O20 A case series of paediatric primary Sjögren’s syndrome: differential diagnoses and multidisciplinary management

Abstract Case report - Introduction Two cases of primary Sjögren’s syndrome presenting in a child with recurrent salivary gland enlargement are described. As a condition which rarely presents in childhood, these cases underline the need to consider more uncommon differentials in a child presenting with recurrent salivary gland swellings. They also highlight how well co-ordinated multidisciplinary care involving medical and dental specialist teams can achieve the best outcomes for patients. Case report - Case description Case 1: An 8-year-old girl presented to Paediatric Rheumatology with non-mealtime related episodes of bilateral parotid pain and swelling and intermittent dry mouth. Dry eyes and joint pain were not reported, and she was systemically well. Anti-Ro, anti-La and rheumatoid factor were positive. Salivary gland ultrasound showed evidence of sialadenitis. Sjögren’s Syndrome was diagnosed and treatment with hydroxychloroquine and azathioprine reduced the swelling frequency and severity. Regular optician reviews were arranged, and she was also noted to have ‘soft teeth’. Review by Paediatric Dentistry revealed her dry mouth had been managed with acidic sweets, leading to erosive tooth surface loss of the primary dentition. Onward referral was made to Oral Medicine and a differential diagnosis of chronic parotitis of childhood was considered. Ultrasound review by Oral and Maxillofacial Radiology confirmed Sjögren’s Syndrome. Yearly ultrasound scanning was arranged to assess for disease progression and lymphoma development. Case 2: A 17-year-old girl was referred to Oral Medicine with a diagnosis of Sjögren’s syndrome. She initially presented to Rheumatology 3 years previously with dry mouth, dry eyes, and intermittent bilateral swellings of the parotid and submandibular glands. The salivary gland swellings were associated with pain on eating and fatigue and improved with short courses of oral corticosteroids. Titres of anti-Ro60/52 antibodies were high, and a right parotid ultrasound guided biopsy showed a focus score of greater than 2 with changes consistent with Sjögren’s Syndrome. Hydroxychloroquine was initiated and the frequency and severity of the swellings improved. Referrals were made to Ophthalmology for a dry eye’s ocular assessment and retinal screening in view of hydroxychloroquine therapy. She regularly attended her dentist and managed her dry mouth with sugar free sweets. On review with Oral Medicine various non-acidic oral lubricants were recommended in addition to yearly ultrasound scanning. Case report - Discussion Sjögren’s syndrome is a multisystem autoimmune disease characterised by focal lymphocytic inflammatory infiltrates within the exocrine glands, predominantly the salivary and lacrimal glands. It is rarely diagnosed in children but should be considered when there is recurrent swelling of the salivary glands. There is a higher incidence of recurrent parotitis, but ocular and oral symptoms are less common in children. Therefore, the usual diagnostic criteria have a lower sensitivity for Sjögren’s syndrome in children compared with adults. The main differential was chronic parotitis of childhood; a poorly defined condition characterised by recurrent parotid inflammation that is generally associated with non-obstructive sialadenitis. It can present with recurrent, self-limiting episodes clinically resembling mumps and has a spectrum of symptoms varying from mild to incapacitating. There can be overlapping features between the two conditions, including similar ultrasonography changes and punctate sialectasis on sialography. However, most cases of chronic parotitis fully resolve over time without any long-term adverse impact, whereas Sjögren’s Syndrome is typically progressive. The risk of developing non-Hodgkin’s lymphoma in Sjögren’s is higher than the normal population. Therefore, patients should regularly undergo ultrasound surveillance, for example, by an Oral and Maxillofacial Radiologist. Immunosuppressant therapy may control symptoms and reduce lymphocytic infiltration and fibrosis of the salivary glands. However, there are no studies on systemic therapy for juvenile Sjögren’s and therefore management is based on that for adults. Hydroxychloroquine is widely used for reducing symptoms of fatigue and joint pain, whereas azathioprine is usually reserved for cases with systemic complications, such as lung disease. More recent studies evaluating the use of Rituximab, an anti-CD20 antibody have given mixed results, although it potentially could be considered in younger patients as long-term treatment with hydroxychloroquine or azathioprine carries an increased risk of side-effects. Case report - Key learning points Several medical and dental specialities were involved in the management of these unusual cases of Sjögren’s Syndrome presenting in childhood and adolescence to deliver high quality, coordinated care. This underlines the importance of a multidisciplinary approach to deliver holistic young adult/child-centred care. Multidisciplinary management of Sjögren’s syndrome should include a General Paediatrician, a Paediatric or general medical Rheumatologist, an Ophthalmologist and Oral Medicine specialist. Involvement of the General Dental Practitioner is also recommended to maintain a functional dentition from an early age. Although rare, Sjögren’s syndrome and recurrent parotitis of childhood should always be considered as differentials in a child with recurrent salivary gland swelling. A lower incidence of sicca complex symptoms can lead to difficulties in diagnosis; therefore, it is probable that Primary Sjögren’s syndrome is underdiagnosed in childhood. Regular ultrasound surveillance should be performed to monitor for non-Hodgkin’s lymphoma. Treatment is largely symptomatic; both patients were managed with hydroxychloroquine and the first was also taking azathioprine. Potentially treatment may continue for several years. Long-term use of hydroxychloroquine carries a dose-dependent risk of retinopathy and requires regular optician and ophthalmology reviews. Long term use of azathioprine carries potential risks of lymphoma, non-melanoma skin cancers and bone marrow suppression. Therefore, careful consideration needs to be given to the consent process to ensure there is shared decision making between the prescribing clinician, patient, and parent.

across. My experience did teach me that there were certain times when medications were not taken as intended due to lack of full understanding by the patient. In a private hospital setting, patient can choose their own compliance with clinic attendance as per their convenience and understanding of the condition. This aspect also contributed towards management challenges and control of her disease. The most limiting and frustrating factor to manage this case has also been the lack of engagement and approval by the insurance provider. I made multiple medical requests for their attention and unfortunately all were rejected. The local healthcare system in Kingdom of Saudi Arabia allows expat patients to be seen primarily in private hospitals under the cover of their employer insurance. This also led to lack of sharing expertise and treatment facilities with the regional specialist rheumatology centre, which is mainly designed to cater for local nationals. I am seriously considering making a "special request" for this case to be accepted in the Ministry hospital so Cyclophosphamide and/or Rituximab can be considered. Case report -Key learningpoints Should we have considered Mycophenolate at very initial presentation and could that have led to different and better clinical outcome? Would renal biopsy change management significantly and how best we can persuade patient and Nephrologist? How else we can engage this young adolescent girl as she was more concerned about her cosmetic appearance and since skin has responded very well, she may not feel too convinced on the need for ongoing treatment and also attending clinic appointment? Perhaps we could have referred her case as a "special request" to local specialist Rheumatology center so she could have been considered for treatment options like Rituximab and cyclophosphamide. The local healthcare in Saudi Arabia permits local nationals to be seen in local and private hospitals whilst expats are catered only in private hospital unless there is exception due to availability of treatment or expertise, where process of acceptance can also be complex and time demanding. Case report -Introduction: Two cases of primary Sjö gren's syndrome presenting in a child with recurrent salivary gland enlargement are described. As a condition which rarely presents in childhood,these cases underline the need to consider more uncommon differentials in a child presenting with recurrent salivary gland swellings. They also highlight how wellco-ordinatedmultidisciplinarycare involvingmedical anddental specialist teamscanachieve the best outcomes forpatients. Case report -Case description: Case 1: An 8-year-old girl presented to Paediatric Rheumatology with non-mealtimerelated episodesof bilateral parotid pain and swelling and intermittent dry mouth. Dry eyes and joint pain were not reported, and she was systemically well. Anti-Ro, anti-La and rheumatoid factor were positive. Salivary gland ultrasound showed evidence of sialadenitis. Sjö gren's Syndrome was diagnosed and treatment with hydroxychloroquine and azathioprine reduced the swelling frequency and severity. Regular optician reviews were arranged, and she was also noted to have 'soft teeth'. Review by Paediatric Dentistry revealed her dry mouth had been managed with acidic sweets, leading to erosive tooth surface loss of the primary dentition. Onward referral was made to Oral Medicine and a differential diagnosis of chronic parotitis of childhood was considered. Ultrasound review by Oral and Maxillofacial Radiology confirmed Sjö gren's Syndrome. Yearly ultrasound scanning was arranged to assess for disease progression and lymphoma development.
Case 2: A 17-year-old girl was referred to Oral Medicine with a diagnosis of Sjö gren's syndrome. She initially presented to Rheumatology 3 years previously with dry mouth, dry eyes, and intermittent bilateral swellings of the parotid and submandibular glands. The salivary gland swellings were associated with pain on eating and fatigue and improved with short courses of oral corticosteroids. Titres of anti-Ro60/52 antibodies were high, and a right parotid ultrasound guided biopsy showed a focus score of greater than 2 with changes consistent with Sjö gren's Syndrome. Hydroxychloroquine was initiated and the frequency and severity of the swellings improved. Referrals were made to Ophthalmology for a dry eye's ocular assessment and retinal screening in view of hydroxychloroquine therapy. She regularly attended her dentist and managed her dry mouth with sugar free sweets. On review with Oral Medicine various nonacidic oral lubricants were recommended in addition to yearly ultrasound scanning.
Case report -Discussion: Sjö gren's syndrome is a multisystem autoimmune disease characterised by focal lymphocytic inflammatory infiltrates within the exocrine glands, predominantly the salivary and lacrimal glands. It is rarely diagnosed in children but should be considered when there is recurrent swelling of the salivary glands. There is a higher incidence of recurrent parotitis, but ocular and oral symptoms are less common in children. Therefore, the usual diagnostic criteria have a lower sensitivityfor Sjö gren's syndrome inchildren compared with adults.
The main differential was chronic parotitis of childhood; a poorly defined condition characterised by recurrent parotid inflammation that is generally associated with non-obstructive sialadenitis. It can present with recurrent, self-limiting episodes clinically resembling mumps and has a spectrum of symptoms varying from mild to incapacitating. There can be overlapping features between the two conditions, including similar ultrasonography changes and punctate sialectasis on sialography. However, most cases of chronic parotitis fully resolve over time without any longterm adverse impact, whereas Sjö gren's Syndrome is typically progressive.
The risk of developing non-Hodgkin's lymphoma in Sjö gren's is higher than the normal population. Therefore, patients should regularly undergo ultrasound surveillance, for example, by an Oral and Maxillofacial Radiologist. Immunosuppressant therapy may control symptoms and reduce lymphocytic infiltration and fibrosis of the salivary glands. However, there are no studies on systemic therapy for juvenile Sjö gren's and therefore management is based on that for adults. Hydroxychloroquine is widely used for reducing symptoms of fatigue and joint pain, whereas azathioprine is usually reserved for cases with systemic complications, such as lung disease. More recent studies evaluating the useof Rituximab, an anti-CD20 antibody have given mixed results, although it potentially could be considered in younger patients as longterm treatment with hydroxychloroquine or azathioprine carries an increasedrisk of side-effects. Case report -Key learning points: Several medical and dental specialities were involved in the management of these unusual cases of Sjö gren's Syndrome presenting in childhood and adolescence to deliver high quality, coordinated care. This underlines the importance of a multidisciplinary approach to deliver holistic young adult/child-centred care. Multidisciplinary management of Sjö gren's syndrome should include a General Paediatrician, a Paediatric or general medical Rheumatologist, an Ophthalmologist and Oral Medicine specialist. Involvement of the General Dental Practitioner is also recommended to maintain a functional dentition from anearly age. Although rare, Sjö gren's syndrome and recurrent parotitis of childhood should always be considered as differentials in a child with recurrent salivary gland swelling. A lower incidence of sicca complex symptoms can lead to difficulties in diagnosis; therefore, it is probable that Primary Sjö gren's syndrome is underdiagnosed in childhood. Regular ultrasound surveillance should be performed to monitor for non-Hodgkin's lymphoma. Treatment is largely symptomatic; both patients were managed with hydroxychloroquine and the first was also taking azathioprine. Potentially treatment may continue for several years. Long-term use of hydroxychloroquine carries a dose-dependent risk of retinopathy and requires regular optician and ophthalmology reviews. Long term use of azathioprine carries potential risks of lymphoma, non-melanoma skin cancers and bone marrow suppression. Therefore, careful consideration needs to begiven to the consent process toensurethere is shareddecision making between the prescribing clinician, patient,and parent.

Alaeldin Mohamednour, Sanna Khan, Kehinde Sunmboye and Alison Kinder Leicester Royal Infirmary, Leicester, United Kingdom
Case report -Introduction: Panniculitides comprise a heterogeneous group of inflammatory diseases involving the subcutaneous fat. They remain the most challenging areas forclinicians. Skin biopsy is commonly needed to confirm diagnosis. Because there are many underlying aetiologies for panniculitis, detailed history and thorough investigations are needed. We present a case of A 20-year male who was admitted with painful lumps treated initially as cellulitis/abscess butturned to be neutrophilic panniculitis on skin biopsy.Extensive workup failed to reveal underlying aetiology. Eventually Imradli (AntiTNF) was thought to be the culprit and therefore was kept onholdwith norecurrence of panniculitis. Case report -Case description: A 20-year-old, Asian Malawian. Moved to the UK at the age of 6. He was diagnosed with Ankylosing spondylitis in November 2016. Initially received Naproxen followed by (Humira) with good clinical response. He was switched to biosimilar Imradli in Nov 2019. He was admitted with 2-3 weeks history of progressive right hip and buttock pain, 1 week of very tender erythematous swelling of the right buttock but without fever or weight loss. He reported mild weakness of lower limbs. Physical examinationrevealed 5x 8 cm swelling on Right buttock, Rest of examinationwas unremarkable. He was reviewed by neurology team who arranged MRI spine and brain, EMG and lumbar puncture which all came back as unremarkable excluding the possibilities of myelitis and myositis. Initially thought to be abscess/cellulitis but absence of fever/inflammatory response, abnormal CT finding and no response to antibiotics made it less likely. While the Right buttock erythema/swelling started toresolve, hedevelopedtwonew migratory erythematouslesions appearing around the left buttock and lower lumbar spine. Working diagnosis of panniculitis was made which was confirmed on biopsy. Due to lack of response to NSAIDs, colchicine or oral steroids, a 3rd biopsy of the freshest lesion was performed to exclude deep-seatedinfection. Investigations -FBC, U&ES, LFT, CRP, CK, ACE -all were unremarkable ASO titre <200, serologyfor Borrelia and TPHA negative. Viral, parasitic, and Autoimmunescreen were unremarkable. CXR clear, MRI/CT: extensive subcutaneous inflammatory changes in the right buttock with sacral oedema. PET-CT -showed resolving inflammatory changes in the right flank, FDG intake in C6 and SI joints presumed secondary to ankylosing spondylitis and sacroiliitis. The underlying cause of panniculitis remains uncertain. Anti TNF was kept on hold and the patient was followed up with no evidence of recurrence of panniculitis Case report -Discussion: Panniculitis (inflammation of subcutaneous fat) is a relatively uncommon condition. It has various aetiologies including infection, trauma, inflammation, and malignancy. Skin biopsy can give valuable information including microbiological studies if infectious panniculitis was suspected. However, clinical correlation and careful consideration of the differential diagnosis is needed in many cases. The diagnosis can be quite challenging as in this case where all investigations and skin biopsy could not point towards the underlying aetiology. Although anti-TNF inhibitors are commonly used in treating a wide range of autoimmune conditions. But their use can lead to the development of secondary autoimmune diseases, such as cutaneous vasculitis, lupuslike syndrome, and interstitial lung disease, paradoxically induced by anti-TNF-a agents. Llamas-Velasco and Requena, reported the first case of panniculitis induced by etanercept injection in a 62-year-old woman with severe psoriasis who developed an erythematous, slightly painful nodule on the skin of the anterior abdominalwall. Adalimumab induced lupus panniculitis was reported in a Rhu-lupus patient. Although the lesions stopped progressing after cessation of adalimumab, they remained unchanged for two more years. The mechanism for adalimumab-induced CLE is uncertain. Although there is not enough data about autoimmunity with biosimilars, we think secondary autoimmune conditions could similarly be induced by biosimilarasillustratedinthiscase.Anti-TNFinducedcutaneouspanniculitisis considered most likely although uncertain. If anti-TNF drug-induced, this should gradually resolve but can be slow (4-6 months). Corticosteroids have been added for an anti-inflammatory response, but there was little benefitwhichmightpointtoadifferentpathogeneticmechanism. NSAIDs has helped to keep his AS relatively stable during the COVID-19pandemic. During the last review, the patient expressed his wishes to go back on biologic. But the question remains whether he will a have a recurrence of panniculitis or not? Case report -Key learning points: 1/Anti-TNF inhibitors sometimes cause secondary autoimmune conditions like cutaneous vasculitis, lupus-like syndrome, but there is not enough data regarding biosimilar induced autoimmunity. 2/This case illustrates the high importance of having a tissue diagnosis.
(wheneverthere is an issue, the diagnosis would bein the tissue). 3/There is still uncertainty whether a recurrence of panniculitis might occur ornot if the patient went again on biologics.