Sarcoidosis is a disease that affects multiple systems and is characterized by an overactive immune system that results in the formation of non-caseating granulomas in multiple organ system. It primarily affects the lungs causing bilateral hilar lymphadenopathy, but it can also affect the skin causing erythema nodosum and can affect the eyes causing uveitis.
Risk factors
- Bimodal age distribution between 25-35 and 45-65
- Female and African American
- Family history
- Environmental risk factors:
- Infection with Mycobacterium tuberculosis and Borrelia burgdorferi
Pathophysiology
Sarcoidosis is a disease in which an overactive immune system results in the formation of non-caseating granulomas in multiple organ systems (non-caseating means that there is no necrotic core as you would see in granulomas of tuberculosis for instance).
Recall that there are 3 main types of antigen presenting cells (APC):
- Macrophages
- B-cells
- Dendritic cells
Normally, when an APC comes into contact with an antigen in the body, it will be engulf that antigen present it on the surface of its cell (MHC-II), travel to the lymph node and present to a naive T helper cell. The T helper cell (in particular usually Th1) gets “activated” which triggers its proliferation. The T helper cells (Th1) then leave the lymph node and release pro-inflammatory cytokines that recruit more APCs including macrophages.
Remember the difference between Th1 and Th2 helper cells! Th1 cells stimulate macrophages and initiate the cellular immune response. Th2 cells stimulate immunoglobulin production and initiate the humoral immune response.
Both Th1 and Th2 are CD4 positive cells, which means they interact only with APC cells that have MHC-II (in contrast to MHC-I which is present on the surface of nearly all cells of the body).
This overactive immune system usually targets specific tissues and as they do so they accumulate in nodules called granulomas. These granulomas have a core of macrophages with a periphery composed of Th1 cells and fibroblasts. As the macrophages huddle in the core of the granuloma they can fuse together to form these giant multinucleated cells known as Langhans giant cells. These granulomas continue to leak cytokines which causes persistent inflammation and fibrosis in that area.
Granulomas are usually found in the hilar lymph nodes causing bilateral hilar lymphadenopathy and interstitial fibrosis, but they can also form in the eyes causing uveitis and the skin forming these tender, erythematous nodules known as erythema nodosum.
These macrophages also produce ACE inhibitors and vitamin D which can result in hypercalcemia.
Clinical Presentation
Acute sarcoidosis remits within 2 years. Symptoms are similar to what you would see in chronic sarcoidosis which includes constitutional symptoms, SOB and cough, uveitis and erythema nodosum.
Chronic sarcoidosis has a gradual progression of symptoms but presents similarly to acute sarcoidosis with the same constitutional symptoms, SOB, cough, uveitis, and erythema nodosum. However, in chronic sarcoidosis they may also have involvement of the
- Heart – arrythmia, restrictive cardiomyopathy
- Liver – liver granuloma
- Kidneys – kidney stones due to hypercalcemia
- Spleen – splenomegaly
- MSK – arthritis
Diagnosis
- Chest x-ray to look for bilateral hilar lymphadenopathy
- Labs
- Increased calcium
- Increased ACE inhibitor levels
- Increased ESR, CRP
- Gold standard: biopsy
Treatment
- Most people have minimal symptoms
- If symptoms are present then first line treatment is with steroids, second line is with other immunosuppressants
- Methotrexate
- Azathioprine
- Hydroxychloroquine