White cell disorders
White cell disorders for FCPS: neutrophilia, neutropenia, lymphocytosis and eosinophilia
Reactive white cell changes for FCPS Part 1: neutrophilia, neutropenia, lymphocytosis, eosinophilia, leukaemoid reactions and glandular fever. Most abnormal counts are reactions to infection, drugs or stress, and the film usually shows which.
Normal values (adult, approximate)
Total white cells 4–11 × 10⁹/L: neutrophils 2–7.5, lymphocytes 1.5–4, monocytes 0.2–0.8, eosinophils 0.04–0.4, basophils under 0.1. Young children have higher lymphocyte counts.
The stress and steroid pattern
- Cortisol (from stress, trauma, surgery or given as a drug) produces neutrophilia, lymphopenia and eosinopenia, the classic white count of Cushing syndrome.
- Neutrophils rise because steroids release them from the marrow and demarginate cells stuck to vessel walls, and they leave the blood more slowly. Lymphocytes and eosinophils fall because cortisol redistributes them into lymphoid tissue and marrow (and promotes eosinophil apoptosis). A man on day one after a femoral fracture with neutrophils 14 and lymphocytes 0.7 × 10⁹/L, afebrile, shows this pattern; check the drug chart before investigating.
Neutrophilia (above 7.5)
- Causes: bacterial infection (with left shift: band forms, toxic granulation, Döhle bodies, vacuoles), inflammation and necrosis (MI, burns, pancreatitis, gout), steroids, adrenaline and exercise, pregnancy, haemorrhage, haemolysis, smoking, malignancy, CML, after splenectomy.
- Leukaemoid reaction: white count over 50 × 10⁹/L with immature cells from severe infection or malignancy.
| Feature | Leukaemoid reaction | CML |
|---|---|---|
| LAP score | High | Low |
| Toxic granulation | Present | Absent |
| Basophilia | No | Yes |
| Splenomegaly | Usually no | Often massive |
| BCR–ABL | Absent | Present |
- Leucoerythroblastic film (immature myeloid cells plus nucleated red cells): marrow infiltration (metastatic breast or prostate cancer, myelofibrosis with teardrop cells), severe sepsis or haemorrhage.
Neutropenia (below 2; severe below 0.5)
- Causes: chemotherapy, other drugs (carbimazole, propylthiouracil, clozapine, sulfasalazine), viral infection (influenza, HIV, hepatitis, EBV), typhoid (the triad of relative bradycardia, neutropenia and hepatosplenomegaly), overwhelming sepsis, B12 or folate deficiency, hypersplenism, marrow failure, SLE, Felty syndrome (rheumatoid arthritis, splenomegaly, neutropenia), benign ethnic neutropenia.
- Chemotherapy nadir: neutrophils are lowest 7–14 days after a dose (circulating neutrophils live hours and the marrow pool is used up within a week); platelets fall a little later; anaemia appears only after several cycles. Patients must report fever most urgently in this window.
- Drug-induced agranulocytosis with carbimazole (usually in the first 3 months): fever and severe sore throat, often a tonsillar ulcer; marrow shows maturation arrest. The mechanism is immune destruction of granulocyte precursors (and neutrophils) by drug-dependent antibodies. Stop the drug; give broad-spectrum antibiotics and G-CSF if needed; avoid propylthiouracil afterwards because of cross-reactivity.
Neutropenic sepsis
- Fever with neutrophils below 0.5 × 10⁹/L: IV broad-spectrum antibiotics with antipseudomonal cover within 1 hour (for example piperacillin–tazobactam), without waiting for a source.
- Why assume infection with a normal examination, clear chest X-ray and no pyuria? Pus, consolidation and urinary white cells are made of neutrophils, so neutropenia blunts the signs of inflammation; fever may be the only sign.
- Avoid rectal examination and rectal temperatures. Gram-negative organisms such as *Pseudomonas* cause rapid shock: endotoxin drives excessive TNF-α and IL-1 release from macrophages.
Lymphocytosis (above 4)
- Causes: viral infection (EBV, CMV, hepatitis, rubella, mumps), pertussis (marked lymphocytosis from pertussis toxin blocking lymphocyte homing), TB, brucellosis, toxoplasmosis, thyrotoxicosis, CLL (small mature lymphocytes with smudge cells).
- An unexplained persistent absolute lymphocytosis in an adult is investigated with a film and flow cytometry (immunophenotyping) to look for a clonal B-cell population.
- Viral meningitis gives a CSF lymphocytosis with normal glucose and mildly raised protein.
Infectious mononucleosis
- EBV infects B cells through CD21; the large atypical lymphocytes on the film are activated CD8 cytotoxic T cells reacting against the infected B cells.
- Sore throat, fever, posterior cervical lymphadenopathy, splenomegaly; amoxicillin or ampicillin causes a widespread rash.
- Diagnosis: the Monospot (heterophile antibody, Paul–Bunnell) test is the key test for a young adult with sore throat, nodes and atypical lymphocytes. Young children often make no heterophile antibodies, so the Monospot can be negative; EBV viral capsid antigen IgM confirms. CMV and toxoplasma cause a similar Monospot-negative picture.
- The spleen is the organ at risk: it can rupture after minor trauma, so avoid contact sports for at least 3–4 weeks.
Lymphopenia (below 1)
- HIV, corticosteroids and stress, chemotherapy, radiotherapy, SLE, sarcoidosis, TB, lymphoma, uraemia, severe illness, malnutrition, congenital immunodeficiency (DiGeorge, SCID).
Eosinophilia (above 0.5)
| Group | Examples |
|---|---|
| Allergic | Asthma, eczema, hay fever, drug reactions (DRESS), ABPA (perihilar shadows with blood and sputum eosinophilia) |
| Parasitic (tissue-invading helminths) | Strongyloides, hookworm, Ascaris (Löffler), filariasis, schistosomiasis, leaking hydatid, toxocara |
| Skin | Pemphigus, bullous pemphigoid |
| Vasculitis | Eosinophilic granulomatosis with polyangiitis (Churg–Strauss) |
| Malignancy | Hodgkin lymphoma (Reed–Sternberg cells CD15 and CD30 positive), T-cell lymphoma |
| Endocrine | Addison disease (low cortisol) |
| Primary | Hypereosinophilic syndrome; FIP1L1–PDGFRA leukaemia (imatinib) |
- Strongyloides and steroids: a patient from rural Sindh or Punjab with eosinophilia must be screened or treated with ivermectin before high-dose steroids. Steroids let larvae multiply and invade (hyperinfection), carrying gut bacteria: abdominal pain, diarrhoea, Gram-negative sepsis, breathlessness. Steroids also suppress the eosinophil count, so a normal count does not exclude it.
- Eosinopenia: steroids, Cushing syndrome, acute stress and infection.
Monocytes and basophils
- Monocytosis: chronic infection (TB, brucellosis, subacute endocarditis, syphilis), recovery from neutropenia, inflammatory bowel disease, sarcoidosis, chronic myelomonocytic leukaemia.
- Basophilia: myeloproliferative neoplasms (CML), hypothyroidism, ulcerative colitis.
Clues on the blood film
| Finding | Meaning |
|---|---|
| Toxic granulation, Döhle bodies | Bacterial infection, inflammation |
| Hypersegmented neutrophils (6 lobes or more) | B12 or folate deficiency |
| Pelger–Huët (bilobed) neutrophils | Inherited, or myelodysplasia |
| Atypical lymphocytes | EBV, CMV, other viruses, drug reactions |
| Smudge cells | CLL |
| Auer rods | AML, especially APL |
| Blasts | Acute leukaemia: refer urgently |
| Giant granules | Chediak–Higashi syndrome |
Functional defects and the spleen
- Chronic granulomatous disease (NADPH oxidase; catalase-positive organisms), leucocyte adhesion deficiency (CD18; delayed cord separation, no pus), Chediak–Higashi, asplenia (Howell–Jolly bodies; encapsulated organisms).
- Massive splenomegaly: CML, myelofibrosis, kala-azar, chronic malaria (hyper-reactive malarial splenomegaly), Gaucher disease, thalassaemia major. Hypersplenism (portal hypertension) sequesters cells, giving pancytopenia; aplastic anaemia, in contrast, has a hypocellular marrow and no splenomegaly.
Remember Stress and steroids push neutrophils up and pull lymphocytes and eosinophils down.
Exam trap A leukaemoid reaction has a high LAP score; CML has a low one with basophilia and BCR–ABL.
Exam trap A normal eosinophil count on steroids does not exclude Strongyloides hyperinfection.
How FCPS asks about this
- Atypical lymphocytes in glandular fever: activated CD8 T cells; Monospot is the test; the spleen may rupture.
- Monospot negative in a 3-year-old: young children often make no heterophile antibody; check EBV VCA IgM.
- Fever 10 days after chemotherapy with normal examination: neutropenia blunts inflammatory signs; nadir is days 7–14; antibiotics within an hour.
- Carbimazole agranulocytosis: immune destruction of granulocyte precursors; avoid PTU afterwards.
- Lymphopenia after trauma or in Cushing syndrome: cortisol redistributes lymphocytes; eosinophils also fall.
- Eosinophilia before steroids: exclude Strongyloides; Hodgkin lymphoma and Addison disease also cause it.
- Relative bradycardia, neutropenia and hepatosplenomegaly: typhoid; pertussis gives marked lymphocytosis.
Test yourself on this topic
5 of the 22 questions in our bank on this topic. Choose an answer to see why every option is right or wrong.
Four weeks after starting carbamazepine, a 30-year-old man has fever, a widespread rash, facial swelling and tender lymph nodes. Eosinophils are 3.8 × 10⁹/L with atypical lymphocytes, and ALT is 420 U/L. What is the most likely diagnosis?
Answer: Drug reaction with eosinophilia
DRESS is a delayed, T cell-mediated drug hypersensitivity that begins 2–8 weeks after the drug is started, typically with aromatic anticonvulsants, allopurinol, sulfonamides or vancomycin. Facial oedema, rash, fever, lymphadenopathy, eosinophilia with atypical lymphocytes and internal organ involvement, especially hepatitis, make up the picture, and reactivation of HHV-6 is often found. The drug must be stopped at once and systemic steroids are usually needed; mortality is around 10%. Stevens–Johnson syndrome instead causes mucosal erosions and skin detachment without eosinophilia.
DRESS
- Starts 2–8 weeks after the drug
- Fever, rash, facial oedema, nodes
- Eosinophilia, atypical lymphocytes
- Hepatitis; stop drug, give steroids
Remember Late rash with eosinophils and a high ALT: think DRESS.
Exam trap Symptoms can continue or relapse for weeks after the drug is stopped.
Why the other options are wrong
- Acute viral hepatitis A infection Hepatitis A would not cause eosinophilia, rash and facial oedema.
- Stevens–Johnson syndrome Causes mucosal ulceration and detachment, without eosinophilia.
- Infectious mononucleosis Would not follow a new drug or cause eosinophilia and facial oedema.
- Acute lymphoblastic leukaemia Blasts, not eosinophilia with atypical lymphocytes, would be seen.
A man from rural Sindh has an eosinophil count of 4.2 × 10⁹/L, intermittent abdominal pain and urticaria. He is due to start high-dose steroids for another condition. What must be done first?
Answer: Test and treat for Strongyloides
Eosinophilia in someone from an endemic area suggests helminth infection. Strongyloides stercoralis can persist for decades through autoinfection. High-dose steroids or immunosuppression can trigger hyperinfection syndrome, with massive larval migration, Gram-negative sepsis and high mortality. Serology and stool tests are done, and ivermectin is given before or alongside immunosuppression.
Eosinophilia before steroids
- Think helminths (endemic area)
- Strongyloides hyperinfection with steroids
- Treat with ivermectin
Remember Worms first, steroids second.
Exam trap Steroids lower the eosinophil count and can hide the clue.
Why the other options are wrong
- Start steroids at once Risks fatal hyperinfection.
- Do a bone marrow biopsy only Not the first step.
- Give antihistamines only Does not address the cause.
- Repeat the count in 6 months Unsafe delay.
A healthy 25-year-old blood donor has a normal full blood count, but the film shows almost all neutrophils with two lobes joined by a thin filament, like spectacles. He is well, with no infections. What is the most likely explanation?
Answer: Inherited Pelger–Huët anomaly
Pelger–Huët anomaly is an autosomal dominant condition caused by mutations in the lamin B receptor gene, which affects nuclear shape. Neutrophils are bilobed or dumbbell shaped but function normally, and the carrier is healthy, so recognition matters only to avoid unnecessary investigation. Acquired pseudo-Pelger–Huët cells, which are usually a minority of neutrophils and often hypogranular, suggest myelodysplasia or severe infection. B12 deficiency does the opposite, causing hypersegmentation.
Pelger–Huët anomaly
- Lamin B receptor mutation
- Neutrophils bilobed, like spectacles
- Function and counts normal
- Pseudo form: myelodysplasia, sepsis
Remember Odd-shaped nuclei in a well person: inherited, not disease.
Exam trap Do not report a healthy carrier as having myelodysplasia; look at the counts and the patient.
Why the other options are wrong
- Myelodysplastic syndrome Pseudo-Pelger cells affect only some neutrophils and come with cytopenias.
- Severe B12 deficiency Causes hypersegmented, not hyposegmented, neutrophils.
- Chronic myeloid leukaemia Would show a high white count with a left shift and basophilia.
- Reactive change from infection Reactive change gives toxic granulation and band forms.
A 3-year-old has fever, sore throat, cervical nodes and 30% atypical lymphocytes on the film. The heterophile (Monospot) test is negative, but EBV-specific IgM against viral capsid antigen is positive. Which of the following best explains the negative Monospot test?
Answer: Young children often make no heterophile antibodies
The heterophile antibodies detected by the Monospot test are IgM antibodies that agglutinate animal red cells and are produced as a by-product of the intense B cell response in infectious mononucleosis. Children under about 4 years often fail to produce them, so the test is negative in up to half of young children with proven EBV infection. EBV-specific serology, with IgM to viral capsid antigen, is then needed. The atypical lymphocytes themselves are reactive CD8 T cells.
Monospot limits
- Detects heterophile IgM
- Often negative in children < 4
- Also negative early in illness
- Then use EBV-specific IgM
Remember A negative Monospot in a child does not exclude EBV.
Exam trap Toxoplasma and CMV can cause a similar picture with a negative Monospot in adults.
Why the other options are wrong
- The test detects only reactivated infection It detects acute primary infection, not reactivation.
- Atypical lymphocytes absorb the antibodies Lymphocytes do not absorb heterophile antibodies.
- The test needs at least 6 weeks of illness Heterophile antibodies appear in the first weeks and then fall.
- Antibiotics given earlier blocked the test Antibiotics do not interfere with the test.
On the first day after a road traffic injury with a femoral fracture, a man has a white cell count of 16 × 10⁹/L with neutrophils 14 and lymphocytes 0.7 × 10⁹/L. He is afebrile and has no infection. What best explains the low lymphocyte count?
Answer: Cortisol-driven redistribution into lymphoid tissue
Injury and surgery cause a surge of cortisol and catecholamines. Cortisol redistributes circulating lymphocytes into lymph nodes, spleen and marrow and also promotes apoptosis of some subsets, so the lymphocyte count falls within hours while neutrophils rise from demargination. This neutrophilia with lymphopenia is the normal stress pattern and needs no investigation, though persistent lymphopenia is associated with later infection. Thymic output contributes little in adults.
Stress leucocyte pattern
- Neutrophilia with lymphopenia
- Driven by cortisol and catecholamines
- Lymphocytes redistributed, not destroyed
- Normal after injury or surgery
Remember Up neutrophils, down lymphocytes: stress, not sepsis.
Exam trap The same pattern occurs with steroids, so review the drug chart before investigating.
Why the other options are wrong
- Destruction of lymphocytes by injured tissue Tissue injury does not destroy circulating lymphocytes directly.
- Dilution by resuscitation fluids Dilution would lower all cell lines, not just lymphocytes.
- Loss of lymphocytes into the fracture haematoma Lymphocyte loss into a haematoma is trivial.
- Suppression of thymic output after injury Adults depend little on thymic output for their lymphocyte count.
Where this sits in the CPSP syllabus
- Medicine & Allied, Paper 2: Haematopoietic and lymphoid disorders, Non-neoplastic white cell disorders: leucocytosis, leucopenia, eosinophilia, reactive changes
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