Sarcoidosis

1. Sarcoidosis T. Lianne Beck, MD Assistant Professor Emory Family & Preventive Medicine

2. Objectives • Epidemiology • Pathogenesis • Clinical presentation • Organ systems involved • Diagnostic evaluation • Current evidence on treatment

3. Sarcoidosis • Multisystem disorder of unknown etiology that most commonly affects the lungs, but can also affect other organs. • Beethoven is thought to have been the first person described with this condition.

4. Epidemiology • 3rd or 4th decade of life. • More predominant in women with an incidence of 6.3 vs 5.9 cases per 100,000 person-years. • Lifetime risk for US whites is 0.85 percent compared with 2.4 percent in US blacks. • More prevalent in Swedes, Danes, and US blacks.

5. Epidemiology • Annual incidence in the U.S. is 10/100,000 among whites and 36/100,000 among African Americans. • Most commonly seen in the mid-Atlantic and Southern Atlantic states but rare in the Southwest. • Affects siblings of first- or second- degree relatives in 15% of patients with sarcoidosis. • Familial cases described in 17% of African Americans, but only 6% of whites.

6. Etiology and Pathogenesis • Cause is unknown, although both genetic and environmental factors suspected. • Theory that disease develops in genetically predetermined hosts who are exposed to certain environmental agents that trigger an exaggerated inflammatory immune response leading to granuloma formation.

7. Etiology and Pathogenesis • Hallmark is noncaseating granulomas, composed of a central core of epithelioid histocytes and multinucleated giant cells. • Activated T cells and macrophages accumulate at site of inflammation. • Release chemoattractants and GF’s lead to cellular proliferation and granuloma formation. • Progressive granulomatous inflammation leads to injury, dysfunction, and destruction of the affected organs.

8. Pathogenesis T cells, Macrophages Chemoattractants Growth Factors Cellular proliferation Granuloma Fibrosis

9. Clinical Presentation • 30-50% of patients are asymptomatic and are diagnosed on routine CXR. • One third have non-specific symptoms of fever, fatigue, weight loss and malaise. • A clinical variant of sarcoidosis, Lofgren’s syndrome, includes constellation of erythemanodosum, polyarthritis, and BHL. Remission occurs in 80%.

10. Clinical Presentation • Onset of sarcoidosis in white patients is usually asymptomatic. • African Americans tend to present with an earlier onset and a more aggressive and severe clinical course. • Chronic pulmonary sarcoidosis and the disfiguring cutaneous lesions of lupus pernio are also more common in African Americans.

11. Clinical Presentation • Spontaneous remission in two-thirds of patients within 2 years of presentation • 10%-30% experience chronic disease causing progressive organ damage • Leads to death in 4% of patients, usually those with pulmonary, cardiac, or CNS involvement

12. Systems affected by Sarcoidosis Signs and symptoms

13. ErythemaNodosum

14. Lupus Pernio

15. Systems affected by Sarcoidosis Signs and symptoms

16. Clinical Presentation • A progressive course is more likely in: • Age of onset > 40 yrs • Black race • Cardiac or renal involvement • Lupus pernio • Chronic uveitis • Hypercalcemia • Nasal mucosal involvement • Cystic bone lesions • Neurosarcoidosis • Pulmonary fibrosis

17. Clinical Presentation • Most patients have the pulmonary manifestations, most commonly presenting with incidental findings on CXR. • Interstitial disease • Symptoms include dry cough, dyspnea, and chest discomfort • Unpredictable course

18. 4 Stages of Pulmonary Sarcoidosis

19. Stages

20. Approach to Suspected Sarcoid • History (occupational and environmental) • PE (lungs, skin, eyes, liver, and heart) • CXR, PFT’s and EKG • CBC, CMP, ACE level • PPD • Biopsy for histological confirmation of noncaseatinggranulomas and culture and/or special staining to R/O fungal or TB • Ophthalmologic evaluation

21. Approach to Suspected Sarcoid • Follow-up • Monitor for resolution or progression of disease and for additional organ involvement. • Refer if there is evidence of disease progression or additional organ involvement. • Coordinate care.

22. Approach to Suspected Sarcoid • An aggressive work up may be unnecessary in asymptomatic patients with symmetric BHL, unremarkable exam, no history of malignancy, and normal results on routine bloodwork. • The course of disease usually becomes evident within 2 years of presentation. Absence of remission within this period predicts a chronic, persistent, or stable course.

23. Differential Diagnosis of BHL • Granulomatous infections • TB • Histoplasmosis • Coccidiomycosis • Autoimmune disorders • Malignancy (Lymphoma)

24. Differential Diagnosis of Noncaseating Granulomas • TB • Fungal infections • Lymphoma • Epithelioid tumors of the breast • Lung cancer

25. Treatment • Observation • Initiating corticosteroid therapy when appropriate • Monitoring response to therapy • Discontinuing corticosteroids when clinically or physiologically indicated.

26. Treatment • Topical therapy for cutaneous or ophthalmic disease. • Systemic corticosteroids for patients with unresponsive ophthalmic manifestations, cardiac, neurologic and progressive pulmonary involvement. • Systemic therapy for patients with hypercalcemia.

27. Treatment • Prednisone, 20 to 40 mg/d in divided doses or alternate-day dosing is used for organ involvement that is not life threatening. • Higher dosage is used off-label for potentially life threatening disease. • High-dose inhaled corticosteroids may be useful in patients with symptomatic pulmonary disease.

28. Treatment • Clinical improvement should be assessed after 3 months of corticosteroids. • If no improvement is found, further treatment is unlikely to be beneficial. • Long term adverse affects of therapy include weight gain, mood swings, cataracts, GERD, osteoporosis

29. Alternatives

30. Thank You!