Case Study: Cough and a Bad Case Study: Cough and a Bad HeadacheHeadache

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 HistoryPast 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

MedicationsMedications

Aspirin 81mg per daySimvastatin 20mg at hsValsartan 80mg per dayGlucosamineMVI

Social HistorySocial 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 HistoryFamily History

Brother who died at age 53 of acute MIBrother with throat cancer in his 60sSon with Acute Intermittent Porphyria

Visit 1Visit 1

No distress, vitals unremarkableExam normal except for some edema in the

nares and posterior nasal drainage.

Diagnosed with sinusitisTreated with 5 day course of Azithromycin

Visit 2Visit 2

Cough persists (now 4 weeks)Dyspnea on exertion slightly worseDifficulty sleeping (supine or sitting) due to

coughBifrontal headache persistsNo sputum, fevers or chillsExam and vitals normal

Visit 2…Visit 2…

CXR read as negativePPD (read as negative)Office spirometry:

FEV1 3.11 (90%) FVC 4.14 (94%) No drop in O2 saturation with ambulation

Levofloxacin 500mg per day

Visit 3Visit 3

Cough persisting (now 6 weeks)Ongoing mild dyspnea on exertionAfebrile without sputum productionBifrontal headache persisting, right side

greater than leftExam and vitals remain unremarkable

Visit 3…Visit 3…

Sinusitis with cough from post nasal drip vs.

Separate conditions? (sinus disease + pulm)

CT chest and CT sinusLevofloxacin 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 callTelephone call

Patient started on prednisone 40mg with taper over 8 days

Antibiotics continued (day # 18)

Visit 4Visit 4Cough improved Dyspnea improvedHeadache resolved rapidlyExam and vitals normalPrednisone taper continuedLevaquin continued (day #20)Referred to pulmonary medicine

Pulmonary consultPulmonary 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

Visit 5Visit 5Headache 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 improvedDyspnea improved but still presentVitals and exam remain unremarkableESR 53, CBC nc/nc anemia (11.3/34%)

Visit 5…Visit 5…

High dose Steroids started

Temporal artery biopsy arranged

Follow 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 2Pulmonary 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

Pulmonary follow up 3Pulmonary follow up 3

Lung biopsy showed findings of Usual Interstitial Pneumonia

Started N-acetylcysteine 600mg po BIDProton pump inhibitor BID

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

Occam’s RazorOccam’s Razor(entities should not be multiplied beyond necessity)(entities should not be multiplied beyond necessity)

vs.vs.

Hickham’s DictumHickham’s Dictum(patients can have as many diseases as they please)(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?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

Usual Interstitial PneumoniaUsual Interstitial PneumoniaStandard treatment has been steroids with

either azathioprine or cyclophosphamideAzathioprine 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…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.

Usual Interstitial Pneumonia…Usual Interstitial Pneumonia…Acid SuppressionInterferon gamma-bPirfenidone (TGF-b inhibitor)ColchicineMethotrexatePenicillamineCyclosporineTransplant

Usual Interstitial Pneumonia…Usual Interstitial Pneumonia…N-acetylcysteine may be effective via the

anti-oxidant effect of increased glutathione levels in the lung

EBM evaluation of Acetylcysteine EBM evaluation of Acetylcysteine Trial Trial

(Demedts et al. NEJM 2005; 353:2229)(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

EBM evaluation of Acetylcysteine EBM evaluation of Acetylcysteine Trial…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

EBM evaluation of Acetylcysteine EBM evaluation of Acetylcysteine Trial…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)

Printout of Slides and Printout of Slides and References are availableReferences 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.