150. Refractory ANCA associated Vasculitis (AAV) post Pfizer COVID-19 Vaccine

Presentation of Case: A 57-year-old male with a history of hypertension and rosacea treated with hydralazine and minocycline respectively, presented to the hospital with dyspnea and lower extremity skin rash a week after completing the 2^nd dose of Pfizer COVID-19 mRNA vaccine. Skin rash started after the initial dose and got exacerbated by the subsequent dose. Physical exam was unremarkable except for lower extremity tender purpuric rash and pitting edema.

Diagnostic Testing: Laboratory tests revealed hemoglobin of 5.7 g/dL, elevated LDH (254 U/L), schistocytes on peripheral smear, and serum creatinine (sCr) of 5.2 mg/dL. Further evaluation showed serum albumin of 3.2 g/dL, CRP of 1.9 mg/dL, and negative anemia workup. Urinalysis showed microscopic hematuria, red blood cell casts, and a spot UPCR of 1.15 g/g. Serologies were notable for positive MPO-ANCA antibodies >100 units, and negative PR3. HIV and all hepatitis serologies were negative. Chest CT revealed bilateral upper and lower lobe perihilar ground-glass opacities. SARS-CoV-2 was ruled out.

Kidney biopsy demonstrated 14 nonsclerotic glomeruli, with 2 showing crescentic pauci-immune glomerulonephritis (GN) with 30% interstitial fibrosis and tubular atrophy.

Differential & Final Diagnosis: While pulmonary renal syndrome is the prototype presentation of anti -GBM disease, it can also be seen in, AAV and immune complex mediated GN. We infer our patient has AAV with microscopic polyangiitis involving skin, kidney, and lung, likely triggered by the vaccine given the temporal association with the receipt of the vaccine.

Discussion of Management: Patient received induction with methylprednisolone followed by prednisone taper and rituximab with a decrease in sCr to 3.36 mg/dL at the time of discharge. Hydralazine and minocycline were discontinued. Repeat rituximab was administered in a 2-week interval reaching a sCr nadir of 2.7 mg/dL, however, a week later patient was re-admitted with recurrent skin rash and worsening kidney function, sCr peaked at 6.7 mg/dL, p-ANCA titters increased to 1:640. In the setting of refractory vasculitis, he was treated with pulse methylprednisolone, plasma exchange, and a short course of oral cyclophosphamide. Gradual improvement of renal function ensued no requirement of dialysis in the interim. His vasculitis remains in remission with a sCr of 1.63 mg/dL.

Conclusions: Although the constellation of findings in our patient is suggestive of drug induced AAV set off by hydralazine and minocycline, the temporal relation between vaccine administration and the onset of vasculitis cannot be ignored.  Recent literature has described increasing evidence of SARS-CoV-2 vaccine induced glomerular disease; thus far 6 cases of crescentic GN have been reported, 5 of them de novo and 1 relapsing, all had positive ANCA serology. While causality cannot be established, and its occurrence is rare, it is important to clarify whether the autoimmune response is a consequence of molecular mimicry, vaccine adjuvants, or a transient systemic proinflammatory cytokine response having T cells as important mediators triggering podocytopathies in genetically predisposed individuals. If this response could be a direct reaction to RNA- based vaccines remains to be elucidated. We suspect that a dysregulated immune response may have a role given suboptimal response to rituximab induction. It is imperative mechanisleading to de novo or relapsing glomerular disease are identified with continued reporting and surveillance of these rare occurrences.

Disclosures: None.