U.S. Department of Health and

Human Services

Public Health Service

National Institutes of Health

National Institute of Arthritis and 

Musculoskeletal and Skin Diseases

NIH Publication No. 04-4179

Revised May 2004
This booklet is not copyrighted. Readers are 

encouraged to duplicate and distribute as many 

copies as needed.

Additional copies of this booklet are available from

the National Institute of Arthritis and Musculoskeletal

and Skin Diseases Information Clearinghouse,

NIAMS/National Institutes of Health, 1 AMS Circle,

Bethesda, MD 20892–3675, and on the NIAMS Web

site at http://www.niams.nih.gov/hi/topics/arthritis/

rahandout.htm.
Features of Rheumatoid Arthritis . . . . . . . . . . . . . . . 

How Rheumatoid Arthritis Develops and Progresses 

Occurrence and Impact of Rheumatoid Arthritis . . . 

Searching for the Causes of Rheumatoid Arthritis . . 

Diagnosing and Treating Rheumatoid Arthritis . . . . 

Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 

Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 

Current Research . . . . . . . . . . . . . . . . . . . . . . . . . . . . 

Hope for the Future . . . . . . . . . . . . . . . . . . . . . . . . . . 

For More Information . . . . . . . . . . . . . . . . . . . . . . . . 

Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . 

Illustration

Normal Joint and Joint Affected by 

Rheumatoid Arthritis . . . . . . . . . . . . . . . . . . . . . 

Information Boxes

Features of Rheumatoid Arthritis . . . . . . . . . . . . . . . 

Goals of Treatment and Current Treatment 

Approaches . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 

Medications Commonly Used To Treat 

Rheumatoid Arthritis . . . . . . . . . . . . . . . . . . . . . . 

This booklet is for people who have rheumatoid arth

as well as for their family members, friends, and oth

who want to find out more about this disease. The bo

describes how rheumatoid arthritis develops, how it 

diagnosed, and how it is treated, including what peo

can do to help manage their disease. It also highligh

current research efforts supported by the National

Institute of Arthritis and Musculoskeletal and Skin

Diseases (NIAMS) and other components of the

Department of Health and Human Services’ Nationa

Institutes of Health (NIH). If you have further questi

after reading this booklet, you may wish to discuss th

with your doctor.

Features of Rheumatoid Arthritis

R heumatoid arthritis is an inflammatory disease th

causes pain, swelling, stiffness, and loss of funct

in the joints. It has several special features that make 

different from other kinds of arthritis. (See “Features 

Rheumatoid Arthritis,” page 4.) For example, rheum

arthritis generally occurs in a symmetrical pattern,

meaning that if one knee or hand is involved, the oth

one also is. The disease often affects the wrist joints 

the finger joints closest to the hand. It can also affec

other parts of the body besides the joints. (See “Othe

Parts of the Body,” page 7.) In addition, people with

rheumatoid arthritis may have fatigue, occasional fev

and a general sense of not feeling well. 
4

people, it lasts only a few months or a year 

goes away without causing any noticeable 

people have mild or moderate forms of the 

periods of worsening symptoms, called flar

Features of Rheumatoid Arth

■ Tender, warm, swollen joints

■ Symmetrical pattern of affected joint

■ Joint inflammation often affecting th

finger joints closest to the hand

■ Joint inflammation sometimes affecti

joints, including the neck, shoulders, 

hips, knees, ankles, and feet

■ Fatigue, occasional fevers, a general 

feeling well

■ Pain and stiffness lasting for more th

minutes in the morning or after a lon

■ Symptoms that last for many years

■ Variability of symptoms among peop

disease

periods in which they feel better, called rem

others have a severe form of the disease tha

most of the time, lasts for many years or a 

leads to serious joint damage and disability
on a person’s life and well-being, current treatment

strategies—including pain-relieving drugs and medi

that slow joint damage, a balance between rest and

exercise, and patient education and

support programs—allow most people

with the disease to lead active and

productive lives. In recent years,

research has led to a new

understanding of rheumatoid arthritis

and has increased the likelihood that,

in time, researchers will find even

better ways to treat the disease. 

How Rheumatoid Arthritis

Develops and Progresses

The Joints

Ajoint is a place where two bones

meet. The ends of the bones are

covered by cartilage, which allows 

for easy movement of the two bones.

The joint is surrounded by a capsule

that protects and supports it. (See

illustration, page 6.) The joint capsule is lined with a 

of tissue called synovium, which produces synovial 

clear substance that lubricates and nourishes the carti

and bones inside the joint capsule. 

Like many other rheumatic diseases, rheumatoid arth

an autoimmune disease (auto means self), so-called 

a person’s immune system, which normally helps pr

the body from infection and disease, attacks joint tis

for unknown reasons. White blood cells, the agents 

immune system, travel to the synovium and cause

inflammation (synovitis), characterized by warmth, 

Curr

treat

strategi

most peo

the dise

lead act

producti
6

Synovial Fluid

Joint Capsule

Synovium

Bone 

Bone Loss/Erosion

Cartilage Loss

Swollen Joint Capsule

Bone Loss Inflamed Syn

(Generalized)

A joint (the place where two bones meet) is surrou

that protects and supports it. The joint capsule is lin

of tissue called synovium, which produces synovia

lubricates and nourishes joint tissues. In rheumatoi

synovium becomes inflamed, causing warmth, redn

and pain. As the disease progresses, the inflamed s

and damages the cartilage and bone of the joint. Su

muscles, ligaments, and tendons become weakened

arthritis also can cause more generalized bone loss 

osteoporosis (fragile bones that are prone to fractur
arthritis. During the inflammation process, the norm

thin synovium becomes thick and makes the joint

swollen and puffy to the touch. (See illustration, pag

As rheumatoid arthritis progresses, the inflamed

synovium invades and destroys the cartilage and bon

within the joint. The surrounding muscles, ligaments

and tendons that support and stabilize the joint becom

weak and unable to work normally. These effects lea

the pain and joint damage often seen in rheumatoid

arthritis. Researchers studying rheumatoid arthritis n

believe that it begins to damage bones during the fir

year or two that a person has the disease, one reason 

early diagnosis and treatment are so important.

Other Parts of the Body

Some people with rheumatoid arthritis also have

symptoms in places other than their joints. Many peo

with rheumatoid arthritis develop anemia, or a decre

in the production of red blood cells. Other effects th

occur less often include neck pain and dry eyes and

mouth. Very rarely, people may have inflammation o

blood vessels, the lining of the lungs, or the sac

enclosing the heart.

Occurrence and Impact of 

Rheumatoid Arthritis

S cientists estimate that about 2.1 million people, 

between 0.5 and 1 percent of the U.S. adult

population, have rheumatoid arthritis. Interestingly, s

recent studies have suggested that the overall numbe

new cases of rheumatoid arthritis actually may be go

down. Scientists are investigating why this may be

happening. 
8

groups. Although the disease often begins i

and occurs with increased frequency in old

children and young adu

develop it. Like some o

arthritis, rheumatoid art

much more frequently i

in men. About two to th

many women as men ha

disease. 

By all measures, the fin

social impact of all type

including rheumatoid ar

substantial, both for the 

for individuals. From an 

standpoint, the medical 

treatment for rheumatoi

the wages lost because 

caused by the disease ad

billions of dollars annua

joint pain is an inevitab

consequence of the dise

patients also experience 

of depression, anxiety, a

helplessness. For some 

rheumatoid arthritis can 

normal daily activities, limit job opportunit

the joys and responsibilities of family life. 

there are arthritis self-management program

people cope with the pain and other effects 

and help them lead independent and produc

(See “Diagnosing and Treating Rheumatoid 

page 11.)

The financial and

social impact of all

types of arthritis,

including

rheumatoid

arthritis, is

substantial, both

for the Nation and

for individuals.
Rheumatoid Arthritis

Scientists still do not know exactly what causes th

immune system to turn against itself in rheumato

arthritis, but research over the last few

years has begun to piece together the

factors involved.

Genetic (inherited) factors: Scientists

have discovered that certain genes

known to play a role in the immune

system are associated with a tendency

to develop rheumatoid arthritis. Some

people with rheumatoid arthritis do

not have these particular genes; still

others have these genes but never

develop the disease. These somewhat

contradictory data suggest that a

person’s genetic makeup plays an

important role in determining if he or

she will develop rheumatoid arthritis,

but it is not the only factor. What is

clear, however, is that more than one

gene is involved in determining whether a person

develops rheumatoid arthritis and how severe the dis

will become.

Environmental factors: Many scientists think that

something must occur to trigger the disease process 

people whose genetic makeup makes them susceptib

rheumatoid arthritis. A viral or bacterial infection ap

likely, but the exact agent is not yet known. This doe

not mean that rheumatoid arthritis is contagious: a p

cannot catch it from someone else. 

Resear

begun t

togeth

factors in

caus

rheum

arthr
10

of hormonal factors may be involved. Wom

likely to develop rheumatoid arthritis than 

pregnancy may improve the disease, and th

flare after a pregnancy. 

may also aggravate the 

Contraceptive use may 

likelihood of developing 

arthritis. Scientists think 

the immune system mol

interleukin 12 (IL-12) a

necrosis factor-alpha (T

change along with the c

hormone levels seen in 

women. This change m

to the swelling and tissu

seen in rheumatoid arth

hormones, or possibly d

changes in certain horm

promote the developme

rheumatoid arthritis in a genetically suscep

who has been exposed to a triggering agent 

environment.

Even though all the answers are not known

certain: rheumatoid arthritis develops as a r

interaction of many factors. Researchers ar

understand these factors and how they wor

(See “Current Research,” page 21.)

Rheumatoid

arthritis develops

as a result of an

interaction of

many factors.
Rheumatoid Arthritis

Diagnosing and treating rheumatoid

arthritis requires a team effort

involving the patient and several

types of health care professionals. 

A person can go to his or her family

doctor or internist or to a

rheumatologist. A rheumatologist is a

doctor who specializes in arthritis 

and other diseases of the joints,

bones, and muscles. As treatment

progresses, other professionals often

help. These may include nurses,

physical or occupational therapists,

orthopaedic surgeons, psychologists,

and social workers.

Studies have shown that patients who

are well informed and participate

actively in their own care have less

pain and make fewer visits to the

doctor than do other patients with

rheumatoid arthritis.

Patient education and arthritis selfmanagement programs, as well as

support groups, help people to become better inform

and to participate in their own care. An example of a 

management program is the Arthritis Self-Help Cour

offered by the Arthritis Foundation and developed at 

NIAMS-supported Multipurpose Arthritis and

Musculoskeletal Diseases Center. (See the Arthritis

Foundation listing in “For More Information,” page 

Self-management programs teach about rheumatoid

People w

well inf

and par

actively 

own 

experien

pain an

fewer v

the do
12

approaches, communication between patien

care providers, and problem solving. Resea

programs has shown that they help people:

■ understand the disease

■ reduce their pain while remaining a

■ cope physically, emotionally, and m

■ feel greater control over the disease 

sense of confidence in the ability to 

lead full, active, and independent liv

Diagnosis

Rheumatoid arthritis can be difficult to diag

early stages for several reasons. First, there 

test for the disease. In addition, symptoms 

person to person and can be more severe in 

people than in others. Also, symptoms can 

those of other types of arthritis and joint co

it may take some time for other conditions 

out. Finally, the full range of symptoms dev

time, and only a few symptoms may be pre

early stages. As a result, doctors use a varie

following tools to diagnose the disease and 

other conditions:

Medical history: This is the patient’s descr

symptoms and when and how they began. G

communication between patient and doctor 

important here. For example, the patient’s d

pain, stiffness, and joint function and how t

over time is critical to the doctor’s initial a

the disease and how it changes over time.
examination of the joints, skin, reflexes, and muscle

strength.

Laboratory tests: One common test is for rheumatoi

factor, an antibody that is present eventually in the b

of most people with rheumatoid arthritis. (An antibo

a special protein made by the immune system that

normally helps fight foreign substances in the body.) 

all people with rheumatoid arthritis test positive for

rheumatoid factor, however, especially early in the

disease. Also, some people test positive for rheumato

factor, yet never develop the disease. Other common

laboratory tests include a white blood cell count, a b

test for anemia, and a test of the erythrocyte

sedimentation rate (often called the sed rate), which

measures inflammation in the body. C-reactive prote

another common test that measures disease activity.

X rays: X rays are used to determine the degree of jo

destruction. They are not useful in the early stages o

rheumatoid arthritis before bone damage is evident, 

they can be used later to monitor the progression of 

disease.

Treatment

Doctors use a variety of approaches to treat rheumat

arthritis. These are used in different combinations an

different times during the course of the disease and a

chosen according to the patient’s individual situation

matter what treatment the doctor and patient choose,

however, the goals are the same: to relieve pain, redu

inflammation, slow down or stop joint damage, and

improve the person’s sense of well-being and ability 

function.
necessary for effective treatment. Talking t

can help ensure that exercise and pain man

programs are provided as needed, and that 

prescribed appropriately. Talking to the doc

help people who are making decisions abou

Health behavior changes: Certain activitie

improve a person’s ability to function indep

maintain a positive outlook.

Rest and exercise: People with rheuma

need a good balance between rest and e

more rest when the disease is active an

14

Goals of Treatment

■ Relieve pain

■ Reduce inflammation

■ Slow down or stop joint damage

■ Improve a sense of well-being and ab

to function

Current Treatment Approac

■ Health behavior changes

■ Medications

■ Surgery

■ Routine monitoring and ongoing care
joint inflammation and pain and to fight fatigue. 

length of time for rest will vary from person to

person, but in general, shorter rest

breaks every now and then are

more helpful than long times

spent in bed. 

Exercise is important for

maintaining healthy and strong

muscles, preserving joint

mobility, and maintaining

flexibility. Exercise can also help

people sleep well, reduce pain,

maintain a positive attitude, and

lose weight. Exercise programs

should take into account the

person’s physical abilities,

limitations, and changing needs.

Joint care: Some people find using a splint for a

short time around a painful joint reduces pain an

swelling by supporting the joint and letting it res

Splints are used mostly on wrists and hands, but 

on ankles and feet. A doctor or a physical or

occupational therapist can help a person choose 

splint and make sure it fits properly. Other ways 

reduce stress on joints include self-help devices 

example, zipper pullers, long-handled shoe horn

devices to help with getting on and off chairs, to

seats, and beds; and changes in the ways that a

person carries out daily activities.

People 

rheum

arthritis 

good b

betwee

and exe
face emotional challenges as well as ph

The emotions they feel because of the d

anger, and frustration—combined with 

physical limitations can 

stress level. Although th

evidence that stress play

causing rheumatoid arth

make living with the dis

at times. Stress also ma

amount of pain a person 

are a number of success

for coping with stress. R

periods can help, as can 

distraction, or visualizat

Exercise programs, part

support groups, and goo

communication with the 

team are other ways to r

Healthful diet: With th

several specific types of 

“Current Research,” page 37), there is n

evidence that any specific food or nutri

harms people with rheumatoid arthritis. 

overall nutritious diet with enough—bu

excess of—calories, protein, and calciu

important. Some people may need to be 

drinking alcoholic beverages because o

medications they take for rheumatoid a

taking methotrexate may need to avoid 

altogether because one of the most serio

side effects of methotrexate is liver dam

16

An overall 

nutritious diet

with enough 

calories, protein,

and calcium is

important.
worse when there is a sudden change in the weat

However, there is no evidence that a specific clim

can prevent or reduce the effects of rheumatoid

arthritis. Moving to a new place with a different

climate usually does not make a long-term differ

in a person’s rheumatoid arthritis.

Medications: Most people who have rheumatoid arth

take medications. Some medications are used only fo

pain relief; others are used to reduce inflammation. S

others, often called disease-modifying antirheumatic

drugs (DMARDs), are used to try to slow the course 

the disease. The person’s general condition, the curre

and predicted severity of the illness, the length of tim

or she will take the drug, and the drug’s effectivenes

and potential side effects are important consideration

prescribing drugs for rheumatoid arthritis. The table

starting on page 22 shows currently used rheumatoid

arthritis medications, along with their uses and effec

side effects, and monitoring requirements.

Biologic response modifiers are new drugs used for 

treatment of rheumatoid arthritis. They can help redu

inflammation and structural damage to the joints by

blocking the action of cytokines, proteins of the bod

immune system that trigger inflammation during nor

immune responses. Three of these drugs, etanercept

(Enbrel*), infliximab (Remicade), and adalimumab

(Humira), reduce inflammation by blocking the reac

* Brand names included in this booklet are provided as examp

and their inclusion does not mean that these products are endo

the National Institutes of Health or any other Government age

Also, if a particular brand name is not mentioned, this does no

or imply that the product is unsatisfactory.
18

(Kineret), works by blocking a protein call

interleukin 1 (IL-1) that is seen in excess i

with rheumatoid arthritis. 

For many years, doctors initially prescribe

other pain-relieving drugs for rheumatoid a

well as rest and physical therapy. They usu

prescribed more powerful drugs later only 

disease worsened. 

Today, however, many doctors have chang

approach, especially for patients with seve

progressing rheumatoid arthritis. Studies sh

early treatment with more powerful drugs, 

of drug combinations instead of one medic

may be more effective in reducing or preve

damage. Once the disease improves or is in 

the doctor may gradually reduce the dosag

prescribe a milder medication. 

Surgery: Several types of surgery are avai

patients with severe joint damage. The prim

purpose of these procedures is to reduce pa

the affected joint’s function, and improve t

ability to perform daily activities. Surgery 

everyone, however, and the decision shoul

only after careful consideration by patient 

Together they should discuss the patient’s 

health, the condition of the joint or tendon 

operated on, and the reason for, as well as 

benefits of, the surgical procedure. Cost m

another factor. Commonly performed surgi

procedures include joint replacement, tend

reconstruction, and synovectomy.
performed surgery for rheumatoid arthritis, and i

done primarily to relieve pain and improve or

preserve joint function. Artificial joints are not

always permanent and may eventually have to b

replaced. This may be an important consideratio

young people.

Tendon reconstruction: Rheumatoid arthritis ca

damage and even rupture tendons, the tissues tha

attach muscle to bone. This surgery, which is use

most frequently on the hands, reconstructs the

damaged tendon by attaching an intact tendon to 

This procedure can help to restore hand function

especially if the tendon is completely ruptured.

Synovectomy: In this surgery, the doctor actuall

removes the inflamed synovial tissue. Synovecto

by itself is seldom performed now because not a

the tissue can be removed, and it eventually grow

back. Synovectomy is done as part of reconstruc

surgery, especially tendon reconstruction.

Routine monitoring and ongoing care: Regular me

care is important to monitor the course of the diseas

determine the effectiveness and any negative effects 

medications, and change therapies as needed.

Monitoring typically includes regular visits to the do

It also may include blood, urine, and other laborator

tests and x rays.

People with rheumatoid arthritis may want to discus

preventing osteoporosis with their doctors as part of 

long-term, ongoing care. Osteoporosis is a condition 

which bones become weakened and fragile. Having
20

osteoporosis for both men and women, part

person takes corticosteroids. Such patients 

discuss with their doctors the potential bene

and vitamin D suppleme

therapy, or other treatme

osteoporosis.

Alternative and comple

therapies: Special diets

supplements, and other 

approaches have been su

treating rheumatoid arth

many of these approach

harmful in and of thems

controlled scientific stud

not been conducted on t

found no definite benefi

therapies. Some alternat

complementary approac

the patient cope or redu

stress associated with li

chronic illness. As with 

patients should discuss 

and drawbacks with the

before beginning an alte

type of therapy. If the d

approach has value and 

harmful, it can be incorporated into a patien

plan. However, it is important not to neglec

health care. The Arthritis Foundation publis

on alternative therapies as well as establish

and patients may want to contact this organ

information. (See the “For More Informatio

this booklet, page 41.)

Patients may

want to discuss

preventing

osteoporosis 

with their

doctors as part

of their 

long-term, 

ongoing care.
O ver the last several decades, research has greatly

increased our understanding of the immune syste

genetics, and biology. This research

is now showing results in several

areas important to rheumatoid

arthritis. Scientists are thinking about

rheumatoid arthritis in exciting ways

that were not possible even 10 

years ago. 

The National Institutes of Health

(NIH) funds a wide variety of

medical research at its headquarters

in Bethesda, Maryland, and at

universities and medical centers

across the United States. One of the

NIH institutes, the National Institute

of Arthritis and Musculoskeletal and

Skin Diseases (NIAMS), is a major

supporter of research and research

training in rheumatoid arthritis

through grants to individual

scientists, Specialized Centers of

Research, Multidisciplinary Clinical

Research Centers, and Multipurpose Arthritis and

Musculoskeletal Diseases Centers.

Following are examples of current research direction

rheumatoid arthritis supported by the Federal Gover

through the NIAMS and other parts of the NIH.

Scientists are looking at the immune systems of peo

with rheumatoid arthritis and in some animal model

the disease to understand why and how the disease

Scientis

thinking 

rheum

arthr

exciting 

that we

possibl

10 year
22

Medications Commonly Used To Treat Rheumatoid Arthriti

* NOTE: Brand names included in this bookle

only, and their inclusion does not mean that th

by the National Institutes of Health or any oth

Also, if a particular brand name is not mention

imply that the product is unsatisfactory.

g

Nonsteroidal Antiinflammatory Drugs

(NSAIDs)

g

NSAID

reduce 

Acetaminophen Nonpr

medica

relieve 

aspirin

Excedr

Tyleno

Arthrit

Aspirin

Buffered

Plain

Aspirin 

pain, s

inflam

patient

easily 

norma

genera

ongoin
s

(con

p, pp

ulcer, bleeding, renal

failure. Use of NSAIDs

may increase rate of

miscarriage for pregnant

women.

Before taking these drugs, le

your doctor know if you dri

alcohol or use blood thinner

if you have any of the

following: sensitivity or alle

to aspirin or similar drugs,

kidney or liver disease, hear

disease, high blood pressure

asthma, or peptic ulcers.

Usually no side effects

when taken as directed.

Not to be taken with alcoho

or with other products

containing acetaminophen.

Not to be used for more tha

10 days unless directed by 

physician.

Upset stomach;

tendency to bruise

easily; ulcers, pain, or

discomfort; diarrhea;

headache; heartburn or

indigestion; nausea or

vomiting.

Doctor monitoring is

needed.
24

Medications (continued)

COX-2 inhibitors, like

traditional NSAIDs, block

COX-2, an enzyme in the

body that stimulates an

inflammatory response.

Unlike traditional

NSAIDs, however, they do

not block the action of

COX-1, an enzyme that

protects the stomach

lining. This results in

reduced risk of gastrointestinal ulceration and

bleeding. Reduces joint

pain and inflammation. 

COX-2 Inhibitor

NSAIDs

Celecoxib Valdecoxib

Corticosteroids These are steroids given

by mouth or injection.

They are used to relieve

inflammation and reduce

swelling, redness, itching,

and allergic reactions.

Medications

Traditional NSAIDs

Ibuprofen

Ketoprofen

Naproxen

Uses/Effects

NSAIDs help relieve pain

within hours of administration in dosages

available over-the-counter

(available for all three

medications). They relieve

pain and inflammation in

dosages available in

prescription form (ibuprofen and ketoprofen). It

may take several days to

reduce inflammation.
(co

o

Stomach irritation,

ulceration, and bleeding

may occur. Caution is

advisable for patients

with a history of

bleeding or ulcers, decreased renal function,

hepatic disease, hypertension, or asthma. 

Use of COX-2s with lowdose aspirin is permitted bu

may slightly increase ulcer

risk. Doctor monitoring is

recommended before taking

a COX-2 inhibitor, especial

if you have had a heart

attack, stroke, angina, blood

clot, hypertension, or

sensitivity to aspirin or othe

NSAIDs. Doctor monitorin

for possible allergic

responses to valdecoxib and

celecoxib is important. 

Increased appetite,

indigestion, nervousness, or restlessness.

For all corticosteroids, let y

doctor know if you have on

of the following: fungal inf

tion, history of tuberculosis

underactive thyroid, herpes

simplex of the eye, high blo

pressure, osteoporosis, or

stomach ulcer.

For all traditional

NSAIDs: Abdominal or

stomach cramps, pain, or

discomfort; diarrhea;

dizziness; drowsiness or

light-headedness; headache; heartburn or indigestion; peptic ulcers;

nausea or vomiting;

possible kidney and liver

damage (rare).

For all traditional NSAIDs:

Before taking these drugs, l

your doctor know if you

drink alcohol or use blood

thinners or if you have or

have had any of the

following: sensitivity or

allergy to aspirin or similar

drugs, kidney or liver

disease, heart disease, high

blood pressure, asthma, or

peptic ulcers.
26

Medications (continued)

Methylprednisolone

Prednisone

These 

availab

as an i

joint. I

seen in 

to 24 h

admini

potenti

effects

doses. 

severe 

the dis

respon

DMAR

Disease-modifying

antirheumatic drugs

(DMARDs)

These 

arthrit

relieve 

joints 

damag

DMAR

over th

They t

month

and m

cant im

many 

how th

unkno
Osteoporosis, mood

changes, fragile skin,

easy bruising, fluid

retention, weight gain,

muscle weakness, onset

or worsening of diabetes,

cataracts, increased risk

of infection, hypertension (high blood

pressure).

Doctor monitoring for

continued effectiveness of

medication and for side

effects is needed.

y

Side effects vary with

each medicine. DMARDs

may increase risk of

infection, hair loss, and

kidney or liver damage.

Doctor monitoring allows t

risk of toxicities to be weig

against the potential benefit

individual medications.

(co
28

Medications (continued)

AzathioprineThis d

higher 

chemo

transpl

in pati

respon

and in 

therap

Hydroxychloroquine

Cyclosporine This m

used in 

ation t

It is us

have n

other d

It may 

to noti

this dru

reducin

sympto

arthriti

Gold sodium thiomalate This w

DMAR

rheuma
n

Cough or hoarseness,

fever or chills, loss of

appetite, lower back or

side pain, nausea or

vomiting, painful or

difficult urination,

unusual tiredness or

weakness.

Before taking this drug, tel

your doctor if you use

allopurinol or have kidney 

liver disease. This drug can

reduce your ability to fight

infection, so call your docto

immediately if you develop

chills, fever, or a cough.

Regular blood and liver

function tests are needed.

Bleeding, tender, or

enlarged gums; high

blood pressure; increase

in hair growth; kidney

problems; trembling and

shaking of hands.

Before taking this drug, tell

your doctor if you have one 

the following: sensitivity to

castor oil (if receiving the d

by injection), liver or kidney

disease, active infection, or 

blood pressure. Using this d

may make you more suscep

to infection and certain canc

Do not take live vaccines w

on this drug.

Diarrhea, eye problems

(rare), headache, loss of

appetite, nausea or

vomiting, stomach

cramps or pain.

Doctor monitoring is

important, particularly if yo

have an allergy to any

antimalarial drug or a retina

abnormality.

Redness or soreness of

tongue; swelling or bleeding gums; skin rash or

itching; ulcers or sores on

lips, mouth, or throat;

irritation on tongue. Joint

pain may occur for one or

two days after injection.

Before taking this drug, tel

your doctor if you have any 

the following: lupus, skin r

kidney disease, or colitis.

Periodic urine and blood te

are needed to check for sid

effects.

(co
30

Medications (continued)

Leflunomide

This d

and sy

structu

joints 

Methotrexate This d

by mo

and re

improv

takes 3

workin

be very 

especia

with in

etanerc

produc

long-te

compa

DMAR

sulfasa

sodium 

hydrox

Sulfasalazine This d

the sig

rheum

suppre

system
Bloody or cloudy urine;

congestion in chest;

cough; diarrhea; difficult,

burning, or painful

urination or breathing;

fever; hair loss;

headache; heartburn; loss

of appetite; nausea and/or

vomiting; skin rash;

stomach pain; sneezing;

and sore throat.

Before taking this medicati

let your doctor know if you

have one of the following:

active infection, liver disea

known immune deficiency,

renal insufficiency, or

underlying malignancy. You

will need regular blood test

including liver function tes

Leflunomide must not be

taken during pregnancy

because it may cause birth

defects in humans.

Abdominal discomfort,

chest pain, chills,

nausea, mouth sores,

painful urination, sore

throat, unusual tiredness

or weakness.

Doctor monitoring is

important, particularly if yo

have an abnormal blood co

liver or lung disease,

alcoholism, immune-system

deficiency, or active infecti

Methotrexate must not be

taken during pregnancy

because it may cause birth

defects in humans.

f

Abdominal pain, aching

joints, diarrhea, headache,

sensitivity to sunlight,

loss of appetite, nausea or

vomiting, skin rash.

Doctor monitoring is impor

particularly if you are allerg

sulfa drugs or aspirin, or if 

have a kidney, liver, or bloo

disease. 

(co
32

Medications (continued)

Biologic Response

Modifiers

These 

block 

immun

cytoki

a role 

Long-

safety 

Tumor Necrosis Factor

Inhibitors 

Etanercept

Infliximab

Adalimumab

These 

highly 

treatin

inadeq

DMAR

prescri

with so

particu

Etaner

subcut

skin) i

per we

taken i

during 

It is ad

metho

Adalim

injecti

Long-t

safety 

Interleukin1 Inhibitor

Anakinra

This m

daily i

term e

are un
Increased risk of

infection, especially

tuberculosis. Increased

risk of pneumonia, and

listeriosis (a foodborne

illness caused by the

bacterium Listeria

monocytogenes).

It is important to avoid eati

undercooked foods (includi

unpasteurized cheeses, cold

cuts, and hot dogs) because

undercooked food can caus

listeriosis for patients taking

biologic response modifiers

Etanercept: Pain or

burning in throat;

redness, itching, pain,

and/or swelling at

injection site; runny or

stuffy nose.

Infliximab: Abdominal

pain, cough, dizziness,

fainting, headache,

muscle pain, runny

nose, shortness of

breath, sore throat,

vomiting, wheezing.

Adalimumab: Redness,

rash, swelling, itching,

bruising, sinus infection,

headache, nausea.

Long-term efficacy and safe

are uncertain. Doctor

monitoring is important,

particularly if you have an

active infection, exposure to

tuberculosis, or a central

nervous system disorder.

Evaluation for tuberculosis 

necessary before treatment

begins.

Redness, swelling,

bruising, or pain at the

site of injection; headache; upset stomach;

diarrhea; runny nose;

and stomach pain.

Doctor monitoring is

required.
34

role of T cells, which play an important rol

and in the progression of rheumatoid arthri

from these studies may lead to precise, targ

that could stop the inflammatory process in 

stages. They may even lead to a vaccine th

prevent rheumatoid arthritis. 

Researchers are studying genetic factors th

some people to developing rheumatoid arth

as factors connected with disease severity. 

by studying genetically engineered mice, s

supported by the NIH discovered that imm

called mast cells play a key role in the dev

rheumatoid arthritis. Findings from these s

increase our understanding of the disease a

develop new therapies, as well as guide tre

decisions.

In a major effort aimed at identifying gene

rheumatoid arthritis, the NIH and the Arthr

Foundation have joined together to support 

American Rheumatoid Arthritis Consortium

of 10 research centers around the United S

collecting medical information and genetic 

1,000 families in which two or more siblin

rheumatoid arthritis. It serves as a national 

genetic studies of this disease.

To help identify the multiple factors that pr

course and outcomes in rheumatoid arthriti

Americans, the NIH is supporting the Cons

Longitudinal Evaluations of African Ameri

Early Rheumatoid Arthritis (CLEAR) Regi

University of Alabama at Birmingham. Thi
scientists analyze genetic and nongenetic factors tha

predict disease course and outcomes of rheumatoid

arthritis. 

Scientists are also unearthing the genetic basis of

rheumatoid arthritis by studying rats with a conditio

that resembles rheumatoid arthritis in humans. NIAM

researchers have identified several genetic regions th

affect arthritis susceptibility and severity in these an

models of the disease. These genetic regions are

important because they can assist scientists in predic

the symptoms and severity of rheumatoid arthritis.

Replacing malfunctioning genes with healthy genes

(gene transfer) is being tested in mice, and it may

eventually be used in humans to treat rheumatoid

arthritis.

Researchers are also uncovering the complex

relationships between the hormonal, nervous, and

immune systems in rheumatoid arthritis. For exampl

they are exploring whether and how the normal chan

in the levels of naturally produced steroid hormones

(such as estrogen and testosterone) during a person’

lifetime may be related to the development,

improvement, or flares of the disease. Scientists also 

researching how these systems interact with

environmental and genetic factors. The results of thi

research may suggest new treatment strategies.

Scientists are exploring why so many more women 

men develop rheumatoid arthritis. In hopes of findin

clues, they are studying female and male hormones 

other differences between women and men.
36

improves during pregnancy. Results of one 

that the explanation may be related to diffe

certain special proteins that pass between a 

her unborn child. These 

the immune system dist

between the body’s own 

foreign cells. Such diffe

scientists speculate, ma

activity of the mother’s 

system during pregnanc

A growing body of evid

that infectious agents, s

and bacteria, may trigge

arthritis in people who 

inherited predisposition 

disease. Scientists are tr

discover which infectio

be responsible and how 

arthritis.

Researchers are searchi

drugs or combinations o

can reduce inflammation and slow or stop t

progression of rheumatoid arthritis with few 

Already, the new biologic response modifie

and etanercept are proving to be extremely 

some people. Studies show that these treatm

effective at slowing joint damage than meth

alone. Combination treatment with etanerce

methotrexate or infliximab and methotrexa

found even more effective than either of th

treatments alone. (Methotrexate was used f

because it is a commonly prescribed “front

Scientists are

searching for 

new drugs that

can slow or stop

the progression

of rheumatoid

arthritis.
recently approved adalimumab (Humira) for slowing 

progression of structural damage in adults with mod

to severe rheumatoid arthritis who have not responde

well to one or more disease

modifying antirheumatic drugs.

Investigators have also shown that

treatment of rheumatoid arthritis with

minocycline, a drug in the

tetracycline family, has a modest

benefit. Other studies have shown

that the omega-3 fatty acids in

certain fish or plant seed oils also

may reduce rheumatoid arthritis

inflammation. However, many

people are not able to tolerate the

large amounts of oil necessary for

any benefit.

Scientists are examining many issues

related to quality of life for people

with rheumatoid arthritis and the

quality, cost, and effectiveness of the

health care services they receive.

Some new techniques for managing

symptoms under investigation include tai chi (a form 

movement-based meditation), and cognitive-behavio

therapy (a technique that teaches you to anticipate an

prepare yourself for the situations and bodily sensati

that may trigger painful symptoms). Scientists have

found that even a small improvement in a patient’s s

of physical and mental well-being can have an impa

his or her quality of life and use of health care servic

Even a 

improvem

patient’s 

physic

mental w

can ha

impact o

her qualit
38

Scientists are making rapid progress in u

the complexities of rheumatoid arthritis

why it develops, why some people get it an

not, why some people get it more severely 

Results from research are having an impact 

enabling people with rheumatoid arthritis to 

active in life, family, and work far longer th

possible 20 years ago. There is also hope fo

as researchers begin to apply new technolo

stem cell transplantation and novel imaging 

(Stem cells have the capacity to differentiat

cell types, which gives them the potential t

damaged tissue in which they are placed.) T

other advances will lead to an improved qu

for people with rheumatoid arthritis.
National Institute of Arthritis and 

Musculoskeletal and Skin Diseases

National Institutes of Health

1 AMS Circle

Bethesda, MD 20892–3675

(301) 495–4484 or 

(877) 22-NIAMS (226-4267) (free of charge)

Fax: (301) 718–6366

TTY: (301) 565–2966

E-mail: niamsinfo@mail.nih.gov

www.niams.nih.gov

The National Institute of Arthritis and Musculoskele

Skin Diseases provides information about various fo

arthritis and rheumatic diseases. It distributes patien

professional education materials and also refers peop

other sources of information.

The National Institute of Allergy and Infectious D

National Institutes of Health

Building 31, Room 7A50

31 Center Drive, MSC 2520

Bethesda, MD 20892-2520

(301) 496-5717

Fax: (301) 402-0120

www.niaid.nih.gov

The National Institute of Allergy and Infectious Dise

conducts and supports research that strives to unders

treat, and ultimately prevent the myriad infectious,

immunologic, and allergic diseases that threaten hun

millions of people worldwide. The Institute’s missio

driven by a strong commitment to basic research and 

understanding that the fields of immunology, microb

and infectious disease are related and complementar
and Alternative Medicine

NCCAM Clearinghouse

P.O. Box 7923

Gaithersburg, MD 20898-7923

(301) 519-3153 or

(888) 644-6226 (free of charge)

Fax: (866) 464-3616

TTY: (866) 464-3615

www.nccam.nih.gov

The National Center for Complementary an

Alternative Medicine is dedicated to explor

complementary and alternative healing prac

context of rigorous science, training compl

and alternative medicine researchers, and d

authoritative information to the public and

professionals. 

American Academy of Orthopaedic Surg

P.O. Box 2058

Des Plains, IL 60017

(800) 824–BONE (2263) (free of charge)

www.aaos.org

The Academy provides education and pract

management services for orthopaedic surge

allied health professionals. It also serves as 

for improved patient care and informs the p

the science of orthopaedics. The orthopaed

of practice includes disorders of the body’s 

joints, ligaments, muscles, and tendons. Fo

copy of an AAOS brochure, send a self-add

stamped envelope to the address above or v

AAOS Web site.

40
1800 Century Place, Suite 250

Atlanta, GA 30345

(404) 633–3777

Fax: (404) 633–1870

www.rheumatology.org

The College provides referrals to rheumatologists an

physical and occupational therapists who have exper

working with people who have rheumatoid arthritis. 

organization also provides educational materials and

guidelines.

Arthritis Foundation

1330 West Peachtree Street

Atlanta, GA 30309

(404) 872–7100 or

(800) 283–7800 (free of charge) or your local chapte

listed in the telephone directory 

www.arthritis.org

The Arthritis Foundation is the major voluntary

organization devoted to supporting arthritis research 

providing educational and other services to individu

with arthritis. The Foundation publishes a free pamp

on rheumatoid arthritis and a magazine for members 

all types of arthritis. It also provides up-to-date

information on research and treatment, nutrition,

alternative therapies, and self-management strategies

Chapters nationwide offer exercise programs, classe

support groups, physician referral services, and free

literature.
The NIAMS gratefully acknowledges the a

the following people in the preparation and 

and earlier versions of this publication: Joh

M.D., Arthritis Foundation, Washington, D

Leong, Paris, France; Michael D. Lockshin

Barbara Volcker Center for Women and Rh

Disease, Hospital for Special Surgery, New 

York; Kate Lorig, R.N., Dr.P.H., Stanford U

Stanford, California; J. Lee Nelson, M.D., 

Hutchinson Cancer Research Center, Seattl

Washington; Paul G. Rochmis, M.D., Fairf

Ronald L. Wilder, M.D., Ph.D., MedImmun

Gaithersburg, Maryland; Stanley R. Pillem

and Reva Lawrence, M.P.H., Paul H. Plotz

Susana Serrate-Sztein, M.D., NIAMS, NIH

thanks also go to Cheryl Yarboro, R.N., B.S

NIAMS, NIH, and to the patients who revi

publication and provided valuable input.

42


This booklet is not copyrighted. Readers are 

encouraged to duplicate and distribute as many 

copies as needed.

Additional copies of this booklet are available from

the National Institute of Arthritis and Musculoskeletal

and Skin Diseases Information Clearinghouse,

NIAMS/National Institutes of Health, 1 AMS Circle,

Bethesda, MD 20892–3675, and on the NIAMS Web

site at http://www.niams.nih.gov/hi/topics/arthritis/

rahandout.htm.
U.S. Department of Health and

Human Services

Public Health Service

National Institutes of Health

National Institute of Arthritis and 

Musculoskeletal and Skin Diseases

NIH Publication No. 04-4179

Revised May 2004