15. Eosinophilic pneumonitis secondary to baricitinib

Abstract Introduction We present a case of drug-induced pneumonitis in a patient taking baricitinib. Case description A 63-year-old patient with longstanding sero-positive erosive RA (anti-CCP &gt;340) on long term methotrexate started taking baricitinib for his poorly-controlled arthritis 5 weeks prior to the hospital admission with two-week history of increasingly short of breath, productive cough with yellow sputum and right sided pleuritic chest pain. On examination, he was febrile with temperature 38.2, tachypnoeic, respiratory rate 22/min and O2 saturation 92% on room air, with stable blood pressure 130/75 and normal sinus rhythm. He had some crepitations and reduced air entry in both lung bases on auscultation. He had no rash. CRP was &gt; 190, total white cell 4.5, neutrophils 2.9, and eosinophils 0.56 (0.02-0.5). He had a transient rise in liver enzyme ALT (52) and bilirubin (22), both normalised on discharge. Kidney functions remained normal. Influenza A, B and respiratory virus PCR, urinary legionella and pneumococcal antigen, blood, urine and sputum cultures were negative. CXR showed no obvious consolidations or acute changes. CT angiogram to exclude pulmonary embolism showed scattered ground glass opacification throughout both lungs affecting multiple zones with no architectural distortion and no confluent consolidation. Despite treatment with IV antibiotics for suspected community acquired pneumonia, he continued to spike temperatures and was dependent on oxygen. When we reviewed him, our impression was that his symptoms, clinical findings and CT changes were consistent with drug-induced pneumonitis, most likely due to baricitinib. Methotrexate and baricitinib were suspended. He responded well to 40 mg of prednisolone; his fever subsided and he became less dyspnoeic and CRP and eosinophil counts improved. He went home after 7 days of admission. A repeat CT chest 8 weeks later showed a complete resolution of the pneumonitis. He was still on a low but reducing dose of prednisolone and methotrexate was restarted and tolerated well. Discussion We believe this is one of the first few reported cases of drug-induced pneumonitis to baricitinib. The patient had been treated in the community with antibiotics for 2 weeks as well as during admission with very poor response. Baricitinib was the only new medication he took 4-5 weeks before the symptoms developed. Previously, he had been stable on his usual medications including methotrexate for over 10 years. The temporal relationship between the start of the new medication and the onset of the symptoms, clinical and laboratory findings and radiological changes suggested that this was baricitinib-induced pneumonitis. Key learning points It is important to have a high index of suspicion for hypersensitivity pneumonitis in patients presenting with acute lung injury shortly after starting a new treatment as early diagnosis and treatment can lead to the complete resolution of the condition. Conflict of interest The authors declare no conflicts of interest. </jats:sec

EP33 Sjögren’s and lymphoproliferative disorders

Abstract Case report - Introduction Sjögren’s syndrome (SS) is a chronic autoimmune inflammatory condition characterised by lymphocytic infiltration of predominantly exocrine glands as well as other organs involving more commonly in skin, lungs, and neurological system. It is associated with increased risk of both benign and malignant lymphoproliferative disorders. Case report - Case description A 29-year-old woman with 5-year history of Primary SS (ANA, Ro/La positive) was reviewed in a routine follow up. She has mild dry eyes, intermittent vasculitic rash around the ankles, occasional pleuritic chest pain but no cough or dyspnoea initially. She used artificial tears but took no regular mediations. Oxygen saturation at rest was 99% and BP 127/70. Heart sounds were normal, and chest was clear. Blood results showed alanine transaminase (ALT) had risen from 50 (normal 5-45) to 145 over 6 months. Viral screen (hepatitis, HIV, CMV, EBV) and liver ANA panel were negative. C4 was low 0.09 (n 0.15-0.55), C3 normal and DsDNA antibodies 1 (n 0-15.1). Ig G was high, fluctuating between 27 - 33 (n 7.67-15.9). ESR had been mildly elevated at 26 (n 0-19). CRP had always been within normal limits. Ultrasound abdomen showed enlarged spleen (15 cm). CT chest abdomen and pelvis showed multifocal groundless opacification affecting mid to upper zones, bilateral cyst formation, solid nodularity, and mild septal thickening with no pleural effusion. There were multiple prominent bilateral axillary and mediastinal lymph nodes measuring upto15 mm. The spleen measured 15.4 cm. Six months later, she developed mild dyspnoea on exertion. Examination revealed fine basal crackles. Oxygen saturation remained 99% at rest. TLco was mildly reduced and Kco in lower limit of normal. Echocardiogram was normal. Ultrasound guided core biopsy of axillary lymph node showed benign reactive features with follicular hyperplasia and plasmacytosis. The diagnosis of lymphocytic interstitial pneumonitis was made. She was started on a reducing dose of Prednisolone 30 mg and Mycophenolate stepwise increment to 1 gm BD. Chest pain resolved shortly after starting glucocorticoid therapy and exercise tolerance improved. Liver enzyme normalised. Case report - Discussion The diagnosis of lymphocytic interstitial pneumonia (LIP) in this patient was incidental from the retrospective investigation of the persistently abnormal unexplained liver function test. Splenomegaly is a recognised manifestation of active systemic SS. The main differential diagnoses are lymphoma and other types of interstitial lung diseases (ILD). Her presentation was insidious and there were no constitutional symptoms. Her ANA, Ro, La and Rheumatoid factor were strongly positive. She has hypergammaglobulinemia which is commonly associated with LIP. Histological findings were typical reactive changes with characteristic polymorphic plasmacytosis. In the absence of malignant lymphoid cells and radiological features of ground glass changes and bilateral cysts formation suggested that the most likely diagnosis was LIP secondary to primary SS. The management strategies vary for different types of ILD based on their etiological conditions. There are no specific guidelines for the treatment of LIP. For initial acute stage, glucocorticoid therapy is usually prescribed for symptomatic improvement. For later stages and cysts, immunosuppressants are used and depending on the severity, azathioprine, cyclosporin, rituximab and cyclophosphamide have been used. Median survival for LIP is 11.2 years. Increased risk of secondary infection because of immunosuppressive therapy is common and there are recommendations for atypical chest infection prophylaxis. Case report - Key learning points Interstitial lung disease is commonly associated with SS and predicts a higher mortality rate. Glucocorticoid is the main stay of treatment for ILD acute stage with active inflammatory changes. For refractory cases and chronic cystic stages on radiological findings, further immunosuppression therapy may be required. Standardised treatment guidelines are not available. Secondary chest infections may be seen in those with cystic disease and on immunosuppression. Close monitoring and MDT approach is required in the management of LIP. LIP may transform into lymphoma or co-present with lymphoma associated with SS. </jats:sec

C-Reactive protein rise in rheumatology patients following COVID-19 vaccination

Abstract Objective The aim was to determine the proportion of patients with inflammatory arthritis who have a flare of their rheumatological disease within 4 weeks of receiving a coronavirus disease 2019 (COVID-19) vaccine, using CRP as a surrogate marker. Methods A retrospective review was conducted of notes for patients with inflammatory arthritis within 30 days of their COVID-19 vaccine. An electronic database (DAWN) was used to identify all patients who were currently on a DMARD or biologic therapy. This was then correlated with vaccine data from the National Immunisation and Vaccination System (NIVS) and CRP within 30 days of their vaccination. Results From the DAWN database, 1620 adults were identified (mean age 61 years, 64% female). Three types of vaccinations were administered: AstraZeneca (AZ), BioNTech-Pfizer or Moderna. Vaccine uptake was 1542 of 1620 (95.2% for the first dose), 1550 of 1620 (95.7% for the second dose) and 1437 of 1620 (88.7% for the third dose). One hundred and ninety-two of 1542 patients (12.5%) had a CRP rise of &amp;gt;10 mg/l within 30 days of their vaccine, which was higher than the baseline flare rate of 8.6% (P = 0.0004). Conclusion Patients with inflammatory arthritis and on DMARDs have a high uptake of COVID-19 vaccine (95%), which is greater than the national average. A CRP rise &amp;gt;10 mg/l within 30 days of vaccination was observed in ∼1 in 10 patients in our study population after all three doses. There might be a slight increase in disease flare in patients with inflammatory arthritis after COVID-19 vaccinations, and additional research is required to assess this association further. </jats:sec

39. Atypical presentation of giant cell arteritis confirmed on brain biopsy

Abstract Introduction This intriguing case describes a patient in who initial giant cell arteritis (GCA)/temporal arteritis (TA) presentation was preceded by bilateral acute anterior uveitis. He presented several months later after being treated for GCA with new neurological symptoms not typical of ischaemic cerebrovascular accident (CVA) on brain imaging. After ruling out a variety of differentials including an infection, he was treated for cerebral vasculitis secondary to temporal arteritis confirmed on brain biopsy which remains gold standard for diagnosis. Case description A 73-year-old patient with a background history of hypertension and mild asthma presented with three week history of ocular pain, headache and photosensitivity after a fall. CT head and lumbar puncture (LP) were unremarkable. He was diagnosed with bilateral acute anterior uveitis by ophthalmologists and treated with topical cyclopentolate and dexamethasone . In view of headaches, scalp tenderness, jaw claudication and raised inflammatory markers he was treated with 60mg of prednisolone for presumed giant cell arteritis (GCA) and temporal artery biopsy (TAB) was organised. He showed marked symptomatic improvement on steroids. Inflammatory markers normalised (erythrocyte sedimentation rate (ESR) 77 → 5 and C-reactive protein (CRP) 130 → &lt;1). Temporal artery biopsy was negative, but took more than four weeks after starting steroids and was only 9mm in length. Serum screening was unremarkable for complements C3,4, antinuclear antibodies (ANA), anti neutrophil cytoplasmic antibodies (ANCA), bacterial or viral antibodies. Ten months later he was admitted with a two-week history of gradually worsening bilateral lower limb weakness on the background of chronic lower back pain. Magnetic resonance imaging (MRI) head showed parasagittal abnormalities which were thought to be atypical for ischemic infarction. Intracranial angiogram did not reveal any pathology. LP demonstrated elevated white cells (18 × 106/L – normal &lt;5 × 106/L) and protein 0.61g/L (normal &lt; 0.15-0.45g/L) with negative oligoclonal bands. The serology for neuronal autoantibodies and quantiferon was negative. ESR was elevated (50). Echocardiogram showed no vegetations. He was managed for acute cerebral vasculitis with methylprednisolone and pulsed cyclophosphamide (CYC). He also underwent a repeat TAB which was normal. In view of clinical deterioration he underwent repeat MRI head and spine which showed persistent active inflammation. Brain biopsy was organised which confirmed granulomatous inflammation with multinucleated giant cells. Unfortunately he continued to deteriorate, suffered from multiple infections and sadly passed away at his home with his family. Discussion Giant cell arteritis is a systemic vasculitis characterized by granulomatous inflammation of aorta and its main vessels. Visual complications are mostly due to vasculitis of posterior ciliary arteries. Uveitis as a presenting feature of GCA is uncommon. We should be aware that, although unusual, uveitis in elderly patients can be a presenting feature of GCA. Cardiovascular risk is increased in these patients. Several case series of myocardial infarction and stroke have been reported. About 30% of patients present with neurological manifestations, the most common are neuropathies (14%), including mono- and polyneuropathies of the limbs; stroke has been extensively described (5-20%), particularly vertebrobasilar ischemia. Cerebral vasculitis may occur as primary angiitis of the central nervous system (PACNS) or as CNS manifestation of systemic vasculitis. In GCA, the involvement of CNS arteries is very rare (&lt;2%). Our patient’s imaging revealed bilateral parafalcine frontal lobe changes in anterior cerebral artery territory. However, infarction in this territorial area is quite rare unless there is space occupying lesion or anatomical anomalies of vasculature. In our patient the MRI appearances were not convincing for ischaemic infarction. Major symptoms of cerebral vasculitis are stroke, headache and encephalopathy. Diagnosis is based on a combination of clinical, laboratory and imaging findings. In systemic vasculitis an acute inflammatory response with raised ESR and CRP may be present. CSF studies reveal mild lymphomonocytic pleocytosis or protein elevation in more than 90%. Magnetic resonance imaging, with or without contrast, is the investigation of choice to detect and monitor cerebral involvement. The treatment recommendations are derived from protocols for systemic vasculitides. A combination of steroids and pulse cyclophosphamide (CYC) is recommended for induction treatment. Methotrexate, azathioprine and mycophenolate mofetil can be used for maintenance therapy similar to ANCA associated vasculitis. Key learning points Our case highlighted the rare presenting feature of GCA in the form of bilateral uveitis. Our patient was at high risk for developing ischaemic cerebral vascular event in view of large vessel vasculitis, his age and co-morbid hypertension but radiological imaging wasn’t typical for this and raised the suspicion of active cerebral vasculitis.  One should suspect multifocal brain disease like vasculitis when neurological deficit can’t be explained easily by territorial distribution of cerebral circulation. Cerebral vasculitis can be suspected on brain imaging and confirmed with biopsy. It is important to make this diagnosis as the treatment is immunosuppression different from that of a typical stroke and can be rewarding. Our patient was managed with immunosuppressive therapy but continued to deteriorate that prompted the need for brain biopsy which remains the gold standard for diagnosing cerebral vasculitis. Conflicts of interest The authors have declared no conflicts of interest. </jats:sec