Reasoning GP · Algorithm · 1-page summary
Lymphopenia (low lymphocyte count)
For: adults with a low absolute lymphocyte count on FBC in primary care. Not for: children (age-specific ranges; discuss with paediatrics) or inpatients with severe sepsis or COVID-19 (hospital team). Known HIV, CVID or SLE: follow the specialist plan, plus blocks 0 and 8.
Core rule: most lymphopenia is transient and reactive, so confirm and trend it; offer an HIV test with a low threshold if it is unexplained or persistent; never start PCP prophylaxis or stop a DMARD on the total lymphocyte count alone.
0Act now — hospital today
- Severely unwell + fever + cytopenias with organomegaly, hepatitis, coagulopathy, neurological features or very high ferritin (HLH/MAS) → Immediate hospital; discuss with haematology. Do not start dexamethasone or etoposide in primary care.
- Fever or sepsis with severe lymphopenia (<0.5 × 10⁹/L), or suspected PCP, CMV, toxoplasmosis, disseminated fungal infection or TB → Same-day hospital. Offer an HIV test.
- Severe respiratory, neurological or systemic symptoms; pancytopenia, blasts or a major blood-film abnormality → Same-day hospital
- New HIV with CD4 <200: same day if opportunistic infection or unwell; if stable → urgent HIV-service review, not admission for the CD4 alone.
1Triage by count — after a repeat FBC + differential
| Lymphocytes | Action |
|---|---|
| Mild 1.0–1.5 | Usually reactive: repeat FBC at 4–8 weeks. Persists → offer HIV test; immunoglobulins if recurrent infections. |
| Moderate 0.5–1.0 | Offer HIV test, drug review, blood film. Persistent, progressive or other cytopenias → haematology/immunology. |
| Severe <0.5 | Offer HIV test promptly; film. Fever or opportunistic infection → Same-day; otherwise prompt immunology/haematology discussion. |
× 10⁹/L. Practical descriptors, not validated national severity categories; local lab ranges take precedence. Weigh trend, infection, other cytopenias, film, nodes, spleen, drugs, HIV risk. Unwell: no repeat first.
2Screen — one row is enough
- Fever, night sweats, weight loss + lymphadenopathy, splenomegaly or mediastinal mass → Urgent suspected-cancer pathway (NG12). Do not wait for LDH or CT.
- Progressive lymphopenia on serial FBCs → Urgent haematology
- Positive HIV test, suspected acute HIV, low CD4 → HIV service ≤2 weeks; same day if unwell, pregnant or seroconverting.
- On a DMARD/biologic: significant or progressive cytopenia, serious infection, abnormal film or drug threshold → withhold, contact specialist ≤7 days
- Persistent unexplained severe lymphopenia → haematology/immunology ≤7 days
3Assess
☐ Previous FBCs: new, persistent or progressive? ☐ Fever, sweats, weight loss ☐ Recurrent or opportunistic infections ☐ Steroids, DMARDs, biologics, chemotherapy ☐ Sexual history, injecting drugs, travel ☐ Nodes, spleen, oral candida, skin
☐ Repeat FBC; film if persistent or marked ☐ HIV 4th-generation test ☐ Immunoglobulins if recurrent bacterial infections. EBV/CMV, CRP/ESR, ANA, LDH, CXR only as history directs; subsets only with HIV, opportunistic infection, severe persistent lymphopenia or specialist advice. Not routine: CD4 for mild isolated lymphopenia, or zinc testing.
4Classify — only if blocks 0–2 are negative
- Reactive — recent viral illness, surgery, stress → repeat FBC at 4–8 weeks.
- Drug — steroids (commonest), DMARDs, biologics, chemotherapy, radiotherapy → review with the prescriber (shared-care protocol).
- HIV — risk factors or indicator conditions (unexplained leukopenia, oral candida, nodes, weight loss, mononucleosis-like illness) → offer and recommend a test.
- Autoimmune — SLE, sarcoidosis, RA → rheumatology if active.
- Antibody deficiency (CVID) — recurrent sinopulmonary infections, low IgG/IgA/IgM → clinical immunology.
- Uncertain — persistent and unexplained: film, HIV test, haematology/immunology per local pathway.
5Treat today
- Steroids: review dose with the prescriber; never stop abruptly. Prednisolone ≥5 mg/day for ≥4 weeks → Steroid Emergency Card and sick-day rules.
- DMARD, isolated mild lymphopenia: usually continue and repeat; falling trend → discuss with rheumatology.
- Vaccines: Green Book chapter 6, by the specific immune defect, not the count. Inactivated vaccines generally safe; Shingrix, not Zostavax.
- Oral candida: topical nystatin or miconazole if mild (not fluconazole 150 mg single dose); recurrent → check HIV, diabetes, inhaled steroid. Doses: NICE/SPC, BNF, local formulary.
6Refer routinely — and leave to specialists
- Clinical immunology: recurrent or unusual infections, low immunoglobulins, suspected primary immunodeficiency.
- Rheumatology: active SLE or inflammatory disease needing immunosuppression adjustment.
- Specialist-led only: ART, immunoglobulin replacement, PCP, antifungal and herpes prophylaxis. Non-immune, immunosuppressed, exposed to chickenpox or shingles → Same-day advice (oral antivirals per UKHSA).
7Never reassure by
- Blaming a virus or steroid without a repeat FBC to confirm recovery.
- Not offering an HIV test because the patient "is not at risk".
- A total lymphocyte count to infer CD4, or to start PCP prophylaxis.
- Labelling CD4 <200 as AIDS without confirmed HIV.
- Stopping a DMARD only because lymphocytes are below range.
- A single "mild" result with no trend, film or other cell lines.
8Safety-net — say it, then document it
Same day “If you get a fever or signs of a new infection, or feel very unwell, contact us the same day — don't wait it out.” 999 On steroids: “If you keep vomiting or have persistent diarrhoea, use your emergency hydrocortisone injection if you have one, and call 999.”
Follow-up: repeat FBC booked at 4–8 weeks with a named result owner; not normalised → film, HIV test and targeted tests.
✓Safe to manage in primary care only if — all five, documented
No block 0–2 feature
Other cell lines, film and trend reviewed
HIV test offered (or reason documented)
Drugs reviewed; card or shared-care plan in place
Repeat FBC date set; safety-net given
Summary of the full Reasoning GP lymphopenia algorithm, which holds the causes, investigations, prophylaxis, vaccination and follow-up detail. Sources: NICE NG60, QS157, NG12 (updated April 2026), NG243; BHIVA/BASHH/BIA HIV testing (2020); Green Book chapters 6, 7 and 25; UKHSA varicella PEP; BSR csDMARD (2025); local shared-care protocols. Clinical reference — check doses: NICE/SPC, BNF.