These data suggest that multiple biological mechanisms underlie the DRB1 association with rheumatoid arthritis severity.

Several recent publications have established a strong association between anti-cyclic citrullinated peptide antibody (anti-CCP)-positive rheumatoid arthritis (RA) and carriage of shared epitope (SE) alleles. Although anti-CCP have also been associated with more severe RA, the issue of whether this is independent of rheumatoid factor (RF) has not been addressed. To identify associations between RF, anti-CCP, SE status and radiological damage, we studied a large cross-sectional cohort with longstanding RA. Individuals (n = 872) enrolled in the study all fulfilled the American College of Rheumatology criteria for RA, had a minimum disease duration of 3 years, and at least one definite radiographic erosion was present in hands or feet. Radiographs were scored blind at study entry by a single musculoskeletal radiologist using a modified Larsen's score. Anti-CCP and RF levels were determined using enzyme-linked immunosorbent assay, and DRB1 typing was performed using polymerase chain reaction based methodology. Both anti-CCP and RF levels were strongly associated with radiographic severity (P < 0.0001). In subgroups stratified for both anti-CCP and RF status, evidence of independent associations of both antibodies with radiographic outcome was found (P < 0.0001). An association of SE alleles with radiographic severity was present only in RF-negative individuals. Anti-CCP positivity was associated with SE status with evidence of a gene-dose effect, most markedly in RF-negative individuals (P < 0.01). Anti-CCP and RF status are independent severity factors for RA, with SE alleles playing at most a secondary role. Our data support the view that previously described associations between SE and radiological severity, especially in RF-negative patients, may be indirect and due to an association with anti-CCP.

Background/Aims Giant cell arteritis (GCA) is the most common of the vasculitides. Visual loss due to vascular occlusion is a well recognised complication of GCA. It is important to remember that other ischaemic complications can occur, leading to atypical clinical features. We present a case of a patient with GCA who did not complain of headaches, but presented with at least five cranial neuropathies, including a right optic neuropathy, ischaemic ulceration of her tongue and a large area of scalp necrosis. Methods We present the results of our patient case review and literature search. Results An 82-year-old retired landlady who was an ex-smoker presented with haemoptysis and was diagnosed with non-small-cell lung cancer. She was treated with chemotherapy and radiotherapy in 2020, then had possible disease progression on CT thorax in 2021. She developed thigh pain, swallowing difficulties and decreased oral intake in 2021, and subsequently developed severe oral ulceration, dehydration and delirium and was admitted to the frailty unit. On examination she had a very large scalp lesion, oral lesions, and multiple cranial neuropathies (right optic neuropathy, right partial third nerve, right seventh nerve, recurrent laryngeal, and bilateral twelfth nerve palsies). Her anterior ischemic optic neuropathy meant she could only see hand movements with the right eye. Blood tests revealed anaemia of chronic disease and a CRP of over 200 mg/L. Ultrasound scan of the temporal arteries showed a halo sign confirming the diagnosis of GCA. CT angiography showed vertebral artery wall thickening and stenosis. She was treated with intravenous methylprednisolone followed by high dose oral prednisolone, and started on methotrexate. She improved symptomatically. The cranial neuropathies resolved and the area of scalp necrosis and ischemic tongue ulceration healed, but vision was not regained. Her inflammatory markers never normalised and she was subsequently started on tocilizumab, with the approval of her oncologist. Her ESR and CRP quickly fell to normal. It remains to be seen how biologic treatment may impact her malignancy. Conclusion This case highlights multiple atypical presenting features of GCA and the need for a high index of suspicion to treat early and avoid irreversible visual loss. A review of the literature reveals that cranial neuropathies secondary to ischemia can be the presenting feature in GCA and multiple cranial neuropathies can occur. This is the first case in the literature, that we are aware of, which involves this number of cranial neuropathies alongside extensive scalp and tongue infarction. These features have all resolved with treatment, with the exception of unilateral permanent visual loss. Disclosure J. Jade: None. V. Barradell: None. A. Coote: None.

Background A 32 year old gentleman was assessed in the rheumatology department in August 2018 having been referred for investigation into the cause of multi-site avascular necrosis (AVN). Methods He had mild Raynaud's symptoms in his hands and recurrent oral ulceration. He was previously fit and well without any history of thrombotic events or family history. He smoked 2 cigarettes a day and denied any alcohol intake. Results In February 2011 he was diagnosed with T-cell lymphoma while in the Navy. He underwent chemotherapy in a medical oncology department at a tertiary care centre. His chemotherapy regime involved 2 cycles of cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP) and 4 cycles of cyclophosphamide, cytarabine, vincristine, doxorubicin, methotrexate, ifosfamide, etoposide, cytarabine (CODOX-M IVAC) which finished in September 2011. He developed severe bilateral hip pain 6 months after completing his chemotherapy. X-rays revealed bilateral avascular necrosis (AVN). He was discharged from the Navy on medical grounds and underwent bilateral total hip replacements in 2013. In March 2014 he developed pain involving both shoulders. An MRI scan revealed extensive bilateral humeral head AVN. He was seen by an orthopaedic surgeon at a tertiary centre and underwent re-surfacing surgery on both shoulders. Meanwhile he was reviewed by the pain team and a palliative care consultant in June- July 2014 for ongoing widespread pain in his elbows, wrists, knees and ankles. He also suffered from depression, poor sleep and expressed frustration regarding his general health and inability to work. Multiple analgesic agents used included amitriptyline, dothiepin, pregabalin, oxycodone, oxynorm and clonazepam. He also tried cognitive behavioural therapy (CBT). He developed a headache and saw a neurologist who investigated this and concluded the patient had an analgesia overuse headache. In December 2017 he developed more pain in his knees and ankles and X-rays revealed AVN of both knees. He underwent a right total knee replacement in June 2018. An MRI scan of his ankles revealed signs of bilateral AVN with bone infarction of the distal tibia and a small area of the talus bilaterally. When he was assessed in the rheumatology clinic in August 2018, he had a number of investigations which revealed normal blood counts, haemoglobin electrophoresis and clotting screen. An autoimmune screen was negative including ANA, ENA and antiphospholipid antibodies. An infection screen including HIV was also negative. A lipid screen revealed a triglyceride level of 10.9, cholesterol 8.1 and HDL ratio of 9.3. Conclusion This challenging case involves a young patient with AVN in 8 sites which is rare. The AVN is likely related to chemotherapy, steroids and untreated hyperlipidaemia. There have been devastating painful and psychological consequences to his daily functioning. Ongoing issues include widespread pain and further sites of AVN. Disclosures A. Haque None. A. Coote None.

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