Pathology - Autoimmune Diseases Flashcards
What is autoimmune disease a prototype of?
Hypersensitivity
- Type II (cytotoxic) - organ specific
- Type III (immune complex) - SLE, RA
What is Systemic Lupus Erythematosus (SLE) and what does it involve?
Multisystem inflammatory disease which characteristically involves:
1) skin
2) Joints
3) Kidney
4) Other organ systems
In SLE what is the most important diagnostic Ab?
- Ab against nuclear proteins (ANA; is generic)
- 2x (double stranded)
- Sm (anti Smith) - and Antihistone Ab
- PRESENCE OF BOTH ARE Dx OF SLE
What is very characteristic of SLE in an ANA test?
- “rim” pattern.
What is most damage caused by in SLE?
What sex is SLE more prevalent in?
Vasculitis; immune complexes deposit in essentially all tissues, –> all organs can be involved. Type III hypersensitivity.
- women 9:1, 2x-3x higher in blacks and hispanics, most cases occur in 20s and 30s
What are the clinical manifestations on the skin?
What is the defining histological characteristic of dermal and epidermal border of skin anywhere?
- Erythematous rash in sun - exposed sites ( malar, mid facial “butterfly” rash being most characteristic. Lupus purpura also diffuse (raised rash)
- will see immunoglobulin/ complement deposits AKA “lupus band”
What are the characteristic of joint disease due to lupus?
- > 90% SLE patients have polyarthralgia
- -> inflammatory synovitis w/o joint destruction ( as in RA)
- ->Usually first sign
- ->bilateral pain at same time
- ->joints look inflammed and warm
- -> inflammatory synovitis w/o joint destruction ( as in RA)
What are is characteristic of Renal disease in Lupus?
What are the 4 main types of renal disease in lupus?
- 75% have glomerularnephritis, IgG mainly involved
- 4 main types of Glomerularnephritis:
1) Mesangial lupus GN - Mildest form- immune complexes and complement found in mesangium
2) Focal proliferative lupus nephritis
3) Diffuse proliferative lupus nephritis***- MOST SEVERE of renal disease. Epithelial crescents present (hallmark of serious renal disease). May patients progress–>renal failure
4) Membranous lupus nephritis
- immune complexes and complement found in mesangium
What are the respiratory symptoms of SLE?
- Pleural effusions
- Upper airway involvement
- Pneumonitis
- Progressive interstitial fibrosis
- Pulmonary hypertension
- According to the Mayo Clinic, difficulty with breathing, wheezing and chest pain during physical activity are respiratory symptoms of lupus.**
What are the CNS implications in SLE?
- Life threatening complication
- ->vasculitis leading to hemorrhage infarction
- Memory loss, anxiety, and depression are neurological symptoms of lupus that may become sever if not treated
What are the Cardiac disease implications in SLE?
- Pericarditis most common finding***
- Libman-Sacks endocarditis***
- ->sterile vegetative growths on valve leaflets (not clinically significant- cause they’re not large and rarely vegetate)
- 33% of patients have and increase in concentrations of antiphospholipid Ab which leads to thromboembolisms
What drugs could cause Drug-induced Lupus?
What is are 3 differences betwen SLE and drug-induced lupus?
- Procainamide (arrhythmias) temporary
- Hydralazine ( hypertension)
- Isoniazid (TB)
- 1) no sex predominance
2) Unlike SLE, no CNS nor RENAL involvement
3) Ab to histones ( giving (+) ANA test)
What are differences between SLE and Chronic Discoid Lupus (DLE)?
- DLE which affect eh skin ( but only in sun exposed region) and no organ system involvement.
- The most common symptom in DLE is a circular rash.
What is the main distinguishing factor of Subacute Cutaneous Lupus?
- Papular and anular rings on trunk which are aggravated by sunlight.
What are the main clinical manifestations of Sjogrens syndrome?
- Keratoconjunctivitis (dry eyes)
- xerostomia ( dry mouth)
- Both the above are associated with primary SS.
- Sicca (keratoconjunctivitis and xerostomia)
What sex/age group is Sjogrens most common in?
- Women 30-65 yrs
What other glandular issues might be relevent in Sjogrens?
- immune cells attack and destroy the exocrine glands that produce tears and saliva -therefore bilateral parotid gland enlargement might occur.
What is the relevance of Skin lymphoma with Sjogrens?
40x increase risk of skin lymphoma***, chronic thyroiditis, interstitial nephritis.
What is Scleroderma (Progressive Systemic Sclerosis)?
- PSS characterized by widespread collagen deposition (type III- granulation tissue)
- Could be activated via TGF-Beta
What organs are involved in Scleroderma?
- Skin
- internal organs
- lungs
- GI tract
- heart
- Kidney - vasculature becomes very narrow and decreases blood flow and therefore increases renin release leading to hypertension.
What is the sex/age prevalence of Scleroderma?
What Ab are specific for Scleroderma?
What factor is commonly found?
What do the antibodies target?
- 4:1 women vs. men; 25-50 yrs
- nucleolar Ab to RNA polymerase. Ab to Scl-70 (most common)***
- RA factor
- collagen I, IV ( renal basement membrane)
What pattern of immunofloresece is suggestive of PSS?
- nucleolar pattern of staining in which the bright fluorescence is seen within the nucleoli of the Hep2 cells.
What are some symptoms of Scleroderma?
- Skin edema and collagen deposits
- arteries, arterioles and capillary destruction (increased vascular permeability) ***
- fibrosis with thickening –>Telangiectasia ***
How does Scleroderma affect the kidneys?
Kidneys involved ini more than 50%
-fibrinoid necrosis common in afferent arterioles (ischemia with increased plasma renin–>hypertension)
What 2 variants do patients with PSS present with?
- generalized progressive systemic
2. diffuse cutaneous (“Crest”)
What are the main features of generalized progressive systemic sclerosis?
- Severe and progressive disease of the skin and organs. Early symptoms present with Raynaud’s (intermittent episodes of ischemia in the fingers)
- Next follows edema of fingers and hands, and thickening and “tightening” of skin
- -> patients present with “stone” face with restricted motion of the mouth
- then organ involvement
What are the main symptoms of Raynaud’s?
- When the fingers become cold-sensitive –>due to vasoconstriction
- Patients fingers go from white (lack of blood flow) –>blue as vessels dilate to keep blood in tissue–>red as blood finally returns
What are the outward symptoms of Scleroderma?
- Stone Face - drawn pursed lips, shiny skin over cheeks and forehead, atrophy of muscles in the temple, face, and neck. AKA “Mauskopf”
- hypo- and hyperpigmentation and alopecia are also symptoms
What are the main features of diffuse cutaneous form of Scleroderma?
CREST
- Calcinosis (calcium deposits on skin)
- Raynaud phenomenon
- Esophageal dysmotility (acid reflux and decrease in motility of esophagus)
- Sclerodactyly (thickening and tightening of skin on the fingers and hands)
- Telangiectasia (dilation of capillaries causing red marks on surface of skin)
*** Only 2 of the five symptoms of CREST syndrome is necessary to be diagnosed with the disease
What are the main symptoms of Polymyositis/Dermatomyositis?
- Chronic autoimmune diseases of muscle, most common form is juvenile dermatomyositis, 3:1 prevalence in blacks vs. whites, 2:1 female
What diseases might Polymyositis/Dermatomyositis be mixed with
SLE, PSS, mixed connective tissue disease, and Sjogren syndrome
What are the clinical features of Polymyositis?
- Usually affects adults 40-50’s ***
- No cutaneous involvement ***
- Chronic inflammatory muscle disease
- Symmetric proximal muscle involved
What are the symptoms of long-standing, uncontrolled polymyositis?
- Muscle atrophy, decreased ROM,
What are the main features of dermatomyositis?
- Inflammatory involvement of skin and muscles.
- Bilateral symmetric proximal muscle weakness first to occur
- difficulty standing or climbing stairs
- Fine distal muscle weakness occurs latter
What is the skin issue that occur with dermatomyositis?
- Lilac rash (heliotrope)** on the upper eyelid with periorbital edema
- Grotton lesions** -erythematous patches over knuckles
What percentage go on to develop cancer?
What is involved in the juvenile form?
20-25%
- GI tract involvement (pain)
For mixed connective tissue disease what are the combined features?
-SLE, Sleroderma (PSS), polymyositis/dermatomyositis
What are the clinical features of mixed connective tissue disease?
- Ab direct to ribonucleoprotein particle, containing U1 ribonucleoprotein***
- Not directed at double stranded DNA***
- Nuclear proteins include Jo-1 and PM-1***
- respond well to glucocorticoid Tx
- Etiology and pathogenesis unknown
NO RIM PATTERN
What type of immunofloresent pattern is seen in mixed connective tissue disease?
- “speckled” pattern of staining which is more characteristic of the presence of autoantibodies to extractable nuclear antigens, particularly ribonucleoprotein . Not specific
