P27 Lymphoma-mimicker of IgG4-related dacryoadenitis and sialadenitis

Abstract Case report - Introduction Major salivary gland (sialadenitis) and lacrimal gland (dacryoadenitis) involvement can be a common feature of IgG4-related disease. There can be involvement of lacrimal and parotid gland which was previously called as Mikulicz disease and/or submandibular gland enlargement which was previously called Küttner tumour. These were previously mistakenly considered to be subcategories of Sjogren’s syndrome, but are now classified as IgG4-related disease. Here we discuss a case report of a patient who presented with bilateral dacryoadenitis and unilateral submandibular gland enlargement which initially was thought to be IgG4-related disease but turned out to be low-grade lymphoma. Case report - Case description A 15-year-old boy presented with 6-month history of bilateral eyelid swelling. The swelling was more on the lateral side of the eyelids and was painless. It had come on suddenly over a couple of days. No history of weight loss, dry eyes, dry mouth, joint issues or skin rashes or any other symptoms. Physical examination revealed bilateral ptosis, no visual impairment and systemic examination revealed an enlarged right submandibular gland. He had initially been to a local hospital where he had investigations which included autoimmune screen including ANA, ENA, ANCA, dsDNA, serum ace and complement levels which were all negative. C1 esterase inhibitor was normal. Routine bloods including complete blood count, urea and electrolytes, thyroid stimulating hormone and erythrocyte sedimentation rate were within normal limits. Urine albumin to creatinine ratio was not raised. Hepatitis serology including Hepatitis B & C and HIV was negative. Ultrasound abdomen was unremarkable. CT scan of orbits showed bilateral enlarged lacrimal glands with patchy post contrast enhancement and the glands extending up to insertion of lateral rectus muscle. CT chest some enlarged axillary lymph nodes and nodes in lung query infective etiology. CT abdomen and pelvis was unremarkable. Ultrasound neck showed right submandibular node enlargement with colour doppler showing increased vascularity. Fine needle aspirate of the submandibular gland showed reactive lymphoid hyperplasia. He was given two short courses of steroids and each time the swelling rapidly responded to the steroids but recurred on cessation of the steroids. IgG subset analyses revealed elevated IgG4 levels of 1152mg/dl. The differential here was IgG4-related disease but as there was no clear tissue diagnosis a core biopsy of the right submandibular gland was done. This revealed tissue suspicious of low grade (extranodal marginal zone and mucosa-associated lymphoid tissue [MALT]) lymphoma and excision biopsy was performed for definitive diagnosis. Case report - Discussion IgG4-related disease is an immune mediated fibroinflammatory condition which can affect a variety of organs and can present as tumour-like enlargement and/or organ dysfunction. The pathological findings in IgG4-related disease are lymphoplasmocytic infiltrates of IgG4-positive cells along with increased levels of serum IgG4 levels. Salivary and lacrimal glands can be commonly affected and present as enlargement, which is usually painless and bilateral. The combination of lacrimal gland enlargement with both parotid and submandibular gland enlargement is called IgG4-related Mikulicz disease. Apart from salivary glands, another commonly affected organ is the pancreas which can present as a pancreatic mass and painless jaundice, sclerosing cholangitis, retroperitoneal fibrosis, aortitis and periaortitis. Less commonly it can affect thyroid, kidney and lungs. Early recognition, diagnoses and treatment is important due to the fibroinflammatory nature of the disease. Malignancy is always in the differential and should be excluded. Steroids are the mainstay of treatment. If patients experience flare, rituximab can be added. Diagnosis should be confirmed with biopsy but histopathological findings are never alone diagnostic of IgG4-related disease and should be interpreted with clinical, serological and radiological findings. Case report - Key learning points Although this patient had typical presentation of IgG4-related disease with painless enlargement of salivary and lacrimal glands and elevated IgG4 serum levels, biopsy was imperative to get to the diagnoses of low-grade lymphoma and fine needle aspirate was not adequate. As mentioned above, biopsy in IgG4-related disease will confirm the diagnosis provided there are other supporting features (radiological and serological). However, it is imperative for excluding other important diseases like lymphoproliferative disorders.

Following 12 months of chemotherapy, radiotherapy, and an autologous stem cell transplant, she went into remission. Her rituximab therapy was changed back to 6-monthly, and her RA remains stable with no further ocular complications. Case report -Discussion: RA is associated with an increased risk of cancer; however, the aetiopathogenesis is unclear, though the role of chronic inflammation has been reported. A study by Wolfe et al. found that in patients with chronic inflammation, the risk of developing NHL was 9-times higher. Similarly, a Swedish study following 378 RA patients and 378 control patients reported that in patients with severe longstanding RA, the risk of developing cancer was significantly greater in those with higher disease activity. Furthermore, the role of immunomodulatory agents such as rituximab in altering the risk of malignancy is unclear. Rituximab inhibits B-cell activity, which may play a role in supressing the development of B-cell malignancies. A review of the literature found no studies about rituximab and reduced incidence of lymphoma in RA specifically; however, several studies in other diseases have reported a reduction in the incidence of lymphoma in patients taking rituximab. A study by Gé rard et al. followed 113 patients with HIV-associated multicentric Castleman disease for 15 years, where 48 patients were given rituximab therapy and 65 patients were not. Only one patient in the rituximab cohort developed NHL, whereas 17 patients in the other cohort developed NHL. In another study using patient-derived xenografts, immunocompromised mice with high susceptibility of lymphoproliferative disease were implanted with gastric carcinomas. Over 30% of them developed human B-cell lymphomas; however, they found that if the mice were injected with rituximab upon implantation, lymphoma would cease to develop. Case report -Key learning points: Several studies have demonstrated that rituximab therapy plays a significant role in reducing the incidence of lymphoma. In our case report, the development of lymphoma coincided in a reduction in the frequency of rituximab therapy. Therefore, it is possible that the loss of the suppressive effect of rituximab in our patient played a role in the development of lymphoma. Data from real-world drug registries such as the British Society of Rheumatology Biologics Registry for Rheumatoid Arthritis (BSRBR-RA) could provide insight into the incidence and age of onset of B-cell malignancies in patients taking rituximab, compared to those taking non-B-cell-modulating therapy. Similarly, these data could provide insight into whether this protective effect also applies to T-cell-modulating therapy and the risk of T-cell malignancies. Finally, rituximab was also integral in managing the ocular manifestations of her disease. Therefore, this case reinforces that rituximab remains a good treatment option for RA patients with ocular involvement. In conclusion, rituximab is an effective treatment option in managing the ocular manifestations of RA, and may play a role in suppressing the development of lymphoma.

Taha Akhtar
Shifa International Hospital, Islamabad, Pakistan. Shifa Medical Center F11, Islamabad, Pakistan Case report -Introduction: Major salivary gland (sialadenitis) and lacrimal gland (dacryoadenitis) involvement can be a common feature of IgG4-related disease. There can be involvement of lacrimal and parotid gland which was previously called as Mikulicz disease and/or submandibular gland enlargement which was previously called Kü ttner tumour. These were previously mistakenly considered to be subcategories of Sjogren's syndrome, but are now classified as IgG4-related disease.
Here we discuss a case report of a patient who presented with bilateral dacryoadenitis and unilateral submandibular gland enlargement which initially was thought to be IgG4-related disease but turned out to be low-grade lymphoma. Case report -Case description: A 15-year-old boy presented with 6month history of bilateral eyelid swelling. The swelling was more on the lateral side of the eyelids and was painless. It had come on suddenly over a couple of days. No history of weight loss, dry eyes, dry mouth, joint issues or skin rashes or any other symptoms. Physical examination revealed bilateral ptosis, no visual impairment and systemic examination revealed an enlarged right submandibular gland. He had initially been to a local hospital where he had investigations which included autoimmune screen including ANA, ENA, ANCA, dsDNA, serum ace and complement levels which were all negative. C1 esterase inhibitor was normal. Routine bloods including complete blood count, urea and electrolytes, thyroid stimulating hormone and erythrocyte sedimentation rate were within normal limits. Urine albumin to creatinine ratio was not raised. Hepatitis serology including Hepatitis B & C and HIV was negative. Ultrasound abdomen was unremarkable. CT scan of orbits showed bilateral enlarged lacrimal glands with patchy post contrast enhancement and the glands extending up to insertion of lateral rectus muscle. CT chest some enlarged axillary lymph nodes and nodes in lung query infective etiology. CT abdomen and pelvis was unremarkable. Ultrasound neck showed right submandibular node enlargement with colour doppler showing increased vascularity. Fine needle aspirate of the submandibular gland showed reactive lymphoid hyperplasia. He was given two short courses of steroids and each time the swelling rapidly responded to the steroids but recurred on cessation of the steroids. IgG subset analyses revealed elevated IgG4 levels of 1152mg/dl. The differential here was IgG4-related disease but as there was no clear tissue diagnosis a core biopsy of the right submandibular gland was done. This revealed tissue suspicious of low grade (extranodal marginal zone and mucosa-associated lymphoid tissue [MALT]) lymphoma and excision biopsy was performed for definitive diagnosis. Case report -Discussion: IgG4-related disease is an immune mediated fibroinflammatory condition which can affect a variety of organs and can present as tumour-like enlargement and/or organ dysfunction. The pathological findings in IgG4-related disease are lymphoplasmocytic infiltrates of IgG4-positive cells along with increased levels of serum IgG4 levels. Salivary and lacrimal glands can be commonly affected and present as enlargement, which is usually painless and bilateral. The combination of lacrimal gland enlargement with both parotid and submandibular gland enlargement is called IgG4-related Mikulicz disease. Apart from salivary glands, another commonly affected organ is the pancreas which can present as a pancreatic mass and painless jaundice, sclerosing cholangitis, retroperitoneal fibrosis, aortitis and periaortitis. Less commonly it can affect thyroid, kidney and lungs. Early recognition, diagnoses and treatment is important due to the fibroinflammatory nature of the disease. Malignancy is always in the differential and should be excluded. Steroids are the mainstay of treatment. If patients experience flare, rituximab can be added. Diagnosis should be confirmed with biopsy but histopathological findings are never alone diagnostic of IgG4-related disease and should be interpreted with clinical, serological and radiological findings. Case report -Key learning points: Although this patient had typical presentation of IgG4-related disease with painless enlargement of salivary and lacrimal glands and elevated IgG4 serum levels, biopsy was imperative to get to the diagnoses of low-grade lymphoma and fine needle aspirate was not adequate. As mentioned above, biopsy in IgG4-related disease will confirm the diagnosis provided there are other supporting features (radiological and serological Case report -Introduction: Bisphosphonates are known to rarely cause multi-system inflammation, including multiple cranial neuropathies. This is possibly via provoking transient cytokine storm. The literature reports bisphosphonate-associated orbital inflammatory syndrome, and one case of retrobulbar optic neuritis following zoledronate. Bisphosphonate manufacturers report conjunctivitis, blurred vision, scleritis, orbital inflammation, uveitis and episcleritis as ocular side effects. Separately, neurological sequalae, including cranial neuropathies, are reported following COVID-19 infection and vaccination.
Here, we report the first case of cavernous sinus inflammation temporally related to both zoledronate infusion, and more remotely, to Pfizer-BioNTech COVID-19 vaccination.
Case report -Case description: A 76-year-old white man developed fever, bony leg pain -which rendered him unable to walk -and frontal headache, within 8 hours of his first zoledronate infusion for osteoporosis. A few weeks earlier he received his first Pfizer-BioNTech COVID-19 https://academic.oup.com/rheumap i37 POSTERS