Systemic Lupus Erythematosus! Flashcards
What genetic markers are associated with SLE? Including complement issues.
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
What mediates tissue destruction in lupus?
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.
Is it more common to have systemic or cutaneous lupus? Which one is drug-induced lupus most similar to?
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.
What is neonatal lupus? What antibodies are associated with? What problem does it cause?
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)
What are common causes of drug-induced lupus?
Interferon-alpha - sketchy Hydralazine Procainamide - prom king Minocycline Chlorpromazine Isoniazide Penicillamine Methyldopa
What are the features of SLE?
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
What are the characteristics of the malar vs the discoid lupus rash?
Malar -> erythematous photodistributed patches which SPARE the nasolabial folds
Discoid - Raised patches with keratotic scaling. These lesions may cause SCARRING
What are the serositis and arthritis manifestations of SLE?
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.
What are the hematologic and immunologic manifestations of SLE?
Hemolytic anemia, leukopenia (<5k) , thrombocytopenia (<100k)
Immunologic: Antibodies to dsDNA, anti-Smith, or antiphospholipid
How are the oral ulcers of SLE differentiated from herpes?
Where does a discoid rash most characteristically appear?
They are painless
Most pathognomonic for discoid rash: Conchal bowl (ear) involvement
What does subacute cutaneous lupus erythematosus look like?
Annular, polycyclic lesions with erythematous, scaly border and central clearing,(like tinea corporis)
How is lupus rash told apart from dermatomyositis?
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
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?
Livedo reticularis
On the palms and soles, you can find small vessel vasculitis findings (rash) not dissimilar from Kawasakii disease
What is a rare form of arthropathy which may be present in SLE looking like RA and how does it differ from RA?
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.
What are common pulmonary complications of SLE?
Pleuritis, pleural effusion, progressive interstitial lung disease (inflammatory -> fibrotic with honeycombing), pulmonary hypertension
What causes neurologic complications in SLE?
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)
Why might someone with lupus have dryness of the eyes and mouth?
keratoconjuncitivitis sicca -> often associated with SS-A and SS-B antibodies in lupus. Similar presentation to Sjogren’s syndrome
What markers often precede inflammation of active SLE?
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.
What is meant by disease activity vs severity in lupus?
Activity = degree of active inflammation
Severity = degree of impairment of organ structure or function
What antibodies are present in drug-induced lupus?
Anti-histone antibodies
Why might you want to avoid high dose contraceptives in patients with SLE?
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.
What is the initial treatment of choice for lupus?
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.
What are the more radical therapies used for lupus treatment?
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
What are the typical causes of death in late-stage lupus?
Renal failure, infection (due to immunosuppressive therapy), or accelerated coronary artery atherosclerosis
What is the trigger for Reynaud’s phenomenon and what are the three stages?
Cold or emotion stress -> arteriolar vasospasm
- Fingers become white -> ischemia
- Fingers turn blue -> blood vessels dilate as they become hypoxic
- Fingers turn red -> as blood returns into dilated blood vessels
What is primary Reynaud’s disease? Who gets it? Will it cause damage? Is it symmetrical?
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.
What is secondary Reynaud’s? Who gets it? Will it cause damage? Is it symmetrical
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.
How are primary and secondary Reynaud’s diagnostically told apart?
Via nailfold capillary testing. Primary disease will be normal, secondary disease will show evidence of microvascular disease with irregular enlarged capillary loops.
How is Reynaud’s treated?
Calcium channel blockers and topical nitrates
What is the definition of antiphospholipid syndrome (APS)? Does it always happen in lupus?
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
What antibodies are associated with antiphospholipid syndrome?
- Lupus anticoagulant
- Anticardiolipin antibody
- Anti-Beta2 glycoprotein (an apolipoprotein).
These are all pro-thrombotic
What is the clinical evidence for a vascular thrombosis or pregnancy morbidity (one of these two has to be present for diagnosis of APS)?
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
What are the laboratory criteria for APS diagnosis?
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
What is the treatment for APS?
Lifelong anticoagulation, with heparin products if trying to get pregnant, or warfarin if not trying to get pregnant
