C7 Deficiency and Recurrent Meningitis Michael Kaplan, DO LT MC USN 2nd Year Allergy/ Immunology Fellow Walter Reed Army Medical Center Washington, DC History A 39 year old African-American male, active duty US Navy sailor with a history of bacterial meningitis 17 years prior on 2 separate occasions, presented with a 3 day history of progressively worsening fevers, chills, occipital headache and nuchal rigidity. Past Medical History: N. meningiditis meningitis x 2, N. gonorrhea urethritis Past Surgical History: No surgeries Medications: No prescriptions or recent Antibiotics Family History: No family history of meningitis or gonorrhea infections Social History: Occasional alcohol, acetaminophen & ibuprofen as needed, No tobacco, no herbal supplements Allergy: Terbinafine and Itraconazole: macular papular rash. Ampicillin: desquamation Physical Examination Vitals: T=38.1 C, BP=121/79, P =104 RR=27, 02 Sat=100% General: Initially asleep, but easily arousable in no acute distress HEENT: Normal appearing ears, eyes, nose, 2 eythematous macular lesions in oropharynx (3 mm wide), Nuchal rigidity present CVS: Tachycardia otherwise normal Lungs: Normal ABD: Normal EXT: Normal Neuro: alert, and oriented - slowed mental process, no Kernigs or Brudzinski sign. Cranial Nerves, strength, reflexes , gait and sensation all normal. Skin: 2 cm wide, normal skin color, bullous, vesicular lesions noted on abdomen and left arm. No other lesions or rashes noted. Admission Labs Complete Blood Count WBC: 20.1 with left shift Cerebral Spinal Fluid FLUID :HAZY, COLORLESS PROTEIN: 245 MG/DL (12-50) GLUCOSE: <20 MG/DL (40-75) FLUID WBC TOTAL: 4425 /cumm (7) FLUID RBC : 74 / cumm FLUID PMN: 90 % FLUID LYMPH: 3% FLUID MONO: 7% Electrolytes Normal except for slight increase in Cr and Glucose CSF Gram Stain Many white blood cells, predominantly PMNs. Moderate intracellular gram negative diplococci and few extracellular gram negative diplococci. Management Patient was admitted to a monitored bed with respiratory precautions Ceftriaxone & Vancomycin IV started with IV fluids Screened for complement deficiency which could account for multiple neisseria infections. Skin biopsy Patient required approximately 3 days before his presenting symptoms completely subsided. Patient received the polysaccharide meningococcal vaccine at time of discharge. Patient was scheduled to follow up with Allergy/ Immunology clinic to obtain results of complement testing. History of multiple Neisseria infections prompted screening with Total Hemolytic Complement (CH50) (Immune Deficiency Foundation guidelines) Complement Measured Profiles C1 Inh C1Q C2 C3 C4 C4bp C5 C6 C7 C8 C9 Properdin Factor H Factor I 37.2 mg/dl 8.7 mg/dl 5.3 mg/dl 167 mg/dl 38 mg/dl 162 mg/dl 13 mg/dl 9.5 mg/dl 0.0 mg/dl 6 mg/dl 11 mg/dl 4.9 mg/dl 97.7 mg/dl 6.3 mg/dl Reference Range 12-20 5.1 – 7.5 1.9-3.6 71-150 15-47 61-116 3.8-7.6 4-6.9 3.5-7.5 3.0-5.8 2.5-7.5 1.7-3.5 37-68 2.4-4.9 CH50 Undetectable (need to check individual complement components to localize the defect) Late complement components C9 C5a C7 C6 C8 C5 Cell C5b C5 Convertase Lysis C6 C7 C8 C5b C6 C7 C8 C5b C3b Bb C3b Bb Plasma Membrane Membrane attack complex Follow up Patient was educated about his primary immune deficiency and that he should seek early treatment for similar symptoms in the future. Medic-Alert bracelet was provided. Monthly chemoprophylaxis with benzathine penicillin injections were discussed with patient but declined due to the inconvenience and concern for promoting resistance. He had no children therefore, no genetic screening was indicated. References Potter PC, Frasch CE, van der Sande WJ, Cooper RC, Patel Y, Orren A. Prophylaxis against Neisseria meningitidis infections and antibody responses in patients with deficiency of the sixth component of complement. J Infect Dis. 1990 May;161(5):932-7. Drogari-Apiranthitou M, Fijen CA, Van De Beek D, Hensen EF, Dankert J, Kuijper EJ. Development of antibodies against tetravalent meningococcal polysaccharides in revaccinated complement-deficient patients. Clin Exp Immunol. 2000 Feb;119(2):311-6 Corvini M, Randolph C, Aronin SI. Complement C7 deficiency presenting as recurrent aseptic meningitis. Ann Allergy Asthma Immunol. 2004 Aug;93(2):200-5 Andreoni J, Kayhty H, Densen P. Vaccination and the role of capsular polysaccharide antibody in prevention of recurrent meningococcal disease in late complement component-deficient individuals. J Infect Dis. 1993 Jul;168(1):227-31. Immune Deficiency Foundation. Diagnostic and Clinical Care Guidelines for Primary Immunodeficiency Diseases. 2006. p. 8, 16-18.