Sarcoidosis

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Sarcoidosis

• T. Lianne Beck, MD
• Assistant Professor
• Emory Family Preventive Medicine

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Objectives

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

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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.

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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.

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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.

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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.

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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 GFs lead to
  cellular proliferation and granuloma formation.
• Progressive granulomatous inflammation leads to
  injury, dysfunction, and destruction of the
  affected organs.

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Pathogenesis
T cells, Macrophages
Chemoattractants Growth Factors
Cellular proliferation Granuloma
Fibrosis
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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, Lofgrens
  syndrome, includes constellation of erythema
  nodosum, polyarthritis, and BHL. Remission occurs
  in 80.

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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.

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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

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Systems 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
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Erythema Nodosum
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Lupus Pernio
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Systems 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
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Clinical 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

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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

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4 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
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Stages
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Approach 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

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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.

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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.

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Differential Diagnosis of BHL

• Granulomatous infections
• TB
• Histoplasmosis
• Coccidiomycosis
• Autoimmune disorders
• Malignancy (Lymphoma)

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Differential Diagnosis of Noncaseating Granulomas

• TB
• Fungal infections
• Lymphoma
• Epithelioid tumors of the breast
• Lung cancer

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Treatment

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

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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.

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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.

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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

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Alternatives
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
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Thank You!