A 67-year-old man with uncontrolled diabetes mellitus, peripheral neuropathy, and 40 lbs. unintentional weight loss within the past year presented to an outside hospital with 2 days history of left facial weakness, flattening of the left nasolabial fold, and inability to close his left eyelid. He was afebrile, hemodynamically stable, without systemic complaints or other pertinent findings. Routine laboratory data were unremarkable, including urinalysis, red and white blood cell counts, basic metabolic panel, and chest X-ray. Magnetic resonance imaging (MRI) and computed tomography scans (CT) of the brain were unremarkable. He was diagnosed with Bell’s palsy and discharged on prednisone 60 mg/day for 7 days and empiric Acyclovir.
The patient’s symptoms continued to worsen progressively despite the steroid treatment. Two weeks later he was admitted with bilateral facial and eyelid weakness. He had difficulty swallowing and was unable to take his oral medications for the last several days. He denied fever, chills, cough, hemoptysis, epistaxis, hearing impairment, headache, chest pain and palpitations, dysuria, hematuria, rash, and joint swelling. His family history was notable for a mother who died of throat cancer and a father who died from leukemia.
On examination, he was afebrile with normal heart rate and blood pressure, but was tachypneic at 32 breaths per minute. He was pale with marked temporal wasting, had a scaphoid abdomen and bilateral pedal edema. Neurologically, he had findings consistent with bilateral 7th nerve palsy (Fig. 1), was unable to close his eyes and had excessive lacrimation as well as difficulty swallowing. Otoscopic examination did not show any abnormality. No skin rash, lymphadenopathy, or synovitis were noted. Laboratory data revealed neutrophilia of 11.4 k/mm3 (normal range 1.8–7) with a white cell count (WBC) of 16.3 k/mm3, serum creatinine of 0.92 mg/dL, estimated glomerular filtration rate 82 mL/min and normal urinalysis. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and rheumatoid factor (RF) were all mildly elevated. Multiple studies including brain MRI, Lyme disease serology, antinuclear antibodies (ANA), HIV, HSV type 1 and 2, EBV-specific IgM, acetylcholine receptor (AChR) antibody, muscle specific kinase (MuSK) antibody, Hep C antibody, Treponema pallidum RPR with reflex to titer, angiotensin converting enzyme (ACE), aldolase, TSH, and B12 were all negative or normal. Full body positron emission tomography (PET) CT showed segmental mural thrombus (Fig. 2a, b) involving the descending thoracic and abdominal aorta with up to 50% narrowing, but no aortic aneurysm or any neoplasia. Antiphospholipid antibodies, and protein C and S plasma levels were normal. Transthoracic ECHO-cardiogram showed no cardiac pathology. He was started on aspirin, atorvastatin, and clopidogrel. Based on collected data and symptoms he was clinically diagnosed with bilateral Bell’s palsy and discharged.
A month later the patient was seen in his primary care’s office with continued inability to close his eyelids. He was prescribed lubricant eye drops along with warm compresses to the eyelids.
Six weeks later, he was admitted again with additional weight loss, dysphagia, foul smelling urine, and progressive facial palsy. He endorsed chills for several days, but denied dysuria, or abdominal pain. Laboratory investigation revealed leukocytosis, mild anemia, serum creatinine of 6.8 mg/dL, lactic acid of 3.7 mmol/L, and serum glucose of 242 mg/dL. Arterial blood gases showed respiratory alkalosis and urinalysis was significant for hematuria, proteinuria, and numerous white blood cells. The working diagnosis at this time included sepsis due to urinary tract infection with acute kidney injury. Initially, the renal function of the patient improved slightly with intravenous fluid replacement, indwelling urinary bladder catheter insertion, and Ceftriaxone 1 gr/iv/daily. However, his serum creatinine continued an overall upward trend subsequently. Urine and blood cultures were negative. The differential diagnosis was expanded to include vasculitis and lupus nephritis. CT of neck and soft tissues found no evidence of subglottic airway narrowing or paranasal sinuses opacification (not shown). A percutaneous renal biopsy was performed. On light microscopy, glomeruli showed glomerular basement membrane (GBM) breaks, necrosis, and crescents at various stages of organization, moderate interstitial fibrosis and lymphocytic infiltrates within expanded interstitial spaces. Red cells and red cell casts were identified in the lumen of tubules (Fig. 2c). Immunofluorescent histology revealed a paucity of immunoglobulin deposits, negative C1q, and some fibrinogen irregular capillary wall staining (Fig. 2d). Assays for antineutrophil cytoplasmic antibodies (ANCA) revealed positive cytoplasmic staining pattern (c-ANCA), and positive anti-proteinase 3 antibodies (PR3-ANCA). The combination of pauci-immune crescentic glomerulonephritis and serum PR3-ANCA positivity confirmed the diagnosis of GPA. He received intravenous methylprednisone, 1 gm. daily for 3 days, and then transitioned to oral prednisone 1 mg/kg daily. He was started on cyclophosphamide 500 mg/m2 with renal adjustment once a month for 6 months. Atovaquone was started for Pneumocystis jiroveci pneumonia (PJP) prophylaxis. 4 months after initiation of immunosuppressive therapy the patient required hemodialysis due to end-stage renal disease. He showed improved facial impairment and reported no functional limitations from it.