A 27-year-old, right-handed Caucasian male with 13-year history of UC with primary sclerosing cholangitis presented to the ER with acute onset of left sided headache, left eye proptosis, erythema, and painful eye movements without any visual changes. He reported a recent trip to Spain and denied trauma, sick contacts, urinary symptoms, fever, weight loss, sexually transmitted diseases, or similar illness in family and friends.
He was diagnosed with UC with primary sclerosing cholangitis at age of 14 following chronic diarrhea, weight loss, guaiac positive stools, and elevated GGT. The colonoscopy then showed pancolitis extending throughout the colon with no evidence of granuloma. Liver biopsy showed onion skinning around the bile ducts. He was initially treated with steroids, mesalamine, and ursodiol. His last flare was a year ago. He had 4-5 blood streaked loose stools per day treated with tapering dose of steroids. Since then he has had no further UC flare and has been on mesalamine and ursodiol.
Clinical examination revealed left eye ecchymosis, hemorrhagic chemosis, unilateral proptosis, with no evidence of uveitis, and normal fundus (see Figures 1(a) and 1(b)). Magnetic resonance imaging (MRI) of the face and orbit showed left eye proptosis with inflammation of the extraocular muscle and the periorbital tissue with normal brain and cavernous sinuses. He was treated with high dose steroids (one gram IV methyl prednisone for 3 days) and empiric antibiotics for orbital inflammatory syndrome and an autoimmune and infectious workup was started. His eye symptoms improved on steroids. However, on the third day of hospital admission, he complained of left arm weakness and numbness. A repeat MRI brain showed an interval development of multifocal deep gray nuclei signal abnormalities including diffusion restriction in the caudate nuclei, right globus pallidus, and posterior limb of the internal capsule (see Figure 2(a)). His CSF was essentially normal with 2 WBCS, normal protein, and glucose with few RBCs. He was empirically started on acyclovir. Within the next 36 hours, he rapidly worsened neurologically, became encephalopathic with left side hemiparesis, and had to be intubated for airway protection. His subsequent MRI brain showed further progression of lesions involving the caudate nuclei, thalami, striatum, and brainstem with new areas of hemorrhage and enhancement (Figure 2(b)). Cerebral arteriogram did not show any vasculitis.
Laboratory workup revealed mild leukocytosis with normal liver function tests, ESR, CRP, and thyroid function test. His laboratory findings were negative for HIV, hepatitis, toxoplasmosis, Saccharomyces cerevisiae, Ehrlichia, Brucella, Rocky Mountain spotted fever, Q fever, and Lyme disease. His CSF was negative for herpes simplex viruses 1 and 2, Adenovirus, Enterovirus, Cryptococcus, and Mycobacterium tuberculosis. His CSF and blood flow cytometry were negative for lymphoma/leukemia cells. Blood, stool, urine, and sputum cultures were sterile. An eye swab was negative for Chlamydia trachomatis. Skin biopsy was normal. Echocardiogram and CT scan of chest, abdomen, and pelvis were unremarkable. IgG4 was normal. Anticardiolipin antibody and beta 2 glycoprotein were both mildly elevated. He was treated empirically with antibiotics, antivirals, and steroids.
He had an ANA titer of 1 : 40 and PANCA titer of 1 : 320; his PR3 antibody was 157 AU per milliliter (normal range, 0 to 19). The brain biopsy showed necrotizing vasculitis (Figure 3) with no evidence of granuloma. Absence of granuloma, in addition to normal lung, kidney, and sinuses ruled out GPA. Based on the serology and brain biopsy results we diagnosed PR3ANCA mediated cerebral and orbital vasculitis. He was treated similar to GPA involving the brain and eye with cyclophosphamide, plasmapheresis, and high dose of steroids. He dramatically improved with residual hemiparesis and was discharged to rehabilitation.