Clinical Pearls & Morning Reports

Posted by Carla Rothaus, MD

Published February 28, 2024


What tests are used to detect the different types of ANCA?

Optic perineuritis has been increasingly recognized as a feature of granulomatosis with polyangiitis. Limited forms of granulomatosis with polyangiitis can manifest with neuro-ophthalmic findings and with minimal or no systemic findings, lacking components of the full triad. Read the NEJM Case Records of the Massachusetts General Hospital here.

Clinical Pearls

Q: What diagnoses should be considered in a patient with bilateral optic perineuritis?

A: Optic perineuritis is characterized by inflammation restricted to the nerve sheath, whereas inflammation of the optic-nerve axons occurs with optic neuritis. Primary optic perineuritis is typically unilateral and idiopathic in nature. Bilateral idiopathic optic perineuritis is rare such that bilateral findings should prompt a search for an underlying infection such as syphilis, tuberculosis, herpes simplex, or herpes zoster; a systemic autoimmune disease such as antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis, giant-cell arteritis, myelin oligodendrocyte glycoprotein (MOG) antibody disease, sarcoidosis, Graves’ disease, Behҫet’s disease, or IgG4-related disease; or a malignant condition such as leukemia or primary or metastatic cancer.

Q: Is it important to distinguish between primary optic perineuritis and optic neuritis with perineuritis?

A: The distinction between primary optic perineuritis and optic neuritis with perineuritis is relevant because the cause, manifestations, treatment, and prognosis differ between the two conditions.

Morning Report Questions

Q: What are the ANCA-associated vasculitides?

A: ANCAs are autoantibodies directed against antigens in the cytoplasmic granules of neutrophils and monocytes. There are many target antigens, including bactericidal–permeability-increasing protein, lactoferrin, cathepsin G, elastase, myeloperoxidase (MPO), and proteinase 3 (PR3). However, only ANCAs directed against MPO or PR3 are associated with systemic vasculitis. ANCA-associated vasculitis refers to systemic necrotizing vasculitis that predominantly affects small vessels and includes a spectrum of clinical phenotypes — namely, granulomatosis with polyangiitis, microscopic polyangiitis, eosinophilic granulomatosis with polyangiitis, and isolated pauci-immune necrotizing and crescentic glomerulonephritis (renal-limited vasculitis). The phenotypes can differ with respect to the predominant clinical features, the detection of granulomatous lesions on histologic examination, the ANCA serotype (in which PR3 antibodies are typically detected with granulomatosis with polyangiitis, and MPO antibodies are typically detected with microscopic polyangiitis), and the presence of asthma and eosinophilia; however, the phenotypes can have overlapping features.

Q: What tests are used to detect the different types of ANCA?

A: ANCA testing includes two distinct tests: a microscopic examination with indirect immunofluorescence staining and an enzyme-linked immunosorbent assay (ELISA). Indirect immunofluorescence staining can detect ANCAs, but the findings are nonspecific. Positive indirect immunofluorescence staining can reveal ANCA with a cytoplasmic pattern (c-ANCA) or with a perinuclear pattern (p-ANCA). However, a positive test does not specify which autoantigen is being targeted. An antigen-specific ELISA for MPO and PR3 is essential to confirm the diagnosis. Moreover, the presence of antinuclear antibodies can lead to an erroneous interpretation of indirect immunofluorescence staining as positive for p-ANCA. This point further underscores the importance of the ELISA results.

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