Approach to Hypersensitivity and Autoimmune Conditions

Question 1

Type 1 Immediate Hypersensitivity

Answer 1

antigen exposure
IgE cross-linking on mast cell/basophil surfaces
histamine, leukotriene, prostaglandin, tryptase (mediators) release
symptoms of urticaria, rhinitis, wheezing, diarrhea, vomiting, hypotension, and anaphylaxis within minutes of exposure
*may have symptom return 4-8 hours after exposure

Question 2

examples of type 1 hypersensitivity

Answer 2

pollen allergies, dust mite allergy, bee sting

Question 3

Type 2 Cytotoxic Hypersensitivity

Answer 3

IgM or IgG antibody destroys cells by

• opsonization
• complement-mediated lysis
• antibody-dependent cellular cytotoxicity

Question 4

examples of type 2 cytotoxic hypersensitivity

Answer 4

ABO mismatch, Grave’s disease, myasthenia gravis

Question 5

treatment for type 1

Answer 5

antihistamines

Question 6

treatment for type 2

Answer 6

acetylcholinesterase inhibitors, plasmapheresis

Question 7

Type 3 Immunocomplex Hypersensitivity

Answer 7

antigen-antibody complex formation
complexes activate complement and neutrophil infiltration of tissue
tissue inflammation leading to fever, urticaria, generalized lymphadenopathy, arthritis, glomerulonephritis, vasculitis

Question 8

examples of type 3

Answer 8

systemic lupus erythematosus, rheumatoid arthritis, farmer’s lung

Question 9

treatment of type 3

Answer 9

supportive and avoidance of antigen

Question 10

Type 4 Cell-Mediated Hypersensitivity

Answer 10

antigen exposure activates sensitized T-cells

T-cell activation leads to tissue inflammation 48-96 hours after exposure to antigen

Question 11

examples of type 4

Answer 11

poison ivy rash, PPD testing for TB

Question 12

type 4 treatment

Answer 12

symptomatic, steroids (rxn is result of T-cell activation, not histamine)

Question 13

rheumatoid arthritis mechanism

Answer 13

systemic inflammatory disease affecting synovial membranes
granulation tissues develops in joint spaces and erodes into articular cartilage and bone
females moreso
genetic component

Question 14

rheumatoid arthritis presentation

Answer 14

joint swelling, warmth, erythema, and decreased ROM
morning stiffness >1 hour
PIP, MCP, wrist, knees, and ankles are most commonly affected

Question 15

rheumatoid arthritis treatment

Answer 15

disease-modifying anti-rheumatic drugs (DMARDs), NSAIDs, steroids, physical therapy

Question 16

rheumatoid arthritis treatment risks

Answer 16

increased risk of infection from immunosuppression, 2x increase in incidence and mortality from leukemia or lymphoma, increased risk of CVD

Question 17

juvenile idiopathic arthritis mechanism

Answer 17

collagen vascular disorder with persistent inflammation in 1 or more joints for 6 or more weeks in pt <16 y/o
onset at 1-3 y/o
females>males

Question 18

juvenile idiopathic arthritis presentation

Answer 18

pauciarticular - large joints, asymmetric, iridocyclitis, uveitis
polyarticular - large and small joints, symmetric
systemic (Still’s disease) - recurrent high fevers, myalgias, pericarditis, lymphadenopathy, anemia, leukocytosis

Question 19

juvenile idiopathic arthritis treatment

Answer 19

NSAIDs, steroids, methotrexate, anti-TNF therapy, stretching, morning baths, weight-bearing exercises

Question 20

complications of juvenile idiopathic arthritis

Answer 20

pauciarticular - 70% of pts go into remission after several years
polyarticular - symptoms wax and wane
systemic - 50% develop destructive arthritis, complete resolution is rare

Question 21

systemic lupus erythematosus

Answer 21

inflammatory disease
females moreso, especially African American
recurrent exacerbations and remissions, secondary to autoantibody formation and immune complex deposition (type 3 hypersensitivity)
genetic component, HLA-DR2 and -DR3

Question 22

systemic lupus erythematosus presentation

Answer 22

pleuritis, pericarditis, myocarditis
oral aphthous ulcers
arthritis
photosensitivity
hemolytic anemia, thrombocytopenia, leukopenia, lymphopenia
proteinuria or urinary cellular casts
positive ANA
positive anti-dsDNA, anti-SM, antiphospholipid
lupus cerebritis, seizures, psychosis
malar rash (photosensitive butterfly rash)
discoid rash

Question 23

diagnosis of SLE

Answer 23

at least 4 of manifestions

Question 24

differences between SLE and RA

Answer 24

ESR and CRP highly elevated in untreated RA
erosions are common in RA
morning stiffness lasts for hours in RA, but only minutes in SLE
RA commonly deforms

Question 25

SLE treatment

Answer 25

depends on manifestations steroids for flares disease-modifying antirheumatic drugs (DMARDs)

Question 26

SLE prognosis

Answer 26

survival with treatment is 90-95% at 2 years, 75% at 20 years mortality from end-organ damage (renal failure) opportunistic infections secondary to immunosuppression

Question 27

Psoriasis

Answer 27

chronic, hyperproliferative inflammatory disorder characterized by thick adherent scales females/males affected equally

Question 28

psoriasis presentation

Answer 28

mild pruritis, salmon-pink plaques, extensor surface involvement, bilateral, nail pitting, genetic component

Question 29

psoriasis diagnosis

Answer 29

history and physical exam Auspitz sign - pinpoint bleeding after removal of scale biopsy

Question 30

psoriasis treatment

Answer 30

topical steroids, topical vitamin D analogs, other topicals, UV light, systemic immunosuppression

Question 31

psoriasis prognosis

Answer 31

higher frequency of CVD, malignancy, diabetes, hypertension, metabolic syndrome, inflammatory bowel disease, serious infections, other autoimmune disorders -psoriatic arthritis present in 7-48% of pts

Question 32

multiple sclerosis

Answer 32

demyelinating disorder of CNS females>males peak incidence 20-40 y/o

Question 33

MS presentation

Answer 33

vision changes, vertigo, weakness, numbness/tingling/pain, urinary incontinence or retention Lhermitte's sign = electrical sensation running down the spine and lower extremities with neck flexion

Question 34

MS diagnosis

Answer 34

MRI, CSF

Question 35

MS treatment

Answer 35

immunomodulatory, immunosuppressive, IV steroids for acute exacerbations, physical therapy

Question 36

MS prognosis

Answer 36

15 years after diagnosis: 20% have no functional limitations 70% limited or unable to perform major ADLs 75% are unemployed

Question 37

Primary Immunodeficiencies

Answer 37

t-cell specific b-cell specific t-cell/b-cell combined phagocytic disorders

Question 38

clinical signs suggestive of primary immunodeficiency disease

Answer 38

positive family history, infections in multiple locations, increasing frequency/severity of infections with age, unusual and common pathogens

Question 39

t-cell primary immunodeficiency

Answer 39

present in first 3-4 months of life disseminated intracellular diseases ex: DiGeorge syndrome

Question 40

b-cell primary immunodeficiency

Answer 40

present after 6 months of age (maternal antibodies disappear) sinopulmonary and GI infections ex: common variable immunodeficiency (CVID)

Question 41

t-cell/b-cell combined primary immunodeficiency

Answer 41

combined features ex: severe combined immunodeficiency (SCID) - onset at 3 months of age - diarrhea, pneumonia, otitis, sepsis - failure to thrive - treat with antibiotics, recombinant adenosine deaminase, bone marrow transplant

Question 42

phagocytic primary immunodeficiency

Answer 42

sinopulmonary and soft tissue infections ex: chediak-higashi syndrome - defect in microtubular function -- decreased phagocytosis - partial oculocutaneous albinism, progressive neuropathy - treat with antibiotics, bone marrow transplant

Question 43

HIV/AIDS

Answer 43

spread almost exclusively through body fluids 5 million new pts worldwide annually more prevalent in males

Question 44

HIV/AIDS presentation

Answer 44

initially asymptomatic, flu-like symptoms | myalgias, fever, anorexia, headache, fatigue, pharyngitis

Question 45

HIV Diagnosis

Answer 45

ELISA screen, Western blot confirmation, HIV RNA viral load

Question 46

HIV Treatment

Answer 46

recommendation to screen all pts between ages 13-64 at least once, depends on CD4 count, highly active antiretroviral therapy (HAART), prophylaxis of opportunistic infections

Question 47

AIDS diagnosis

Answer 47

CD4 count <200 cell/mm3 or presence of an AIDS-defining illness (cytomegalovirus, mycobacterium avium-intracellulare, candidal esophagitis)