Multimodal Assessment and Characterization of Sicca Syndrome

Background: Sicca syndrome represents a heterogeneous group of conditions, such as Sjögren syndrome, causing xerophthalmiaand xerostomia. This study characterizes in depth patients with Sicca syndrome and evaluates salivary gland ultrasound (SGUS).Methods: Principal component analysis and hierarchical clustering of clinical parameters, such as ESSPRI, ESSDAI and laboratory data, were performed on all referrals for assessment of Sicca symptoms between October 2018 and March 2021. SGUS and labial gland biopsies were compared across groups.Results: A total of 583 patients were assessed. Objective dryness was confirmed in 73% of the patients. Cluster analysis identified 3 groups with post-hoc analysis confirming distinct phenotypes: Somatic Group (283/583; 49%) with more frequent symptoms but limited objective dryness; Dry Without Autoimmune Features (DAFneg, 206/584; 35%), and Dry With Autoimmune Features (DAFpos, 94/584;16%). DAFpos patients had highest autoantibody titers (anti-SSA(Ro) 240 vs. 3.6 vs. 3.8; p < 0.001), most extra-glandular manifestations (p < 0.001), and highest median SGUS Score (DAFpos: 8 [IQR 4–10] vs. SG: 2 [1–4] vs. DAFneg 4 [2–5]; p < 0.001). No tangible correlation with primary Sjögren syndrome criteria was observed.Discussion: SGUS score correlated with a subset of patients with Sjögren syndrome, identified in the DAFpos cluster. This study highlights heterogeneity within sicca and, indeed, Sjögren syndrome, highlighting the need for further studies.

Diagnostic Delay in Patients with Primary Sjögren’s Syndrome: A Population-Based Cohort Study in Taiwan

The diagnosis of primary Sjögren’s syndrome (pSS) can be challenging because the cardinal sicca syndromes may be subjective and subclinical. Diagnostic delay is common among patients with pSS. The aim of this study was to assess the time of lag between the onset of sicca symptoms and a subsequent diagnosis of pSS. We used population-based data from Taiwan’s National Health Insurance (NHI) claims directory spanning up to 6 years between 2006 and 2011. All NHI-covered patients receiving a first-time approved catastrophic illness certificate (CIC) for pSS in 2011 were included; their sicca symptoms and utilization of medical resources were then traced retrospectively over five years to 2006. The time of lag was identified by observing the onset of sicca symptoms, a diagnosis of Sjögren’s syndrome, and the related claim for CIC. A total of 1970 pSS patients were included in this study. The median time of lag between the onset of sicca symptoms and pSS diagnosis was 115 weeks (interquartile range [IQR] 27–205), and between pSS diagnosis and approval of CIC, was 6 (IQR 2–37) weeks. During the time of lag between sicca symptoms, diagnosis, and approval of a CIC for pSS, the median numbers of outpatient visits were 3 (IQR 1–8) and 3 (IQR 2–7), respectively. These numbers were higher in female and elderly groups. Patients experience a significant diagnostic delay of pSS and in the initiation of regular follow-up care. Targeted guardian programs or public health interventions are required to inform symptom interpretation and reduce delays.

A Presentation of Pediatric Sjögren's Syndrome with Abducens Nerve Palsy

Sjögren's syndrome is a systemic autoimmune disease that classically presents with xerophthalmia and xerostomia. However, neurological manifestations occur in 10 to 60% of patients with Sjögren's syndrome and can often precede classic sicca symptoms in Sjögren's syndrome in some cases up to several years. Rarely, cranial neuropathy can be the initial presentation. Here, we present the first case of a 15-year-old girl with left abducens palsy in the setting of a new diagnosis of Sjögren's syndrome. Comprehensive evaluation revealed elevated Sjögren's syndrome–related antigen A-60 antibody. Cerebrospinal fluid analysis was unremarkable. Radiological studies demonstrated evidence of chronic parotitis. Acute treatment included high-dose methylprednisolone and rituximab, and symptoms resolved by follow-up at 2 weeks. The most common neurological disorder of Sjögren's syndrome is pure sensory neuropathy. In pediatric Sjögren's syndrome, neurological complications are rare but include aseptic meningoencephalitis, acute disseminated encephalomyelitis, transverse myelitis, optic neuritis, and cranial neuropathies. In the circumstance of a cranial neuropathy, the trigeminal nerve is most commonly involved but oculomotor nerves can occasionally be affected. Abducens palsies have been described in four patients with Sjögren's syndrome, typically women and all middle aged or older, with our patient being the first pediatric case. Thus, it is important to consider screening for Sjögren's syndrome in the evaluation of pediatric patients with new onset of isolated cranial neuropathy even in the absence of classic sicca symptoms.

Childhood Sjögren syndrome: features of an international cohort and application of the 2016 ACR/EULAR classification criteria

Objective Sjögren syndrome in children is a poorly understood autoimmune disease. We aimed to describe the clinical and diagnostic features of children diagnosed with Sjögren syndrome and explore how the 2016 ACR/EULAR classification criteria apply to this population. Methods An international workgroup retrospectively collected cases of Sjögren syndrome diagnosed under 18 years of age from 23 centres across eight nations. We analysed patterns of symptoms, diagnostic workup, and applied the 2016 ACR/EULAR classification criteria. Results We identified 300 children with Sjögren syndrome. The majority of patients n = 232 (77%) did not meet 2016 ACR/EULAR classification criteria, but n = 110 (37%) did not have sufficient testing done to even possibly achieve the score necessary to meet criteria. Even among those children with all criteria items tested, only 36% met criteria. The most common non-sicca symptoms were arthralgia [n = 161 (54%)] and parotitis [n = 140 (47%)] with parotitis inversely correlating with age. Conclusion Sjögren syndrome in children can present at any age. Recurrent or persistent parotitis and arthralgias are common symptoms that should prompt clinicians to consider the possibility of Sjögren syndrome. The majority of children diagnosed with Sjögren syndromes did not meet 2016 ACR/EULAR classification criteria. Comprehensive diagnostic testing from the 2016 ACR/EULAR criteria are not universally performed. This may lead to under-recognition and emphasizes a need for further research including creation of paediatric-specific classification criteria.

EP27 Sjögren’s or not: an anxious diagnosis

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 mildUnlike other autoimmune disorders, in SS there is a lack of standardised criteria for diagnosis and classificationSome features can be non- specific and like features of fibromyalgia and sarcoidosisIn unclear cases, like this, objective markers like serology or histology (labial gland biopsy) may be more helpfulIn 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

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.