EP31 Setting fire to sleeping giants: multiple autoimmune inflammatory diseases set off by chronic viral infection

Abstract Case report - Introduction Autoimmune diseases are a group of disorders where the body produces an immune response against its own tissue constituents. The understanding of the immune mechanisms underlying autoimmunity has significantly deepened and broadened recently. The viral infection is a well-known trigger of autoimmunity and chronic hepatitis is known to cause various auto-immune diseases; organ-specific or systemic. Self-reactivity is part of the normal regeneration and healing. Auto-reactive T&B cells are kept dormant by the concerted action of a variety of mechanisms. Hepatitis C can disrupt this by molecular mimicry, by providing adjuvant and even by directly affecting B cell function. Case report - Case description We report a case of a 77 yr old Caucasian lady from South Africa who presented to Addenbrooke's hospital complaining of general decline, multiple constitutional symptoms, and low-grade fever for nearly 6 weeks. She did not have any infective symptoms. She had a past medical history of Type 1 DM, Hypothyroidism, Sjögren’s syndrome Osteoporosis and chronic hepatitis C infection which was treated 4 years ago. Family history was not significant, and she was a non-smoker. She was found to be thin with a BMI of 18, pyrexical with a temperature 37-38'c; otherwise, examination findings were unremarkable. Initial investigations revealed high inflammatory markers with an ESR of 99 and CRP of 120. WCC was within the normal range as were her renal and liver function tests. She was thoroughly investigated for Pyrexia of Unknown Origin. Her septic screen including Echocardiogram was negative. There was no detectable serum Para-protein and tumour markers were negative. Her CT scan of the chest abdomen and pelvis, MRI scan of the spine and PET scan were reported to be normal. The Serum Pro-calcitonin was low. Rheumatology team was enlisted at this point. On further assessment, the patient mentioned of having an ongoing mild generalised headache - described as a 'fullness in the head' and mild generalised scalp tenderness. She also had an aching pain in her legs. There was no history of visual symptoms, jaw, or tongue pain. On examination, she had generalised scalp tenderness which was worse over the left temporal artery. She had a temporal artery biopsy which showed typical features of GCA (disruption of IEL and giant cell) Following which she was commenced on steroids to which she had a remarkable response. After a month she was commenced on Tocilizumab with quick wean off steroids in view of her elevated risk for fractures. Case report - Discussion This lady believes to have contracted Hepatitis C in the early 80s during a surgical procedure for removal retained products of conception following an incomplete miscarriage in South Africa. She was found to be positive for hepatitis C in the early 90s when she tried to donate blood in the UK. She had genotype 1 hep C. on diagnosis her fibro scan was normal and live biopsy showed mild fibrosis. After regular surveillance during the following years, she was treated with AbbVie 3D regime and ribavirin in 2016 and she was declared to be clear in 2017 (Hepatitis C was undetectable). This lady received a diagnosis of Sjögren’s syndrome in the early 2000s which was based on the fact that she had Sicca symptoms, Positive ANA of 9.2, positive anti-La and anti-Ro, Rheumatoid factor of 13 and lymphocytic clusters in lip biopsy. There are many studies linking Hepatitis C and Sjögren’s syndrome. Sicca symptoms are common in hepatitis C, as chronic sialadenitis is a well-known extrahepatic manifestation. A recent meta-analysis showed a strong association between Hepatitis C infection and Sjögren’s syndrome (OR3.31). This lady was diagnosed with hypothyroidism in the early 90s. Thyroid autoantibodies were not checked then. Thyroid autoimmunity is quite common in Hepatitis C positive patients. Higher prevalence of anti-TPO (21%) and anti-thyroglobulin antibodies (17%) has been demonstrated in Hepatitis C positive population even before they develop hypothyroidism. She was diagnosed with Type 1 Diabetes mellitus in 1997 at the age of 55 after she presented with Diabetic ketoacidosis. She was strongly positive for Anti-GAD antibody (>2000). Again, pancreatic autoimmunity is highly prevalent in non-diabetic Hepatitis C population (1.4% vs 0.4%). There are several case reports of patients who developed type 1 DM after acute hepatitis C infection. Case report - Key learning points As chronic infections are known to trigger autoimmune diseases, it is advisable to screen for them in patients with multiple or atypical autoimmune diseases. Treating the infection itself will lead to complete remission of these autoimmune conditions.


University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom
Case report -Introduction: Primary Sjö gren's syndrome is a systemic autoimmune disease affecting the exocrine glands, commonly resulting in dryness of mouth and eyes. It can also rarely present with neurological symptoms most commonly peripheral neuropathies. The case highlights a rare case of sensory and motor neuropathy with some features suggestive of Sjö gren's syndrome as an underlying diagnosis. Case report -Case description: A 54-year-old Caucasian lady was transferred from a local hospital for specialist neurology care. She described widespread paraesthesia over two months progressing to lower limb weakness worsening over a two-day period. Her symptoms further progressed to involve her arms and new blurred vision. On further questioning she reported previous severe mouth ulcers, possible genital ulcers and painful jaw swelling with long standing history of dry mouth. On thorough neurological examination, the positive findings were mild ptosis of the right eye, paraesthesia on palpation of face, upper limbs had a flaccid tone with reduced power and pseudoathetosis of outstretched arms, reduced proprioception, and absent reflexes. Lower limbs were more affected with worse power and absent proprioception. Schirmer's test showed normal tear production but saliva production was reduced. MRI brain and spine were reported as pathological enhancement in both optic nerves, no obvious brain parenchymal abnormality, no obvious spinal cord abnormality. Lumbar puncture CSF pro 0.38, white cells 12 (poly 50%, mono 50%), red cells 3700, no organisms on gram stain, opening pressure 21.5 cmH 2 O. Sural nerve biopsy demonstrated profound loss of sensory axons, severe loss of large myelinated fibres in all fascicles with motor nerve involvement. Muscle biopsy demonstrated chronic neurogenic atrophy. Rheumatology screen showed positive anti Ro 52 antibodies (on an extended myositis screen). EMG demonstrated neurophysiological evidence of widespread marked loss of sensory axons in the upper and lower limbs and partial loss of motor axons in several lower limb territories. USS parotid glands showed some possibly mildly abnormal areas, minor salivary gland biopsy was normal. She received methylprednisolone, IV immunoglobulin and two courses of plasma exchange. Given some improvement following this treatment, further immunosuppression was felt to be appropriate. Initially Mycofenolate mofetil was started and Rituximab is now being considered. Case report -Discussion: This case demonstrates a mixed neuropathy picture. Following thorough investigations, many differential diagnoses of mixed neuropathy were considered and excluded (e.g. Guillain Barre, Syphilis, MS, HIV, Hepatitis). Neurological symptoms can develop before the onset of sicca symptoms in Sjö gren's syndrome. With a positive Anti Ro52, xerostomia and clinical improvement with methylprednisolone and plasmaphereses it seems likely there is an underlying autoimmune diagnosis in this case and despite a normal biopsy she would meet the 2016 ACR/EULAR classificationcriteria forSjö gren's syndrome. Case report -Key learning points: Sjö gren's syndrome should be considered as a potential underlying cause in patients with a sensory ganglionopathy. Neurological symptoms can develop before the onset of sicca symptoms in Sjö gren's syndrome.

Premila Kadamban and Jobie Evans
Addenbrooke's Hospital, Cambridge, United Kingdom Case report -Introduction: Autoimmune diseases are a group of disorders where the body produces an immune response against its own tissue constituents. The understanding of the immune mechanisms underlying autoimmunity has significantly deepened and broadened recently. The viral infection is a well-known trigger of autoimmunity and chronic hepatitis is known to cause various auto-immune diseases; organ-specific orsystemic. Self-reactivity is part of the normal regeneration and healing. Auto-reactive T&B cells are kept dormant by the concerted action of a variety of mechanisms. Hepatitis C can disrupt this by molecular mimicry, by providing adjuvant and even bydirectly affecting B cell function. Case report -Case description: We report a case of a 77 yr old Caucasian lady from South Africa who presented to Addenbrooke's hospital complaining of general decline, multiple constitutional symptoms, and low-grade fever for nearly 6 weeks. She did not have any infective symptoms. She had a past medical history of Type 1 DM, Hypothyroidism, Sjö gren's syndrome Osteoporosis and chronic hepatitis C infection which was treated 4 years ago. Family history was not significant, and shewas a non-smoker. She was found to be thin with a BMI of 18, pyrexical with atemperature 37-38'c; otherwise, examinationfindings wereunremarkable. Initial investigations revealed high inflammatory markers with an ESR of 99 and CRP of 120. WCC was within the normal range as were her renal and liver function tests. She was thoroughly investigated for Pyrexia of Unknown Origin. Her septic screen including Echocardiogram was negative. There was no detectable serum Para-protein and tumour markers were negative. Her CT scan of the chest abdomen and pelvis, MRI scan of the spineand PETscan were reported tobenormal. TheSerumPro-calcitonin was low. Rheumatology team was enlisted at this point. On further assessment, the patient mentioned of having an ongoing mild generalised headachedescribed as a 'fullness in the head' and mild generalised scalp tenderness. She also had an aching pain in her legs. There was no history of visual symptoms, jaw, or tongue pain. On examination, she had generalised scalp tenderness which was worse over the left temporal artery. She had a temporal artery biopsy which showed typical features of GCA (disruption of IEL and giant cell) Following which she was commenced on steroids to which she had a remarkable response. After a month she was commenced on Tocilizumab with quick wean off steroids in view of her elevatedrisk for fractures. https://academic.oup.com/rheumap i32 EPOSTER Case report -Discussion: This lady believes to have contracted Hepatitis C in the early 80s during a surgical procedure for removal retained products of conception following an incomplete miscarriage in South Africa. She was found to be positive for hepatitis C in the early 90s when she tried to donate blood in the UK. She had genotype 1 hep C. on diagnosis her fibro scan was normal and live biopsy showed mild fibrosis. After regular surveillance during the following years, she was treated with AbbVie 3D regime and ribavirin in 2016 and she was declared to be clear in 2017 (Hepatitis Cwas undetectable). This lady received a diagnosis of Sjö gren's syndrome in the early 2000s which was based on the fact that she had Sicca symptoms, Positive ANA of 9.2, positive anti-La and anti-Ro, Rheumatoid factor of 13 and lymphocytic clusters in lip biopsy. There are many studies linking Hepatitis C and Sjö gren's syndrome. Sicca symptoms are common in hepatitis C, as chronic sialadenitis is a well-known extrahepatic manifestation. A recent meta-analysis showed a strong association between Hepatitis C infection and Sjö gren's syndrome (OR3.31). This lady was diagnosed with hypothyroidism in the early 90s. Thyroid autoantibodies were not checked then. Thyroid autoimmunity is quite common in Hepatitis C positive patients. Higher prevalence of anti-TPO (21%) and anti-thyroglobulin antibodies (17%) has been demonstrated in Hepatitis C positive population even before they develop hypothyroidism. She was diagnosed with Type 1 Diabetes mellitus in 1997 at the age of 55 after she presented with Diabetic ketoacidosis. She was strongly positive for Anti-GAD antibody (>2000). Again, pancreatic autoimmunity is highly prevalent in non-diabetic Hepatitis C population (1.4% vs 0.4%). There are several case reports of patients who developed type 1 DM after acute hepatitis C infection.
Case report -Key learning points: As chronic infections are known to trigger autoimmune diseases, it is advisable to screen for them in patients with multiple or atypical autoimmune diseases. Treating the infection itself will leadto completeremissionof these autoimmuneconditions.

North West Anglia NHS Foundation Trust, Peterborough, United Kingdom
Case report -Introduction: We present a case of a young woman with long-standing history of difficulty swallowing and progressively worsening abdominal pain who was later found to have weakly positive ANA and microcystic changes in submandibular glands bilaterally. Barium swallow demonstrated gastroparesis and the diagnosis of primary Sjö gren's syndrome (pSS) was made. There is conflicting evidence in the literature onthe prevalence of gastroparesis in pSS population. The case is remarkablebecauseabdominalsymptoms and problemswith swallowing rather than sicca syndrome prompted investigations and later confirmed the diagnosis.
Case report -Case description: A nineteen-year old woman had longstanding issues with dry throat, problems with swallowing and sensation of phlegm in the throat, which she felt had started after she swallowed a bone. Provisional diagnoses of globus pharyngeus and chronic throat clearing were made by ENT team. She had trials of sodium bicarbonate, Gaviscon and PPI. She then had a neck USS to exclude goitre and was found to have microcystic changes in submandibular salivary glands bilaterally. This prompted referral to Rheumatology clinic. She reported post-prandial abdominal pain with bloating and early satiety. She had transient pruritic rashes. Therewas no history of joint pains or swelling. She had dry eyes. There was no other history suggestive of connective tissue disorder. Her past medical history included tonsillectomy and iron deficiency anaemia secondary to heavy menses. Her family history was unremarkable. Examination did not demonstrate synovitis or rashes. Her cardiovascular and abdominal examination was normal. Her blood tests showed negative anticardiolipin antibody, negative ds-DNA, negative MPO and PR3, negative ANA by HEp2 and negative rheumatoid factor. She had a weakly positive smooth muscle antibody and a positive ANA by CIA which was negative by HEp2 and therefore thought to be of doubtful clinical significance. She had normal complement, creatine kinase and CRP, and a low ferritin with low haemoglobin, in keeping with known iron-deficiency anaemia.
In view of iron deficiency and low vitamin D levels coeliac screen was performed which was negative. Her chest x-ray was normal. Barium swallow demonstrated significant gastroparesis thus solidifying the diagnosis of Sjö gren's disease. She had a trial of metoclopramide to improve gastric motility, which was not effective. Following a consultation with Gastroenterologist shehad atrial of erythromycin which greatly improved her abdominalsymptoms and swallowing. Sheremains well.
Case report -Discussion: pSS is a chronic systemic autoimmune disease which primarily affects the exocrine glands, most commonly the salivary and lacrimal glands. The prevalence of pSS is estimated to be about 7 per 100,000 person-years. It is characterised by a high female-tomale ratio of 9:1 and the mean age of onset is around the 4th to 5th decade of life. Signs of an autonomic nervous system dysfunction involving the gastrointestinal and the urinary systems can be observed in the majority of pSS patients. However,thishighoccurrenceis rarelyassociatedwith clinically significant symptoms, according to one study. Nevertheless, another study of 38 patients with pSS, demonstrated a higher prevalence of selfreported symptoms of autonomic parasympathetic dysfunction, such as urinary disorder, and gastroparesis (females only) in comparison to controls. Our patient's presentation was unusual due to the early age of onset as well as the fact that it was the swallowing problems that triggered autoimmune investigations. She did not report classic sicca symptoms initially, therefore the index of suspicion of underlying primary Sjö gren's syndrome was low. The most prominent clinical symptom was abdominal pain and bloating as well as a feeling of fullness after meals. Her immunology screen was not typical of Sjö gren's syndrome with negative anti-Ro and anti-La antibodies, negativerheumatoid factor, and normal CRP. The patient does not meet ACR criteria for diagnosis of Sjö gren's syndrome, as there is no tissue diagnosis and lacrimation and salivary tests have not been performed yet. However, the presentation with gastroparesis, sicca symptoms, microcystic changes in salivary glands and raised ESR are highly suggestive of primary Sjö gren's syndrome.
Case report -Key learningpoints: Rarity of pSS and consequently small numbers of patients recruited in the studies of abdominal disorders in pSS make data interpretation difficult. Symptoms arise from impaired function of exocrine glands located across the entiregastrointestinalsystem.Theautonomic nervous system (ANS) may also be involved in the disease manifested by various autonomic dysfunction (AD) symptoms. In pSS, the degree of exocrine gland destruction and function often correlate poorly. Since exocrine secretion is modulated by the ANS, impaired secretion could partly be due to interferencewith nervous signals to the exocrine glands. There is also an immunological hypothesis of symptoms progression in pSS. Such an association between autoimmunity and GI dysfunction has been suggested previously, as there have been reports of coexisting inflammatory bowel disease and severe dysmotility. There is evidence that patients with pSS have antibodies against muscarinic receptors located in vascular smooth muscle cells, particularly in gastrointestinal and genitourinary systems as well as exocrinegland cells.
Gastroparesis is perhaps better known in association with diabetes, with a prevalence between 30% and 50%. However, in one study involving 28 patients with pSS 43% of patients showed signs of impaired gastric emptying, while 29% fulfilled the criteria for gastroparesis. Another study demonstrated that a pathological delay in gastric emptying was present in 70%of patients with pSS. By presenting this case report we are hoping to generate a discussion and learn from experience of other centres in management of these patients. Given the early age and childbearing potential of the patient treatment options are limited. There are reports of successful use of intravenous immunoglobulin in patients with pSS which was shown to neutralize antimuscarinic M3 receptor antibodies and may improve symptoms of autonomic dysregulation.

Khin Yein and Elizabeth Price
Great Western Hospital, Swindon, United Kingdom Case report -Introduction: Sjö gren's syndrome (SS) is a chronic autoimmune inflammatory condition characterised by lymphocytic infiltration of predominantly exocrine glands as well as other organs involving more commonly in skin, lungs, and neurological system. It is associated with increased risk of both benign and malignant lymphoproliferative disorders.
Case report -Case description: A 29-year-old woman with 5-year history of Primary SS (ANA, Ro/La positive) was reviewed in a routine follow up. She has mild dry eyes, intermittent vasculitic rash around the ankles, occasional pleuritic chest pain but no cough or dyspnoea initially. She used artificial tears but took no regular mediations. Oxygen saturation at rest was 99% and BP 127/70. Heart sounds were normal, and chestwas clear. Blood results showed alanine transaminase (ALT) had risen from 50 (normal 5-45) to 145 over 6 months. Viral screen (hepatitis, HIV, CMV, EBV) and liver ANA panel were negative. C4 was low 0.09 (n 0.15-0.55), C3 normal and DsDNA antibodies 1 (n 0-15.1). Ig G was high, fluctuating