EP36 Caecal vasculitis: a rare and dangerous complication of Sjögren’s syndrome

Case report - Introduction We present the case of a patient with Primary Sjögren’s syndrome (pSS) who presented via the general surgical take with an acute abdomen, necessitating emergency subtotal colectomy. Histology demonstrated vasculitis of the caecum, and in combination with elevated type II cryoglobulins and unmeasurable complements, a diagnosis of cryoglobulinaemic vasculitis was made. Vasculitis has a recognised association with pSS, particularly in the context of elevated cryoglobulins, but bowel involvement is rare. Clinicians involved in the care of pSS patients should be alert to the possibility of rare but severe multi-system manifestations, due to their high burden of morbidity and mortality. Case report - Case description This 54-year-old female is under the care of Rheumatology for pSS. She initially presented with sicca symptoms, fatigue, arthralgia, and parotid swelling for which she had undergone a superficial parotidectomy. She had longstanding constitutional symptoms of night sweats, weight loss and fever. She also reported chronic constipation as well as a photosensitive urticarial rash. At diagnosis, her ENA panel demonstrated SS-A, SS-B and SCLER-70 positivity with type II cryoglobulins of 0.56 and hypocomplementemia (C4 < 0.01). At this stage there were no clinical or laboratory markers of end organ damage. Initial treatments included Hydroxychloroquine and Azathioprine with recent switch to Methotrexate due to inefficacy. 2 years later, she presented emergently via the general surgical team with a one-day history of generalised abdominal pain and vomiting. On examination she had right lower quadrant peritonism. CT scan demonstrated severe caecal colitis with associated ascites, requiring emergency sub-total colectomy. Histology from the resected bowel demonstrated ischaemia with numerous foci of submucosal vasculitis. On inpatient Rheumatology review there were no cutaneous, pulmonary, musculoskeletal features of vasculitis. She had reduced pinprick sensation to her feet, associated with allodynia. Laboratory tests showed a haemoglobin of 106, platelets of 866 and albumin of 27 (all markers felt to reflect recent critical illness). Her eGFR was 71 (from a baseline of 90) with urine PCR of 11.7 but no blood. Faecal calprotectin was normal. EBV, CMV, Hepatitis B and C and HIV were negative. Repeat immunology confirmed a type II cryoglobulinemia of 0.95 and C4 of 0.01. Following MDT discussion with colleagues in both Gastroenterology and Renal medicine it was agreed that her colitis likely represented a cryoglobulinaemic vasculitis secondary to pSS. She was treated with oral prednisolone and six intravenous pulses of cyclophosphamide. After six months she is symptomatically improved with negative cryoglobulins and normal complement. Case report - Discussion pSS is an immune-mediated condition classically associated with sicca symptoms commonly affecting the eyes and mouth. These symptoms derive from immune mediated inflammation and damage of secretory glands and resultant drying of mucosal surfaces. However, extra-glandular involvement in pSS is common, both at presentation and later in the disease course. Organ systems most associated include joints, lungs, skin, and peripheral nerves. However, involvement of other organ systems, particularly gastrointestinal or pulmonary are associated with significant morbidity and mortality. Gastrointestinal involvement in pSS is well recognised and encompasses manifestations from dysphagia to pancreatitis. Symptoms related to irritable bowel syndrome, including constipation as in our patient, are common but generally follow a benign course. Our patient never experienced any symptoms suggesting inflammation of the bowel, such as diarrhoea or rectal bleeding prior to her acute presentation. Several prognostic markers have been proposed for pSS, including SS-A/ SS-B positivity, hypocomplementemia and cryoglobulinemia. These immunological markers, particularly low C4, are implicated in an increased risk of developing vasculitis. These markers were present in our patient at the time of diagnosis; at this point there were no clinical features suggestive of vasculitis. Vasculitis in pSS, when seen, is most associated with the skin and kidneys, although involvement of the small bowel has been observed. Ileal biopsies for our patient, performed prior to immunosuppression, were normal suggesting that in this case the vasculitis was limited to the large bowel. Cryoglobulinaemic vasculitis, secondary to mixed cryoglobulinemia, is seen in association with connective tissue diseases, most commonly pSS. Gastrointestinal involvement has also been recognised in this context, but again is uncommon, compared to other vasculitides. After immunosuppression, our patient’s cryoglobulins resolved and she has remained clinically stable. Her case provides an important lesson regarding the possibility of severe extra-glandular vasculitic manifestations in pSS patients. Case report - Key learning points Systemic involvement in pSS is relatively commonImmunological markers exist which can prognosticate both the risk of systemic involvement and the development of vasculitisCaecal vasculitis is rarely seen in pSS; when present it carries a large burden of morbidity and mortalityIncreasing awareness of pSS and its systemic manifestations is essential to facilitate better recognition of unusual presentations.

EP45 What’s the chance of precipitation?

Background This project was undertaken to review patients testing positive for cryoglobulins. We wanted to establish the numbers of patients with different types of cryoglobulins, to determine whether there were any shared characteristics and whether there was any consensus on management. Methods Retrospective review of records of Sheffield Teaching Hospital patients testing positive for cryoglobulins January 2014-December 2018. Results 374 cryoglobulin tests were requested. 43 were positive (in 33 patients).There were 9 Type I cryoglobulins, including IgG and IgM lambda and kappa. Titres ranged from 0.07-47.5g/L. All patients had an underlying haematological condition. 2 patients had rash and 1 acute kidney injury (AKI), but there were no other clinical features of cryoglobulinaemia. 1 patient received treatment for cryoglobulinaemia secondary to MGUS with prednisolone, plasma exchange and Velcade/Thalidomide/Dexamethasone. Otherwise the cryoglobulins appear to be a laboratory finding with minimal clinical significance.There were 17 Type II cryoglobulins in 12 patients. The most common pattern was IgM kappa monoclone with polyclonal immunoglobulin (71%). Titres ranged from 0.03-5.4g/L. Patients’ underlying conditions were malignant, infective and inflammatory. 7 patients had rash, 2 arthralgia/arthritis, 4 Raynaud’s, 3 paraesthesia and 2 AKI. The presence of cryoglobulins was not considered significant in 5 patients (titres 0.03-0.39g/L). 3 patients were treated for underlying malignancy or infection and cryoglobulins monitored. 2 patients (titres 0.16 and 1.97g/L) were treated for renal disease in the presence of cryoglobulins with prednisolone and Rituximab in 1 case and prednisolone, Cyclophosphamide and plasma exchange in the other. 2 patients were diagnosed with cryoglobulinaemic vasculitis (titres 0.5g/L and 0.03g/L). 1 was treated with prednisolone and Azathioprine. The other had previously been treated with prednisolone and cyclophosphamide, then azathioprine maintenance therapy; the relapse during this study period was treated with methylprednisolone, plasma exchange and Rituximab.There were 16 Type III cryoglobulins in 14 patients. By definition all had polyclonal immunoglobulins. Titres ranged from 0.06-4.64g/L. Patients’ underlying conditions were malignant, infective and inflammatory. 7 patients had rash, 4 arthralgia/arthritis, 2 paraesthesia and 1 AKI. The presence of cryoglobulins was not thought significant in 5 patients (titres 0.08 to 0.45g/L). 7 patients were treated for underlying infection or rheumatological condition and the cryoglobulins monitored. 1 patient (already reported in the Type II section) was treated for renal disease in the presence of cryoglobulins. 1 patient (titre 0.12g/L) with a diagnosis of cryoglobulinaemic vasculitis was treated with prednisolone and azathioprine, then mycophenolate. Conclusion The study confirms that cryoglobulins are rare and that clinically significant disease related to them is even rarer. Given the small numbers it is difficult to identify strong trends in presentation or treatment. However, it does show that higher cryoglobulin titres do not correlate with higher rates of disease activity in terms of cryoglobulinaemia or cryoglobulinaemic vasculitis. Disclosures: R. Smith: None. G. Wild: None. S. Carter: None.

Rare cause of bilateral foot gangrene: coexisting essential cryofibrogenaemia and cryoglobulinaemic vasculitis

Cryofibrinogenaemia is a rare haematological disorder characterised by cold temperature-induced precipitation of plasma proteins causing small-vessel occlusive vascular disorder with a hallmark of skin ulceration. It remains an underdiagnosed entity because of a lack of diagnostic criteria. Cryoglobulinaemia vasculitis is a small-vessel vasculitis involving the skin, the joints, the peripheral nerve system and the kidneys. Its association with cryofibrinogenaemia causes more severe phenotype with poor prognosis. We describe the case of a 59-year-old woman presenting with cold-induced extensive bilateral foot gangrene due to coexisting cryofibrinogenaemia and cryoglobulinaemic vasculitis that required bilateral amputation and rituximab perfusions as maintenance therapy.

Resistant type II cryoglobulinaemic vasculitis successfully treated with bortezomib in a patient with SLE

We report an interesting case of hepatitis C virus-negative type II cryoglobulinaemic vasculitis (CV) in a patient with a background history of systemic lupus erythematosus. The type II CV became less responsive to traditional treatments over time and culminated in an intensive care unit admission with critical multiorgan failure. A detailed flow cytometric evaluation of the bone marrow proved to be helpful in treatment. It demonstrated that bortezomib was a viable alternative treatment option for the type II CV. The patient received bortezomib and has made a full and durable recovery.