Characteristics and course of patients with AA amyloidosis: single centre experience with 174 patients from Turkey.

OBJECTIVES: This study aimed to evaluate the clinical, laboratory and genetic characteristics and outcomes of patients with AA amyloidosis. METHODS: Patients followed up in a tertiary referral centre in Turkey with the diagnosis of inflammatory rheumatic diseases and immunohistologically proven AA amyloidosis were included in the study and retrospectively analysed. RESULTS: Among 184 patients with the diagnosis of AA amyloidosis, 174 (83 female, 91 male) were included in the analysis. The most common cause of AA amyloidosis was FMF (78.7%), and 91% of FMF-AA amyloidosis patients were carrying the p.M694V variant (74.1% homozygous). AA amyloidosis was identified earlier in patients with homozygous or compound heterozygous MEFV exon 10 variants compared with the heterozygous patients (27, 30 and 41 years, respectively). Patients with an estimated glomerular filtration rate <60 ml/min at admission had a higher frequency of progression to end-stage renal disease (P < 0.001). The overall mortality rate was 15.3% and it increased gradually in association with the amyloid burden (10% in patients with renal, 15% in renal + gastrointestinal and 43% in those with additional cardiac involvement). Renal findings responded completely to treatment in 31% of the patients, a partial response was observed in 4%, a stable course in 23.6% and progression in 38.5%. Amyloid storm was identified in nine patients and was found to be associated with increased mortality within 1 year. CONCLUSION: FMF patients still constitute the majority of AA amyloidosis patients in Turkey. The MEFV genotype and associated inflammatory load may affect the age of onset of AA amyloidosis, and earlier diagnosis and stricter follow-up and treatment may delay progression of the disease.

Criteria for Hyperinflammation Developing in COVID-19: Analysis of 2 Cohorts From Different Periods of the Pandemic.

OBJECTIVE: Hyperinflammation (HI) that develops in week 2 of COVID-19 contributes to a worse outcome. Because week 2 laboratory findings can be relatively mild, the available criteria for classification of hemophagocytic lymphohistiocytosis or macrophage activation syndrome are not helpful. METHODS: Our study included a discovery cohort of patients from Turkey with symptomatic COVID-19 who were followed up while hospitalized during the initial wave and a replication cohort of hospitalized patients from a later period, all of whom required oxygen support and received glucocorticoids. Diagnosis of HI was made by an expert panel; most patients with COVID-19-associated HI (HIC) received tocilizumab or anakinra. Clinical and laboratory data from start day of treatment with tocilizumab or anakinra in HIC patients were compared with the data from day 5-6 in patients without HIC. Values maximizing the sensitivity and specificity of each parameter were calculated to determine criteria items. RESULTS: The discovery cohort included 685 patients, and the replication cohort included 156 patients, with 150 and 61 patients receiving treatment for HI, respectively. Mortality rate in HI patients in the discovery cohort (23.3%) was higher than the rate in patients without HI (3.7%) and the rate in patients in the overall replication cohort (10.3%). The 12-item criteria that we developed for HIC showed that a score of 35 provided 85.3% sensitivity and 81.7% specificity for identification of HIC. In the replication cohort, the same criteria resulted in 90.0% sensitivity for HIC; however, lower specificity values were observed because of the inclusion of milder cases of HIC responding only to glucocorticoids. CONCLUSION: The use of the 12-item criteria for HIC can better define patients with HIC with reasonable sensitivity and specificity and enables an earlier treatment start.

Course and Prognosis of AA Amyloidosis in Patients with Psoriatic Arthritis: Report of Three Cases from a Single Center Cohort and Review of the Literature.

Objective: Herein, we aimed to evaluate the frequency and clinical features of AA amyloidosis in patients with PsA followed up in our tertiary referral clinic. Methods: We retrospectively evaluated PsA patients classified according to CASPAR classification criteria followed-up in our tertiary referral clinic for AA amyloidosis. The literature search was also done by three independent researchers using the keywords "psoriatic arthritis AND amyloidosis", "spondyloarthritis AND amyloidosis", "AA amyloidosis", "secondary amyloidosis". Results and conclusions: A total of 253 patients were included into the analysis. Two thirds of (n=162; 64%) the patients were women, and the mean age of the patients was 50.6 ± 13.4 (range, 20-90). We identified three patients with AA amyloidosis in 253 patients with PsA (1.2 %). The frequency of PsA-related amyloidosis in our AA amyloidosis cohort (n=165) was 1.8 %. Literature search revealed only a retrospective cohort study and 17 case reports, and we analysed these 31 cases. Nearly half of the cases were male, mean age of the patients was 50.7±15.3 and mean age of amyloidosis diagnosis was 47.2±16.7 years. Most of these patients had both polyarticular and axial involvement (81.3%). AA amyloidosis is a rare in patients with PsA. It should be kept in mind that patients with PsA who have not received appropriate treatment for a long time and/or have refractory disease may develop AA amyloidosis.

Antineutrophil Cytoplasmic Antibody-Associated Vasculitis and COVID-19: The Clinical Course and Prognosis of 15 Patients From a Tertiary Care Center.

OBJECTIVE: The aim of this study was to evaluate incidence rates, prognoses, and disease-related factors associated with poor outcomes in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV) who had coronavirus disease (COVID-19). METHODS: Patients with AAV were questioned for a history of COVID-19 in the outpatient setting. Cumulative clinical findings and treatment history were obtained from the patients' medical records. The clinical, laboratory, and imaging findings of inpatients with COVID-19 were recorded. The data of patients who developed symptomatic COVID-19 and/or died of the disease were used for comparison. RESULTS: Eighty-nine patients (47.2% female; mean age, 56 ± 12.5 years) were included. The diagnosis was granulomatosis with polyangiitis in 56 patients (62.9%) and microscopic polyangiitis in 33 (37.1%). Sixty-one (68.2%) and 21 patients (23.6%) had renal and peripheral nerve involvement, respectively. Ten patients had a history of diffuse alveolar hemorrhage. Fifteen patients (16.9%) had COVID-19, including 9 (60%) with severe pneumonia. Twelve patients (85.7%) were hospitalized, 6 (42.9%) were admitted to the intensive care unit, and 5 (35.7%) died. All deceased patients had hypogammaglobulinemia (IgG levels <700 mg/dL) during hospital admission. Symptomatic COVID-19 was associated with higher disease activity, glucocorticoid and rituximab treatments, and glomerular filtration rate <30 mL/min. A history of peripheral nerve involvement, higher organ damage scores, and hypogammaglobulinemia was associated with mortality. CONCLUSIONS: The prognosis was poor in our patients with AAV who had COVID-19, especially those with severe multisystem involvement. Hypogammaglobulinemia was associated with mortality. Serum IgG level monitoring in patients with AAV would be beneficial during the COVID-19 pandemic.

A Case of Takayasu Arteritis with Thrombotic Microangiopathy Secondary to Malignant Hypertension Due to Bilateral Renal Artery Stenosis.

A 20 year old woman presented with right arm pain. Pulses of right upper extremity were weak, acute phase reactants were elevated and MR angiography demonstrated total occlusion of subclavian artery and right axillary artery with collaterals. The diagnosis was Takayasu arteritis and she was treated with prednisolone, azathioprine and acetylsalicylic acid. During follow up, azathioprine was switched to methotrexate. Three years later, patient presented with elevated blood pressure. CT angiography demonstrated reduced calibration of the aorta and almost total occlusion of the lumen of proximal parts of left and right renal arteries. C-reactive protein was elevated. Steroid dose was increased, methotrexate was discontinued and IV tocilizumab and antihypertensive medications were initiated. One month later, she presented to emergency department with elevated blood pressure and blurred vision in the left eye. Fundoscopic examination revealed bilateral grade 3 hypertensive retinopathy and serous detachment of retina in the left eye. Laboratory results revealed normal CRP, elevated creatinine, elevated lactate dehydrogenase, thrombocytopenia, low hemoglobin and low haptoglobin. Peripheral blood smear revealed 2-3 schistocytes in every field. She was admitted to rheumatology department with the diagnosis of thrombotic microangiopathy secondary to malignant hypertension. IV tocilizumab was administered, and methylprednisolone was maintained at a dose of 20 mg/day. Despite treatment with maximum dose of six antihypertensive medications, her blood pressure was not controlled adequately and she became hypervolemic. After undergoing ultrafiltration, balloon dilation was performed in the left renal artery, and a stent was placed there. After stent placement, creatinine and platelet count normalized, hemoglobin increased and hypertension was controlled. In this case, malignant hypertension which was triggered by bilateral renal artery stenosis due to Takayasu arteritis had caused acute kidney injury and advanced stage hypertensive retinopathy. In addition, unlike other Takayasu arteritis cases with malignant hypertension, thrombotic microangiopathy was also detected.

A single center survey study of systemic vasculitis and COVID-19 during the first months of pandemic

Introduction: COVID-19 pandemic created concerns among patients receiving immunosuppressive therapy. Frequency of COVID-19 and impact of lockdown on treatment compliance in patients with vasculitis are largely unknown. Patients and method: Patients with ANCA-associated and large vessel vasculitis that have been followed-up in our clinic were contacted by phone and a questionnaire containing home isolation status, treatment adherence and history of COVID -19 between March 1st and June 30th, 2020 was applied. Results: The survey was applied to 103 patients (F/M: 59/44, mean age: 53.2±12.5). Thirty-three (32%) patients didn?t attend at least one appointment; 98(95.1%) noted that they spent 3 months in home isolation. Five patients (4.8%) received immunosuppressives irregularly and 3(2.9%) developed symptoms due to undertreatment. Four (3.9%) patients admitted to hospital with a suspicion of COVID-19, but none of them had positive PCR or suggestive findings by imaging. COVID-19 diagnosed in a patient with granulomatosis with polyangiitis during hospitalization for disease flare and she died despite treatment. Discussion: Frequency of COVID-19 was low in patients with vasculitis in our single center cohort. Although outpatient appointments were postponed in one-third of our patients, high compliance with treatment and isolation rules ensured patients with vasculitis overcome this period with minimal morbidity and mortality.