Sle + Related Ana Diseases; Vasculitides, Pharm 1

Front 1

Lupus is mostly a disease of what demographic group?

Back 1

Young women (age 15-45 at diagnosis)

Front 2

Pathologic lesions in lupus involve what two primary things?

Back 2

Immune complex deposition

Vascular involvement

Front 3

What autoantibodies are present in lupus?

Back 3

Anti-nuclear (ANA) in almost ALL patients

Front 4

increased frequency of HLA-
____ and ____ in lupus.

Back 4

DR2 & DR3

Front 5

Organ systems most frequently involved in lupus

Back 5

skin and MSK

Front 6

Clinical manifestations of lupus

Back 6

HIGHLY variable, vague in some patients - fatigue, arthralgia/myalgia, fever, weight loss common

Front 7

Organs systems which when affected by lupus carry the worst prognosis

Back 7

Renal disease
Severe CNS involvement

Front 8

Discoid lupus: defn.

Back 8

raised plaques or papules may lead to chronic scarring, pigment changes, irreversible alopecia

Front 9

best recognized cutaneous lesion in lupus

Back 9

Malar "butterfly" rash

Front 10

Cutaneous manifestations of lupus

Back 10

50% at presentation, 75% eventually

Photosensitivity (all exacerbated by sun)

Malar rash

Discoid

Alopecia

Mucous membrane ulcers

Front 11

MSK manifestations of lupus

Back 11

Most common: symmetric polyarticular arthritis/arthralgia involving hands, wrists, knees, ankles

Virtually indistinguishable from rheumatoid arthritis in early disease.

Front 12

Jaccoud's arthropathy: defn

Back 12

deforming, non-erosive arthritis in lupus

Front 13

Serositis: defn

Back 13

inflammation of serosa, common in lupus

Front 14

How does Serositis normally present in lupus? Eventually?

Back 14

pleuritic chest pain or pericarditis is most common

Eventually 30% will experience pleural or pericardial effusions. Can lead to tamponade.

Front 15

Renal disease in lupus: characteristics (LUPUS NEPHRITIS)

Back 15

Proteinuria and/or hematuria

Common but variable in severity.

Active sediment (cellular cast + protein) suggest worse disease.

Front 16

Which pattern on renal biopsy has the WORST prognosis in lupus?

Back 16

Diffuse proliferative glomerulonephritis

Front 17

Predictors of worse renal disease

Back 17

Positive anti-dsDNA antibodies
Low complement levels (C3 and C4)

Front 18

CNS disease in lupus: what is seen?

Back 18

Most serious: psychosis and seizures

Also see central lesions, peripheral neuropathies, headaches, depression, all sorts of stuff

Diagnosis is one of exclusion

Front 19

Libman-Sacks endocarditis: defn

Back 19

Sterile vegetations that can lead to valve failure. Immune complex deposition. Common in lupus.

Front 20

Sjogren's syndrome: defn

Back 20

dry eyes and mouth, salivary enlargement due to sialadenitis

Front 21

hematologic manifestations of lupus

Back 21

1) CYTOPENIAs are common.

2) anemia: 2 kinds

3) Hypercoagulable state

Front 22

Antiphospholipid syndrome: defn

Back 22

When labs are positive for lupus anticoagulant, anticardiolipin, or β2glycoprotein antibodies twice 12 weeks apart + clinical event (thrombosis or miscarriage)

Front 23

Antiphospholipid syndrome: assns with other diseases

Back 23

Can be primary (no underlying disease) or secondary (ie, LUPUS)

Front 24

What autoantibodies are present in SLE?

Back 24

Anti-Nuclear Antibodies (ANA) in 95+%

Anti-dsDNA and anti-Smith antibodies: more specific but less sensitive

Anti-RNP

Anti-SSA and SSB

Front 25

Anti-SSA and SSB antibodies associated with what?

Back 25

Sjogren's syndrome

Neonatal lupus

Congenital heart block
(when the antibodies cross placenta, can affect baby)

Front 26

neonatal lupus: defn

Back 26

When autoantibodies from mothers (specifically anti SSA and SSB) cross placenta and attack skin (and potentially heart nodes) of baby

Front 27

What two types of anemia are seen in lupus?

Back 27

1) Anemia of chronic inflammatory disease

2) Autoimmune hemolytic anemia (Coombs test+)

Front 28

Criteria for dx of lupus:

Back 28

4 of 11 cardinal symptoms required

Front 29

What are the 11 symptoms required for SLE dx?

Back 29

1) Malar rash
2) Discoid rash
3) Photosensitivity
4) Mucositis
5) Arthritis
6) Serositis
7) Renal disorder
8) Neurologic disorder
9) Hematologic disorder
10) Immunologic disorder
11) Antinuclear antibody: +ANA test

Front 30

Categories of drugs used for SLE

Back 30

NSAIDs

Antimalarial drugs

Corticosteroids

Immunosuppressants

Biologic agents (monoclonal antibodies)

Front 31

Common causes of early death from lupus

Back 31

Active renal, neurologic, and other multisystem illness.

ESRD requiring transplant and dialysis a big problem.

Front 32

Common causes of later (long time from diagnosis) death from lupus

Back 32

Premature atherosclerotic disease.

Front 33

Systemic sclerosis is aka

Back 33

Scleroderma

Front 34

Characteristics of scleroderma

Back 34

rare, slowly progressive with fibrosis and vascular lesions.

Front 35

Two types of systemic sclerosis

Back 35

Limiting (CREST) syndrome

Diffuse

Front 36

What drugs commonly cause drug-induced lupus?

Back 36

INH
minocycline
procainamide
hydralazine
anti-epileptics
anti-TNF agents

Front 37

microchimerism: defn

Back 37

most common form is fetomaternal microchimerism (also known as fetal cell microchimerism or fetal chimerism) whereby cells from a fetus pass through the placenta and establish cell lineages within the mother.

Similar to graft-vs-host disease.

May be etiologic factor in systemic sclerosis

Front 38

What is pathogenesis of systemic sclerosis?

Back 38

Fibrosis in vessels, skin, visceral organs

Vascular intimal hyperplasia and fibrosis

Front 39

What is CREST syndrome?

Back 39

A more limited form of systemic sclerosis:

C- calcinosis
R- Raynaud’s
E- esophageal disorder
S- sclerodactyly
T- telangectasia

Front 40

sclerodactyly: defn

Back 40

thickening and tightening of fingers with contracture

Front 41

What is the Esophageal disorder in CREST syndrome?

Back 41

Esophageal hypermotility and loss of LES pressure --> reflux, dysphagia, stricture formation

Front 42

Most frequent cause of death in scleroderma

Back 42

Lung involvement: alveolitis and PROGRESSIVE PULMONARY FIBROSIS

Front 43

Scleroderma renal crisis: defn

Back 43

The acute onset of renal failure.
There is usually an abrupt onset of moderate to marked hypertension (although some patients remain normotensive).

A urine sediment that is usually normal or reveals only mild proteinuria with few cells or casts.

Front 44

Scleroderma renal crisis: treatment

Back 44

Blood pressure control with angiotensin-converting enzyme (ACE) inhibitors with gradual reduction of malignant hypertension is the cornerstone of treatment.

Front 45

Only situation where ACE inhib should be used in acute renal insufficiency

Back 45

Scleroderma renal crisis (it's characterized by HIGH RENIN)

Front 46

Scleroderma: prognosis and outcome

Back 46

CREST patients fare better, but pulmonary htn is BAD.

Diffuse scleroderma: 50% mortality at 5 years.

poor prognostic markers: renal disease, cardiac involvement, progressive pulmonary disease.

Front 47

Polymyositis and Dermatomyositis: defn

Back 47

idiopathic autoimmune inflammatory diseases characterized by inflammation of the muscles and the skin.

Front 48

What drug class is associated with Polymyositis and Dermatomyositis?

Back 48

statins

Front 49

Polymyositis and Dermatomyositis: clinical features

Back 49

1) Muscle weakness (proximal): elevated muscle enzymes, showing evidence of necrosis and irritation

2) Rashes

3) Other features, including pulmonary disease (interstitial pattern), cutaneous vasculitis and calcinosis

Front 50

When an older adult is dxed with Polymyositis and Dermatomyositis, what should you think of?

Back 50

Often associated with MALIGNANCY in older adults

Front 51

Some characteristic rashes in Dermatomyositis

Back 51

Periorbital edema
Violet rash on eyelids (heliotrope rash)
Scaly rash dorsal knuckles (Gottron’s papules)
Shawl sign

Front 52

Polymyositis and Dermatomyositis: how to dx?

Back 52

Muscle weakness, rash, muscle enzymes, EMG, muscle biopsy

Front 53

Secondary Sjogren’s syndrome commonly seen in what diseases?

Back 53

RA and SLE

Front 54

Typical symptoms of Sjogren's syndrome

Back 54

Typical symptoms
Dry eyes
Dry mouth - xerostomia
Salivary gland enlargement

Front 55

What other disease are Sjogren's syndrome patients at risk for?

Back 55

Non-Hodgkins lymphoma - risk is 44x that of healthy population

Front 56

General pathogenesis of all vasculitis

Back 56

Vessel-based inflammation .

Leukocytes in vessel walls --> damage (loss of integrity, vessel lumen occlusion) --> bleeding and tissue ischemia/necrosis

Front 57

T/F Vasculitis may be a primary process or secondary to another underlying disease

Back 57

T

Front 58

What are the general, simple classifications of vasculitis?

Back 58

1) Small-vessel
2) Medium-vessel
3) Large-vessel

Front 59

4 Small-Vessel Vasculitides

Back 59

1) Hypersensitivity vasculitis
2) Henoch-Schonlein purpura (HSP)
3) Wegener's granulomatosis
4) Microscopic polyangiitis

Front 60

Hypersensitivity vasculitis
: clinical characteristics

Back 60

Mostly cutaneous: purpura or maculopapular rash

Often associated with a drug/medication

Front 61

Henoch-Schonlein purpura (HSP): : clinical characteristics

Back 61

Similar to hypersensitivity vasculitis but see deposition of IgA on skin or renal biopsy

Age <20 years at onset

Findings: palpable purpura, bowel angina, GI bleed, hematuria

Front 62

Wegener’s Granulomatosis: defn

Back 62

Granulomatous inflammation of arteries (small and medium), venules, and arterioles

Classic triad of upper airway, lower airway, and renal disease.

Front 63

Wegener’s Granulomatosis: classic triad

Back 63

Classic triad of upper airway, lower airway, and renal disease.

Front 64

Wegener’s Granulomatosis: male:female ratio

Back 64

more men than women

Front 65

Wegener’s Granulomatosis: what is seen on renal biopsy?

Back 65

pauci-immune (no Ig deposition) necrotizing glomerulonephritis

Front 66

Other than the classic triad, what other sx can be seen in Wegener’s Granulomatosis?

Back 66

Ocular disease
Cutaneous
Arthritis
Neurologic

Front 67

Wegener’s Granulomatosis: how to diagnose?

Back 67

1) Traditional approach Biopsy showing granulomatous arteritis
2) Anti-neutrophil cytoplasmic antibodies (cytoplasmic pattern) - c-ANCA

Front 68

What are the lung findings in Wegener’s Granulomatosis?

Back 68

See cavitary pulmonary lesions

Front 69

What autoantibodies are seen in Wegener's?

Back 69

Anti-neutrophil cytoplasmic antibodies (cytoplasmic pattern) - c-ANCA

Front 70

Anti-neutrophil cytoplasmic antibodies (cytoplasmic pattern) - c-ANCA: are they more specific or sensitive?

Back 70

More SPECIFIC - that is, if they're positive, they're very likely to have it.

Front 71

Polyarteritis Nodosa (PAN): defn

Back 71

medium-vessel, systemic necrotizing vasculitis

Front 72

Polyarteritis Nodosa (PAN): clinical presentation

Back 72

fever, malaise, weightloss

Front 73

Polyarteritis Nodosa (PAN): association with what other disease?

Back 73

hepB

Front 74

Polyarteritis Nodosa (PAN): preferentially affects what part of medium-sized vessels?

Back 74

Bifurcations. It leads to aneurysms

Front 75

Polyarteritis Nodosa (PAN): what other organs involved?

Back 75

In order of most to least common:

Arthritis, Peripheral nerve (wrist and foot drop), renal, cutaneous, ocular, ENT, testicular (rare)

Front 76

Takayasu’s Arteritis: defn

Back 76

Chronic arteritis involving aorta and its branches, most common in young women (<40) of Asian descent

Front 77

Takayasu’s Arteritis: clinical presentation

Back 77

malaise, arthralgias, fevers

headaches, dizziness

ARM CLAUDICATION due to upper extremity involvement

Decreased pulses in almost all patients -- "Pulseless disease"

HTN due to aortic/renal involvement

Front 78

Takayasu’s Arteritis: gold standard of diagnosis

Back 78

Arteriogram of aortic arch

Front 79

Giant Cell Arteritis: aka

Back 79

Temporal arteritis

Front 80

Giant Cell Arteritis: defn

Back 80

Systemic inflammatory arteritis.

Most commonly involves the branches of the arteries originating from the aortic arch.

Front 81

Polymyalgia Rheumatica (PMR): defn

Back 81

Syndrome characterized by diffuse aching of shoulder and hip girdles

Front 82

Which two large-vessel arterites are confined to elderly populations?

Back 82

Giant cell arteritis and polymyalgia rheumatica

Front 83

Giant Cell Arteritis: clinical features

Back 83

1) Headache
2) Weight loss
3) Fever
4) PMR
5) Visual disturbance
6) Jaw claudication (pain)

Front 84

Major risk of giant cell arteritis (GCA)

Back 84

blindness

Front 85

Giant Cell Arteritis: when should it be suspected?

Back 85

Patients over age 50, new onset HA, visual disturbance, jaw claudication, elevated sed rate (ESR)

Front 86

Giant Cell Arteritis: gold standard to dx

Back 86

temporal artery biopsy : will see infiltration with chronic mononuclear inflammatory cells with/out giant cells, and destruction of internal elastic lamina

See skip lesions too, so bx might not pick it up.

Front 87

Polymyalgia Rheumatica: when should it be suspected?

Back 87

Patients >50, new onset aching and stiffness esp in hips and shoulders, elevated ESR, dramatic improvement with low dose steroid.

Front 88

Cryoglobulinemia: defn

Back 88

small vessel vasculitis, mostly cutaneous involvement - secndary to other disease

associated with HepC infection or paraproteinemia

Thrombosis and plugging of vessels --> ischemia of digits or glomerulonephritis in kidneys

Front 89

Cryoglobulinemia: associated with what disease?

Back 89

HepC

Front 90

Vasculitis:Therapy in general

Back 90

STEROIDS. Mostly high dose except PMR

Front 91

Cryoglobulins : defn

Back 91

antibodies which precipitate in the cold

Front 92

Difference between COX1 and COX2

Back 92

COX1: present in all tissues

COX2: present in brain and kidney and is induced in most tissues during inflamm and injury.

Front 93

Functions of thromboxane A2

Back 93

Induce platelet aggregation and smooth muscle contraction

Front 94

thromboxane A2: made by COX1 or COX2?

Back 94

COX1

Front 95

Aspirin: MOA

Back 95

Irreversibly inhibits COX1 and COX2

Front 96

NSAIDS: MOA (other than aspirin)

Back 96

reversibly inhibit COX1 and COX2

Front 97

celecoxib: MOA

Back 97

COX2 selective inhibitor (protects GI mucosa and induce platelet aggregation)

Front 98

zileuton: MOA

Back 98

5 lipoxygenase enzyme inhibitor. Produces bronchiolar dilation

Front 99

zafirlukast and montelukast: MOA

Back 99

competitive Leukotriene receptor blockers

Front 100

How do PGs affect nervous system?

Back 100

In general, they're thought to be modulators of neuronal activity. They can increase or decrease release of NTs.

Can cause fever, sensitize pain receptors, etc.

Front 101

_________ binds to marijuana receptors and causes analgesia and decreased locomotion

Back 101

Anandamide.

Front 102

PGs that are produced by platelets and cause aggregation

Back 102

PGG2, PGH2, TXA2

Front 103

PGs that inhibit gastric acid secretion and increase GI mucous secretion.

Back 103

PGE2 and PGI2

Front 104

NF&kappa;B: what does it do?

Back 104

When induced, it stimulates formation of pro-inflammatory molecules

Front 105

Basis of aspirin's anti-thrombotic effects

Back 105

By inhibiting COX1, it prolongs bleeding time by decreasing ability of platelets to aggregate --> prevents formation of thromboxane

Front 106

Salicylism: defn and symptoms

Back 106

mild chronic salicylate poisoning.

Headache, dizziness, tinnitus, difficulty hearing, dim vision, mental confusion, lassitude, drowsiness, etc.

Usually stop when salicylate dose is lowered.

Front 107

Aspirin hypersensitivity: symptoms

Back 107

AKA Aspirin allergy.

rhinorrhea, urticaria, bronchospasm, hypotension, vasomotor collapse. Tx with epinephrine.

Front 108

Diflunisal: MOA

Back 108

salicylate, competitive inhibitor of COX.

More potent anti-inflam than aspirin but no anti-pyretic fx.

Front 109

Diflunisal: Use

Back 109

RA, sprains, OA

Front 110

Sulfasalazine: MOA

Back 110

Poorly absorbed in GI tract sulfonamide. Anti-microbial and anti-inflammatory. Used to treat inflamm bowel disease but also RA and ankylosing spondylitis

Front 111

Sulfasalazine: Use

Back 111

Used to treat inflamm bowel disease but also RA and ankylosing spondylitis

Front 112

Olsalazine: what is it?

Back 112

dimer of 5-aminosalicylate (active anti-inflam agent produced by metabolism of sulfasalazine)

Front 113

WHat is the active anti-inflam agent produced by metabolism of sulfasalazine?

Back 113

5-aminosalicylate

Front 114

T/F People allergic to aspirin are also allergic to NSAIDs

Back 114

T

Front 115

NSAIDs: should be used w/ caution in what patients?

Back 115

Renal failure and CHF

Front 116

_____ from the adeno-hypophysis stimulates synthesis of glucocorticoids from the adrenal cortex

Back 116

ACTH

Front 117

Broadly, how do steroids work?

Back 117

They inhibit early and later phenomena associated with inflammation. They inhibit formation and action of NF&kappa;B.

Front 118

Two main short-acting (8-12 hours )corticosteroids

Back 118

hydrocortisone (cortisol) and cortisone

Front 119

3 main intermediate-acting (12 - 36 hours) corticosteroids

Back 119

prednisone

prednisolone

triamcinolone

Front 120

2 main long-acting (36 - 72 hours) corticosteroids

Back 120

Betamethasone

Dexamethasone

Front 121

What are the two main categories of steroid poisoning?

Back 121

Those due to use of steroids; Those which occur when steroids are terminated or reduced.

Front 122

Acute adrenal insufficiency: how does it relate to steroids?

Back 122

Too rapid steroid withdrawal after prolonged therapy.
fever, myalgia, arthralgia, malaise, weight loss.

Protect from stress until endogenous synthesis returns to normal.

Front 123

Prolonged steroid therapy: effects

Back 123

1) pituitary-adrenal suppression
2) hypokalemic alkalosis and edema
3) Glucosuria -diabetes
4) Increased susceptibility to infection
5) peptic ulceration
6) myopathy - proximal muscle weakness
7) behavioral disturbances
8) osteoporosis
9) growth inhibition and/or arrest
10) cataracts
11) hypertension
12) increased capillary fragility and severity of bruising
13) thinning of skin

Front 124

Alternate day therapy of steroids

Back 124

to minimize metabolic effects and keep anti-inflammatory effects and to simulate normal cyclical steroid levels.