Transcript No Slide Title

Johns Hopkins CPC#4
David R. Moller, M.D.
Johns Hopkins University
Baltimore, USA
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
History of Present Illness
The patient is a 39 year old African American female who was diagnosed with pulmonary
sarcoidosis 1.5 years prior to JHH admission after presenting with shortness of breath. At that
time, radiologic studies showed parenchymal infiltrates and mediastinal adenopathy. The
pathology of a lung wedge resection 1 year prior to admission was reviewed at JHH and showed
granulomatous inflammation (should be good for sarc; exceptions: mycobact, fungal, rare malig).
Her FVC was 70% predicted and DLCO 57% predicted. She began oral corticosteroid therapy
without significant symptomatic improvement (red flag). Six months prior to admission, the
patient had continued dypsnea and a transthoracic ultrasound and right heart catheterization
showed the presence of pulmonary hypertension with mean PA pressure 50-55 mmHg (out of
proportion to ILD/PFTs). She was started on an oral endothelin antagonist (Bosentan) which
was discontinued after 5 months due no improvement in symptoms (soft flag). The patient was
admitted two separate times to an outside hospital 3 and 1 month prior to JHH admission for
suspected pneumonia (red flag—not pulm sarc if compliant; predisposing factors for recurrent
infection—bronchial stenosis? CVID? Chronic infections eg fungal, mycobact? Alt dx: e.g.
COP). At that time, during a 6 minute walk test, her SaO2 fell from 94% to 83% while inspiring
4 L/min nasal oxygen ( out of proportion to PFTs).
Two days prior to JHH admission, the patient was again admitted to the critical care unit of an
outside hospital for worsening shortness of breath and increased oxygen need. By report, a chest
x-ray showed a bilateral lung infiltrate with the left lung being worse than the right (not pulm
sarc). She was started on cefotaxime and azithromicin for bacterial pneumonia and due to a
persistent pulmonary infiltrate, the patient was transferred to JHH for further evaluation and
management.
Social History
The patient lives at home with her husband, daughter, and son. She is a registered nurse. Prior
to her decline in health, she had worked with mentally handicapped individuals. (exposure to TB,
HIV, other infections) The patient has a remote smoking history of one year. She occasionally
drinks alcohol.
Medications (prior to presentation to outside ED)
Bactrim 1 single strength/day (should be good PCP prophylaxis, esp in sarc, only on pred)
Prednisone 20 mg/day (if compliant, treats pulm, most cardiac, most pulm vasc inflammation
from sarcoidosis, but not fibrosis)
KCl
Lasix 20 mg/day
Nystatin
Oxygen 4 L/min
Allergies
No known drug allergies.
Review of Systems
The patient reports pink frothy sputum production, wheezing, and a 3 pillow orthopnea. The
patient does not report chest pain.
Physical Exam (upon transfer)
 T: 36.2 C BP: 99/79 P: 94 RR: 33 SaO2: 95% on 4L NC
 General: NAD, obese African American female, awake and alert.
 HEENT: Normocephalic, atraumatic, extra-ocular movements intact, sclera anicteric,
mucosal membrane moist. A white papular lesion was present on the glossal surface.
(?candida?other-TB, fungal, malig, red herring)
 CV: Regular rate and rhythm. Jugular venous distension to the mid-neck while reclining
at 30o. Normal S1 with a wide S2 and prominent P2. There is a 2-3/6 systolic murmur at
the midsternum that is not heard at the apex or the axilla (most c/w TR, no bruit).
 Lungs: No wheezes, crackles, or rhonci. (typical for sarcoidosis, equal breath sounds?)
 Abdomen: Soft, nontender, nondistended, positive bowel sounds.
 Extremities: No clubbing, cyanosis, or edema,, capillary refill <2s, 2+ pulses throughout.
Neuro: Alert and oriented x 3, cranial nerves II-XII intact, sensation intact to fine touch, normal
muscle bulk and tone, coordination grossly normal.
Laboratory Values (upon transfer)
 Na 134; K 4.5; Cl 101; HCO3 18 (suggests no chronic hypercapnia); BUN 20; Cr 1.0;
Glucose 159; Calcium 7.6
 WBC 12.6;Hct 34.8%; Platelet 233k;
Pulmonary Function Tests (outside hospital 1 month prior to admission)
FEV1/FVC 85%, FVC 60% predicted, DLCO 53% predicted (mod restriction, modsevere
reduction in diffusing capacity: worse— and does not explain degree of 02 desaturation,
pulm htn)
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
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
Air bronchograms
No med
shift,atelectasis
Med-widened
?LNs only
Cavity?
Prob RV
enlargement?cardiac sarc
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 lymphadenopathygeneralized LN: Not consistent with sarcoidosis esp with tx
• matted LN mass: histo,TB, other fungal >lymphoma
Differential Diagnosis of Granulomatous
Lung Disease
Non-infectious
Infectious
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Sarcoidosis*
• Mycobacterial*
Chronic beryllium disease*
• Fungal—histo, blasto, cocci, etc*
Hypersensitivity pneumonitis
• Protozoal—toxoplasmosis
Wegener’s granulomatosis
• Spirochetal- T. pallidum
Churg-Strauss Syndrome
• Bacterial-brucella, yersinia
Necrotizing sarcoid granulomatosis
Lymphoma*
Misc.
Lung cancer, other metastatic cancer
• Bronchiolitis obliterans organizing
Lymphomatoid granulomatosis
pneumonia (BOOP)
Crohn disease
• Lymphocytic interstitial pneumonitis
Pneumoconiosis (silicosis)
• Sjogren’s syndrome
Common variable immunodeficiency
Blau syndrome
*show typical compact epithelioid granulomas
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
Sarcoidosis Associated Pulmonary Hypertension
• Pulmonary hypertension prevalence
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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
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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)
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
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
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
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
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