Sarcoidosis Flashcards
What is Sarcoidosis?
Sarcoidosis is a multisystem inflammatory disease of unknown etiology characterized by non-caseating granuloma
Explain the organ involvement in sarcoidosis?
Lungs and lymphatics 90%
Skin 25%
Eyes 25%
Musculoskeletal system 10-15%
Nervous system 5-10%
Heart disease present in 28% of patients although only about 5% of patients report having any heart-related symptoms.
Liver 50-80% granulomas usually asymptomatic
Renal/Endocrinehypercalcemia 2-10% of patients
Reproductive primarily males (testes)
Other organs Cytopenia
Depression up to 2/3 of patients
Prevalence of Sarcoidosis?
- USA – 60 per 100,000 adults – More prevalent and more severe in blacks than whites – Blacks 35/100,000 Whites 11/100,000
- World – Scandinavia and Northern Europe – incidence as high as 3.2/10,000 – China, S. East Asia, Middle East – Rare
- Female: Male ratio – All patients with sarcoidosis – 3:2
- Peak incidence – 55 years of age; rare < 10 or > 70
- Tends to occur sporadically, clustering and familial occurrences have been reported
- Afro-Americans increased risk compared to whites.
What causes sarcoidosis?
Triggers → Increased activity of the immune system
- Environmental/Occupational
- Genetics
- Race No evidence of active infection Improves with medications that suppress the immune system
pathogenesis of sarcoidosis?
explain the lymphocytes in sarcoidosis?
delayed skin test responses in sarcoidosis?
TB skin test response in sarcoidosis?
Latent TB diagnosis affected by sarcoid?
Interferon Gamma Release Assay (IGRA): Quantiferon TB Gold (QFT) or T-Spot Unaffected by sarcoidosis activity
B Lymphocyte Activity in Peripheral Blood during sarcoids?
Clinical features of sarcoidosis?
• A Systemic Disorder granulomas (noncaseating)
A. Thoracic manifestations – Parenchymal lung disease – Lymph node limited disease (more favorable outcome) – Both
B. Extrathoracic manifestations – Numerous tissue or organ system involvement
Types of sarcoidosis?
Parenchymal Pulmonary Sarcoidosis
- Outcomes less favorable compared to lymph node limited disease
- Relapsing disease more common
- Can progress to pulmonary fibrosis
Lymph Node Limited Disease
• More favorable outcomes compared to parenchymal pulmonary sarcoidosis
Explain constitutional symptoms? and pulmonary symptoms?
- Constitutional – Low grade fever – Night sweats – Weight loss – Depression – Cranial nerve palsy – Erythema nodosum
- Pulmonary – Cough present in 90% of patients with acute pulmonary disease doesn’t correlate with spirometry or chest x-ray – Dyspnea – Wheeze – Chest pain/pleurisy
Common findings in sarcoidosis?
- Lymphadenopathy
- Mucocutaneous discoloration, granulomas
- Uveitis • Hepatomegaly
- Splenomegaly
- Enlarged parotid salivary glands
- Lupus pernio
Explain the radiographic staging of sarcoidosis?
Symptom status of patients with sarcoidosis?
40% asymptomatic
60% symptomatic
Differential diagnosis of isolated hilar lymphadenopathy?
- Sarcoidosis (Stage I)
- Tuberculosis
- Fungal infection
- Lymphoma (especially Hodgkins)
Explain stage 4 of sarcoidosis? difference in race?
- 5 - 9% of patients
- Severe parenchymal abnormality with fibrobullous changes
- Black: White approximately 2:1
- Blacks: honeycomb scar: restrictive
- Whites: Bronchovascular distortion: obstruction
Criteria for diagnosis of sarcoidosis?
- Clinicoradiographic findings
- Histologic evidence of noncaseating granuloma
- Exclusion of known causes of granulomatous disease
- Evidence of disease in at least two organs
Recommended tests for the initial evaluation of sarcoidosis?
Pulmonary Function Test
Renal panel: BUN, creatinine, urinalysis
Liver panel: Alkaline phosphatase, ALT, AST, bilirubin, serum calcium level
Electrocardiogram
PPD or an interferon-γ release assay (IGRA)
Slit lamp eye exam
Chest x-ray
CBC
how to diagnosis neurosarcoidosis? Cardiac?
Neurosarcoidosis: MRI with gadolinium enhancement Cerebral spinal fluid examination Nerve conduction studies
Cardiac Sarcoidosis: Holter monitor 2-D echocardiogram PET CT and/or cardiac MRI
PFT’s with sarcoidosis?
- The most common abnormality is a restrictive ventilator impairment with an abnormal diffusion capacity (DLCO)
- Some patients can demonstrate: – Small and/or large airways obstruction – Methacholine hypersensitivity – Exercise desaturation
Sarcoidosis do we alter the diagnosis?
Clinical presentations that may be assumed to be sarcoidosis without tissue confirmation provided the history and clinical evaluation does not suggest an alternative diagnosis.
Bilateral hilar adenopathy on chest x-ray without symptoms
Lofgren Syndrome
Lupus Pernio
Heerfordt syndrome (parotitis, uveitis, facial palsy, and fever)
what do you have to do to diagnose sarcoidosis?
- Need to exclude other causes of granulomatous infiltration
- Most commonly need to rule out – Lymphoma – Typical and atypical mycobacteria – Hypersensitivity pneumonitis – Berylliosis – Fungus – Granulomatous vasculitis – Foreign body granulomas – Granulomatous reaction in a lymph node, draining lymphoma, breast cancer, renal cell cancer
Approach to a patient with sarcoidosis?
- Establish the diagnosis
- Evaluate extent and severity of organ involvement
- Evaluate degree of activity of patient’s disease
Explain ACE testing in sarcoidosis?
- Produced by the epithelial cell of the sarcoid granuloma
- Reflects the total granuloma burden in sarcoidosis
- ACE elevated in 50 – 80% of patients
- Usually highest in untreated with active disease
- Falls toward normal during remission
- Approximately 15% false positives
What is Lofgren syndrome?
Triad
– Erythema nodosum
– Hilar lymphadenopathy
– Arthralgias (ankle)/arthritis (often)
– Fever (often)
Goals of treating sarcoidosis?
Relieve symptoms
Improve organ function
Control inflammation
Prevent disease progression to pulmonary fibrosis
Indications for treatment of sarcoidosis?
Recommendations vary based on the target organ and symptom severity Pulmonary:
- Deteriorating FVC, DLCO, and worsening imaging studies
- Hemoptysis Hypercalcemia: Sight threatening ocular sarcoidosis Neurosarcoidosis Cardiac sarcoidosis
Explain the treatment of sarcoidosis?
None: For stage I and II pulmonary disease. Monitor symptoms, CXR, PFT (FVC and DLCO). Spontaneous remission occurs in up to 40% of patients within the 1st 6months and 80% in 1st 2 years
For those needing treatment:
- Oral corticosteroid Backbone of therapy initial visits (weeks) followed by limited maintenance (months)
- Non-corticosteroids indications: a. Steroid resistance b. Intolerant side effects of steroids c. Patient desires not to take corticosteroids
What drugs for refractory sarcoids? Mucocutaneous? When is Pentoxifylline? When are biologics used?
Methotrexate/Azathioprine used in refractory disease Chloroquine/Hydroxychloroquine used for mucocutaneous skin disease Pentoxifylline used for its cortico-sparing effect
Biologics used in refractory disease and special circumstances: Infliximab appears to be effective for patients with systemic manifestations such as lupus pernio, uveitis, hepatic and neurosarcoidosis
For patients with pulmonary fibrosis from sarcoids what is the hope for long term survival?
For patients with advanced pulmonary fibrosis from sarcoidosis, lung transplantation remains the only hope for long-term survival.
What is the course of disease for sarcoids?
- Approximately 2/3 resolve spontaneously with no or minor residual
- One third smolder or worsen
- 15 – 20% suffer permanent loss of lung function
What are the absolute indications for using corticosteroids? Relative?
Absolute: – Ocular – Myocardial – Central nervous system
Relative: – Hypercalcemia – Skin lesions
Predisone treatment in sarcoidosis?
- The cornerstone of treatment
- Initial dose of 30 mg/day
- Symptomatic improvement generally seen within 1 to 2 weeks
- Maximal improvement at 1 to 2 months
- Alternate-day therapy minimizes side effects
- Safe to use in pregnancy
Indicators for good prognosis in sarcoidosis?
– Acute onset
– Erythema nodosum
– Acute iritis
– Radiographic Stage I
– Lofgren syndrome
– Paucity of extrathoracic disease
Indicators of poor prognosis of sarcoidosis?
- Do persistent abnormalities on the chest x-ray predict active or need for therapy?
Some points to keep in mind in evaluating and treating an individual with sarcoidosis: 1. Do persistent abnormalities on the chest x-ray predict active or need for therapy? The answer is no, but progressive worsening on chest x-ray will predict active disease or the need for therapy.
- Do persistent abnormalities on pulmonary function tests predict active disease or the need for therapy?
- Do persistent abnormalities on pulmonary function tests predict active disease or the need for therapy? No, but progressive worsening on pulmonary function studies predict active disease and need for further therapy.
- Do persistent extrapulmonary manifestations predict active disease or need for therapy?
- Do persistent extrapulmonary manifestations predict active disease or need for therapy? Yes, often they do. Usually worsening of extrapulmonary manifestations predict active disease and need for therapy.
Can chronic disease stabilize? Is there conclusive evidence that corticosteroids alter the natural history of the disease?
- Can chronic disease stabilize? Yes.
- Is there conclusive evidence that corticosteroids alter the natural history of the disease? No.
What is the mortality of sarcoidosis?
• 1 – 5%
– Respiratory failure + cor pulmonale and pulmonary hypertension
– Hemoptysis
– Arrhythmia
– Uremia
