Search

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.

Introduction The anti-neutrophil cytoplasmic antibody (ANCA) - associated vasculitides are a heterogeneous group of rare multisystem disorders characterised by inflammation and necrosis of small and medium blood vessels. Early diagnosis and prompt initiation of immunosuppressive treatment are essential to induce and maintain remission of disease, and thereby prevent severe life- or organ-threatening complications. We present a challenging case of a patient presenting with progressive lung lesions in the context of known ANCA-associated vasculitis (AAV), despite escalating immunosuppressive treatment. Case description A 66-year old-female was diagnosed in 2010 with cANCA (PR3) positive vasculitis with lung involvement. Remission was induced with high dose steroids and cyclophosphamide. Methotrexate was given as maintenance treatment until 2013 when she had a significant renal relapse treated with plasma exchange, steroids and cyclophosphamide. Her maintenance treatment was changed to mycophenolate. She had a further lung relapse in 2014, treated successfully with high dose steroids and rituximab. She was eventually weaned off all treatment in 2017. She was admitted to hospital in 2019 with dry cough, dyspnoea and sinus congestion. She was noted to have several purpuric lesions on her limbs. Her CRP was elevated at 123 with a stable eGFR of 77. ANCA screen was negative. Chest Xray revealed bilateral consolidation. She was initially treated with six pulses of 500mg of IV methylprednisolone and one pulse of rituximab as an inpatient over the course of 2 weeks, with broad spectrum antibiotic cover. Despite this, she continued to deteriorate with a worsening purpuric rash and increasing oxygen requirement. She underwent plasma exchange with little improvement. CT of her chest revealed multiple progressive bilateral cavitating lesions. It was noted that her IgG levels were low (3.72) following rituximab, increasing her risk of infection. An atypical infection screen was performed and she was discovered to have cytomegalovirus (CMV) reactivation with high viral titres of 56889. She underwent bronchoscopic alveolar lavage which was positive for CMV on PCR. CT guided lung biopsy revealed necrotising granulomatous inflammation with occasional CMV positive nuclei. She was given valganciclovir and IV immunoglobulin, and her prednisolone dose was reduced to 10mg. This resulted in her viral load reducing to undetectable levels, her CRP improving to 23 and immunoglobulins normalising. This correlated with a clinical improvement allowing the patient to be discharged home. Discussion The patient in this case appeared in the first instance to have another flare of her AAV. However the flare was atypical in that it was not associated with an increase in her cANCA titre and it did not respond quickly to steroids as had been the case on each previous occasion. This prompted a reassessment of her case and investigation into other potential causes for her deterioration. CMV is a persistent herpesvirus which can affect up to 75% of healthy individuals. The primary infection is rarely symptomatic but can be associated with significant morbidity and mortality in immunocompromised patients. Pulmonary CMV disease can mimic pulmonary disease associated with vasculitis. CMV can also directly damage endothelial cells and cause an occlusive vasculitis itself. The patient was immunosuppressed, increasing her risk of acquiring primary CMV infection or developing CMV reactivation. She was given further potent immunosuppression during her admission. Serology is often unreliable in immunosuppressed patients and in this case her CMV IgG was positive with a negative IgM, indicating past CMV infection only. It is important to send samples for viral PCR to detect and diagnose active infection, and allow treatment to be initiated promptly. The lung biopsy was felt to be more in keeping with active AAV, although occasional CMV positive nuclei were present. The patient was therefore managed as having CMV reactivation in the context of active AAV. Treatment of viral infection can pose further challenges when trying to manage coexistent active vasculitis as highlighted in this case. Close monitoring of the patient was required, together with a multidisciplinary approach involving input from colleagues in infectious diseases and immunology, to allow the patient to be managed safely and effectively. Prophylactic antiviral therapy may need to be considered if further immunosuppression is required in future. Key learning points CMV reactivation can complicate treatment of ANCA associated vasculitis. Clinicians should have a low threshold to test for CMV in immunocompromised patients with vasculitis, particularly in cases which are atypical or refractory to standard treatment. Viral PCR should be tested, as serology can often be unreliable in immunosuppressed patients. Conflict of interest The authors declare no conflicts of interest.

Introduction Myositis can be infective, metabolic or immune-mediated. Idiopathic inflammatory myopathy, which is immune-mediated, tends to be subacute, with symmetrical symptoms, overlap clinical features and positive autoimmune serology. We present a case of acute onset lower limb seronegative inflammatory myopathy with a normal creatinine kinase (CK), a marked acute phase response that responded promptly to immunomodulatory therapy. Case description A 68-year-old man presented with a 2-week history of lower limb pain with subjective weakness, on a background of well-controlled type 2 diabetes mellitus and hypertension. He was admitted with worsening symptoms of marked left thigh pain, night sweats, and fevers. On admission, he had swinging pyrexia (above >39 °C) while remaining haemodynamically stable. He had focal tenderness over the left anterolateral thigh, with a good range of movement, normal power and no signs of focal collection or cellulitis. There were no extra-muscular features to suggest systemic infection or overlap connective tissue disease. Bloods showed C-reactive protein (CRP) 225, normal CK 212 and negative blood cultures. X-rays knee, femur and pelvis were normal. Magnetic resonance imaging (MRI) on T2, fat-suppressed STIR sequences demonstrated increased signal/oedema both thighs throughout the anterior muscle compartment and along the fascial plane, notably most severe in the left vastus lateralis. He was treated empirically for infective myositis. Despite 14 days of broad-spectrum antibiotics, he remained febrile with persistently elevated CRP. There was no focal collection, lymphadenopathy or occult malignancy on CT abdomen and pelvis. Trans-oesophageal echocardiogram showed no evidence of infective endocarditis but revealed incidental moderate aortic stenosis. The patient described persistent now bilateral thigh pain with continued normal CK and high CRP. Full autoimmune screen (ANA, ANCA, ACE and complement studies) was negative. Despite negative nuclear and cytoplasmic HEp-2 immunofluorence, extended myositis immunoblot was negative. Muscle biopsy from the left vastus lateralis demonstrated inflammation within the perimysium and perivasculature. In view of biopsy findings and no response to anti-microbial therapy, prednisolone (0.5mg/kg) with significant clinical response (resolution of fever and pain) with concurrent normalisation in CRP. The patient remains in remission following steroid reduction with no additional immunomodulatory therapy required. Discussion We report a case of idiopathic inflammatory myopathy presenting with predominantly asymmetrical symptoms, normal CK, marked inflammatory response and negative myositis autoantibodies. Diagnosis was confirmed on MRI and muscle biopsy. The normal CK can be explained by the histology demonstrating inflammation in perivascular regions and around muscle fibres, rather than inflammation or necrosis in the muscle fascicles and fibres themselves. Idiopathic inflammatory myopathy including sporadic inclusion-body myositis, dermatomyositis, overlap CTD myositis and polymyositis/necrotising myopathy subsets are distinguishable based on clinical features, autoantibodies, MRI and biopsy features. The table below summarises the atypical aspects of this case. Differential diagnoses for this case include atypical infection, sarcoid myopathy and amyloid myonecrosis secondary to diabetes. Table: Features of typical idiopathic inflammatory myopathy compared with this atypical case.Idiopathic inflammatory myopathiesOur patient- typical featuresOur patient- atypical featuresSymptomsPain, fever, weakness.Pain and fever.Normal power.Clinical distributionSymmetrical, proximal muscle groups.Predominantly asymmetrical (worse on left), only in thighs.AntibodiesMyositis associated autoantibodiesSeronegativeMuscle enzymesElevated CKNormal CK.Inflammatory markersNormal to slightly elevated CRPMarkedly raised CRP and WCC.MR imaging resultsFocal muscle oedema in affected musclesDiffuse and speckled muscle oedema Key learning points Early idiopathic inflammatory myopathy can have inflammation around the muscle fascicles in the perimysium. Normal CK does not rule out a diagnosis of idiopathic inflammatory myopathy. Idiopathic inflammatory myopathies can present atypically with fevers >39 °C, significantly raised inflammatory markers, and asymmetrical symptoms and MRI findings. In the absence of overlap features, normal CK and negative serology, MRI and biopsy can delineate the type of myositis and direct management. Conflicts of interest The authors have declared no conflicts of interest.