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The underlying immunologic events include: (1) exposure to one or more (unknown) antigens, (2) activation of antigen-presenting cells (macrophages and dendritic cells), (3) a T cell response in an effort to eliminate the antigen, and (4) granuloma formation. - Exaggerated immune response to far unidentified antigens most likely pathogen-associated molecular patterns of killed and partly degraded mycobacteria and propionibacteria
- Innate and Adaptive Immune mechanisms are involved in pathogenesis.
- Phagocytic defects:
Mycobacteria and propionibacteria persist in macrophage phagosomes because their high lipid content in membranes makes them acid-fast, and many of their glycolipoproteins are not very soluble and resist degradation. - Cell Signaling: Antigen-associated molecular pattern trigger
- 4 types:
- 2 Membrane-bound
- TLR (7 types) TLR2 and TLR9
- Also, alveolar macrophage in response to antigen via TLR 4 signal pathway leads to TNF alpha production
- CLR (5 types) C-Type Lectin
- 2 Cytoplasmic
- NLR (6 Types) NOD Like Receptors
- RIG - 1 Helicase receptors (2 Types)
- Complement (Alternate and Lectin Pathways)
- Adaptive Immune System
- T-Cell
- T-Cell Development
- T-Cell Maturation
- T-Cell Activation and antigen presentation or Functioning: Macrophage activation and phagocyte defects lead to T-cell activation. TNF alpha through e.
- Th1: There is also the influx of Th1 cells in organs with sarcoid manifestation. In-situ activation of T-Lymphocytes causes the production of interferon γ, TNF alpha, IL 2
- These Th1 cytokines in turn, activate more antigen-presenting macrophages
- Th2: IL4, TGF Beta
- Th17: Even though there is increased IL17 in sarcoidosis, the role of the Th17 pathway is still undefined.
- B-Cell
- Impaired Development
- Why some patients have spontaneous resolution of sarcoidosis and others have persistent disease is not clear. In progressive disease, the antigen is postulated to persist, thereby inducing a chronic immune response. However, in patient with spontaneous resolution, there is increased release of IMMUNOSPPRESSIVE cytokine TGF Beta
- Impaired Functioning
- T-cell mediated
- T-cel independent
- Regulatory Immune System
- Innate System Regulation
- Adaptive System Regulation
- Absence of negative immunological feedback signals delivered. ie. Tregs leads to further exaggerated Th1 response
- Summary of pathogenesis: Increased inflammation by TNF alpha. Suppression by TGF Beta leads to spontaneous resolution.
Most common clinical presentations are : - persistent cough,
- localization of disease in the skin,
- eye, and
- peripheral lymph nodes,
- erythema nodosum,
- fatigue, and
- incidental abnormal chest radiograph
DDx - infections, particularly tuberculosis;
- occupationally
induced, environmentally induced, and drug-induced
granulomatosis; chronic pulmonary berylliosis is dependent on a focused questionnaire and on beryllium hypersensitivity
- common variable immune deficiency. Diagnosis of common variable immune deficiency relies on hypogammaglobulinaemia,
- Blau’s syndrome;
- sarcoid-like reactions in cancers and
lymphomas, and
- other idiopathic granulomatosis.
Three most important advancement in diagnosis has been: - PET scan
- Rapid on-site assessment by the well trained cytologists
- EUS guided Needle aspirations
Diagnosis is based on the following. The weight of each of them depends on the clinical scenarios. - Clinical Picture and Radiological Picture
- Caseating granulomas, and
- evidence of no alternative findings
Most common diagnostic signs are - bilateral
intrathoracic hilar lymphadenopathy or diffuse
micronodular pulmonary infiltration at chest radiograph,
- associated with a typical lymphatic distribution or a
galaxy sign on CT and
- the presence of some
extrapulmonary localisations of disease—eg, in the eye
and skin
Sarcoidosis Lancet 2014
Sarcoidosis Lancet 2014
- Constitutional symptoms such as fatigue may predominate.
- Cardiac sarcoidosis is much more common than reported previously and may cause loss of ventricular function and
sudden death.
- Cardiac and neurologic sarcoidosis may occur without apparent disease activity in other organs.
- Chest radiographic patterns (stages 1, 2, and 3) do not reflect the chronology of the disease.
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- A response to corticosteroid therapy does not establish the diagnosis of sarcoidosis.
- Measurement of the serum angiotensin-converting–enzyme level is an insensitive and nonspecific diagnostic test and
a poor therapeutic guide.
- For patients without apparent lung involvement, 18FDG PET is useful in identifying sites for diagnostic biopsy.
- 18FDG PET and MRI with gadolinium detect cardiac and neurologic involvement.
- CT imaging is unnecessary for most patients with sarcoidosis. CT is indicated when the chest radiograph is atypical for
sarcoidosis or when hemoptysis occurs.
Clinical Course - Acute : ≤2 years
- Chronic : ≥3–5 years
- Refractory : progressing despite treatment
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