Navigating Giant Cell Arteritis (Gca) Service during and Post Covid-19 Pandemic: An Audit of Gca Care at North Bristol Nhs Trust against the Bsr Quality Standards

Background/Aims GCA is a systemic vasculitis predominantly affecting the large vessels that requires prompt diagnosis and management. This clinical audit aims to study the impacts of COVID-19 pandemic on our GCA service and to identify areas for improvement to ensure good and safe practice amid healthcare crisis. Methods We audited referrals for suspected GCA from February 2021 until September 2022 and measured our patient care against the BSR quality standards. We performed retrospective data collection from digital care record systems and analysed our data using the IBM SPSS Statistics version 29. Results 106 patients with suspected GCA were included, 73% were female and the mean age was 70 years. 75% of the referrals were from primary care. Main presenting symptoms were headaches (95.7%), scalp tenderness (69.6%), tongue/jaw claudication (52.2%), visual symptoms (47.8%), constitutional symptoms (43.5%) and polymyalgic symptoms (21.7%). 33% of patients were diagnosed and treated as GCA. Mean CRP was 23.9mg/L and mean plasma viscosity was 1.89mPA. The mean referral-to-specialist review time has reduced to 1.6 days, compared with 2.7 days pre-pandemic. All patients had vascular ultrasound but only 7.5% had a temporal artery biopsy (TAB), compared with 41% pre-pandemic. Table 1 compares expected and achieved BSR quality standards. Conclusion Changes in work pattern during the pandemic meant that the time from referral to specialist review was significantly reduced, by implementing twice weekly registrar-led 'Hot' clinics and reserving ad hoc slot(s) in on-call consultant's clinics for GCA referrals. We have ramped up our vascular imaging capacity for vascular ultrasound during the pandemic in response to reduced surgical operating capacity for TAB. Strategies to address areas for improvement identified in this audit include: (1) clear and timely communication with referrer about steroid initiation and dosage, at the time of referral;(2) improving communication with primary care, emphasising need for urgent Ophthalmology input in patients with suspected GCA-related visual symptoms, through updating our regional GCA guideline for primary care;(3) standardising and implementing a GCA review proforma or checklist in our department to ensure that the BSR GCA care bundle is being implemented and addressed at the earliest opportunity. (Table Presented).

Inflammatory and Infectious Vasculopathies

Inflammatory and infectious disorders have been important, if uncommon, causes of stroke. Primary and secondary vasculitides may cause stroke affecting large and small blood vessels of the central nervous system. The pathology may include granulomatous, lymphocytic, and necrotizing lesions. The underlying antigens leading to vasculitis may include amyloid deposition from amyloid angiopathy, or even from infectious agents, although the mechanisms for these disorders remain poorly understood. Many of these conditions have a poor prognosis, although steroid and other immunosuppressive therapies may improve outcomes. Further research, including well-designed clinical trials, are needed. Although infections, such as syphilis, have been associated with stroke risk for more than a century, understanding the relationship between infection and stroke has taken on even greater urgency in the era of the coronavirus disease 19 pandemic. A multitude of pathogens, including bacteria, viruses, parasites, and fungi, have been associated with specific stroke syndromes, through a number of different mechanisms, including large vessel vasculopathy, aneurysmal dilatation, thrombophilia, and cardioembolism. Some infections may also contribute to the atherosclerotic process. This chapter will cover the clinical features, pathophysiology, and potential treatment (where available) for inflammatory and infectious causes and contributors to stroke risk. © 2022 Elsevier Inc.

Challenges in the Diagnosis and Investigation of Giant Cell Arteritis during Covid- 19 Pandemic Restrictions: Does the Southend Pretest Probability Score Help to Guide Clinical Diagnosis?

Background/Aims During 2020-2021 many usual hospital services were affected as focus turned towards managing COVID-19. Elective outpatient surgery ceased and rheumatology staff were redeployed to covid wards. This reduced the availability of temporal artery biopsy (TAB) and temporal artery ultrasound (TAUS) to aid in diagnosing giant cell arteritis (GCA). The rheumatology team making diagnoses of GCA or not-GCA were doing so often based entirely on clinical and laboratory findings. We aimed to determine referral patterns and investigations for suspected GCA during the covid pandemic, compare diagnoses at 6 months after initial assessment and retrospectively apply the Southend Pretest Probability Score (PTPS) and correlate with the diagnosis of GCA or not-GCA. Methods We reviewed all electronic referrals for suspected GCA from July 2020 - June 2021. Clinical details and investigations reviewed. PTPS applied giving a result of low, intermediate or high probability of GCA. Results 84 referrals for suspected GCA over 12 months. 20 diagnosed GCA/ large vessel vasculitis (LVV), 64 not-GCA. Peak referral months Nov 2020 and April 2021 with 13 and 16 referrals. Lowest in October 2020 with 1 referral. 57 female, 27 male. Mean age 70.1 years. 19% male referrals diagnosed GCA, 26% female diagnosed GCA. All LVV and PMR diagnoses were female. 27 TAUS, 6 TAB, 7 PET, 13 CT, 3 MRI performed. 30 patients had no additional investigations. Of 20 GCA;14 had supporting investigations, 6 were clinical diagnoses. All GCA diagnoses were consistent at 6 months. One not-GCA case was subsequently diagnosed with LVV on CTPET. All other not-GCA diagnoses were consistent at 6 months. The PTPS was retrospectively applied based on available clinical information in all except 2 cases, and compared to GCA/not-GCA diagnosis and investigations undertaken. Conclusion Referral numbers for suspected GCA were higher than previous years however the number of actual GCA diagnoses was similar. With limitations on diagnostic investigations due to covid, diagnoses of GCA with and without additional tests were accurate at 6 months, and correlated with a high probability score. The PTPS is a therefore valuable clinical tool in the assessment of GCA. (Table Presented).

Outcomes of Sars-Cov-2 Infection in Patients with Anca Associated Vasculitis. Data from the National Sar-Covid Registry

Objectives: To describe the clinical characteristics and outcomes of SARSCoV-2 infection in patients with systemic vasculitis. Method(s): Observational, multicenter, cross-sectional analytical study in patients 18 or older diagnosed with systemic vasculitis with confirmed SARSCoV-2 infection (RT-PCR or serology) included in the SAR-COVID registry. Patients were evaluated from July 2020 to February 2022. Patients diagnosed with ANCA-associated vasculitis (AAV), other systemic vasculitides (Giant cell arteritis, Takayasu), and a control group of patients with other rheumatological diseases matched by age, sex, comorbidities, and date of SARS-CoV-2 infection. The survival curve of the groups was studied by Kaplan-Meier and compared through the Log-Rank Test. A Cox regression model will be performed to adjust survival for different variables (sex, age, treatments for underlying disease, treatments for viral infection, smoking, obesity, d-dimer level, and disease activity). Result(s): A total of 282 out of 2694 patients in the SAR-COVID registry were included, 57.4%women with a mean age of 55.7 years (SD 14.1). Fifty-four patients in the AAV group, 32 in the other vasculitis group, and 196 controls were studied. Hospitalization was required in 53.7% of the AAV group, 37.5% in other vasculitides, and 26.2% in the control group. 5.6% of patients in the control group presented acute respiratory distress syndrome (ARDS), 15.6% in the other vasculitis group, and 22.2% in the AAV group (p alpha 0.001). Complete recovery was observed in 82.3% of patients in the control group, 75%in the other vasculitis group, and 63%in the AAV group.We observed that 5.7% of the patients in the control group died from COVID-19, 9.4%from other vasculitides, and 27.8% in the AAV group (p alpha 0.001). We found a lower survival in the AAV group compared to the control group (p alpha 0.005). In the multivariate Cox regression model, older age (HR:1.05 IC95%1.01-1.09 p = 0.01), BMI > 40 (HR:13.2 IC95% 2.1-83.2 p = 0.01), and high activity of the underlying disease (HR:16 95% CI 3.7-69.4 p alpha 0.005) were associated with lower survival. Conclusion(s): In conclusion, patients diagnosed with AAV presented a worse disease course during SARS-CoV-2 infection with a more frequent requirement for invasive mechanical ventilation. Likewise, these patients showed lower survival compared to patients with other autoimmune diseases.

An Audit of Demographics, Symptoms & Investigations: Part of the Survey of Gca in the Sehsct during the Covid-19 Pandemic

Background/Aims Giant cell arteritis (GCA) is the most common vasculitis in adults aged over 50 years old with the highest incidence among persons aged 70- 79. It is more commonly seen in female patients. Most cases have been reported in whites of Northern European descent. A broad range of symptoms can be reported including headache, jaw or tongue claudication, visual disturbances, PMR and other systemic features including weight loss, fever and sweats. In recent years new evidence has emerged regarding the investigation and treatment of GCA. This audit is to review the demographics, symptoms and investigations of patients who presented to the Rheumatology Department in SEHSCT with features concerning for possible GCA. Methods Retrospective collection of data from January 2020 to July 2021 using the regional Electronic Care Record NI with reference to presentations, investigation results, clinic records and follow-up letters. Results 70 patients were included (24 males and 46 females). Mean age was 72 years old. Table 1 shows the percentages of clinical symptoms reported. All patients investigated had an ESR (mean 57.8) and CRP (mean 54.1) checked. 43 patients had ANCA checked with 3 positive results. 40 patients underwent CT brain with 2 abnormalities reported unrelated to GCA. TA ultrasound was performed on one occasion with a positive result demonstrating ''halo'' sign recorded. 6 patients underwent CTPET with 3 diagnoses of LVV and 1 of PMR. 70 TAB performed with 12 positive results and 4 'suggestive' of GCA. Conclusion Our cohort of patients demonstrated demographics similar to the current global geographic trends in GCA. There are a broad range of clinical symptoms that can present in GCA, none of which are entirely specific or pathognomonic. Clinical diagnosis is based on clinical symptoms, signs and laboratory tests, each of which are imperfect markers for GCA. Our audit demonstrated that the use of additional confirmatory diagnostic tests including temporal artery ultrasound and CTPET was being under-utilized in the SEHSCT. Use of these tests may improve the diagnostic yield in this challenging condition. As a result of this audit, a quality improvement project to provide a rapid access GCA pathway is being designed. (Table Presented).

A Systematic Review of New Rheumatic Immune-Mediated Inflammatory Diseases (R-Imid) Following Sars-Cov-2 Vaccinations

Background/Aims There are sporadic reports about the development of new rheumatic immune-mediated inflammatory diseases (R-IMIDs) in adults after receiving SARS-CoV-2 vaccines. This systematic review (SR) aimed to critically review and summarize the clinical profile, patient demographics, treatment, and prognosis of new-onset R-IMIDs following SARS-CoV-2 vaccination. Methods We retrieved English-language articles (Case reports and series and observational studies) on new-onset R-IMIDs following SARS-CoV-2 vaccination, published until June 2022, from standard databases (MEDLINE, Embase, Cochrane). The search strings used during the literature search incorporated 'SARS-CoV-2 vaccination' (along with related MeSH terms) and various key terms for R-IMIDs [which included (but was not limited to) inflammatory arthritis, connective tissue disease (CTD), vasculitis, systemic lupus erythematosus, Sjogren's syndrome, sarcoidosis, systemic sclerosis, idiopathic inflammatory myositis, anti-synthetase syndrome, Adult-onset Stills disease (AOSD), giant cell arteritis (GCA), and polymyalgia rheumatica (PMR)]. The protocol was registered in PROSPERO (CRD42022318561). Results Of the total 2179 articles retrieved, 1986 articles were excluded following the title- screening, and 107 articles that did not meet inclusion criteria. We included the remaining 86 articles (130 cases) upon full-text screening. Furthermore, we added four articles (six cases) based on a manual search, comprising 90 articles (136 cases) for final analysis. These 136 new R-IMID cases were reported from 27 different countries. Of these, more than one-third of the cases were reported from three countries (viz., Italy, Japan, and the USA). The patients had a mean age of 57 (range:17-90) years, and the majority were females (63.0%). Most patients developed R-IMIDs after receiving Pfizer-BioNTech vaccine (76;55%), followed by Oxford AstraZeneca vaccine (35;25%). The mean duration between SARSCoV- 2 vaccination and R-IMIDs development was 9.2 (range:1-90) days. The second dose of the vaccine resulted in more R-IMIDs (74;54%) than the first (53;39%). CTDs (34;25%) and small vessel vasculitis (33;24%) were the commonest R-IMID manifestations, followed by inflammatory arthritis and AOSD, each in 13 (9.5%) cases. Nearly half of the patients with CTDs had Idiopathic Inflammatory Myositis. PMR and GCA accounted for 16 (11.7%) and 5 (3.6%) cases, respectively. However, no cases of axial spondylarthritis were reported. Most (118;86%) R-IMID patients were treated with corticosteroids, with a small number receiving steroid-sparing drugs, such as methotrexate, rituximab and cyclophosphamide. Most (125;91%) went into either disease remission or improvement following the treatment. Only three patients were admitted to the intensive care unit (ICU) to manage their disease;One of them died due to fatal myositis and rhabdomyolysis;two surviving ICU patients had ANCA-associated vasculitis with lung involvement. Conclusion Although rare, this SR highlights the emergence of de novo R-IMIDs following SARS-CoV-2 vaccination. We cannot confirm the causality between the vaccination and the onset of R-IMID. However, further research is warranted in this area.

Activated CD8 T-cell hepatitis in children: a single institution experience

Background: Pediatric acute liver failure is a rare and serious life-threatening situation, principally for the 30 to 50% of children in whom the etiology of their liver failure is unclear or indeterminate. Treating these patients is challenging, requiring constant assessment over time with regular evaluation for possible liver transplantation. Children with pediatric acute liver failure of undetermined etiology have lower spontaneous survival and higher rates of transplantation and death than other diagnostic groups. Emerging evidence suggests that a subgroup of patients with indeterminate pediatric acute liver failure have clinical, laboratory, and liver biopsy features of immune dysregulation with a dense infiltration of CD8 T cells. Method(s): In 2022, we received percutaneous liver biopsies from three children with acute hepatic dysfunction that showed an increased number of lymphocytes including CD8 T cells. For each case, routine H&E stains with levels, special stains and immunostains were performed. The first biopsy was from an 18-month-old male who presented with COVID infection, pancytopenia, elevated transaminases, and synthetic liver dysfunction (elevated INR). The second was from a 9-year-old female with a history of elevated liver enzymes with no clear cause. The third case was from a 2-year-old male with elevated liver enzymes, coagulopathy, and cholestasis. Result(s): The three cases showed similar histopathologic findings;an acute liver injury pattern with lobular architectural disarray, giant cell formation, reactive changes, single cell necrosis, cholestasis and marked mixed lymphocytic infiltrates. The infiltrates were predominantly composed of CD8-positive T-lymphocytes with scattered neutrophils, eosinophils and rare plasma cells. Portal areas were mildly expanded with mild bile ductular proliferation and mild to moderate lymphocytic infiltrates. Immunostains for CD8 demonstrated that the infiltrates were predominantly composed of CD8-positive T-lymphocytes. All three patients received steroids and responded to treatment evidenced by normalization of liver enzymes and function. Conclusion(s): Dense hepatic CD8 T-cell infiltration is a major finding inactivated CD8 T-cell hepatitis. However, the percentage distribution of lymphocyte subtypes in the setting of hepatitis is not well established, and CD8 T-cell infiltration has also been described in cases of drug-induced hypersensitivity reactions, viral hepatitis, hemophagocytic lymphohistiocytosis, and macrophage activation syndrome, as well as autoimmune hepatitis. Further investigation is needed to better understand the diagnostic criteria in this disease.

Unusual Myositis of the Temporalis Muscle Occurring with Acute Covid-19

Background. SARS-CoV-2 infection can be accompanied by neuromuscular disorders. Rhabdomyolysis and Guillain-Barre syndrome have been described repeatedly. There are case reports of inflammatory myopathies manifesting during COVID-19, presenting as dermatomyositis, polymyositis or immune-mediated necrotizing myopathy, with dermatomyositis-like presentations most commonly reported. Larger cases series are from postmortem examinations of COVID-19 patients, where variable inflammatory pathology of the skeletal muscle has been found frequently but without local detection of the actual virus. Thus, autoimmune mechanisms or the systemic interferon response are discussed as causes. We report a case of focal inflammatory myopathy with perimysial pathology of the temporalis muscle occurring with acute, but mild COVID-19. Methods. Case report of clinical observations, cranial MRI, histopathological, and laboratory findings. 3T cranial MRI was performed with gadolinium contrast. Open temporalis muscle biopsy was performed. The sample underwent standard cryohistological studies as well as immunohistochemistry with antibodies against MHC-I and II, CD3, CD4, CD19, CD68, anti-MAC, p62 and MxA. Testing for auto-antibodies was based on immunoblots or ELISA. RT-PCR for SARS-CoV-2 was run with RNA extracted from cryopreserved muscle. Results. A Caucasian woman in her 60s with no history of autoimmune or muscle complaints developed swelling and pain of the right jaw musculature five days after testing positive for SARS-CoV-2 due to respiratory tract symptoms. In addition, she experienced trismus, but no further neuromuscular complaints. The course of respiratory tract symptoms stayed mild. She had been vaccinated previously with single shot SARS-CoV-2 vector vaccine. Due to persistent swelling and complaints, giant cells arteritis was excluded by unresponsiveness to five days oral steroids and sonography of the temporal artery. Cranial MRI was performed nearly four weeks after the SARS-CoV-2 infection and showed marked swelling and oedema of the temporalis muscle. Its biopsy showed numerous CD68 and acid phosphatase positive cells infiltrating from perimysial perivascular foci towards the endomysium with perimysial damage but little damage of adjacent, perifascicular muscle fibres. Muscle fibres did not react with anti-MHC-II, anti-MAC or -MxA. Capillaries did not react with anti-MAC or -MxA. SARS-CoV-2 RNA was not detected in muscle tissue. Serum creatine kinase was not elevated in the subacute phase. Slightly elevated ANA titre led to detection of autoantibodies against proliferating cell nuclear antigen (PCNA). No pathological results for other autoantibodies, including myositis-specific antibodies and anti-ds-DNA, were found in blood. Neither were antibodies against hepatitis C and B viruses. Retesting 15 weeks after infection, anti-PCNA immunoblot was still positive, but ELISA did not indicate a pathologic titre. The swelling, myalgia and trismus regressed spontaneously a month after onset, yet the latter still persists at the time of reporting. Conclusion. Our case diverges from the majority of COVID-19 associated my-ositis reports in the unusual location of the focal myositis and the histopathological pattern of predominantly perimysial damage and histiocytic infiltration. It concurs with the literature as no SARS-CoV2 RNA could be detected in the muscle. Anti-PCNA is associated very rarely with myositis. Other associated disorder (systemic lupus erythematosus, chronic viral hepatitis B or C) were not found. Increased levels of autoantibodies are reported in COVID-19 and mostly attributed to loss of self-tolerance during the acute disease phase. Interestingly, the structural protein M of SARS-CoV-2 appears to interact notably with PCNA in infected cells. Still, the causal connection between the myositis and COVID-19 in this case is based on the close temporal association in the absence of alternative, competing explanations from the medical history and findings.

HLA DRB1*15/DRB1*16 might not be protective alleles in COVID-19- induced large vessel giant cell arteritis

Case report Background: Giant cell arteritis (GCA) is an immune-mediated vasculitis affecting large arteries. It has been hypothesized that pathogens including viruses may trigger inflammation within the vessel walls. Human leukocyte antigens' (HLA) genetic studies have previously reported HLA-DR4 (HLA-DRB1* 04 and HLA-DRB1* 01) as susceptibility, and HLA-DR2 (HLA-DRB1* 15 and HLA-DRB1* 16) as protective alleles for GCA. Here we report two cases of large vessel (LV) GCA diagnosed in patients previously suffered from mild coronavirus disese 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV- 2). Case presentation: First case, a 69-year- old male, had a mild COVD-19 three months before the appearance of headache, malaise, and a febrile state associated with extremely increased inflammatory parameters (CRP 2847 mg/dl and IL-6 802.3 pg/ml). Computed tomography examination of the aorta (CTA) and the branches, performed in two occasions six months apart, showed an interesting picture of a migratory arteritis. HLA typing showed: HLA-A* 2,-A* 24;-B* 51,-B* 57;-DRB1* 15,-DRB1* 16;-DQB1* 05,-DQB1* 06;Second case, a 64-year- old female, was evaluated for LV-GCA two months after a mild COVID-19, when she presented with elevated CRP (183mg/dl) and systemic symptoms. Thickening of the ascending aorta and the aortic arch was seen on CTA. Typing of HLA revealed: HLA-A* 2,-A* 11;-B* 27,-B* 35;-DRB1* 14,-DRB1* 15;-DQB1* 05,-DQB1* 06;A whole-body 18F-FDG- PET/ CT performed in both cases revealed inflammation of the ascending, aortic arch, thoracic and abdominal aorta. The first patient had appearance of the inflammatory involvement of the iliac and femoral arteries, while the second patient had an additional pulmonary trunk inflammation. Corticosteroid treatment was introduced in both cases. Due to a progressive inflammatory course of LV-GCA in the first case, the IL-6 inhibitor (tocilizumab) was initiated, leading to a clinical and laboratory improvement. In conclusion, LV-GCA may be considered as an autoimmune disease triggered by SARS-CoV- 2, as one of the broad spectrum of manifestation within the post acute COVID-19. None of the previously known HLA susceptibility alleles for GCA were detected in our patients. In contrast, both patients had DRB1*15 allele, and one of them was DRB1*15/DRB1*16 carrier, suggesting a possibility of losing their protective effect in LV-GCA induced by COVID-19.

Management of Patients Affected by Giant Cell Arteritis during the COVID-19 Pandemic: Telemedicine Protocol TELEMACOV.

Giant cell arteritis (GCA) is the most common primary systemic vasculitis in western countries, prevalently affecting elderly people. Both early diagnosis and regular monitoring are necessary for the correct management of GCA. Following the outbreak of the COVID-19 pandemic, government decisions aiming at reducing the contagion led to reductions in health activities, limiting them to urgent cases. At the same time, remote monitoring activities have been implemented through telephone contacts or video calls carried out by specialists. In line with these deep changes affecting the worldwide healthcare system and in consideration of the high risk of GCA morbidity, we activated the TELEMACOV protocol (TELEmedicine and Management of the patient affected by GCA during the COVID-19 pandemic) in order to remotely monitor patients affected by GCA. The aim of this study was to evaluate the effectiveness of telemedicine in the follow-up of patients already diagnosed with GCA. This was a monocenter observational study. Patients with a previous diagnosis of GCA admitted to the Rheumatology Unit of the University Hospital "Città della Salute e della Scienza" in Turin were monitored every 6-7 weeks by means of video/phone calls from 9 March to 9 June 2020. All patients were asked questions concerning the onset of new symptoms or their recurrence, exams carried out, changes in current therapy, and satisfaction with video/phone calls. We performed 74 remote monitoring visits in 37 GCA patients. Patients were mostly women (77.8%) and had a mean age of 71.85 ± 9.25 years old. The mean disease duration was 5.3 ± 2.3 months. A total of 19 patients received oral glucocorticoids (GC) alone at the time of diagnosis with a daily dose of 0.8-1 mg/kg (52.7 ± 18.3 mg) of prednisone, while 18 patients were treated with a combination of oral steroids (at the time of diagnosis, the prednisone mean dose was 51.7 ± 18.8 mg) and subcutaneous injections of tocilizumab (TCZ). During the follow-up, patients additionally treated with TCZ reduced their GC dose more than patients treated with GC alone (p = 0.03). Only one patient, who was treated with GC alone, had a cranial flare and needed to increase the dosage of GC, which led to rapid improvement. Furthermore, all patients proved very adherent to the therapies (assessed by Medication Adherence Rating Scale (MARS)) and considered this type of monitoring very satisfactory according to a Likert scale (mean score 4.4 ± 0.2 on a 1-5 range). Our study shows that telemedicine can be safely and effectively used in patients with GCA under control as a possible alternative, at least for a limited period of time, to traditional visits.

Increased incidence of giant cell arteritis and associated stroke during the COVID-19 pandemic in Spain: A nation-wide population study.

INTRODUCTION: SARS-CoV-2 infection and COVID-19 vaccines might have increased the incidence of giant-cell arteritis (GCA) and the risk of associated stroke in Spain. METHODS: Retrospective nation-wide observational analysis of all adults hospitalized with GCA in Spain during 5 years (Jan-2016 and Dec-2021). The incidence and proportion of admissions with or because of GCA and GCA-associated stroke were compared between pre-pandemic (2016-2019) and pandemic (2020 and 2021) years. Sensitivity analyses were conducted for the different COVID-19 waves and vaccine timing schedules. RESULTS: A total of 17,268 hospital admissions in patients diagnosed with GCA were identified. During 2020 there were 79.3 and 8.1 per 100,000 admissions of GCA and GCA-associated stroke, respectively. During 2021 these figures were 80.8 and 7.7 per 100,00 admissions, respectively. As comparison, yearly admissions due to GCA and GCA-associated stroke were 72.4 and 5.7 per 100,00, respectively, during the pre-pandemic period (p < 0.05). Coincident with the third wave of COVID-19 (and first vaccine dosing), the rate of GCA-associated stroke admissions increased significantly (from 6.7 to 12%; p < 0.001). Likewise, there was an increase in GCA-associated stroke (6.6% vs 4.1%, p = 0.016) coincident with the third dose vaccination (booster) in patients older than 70 at the end of 2021. In multivariate analysis, only patients admitted during the third COVID-19 wave (and first vaccine dosing) (OR = 1.89, 95% CI 1.22-2.93), and during the third vaccination dosing in patients older than 70 (booster) (OR = 1.66, CI 1.11-2.49), presented a higher GCA-associated stroke risk than the same months of previous years after adjustment by age, sex, classical cardiovascular risk factors and COVID-19 diagnosis. CONCLUSIONS: The COVID-19 pandemic led to an increased incidence of GCA during 2020 and 2021. Moreover, the risk of associated stroke significantly risen accompanying times of COVID-19 vaccine dosing, hypothetically linked to an increased thrombotic risk of mRNA-SARS-CoV-2 vaccines. Hence, forthcoming vaccine policies and indications must weigh the risk of severe COVID-19 with the risk of flare or stroke in patients with GCA.

Outcomes during and after long-term tocilizumab treatment in patients with giant cell arteritis.

OBJECTIVE: To assess outcomes in giant cell arteritis (GCA) patients during and after long-term tocilizumab (TCZ) treatment. METHODS: Retrospective analysis of GCA patients treated with TCZ at a single centre (2010-2022). Time to relapse and annualised relapse rate during and after TCZ treatment, prednisone use, and safety were assessed. Relapse was defined as reappearance of any GCA clinical manifestation that required treatment intensification, regardless of C reactive protein levels and erythrocyte sedimentation rate. RESULTS: Sixty-five GCA patients were followed for a mean (SD) of 3.1 (1.6) years. The mean duration of the initial TCZ course was 1.9 (1.1) years. The Kaplan-Meier (KM)-estimated relapse rate at 18 months on TCZ was 15.5%. The first TCZ course was discontinued due to satisfactory remission achievement in 45 (69.2%) patients and adverse events in 6 (9.2%) patients. KM-estimated relapse rate at 18 months after TCZ discontinuation was 47.3%. Compared with patients stopping TCZ at or before 12 months of treatment, the multivariable adjusted HR (95% CI) for relapse in patients on TCZ beyond 12 months was 0.01 (0.00 to 0.28; p=0.005). Thirteen patients received >1 TCZ course. Multivariable adjusted annualised relapse rates (95% CI) in all periods on and off TCZ aggregated were 0.1 (0.1 to 0.2) and 0.4 (0.3 to 0.7), respectively (p=0.0004). Prednisone was discontinued in 76.9% of patients. During the study, 13 serious adverse events occurred in 11 (16.9%) patients. CONCLUSION: Long-term TCZ treatment was associated with remission maintenance in most patients with GCA. The estimated relapse rate by 18 months after TCZ discontinuation was 47.3%.

Neuro-Ophthalmic Complications of COVID-19 Infection and Vaccination.

The COVID-19 pandemic has led to the identification of new disease phenotypes associated with infection by the SARS-CoV-2 virus. This includes multiple neuro-ophthalmological sequelae, which have been associated with COVID-19 infection and administration of COVID-19 vaccines. Some of these associations have a plausible pathophysiological link to the infection or vaccination but true causation has yet to be established. We review the literature for associations reported between COVID-19 infection or vaccination and neuro-ophthalmic sequelae and review the potential pathophysiological processes that may underlie these associations.

An Unusual Case of Cardiogenic Shock in a Cardio-Oncologic Patient

Background Graft versus host disease (GVHD) most often occurs 100-365 days after hematopoietic stem cell transplant (HSCT). Manifestations most often are dermatologic, hepatic or pulmonic, and are rarely cardiac. We present a unique case of GVHD inducing cardiogenic shock necessitating advanced heart failure therapies. Case This is a 34 year-old male with a history of acute lymphoblastic leukemia who completed chemoradiation and HSCT from an HLA perfect sibling in 1992. In May 2020, he presented with dyspnea for 6 weeks. An echocardiogram at that time showed an EF of 10% and severe biventricular dilatation. He was originally hospitalized at an outside institution for hypoxia where a left heart catheterization showed normal coronaries and goal directed therapy was initiated. After 2 negative COVID tests, he was discharged with a LifeVest. One month later, despite medication compliance, he returned in cardiogenic shock after his LifeVest was activated for ventricular tachycardia (VT). Decision-making He was started on inotropic therapy and an intra-aortic balloon pump (IABP) was placed 1:1 prior to transfer to our tertiary center. After support was started, a right heart catheterization showed a right atrial pressure of 13 mmHg, a wedge of 17, and a cardiac index of 2.6. His course was complicated by VT storm. Differentials for his non-ischemic cardiomyopathy (NICMO) included myocarditis (viral vs. giant cell) with a possible component of chemotherapy/radiation induced NICMO. Immediate AHFT work-up was started. He was unable to be weaned off his IABP or inotropic support. The decision was made to pursue emergent left ventricular assist device placement (LVAD) and achieve a definitive diagnosis with a core biopsy. Pathology resulted with myocyte hypertrophy, chronic inflammation with eosinophils concerning for chronic GVHD. Conclusion There have only been a handful of case reports describing cardiac manifestations of GVHD, and none with NICMO and cardiogenic shock requiring an LVAD. Despite this, suspicion should remain present for GVHD in HSCT patients regardless of time frame from oncologic therapies or specificity of HLA match when presenting in cardiogenic shock.Copyright © 2023 American College of Cardiology Foundation

Clinical and Cytopathological Traits of Herpes Zoster: A Report of Two Cases

Introduction: Varicella zoster virus is a highly infectious alpha-herpesvirus, pathogenic only to humans. The primary infection of varicella zoster virus causes chickenpox, which is contagious and primarily infects children and adolescents in India. Following the primary infection, the virus remains dormant in sensory root ganglia. Activation of the dormant virus in later stages of life causes herpes zoster infection which may vary from subclinical infection to typical zoster, scattered vesicles, zoster sine herpete or disseminated zoster, which depends on the individual's immune status. Case report: In this case series, we present two patients with herpes zoster involving the mandibular branch of the trigeminal nerve. Cytology revealed characteristic features of the infection including nuclear moulding, multinucleated giant cells and ballooning degeneration. Conclusion(s): More recently, patients presenting with herpes zoster have been reported to have sub-clinical Covid-19 infection, suggesting a possibility that herpes zoster might be an indicator for latent Covid-19. Timely detection and treatment of this infection can reduce the risk of post herpetic neuralgia.Copyright © 2022 Sciendo. All rights reserved.

PATHOMORPHOLOGICAL FEATURES OF ACUTE RESPIRATORY DISTRESS SYNDROME IN COMPETING LUNG DISEASES: COVID-19 AND SARCOIDOSIS

The COVID-19 pandemic is a worldwide problem. The clinical spectrum of SARS-CoV-2 infection varies from asymptomatic or paucity-symptomatic forms to conditions such as pneumonia, acute respiratory distress syndrome and multiple organ failure. Objective was to describe a clinical case of SARS-CoV-2 infection in the patient with sarcoidosis and cardiovascular pathology developing acute respiratory syndrome and lung edema. Material and methods. There were analyzed accompanying medical documentation (outpatient chart, medical history), clinical and morphological histology data (description of macro- and micro-preparations) using hematoxylin and eosin staining. Results. Lung histological examination revealed signs of diffuse alveolar damage such as hyaline membranes lining and following the contours of the alveolar walls. Areas of necrosis and desquamation of the alveolar epithelium in the form of scattered cells or layers, areas of hemorrhages and hemosiderophages are detected in the alveolar walls. In the lumen of the alveoli, a sloughed epithelium with a hemorrhagic component, few multinucleated cells, macrophages, protein masses, and accumulated edematous fluid were determined. Pulmonary vessels are moderately full-blooded, surrounded by perivascular infiltrates. Signs of lung sarcoidosis were revealed. Histological examination found epithelioid cell granulomas consisting of mononuclear phagocytes and lymphocytes, without signs of necrosis. Granulomas with a proliferative component and hemorrhage sites were determined. Giant cells with cytoplasmic inclusions were detected — asteroid corpuscles and Schauman corpuscles. Non-caseous granulomas consisting of clusters of epithelioid histiocytes and giant Langhans cells surrounded by lymphocytes were detected in the lymph nodes of the lung roots. Hamazaki–Wesenberg corpuscles inside giant cells were found in the zones of peripheral sinuses of lymph nodes. In the lumen of the bronchi, there was found fully exfoliated epithelium, mucus. Granulomas are mainly observed subendothelially on the mucous membrane, without caseous necrosis. Histological examination of the cardiovascular system revealed fragmentation of some cardiomyocytes, cardiomyocyte focal hypertrophy along with moderate interstitial edema, erythrocyte sludge. Zones of small focal sclerosis were determined. The vessels of the microcirculatory bed are anemic, with hypertrophy of the walls in small arteries and arterioles. Virological examination of the sectional material in the lungs revealed SARS-CoV-2 RNA. Conclusion. Based on the data of medical documentation and the results of a post-mortem examination, it follows that the cause of death of the patient R.A., 50 years old, was a new coronavirus infection COVID-19 that resulted in bilateral total viral pneumonia. Сo-morbidity with competing diseases such as lung sarcoidosis and cardiovascular diseases aggravated the disease course, led to the development of early ARDS and affected the lethal outcome. © 2022 Saint Petersburg Pasteur Institute. All rights reserved.

Melanized (dematiaceous) fungal infections simulating skin cancer in African organ transplant recipients

Fungi are the most frequent skin infections in organ transplant recipients (OTRs) and usually present as superficial mycoses. Deeper infections are much less common, potentially more serious and the incidence is higher in the first few months post-transplant. We report two African OTRs with deep fungal infections caused by dematiaceous (melanized, pigmented or black) fungi, who both presented with suspected skin malignancies. A 60-year-old Nigerian man developed a painful, ulcerated, amelanotic, bleeding nodule on his right fourth toe 2 months after renal transplantation. Clinical differential diagnoses included Kaposi sarcoma (KS), amelanotic acral melanoma and subungual squamous cell carcinoma (SCC). However, histology showed pseudoepitheliomatous hyperplasia, extensive mixed inflammation, multinucleated giant cells and pigmented septate hyphae with rounded 'budding' forms. Periodic acid-Schiff, Grocott and Masson-Fontana stains were positive, and Alcian blue stain was negative, consistent with infection by a dematiaceous fungus. Fungal 18S polymerase chain reaction (PCR) was positive and culture identified Nigrograna mackinnonii. Treatment with oral itraconazole was supervised virtually during the COVID-19 pandemic. After 6 months there was minimal response and he opted for amputation of the digit. A 61-year-old Nigerian man presented 2 months after renal transplantation with a 2-cm diameter nodule on his left thigh at the site of a previous burn. This failed to respond to antibiotics. Magnetic resonance imaging was suggestive of possible malignancy, but surgery was deferred because of the COVID-19 pandemic. Two months later the lesion was 5 cm in diameter and verrucous with an 8-cm sessile, purplish plaque on his right forearm. Atypical KS, lymphoma and chronic burns-associated SCC were all considered. However, histology from both lesions was similar to the first patient. Fungal culture and 18S PCR confirmed infection with the dematiaceous fungus Alternaria alternata. At his request, the right thigh lesion was excised. The lesion on his forearm has partially responded to 8 months of ongoing oral itraconazole. In our African OTR cohort, KS is more common than deep fungal infection. However, despite this suspicion of skin malignancy, both patients had phaeohyphomycoses caused by dematiaceous fungi. Characterized by the presence of melanin in their cell walls, > 130 species of these plant pathogens and soil saprophytes are implicated in human disease, particularly in immunocompromised individuals. Although localized skin diseases (phaeohyphomycoses, chromoblastomycosis and mycetoma) are the most common manifestations, rare disseminated, central nervous system and pulmonary infections may prove fatal. Although uncommon, deep fungal infection should be considered in atypical skin lesions in OTRs;histology, tissue culture and fungal PCR are critical to confirming this diagnosis.