Systemic Lupus Erythematosus!

Question 1

What genetic markers are associated with SLE? Including complement issues.

Answer 1

2,3 SLE

HLA-DR2 and HLA-DR3

Complement: C1, C2, and C4 deficiencies are associated with lupus since early complement is needed to clear immune complexes

Question 2

What mediates tissue destruction in lupus?

Answer 2

Antigen-antibody complexes are generated at low levels. Activation of TLRs on APCs via nucleic acid autoantigens activates further inflammation which stimulates the release of more antibodies.

Myeloid cells bind the autoreactive antibodies via their Fc receptors and degranulate -> inflammation and tissue destruction.

Question 3

Is it more common to have systemic or cutaneous lupus? Which one is drug-induced lupus most similar to?

Answer 3

More common to have systemic lupus (70%)

Drug-induced lupus is most similar to systemic lupus, as there is internal organ involvement. The difference is that the symptoms generally subside with removal of the offending drug.

Question 4

What is neonatal lupus? What antibodies are associated with? What problem does it cause?

Answer 4

Congenital condition associated with anti-SS-A (Ro) or anti SS-B (La) antibodies from the mother that affect the fetus.

Can cause heart block of varying degrees in utero (congenital heart block)

Question 5

What are common causes of drug-induced lupus?

Answer 5

Interferon-alpha - sketchy
Hydralazine
Procainamide - prom king
Minocycline
Chlorpromazine
Isoniazide
Penicillamine
Methyldopa

Question 6

What are the features of SLE?

Answer 6

SOAP BRAIN MD

Serositis
Oral ulcers - usually painless
ANA positive
Photosensitivity

Blood / hematologic
Renal involvement
Arthritis
Immunologic / hematologic
Neurologic symptoms (delusions, psychosis)

Malar Rash
Discoid Rash

Question 7

What are the characteristics of the malar vs the discoid lupus rash?

Answer 7

Malar -> erythematous photodistributed patches which SPARE the nasolabial folds

Discoid - Raised patches with keratotic scaling. These lesions may cause SCARRING

Question 8

What are the serositis and arthritis manifestations of SLE?

Answer 8

Pericarditis - fluid around heart
Pleuritis - fluid around lungs

Arthritis - nonerosive inflammatory arthritis in 2+ peripheral joints. Usually the hands. Assymmetric and migratory, but non-deforming.

Question 9

What are the hematologic and immunologic manifestations of SLE?

Answer 9

Hemolytic anemia, leukopenia (<5k) , thrombocytopenia (<100k)

Immunologic: Antibodies to dsDNA, anti-Smith, or antiphospholipid

Question 10

How are the oral ulcers of SLE differentiated from herpes?

Where does a discoid rash most characteristically appear?

Answer 10

They are painless

Most pathognomonic for discoid rash: Conchal bowl (ear) involvement

Question 11

What does subacute cutaneous lupus erythematosus look like?

Answer 11

Annular, polycyclic lesions with erythematous, scaly border and central clearing,(like tinea corporis)

Question 12

How is lupus rash told apart from dermatomyositis?

Answer 12

Lupus rashes are photosensitive, will appear on the skin that’s not wrinkling (i.e. will not appear on joints)

Gottron’s papules of dermatomyositis appear on the joints

Question 13

What is a vascular finding which can be seen in lupus which gives the extremity a lacy purple appearance due to sluggish venous bloodflow?

What vascular finding can be seen on the palms and soles?

Answer 13

Livedo reticularis

On the palms and soles, you can find small vessel vasculitis findings (rash) not dissimilar from Kawasakii disease

Question 14

What is a rare form of arthropathy which may be present in SLE looking like RA and how does it differ from RA?

Answer 14

Jaccoud’s arthropathy

Shows MCP subluxation, swan-neck deformity, and ulnar deviation of the fingers.

Difference from RA: no true joint narrowing / erosion, deformity is caused by tendon laxity. As a result, the deformity is REDUCIBLE.

Question 15

What are common pulmonary complications of SLE?

Answer 15

Pleuritis, pleural effusion, progressive interstitial lung disease (inflammatory -> fibrotic with honeycombing), pulmonary hypertension

Question 16

What causes neurologic complications in SLE?

Answer 16

Can be due to the antibodies, but often is caused by the glucocorticoids used to treat the condition (psychosis and depression are known complications of longterm steroid treatment)

Question 17

Why might someone with lupus have dryness of the eyes and mouth?

Answer 17

keratoconjuncitivitis sicca -> often associated with SS-A and SS-B antibodies in lupus. Similar presentation to Sjogren’s syndrome

Question 18

What markers often precede inflammation of active SLE?

Answer 18

Rise in IgG dsDNA titers

Fall in C3/C4 and CH50

Elevation in CRP / ESR

Ch50 is a test of how much complement is remaining in a patient’s serum which is available to lyse RBCs with anti-RBC antibodies attached to them. This level is decreased in SLE since most of the complement has been used up.

Question 19

What is meant by disease activity vs severity in lupus?

Answer 19

Activity = degree of active inflammation

Severity = degree of impairment of organ structure or function

Question 20

What antibodies are present in drug-induced lupus?

Answer 20

Anti-histone antibodies

Question 21

Why might you want to avoid high dose contraceptives in patients with SLE?

Answer 21

Oral contraceptives contain estrogens which increased risk for DVT, Raynaud’s phenomenon, and pro-coagulation in general
-> many patients have antiphospholipid antibodies which make them pro-coagulated.

Question 22

What is the initial treatment of choice for lupus?

Answer 22

Avoidance of smoking and sun, with NSAIDs for musculoskeletal complaints and serositis.

Antimalarials such as hydroxychloroquine are useful for skin / MSK involvement.

Low dose glucocorticoids may also be used

MTX may be used in refractory arthritis or rash.

Question 23

What are the more radical therapies used for lupus treatment?

Answer 23

High dose oral glucocorticoids are reserved for those with severe renal or CNS involvement.

Belimumab - B cell stimulator inhibitor - BLyS

Rituximab, azathioprine, and mycophenolate all have a role in treating vasculitis / nephritis

Calcineurin inhibitors may be added

Question 24

What are the typical causes of death in late-stage lupus?

Answer 24

Renal failure, infection (due to immunosuppressive therapy), or accelerated coronary artery atherosclerosis

Question 25

What is the trigger for Reynaud’s phenomenon and what are the three stages?

Answer 25

Cold or emotion stress -> arteriolar vasospasm

1. Fingers become white -> ischemia
2. Fingers turn blue -> blood vessels dilate as they become hypoxic
3. Fingers turn red -> as blood returns into dilated blood vessels

Question 26

What is primary Reynaud’s disease? Who gets it? Will it cause damage? Is it symmetrical?

Answer 26

Idiopathic Reynaud’s, usually in younger adults 15-30 years old. It is benign and will not cause gangrene or digital ischemic injury. Capillaries in fingers are normal.

Attacks are symmetrical in both hands.

Question 27

What is secondary Reynaud’s? Who gets it? Will it cause damage? Is it symmetrical

Answer 27

Reynaud’s disease secondary to a disease process such as mixed connective tissue disease, SLE, or CREST syndrome.

Tends to occur in older individuals. Attacks are asymmetrical and may cause gangrene and digital ulceration.

Question 28

How are primary and secondary Reynaud’s diagnostically told apart?

Answer 28

Via nailfold capillary testing. Primary disease will be normal, secondary disease will show evidence of microvascular disease with irregular enlarged capillary loops.

Question 29

How is Reynaud’s treated?

Answer 29

Calcium channel blockers and topical nitrates

Question 30

What is the definition of antiphospholipid syndrome (APS)? Does it always happen in lupus?

Answer 30

Arterial or venous thrombosis or recurrent miscarriage in association with evidence of persistent antiphospholipid antibodies

Often arises in the setting of another CT disorder i.e. Lupus or systemic sclerosis, called secondary APS

Primary APS also occurs more commonly, not associated with anything else

Question 31

What antibodies are associated with antiphospholipid syndrome?

Answer 31

1. Lupus anticoagulant
2. Anticardiolipin antibody
3. Anti-Beta2 glycoprotein (an apolipoprotein).

These are all pro-thrombotic

Question 32

What is the clinical evidence for a vascular thrombosis or pregnancy morbidity (one of these two has to be present for diagnosis of APS)?

Answer 32

Vascular thrombosis - arterial or venous or capillary thrombosis confirmed by ultrasound or histopathology

Pregnancy:
1. Fetal death after 10th week of gestation
or
2. Three consecutive spontaneous abortions before 10 weeks of gestation
or
3. One premature birth due to pre-eclampsia or placental insufficiency

Question 33

What are the laboratory criteria for APS diagnosis?

Answer 33

Presence of elevated titers of anti-beta2 glycoprotein or anticardiolipin antibodies greater than 12 weeks apart

OR

Presence of any lupus anticoagulant in two samples greater than 12 weeks apart

Question 34

What is the treatment for APS?

Answer 34

Lifelong anticoagulation, with heparin products if trying to get pregnant, or warfarin if not trying to get pregnant