Case Study: Cough and a Bad Headache

1. Case Study: Cough and a Bad Headache entia non sunt multiplicanda praeter necessitatem Doug Kutz MD

3. 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

4. Medications Aspirin 81mg per day Simvastatin 20mg at hs Valsartan 80mg per day Glucosamine MVI

5. Social History

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

7. 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

8. 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

9. 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

10. 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

11. Visit 3� Sinusitis with cough from post nasal drip vs. Separate conditions? (sinus disease + pulm) CT chest and CT sinus Levofloxacin continued (day # 14)

13. Telephone call Patient started on prednisone 40mg with taper over 8 days Antibiotics continued (day # 18)

14. Visit 4 Cough improved Dyspnea improved Headache resolved rapidly Exam and vitals normal Prednisone taper continued Levaquin continued (day #20) Referred to pulmonary medicine

15. 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

16. 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%)

17. Visit 5�

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

19. Temporal artery biopsy: Granulomatous changes consistent with temporal arteritis

20. 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

21. Pulmonary follow up 3 Lung biopsy showed findings of Usual Interstitial Pneumonia Started N-acetylcysteine 600mg po BID Proton pump inhibitor BID

22. 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

23. 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

24. 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

25. 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

26. 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.

27. Usual Interstitial Pneumonia� Acid Suppression Interferon gamma-b Pirfenidone (TGF-b inhibitor) Colchicine Methotrexate Penicillamine Cyclosporine Transplant

28. Usual Interstitial Pneumonia� N-acetylcysteine may be effective via the anti-oxidant effect of increased glutathione levels in the lung

29. EBM evaluation of Acetylcysteine Trial (Demedts et al. NEJM 2005; 353:2229) 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

30. 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

31. 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)

32. Printout of Slides and References are available