Autoimmune Diseases Flashcards
1
Q
HLA Associations
A
2
Q
Type I Hypersensitivity Reaction
(Anaphylactic)
A
Systemic anaphylaxis
Local anaphylaxis
3
Q
Type II Hypersensitivity Reaction
(Cytotoxic)
A
Complement-dependent reactions
Transfusion reactions
Erythroblastosis fetalis
Autoimmune hemolytic anemia
Pemphigus vulgaris
Some drug reactions
Goodpasture syndrome
Ab-dependent cell-mediated cytotoxicity
Ab-mediated cellular dysfunction
Myasthenia gravis
Grave disease (Ab against TSH receptor)
4
Q
Type III Hypersensitivity Reaction
(Immune Complex Mediated)
A
- Antigens can be exogenous or endogenous
-
Systemic immune complex disease
- Form Ag-Ab complexes in circulation
- Deposit immune complexes in several tissues
- Inflammatory reaction in several tissues
-
Local immune complex disease (Arthus reaction)
- Tissue necrosis d/t acute immune complex vasculitis
5
Q
Type IV Hypersensitivity Reaction
(Cell Mediated)
A
-
Delayed type hypersensitivity
- E.g. Granulomatous inflammation
- T-cell mediated cytotoxicity
6
Q
Autoimmune Diseases
Local vs Systemic
A
7
Q
Autoimmunity
Genetic Factors
A
- Familial clustering of autoimmune diseases
- SLE, autoimmune hemolytic anemia
- Linkage of autoimmune diseases w/ HLA antigens
- E.g. HLA B27
- Induction of autoimmune disease in transgenic mice
8
Q
Microbial Agents
in
Autoimmunity
A
- Viral antigens and autoantigens may become ass. to form immunogenic units ⇒ bypass T-cell tolerance
- Microbial infections ⇒ tissue necrosis and inflammation ⇒ ↑ co-stimulatory molecules on resting APC’S in tissue ⇒ breakdown of T-cell anergy
- Inflammatory response ⇒ presentation of cryptic antigens ⇒ epitope spreading
- Superantigens and other microbial products (e.g. LPS) ⇒ ⊕ large pool of T and B-cells, some of which may be autoreactive
9
Q
Autoimmune Injury
Pathogenesis
A
10
Q
Autoimmune Diseases to Know
A
- Systemic lupus erythematosus
- Sjogren’s syndrome
- Systemic sclerosis (scleroderma)
- Inflammatory myopathies
- Dermatomyositis
- Polymyositis
- Inclusion body myositis
- Mixed connective tissue disease
11
Q
Systemic Lupus Erythematosus (SLE)
Overview
A
- Chronic multi-systemic inflammatory autoimmune disease
- Remitting and relapsing in nature
- Characterized by production of a variety of auto-Ab
12
Q
Systemic Lupus Erythematosus (SLE)
Epidemiology
A
- F:M ratio is 9:1
-
Ages 15 to 45 ⇒ child-bearing age
- Affects 1 in 700 women between ages 20-64
-
↑ incidence in African Americans, Hispanics, and Asians
- Incidence is particularly high in black women
13
Q
Systemic Lupus Erythematosus (SLE)
Global Impact
A
- Survival improved over past 50 yrs to 90% at 10 years
- Better treatments for SLE and infections
- Many more mild cases are dx
- Non-fatal cumulative damage occurs in ~ 50% of survivors
- Most often in MSK system
- 25% with avascular necrosis and/or osteoporosis
14
Q
SLE
Pathogenesis
A
- Strong genetic predisposition to disease
- 3-10x ↑ in clinical disease in MZ vs DZ twins
- Emphasis recently on defects in apoptosis
- Impaired removal of apoptotic cells ⇒ overload of Ag in circulating or target tissues
- Breakdown of immunologic self-tolerance
- Auto-antigens recognized as foreign ⇒ inflammatory response ⇒ activated complement, leukocytes, coagulation system, pro-inflammatory cytokines ⇒ local tissue damage
15
Q
Systemic Lupus Erythematosus (SLE)
Immunologic Factors
A
-
Failure of self-tolerance in B-cells due to:
- Defective elimination of self-reactive B-cells in bone marrow
- Defects in peripheral tolerance
-
CD4+ helper T-cells specific for nucleosomal antigens
- Escape tolerance ⇒ contribute to production of high-affinity pathogenic auto-Ab
- TLR engagement by nuclear DNA and RNA contained in immune complexes ⇒ ⊕ B-cells
- Type I interferons ⇒ activated lymphocytes
- Other cytokines that may play a role including TNF family member BAFF
16
Q
SLE
Clinical Heterogeneity
A
Hypothesis to Explain Clinical Heterogeneity of SLE:
- Environmental Etiologic Factor
-
Genetic Constitution Influences Immune Response
- HLA Antigens
- T-Cell Receptor Genes
- Immunoglobulin Genes
- Complement Component Genes
- Complement Regulatory Genes
- Cytokine Regulatory Genes
- Particular Auto-Ab Arise
- Particular set of auto-Ab present ⇒ clinical disease expression
17
Q
Systemic Lupus Erythematosus (SLE)
Diagnosis
A
Old SLE diagnostic criteria:
Diagnosed using the criteria below
Need ≥ any 4 / 11 criteria present serially or simultaneously during any interval of observation
- Malar rash
- Discoid rash
- Photosensitivity
- Oral ulcers
- Arthritis of two or more peripheral joints w/ tenderness, swelling, or effusion
- Serositis ⇒ pleuritis or pericarditis
- Renal disorder ⇒ persistent proteinuria or cellular casts
- Neurologic disorder ⇒ seizures or psychosis in absence of offending drugs or known metabolic derangements
-
Hematologic disorder
- Hemolytic anemia w/ retiuculocytosis
- Leukopenia on two or more occasions
- Lymphopenia on two or more occasions
- Thrombocytopenia in absence of offending drugs
-
Immunologic disorder
- Anti-DNA Ab to native DNA in abnormal titer
- Anti-Sm ⇒ presence of Ab to Sm nuclear antigen
- Positive finding of antiphospholipid Ab based on:
- Abnormal serum level of IgG or IgM anticardiolipin Ab
- Positive test for lupus anticoagulant
- False positive serologic test for syphilis
- Known to be positive for at least 6 months
- Confirmed by a negative treponema pallidum immobilization or FTAA test
- Antinuclear Ab ⇒ abnormal titer in absence of drugs known to cause drug-induced Lupus syndrome
New SLE Diagnostic Criteria
Starts with presence of a positive ANA (or an equivalent test)
Includes points for many of the same criteria of old system
Uses a weighting system with different points for different sx
18
Q
Anti-Nuclear Antigens (ANA)
Types
A
-
4 categories of ANA:
- Ab to DNA
- Ab to histones
- Ab to non-histone proteins bound to RNA
- Ab to nucleolar antigen
19
Q
Anti-Nuclear Antigens (ANA)
Patterns
A
See 4 patterns w/ immunofluorescence:
20
Q
Anti-Nuclear Ab (ANA)
Test
A
-
ANA test is sensitive but not specific
- 5-15% of normal individuals have ANAs
- Incidence ↑ w/ age
- Ab to double-stranded (ds) DNA and Smith Antigen are virtually diagnostic of SLE
- Smith Antigen ⇒ particles composed of RNA and protein
- High ds DNA Ab titer is often seen in pts w/ active renal disease
-
Lupus anticoagulant ⇒ actually is a pro-coagulant in vivo
- Blamed for miscarriages and ischemia
21
Q
Systemic Lupus Erythematosus (SLE)
Genetic Factors
A
- ↑ incidence in families
- 20% of clinically unaffected relatives have auto-Ab
- 34% concordance in MZ twins
- If discordant, twin often has auto-Ab but is clinically ok
- This twin may lack environment needed for tissue injury
22
Q
Systemic Lupus Erythematosus (SLE)
Non-Genetic Factors
A
-
Drugs ⇒ hydralazine, procainamide, d-penicillamine
- Get SLE-like response
- Ultraviolet light
- Viruses ⇒ no hard evidence
- Sex hormones
23
Q
Systemic Lupus Erythematosus (SLE)
Mechanism of Tissue Injury
A
- Most visceral lesions mediated by immune complexes
- Type III deposit ⇒ e.g. DNA-antiDNA deposits in glomeruli
- Auto-Ab against RBC, WBC, platelets ⇒ opsonization ⇒ phagocytosis
-
Antiphospholipid Ab syndrome ⇒ venous and arterial thromboses
- Can see spontaneous miscarriages, etc.
24
Q
Morphology Of SLE
A
-
Characteristic lesions result from deposition of immune complexes
- Found in the blood vessels, kidneys, connective tissues, and skin
-
Acute necrotizing vasculitis
- Involves small arteries and arterioles
- May be present in any tissue
- Fibrinoid deposits in vessel walls
- Chronic stage ⇒ vessels undergo fibrous thickening w/ luminal narrowing
25
SLE
“Typical” Clinical Presentation
_Young woman \< 40 y/o:_
* Arthritis or arthralgia ⇒ 55%
* Skin involvement/Malar rash ⇒ 20%
* Nephritis/Proteinuria ⇒ 10%
* Fever/Fatigue/Malaise/Wt Loss ⇒ 15%
* Other ⇒ 10%
* Most pts have sx in only 1-2 systems at onset
* Nany accumulate organ-system involvement over several years
26
Systemic Lupus Erythematosus (SLE)
Clinical Manifestations
27
Renal Lupus
* **Up to 50% of SLE have clinically significant renal involvement**
* _Manifestations may include:_
* Persistent proteinuria \> 500 mg/24 hr or \> 3+
* Cellular casts (red cell, granular, tubular or mixed)
* Nephrotic syndrome
* End-Stage Renal Disease
* Best studied SLE organ involvement
* Excellent clinic-pathological correlates in SLE
* **Kidney biopsy eval. w/ LM, EM, and IF**
28
SLE
Class I ‐ Minimal Mesangial Lupus Nephritis
* Least common type
* Can appear normal on LM
* **Granular mesangial deposits of Ig and complement on EM and IF**
29
SLE
Class II ‐ Mesangial Proliferative Lupus Nephritis
* Seen in 5-10% of biopsies in SLE
* _Clinical_ ⇒ **microscopic hematuria and proteinuria**
* Histology:
* **Moderate ↑ in mesangial matrix and # of mesangial cells**
* **Granular mesangial deposits of Ig and complement** on EM and IF
30
SLE
Class III ‐ Focal Lupus Nephritis
* **\< 50% of glomeruli involved**
* **Either segmental or global lesions**
* Seen in 20% to 35% of pts
* _May see:_
* Crescent formation
* Fibrinoid necrosis
* Proliferation of endothelial and mesangial cells
* Infiltrating WBCS
* Intracapillary thrombi
* _Clinical_: **hematuria and proteinuria**
* Active (proliferative) inflammatory lesions can heal completely or lead to chronic glomerular scarring
31
SLE
Class IV ‐ Diffuse Proliferative Lupus Nephritis
* **Most common and most severe form of lupus nephritis**
* Occurs in 35% to 60% of pts
* Looks like class III but **affects \> 50% of glomeruli**
* Either segmental or global lesions
* Histology:
* **Subendothelial immune complex deposits** ⇒ thickened capillary wall
* See ‘**wire loops**’ on LM
* _Clinical:_
* Hematuria and proteinuria along
* Hypertension
* Mild to severe renal insufficiency
32
SLE
Class V - Membranous GN
* **Seen in 10-15% of lupus nephritis pts**
* **See diffuse thickening of the capillary walls**
* Similar to idiopathic membranous glomerulonephritis
* **Severe proteinuria or nephrotic syndrome**
* Can occur concurrently w/ focal or diffuse lupus nephritis
33
SLE
Class VI – Advanced Sclerosing
* **Sclerosis of \> 90% of glomeruli**
* Represents **end-stage renal disease**
* Can also see changes in interstitum and tubules
* **Immune complexes in tubular or peritubular capillary basement membranes**
34
Mucocutaneous Lupus
* _Rashes:_
* **Malar/butterfly rash** ⇒ spares nasolabial folds
* Seen in 50% of pts
* **Discoid** ⇒ peripheral hyperpigmentation with central atrophy/scarring, usually on face, scalp, ears, neck and extensor surfaces of the arms
* **Subacute cutaneous (SCLE)** ⇒ raised erythematous lesions (annular or serpiginous) usually on chest, back and outer arms
* **Oral/nasopharyngeal ulcers** ⇒ usually painless
* **Alopecia**
* Scarring (discoid)
* Non-scarring (active systemic disease and drugs)
* **Vasculitic lesions**
* Nail fold infarcts
* Frank digital ulcers
* **Livedo Reticularis** ⇒ netlike pattern of reddish-blue skin discoloration
* **Photosensitivity** ⇒ worse in sunlight
* Sunlight can incite or accentuate erythema
35
SLE
Skin Histology
* Liquefactive degeneration of basal layer of epidermis
* **Edema at D-E junction**
* Perivascular mononuclear infiltrates
* Fibrinoid vasculitis
* **See Ig and complement along D-E junction w/ IF**
36
Lupus Arthritis
* **Arthralgias** ⇒ common (89-90%) ⇒ MCP/IP and wrist joints
* **Non-erosive arthritis** ⇒ Joint deformities unusual
* Polys and fibrin seen in the synovium
* Secondary to ligament loosening/reducible (**Jaccoud’s arthritis**)
* Differential Dx ⇒ Rheumatoid arthritis
* **Osteonecrosis** common (~5-15 %)
37
CNS Lupus
Clinical Manifestations
* **Cognitive disorder**
* **Headaches**
* **Depression, Psychosis**
* **Seizures** - in the absence of offending drugs or metabolic derangements
* **Stroke/TIA**
* **Aseptic Meningitis**
* **Mono/Poly-neuropathy, Transverse Myelitis**
38
CNS Lupus
Pathogenesis
* **Acute vasculitis** ⇒ focal neurologic symptoms
* Not histologically proven
* **Non-inflammatory occlusion** of small vessels by _intimal proliferation_
* **Antiphospholipid Ab** may cause _damage to endothelium_ of vessel
39
Cardiopulmonary SLE
* **Accelerated atherosclerosis**
* **Pleuro-pericarditis/Effusions**
* Seen in vast majority of SLE pts
* Valve can be affected by **non-bacterial verrucous endocarditis** (**Libman-sacks**)
* **Pneumonitis** with or without **pulmonary hemorrhage**
* **Interstitial fibrosis**
* **Pulmonary Hypertension**
* **Pulmonary embolism/Secondary infection**
* **“Shrinking lung syndrome”**
40
Hematologic SLE
* Anemia (of chronic disease)
* Leukopenia (\<4000/L)
* Lymphopenia (\<1500/L)
* Thrombocytopenia (\<100,000/L) Lymphadenopathy
* Splenomegaly
* Hemolytic anemia with reticulocytosis
41
Chronic Discoid Lupus
* Rarely see systemic manifestations
* 5-10% get multisystem disease after many years
* **Characterized by skin plaques which can have:**
* Edema
* Erythema
* Scaliness
* Follicle plugging
* Skin atrophy
* Surrounding erythematous border
* **35% of these pts ANA positive**
* **Rarely positive for dsDNA**
42
SLE Management
General Principles
* **Monitoring every 3-6 months for disease activity**
* **Photoprotection**
* **Avoid possible triggers** ⇒ sulfa drugs, birth control, alfalfa sprouts
* **Prevent atherosclerosis** ⇒ stop smoking, control BP and cholesterol
* **Prevent osteoporosis** ⇒ Calcium, Vit D, Bisphosphonates
* **Infection Control**
* Pneumococcal/Influenza Immunization
* Antibiotic Prophylaxis
* **Planned Pregnancy**
43
SLE
Acute Treatment
* Monitoring every 3-6 months for disease activity for those who are doing well
* Corticosteroids ⇒ for acute issues
* Can be given in very high doses (“pulse steroids”) for life-threatening complications
* **Non-steroid treatment options**
* **“Steroid sparing” agents** (i.e. disease modifying drugs)
* Hydroxychloroquine
* Methotrexate
* Azathioprine
* Leflunomide
* Mycophenylate Mofetil
* **Biologicals** ⇒ Rituximab (B-cell depletion)
* **Cyclophosphamide** ⇒ standard for steroid resistant SLE
44
SLE Mortality
Common Causes:
* **Infections**
* **Lupus nephritis, renal failure**
* **Cardiovascular disease**
* **CNS lupus**
45
Neonatal Lupus Syndromes
46
Drug-Induced Lupus
Etiologies
* _Drugs:_
* Hydralazine ⇒ HLA DR4 has greater risk
* Procainamide
* Isoniazid
* D-penicillamine
* **Pts develop ANAs while taking these meds**
* Rarely see renal and CNS involvement
* Anti-dsDNA Ab rarely develops
* **High frequency of anti-histone positivity**
47
Drug-Induced Lupus
Manifestations
48
Sjogren’s Syndrome
Overview
* **Immune destruction of lacrimal and salivary glands**
* Primary form ⇒ **Sicca syndrome**
* _Results in:_
* **Keratoconjunctivitis sicca** (dry eyes) ⇒ blurring, burning, itching, thick secretions
* **Xerostomia** (dry mouth) ⇒ swallowing difficulty, ↓ sense of taste, dry mucosa
* If these develop in a _pt w/ another autoimmune disease_ (most often RA) ⇒ **secondary form of Sjogren’s syndrome**
49
Sjogren’s Syndrome
Labs
* **Lymphoid infiltration of lacrimal and salivary glands** by activated _CD4+ T-cells and B-cells_
* 75% ⇒ **⊕ Rheumatoid factor**
* 50-80% ⇒ **⊕ ANA**
* 25% ⇒ **⊕ LE test**
50
Sjogren’s Syndrome
Antibodies
* Ab vs _two RNP antigens_ ⇒ SS-A (Ro) and SS-B (La)
* Detected in up to 90% of pts
* High titers of **anti SS-A Ab** are more likely to have extra-glandular manifestations
* Ab can also be seen in SLE pts
* Certain HLA types predominate
* EBV may play a role
51
Sjogren’s Syndrome
Clinical Characteristics
* **Monoclonal B-cell population in salivary gland**
* **Can be a precursor of lymphoma**
* 40x higher incidence of lymphoma vs those w/o Sjogren’s
* Often B-cell, marginal zone type
52
Mikulicz’s Syndrome
**Lacrimal and salivary gland enlargement**
Can be secondary to sarcoid, leukemia, lymphoma, Sjogren’s
53
Sjogren’s Diagnose
**By lip biopsy** to examine minor salivary glands
Presence of **periductal and perivascular inflammation and lymphoid follicles w/ germinal centers**
54
Systemic Sclerosis
(Scleroderma)
Overview
* **Characterized by the presence of excess fibrosis throughout the body**
* Skin most commonly affected
* Also GI tract, kidneys, heart, muscles, and lungs
* **F:M = 3:1**
* Peak from **age 50-60**
* Most severe in black pts, particularly black women
* In a majority of pts (diffuse scleroderma), **the** **disease progresses to visceral involvement**
* Death from renal failure, cardiac failure, pulmonary insufficiency, or intestinal involvement
55
Scleroderma
Epidemiology
* About 150,000 people in the U.S.
* Women \> men (7-9:1)
* Usu. 4th/5th decade of life
56
Scleroderma
Pathogenesis
**Progressive fibrosis**
_Three interrelated processes:_
1. **Autoimmune response**
* Unclear triggers: some pts have environmental exposure to silica dust
* Not clearly an autoimmune disease although associated w/ autoantibodies
* Other autoantibodies, specifically anti-epithelial cell Ab, may be pathogenic by triggering apoptosis of endothelial cells
2. **Vascular damage**
3. **Fibrosis**
57
Scleroderma
Autoimmunity
Unknown Ag ⇒ T-cells response ⇒ cytokine and other mediator release ⇒ ⊕ collagen synthesis by fibroblasts
Also see inappropriate activation of humoral immunity
58
Scleroderma
Antibodies
Disordered humoral immunity also seen
_Two ANAs unique to systemic sclerosis:_
* **Anti-Sc170 Ab**: anti-DNA topoisomerase I
* Highly specific
* More likely to have pulmonary fibrosis and peripheral vascular disease if Ab present
* **Anti-centromere Ab**
* 96% w/ this Ab have crest syndrome (limited systemic sclerosis)
59
Scleroderma
Diagnosis
* **Skin biopsy** can be done although the dx is often based on exam
* Biopsy revealing **dermal fibrosis, ↑ collagen deposition tests**
* _Blood tests:_
* **Antinuclear Ab** (80-95% + depending on how the test is done)
* **Scl-70 Ab**: topoisomerase Ab
* Mainly in diffuse scleroderma, less commonly in limited)
* Can predict interstitial lung disease
* **Anti-centromere Ab**
* Mainly in limited scleroderma
* Less commonly in diffuse scleroderma
* Usu. Present early in disease course
* Predicts limited cutaneous involvement and less aggressive disease
* **Anti-PM-Scl Ab**
* Can be seen in pts w/ polymyositis/ scleroderma overlap syndrome
* **Generally ESR/CRP are not elevated**
* **Raynaud’s phenomenon is nearly universal**
* Can occur w/o Scleroderma
60
Scleroderma
Vascular Injury
* Endothelial injury (cause unknown) ⇒ platelet aggregation ⇒ release of platelet
* Factors ⇒ periadventitial fibrosis
* Activated endothelial cells ⇒ release **PDGF** and **fibroblasts chemotactic factors**
* Narrowed microvasculature ⇒ **ischemic injury**
* **See e/o capillary dilatation and destruction**
61
Scleroderma
Fibrosis
_Multiple factors:_
* Accumulation of **alternatively activated macrophages**
* Actions of fibrogenic cytokines produced by infiltrating leukocytes
* **Hyperresponsiveness of fibroblasts** to cytokines
* Vascular lesions ⇒ ischemic damage ⇒ scarring
62
Diffuse Scleroderma
Clinical Manifestations
Skin thickening and tightening
Usu. Starts in hands/feet and progresses centrally
Rapid progression is associated w/ worse disease
Raynaud’s: affects nearly all pts w/ scleroderma
Esophageal dysmotility
Digital ischemia and gangrene
Pulmonary fibrosis and interstitial lung disease: higher risk in pts w/ anti-Scl-70 Ab
* **Alimentary Tract**
* Affected in \> 90% of pts
* Most severe in esophagus
* Muscle atrophies and is replaced w/ collagen
* Mucosa thin and prone to ulceration
* **Musculoskeletal**
* **Synovitis w/ progression to fibrosis, no joint destruction**
* **Lungs**
* Pulmonary fibrosis and interstitial lung disease
* Can get cyst-like cavities and thickening of small pulmonary vessels
* Higher risk in pts w/ anti-Scl-70 Ab
* **Heart**
* **Pericarditis or myocardial fibrosis** can occur
* **Kidneys**
* 2/3 have renal abnormalities
* See **intimal thickening w/ collagen deposition** in the walls of interlobular arteries and **concentric proliferation of intimal cells**
63
CREST Syndrome
* **Localized scleroderma**
* Relatively limited skin involvement w/ later visceral involvement
* **Ass. w/ anti-centromere Ab**
* Pts have a higher incidence of CREST
* **Calcinosis**
* **Raynaud’s phenomenon** ⇒ episodic vasoconstriction of arteries and arterioles of extremities, often precedes other symptoms)
* **Esophageal dysmotility**
* **Sclerodactyly**: tightened skin of fingers and toes causing joint contractures
* **Telangiectasia:** visible small linear red blood vessels
* Often coincides w/ pulmonary HTN, especially in pts w/ anti-centromere Ab
64
Scleroderma
Renal Crisis
* Malignant HTN, ↓ kidney function
* More common in diffuse scleroderma than limited although can happen in both
* Less common than previously w/ improved recognition and treatment
65
Scleroderma
Prognosis
* Most common cause of death is related to pulmonary fibrosis in diffuse scleroderma
* Pts w/ limited scleroderma may have normal life expectancy, especially if the cutaneous disease is mild
66
Scleroderma
Differential Diagnosis
* Nephrogenic systemic fibrosis
* Eosinophilic fasciitis
* Medication reaction or environmental exposure
67
Scleroderma
Treatment
* No proven effective treatments although many have been tried
* Treatment of organ-specific symptoms in limited scleroderma
* Early recognition/treatment/prevention of scleroderma renal crisis: ACE-inhibitors
68
Inflammatory Myopathies
* **ANA Ab** can be present in some cases
* **Anti-Jo-1** ⇒ Ab vs tRNA synthetase
* Somewhat specific for inflammatory myopathies
* Present in 15-25% of pts w/ inflammatory myopathy
* Also a marker of **coexisting interstitial pulmonary fibrosis**
* Diagnosis made by study of the clinical picture, EMG, enzyme levels, and muscle biopsy
69
Dermatomyositis
Overview
**Seen in adults and children**
_Clinical manifestations:_
* **Distinctive lilac (heliotrope) skin rash**
* Discoloration of the upper eyelids
* **Periorbital edema**
* **Grotton’s lesion** ⇒ scaling red eruption on knuckles, elbows, and knees
* **Muscle weakness** ⇒ bilaterally symmetric and first affects proximal muscles
* _Children_ can also get **GI ulcers, soft tissue calcification**
70
Dermatomyositis
Pathogenesis & Histology
Mechanism involves _capillary attack by Ab and complement_ ⇒ **myocyte necrosis**
Women w/ dermatomyositis have **↑ incidence of some visceral cancers**
71
Polymyositis
* Mainly seen in adults
* **Lacks cutaneous involvement**
* Mechanism involves **cell-mediated immunity w/ CD8+ T-cells**
* Microscopically see **endomysial inflammation w/o evidence of vascular injury**
72
Inclusion Body Myositis
* **Involves distal muscles first**
* May be **asymmetric**
* Pts usually **over age 50**
* Mechanism involves **cell-mediated immunity w/ CD8+ T-cells**
* _Micro_: rimmed vacuoles in myocytes on frozen section
73
Mixed Connective Tissue Disease
* **Clinically has elements of SLE, polymyositis, and systemic sclerosis**
* High titers of **Ab to RNP-particle-containing U1 RNP**
* Pts show little renal disease and a good response to steroids
