Peripheral Neuropathy — Written Clinical Reasoning

Part A — Diagnostic approach and classification

The first discipline is to classify the neuropathy before generating a differential. This patient has two superimposed patterns — a chronic distal symmetric polyneuropathy (the 3-year burning numbness, stocking-distribution sensory loss, absent ankle reflexes, and painless foot ulcer) and a subacute mononeuritis multiplex (the 6-week history of painful, asymmetric, stepwise involvement of the right peroneal nerve and the right ulnar nerve, with weight loss and night sweats). ^[1]

The chronic distal symmetric pattern is, by far, most likely diabetic distal symmetric polyneuropathy (DSPN) in a man with a 15-year history of type 2 diabetes and an HbA1c of 78 mmol per mol — the poor glycaemic control, the length-dependent sensory loss, the absent ankle reflexes, and the painless foot ulcer (the classic triad of neuropathy, ischaemia, and deformity) are all consistent ^[1].

The superimposed subacute mononeuritis multiplex is the concerning new development. Mononeuritis multiplex — painful, asymmetric, stepwise involvement of multiple individual named nerves — is the signature of vasculitic neuropathy until proven otherwise ^[4], and the systemic symptoms of weight loss and night sweats raise the possibility of an underlying systemic vasculitis or a paraproteinaemic process. The small IgM kappa paraprotein adds a further layer — it may be an incidental MGUS, or it may be relevant (anti-MAG neuropathy is typically a chronic distal demyelinating sensory neuropathy, not a mononeuritis multiplex, but paraproteinaemic disease and vasculitis can coexist, and cryoglobulinaemic vasculitis is classically associated with a paraprotein and hepatitis C).

Key point: Never assume that all neuropathy in a diabetic patient is due to diabetes. A substantial minority of neuropathy in diabetics has an alternative or additional cause. The new, subacute, asymmetric, painful, stepwise pattern in this patient demands investigation for vasculitis and paraproteinaemic disease. ^[1]