A 19-year-old woman with sickle cell disease (HbSS) presents with acute onset severe bone pain in the femur and tibia, along with fever (37.8°C) and malaise. She reports similar episodes in the past. On examination, there is localized swelling and tenderness over the affected bones. X-ray shows areas of lucency and sclerosis in the metaphyseal regions. Blood culture grows *Salmonella typhimurium*. Which of the following best explains the predisposition to osteomyelitis in this patient?

Question

Accepted Answer

C. Functional asplenia leading to impaired opsonization and complement-mediated killing. ## Pathophysiology of Osteomyelitis in Sickle Cell Disease

### Why Functional Asplenia?

**Key Point:** Patients with sickle cell disease develop **functional asplenia** by age 5–6 years due to repeated splenic infarction from vaso-occlusion. This is the PRIMARY mechanism predisposing to encapsulated and atypical infections.

### Mechanism of Functional Asplenia

1. **Sickling in splenic microvasculature** → vaso-occlusion
2. **Repeated splenic infarction** → fibrosis and autoinfarction
3. **Loss of splenic function** → impaired:
   - **Opsonization** (coating of pathogens with IgG and complement)
   - **Complement-mediated killing** (especially alternative pathway)
   - **Clearance of unopsonized bacteria**
   - **Marginal zone B-cell function** (antibody production to polysaccharide antigens)

### Why *Salmonella* Specifically?

**High-Yield:** *Salmonella* (non-typhi species) is the **classic pathogen of osteomyelitis in SCD**, occurring 50–100 times more frequently than in the general population.

**Clinical Pearl:** While *Staphylococcus aureus* is the most common cause of osteomyelitis overall, *Salmonella* is the **most common in SCD**—a critical distinction for NEET PG.

### Comparison of Osteomyelitis Pathogens in SCD

| Pathogen | Frequency in SCD | Reason | Clinical Feature |
|----------|------------------|--------|------------------|
| ***Salmonella* (non-typhi)** | Most common | Asplenia + gut translocation | Metaphyseal |
| *Staphylococcus aureus* | Second most common | Still occurs; asplenia is not absolute | Metaphyseal/diaphyseal |
| *Streptococcus pneumoniae* | Encapsulated; asplenia | Sepsis/meningitis more than osteomyelitis | Systemic |
| *Haemophilus influenzae* | Encapsulated; asplenia | Rare post-vaccination | Systemic |

### Why Not the Other Options?

**Increased bone marrow cellularity** does occur in SCD (extramedullary hematopoiesis), but it does not directly impair blood flow to bone or predispose to infection. It is a consequence of chronic hemolysis, not a cause of osteomyelitis.

**Defective neutrophil chemotaxis** is not a feature of SCD. Neutrophil counts are often elevated due to chronic hemolysis and inflammation. The problem is not neutrophil function but rather the loss of splenic opsonization.

**Chronic hypoxia-induced impaired wound healing** is not the mechanism. Bone is well-vascularized in SCD (paradoxically, due to chronic anemia-driven hyperemia), and the issue is immunologic, not vascular.

### Mnemonic: ASPLENIA in SCD

**A** — Autoinfarction of spleen (repeated vaso-occlusion)  
**S** — Susceptibility to encapsulated organisms (*Streptococcus pneumoniae*, *Haemophilus*)  
**P** — Predisposition to *Salmonella* osteomyelitis  
**L** — Loss of opsonization and complement-mediated killing  
**E** — Encapsulated pathogens + atypical organisms (*Mycoplasma*, *Salmonella*)  
**N** — Neisseria meningitidis also increased risk  
**I** — Impaired IgG and complement responses  
**A** — Asplenic crisis (acute hemolytic episode)

### Clinical Management
- **Prophylaxis:** Penicillin V (or amoxicillin) from infancy until age 5, then reassess
- **Vaccination:** Pneumococcal, *Haemophilus influenzae* type b, meningococcal (before asplenia develops)
- **Acute osteomyelitis:** Broad-spectrum antibiotics covering *Salmonella*, *Staph*, and atypical organisms

**Warning:** Do not assume *Staph aureus* in SCD osteomyelitis—always include *Salmonella* coverage.

[cite:Robbins 10e Ch 14; Harrison 21e Ch 104]

![Sickle Cell Disease diagram](https://mmcphlazjonnzmdysowq.supabase.co/storage/v1/object/public/blog-images/explanation/2625.webp)

Answer

A. Chronic hypoxia-induced impaired wound healing in bone

Answer

B. Defective neutrophil chemotaxis due to sickling of white blood cells

Answer

D. Increased bone marrow cellularity causing mechanical obstruction of blood flow

Explanation

Pathophysiology of Osteomyelitis in Sickle Cell Disease

Why Functional Asplenia?

Mechanism of Functional Asplenia

Why Salmonella Specifically?

Comparison of Osteomyelitis Pathogens in SCD

Why Not the Other Options?

Mnemonic: ASPLENIA in SCD

Clinical Management

Practice similar questions

Join our NEET PG community

Pathogen	Frequency in SCD	Reason	Clinical Feature
**Salmonella (non-typhi)**	Most common	Asplenia + gut translocation	Metaphyseal
Staphylococcus aureus	Second most common	Still occurs; asplenia is not absolute	Metaphyseal/diaphyseal
Streptococcus pneumoniae	Encapsulated; asplenia	Sepsis/meningitis more than osteomyelitis	Systemic
Haemophilus influenzae	Encapsulated; asplenia	Rare post-vaccination	Systemic