1. David R. Moller, M.D. Johns Hopkins University Baltimore, USA
Johns Hopkins CPC#4
David R. Moller, M.D.
Johns Hopkins University
Baltimore, USA

2. General Approach to Difficult to Manage Sarcoidosis
Biopsy never diagnostic.
Always revisit diagnosis or consider additional pathologic processes when either clinical course or clinical manifestations deviate from the expected or the typical.
Consider:
Not sarcoidosis
Sarcoidosis plus independent process-e.g. infection, PE, CHF
Sarcoidosis plus associated process- e.g. CVID, CTD, others
Treatment effects
Rare manifestations of sarcoidosis do occur

7. Asymmetric infiltrates not pulm sarc
Bilateral gg-not pulm sarc with tx.
Denser peripheral infiltrates, air bronchograms prob pneumonia
? More bronchiectasis, cystic lesions on L--?structural abn

8. Matted extensive anterior/middle mediastinal LA: very unusual distribution, asym for sarc--
! Assume not sarcoidosis
Big SVC, Big PAs, c/w pulm htn
Hilar LA and central infiltrates:
Narrowed, thickened bronchi

10. Air bronchograms
No med shift,atelectasis
Med-widened
?LNs only
Prob RV enlargement-?cardiac sarc
Cavity?

11. Clues from the chest CT and radiograph
Possibly explained by multisystem sarcoidosis
RV enlargement from pulmonary htn (?cardiac sarc)
Bilateral hilar lymphadenopathy + mild ILD
Bronchiectasis
Not explained by pulmonary sarcoidosis:
Bilat ground glass—not pulm sarcoidosis on Pred 20mg/d, ?infection ?CHF
Denser L pulm infiltrate: acute/subacute pneumonia
More extensive L bronciectasis/cystic changes suggest possible chronic process ?bronchial stenosis—but no atelectasis, no obstructive impairment
Left sided paraaortic upper mediastinal lymphadenopathy-generalized LN: Not consistent with sarcoidosis esp with tx
matted LN mass: histo,TB, other fungal >lymphoma

12. Differential Diagnosis of Granulomatous Lung Disease
Non-infectious
Infectious
Sarcoidosis*
Chronic beryllium disease*
Hypersensitivity pneumonitis
Wegener’s granulomatosis
Churg-Strauss Syndrome
Necrotizing sarcoid granulomatosis
Lymphoma*
Lung cancer, other metastatic cancer
Lymphomatoid granulomatosis
Crohn disease
Pneumoconiosis (silicosis)
Common variable immunodeficiency
Blau syndrome
Mycobacterial*
Fungal—histo, blasto, cocci, etc*
Protozoal—toxoplasmosis
Spirochetal- T. pallidum
Bacterial-brucella, yersinia
Misc.
Bronchiolitis obliterans organizing pneumonia (BOOP)
Lymphocytic interstitial pneumonitis
Sjogren’s syndrome
*show typical compact epithelioid granulomas

13. What is the differential diagnosis of granulomatous inflammation in the lung in this patient?
Differential diagnosis of bilateral hilar and mediastinal lymphadenopathy plus interstitial lung disease
Surgical lung bx should reasonably exclude noninfectious granulomatous lung disease e.g. Wegener granulomatosis, hypersensitivity pneumonitis, cryptogenic organizing pneumonia
Never can completely exclude infection e.g., mycobacterial, fungal disease or (rarely) malignancy e.g., lymphoma
Look for extrapulm manifestations of sarcoidosis to confirm diagnosis

14. Sarcoidosis Associated Pulmonary Hypertension
Pulmonary hypertension prevalence
6% unselected pulm sarcoidosis patients
50% patients with dyspnea disproportionate to PFTs
70-80% in advanced lung disease
Higher when measuring exercise induced pulm htn
Multiple potential mechanisms
Bronchovascular distribution of inflammation
Advanced fibrocystic lung disease (loss of pulmonary capillary bed)
Extrinsic compression of pulmonary arteries by LN, mediastinal fibrosis
Cardiac sarcoidosis with systolic, diastolic dysfunction
Hypoxic vasoconstriction
Primary pulmonary vascular involvement (granulomatous arteritis)
Veno-occlusive disease (rare)

15. What is the most likely cause of her pulmonary hypertension?
Common causes of pulmonary hypertension in sarcoidosis
Sleep apnea (mild pulm htn)
Advanced interstitial lung disease (stage 3, 4 fibrocystic sarc)
Chronic pulmonary embolism (must rule out)
L heart failure ( diastolic dysfunction, cardiac sarcoidosis)
Pulmonary vascular sarcoidosis
Interstitial lung disease does not explain pulm htn
Diffusing capacity does not correlate with pulm htn
DLCO decreased in pulm htn secondary to fibrocystic pulm sarcoidosis
Note: these same causes may be present in infectious granulomatous diseases

16. Cardiac Sarcoidosis: Clinical Manifestations
Common
Arrhythmias
Heart block/conduction defects
Congestive heart failure
Sudden death
Rare (<10% all cardiac sarcoidosis)
R ventricular involvement
Valvular dysfunction
Pericarditis
Myocardial mass
Coronary vessel involvement

17. What are the possible causes of the patient’s worsening shortness of breath over months and eventual demise??
Chronic slowly progressive dyspnea possibly explained by multisystem sarcoidosis with
Interstitial lung disease (in part)
Pulmonary hypertension- secondary pulm arterial/arteriolar involvement
? cardiac sarcoidosis
Treatment unresponsiveness ? Suspect pulm htn and fibrosis
Worsening dyspnea over months not explained by sarcoidosis:
Left sided infiltrates/pneumonia
L sided mediastinal lymphadenopathy ?new

18. What are the possible causes of the patient’s worsening shortness of breath over months and eventual demise?
Multisystem sarcoidosis + infection
pulmonary (ILD)+BHA plus L>R bronchiectasis
pulmonary hypertension from pulm vascular involvement-?prox or distal arterial; possible cardiac involvement
L sided infiltrates: Secondary CAP or HAP (?bronchial stenosis, rule out CVID)
L mediastinal LA: ? secondary to histoplasmosis, mycobacterial, other fungal infection or nocardia which could also explain L pneumonia
Infection—chronic histoplasmosis vs tuberculosis
Infiltrates, mediastinal lymphadenopathy, tongue papule?, pulm htn+ from pulm artery involvement from med/hilar LN, fibrosis
Lymphoma ± sarcoidosis plus infection

19. What are the possible causes of the patient’s worsening shortness of breath over months and eventual demise?
PEA arrest
Pulmonary - Respiratory arrest with hypoxia
Mechanical –
tension pneumothorax: fibrocystic lesions
cardiac rupture with severe CHF (papillary muscles, aneursym)
cardiac tamponade: pericarditis
Preload and afterload changes (severe pulm htn)
pulmonary embolus
sepsis (pneumonia, ?mediastinitis)
Metabolic changes –no evidence
Note: if arrhythmia, heart block at CP arrest, suspect cardiac sarc