What Is SarcoidosisWhat Is Sarcoidosis? ?

****Sarcoidosis Sarcoidosis ((sarsar--koykoy--DODO--sissis) ) is a disease is a disease of unknown cause that leads to of unknown cause that leads to inflammationinflammation. . It can affect various It can affect various organs in the bodyorgans in the body. .

****Normally, your immune system defends your body Normally, your immune system defends your body against foreign or harmful substancesagainst foreign or harmful substances. . For example, it For example, it sends special cells to protect organs that are in dangersends 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.

**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.

PahtophsiologyPahtophsiology: :

11 - -T helper 1 lymphocytes play a central T helper 1 lymphocytes play a central role in the immune response , the initial role in the immune response , the initial response to some infectious, genetic, or response to some infectious, genetic, or environmental antigen is a release of environmental antigen is a release of interleukin-2 and tumor necrosis factor interleukin-2 and tumor necrosis factor gamma gamma ((TNFTNF--gammagamma)) from Th cells from Th cells which in turn recruits more immune cells which in turn recruits more immune cells to the area of inflammationto the area of inflammation. .

22 - -The net result is an amplification loop The net result is an amplification loop involving antigen-recognition, involving antigen-recognition, proinflammatory cytokine release, cell proinflammatory cytokine release, cell activation, and recruitmentactivation, and recruitment

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.

What can happen as What can happen as the disease progressesthe disease progresses ? ? 11--In many people with sarcoidosis, In many people with sarcoidosis,

the disease appears briefly and then the disease appears briefly and then disappears without the person even disappears without the person even knowing they have the diseaseknowing they have the disease..

22 - - Twenty percent to 30 percent of Twenty percent to 30 percent of people have some permanent lung people have some permanent lung damagedamage..

33 - - For 10 percent to 15 For 10 percent to 15 percent, sarcoidosis is a percent, sarcoidosis is a chronic conditionchronic condition..

44 - -In some people, the disease In some people, the disease might result in the might result in the deterioration of the affected deterioration of the affected organorgan. . Sarcoidosis can be fatal Sarcoidosis can be fatal in up to 5 percent of patientsin up to 5 percent of patients

Clinical PresentationClinical Presentation

What Are the Signs What Are the Signs and Symptoms of and Symptoms of SarcoidosisSarcoidosis??

11 - -Many people who have sarcoidosis have Many people who have sarcoidosis have no symptoms or mild symptomsno symptoms or mild symptoms. . Often, Often, the disease is found during achest x- ray the disease is found during achest x- ray done for other reasondone for other reason. .

22 - -Lofgren's SyndromeLofgren's Syndrome : : Lofgren's syndrome is a classic set of Lofgren's syndrome is a classic set of

signs and symptoms that appear in some signs and symptoms that appear in some people when they first develop people when they first develop sarcoidosis. Signs and symptoms may sarcoidosis. Signs and symptoms may includeinclude::

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 .

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)..

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

What Causes What Causes Sarcoidosis? Sarcoidosis?

The cause of sarcoidosis isn't The cause of sarcoidosis isn't knownknown. . More than one factor may More than one factor may play a role in causing the diseaseplay a role in causing the disease..

11 - -Some researchers think that Some researchers think that sarcoidosis develops when your sarcoidosis develops when your immune system responds to a immune system responds to a trigger, such as bacteria, viruses, trigger, such as bacteria, viruses, dust, or chemicalsdust, or chemicals..

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.

Diagram of the stages of Sarcoidosis

Who Is At Risk for Who Is At Risk for SarcoidosisSarcoidosis? ?

11 - -Sarcoidosis affects people of all ages Sarcoidosis affects people of all ages and racesand races. . However, it's more common However, it's more common among African Americans and Northern among African Americans and Northern EuropeansEuropeans. . In the United States, the In the United States, the disease affects African Americans disease affects African Americans somewhat more often and more severely somewhat more often and more severely than Whitesthan Whites . .

22 - -Studies have shown that Studies have shown that sarcoidosis tends to vary in different sarcoidosis tends to vary in different ethnic groupsethnic groups. . For example, eye For example, eye problems due to the disease are problems due to the disease are more common in Japanese peoplemore common in Japanese people..

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.

DiagnosisDiagnosis: :

11 - -Physical ExamPhysical Exam: : red bumps on your skin; swollen red bumps on your skin; swollen

lymph nodes; an enlarged liver, lymph nodes; an enlarged liver, spleen, or salivary glands; or spleen, or salivary glands; or redness in your eyes. Abnormal redness in your eyes. Abnormal breathing and heartbeat sounds breathing and heartbeat sounds may be a sign that sarcoidosis is may be a sign that sarcoidosis is affecting your lungs or heartaffecting your lungs or heart. .

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 .

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

33 - -BiopsyBiopsyconfirm a diagnosis or rule out other confirm a diagnosis or rule out other

causes of your symptomscauses of your symptoms. . A biopsy A biopsy involves taking a small sample of tissue involves taking a small sample of tissue from one of your affected organsfrom one of your affected organs . .

Sarcoidosis. Lung biopsy specimen showing noncaseating granulomas consistent with the diagnosis of sarcoidosis .

4-Blood tests :4-Blood tests :

To check for a variety of factors :To check for a variety of factors :A- A complete blood count to check for A- A complete blood count to check for anaemia .anaemia .

B- Liver function tests to check for B- Liver function tests to check for liver abnormalitiesliver abnormalities

C- Increased calcium levels, which can C- Increased calcium levels, which can occur with sarcoidosisoccur with sarcoidosis

D- Elevated levels of angiotensinD- Elevated levels of angiotensin--converting enzyme converting enzyme ((ACEACE)), which is , which is often released by the granulomas.often released by the granulomas.

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

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.

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.

How Is Sarcoidosis How Is Sarcoidosis TreatedTreated??

The goals of treatment are toThe goals of treatment are to::

****Relieve symptomsRelieve symptomsImprove organ functionImprove organ function****

****Control inflammation and reduce Control inflammation and reduce the size of granulomas the size of granulomas ((inflamed inflamed

lumps)lumps).. ) )****Prevent pulmonary fibrosis Prevent pulmonary fibrosis ((lung lung

scarringscarring) ) if your lungs are affectedif your lungs are affected

SelfSelf--carecare: : To help minimize your symptoms, To help minimize your symptoms,

follow these guidelinesfollow these guidelines: : Don't smokeDon't smoke. . If you smoke, quitIf you smoke, quit..11 - -

22 - -Avoid exposure to dust and Avoid exposure to dust and chemicalschemicals

33--Notify your doctor at once if any Notify your doctor at once if any symptoms develop or worsensymptoms develop or worsen..

PreventionPreventionDon't smokeDon't smoke. . If you smoke, quitIf you smoke, quit . .

Avoid exposure to chemicals and toxinsAvoid exposure to chemicals and toxins . .

To prevent infection, wash your hands To prevent infection, wash your hands before eating or preparing food and before eating or preparing food and after using the bathroomafter using the bathroom..

ETANRCEPTETANRCEPT: :

DEFINITION : INTERFER TNF BY ACTING AS TNF DEFINITION : INTERFER TNF BY ACTING AS TNF INHIBITORINHIBITOR. .

MECHANISM OF ACTIONMECHANISM OF ACTION: : Etanercept mimics the inhibitory effects of Etanercept mimics the inhibitory effects of

naturally occurring soluble TNF receptors, the naturally occurring soluble TNF receptors, the difference being that etanercept, because it is a difference being that etanercept, because it is a fusion protein rather than a simple TNF fusion protein rather than a simple TNF receptor, has a greatly extended half-life in the receptor, has a greatly extended half-life in the bloodstream, and therefore a more profound and bloodstream, and therefore a more profound and long-lasting biologic effect than a naturally long-lasting biologic effect than a naturally occurring soluble TNF receptoroccurring soluble TNF receptor

InfliximabInfliximab ( (RemicadeRemicade)) DEFINITION : it is called a DEFINITION : it is called a

chimeric monoclonal antibodychimeric monoclonal antibody..

Infliximab blocks the action of Infliximab blocks the action of TNFTNFα α by preventing it from by preventing it from binding to its RECEPTOR IN THE binding to its RECEPTOR IN THE CELL . CELL . inin..

HUMIRAHUMIRA