O23 A series of catastrophic events

Abstract Case report - Introduction Catastrophic antiphospholipid syndrome (CAPS) is a rare, life-threatening disease occurring in up to 1% of antiphospholipid syndrome (APS) cases. It was first defined in 1992 and remains a difficult to treat entity with a mortality rate of 37%. We describe a patient with systemic lupus erythematosus (SLE) and CAPS presenting with simultaneous multi-organ injuries who was successfully managed with ‘triple’ therapy including cyclophosphamide. Case report - Case description A 42-year-old female presented to her local hospital with chest pain and worsening vision. She had a background of SLE, triple antibody-positive APS (previous DVT, pregnancy loss and strokes), hypertension, a metallic mitral valve, a previous myocardial infarction and pre-existing visual impairment due to a prior intra-cerebral bleed related to anticoagulation. Examination revealed a faint malar rash, cortical blindness and long tract neurological signs. Her ECG showed ischaemic changes and the admission troponin was significantly raised (3773ng/L). An echocardiogram showed new left ventricular dysfunction and a subsequent cardiac MRI was in keeping with coronary artery disease. Investigations showed an acute kidney injury, newly deranged liver function tests and a raised INR (>11, with no bleeding). Complement was normal with a low dsDNA titre. Urinalysis revealed proteinuria and a protein creatinine ratio measured 176mg/mmol. MRI diffusion weighted brain imaging showed acute bilateral occipital and left fronto-parietal infarcts. She had symptoms of a lupus flare with arthralgia and a butterfly facial rash. COVID-19 PCR tests were negative and she had not been recently vaccinated. She was diagnosed with CAPS and transferred to St Thomas’ hospital intensive care. On arrival, she received 1mg intravenous vitamin K followed by triple therapy for CAPS: an unfractionated heparin infusion, oral prednisolone 40mg daily, 5 days of plasma exchange and, given her background of SLE, she was treated with intravenous cyclophosphamide (according to the EUROLUPUS regimen). Intravenous methylprednisolone was avoided due to a previous hypertensive encephalopathy reaction. She responded rapidly. Her troponin fell from a peak of 5054 to 294ng/L, her creatinine settled at a new baseline (232umol/L) and her liver function normalised. She was switched back to warfarin due to her metallic valve and started on aspirin for cardiovascular secondary prevention. She required physical and occupational therapy due to her strokes but recovered well. Case report - Discussion According to the 2003 criteria, CAPS can be classified as definite when there is evidence of: ≥3 organs involved, development of manifestations simultaneously or within a week, confirmation by imaging and/or histopathology of small vessel occlusion and positive antiphospholipid antibodies. Probable CAPS is when 3 out of the 4 criteria are present. In this case, three organs were confirmed to be involved with imaging showing cerebral and cardiac ischaemia. Her creatinine rose from a base of 190 to 289umol/L coupled with a high protein creatinine ratio confirming renal involvement. A Budd-Chiari syndrome was also suspected due to deranged liver function tests and INR, though imaging performed after therapy did not confirm this. A biopsy of any of these four organs was not feasible given the severity of her presentation and coagulopathy. There are no randomised controlled trials but data from the CAPS registry guides treatment and management follows a logical approach: anticoagulation to treat thrombosis, glucocorticoids for inflammation and plasma exchange (or IVIG) to remove the circulating autoantibodies. Triple therapy was associated with a reduced mortality compared to no treatment (28.6% versus 75%, respectively). Following analyses from the CAPS registry we also chose to treat with cyclophosphamide, which is associated with improved survival in patients with SLE. This decision was based on the clinical features of an SLE flare as opposed to serological grounds. There have been reports of rituximab and eculizumab being used successfully in CAPS, though generally as a last resort. As complement activation is seen in animal models of antiphospholipid syndrome thrombosis and rituximab is often used in refractory SLE, they may prove to be promising agents for refractory CAPS. Case report - Key learning points Prompt recognition and early treatment is vital in managing CAPS Triple therapy with anticoagulation, glucocorticoids and plasma exchange / IVIG is associated with better survival in CAPS Cyclophosphamide is associated with better survival in patients with CAPS and concomitant SLE

Studies suggest that women with non-criteria APS may benefit from standard treatment for obstetric APS which includes LMWH in addition to aspirin, with good pregnancy outcomes. HCQ has a dose-dependent effect in preventing thrombosis through inhibition of platelet aggregation and aPL Ab-related thrombosis. However, pregnancy itself is a prothrombotic condition and in the presence of persistent triple positive aPL is a risk factor for adverse pregnancy outcomes. Further studies are needed to define the risk of non-criteria APS on pregnancy outcomes and define optimal treatment strategies. Case report -Key learning points: 1. Obstetric APS carries significant risk for maternal foetal morbidity including miscarriage and pre-term birth. 2. Significant maternal psychological effects are recognised even following a single miscarriage. 3. The international consensus (revised Sapporo) criteria for diagnosis of obstetric antiphospholipid syndrome exclude certain noncriteria clinical and laboratory manifestations that may confer adverse pregnancy outcomes. 4. First pregnancies are challenging to risk stratify in patients with identified aPL as there will be no prior pregnancy history to reference. 5. Ultrasound doppler velocimetry is a useful non-invasive tool to diagnose poor placental perfusion, a predictor of obstetric complications, hence identifying high-risk pregnancies. 6. Further research is required to establish the diagnostic validity, predictive value, and treatment implications of non-criteria manifestations of obstetric APS. Case report -Introduction: Catastrophic antiphospholipid syndrome (CAPS) is a rare, life-threatening disease occurring in up to 1% of antiphospholipid syndrome (APS) cases. It was first defined in 1992 and remains a difficult to treat entity with a mortality rate of 37%. We describe a patient with systemic lupus erythematosus (SLE) and CAPS presenting with simultaneous multi-organ injuries who was successfully managed with 'triple' therapy including cyclophosphamide. Case report -Case description: A 42-year-old female presented to her local hospital with chest pain and worsening vision. She had a background of SLE, triple antibody-positive APS (previous DVT, pregnancy loss and strokes), hypertension, a metallic mitral valve, a previous myocardial infarction and pre-existing visual impairment due to a prior intra-cerebral bleed related to anticoagulation. Examination revealed a faint malar rash, cortical blindness and long tract neurological signs. Her ECG showed ischaemic changes and the admission troponin was significantly raised (3773ng/L). An echocardiogram showed new left ventricular dysfunction and a subsequent cardiac MRI was in keeping with coronary artery disease. Investigations showed an acute kidney injury, newly deranged liver function tests and a raised INR (>11, with no bleeding). Complement was normal with a low dsDNA titre. Urinalysis revealed proteinuria and a protein creatinine ratio measured 176mg/mmol. MRI diffusion weighted brain imaging showed acute bilateral occipital and left fronto-parietal infarcts. She had symptoms of a lupus flare with arthralgia and a butterfly facial rash. COVID-19 PCR tests were negative and she had not been recently vaccinated. She was diagnosed with CAPS and transferred to St Thomas' hospital intensive care. On arrival, she received 1mg intravenous vitamin K followed by triple therapy for CAPS: an unfractionated heparin infusion, oral prednisolone 40mg daily, 5 days of plasma exchange and, given her background of SLE, she was treated with intravenous cyclophosphamide (according to the EUROLUPUS regimen). Intravenous methylprednisolone was avoided due to a previous hypertensive encephalopathy reaction. She responded rapidly. Her troponin fell from a peak of 5054 to 294ng/ L, her creatinine settled at a new baseline (232umol/L) and her liver function normalised. She was switched back to warfarin due to her metallic valve and started on aspirin for cardiovascular secondary prevention. She required physical and occupational therapy due to her strokes but recovered well. Case report -Discussion: According to the 2003 criteria, CAPS can be classified as definite when there is evidence of: 3 organs involved, development of manifestations simultaneously or within a week, confirmation by imaging and/or histopathology of small vessel occlusion and i14 https://academic.oup.com/rheumap positive antiphospholipid antibodies. Probable CAPS is when 3 out of the 4 criteria are present. In this case, three organs were confirmed to be involved with imaging showing cerebral and cardiac ischaemia. Her creatinine rose from a base of 190 to 289umol/L coupled with a high protein creatinine ratio confirming renal involvement. A Budd-Chiari syndrome was also suspected due to deranged liver function tests and INR, though imaging performed after therapy did not confirm this. A biopsy of any of these four organs was not feasible given the severity of her presentation and coagulopathy.

O23 A SERIES OF CATASTROPHIC EVENTS
There are no randomised controlled trials but data from the CAPS registry guides treatment and management follows a logical approach: anticoagulation to treat thrombosis, glucocorticoids for inflammation and plasma exchange (or IVIG) to remove the circulating autoantibodies. Triple therapy was associated with a reduced mortality compared to no treatment (28.6% versus 75%, respectively). Following analyses from the CAPS registry we also chose to treat with cyclophosphamide, which is associated with improved survival in patients with SLE. This decision was based on the clinical features of an SLE flare as opposed to serological grounds. There have been reports of rituximab and eculizumab being used successfully in CAPS, though generally as a last resort. As complement activation is seen in animal models of antiphospholipid syndrome thrombosis and rituximab is often used in refractory SLE, they may prove to be promising agents for refractory CAPS.
Case report -Key learning points: Case report -Introduction: Antiphospholipid syndrome (APS) is a rare autoimmune disease that can cause venous and arterial thrombosis in virtually any organ. The spectrum of vascular events can range from superficial thrombosis to life-threatening multiple organ thromboses (catastrophic APS or CAPS). CAPS occurs in genetically susceptible individuals in response to a "trigger" such as infection, cancer, trauma, surgery, anticoagulation/immunosuppression withdrawal and SLE flares. The diagnosis of CAPS can be extremely challenging and is associated with a high morbidity and mortality. Thus, early diagnosis and treatment are critical to prevent the progression of disease and improve the prognosis.
Case report -Case description: We report the case of a 78-year-old gentleman who was diagnosed with systemic lupus erythematosus and antiphospholipid syndrome in 2001 after he presented with a DVT, PE, rash and arthralgia. He had positive anti-cardiolipin antibodies, Rheumatoid Factor, Ro and La antibodies, but negative anti-dsDNA. He had remained stable on warfarin, hydroxychloroquine 400mg and prednisolone 7mg for 17 years. In 2018, hydroxychloroquine was reduced to 200mg OD and steroid taper was started. Unfortunately, he presented to the Emergency Department in July 2020 with a left leg swelling. DVT was confirmed on ultrasound, despite a therapeutic INR of 2.4. He was also noted to have thrombocytopenia. Haematology advised this was in keeping with ITP and started him on 70mg of prednisolone daily. No cause for the DVT was seen on CT. However, it did show subpleural nodules within the right costophrenic angle and a repeat CT in 4 months' time was advised. INR target was increased to 3.0-4.0 and patient was discharged.
He was re-admitted 4 days later with an acute drop in haemoglobin, raised inflammatory markers and worsening kidney function. CT showed extensive retroperitoneal haematoma. It also revealed a PE as well as colonic distension with gradual tapering to normal calibre, thought to represent pseudo-obstruction. Rheumatology, haematology, general surgery and ITU were involved in the management. He was started on treatment dose clexane, given intravenous immunoglobulins and supportive blood transfusions. IVC filter was put in. Unfortunately, he dropped his GCS and an urgent CT brain showed a left posterior fossa mass with a bleed. The case was discussed with neurosurgery and neuroradiology who felt that the top differential for the intracranial lesion was an underlying metastasis -particularly a colonic met. Colonoscopy was advised. However, due to severe frailty and multiple pathologies, the patient was made palliative and was fasttracked home. Case report -Discussion: Definite CAPS is defined as thromboses in three or more organs developing in less than a week, microthrombosis in at least one organ and persistent antiphospholipid antibody (aPL) positivity. The diagnosis of probable CAPS requires three out of these four criteria. Although pathological confirmation of microthrombosis is one of the requirements for CAPS, biopsy may not be possible during an acute episode due to severe thrombocytopenia and/or unstable clinical course, as in our case. There is another category called 'CAPSlike' disease, where aPL-positive patients do not fulfil the definite or probable CAPS criteria. However, they still represent a significant challenge for physicians and require close monitoring and aggressive treatment.
Initially, we felt that we had triggered probable CAPS or 'CAPS-like' disease, by reducing his hydroxychloroquine and steroids. However, he did not improve with high-dose steroids given for his thrombocytopenia. Also, autoimmune screen including anti-dsDNA and complement levels were not significant. CAPS occurs in 46% of patients with a previous diagnosis of APS, and a precipitating factor is present in half the patients. It is speculated that aPL-related clinical events respond to the two-hit theory: a second hit or trigger is needed to activate the prothrombotic properties of aPL, which is the first hit. In CAPS, the most frequently recognised trigger is infection, followed by cancer. A study showed that 9% of patients with CAPS presented with an underlying malignancy, with haematological malignancies being most common, followed by lung and colon carcinoma. Similarly, Ozguroglue et al. showed an association between high level of anticardiolipin antibody and thromboembolic events in patients with colorectal, breast, ovarian, lung, and pancreatic cancer. Recent studies also suggest an increased prevalence of certain cancers in aPL-positive patients, thereby prompting an extensive search for an occult malignancy in such cases.
Case report -Key learning points: Given the increased prevalence of cancers in aPL-positive patients, this case highlights the need to thoroughly investigate for an occult malignancy as a trigger for APS (classic form or CAPS) with a new episode of thrombosis, despite adequate anticoagulation. While we were focusing on tapering of the immunosuppressive medication as a possible trigger, this episode was most likely triggered by the possible metastatic malignancy -especially given the lag of almost 2 years between reduction in hydroxychloroquine and steroids and development of symptoms. It is also important to bear in mind, especially in elderly patients, that thrombotic events associated with aPL can be the first manifestation of malignancy. This emphasises the need for continuing research on the association between antiphospholipid syndrome and malignancies. While the survival rate of patients with CAPS is poor overall, the outcome of patients with CAPS is worse in the presence of malignancy. A study showed that only 40% of CAPS patients with malignancies improved. This may be due to the presence of the malignancy as well as the older age of the patients. We are looking forward to discussing CAPS at the BSR case-based conference and hope it will shed more light on diagnosis and management of this incredibly challenging condition. ORAL ABSTRACT PRESENTATIONSANTI-PHOSPHOLIPID SYNDROME O25 CATASTROPHIC ANTIPHOSPHOLIPID CRISIS TRIGGERED BY ANTICOAGULANT SWITCH Case report -Introduction: The COVID-19 pandemic led to drastic changes for some patients on warfarin for venous thromboembolic (VTE) disease and atrial fibrillation. Warfarin monitoring necessitates frequent interaction with healthcare workers, which is sufficiently risky for COVID-19 transmission. As a result, selected patients were swapped over to novel oral anticoagulants (NOACs). Our patient was changed without investigating for antiphospholipid syndrome (APLS); it later transpired he was triple antibody positive. He presented in a crisis and we describe his narrative. Patients on warfarin due to presumed unprovoked venous thromboembolic disease should not be swapped to NOACs without completing, or checking, previous antiphospholipid antibody testing. Case report -Case description: A 73-year-old gentleman presented locally in August 2020 with erythema over the anterolateral surface of his left leg. He was initially treated with antibiotics for presumed