Case Conference

Kenny Ecker, MD

September 22, 2010

CC: "I have a headache and some fevers"

HPI: 27 y/o AAM with a h/o HIV and Hodgkin's Lymphoma (s/p 6 cycles ABVD in 2009), now in remission, presenting with a 5-day h/o a diffuse, dull HA with accompanying photophobia/phonophobia. No meningismus. Has had occasional nausea with NBNB vomiting twice. Also states he developed low-grade fevers (up to 101.0) over the past 3 days, prompting him to come to the ED. Notes that he had a mild cough with some congestion about 3 weeks ago, though this has since dissipated before new symptoms began.

ROS: (+) Fatigue, 20 lb unintentional wt loss over past 4 weeks(-) SOB, Chest pain, Abd pain, Productive cough, Hemoptysis,

Diarrhea/Constipation

PMHx:1. Hodgkins Lymphoma, Stage IV: Dx in 2008 when presented with

pancytopenia; had PET with diffuse skeletal uptake. S/p 6 cycles ABVD in 2009 with CT scans negative for recurrence and repeat PET negative in 3/10.

2. HIV: Dx in 2008. Last CD4 >900 in 4/10 with viral load undetect.3. Chronic Hepatitis B4. Bipolar Disorder5. GSW to L ankle

PSHx: 1. Remote L ankle surgery s/p GSW

Soc Hx: Lives with GF. Currently unemployed.

(+) weekly MJ use. Denies Tobacco, EtOH, IV drug use.

H/o incarceration 2 years ago

Fam Hx:

Mother deceased from Breast CA

Father with h/o HTN, DMII. Thinks dad was diagnosed with TB “a few months ago”

All: NKDA

Meds:

1. Atazanavir 300mg daily

2. Ritonavir 100mg daily

3. Truvada 200/300mg daily

4. Geodon 80mg qAM, 200mg qPM

5. Cogentin 1mg BID

6. Duloxetine 60mg daily

Physical ExamVS: T 99.6, 84, 18, 134/82, 98% on RA

Gen: Obese male in NAD. Lying in bed. A&Ox3. Mild increased sweating noted.

HEENT: PERRL. EOMI. MMM. No sinus tenderness..

Neck: No nuchal rigidity. FROM.

CV: RRR. No m/r/g. Normal S1 and S2.

Pulm: CTAB. No w/r/r.

Abd: Obese and soft. NT/ND. (+) BS. No hsm.

Ext: Warm. 2+ distal pulses. No edema. Scar at L ankle from previous bullet wound.

Neuro: CN II-XII intact. No focal deficits noted.

ED LabsCBC: WBC 10.8 (72N, 19L, 7M), Hb 15.2, Hct 45, Plt 204

Chem: Na 137, K 3.9, Cl 102, CO2 24, BUN 14, Cr 1.16, Glu 97

LFTs: Tbili 1.2, Dbili 0.1, Alb 4.3, TPr 7.6, AST 22, ALT 21, AP 134

LDH 138, Uric acid 7.6

Head CT: No acute intracranial process. No abnormal meningeal enhancement. Partial visualization of the paranasal sinuses demonstrating air/fluid level in R maxillary sinus.

CXR

LP performed:

1130 WBC (99%L, 1%M, 0%N), 6 RBC

Protein 170, Glucose 52

Gram stain negative

HSV, Cultures sent

ED Course- Blood, Urine Cx obtained. Sputum Cx ordered but unable

to obtain 2/2 lack of productive cough

- Given empiric dose of Vancomycin, Ceftriaxone and Acyclovir. Also given 40mg IV Dexamethasone.

- Admitted to Heme1 in Negative Airflow room for induced sputums to r/o TB.

Our initial thoughts…

1. Viral (? HIV) vs TB Meningitis

2. Lymphoma recurrence +/- CNS involvement

Plan:

- ID consult- AFB stain of CSF- CSF flow cytometry- PPD, TB Quant

- Check EBV, HSV, HIV viral load

More Labs/Floor Data- BCx, UCx NGTD

- AFB negative x1

- PPD negative, TB quant pending

- EBV, HSV negative

- HIV viral load undetectable

- CSF Flow: No B cells. No abnormal population of T cells.

** ID c/s note: “Spoke with Columbus Health Department and pt’s father does NOT have TB”

“Oh, by the way”

Returned to patient to ask more about NSAID use.

His girlfriend stated he was taking 800mg Ibuprofen every 6 hours for the past 3 weeks to help his coughing/headaches

Hospital Course

- Remained afebrile throughout admission. Cx negative -> Abx stopped.

- Headache improved

- Brief elevation of Cr to 1.6, normalized with IV fluids to baseline (1.1)

- Discharged home and told to avoid NSAIDs for pain/headache

Aseptic MeningitisMeningitis = Normal cerebral functionEncephalitis = Cerebral function impaired

Definition: Clinical and lab evidence of meningeal inflammation with negative bacterial cultures.

- #1 cause = Enterovirus (Coxsackie, Echovirus)- Other causes = Other virus (HIV, HSV), Mycobacterial infection, Fungal, Spirochete,

Malignancy and Medications- HIV meningitis = Mono-like syndrome plus HA, +/- meningeal signs; CSF with lymphocytic

pleocytosis, high protein, low glucose

- HSV meningitis = Usually HSV-2 in immunocompetent, usually accompanied by genital lesions; similar CSF to HIV

- Mollaret’s meningitis = Recurrent benign lymphocytic meningitis with >3 episodes of fever and meningismus lasting 2-5 days with spont resolution. Usually HSV-2. CSF with large granular plasma cells on staining

- TB Meningitis = Usually HA, vomiting, confusion; CSF with high protein, low glucose, high lymphocytes and high monocytes

- Major difference from bacterial meningitis is self-limited course

• Most common agents = NSAIDs, IVIG, certain Abx (Bactrim), various chemotherapeutic antibodies

• 2 proposed mechanisms = Delayed hypersensitivity rxn vs. Direct meningeal irritation– Drug combines with CSF or meningeal protein

that acts as hapten leading to inflammatory response in meninges

• Diagnosis of exclusion– CSF with neutrophilic pleocytosis

NSAID-related Meningitis

• First described in 1978 in a patient with SLE using Ibuprofen– 4 episodes of aseptic meningitis, challenged with 400mg Ibuprofen and

developed Sx

• Other NSAIDs reported: Naproxen, Diclofenac, Ketoprofen, Sulindac, Tolmentin, Prioxicam, Indomethacin, Rofecoxib

• Similar presentation to other aseptic meningitis – High CSF pressure common

• Possible link to SLE– Review of 43 patients with NSAID-induced aseptic meningitis, 14 had

SLE

• Not tons of info, but some case reports and brief reviews:– Appears to be independent of dose

• Case reports with 200mg Ibuprofen/day

• Rxn with 1 NSAID does not mean pt will have issue with all NSAIDs (unsure why)– Usually see symptoms within 4 weeks of drug

exposure

Does NSAID dose matter?

Approach to patient

• Look for fever, HA, n/v, photophobia, stiff neck/nuchal rigidity• Comprehensive travel and exposure history• Detailed questioning about medications used• Look on exam for evidence directing to other diagnosis (rash,

thrush, etc)• Give empiric Abx (with Acylovir and usually steroids) even if

viral is most likely– Most important in elderly, immunocompromised or if received recent

antibiotic treatment

• If symptoms improve and cultures negative, can stop Abx in 24-48 hours

References1. Agarwal & Gutneckcht (December, 2007). Nonsteroidal Antiinflammatory Drug-induced

Aseptic Meningitis. Resident and Staff Physician. Retrieved from http://www.hcplive.com/general/publications/Resident-and-Staff/2005/2005-12/2005-12_04

2. Ashwath & Katner (2003). Recurrent aseptic meningitis due to different non-steroidal anti-inflammatory drugs including rofecoxib. Postgrad Med J 2003;79:295-6. Retrieved from http://pmj.bmj.com/content/79/931/295.full

3. Johnson, Hirsch & McGovern (2010). Aseptic Meningitis in Adults. Retrieved from http://www.uptodate.com/online/content/topic.do?topicKey=cns_infe/7136&selectedTitle=1%7E150&source=search_result

4. Nguyen & Juurlink (January, 2003). Recurrent Ibuprofen-induced Aseptic Meningitis. The Annals of Pharmacotherapy Vol. 38, No.3, pp. 408-410. Retrieved from http://www.theannals.com/cgi/content/full/38/3/408

THE END