Systemic Lupus Erythematosus - Rheumatology Flashcards
SLE definition and causes?
Definition:
б It is a systemic inflammatory disease due to autoimmune disorder characterized by tissue and cell damage.
б In which the body’s immune system mistakenly attacks healthy tissue in many parts of the body
Causes:
The cause of SLE is not clear, but it is thought to involve:
1. Genetic (inherited): abnormality in MHC, HLA DR 2,3
2. Environmental (Ecological):
1. Sun exposure:
» due to ultraviolet rays
2. Diseases:
» viral and mycoplasma
3. Drugs:
a. hydralazine,
b. monoxide,
c. carbamazepine,
d. phenytoin,
e. CCP
4. Diet:
» food color, » flavor, » preservative
5. Hormonal:
» estrogen, » androgen
6. Physical or emotional stress
7. Trauma
Pathophysiology of SLE?
б SLE is triggered by
» environmental factors that causing the body’s immune system produces antibodies against self-protein,
» particularly against proteins in the cell nucleus.
б SLE is
» a chronic inflammatory disease believed to be a type III hypersensitivity response
» with potential type II involvement
- Cell death signaling
- Apoptosis is increased in monocytes and keratinocytes
- Expression of Fas by B cells and T cells is increased
- T here are correlations between the apoptotic rates of lymphocytes and disease activity.
- Necrosis is increased in T lymphocytes
- Clearance deficiency
- Defect in phagocytic activity of macrophages and dendritic cells.
- Apoptotic debris captured instead by antigen-presenting cells, which leads to the development of antinuclear antibodies
- Diminished serum components like complement factors
- Germinal centers
- The tingible body macrophages (TBM), free from apoptotic and potential autoantigenic material
- Antigen planted on follicular dendritic cells
- B and T cell tolerance for apoptotic cells is abrogated—autoreactive
- Anti-nRNP autoimmunity
б The similarity and cross-reactivity between the initial targets of nRNP and Sm autoantibodies identifies a likely commonality in cause and a focal point for intermolecular epitope spreading. - H.MGB1
б Elevated expression of HMGB1 was found in the sera of people and mice with systemic lupus erythematosus,
Symptoms of SLE (General and specific)
б SLE is more common in women than men by nearly 10: 1.
б It may occur at any age but commonly 30:50y.
б Symptoms
» vary from person to person and may come and go (exacerbation and remission).
» Everyone with SLE has
1. skin manifestation,
2. muscle & joint pain
3. swelling at some time.
4. Some develop arthritis.
» SLE often affects the small joints such as fingers, hands, wrists, and knees.
General symptoms:
1. Anorexia, nausea, vomiting
2. Fever with no other cause, headache, malaise.
3. General discomfort, uneasiness, or ill feeling.
4. Weight loss.
5. Sensitivity to sunlight.
6. Skin rash – A “butterfly” rash, in acute exacerbation
7. Discoid rash in chronic case
8. Periungual telangiectasia
9. Lupus panniculitis
Specific symptoms:
1. Brain and nervous system
a. Central:
1. Headaches,
2. confusion,
3. convulsion comma,
4. memory,
5. personality changes
b. Peripheral:
1. Mononeuropathy: vision problem
2. Polyneuropathy: weakness, numbness, tingling
3. Mononeuropathy multiplex: different Neuropathy in different areas.
- Digestive tract
- Inflammation of GIT: gastric, small, and large intestine,
» Abdominal pain, » nausea, » vomiting - Hepatic inflammation: autoimmune hepatitis
- Pancreatic inflammation: DM, indigestion
- Heart
- Inflammation of heart muscle (myocardium) or
- inflammation of heart covering (pericardium) and
- Inflammation of heart lining (endocardium including valves)
- Lung
б Inflammation of pleura, lung and air way passage - Skin
б Sores, hypo-hyperpigmentation, purpura, petechy, ecchymosis, alopecia, malar and discoid rash. - Kidney
б Nephritis: Swelling in the legs - Circulation
a. Clots in veins or arteries, inflammation of blood vessels, constriction of blood vessels in response to cold (Raynaud phenomenon)
b. Blood abnormalities including
» anemia,
» low white blood cell or platelet count.
Blood and serology tests in SLE?
- Inflammatory:
- ESR (elevated),
- CRP (elevated),
- CBC (anemia, thrombocytopenia, leukopenia)
- Autoimmune disease:
- Antinuclear antibody (ANA) panel → elevated
- Extractable nuclear antibody (ENA)
- Antibodies to double-stranded DNA → positive
- Complement components (C3 and C4) → decreased
- Comb test (autoimmune hemolytic anemia)
- Cryoglobulins
- Rheumatoid factor
- Antiphospholipid antibodies and lupus anticoagulant
- Tissue and cell destruction:
- Kidney function blood tests
- Liver function blood tests
- Imaging tests of the heart, brain, lungs, joints, muscles.
Classification criteria (ACR, clinical and labratory) (A++)
After excluding alternative diagnoses, we diagnose SLE in the patient who fulfills the 1997 ACR criteria or the 2012 SLICC criteria.
» As previously mentioned, the ACR criteria require that a patient satisfy at least 4 of 11 criteria.
» The SLICC criteria require either that a patient satisfy at least 4 of 17 criteria, including at least 1 of the 11 clinical criteria and one of the six immunologic criteria,
б or that the patient has biopsy-proven nephritis compatible with SLE in the presence of antinuclear antibodies (ANA)
б or antidouble-stranded DNA (anti-dsDNA) antibodies.
A. The American College of Rheumatology (ACR) classification criteria.
Need four from 11ch.
1. Photosensitivity:
» Skin rash as a result of unusual reaction to sunlight,
» by patient history or physician observation.
2. Malar (butterfly) rash:
» Fixed erythema,
» flat or raised,
» over the malar eminences,
» tending to spare the nasolabial folds.
3. Discoid rash:
» Erythematous raised patches with adherent keratotic scaling and follicular plugging;
» atrophic scarring may occur in older lesions.
4. Oral Ulcers:
» Oral or nasopharyngeal ulceration,
» usually painless,
» observed by physician.
5. Synovitis: arthritis,
» which is swelling or tenderness of the small joints of the hands, feet, knees, and wrists, 2 joints or more , non-erosive.
6. Serositis:
» signs of cardiac (pericarditis)
» or lung (pleurisy) involvement,
7. Blood:
» anemia, » thrombocytopenia, » leukopenia
8. Kidney:
» proteinuria, » casts
9. Neuro: psychosis, seizure
10. Antibodies: ANA,
11. Ads DNA, anti-smith, anti RO & LA, hypocomplementemia
B. Clinical criteria
1. Acute cutaneous lupus:
1. Malar rash/butterfly.
» Fixed erythema,
» flat or raised,
» over the malar eminences,
» tending to spare the nasolabial
folds.
» Occurs in up to 50%.
2. Bullous lupus,
3. toxic epidermal necrolysis variant of SLE,
4. maculopapular lupus rash,
5. photosensitive lupus rash,
6. or subacute cutaneous lupus
» nonindurated psoriasiform and/or annular polycyclic lesions that re- solve without scarring.
2. Chronic cutaneous lupus:
a. Discoid rash,
» erythematous raised patches
» with adherent keratotic scales and follicular plugging ± atrophic scarring.
b. Think of it as a three-stage rash affecting ears, cheeks, scalp, forehead, and chest:
» erythema
» pigmented hyperkeratotic edematous papules
» atrophic depressed lesions
3. Non scarring alopecia: (In the absence of other causes.)
4. Oral/nasal ulcers: (In the absence of other causes.)
5. Synovitis:
» Involving two or more joints or two or more tender joints with >30 minutes of morning stiffness.
6. Serositis:
a. Lung
» pleurisy for >1 day, » or pleural effusions, » or pleural rub;
b. Heart
» pericardial pain for >1 day,
» or pericardial effusion,
» or pericardial rub,
» or pericarditis on ECG.
7. Urinalysis:
» Presence of proteinuria (>0.5g/d) or red cell casts.
8. Neurological features:
» Seizures;
» psychosis;
» mononeuritis multiplex
» myelitis;
» peripheral or cranial neuropathy;
» cerebritis/acute confusional state in absence of other causes.
9. Haemolytic anaemia.
10. Leucopenia:
» (WCC <4.) At least once, or lymphopenia (lymphocytes <1) at least once.
11. Thrombocytopenia
» (Platelets <100.) At least once.
C. Laboratory criteria
1. +ve ANA (+ve in >95%).
2. Anti-dsDNA.
3. Anti-Smith antibodies present.
4. Antiphospholipid Abs present.
5. Low complement (C3, C4, or C50).
6. +ve Direct Coombs test.
7. elevated ESR and CRP
Probable and possible SLE criteria ?
Probable SLE
» As a loose guide, we diagnose SLE in patients who have two or three of the ACR or SLICC criteria,
» along with at least one other feature that may be associated with but is not specific for SLE.
» Some of these features include the following:
1. Optic neuritis, aseptic meningitis
2. Glomerular hematuria
3. Pneumonitis, pulmonary hemorrhage, pulmonary hypertension, interstitial lung disease
4. Myocarditis, verrucous endocarditis (Libman-Sacks endocarditis)
5. Abdominal vasculitis
6. Raynaud phenomenon
7. Elevated acute phase reactants (e.g., erythrocyte sedimentation rate [ESR] and C-reactive protein [CRP])
Possible SLE
1. We consider SLE
» a possible diagnosis in individuals who have only one of the ACR/SLICC criteria,
» in addition to at least one or two of the other features listed above.
2. Other terms
» that have been used to describe patients with probable or possible SLE include incipient or latent lupus,
» which has been defined as patients who have three or fewer of the ACR or SLICC criteria.
Differential diagnosis of SLE?
- Rheumatoid arthritis
- Rhupus
- Mixed connective tissue disease
- Undifferentiated connective tissue disease
- Systemic sclerosis
- Sjögren’s syndrome
- Vasculitis
- Behçet syndrome
- Dermatomyositis and polymyositis
- Adult-onset Still’s disease
- Serum sickness
- Fibromyalgia
- Infections
- Multiple sclerosis
- Thrombotic thrombocytopenic purpura
- Malignancies
Treatment of SLE?
- General measures:
- High-factor sunblock.
- Hydroxychloroquine,
» unless contraindicated,
» reduces disease activity,
» improves survival. - Screen for co-morbidities and medication toxicity.
- For skin flares, first trial topical steroids.
- Maintenance:
- NSAIDs (unless renal disease) and hydroxychloroquine for joint and skin symptoms.
- Steroid-sparing agents:
» Azathioprine, » methotrexate, » mycophenolate - Belimumab (monoclonal antibody)
» used as an add-on therapy for autoantibody positive disease where disease activity is high. - Mild forms (No serious organ damage.) of the disease may be treated with:
- NSAIDs
» for joint symptoms and pleurisy.
» Talk to your provider before taking these medicines. - Low doses of corticosteroids, such as prednisone, for skin and arthritis symptoms.
- Corticosteroid creams for skin rashes.
- Hydroxychloroquine, a medicine also used to treat malaria.
- Methotrexate
» may be used to reduce the dose of corticosteroids - Belimumab, a biologic medicine, may be helpful in some people
- Treatments for more severe SLE may include (If life- or organ-threatening,)
- High-dose corticosteroids.
- Immunosuppressive medicines (these medicines suppress the immune system).
» These medicines are used if you have severe lupus that is affecting the nervous system, kidney, or other organs.
» They may also be used if you do not get better with corticosteroids, or if your symptoms get worse when you stop taking corticosteroids. - Medicines commonly used include
a. Mycophenolate,
b. Azathioprine
c. Cyclophosphamide.
» Because of its toxicity, cyclophosphamide is limited to a short course of 3 to 6 months.
d. Rituximab (Rituxan) is used in some cases as well. - Blood thinners, such as warfarin (Coumadin),
» for clotting disorders such as antiphospholipid syndrome.
-
If you have SLE:
1. Get preventive heart care.
2. Have tests to screen for thinning of the bones (osteoporosis).
3. Avoid: tobacco and drink minimal amounts of alcohol.
4. Avoid: ultraviolet rays
5. Take: Vitamin D. and calcium supplements
6. Wear: protective clothing, sunglasses, and sunscreen when in the sun.
7. Maintain: Regular exercise
8. Maintain: Stay up to date with immunizations
Long-term complications of SLE? (A++)
б Over time, SLE can damage or cause complications in systems throughout your body.
б Possible complications may include:
1. Blood clots and inflammation of blood vessels or vasculitis
2. Inflammation of the heart, or pericarditis
3. A heart attack
4. A stroke
5. Inflammation of lung tissue and the lining of the lung, or pleuritis
6. Memory changes
7. Behavioral changes
8. Seizures
9. Kidney inflammation
10. Decreased kidney function
11. kidney failure
Drug induced lupus
- Drug-induced lupus Causes (>80 drugs)
a. include - isoniazid,
- hydralazine,
- procainamide,
- quinidine,
- chlorpromazine,
- minocycline,
- phenytoin,
- anti-TNF agents.
b. It is associated with antihistone antibodies in >95% of cases.
c. Skin and lung signs prevail (renal and CNS are rarely affected). - The disease remits if the drug is stopped.
- Sulfonamides or the oral contraceptive pill may worsen idiopathic SLE
Mixed connective tissue disease
- Commonly abbreviated as MCTD,
» is an autoimmune disease characterized by the presence of elevated blood levels of a specific autoantibody,
» now called anti-U1 ribonucleoprotein (RNP) together with a mix of symptoms of systemic lupus erythematosus (SLE), scleroderma, and polymyositis. - The idea behind the “mixed” disease
» is that this specific autoantibody is also present in other autoimmune diseases such as systemic lupus erythematosus, polymyositis, scleroderma, etc.
» MCTD was characterized as an individual disease in 1972. - It is sometimes said to be
» the same as undifferentiated connective tissue disease.
