Immunology · Year 2 · from Immunology
Case 3: Complement C5 Deficiency
Patient Demographics
- Age: 19 years old
- Sex: Male
- Ethnicity: African American
Chief Complaint
Second episode of meningococcal meningitis
History of Present Illness
A 19-year-old male college student presents with fever, severe headache, neck stiffness, and photophobia for 1 day. Three years ago, he was hospitalized for meningococcal meningitis (Neisseria meningitidis serogroup Y) and made a full recovery. He had received the meningococcal conjugate vaccine before college.
Past Medical History
- Meningococcal meningitis at age 16
- Otherwise healthy
- Up to date on vaccinations including meningococcal conjugate and serogroup B vaccines
Family History
- Older brother had gonococcal arthritis at age 25
- No other family history of unusual infections
Physical Examination
- General: Ill-appearing, lethargic
- Vital Signs: T 39.5C, HR 120, RR 24, BP 100/65
- HEENT: Photophobia, positive Kernig and Brudzinski signs
- Skin: Several petechiae on lower extremities
- Neurological: GCS 14, neck rigidity
Laboratory Workup
| Test | Result | Reference Range |
|---|---|---|
| WBC | 22,000/uL | 4,500-11,000/uL |
| CSF WBC | 2,500/uL (95% PMNs) | 0-5/uL |
| CSF protein | 250 mg/dL | 15-45 mg/dL |
| CSF glucose | 25 mg/dL | 40-70 mg/dL |
| CSF Gram stain | Gram-negative diplococci | -- |
| Blood culture | N. meningitidis serogroup W | -- |
| CH50 | <10 U/mL (undetectable) | 30-75 U/mL |
| AH50 | <10 U/mL (undetectable) | Normal |
| C3 | Normal | -- |
| C5 | Undetectable | -- |
Clinical Image
Image source: Wikimedia Commons (https://commons.wikimedia.org/wiki/File:Meningococcal_disease_-_purpuric_rash.jpg). Licensed under CC BY-SA 3.0.
Diagnosis
Terminal Complement (C5) Deficiency with recurrent Neisseria meningitidis infection.
Discussion
Terminal complement pathway deficiencies (C5, C6, C7, C8, or C9) cause specific susceptibility to invasive Neisseria infections (meningococcal and gonococcal disease). These patients have up to 1000-fold increased risk of meningococcal disease compared to the general population. The membrane attack complex (MAC), formed by C5b-C9, is essential for complement-mediated lysis of Neisseria species, which are uniquely dependent on this mechanism for immune control.
Key features:
- Recurrent Neisseria infections (meningitis, disseminated gonococcal infection)
- Both CH50 and AH50 are undetectable (all pathways converge at terminal pathway)
- C3 is normal (distinguishing from C3 deficiency)
- Interestingly, mortality from individual episodes may be lower, possibly due to attenuated inflammatory response
- The brother's gonococcal arthritis suggests inherited complement deficiency
Treatment
- Acute management: Appropriate antibiotics for meningitis (ceftriaxone)
- Vaccination: Quadrivalent meningococcal conjugate vaccine AND serogroup B vaccine (though response may be suboptimal without complement)
- Education: Prompt evaluation for any febrile illness
- Family screening: Test siblings and parents for complement deficiency
- Consider prophylactic antibiotics: Some experts recommend penicillin prophylaxis