Sarcoidosis

• 1. Sarcoidosis Dr. Angelo Smith M.D WHPL

2. 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. 3. Sarcoidosis is manifested by the presence of noncaseating granulomas (NCGs) in affected organ tissues. 4. History of sarcoidosis In 1899, the pioneering Norwegian dermatologist Caesar Boeck describe skin nodules characterized by compact, sharply defined foci of "epithelioid cells with large pale nuclei and also a few giant cells . Thinking this resembled sarcoma, he called the condition "multiple benign sarcoid of the skin. 5. Epidemiology All racial . All ethnic groups. More prevalent in Swedes, Danes, and US blacks All ages (with the incidence peaking at 20 to 39 years). M-F ratio 2:1. Affects siblings of first- or second- degree relatives in 15% of patients with sarcoidosis. 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. 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 chemo attractants and GFs lead to cellular proliferation and granuloma formation. Progressive granulomatous inflammation leads to injury, dysfunction, and destruction of the affected organs. 8. T cells, Macrophages Chemoattractants Growth Factors Cellular proliferation Granuloma Fibrosi s Pathogenesis 9. The following have been suggested as possible candidates that might play a role in causing sarcoidosis: Mycobacteria, such as Mycobacterium tuberculosis, and atypical pathogens have been suggested. Fungi and viruses, particularly Mycoplasma, Chlamydia, and Epstein-Barr virus, have been unconvincingly implicated. 10. Environmental Causes Some of the earliest studies of sarcoidosis reported associations with exposures to irritants found in rural settings, such as emissions from wood-burning stoves and tree pollen. More recently, associations with sarcoidosis and exposure to inorganic particles, insecticides, and moldy environments have been reported. Occupational studies have shown positive associations with service in the U.S. Navy, metalworking, firefighting, and the handling of building supplies. 11. Common Clinical Features 12. 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%. 13. 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. 14. 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 15. Systems affected by Sarcoidosis Cardiac 30% Palpitations, syncope, dizziness, chest pain, arrhythmia, sudden death Cutaneous 25% Erythema nodosum, lupus pernio, plaques, subcutaneous nodules, maculopapular eruption, alopecia, hyper/hypopigmentation Endocrin e 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 Signs and symptoms 16. Erythema Nodosum 17. Lupus Pernio 18. Systems affected by Sarcoidosis 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 Signs and symptoms 19. 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% 20. Stages 21. Lfgren's syndrome, an acute presentation consisting of: Fever. Arthralgia. erythema nodosum. bilateral hilar adenopathy. occurs in 9 to 34% of patients. Heerford's syndrome : Anterior Uveitis Fever Parotid enlargment Facial palsy 22. Laboratory Studies Routine lab evaluation often is unrevealing. Hypercalcemia or hypercalciuria may occur (NCGs secrete 1,25 vitamin D). Hypercalcemia is seen in about 10-13% of patients, whereas hypercalciuria is 3 times more common. An elevated alkaline phosphatase level suggests hepatic involvement. Angiotensin converting enzyme (ACE) levels may be elevated. 23. NCGs secrete ACE, which may function as a cytokine. Serum ACE levels are elevated in 60% of patients at the time of diagnosis. Levels may be increased in fluid from bronchoalveolar lavage or in CSF. Sensitivity and specificity as a diagnostic test is limited (60 and 70%, respectively). There is no clear prognostic value. Serum ACE levels may decline in response to therapy. Decisions on treatment should not be based on the ACE level alone. 24. Imaging Studies A chest radiograph is central to evaluation. Routine chest CT scan adds little. HRCT of the chest may be helpful. 25. Biopsy specimen A biopsy specimen should be obtained from the involved organ that is most easily accessed, such as the skin, peripheral LN, lacrimal glands, or conjunctiva. If diagnosis requires pulmonary tissue, transbronchial biopsy by means of bronchoscopy has a diagnostic yield of at least 85% when multiple lung segments are sampled. 26. The central histologic finding is the presence of NCGs with special stains negative for fungus and mycobacteria. 27. Sarcoidal granulomas have no unique histologic features to differentiate them from other granulomas. Special stains for acid-fast bacilli and fungi, as well as cultures of such organisms, are essential. If the results of lung biopsy with bronchoscopy are negative and other organs are not obviously involved, biopsy of intrathoracic lymph nodes, which are often enlarged in patients with sarcoidosis, may be necessary to confirm the diagnosis. 28. Differential Diagnosis of Noncaseating Granulomas TB Fungal infections Lymphoma Epithelioid tumors of the breast Lung cancer 29. Treatment Observation Initiating corticosteroid therapy when appropriate Monitoring response to therapy Discontinuing corticosteroids when clinically or physiologically indicated. 30. 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. 31. 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. 32. 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 33. Prognosis Many patients do not require therapy, and their conditions will spontaneously improve. Markers for a poor prognosis include : Advanced CXR stage. Extrapulmonary disease (predominantly cardiac and neurologic) Evidence of pulmonary hypertension. Multiple studies have demonstrated that the most important marker for prognosis is the initial CXR stage. 34. Remission 2/3 of patients with sarcoidosis generally have a remission within a decade after diagnosis, with few or no consequences; remission occurs for more than half of patients within 3 years. Unfortunately, up to 1/3 of patients have progressive disease, leading to clinically significant organ impairment. A recurrence after 1 or more years of remission is uncommon (affecting