Bone marrow in asof
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Bone marrow in asod
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Bone marrow in stills disease
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Bone Marrow in Still's Disease (AOSD / sJIA)
Background
Adult-onset Still's disease (AOSD) and systemic juvenile idiopathic arthritis (sJIA) are considered the same IL-1-driven autoinflammatory entity, differing only in age of onset. AOSD typically presents with quotidian fever, salmon-pink rash, and arthritis, and is accompanied by striking laboratory abnormalities that can mimic primary hematologic disease.
Bone Marrow Findings in AOSD
Bone marrow examination is not required for diagnosis but is often performed to exclude hematologic malignancy or when MAS/HLH is suspected. The findings include:
1. Granulocytic Hyperplasia (Universal Finding)
- Hyperplasia of granulocytic precursors is seen in all patients examined by bone marrow biopsy
- This reflects the marked neutrophilia characteristic of AOSD (WBC >10,000/mm³ with >80% neutrophils)
- The marrow is hypercellular overall
2. Hemophagocytosis (Seen in Some Patients)
- Hemophagocytosis (macrophages engulfing red cells, platelets, and white cells) may be present
- This occurs when AOSD is complicated by Macrophage Activation Syndrome (MAS), which is classified as a form of secondary HLH (MAS-HLH)
- Both AOSD and sJIA are recognized causes of autoimmune-associated HLH
3. Findings in Overt MAS-HLH Complicating Still's Disease
When MAS develops, the bone marrow shows:
- Hemophagocytosis - activated macrophages phagocytosing hematopoietic cells
- Hypercellularity progressing to possible hypocellularity over time with severe/prolonged disease
- Cytopenias of all three cell lines (bicytopenia or pancytopenia)
- This carries life-threatening implications and requires urgent high-dose corticosteroids or IL-1/IL-6 inhibitors
Associated Laboratory Context
The peripheral blood picture that drives bone marrow investigation in AOSD:
| Finding | Detail |
|---|---|
| Leukocytosis | WBC >10,000/mm³, >80% neutrophils |
| Anemia | Normocytic normochromic (anemia of chronic inflammation) |
| Thrombocytosis | Common (thrombocytopenia suggests MAS) |
| Ferritin | Markedly elevated (>5x ULN) in 70% of patients; glycosylated ferritin <20% raises specificity for AOSD to 93% |
| ESR/CRP | Almost invariably elevated |
| ANA/RF | Typically negative (a diagnostic criterion) |
Key Clinical Point
Because the hematologic abnormalities can sometimes reach extreme levels, bone marrow biopsy is commonly performed to exclude hematologic malignancy before or alongside establishing the AOSD diagnosis. The finding of isolated granulocytic hyperplasia without dysplasia helps support a reactive/inflammatory etiology rather than a primary marrow disease.
Sources: Rheumatology 2-Volume Set (Elsevier, 2022), p. 1577 | Firestein & Kelley's Textbook of Rheumatology | Harrison's Principles of Internal Medicine 22E (2025)
Hlh vs dac
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HLH vs DIC - Comparison
These two conditions can co-exist (DIC can complicate severe HLH), but they are mechanistically distinct and differ in key diagnostic parameters.
Pathophysiology
| HLH | DIC | |
|---|---|---|
| Core mechanism | Unbridled macrophage/T-cell activation → cytokine storm (IFN-γ, TNF, IL-6) → macrophages phagocytose blood cells and precursors | Systemic activation of the coagulation cascade → widespread intravascular thrombin generation → consumption of clotting factors and platelets → simultaneous thrombosis + bleeding |
| Trigger | Infection (EBV, CMV, etc.), rheumatologic disease (Still's, SLE, sJIA), malignancy, genetic defects (PRF1, UNC13D, etc.) | Sepsis, trauma, malignancy (esp. APL), obstetric emergencies, liver disease, burns |
| Primary defect | Failure of cytotoxic lymphocytes (CD8+ T cells, NK cells) to kill targets → persistent macrophage activation | Excessive thrombin generation → fibrin deposition → secondary fibrinolysis |
Clinical Features
| Feature | HLH | DIC |
|---|---|---|
| Fever | Universal, high-grade | May be present (reflects underlying cause) |
| Splenomegaly | Prominent | Not a feature |
| Hepatomegaly | Common | Not specific |
| Lymphadenopathy | Common | Absent |
| Bleeding | Seen in severe disease | Prominent - bleeding at multiple sites |
| Thrombosis | Less prominent | Microvascular thrombosis - purpura fulminans, acral ischemia |
| CNS involvement | Common (seizures, altered consciousness) | Rare unless severe |
Key Laboratory Differences
This is the most important differentiating table clinically:
| Lab Test | HLH | DIC |
|---|---|---|
| Ferritin | Markedly elevated (often >10,000 µg/L) - hallmark | Mildly elevated (acute phase reactant only) |
| Fibrinogen | Low (hypofibrinogenemia ≤1.5 g/L is a diagnostic criterion) | Low - consumed by coagulation |
| D-dimer / FDPs | Mildly elevated | Markedly elevated - hallmark |
| PT/aPTT | Mildly prolonged | Both prolonged - factor consumption |
| Platelet count | Low (thrombocytopenia) | Low (consumed) |
| Triglycerides | Elevated (≥3 mmol/L) - diagnostic criterion | Normal |
| Soluble IL-2 receptor (sCD25) | Markedly elevated - diagnostic criterion | Not elevated |
| NK cell activity | Low or absent | Normal |
| Schistocytes | Rare | Present - microangiopathic picture |
| Transaminases | Elevated (hepatitis from macrophage infiltration) | Variable |
| Ferritin:ESR ratio | Very high | Lower |
Bone Marrow
| HLH | DIC | |
|---|---|---|
| Bone marrow biopsy | Hemophagocytosis - macrophages phagocytosing RBCs, platelets, nucleated cells | No specific bone marrow finding; may show hypercellularity of underlying cause |
| Cellularity | May become hypocellular with prolonged disease | Not directly affected |
HLH Diagnostic Criteria (HLH-2004)
Diagnosis requires 5 of the following 8 criteria (or a known genetic defect):
- Fever
- Splenomegaly
- Cytopenias (≥2 cell lines): Hb <90 g/L, platelets <100×10⁹/L, neutrophils <1×10⁹/L
- Hypertriglyceridemia ≥3 mmol/L and/or hypofibrinogenemia ≤1.5 g/L
- Hemophagocytosis on bone marrow/spleen/lymph node biopsy
- Low or absent NK cell activity
- Ferritin ≥500 µg/L
- Elevated soluble CD25 (sIL-2R) ≥2400 U/mL
Important Overlap - Why They Are Confused
- Both cause: low platelets, low fibrinogen, elevated PT/aPTT, organ dysfunction, and can arise from sepsis/infection
- DIC can complicate severe HLH - in HLH, the cytokine storm can secondarily trigger coagulation cascade activation
- The key distinguishing features that point toward HLH over DIC are:
- Extreme hyperferritinemia (>10,000 µg/L strongly favors HLH)
- Splenomegaly + lymphadenopathy
- Hypertriglyceridemia
- Hemophagocytosis on marrow biopsy
- Low NK cell activity
- Markedly elevated sCD25
Treatment Comparison
| HLH | DIC | |
|---|---|---|
| Primary goal | Suppress cytokine storm; treat trigger | Treat underlying cause; correct coagulopathy |
| First line | Dexamethasone + etoposide (HLH-94/2004 protocol); cyclosporin A | Treat precipitant + supportive (FFP, platelets, cryoprecipitate) |
| Specific agents | Emapalumab (anti-IFN-γ), anakinra (IL-1 block), ruxolitinib (JAK inhibitor) | Heparin in select cases (fibrin-predominant DIC, e.g., APL) |
| Curative (primary HLH) | Allogeneic HSCT | N/A |
Sources: Harrison's Principles of Internal Medicine 22E (2025) | Robbins & Kumar Basic Pathology | Rosen's Emergency Medicine | Rheumatology 2-Volume Set (Elsevier, 2022)
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