Sarcoidosis

1. ”ق الوا سبحانك لا علم لنا إلا ما
علمتنا إنك أنت العليم الحكيم ”
صدق ا لله العظيم ) البقرة – 32 )
بسم الله الرحمن الرحيم

2. CASE PRESENTATION
•A 41-year-old African-American woman with a history of asthma presents to her primary care physician’s office complaining of a rash on her arm.
•The rash has been there for approximately 1 month. She denies the use of new detergents, new clothing, or recent insect bites.
•The patient feels well, other than generalized fatigue. She states that her asthma, which was diagnosed 5 years ago, is slightly worse. She continues to feel short of breath with exertion, and her inhalers help minimally.

3. CASE PRESENTATION
•She had a recent cardiac work-up that was negative.
•On exam, the rash is well-circumscribed and limited to the forearm. It is violaceous and plaque-like in appearance.
•The patient returns 2 weeks later, and her rash has not improved.
•She als ocomplains that her dyspnea and dry cough seem to be worsening.
•You refer her to dermatology where a biopsy is performed.
•Noncaseating granulomas are noted on biopsy.
• A chest radiograph is also done, which reveals evidence of bilateral interstitial process.

4. KEY CLINICAL QUESTIONS
1.When should the diagnosis of Sarcoidosis be suspected in a patient?
2.How does Sarcoid normally present, and what are atypical but not uncommon presentations?
3. What is the appropriate treatment of this patient?
4.What is the appropriate follow-up and management of this patient?

6. •Definition
•Epidemiology
•Pathogenesis
•Clinical presentation
•Organ systems involved
•Diagnostic evaluation
•Treatment
•Prognosis

7. •Sarcoidosis (from sarc meaning flesh, -oid, like, and -osis, process),i.e flesh like
•Also called sarcoid or
•Besnier-Boeck disease or
•Besnier-Boeck-Schaumann disease

8. •In 1899, Cæsar Peter Møller Boeck (1845- 1917), Professor of Dermatology in Oslo, published his pioneer article called ''Multiple benign sarkoid of skin''.
•Boeck coined the name Sarcoidosis which stems from the Greek words “sark“ (meaning flesh) and “oid“(meaning like).
•Together with Boeck, the English physician, Jonathan Hutchinson (1828-1913), and the French physicians, Ernest Besnier (1831-1909), and, Henri Tenneson (1836-1913) were all pioneers in sarcoidosis work.
•The swede, Jörgen Schaumann (1879-1953), demonstrated early the generalized character of the disease.

9. History of sarcoidosis

11. Question
What is the definition of Sarcoidosis ?

12. ATS, ERS and the World Association of Sarcoidosis and Other Granulomatous Disorders (WASOG) 1999
☻Sarcoidosis is a multisystem disorder of unknown cause(s) commonly affects young and middle-aged adults and frequently presents with bilateral hilar lymphadenopathy, pulmonary infiltration, and ocular and skin lesions.
☻The liver, spleen, lymph nodes, salivary glands, heart, nervous system, muscles, bones, and other organs may also be involved.

13. ATS, ERS and the World Association of Sarcoidosis and Other Granulomatous Disorders (WASOG) 1999
☻The diagnosis is established when clinicoradiological findings are supported by histological evidence of noncaseating epithelioid cell granulomas.
☻Granulomas of known causes and local sarcoid reactions must be excluded.
☻Frequently observed immunological features are depression of cutaneous delayed-type hypersensitivity and a heightened helper T cell type 1 (Th1) immune response at sites of disease.

14. ATS, ERS and the World Association of Sarcoidosis and Other Granulomatous Disorders (WASOG) 1999
☻The course and prognosis may correlate with the mode of the onset and the extent of the disease.
☻An acute onset with erythema nodosum or asymptomatic bilateral hilar lymphadenopathy usually heralds a self-limiting course,
☻whereas an insidious onset, especially with multiple extrapulmonary lesions, may be followed by relentless, progressive fibrosis of the lungs and other organs.

15. •Sarcoidosis is defined as a systemic disorder in which granulomas, typically described as noncaseating, can be found in affected tissues or organ systems.
•An important qualification is that these granulomas occur in the absence of any exogenous (infectious or environmental) agents known to be associated with granulomatous inflammation.

16. •The lung is the most frequently involved organ, with potential manifestations including parenchymal lung disease, enlargement of hilar and mediastinal lymph nodes, or both.
•Sarcoidosis commonly involves the respiratory system, but can affect nearly all organs

17. •The fundamental etiology of sarcoidosis remains as mysterious as it was when the disease was first described more than a century ago.
•It has been hypothesized that sarcoidosis represents an immunologic response to an exogenous agent in a genetically susceptible individual.

18. •A Chronic multisystem inflammatory disorder, of unknown cause , although both genetic and environmental factors suspected.
•Characterized by non-caseating granulomata and CD4 Th1-biased T cell response in affected organs

19. Epidemiology
•Annual incidence in the U.S. is 10/100,000 among whites and 36/100,000 among African Americans.
•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.
•3rd or 4th decade of life.
•A second peak incidence after the age of 50 has been described most commonly in the Japanese and Scandinavian populations

20. •Sarcoidosis affects people of all ages, races, and sexes.
•Black women : black men – 2 : 1
•The clinical appearance and presenting symptoms are diverse, and the clinical course is equally varied.
•50-60% of people have spontaneous remissions , others may develop chronic progressive disease.
Epidemiology

21. •Cause is unknown, although both genetic and environmental factors suspected.
•Theory states 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.

22. •Current investigation points strongly towards genetic predisposition as the major etiology behind sarcoidosis.
•There is a five fold increase in the relative risk of developing sarcoid among first-degree relatives
•Moreover, certain ethnic and racial groups such as African Americans are at greater risk of developing sarcoid (four times greater than whites) and tend to have a more protracted course

23. Pathology
•Accumulation of mononuclear inflammatory cells and T helper lymphocytes
•Formation of a non-caseating granuloma, aggregates of macrophages, epithelioid cells and multinucleated giant cells

24. Noncaseating granuloma in lung is the characteristic lesion of sarcoidosis.

25. Langhans' giant cell in center of granuloma is surrounded by epithelioid cells .

26. CASEOUS NECROSIS Cellular destruction in TB granuloma appears as clumped debris (arrows). This necrosis does not occur in sarcoidosis.

29. 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.

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

32. Patients with sarcoidosis seek consultation most frequently either as a result of :
1)Abnormalities detected on an incidental chest radiograph or
2)Respiratory symptoms, mainly dyspnea or a nonproductive cough.

33. •Because many other organ systems may be involved with noncaseating granulomas, other manifestations occur but are less common.
•Eye involvement and skin involvement are particularly common extrathoracic manifestations of sarcoidosis
•Cardiac, neurologic, hematologic, hepatic, endocrine, and peripheral lymph node findings also may be seen.

34. •Although symptoms often are insidious in onset, some patients with sarcoidosis have a more acute presentation called Löfgren’s syndrome:
1)bilateral hilar lymphadenopathy
2)erythema nodosum
3)often fever and arthralgias.
•For unknown reasons, patients who present with Löfgren’s syndrome typically have an excellent prognosis with a spontaneous remission rate greater than 80%

35. •Sarcoidosis is a systemic disease, The clinical presentation of sarcoidosis is heterogenous.
•Approximately 30% of patients are asymptomatic; they are discovered to have sarcoidosis when a characteristic chest radiograph is performed for other reasons.
•One third of patients with sarcoidosis, complain of nonspecific constitutional symptoms including fever, weight loss, anorexia, and malaise.

36. •Asymptomatic to organ failure
•20 to 30% patients are asymptomatic and are diagnosed on routine CXR.
•One third have non-specific symptoms of fever, fatigue, weight loss and malaise.
•Onset is usually insidious but can be acute

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

38. Sarcoidosis may affect any organ in the body
•The lungs are the most common organ involved with sarcoidosis.
•Other organs that are frequently affected include the skin, the eyes, the liver, and the lymphatic system.
•Heart and neurologic involvement are less common but may be life threatening.

39. Sarcoidosis may affect any organ in the body
•Sarcoidosis may also affect the muscles, bones , bone marrow, sinuses, breast, spleen, and salivary glands.
•Sarcoidosis can cause a disorder in calcium metabolism leading to hypercalcemia, hyperkaluria, and nephrolithiasis.

42. •Sarcoidosis not only has a large spectrum of initial presentation, but its clinical course and prognosis is also diverse and varied.
•Spontaneous remission or stabilization of the disease occurs in approximately two-thirds of cases.
•On the other side of the continuum, 10 to 30% suffer from a chronic and progressive course
•Mortality rates have been reported as high as 1 to 5%

44. pulmonary Sarcoidosis
•Lung parenchyma
•Endobronchial
•Intrathoracic lymph nodes (hilar, paratracheal, mediastinal)

45. •More than 90% of patients with sarcoidosis have thoracic involvement, with an abnormal CXR , even if subclinical.
•Pulmonary sarcoidosis can be an incidental CXR finding.
pulmonary Sarcoidosis

46. Lofgrens syndrome: Excellent Prognosis
1.Bilateral hilar lymphadenopathy
2.Erythema nodosum
3.Arthralgias
4.Fever
• Remission occurs in 80% of cases within 1-2 years.. .

47. Typical features of pulmonary Sarcoidosis
•Many patients with pulmonary sarcoidosis are asymptomatic, even if their chest radiograph is abnormal
•Sarcoid granulomas develop throughout the lung parenchyma, but they present most prominently in the upper two-thirds of the lung and also in the airways.

48. •Nonproductive cough and dyspnea are the most common symptoms.
•Substernal pleuritic chest pain is also common.
•Because sarcoidosis may involve the airways, wheezing can be a prominent symptom and is often underappreciated.
Typical features of pulmonary Sarcoidosis

49. •Lymphadenopathy is a hallmark of sarcoidosis with hilar lymph node involvement occurring in 90% of patients with sarcoid
•Airway hyperactivity and expiratory wheezing can also be noted in up to 20% of patients, making sarcoidosis a diagnostic challenge
•Chest pain is most often retrosternal in position
•Dry rales are appreciated on physical exam in advanced stages.

50. •In contrast to idiopathic pulmonary fibrosis (IPF), auscultation typically reveals a quiet chest without crackles.
•Finger clubbing is rare unless there is associated bronchiectasis
Typical features of pulmonary sarcoidosis

51. 4 Stages of Pulmonary Sarcoidosis
I
Bilateral hilar lymphadenopathy and paratracheal adenopathy, normal lung parenchyma
55-90%
remission
II
Mediastinal adenopathy with pulmonary parenchymal infiltrate
40-70%
III
Pulmonary parenchymal infiltrate without adenopathy
10-20%
IV
Pulmonary fibrosis with honeycombing, irrespective of adenopathy
0-5%

53. •Chest roentgenographic abnormalities occur in 90- 95% of patients with pulmonary sarcoidosis.
•Bilateral hilar adenopathy is present in 50-85% of patients at diagnosis
•Parenchymal disease is seen in 25-50% of patients.
•In general, as the radiographic stage increases, the pulmonary function worsens and the likelihood of spontaneous remission decreases

54. Pulmonary Sarcoidosis
Chest radiographs:
1.Upper, mid lung zone predominance
2.Alveolar or interstitial infiltrates.
3.Bilateral hilar lymphadenopathy.

55. •This is a characteristic feature of sarcoidosis.
•It is often symptomless, simply detected on a routine chest X-ray.
•Occasionally associated with cough , a dull ache in the chest, malaise and a mild fever

56. Hilar/mediastinal lymphadenopathy
–Often bilateral and symmetrical
–Important to exclude other causes of lymphadenopathy, such as TB and lymphoma. May need HRCT and lymph node aspirate or biopsy.
–Stage I: 85% resolve spontaneously over 2 years, 15% develop lung infiltrates.
–The average time for bilateral hilar lymphadenopathy resolution is 8 months
–Does not require systemic steroid treatment.

57. STAGE I Thoracic lymphadenopathy. Normal lung parenchyma. (50%)

58. Stage I sarcoidosis. Posteroanterior chest radiograph demonstrates bilateral hilar and right paratracheal lymphadenopathy. Lung fields are clear.

59. Marked enlarged hilar and mediastinal lymph nodes.

60. Enlarged bilateral hilar, right paratracheal (arrow), and aortopulmonary window (arrowhead) nodes.

61. Differential Diagnosis of BHL
•TB
•Histoplasmosis
•Coccidiomycosis
•Hypogammaglobulinaemia and recurrent infections
•Lymphoma
•Leukaemia
•Berylliosis

62. Stage II sarcoidosis. Posteroanterior chest radiograph demonstrates massive bilateral hilar lymphadenopathy as well as bilateral parenchymal infiltrates. Note the predilection for mid and upper lung zones.

63. Stage II Hilar adenopathy characteristic of sarcoidosis and upper lobe infiltrates

64. STAGE II Hilar and mediastinal lymphadenopathy. Abnormal lung parenchyma. ( 30% )

65. Stage III Sarcoidosis. Posteroanterior chest radiograph demonstrates extensive ground- glass, miliary infiltrates throughout both lung fields in a 22-year-old black female with a 4-month history of dyspnea. Transbronchial lung biopsies demonstrated confluent, noncaseating granuloma. Special stains and cultures for acid-fast bacilli and fungi were negative. Corticosteroids (prednisone 40 mg/day) led to dramatic improvement.

66. STAGE III Abnormal lung parenchyma. No lymphadenopathy. ( 15% )

67. STAGE IV Permanent lung fibrosis. (20%)

68. STAGE IV Extensive pulmonary fibrosis is typically worst in the upper lobes.

69. STAGE IV Broad bands of fibrosis in the upper lobes.

70. Stage IV pulmonary sarcoidosis in a 60-year-old man. Chest CT scan demonstrates extensive fibrotic change and cavitary lesions with a central distribution (arrows) that distort the lung parenchyma. Irregular thickening of the pleura (arrowheads) and overinflation of the peripheral lung parenchyma are also seen.

71. High-resolution computed tomographic scan (1.5 mm collimation) in a patient with stage IV sarcoidosis demonstrates bulla formation, central bronchovascular thickening, and architectural distortion with rotation of the hila toward the spine. The lung interface with the pleura is irregular because of subpleural nodules.

72. Severe fibrocystic sarcoidosis. Computed tomographic scan from a patient with severe, end-stage sarcoidosis. The right lung is virtually completely replaced by a bulla. The left lung shows thickened interlobular septa, scattered nodules, broad fibrous bands, and cystic radiolucencies.

74. Systemic involvment
Lung lesions – 95%
Thoracic lymph nodes – 50%
Skin lesions – 30%
Eyes – 30%
74

75. Cutaneous Sarcoidosis
•Skin lesions more common in African American than caucasians
- Exception Erythema nodosum
•Seven different skin lesions
- Erythema nodosum - Hyper pigmentation
- Maculo-papular lesions - Hypo pigmentation
- Subcutaneous nodule - Lupus pernio
- Keloid

76. http:// im.knuh.or.kr
Skin
Symptoms

77. Erythema Nodosum

78. Lupus pernio

79. •Skin lesions generally do not cause pain or pruritis and do not ulcerate
•Two dermatological conditions that should prompt clinicians to suspect an underlying presence of sarcoidosis,are important prognostic indicators
I.Erythema nodosum
II.Lupus pernio
Cutaneous Sarcoidosis

80. •Lupus pernio is the most specific skin lesion of sarcoidosis , It is associated with chronic fibrotic pulmonary sarcoidosis and poor prognosis
•Erythema nodosum , is not diagnostic of sarcoidosis , as it can be seen with infections, neoplasms, vasculitides, and drug reactions
•Erythema nodosum usually suggests a good prognosis
Cutaneous Sarcoidosis

81. •33% have skin lesions
•Cutaneous anergy is common.
•LOFGREN'S SYNDROME
acute triad of
1.Erythema nodosum,
2. Joint pains
3.Bilateral hilar adenopathy
Cutaneous Sarcoidosis

82. Eye lesions
●25% have eye lesions
●All parts of the eye have the potential to be affected
●Acute uveitis (anterior or posterior), resulting in blurred vision, pain, photophobia and dry eyes , are the most common complaints.
●Chronic uveitis leads to glaucoma, cataracts and blindness
●Keratoconjunctivitis sicca
●Papilledema
●Some recommend that all newly diagnosed patients with sarcoidosis , have slit lamp examination

83. Cardiac Sarcoidosis
•Cardiac involvement is uncommon (5%).
•Conduction abnormalities (heart block).
•Intractable arrythmias ( ventricular tachycardia ).
•Cardiomyopathy
•Congestive heat failure
•Chest pain
•Sudden death
•is often undiagnosed
•In clinic Perform a screening ECG on all patients with sarcoidosis perhaps every 6 months

84. Metabolic manifestations
•It is rare for sarcoidosis to present with problems of calcium metabolism
•Hypercalcaemia is found in 10% of established cases, whereas hypercalciuria is more common..
•Hypercalcaemia and hypercalciuria can lead to the development of renal calculi.

85. Disturbances in calcium metabolism in sarcoidosis
•The primary defect involves excessive alpha 1 hydroxylation of 25-hydroxyvitamin D to 1,25- dihydroxyvitamin D. active form of vitamin D by activated macrophages in granulomas
•This may lead to increased gut absorption of calcium, hypercalciuria, and less frequently, hypercalcemia.
•The most common clinically important consequence of abnormal calcium is nephrolithiasis and nephrocalcinosis

86. •Between 5 and 16% of patients with sarcoid have neurological complaints
•Cranial nerves, and peripheral nerves can be involved
•7th nerve facial palsy is most common
•Optic nerve dysfunction
•Encephalopathy
HEREFORDT'S SYNDROME facial palsy accompanied by fever, uveitis, and enlargement of the parotid gland
Neurosarcoidosis

87. Musculoskeletal Lesions
•Arthralgia is common in sarcoidosis, but arthritis is unusual.
•Arthralgia commonly affects the ankles and feet, but also hands, wrists and elbows.
•Subacute, proximal myopathy can occur, as well as bone cysts, especially of terminal phalanges.

88. Hepatosplenomegaly
•Sarcoidosis is a cause of hepatosplenomegaly, though it is rarely of any clinical consequence.
•60% of liver biopsies on patients with sarcoidosis show granuloma. Frequently asymptomatic or abdominal pain, abnormal LFT’s suggestive if >3 times normal.

89. Haematological manifestations
•Associated anaemia in 4 - 20% of sarcoid patients.
•Leukopenia, although mild, can occur in up to 40% of patients with sarcoidosis.
•Thrombocytopenia can occur in the setting of significant splenomegaly
•Lymphopenia often seen.

90. ENT
•Nasal or laryngeal granuloma , Sinus invasion, Parotid and other salivary gland enlargement, dry mouth.
Endocrine
•Hypo/hyperthyroidism, adrenal insufficiency and pituitary dysregulation can all occur
Rarely:
•breast disease, ovarian or testicular masses

92. Investigations
1)Thoracic HRCT scan
•Hilar and mediastinal lymphadenopathy
•Micronodules in a subpleural and bronchovascular distribution.
•Fissural nodularity and bronchial distortion.
•Irregular linear opacities, ground-glass shadowing related to bronchovascular bundles
•Air-trapping due to small airway granulomata.
•Endobronchial disease in 55%.
•Honeycomb lung.

93. 2)Bronchoscopy (transbronchial biopsy, or BAL)
A.May not be necessary if there is no diagnostic doubt clinically and radiologically.
B.Positive yield of transbronchial biopsy is 40-90%.
C.BAL in sarcoidosis shows a CD4 : CD8 ratio of >3.5 . If this test is not available, a lymphocytosis of > 40% supports the diagnosis, but is not diagnostic.
(Lymphocytosis is also seen in UIP, COP, hypersensitivity pneumonitis, and smokers)

94. BAL pattern NORMAL NONSMOKER SUBJECT: YIELD APPROXIMATELY 10 MIO CELLS, WITH
> 85% Alveolar macrophages
< 15% Lymphocytes
< 3% Neutrophils
< 0.5% Eosinophils
< 0.5% Basophils, Mast cells

95. BAL pattern
•Neutrophilic
IPF etc.
•LYMPHOCYTIC Sarcoidosis,
Extrinsic allergic alveolitis, etc.
•Eosinophilic
CEP, Churg-Strauss-Syndrome, etc
•Mixed cellularity
BOOP, etc

96. 3)Mediastinoscopy for central or paratracheal nodes or open lung biopsy:
•90% positive yield.
• May be necessary to exclude lymphoma
4)Biopsy other affected areas such as skin, liver, etc.

97. 5)Mantoux/Heaf test
•Delayed-type hypersensitivity reactions are depressed in sarcoidosis
•May show minimal reaction/grade 0 in sarcoid (peripheral cutaneous anergy to tuberculin due to migration of T lymphocytes cells to active sites of disease ), with resultant peripheral blood lymphopenia.
•A positive Mantoux or Heaf test therefore make sarcoidosis less likely as a diagnosis

98. 6)Kveim test
•No longer performed clinically, due to risks of transmissible diseases.
•It involved injecting homogenized splenic tissue from a patient with sarcoidosis to see if a granulomatous reaction occurred.

99. 7)Serum angiotensin-converting enzyme (ACE)
•levels are elevated in about two-thirds of patients with active sarcoidosis , Levels become normal as disease resolves
•This is not a specific test lacks sensitivity and specificity and is therefore of limited value in diagnosis or in monitoring the course of the disease

100. 8)Gallium scanning
•Not thought to provide clinically useful information regarding the “activity” of the disease. Therefore, these techniques are not widely accepted for clinical use in evaluating sarcoidosis.
•Gallium scan rarely used now, as non-specific and expensive

101. Pulmonary function tests
•Sarcoidosis may involve the airways. Therefore, unlike most interstitial lung diseases that demonstrate a restrictive ventilatory defect, pulmonary sarcoidosis may manifest as an :
1)Restrictive lung disease, or
2)Obstructive lung disease or
3)Obstruction and restriction may occur concomitantly.

102. •Gas exchange remains normal until late in the disease course.
•Resting hypoxemia and reductions in carbon monoxide diffusion in the lung (DLCO) are not commonly seen except with fibrocystic ( Stage 4) disease or pulmonary hypertension
Pulmonary function tests

103. Diagnosis of Sarcoidosis

104. •Sarcoidosis can be diagnosed without a biopsy if the clinical features are so typical for the diagnosis that alternative diagnoses are extremely unlikely
•An example of such a presentation is Löfgren's syndrome

105. 1)When the clinical diagnosis strongly suggests sarcoidosis, tissue confirmation is sometimes unnecessary.
•An example of such a presentation is bilateral hilar lymphadenopathy found on an incidental CXR in a symptom-free young African-American woman.
2)On the other hand, when the patient has symptoms or when there is a question about the diagnosis, tissue sampling usually is undertaken to look for noncaseating granulomas and to rule out other causes.

106. •Other diseases capable of producing similar clinical and histological picture, particularly tuberculosis and lymphoma, should be excluded
•The diagnosis of sarcoidosis is usually established when suggestive clinical or radiologic findings are supported by histologic evidence of noncaseating granulomatous inflammation.

107. •The lung is generally the most appropriate source of tissue.
•Interestingly, even when the chest radiograph shows only hilar adenopathy without obvious parenchymal lung disease, the alveolar walls usually are studded with granulomas that may be seen on transbronchial lung biopsy

108. •Ideally, noncaseating granulomatous inflammation should be demonstrated in at least two organs because sarcoidosis is a systemic disease.
•In clinical practice, however, once biopsy-confirmed granulomas have been demonstrated in a single organ, sarcoidosis can be assumed to be present in a second organ without biopsy

109. •If the clinician suspects Sarcoidosis and the chest radiograph is not clear, a CT scan can often more clearly depict the extent of disease
•After acquiring a clinical history suggestive of Sarcoid and imaging compatible with this disease, the next step in the diagnostic pathway is to obtain tissue confirmation of noncaseating granulomas.

110. Sarcoidosis: tissue confirmation
•FOB (TBL , TBNA , EBUS )
•Lymph nodes (mediastinoscopy)
•Cutaneous lesions & extra Thoracic LNs
•Surgical lung Bx usually not required

111. •The most appropriate site of biopsy for histiological confirmation is that which is least invasive.
•Skin lesions (except erythema nodosum) and peripheral lymph nodes are easily accessible for biopsy , safe, and can rule out lymphoma
If such sites are not available, endobronchial and transbronchial lung biopsy via bronchoscopy is the next recommended procedure in most scenarios. This is generally safe, however, a limited sample can miss granulomas or be insufficient for culture of fungus or mycobacterium

112. •Broncho-alveolar lavage may show a predominance of lymphocytes with an increase CD4 to CD8 ratio higher than 3.5
•Cultures of fungus or mycobacterium can also be sent from the broncho-alveolar lavage washings

113. •Mediastinoscopy can also be performed with biopsy of the right paratrachael lymph nodes when seen on chest CT, and is very helpful in distinguishing sarcoid from lymphoma.
•Open lung biopsy via video-assisted thoracoscopy is usually performed in an effort to distinguish between other causes of interstitial pulmonary fibrosis, but this procedure is associated with significantly greater risk than brochoscopy

114. •If biopsy and histiology confirmation is not reasonable (e.g., if the patient refuses or lung disease is too severe to tolerate a procedure), other clinical markers can be used.
Nonspecific labs such as
I.Anemia, leukopenia, thrombocytopenia
II.Hypercalcemia, hypercalciuria,
III.An elevated alkaline phosphatase, and hyperbilirubinemia.

115. •Once sarcoid has been diagnosed by clinical and radiographic features and supported by histological features, additional tests are necessary to assess the extent of disease.
1.A full Neurological exam should be performed
2.A full ophthalmological exam. should be performed
3.A baseline ECG should be documented, looking for the presence of rhythm or conduction abnormalities

116. •Serial clinical exams remain the standard for monitoring and predicting the clinical course of sarcoidosis.
•Surveillance should be most intense in the first 2 years to determine the need for treatment and likelihood of progression.
•Patients should be seen every 3 to 4 months if stage III or IV disease is present, and every 6 months if stages I or II is present.
•A full physical exam chest radiograph, and spirometry should be performed at each visit

117. Serial labs including
1)Complete blood count
2)liver function tests
3)Serum calcium levels
4)Blood urea nitrogen, and creatinine
•Should be documented again for future comparisons
•There is no definitive test specific for sarcoid

119. SARCOID PROGNOSTICS

120. •The natural history of sarcoidosis is quite variable. In some patients, all clinical and radiographic manifestations resolve within 1 to 2 years.
•In general, nearly two thirds of patients have spontaneous remissions.
•Other patients have persistent radiographic changes, either with or without persisting symptoms.
SARCOID PROGNOSTICS

121. SARCOID PROGNOSTICS
•A minority of patients (10%–30%) show continued progression of radiographic abnormalities, with or without additional extrathoracic disease, and may have debilitating respiratory symptoms.
•The course of disease usually becomes evident within 2 years of presentation. Absence of remission within this period predicts a chronic (with exacerbations and remissions), persistent, or stable course.

122. Prognosis of Sarcoidosis
•Spontaneous remission defines an excellent long-term prognosis ( Lofgren's syndrome has complete resolution in 80% of people )

123. •A progressive course , Adverse prognosis is more likely in:
–Age of onset > 40 yrs
–Black race
–Cardiac sarcoidosis
–Lupus pernio
–Chronic uveitis
–Hypercalcemia , nephrocalcinosis
–Nasal mucosal involvement
–Cystic bone lesions
–Neurosarcoidosis
–Progressive Pulmonary fibrosis

124. Sarcoidosis: prognosis
X-ray stage Spont. remissions
I 70-95%
II 40-70%
III < 20%

125. Sarcoidosis: HRCT
Potentially reversible if:
•Ground glass opacities
•Nodules
•Consolidation

126. Sarcoidosis: HRCT
Potentially irreversible if:
•Honeycomb cysts
•Traction bronchiectasis
•Broad septal bands
•Distortion

127. •The most common cause of death from sarcoidosis in the United States is from lung involvement which manifests as the insidious onset of respiratory failure over several years
•Cardiac sarcoidosis and neurosarcoidosis account for the remainder of deaths attributable to sarcoidosis

128. • therapeutic
Treatment

129. Treatment of Sarcoidosis
•Corticosteroids
•Immunosuppressive or cytotoxic agents
•Lung transplantation

130. Does Sarcoidosis mandate treatment

131. •The initial treatment decision confronting the clinician is whether or not to institute therapy for the patient with sarcoidosis.
•Many patients do not require treatment, especially when the disease is causing neither significant symptoms nor significant functional organ involvement..

132. •Sarcoidosis does not mandate treatment because the disease may undergo spontaneous remission and there are significant potential toxicities from therapy.
• For patients with asymptomatic disease and stage I disease there is no evidence to support the need for corticosteroids.
•Many of these patients resolve spontaneously and therefore can be monitored closely for signs of progression

133. •In most patients sarcoidosis is a self-limiting disease which resolves spontaneously without treatment. However, a minority of patients with chronic sarcoidosis develop progressive fibrosis.
•
Systemic corticosteroids have been the mainstay of therapy for decades, and is still widely used today

134. •Indications of therapy
1.Symptomatic or progressive stages II and III disease ( Increasing symptoms, deteriorating PFTs, and worsening CXR infiltrates)
2.Cardiac sarcoidosis
3.Neurosarcoidosis
4.Sight-threatening ocular sarcoidosis
5.Hypercalcaemia
6.Lupus pernio
7.Splenic, hepatic, or renal sarcoidosis.

135. Corticosteroids are the drug of choice
•The initial dose is usually 20 to 40 mg per day, although the dose may be higher in cases of ocular or neurological involvement.
•The patient should be monitored closely for 8 to 12 weeks after the initiation of steroids.
•If there are signs of clinical improvement, the steroids can be tapered over the next 6 to 12 months , as shorter courses of therapy are associated with relapse.

136. Corticosteroids in Sarcoidosis
Individualize prednisolone dose:
•Initial: 40 mg/day
•For CNS or Cardiac, 1 mg/kg/d and
taper to 40 mg q.o.d < 3 months
•In steroid responders we decrease gradually to 5 -10 mg/d or alternatively.

137. •Relapses often occur when treatment is stopped and may require the reintroduction of steroids, or the increase of steroid dose.
•Duration and dose of steroids is dictated by site and response to treatment
•Prescribe gastric and bone protection with steroids when necessary

138. •Avoid futile steroid treatment for end-stage disease, such as honeycomb lung
•No effect on established fibrosis or destroyed lung architecture

139. •In patients with refractory disease, a variety of other agents, especially immunosuppressive drugs such as methotrexate and cyclophosphamide, have been used, either with or instead of corticosteroids.
•More recently, there has been interest in using infliximab, an antagonist of TNF-, in selected cases.

140. •Uveitis may be treated by topical steroids, and skin manifestations may be amenable to steroid creams or steroid injections. Inhaled steroids have been tried for pulmonary disease

141. •Clinical improvement should be assessed after 3 months of corticosteroids.
•If no improvement is found, further treatment is unlikely to be beneficial.
•If steroid treatment fails, or sarcoidosis is life- threatening, other immunosuppressive regimes may be indicated (azathioprine and methotrexate..)

142. Sarcoidosis: Steroid failures
•Immunosuppressive agents
(methotrexate, azathioprine, cyclosporine, cytotoxic agents, antimalarials, TNF inhibitors)
•Combination therapy
•Lung transplantation

143. 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

144. Lung Transplant
•Sarcoidosis is a rare indication for lung transplant.
•Consider if patient has end-stage lung disease, rapidly progressive disease despite treatment, or if they are oxygen dependent.
•Sarcoid Granulomata recur in transplanted lung, but do not cause higher rates of graft failure , which suggests that the disease involves a transmissible agent or, possibly, permanent alteration of the host's immune response.

145. •Organ transplantation for pulmonary sarcoidosis should be considered when all alternative treatments for sarcoidosis have been exhausted
•This should include, at a minimum, a reasonable trial of corticosteroids and at least one alternative agent.
•In the cases of pulmonary sarcoidosis, transplantation should be considered if the disease is not only severe but also progressive..
Lung Transplant

146. Is Sarcoidosis fatal
Sarcoidosis is rarely fatal. It is estimated that 3-5% of Sarcoidosis patients will die from the disease.
•In United States, three-quarters of the sarcoidosis deaths are from pulmonary sarcoidosis due to respiratory failure that develops over 5-25 years. .
These patients have stage 4 fibrocystic sarcoidosis.
•The remaining deaths result from cardiac sarcoidosis and neurosarcoidosis

147. WAKE UP PLEASE!!!!!!!! ITS OVER!!!!!!