Reappraisal of large artery involvement in giant cell arteritis: a population-based cohort over 70 years.

OBJECTIVE: To evaluate the incidence and outcomes of large artery (LA) involvement among patients with giant cell arteritis (GCA) and to compare LA involvement to non-GCA patients. METHODS: The study included Olmsted County, Minnesota, USA residents with incident GCA between 1950 and 2016 with follow-up through 31 December 2020, death or migration. A population-based age-matched/sex-matched comparator cohort without GCA was assembled. LA involvement included aortic aneurysm, dissection, stenosis in the aorta or its main branches diagnosed within 1 year prior to GCA or anytime afterwards. Cumulative incidence of LA involvement was estimated; Cox models were used. RESULTS: The GCA cohort included 289 patients (77% females, 81% temporal artery biopsy positive), 106 with LA involvement.Reported cumulative incidences of LA involvement in GCA at 15 years were 14.8%, 30.2% and 49.2% for 1950-1974, 1975-1999 and 2000-2016, respectively (HR 3.48, 95% CI 1.67 to 7.27 for 2000-2016 vs 1950-1974).GCA patients had higher risk for LA involvement compared with non-GCA (HR 3.22, 95% CI 1.83 to 5.68 adjusted for age, sex, comorbidities). Thoracic aortic aneurysms were increased in GCA versus non GCA (HR 13.46, 95% CI 1.78 to 101.98) but not abdominal (HR 1.08, 95% CI 0.33 to 3.55).All-cause mortality in GCA patients improved over time (HR 0.62, 95% CI 0.41 to 0.93 in 2000-2016 vs 1950-1974) but remained significantly elevated in those with LA involvement (HR 1.89, 95% CI 1.39 to 2.56). CONCLUSIONS: LA involvement in GCA has increased over time. Patients with GCA have higher incidences of LA involvement compared with non-GCA including thoracic but not abdominal aneurysms. Mortality is increased in patients with GCA and LA involvement highlighting the need for continued surveillance.

Large vessel involvement in antineutrophil cytoplasmic antibody-associated vasculitis.

OBJECTIVES: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is currently categorized under the small vessel vasculitides. There is limited knowledge about large vessel involvement in AAV (L-AAV), mainly described in case reports and small series. L-AAV can involve temporal arteries (TA-AAV), aorta (A-AAV), and periaortic soft tissue (PA-AAV). We sought to characterize the features of patients with L-AAV. METHODS: Patients older than 18 years at diagnosis of TA-AAV, A-AAV and PA-AAV seen at the Mayo Clinic, Rochester between January 1, 2000, and December 31, 2021, were identified through a proprietary medical text search algorithm. Patients were included if diagnosed with L-AAV, fulfilled 2022 ACR/EULAR classification criteria for GPA, MPA, or EGPA, had positive ANCA test results, and had more than one outpatient or inpatient visit. RESULTS: The study cohort consists of 36 patients with L-AAV. Of those, 23 had p-ANCA and/or MPO-ANCA; 13 had c-ANCA and/or PR3-ANCA. Mean (SD) age at AAV diagnosis was 63.4 (12.79); 20 (56%) were male. Seventeen patients had TA-AAV, 10 had A-AAV and 9 had PA-AAV. Most patients (n = 25, 69%) were diagnosed with large vessel vasculitis and AAV within a one-year timespan. Twenty-five (69%) patients had histopathologic confirmation of AAV diagnosis in a location other than temporal artery, aorta, or periaortic soft tissue. Glucocorticoids (36/36), rituximab (19/36), and methotrexate (18/36) were the most frequent treatments. CONCLUSIONS: This is the largest single-center cohort of patients with L-AAV to date. AAV can involve large arteries, albeit infrequent. AAV-targeted therapy should be considered in patients with L-AAV.

Persistent aortic inflammation in patients with giant cell arteritis.

OBJECTIVES: To investigate the clinicopathologic features of patients with giant cell arteritis (GCA) who had thoracic aorta aneurysm or dissection surgery. METHODS: Patients who had thoracic aorta surgery between January 1, 2000, and December 31, 2021, at the Mayo Clinic, Rochester, Minnesota, were identified with current procedural terminology (CPT) codes. The identified patients were screened for a prior diagnosis of GCA with diagnostic codes and electronic text search. The available medical records of all the patients of interest were manually reviewed. Thoracic aorta tissues obtained during surgery were re-evaluated in detail by pathologists. The clinicopathologic features of these patients were analyzed. Overall observed survival was compared with lifetable rates from the United States population. RESULTS: Of the 4621 patients with a CPT code for thoracic aorta surgery, 49 had a previous diagnosis of GCA. Histopathologic evaluation of the aortic tissue revealed active aortitis in most patients with GCA (40/49, 82%) after a median (IQR) of 6.0 (2.6-10.3) years from GCA diagnosis. All patients were considered in clinical remission at the time of aortic surgery. The overall mortality compared to age and sex-matched general population was significantly increased with a standardized mortality ratio of 1.55 (95% CI, 1.05-2.19). CONCLUSION: Histopathologic evaluation of the thoracic aorta obtained during surgery revealed active aortitis in most patients with GCA despite being considered in clinical remission several years after GCA diagnosis. Chronic, smoldering aortic inflammation likely contributes to the development of aortic aneurysm and dissection in GCA.

The epidemiology of pathologically confirmed clinically isolated aortitis: a North American population-based study.

OBJECTIVES: Clinically isolated aortitis (CIA) refers to inflammation of the aorta without signs of systemic vasculitis or infection. Population-based data on the epidemiology of CIA in North America is lacking. We aimed to investigate the epidemiology of pathologically confirmed CIA. METHODS: Residents of Olmsted County, Minnesota were screened for thoracic aortic aneurysm procedures with current procedural terminology codes between January 1, 2000, and December 31, 2021, using the resources of the Rochester Epidemiology Project. The medical records of all patients were manually reviewed. CIA was defined as histopathologically confirmed active aortitis diagnosed by evaluation of aortic tissue obtained during thoracic aortic aneurysm surgery in the absence of any infection, rheumatic disease, or systemic vasculitis. Incidence rates were age and sex adjusted to the 2020 United States total population. RESULTS: Eight incident cases of CIA were diagnosed during the study period; 6 (75%) of them were female. Median (IQR) age at diagnosis of CIA was 78.3 (70.2-78.9) years; all were diagnosed following ascending aortic aneurysm repair. The overall age and sex adjusted annual incidence rate of CIA was 8.9 (95% CI, 2.7-15.1) per 1,000,000 individuals over age 50 years. The median (IQR) duration of follow-up was 8.7 (1.2-12.0) years. The overall mortality compared to the age and sex matched general population did not differ (standardised mortality ratio: 1.58; 95% CI, 0.51-3.68). CONCLUSIONS: This is the first population-based epidemiologic study of pathologically confirmed CIA in North America. CIA predominantly affects women in their eighth decade and is quite rare.

Lower Frequency of Comorbidities Prior to Onset of Giant Cell Arteritis: A Population-Based Study.

OBJECTIVE: To assess the frequency of comorbidities and metabolic risk factors at and prior to giant cell arteritis (GCA) diagnosis. METHODS: This is a retrospective case control study of patients with incident GCA between January 1, 2000, and December 31, 2019, in Olmsted County, Minnesota. Two age- and sex-matched controls were identified, and each assigned an index date corresponding to an incidence date of GCA. Medical records were manually abstracted for comorbidities and laboratory data at incidence date, 5 years, and 10 years prior to incidence date. Twenty-five chronic conditions using International Classification of Diseases, 9th revision, diagnosis codes were also studied at incidence date and 5 years prior to incidence date. RESULTS: One hundred and twenty-nine patients with GCA (74% female) and 253 controls were identified. At incidence date, the prevalence of diabetes mellitus (DM) was lower among patients with GCA (5% vs 17%; P = 0.001). At 5 years prior to incidence date, patients were less likely to have DM (2% vs 13%; P < 0.001) and hypertension (27% vs 45%; P = 0.002) and had a lower mean number (SD) of comorbidities (0.7 [1.0] vs 1.3 [1.4]; P < 0.001) compared to controls. Moreover, patients had significantly lower median fasting blood glucose (FBG; 96 mg/dL vs 104 mg/dL; P < 0.001) and BMI (25.8 vs 27.7; P = 0.02) compared to controls. Multivariable logistic regression analysis revealed negative associations for FBG with GCA at 5 and 10 years prior to diagnosis/index date. CONCLUSION: DM prevalence and median FBG and BMI were lower in patients with GCA up to 5 years prior to diagnosis, suggesting that metabolic factors influence the risk of GCA.

Journal Club Review of "Comparison of Two Rituximab Induction Regimens for Antineutrophil Cytoplasm Antibody-Associated Vasculitis: Systematic Review and Meta-Analysis".

OBJECTIVE: The objective of this study was to compare the efficacy and safety of two rituximab (RTX) regimens for the induction of remission in severe antineutrophil cytoplasm antibody-associated vasculitis (AAV): the four-dose (375 mg/m2 intravenously weekly) versus the two-dose (1000 mg intravenously biweekly) regimen. METHODS: A systematic review was performed to identify studies using the four- and/or two-dose RTX regimens for induction of remission in severe AAV. Disease status 6 months after RTX infusion was required for inclusion. Patients were excluded if they received concomitant cyclophosphamide or plasma exchange. The primary end point was the proportion of patients in complete remission at 6 months. The pooled estimate was obtained by using meta-analysis methods for proportions with random effects. Secondary end points included antineutrophil cytoplasm antibody status, number of patients with B-cell depletion, mean prednisone dose, infections, and death. RESULTS: A total of 27 studies and 506 patients were included for analysis: 361 patients received the four-dose regimen, and 145 patients received the two-dose regimen. Most patients had relapsing disease at inclusion (83% and 92% of patients, respectively). There was no significant difference between the four- and two-dose regimens, with a complete remission achieved in 85% (95% confidence interval [CI]: 70-96) and 91% (95% CI: 79-99) of patients, respectively. At 6 months, both regimens were associated with a similar mean daily prednisone dose (8.1 mg), infections (12% in both), and death (1% vs. 0%, respectively). CONCLUSION: No difference was found in terms of efficacy or safety between the four- and two-dose RTX regimens for induction of remission in severe AAV. https://onlinelibrary.wiley.com/doi/10.1002/acr2.11274 Bénard V, Farhat C, Zarandi-Nowroozi M, Durand M, Charles P, Puéchal X, et al. Comparison of two rituximab induction regimens for antineutrophil cytoplasm antibody-associated vasculitis: systematic review and meta-analysis. ACR Open Rheumatol 2021;3:484-94.

Intestinal Pseudo-Obstruction as the Initial Clinical Presentation in Systemic Lupus Erythematosus: A Rare and Severe Disorder.

Intestinal pseudo-obstruction (IPO) is a rarely recognized complication of systemic lupus erythematosus (SLE). We present a 36-year-old African American female, with only known past medical history of anemia, admitted for frequent vomiting, abdominal distension, abdominal pain, diarrhea, and fever that had been ongoing for 5 days. Laboratory results revealed leukopenia and thrombocytopenia. Imaging revealed dilated small bowel loops, abdominal ascites, as well as mild bilateral hydroureteronephrosis without obstructing calculus. Serologic testing confirmed a diagnosis of SLE. The patient was placed on immunosuppressive therapy and responded well. IPO has previously been described as a rare finding in patients with SLE, with bilateral hydroureteronephrosis and lupus interstitial cystitis having been noted as common concomitant factors. One must have a high level of suspicion to recognize it as being one of the initial clinical presentations. Early recognition and appropriate management preclude unnecessary invasive procedures that do not take into account the pathophysiology of the condition and allow for appropriate management and return of peristaltic function.

Monckeberg Medial Calcific Sclerosis of the Temporal Artery Masquerading as Giant Cell Arteritis: Case Reports and Literature Review.

Monckeberg medial calcific sclerosis (MCS) is an infrequent finding in the temporal artery and can clinically present almost indistinguishably from giant cell arteritis (GCA). To our knowledge, there have been only two case reports of suspected GCA found to be MCS only after a temporal artery biopsy (TAB). Herein, we present two cases. The first case is a 69-year-old female with hypertension, type-2 diabetes mellitus, and chronic headaches who presented with left temporal headaches and scalp tenderness. She had a prominently dilated, tortuous, and tender left temporal artery. Initial labs showed a leukocyte count of 11.1x103/L, erythrocyte sedimentation rate (ESR) of 29 mm/hr, and C-reactive protein (CRP) of 5.8 mg/L. The patient was started on prednisone 60 mg for presumptive GCA. Left TAB was negative for inflammatory changes, with findings consistent with MCS. Steroids were discontinued, and symptoms resolved. The second case is a 67-year-old male with hypertension, asthma, hyperlipidemia, status-post left eye cataract phacoemulsification, with intraocular lens insertion one-month prior, who presented with left eye blurriness in the inferior visual field and intermittent headache for 15 days. Left ophthalmoscopy showed retinal pallor and edema. Initial labs revealed ESR of 25 mm/hr, CRP of 11.2 mg/L, leukocyte count of 13.01x103/L. The patient was given solumedrol 120 mg once and prednisone 70 mg daily for presumptive GCA. Left TAB was negative for GCA but reported damaged elastic fibers by calcification consistent with MCS. Partial visual blurriness remained, and steroids were discontinued. This report accentuates the importance of MCS as a temporal GCA simulator. Physicians should be aware that TAB potentially changes management and may help surface underlying conditions.

Dapagliflozin-Induced Acute Pancreatitis: A Case Report and Review of Literature.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are increasingly used as add-on therapy in patients with poorly controlled type 2 diabetes mellitus (T2DM). Although pancreatitis is not a known side effect of SGLT-2 inhibitors, there have been case reports of SGLT-2 inhibitor use being associated with pancreatitis. Case Presentation. A 51-year-old male with a history of type 2 diabetes, dyslipidemia, and status-post cholecystectomy presented to the emergency room with a four-day history of periumbilical pain radiating to the back. He denied any history of recent alcohol intake or prior episodes of pancreatitis. On physical examination, his abdomen was diffusely tender to palpation without guarding or rebound. Initial labs were notable for a leukocyte count of 9.3 × 109/L, creatinine level of 0.72 mg/dL, calcium level of 9.5 mg/dL, lipase level of 262 U/L, and triglyceride level of 203 mg/dL. His last HbA1c was 8.5%. CT scan of his abdomen and pelvis showed findings consistent with acute pancreatitis with no biliary ductal dilatation. Careful review of his medications revealed the patient was recently started on dapagliflozin five days prior to admission in addition to his longstanding regimen of insulin detemir, sitagliptin, metformin, and rosuvastatin. His symptoms resolved after discontinuation of sitagliptin and dapagliflozin. A year later, due to increasing HbA1c levels, a decision was made to rechallenge the patient with dapagliflozin, after which he developed another episode of acute pancreatitis. His symptoms resolved upon cessation of dapagliflozin. Conclusion. This case highlights the possible association of SGLT-2 inhibitors and pancreatitis. Patients should be informed about the symptoms of acute pancreatitis and advised to discontinue SGLT-2 inhibitors in case such symptoms occur.

Changes in the Presentation of Incident Gout and the Risk of Subsequent Flares: A Population-based Study over 20 Years.

OBJECTIVE: To examine whether a change in the presentation of incident gout happened over the last 20 years and to determine the risk of subsequent gout flares after an initial gout attack. METHODS: All incident cases of gout were identified among residents of Olmsted County, Minnesota, diagnosed in 1989-1992 and 2009-2010 according to the earliest date fulfilling the 1977 American Rheumatism Association preliminary criteria, or the New York or Rome criteria for gout. Patients in both cohorts were then followed for up to 5 years. Cumulative incidence and person-year methods were used to compare flare rates, and conditional frailty models were used to examine predictors. RESULTS: A total of 429 patients with incident gout (158 patients in 1989-1992 and 271 patients in 2009-2010) were identified and followed for a mean of 4.2 years. The majority of patients were male (73%) and the mean age (SD) at gout onset was 59.7 (17.3) years. Classic podagra decreased significantly from 74% to 59% (p < 0.001). Cumulative incidence of first flare was similar in both cohorts (62% vs 60% by 5 yrs in 1989-1992 and 2009-2010, respectively; p = 0.70), but overall flare rate was marginally higher in 2009-2010 compared to 1989-1992 (rate ratio: 1.24). Hyperuricemia (HR 1.59) and kidney disease (HR 1.34) were significant predictors of future flares. CONCLUSION: Gout flares were common in both time periods. Hyperuricemia and kidney disease were predictors of future flares in patients with gout. Podagra as a presentation of gout has become relatively less frequent in recent years.

Urethral involvement in granulomatosis with polyangiitis: a case-based review.

Granulomatosis with polyangiitis (GPA) commonly presents with glomerulonephritis and inflammation of upper and lower respiratory tracts. It can also involve other organs including those of the urinary tract. The involvement of the urethra is very rarely reported. We present a case of GPA in a patient who had recurrent urinary tract infections and an acute bladder outlet obstruction due to a urethral thickening by GPA. In this report, we discuss urethral involvement with GPA. The incidence of such involvement, as with other urinary tract organs, might be underestimated. It can affect both sexes, with male predominance, and can occur at any age. It responds to standard GPA medical treatment but may require surgical intervention. Rheumatologists should be aware of this limited form of GPA as early recognition and treatment can decrease the risk of complications.

HLA Class I in Egyptian patients with Behçet's disease: new association with susceptibility, protection, presentation and severity of manifestations.

INTRODUCTION: Behçet's disease is an autoimmune disease with diverse clinical manifestations with vasculitis being the hallmark of the disease. The aim of this work is to study the genetic association between human leukocyte antigen (HLA) class-I molecules of Egyptians with Behçet's disease and the disease susceptibility and clinical patterns. METHODS: Fifty-seven patients diagnosed with Behçet's disease according to the 1990 International Study Group (ISG) criteria for Behçet's disease coming from Egyptian origin up to the third grandfather were included in the study. Healthy controls were taken from HLA Class-I case control studies in Egyptian population yielding a pool of 221 healthy controls. HLA Class-I typing for patients was done using Reverse Sequence specific oligonucleotide probes (rSSO). RESULTS: Male patients represented 89% of the sample. Mean age of onset was 25.81 (± 6.7) years and mean disease duration was 9.47 (± 7.4) years. Behçet's disease was associated with HLA-A*24 and HLA-B*42 (p = 0.001) and highly associated with HLA-A*68 and B*15 and B*51 (p < 0.001). While HLA A*03 and B*52 were protective for Behçet's (p = 0.002 and 0.007). Interestingly, HLA-B*51 and HLA-A*68 (p = 0.005 and 0.023) were associated with the blinding eye disease. HLA-B*51 was protective from Neurological and vascular involvement (p = 0.005 and 0.032, respectively). CONCLUSION: Behçet's disease is associated with HLA Class-I A*24, A*68 and B*15, B*42 and B*51 in Egyptian patients while A*03 and B*52 were found to be protective. Interestingly, HLA B*51 and A*68 could be considered as poor prognostic factor for eye involvement.

Subcutaneous formulation of belimumab in treatment of systemic lupus erythematosus: a critical review with focus on safety and satisfaction.

Belimumab is a novel add-on therapy that has been approved for patients with active and antibody-mediated systemic lupus erythematosus. It is a monoclonal antibody that decreases the activation of B-cells and consequently decreases antibodies' production. Recently, the US Food and Drug Administration approved subcutaneous belimumab for patients who have received training on using it. Subcutaneous belimumab can be administered using either a prefilled syringe or an auto-injector device. Weekly subcutaneous belimumab seems to be as effective as monthly intravenous belimumab with a similar safety margin. In this article, we reviewed the literature on subcutaneous belimumab focusing on safety and patients' experiences and satisfaction. Overall, subcutaneous belimumab appears to be preferred over intravenous belimumab for a number of reasons. However, more studies are still required to prove these findings.

Hospitalization Increases the Risk of Acute Arthritic Flares in Gout: A Population-based Study over 2 Decades.

OBJECTIVE: To assess in-hospital gout flares in patients with gout. METHODS: Hospitalizations were evaluated for gout flares in a cohort of Olmsted County, Minnesota, residents with incident gout in 1989-1992 or 2009-2010. RESULTS: There were 429 patients followed up to 5 years. Of these, 169 patients experienced 454 hospitalizations. Hospitalization rates increased without reaching statistical significance from 1989-1992 to 2009-2010 [rate ratio (RR) 1.19, 95% CI 0.98-1.45]. The gout flare rate increased significantly during hospitalization (RR 10.2, 95% CI 6.8-14.5). In-hospital gout flare increased the average hospital stay by 1.8 days (p < 0.001). CONCLUSION: Hospitalization increased the risk of gout flares 10-fold. In-hospital gout flares were associated with longer hospitalization.