Diminished ability of erythrocytes from patients with systemic lupus

erythematosus to limit opsonized immune complex deposition on leukocytes and

activation of granulocytes.
Nielsen CH, Rasmussen JM, Voss A, Junker P, Leslie RG.

Source

Odense University, Denmark.

Abstract
OBJECTIVE:
To compare the ability of normal erythrocytes and erythrocytes from systemic lupus erythematosus (SLE) patients to
bind immune complexes (IC), thereby inhibiting IC deposition on polymorphonuclear leukocytes (PMN) and the
consequent induction of a PMN respiratory burst (RB).

METHODS:
The binding of fluorescein isothiocyanate-labeled IC in 75% autologous serum to whole blood cells or isolated
leukocytes from 17 SLE patients and 10 controls was assessed by flow cytometry. Reactive oxygen metabolite
(ROM) production by PMN was measured as the intracellular oxidation of dihydrorhodamine 123, on stimulation with
unlabeled IC.

RESULTS:
Erythrocyte-mediated inhibition of IC uptake by PMN reached a mean +/- SD maximum of 68 +/- 18% in controls and
29 +/- 51% in SLE patients (P < 0.05) and, in the patients, correlated inversely with disease activity. In the presence
of erythrocytes from various donors, IC binding to a standard preparation of PMN and their ROM production were
inversely proportional to the number of type 1 complement receptors (CR1) per donor erythrocyte. Thus, the ROM
production was higher in the presence of SLE patients' erythrocytes (125 +/- 67 CR1/erythrocyte) than with
erythrocytes from controls (235 +/- 118 CR1/erythrocyte).

CONCLUSION:
Erythrocytes from SLE patients are defective in protecting their PMN against IC deposition and induction of the RB.
Mode of Inheritance of Decreased C3b Receptors on Erythrocytes
of Patients with Systemic Lupus Erythematosus
James G. Wilson, M.D., Winnie W. Wong, B.S., Peter H. Schur, M.D., and Douglas T. Fearon, M.D.

N Engl J Med 1982; 307:981-986October 14, 1982

Abstract
The erythrocytes of patients with systemic lupus erythematosus have been shown to have a decreased number
of receptors for the major cleavage fragment of the third component of complement (C3b). We studied the
basis for this decreased number of C3b receptors by measuring the uptake of anti-C3b-receptor antibody on
cells from 113 normal subjects, 38 patients with systemic lupus erythematosus, 14 of their spouses, and 47 of
their relatives.
The normal subjects had 5014±155 (mean ±S.E.M.) receptor sites per cell, but the patients and their relatives
had significantly fewer sites — 2804±241 and 3167±196, respectively (P<0.0005). The number of sites in the
patients' spouses did not differ from normal (P>0.3).
Three phenotypes, indicated by the numbers of receptors, occurred in the normal population: a high phenotype
(HH, with 5500 to 8500 sites per cell), an intermediate phenotype (HL, with 3000 to 5499), and a low phenotype
(LL, <3000). These three phenotypes were present in 34, 54, and 12 per cent, respectively, of the normal
subjects; in contrast, 5, 42, and 53 per cent of patients had these respective phenotypes. Pedigree analyses
indicated that these phenotypes were inherited in an autosomal codominant manner. We conclude that the
decreased number of C3b receptors in lupus is inherited, not acquired. (N Engl J Med. 1982; 307:981–6.)
Supported in part by grants (AI-07722, AI-10356, AI-17917, AM-11414, AM-05577, and RR-05669) from the
National Institutes of Health, and also in part by grants from the New England Peabody Home Foundation, the
Lupus Foundation, and the Arthritis Foundation. Dr. Wilson is a research fellow of the Arthritis Foundation.
SOURCE INFORMATION

From the Department of Medicine, Harvard Medical School, and the Department of Rheumatology and Immunology, Division
of Brigham and Women's Hospital, Boston. Address reprint requests to Dr. Wilson at 617 Seeley Mudd Bldg., 250 Longwood
Ave., Boston, MA 02115.
Hematologic Aspects of Systemic Lupus
Erythematosus
Current Concepts
1. DANIEL R. BUDMAN, M.D.; and
2. ALFRED D. STEINBERG, M.D.
+Author Affiliations
1. Bethesda, Maryland

Abstract

Anemia occurs in more than one half of patients with systemic lupus erythematosus
and is usually attributed to "chronic disease." Approximately 10% of patients with a
positive Coombs' test manifest clinically significant hemolysis. Leukopenia affects
both granulocytic and lymphocytic lines and may be caused by autoantibodies.
Nevertheless, enhancement of B lymphocyte function occurs in active disease,
perhaps due to a loss of regulatory T cells. Most patients have increased production
and increased peripheral destruction of thrombocytes, with a normal circulation
platelet count. Thrombocytopenia is usually caused by increased destruction.
Qualitative abnormalities of platelet aggregation also occur. Circulation
anticoagulants are not rare; however, spontaneous bleeding is uncommon. The
anticoagulants, immunoglobulins directed against clotting factors, assume
importance for invasive procedures. Most clinically significant hematopoietic
abnormalities can be suppressed by corticosteroids; however, splenectomy, or
immunosuppressive agents, or both, may be indicated for patients who respond
inadequately to corticosteroids.
Erythrocyte sedimentation rate
From Wikipedia, the free encyclopedia

The erythrocyte sedimentation rate (ESR), also called a sedimentation rate or Biernacki Reaction, is the
rate at which red blood cells sediment in a period of 1 hour. It is a common hematology test that is a non-
specific measure of inflammation. To perform the test, anticoagulated blood is placed in an upright tube, known
as a Westergren tube, and the rate at which the red blood cells fall is measured and reported in mm/h.

Since the introduction of automated analyzers into the clinical laboratory, the ESR test has been automatically
performed.

The ESR is governed by the balance between pro-sedimentation factors, mainly fibrinogen, and those factors
resisting sedimentation, namely the negative charge of the erythrocytes (zeta potential). When an inflammatory
process is present, the high proportion of fibrinogen in the blood causes red blood cells to stick to each other.
The red cells form stacks called 'rouleaux,' which settle faster. Rouleaux formation can also occur in
association with some lymphoproliferative disorders in which one or more immunoglobulin are secreted in high
amounts. Rouleaux formation can, however, be a normal physiological finding in horses, cats, and pigs.

The ESR is increased by any cause or focus of inflammation. The ESR is increased
in pregnancy or rheumatoid arthritis, and decreased in polycythemia, sickle cell anemia, hereditary
spherocytosis, and congestive heart failure. The basal ESR is slightly higher in females.[1]
 Contents

• 1 History

• 2 Uses

• 3 Normal Values

o 3.1 Adults

o 3.2 Children

• 4 Relation to C-

reactive protein

• 5 External links

• 6 References

[edit]History

This test was invented in 1897 by the Polish doctor Edmund Biernacki.[2] In some parts of the world the test
continues to be referred to as the Biernacki Test (Polish abbreviation: OB = Odczyn Biernackiego.) In 1918 the
Swedish pathologist Robert Sanno Fåhræusdeclared the same and along with Alf Vilhelm Albertsson
Westergren are eponymously remembered for the Fåhræus-Westergren test (abbreviated as FW test; in the
UK, usually termed Westergren test),[3] which uses sodium citrate-anticoagulated specimens.[4]

[edit]Uses

Although it is frequently ordered, ESR is of limited use as a screening test in asymptomatic patients. It is useful
for diagnosing diseases, such as multiple myeloma, temporal arteritis, polymyalgia rheumatica, various auto-
immune diseases, systemic lupus erythematosus, rheumatoid arthritis, and chronic kidney diseases. In many of
these cases, the ESR may exceed 100 mm/hour.[5]

It is commonly used for a differential diagnosis for Kawasaki's disease and it may be increased in some chronic
infective conditions like tuberculosis and infective endocarditis. It is a component of the PDCAI, an index for
assessment of severity of inflammatory bowel disease in children.

The clinical usefulness of ESR is limited to monitoring the response to therapy in certain inflammatory diseases
such as temporalarteritis, polymyalgia rheumatica and rheumatoid arthritis. It can also be used as a crude
measure of response in Hodgkin's lymphoma. Additionally, ESR levels are used to define one of the several
possible adverse prognostic factors in the staging of Hodgkin's lymphoma. There is also a wintrobe method.

The use of the ESR as a screening test in asymptomatic persons is limited by its low sensitivity and specificity.
When there is a moderate suspicion of disease, the ESR may have some value as a "sickness index."
An elevated ESR in the absence of other findings should not trigger an extensive laboratory or radiographic
evaluation.[citation needed]

[edit]Normal Values
Note: mm/hr. = millimeters per hour.

Westergren's original normal values (men 3mm and women 7mm)[6] made no allowance for a person's age and
in 1967 it was confirmed that ESR values tend to rise with age and to be generally higher in women.[7] Values
are increased in states of anemia,[8]and in black populations.[9]

[edit]Adults

The widely used[10] rule for calculating normal maximum ESR values in adults (98% confidence limit) is given by
a formula devised in 1983:[11]

ESR reference ranges from a large 1996 study with weaker confidence limits:[12]

Age 20 55 90

Men 12 14 19

Women 18 21 23

[edit]Children

Normal values of ESR have been quoted as 1[13] to 2[14] mm/hr at birth, rising to 4 mm/hr 8 days after
delivery,[14] and then to 17 mm/hr by day 14.[13]

Typical normal ranges quoted are:[15]

 Newborn: 0 to 2 mm/hr

 Neonatal to puberty: 3 to 13 mm/hr, but other laboratories place an upper limit of 20.[16]

[edit]Relation to C-reactive protein

C-reactive protein is an acute phase protein produced by the liver during an inflammatory reaction. Since
C-reactive protein levels in the blood rise more quickly after the inflammatory or infective process begins,
ESR is often replaced with C-reactive protein measurement. There are specific drawbacks, however, for
example, both tests for ESR and CRP were found to be independently associated with a diagnosis
of acute maxillary sinusitis [17] so in some cases the combination of the two measurements may improve
diagnostic sensitivity and specificity.
[edit]External links

 Interpret ESR BLood Test

 Erythrocyte Sedimentation Rate

[edit]References

1. ^http://www.nlm.nih.gov/medlineplus/ency/article/003638.htm

2. ^ Edmund Faustyn Biernacki and eponymously namedBiernacki's test at Who Named It?

3. ^ Robert (Robin) Sanno Fåhræus and Alf Vilhelm Albertsson Westergren who are

eponymously named for theFåhræus-Westergren test (aka Westergren test) at Who Named It?

4. ^ International Council for Standardization in Haematology (Expert Panel on Blood

Rheology) (1993). "ICSH recommendations for measurement of erythrocyte sedimentation rate.". J.

Clin. Pathol. 46 (3): 198–203.doi:10.1136/jcp.46.3.198. PMC 501169. PMID 8463411.

5. ^ "Sedimentation Rate". WebMD. 2006-06-16. Retrieved 2008-03-01.

6. ^ Westergren A (1957). "Diagnostic tests: the erythrocyte sedimentation rate range and

limitations of the technique".Triangle 3 (1): 20–5. PMID 13455726.

7. ^ Böttiger LE, Svedberg CA (1967). "Normal erythrocyte sedimentation rate and age". Br

Med J 2 (5544): 85–7.doi:10.1136/bmj.2.5544.85. PMC 1841240.PMID 6020854.

8. ^ Kanfer EJ, Nicol BA (1997). "Haemoglobin concentration and erythrocyte sedimentation

rate in primary care patients"(Scanned & PDF). Journal of the Royal Society of Medicine 90(1): 16–

8. PMC 1296109. PMID 9059375.

9. ^ Gillum RF (1993). "A racial difference in erythrocyte sedimentation". Journal of the

National Medical Association85 (1): 47–50. PMC 2571720. PMID 8426384.

10. ^ Reference range (ESR) at GPnotebook

11. ^ Miller A, Green M, Robinson D (1983). "Simple rule for calculating normal erythrocyte

sedimentation rate". Br Med J (Clin Res Ed) 286 (6361):

266.doi:10.1136/bmj.286.6361.266. PMC 1546487.PMID 6402065.

12. ^ Wetteland P, Røger M, Solberg HE, Iversen OH (1996). "Population-based erythrocyte

sedimentation rates in 3910 subjectively healthy Norwegian adults. A statistical study based on men

and women from the Oslo area". J. Intern. Med. 240(3): 125–31. doi:10.1046/j.1365-

2796.1996.30295851000.x.PMID 8862121. - listing upper reference levels expected to be exceeded

only by chance in 5% of subjects

13. ^ a b Adler SM, Denton RL (1975). "The erythrocyte sedimentation rate in the newborn

period". J. Pediatr. 86 (6): 942–8. doi:10.1016/S0022-3476(75)80233-2.PMID 1168702.

 14. ^ a b Ibsen KK, Nielsen M, Prag J, et al. (1980). "The value of the micromethod erythrocyte

sedimentation rate in the diagnosis of infections in newborns". Scand J Infect Dis SupplSuppl 23:

143–5. PMID 6937959.

15. ^ MedlinePlus Encyclopedia ESR

16. ^ Mack DR, Langton C, Markowitz J, et al. (2007). "Laboratory values for children with

newly diagnosed inflammatory bowel disease". Pediatrics 119 (6): 1113–9. doi:10.1542/peds.2006-

1865. PMID 17545378. - as commented on at

* Bauchner H (2007-06-13). "Lab Screening in Children with Suspected Inflammatory Bowel

Disease". Journal Watch Pediatrics and Adolescent Medicine. Retrieved 2008-03-01.

17. ^ Jens Georg Hansen, Henrik Schmidt, Jorn Rosborg, Elisabeth Lund (22 July

1995). "Predicting acute maxillary sinusitis in a general practice population". BMJ 311 (6999): 233–
236. PMC 2550286. PMID 7627042.

v · d · eInfectious and inflammatory blood tests

syphilis (VDRL, rapid plasma reagin, Wassermann test, FTA-ABS) · Rickettsia (Weil
Bacterial infection
test) · Helicobacter(HelicoCARE direct) · Streptococcus (antistreptolysin O titre)

HIV (HIV test, BDNA test) · Epstein-Barr virus (monospot test) · Dengue fever (NS1
Infections Viral infection
test)

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toxoplasmosis (Sabin-Feldman dye test)
infection

Inflamma C-reactive protein · procalcitonin · erythrocyte sedimentation rate · MELISA · RAST test · CBC (lymph
tion count)

M: BAC bact (clas) gr+f/gr+a(t)/gr-p(c)/gr-o drug(J1p, w, n, m

M: VIR virs (prot) cutn/syst (hppv, hiva, infl, zost, zoon),epon drugJ(dnaa, rnaa,

M: PRO ambz, excv, chrm (strc) ambz, excv, chrm ambz, excv, c

M: LMC cell/phys/auag/auab/comp, imrc, tcrp imdf/ipig/hyps/tumr proc, drug(L

Categories: Blood tests | Hematology

What is lupus? What are the types of lupus?

Lupus is an autoimmune diseasecharacterized by acute and chronic inflammation of various tissues of

the body. Autoimmune diseases are illnesses that occur when the body's tissues are attacked by its own
immune system. The immune system is a complex system within the body that is designed to fight
infectious agents, such as bacteria and other foreign microbes. One of the ways that the immune system
fights infections is by producing antibodies that bind to the microbes. People with lupus produce abnormal
antibodies in their blood that target tissues within their own body rather than foreign infectious agents.
Because the antibodies and accompanying cells of inflammation can affect tissues anywhere in the body,
lupus has the potential to affect a variety of areas. Sometimes lupus can cause disease of the skin, heart,
lungs, kidneys, joints, and/or nervous system. When only the skin is involved, the condition is called lupus
dermatitis or cutaneous lupus erythematosus. A form of lupus dermatitis that can be isolated to the skin,
without internal disease, is called discoid lupus. When internal organs are involved, the condition is
referred to as systemic lupus erythematosus (SLE).

Both discoid and systemic lupus are more common in women than men (about eight times more
common). The disease can affect all ages but most commonly begins from 20-45 years of age. Statistics
demonstrate that lupus is somewhat more frequent in African Americans and people of Chinese and
Japanese descent.

What causes lupus? Is lupus hereditary?

The precise reason for the abnormal autoimmunity that causes lupus is not known. Inherited genes,
viruses, ultraviolet light, and certain medications may all play some role.

Genetic factors increase the tendency of developing autoimmune diseases, and autoimmune diseases
such as lupus, rheumatoid arthritis, and autoimmune thyroid disorders are more common among relatives
of people with lupus than the general population. Some scientists believe that the immune system in
lupus is more easily stimulated by external factors like viruses or ultraviolet light. Sometimes, symptoms
of lupus can be precipitated or aggravated by only a brief period of sun exposure.

It also is known that some women with SLE can experience worsening of their symptoms prior to
their menstrual periods. This phenomenon, together with the female predominance of SLE, suggests that
female hormones play an important role in the expression of SLE. This hormonal relationship is an active
area of ongoing study by scientists.

More recently, research has demonstrated evidence that a key enzyme's failure to dispose of dying cells
may contribute the development of SLE. The enzyme, DNase1, normally eliminates what is called
"garbage DNA" and other cellular debris by chopping them into tiny fragments for easier disposal.
Researchers turned off the DNase1 gene in mice. The mice appeared healthy at birth, but after six to
eight months, the majority of mice without DNase1 showed signs of SLE. Thus, a genetic mutation in a
gene that could disrupt the body's cellular waste disposal may be involved in the initiation of SLE.

What is drug-induced lupus?

Dozens of medications have been reported to trigger SLE. However, more than 90% of cases of "drug-
induced lupus" occurs as a side effect of one of the following six drugs: hydralazine (Apresoline is used
forhigh blood pressure); quinidine (Quinidine Gluconate, Quinidine Sulfate) andprocainamide (Pronestyl;
Procan-SR; Procanbid) are used for abnormal heart rhythms; phenytoin (Dilantin) is used
forepilepsy; isoniazid ([Nydrazid, Laniazid] used for tuberculosis); and d-penicillamine (used
for rheumatoid arthritis). These drugs are known to stimulate the immune system and cause SLE.
Fortunately, drug-induced SLE is infrequent (accounting for less than 5% of all people with SLE) and
usually resolves when the medications are discontinued.

What are lupus symptoms and signs?

People with SLE can develop different combinations of symptoms and organ involvement. Common
complaints and symptoms include fatigue, low-grade fever,loss of appetite, muscle aches, arthritis, ulcers
of the mouth and nose, facial rash("butterfly rash"), unusual sensitivity to sunlight (photosensitivity),
inflammation of the lining that surrounds the lungs (pleuritis) and the heart (pericarditis), and poor
circulation to the fingers and toes with cold exposure (Raynaud's phenomenon). Complications of organ
involvement can lead to further symptoms that depend on the organ affected and severity of the disease.

Skin manifestations are frequent in lupus and can sometimes lead to scarring. In discoid lupus, only the
skin is typically involved. The skin rash in discoid lupus often is found on the face and scalp. It usually is
red and may have raised borders. Discoid lupus rashes are usually painless and do not itch,
but scarring can cause permanent hair loss (alopecia). Over time, 5%-10% of those with discoid lupus
may develop SLE.

Over half of the people with SLE develop a characteristic red, flat facial rash over the bridge of their nose.
Because of its shape, it is frequently referred to as the "butterfly rash" of SLE. The rash is painless and
does not itch. The facial rash, along with inflammation in other organs, can be precipitated or worsened
by exposure to sunlight, a condition called photosensitivity. This photosensitivity can be accompanied by
worsening of inflammation throughout the body, called a "flare" of the disease.

Picture of a butterfly rash on the face, a characteristic sign of systemic

lupus erythematosus (SLE)

Typically, with treatment, this rash can heal without permanent scarring.

Most people with SLE will develop arthritis during the course of their illness. Arthritis in SLE commonly
involves swelling, pain, stiffness, and even deformity of the small joints of the hands, wrists, and feet.
Sometimes, the arthritis of SLE can mimic that of rheumatoid arthritis (another autoimmune disease).

More serious organ involvement with inflammation occurs in the brain, liver, and kidneys. White blood
cells and blood-clotting factors also can be characteristically decreased in SLE, known as leukopenia
(leucopenia) and thrombocytopenia, respectively. Leukopenia can increase the risk of infection, and
thrombocytopenia can increase the risk of bleeding.

Inflammation of muscles (myositis) can cause muscle pain and weakness. This can lead to elevations of
muscle enzyme levels in the blood.

Inflammation of blood vessels (vasculitis) that supply oxygen to tissues can cause isolated injury to a
nerve, the skin, or an internal organ. The blood vessels are composed of arteries that pass oxygen-rich
blood to the tissues of the body and veins that return oxygen-depleted blood from the tissues to the lungs.
Vasculitis is characterized by inflammation with damage to the walls of various blood vessels. The
damage blocks the circulation of blood through the vessels and can cause injury to the tissues that are
supplied with oxygen by these vessels.

Inflammation of the lining of the lungs (pleuritis) and of the heart (pericarditis) can cause sharp chest pain.
The chest pain is aggravated by coughing, deep breathing, and certain changes in body position. The
heart muscle itself rarely can become inflamed (carditis). It has also been shown that young women with
SLE have a significantly increased risk of heart attacks due to coronary artery disease.

Kidney inflammation in SLE can cause leakage of protein into the urine, fluid retention, high blood
pressure, and even kidney failure. This can lead to furtherfatigue and swelling of the legs and feet. With
kidney failure, machines are needed to cleanse the blood of accumulated waste products in a process
called dialysis.

Involvement of the brain can cause personality changes, thought disorders (psychosis), seizures, and
even coma. Damage to nerves can cause numbness, tingling, and weakness of the involved body parts
or extremities. Brain involvement is referred to as lupus cerebritis.

Many people with SLE experience hair loss (alopecia). Often, this occurs simultaneously with an increase
in the activity of their disease. The hair loss can be patchy or diffuse and appear to be more like hair
thinning.

Some people with SLE have Raynaud's phenomenon. In this condition, the blood supply to the fingers
and/or toes becomes compromised upon exposure to cold, causing blanching, whitish and/or bluish
discoloration, and pain and numbness in the exposed fingers and toes.

Other conditions that can accompany lupus include fibromyalgia, coronary heart disease, nonbacterial
valvular heart disease, pancreatitis, esophagus disease with difficulty swallowing (dysphagia), liver
disease (lupoid hepatitis), and infections.

How is lupus diagnosed?

Since individuals with SLE can have a wide variety of symptoms and different combinations of organ
involvement, no single test establishes the diagnosis of systemic lupus. To help doctors improve the
accuracy of the diagnosis of SLE, 11 criteria were established by the American Rheumatism Association.
These 11 criteria are closely related to the symptoms discussed above. Some people suspected of having
SLE may never develop enough criteria for a definite diagnosis. Other people accumulate enough criteria
only after months or years of observation. When a person has four or more of these criteria, the diagnosis
of SLE is strongly suggested. Nevertheless, the diagnosis of SLE may be made in some settings in
people with only a few of these classical criteria, and treatment may sometimes be instituted at this stage.
Of these people with minimal criteria, some may later develop other criteria, but many never do.

The 11 criteria used for diagnosing systemic lupus erythematosus are

• malar (over the cheeks of the face) "butterfly" rash,

 • discoid skin rash (patchy redness with hyperpigmentation and hypopigmentation that can cause
scarring),

• photosensitivity (skin rash in reaction to sunlight [ultraviolet light] exposure),

• mucous membrane ulcers (spontaneous ulcers of the lining of the mouth, nose, or throat),

• arthritis (two or more swollen, tender joints of the extremities),

• pleuritis or pericarditis (inflammation of the lining tissue around the heart or lungs, usually
associated with chest pain upon breathing or changes of body position),

• kidney abnormalities (abnormal amounts of urine protein or clumps of cellular elements called
casts detectable with a urinalysis),

• brain irritation (manifested by seizures [convulsions] and/or psychosis),

• blood-count abnormalities (low counts of white or red blood cells, or platelets, on routine blood
testing),

• immunologic disorder (abnormal immune tests include anti-DNA or anti-Sm [Smith] antibodies,
falsely positive blood test for syphilis, anticardiolipin antibodies, lupus anticoagulant, or positive LE
prep test),

• and antinuclear antibody (positive ANA antibody testing [antinuclear antibodies in the blood]).

In addition to the 11 criteria, other tests can be helpful in evaluating people with SLE to determine the
severity of organ involvement. These include routine testing of the blood to detect inflammation (for
example, tests called the sedimentation rateand C-reactive protein), blood-chemistry testing, direct
analysis of internal body fluids, and tissue biopsies. Abnormalities in body fluids and tissue samples
(kidney, skin, and nerve biopsies) can further support the diagnosis of SLE. The appropriate testing
procedures are selected for the patient individually by the doctor.

What is the treatment for systemic lupus erythematosus?

There is no permanent cure for SLE. The goal of treatment is to relieve symptoms and protect organs by
decreasing inflammation and/or the level of autoimmune activity in the body. The precise treatment is
decided on an individual basis. Many people with mild symptoms may need no treatment or only
intermittent courses of anti-inflammatory medications. Those with more serious illness involving damage
to internal organ(s) may require high doses of corticosteroids in combination with other medications that
suppress the body's immune system.

People with SLE need more rest during periods of active disease. Researchers have reported that
poor sleep quality was a significant factor in developing fatigue in people with SLE. These reports
emphasize the importance for people and physicians to address sleep quality and the effect of
underlying depression, lack ofexercise, and self-care coping strategies on overall health. During these
periods, carefully prescribed exercise is still important to maintain muscle tone and range of motion in the
joints.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are helpful in reducing inflammation and pain in muscles,
joints, and other tissues. Examples of NSAIDs includeaspirin, ibuprofen (Motrin), naproxen (Naprosyn),
and sulindac (Clinoril). Since the individual response to NSAIDs varies, it is common for a doctor to try
different NSAIDs to find the most effective one with the fewest side effects. The most common side
effects are stomach upset, abdominal pain, ulcers, and even ulcer bleeding. NSAIDs are usually taken
with food to reduce side effects. Sometimes, medications that prevent ulcers while taking NSAIDs, such
as misoprostol(Cytotec), are given simultaneously.

Corticosteroids are more potent than NSAIDs in reducing inflammation and restoring function when the
disease is active. Corticosteroids are particularly helpful when internal organs are affected.
Corticosteroids can be given by mouth, injected directly into the joints and other tissues, or administered
intravenously. Unfortunately, corticosteroids have serious side effects when given in high doses over
prolonged periods, and the doctor will try to monitor the activity of the disease in order to use the lowest
doses that are safe. Side effects of corticosteroids include weight gain, thinning of the bones and skin,
infection, diabetes, facial puffiness, cataracts, and death (necrosis) of the tissues in large joints.

Hydroxychloroquine (Plaquenil) is an antimalarial medication found to be particularly effective for SLE

people with fatigue, skin involvement, and joint disease. Consistently taking Plaquenil can prevent flare-
ups of lupus. Side effects are uncommon but include diarrhea, upset stomach, and eye-pigment changes.
Eye-pigment changes are rare but require monitoring by an ophthalmologist (eye specialist) during
treatment with Plaquenil. Researchers have found that Plaquenil significantly decreased the frequency of
abnormal blood clots in people with systemic lupus. Moreover, the effect seemed independent of immune
suppression, implying that Plaquenil can directly act to prevent the blood clots. This fascinating study
highlights an important reason for people and doctors to consider Plaquenil for long-term use, especially
for those SLE people who are at some risk for blood clots in veins and arteries, such as those with
phospholipid antibodies (cardiolipin antibodies, lupus anticoagulant, and false-positive venereal disease
research laboratory test). This means not only that Plaquenil reduces the chance for re-flares of SLE, but
it can also be beneficial in thinning the blood to prevent abnormal excessive blood clotting. Plaquenil is
commonly used in combination with other treatments for lupus.
For resistant skin disease, other antimalarial drugs, such as chloroquine (Aralen) orquinacrine, are
considered and can be used in combination with hydroxychloroquine. Alternative medications for skin
disease include dapsone and retinoic acid (Retin-A). Retin-A is often effective for an uncommon wart-like
form of lupus skin disease. For more severe skin disease, immunosuppressive medications are
considered as described below.

Medications that suppress immunity (immunosuppressive medications) are also called cytotoxic drugs.
Immunosuppressive medications are used for treating people with more severe manifestations of SLE,
such as damage to internal organ(s). Examples of immunosuppressive medications
include methotrexate(Rheumatrex, Trexall), azathioprine (Imuran), cyclophosphamide (Cytoxan),
chlorambucil (Leukeran), and cyclosporine (Sandimmune). All immunosuppressive medications can
seriously depress blood-cell counts and increase risks of infection and bleeding. Immunosuppressive
medications may not be taken during pregnancyor conception because of risk to the fetus. Other side
effects are specific for each drug. For examples, Rheumatrex can cause liver toxicity, while Sandimmune
can impair kidney function.

In recent years, mycophenolate mofetil (CellCept) has been used as an effective medication for lupus,
particularly when it is associated with kidney disease. CellCept has been helpful in reversing active lupus
kidney disease (lupus renal disease) and in maintaining remission after it is established. Its lower side-
effect profile has advantage over traditional immune-suppression medications.

In SLE patients with serious brain or kidney disease, plasmapheresis (a process of removing and treating
the blood before it is returned to the body) is sometimes used to remove antibodies and other immune
substances from the blood to suppress immunity. Rarely, people with SLE can develop seriously low
platelet levels, thereby increasing the risk of excessive and spontaneous bleeding. Since the spleen is
believed to be the major site of platelet destruction, surgical removal of the spleen is sometimes
performed to improve platelet levels. Other treatments have included plasmapheresis and the use of male
hormones. Plasmapheresis has also been used to remove proteins (cryoglobulins) that can lead to
vasculitis. End-stage kidney damage from SLE requires dialysis and/or a kidney transplant.

Most recent research is indicating benefits of rituximab (Rituxan) in treating lupus. Rituximab is an
intravenously infused antibody that suppresses a particular white blood cell, the B cell, by decreasing their
number in the circulation. B cells have been found to play a central role in lupus activity, and when they
are suppressed, the disease tends toward remission. This may particularly helpful for people with kidney
disease.

Another new B-cell-suppressing treatment is belimumab (Benlysta). Belimumab blocks the stimulation of
the B cells (a B-lymphocyte stimulator or BLyS-specific inhibitor) and is indicated for the treatment of adult
patients with active, autoantibody-positive systemic lupus erythematosus who are receiving standard
therapy. It is important to note that the efficacy of belimumab has not been evaluated in patients with
severe active lupus nephritis or severe active central nervous system lupus. Belimumab has not been
studied in combination with other biologic therapies or intravenous cyclophosphamide.

Scientists have also found that low-dose dietary supplementation with omega-3 fish oils could help
patients with lupus by decreasing disease activity and possibly decreasing heart-disease risk.

How can a lupus patient help prevent disease activity (flares)?

SLE is undoubtedly a potentially serious illness with involvement of numerous organ systems. However, it
is important to recognize that most people with SLE lead full, active, and healthy lives. Periodic increases
in disease activity (flares) can usually be managed by varying medications. Since ultraviolet light can
precipitate and worsen flares, people with systemic lupus should avoid sun exposure. Sunscreens and
clothing covering the extremities can be helpful. Abruptly stopping medications, especially corticosteroids,
can also cause flares and should be avoided. People with SLE are at increased risk of infections,
especially if they are taking corticosteroids or immunosuppressive medications. Therefore, any
unexpected fever should be reported and evaluated.

The key to successful management of SLE is regular contact and communication with the doctor, allowing
monitoring of symptoms, disease activities, and treatment of side effects.

How can systemic lupus erythematosus affect pregnancy or the newborn?

Women with SLE who become pregnant are considered "high risk." Women with SLE who are pregnant
require close observation during pregnancy, delivery, and the postpartum period. This includes fetal
monitoring by the obstetrician during later pregnancy. These women can have an increased risk
of miscarriages (spontaneous abortions) and can have flares of SLE during pregnancy. The presence of
phospholipid antibodies, such as cardiolipin antibodies or lupus anticoagulant, in the blood can identify
people at risk for miscarriages. Cardiolipin antibodies are associated with a tendency toward blood
clotting. People with SLE who have cardiolipin antibodies or lupus anticoagulant may need blood-thinning
medications (aspirin with or without heparin) during pregnancy to prevent miscarriages. Other reported
treatments include the use of intravenous gamma globulin for selected people with histories of premature
miscarriage and those with low blood-clotting elements (platelets) during pregnancy. Pregnant women
who have had a previous blood-clotting event may benefit by continuation of blood-thinning medications
throughout and after pregnancy for up to six to 12 weeks, at which time the risk of clotting associated with
pregnancy seems to diminish. Plaquenil has now been found to be safe for use to treat SLE during
pregnancy.

Lupus antibodies can be transferred from the mother to the fetus and result in lupus illness in the newborn
("neonatal lupus"). This includes the development of low red cell (anemia) and/or white blood cell and
platelet counts and skin rash. Problems can also develop in the electrical system of the baby's heart
(congenital heart block). Occasionally, a pacemaker for the baby's heart is needed in this setting.
Neonatal lupus and congenital heart block are more common in newborns of mothers with SLE who carry
antibodies referred to as anti-Ro (or SS-A) and anti-La (or SS-B). (It is wise for the newborn baby's doctor
to be made aware if the mother is known to carry these antibodies, even prior to delivery. The risk of heart
block is 2%; the risk of neonatal lupus is 5%.) Neonatal lupus usually clears after 6 months of age, as the
mother's antibodies are slowly metabolized by the baby.

What does the future hold for people with lupus?

Overall, the outlook for people with systemic lupus is improving each decade with the development of
more accurate monitoring tests and treatments.

The role of the immune system in causing diseases is becoming better understood through research. This
knowledge will be applied to design safer and more effective treatment methods. For example, completely
revising the immune system of people with extremely aggressive treatments that virtually temporarily wipe
out the immune system is being evaluated. Current studies involve immune eradication with or without
replacement of cells that can re-establish the immune system (stem cell transplantation).
It should be noted that people with SLE are at a somewhat increased risk for developing cancer. The
cancer risk is most dramatic for blood cancers, such asleukemia and lymphoma, but is also increased
for breast cancer. This risk probably relates, in part, to the altered immune system that is characteristic of
SLE.

Women with SLE appear to be at increased risk for heart disease (coronary artery disease) according to
recent reports. Women with SLE should be evaluated and counseled to minimize risk factors for heart
disease, such as elevated bloodcholesterol, quitting smoking, high blood pressure, and obesity.

DHEA (dehydroepiandrosterone) has been helpful in reducing fatigue, improving thinking difficulties, and
improving quality of life in people with SLE. Recent research indicates that DHEA has been shown to
improve or stabilize signs and symptoms of SLE. DHEA is commonly available in health-food stores,
pharmacies, and many groceries.

Landmark research has shown clearly that oral contraceptives do not increase the rate of flares of
systemic lupus erythematosus. This important finding is opposite to what has been thought for years. Now
we can reassure women with lupus that if they take birth-control pills, they are not increasing their risk for
lupus flares. NOTE: Birth-control pills or any estrogen medications should still be avoided by women who
are at increased risk of blood clotting, such as women with lupus who have phospholipid antibodies
(including cardiolipin antibody and lupus anticoagulant).

Individuals with SLE can improve their prognosis by learning about the many aspects of the illness as well
as closely monitoring their own health with their doctors.

Where can one get more information about lupus?

For more information about systemic lupus erythematosus, see the following sites:

The Arthritis Foundation (http://www.arthritis.org)

PO Box 19000
Atlanta, GA 30326

Lupus Foundation of Minnesota (http://www.lupusmn.org)

Systemic Lupus Erythematosus At A Glance

• Systemic lupus erythematosus (SLE) is an autoimmune disease.

• SLE is characterized by the production of unusual antibodies in the blood.

• SLE is eight times more common in women than men.

• The cause(s) of SLE is (are) unknown, however, heredity, viruses, ultraviolet light, and drugs all
may play some role.

• Up to 10% of people with lupus isolated to the skin will develop the systemic form of lupus (SLE).

• Eleven criteria help doctors to diagnose SLE.

• Treatment of SLE is directed toward decreasing inflammation and/or the level of autoimmune
activity.
• People with SLE can prevent "flares" of disease by avoiding sun exposure and not abruptly
discontinuing medications and monitoring their condition with their doctor.