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It is estimated that between 500,000 to 1.5 million Americans have lupus. More than 16,000 Americans develop lupus each year. Both men and women can get lupus, however, lupus is 10-15 times more common in females than males. 80-90% of lupus patients are female. Although children, teenagers and the elderly can get lupus, it most commonly affects women of childbearing years between the ages of 22 and 40. 80% of lupus patients are between 15 and 45 years of age. Lupus disproportionately affects African Americans, Asian Americans, Hispanics, and Native Americans. African American women are 3 times more likely than Caucasian women to be affected by lupus.
Lupus is an extremely complex disease, and although scientists are making progress in understanding the causes of lupus, there is still no single known cause. It is thought that a combination of genetics, environment, and possibly hormones act together to trigger the disease. Genetics: There is considerable evidence indicating that genes play a major role in the disease process. Researchers believe that there may be as many as 100 genes, which contribute to the genetic predisposition and development of SLE, and they have recently discovered a single gene that causes a lupus-like illness in mice. Hormones: The effect of hormones in humans with lupus is not clear. However, because the majority of lupus patients are women in their childbearing years, it seemed a logical aspect to study. Female hormones tend to stimulate the immune system or promote an immune response, (remember that having lupus means having an overactive immune system), whereas male hormones have the opposite effect and are more immunosuppressive. There does not seem to be any evidence that men or women with lupus produce abnormal levels of hormones, however, there may be differences in the way people with lupus process these hormones. Environment: Although it has not yet been fully proven, there may be certain environmental factors that play a role in initiating or triggering lupus in a genetically predisposed person.
Since lupus can attack any organ or organ system in the body, it affects everyone differently and there are no two cases that are alike. It can range from mild to life threatening and anywhere in between. People with lupus generally go through periods of flares, which are sudden increases in disease activity or development of new symptoms, and remissions, which are periods of disease-free activity.
Systemic lupus erythematosus (SLE) can affect any system or organ in the body including the joints, skin, lungs, heart, blood, kidney, or nervous system. Symptoms of SLE can range from being minor to very serious or life threatening. A person may experience very little to no pain or they may experience extreme pain, especially in the joints. There may be no skin involvement or rashes that are disfiguring. They may have no organ involvement or extreme organ damage. Generally, no two people with systemic lupus will have identical symptoms. Most often when people mention &quot;lupus,&quot; they are referring to the systemic form of the disease.
In many people with lupus, only one system of the body such as the skin or joints is affected. Other people experience symptoms in many parts of their body. Just how seriously a body system is affected can also vary from person to person. The following systems in the body can be affected by lupus: Kidneys Lungs Central nervous system Blood vessels Blood Heart
The term &quot;lupus&quot; is commonly used when talking about any form of the disease. When someone says, &quot;I have lupus,&quot; he or she could be affected in many different ways depending on the type of lupus present. Even within the same type of lupus, each case is different. The different types of lupus include: · Discoid or Cutaneous Lupus (DLE) · Drug Induced Lupus (DIL) · Neonatal Lupus · Systemic Lupus Erythematous (SLE)
Because lupus symptoms can come and go, are usually vague and often mimic other illnesses, it can be a very difficult disease to diagnose. It may take months or even years for doctors to piece together the symptoms to diagnose this complex disease. The onset of lupus may be acute, resembling an infectious process consisting of fever, pleurisy and muscle aches or it may be a progression of vague symptoms over a long period of time. Because there is no one single test that can tell if a person has lupus, diagnosis is usually made by a careful review of a person’s entire medical history (including family history), complete physical examination, and analysis of laboratory tests. Sometimes a biopsy of the skin or kidney may be used to help with the diagnosis. The symptoms described by the patient may appear to be totally unrelated; therefore an open mind and good communication is necessary when assessing the patient.
To assist the physician in the diagnosis of lupus, the American College of Rheumatology (ACR) has developed a set of classification criteria used to help distinguish lupus from other diseases. A person should have four or more of these symptoms to suspect lupus. It is important to remember that the symptoms do not have to occur at the same time, and the criteria do not include all possible symptoms of lupus like fever, fatigue, hair loss, or Raynaud&apos;s phenomenon. The criteria are meant only to help with diagnosis. Butterfly or Malar Rash Rash over the cheeks and/or nose. Discoid Rash Red raised patches anywhere on the skin, but usually in the sun exposed areas of the face, arms, neck, hands. Photosensitivity Reaction to sunlight, resulting in the development or increase in skin rash or general feeling of illness. Oral Ulcers Ulcers in the nose or mouth, usually painless. Arthritis Non-erosive arthritis involving two or more peripheral joints (arthritis in which the bones around the joints do not become destroyed). Serositis Pleuritis or pericarditis – pain in the chest with deep breathing. Renal Disorder Excessive protein and/or cellular casts (abnormal elements the urine, derived from red and/or white cells and/or kidney tubule cells) in the urine. Neurologic Disorder Seizures (convulsions) and/or psychosis. Hematologic Disorder Hemolytic anemia (low red blood cell count), leukopenia (low white blood cell count) or thrombocytopenia (low platelet count). Immunologic Disorder Positive LE prep test, positive anti-DNA test, positive anti-Sm test or false positive syphilis test (VDRL). Antinuclear Antibody Positive test for antinuclear antibodies.
No single test can determine whether a person has lupus, but several laboratory tests may help the doctor to make a diagnosis. The most useful tests identify certain autoantibodies often present in the blood of people with lupus. Initial screening usually includes the antinuclear antibody test (ANA). This test is positive in 95-98% of people with lupus. However, just because a person has been told they have a positive antinuclear antibody test (ANA), does not mean they have lupus. The ANA is NOT a lupus test. It is only a test that points the doctor in several different directions. People with other rheumatic diseases and healthy relatives of people with autoimmune diseases can also have a positive ANA. It can also become positive with many other things like aging, pregnancy, viral infections and also as the result of taking certain medications. About 10 million Americans have a positive ANA and only about 1 million of them have SLE. If three or more clinical features, such as skin, joint, kidney, pleural, pericardial, hematological, or central nervous system findings are present, a positive test can confirm the disease. Anti-DNA- Are present in about 60-80% of patients with active SLE. The test is highly specific for SLE and not found in patients with other rheumatic diseases. It is also associated with a greater risk of lupus nephritis. Anti-Sm- Are present in about 30% of lupus patients. This test is highly specific for patients with SLE and rarely found with other rheumatic diseases. It is often used to confirm a lupus diagnosis. Anti-RNP is seen in SLE and mixed connective tissue disease. Anti-Ro(SSA) and Anti-La(SSB)- Anti-Ro is found in about 30% of SLE patients. It is also highly associated with photosensitivity. Anti-La is found in about 15% of lupus patients. Both of these are almost always found in babies who are born with neonatal lupus. They are also present in people with subacute cutaneous lupus, and Sjögren’s Syndrome.
Other laboratory tests that may be helpful include: CBC/Complete blood count- RBC/Red blood count- About 40% of patients with SLE will have problems with their RBC’s (anemia), which may be caused by iron deficiency, GI bleeding, medications or autoantibody formation to RBC’s. WBC/White blood count- About 15-20% of lupus patients have a decrease in WBC’s (leukopenia). Platelets- About 25-35% of patients with lupus have low platelets (thrombocytopenia). Urinalysis: There is no one test to tell if there is lupus disease in the kidneys. A doctor can test for kidney problems by using urine tests, kidney function tests, blood tests and/or x-rays. If red blood cells, protein and/or cell casts (fragments of dead cells from blood cells or the kidney tubes themselves) are found in a urinalysis, it may mean that the kidney is not working correctly or that there is major damage to the kidneys. In these cases, further testing may need to be done. Blood Chemistry: tests are important, especially the creatinine and urea which are raised if there has been evidence of kidney disease. ESR (erythrocyte sedimentation rate) and CRP (C-reactive protein) - These tests frequently rise with generalized inflammation. The levels are usually increased with patients who have active lupus and decrease with corticosteroid or NSAID use. Antiphospholipid Antibodies- These tests are associated with the problem of &apos;sticky blood&apos;. Patients with high levels of antiphospholipid antibodies have an increased tendency to clotting or thrombosis, both in the veins and arteries, and in pregnant women with this condition, there is a risk of thrombosis leading to miscarriage. The most widely measured are the lupus anticoagulant and the anticardiolipin antibody. Rheumatoid factor is positive in 20-30% of SLE patients and 80% of Rheumatoid Arthritis patients. High levels of rheumatoid factor with low levels of ANA are more indicative of RA and not SLE. It is also seen in people with Sjögren’s Syndrome. Complement (C-3, C-4 and CH50)- If the total blood complement level is low, or the C3 or C4 values are low and the person also has a positive ANA, some weight can be added to the diagnosis of lupus. Low C3 and C4 levels in patients with a positive ANA may show the presence of active disease, especially kidney involvement. Syphilis test (VDRL or RPR)- This test may be falsely positive in lupus patients. Biopsy or tissue sample- Can be helpful in making a diagnosis and also helps to evaluate organs. The most common sites are the skin and kidney. The doctor removes a small piece of tissue and looks at it under a microscope. All of these tests serve as tools to give the doctor clues and information in making a diagnosis. The doctor will look at the entire picture--medical history, symptoms, and test results--to determine if a person has lupus.
An increase in lupus activity usually causes the following test results to rise CRP, sed rate, anti DNA, liver and kidney function tests (AST, ALT, BUN, Creatinine- with kidney or liver involvement), CPK (if muscle involvement is present), urine protein or cellular casts. An increase in lupus activity usually causes the following test results to fall: CBC (WBC, RBC, platelets), complement, serum albumin.
Medications play an important role in the care of people with SLE. For most people with lupus, effective treatment can minimize symptoms, reduce inflammation, and maintain normal body functions. Treatment approaches are based on the specific needs and symptoms of each person. The medication prescribed usually depends on which organ(s) are involved and the severity of the involvement. The choice of drugs is highly individualized and typically changes often during the course of the disease. The medications used in the management of lupus include: · NSAIDs · Antimalarials · Corticosteroids · Immunosuppressants · Investigational (research)
In combination with medications, there are preventive measures which can help to reduce the risk of lupus flares. Photosensitivity is an abnormal reaction to UV rays and results in exacerbation of lupus symptoms. About 1/3 of lupus patients are photosensitive and should avoid prolonged direct exposure to the sun. All patients should use sun precautions and apply a sunscreen with an SPF 15 or greater; avoid sun exposure between 10 a.m. and 4 pm and wear protective clothing and wide-brimmed hats. Fluorescent and halogen lights can also emit UV rays, which can aggravate lupus. There are plastic light shields available that block UV emissions. The fatigue found in lupus can be an overwhelming and debilitating symptom therefore proper and adequate rest is vital in dealing with the disease. Some patients require a nap during the day as well as 8 to 10 hours of sleep at night. Lupus patients also need to learn how to alternate activities with periods of rest. Staying in bed can cause weakness, but overdoing it can cause lupus to flare.
Nutrition and a well-balanced diet are also essential components to successfully living with a chronic disease like lupus. There is no &quot;lupus diet.&quot; People with lupus should eat well-balanced meals that are low in fat, low in salt, high in fiber and low in sugar. People on corticosteroids (Prednisone) should limit their sugar, fat and salt. A restricted diet may be prescribed when hypertension, kidney disease, edema or diabetes is present. Nutritional counseling may also be beneficial to some people. If you find that certain foods make you feel bad or cause a &quot;flare-up&quot; of your lupus, you should avoid those foods. Lupus patients are encouraged to do low impact exercise as tolerated. This can prevent muscle weakness and fatigue. Walking, stretching, range of motion, swimming, low impact aerobics and bicycling can help keep you strong and prevent thinning of bones or osteoporosis. Remember to alternate your activities with rest periods. Be careful of doing heavy weight lifting or high impact exercises as this may make your lupus worse. If you feel overly tired or have increased discomfort for more than two hours after exercising, the session was probably too much and the next session should be made shorter. Moist heat is better for aching joints than dry heat. Soaking in a tub, Jacuzzi or taking a warm shower can help make your joints feel better. The time to use ice and/or cold packs is within 36 hours of an injury. Moist heat and topical analgesic cremes are usually beneficial for muscle and joint pain but should be approved by the patient’s physician. Call your doctor if your temperature is over 99.6. It could be an infection or a lupus flare. Smoking is detrimental to anyone’s health, especially those suffering from chronic disease. Cigarette smoke contains chemicals, which can cause flares of cutaneous lupus. It can make symptoms of Raynaud&apos;s disease worse by impairing circulation (blood flow), and there can also be stomach problems from medications in people who use tobacco.
Although the exact cause is unknown, Drug Induced Lupus can develop after long-term use of certain medications. It is most common in men over 50 years of age (because they are given the offending drugs more often). The symptoms of drug-induced lupus are similar to those of systemic lupus and are mild in most people, but can become debilitating if the person continues to take the offending medication. It usually takes several months to years of continuous therapy with the medication before symptoms appear. Once the suspected medication is stopped, symptoms should go away within days. Usually symptoms disappear within one or two weeks and the symptoms usually disappear completely within six months. The antinuclear antibody test (ANA) may stay positive for years.
At least 38 drugs currently in use can cause DIL. However, most cases have been associated with the following: Hydralazine (Apresoline) Procainamide (Procan, Pronestyl) Methyldopa (Aldomet) Quinidine (Quinaglute) Isoniazid (INH) Some anti-seizure medications such as phenytoin (Dilantin) or carbamazepine (Tegretol)
The most important aspect of treating drug-induced lupus is to recognize the medication that is causing the problem and discontinue its use. This step is often sufficient to improve the symptoms within a few days. Individuals sometimes improve more quickly if non-steroidal anti-inflammatory drugs (NSAIDs) are then used and corticosteroids may be used for patients with severe symptoms of DIL.
Neonatal lupus is not SLE or Cutaneous lupus. Neonatal lupus occurs when the mother’s antibodies cross over the placenta to the baby. This can affect the skin, heart, liver and/or blood of the fetus and newborn. It is associated with a rash that appears within the first several weeks of life and may persist for about six months before disappearing. Some babies with neonatal lupus may have a serious heart defect called congenital heart block. This disorder can usually be controlled by placing a pacemaker in the baby. Congenital heart block is much less common than the skin rash. Early detection and treatment is vital in achieving a positive outcome for the baby and because doctors can now identify most at risk patients, neonatal lupus is very rare and most infants of mothers with SLE are entirely healthy.
systemic lupus erythematosus
Grace College of Pharmacy
Diagnosis of SLE
Systemic lupus erythematosus (SLE) is
a multi-system auto-immune disease in
which organs and cells undergo
damage, mediated by tissue binding
autoantibodies and immune complexes.
It is characterized by states of
exacerbation and remission
The immune system loses the ability to
differentiate between foreign cells and it’s
own cells and tissues
Antibodies against the immune system are
The immune complexes that are formed
build up in the tissue causing inflammation,
injury to the tissue, and pain,
Organ system commonly affected includes
kidneys, CNS, PNS, heart, lungs and
Results from the gross disturbance of the
Etiology of abnormal autoantibody
formation and development of SLE is
• Non MHC
SLE IS A…SLE IS A…
Major collagen disease with many clinical
Different for each person.
A disease that ranges from mild to life
Abnormal immunolgic function formation
of antibodies against self antigen
underlies the pathogenesis of SLE
SLE represents a clinical syndrome rather
than a discrete disease with a unique
Triggering agents abnormal immune
regulation T-cells B-cells autoantibody
formation immune complex formation and
complement activation tissue injury and
SYSTEMIC LUPUSSYSTEMIC LUPUS
Can affect any organ in the body
including the joints, skin, lungs, heart,
blood, kidney, or nervous system.
Can range from mild to life threatening.
No two people will have identical
WITH LUPUSWITH LUPUS
DIAGNOSING LUPUSDIAGNOSING LUPUS
Medical history (including family history)
Complete physical examination
Skin or kidney biopsy
Malar Rash Rash over the cheeks
Discoid Rash Red raised patches
Photosensitivity Reaction to sunlight, resulting in the development of or increase
in skin rash
Oral Ulcers Ulcers in the nose or mouth, usually painless
Arthritis Nonerosive arthritis involving two or more peripheral joints
(arthritis in which the bones around the joints do not become
Serositis Pleuritis or pericarditis (inflammation of the lining of the lung or
Renal Disorder Excessive protein in the urine (greater than 0.5 gm/day or 3+ on
test sticks) and/or cellular casts (abnormal elements the urine,
derived from red and/or white cells and/or kidney tubule cells)
Seizures (convulsions) and/or psychosis in the absence of
drugs or metabolic disturbances which are known to cause
Hemolytic anemia , leukopenia , lymphopenia or
thrombocytopenia. The leukopenia and lymphopenia must be
detected on two or more occasions. The thrombocytopenia
must be detected in the absence of drugs known to induce it.
Positive test for antinuclear antibodies (ANA) in the absence
of drugs known to induce it.
Positive anti-double stranded anti-DNA test, positive anti-Sm
test, positive antiphospholipid antibody such as anticardiolipin,
or false positive syphilis test (VDRL).
EFFECT OF LABORATORY TESTSEFFECT OF LABORATORY TESTS
WITH INCREASED LUPUSWITH INCREASED LUPUS
C reactive protein (CRP)
Sedimentation rate (ESR)
Liver and Kidney
Urine protein or cell casts
CBC (WBC, RBC,
DRUG CLASS DRUG AND DOSE MAJOR INDICATIONS
NSAIDs • Various agents
• Anti-inflammatory dose
Mild disease: fever, arthritis
,skin rash, serositis
Antimalarial • Hydroxychloroquine, 200-400mg, PO
• Chloroquine, 250-500mg, PO daily
Mild disease: arthritis, skin rash,
Corticosteroid • Prednisone, 1-2mg/kg/d, PO daily (or
equivalent) <1mg/kg/d (or equivalent)
• Methyl prednisolone, 500-600mg IV
daily * 3-6 days
Initial control of severe disease
Control of mild disease or
maintenance after disease
Suppression with higher doses.
Life threatening disease
Cytotoxic • Cyclophosphamide, 0.5-1.0g/m2 IV
monthly for 6 months, then every 3
months for 2 years or 1 year after
• Azathioprine 1-3mg/kg PO daily
1-3mg/kg PO daily
• Mycophenolate mofetil, 1-3g PO daily
Most commonly used in severe
lupus nephritis: may be
necessary for other severe
Balanced routine of rest and exercise while
avoiding overexertion is essential in
Avoidance of smoking
Fish oil derivatives in pregnant women
Limit exposure to sunlight
DRUG INDUCED LUPUSDRUG INDUCED LUPUS
Develops after long-term use of certain
To meet the criteria for DIL, a patient should have
exposure to a suspected drug, no prior history of
idiopathic SLE prior to the use of drug,
development of ANAs (anti-histone antibody), and
at least one clinical feature of SLE and rapid
improvement of symptoms with a gradual decline in
ANAs following drug discontinuation.
Most common in men over 50 years old.
Symptoms are similar to SLE.
Musculoskeletal symptoms, fever, fatigue,
pericarditis, pleurisy and weight loss.
+ve ANA test (>90%)
Antibodies are primarily against ssDNA and
not dsDNA as in idiopathic SLE.
Most important treatment is to recognize
medication and discontinue use.
Once medication is stopped, symptoms
usually disappear completely within 6
Medications implemented in drug induced lupus
Acebutolol Clonidine Interleukin
Minocycline Pindolol Sulfasalazi
Amiodarone Clozapine Isoniazid Nifedipine Primidone Tetracyclin
Anti-TNF therapies Diltiazem Labetalol Oral
Atenolol Ethosuximide Lisinopril Para-amino
Captopril Gold salts Lithium Penicillamin
Carbamazepine Griseofulvin Mephenyto
Penicillin Quinidine Tocainide
Chlorpromazine Hydralazine Methimazo
Phenytoin Reserpine Valproate
Ciprofloxacin hydroxyurea Methyldo
Metoprolol phenelzine Streptomycin Zafirlukast
SLE in pregnancy
Exacerbation is likely, if the disease is in
remission at conception.
Hydroxychloroquine is safer to use in
There is increased risk of abortions (2-3
times), intrauterine growth retardation and
stillbirth. Pregnancy increases the risk of
disease flare (40%-50% probability).
The risk of flare is doubled in women who
have active disease at the time of
Laboratory monitoring during
Initial evaluation: Hb, WBC, DLC, platelets, urinalysis with
microscopy, 24-hour urinary estimation of protein and
creatinine, blood urea, glucose and serum creatinine, serum
lipids if patient is nephrotic or on steroids, Coombs’ test, aPL
VDRL, anti-dsDNA, C3. Anti-Ro and anti-La should be done if
there is a past history of giving birth to a baby with neonatal
Monthly Laboratory assessment includes Hb, WBC, DLC,
platelets, urinalysis (with 24-hr analysis if nephritis), chemistry
panel as above, anti-dsDNA and C3. Elevated anti-dsDNA and
low C3 indicate active SLE or impending flare in over 80% of
In case anaemia develops, peripheral smear should be
reviewed and Coombs’ test repeated.
Medication use during SLE pregnancy
Medication to continue in
Medication to discontinue
prior to pregnancy
Prenatal multivitamin Cyclophosphamide
Low-dose Aspirin Mycophenolate mofetil
Aspirin 81 mg
NEONATAL LUPUSNEONATAL LUPUS
Occurs when the mother’s antibodies cross
over the placenta to the baby.
Can affect the skin, heart, liver and/or blood of
the fetus and newborn.
Good prenatal care can prevent most problems.
Estrogen containing oral contraceptives are
avoided in women with SLE.
Combined oral contraceptives ,progestin only
contraceptives and IU devices are suggested
for women with SLE.
Presence of anti-phospholipid antibodies may
lead to thrombosis.
Low dose Aspirin (81-325mg/day)
Patient with acute thrombotic event – standard
treatment with anti-coagulants like Heparin.
Lupus nephritis is currently defined as the presence of more
than +++ or 0.5 gram/24 hr proteinuria or presence of cellular
casts of any type.
Principles of treatment of lupus nephritis
General measures: It is advisable to restrict salt if
hypertension is present, fat if hyperlipidemia or nephrotic
syndrome is present, protein should be restricted if azotemia
is present and calcium should be supplemented with steroid
therapy. Meticulous control of hypertension is desirable.
Pregnancy should be avoided during active lupus nephritis
with suitable contraception (vide infra). NSAIDs should be
avoided in the presence of impaired renal function
Immunosuppressive therapy: This is generally
guided by the WHO Class of lupus nephritis
Class I: Immunosuppressive therapy is not indicated.
Class IIa: -do
Class IIb: If proteinuria is > 1 gram/24 hours, anti-
dsDNA is high and C3 is low, prednisolone should be
administered at a dose of 20 mg daily for 6-12 weeks,
followed by tapering over next 3 months
Monitoring the toxicities of drugs used in SLE
Drug Toxicities to monitor Baseline evaluation Monitoring
System review Laboratory
GI bleeding, hepatic and renal
urinalysis, AST, ALT
Dark/black stool, dyspepsia,
nausea, vomiting, abdominal
pain, shortness of breath,
CBC yearly, Creatinine
Corticosteroids Hypertension, hyperglycemia,
osteoporosis, avascular necrosis,
cataract, weight gain, infections,
BP, bone densitometry,
triglycerides, HDL, LDL
Polyuria, polydipsia, edema,
shortness of breath, BP, visual
changes, bone pain
Urinary dipstick for glucose
every 3-6 months, total
cholesterol yearly, bone
densitometry yearly to
Macular damage None unless patient is
over 40 years of age or
has previous eye
Visual changes Funduscopic and visual
fields every 6-12 months
Azathioprine Myelosuppression, hepatotoxicity,
CBC, platelet count,
creatinine, AST, ALT
Symptoms of myelosuppression CBC and platelet count
every 1-2weeks with
changes in dose (every 1-3
months thereafter), AST
PAP test at regular
hemorrhage, cystitis, secondary
CBC and differential
and platelet count,
CBC and urinalysis
monthly ,urine cytology,
and PAP test yearly for life