Vasculitic, paraneoplastic and paraprotein neuropathies
- Lesion
Inflamed vessels starve nerves one by one; cancers trigger antibodies against sensory neurons; abnormal plasma cells and amyloid damage nerves.
What it is
Several systemic diseases injure nerves from outside the nerve itself. In vasculitis, inflammation of small epineurial arteries causes nerve infarcts in a patchy pattern, usually mononeuritis multiplex, in polyarteritis nodosa, ANCA vasculitides, cryoglobulinaemia and rheumatoid arthritis. Sjögren disease can attack dorsal root ganglia. Cancers cause neuropathy by direct infiltration or compression (Pancoast tumour, lymphoma), by paraneoplastic immunity, most often anti-Hu sensory neuronopathy with small cell lung carcinoma, and by plasma cell disorders: IgM anti-MAG neuropathy, POEMS syndrome and AL amyloid. Radiation can damage plexuses years later.
Structure
- Vasculitis: transmural inflammation and fibrinoid necrosis of small epineurial arteries, thrombosis and scarring; asymmetric loss of fascicles.
- Paraneoplastic ganglionitis: lymphocytes and loss of dorsal root ganglion neurons with nodules of Nageotte.
- Amyloid: Congo red-positive deposits with apple-green birefringence in vessel walls and endoneurium.
- Anti-MAG: widened myelin lamellae on electron microscopy.
Step by step
- Immune complexes or ANCA-activated neutrophils inflame the small arteries of the vasa nervorum.
- Arteries necrose and thrombose, and watershed regions of individual nerves infarct.
- Axons in the infarcted segment degenerate; nerves are hit one after another.
- In paraneoplastic disease, tumour neural antigens (HuD) provoke T cells that kill sensory neurons.
- Paraproteins bind myelin (anti-MAG) or deposit as amyloid, and VEGF in POEMS makes vessels leaky.
Clinical notes
- Sudden foot drop then wrist drop in a patient with fever, weight loss and raised inflammatory markers: think of vasculitic neuropathy.
- Subacute sensory ataxia and pain in a smoker: look for small cell lung cancer and anti-Hu.
- An unexplained neuropathy deserves serum and urine protein electrophoresis with immunofixation.
Test yourself
Think of the answer, then tap the question to see it.
What pattern of neuropathy does vasculitis typically cause?
Mononeuritis multiplex, painful and asymmetric.
Which tumour is linked to anti-Hu sensory neuronopathy?
Small cell lung carcinoma.
What does POEMS stand for?
Polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes.
Which stain shows amyloid in a nerve biopsy?
Congo red, with apple-green birefringence under polarized light.
Elsewhere in DurgiPedia
Connections
Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: Amyloidosis: MedlinePlus (MedlinePlus, US National Library of Medicine, 2025); Transthyretin amyloidosis: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2025); Small Cell Lung Cancer (StatPearls (NCBI Bookshelf), 2025).
Spotted a mistake?We are always improving for the community. Tell us what is wrong and our team will review it.Report a mistake
Representative model, for educational purposes only.