Gen Path Exam 3 - Autoimmune Disease - Lupus Flashcards
1
Q
Caused by immune rxn against self
A
Autoimmune disease
2
Q
What 3 things classify autoimmune diseases?
A
Autoimmune rxn
Rxn is not secondary to tissue damage
Absence of another cause of disease
3
Q
Autoimmune diseases affect what % of US population?
A
1-2%
4
Q
What is the spectrum of autoimmune diseases?
A
Organ-specific to generalized/systemic
5
Q
Conditions in which immune response is directed against a single organ or tissue
A
Organ-specific
6
Q
Autoimmune rxn is against widespread antigens
A
Generalized/systemic
7
Q
What are the 2 forms of lupus?
A
Systemic
Cutaneous
8
Q
Cutaneous lupus is divided into what 3 subtypes?
A
Acute
Subacute
Chronic
9
Q
Common form of chronic cutaneous lupus
A
Discoid lupus
10
Q
Occurs in absence of systemic disease, or may occur in association with Systemic Lupus
A
Discoid lupus
11
Q
Risk of progression to Systemic Lupus is 16.7% within 3 years of diagnosis
A
Discoid lupus
12
Q
Many features in common with Systemic Lupus and characteristically develops in people w/o history of systemic autoimmune diseases
A
Drug-induced lupus
13
Q
What are the 2 drugs with the highest risk of Drug-induced lupus?
A
Procainamide
Hydralazine
14
Q
Prototypical multisystem autoimmune disease characterized by production of numerous autoantibodies, especially antinuclear anitbodies (ANAs)
A
Systemic lupus
15
Q
15-17% of Systemic lupus cases occur prior to the age of ____, with peak incidence being in the age range of ______ years
A
16; 20-40
16
Q
Systemic lupus occurs ____ times more frequently in females age 17 to 55 years
A
9
17
Q
Has a 2-3x higher prevalence among blacks and hispanics than in whites
A
Systemic lupus
18
Q
What disease?
Autoantibodies are directed against nucleoproteins, erythrocytes, leukocytes, platelets, coagulation factors, and organs such as the liver, kidneys, heart
A
Systemic lupus
19
Q
T/F: Systemic lupus has a variety of clinical manifestations
A
True
20
Q
What disease?
Specific etiology is not known with certainty, but immunocomplexes, autoantibodies, and genetic, infectious, environmental, and endocrine factors play significant roles
A
Systemic lupus
21
Q
What is the fundamental systemic pathogen mechanism in Systemic lupus?
A
Failure to maintain immunological self-tolerance
22
Q
In systemic lupus, what does failure to maintain immunological self-tolerance lead to?
A
Production of lots of autoantibodies -> damages tissues secondary to immune complex deposition
23
Q
In systemic lupus, failure to maintain immunological self-tolerance, production of autoantibodies, and damage to tissues secondary to immune complex deposition are consistent with what type of rxn?
A
Type III hypersensitivity rxn
24
Q
In systemic lupus, autoantibodies specific for RBCs, WBCs, and platelets opsonize these cells and promote their _____________, resulting in _________
A
phagocytosis; cytopenias
25
In systemic lupus, autoantibodies specific for RBCs, WBCs, and platelets are consistent with what type of rxn?
Type II hypersensitivity rxn
26
In systemic lupus, the formation of what is thought to be related to the decreased functioning of suppressor T-cells and hyper-autoreactive B-cells?
Autoantibodies
27
What accounts for majority of tissue damage seen in systemic lupus?
Immunocomplexes
28
What do the immunocomplexes that account for majority of tissue damage in systemic lupus mostly consist of?
Nucleic acid + IgG
29
What do the immunocomplexes that account for majority of tissue damage in systemic lupus activate and attract?
Activate complement
Attract neutrophils + macrophages
30
In systemic lupus, what 3 things are the result of immunocomplexes activating complement and attracting neutrophils + macrophages?
Vasculitis
Fibrosis
Tissue necrosis
31
In systemic lupus, pts with increased circulating immunocomplexes have more severe damage, particularly affecting which organ?
Kidney
32
In systemic lupus, immunocomplexes also account for tissue damage in which 3 organs in the body (besides kidney)?
CNS
Skin
Lungs
33
T/F: There is familial association with Systemic lupus, meaning family members have an increased risk of developing it
True
34
What disease?
High rate of concordance in monozygotic twins vs dizygotic twins
Systemic lupus
35
What disease?
Relative risk for persons with HLA-DR2 or HLA-DR3 is 2 to 3, and if both haplotypes are present, the risk is about 5
Systemic lupus
36
What disease?
Genetic deficiencies of complement proteins, (especially C1q, C2, or C4) are seen in ~ 10% of patients
Systemic lupus
37
In systemic lupus, genetic deficiencies of complement proteins may result in defective clearance of immune complexes and ________ cells, and failure of ____ cell tolerance
apoptotic; B
38
What exacerbates the lesions of systemic lupus?
UV radiation
39
In systemic lupus, UV radiation causes _________ of host cells, leading to an
increased burden of nuclear fragments and
inflammatory responses to the products of dead cells
apoptosis
40
What has been associated with the development of systemic lupus since it modulates the production of autoantibodies?
Cig smoking
41
What disease?
10x more common in women during reproductive years than in men of similar ages, but only 2-3x more common in women during childhood or after the age of 65
Systemic lupus
42
What disease?
Tx of women with oral contraceptives w/ high doses of estrogen and progesterone did NOT influence the frequency or severity of disease flares, suggesting that factors other than hormones may account for increased risk of this disease in women
Systemic lupus
43
Virus-like particles of ______ viruses have been detected in tissues of pts w/ Systemic lupus
RNA
44
What specific viruses have been reported to occur with increased frequency in pts with Systemic lupus?
Epstein-Barr (EBV)
Cytomegalovirus (CMV)
Varicella-Zoster (VZV)
45
What 3 components of the immune system play a role in the pathogenesis of Systemic lupus?
Type 1 interferons
Toll-like receptors
Failure of B cell tolerance
46
Which component of immune system in Systemic lupus?
Blood cells show molecular signature that indicates exposure to IFN-α; may also produce abnormally large amounts of IFN-α
Type 1 interferons
47
Which component of immune system in Systemic lupus?
Recognize DNA and RNA, notably the DNA-
recognizing TLR9 and the RNA-recognizing TLR7
Toll-like receptors
48
Which component of immune system in Systemic lupus?
Produce signals that activate B cells specific for self nuclear antigens
Toll-like receptors
49
Which component of immune system in Systemic lupus?
Defects in both central & peripheral B cell tolerance result in a higher frequency of autoreactive B cells
Failure of B cell tolerance
50
What disease?
Disease with multi-organ involvement
Systemic lupus
51
In systemic lupus, immunocomplex deposition causes ____________, which leads to renal, cardiovascular, mucocutaneous, and CNS destruction
small-vessel vasculitis (aka lupus vasculitis)
52
In systemic lupus, inflammation of ________ ___________ results in joint, peritoneal, and pleuropericardial symptoms
serous membranes
53
What disease?
As there is no typical pattern of presentation; one patient may present with dermatitis and kidney disease whereas another may present with arthritis, anemia, and pleurisy
Systemic lupus
54
When a patient demonstrates signs/symptoms of multi-organ involvement, what disease should be considered in the differential diagnosis, especially for a female who is 20 to 40 years of age?
Systemic lupus
55
What are many of the pathologic changes seen in Systemic lupus due to?
Lupus vasculitis
56
Why does lupus vasculitis occur in Systemic lupus?
Autoimmune-mediated inflammatory changes
57
In Systemic lupus, where do autoimmune-mediated inflammatory changes most commonly occur?
Small blood vessels
58
Lupus vasculitis can affect any organ system, but where are the 4 most frequent manifestations?
Cutaneous
PNS/CNS
GI
Renal
59
Which manifestation of lupus vasculitis?
The most frequent manifestation of lupus vasculitis
Cutaneous vasculitis
60
Which manifestation of lupus vasculitis?
Responsible for the many of the skin lesions (e.g., rashes ulcerations, cutaneous infarction & necrosis) seen in Systemic lupus
Cutaneous vasculitis
61
Which manifestation of lupus vasculitis?
Results in mononeuritis multiplex causing
tingling, numbness, sensory loss and pain
PNS vasculitis
62
Which manifestation of lupus vasculitis?
Results in cognitive dysfunction, demyelinating
syndrome, cerebrovascular disease, and seizure disorders
CNS vasculitis
63
Which manifestation of lupus vasculitis?
Manifests as lupus mesenteric vasculitis; can result in bowel ischemia and potentially fatal necrosis of the small or large intestine
GI vasculitis
64
Which manifestation of lupus vasculitis?
Results in renal microvascular lesions (lupus nephritis) leading to chronic renal failure
Renal vasculitis
65
What is seen in the spleen of pts with Systemic lupus at autopsy?
Periarteriolar fibrosis
Concentric intimal + SM hyperplasia ("onion skin lesion")
66
What is seen in at least 50% of patients with Systemic lupus, and is termed "lupus nephritis"?
Glomerular destruction
67
In systemic lupus, what results in deposition of complement and immunocomplexes in BM of glomerular capillaries?
Lupus nephritis
68
How many patterns of lupus nephritis are recognized in the current classification system?
6
69
Some pts with Systemic lupus progress to advanced sclerosing lupus nephritis (class VI), which represents what?
End stage renal disease
70
Pts with Systemic lupus that progress to advanced sclerosing lupus nephritis (class VI, representing end stage renal disease require what 2 things for tx?
Hemodialysis
Transplant
71
What results from massive destruction and is a common cause of death in Systemic lupus pts?
Nephrotic syndrome
72
What is often a good indication of the overall prognosis of pts with Systemic lupus?
Severity of kidney disease
73
What is the most common form of lupus nephritis?
Diffuse lupus nephritis (class IV)
74
Glomerulus with thickened capillary loops
Wire loops
75
What are wire loops associated with?
Diffuse lupus nephritis (class IV)
76
Most specific ANA associated with SLE = anti-double stranded DNA
77
Class IV lupus nephritis
Diffuse lupus nephritis
78
Class VI lupus nephritis
Sclerosing lupus nephritis
79
What is an important clinical problem in pts with Systemic lupus resulting primarily from lupus vasculitis?
Accelerated atherosclerosis w/ CAD
80
In Systemic lupus, what may result from myocarditis, hypertension, or valvular disease?
Heart failure
81
Common cardiovascular manifestation in patients with Systemic lupus
Cardiac arrhythmias
82
In a community-based study, woman with Systemic lupus were at significantly increased risk for what 3 cardiac manifestations?
MI
Heart failure
Stroke
83
What type of cardiac abnormalities were found in 25-50% of patients who have Systemic lupus?
Valvular
84
The most common of all cardiac lesions in Systemic lupus involves the ____________ and was originally described as __________ valvular lesions/vegetations
endocardium; verrucous
85
Most frequently affect the mitral valve, but may occur on any valve or even on endocardial surfaces in pts with Systemic lupus
Verrucous valvular lesions/vegetations
86
Verrucous valvular lesions/vegetations most frequently affect which valve?
Mitral
87
Represent an increased risk for the development of bacterial endocarditis in pts with Systemic lupus
Verrucous valvular lesions/vegetations
88
Verrucous valvular lesions/vegetations represent an increased risk for the development of what?
Bacterial endocarditis
89
Lupus-related valvular pathoses can include _______ ________ ___________, with or without regurgitation
valve leaflet thickening
90
Another name for verrucous valvular lesions/vegetations
Libman-Sacks
91
What are the 3 primary hematologic diseases among pts with Systemic lupus?
Leukopenia
Anemia
Thrombocytopenia
92
Which primary hematologic disease among pts with Systemic lupus?
Common and usually reflects lymphopenia but can also be due to immunosuppressive therapies
Leukopenia
93
WBC < 4,000
Leukopenia
94
Which primary hematologic disease among pts with Systemic lupus?
Occurs in most patients during periods of disease activity but is also often due to hemodialysis
Anemia of chronic disease
95
Which primary hematologic disease among pts with Systemic lupus?
ABs to RBCs; occurs in a small proportion of pts
Coombs-positive hemolytic anemia
96
Which primary hematologic disease among pts with Systemic lupus?
Results from increased phagocytosis of autoantibody-coated platelets by spleen, liver, bone marrow and lymph node macrophages; can occur in up to 25% of patients
Thrombocytopenia
97
Platelet count < 100,000
Thrombocytopenia
98
In systemic lupus, what are pts prone to when antiphospholipid antibodies are present?
Episodic thrombosis
99
Increased risk for stroke, DVT, MI, and spontaneous abortion
Episodic thrombosis
100
In systemic lupus, pts are prone to episodic thrombosis when what antibodies are present?
Antiphospholipid ABs
101
What are the 4 mucocutaneous manifestations of Systemic lupus?
Skin rashes/lesions
Skin ulcerations, cutaneous infarction/necrosis
Non-scarring alopecia
Raynaud's
102
In systemic lupus, skin rashes/lesions can be described as...
Acute
Subacute
Discoid
103
Exaggerated vasoconstrictive response to cold
temperature and emotional stress
Raynaud's
104
Affects arteries and arterioles in the extremities, particularly the fingers and toes, but also sometimes the nose, earlobes, or lips
Raynaud's
105
Which form of Raynaud's?
Occurs in the absence of any associated disorders
Primary Raynaud's
106
Which form of Raynaud's?
Occurs due to systemic disease such as Systemic lupus or scleroderma
Secondary Raynaud's
107
What are the 2 most characteristic skin rashes of Systemic lupus?
Malar/butterfly rash
Discoid rash
108
What type of rash seen in Systemic lupus?
Photosensitive rash; fixed flat or raised erythematous rash over the cheeks and bridge of the nose, and often also involves the chin and ears
Malar/butterfly rash
109
don't need to know slide 88, 103
110
What type of rash seen in Systemic lupus?
Exacerbated by sunlight/UV radiation
Malar/butterfly rash
111
What type of rash seen in Systemic lupus?
A more diffuse erythematous maculopapular rash, mainly occurring in sun-exposed areas, is also common
Malar/butterfly rash
112
What type of rash seen in Systemic lupus?
Round, coin-shaped, thick, scaly, erythematous patches most commonly on
the skin of the face, ears, scalp, neck, and hands
Discoid rash
113
Other vasculitic skin lesions seen in Systemic lupus include what 3 things?
Superficial skin ulceration
Infarcts/necrosis of skin/digits
Panniculitis
114
Inflammation of subcutaneous fat
Panniculitis
115
What are the 3 primary musculoskeletal disorders associated with Systemic lupus?
Arthritis (w/ synovitis)
Arthralgia
Myalgia
116
What is the most common initial manifestation of Systemic lupus?
Arthralgia w/ morning stiffness
117
More than 75% of Systemic lupus pts develop a true __________ (specifically inflammatory polyarthritis with synovitis), which is symmetrical and non-erosive and which usually involves the hands, wrists, and knees
arthritis
118
Significant ____________ signs and symptoms are found in 10% - 20% of patients who have Systemic lupus
neuropsychiatric
119
What are the diffuse and focal cerebral dysfunctions observed in Systemic lupus?
Psychoses
Delirium
Seizures
Cerebrovascular accidents (strokes)
120
Which diffuse and focal cerebral dysfunction observed in Systemic lupus is secondary to the presence of antiphospholipid antibodies?
Cerebrovascular accidents (strokes)
121
What is a poor prognostic sign in patients with Systemic lupus?
CNS involvement
122
What type of lesions develop in at least 5-25% of patients with Systemic lupus?
Oral
123
What are the 6 oral lesions seen in pts with Systemic lupus?
Mucosal inflammation
Ulcerations
Lichenoid lesions
Angular cheilosis
Mucositis
Glossitis
124
What are the 4 signs and symptoms of oral conditions seen in pts with Systemic lupus?
Glossodynia
Dysgeusia
Dysphagia
Xerostomia
125
1/3 of pts with Systemic lupus also have what disease?
Sjogren syndrome
126
In Systemic lupus, lip lesions often involve the _________ zone of the ________ lip, and have a central atrophic and ulcerated area with small white dots, surrounded by keratinized border of small radiating white striae
vermilion; lower
127
What type of oral manifestation in Systemic lupus?
Composed of a central depressed red atrophic area surrounded by a 2-4 mm elevated keratotic zone that dissolves into small white lines or a fine stippling of white dots
Lichenoid lesions
128
What is the most frequently positive (most sensitive) diagnostic lab test for Systemic lupus?
Antinuclear antibody ANA test
129
T/F: Clinicians should remember that the ANA test is not specific for any one disease and is frequently positive in patients with autoimmune diseases other than Systemic lupus, including scleroderma, RA, and Sjögren's syndrome
True
130
T/F: The ANA test is specific for Systemic lupus
FALSE, it is not specific for any one disease
131
What is the most commonly used method to detect a variety of nuclear autoantibodies in Systemic lupus?
Indirect immunofluorescence assay (IFA)
132
What are 3 nuclear autoantibodies that are detected in indirect immunofluorescence assays when diagnosing Systemic lupus?
DNA
RNA
Proteins
133
Nuclear autoantibodies like DNA, RNA, and proteins are collectively referred to as what?
Antinuclear antibodies (ANA)
134
What is a first-line test for detecting the presence for up to ~150 different autoantibodies seen in numerous autoimmune diseases?
Indirect immunofluorescence assay (IFA)
135
Name the 5 ANAs produced in Systemic lupus
Anti-ds DNA
Anti-Smith antibodies
Rheumatoid factor
Anti-Ro antibodies
Anti-La antibodies
136
Which ANA has the highest correlation and specificity for Systemic lupus?
Anti-ds DNA
137
T/F: When considering a diagnosis of Systemic lupus, the presence of one or more of the ANAs must be viewed in light of the total clinical picture of the patient’s other signs/symptoms
True
138
What has become an important aid when doing biopsies in the diagnosis of mucosal or skin lesions in Systemic lupus?
Direct fluorescent AB staining
139
Pts with Systemic lupus or Discoid lupus have deposits of what 2 things in the BM zone?
Immunoglobulin
C3
140
Pts with what 2 forms of lupus typically have deposits of immunoglobulin and C3 in the BM zone?
Systemic lupus
Discoid lupus
141
What are 3 other important findings on routine lab tests in patients with Systemic lupus?
Decreased complement levels (C3 and C4)
Increased globulin levels
False + for syphilis
142
What contributes to the false + test result for syphilis in pts with Systemic lupus?
Anticardiolipins
143
Systemic lupus or Discoid lupus?
IFA pattern seen only in skin involved by a rash
Discoid lupus
144
Systemic lupus or Discoid lupus?
IFA pattern appears even in skin that is NOT involved by a rash
Systemic lupus
