Title: Sarcoidosis
1Sarcoidosis
- T. Lianne Beck, MD
- Assistant Professor
- Emory Family Preventive Medicine
2Objectives
- Epidemiology
- Pathogenesis
- Clinical presentation
- Organ systems involved
- Diagnostic evaluation
- Current evidence on treatment
3Sarcoidosis
- 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.
4Epidemiology
- 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.
5Epidemiology
- 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.
6Etiology 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.
7Etiology 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 GFs lead to
cellular proliferation and granuloma formation. - Progressive granulomatous inflammation leads to
injury, dysfunction, and destruction of the
affected organs.
8Pathogenesis
T cells, Macrophages
Chemoattractants Growth Factors
Cellular proliferation Granuloma
Fibrosis
9Clinical 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, Lofgrens
syndrome, includes constellation of erythema
nodosum, polyarthritis, and BHL. Remission occurs
in 80.
10Clinical 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.
11Clinical 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
12Systems affected by Sarcoidosis
Signs and symptoms
Cardiac 30 Palpitations, syncope, dizziness, chest pain, arrhythmia, sudden death
Cutaneous 25 Erythema nodosum, lupus pernio, plaques, subcutaneous nodules, maculopapular eruption, alopecia, hyper/hypopigmentation
Endocrine Hypo/hyperthyroidism, adrenal insufficiency
Exocrine Painless swelling of parotid gland, keratocon-junctivis sicca
Hepatic 50-80 Asymptomatic or abdominal pain, abnormal LFTs, hepatomegaly
Lymphatic Extrapulmonary lymphadenopathy, splenomegaly
13Erythema Nodosum
14Lupus Pernio
15Systems affected by Sarcoidosis
Signs and symptoms
Neurologic 5 Cranial nerve palsy, seizures, basal granulomatous meningitis, hypothalamic or pituitary lesions, hydrocephalus, peripheral neuropathy, psychiatric
Ocular 20 Uveitis, chorioretinitis, keratoconjunctivitis, glaucoma, cataracts, blindness, Heerfordt syndrome
Pulmonary 90 Asymptomatic or dyspnea, nonproductive cough, wheezing, radiographic findings from hilar adenopathy to fibrosis
Renal Hypercalcemia, hypercalciuria, renal insufficiency
16Clinical Presentation
- A progressive course is more likely in
- Age of onset gt 40 yrs
- Black race
- Cardiac or renal involvement
- Lupus pernio
- Chronic uveitis
- Hypercalcemia
- Nasal mucosal involvement
- Cystic bone lesions
- Neurosarcoidosis
- Pulmonary fibrosis
17Clinical 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
184 Stages of Pulmonary Sarcoidosis
I Bilateral hilar lymphadenopathy and paratracheal adenopathy 55-90 remission
II Mediastinal adenopathy with pulmonary parenchymal involvements 40-70
III Pulmonary parenchymal without adenopathy 10-20
IV Pulmonary fibrosis with honeycombing 0-5
19Stages
20Approach to Suspected Sarcoid
- History (occupational and environmental)
- PE (lungs, skin, eyes, liver, and heart)
- CXR, PFTs and EKG
- CBC, CMP, ACE level
- PPD
- Biopsy for histological confirmation of
noncaseating granulomas and culture and/or
special staining to R/O fungal or TB - Ophthalmologic evaluation
21Approach 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.
22Approach 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.
23Differential Diagnosis of BHL
- Granulomatous infections
- TB
- Histoplasmosis
- Coccidiomycosis
- Autoimmune disorders
- Malignancy (Lymphoma)
24Differential Diagnosis of Noncaseating Granulomas
- TB
- Fungal infections
- Lymphoma
- Epithelioid tumors of the breast
- Lung cancer
25Treatment
- Observation
- Initiating corticosteroid therapy when
appropriate - Monitoring response to therapy
- Discontinuing corticosteroids when clinically or
physiologically indicated.
26Treatment
- 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.
27Treatment
- 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.
28Treatment
- 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
29Alternatives
Drug, dosage Use in sarcoidosis Comment
Methotrexate, 10-25 mg once weekly to max of 1 g or 2 yrs Chronic or worsening disease, common second line drug Effect may take 6 mo, Nausea, neutropenia, and liver toxicity
Azathioprine (Imuran), 50-200 mg QD Chronic or worsening disease, advanced fibrotic sarcoidosis Nausea, neutropenia
Cyclophosphamide (Cytoxan) 50-150 mg QD or 500-2,000 mg q 2wk IV Refractory cases only Toxicity limits use, Nausea, neutropenia Requires intense monitoring and F/U
Hydroxychloroquine (Plaquenil), 200-400 mg QD Cutaneous manifestations, hypercalcemia, chronic pulmonary fibrotic disease Corneal deposits, retinopathy. Ophtho exam prior to treat-ment and q 6 mo
30Thank You!