cc: cough and dyspnea HPI: 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 distress HEENT -normocephalic atraumatic Neck -supple, no thyromegaly, no cervical lymphadenopathy CV -regular rate and rhythm, normal S1/S2, no murmurs, rubs, or gallops Pulmonary -bilateral fine inspiratory crackles Abdomen -soft, nontender, nondistended, + BS, no hepatosplenomegaly Extremities -mild clubbing Skin -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 Ca 2+ ALT/AST/alkaline phosphatase/bilirubin BUN/SCr UA PPD ECG Pulmonary Function Tests (PFTs) Opthalmologic Angiotensin Converting Enzyme (ACE) levels Imaging: CXR

WBC7,200/µL Lymphocytes10% (18-44%) Hemoglobin13.5 g/dL Platelet count230,000/µL Sodium 140 meq/L Potassium4.1 meq/L Chloride95 meq/L Bicarbonate23 meq/L BUN18 mg/dL Creatinine1 mg/dL Calcium11.5 mg/dL ALT/AST/alk phos/bilirubinnormal Urinalysis24-hr urine calcium elevated PPDnegative ACE levelselevated 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

Sarcoidosis Epidemiology: Prevalence est at 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 years, but not uncommon to diagnose in patients <20 years old Etiology: Unknown

Sarcoidosis Pathophysiology: Accumulation of T lymphocytes, mononuclear phagocytes, and noncaseating granulomas The noncaseating granulomas have a tightly packed central area composed of- 1.Macrophages 2.Epithelioid cells 3.Multinucleated giant cells The granulomas are then surrounded by lymphocytes, monocytes, mast cells, and fibroblasts

Sarcoidosis Noncaseating granuloma Lymphocytes 2.Fibroblast 3.Epitheloid cell 4.Multinucleated giant cell

Sarcoidosis Pathophysiology: 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

Sarcoidosis Extrapulmonary manifestations: 1. Dermatologic -maculopapular lesions, waxy pink nodular lesions, plaque like lesions, erythema nodosum 2. Ophthalmologic -anterior uveities, keratoconjunctivitis, retinal vasculitis 3. Upper respiratory tract involvement -involvement of the larynx, pharynx, nares, and/or sinuses 4. Reticuloendothelial system -lymphadenopathy, hepatomegaly, splenomegaly 5. Musculoskeletal -polyarthritis, granulomatous myositis 6. Exocrine glands -swelling of the salivary glands, xerostomia 7. Renal and electrolyte -abnormalities related to calcium 8. Cardiovascular- granulomatous involvment of the ventricular system leading to conduction blocks 9. Neurologic- central and peripheral involvement 10. Gastrointestinal- involvement of the stomach, esophagus, appendix, colon, rectum 11. Reproductive- involvement of the ovaries, endometrium, uterus, testes 12. Thyroid- can cause a diffuse goiter, thyroid nodule

Sarcoidosis Examples of extrapulmonary manifestations: Erythema nodosum 2.Sarcoid of spleen 3.Neurosarcoidosis 4.Sarcoid arthropathy 5.Testicular sarcoidosis 6.Anterior Uveitis

Sarcoidosis Treatment: Glucocorticoids most commonly used Alternative approaches include immunosuppressive, cytotoxic, and antimalarial drugs Irradiation and organ transplantation have also been performed

Sarcoidosis Follow-up: Monitor pulmonary function and CXR every 6-12 months Assess for progression or resolution Be vigilant for previously uninvolved organs becoming affected Prognosis: 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, 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; Accessed November 20, Vardhanabhuti V, Venkatanarasimha N, Bhatnagar G, et. Al. Extra- pulmonary manifestations of sarcoidosis. Clinical Radiology. 2012; 67: Unknown author. “Noncaseating Granuloma.” Online image. Accessed on Nov 20, American Academy of Ophthalmology. “Anterior Uveitis.” Online image. Accessed on Nov 20, 2012.