Case Study: Cough and a Bad Headache

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Case Study Cough and a Bad Headache

• entia non sunt multiplicanda praeter necessitatem
• Doug Kutz MD

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• 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

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Past Medical History

• 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

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Medications

• Aspirin 81mg per day
• Simvastatin 20mg at hs
• Valsartan 80mg per day
• Glucosamine
• MVI

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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
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Family History

• Brother who died at age 53 of acute MI
• Brother with throat cancer in his 60s
• Son with Acute Intermittent Porphyria

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Visit 1

• No distress, vitals unremarkable
• Exam normal except for some edema in the nares
  and posterior nasal drainage.
• Diagnosed with sinusitis
• Treated with 5 day course of Azithromycin

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Visit 2

• 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

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Visit 2

• 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
• Levofloxacin 500mg per day

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Visit 3

• 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

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Visit 3

• Sinusitis with cough from post nasal drip vs.
  Separate conditions? (sinus
  disease pulm)
• CT chest and CT sinus
• Levofloxacin continued (day 14)

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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.
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Telephone call

• Patient started on prednisone 40mg with taper
  over 8 days
• Antibiotics continued (day 18)

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Visit 4

• Cough improved
• Dyspnea improved
• Headache resolved rapidly
• Exam and vitals normal
• Prednisone taper continued
• Levaquin continued (day 20)
• Referred to pulmonary medicine

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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
• Recommended Full PFTs, finish 28 days of
  antibiotics, taper off prednisone, then repeat
  sinus CT

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Visit 5

• 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)

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Visit 5

• High dose Steroids started
• Temporal artery biopsy arranged
• Follow up Sinus CT changed to MRI brain

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• MRI brain showed a 4mm aneurysm (after MRA added)
  adjacent to the origin of the left middle
  cerebral artery
• Sinuses clear

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• Temporal artery biopsy Granulomatous changes
  consistent with temporal arteritis

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Pulmonary Follow up 2

• 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

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Pulmonary follow up 3

• 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
• Interstitial Lung Disease, Sinusitis
• Then
• Cerebral Aneurysm, ILD, Sinusitis
• Then
• Temporal Arteritis, Cerebral Aneurysm, Idiopathic
  Pulmonary Fibrosis, Sinusitis

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Occams Razor(entities should not be multiplied
beyond necessity)vs.Hickhams 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

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Reconcilliation?

• 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

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Usual Interstitial Pneumonia

• 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

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Usual Interstitial Pneumonia

• 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.

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Usual Interstitial Pneumonia

• Acid Suppression
• Interferon gamma-b
• Pirfenidone (TGF-b inhibitor)
• Colchicine
• Methotrexate
• Penicillamine
• Cyclosporine
• Transplant

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Usual Interstitial Pneumonia

• N-acetylcysteine may be effective via the
  anti-oxidant effect of increased glutathione
  levels in the lung

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EBM evaluation of Acetylcysteine Trial (Demedts
et al. NEJM 2005 3532229)

• 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 lt 80, TLC lt 90, DLco lt 80 predicted
• Dyspnea on exertion

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EBM evaluation of Acetylcysteine Trial

• 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
• Intention to treat
• Groups simillar at baseline

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EBM evaluation of Acetylcysteine Trial

• 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)

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Printout of Slides and References are available

• 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.