Amyloidosis in chronic inflammatory disease

AA amyloidosis connects cumulative inflammatory exposure to organ deposition. Reconstruct years rather than the latest clinic visit: disease activity, febrile attacks, CRP or SAA, infection burden, missed medicines and periods without specialist care. Ask about frothy urine, oedema, orthostatic symptoms, diarrhoea, bleeding, weight loss, thrombosis and infection. Examine volume state, blood pressure including standing values, joints, skin and infection sources, liver, spleen and neuropathy.

Screen high-risk patients with serum creatinine, eGFR, albumin and urine ACR or PCR at intervals matched to inflammatory control. Confirm persistent protein and exclude urine infection, menstruation, heavy exercise and transient febrile change. Nephrotic-range protein, falling albumin or kidney decline requires renal referral and usually tissue diagnosis rather than being attributed automatically to chronic inflammation.

Measure CRP and serum amyloid A when accessible. SAA is the actual precursor and can stay elevated between obvious attacks, whereas CRP may not track it perfectly. The aim is sustained suppression rather than a single reassuring value. Review infection, adherence, obesity, smoking and occult inflammatory activity when SAA remains high despite apparently quiet joints or fewer fevers.

Before labelling AA, screen for AL with serum and urine immunofixation and serum free light chains. Kidney impairment widens the physiological light-chain ratio, so use renal interpretation rather than declaring a clone from a modest abnormality. Conversely, a small monoclonal protein in an older adult does not establish AL; the amyloid deposit must be typed because coincidental MGUS and chronic inflammation can coexist.

Tissue confirmation shows apple-green birefringence of Congo-red-stained fibrils under polarised light. Abdominal fat, minor salivary gland or gastrointestinal tissue may be less invasive but has variable sensitivity; kidney biopsy is often most informative when renal disease dominates and can also identify a second glomerulopathy. Send adequate fixed tissue to an expert amyloid pathology service for immunohistochemistry and mass-spectrometric typing.

The National Amyloidosis Centre can confirm fibril type, assess systemic burden and use serum amyloid P component scintigraphy in suitable non-cardiac amyloid to map deposits and longitudinal change. Baseline assessment also includes ECG, cardiac biomarkers and echocardiography when symptoms or typing raise concern, liver and alkaline phosphatase, gastrointestinal and autonomic review and renal staging. Cardiac dominance should reopen AL and ATTR strongly.

Treatment targets the inflammatory source. In rheumatoid or spondyloarthritis use contemporary treat-to-target escalation; an IL-6 inhibitor can markedly suppress SAA when clinically appropriate. In Still disease or periodic fever choose IL-1 or IL-6 blockade according to phenotype and licence or commissioning. In chronic infection, immune escalation without microbiological source control may worsen both the trigger and amyloid production.

FMF deserves explicit prevention. Colchicine is taken continuously, not just during attacks, and reduces attacks and AA risk. Confirm adherence and interaction, increase toward the maximum tolerated specialist dose and monitor SAA. Canakinumab or anakinra is considered for colchicine-resistant or intolerant inflammatory activity; colchicine is generally continued because its independent protection remains important.

Renal protection follows CKD principles while respecting nephrotic physiology. Offer an ACE inhibitor or ARB for albuminuria when blood pressure, potassium and renal perfusion permit and titrate with creatinine and potassium checks. Restrict dietary salt and use loop diuretic cautiously for oedema. A large creatinine rise, symptomatic hypotension or intercurrent volume loss requires temporary reassessment rather than automatic escalation.

Assess venous thrombosis individually using albumin, proteinuria severity, prior thrombosis, bleeding and immobility; there is no universal anticoagulation threshold for AA nephrosis. Vaccination, rapid infection treatment, lipid and cardiovascular management, nutrition and avoidance of NSAIDs and other nephrotoxins reduce secondary harm. Adjust all anti-inflammatory medicine doses to eGFR and dialysis where required.

Refer early for kidney-replacement education when progression is sustained. Dialysis modality is individualised around blood pressure, infection, abdominal and social factors. Transplantation can provide good outcomes when inflammatory control is durable, but recurrent high SAA risks graft deposition; the rheumatology, infection or autoinflammatory plan must therefore remain active before and after transplant.

Judge disease modification using repeated SAA where available, CRP, inflammatory phenotype and adherence alongside urine protein, albumin and eGFR. Proteinuria may improve slowly after SAA falls, while advanced CKD may progress despite precursor control. Conversely, fewer attacks without biochemical suppression is not adequate protection. State separately whether inflammation, deposition and irreversible renal damage are improving.