cc: cough and dyspneaHPI: A 37-year old otherwise healthy, nonsmoker, African

American female presents to the clinic with complaints of progressive dyspnea on exertion, persistent cough, chest discomfort, and weight loss with decreased appetite.

She also complains of painful red lumps over both her legs and arms that are somewhat transient as well as a purplish rash over her face. Her symptoms have seemed to progress over the past 6 months. She doesn’t take any medications, and doesn’t recall any family history of similar symptoms. She consumes alcohol occasionally, denies IV drug use, works as a magazine editor, and lives at home with her husband and two cats.

Physical Exam

vs: temp-38.1°C (100.5°F), BP-132/82, HR-76, RR-20

General-no acute distressHEENT-normocephalic atraumaticNeck-supple, no thyromegaly, no cervical lymphadenopathyCV-regular rate and rhythm, normal S1/S2, no murmurs, rubs, or gallopsPulmonary-bilateral fine inspiratory cracklesAbdomen-soft, nontender, nondistended, + BS, no hepatosplenomegalyExtremities-mild clubbingSkin-bluish-purple maculopapular lesions over the bridge of the nose, eyes,

and cheeks, as well as multiple 2-3 cm erythematous nodules on the bilateral upper and lower extremities.

Physical Exam: Skin findings

Differential Diagnosis?

Differential Diagnosis• Sarcoidosis• Cat scratch Disease• Lofgren’s syndrome• Tuberculosis• Lymphomas (Follicular, Lymphoblastic, Mediastinal, Non-

Hodgkin)• Systemic Lupus Erythematosus• Histoplasmosis• Idiopathic pulmonary fibrosis• Pneumonconiosis• Lung Cancer (Non-Small Cell, Oat Cell, Diffuse Large Cell)

What labs/imaging would you like to order?

Labs:• CBC, electrolytes • Ca2+ • ALT/AST/alkaline phosphatase/bilirubin• BUN/SCr• UA• PPD• ECG• Pulmonary Function Tests (PFTs)• Opthalmologic • Angiotensin Converting Enzyme (ACE) levels

Imaging:• CXR

WBC 7,200/µLLymphocytes 10% (18-44%)Hemoglobin 13.5 g/dLPlatelet count 230,000/µL

Sodium 140 meq/LPotassium 4.1 meq/LChloride 95 meq/LBicarbonate 23 meq/LBUN 18 mg/dLCreatinine 1 mg/dLCalcium 11.5 mg/dL

ALT/AST/alk phos/bilirubin normal

Urinalysis 24-hr urine calcium elevatedPPD negative ACE levels elevated

Lab Results

Results: Imaging-CXR

What is your diagnosis?

Sarcoidosis• A multisystem granulomatous disorder of unknown

etiology. • Characterized pathologically by the presence of

noncaseating granulomas in the involved organs.• Most frequently involves the lungs commonly presenting

with cough, dyspnea, and chest pain• Other initial presentations include:– Bilateral hilar adenopathy– Pulmonary reticular opacities– Extrapulmonary manifestations such as skin (erythema

nodosum), joint, and/or eye lesions

SarcoidosisEpidemiology:• Prevalence est at 10-20 per 100,000 population• Varies in incidence among geographical regions and

can aggregate in families and specific races• 3-4 times more common in African Americans, F>M• Most commonly seen between the ages 20-40 years,

but not uncommon to diagnose in patients <20 years old

Etiology: Unknown

SarcoidosisPathophysiology:• Accumulation of T lymphocytes, mononuclear

phagocytes, and noncaseating granulomas • The noncaseating granulomas have a tightly packed

central area composed of-1. Macrophages2. Epithelioid cells3. Multinucleated giant cells

• The granulomas are then surrounded by lymphocytes, monocytes, mast cells, and fibroblasts

SarcoidosisNoncaseating granuloma

1

12

3

4

1. Lymphocytes2. Fibroblast3. Epitheloid cell4. Multinucleated

giant cell

SarcoidosisPathophysiology: Proposed Model• Antigen presenting cells present unknown antigen to

helper T cells and form a complex• This complex leads to release of multiple cytokines

including IFN-gamma, IL-2, IL-8, IL-12, IL-18, IFN-gamma, TNF, endothelin

• This leads to the formation of a granuloma

SarcoidosisExtrapulmonary manifestations:1. Dermatologic-maculopapular lesions, waxy pink nodular lesions, plaque like

lesions, erythema nodosum2. Ophthalmologic-anterior uveities, keratoconjunctivitis, retinal vasculitis3. Upper respiratory tract involvement-involvement of the larynx, pharynx, nares,

and/or sinuses4. Reticuloendothelial system-lymphadenopathy, hepatomegaly, splenomegaly5. Musculoskeletal-polyarthritis, granulomatous myositis6. Exocrine glands-swelling of the salivary glands, xerostomia7. Renal and electrolyte-abnormalities related to calcium8. Cardiovascular-granulomatous involvment of the ventricular system leading to

conduction blocks9. Neurologic-central and peripheral involvement 10. Gastrointestinal-involvement of the stomach, esophagus, appendix, colon, rectum11. Reproductive-involvement of the ovaries, endometrium, uterus, testes12. Thyroid-can cause a diffuse goiter, thyroid nodule

SarcoidosisExamples of extrapulmonary manifestations:

1 2 3 4

5 6

1. Erythema nodosum2. Sarcoid of spleen3. Neurosarcoidosis4. Sarcoid arthropathy5. Testicular sarcoidosis6. Anterior Uveitis

SarcoidosisTreatment:• Glucocorticoids most commonly used• Alternative approaches include immunosuppressive,

cytotoxic, and antimalarial drugs• Irradiation and organ transplantation have also been

performed

SarcoidosisFollow-up:• Monitor pulmonary function and CXR every 6-12 months• Assess for progression or resolution• Be vigilant for previously uninvolved organs becoming

affectedPrognosis:• Risk of loss of organ function is low• Many patients have acute self-limiting sarcoidosis and

resolve within 2-5 years• Others may have chronic disease that does not resolve

early

References:1 King Jr., TE. Clinical manifestations and diagnosis of sarcoidosis. In:

UpToDate, Flaherty, K, Hollingsworth, H, eds. UpToDate, Waltham, MA, 20122 Baughman RP, Lower EE. Chapter 329. Sarcoidosis. In: Longo DL, Fauci AS,

Kasper DL, Hauser SL, Jameson JL, Loscalzo J, eds. Harrison's Principles of Internal Medicine. 18th ed. New York: McGraw-Hill; 2012. http://www.accessmedicine.com/content.aspx?aID=9138725. Accessed November 20, 2012

3 Vardhanabhuti V, Venkatanarasimha N, Bhatnagar G, et. Al. Extra-pulmonary manifestations of sarcoidosis. Clinical Radiology. 2012; 67:263-376.

4 Unknown author. “Noncaseating Granuloma.” Online image. http://www.flickr.com/photos/78147607@N00/413882702. Accessed on Nov 20, 2012.

5 American Academy of Ophthalmology. “Anterior Uveitis.” Online image. http://www.aao.org/theeyeshaveit/red-eye/anterior-uveitis.cfm. Accessed on Nov 20, 2012.