some residual synovitis in both ankles and ongoing minimal redness of both eyes. He was commenced on methotrexate at 15mg once weekly, and 6 weeks later was completely asymptomatic, with complete resolution of synovitis. CRP fell to 8.
IGDA was first described in 1993. It has many cutaneous manifestations, including linear or archiform dermal bands on the trunk, erythematous indurated plaques on the lower limbs, or erythematous papular eruptions on the hands (see figures). These skin lesions are associated with arthritis, which is typically non-erosive. From current review of the literature, there have not been any reports of eye involvement associated with IGDA as in our patient. Histology is defined by an interstitial and palisading granulomatous dermatitis. IGDA tends to follow a chronic relapsing and remitting course.
Reported successful therapies in IGDA include low doses of systemic corticosteroids, cyclosporine and methotrexate.
Our case highlights the heterogeneity of IGDA, and also how rarely it is considered in the differential diagnosis of cutaneous lesions with arthritis. Further, we highlight the occurrence of iritis in IGDA, a previously unreported association.
5) Complete resolution of anti-CCP positive paraneoplastic polyarthritis with resection of underlying lung adenocarcinoma
Dr Ashley Spencer, Dr Taj Saber, Dr Nicola Tugnet and Dr Josh Dixey
Department of Rheumatology, Royal Wolverhampton Hospitals NHS Trust, UK
Background:
Paraneoplastic arthritis is a rarely encountered, but well reported phenomenon. Characteristically, patients are seronegative for rheumatoid factor (RhF) and this has been proposed as a diagnostic criteria 1 . To date, there has been only one case report of a patient who was diagnosed with RhF and anti-CCP positive rheumatoid arthritis (RA), and found to have an underlying adenocarcinoma of the lung 2 . However, this patient died within weeks of the diagnosis before any treatment could be started and effects observed.
Case :
A 50 year old Caucasian woman presented in November 2011 with a 6 month history of inflammatory polyarthritis. She had previously undergone a cadaveric left renal transplant for ischaemic nephropathy in 2007, and right nephrectomy for renal cell carcinoma in 2009. Examination revealed symmetrical synovitis of the MCP and PIP joints of the hands and wrists. The clinical presentation, positive RhF and anti-CCP antibodies were consistent with a diagnosis of Rheumatoid Arthritis [see table]. Methotrexate 10mg weekly was added to the patient’s triple immunosuppressive therapy. In
April 2013, a PET scan demonstrated areas of high uptake in the left kidney and upper left paramediastinum. Biopsy of the left kidney found a benign oncocytoma, however a diagnosis of adenocarcinoma was confirmed following wedge resection of the lung lesion (stage T2N0M0). The inflammatory polyarthritis disappeared immediately afterwards.
Discussion:
The clinical picture is not in keeping with hypertrophic pulmonary osteoarthropathy (HPOA), as there was no radiological evidence of periostitis. We believe the most likely explanation to be that of paraneoplastic polyarthritis. This is the first case of a typical seropositive RA presentation with underlying lung adenocarcinoma, where resection of the tumor has corresponded with complete remission. We encourage clinicians to report similar observations, as a case series may help to further characterize this subset of patients and highlight a need to consider paraneoplastic arthritis in certain seropositive patients.

Investigation Result
Hb (Haemoglobin 11.5 - 16.0g/dL)
ESR (Erythrocyte sedimentation rate 1-12 mm/hr)
Creatinine (60-120 umol/l)
CRP (C-reactive protein 1-6 mg/l)
RF (Rheumatoid factor 0-20 IU/mL)
Anti-CCP (anti-cyclic citrullinated protein antibody 0-7 U/ml)
14
38
92
17
85
314
Disclosure statement: The authors have declared no conflicts of interest.
References:
1.
Morel J, Deschamps V, Toussirot E, Pertuiset E, Sordet C et al. Characteristics and survival of
26 patients with paraneoplastic arthritis. Ann Rheum Dis. 2008 67(2):244 –247
2.
Larson E, Etwaru D, Siva C, Lawlor K. Report of anti-CCP antibody positive paraneoplastic polyarthritis and review of the literature. Rheumatol Int. 2011 Dec;31(12):1635-8
6) Fever and meningism in a women with Rheumatoid arthritis and chronic immune mediated thrombocytopenia in her second trimester of pregnancy
Adam P. Croft 1,2 , Caroline Gordon 1,2 and Elizabeth A Justice 3
1. Rheumatology Research Group, Centre for Translational Inflammation Research, University of
Birmingham, Birmingham, UK. 2. Lupus UK Centre for Excellence Sandwell and West Birmingham
Hospitals NHS trust, West Midlands UK. 3. University Hospital Birmingham NHS Trust, Birmingham,
West Midlands, UK.
A 34-year old pregnant women of 26 weeks gestation and a background of rheumatoid arthritis (RA), chronic immune mediated thrombocytopenia (ITP) and hypothyroidism presented with an acute frontal headache and fever associated with signs of meningism. She was on high dose immunosuppressant therapy including prednisolone 50mg once a day, hydroxychloroquine 200mg twice a day and tacrolimus 1.5mg once a day. She had recently received a course of intravenous immunoglobulin G
(IVIG) for refractory thrombocytopenia having her second infusion only 12 hours before the onset of her symptoms. Clinical examination revealed no focal neurological deficit but she was photophobic with neck stiffness and looked unwell with a temperature was 38

C. On admission her platelet count was 116 (150-400 cells x10 9 ), WBC 6.8 (3-11 cellsx10 9 /L), Hb 111 g/L (120-160 g/l) and CRP 53. Due to risk of infection she was initially treated with intravenous ceftrixone and amoxicillin. A lumbar puncture was attempted following platelet transfusion and was unsuccessful. A repeat procedure was thought to be too high risk and her symptoms had now resolved. After 48 hours antibiotics were discontinued and the patient was observed in hospital for a further 3 days without any relapse in symptoms or fever. A diagnosis of sterile meningitis secondary to IVIG was made given the temporal relationship between the administration of the drug and onset of symptoms.
IVIG is a pooled blood product widely used in the treatment of inflammatory and autoimmune diseases including ITP. There are a number of reported IVIG induced adverse reactions including headache, facial flushing nausea, diarrhoea and rash as well as acute renal failure and anaphylaxis (1). Aseptic meningitis secondary to IVIG has rarely been reported but is has a reported frequency of 1% (2). It can develop with 48 hours of administration and usually resolves without complication within a few days. Antibiotics are not required but where possible lumbar puncture should be performed to exclude infection. Steroids have been used to treat symptoms but there is no definitive evidence of benefit and probably best avoided where there sole indication is for symptomatic relief from sterile meningitis.
References

1.
Kato E, Shindo S, Eto Y, Hashimoto N, Yamamoto M, Sakata Y. et al. Administration of immune globulin associated with aseptic meningitis. JAMA. 1988:259:3269 –3271.
2.
Orbach H, Katz U, Sherer Y, Shoenfeld Y. Intravenous immunoglobulin: adverse effects and safe administration. Clin Rev Allergy Immunol. 2005: 29:173 –184.
7) Paediatric musculoskeletal foot consultations in primary care
Authors: Albert Tan, Kate M. Dunn, Jo Protheroe
Affiliations: Research Institute for Primary Care and Health Sciences, Keele University
Introduction
Musculoskeletal problems account for up to 18% of the primary care workload, but the majority of musculoskeletal research examines an adult population. In paediatric populations, few studies have investigated the range and prevalence of musculoskeletal problems presenting in primary care. 8% of children consult in primary care each year with musculoskeletal problems. In this population, the foot is the most common body region for musculoskeletal presentation, with 1% of children consulting each year in primary care. This study aims to describe the range of paediatric musculoskeletal foot problems presenting in primary care, and determine the proportion of foot consulters with repeat consultations.
Methods
A clinical cohort of paediatric (aged 3-17 years) foot consulters (having a consultation containing a musculoskeletal foot Read code) was constructed using a North Staffordshire general practice consultation database. The Read clinical classification system is used to code consultations occurring in primary care. Musculoskeletal foot Read codes were categorised as symptom codes, trauma diagnosis codes or non-trauma diagnosis codes. Additional foot consultations three months, six months, one year and two years after the index consultation were identified. Analysis was stratified by age, gender and Read code category at index consultation. Binary logistic regression was used to calculate unadjusted odds ratios to assess the association of these factors with further consultation at each outcome point. Read code categories and individual Read codes were analysed to describe the range of musculoskeletal foot problems presenting in primary care.
Results
Within three months of initial consultation, 21% of patients had consulted again with a foot problem.
31% of foot consulters had consulted again within two years. Boys were more likely than girls to have a further consultation. Patients whose initial consultation was coded with a trauma diagnosis Read code were more likely to consult further than those receiving a symptom code at initial consultation.
The majority (72%) of foot consultations were coded using symptom codes (rather than diagnosis codes) and trauma was the most common cause. Foot trauma was more common in boys than in girls.
Discussion
The prognosis for the majority of children consulting with foot problems in primary care appears to be good with no further foot consultations in the two years following initial consultation. However this data only reflects consultations and it is possible that some children continue to experience symptoms without consulting further. A minority of children consult further, possibly indicating persistent foot symptoms. Previous studies have demonstrated that in paediatric populations, boys consult more often than girls with a musculoskeletal problem. This study suggests that in the foot region, this difference is largely attributable to higher rates of trauma in boys.
8) Diagnosis and Early Management of Rheumatoid Arthritis: The Haywood Experience
Paul Arkell, Cath Thwaites, Tilly Birchall, Jon Packham Stoke on Trent.
Background : Rheumatoid arthritis (RA) is a common autoimmune condition causing inflammatory polyarthritis, joint erosion and deformity. National Institute for Health and Care Excellence (NICE) guidance supports the notion of prompt and aggressive medical management aiming for early disease control using glucocorticoids and combination Disease Modifying Antirheumatic Drugs (DMARDs), and a phase of intensive monitoring with monthly disease activity assessment.
At the Haywood Rheumatology Centre patients with newly diagnosed RA should be referred into the
Nurse-Led Disease Management and Education Service for coordination of care during their first 16

weeks. Assessment for intra-muscular (IM) steroid injection and/or DMARD escalation is made every month according to a locally agreed protocol.
This audit of RA diagnosis and early management against NICE guidance also assessed patient outcomes in the year following diagnosis, comparing those seen by the nurse-led service with those receiving only routine follow-up.
Methods: All new patients during Jan-Apr 2012 subsequently receiving DMARDs for diagnosis of RA were included. Data were collected by retrospective case-note review looking for demographic, disease-related, diagnostic, patient-flow, and treatment variables. Analysis was with descriptive statistics and Student T- /Mann-Whitney-U tests for associations in parametric/non-parametric data.
Results: Forty two new RA diagnoses were made over a four month sample period, representing 8% of all new patients and 43% of all patients going on to receive DMARDs. Estimated local RA incidence was 0.25 per 1000 patients per year. Patients were 57% female, 93% White British, and had median age of 61 years.
Median symptom duration at presentation was 7 months. 64% and 74% of cases were positive for
Rheumatoid Factor and anti-Citrullinated Protein Antibody respectively, and musculoskeletal ultrasound scanning (USS) was used in 64% of diagnoses. 72% were referred into the nurse-led clinic, and these individuals were more likely to have shorter symptom duration, initial assessment in
ESC, and absence of tenosynovitis on ultrasound scan.
Patients seen in the nurse-led service received more aggressive early management (significantly higher rate of triple therapy and number of IM depo steroids given), and appeared to have better disease control (significantly lower ESR as proportion of baseline at 2, 3, 6 and 12 months from diagnosis). There was also a higher rate of advice-line contact in this group.
Discussion: This work provides a wealth of information about local assessment, diagnosis and early management of RA. Findings are interesting and relevant to healthcare professionals and policy makers at other units, in particular those relating to improved outcomes among patients seen in our nurse-led service. The development of similar nurse-led services should improve tha quality of care for early synovitis patients.