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

Abstract 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 common Immunological markers exist which can prognosticate both the risk of systemic involvement and the development of vasculitis Caecal vasculitis is rarely seen in pSS; when present it carries a large burden of morbidity and mortality Increasing awareness of pSS and its systemic manifestations is essential to facilitate better recognition of unusual presentations.

bulinaemic vasculitis aside from the sine qua non of positive cryoglobulins include hypocomplementemia (especially complement C4), positive rheumatoid factor, and apositive serum monoclonal component. We suspect that her cryoglobulinaemic vasculitis was most likely due to Sjö gren's syndrome, although it could have been triggered by the preceding Epstein-Barr virus infection, as this can be associated with cryoglobulinemia also. The decision to treat aggressively with pulsed intravenous cyclophosphamide and prednisolone was made given the severity of the patient's symptoms, especially her progressive peripheral neuropathy. Given the paucity of data in the literature on the management of cryoglobulinaemic vasculitis secondary to rheumatological conditions, cyclophosphamide and prednisolone were chosen as these are proven in the other small vessel vasculitides, such as ANCA-associated vasculitis. This case is of interest as cryoglobulins are found in approximately 7-16% of patients with Sjö gren's syndrome, with cryoglobulinaemic vasculitis seen in only 3-4% of patients with the disease. Case report -Key learning points: Cryoglobulins are uncommon in Sjö gren's syndrome, occurring in 7-16% of those with the disease. Symptomatic cryoglobulinaemic vasculitis among those with Sjö gren's syndrome is rare, seen inonly 3-4% of cases. The presence of cryoglobulins in Sjö gren's syndrome is of clinical significance, as it is associated with higher global systemic disease activity and extra glandular involvement. Compared to non-cryoglobulinaemic patients with Sjö gren's syndrome, those with cryoglobulinemia are more likely to have lymphadenopathy, constitutional symptoms, peripheral nervous system and pulmonary involvement, and glandular, articular, and cutaneous features of the disease. The type of cryoglobulinemia found in Sjö gren's syndrome is the mixed type, which are either formed from a monoclonal immunoglobulin (usually IgM)and apolyclonal immunoglobulin(type II),ortwo polyclonal immunoglobulins (type III). Other conditions associated with mixed cryoglobulinemia include rheumatoid arthritis and systemic lupus erythematosus (SLE), although the most common cause of these is chronic hepatitis C (80-90% of cases). Other causes of mixed cryoglobulinemia include other viral infections, including Epstein-Barr virus and hepatitis B, and certain bacterial and parasitic infections. Most of the literature on the management of cryoglobulinaemic vasculitis is in the context of patients with this due to chronic hepatitis C and revolves around treating this with the appropriate antiviral therapy. Consequently, the current treatment options for moderate-to-severe cryoglobulinaemic vasculitis secondary to rheumatological conditions are the same as those for the other small vessel vasculitides, using a combination of cyclophosphamide and glucocorticoids to induce remission, and azathioprine as maintenance therapy. In severe cases, plasma exchange and rituximab can also be considered as agents to induce remissionin cryoglobulinaemic vasculitis.

North Bristol NHS Foundation Trust, Bristol, United Kingdom
Case report -Introduction: We present the case of a patient with Primary Sjö gren'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 Azathioprinewith 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 subtotal 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 negativecryoglobulins 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-glandularinvolvementinpSSiscommon, bothatpresentation 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 morbidityand mortality. Gastrointestinal involvement inpSS 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 orrectal 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, comparedto 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 learningpoints . Systemic involvement in pSS is relatively common . Immunological markers exist which can prognosticate both the risk of systemic involvement and the development of vasculitis . Caecal vasculitis is rarely seen in pSS; when present it carries a large burden of morbidity and mortality . Increasing awareness of pSS and its systemic manifestations is essential to facilitate better recognition of unusual presentations.

MUSCULOSKELETAL ULTRASOUND SCANNING. HOW DO WE MOVE FORWARD?
Fatemeh Jenabi, Katie Mageean, Alice Leahy, Brian Davidson and Hans de Graaf University Hospital of Southampton, Southampton, UK Case report -Introduction: Musculoskeletal ultrasound is used by clinicians around the world and learning this skill is included in paediatric rheumatology training programmes in several countries. However, in the UK only a few clinicians use it in their daily practice. British Society of Rheumatologists has recently shown interest in ultrasound scan training in paediatric rheumatology. Paediatric rheumatologist team in Wessex would like to set up an ultrasound training module for paediatric rheumatology for anyone interested, including trainees and consultants. The team aimed to check the clinicians' interest and demand for it nationally.
Case report -Case description: A brief questionnaire was sent to 45 paediatric rheumatologist consultants in the UK and 14 paediatric rheumatology trainees to gain more information about the use of MSK-USS in clinic. We also sought the clinicians' opinion to ensure the potential ultrasound scan module will meet their needs. 40 out of 45 paediatric rheumatologists replied (response rate of 89%) and 7out of 14 specialist trainees responded (response rate 50%). 80% (32) consultants and all paediatric rheumatology trainees felt that musculoskeletal ultrasound (MSK-USS) performed by a clinician in clinic would benefit their patients. Majority stated that for urgent cases, it could take up to 2 weeks in their centre for a departmental USS to be done and reported. Only 32.5% (13) could arrange MSK-USS on the same day for urgent scans. The number of MSK-USS and MRI scans requested per month were similar. 70% (28) of the clinicians and trainees have access to an ultrasound scanner. Majority of clinicians expressed their enthusiasm (median of 80%) for an interactive paediatric rheumatology musculoskeletal ultrasound online module as well as the platform in which images and clips. 100% (7) of trainees were keen to learn MSK-USS as part of their training and majority felt that they could dedicate regular time for it alongside their other clinical duties.
Case report -Discussion: This study highlighted that various paediatric rheumatology departments within the UK already had discussions about the use of MSK-USS as part of clinical practice without making progress.
Majority of paediatric consultants in the UK feel that USS performed by the clinician is beneficial for the patients, particularly for image guided injections and performing synovial biopsies. However, a small group reported reservations due to inter-operator variation and challenges of interpreting non classical signs on scan as well as the risk of over-interpretation of scan findings regarding inflammation. Moreover, another obstructing factor for some consultants to use MSK-USS can be time constraints in terms of becoming proficient in MSK-USS and time to perform USS in the clinic. Case report -Key learning points: This study highlighted that various paediatric rheumatology departments within the UK already had discussions about the use of MSK-USS as part of clinical practice without making progress. Majority of paediatric consultants in the UK feel that USS the clinician is beneficial for the patients, particularly for injections and performing synovial biopsies. However, a reservations. atology team is in the process of setting up an ultrasound le for paediatric rheumatology which could be what push discussion into action. We intend to carry out the other European countries such as Italy, Netherlands, to gather more evidence. Given the lack of evidence in this area, such studies would be important in shaping the future clinical practice of paediatric rheumatology. Taking the high interest rate of current trainees, we also recommend addition of a specific ultrasound training module for paediatric rheumatology trainees as part of the GRID (specialist) curriculum.