Reasoning GP · Algorithm · 1-page summary
Abnormal immunoglobulins and paraprotein
For: adults in primary care with a paraprotein, abnormal serum free light chains (FLC), a polyclonal rise or low immunoglobulins. Not for: diagnosing or treating myeloma, Waldenström, amyloid or CVID (specialist-led). Suspected cord compression: MSCC protocol. Local laboratory comments and haematology advice take precedence.
Core rule: a paraprotein level alone neither diagnoses nor excludes myeloma, and no single test excludes it. Attributable CRAB features, serum FLC and symptoms decide the route; MGUS is monitored only to a written haematology plan.
0Emergency now — do not delay transfer for imaging or specialist confirmation
- Leg weakness, gait disturbance, sensory loss, radicular pain, saddle anaesthesia, bladder or bowel dysfunction (suspected MSCC) → Immediately MSCC coordinator / acute oncology; whole-spine MRI within 24 h; dexamethasone 16 mg orally as soon as possible.
- IgM paraprotein + visual disturbance, headache, mucosal bleeding, confusion, dizziness or breathlessness (hyperviscosity) → Immediately haematology / acute oncology discussion; severe → emergency admission.
- Severe or symptomatic hypercalcaemia → Same-day hospital; emergency with confusion, reduced consciousness, vomiting, dehydration, arrhythmia, AKI or calcium around/above 3.0 mmol/L.
- AKI with suspected myeloma · sepsis on myeloma treatment · unstable pathological fracture → Emergency acute oncology / emergency pathway.
1Triage — what is the pattern?
| Result | Means / next |
|---|---|
| Paraprotein | Most often MGUS → immunofixation, serum FLC, CRAB bloods |
| Abnormal FLC | Light chain myeloma or AL amyloid; mild changes common in CKD |
| Polyclonal rise | Infection (HIV, hepatitis, TB), cirrhosis, autoimmune, sarcoid, lymphoma → find the cause |
| Low IgG ± IgA/IgM | CVID, or secondary (CLL, lymphoma, rituximab, protein loss) |
| Low IgA only | Selective IgA deficiency (<0.07 g/L); usually asymptomatic |
2Screen — suspected myeloma
- Paraprotein or abnormal FLC + attributable CRAB: calcium >2.75 mmol/L (or >0.25 above upper limit) · creatinine >177 µmol/L or clearance <40 mL/min · Hb <100 g/L (or >20 g/L below lower limit) · lytic lesion → Suspected cancer haematology.
- Paraprotein or abnormal FLC with bone pain, fracture, IgD/IgE, IgG >15 g/L, IgA/IgM >10 g/L → Suspected cancer haematology.
- 60+ with persistent bone or back pain, or unexplained fracture → myeloma bloods incl. SPEP and serum FLC (NG12).
- Restrictive cardiomyopathy, nephrotic syndrome, neuropathy, macroglossia → amyloid screen (SPEP, immunofixation, FLC).
3Assess
☐ SPEP + immunofixation ☐ Serum FLC and ratio (renal-adjusted range) ☐ FBC, adjusted calcium, eGFR, IgG/IgA/IgM, ESR or PV ☐ Urine Bence Jones only if FLC unavailable
Not in primary care: myeloma imaging (via haematology; no isotope bone scan), bisphosphonate, denosumab, immunoglobulin replacement.
4Classify — a haematology diagnosis; only if blocks 0–2 negative
- MGUS — paraprotein <30 g/L, marrow plasma cells <10%, no CRAB; about 1% a year progress.
- Smouldering myeloma — paraprotein >30 g/L or 10–60% plasma cells, no CRAB → haematology-led.
- Myeloma — clonal plasma cells + CRAB or SLiM (e.g. FLC ratio ≥100, involved FLC ≥100 mg/L).
- IgM paraprotein — Waldenström more often than myeloma; ask about hyperviscosity.
- Uncertain — local haematology advice and guidance.
5Treat today — only these
- Coeliac testing: always check total IgA with anti-tTG IgA; IgA deficient → anti-tTG IgG or anti-DGP IgG.
- Possible myeloma: keep hydrated; avoid NSAIDs, iodinated contrast, aminoglycosides.
- Myeloma or antibody deficiency: prompt antibiotics; vaccines per Green Book, no live vaccines. Lenalidomide: thromboprophylaxis and pregnancy prevention in place. Doses: NICE/SPC, BNF, local formulary.
- IgA deficiency: transfusion alert, not drug allergy; past severe reaction → ≤7 days transfusion medicine advice.
6Refer routinely
- New paraprotein, no concerning features or CRAB → Routine haematology or advice and guidance to stage MGUS risk.
- Persistent low IgG with recurrent sinopulmonary infections, bronchiectasis or poor vaccine responses → clinical immunology.
- GP-monitored MGUS only if the haematology letter delegates it: about 6 months, then yearly or longer if low risk.
- MGUS: M-protein up >25% and ≥5 g/L → ≤7 days re-refer; new anaemia or renal impairment → Suspected cancer.
7Never reassure by
- A low paraprotein, or a normal SPEP when suspicion persists.
- Never diagnose myeloma from a paraprotein level or isolated FLC ratio.
- A negative anti-tTG IgA without a total IgA.
- A polyclonal rise without looking for its cause.
- Never start bisphosphonate or denosumab in primary care for suspected myeloma.
8Safety-net — say it, then document it
999 “Call 999 or go to A&E straight away for new leg weakness or numbness, loss of bladder or bowel control, confusion, sudden blurred vision, severe headache or unusual bleeding, or fever during myeloma treatment.” Same-day “Contact us the same day for new or severe bone or back pain, extreme thirst or passing lots of urine, or a new infection.”
Review: MGUS checks per the haematology plan; contact us sooner for tiredness, repeated infections or new swelling. MGUS is not myeloma; most never progress.
✓Safe to leave primary care only if — all five, documented
No block 0–2 row applies
SPEP, immunofixation, serum FLC and CRAB bloods done
Pattern named, or uncertainty stated with haematology advice
Monitoring owner, tests and interval in writing
Safety-net given and documented
Summary of the full Reasoning GP abnormal immunoglobulin algorithm, which holds the detail and evidence. Sources: NICE NG35, NG12 (updated April 2026), NG234; BSH MGUS 2023, smouldering myeloma 2024, transfusion reactions 2023; Myeloma UK GP guide; UKHSA Green Book; local pathways. Clinical reference — follow local pathways and check doses: NICE/SPC, BNF.