Antineutrophil cytoplasmic antibodies (ANCA) are central to the diagnosis and classification of systemic vasculitides, including granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA).¹⁾ In ANCA-associated vasculitis (AAV), antibodies against proteinase 3 (PR3) or myeloperoxidase (MPO) serve as key diagnostic markers, with PR3-ANCA most strongly associated with GPA and MPO-ANCA with MPA.¹⁾ AAV primarily involves small- and medium-sized vessels, causing multi-organ injury and significant morbidity and mortality.²⁾

AAV is uncommon, with an estimated prevalence of 46–184 cases per million in Europe.¹⁾ Among subtypes, MPA carries the highest risk of severe outcomes, often presenting with rapidly progressive glomerulonephritis (RPGN) and pulmonary capillaritis.^1,2) Five-year survival is lower in MPA (45%–76%) compared with GPA (74%–91%) or EGPA (60%–97%),³⁾ emphasizing the importance of early recognition and intervention.

Age significantly influences clinical presentation, with disease typically arising in mid-adulthood (median 50–60 years), whereas onset in older adults is uncommon and often underrecognized.³⁾ Younger patients often present with aggressive multi-organ involvement, while seniors frequently have nonspecific constitutional symptoms, which can obscure diagnosis and delay treatment.³⁾

We report the case of a 90-year-old female with MPO-ANCA-positive MPA presenting with RPGN and concurrent deep vein thrombosis (DVT). Her comorbidities—including chronic kidney disease, diabetes, resistant hypertension, and heart failure—complicated the clinical picture and delayed recognition. This case also highlights the thromboembolic risk associated with active vasculitis and underscores the importance of prompt, individualized immunosuppressive therapy to prevent irreversible organ injury.

A 90-year-old Caucasian female with a history of type 2 diabetes, resistant hypertension, chronic kidney disease (CKD), and heart failure with preserved ejection fraction (60%–65%), presented with several weeks of progressive shortness of breath, lower extremity edema, and fatigue. Her blood pressure had been difficult to control over the past year despite multiple antihypertensives, and outpatient work-up for secondary causes was unremarkable.

A structured evaluation of her premorbid functional status was performed using the Clinical Frailty Scale (CFS).⁴⁾ Her baseline CFS score was 2 (“well”), reflecting complete independence in all activities of daily living and instrumental activities of daily living. Prior to hospitalization, she maintained a large “life space,” regularly traveling for her missionary work, ambulating without assistive devices, and engaging actively in social and spiritual activities. She exhibited no delirium or cognitive impairment during hospitalization, and collateral history confirmed intact baseline cognition and a self-perceived health status of “very good.” These characteristics indicated preserved physiologic reserve despite her advanced age and suggested a physiologic age younger than her chronologic age.

On presentation, she was hypertensive (164/74 mmHg) but otherwise hemodynamically stable. Examination revealed elevated jugular venous distention, positive abdominojugular reflux, bilateral crackles, anasarca, and a systolic murmur. Labs showed normocytic anemia (hemoglobin 6.3 g/dL), acute kidney injury (creatinine 8.4 mg/dL; baseline 1.5 mg/dL), markedly elevated B-type natriuretic peptide (BNP; 34,700 pg/mL), and modestly elevated inflammatory markers (erythrocyte sedimentation rate 38 mm/hr, C-reactive protein 16.51 mg/dL). Urinalysis demonstrated significant hematuria and proteinuria (protein/creatinine ratio 2.85). A computed tomography scan of the chest revealed mild nodular and ground-glass opacities with interlobular septal thickening consistent with pulmonary edema (Fig. 1), and echocardiogram showed preserved systolic function with grade I diastolic dysfunction.

To evaluate for pulmonary embolism (PE), a D-dimer assay was obtained (3.21 µg/mL). V/Q scan showed low probability for PE, but Doppler ultrasound identified a DVT in the right gastrocnemius vein and a superficial thrombus in the right saphenous vein. Anticoagulation was temporarily withheld due to anemia requiring transfusion, and interval Doppler ultrasounds revealed resolution of the DVT.

Renal function trends demonstrated that her serum creatinine had been steadily increasing over the past year, with an abrupt rise around the time of admission (Fig. 2). Given rapidly progressive renal failure with hematuria and proteinuria in the absence of an identifiable cause, an autoimmune work-up was performed, revealing positive pANCA (>1:640), MPO IgG 105 AU/mL, C3 124 mg/dL, C4 19 mg/dL, and negative PR3.

Renal biopsy demonstrated pauci-immune, crescentic, and necrotizing glomerulonephritis with fibrocellular crescents (Fig. 3). Red blood cell casts indicated ongoing glomerular injury, while fibrocellular crescents suggested a subacute process (Fig. 4). The biopsy also revealed moderate diabetic nephropathy with diffuse and nodular glomerulosclerosis and focally prominent obliterative microvascular changes from long-standing hypertension and diabetes. Overall, the findings reflect active MPA superimposed on chronic kidney injury, correlating with her rapidly progressive renal decline.

Given her preserved physiologic reserve—reflected in a premorbid CFS score of 2—the decision was made to proceed with immunosuppressive therapy. The patient received high-dose intravenous methylprednisolone for 3 days, followed by a gradual oral prednisone taper and weekly rituximab, with trimethoprim–sulfamethoxazole prophylaxis for Pneumocystis jirovecii. Supportive hemodialysis was initiated for metabolic and volume management. This regimen resulted in meaningful improvement in renal function, as illustrated in Fig. 2.

MPA is a small-vessel ANCA-associated vasculitis characterized by pauci-immune necrotizing inflammation, most commonly affecting the kidneys.^5,6) Renal involvement ranges from asymptomatic urinary abnormalities to RPGN, as observed in our patient.⁷⁾ Pulmonary, cutaneous, gastrointestinal, and neurologic involvement may occur but were not prominent in this case.^1,7)

Diagnosing MPA in seniors may be challenging due to multiple comorbidities. Our patient had pre-existing CKD, type 2 diabetes mellitus, resistant hypertension, and heart failure - each of which could independently contribute to renal decline. While her serum creatinine had gradually increased over the prior year, the abrupt rise with hematuria and proteinuria prompted an autoimmune work-up. Renal biopsy confirmed pauci-immune, crescentic, and necrotizing glomerulonephritis, consistent with MPO-ANCA-associated MPA superimposed on chronic vascular and diabetic changes. Fibrocellular crescents suggested a subacute process, highlighting coexisting chronic injury and active vasculitic damage. According to the 2022 American College of Rheumatology/European League Against Rheumatism classification criteria,⁸⁾ our patient surpassed the diagnostic threshold of ≥5 points with a total of 9 points as described in Table 1.

AAV can be associated with a hypercoagulable state.⁹⁾ Our patient developed a DVT, likely related to active vasculitis, renal impairment, advanced age, and reduced mobility. Management was complicated by anemia requiring transfusion, necessitating temporary cessation of anticoagulation. Interval Doppler monitoring confirmed resolution of her DVT, underscoring the need to individualize anticoagulation decisions in seniors with active vasculitis.⁹⁾

Systemic AAV carries a poor prognosis if untreated, with up to 90% mortality within the first year.³⁾ Although corticosteroids and immunosuppressive therapy have improved outcomes, 25%–30% of MPA patients still progress to end-stage renal disease within 5 years.³⁾ Management must therefore be tailored to disease severity, comorbidities, and age. Older patients often present with nonspecific symptoms and reduced physiological reserve, delaying diagnosis and increasing the risk of treatment-related complications.³⁾

Standard induction therapy typically combines high-dose glucocorticoids with cyclophosphamide or rituximab. Rituximab is often favored in senior or comorbid patients to minimize toxicity.⁷⁾ Our patient received intravenous methylprednisolone followed by an oral prednisone taper and weekly rituximab. The RAVE trial demonstrated that rituximab is non-inferior to cyclophosphamide for induction, including in patients with renal involvement, with similar remission rates and renal improvement.¹⁰⁾ Prophylaxis against Pneumocystis jirovecii is recommended during induction,⁶⁾ and maintenance therapy should be individualized based on age, comorbidities, and tolerance.

Seniors are particularly vulnerable to immunosuppressive toxicity, with prospective studies demonstrating substantial 12-month complication rates from high-dose glucocorticoids—including hypertension (19%), diabetes (13%), muscle atrophy and weakness (13%), osteoporosis (8%), and cataracts (8%).¹¹⁾ Accordingly, treatment decisions in seniors with AAV must balance disease severity with physiologic reserve and individualized goals of care. Chronologic age alone is a poor predictor of treatment tolerance; geroscience instead emphasizes physiologic age, functional capacity, and cognitive resilience.¹²⁾ CFS is increasingly recognized as a validated tool to quantify this reserve.^4,13) In our patient, a premorbid CFS score of 2 reflected low frailty burden and preserved physiologic reserve. Her positive self-perceived health, optimistic outlook, and strong religious and social supports—factors consistently associated with improved functional outcomes, frailty status, and recovery trajectories in older adults^12,14,15)—further suggested a physiologic age younger than her chronologic age of 90 and supported proceeding with immunosuppressive induction. This approach aligns with evidence from validated prognostic indices, which demonstrate that functional status, cognition, comorbidity burden, and mobility predict mortality more accurately than chronologic age alone.^12,14,15) Collectively, her favorable geriatric profile supported an individualized therapeutic approach that balanced disease control with her personal values and goals of care.