Case Presentation: A 57-year-old female with a history of herpes simplex virus was seen at Rheumatology clinic for 3 weeks of myalgias and arthralgias, positive rheumatoid factor and elevated inflammatory markers. By her first visit, her symptoms resolved. Review of systems revealed chronic sinusitis associated with nasal septal deviation and nasal polyps, which previously failed antibiotics, but improved with steroids prescribed by ENT. She also noted recent development of intermittent pain and paresthesias to the dorsum of her right foot, which she attributed to a fall. Her exam was significant for normal vital signs and brown nasal discharge. She had no synovitis. Due to the chronic sinusitis, rheumatologic workup was started to evaluate for antineutrophil cytoplasmic antibodies (ANCA)-associated limited granulomatosis with polyangiitis (GPA). Results were significant for elevated erythrocyte sedimentation rate (ESR) 73 mm/hr (normal 0-20 mm/hr), C-reactive protein (CRP) 6.5 mg/dl (normal 0.0-0.5 mg/dl) and c-ANCA titer 1:160 with a positive proteinase 3 antibody (PR3) level 31.0 (normal < 0.4).The patient presented to the Emergency Department 2 weeks later for worsening paresthesias in both feet, and was found to have new ulcers in the nasal cavity, nasal septum, upper uvula and soft palate. A neurology consultant noted weakness of the left extensor hallucis longis, altered sensation of the left lateral calf, and numbness in the anterior right third finger. Admission laboratories revealed a mild leukocytosis 11.4 k/mm3 (normal 4.0-11.0 k/mm3) with eosinophilia [absolute eosinophil count 0.7 k/mm3 (0.0-0.4 k/mm3)], ESR 62 mm/hr, CRP 6.1 mg/dL, and microscopic hematuria with mild proteinuria. High dose prednisone was started due to clinical concern for GPA-related mononeuritis multiplex (MM) in the setting of positive ANCA. Further workup revealed pulmonary nodules on chest CT and a negative EMG. A nasal biopsy showed evidence of ulceration, granulation tissue and acute inflammation. Left sural nerve biopsy exhibited necrotizing arteritis, histologically confirming the diagnosis of GPA. After starting steroids, the patient improved with some residual numbness to her soles at time of discharge. She was also started on rituximab in outpatient follow-up with Rheumatology.

Discussion: GPA is an ANCA-associated small to medium vessel vasculitis. It results in necrotizing granulomatous lesions, often affecting the upper and lower respiratory tracts, skin and kidneys. If involved, peripheral nerves are usually affected within 2 years of developing GPA. However, presenting with MM is rare. De Groot, et al. found that only 2 of 128 GPA patients initially presented with a peripheral neuropathy, not specifying if either were classified as MM. They also found a median time of 3 months between onset of neuropathy to its diagnosis. Due to the clinicians’ high index of suspicion in this case, the patient’s MM and GPA were both diagnosed within 1 month.

Conclusions: Our case highlights MM as an initial presentation of systemic GPA. While peripheral nerve involvement is not uncommon, it is rare for MM to be the first manifestation of systemic GPA. Since delay in diagnosis of GPA can result in serious and irreversible sequela and mortality, clinicians should maintain a high index of suspicion of GPA as a potential cause of MM with thorough history and exam. Prompt involvement of a multidisciplinary team including Neurology, Rheumatology, ENT and Nephrology mediated the patient’s early diagnosis and treatment.