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Clinical Immunology > Rheumatoid arthritis & Lupus Erythmatosus > Flashcards

Rheumatoid arthritis & Lupus Erythmatosus Flashcards

1
Q

Know the different forms of Lupus

A

Discoid
Systemic lupus Erythematosus
Drug induced
Neonatal

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2
Q

Difference between Discoid Lupus and Systemic lupus

A

Discoid: Is limited to skin (Cutaneous)
-Generally does NOT involve internal organs
-10% of cases
Can evolve into systemic

Systemic: Multisystem (MORE severe) can affect - skin, joints, any organ (50% have a major organ affected)
-More symptoms = active flare
-Less symptoms = remission
-70% of cases

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3
Q

Drug induced lupus

A

-Occurs after taking prescribed drugs BUT usually fade when drug is stopped
-Most frequently hydralazine hydrochloride & Procainamide hydrochloride
-4% of people will develop Abs suggestive if lupus and ONLY small & will develop into lupus

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3
Q

Etiology of lupus

A

Cause is unclear BUT development of SLE autoantibodies is due to defective B cell tolerance for self Ags
-Primary defect in regulation of immune system is Important to pathogenesis

Genetic predisposition (BUT NO I.D. gene yet)
-Known to occur in families. 10% of Pts with lupus have Parent/sibling w/ disease

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3
Q

Neonatal lupus

A

-Condition is rare & is NOT systemic
-Rash will appear w/in first several weeks of life (may persist for 6months)

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3
Q

What factors affect Lupus

A

Gut microbes
-West Africans have lower incidence
Hormonal Influence
-Probable link w/ estrogen. Postmenopausal women who begin estrogen therapy MORE likely to develop SLE
Antibiotics (Sulfa, tetracycline-related, penicillin-related)
-Kill microbes => may trigger lupus
-African-Americans Use Abx more than West Africans => may affect lupus severity/prevalence
Vitamins
-(Vitamin D, A, & Omega-3) => modulate lupus onset or flares

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4
Q

Epidemiology of Lupus

A

-10-15x more frequent in Women than men
-2-3x more prevalent in people of color
-Highest mortality in Ppl of w/ renal involvement or CNS disease
-2 most frequent causes of death is renal failure & infectious complications

Survival at 90% AFTER 10yrs of diagnosis

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5
Q

Signs & symptoms of acute & chronic inflammation of Lupus

A

-joint pain
-arthritis
-Butterfly rash
-Fever
-weight loss
-malaise

J A B + F W M

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6
Q

Other characteristics of Lupus

A

-Elevated Abs - anti-dsDNA & anti-ribosomal P Abs
-Reduced lvls of complement & leukopenia

-Immune complex can cause clinical manifestations - photosensitive facial rash; transient diffuse arthritis; & CNS, renal, cardiac, or respiratory system

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7
Q

Cutaneous features of Lupus

A
  • 20-25% develop dermal disorders (initial manifestation)
    -65% with Butterfly rash (UV light will exacerbate Rash)
    -Rash can also be found on arms & trunk
    -Alopecia
    -1/3 w/ Raynaud phenomenon
    -Discoid lupus

-Uticaria, angioedema, nonthrombocytopenic, scale formation, ulcerations in mouth & genital mucus membranes.

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8
Q

True or False:

Treatment of lupus by steroids can lead to

a) opportunistic infections
b) interference of host defense
c) Increase host immune system
d) A & B

A

D) opportunistic infections & can interfere w/ host defenses

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9
Q

What does lupus affect the kidneys

A

-Immune complexes cause injury to renal system
-Acute/chronic glomerulonephritis (unpredictable progression)

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10
Q

True or False:

Lupus can cause lymph enlargement the lymph nodes but NOT the spleen

A

FALSE

Both Lymph enlargement & splenomegaly can occur

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11
Q

True or False:

Specific gastrointestinal issues are commonly associated w/ Lupus

A

False:

NON-specific GI issues are common

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12
Q

What is Serositis

A

-An inflammation of the mesothelium (thin layer of connective tissue enclosing body cavity)
-Its a cardinal finding of SLE & can lead to Peritonitis, pleuritis, or pericarditis (All associated w/ severe pain)

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13
Q

What are the cardiopulmonary characteristics associated with lupus

A

-Inflammation of myocardium => lead to tachycardia & (occasionally) congestive heart failure

-Occult diffusion & obstructive abnormalities shown by pulmonary function studies

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14
Q

What are musculoskeletal features of lupus

A

-symmetrical transient and peripheral polyarthritis of small & large joints

-Can result in chronic deformities & disabilities
-10% w/ rheumatoid hand deformities
-25% w/ osteonecrosis

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15
Q

What are the neuropsychiatric features of lupus

A

-Its secondary to central/peripheral nervous system involvement & can cause - mild confusion, memory deficiency, orientation & perception impairment
-Psychiatric disturbances like hypomania, delirium, schizophrenia

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16
Q

At what age does Late onset lupus typically occur?

A

It can occur at any age but has an Average of 62yrs
-More prevalent in Caucasians
-x8 more in women
-mild symptoms (makes it hard to diagnose)

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17
Q

Which specific cells are involved in the pathogenesis of lupus

A

B-lymphs
T-lymphs
Dendritic

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18
Q

What are the characteristics of pathogenesis for lupus

A

-Loss of tolerance to nuclear Antigens (Ags)
-Deposition of immune complexes in tissues
-multiorgan involvement
-Auto-antibodies against that react with Naive or altered self-Antigens

Demonstrable antibodies to - nuclear components, cell surface Ags, cytoplasmic Ags of PMNs, lymphocytic leukocytes, RBCs, Plts, neuronal cells, & IgGs

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19
Q

Characteristics of antibodies and lupus

A

-Antibodies will attach to their corresponding antigens and form immune-complexes => These get deposited into tissued b/c monocyte phagocyte system is unable to eliminate them.

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20
Q

What are the lab features of SLE

A

-Presence of Antinuclear antibodies (ANA)
-immune complexes
-Tissue disposition of immunoglobulins & complement
-circulating anticoagulants & other autoantibodies

-decreased complement levels

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21
Q

What are the cellular aspects of SLE

A

-SLE results form defects in the regulatory mechanism of the immune system
-Lymphocyte subset abnormalities are a major immunologic feature of SLE (variety of abberations in T-cell & B-cell function)
-T cell subsets:
1. HYPER-production of Helper T cell
2. lack/reduced Tcell suppressor
-B cells:
1. Spontaneous B lymphocyte HYPERactivity => uncontrolled production of antibodies to HOST & exogenous antigens

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22
Q

What are the Humoral aspects of SLE

A

Hallmark of SLE is circulating Immune complexes
-Autoantibodies to almost any tissue or organ
-Absence of ANAs ≠ diagnose w/ SLE Unless Pt is being chemically immunosuppressed

-ANA can also be found in other diseased (Rheumatic or nonrheumatic), like some Pts under drug therapy or older healthy ppl.

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23
Q

What are the diagnostic evaluations for SLE

A

-Histologic changes
-Hematologic finding
-Hemostatic changes
-Serologic findings

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24
Q

What are the Histologic changes of SLE

A

-Acute Vasculitis
-Supportive tissue gets infiltrated w/ neutrophils -> then plasma cells & lymphocytes
-Glomerulonephritis & membranous nephritis

25
Q

What are the Hematologic finding of SLE

A

-Moderate anemia (normocytic & normochromic)
-Lymphocytopenia
-Thrombocytopenia (50-100 x10^ 9/L)

26
Q

What are the Hemostatic testings of SLE

A

-Lupus anticoagulants - Inhibitor or prothrombin activator — Often see thrombosis (clot) instead of bleeding
-20% w/ antiphospholipids
-circulating anticoagulants => False POSITIVE for syphilis
-Prolonged Prothrombin time (PT) & partial thromboplastin time (PTT)

27
Q

What are the serologic findings of SLE

A

-High lvls of Anti-DNA antibodies
-Increased gamma globulins (hyper-viscosity & renal tube acidosis)
-Serum cryoglobulins - mixed IgM & IgG types. lvl are proportional w/ severity of SLE

-Reduced complement lvls (breakdown products of C3 -> c3d & c3b)

28
Q

What are Antinuclear antibodies (ANAs)

A

Antinuclear antibodies are autoantibodies that bind to contents of all sub-cellular structure and cell organelles
Including
-cell surfaces
-cytoplasm
-nuclei
-nucleus

Proteins recognized are mainly proteins
-macromolecular complexes
-protein nucleic acid complexes
-nucleic acids

Clinically useful target RNA-protein & DNA-protein complexes

29
Q

What is the cut off for positive ANA titer dilution

A

31.7% (of all normal individuals were) Positive at 1:40 dilution

-13.3% @ 1:80
-5% @ 1:160

Negative cutoff titer at 1:160

30
Q

Which specific autoantibodies are used to monitor SLE?

A

Anti-dsDNA antibodies are used

Generally ANAs
-don’t have organ or species specificity
-capable of reacting w/ nuclear material or animal tissues

ANAs in other diseases can’t be used ≠ confirm SLE
BUT can rule it out

31
Q

What are the 5 subgroups of ANAs

A

-Antibodies to DNA
-Antibodies to centromere
-Antibodies to histone
-Antibodies to non-histone
-Antibodies to nuclear antigens

32
Q

What is immunofluorescence and what is it used for?

A

Technique for determining the location of an antigen (or antibody) in tissues by reaction with an antibody (or antigen) labeled with a fluorescent dye.
-Extremely sensitive (uses fluorescein-conjugated antiglobulin)
-Patterns of reactivity are dependent on what the ANA reacted with

Negative reaction in normal person = no green or gold fluorescence.

33
Q

Know pattern of homogeneous or Diffused

A

-High titers of SLE
-Characterizes anti-DNA nucleoprotein antibodies -> nDNA, dsDNA, ssDNA, DNP or histones
-Nucleus fluoresces evenly (may see Vacuoles)
-Typically seen in rheumatoid disorders

-Low titers can also indicate SLE, and RA Sjogren syndrome, mixed connnective tissue disease (MCTD).

34
Q

Describe the speckled pattern

A

Is a grainy patterns w/ numerous round dots. W/out staining of the nucleoli
-Occurs in presence of Ab to any extractable nuclear Ag devoid of DNA or histone.
-Detected against saline extractable nuclear antigens-> Anti-RNP & anti-Sm

Anti-Sm = high specific for SLE

Anti-RNP = RA, Sjogrens & SLE, PSS, MCTD, dermatomyositis

picture show A w/ speckled staining in the nucleus of the interphase cells & B w/ speckling in the area outside of the chromosomal area

35
Q

Know the nucleolar pattern

A

A few smooth round nucleoli w/ variation in size will fluoresce
-Reflects an antibody to nucleolar RNA (4-6S RNP)
-Present in about 50% of patients with Scleroderma (PSS), Sjogrens & SLE (Also seen in Raynaud phenomenon)

picture shows B w/ chromosomal area & A w/ staining in the nucleoli of the interphase cells

36
Q

Know the Centromere pattern

A

Anticentromere antibody reacts w/ centromeric chromatin of metaphase & interphase cells
-HIGHLY selected for CREST variant of PSS
-discrete & speckled (46 speckles one for each set of chromosomes)

-Found infrequently in SLE MCTD, PSS

picture shows A w/ discrete speckles in the nucleus of the interphase cells = staining of the. B w/ discrete speckling seen in the chromosomal area of the metaphase mitotics

37
Q

Other Assays

What autoimmune does the rapid slide test best used for?

A

Its the a latex slide test

Positive in SLE, RA, scleroderma, Sjogrens

38
Q

Other assay

Whats the autoimmune enzyme Immunoassay (EIA)

A

It a Qualitative screening test & an alternative to IFA’s

39
Q

Other assay

Multiplex Assay

A

-Rapid, sensitive & specific method
-Absence of subjective error in interpretation of result
-only limited number of antigens is tested -> can lead to FALSE Negative results

40
Q

How is SLE treated

A

Medications: NSAIDS, acetaminophen, steroids, immunosuppressants, anticoagulants, biological disease-modifying antirheumatic drug therapy, monoclonal antibody therapy

-treatment/prevention methods will minimize symptoms, reduce inflammation & maintain normal body functions
-AVOID sun & use sunscreen to help prevent rashes
-exercise to prevent muscle weakness & fatigue

-Immunizations to prevent illnesses

41
Q

Define arthritis

A

Arth (join) & -itis (inflammation)

-more then 100 forms (growing problem in U.S.)
-Estimated 22.7% of adults (>18) are diagnosed arthritis
-Females (24.5%) at higher incidence
-OBESITY & physically inactive = are risk factors

42
Q

Etiology of RA

A

Oldest diseases (SLE, RA, gout) - cause is unknown
-May represent an unusual host response to one or maybe many causative agents

43
Q

What are the important factors influencing RA

A

-Genetic
-Hormonal
-Psychosomatic
-Immunologic

44
Q

Epidemiology of RA

A

Occurs Mr. Worldwide

-Increased frequency of local or extra-articular infections
-Cardiovascular disease = most frequent cause of death

-No specific genetic relationship (Small increase w/ 1˚relative)
-Shortened lifespan

45
Q

Signs & symptoms of RA

A

RA is chronic, multi-system, autoimmune disorder; Progressive inflammation of joints
-Highly variable disease
-Ranges from: mild - destructive disease associated w/ vasculitis

46
Q

Pathogenesis of RA. What are the three distinct phases?

A
  1. Initiation of synovitis by the primary causative factor
  2. Subsequent immunologic events that perpetuate the initial inflammatory reaction
  3. Transition of an inflammatory reaction in the synovium to a proliferative, destructive tissue process
47
Q

Initial symptoms of RA?
&
when do joint symptoms appear?

A

Often begins w/ fatigue, anorexia, weakness & generalized aches. Strffness not localized to articular structures

Joint symptoms appear gradually over weeks to MONTHS

48
Q

What are extraarticular manifestations of RA

A

-weight loss, fatigue
-Subcutaneous rheumatoid nodules
-ocular abnormalities
-Vasculitis
-Neuropathy
-Myopathy
-Cardia (pericarditis)
-Pulmonary (pleural effusion)
-osteoporosis
-Felty syndrome (Complex of chronic RA, splenomegaly, anemia, thrombocytopenia & neutropenia)

49
Q

What is the synovium

A

Its the synovial membrane lined w/ synovial cells that synthesize protein & are phagocytic

50
Q

What is the synovial fluid

A

Transparent, viscous fluid; lubricates the joind space & transports nutrients to the articular cartilage
-Inflammatory joints fluids contain lytic enzymes that interfere w/ hyaluronic acid & impairs lubrication

51
Q

Routine analysis of synovial fluid

A

Cell count & differential crystals, gram stain & culture
-volume, appearance, viscosity, chemical analysis

52
Q

What are the 2 (hypothesized) pathogenic mechanisms for RA

A
  1. The extravascular immune complex => interaction of antigens & antibodies in synovial tissues & fluid
  2. Alternative => Cell-mediated damage occurs b/c of accumulation of lymphocytes (mostly Tcells) in the rheumatoid synovium, resembling a delayed-type hypersensitivity reaction. (presence of cytokines which affect articular inflammation & destruction supports this hypothesis)
53
Q

Diagnostic evaluation of RA

A

-low serum iron lvls w/ low normal iron-binding capacity
-ESR elevated to a variable degree - parallels disease activity
-Serum protein electrophoreses
1. elevation in Alpha-2 & gamma globulins
2. gamma globulin increase in polyclonal
3. mild - moderate decrease in albumin

-Rheumatoid factor, anti-cyclic citrullinated peptide (anti-CCP), immune complexes, characteristic complement lvls & ANA’s

54
Q

What are Rheumatoid factors

A

Immunoglobulins of any Isotype w/ antibody activity directed against antigenic site on the Fc region of human or animal IgG

RF Positive correlates w/
-severity of disease (in general)
-Nodules
-Other organ system involvement (vasculitis, Felty syndrome, Sjogrens)

-Associated w/ 3 classes -> IgM, IgG, and IgA
-IgM RF = 70% of adults (NOT specific to RA)

55
Q

Agglutination tests for RF

A

-sensitized sheep cells test & latex agglutination
-Generally detects IgM RFs
-Latex is sensitive but high number of false positives

-Presence of all three IgG isotypes (M, G, A) - specificity of 99% for RA

Immunoturbidimetric & ELISA assay - automated methods
RF also associated w/ bacterial/viral infections & old ppl

56
Q

What are cyclic citrullinated peptide antibodies (CCPs)

A

MORE sensitive than RF

Inflammation w/ RA causes some proteins to become altered by a process call Citrullination
-modified proteins = induce autoimmune response

Anti-CCPs
-HIGHLY specific for RA (95%)
-may be present in preclinical phase - 16yrs before symptoms

57
Q

Other Markers

A

-Antibodies to Anti-perinuclear factor (APF)
-Anti-keratin antibody (AKA)

-Soluble circulating immune complexes & cryoprecipitateble proteins - consists of Igs, complement componenst & RFs

-Complement lvls usually normal EXCEPT in VASCULITIS

-ANA’s found in 14-28% of RA patients

58
Q

Juvenile idiopathic arthritis (JIA)

A

Caused by numerous things, like -> infection, autoimmunity & trauma
-Condition where chronic synovitis beginning during childhood
(affects = .1-1.1%/1000)

Associated w/ retroviral particle called human intracisternal A-Type particle (HIAP)
-Abs in high percentage in Pts of JIA
-(also found in Pts w/ SLE, Sjogrens, & Graves)

59
Q

When is JIA typically diagnosed?

A

Onset before age of 16yrs
-presence of arthritis
-exclusions of conditions to cause/mimic arthritis

Immunologic features can include
-presence of RF
-immune complexes
-ANAs

60
Q

How is RA treated?

A

-Traditional drugs -> NSAIDS (ibuprofgen, apirin/salicylates)
^mostly to reduce inflammation
-Corticosteroids (anti-inflammtory) & glucocorticoids (selective COX-2 inhibitors)
-Nonbiological disease-modifying antirheumatic drugs -> methotrexate
-Biological disease-Modifying drugs
genetically engineered proteins designed to inhibit specific components of the immune system

61
Q

What the three main goals in terms of treating arthritis?

A

-Reduce pain & discomfort
-prevent deformities & loss of joint function
-Help Pt maintain a productive & active life

Inflammation must be suppressed & mechanical/structural abnormalities corrected or compensated for

62
Q

Other treatment options for RA

A

-Reduction of joint stress
-physical & occupational therapy
-drug therapy
-surgical intervention

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