Transcript Case Study: Cough and a Bad Headache

Case Study: Cough and a Bad
Headache
entia non sunt multiplicanda praeter necessitatem
Doug Kutz MD
75yo male presents to clinic with 10 day history
of a cough, sore throat, fatigue and difficulty
sleeping at night
• Mild dyspnea with exertion
• Bifrontal headache
• No sputum production
• No fevers or chills
• No nightsweats or weight loss
Past Medical History
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Coronary Artery Disease; MI and PTCA ‘91
Hypertension
Hypercholesterolemia
Remote history of septic arthritis of the hip
Total hip arthroplasty 1985
Total Knee arthroplasty 1995
Medications

Aspirin 81mg per day
 Simvastatin 20mg at hs
 Valsartan 80mg per day
 Glucosamine
 MVI
Social History
Retired civil servant
Married with 3 children
30 pack year history of tobacco through 1983
1 alcoholic beverage per week
No pets at home
Hobbies: fishing and remodeling
Travel to El Salvador for 1 week, 3months earlier, some
diarrhea upon return but no respiratory symptoms
Family History

Brother who died at age 53 of acute MI
 Brother with throat cancer in his 60s
 Son with Acute Intermittent Porphyria
Visit 1
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No distress, vitals unremarkable
 Exam normal except for some edema in the
nares and posterior nasal drainage.
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Diagnosed with sinusitis
 Treated with 5 day course of Azithromycin
Visit 2
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Cough persists (now 4 weeks)
 Dyspnea on exertion slightly worse
 Difficulty sleeping (supine or sitting) due to
cough
 Bifrontal headache persists
 No sputum, fevers or chills
 Exam and vitals normal
Visit 2…
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CXR read as negative
 PPD (read as negative)
 Office spirometry:
FEV1 3.11 (90%) FVC 4.14 (94%)
 No drop in O2 saturation with ambulation
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Levofloxacin 500mg per day
Visit 3
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Cough persisting (now 6 weeks)
 Ongoing mild dyspnea on exertion
 Afebrile without sputum production
 Bifrontal headache persisting, right side
greater than left
 Exam and vitals remain unremarkable
Visit 3…
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Sinusitis with cough from post nasal drip
vs.
Separate conditions? (sinus disease + pulm)
CT chest and CT sinus
 Levofloxacin continued (day # 14)
Chest CT: No infiltrates. Emphysematous
changes with scattered sublpeural bullae in
the bases. Honeycombing in the posterior
right lower lobe. Changes improve slightly
when the patient is placed prone.
Sinus CT: Clear sphenoid, ethmoid and frontal
sinuses. Fluid/mucous on the floor of both
maxillary sinuses, some mucosal thickening
along the lateral and medial walls.
Telephone call
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Patient started on prednisone 40mg with
taper over 8 days
 Antibiotics continued (day # 18)
Visit 4
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Cough improved
 Dyspnea improved
 Headache resolved rapidly
 Exam and vitals normal
 Prednisone taper continued
 Levaquin continued (day #20)
 Referred to pulmonary medicine
Pulmonary consult

Cough more likely due to sinusitis than to
changes on CT of the chest
– Lack of alveolar filling defects
– Slight improvement when the patient is prone
– Bilateral sinusitis on sinus CT
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Recommended: Full PFTs, finish 28 days of
antibiotics, taper off prednisone, then repeat
sinus CT
Visit 5
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Headache recurred with stopping steroids,
now with photophobia, 5-7/10 in severity,
constant, left greater than right, awakens
him at night, no n/v or CNS symptoms.
 Cough still improved
 Dyspnea improved but still present
 Vitals and exam remain unremarkable
 ESR 53, CBC nc/nc anemia (11.3/34%)
Visit 5…
High
dose Steroids started
Temporal artery
Follow
biopsy arranged
up Sinus CT changed to MRI brain
MRI brain showed a 4mm aneurysm (after
MRA added) adjacent to the origin of
the left middle cerebral artery
Sinuses clear
Temporal artery biopsy: Granulomatous
changes consistent with temporal
arteritis
Pulmonary Follow up 2
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Worsening dyspnea on exertion, though
cough improved
 Full PFTs showed FEV1 2.87 (83%) and
FVC 3.90 (85%) as well as a diffusion
capacity of 44% predicted
 Repeat CT chest showed increased
honeycombing and ground glass changes
 Recommend: Lung Biopsy
Pulmonary follow up 3
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Lung biopsy showed findings of Usual
Interstitial Pneumonia
 Started N-acetylcysteine 600mg po BID
 Proton pump inhibitor BID
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Sinusitis with upper air way cough
• Then
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Interstitial Lung Disease, Sinusitis
• Then
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Cerebral Aneurysm, ILD, Sinusitis
• Then
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Temporal Arteritis, Cerebral Aneurysm,
Idiopathic Pulmonary Fibrosis, Sinusitis
Occam’s Razor
(entities should not be multiplied beyond necessity)
vs.
Hickham’s Dictum
(patients can have as many diseases as they please)
How should these effect diagnostic testing?
– Probability of one rare disease vs. several
common ones
– Potential harm if undiagnosed
– Biologic variables and predisposition
Reconcilliation?
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Temporal Arteritis can present with a
chronic cough (his cough resolved with
steroids)
 Temporal Arteritis can be associated with
vascular complications such as intracranial
aneurysms
Usual Interstitial Pneumonia
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Standard treatment has been steroids with
either azathioprine or cyclophosphamide
 Azathioprine with prednisone:
– 27 patients with newly diagnosed UIP
randomly assigned to either prednisone alone or
prednisone + azathioprine
– After 9 years the combination group had
improved DLco, VC and mortality (43% vs.
77%)
– Not statistically significant
Usual Interstitial Pneumonia…
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Cyclophosphamide and Prednisone:
– 43 patients with previously untreated IPF were
randomly assigned to cyclophosphamide with
prednisone vs. prednisone alone for 3 years
– The combination group had improved or stable
symptoms (38% vs. 23%)
– The treatment group had a lower mortality
(14% vs. 45%)
– Not statistically significant.
Usual Interstitial Pneumonia…
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Acid Suppression
 Interferon gamma-b
 Pirfenidone (TGF-b inhibitor)
 Colchicine
 Methotrexate
 Penicillamine
 Cyclosporine
 Transplant
Usual Interstitial Pneumonia…
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N-acetylcysteine may be effective via the
anti-oxidant effect of increased glutathione
levels in the lung
EBM evaluation of Acetylcysteine
Trial
(Demedts et al. NEJM 2005; 353:2229)
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Sponsored by Zambon (makers of fluimicil)
 Inclusion criteria
– Ages 18-75
– Diagnosis based on negative BAL and CT or
biopsy proven UIP
– Minimum 3 months of disease
– VC < 80%, TLC < 90%, DLco < 80% predicted
– Dyspnea on exertion
EBM evaluation of Acetylcysteine
Trial…
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Intervention: 600mg TID N-acetylcysteine
and standard weight based dose of
prednisone and azathioprine
 Outcomes:
– Primary: change in VC and Dlco
– 2nd: Symptoms, exercise, and radiology
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Intention to treat
 Groups simillar at baseline
EBM evaluation of Acetylcysteine
Trial…
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Results
– 30% drop out in both groups
– VC improved mean of 9% or 1.8L
(P= 0.02, CI 0.03-0.32)
– DLco improved 24%
(P= 0.003, CI 0.27-1.23)
– No effect on secondary outcomes (symptoms,
mortality 9% vs 11%)
– Less marrow toxicity in study group (p0.03)
My Opinion:
Does not appear to be any adverse
effects and might help slow the decline
in lung function in the context of
standard therapy.
The authors themselves support
cautious interpretation.
Further studies are needed.
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References are available