Exam #3: Immunopathology III Flashcards
What is Sjogren’s Syndrome?
Autoimmune destruction of the:
- Exocrine glands
- Primary lacrimal glands
- Salivary glands
Is there a sex predominance to Sjogren’s Sydrome?
Yes, females
What is Sicca Syndrome?
Isolated form of Sjogren’s that causes a decrease in tears & saliva
*****Note that Sjogren’s Syndrome is a systemic autoimmune disease
Describe the progression of Sjogren’s Syndrome?
- CD4+ T-cell proliferation against glandular epithelial self-antigens
- Systemic B-cell hyperactivity to antinuclear antigens (ANA)
*****Note that the syndrome may be induced by vial infections e.g. EBV & Hepatitis C
What are hallmark ANAs in Sjogren’s Syndrome?
Anti-nuclear antigens to ribonucleoproteins called:
- SS-A (Ro)
- SS-B (La)
*****These are common & seen in 90% of cases; however, not that ~70% of patients are also positive for Rhematoid Factor (RF)
Describe the pathogenesis of Sjogren’s Syndrome?
- Activated CD4+ T-cells & B-cells infiltrate ducts & vessels in target glands
- Ductal hyperplasia leads to obstruction of the glands
- Acinar atrophy, fibrosis, and replacement of parenchyma w/ fat occurs
Describe the symptomatic progression of Sjogren’s Syndrome.
Dry mucous membranes leads to:
- Xerostomia (dry mouth)
- Keratoconjunctivitis sicca (dry eyes)
- Nasal septal erosion/ perforation
- Dysphagia
- Dypareunia
What are Sjogren’s patients at risk for?
B-cell lymphoma
*****Note that lymph nodes in patients with Sjogren’s Syndrome are often massively hyperplastic
What are the systemic symotoms associated with Sjogren’s Syndrome?
- Systemic vasculitis & extraglandular involvement of the kidneys, lungs, skin, CNS, muscle
Leads to:
- Interstitial nephritis
- Pulmonary fibrosis
- Peripheral neuropathy
- Synovitis
What antibody is associated with more systemic manifestations of Sjogren’s Syndrome?
SS-A (Ro)
**Note that SS-A (Ro) is generally associated with a worse clinical course
What are the symptoms of Systemic Sclerosis?
Involvement of the skin=
- Rigidity
- Loss of specialized skin cells & function
Involvement of the GIT
Is there a sex predominance associated with Systemic Sclerosis?
Female
What is Systemic Sclerosis?
Autoimmune disorder characterized by excessive fibrosis throughout the body; furthermore there is:
1) Chronic inflammation
2) Destruction of small vessels
3) Progressive tissue fibrosis of not only the skin but multiple organs as well
Describe the pathogenesis of Systemic Sclerosis.
The cause of Systemic Sclerosis is unknown.
- It is proposed that there is inappropriate activation of CD4+ T-cells that release cytokines, which activate inflammatory cells & fibroblasts
- There is also blood vessel injury, which causes ischemia leading to fibrosis; cause is unknown
- Also, there is inappropriate humoral activation
What is the predominant growth factor associated with Systemic Sclerosis?
TGF-B
**TGF-B leads to fibroblast activation & fibrosis
What is CREST Syndrome?
There are two subtypes of Systemic Sclerosis, limited & diffuse
- Limited is characterized by:
1) Skin involvement of the face, forearms, & figners
2) Late visceral involvement
**This limited subtype of Systemic Sclerosis is called CREST Syndrome
What does CREST stand for?
Calcinosis Raynaud's phenomenon Esophageal dysfunction Sclerodactyly Telangiectasias
What is Clacinosis?
Ca++ deposits in the skin
What is Raynaud’s phenomenon?
Spasm of blood vessels in response to cold or stress (white fingertips)
What is esophageal dysfunction?
GERD & decreased esophageal motility
What is Sclerodactyly?
Thickening & tightening of the skin on the fingers & hands
What is Telangiectasas?
Dilation of capillaries causing red marks on the surface of skin
What is the severe complication of Reynaud’s Phenomenon?
- Marked pallor of the fingers
- Can lead to necrosis
What is the diffuse variant of Systemic Sclerosis? Symptoms?
This is the second subtype of Systemic Sclerosis that is characterized by:
- Widespread skin involvement at onset
- Early visceral involvement
- Rapid progression
*****A worse clinical course compared to limited/ CREST
What antibody is associated with the diffuse variant of Systemic Sclerosis? What about CREST Syndrome
Antibody to DNA topoisomerase I (anti-Scl-70) is associated with diffuse variant Systemic Sclerosis
*****vs. Anti-cenntromere antibody seen in CREST Syndrome
What are the early skin changes seen with diffuse Systemic Sclerosis?
- Edema
- Lymphocyte (CD4+) infiltrates
What are the late skin changes seen with diffuse Systemic Sclerosis?
- Epidermal thinning
- Dermal/ appendage fibrosis
- Subcutaneous calcifications
Ultimately these lead to contractures i.e. claw fingers & “mask facies”
What are the vascular complications seen with Systemic Sclerosis?
Chronic vascular endothelial damage & fibrosis causes ischemia that leads to autoamputation of digits
What are the esophageal changes that are seen in Systemic Sclerosis?
Collagenization & fibrosis of the muscularis mucosa that leads to:
- Esophageal dysmotility
- LES dysfunction
- GERD
What are the small bowel cahnges seen in Systemic Sclerosis?
- Mucosal thinning
- Loss of villi & microvilli
- Submucosal fibrosis
**All of these pathologic changes result in MALABSORPTION
What are the renal changes that are seen in Systemic Sclerosis? What does this cause?
- Thickening of interlobular arteries by concentric proliferation of intimal cells
- Deposition of collagenous or mucinous material & hyaline
*****These changes result in HTN in 30% of cases
What is the genetic predisposition for RA?
- HLA-DRB1
- PTPN22 (Remember, gene for tyrosine phosphatase that participates in the activation & control of T-cells )
Describe the pathogenesis of RA.
1) Unknown antigenic trigger w/ underlying genetic susceptibility
2) Initiation of synovitis
3) ONGOING AUTOIMMUNE REACTION mediated by CD4+ T-cells
- Produce cytokines
- Activate macrophages
- Activate B-cells
4) Production of Rhematoid Factor
What is RA factor?
IgM auto-antibody to Fc portion of IgG (in same individual)
What are citrullinated peptides?
Certain enzymatic reactions in the body will convert arginine–>citrulline (seen in smokers)
- antibodies that develop to these peptides & contribute to RA
How does RA first present?
Typically, there is a slow & insidious progression starting with malaise, fatigue, and generalized MSK pain
- Several weeks- months later joints become involved
**Joint involvement is typically symmetric with the small joint affected first, then progressing to more proximal joints
What are the hallmark deformaties associated with RA?
Ulnar deviation
Swan-neck
**Note that joints are swollen, warm, painful, & stiff especially following inactivity
How does RA appear on x-ray?
- Loss of joint space
- Ulnar drift of the fingers
**Patients are also diffusely osteopenic (progressing toward osteoporosis)
What is pannus formation?
Inflammatory response that includes:
- Granulation tissue
- Synovial & inflammatory cells
- Fibrous CT
What are the systemic manifestations of RA?
Rheumatoid nodules form at the:
- Skin pressure points
- Viscera
Small vessel vasculitis especially in cases of severe disease w/ high RF titers
Describe the clinical course of RA.
Course is variable, ranging from mild discomfort to progressive disability
What complications are associated with RA?
1) Amlyoidosis
2) Vasculitis
3) Drug complications
- Bleeding
- Infection
What is Juvenile Idiopatic Arthritis?
This is a diagnosis of all forms of arthritis, developing in the patient prior to 16 years-old & persisting for 6 weeks
- Frequently involves large joints
- ANA positive, BUT RF NEGATIVE
What is Still’s Disease?
This is a variant of Juvenile Idiopathic Arthritis that is associated with:
1) Fever
2) Hepatosplenomegaly
3) Rash
4) Increased WBC count
What is mixed connective tissue disease?
Clinical syndrome with overlapping features of SLE & Systemic Sclerosis
**Note that it is DISTINCTIVE b/c of minimal renal disease & good response to steroid therapy
What antibody is associated with MCTD?
anti-U1RNP to ribonucleoprotein
Why is important to remember about MCTD clinically?
Good response to steroid therapy
