2. What Is Sarcoidosis ?
**Sarcoidosis (sar-koy-DO-sis) is a disease of unknown cause that leads to inflammation. It can affect various organs in the body .

3. **Normally, your immune system defends your body against foreign or harmful substances. For example, it sends special cells to protect organs that are in danger
**These cells release chemicals that recruit other cells to isolate and destroy the harmful substance. Inflammation occurs during this process. Once the harmful substance is destroyed, the cells and the inflammation go away .
**In people who have sarcoidosis, the inflammation doesn't go away. Instead, some of the immune system cells cluster to form lumps called granulomas (gran-yu-LO-mas) in various organs in your body .

4. Sarcoidosis can affect any organ in your body
**Sarcoidosis can affect any organ in your body. However, it's more likely to occur in some organs than in others. The disease usually starts in the lungs, skin, and/or lymph nodes (especially the lymph nodes in your chest).
**If many granulomas form in an organ, they can affect how the organ works , These granulomas might alter the normal structure and possibly the function of the affected organs.

5. Pahtophsiology :

6. 1- T helper 1 lymphocytes play a central role in the immune response , the initial response to some infectious, genetic, or environmental antigen is a release of interleukin-2 and tumor necrosis factor gamma (TNF-gamma) from Th cells which in turn recruits more immune cells to the area of inflammation .
2- The net result is an amplification loop involving antigen-recognition, proinflammatory cytokine release, cell activation, and recruitment

7. 3- These cells accumulate within the lungs and other affected tissues, eventually leading to the formation of noncaseating granulomas .
4- This local immune response and granuloma formation leads to the tissue and organ destruction characteristic of sarcoidosis .
5- In the lungs, about 75% of the granulomas are located close to or within the connective tissue sheath of bronchioles and subpleural spaces. The pulmonary vasculature is also involved in more than 50% of patients.
6-Sarcoid granulomas either resolve or leave behind fibrotic changes .

8. What can happen as the disease progresses ?
1-In many people with sarcoidosis, the disease appears briefly and then disappears without the person even knowing they have the disease.
2- Twenty percent to 30 percent of people have some permanent lung damage.

9. 3- For 10 percent to 15 percent, sarcoidosis is a chronic condition.
4- In some people, the disease might result in the deterioration of the affected organ. Sarcoidosis can be fatal in up to 5 percent of patients

10. Clinical Presentation

11. What Are the Signs and Symptoms of Sarcoidosis?
1- Many people who have sarcoidosis have no symptoms or mild symptoms. Often, the disease is found during achest x- ray done for other reason .
2- Lofgren's Syndrome :
Lofgren's syndrome is a classic set of signs and symptoms that appear in some people when they first develop sarcoidosis. Signs and symptoms may include:

12. A- Fever. This symptom only occurs in some people.
B- Enlarged lymph nodes (which can be seen on a chest x ray ) .
C- Arthritis, usually in the ankles. This symptom is more common in men.
D- Erythema nodosum. This is a rash of red or reddish-purple bumps on your ankles and shins. The rash may be warm and tender to the touch. This symptom is more common in women.

13. Cough .
Shortness of breath.
Wheezing.
Chest pain.
Rash (may or may not be raised)..
Fever.
Pain or irritation of eyes.
Fatigue, especially with exertion.
Muscle weakness.
Night sweats.
Loss of appetite.
Weight loss.
Swollen lymph nodes.
Seizures.
Tremors.
Difficulty hearing.
Blurred vision or blindness.
Poor coordination.
Trouble walking.
Irregular heart rate.
Pain, swelling, and stiffness in the joints.
Facial paralysis ( Bells palsy)..

15. Notes :
1- The clinical symptoms of sarcoidosis may present in many different ways depending on the patient's ethnicity and the chronicity, site, extent of involvement of the organ, and the activity of the granulomas
2- Nonspecific symptoms such as fever, fatigue, malaise, and weight loss may occur in up to one third of sarcoidosis patients
3- Patients may have a combination of any of these forms of the disease

16. What Causes Sarcoidosis?
The cause of sarcoidosis isn't known. More than one factor may play a role in causing the disease.
1- Some researchers think that sarcoidosis develops when your immune system responds to a trigger, such as bacteria, viruses, dust, or chemicals.

17. 2- Genetics also may play a role in sarcoidosis
2- Genetics also may play a role in sarcoidosis. Researchers believe that sarcoidosis occurs if :
A- You have a certain gene (or certain genes) that raise your risk for the disease
—And—
B- You're exposed to something that triggers your immune system .
**Triggers may vary depending on your genetic makeup. Certain genes may influence which organs are affected and how severe your symptoms are.

18. Diagram of the stages of Sarcoidosis

19. Who Is At Risk for Sarcoidosis ?
1- Sarcoidosis affects people of all ages and races. However, it's more common among African Americans and Northern Europeans. In the United States, the disease affects African Americans somewhat more often and more severely than Whites.
2- Studies have shown that sarcoidosis tends to vary in different ethnic groups. For example, eye problems due to the disease are more common in Japanese people.

20. 3- Sarcoidosis is somewhat more common in women than in men
3- Sarcoidosis is somewhat more common in women than in men. The disease usually develops between the ages of 20 and 50.
4- People who have certain jobs also may be at higher risk for sarcoidosis. Examples include :
1- Health care workers
2- People whose jobs expose them to agricultural dust, insecticides, pesticides, or mold
3- Suppliers of building materials, hardware, or gardening materials
4- Firefighters
People who have a family history of sarcoidosis also are at higher risk for the disease.

21. Diagnosis : 1- Physical Exam :
red bumps on your skin; swollen lymph nodes; an enlarged liver, spleen, or salivary glands; or redness in your eyes. Abnormal breathing and heartbeat sounds may be a sign that sarcoidosis is affecting your lungs or heart .

22. 2- Chest X Ray :
The test may show granulomas or enlarged lymph nodes in your chest. About 95 percent of people who have sarcoidosis have an abnormal chest x ray.

23. Chest X-ray changes are divided into four stages :
**Stage 1 bihilar lymphadenopathy
**Stage 2 bihilar lymphadenopathy and reticulonodular infiltrates
**Stage 3 bilateral pulmonary infiltrates
**Stage 4 fibrocystic sarcoidosis typically with upward hilar retraction, cystic & bullous changes

24. 3- Biopsy
confirm a diagnosis or rule out other causes of your symptoms. A biopsy involves taking a small sample of tissue from one of your affected organs.
Sarcoidosis. Lung biopsy specimen showing noncaseating granulomas consistent with the diagnosis of sarcoidosis.

25. 4-Blood tests : To check for a variety of factors :
A- A complete blood count to check for anaemia .
B- Liver function tests to check for liver abnormalities
C- Increased calcium levels, which can occur with sarcoidosis
D- Elevated levels of angiotensin-converting enzyme (ACE), which is often released by the granulomas.

26. 7- ECG: test that records the electrical activity of the heart.
5- Urine test—24-hour urine test to check for elevated levels of calcium in the urine
6- biopsy :removal of a sample of the affected tissue for testing
7- ECG: test that records the electrical activity of the heart.
8- Pulmonary function tests (PFTs) :tests to determine how well you can breathe

27. 9 – Bronchoscopy :the insertion of a lighted tube into the lungs to look at the tissue and obtain a sample for biopsy. bronchoalveolar lavage. This involves flushing the lungs with fluid and collecting the fluid for analysis.
10- Gallium scan—the injection of radioactive material into the body. The material collects in areas with sarcoidosis. A machine later scans the body and identifies areas with higher concentrations of the injected material.

28. 11- Eye exam—done with a special lighted instrument that allows the doctor to look inside the eye.
12- CT scan : a type of x-ray that uses a computer to make pictures of the inside of the body.
13- Thyroid function tests :
Sarcoidosis may cause
Hypo or hyperthyrodism .

29. How Is Sarcoidosis Treated?
The goals of treatment are to:
**Relieve symptoms
Improve organ function**
**Control inflammation and reduce the size of granulomas (inflamed lumps).)
**Prevent pulmonary fibrosis (lung scarring) if your lungs are affected

31. Self-care : To help minimize your symptoms, follow these guidelines :
Don't smoke. If you smoke, quit.1-
2- Avoid exposure to dust and chemicals
3-Notify your doctor at once if any symptoms develop or worsen.

32. Prevention Don't smoke. If you smoke, quit.
Avoid exposure to chemicals and toxins.
To prevent infection, wash your hands before eating or preparing food and after using the bathroom.

33. ETANRCEPT : DEFINITION : INTERFER TNF BY ACTING AS TNF INHIBITOR .
MECHANISM OF ACTION :
Etanercept mimics the inhibitory effects of naturally occurring soluble TNF receptors, the difference being that etanercept, because it is a fusion protein rather than a simple TNF receptor, has a greatly extended half-life in the bloodstream, and therefore a more profound and long-lasting biologic effect than a naturally occurring soluble TNF receptor

34. Infliximab (Remicade)
DEFINITION : it is called a chimeric monoclonal antibody.
Infliximab blocks the action of TNFα by preventing it from binding to its RECEPTOR IN THE CELL . in.

35. HUMIRA