The Lupus Book: A Guide for Patients and Their Families, Third Edition (29 page)

Immunologic Anemias

Mary was a healthy college student until she suddenly became profoundly

fatigued and started noticing a yellowish cast to her skin. At a victory

celebration, after her team had won its Saturday football game, she passed

out. Paramedics were called and took her to a hospital, where her hemo-

globin was found to be 6. An internist then undertook an anemia workup.

It turned out that she had SLE with autoimmune hemolytic anemia. Even

though her bone marrow was churning out red blood cells, they were being

destroyed within days upon release into the circulation. A hematologist was

consulted and started her on 60 milligrams of prednisone daily. Twelve

weeks later, she had a hemoglobin of only 9 and azathioprine was added

to the regimen.

Up to 10 percent of patients with lupus develop
autoimmune hemolytic ane-

mia
(AIHA); most of these patients complain of weakness, dizziness, and fevers.

They may appear jaundiced (have a yellowish complexion) as a result of the

rapid destruction of red blood cells. Antibodies to the surface of red blood cells are responsible for AIHA. A red blood cell normally lives for 120 days, but in

AIHA it is destroyed by antibodies much earlier. The bone marrow is then

stimulated to make more red blood cells, which can sometimes compensate for

this early destruction, as evidenced by an elevation in the reticulocyte count

(which measures rate of formation of red blood cells), but most of the time it

is not enough.

Specialized blood testing can help to diagnose AIHA, and the deformed cells

can be seen by looking at a blood smear under the microscope. Suspicions that

AIHA is present can be confirmed by blood tests (such as an elevated reticu-

locyte count, serum LDH, decreased serum haptoglobin, or the presence of an

antibody to red blood cells which is measured using the Coombs’ antibody test).

This potentially serious complication of SLE responds only temporarily to

transfusions and often calls for a prolonged course of high-dose corticosteroids.

Poorly responsive AIHA patients have their steroids supplemented with cyclo-

phosphamide, azathioprine, rituximab or danazol. Occasionally, a splenectomy

or removal of the spleen is necessary, since this organ removes partially dam-

aged red cells, thus contributing to anemia.

In rare cases, circulating plasma factors tell the bone marrow to turn off the

production of red blood cells. The end result of this is a slow-down or shut-

down of the bone marrow, termed
hypoplasia or aplasia
. This usually reflects active disease, and corticosteroids or cytotoxic drugs (especially cyclosporin) may be necessary (see Chapter 27). A careful drug history should be taken,

since many prescription drugs (e.g., sulfa antibiotics) can occasionally cause

aplasia.

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Can the Patient Have a Blood Transfusion?

Several studies have shown that lupus patients have the same blood types and

distribution of blood types as the general population. However, patients with

immune-mediated anemias break down transfused cells more rapidly than oth-

erwise healthy individuals. One study suggested that up to 16 percent of lupus

patients with immune anemias experience a mild allergic-type reaction when

their blood is transfused. This reaction results from red cell antibodies. There is usually no problem transfusing lupus patients without immune anemias. An extra

dose of corticosteriods or an antihistamine such as Benadryl can be ordered

immediately prior to the transfusion to minimize any reactions. With current

screening methods in the United States, the risk of HIV or other transmissible

viruses is on the order of one in tens of thousands, and the use of directed

donors (e.g., having friends or relatives donate blood for you) further decreases this risk. On the other hand, it is not a good idea for lupus patients to donate their blood, since it contains too many antibodies.

HOW IMPORTANT ARE WHITE BLOOD CELLS?

Half of all lupus patients develop low white blood cell counts during the course of their disease. White blood cells, or leukocytes, constitute the body’s defense mechanism. They are responsible for immunologic memory (lymphocytes), bacterial killing (neutrophils), and allergic reactions (eosinophils). Chapter 5 reviews the functions of the five types of white blood cells. White blood cell

counts are elevated by active infections, corticosteroid therapy, and sometimes by active SLE. Low white blood cell counts derive from viral infections or active lupus or are the consequence of chemotherapy for lupus.

The usual reason for low
lymphocyte
levels is the presence of antilymphocyte antibodies, which destroy lymphocytes.
Neutrophil
counts are usually normal in SLE unless suppressed by chemotherapy. Yet though their levels are normal,

there are apparently qualitative defects in neutrophil function which are manifest by a decreased ability to kill bacteria. This helps explain why lupus patients are more susceptible to infection.
Eosinophils
are elevated in 3 to 10 percent of lupus patients, and lupus patients have an increased incidence of allergies compared with the general population (Chapter 29).

CLOTTING AND BLEEDING PROBLEMS

Platelets are the blood components responsible for clotting blood. Increased

numbers of platelets reflect acute inflammation and are observed in a minority

of patients with active lupus. Low platelet counts are associated with bleeding

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Where and How Can the Body Be Affected by Lupus?

disorders. The lupus anticoagulant usually promotes clotting and can damage

the body due to functional abnormalities of the platelets (see Chapter 21).

When Celeste was in the sixth grade, she noticed red spots on her legs.

She told her mother, who took her to see their pediatrician. Dr. Hawkins

obtained a blood count which indicated that Celeste had 30,000 platelets

per cubic milliliter. Celeste was started on prednisone, after which her

platelet count became normal. She was off all medication within a year.

Six years later, after a bad flu, the spots reappeared and her platelet count

dropped to 20,000 cubic milliliters. Her internist also gave her an ANA

test that proved to be positive. Even though she denied any of the signs or

symptoms of lupus and enjoyed being out in the sun, Celeste was told she

had lupus with idiopathic thrombocytopenic purpura. She was started on

prednisone and her platelet counts normalized within a few weeks. Celeste

now feels fine and is off all medication.

Decreased platelet counts along with the presence of platelet antibodies is

called
idiopathic thrombocytopenic purpura (ITP
). It is usually seen in children and young women, most of whom have no symptoms other than that they bruise

easily. Approximately 20 percent of patients with ITP also have a positive an-

tinuclear antibody test, and 20 percent of these patients ultimately develop lupus.

A normal platelet count is between 150,000 and 400,000 per cubic millimeter.

One-sixth of all lupus patients run platelet counts below 100,000 during the

course of their disease. Easy bruising is noted when the counts drop below

50,000, and counts less than 20,000 can be life-threatening in the sense that

these individuals can suffer spontaneous internal bleeding. Anyone who notices

numerous black-and-blue marks, excessive bleeding from the gums, very heavy

periods, or little red spots (petechiae) on the skin should obtain a platelet count.

Many ITP patients lack other signs and symptoms of SLE, and many are not

even sun-sensitive.

I often use a drug called danazol in low doses (Chapter 28) to treat platelet

counts that fall between 60,000 and 100,000 per cubic milliliter and I add steroids only if lupus is active outside the platelet system or the counts drop further.

This condition is usually fairly responsive to steroids, but occasionally I add azathioprine, vincristine, or cyclophosphamide (Chapter 27). Intravenous gamma

globulin and platelet transfusions temporarily raise platelet counts, as does plasmapheresis. Removal of the spleen, the organ that traps platelets coated with

antibodies, is usually curative. Most patients with ITP and lupus also have an-

tiphospholipid antibodies (Chapter 21), some also have AIHA (Evans’ Syn-

drome).

A rare and frightening complication of SLE is
thrombotic thrombocytopenic

purpura (TTP
). Called a ‘‘pentad’’ because of its five signal markers of fever,
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[157]

hemolytic anemia, neurologic impairment, kidney failure, and low platelet

counts, TTP can lead to multiple organ failure when disseminated clots form

throughout the body. It can be brought on by a viral infection or other forms

of sepsis and was fatal until recently. The critical lifesaving element is the

treating doctor’s awareness of this rare disorder as a possibility and the ability to diagnose it promptly. Plasmapheresis can cure the condition, which rarely

comes back once it has been successfully treated.

Lupus patients also have
qualitative platelet defects
. Aspirin, platelet antibodies, and chronic renal failure can all alter functional blood clotting even when platelet counts are in the normal range. Steroids and NSAIDs disrupt platelets

and induce
purpura
, those black-and-blue marks on the skin that result partially from damage to fragile capillaries. This benign but annoying condition causes

no symptoms and need not cause alarm if platelet counts are in the normal

range. No treatment is necessary.

DOES LUPUS CAUSE SWOLLEN GLANDS?

When the disease is active, the increased numbers of inflammatory cells and

immune complexes can cause lymph glands (or nodes) to enlarge. Lymph

glands, loosely arrayed in chains throughout the body, drain and filter particulate materials. Whereas arteries supply blood and nutrients to the body, veins return blood and nutrients to the heart and are helped along by lymph glands. Half of

all lupus patients have enlarged lymph nodes that can be felt on a physical

examination at some point during the course of the disease. On occasion, the

nodes can be up to 1.5 inches in diameter. This prominence has been called

Kikuchi’s syndrome
. Infections also enlarge lymph glands, as can malignancies; before active lupus is treated, these possibilities must be ruled out.
Lymphadenopathy
(another name for swollen lymph glands) from SLE is treated with anti-inflammatory medication.

HOW IS THE SPLEEN INVOLVED IN LUPUS?

In the left upper part of the abdomen lies a large, vascular lymphatic organ

called the
spleen
. The spleen filters the blood and destroys and removes damaged red blood cells, white blood cells, and platelets. It can become larger when a

greater number of cells than usual require removal. This process is part of what rheumatologists and immunologists call the
reticuloendothelial system
(RES).

Circulating immune complexes are also cleared by the spleen, and in SLE

their clearance can be impaired. Impaired RES clearance increases the deposition of immune complexes in tissue, which, in turn, causes damage or inflammation.

About 10 percent of lupus patients have enlarged spleens on physical exami-

nation. Abdominal computed tomography or ultrasound easily shows an en-

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Where and How Can the Body Be Affected by Lupus?

larged spleen. The spleen rarely produces pain unless it is very large and the

capsule is stretched.
The most common cause of left upper abdominal pain in
SLE is pleurisy, since the lung and ribs overlie the spleen
.

On occasion, the spleen is removed to treat AIHA or ITP. Even though we

can live a normal life expectancy without a spleen, some individuals become

vulnerable to numerous infectious agents, especially a form of bacterium that

leads to pneumococcal pneunomia. Every patient who has had the spleen re-

moved (splenectomy) should be vaccinated against this bacterium and watched

closely for infection.

WHAT DOES THE THYMUS DO?

As discussed earlier, the thymus is a lymph organ at the base of the neck; it is responsible for establishing a system of immune surveillance. In adult life, the gland atrophies and is barely recognizable. The thymus in lupus patients does

not look any different than it does in a healthy person. Removing the gland,

with a
thymectomy
, usually has no effect upon the disease.

Summing Up

Anemia, the most common blood abnormality in lupus patients, can cause fa-

tigue and pallor. The anemia can result from a nonimmunological cause—iron

deficiency or chronic disease—or it can result directly from immunological con-

ditions caused by lupus. Immune-mediated anemias are serious and potentially

life-threatening. They often mandate high doses of steroids and other immuno-

suppressive therapies.

Low white blood cell counts are also commonly observed and result from

antilymphocyte antibodies. White blood cells (called neutrophils) do not kill

bacteria as well as they should in SLE, and this increases the risk of infection.

Antibodies to platelets lower platelet counts, especially in patients with the