EP27 Sjögren’s or not: an anxious diagnosis

Abstract Case report - Introduction Sjögren’s syndrome is a chronic, autoimmune condition usually characterised by reduced function of exocrine glands (mainly lacrimal and salivary) resulting in sicca symptoms. Affected patients may also have extra-glandular features including arthritis, neuropathy, and interstitial nephritis. This is a case of possible Sjögren’s syndrome without classical features like positive serology or histology. This makes the patient feel anxious about his overall health. Diagnostic criteria have been debated over the years and whilst some clinical features may be suggestive, more objective evidence can help guide discussions on long term management and prognosis to allay anxiety. Case report - Case description A 63-year-old Asian gentleman has had 6 years of intermittent cervical lymphadenopathy, dry eye and mouth symptoms without weight loss or respiratory complaints. His background includes ulcerative colitis (relatively stable), angina, hypertension, degenerative back pain (confirmed on MRI), dental extraction and diabetes. Interval FNA sampling and excision biopsy of a prominent chain of right cervical nodes on separate occasions showed “reactive changes” with negative Mycobacterium TB screening (serology and lymph nodes). Blood tests show a normal CRP (<5 mg/L), ESR 36 mm/h, raised polyclonal IgG 28.6 g/L (IgG subclass 1, 20.40 g/L, subclass 2, 9.36g/L, subclass 3, 0.954g/L, subclass 4, 9.430g/L) , normal complement and negative results for ANA, HLA B27, Anti CCP and ANCA. Bilateral submandibular gland ultrasound showed hyperechoic lesions consistent with either chronic sialadenitis or Sjögren’s. FNA sampling of an intra-parotid lesion showed a “reactive” lymph node. A left lower lobe 5mm calcified granuloma seen on plain film was confirmed on CT chest imaging along with mild inflammatory changes (lingual area) and multiple soft tissue density nodules up to 1cm in the anterior mediastinum. Initially thought thymoma related, later it was agreed these were benign lymph nodes after noting bilateral, sub-centimetre axillary and pre-tracheal nodes of similar appearance. Following annual surveillance, a recent scan shows persistence of the lingular nodular focus, mediastinal lymphadenopathy and a 4mm ground glass nodule not thought suitable for PET CT or CT guided sampling. The previously seen parotid lymph node appears reduced and scattered low grade nodes are seen in the neck, chest, and porta hepatis. Ophthalmologists note a poor-quality tear film with an equivocal Schirmer’s test. He has been treated for blepharitis and diagnosed with macular oedema. He was due to have a labial gland (lip) biopsy but later declined the procedure. Case report - Discussion Sjögren’s syndrome has a female preponderance and is usually associated with sicca symptoms, a positive Schirmer’s test and autoantibodies (anti-Ro and anti-La). Extra-glandular features may exist, and secondary Sjögren’s features are seen in other autoimmune conditions. Various diagnostic criteria have been proposed using clinical, serological, and/or histological features. This patient has sicca symptoms, lymphadenopathy, and imaging findings suggestive of Sjögren’s. Though not routinely used, salivary gland imaging features include enlarged, hyperechoic lesions and later stage multi-cystic or reticular patterns within atrophic glands. Due to ethnicity, negative autoantibodies and imaging, the differential of tuberculosis (TB) was excluded. A labial gland biopsy was suggested as it may be a potentially sensitive and specific Sjögren’s biomarker. Presence of multiple, periductal, lymphocytic foci can help exclude alternative diagnoses like sarcoidosis, amyloidosis, or lymphoma. However, the patient declined the procedure due to concerns about possible post procedure hypersensitivity. This patient has mild fatigue and non-specific arthralgia but not typical of fibromyalgia which is known to mimic Sjögren’s. Reassuringly, he remains well but anxious about lymphadenopathy which he feels is unrelated to his mild ulcerative colitis managed with prednisolone enemas. In the absence of arthritis or significant organ involvement, he has only been given symptomatic treatment (e.g. eye drops). In Sjogren’s, any increased or persistent lymphadenopathy calls for further investigation. Other predictors include low complement and cryoglobulins which are absent in this patient. This case may add to the evidence of co-existence of secondary Sjögren’s or Sjogren’s like syndrome with IBD which seems uncommon and in other cases, appears to be in conjunction with immunosuppressive treatment and autoantibodies. Duration of follow up required remains uncertain and whilst the patient requires little ongoing monitoring, health anxieties can precipitate frequent contact. Case report - Key learning points Sjögren’s syndrome (SS) can be variable in presentation but in most cases is mild Unlike other autoimmune disorders, in SS there is a lack of standardised criteria for diagnosis and classification Some features can be non- specific and like features of fibromyalgia and sarcoidosis In unclear cases, like this, objective markers like serology or histology (labial gland biopsy) may be more helpful In lymphadenopathy, depending on size and appearance, further investigations require multidisciplinary discussion to check if regular imaging is more appropriate compared to invasive tests. The frequency of imaging and potential radiation exposure needs careful consideration. In this case the patient is unwilling to undergo further invasive tests like a biopsy and the lymphadenopathy seen on imaging is thought relatively stable and not amendable to sampling. The ideal duration of follow up and need for ongoing investigations in this patient remains unclear – advice on monitoring and outcome of similar cases may help guide patient management and reduce anxiety

keeping with bilateral Madelung deformity. MRI has never suggested synovialenhancement of sacroiliac joints. Therapeutically she has trialled conventional disease modifying therapy including azathioprine, mycophenolate, and methotrexate. Disease activity continues to be high despite anti-TNF biologic DMARDs (adalimumab, infliximab and golimumab). Use of anti-TNF therapy has been complicated by development of CMV disease and identification of antiinfliximabantibodies following interruption. Ongoing steroid use from 18 months, hyperthyroidism and a chronic inflammatorystatehas ledto osteoporosis. DEXA Z-scores reveal lumbar -2.7, right femoral neck -3.2 and left femoral neck -4.7. Systemic corticosteroid has tried to be offset through dexamethasone intravitreal implants. Consequentially, uncontrolled disease burden has also led to significant input from orthopaedics, including bilateral total knee replacements by age 28. However, with MS, we are hopeful with the commencement of anti-IL6 receptor therapy (Tocilizumab) that this may represent a new line of effective treatment. Case report -Discussion: Blau syndrome is a juvenile sarcoidosis characterised by the triad of granulomatous arthritis, recurrent uveitis, and dermatitis. It is inherited in an autosomal dominant pattern due to a missense mutation in the gene encoding for nucleotide-binding oligomerisation domain containing protein 2 (NOD2/CARD15). It is proposed that NOD2 as intracellular receptors, for antigen such as lipopolysaccharide, may subsequently act like toll-like receptors to cascade NF-kappa B and downstream inflammatory pathways. Its role is also implicated in other inflammatory conditions such as Crohn's disease. As represented in our case, uveitis presents the highest morbidity, with median age of eye disease presenting at 60 months and remains persistent despite topical or systemic therapy in more than 50% of patients. In comparison to Juvenile idiopathic arthritis, Blau often leads to a pan rather than anterior segment only uveitis and in a greater proportion of cases. In addition to biological factors, much of MS's treatment decisions have been guided by her and her psychology. In attempting to address the difficulties of her condition, including coordinating several specialities clinics whilst developing as a young woman, she has frequently discontinued therapywhich may represent an area that she can exact control given little perceivedbenefit. TNF-alpha inhibitors have been validated through randomised controlled trials for the use of refractory sarcoidosis. However recent literature has highlighted the use of targeting the IL-6 pathway in multisystem chronic sarcoidosis. It is believed this may represent a key cytokine in promoting Th17 effector cells that have been implicated in sarcoidosis bio-pathology. However ongoing case reports and ideally large-scale studies are needed. Case report -Key learning points: Blau syndrome as a rare lifelong form of early onset sarcoidosis offers insight into challenging therapeutic decialtrial data is available. The James Cook University Hospital, Middlesbrough, United Kingdom

SYNDROME AND ITS MIMICS ADING AS CONNECTIVE
Case report -Introduction: Connective tissue diseases are multisystem disorders. Diagnosis and evaluation of suspected cases is not straight forward in most of the cases. This case describes the significance of considering a broader approach when evaluating a suspected case of connective tissue disease. Case report -Case description: We describe a case of 58 years old nonsmoker lady, presented with acute onset livedo reticularis rash on lower limbs and background of sicca symptoms, oral ulcers, fatigue, paraesthesias in feet and arthralgias without any systemic or inflammatory joint symptoms. General examination showed livedo reticularis rash on both elbows and lower legs. There was no evidence of peripheral joint synovitis, but she had nodal osteoarthritis in her hands. Systemic examination was unremarkable.
Investigations revealed anaemia, pancytopenia, ESR of 77, low C4 and urine dipstick positive for leucocytes, nitrates, protein, and blood. Schirmer's test, ANA and ENA screen was positive with positive RNP and SMdp antibody. She also had hypergammaglobulinemia in a polyclonal pattern. Nerve Conduction and EMG studies revealed mild axonal sensory neuropathy. Case report -Discussion: This lady appeared to have mixed connective tissue disease with mixed features of Sjö gren's syndrome and systemic lupus erythematosus. She was started on Hydroxychloroquine but stopped it shortly after developing floaters in her eye. She had poor response to Depomedrone injection. She had ongoing symptoms of fatigue, weight-loss, loose stools, and abdominal pain, investigated further and CT scan showed hyperdense liver lesions and mesenteric lymphadenopathy. Esophagogastroduodenoscopy showed oesophageal candidiasis. She was admitted with progressive symptoms. Further investigationsshowed apositiveHIVtest andliver biopsy camebackpositive for anaplastic lymphoma, later she was diagnosed with advanced HIV disease, rapidly deteriorated with neutropenic sepsis and multiorgan failure, and unfortunately died.
Case report -Key learning points: This lady initially presented with symptoms of connective tissue disease and investigations in keeping with this diagnosis. Unfortunately, by the time she was tested for HIV infection, it was already too late. There could be overlap of symptoms of connective tissue disease and viral infections e.g. HIV infection. Autoantibodies may be falsely positive in infections e.g. HIV and in malignancy. Risk factors of HIV infection should be considered during assessment of multisystem diseases like connective tissue diseases particularly prior to immunosuppression. Viral screening including HIV test should be considered in all high-risk patients and particularly if the symptoms are atypical and do not quite fit well with the diagnosis.

Sharmin Nizam Mid Yorkshire Trust, Wakefield, United Kingdom
Case report -Introduction: Sjö gren's syndrome is a chronic, autoimmune condition usually characterised by reduced function of exocrine glands (mainly lacrimal and salivary) resulting in sicca symptoms.
Affected patients may also have extra-glandular features including arthritis, neuropathy, and interstitial nephritis. This is a case of possible Sjö gren's syndrome without classical features like positive serology or histology. This makes the patient feel anxious about his overall health. Diagnostic criteria have been debated over the years and whilst some clinical features may be suggestive, more objective evidence can help guide discussions on long term management and prognosis to allay anxiety. Case report -Case description: A 63-year-old Asian gentlemanhas had 6 years of intermittent cervical lymphadenopathy, dry eye and mouth symptoms withoutweightlossorrespiratorycomplaints.Hisbackground includes ulcerative colitis (relatively stable), angina, hypertension, degenerative back pain (confirmed on MRI), dental extraction and diabetes.
Interval FNA sampling and excision biopsy of a prominent chain of right cervical nodes on separate occasions showed "reactive changes" with negativeMycobacterium TB screening (serology and lymph nodes). Blood tests show a normal CRP (<5 mg/L), ESR 36 mm/h, raised polyclonal IgG 28.6 g/L (IgG subclass 1, 20.40 g/L, subclass 2, 9.36g/L, subclass 3, 0.954g/L, subclass 4, 9.430g/L) , normal complement and negative results for ANA, HLA B27, Anti CCP and ANCA. Bilateral submandibular gland ultrasound showed hyperechoic lesions consistent with either chronic sialadenitis or Sjö gren's. FNA sampling of an intra-parotid lesion showed a"reactive" lymph node. A left lower lobe 5mm calcified granuloma seen on plain film was confirmed onCT chest imaging along with mild inflammatory changes (lingual area) and multiple soft tissue density nodules up to 1cm in the anterior mediastinum. Initially thought thymoma related, later it was agreed these were benign lymph nodes after noting bilateral, sub-centimetre axillary and pre-tracheal nodes of similar appearance. Following annual surveillance, a recent scan shows persistence of the lingular nodular focus, mediastinal lymphadenopathy and a 4mm ground glass nodule not thought suitable for PET CT or CT guided sampling. The previously seen parotid lymph node appears reduced and scattered low grade nodes areseen inthe neck, chest,and portahepatis.
Ophthalmologists note a poor-quality tear film with an equivocal Schirmer's test. He has been treated for blepharitis and diagnosed with macular oedema. He was due to have a labial gland (lip) biopsy but later declined the procedure. Case report -Discussion: Sjö gren's syndrome has a female preponderance and is usually associated with sicca symptoms, a positive Schirmer's test andautoantibodies (anti-Ro and anti-La). Extra-glandular https://academic.oup.com/rheumap i30 EPOSTER features may exist, and secondary Sjö gren's features are seen in other autoimmuneconditions. Various diagnostic criteria have been proposed using clinical, serological, and/or histological features. This patient has sicca symptoms, lymphadenopathy, and imaging findings suggestive of Sjö gren's. Though not routinely used, salivary gland imaging features include enlarged, hyperechoic lesions and later stage multi-cystic or reticular patterns within atrophic glands. Due to ethnicity, negative autoantibodies and imaging, the differential of tuberculosis (TB) was excluded. A labial gland biopsy was suggested as it may be a potentially sensitive and specific Sjö gren's biomarker. Presence of multiple, periductal, lymphocytic foci can help exclude alternative diagnoses like sarcoidosis, amyloidosis, or lymphoma. However, the patient declined the procedure due to concerns about possible post procedure hypersensitivity. This patient has mild fatigue and non-specific arthralgia but not typical of fibromyalgia whichis known to mimic Sjö gren's. Reassuringly, he remains well but anxious about lymphadenopathy which he feels is unrelated to his mild ulcerative colitis managed with prednisolone enemas. In the absence of arthritis or significant organ involvement, he has only been given symptomatic treatment (e.g. eye drops). In Sjogren's, any increased or persistent lymphadenopathy calls for further investigation. Other predictors include low complement and cryoglobulins which areabsent inthis patient. This case may add to the evidence of co-existence of secondary Sjö gren's or Sjogren's like syndrome with IBD which seems uncommon and in other cases, appears to be in conjunction with immunosuppressive treatment and autoantibodies. Duration of follow up required remains uncertain and whilst the patient requires little ongoing monitoring, health anxieties can precipitate frequent contact.

Case report -Key learningpoints
. Sjö gren's syndrome (SS) can be variable in presentation but in most cases is mild . Unlike other autoimmune disorders, in SS there is a lack of standardised criteria for diagnosis and classification . Some features can be non-specific and like features of fibromyalgia and sarcoidosis . In unclear cases, like this, objective markers like serology or histology (labial gland biopsy) may be more helpful . In lymphadenopathy, depending on size and appearance, further investigations require multidisciplinary discussion to check if regular imaging is more appropriate compared to invasive tests. The frequency of imaging and potential radiation exposure needs careful consideration. . In this case the patient is unwilling to undergo further invasive tests like a biopsy and the lymphadenopathy seen on imaging is thought relatively stable and not amendable to sampling. . The ideal duration of follow up and need for ongoing investigations in this patient remains unclear -advice on monitoring and outcome of similar cases may help guide patient management and reduce anxiety

Shazeen Ayub and Marian Regan Royal Derby Hospital, Derby, United Kingdom
Case report -Introduction: Sjö gren's is an autoimmune multisystem disorder characterised by xerostomia, keratoconjunctivitis sicca and extra glandular manifestations. The presence of sicca symptoms helps with diagnosis but up to 20% patients do not have these. The prevalence of lung involvement hasbeen reportedup to 9-24% and includes changes such as NSIP and organising pneumonia. We present an interesting patient who had no sicca symptoms but positive immunology to suggest Sjö gren's. Changes in sequential CT chest scans were in keeping with Connective Tissue Disease-Associated Interstitial Lung disease (CTAILD). However, presentation with an acute renal injury resulted in a diagnosis of ANCA positive vasculitis. Case report -Case description: A 64-year-old Indian gentleman with medical background of controlled asthma was referred after 9 months of investigations for gluteal weakness. Initial blood tests included normal CK, ESR, CRP, vitamin B12, HbA1c and TFTs. Rheumatoid factor was low positive (20IU/ml), CCP negative. ANAwas 1:80with positive Ro,negative dsDNA. MRI of thighs was normal -no evidence of myositis. Nerve conduction studies showed no active denervation to suggest inflammatory myopathy and muscle biopsy showed myopathic features only. A CT scan revealed 3 small lung nodules recommending repeat scan. When seen in rheumatology clinic, there was additional bilateral shoulder arthralgia with no reports of sicca symptoms or rashes. A repeat autoimmune screen and CT chest was sent. His ANA was 1:1280 with Ro antibodies; CT showed new ground glass changes (with old nodules). Organising Pneumonia was suggested, and respiratory opinion sought. Extended myositis screen was negative. When seen in respiratory clinic he had new haematuria-ANCA screen showed positive anti-PR3 antibody (23U/ml) with normal UþEs, urine PCR and CRP 8mg/L. Based on these results a renal biopsy was performed-which showed no obvious morphological abnormalities. Thus, a suspected diagnosis of CTAILD with Sjö gren's was made.
In clinic 2 months later, there was new shortness of breath and haemoptysis. Urine dip showed haematoproteinuria and Chest X-ray showed increase in peri-hilar masses. He was admitted urgently-blood tests showed a decline in renal function-urea 26.8mmol/L, Creatinine 838umol/L, CRP of 435mg/L and Haemoglobin 100g/L. Urgent repeat renal biopsy was done and CT thorax showed deterioration with bilateral consolidation and new lung lesions. Urgent Plasma exchange and dialysis (9 cycles) was given. Initial results from renal biopsy showed presence of crescents and he was started on cyclophosphamide. On this kidney function has improved-urea 18.4mmol/L and Creatinine 302umol/L; he remains on oral cyclophosphamide. Case report -Discussion: With ongoing symptoms, an underlying autoimmune cause of his symptoms was felt likely. However inflammatory markers remained normal and so did CK. Despite this MRI and muscle biopsies were performed -which again were normal. The only tests that were positive were immunology (Ro antibodies) and a CT chest (showing initial small lung nodules). These findings pointed toward CTAILD with Sjö gren's being the likely diagnosis.
As new lung nodules were seen, repeat CT scans were done-which showed gradual interstitial changes-the main radiological differential diagnosis was Organising pneumonia. Further investigations were delayed due to patient travel and COVID, but ongoing respiratory advice was sought. Even with changes in CT findings the patient remained stable with normal inflammatory markers. However, the clinical picture changed quite rapidly over a month (despite 2þ years of previous symptoms) with presentation of pulmonary-renal vasculitis. Plasma exchange and dialysis were given. A good response with a positive renal biopsy confirmed the most likely diagnosis was Granulomatosis with Polyangiitis (GPA). This case was interesting-the main complaint was of myopathy with no physical signs. Despite this biopsy were performed (muscle and kidney), which were all normal. The red herring in his case was a normal renal biopsy-steering usin the directionof CTD-AILD instead of GPA.
Case report -Key learning points: In patients with clear symptoms matching their investigations the diagnosis is often obvious. When this is not the case and symptomatology does not match results (i.e. no Sicca symptoms but positive immunology to suggest Sjö gren's) suspicion should remain high. Multidisciplinary working can provide insight, which this case does highlight-with input required from Neurology, Respiratory and Renal medicine. Negative results should be taken in context with patients and their symptoms. Initial renal biopsy in this case was normal-however after a review, further comments were made on the sparsity of glomeruli in the sample. Therefore, tissue obtained for diagnosis should always be questioned and clinical suspicion should remain high. In addition, repeat investigations (6 monthly CT scans) canhelp note any interval change. Thorough history and examination in follow up of patients can help look out for evolving changes. With the new symptoms of haemoptysis and haematoproteinuria this pointed us to the eventual diagnosis. The road to diagnosis in this case was prolonged with an acute drop in kidney function and pulmonary haemorrhage needing urgent Plasma exchange and dialysis. Thankfully, the patient continues to make agood recovery. A last point to add is although isolated myalgia has been described as a presentation of systemic vasculitis in the literature, those patients have had elevated CK and positive muscle biopsy. Our patient did not have any positive findings with over 2 years of symptoms. Therefore, we feel this case was unique in presentation and has valid learning points as above. Case report -Introduction: Primary Sjö gren's patients are a higher risk of developing non-Hodgkin lymphoma (NHL) compared with patients with other autoimmune disorders and to the generalpopulation. Parotid and submandibular salivary glands are the most frequent localization of MALT lymphomas in pSS. Here we report a case of marginal zone lymphoma of the breast in a patient with long-standing primary