Systemic Lupus Erythematosus Flashcards by Jing Ji

What is SLE?

an inflammatory, multisystem, autoimmune disease of unknown etiology with protean clinical and laboratory manifestations and a variable course and prognosis

lupus can be a mild disease, a severe and life-treatening illness, or anything inbetween

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What is the epidemiology of lupus?

prevalence is 2-7/100,000 worldwide but as high as 207/100,000

incidence is 1-10/100,000 worldwide

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What population is at highest risk for lupus?

women in their reproductive years

female:male ratio is approximately 9:1 postpuberty and premenopausal

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What is the variation in ethniciy in lupus?

blacks (3x)

hispanics and native americans (2-3x)

asians (2x)

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What are some classification criteria for lupus?

95% specificity, 85% sensitivity

external, systemic, and internal findings

hematologic disorder

antinuclear antibodies (ANA)

immunologic disorder

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What are the external features of lupus?

synovitis

malar rash

oral ulcer

subacute cutaneous lupus erythematosus

discord rash

Jaccoud’s arthropathy (deforming arthritis)

vasculitis

lupus profundus

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What are the internal findings of lupus?

serositis

pericardial effusion

cerebral infarct

brain atrophy

spherocytes

glomerulonephritis

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What are the systemic findings of lupus?

pain

fatigue

memory loss

depression

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What organ systems are affected by lupus?

eyes

skin

pleurisy

kidney

muscle

Raynaud’s vasculitis

joints

blood

heart

ears and nose

CNS

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malar rash

fixed erythema, flat or raised, over the malar eminence, tending to spare the nasolabial folds

“butterfly rash”

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discoid rash

erythematous raised patches with adherent keratotic scaling and follicular plugging

atrophic scarring may occur in older lesions

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serositis from SLE

a) pleuritis; convincing history of pleuritic pain or rub heard by physician or evidence of pleural effusion
b) pericarditis; documented by electrocardiogram or rub or evidence of pericardial effusion

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renal disorder from SLE

a) persistent proteinuria > 500 mg per day or > 3+ if quantitation no performed

b) cellular casts - may be red cell, hemoglobin, granular, tubular, or mixed

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neurologic disorders of SLE

a) seizures or b) psychosis - in the absence of offending drugs or known metabolic derangement

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hematologic disorders of SLE

a) hemolytic anemia - with reticulocytosis
b) leukopenia - < 4000/mm³ total
c) lymphopenia - < 1500/mm³ on two or more occasions
d) thrombocytopenia - < 100,000/mm³

**all in the absence of offending drugs

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immunologic disorders of SLE

a) anti-DNA: antibody to native DNA in abnormal titer
b) anti-SM: presence of antibody to SM nuclear antigen
c) positive finding of antiphospholipid antibodies

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anti-dsDNA Ab

not only of major diagnostic significance but in select patients, particularly those with renal involvement, a valuable means of predicting and assessing disease activity

anti-Sm antibodies

recognize determinants on proteins associated with small ribonucleoproteins involved in processing of messenger RNA

of diagnostic importance but do not track disease

SSA/Ro abd SSB/La antibodies

SSA - presence of antibodies can stain the cytoplasmic component of the cell and accounts for some ANA-negative lupus

SSB - involved in transcription termination, seen in patients with one or more of the following: photosensitivity, dry eyes and dry mouth (secondary Sjogrens), subacute cutaneous lesions, risk of a child with neonatal lupus

What do all lupus patients have in common?

antinuclear antibodies (ANA)

this test is not diagnostic of lupus but almost all patietns have this

immunofluorescence is the most reliable - antibody staining

sensitive but not specific

What are othe conditiosn with positive ANA?

3-4% in normal people

95% in scleroderma

50% in Hashimoto’s thyroididis

50% idiopathic pulmonary fibrosis

incidence increases with age, chronic infections, and other chronic conditions

What are other pathogenic antibodies and what do they cause?

anti-SSA and anti-SSB

causes:

subacute cutaneous lupus
neonatal lupus

complete heart block in utero

What are all of the autoantibodies in SLE?

ANA

anti-dsDNA (nephritis)

anti-Sm

anti-RNP (arthritis, myositis, lung disease)

anti-SSA

anti-SSB

antiphospholipid

What are the phases of lupus pathogenesis?

initiation

amplification and perpetuation

irreversible damage

What are the characteristics of the initiation phase of lupus pathogenesis?

multiple proposed mechanisms that may vary from patient to patient occurs years prior to onset of clnical symptoms

What are the characteristiscs of the amplification and perpetuation phase of lupus pathogenesis?

amplification and perpetuation of dysregulated immune mechanisms and response of target organs to inflammatory insult

What are the characteristics of the irreverisble stage of lupus pathogenesis?

arises from disease and secondary affects of treatment

What are the behavior risks that can lead to lupus?

smoking sun exposure stress toxins

What are the environmental risk factors of lupus?

antigen hormones (estrogen) infections toxins medications sun exposure vitamin D deficiency

What are the changes in B-cells in lupus?

defective selection/signaling autoantibody production

What happens to T-cells in lupus?

increased numbers of Th17 and Th2 cells and decreased numbers of Tregs T-cells are less susceptible ot activation-induced cell death

What are the changes in plasmacytoid dendritic cells in lupus?

produce large amounts of interferon plasmacytoid dendritic cells - symulate activiation and proliferation of autoreactive T- and B-cells

What are predctors of a flare in lupus?

new evidence of complement consumption rising anti-dsDNA titers increased ESR new lymphopenia

What are the characteristics of severe lupus?

abrupt onset of symptoms increased renal, neurologic, hematologic, and serosal involvement rapid accrual of damage (irreversible organ injury) associated with race/ethnicity, younger age, male gender, low SE status

What is the mortality of lupus?

current survival rate is \>90% leading causes of mortality are heart disease, malignancy, and infection

What are the goals of therapy for lupus?

stop and reverse ongoing organ inflammation prevent ro limit irreversible end-organ damage

What are the drugs used in lupus treatment?

corticosteroids cyclophosphamide methotrexate mycophenolate mofetil azathioprine hydroxychloroquine belimumab

What are the side effects for immunosuppressive drugs?

infection cancer infertility

What are the common side effects of corticosteroids?

infection Cushingoid appearance osteoporosis osteonecrosis diabetes mood disturbances hypertension lipid abnormalities

What are new therapeutic strategies for treating lupus?

B-cell directed cytokine inhibitors costimulation blockade peptide inhibitors kinase inhibitors T regulatory cells stem cell transplants

What are the guiding therapeutics strategies in treating lupus?

aimed at **induction of remission, maintenacne therapy, and supportive therapy** **titrate dose** to treat effectively with focus on involved organs, and **minimize toxicity** strategic use of **preventive therapites** - antibiotics and vaccinations cardiovascular, cancer, and osteoporosis **screening**

What is the prognosis of SLE?

over 90% of patients survive at least 2 yeasr after diagnosis, and 80-90% survive up to 10 years patients who die within 5 years of diagnosis usually have active dsease requiring high doses of corticosteroids, immunosuppression, and have concomitant infections late deaths are often the result of CVD