Systemic lupus erythematosus

Systemic lupus erythematosus

Systemic Lupus Erythematosus

Systemic lupus erythematosus is a chronic (persistent) disease that causes inflammation in various parts of the body. It is commonly just called SLE or 'lupus'. The severity of SLE ranges from mild to severe. There are two main forms of lupus. Discoid lupus only affects only the skin . The other form is systemic lupus erythematosus which involves the skin and joints and may involve internal organs such as the heart or kidney as well

Pathophysiology

SLE is an autoimmune disorder characterized by multisystem microvascular inflammation with the generation of autoantibodies. Although the specific cause of SLE is unknown, multiple factors are associated with the development of the disease, including genetic, racial, hormonal, and environmental factors.Many immune disturbances, both innate and acquired, occur in SLE, as illustrated in below.

In systemic lupus erythematosus (SLE), many genetic-susceptibility factors, environmental triggers, antigen-antibody responses, B-cell and T-cell interactions, and immune clearance processes interact to generate and perpetuate autoimmunity.

One proposed mechanism for the development of autoantibodies involves a defect in apoptosis that causes increased cell death and a disturbance in immune tolerance.The redistribution of cellular antigens during apoptosis leads to a cell-surface display of plasma and nuclear antigens in the form of nucleosomes. Thus, dysregulated (intolerant) lymphocytes begin targeting normally protected intracellular antigens.

Immune complexes form in the microvasculature, leading to complement activation and inflammation. Moreover, antibody-antigen complexes deposit on the basement membranes of skin and kidneys. In active SLE, this process has been confirmed based on the presence of complexes of nuclear antigens such as DNA, immunoglobulins, and complement proteins at these sites. Serum antinuclear antibodies (ANAs) are found in virtually all individuals with active SLE, and antibodies to native double-stranded DNA (dsDNA) are relatively specific for the diagnosis of SLE.

History

A detailed and accurate history is crucial to aid in diagnosing the type of AKI and in determining its subsequent treatment. A detailed history and a physical examination in combination with routine laboratory tests are useful in making a correct diagnosis .

• Distinguishing AKI from chronic renal failure is important, yet making the distinction can be difficult. A history of chronic symptoms — fatigue, weight loss, anorexia, nocturia, and pruritus — suggests chronic renal failure.
• Take note of the following findings during the physical examination:
  • Hypotension
  • Volume contraction
  • Congestive heart failure
  • Nephrotoxic drug ingestion
  • History of trauma or unaccustomed exertion
  • Blood loss or transfusions
  • Evidence of connective tissue disorders or autoimmune diseases
  • Exposure to toxic substances, such as ethyl alcohol or ethylene glycol
  • Exposure to mercury vapors, lead, cadmium, or other heavy metals, which can be encountered in welders and miners
• People with the following comorbid conditions are at a higher risk for developing AKI:
  • Hypertension
  • Congestive cardiac failure
  • Diabetes
  • Multiple myeloma
  • Chronic infection
  • Myeloproliferative disorder
• Urine output history can be useful. Oliguria generally favors AKI. Abrupt anuria suggests acute urinary obstruction, acute and severe glomerulonephritis, or embolic renal artery occlusion. A gradually diminishing urine output may indicate a urethral stricture or bladder outlet obstruction due to prostate enlargement.
• Because of a decrease in functioning nephrons, even a trivial nephrotoxic insult may cause AKI to be superimposed on chronic renal insufficiency.

Signs and symptoms

Common initial and chronic complaints include fever, malaise, joint pains, myalgias, fatigue, and temporary loss of cognitive abilities. Because they are so often seen with other diseases, these signs and symptoms are not part of the diagnostic criteria for SLE.





Dermatological manifestations

• Malar rash describes an erythematous rash over the cheeks and nasal bridge, with classic nasolabial fold sparing, as seen in the image below.
  
  

  

  The classic malar rash, also known as a butterfly rash, with distribution over the cheeks and nasal bridge. Note that the fixed erythema, sometimes with mild induration as seen here, characteristically spares the nasolabial folds.

• Photosensitive rash is often macular or diffusely erythematous in sun-exposed areas of the face, arms, or hands, as in the image below.
  
  
  
  

  

  Photosensitive systemic lupus erythematosus (SLE) rashes typically occur on the face or extremities, which are sun-exposed regions. Photo courtesy of Dr. Erik Stratman, Marshfield Clinic.

Musculoskeletal manifestations

Joint symptoms, ranging from intermittent joint pains (arthralgias) to sudden inflammation of multiple joints (acute polyarthritis), occur in about 90% of people and may exist for years before other symptoms appear. In long-standing disease, marked joint deformity may occur (Jaccoud's arthropathy) but is rare. However, joint inflammation is generally intermittent and usually does not damage the joints.



Hematological manifestations

Anemia and iron deficiency may develop in up to 50% of cases. Low platelet and white blood cell counts may be due to the disease or a side-effect of pharmacological treatment. People with SLE may have an association with antiphospholipid antibody syndrome(a thrombotic disorder), wherein autoantibodies to phospholipids are present in their serum. Abnormalities associated with antiphospholipid antibody syndrome include a paradoxical prolonged PTT Partial thromboplastin time (which usually occurs in hemorrhagic disorders) and a positive test for antiphospholipid antibodies; the combination of such findings have earned the term lupus anticoagulant-positive. Another autoantibody finding in SLE is the anticardiolipin antibody, which can cause a false positive test for syphilis.



Renal manifestations

Hypertension or hematuria may signal nephritic SLE. Edema of periorbital or peripheral regions and anasarca are common physical findings related to nephrotic syndrome or volume overload with renal failure.

Pulmonary manifestations

Lung and pleura inflammation can cause pleuritis, pleural effusion, lupus pneumonitis, chronic diffuse interstitial lung disease, pulmonary hypertension, pulmonary emboli, pulmonary hemorrhage, and shrinking lung syndrome.

Lymph Node and Spleen Problems

Wide-spread enlargement of the lymph nodes is common, particularly among children, young adults, and blacks of all ages. Enlargement of the spleen (splenomegaly) occurs in about 10% of people. People may experience nausea, diarrhea, and vague abdominal discomfort. The occurrence of these symptoms may be the forewarning of a flare-up.

Nervous System Problems

Involvement of the brain (neuropsychiatric lupus) can cause headaches, mild impairment of thinking, personality changes, stroke, epilepsy, severe mental disorders (psychoses), or a condition in which a number of physical changes may occur in the brain, resulting in disorders such as dementia. The nerves in the body or spinal cord may also be damaged.

Kidney Problems

Kidney involvement may be minor and without symptoms or may be relentlessly progressive and fatal. The most common result of this impairment is protein in the urine that leads to swelling (edema) in the legs.

Blood Problems The numbers of red blood cells, white blood cells, and platelets may decrease. Platelets assist in blood clotting, so if these numbers decrease greatly, bleeding may occur. Also, and for other reasons, the blood may clot too easily, which accounts for many of the problems that can affect other organs (such as strokes and blood clots to the lungs or recurrent miscarriages).

Gastrointestinal Tract Problems

Impairment of blood supply to various parts of the gastrointestinal tract may result in abdominal pain, damage to the liver or pancreas (pancreatitis), or a blockage or tear (perforation) of the gastrointestinal tract.

Pregnancy Problems

Pregnant women have a higher-than-normal risk of miscarriage and stillbirth.

Diagnostic criteria

Some physicians make a diagnosis on the basis of the American College of Rheumatology (ACR) classification criteria. The criteria, however, were established mainly for use in scientific research including use in randomized controlled trials which require higher confidence levels, so some people with SLE may not pass the full criteria.

The American College of Rheumatology established eleven criteria in 1982, which were revised in 1997 as a classificatory instrument to operationalise the definition of SLE in clinical trials. They were not intended to be used to diagnose individuals and do not do well in that capacity. For the purpose of identifying patients for clinical studies, a person has SLE if any 4 out of 11 symptoms are present simultaneously or serially on two separate occasions.

1. Serositis: Pleuritis (inflammation of the membrane around the lungs) or pericarditis (inflammation of the membrane around the heart); sensitivity = 56%; specificity = 86% (pleural is more sensitive; cardiac is more specific).
2. Oral ulcers (includes oral or nasopharyngeal ulcers).
3. Arthritis: nonerosive arthritis of two or more peripheral joints, with tenderness, swelling, or effusion; sensitivity = 86%; specificity = 37%.
4. Photosensitivity (exposure to ultraviolet light causes skin rash, or other symptoms of SLE flareups); sensitivity = 43%; specificity = 96%.
5. Blood—hematologic disorder—hemolytic anemia (low red blood cell count) or leukopenia (white blood cell count<4000/µl), class="mw-redirect">lymphopenia (<1500/µl) sensitivity =" 59%;" specificity =" 89%.Hypocomplementemia is also seen, due to either consumption of C3 and C4 by immune complex-induced inflammation or to congenitally complement deficiency, which may predispose to SLE.
6. Renal disorder: More than 0.5g per day protein in urine or cellular casts seen in urine under a microscope; sensitivity = 51%; specificity = 94%.
7. Antinuclear antibody test positive; sensitivity = 99%; specificity = 49%.
8. Immunologic disorder: Positive anti-Smith, anti-ds DNA, antiphospholipid antibody, and/or false positive serological test for syphilis; sensitivity = 85%; specificity = 93%.Presence of anti-ss DNA in 70% of cases (though also positive with rheumatic disease and healthy persons)^[45]).
9. Neurologic disorder: Seizures or psychosis; sensitivity = 20%; specificity = 98%.
10. Malar rash (rash on cheeks); sensitivity = 57%; specificity = 96%.^[44]
11. Discoid rash (red, scaly patches on skin that cause scarring); sensitivity = 18%; specificity = 99%.

The mnemonic to remember the 11 symptoms is 'SOAP BRAIN MD'.

Some people, especially those with antiphospholipid syndrome, may have SLE without four criteria, and also SLE may present with features other than those listed in the criteria.

Recursive partitioning has been used to identify more parsimonious criteria. This analysis presented two diagnostic classification trees:

1. Simplest classification tree: SLE is diagnosed if a person has an immunologic disorder (anti-DNA antibody, anti-Smith antibody, false positive syphilis test, or LE cells) or malar rash.
   • sensitivity = 92%
   • specificity = 92%
2. Full classification tree: Uses 6 criteria.
   • sensitivity = 97%
   • specificity = 95%

Other alternative criteria have been suggested.

Treatment

Treatment depends on which organs are affected and how active the inflammation of lupus is. The severity of the lupus is not necessarily the same as the activity of the inflammation. For example, organs may be permanently damaged and scarred from lupus that caused inflammation in the past. Such damage may be referred to as “severe,” even if the lupus is not active (that is, it is not causing any inflammation or any further damage at this time). The goal of treatment is to decrease the activity of lupus—that is, to decrease inflammation, which in turn should prevent damage.

If lupus is not very active (sometimes called mild lupus), treatment may not need to be intensive. Nonsteroidal anti-inflammatory drugs (NSAIDs—see Pain: Nonsteroidal Anti-Inflammatory Drugs) often can relieve joint pain. Hydroxychloroquine Some Trade Names

PLAQUENIL

, chloroquine Some Trade Names

ARALEN

, or quinacrine Some Trade Names

ATABRINE

, sometimes taken in combination, helps relieve joint and skin symptoms. Sunscreen lotions (with a sun protection factor of at least 30) should be used, especially by people who have skin rashes.

Very active lupus (sometimes called severe lupus) is treated immediately with a corticosteroid such as prednisone (see Joint Disorders: Corticosteroids: Uses and Side Effects. The dose and duration of treatment depend on which organs are affected. Sometimes an immunosuppressive drug such as azathioprine Some Trade Names

IMURAN

or cyclophosphamide Some Trade Names

LYOPHILIZED CYTOXAN

is given to suppress the body's autoimmune attack. Mycophenolate mofetil Some Trade Names

CELLCEPT

is an alternative immunosuppressive drug. The combination of a corticosteroid and an immunosuppressive drug is most often used for severe kidney disease or nervous system disease and for vasculitis.

Once the initial inflammation is controlled, a doctor determines the dose that most effectively suppresses inflammation over the long term. Usually, the dose of prednisone is gradually decreased when symptoms are controlled and laboratory test results show improvement. Relapses or flare-ups can occur during this process. For most people who have lupus, the dose of prednisone can eventually be decreased or occasionally discontinued.

Surgical procedures and pregnancy may be more complicated for people who have lupus, and they require close medical supervision. Miscarriages and flare-ups during pregnancy are common. Pregnancy should be avoided during a flare-up, and conception should be delayed until the disease seems likely to be inactive.

People who take corticosteroids should be tested periodically and, if necessary, treated for osteoporosis (thinning of the bones), which can occur with chronic corticosteroid use. People should be monitored closely by a doctor for coronary artery disease. Other risk factors for coronary artery disease (for example, high blood pressure and high cholesterol levels) should be controlled as well as possible.

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