Internal Medicine Correlations and Clinical Scenarios (CCS) USMLE Step 3

CASE 7: Sarcoidosis

Setting: office

CC:I get tired and winded when I walk.”

VS: BP: 110/70 mm Hg; T: 98°F; R: 14 breaths/minute

HPI: A 32-year-old African American woman comes to the office complaining of intermittent episodes of shortness of breath. She has been told she has asthma and is intermittently placed on albuterol inhalers and oral steroids. Her shortness of breath clears up and she stops all medications until it recurs a few months later. She also has a cough that is not productive of sputum.

PMHX:

Image Skin lesions intermittently: undiagnosed

Medications:

Image None routinely; steroids and inhaled beta-agonists intermittently

PE:

Image General: well-nourished

Image Chest: some crepitations bilaterally

Image Skin: dark lesion on face, reddish-brown tender lesions on shins

Image Cardiovascular: loud P2

Initial Orders:

Image Chest x-ray

Image Pulse oximeter

Pulmonary hypertension causes a loud P2.

The patient returns a week later to discuss the findings on the chest x-ray. There is no shortness of breath acutely and no treatment is started.

New visits to the clinic or office should always start with an “Interval History” to see what has been going on since the last visit. In this way, you will assess both new symptoms and the response to new medications.

Interval History: “Patient has some mild decrease in exercise tolerance, but it has not changed recently. No dyspnea with household and work activities.”

Report:

Image Chest x-ray: bilateral hilar adenopathy

Hilar Adenopathy Etiology

• Lymphoma

• Thyroid

• Teratoma

• Sarcoid

• TB

With no fever, weight loss, or palpable peripheral adenopathy, it is hard to conclude that this is lymphoma or malignancy. Tuberculosis should give fever, cough, and sputum and would not give a “waxing and waning” presentation with intermittent episodes. Although there are no interstitial infiltrates, early sarcoid can present just with hilar adenopathy. The majority will never progress to having interstitial infiltrates.

Orders:

Image PFTs

Image Calcium blood

Image Calcium urine

Image Angiotensin-converting enzyme (ACE) level

Image CHEM-20

Reports:

Image Calcium: blood normal, urine elevated

Image ACE: elevated

Granulomas in sarcoid produce vitamin D.

Calcium is freely filtered at the glomerulus.

Report:

Image PFTs

Which of these is consistent with sarcoidosis?

image

Answer c. FEV1 58% [decreased], FVC 60% [decreased], TLC 56% [decreased]

Sarcoidosis is a pulmonary fibrosis that results in restrictive lung disease. All of the lung volumes are decreased, but they are down proportionately. The ratio of FEV1 to FVC is normal. Restrictive lung disease is present in sarcoid even when there is only adenopathy visible on the chest x-ray. Early fibrosis will not be visible on the chest x-ray.

The patient is informed that she likely has sarcoidosis (Figure 7-7). The skin lesions are likely sarcoid as well. Only 10% of patients with sarcoidosis have an elevated blood calcium level, but 60% to 75% have elevated urine calcium levels.

image

Figure 7-7. Proposed immunopathogenesis of sarcoidosis. An antigen, presently unknown, is engulfed and processed by an antigen-presenting cell (macrophage or dendritic cell). The processed antigen is presented to a T-cell receptor (TCR) of a T lymphocyte via an human leukocyte antigen (HLA) class II molecule. Once the HLA receptor and TCR have bound the processed antigen, numerous lymphokines and cytokines of the T helper 1 (Th1) class are released that lead to T-cell proliferation, recruitment of monocytes, and eventual granuloma formation. A few of these lymphokines and cytokines are shown, with those released by the antigen-presenting cells on the left and those released by lymphocytes on the right. IFN, interferon; IL, interleukin; TNF, tumor necrosis factor. (Reproduced with permission from Goldsmith LA, et al. Fitzpatrick’s Dermatology in General Medicine, 8th ed. [online] New York: McGraw-Hill; 2012.)

Which of the following is the most accurate test?

a. Lymph node biopsy on bronchoscopy

b. BAL with increased CD4 cells

c. Biopsy of erythema nodosum on shins

d. ACE level

Answer a. Lymph node biopsy on bronchoscopy

The biopsy of a lymph node is the single most accurate test. You can biopsy a peripheral node if it is present and affected. The BAL should show an increase in the ratio of CD4 helper cells to CD8 suppressor cells. ACE level is neither sufficiently sensitive or specific enough to be the most accurate diagnostic test.

The biopsy of erythema nodosum is specifically incorrect because it will show panniculitis or inflammation of soft tissues, but no granulomas.

Sarcoidosis is characterized by noncaseating granulomas.

Erythema nodosum does not show granulomas in sarcoid!

Which of the following is the most common site of sarcoid outside the lung?

a. Liver

b. Skin

c. CNS

d. Cardiac

e. Salivary gland

Answer b. Skin

All of the listed sites can be involved in sarcoidosis, but the most common area outside the lung is the skin. The liver, spleen, and kidney are involved, but they are almost always clinically silent.

Cardiac Sarcoid

• Atrioventricular (AV) block

• Restrictive cardiomyopathy

Neurosarcoidosis

• Hypothalamus

• Pituitary

• Bilateral facial palsy

The patient undergoes transbronchial biopsy, which shows noncaseating granulomas (Figure 7-8) in the lymph nodes. Currently, she is not short of breath.

image

Figure 7-8. Schematic representation of initial events of sarcoidosis. The antigen-presenting cell and helper T-cell complex leads to the release of multiple cytokines. This forms a granuloma. Over time, the granuloma may resolve or lead to chronic disease, including fibrosis. APC, antigen-presenting cell; HLA, human leukocyte antigen; IFN, interferon; IL, interleukin; TNF, tumor necrosis factor. (Reproduced with permission from Longo DL, et al. Harrison’s Principles of Internal Medicine, 18th ed., Vol 2. New York: McGraw-Hill; 2012.)

What is your next step?

a. Treat with intermittent pulses of prednisone to prevent exacerbations.

b. Treat with cyclophosphamide.

c. Treat with prednisone when episodes of shortness of breath arise.

d. Treat with anti-tumor necrosis factor (TNF) medications.

Answer c. Treat with prednisone when episodes of shortness of breath arise.

Asymptomatic sarcoidosis needs no therapy. When symptoms arise, they should quickly resolve when treated with steroids. This is exactly what has been happening to the patient when she got labeled as asthmatic. Steroid doses would improve the sarcoidosis, but it would seem to the physician as improving asthma.

The diffusing capacity of the lungs for carbon monoxide (DLCO) is low in sarcoid.

Carbon monoxide diffuses through tissue 200 times easier than oxygen.

On CCS, this sarcoidosis case is to be seen “as needed” on the clock. If there are no symptoms, no treatment or testing is needed.



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