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Sarcoidosis
- 2. PRESENTED BY DR.MD.SHARIF AHSAN MDRESIDENT(PULMONOLOGY) PHASE-B
- 3. Chronic multisystemdisorder Unknown cause Most affected organ is the lung Skin, eyes and lymph nodes are frequently involved Acute or sub acute and self limiting Waxing and waning over years
- 4. A defectin the immune system An unidentified toxic substance An unknown environmental cause An inherited or genetic cause A viral or bacterial infection
- 5. In allraces and both sexes Risk greatest in a young black woman(20-40 years) The condition is more frequently described in colder parts of northern Europe(Scandinavian, German, Irish, or Puerto Rican origin) It also appears to be more common and more severe in those from a West Indian or Asian background Eskimos, Arabs and Chinese are rarely affected
- 6. 5/100,000 whitesin the US have sarcoidosis 40/100,000 blacks Black women gets sarcoidosis twice than black men White women equal white men
- 7. Accumulation ofmononuclear inflammatory cells and T helper lymphocytes Formation of granulomas, aggregates of macrophages, epithelioid cells and multinucleated giant cells
- 11. Giant cellsin the central part of the granuloma The central epithelioid and giant cells are surrounded by a rim of lymphocytes, mostly T- helper cells T-cell lymphocytes are increased in areas of active granulomas
- 13. T-helper cellsto T-suppressor cells ratio is increased Exaggerated T-cell activity indicates an altered immune response Hyper globulinemia Mass affect of granulomas damages the tissues
- 14. Asymptomatic: abnormalroutine chest X-ray (~30%) or abnormal liver function tests Respiratory and constitutional symptoms (20– 30%) Erythema nodosum and arthralgia (20–30%) Ocular symptoms (5–10%)
- 15. Skin sarcoid(including lupus pernio) (5%) Superficial lymphadenopathy (5%) Other (1%), e.g. hypercalcaemia, diabetes insipidus, cranial nerve palsies, cardiac arrhythmias, nephrocalcinosis Symptoms reflect the specific organs involved by the granulomas
- 16. First siteinvolved Begins with alveolitis involving small bronchi and small blood vessels Alveolitis either clears up spontaneously or leads to granuloma Fibrosis
- 21. 25% haveeye lesions Blurred vision, pain, photophobia and dry eyes Chronic uveitis leads to glaucoma, cataracts and blindness Keratoconjunctivitis sicca Papilledema
- 25. 33% haveskin lesions Cutaneous anergy is common. LOFGREN'S SYNDROME; acute triad of erythema nodosum, joint pains, and bilateral hilar adenopathy
- 27. Lupus pernio-indurated blue purple swollen shiny lesions on nose, cheeks, lips, ears and fingers. Papules, nodules, and plaques Psoriatic like lesions Lesions in scars and tattoos
- 33. 33% havehepatomegaly or biochemical evidence of disease Symptoms usually absent Cholestasis, fibrosis, cirrhosis, portal hypertension, and the Budd-Chiari syndrome have been seen
- 35. Acute polyarthritiswith fever is common Arthritis is self limited Chronic destructive bone disease with deformity is rare Polymyositis and chronic myopathy Muscle disease is rare
- 41. 5% haveheart involvement Conduction abnormalities Cardiomyopathy Chest pain Intractable arrythmias Sudden death
- 42. Cranial nerves,and peripheral nerves can be involved 7th nerve facial palsy is most common Acute, transient, and can be unilateral or bilateral HEREFORDT'S SYNDROME; facial palsy accompanied by fever, uveitis, and enlargement of the parotid gland
- 45. Optic nervedysfunction Papilledema Palate dysfunction Hearing abnormalities Paresthesias Meningeal granulomas Encephalopathy
- 46. Granulomatous interstitialnephritis produces renal failure Develops over a period of weeks to months Rapid response to steroid therapy Kidney stones (nephrolithiasis) and nephrocalcinosis are very unusual secondary to hypercalcemia and hypercalciuria
- 48. Increased calciumabsorption in the gut Related to high levels of circulating 1,25- dihydroxy vitamin D produced by mononuclear phagocytes in granulomas
- 49. Lymphadenopathy Intrathoracicnodes enlarged in 75-90% patients including hilar nodes and paratracheal nodes. Peripheral lymphadenopathy
- 57. Differential diagnosis ofgranuloma on lung biopsy • Fungal infections: • Cryptococcosis • Aspergillosis • Coccidioidomycosis • Blastomycosis • Aspiration of foreign material • Primary biliary cirrhosis • Sarcoid-like reaction to malignancy. • Sarcoidosis • TB • HP • Wegener’s granulomatosis • Drug reactions • NTM
- 58. Lymphocytopenia Mildeosinphilia Increased E.S.R Hyperglobulenemia
- 59. Elevated levelof angiotensin converting enzyme Calcium :May Rise urea or creatinine :Renal involvement ALP:Liver involvement
- 60. Stage I:BHL (usually symmetrical);paratracheal nodes often enlarged•Often asymptomatic Stage II: BHL and parenchymal infiltrates • Patients may present with breathlessness or cough. Stage III: parenchymal infiltrates without BHL • Disease less likely to resolve spontaneously Stage IV: pulmonary fibrosis • Can cause progression to ventilatory failure, pulmonary hypertension and cor pulmonale.
- 62. Sarcoidosis TB Lymphoma Lung cancer, especially small cell Coccidioidomycosis and histoplasmosis Berylliosis Mycoplasma HP
- 67. Micronodules ina subpleural and bronchovascular distribution. Fissural nodularity and bronchial distortion. Irregular linear opacities, ground-glass shadowing related to bronchovascular bundles, and nodular or ill- defined shadows. Air trapping due to small airway granulomata common. Endobronchial disease in 55%. Minority has UIP pattern, associated with worse prognosis. Hilar and mediastinal lymphadenopathy.
- 68. Computed tomographic imageof pulmonary sarcoidosis with bilateral hilar lymphadenopathy and micronodules with a perilymphatic distribution including spreading along the fissures. Hilario Nunes et al. Eur Respir J 2012;40:750-765 ©2012 by European Respiratory Society
- 69. a) Chest radiographand b) computed tomographic image of “alveolar” sarcoidosis associated with profuse micronodular involvement and cavitary lesions on the left. Hilario Nunes et al. Eur Respir J 2012;40:750-765 ©2012 by European Respiratory Society
- 70. Computed tomographic imagesof a 35-yr-old female with pulmonary sarcoidosis and extensive ground-glass opacification. Hilario Nunes et al. Eur Respir J 2012;40:750-765 ©2012 by European Respiratory Society
- 71. Computed tomographic imagesof a) the “sarcoid galaxy” sign (irregular nodule resulting of the confluence of numerous micronodules), b) the “sarcoid cluster” sign (clusters of micronodules without confluence) and c) the “reversed halo” sign (ring of microno... Hilario Nunes et al. Eur Respir J 2012;40:750-765 ©2012 by European Respiratory Society
- 72. Computed tomographic (CT)images of a 67-yr-old female with fibrosing pulmonary sarcoidosis with honeycombing pattern and pulmonary hypertension. a) Honeycombing predominates in the upper and perihilar regions, and along the bronchovascular bundles. Hilario Nunes et al. Eur Respir J 2012;40:750-765 ©2012 by European Respiratory Society
- 75. (TBB, TBNA,bronchial biopsy, EBUS, or BAL) may not be necessary if no diagnostic doubt May be important to exclude infectious agents Positive yield of bronchial biopsy is 41–57%. BAL in sarcoidosis shows a CD4:CD8 ratio of >3.5
- 76. Central orparatracheal nodes or open lung biopsy: 90% positive yield May be necessary to exclude lymphoma Surgical biopsy is not usually necessary, but, if other procedures have not yielded a definitive diagnosis, it may be required Lymph node ± lung (usually via VATS) can be biopsied
- 77. skin, liver, etc.,if indicated, as these may be easier to biopsy in order to make a diagnosis
- 78. ECG TTE MRI of HEART
- 79. • May bepositive in areas of disease activity. • Not reliable for studying brain or heart.
- 80. Rarely usednow, as non-specific and expensive. Areas of active inflammation are positive, with a classic ‘panda pattern
- 81. Typically grade0 in sarcoidosis. Positive Mantoux or Heaf test make sarcoidosis a less likely diagnosis although does not necessarily make TB more likely.
- 82. No longerperformed 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
- 83. PFT :Pulmonarysarcoidosis gives a restrictive defect with decreased TLC and VC. TLCO provides the most sensitive measurement of change, although many use a properly performed VC as an alternative. Likely to improve with steroids. Airflow obstruction may also occur CXR may improve with time or treatment HRCT can help with determining burden of active disease
- 84. Difficult todifferentiate from chronic infections, fungal diseases, T.B. and lymphoma. Based on combined clinical, radiologic and histologic findings. Exclusion of other defferentials Laboratory tests seldom important
- 88. Good 50%have some permanent organ dysfunction In 15-20% remains active or recurs intermittently. The overall mortality is low (1–5%) and usually reflects cardiac involvement or pulmonary fibrosis
- 89. Age over40 Afro-Caribbean ethnicity Persistent symptoms for more than 6 months The involvement of more than three organs Lupus pernio A stage III/IV chest X-ray In patients with severe disease
- 90. No knowncure Corticosteroids, primary treatment for inflammation and granuloma formation.
- 92. Corticosteroids Immunosuppressiveor cytotoxic agents Biologic agent Lung transplantation
- 93.
- 94. The initialtreatment 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..
- 95. Because thedisease 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
- 96. which resolvesspontaneously 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
- 97. Symptomatic orprogressive stages II and III disease ( Increasing symptoms, deteriorating PFTs, and worsening CXR infiltrates) Cardiac sarcoidosis Neurosarcoidosis Sight-threatening ocular sarcoidosis Hypercalcaemia Lupus pernio Splenic, hepatic, or renal sarcoidosis
- 99. The drugof 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
- 100. in SarcoidosisIndividualize 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
- 101. Relapses oftenoccur 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
- 102. Avoid futilesteroid treatment for end- stage disease, such as honeycomb lungs No effect on established fibrosis or destroyed lung architecture
- 103. Uveitis maybe treated by topical steroids, and skin manifestations may be amenable to steroid creams or steroid injections. Inhaled steroids have been tried for pulmonary disease
- 104. Clinical improvementshould 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..)
- 105. In patientswith 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.
- 106. Immunosuppressive agents (methotrexate,azathioprine, cyclosporine, cytotoxic agents, antimalarials, TNF inhibitors Combination therapy Lung transplantation
- 107. Methotrexate, 10-25 mgonce weekly to max of 1 year or 2 yrs Chronic or worsening disease, common second line drug Effect may take 6 months Azathioprine (Imuran), 50-200 mg QD Chronic or worsening disease Advanced fibrotic sarcoidosis
- 108. Cyclophosphamide (Cytoxan)50-150 mg QD or 500-2,000 mg q 2wk IV Refractory cases only Hydroxychloroquine (Plaquenil), 200-400 mg QD Cutaneous manifestations, hypercalcemia, chronic pulmonary fibrotic disease Corneal deposits, retinopathy. Ophtho exam prior to treatment and q 6 month
- 109. Biologic agentsthat has changed the landscape of treatment of refractory disease Infliximab is the biologic agent with the most comprehensive data More agents, such as canakinumab, roflumilast, and the nicotine patch, are currently being investigated by ongoing clinical trials.
- 110. Rare indicationfor lung transplant Consider if patient has end-stage lung disease, rapidly progressive disease despite treatment, or if they are oxygen dependent Should be considered when all alternative treatments for sarcoidosis have been exhausted
- 111. This shouldinclude, 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
- 112. Sarcoidosis isa systemic disease that can affect any organ, with the lungs and intrathoracic lymph nodes being the most frequently affected sites. The diagnosis of sarcoidosis relies on the presence of noncaseating granuloma on histopathologic examination, compatible clinical presentation, and exclusion of other causes of granulomatous inflammation.
- 113. Treatment isgenerally reserved for patients with disabling symptoms or with progressive organ damage/dysfunction because spontaneous remission is frequent. Glucocorticoids are the first-line therapy, whereas glucocorticoid-sparing agents and biologic agents are used in refractory/recurrent cases.