Transcript 54 year old male with fever, altered mental status

54 year old male with HIV,
fever, altered mental status
Brian Crabtree, MD PGY-3
Maine ACP Conference 2013
September 28, 2013
Identification and Chief Complaint
► 54
year old Cuban American man with a
history of HIV positivity, schizoaffective
disorder, glaucoma, recent diagnosis of
ankylosing spondylitis presents with three
days of fevers and chills, worsening
headache and confusion.
History of Present Illness
► Mr.
B was in his usual state of health until
four days before admission when he reports
developing low grade fevers and night
sweats with generalized malaise. Over the
next two days he developed a worsening
headache, confusion and ataxia. His
significant other brought him to the ED by
car for failure to improve and worsening
mental status.
Review of Systems
General: +malaise, +fever, no weight loss
HEENT: +headache, no photophobia, +ulcer on lip for the
last week, no visual changes
CV: no chest pain, no DOE, no orthopnea
Respi: no cough, no SOB
GI: +nausea, no vomiting, no bowel changes, no abdominal
pain
GU: +polydipsia and polyuria, no dysuria
Neuro: no focal weakness, no sensory deficits or paresthesias
Skin: no rashes, no jaundice
Psych: +somnolence, +confusion, no hallucinations, delusions
MSK: +neck stiffness, +low back pain, no joint pain
Past Medical History
Active
Problem
List
1. Fever
2. AMS
HIV – diagnosed in 1990s, currently on
antiretroviral therapy, most recent CD4 count
369 with low viral load (30)
Schizoaffective disorder – diagnosed in his mid
twenties and on valproic acid
Anklyosing spondylitis – HLA-B27 positive,
diagnosed in the last year
History of uveitis and glaucoma
Gilbert’s disease
Chronic Hepatitis B carrier
Hyperlipidemia
Past Medical History
Active
Problem
List
1. Fever
2. AMS
1.
2.
3.
4.
PMH
HIV
Schizoaffective
disorder
Akylosing
spondylitis
Chronic
Hepatitis B
HIV – diagnosed in 1990s, currently on
antiretroviral therapy, most recent CD4 count
369 with low viral load (30)
Schizoaffective disorder – diagnosed in his mid
twenties and on valproic acid
Anklyosing spondylitis – HLA-B27 positive,
diagnosed in the last year
History of uveitis and glaucoma
Gilbert’s disease
Chronic Hepatitis B carrier
Hyperlipidemia
Past Surgical History
Active
Problem
List
1. Fever
2. AMS
1.
2.
3.
4.
PMH
HIV
Schizoaffective
disorder
Akylosing
spondylitis
Chronic
Hepatitis B
Tonsillectomy
Rectal fistula repair
Social History
Active
Problem
List
1. Fever
2. AMS
1.
2.
3.
4.
PMH
HIV
Schizoaffective
disorder
Akylosing
spondylitis
Chronic
Hepatitis B
Mr. B was born in Cuba and moved to the United
States at age 9. He is homosexual with a
long term partner. He was sexually active in
New York City in the 1980’s and was
diagnosed with HIV in the early 1990’s. He
has a history of drug use including cocaine
and acid. Minimal current alcohol use, history
of social tobacco use. He moved to southern
Maine in 2009 to run a kennel with his
partner. He is on disability for his
schizoaffective disorder.
Medications and Allergies
Active
Problem
List
1. Fever
2. AMS
1.
2.
3.
4.
PMH
HIV
Schizoaffective
disorder
Akylosing
spondylitis
Chronic
Hepatitis B
Ritonavir 100mg cap daily
Atazanavir 300mg cap daily
Emtricitabine-tenofovir 200-300mg tab daily
Valproic acid 500mg 3 tabs at bedtime
Perphenazine 16mg tab twice daily
Bupropion 450mg XR once daily
Pravastatin 20mg tab daily
Etodolac 400mg tab twice daily
Loratadine 10mg tab daily as needed
Dorzolamide-timolol solution one drop twice daily
Loteprednol etabonate 0.5% solution once daily
Physical Examination
Active
Problem
List
1. Fever
2. AMS
1.
2.
3.
4.
PMH
HIV
Schizoaffective
disorder
Akylosing
spondylitis
Chronic
Hepatitis B
T 39.7 HR 107 RR 20 142/88 97% O2
General: drowsy, poor attention, orientedx3
HEENT: PERRL, EOMI, +1cm ulcer on left lower lip,
+nuchal rigidity
CV: regular rhythm, normal rate, normal S1 and S2
without murmurs
Respi: good air movement, clear to auscultation
Abd: soft and nontender, normal bowel sounds, no
organomegaly
Ext: no peripheral edema, good pulses
Neuro: cranial nerves 2-12 tested and intact, 5/5 strength
throughout, normal reflexes, negative Kernig and
Brudzinski signs, normal tone, normal sensation
Initial Lab Testing
Active
Problem
List
1. Fever
2. AMS
1.
2.
3.
4.
PMH
HIV
Schizoaffective
disorder
Akylosing
spondylitis
Chronic
Hepatitis B
CBC: WBC 7.0, Hb 13.2, Hct 37.2, Plt 177
BMP: Na 122, K 3.8, Cl 84, CO2 24
BUN 10, Cr 1.2, Glu 109
UA/sediment: pH 5.0, negative leukocytes and
nitrites, +urobilinogen, no casts, 3-5 RBCs,
occasional WBCs
Differential Diagnosis
Active
Problem
List
1. Fever
2. AMS
3. Hyponatremia
1.
2.
3.
4.
PMH
HIV
Schizoaffective
disorder
Akylosing
spondylitis
Chronic
Hepatitis B
Infectious: Sepsis of any origin,
meningoencephalitis, brain abscess
Autoimmune: CNS vasculitis, Still’s disease
Malignancy: Lymphoma, leukemia
Environmental: Heat stroke
Toxins: Neuroleptic malignant syndrome,
salicylate overdose, serotonin syndrome,
anticholinergic toxicity, sympathomimetic
toxicity
Metabolic: Thyrotoxicosis
Chest X ray
CT Head
MR Brain
Clinical Course in the ED
Active
Problem
List
1. Fever
2. AMS
3. Hyponatremia
1.
2.
3.
4.
PMH
HIV
Schizoaffective
disorder
Akylosing
spondylitis
Chronic
Hepatitis B
Lumbar puncture was attempted six times and was finally
successful. The patient remained febrile.
Results of lumbar puncture showed:
WBC 206/mm3 with 86% lymphocytes
Glucose 52 mg/dL
Protein 91 mg/dL
No RBCs
Gram stain negative
Blood cultures were taken and empiric acyclovir was
initiated.
Interpreting CSF
Active
Problem
List
1. Fever
2. AMS
3. Hyponatremia
1.
2.
3.
4.
PMH
HIV
Schizoaffective
disorder
Akylosing
spondylitis
Chronic
Hepatitis B
Results of lumbar puncture showed:
WBC 206/mm3 with 86% lymphocytes
Glucose 52 mg/dL
Protein 91 mg/dL
No RBCs
Gram stain negative
Etiology
WBC
cells/mm3
Bacterial
1000-5000
Neutrophil
<40
100-500
Viral
50-1000
Mononuclear
>45
50-200
Fungal
20-500
Mononuclear
<45
>45
Tuberculous
50-300
Mononuclear
<40
50-300
0-5
--
45
45
Normal
Primary cell type Glucose
mg/dL
Protein
mg/dL
Differential Diagnosis for Aseptic
Meningitis
Active
Problem
List
1. Aseptic
Meningitis
2. Hyponatremia
1.
2.
3.
4.
PMH
HIV
Schizoaffective
disorder
Akylosing
spondylitis
Chronic
Hepatitis B
Infectious
Viral – enteroviruses, arboviruses, HSV, HIV,
measles, mumps, VZV, CMV, EBV
Bacterial – Parameningeal abscess,
Leptospirosis, Listeria, Brucella, Coxiella,
Borrelia, TB, Syphilis, Rickettsia, Ehrlichia
Fungal – Crypotococcus, coccidiodes,
histoplasma
Parasitic – Toxoplasmosis, taenia solium
Differential Diagnosis for Aseptic
Meningitis
Active
Problem
List
1. Aseptic
Meningitis
2. Hyponatremia
1.
2.
3.
4.
PMH
HIV
Schizoaffective
disorder
Akylosing
spondylitis
Chronic
Hepatitis B
Non-Infectious
Drug Induced – Ibuprofen, TMP-SMX, other
NSAIDs, Azathioprine, Lamotrigine, IVIg,
monoclonal antibodies
Malignancies – Lymphoma, leukemia,
metastases
Autoimmune – Sarcoidosis, Systemic Lupus
Erythematosis, Behcet’s, vaccine reaction
Clinical Course
Active
Problem
List
1. Aseptic
Meningitis
2. Hyponatremia
1.
2.
3.
4.
PMH
HIV
Schizoaffective
disorder
Akylosing
spondylitis
Chronic
Hepatitis B
The patient was admitted to the hospital floor on
a hospitalist team. Neurology and infectious
disease were consulted. The patient
continued having fevers >38ºC multiple times
per day for three days. Vancomycin and
ceftriaxone were added empirically, but he
continued to have fevers that would respond
to acetaminophen. His mental status
continued to fluctuate and he continued to
have back pain and stiff neck.
Clinical Course
Work-up for Aseptic Meningitis
Active
Problem
List
1. Aseptic
Meningitis
2. Hyponatremia
PMH
1. HIV
2. Schizoaffective
disorder
3. Akylosing
spondylitis
4. Chronic
Hepatitis B
Infectious workup:
Blood and CSF cultures – negative at 48 hours
CSF Cryptococcal antigen: negative
T-spot: negative
T pallidum Ab: negative
Lyme IgG and IgM Ab: negative
CSF HSV PCR: negative
CSF arbovirus panel: negative
CD4 count: 342
HIV viral load: 30 copies/mL
Rheumatologic workup:
ESR: 22
CRP: 0.56
Work-up for Aseptic Meningitis
Active
Problem
List
1. Aseptic
Meningitis
2. Hyponatremia
1.
2.
3.
4.
PMH
HIV
Schizoaffective
disorder
Akylosing
spondylitis
Chronic
Hepatitis B
Drug Induced Aseptic Meningitis –
- Most common offending medications include
ibuprofen, other NSAIDs, lamotrigine.
- Difficult to test for and is often a diagnosis
of exclusion. Diagnosis depends on causal
relation with drug administration and is
confirmed with pharmacologic challenge
testing where medication is given and clinical
response is monitored.
= ibuprofen administration
Drug-Induced Aseptic Meningitis
Active
Problem
List
1. Druginduced
Aseptic
Meningitis
2. Hyponatremia
1.
2.
3.
4.
PMH
HIV
Schizoaffective
disorder
Akylosing
spondylitis
Chronic
Hepatitis B
History and Epidemiology
First described in 1978 in a 26 year old female
with lupus who developed meningitis while
taking ibuprofen. The diagnosis was
confirmed with challenge testing.
Body of evidence regarding drug-induced aseptic
meningitis (DIAM) is largely based on case
reports
A 2006 review article reviewed 71 cases of
NSAID-induced meningitis. 61% of cases had
an underlying connective tissue disease
HIV has been mentioned as a predisposing
condition as well
Exact incidence is unknown
Drug-Induced Aseptic Meningitis
Active
Problem
List
1. Druginduced
Aseptic
Meningitis
2. Hyponatremia
1.
2.
3.
4.
PMH
HIV
Schizoaffective
disorder
Akylosing
spondylitis
Chronic
Hepatitis B
Clinical Features
Rodriguez, SC. Characteristics
of meningitis caused by
ibuprofen: report of 2
cases and review of the
literature. Medicine
(Baltimore) 2006 Jul;
85(4) 214-20.
Drug-Induced Aseptic Meningitis
Active
Problem
List
1. Druginduced
Aseptic
Meningitis
2. Hyponatremia
1.
2.
3.
4.
PMH
HIV
Schizoaffective
disorder
Akylosing
spondylitis
Chronic
Hepatitis B
Proposed Mechanism
Thought to be a type III hypersensitivity
reaction against the drug or metabolite
One suggested mechanism is hypersensitivity to
the drug as a hapten with an CSF-protein
which would explain the limitation of the
inflammation to only the central nervous
system.
Some patients have idiosyncratic reactions to
only one NSAID while others have been
described as having reactions to several drugs
within the class
Drug-Induced Aseptic Meningitis
Active
Problem
List
1. Druginduced
Aseptic
Meningitis
2. Hyponatremia
1.
2.
3.
4.
PMH
HIV
Schizoaffective
disorder
Akylosing
spondylitis
Chronic
Hepatitis B
Diagnosis
CSF evidence of meningitis with neutrophil or
lymphocyte predominance, usually elevated
protein and normal glucose
Exclude infectious causes
There must be temporal relationship between a
known offending agent and symptoms
Symptoms should resolve rapidly after
withdrawing offending agent
Can be confirmed with challenge testing, though
no evidence based protocol exists
Drug-Induced Aseptic Meningitis
Active
Problem
List
1. Druginduced
Aseptic
Meningitis
2. Hyponatremia
1.
2.
3.
4.
PMH
HIV
Schizoaffective
disorder
Akylosing
spondylitis
Chronic
Hepatitis B
Management
Discontinue offending agent
Use other drugs in the class with caution
Consider workup for underlying autoimmune
condition
Follow-up with patient
Active
Problem
List
1. Druginduced
Aseptic
Meningitis
2. Hyponatremia
1.
2.
3.
4.
PMH
HIV
Schizoaffective
disorder
Akylosing
spondylitis
Chronic
Hepatitis B
Ibuprofen was discontinued and both ibuprofen
and etodolac were placed on the patient’s
allergy list. Empiric antibiotics were
discontinued as well.
The patient had no further fevers once ibuprofen
was discontinued and delirium improved over
the next 24 hours.
Did well for six months, then began developing
ataxia of hands, cognitive slowing, fixed
dilated right pupil, tremor. He was diagnosed
with Parkinsonism by neurology and it is
unclear if this is related to psychotropic
medications, HIV or underlying Parkinson
disease.
Take Home Points from Case
Active
Problem
List
1. Druginduced
Aseptic
Meningitis
2. Hyponatremia
1.
2.
3.
4.
PMH
HIV
Schizoaffective
disorder
Akylosing
spondylitis
Chronic
Hepatitis B
Drug-induced aseptic meningitis is a syndrome
that can be clinically indistinguishable from
bacterial meningitis but should be suspected
in a patient on commonly offending agents
(NSAIDs, TMP-SMX, lamotrigine, azathioprine,
IV Ig) especially in those with underlying
connective tissue disease.
Ibuprofen and other NSAIDs are widely used
drugs and it is important for physicians to be
aware of the potentially severe side effects
References
1.
2.
3.
4.
5.
Mandell, Douglas, and Bennett. Principles and Practice
of Infectious Disease. Seventh Edition. 2010
Jolles, Stephen. Drug Induced Aseptic Meningitis –
Diagnosis and Management. Drug Safety 2000 Mar;
22(3): 215-226.
Moreno-Ancillo, A. Ibuprofen-Induced Aseptic
Meningoencephalitis Confirmed by Drug Challenge. J
Investig Allergol Clin Immunol 2011; Vol 21(6): 484-487.
Rodriguez, SC. Characteristics of meningitis caused by
ibuprofen: report of 2 cases and review of the literature.
Medicine (Baltimore) 2006 Jul; 85(4) 214-20.
Lee, RZ, Ibuprofen-induced aseptic meningoencephalitis.
Rheumatology. 2002 41(3): 353-355.