The Lupus Book: A Guide for Patients and Their Families, Third Edition (44 page)

were born with limbs missing in whole or in part. Patients who might become

pregnant must not even consider trying this agent. However, the drug has re-

mained available for leprosy patients who had no other alternatives. And in the mid-1970s, dermatologists in Mexico and Germany documented its benefits for

antimalarial-resistant cutaneous lupus. Thalidomide has sedating effects and

should be taken at night. Up to 10 percent of patients develop a peripheral neuropathy, which can be rather annoying, as it produces continuous numbness and tin-

gling. Abnormal blood clotting can occur in higher doses. Further, even though

thalidomide clears most lupus lesions, its benefits usually wear off as soon as the drug is stopped. Most rheumatologists use antileprosy drugs along with antimalarials and stop the former as soon as the patient improves to the point that antimalarials alone can control the problem.

SPECIALIZED TREATMENTS FOR KIDNEY DISEASE

Dialysis
involves using a machine to remove wastes from the blood—wastes that are normally cleared by the kidney. Patients with lupus and kidney failure make up about 5 percent of the SLE population and need dialysis in order to

stay alive. This can be performed with
hemodialysis
, by which the patient’s blood is cleansed three times a week for several hours, or
peritoneal dialysis
, which is often performed continuously at home, with a catheter connected in

the abdominal area. Although moderately unpleasant and time-consuming, both

procedures are usually well tolerated, but hemodialysis may be better at helping
Other Options: Treatments Occasionally Used to Manage Lupus

[233]

decrease lupus disease activity and allowing patients to discontinue steroids. The ideal management for end-stage renal disease is a
kidney transplant
. One-third of lupus patients on dialysis are able to undergo a transplant successfully. The best results are seen when the kidney donor is a sibling under the age of 60

who has normal blood pressure and matches the patient’s blood type. Cadaver

transplants are a second choice. Lupus only rarely returns to the transplanted

kidney, and more than 85 percent of all transplants prove to be successful after 5 years of follow up.

Several preparations help kidney disease by decreasing urine protein leakage,

improving blood flow to the kidney, and lowering blood pressure. These agents

include
angiotensin converting enzyme (‘‘ACE’’) inhibitors
and angiotensin receptor blockers (“ARBs”) such as captopril, lisinopril or losartan.

GAMMA GLOBULIN

Gamma globulin is a protein that circulates in the blood, boosts immunity, and

helps fight and prevent infection. It has been used for years as an intramuscular injection with modest results. Once the technical problems were overcome in

the late 1970s, much larger amounts of the immune globulin could be admin-

istered intravenously (IV). Intravenous gamma globulin has several mechanisms

of action, among the most important of which is its ability to prevent the spleen from destroying platelets. It is very expensive (up to $5000 per treatment course) compared to gamma globulin shots ($50 per injection), but the former can be

lifesaving.

However, IV gamma globulin in lupus is helpful only for short-term use in

autoimmune thrombocytopenia (low platelets) until other agents can become

effective and inflammatory nerve conditions. It may be used monthly for the

occasional lupus patient who has recurrent infections and low gamma globulin

levels (most lupus patients have elevated gamma globulin levels). The majority

of published studies to date suggest that IV gamma globulin has no place in the management of fibromyalgia or chronic fatigue.

THERAPEUTIC BLOOD OR LYMPH GLAND FILTERING

As you recall, lymphocytes are white blood cells that help control the immune

response. Since steroids and chemotherapy work partly by destroying lympho-

cytes, it seemed logical that removing lymphocytes from the body with a filter-

ing machine might be effective and reduce inflammation with fewer side effects.

In the late 1960s, investigators found that draining lymphocytes from the tho-

racic duct (a lymph gland collection site near the left collarbone) was feasible.

At the modest cost of $250,000 per patient,
thoracic duct drainage
, as it was called, drained billions of lymphocytes from patients and decreased disease activity for about 4 months. This led researchers to attempt the removal of lym-

[234]

The Management of Lupus Erythematosus

phocytes directly from the blood, a process called
lymphapheresis
. Performed on a blood filtering device,
apheresis
(meaning ‘‘to remove by force’’ in Greek) was difficult to perform in SLE patients. This is because they had antilymphocyte antibodies which, along with steroids and chemotherapy, decreased lym-

phocyte counts to such a low level that the machine could not remove enough

cells to make a difference. Investigators at Harvard University and Stanford

University then attempted to irradiate lymphocytes in the lymph glands. Known

as
total lymphoid irradiation (TLI)
, it resulted in improvements that lasted for several years. However, 80 percent of the patients developed shingles; they also lost an average of 20 pounds and 10 teeth. Furthermore, the use of TLI prevented further useful chemotherapy from being employed when the disease ultimately

flared. (Prior radiation mixed with alkylating agents such as cyclophosphamide

or chlorambucil greatly increases a patient’s risk for developing cancer.)

Attention was then shifted to depleting plasma on a cell separator device that

resembles a dairy creamer. Removing plasma from whole blood and returning

red blood cells, white blood cells, and platelets to the patient is called
plasmapheresis
. Since many proteins and antibodies promote inflammation, plasmapheresis was tried in a variety of critical lupus complications. This expensive procedure ($50,000 to $100,000 for a several-weeks therapeutic course) is beneficial and lifesaving for some lupus patients with thrombotic thrombocytopenic purpura (TTP), hyperviscosity syndrome, alveolar hemorrhage and cryoglobulinemia. However, attempts to use plasmapheresis for serious organ-threatening

complications of lupus such as nephritis or central nervous system disease have generally been disappointing, although occasional results have been dramatically successful. Researchers are currently manipulating concurrent medications, replacement products, and plasmapheresis schedules in order to improve its effi-

cacy.

In spite of all the scary sounding procedures mentioned in this section, the

technical aspects of plasma or lymphocyte removal are generally well tolerated, with only a 3 percent rate of serious complications, which is very good considering that doctors are dealing with seriously ill patients. Apheresis produces

some temporary light-headedness, dizziness, and cramping; moreover, vascular

access—the ability to find a vein for intravenous infusions—can be a problem.

Apheresis is indicated for TTP, hyperviscosity syndrome, and cryoglobulinemia

and may be helpful in patients with life- or organ-threatening complications that do not respond to steroids or chemotherapy.

MISCELLANY

An old rheumatoid arthritis drug,
gold
, is occasionally effective for lupus arthritis and rashes.
Lasers
have been used to remove discoid lupus lesions and telangiectasias.
Growth factors
such as erythropoietin (e.g., Epogen) or G-CSF

Other Options: Treatments Occasionally Used to Manage Lupus

[235]

(e.g., Neupogen) can improve anemia and decrease infection risks from low

white blood counts. Immune stimulants such as
thymus gland
extracts or
levamisole
have not been shown to be useful for lupus.

Summing Up

Even though NSAIDs, antimalarials, corticosteroids, and chemotherapy account

for the overwhelming majority of all lupus therapies, other treatments are oc-

casionally useful. Antileprosy drugs help resistant skin lesions and joint inflammation; retinoids are also useful for refractory skin rashes. These preparations are only helpful temporarily and act as a bridge to antimalarials. The only hormones that have a role in SLE are danazol for low platelet counts and certain

anemias and postmenopausal estrogen replacement therapy. Immune stimulants

are disappointing. Gamma globulin helps fight immune deficiencies, which pro-

mote infection, and can raise low platelet counts. Machines can act as artificial kidneys or be used to remove antibodies, cells, or proteins from the body. The

role of maintenance dialysis is firmly established, but many uses of apheresis

are still controversial.

29

Fighting Infections, Allergies,

and Osteoporosis

In most recent surveys, infection has now taken second place as one of the most common causes of death among lupus patients, after cardiovascular complications. Why are lupus patients so susceptible to infection and what can be done

about it? Should at-risk patients receive vaccinations, or would that make the

disease worse? And what about allergies and allergy shots? Moreover, one of

the major problems facing women after they go through the change of life is

osteoporosis, and women with lupus are especially vulnerable to this disease.

This chapter outlines a practical approach for dealing with infections and vac-

cines while promoting awareness of the issues involved in infection, allergy,

and lupus. Finally, the management of osteoporosis is reviewed as it applies to lupus.

WHAT IS AN INFECTION?

Patients with systemic lupus have altered abilities to fight common infections

and are susceptible to attack by uncommon organisms that rarely affect healthy

people. Infections of this kind are called
opportunistic
. Opportunistic infections are usually seen only in cancer patients receiving chemotherapy, individuals

suffering from AIDS, and those who have altered immune systems. Autoimmune

diseases fall into the last category, particularly when immunosuppressives or

steroids are being used.

Microbes can attack cells and, in turn, kill cells and damage tissue. The body

produces antibodies to these microbial antigens, killing foreign organisms as

part of an anti-inflammatory and occasionally an allergic response. Many dif-

ferent kinds of organisms can infect the body. Depending on size, structure, life-cycle, and ability to produce certain chemicals, they are called bacteria, viruses, parasites, fungi, or protozoans. Common infections, from streptococcal or staph-ylococcal bacteria, affect healthy people all the time.

Fighting Infections, Allergies, and Osteoporosis

[237]

ARE LUPUS PATIENTS MORE VULNERABLE

TO INFECTION?

Since 80 percent of patients with SLE take corticosteroids during the course of their disease and 10 to 30 percent undergo chemotherapy, it stands to reason

that lupus patients are vulnerable to infectious processes. The NSAIDs and an-

timalarials do not increase susceptibility to infection. Even if you are not receiving steroids or chemotherapy, you are still susceptible to unusual infections.

Lupus patients attacked by common microbes frequently require treatment for

longer periods of time and often project a more severe clinical picture. Their

susceptibility is changed in several ways. First, the microbial killing function of neutrophils, a type of white blood cell, is altered, and, second, certain complement components critical in the killing process are inhibited. Third, there is

evidence to indicate that many lupus patients have circulating blood factors

which inhibit a component of complement (C5) from being attracted to an in-

flamed cell. Finally, cytokine dysfunction in SLE (Chapter 5) decreases the

body’s ability to kill foreign organisms.

Additionally, corticosteroids block cells from destroying other cells and thus

from diminishing inflammation. Chemotherapies prevent the reproduction of

cells with immunologic memories, which can signal the body to kill microbes

and decrease the numbers of cells themselves.

WHAT KIND OF INFECTIONS MIGHT

A LUPUS PATIENT GET?

The principal bacterial infections seen in lupus affect the respiratory tract (
Streptococcus, Staphlococcus
) and urinary tract (
Escherichia coli
). As a lupus patient, you could also be at special risk for developing infections in your joints (septic arthritis), tuberculosis, or salmonellosis. In addition to cold viruses, you might be especially susceptible to herpes zoster, or shingles. Epstein-Barr virus, hepatitis viruses, and cytomegalovirus may be slightly more prevalent in SLE. The

most common fungal process in lupus patients is
Candida
, or yeast. This cheesy-white infiltrate is seen in the throat and esophagus (causing sore throat and

difficulty swallowing) and in the vagina. Rarely, unusual fungal infections such as those caused by
Cryptococcus, Coccidioides immitis
, and
Nocardia
are observed. In the United States, the principal parasitic pathogen seen in lupus patients is called
Strongyloides
, and the protozoan to be aware of is
Pneumocystis
carinii
, which is frequently found in AIDS patients.

HOW ARE INFECTIONS DIAGNOSED?

Active lupus mimics infection, and infectious processes not only mimic lupus