ABSTRACT
BACKGROUND: The novel SARS-CoV-2 vaccines partially exploit intrinsic DNA or RNA adjuvanticity, with dysregulation in the metabolism of both these nucleic acids independently linked to triggering experimental autoimmune diseases, including lupus and myositis. METHODS: Herein, we present 15 new onset autoimmune myositis temporally associated with SARS-CoV-2 RNA or DNA-based vaccines that occurred between February 2021 and April 2022. Musculoskeletal, pulmonary, cutaneous and cardiac manifestations, laboratory and imaging data were collected. RESULTS: In total, 15 cases of new onset myositis (11 polymyositis/necrotizing/overlap myositis; 4 dermatomyositis) were identified in the Yorkshire region of approximately 5.6 million people, between February 2021 and April 2022 (10 females/5 men; mean age was 66.1 years; range 37-83). New onset disease occurred after first vaccination (5 cases), second vaccination (7 cases) or after the third dose (3 cases), which was often a different vaccine. Of the cases, 6 had systemic complications including skin (3 cases), lung (3 cases), heart (2 cases) and 10/15 had myositis associated autoantibodies. All but 1 case had good therapy responses. Adverse event following immunization (AEFI) could not be explained based on the underlying disease/co-morbidities. CONCLUSION: Compared with our usual regional Rheumatology clinical experience, a surprisingly large number of new onset myositis cases presented during the period of observation. Given that antigen release inevitably follows muscle injury and given the role of nucleic acid adjuvanticity in autoimmunity and muscle disease, further longitudinal studies are required to explore potential links between novel coronavirus vaccines and myositis in comparison with more traditional vaccine methods.
ABSTRACT
Case report - Introduction This is the case of an adolescent referred to rheumatology following 5 years of back pain. After years of trying a number of treatments without much success, the cause was found to be a previously undiagnosed urological pathology. The case highlights awareness of non-rheumatological causes and incidental findings which can redirect a patient towards more appropriate treatment and reduce the potential for long-term adverse health issues and anxiety. Case report - Case description B was referred age 16 to rheumatology with a 5-year history of lower back pain. She had previously seen paediatricians with symptoms initially attributed to constipation due to intermittent straining and hard stool. However, constipation remedies had not relieved the pain which progressed gradually to a more persistent dull ache with impact on daily activities. Various analgesics (including paracetamol and non-steroidal anti-inflammatories), exercises and acupuncture had not helped. There was no history of recurrent urinary tract infections or symptom correlation with fluid intake, menstruation or bowel habit. No inflammatory features or connective tissue disease symptoms were noted and family history was unremarkable Clinical examination was normal apart from mild tenderness in the lumbar region. Rheumatoid factor was borderline positive (15 iu/mL) with the rest of blood tests normal including renal function, inflammatory markers (CRP, ESR), anti CCP and ANA. She had minimal microscopic haematuria without proteinuria. MRI spine in 2015 was normal. In view of her young age and symptoms affecting daily activities, STIR sequence spinal MRI was requested. This excluded any new or old inflammatory changes but incidentally identified a dilated left pelvi-calyceal system. Renal ultrasound confirmed a grossly hydronephrotic left kidney with hydroureter and minimal renal tissue suggesting longstanding obstruction. No calculi were seen. The patient was referred to urologists. Further investigations (including MRI abdomen) confirmed similar findings and a distal ureteric stricture. A MAG 3 renogram showed a normal right kidney but only 12% functioning of the left kidney. Urologists have advised surgery (removal of left kidney and ureter) which may relieve symptoms or a conservative non-surgical approach (continue analgesia, physiotherapy and monitoring). The patient and her family are relieved to have a possible cause identified and are considering the surgical option due to ongoing flank discomfort. Case report - Discussion This was an interesting finding of hydroureter and hydronephrosis causing longstanding back pain presenting to rheumatologists. Until completion of the spondyloarthropathy protocol MRI (STIR images), aetiology had been unclear. Hydronephrosis and hydroureter has no specific age or racial predilection. Signs and symptoms may depend on whether obstruction is acute/chronic. Chronic cases may be asymptomatic or present as a dull discomfort (like this case). Some cases may only present in adulthood with pain precipitated by fluid intake. Blood tests may show impaired kidney function. Post-mortem studies suggest 50% of people have at least one renal abnormality (e.g., renal cysts, duplex ureters) with autopsy series incidence of hydronephrosis reported as 3.1%. Causes include anatomical abnormalities such as vesico-ureteric reflux, urethral strictures (usually present in childhood), calculi, benign prostatic hyperplasia, or intrapelvic neoplasms, pregnancy and infections (e.g., TB). Sudden onset unilateral renomegaly was reported in one case of primary Sjogren’s with lymphocytic interstitial nephritis and positive Sjogren’s autoantibodies. Our patient has no clinical or serological evidence of connective tissue disease. Minor pelvi-calyceal distension can occur as a normal finding in well-hydrated patients and pregnancy. However, significant hydronephrosis requires assessment to determine cause as it may affect long term renal function. Imaging via computed tomography ultrasound and urograms can help guide further management. In this case the preceding cause and duration of pathology is unknown. Sterile, giant hydronephrosis treatment options include observation and ureteric stent or nephrostomy in patients unfit for surgery. Nephrectomy is advised for pain and recurrent infection in a non-functioning kidney. Complications may include bowel perforation, vascular injury and urine leakage. Both open and minimally invasive procedures have good reported outcomes. The COVID-19 pandemic and exams have affected timing of any elective procedures and the patient understands surgery may or may not offer complete symptom resolution. Case report - Key learning points Non-inflammatory causes of back pain should always be considered in cases of persistent back pain, particularly in young people to ascertain if there is a treatable cause Hydronephrosis cases can be asymptomatic or present with vague, intermittent, non-specific abdominal symptoms with normal physical examination with or without haematuria. This can cause diagnostic uncertainty and delay referral to urology and appropriate renal investigations Assessment of renal function (including MAG 3 renogram) is important to guide further management Surgical interventions (pyeloplasty/nephrectomy) may ease symptoms long term but there is no guarantee of a successful outcome and operative risks need to be considered too Left undiagnosed, potentially this patient could have had further disruption to daily activities and both physical and mental well being
ABSTRACT
Case report - Introduction This case highlights the dilemma of keeping rheumatoid arthritis disease under control in active cancer cases and establishing a consistent multidisciplinary dialogue during a pandemic and staffing crises. During chemotherapy and active cancer treatment, disease-modifying therapies (conventional and biologic) are often stopped. In some cases, the potential benefits versus risks of restarting usual therapies have to be balanced against risks of suppressing disease activity with high-dose steroids. Risks of infection (common and atypical) need to be considered. Case report - Case description A is a 67-year-old female non-smoker diagnosed with seropositive rheumatoid arthritis (RF, anti –CCP positive) in 2008. Other conditions include type 2 diabetes, atrial fibrillation (on warfarin), hypothyroidism and obstructive sleep apnoea. Due to active disease, despite triple therapy (methotrexate, sulphasalazine and hydroxychloroquine), anti-TNF therapy (etanercept) commenced in 2009 with primary non-response. However, she responded well to B-cell therapy (rituximab) in conjunction with oral methotrexate (25mg weekly) receiving annual infusions from 2010 to 2016. In 2017, an elective sleeve gastrectomy procedure for high BMI was abandoned after peritoneal deposits of concern were noted. Histology and CT imaging were consistent with a primary peritoneal malignancy (Stage 3c low-grade serous adenocarcinoma). Treatment involved debulking surgery (total abdominal hysterectomy, bilateral salpinoophorectomy, omentectomy) and tamoxifen. Treatment for rheumatoid arthritis stalled during this period but as frequent steroids were required for active joint inflammation, in agreement with the oncologists, she had a rituximab cycle in 2018. Unfortunately, in 2019 she had signs of cancer progression (elevated tumour markers, CT imaging) and has subsequently started carboplatin chemotherapy. She has been unable to continue methotrexate or rituximab pending completion of the chemotherapy cycles (ongoing). However, her arthritis is now uncontrolled without increased steroids. Due to recurrent flares, her maintenance dose has been increased from 5mg to 7.5—10mg prednisolone daily until we can establish if it is safe and appropriate to recommence her usual arthritis regime. Even without disease-modifying therapy like methotrexate and rituximab, risk of infection (including atypical ones) is still significant with the combination of chemotherapy and steroids. Risk of progressive joint damage and adverse quality of life with active arthritis also needs to be considered. Staffing crises, exacerbated by COVID pandemic issues, have added to complexity of decision making and coordination of regular multidisciplinary discussions regarding treatment. Case report - Discussion Cancer is a known association in rheumatoid arthritis patients with a twofold higher risk of lymphoma compared to the general population. Whether condition or treatment affects risk remains unclear as immune dysregulation is relevant in both autoimmunity and cancer. Paraneoplastic, recent onset arthritis, chemotherapy- or immunotherapy-induced arthralgia/arthritis are also well documented. This case had a seropositive rheumatoid arthritis phenotype quite a few years prior to cancer diagnosis. Primary peritoneal cancer is uncommon, often presenting as in this case as an incidental finding. It is usually treated like ovarian cancer Whilst methotrexate has been implicated in lung cancer, melanoma and non-Hodgkin lymphoma, overall safety data suggest any risk is quite low (e.g., EBV-associated lymphoproliferative disorders usually resolve with drug discontinuation). It is also a known chemotherapeutic agent. Anti-TNF treatment algorithms generally exclude patients with recent cancer. Rituximab, originally developed as a cancer drug, is not thought to affect risk of cancer development or progression. Treatment with disease-modifying therapy (conventional and biologics) is often withheld in patients with active malignan y undergoing chemotherapy due to a theoretical risk of potentiated immunosuppression and toxicity, particularly cytopaenias. However, maintaining arthritis control with glucocorticoids also has short- and long-term risks. Combining chemotherapy agents like carboplatin with methotrexate has been used for urothelial carcinoma and can be well tolerated with close monitoring of haematological parameters. Thus, it could be argued this patient is at risk of infections whichever treatment approach is taken and regaining control of arthritis with recommencement of methotrexate and rituximab is much better for her quality of life. Regular multidisciplinary discussions are important to outline risks versus benefits of combined treatment. This may be difficult in practice during staffing crises. Covid risk in patients receiving rituximab and/or chemotherapy, timing and response to COVID vaccination are also important considerations. Case report - Key learning points Primary peritoneal cancer is uncommon and can present as an incidental finding Whilst treatment for progressive cancer is important, withholding rheumatoid arthritis treatment can have a significant adverse impact on quality of life Morbidity and mortality risks of stopping treatment versus combined treatment (cancer therapy and disease-modifying therapy) ideally needs to be fully discussed and agreed with the patient and all care providers – lack of “named” providers, restructuring, redeployment, multi-specialty care and a global pandemic can make coordination of this difficult