Case Presentation: A 66 year-old woman presents with three weeks of acute onset bilateral lower extremity pain and foot weakness; two weeks of dyspnea, non-productive cough, epistaxis; and one week of oliguria and lower extremity edema. Her past medical history includes COPD, prior heavy tobacco use, and pre-diabetes. Medications and allergies are non-contributable. Her father is deceased from “kidney failure.” Physical exam is notable for diffuse rhonchi and crackles, 1+ bilateral lower extremity edema, 3/5 left dorsiflexion, 4/5 right dorsiflexion, and decreased sensation of bilateral feet. Her labs are notable for Hgb 7.0 g/dL, K 5.9 mEq/L, HCO3 13 mEq/L, BUN 89 mg/dL, and Cr 8.2 mg/dL. Hepatitis C, HIV, ANA, dsDNA, and anti-GBM are negative. Urinalysis shows proteinuria, hematuria, and granular casts. CT chest reveals multifocal pneumonia. The patient is urgently intubated and initiated on dialysis. Bronchoscopy reveals diffuse alveolar hemorrhage (“DAH”). ANCA antibody returns positive with high titers of PR3 antibody, concerning for granulomatosis with polyangiitis. The patient is initiated on methylprednisolone, cyclophosphamide, and plasmapheresis.
Discussion: Granulomatosis with polyangiitis (“GPA”) is an autoimmune disease with granulomatous inflammation of the respiratory tract as well as ANCA-associated necrotizing vasculitis of small-medium sized blood vessels of the lungs and kidneys. This is a case of GPA first presenting with peripheral neuropathy and later evolving to glomerulonephritis and DAH.Peripheral nervous system involvement, such as mononeuritis multiplex, occurs in 15-25% of GPA patients due to arteritis of the vasa nervorum leading to ischemic neuropathy. As such, patients develop asymmetric and abrupt onset peripheral neuropathy, most commonly of the fibular or tibial nerves. Polyneuropathy is more likely to develop in men, the elderly, or those with renal involvement, large disease burden, or high ANCA titers.Initial treatment of GPA consists of glucocorticoids and either cyclophosphamide or rituximab, as two-year mortality of untreated GPA is ~90%. Both cyclophosphamide and rituximab are highly efficacious in treating GPA. Plasmapheresis is controversial but often favored in those with glomerulonephritis, DAH, or those with concurrent anti-GBM. Given our patient’s fulminant clinical course, she received high dose corticosteroids, cyclophosphamide, and five sessions of plasmapheresis.
Conclusions: This case demonstrates the importance of recognizing GPA as a systemic disease that can present as peripheral neuropathy, a chief concern often encountered in the hospital medicine setting. Given the potentially devastating consequences of untreated GPA, this should be on the differential for acute onset neuropathy. Initial treatment consists of glucocorticoids and either cyclophosphamide or rituximab; with consideration of plasmapheresis in patients with severe features.