Lupus Flashcards
What are the 5 types of Lupus?
Subacute Lupus Erythematosus Discoid Lupus Drug Induced Lupus Systemic Lupus Erythematosus Neonatal Lupus*
What is Lupus?
- Lupus is a systemic autoimmune disease in which the body loses tolerance to self
- Can affect virtually any organ in the body and initial symptoms are often nonspecific, making it very difficult to diagnose
- Typical autoantibodies seen are those reacting against nuclear components of the cell
- Most commonly seen in women of childbearing age but 10% of patients are men
Systemic Lupus Erythematosus (SLE) diagnosis/ definition
Prototype of auto-immune disease
Onset maybe acute, episodic, or insidious
Anything can happen to any organ system at any time.
Antinuclear antibodies are almost always present
Serositis & Immune complexes can be the hallmark and pathogenesis of the disease.
What is the average time to diagnose SLE?
Average time of two years between initial symptomatology and definitive diagnosis¹.
Analysis of stored serum of 130 military recruits who later developed lupus revealed that autoantibodies were present in the serum up to 9 years prior to the onset of clinical disease²
Epidemiology of SLE
Prevalence rates 40-50 per 100,000 in U.S.
Incidence has tripled in the last 40 years
Incidence rate 2 to 8 per 100,000/year in NA, SA, and Europe
Women affected 9x more frequently- 20-40 year olds most frequent onset in age
African-Americans and Hispanics are affected more frequently than whites and have a higher disease mortality
Urban areas > rural areas
Cases of lupus increase the closer to the equator
65% of patients are between 16 and 55
20% prior to age 16, 15% after age 55
Men have a higher 1 yr mortality rate
The elderly tend to have milder SLE
ACR Criteria for Classification of SLE
Rules for using the criteria:
A patient who exhibits any 4 of these 11 criteria is classified as having SLE Criteria need not be present simultaneously SLE evolves over time.
What are the 11 ACR criteria for classification of SLE
- Malar rash 6. Serositis
- Discoid rash 7. Renal disorder
- Photosensitivity 8. Neurologic disorder
- Oral ulcers 9. Hematologic disorder
- Arthritis 10. Immunologic disorder
11. Antinuclear antibody
Malar Rash
Photosensitive
Spares nasolabial folds*
Fixed erythema, flat or raised, over malar eminences
May be hyperpigmented in darker skinned individuals
Ddx for malar rash
Glucocorticoid-induced atrophy Chloasma/ Melasma Benign flushing Rosacea Dermatitis
Mucocutaneous Lesions Patterns
Acute - localized or generalized
Subacute – Annular or psoriaform
Chronic – Discoid localized or generalized
Nonspecific – Vasculitis, alopecia, livedo reticularis, Raynaud’s, urticaria, lichen planus
Lupus alopecia
Most SLE patients
Localized or generalized
Scalp, eyebrows,
eyelashes, body hair
Increased with disease
activity
Subsides as disease subsides
Discoid Lupus subset
Patients with DLE have 90-95% do not go on to SLE
5 to 10% risk of developing SLE
This form of SLE tends to be mild
The more numerous and widespread the lesions are the higher the risk of developing SLE
Occurs in 25% of lupus patients but can occur in patients without systemic lupus
How would you describe discoid rash
Erythematous raised patches Adherent keratotic scale Follicular plugging Atrophic scarring may occur as lesions age
LOOK IN EARS!
DLE on arm
DLE in ear
Subacute Cutaneous Lupus Subset
50% of patients with SCLE will have SLE Positive anti –Ro (SS-A) and anti – LA (SS-B) Photosensitive Face usually spared Nonscarring Fatigue common Arthralgia and arthritis
Photosensitivity
Skin rash as an unusual reaction to sunlight
Mucocutaneous Ulcers
Oral or nasopharyngeal ulcerations
Must be observed by physician/ health care provider
Often painless
Arthritis
Nonerosive arthritis involving 2
or more peripheral joints
Characterized by tenderness
swelling, or joint effusion.
Jaccoud’s Arthropathy
Reducible deformities
No erosions
Periarticular fibrosis and ligamentous laxity
Swan neck deformities
SLE - Musculoskeletal Disease
Arthralgia/Arthritis
Myalgia/Myositis
Ischemic necrosis of bone - AVN
Serositis
- Pleuritis - convincing history of pleuritic pain or rub heard by a physician or evidence of pleural effusion
or - Pericarditis - documented by ECG or rub or evidence of pericardial effusion
SLE - Pleuropulmonary disease
Pleuritis/Pleural effusion* Infiltrates/Atelectasis Acute lupus pneumonitis Pulmonary hemorrhage “Shrinking lung” - diaphragm dysfunction Subclinical restrictive disease
SLE- Cardiac Involvement
Pericarditis
Myocarditis
Endocarditis, Libman-Sacks
Accelerated atherosclerosis
SLE- Renal Disorder
1. Persistent proteinuria greater than 0.5 grams per day or greater than 3+ if quantitation not performed. Protein in the urine Usually asymptomatic Gross hematuria Nephrotic syndrome Acute renal failure Hypertension End stage renal failure
SLE- Nephritis
Nephritis remains the most frequent cause of disease-related death.
SLE - NEUROPSYCHIATRIC INVOLVEMENT
Behavior/Personality changes Depression Cognitive dysfunction Psychosis Seizures
Thrombocytopenic Purpura
Non blanching Purplish discoloration Purpura is not a disease but indicates underlying bleeding disorder Usually lower extremities < 1 cm is petechiae
Hematologic D/O
Hemolytic anemia with reticulocytosis
OR
Leukopenia—less than 4000/mm 3 total on two separate occasions
OR
Lymphopenia—less than 1500/m 3 on two or more occasions
OR
Thrombocytopenia—less than 100,000/m 3 in the absence of
offending drugs
Immunologic D/O
- Anti-dsDNA: antibody to native DNA in abnormal titer
or - Anti-Sm: presence of antibody to Sm nuclear antigen
or - Antiphospholipid antibodies by positive IgG or IgM anticardiolipin antibodies (not IgA) or a positive test for lupus anticoagulant, or a false positive test for syphilis (RPR) for 6 months
SLE labs
Antibodies to dsDNA are present in 70% of lupus patients and are >95% specific for lupus
Anti-Sm (Smith) + in up to 30% of lupus patients and is pathognomonic
Decreased C3 and C4 indicate activity
Anti-Ro (SS-A) congenital heart block
Antinuclear Antibodies—ANA
Low titer positive ANA in normal population increases with age
Patterns of ANA immunofluorescence vary.
- SLE is commonly associated with peripheral or speckled patterns
- Homogeneous patterns are associated with drug induced lupus.
- First degree relatives of patients with SLE are likely to be ANA positive
32% of relatives had antinuclear antibodies, compared with 1.5% of the healthy controls
ANA sensitivity and specificity
Sensitivity 95%
Specificity very low
Positive in many autoimmune diseases
10 to 35% of adults aged >65 have + ANAs
and do not have Lupus or other autoimmune disease
Negative ANA occurs in less then 3% of lupus patients, (+ SS-A or + RNP)
ANAs do not?
ANAs do not correlate with disease activity
Do not forget other causes of a positive ANA
A patient with a negative ANA has less than a 3% chance of developing SLE
Other causes for a positive ANA
RA, Sjogren’s, Scleroderma, Myositis Infections (viral or bacterial) Thyroiditis or Graves Cancers such as melanoma, breast, lung GI ( hepatitis, UC, Crohn’s, Primary Biliary Cirrhosis Lung (pulmonary fibrosis, TB) Medications
Common manifestations not a part of ACR criteria
Fever and Constitutional Symptoms 42%
Raynaud’s Phenomenon 22%
Alopecia 18%
Cutaneous Vasculitis
SLE clustering symptoms
Cutaneous, articular and renal manifestations tend to appear “together”
CNS thrombotic and muscular symptoms also cluster, although to a lesser extent
Summary of Lupus
Do not order ANAs for broken bones
Most ANAs do not mean Lupus
Know what you are going to do with the result of an ordered lab test.
Numerous potential complications loom behind the scenes and must be anticipated and monitored
Lupus can be treated
Lupus patients can live and accomplish goals just like everyone else
Management Goals for SLE
Counseling, education
Recommend adequate rest and activity (30 to 60 min pm nap)
Decrease inflammation; prevent end-organ injury failure
Preserve renal function; provide HBP Rx; prevent flare
Provide photo protection
Maintain up-to-date immunizations
Management of infection
Minimize osteoporosis
Eye examinations for Plaquenil toxicity (q 6 to 12 months)
Identify patients at risk of thrombo-occlusive events
Evaluate and treat ASHD risk; dyslipoproteinemia, etc.
Family planning/contraceptive issues
Lupus support groups and Arthritis Foundation
Medications for SLE
Steroid sparing agents ****Hydroxychloroquine (Plaquenil) Thalidomide (for mucocutaneous manifestations) Dapsone (for panniculitis, vasculitis) Danazol (for thrombocytopenia) General Immunosuppressants ****Azathioprine (Imuran) Cyclophosphamide (Cytoxan) Leflunomide (Arava) Methotrexate ***Mycophenolate Mofetil (CellCept) Biologics Abatacept (Orencia) Rituximab (Rituxan) *** Belimumab (Benlysta) NEW Other IVIg
Drug induced lupus
Minocycline (Minocin) Procainamide Isoniazid (INH) Phenytoin (Dilantin) Carbamazepine (Tegretol) Hydralazine (Apresoline) Quinidine (Quinaglute) Infliximab, Etanercept, Adalimumab, Simponi™, Cimzia™
Dx and treatment of drug induced lupus
15,000 to 20,000 new cases/yr in U.S.
Positive ANA and one clinical feature of Lupus
Antihistone antibody in 95% of cases
Fever, myalgias, rash, arthritis, serositis
Stop drug, consider anti-histone ABs
Rx with NSAIDS, steroids
