FW: [JRAnewsandviews] SEA Syndrome (Seronegativity, Enthesopathy, Arthropathy)

[Guest guest]

From: Georgina

[mailto:gmckin@...]

Sent: Thursday, November 14, 2002

9:39 PM

* JRA News & Views

Subject: [JRAnewsandviews] SEA

Syndrome (Seronegativity, Enthesopathy, Arthropathy)

Juvenile Spondyloarthopathy

http://www.arthritis.org/conditions/DiseaseCenter/juvenilespondyloarthopathy.asp

What

is It?

Some

types of arthritis involve the spine as well as tendons, especially at the

spots where the tendons attach to the bone (enthesis or enthesopathy). This

family of disorders is called seronegative spondyloarthropathies. When seen in

children, they are referred to a Juvenile Spondyloarthropathies (JSp).

Terminology

of Juvenile Spondyloarthropathy

It

is important to determine if your child has arthritis or one of the

arthritis-related conditions that affect children because treatments vary for

each type. Early diagnosis and treatment are keys to slowing or preventing

joint and tissue damage.

There

are several kinds of JSp. They include: Juvenile Ankylosing Spondylitis,

Juvenile Psoriatic arthritis, the arthritis associated with Inflammatory Bowel

Disease (Enteropathogenic arthritis), reactive arthritis, (Reiter's syndrome is

one type of reactive arthritis), and the SEA syndrome (seronegativity, enthesopathy,

arthropathy).

There

are similar features that are often found in people with these diseases that

make them a " family " of conditions. The JSp tend to: 1). involve the

spine and especially the sacroiliac joints; 2). affect a particular joint on

one side of the body rather than both sides at the same time (both sides

involved is called " symmetrical arthritis " ); 3) affect mostly large

joints; 4). cause eye inflammation; 5). involve the entheses; 6). be found in

people with a certain genetic tissue type, HLA-B27.

There

is no single test to diagnose JSp. The diagnosis is made when there have been

persistent symptoms for at least 6 weeks after other possible illnesses have

been ruled out. Sometimes, a variety of tests may be necessary to come to a

firm diagnosis. Once your child's physician suspects or makes this diagnosis,

your child may be referred to a pediatric rheumatologist. This is a physician

who specializes in the diagnosis and treatment of children with arthritis and

arthritis-related conditions.

SEA Syndrome

(Seronegativity, Enthesopathy, Arthropathy)

Children

who appear to have one of the juvenile

spondyloarthropathies, but whose illness cannot be classified specifically

into one of the more clear-cut categories, can be diagnosed with SEA syndrome.

Signs and Symptoms

Negative rheumatoid factor (seronegativity)

Affects large joints, such as the hips, knees

and ankles

Joints are affected on one side of the body only

(arthropathy)

Inflammation and tenderness where the tendons

meet the bones (enthesopathy)

Long-Term Effects

Some children's condition will never progress from the SEA syndrome stage.

Others, however, will go on to develop juvenile

psoriatic arthritis, juvenile

enteropathic arthritis or juvenile

ankylosing spondylitis. Your doctor will review any new symptoms or

problems at each visit to determine if your child has any of these diseases.

*************************************************************************

http://www.arthritis.org/conditions/DiseaseCenter/Spondyloarthropathy/treatment_meds.asp

The

following medications may be used to treat children with arthritis and related

conditions.

NSAIDs

Nonsteroidal

anti-inflammatory drugs (NSAIDs) are the first line of medication used in

juvenile arthritis and are the mainstay of the initial therapy. NSAIDs must be

taken for at least three to four weeks to tell whether they are helping control

pain and inflammation. Laboratory tests may be done a few times a year to

monitor medication side effects. These medications come in liquid or pill form

and are taken from one to four times per day, depending on the drug prescribed.

Some common NSAIDs on the market approved for children include: ibuprofen,

naproxen, tolmentin, aspirin, choline magnesium trisalicylate and indomethacin.

Indomethacin is often one of the first NSAIDs tried for children with JSp since

it seems to work very well for these types of arthritis. Children with JEA may

be harder to treat with these drugs due to the problems with colitis that the

child already has.

Possible side effects of NSAIDs include: occasional

stomach pain, nausea and vomiting; anemia; headache; and uncommonly, blood in

the urine; fluid retention; thinning and scarring of the skin (especially with

naproxen); difficulty concentrating; and rarely, stomach ulcer.

Slow-Acting Anti-Inflammatory Drugs

These

drugs do not relieve pain or inflammation right away; instead, they are given

to change the progress of joint disease (such as joint erosions or cartilage

and bone destruction) weeks to months after therapy is begun. Therefore, they

are referred to as slow-acting anti-rheumatic drugs (SAARDs) or disease

modifying anti-rheumatic drugs (DMARDs). These drugs are often used in

combination with NSAIDs. Because they are more powerful medications, children

will need to have more frequent laboratory tests for monitoring of possible

side effects. Some of these medications are described below

Sulfasalazine

Sulfasalazine (Azulfadine) is one

of the most commonly used SAARDs for the JSp. It is given in pill form. This medication

helps the joint pain, stiffness and swelling. In cases with JEA, it can also

help the symptoms of colitis. It has a sulfa antibiotic component in it, so

cannot be used by people with sulfa allergies. It takes 6-12 weeks to

work.

Side

effects may include stomach upset, achiness, diarrhea, dizziness, headache,

light sensitivity, itching, appetite loss, liver abnormalities, lowered blood

count, nausea, vomiting or rash. Blood work is checked within a few weeks of

starting this medication then every few months to check for these changes.

Doxycyline and Antibiotic Therapy

With the strong association of the JSp and infections,

especially JReA, antibiotics play an important role in the treatment of some of

these children. Tetracycline antibiotics, most often doxycycline, have been

shown to help some of these children. These antibiotics must not be given to

children under 8 years old due to bone and teeth side effects. The medication

is taken twice a day and may cause nausea and sun sensitivity of the skin. It

may take 2-3 months for these medications to be effective. Doxycycline may be

taken as the sole SAARD or in conjunction with other agents.

Immune System Medications

Methotrexate

Methotrexate (Rbeumatrex) is

given weekly either orally as a liquid or in pill form, or by injection. It is

one of the most commonly prescribed SAARDs for children with the JSp. It works

best for JPsA, JEA and less so for JAS. It can help control eye inflammation

(uveitis, scleritis) in more severe cases. It takes 4-8 weeks to work.

Few

side effects are typically reported at the low doses at which methotrexate is

usually prescribed (typically 7.5 to 25 mg a week), but regular laboratory

monitoring is still important. Blood tests are usually checked every month at

first then every 6-8 weeks later on. This is also a cancer chemotherapy drug

but the dosages used in children with JRA are much lower. Therefore, the side

effects are less frequent.

Side

effects may include nausea, mouth sores, moodiness, diarrhea, low white blood

cell count, lung irritation, infections and liver irritation. Avoid all alcohol

intake and smoking while on this medication.

Etanercept and Other Biologic Agents

Biological agents are a new class of medications made of

synthetic proteins. These drugs may be made of antibodies that block high

levels of inflammatory proteins in patients with arthritis. The drugs available

include etanercept (Enbrel) which

blocks the protein TNF, and was approved in 1998 by the FDA for RA treatment in

adults, and in 1999 for the treatment of JRA. Infliximab (Remicade) is another anti-TNF medication

that is approved to treat RA and has begun testing in JRA. Both these agents

have been studied in Europe and the United States for the

spondyloarthropathies. They show great promise and will likely be approved to

treat JPsA in the near future.

Intravenous

immunoglobulin (IVIG) is used to treat several childhood rheumatic diseases. It

is usually given intravenously once a month. It is sometimes used as part of

the treatment of systemic JRA. Side effects include the risk of allergic

reactions, headaches, stomachache and flu-like symptoms.

Researchers

are developing other experimental biologic therapies that are aimed at specific

proteins to control a variety of different diseases.

*************************************************************************

http://www.emedicine.com/med/topic2700.htm

Medical Care: Treatment of AS is divided into

medical care, physical therapy, and surgical care. Patient education is

important in the management of any chronic disease so that the patient is

familiar with the symptoms, course, and treatment of the disease. No drugs

modify the course of the disease.

Nonsteroidal anti-inflammatory drugs

NSAIDs improve the symptoms of

the disease. Indomethacin may be more effective than other NSAIDs,

although this has not been proven.

Salicylates seldom give

adequate relief. Cyclooxygenase-2 (COX-2) inhibitors probably are as

effective as nonselective NSAIDs but have not been studied.

Give NSAIDs in full

anti-inflammatory doses. Common toxicities involve the gastrointestinal

(nausea, dyspepsia, ulceration, bleeding), renal, and central nervous

systems.

Sulfasalazine

Sulfasalazine is an effective

treatment in AS and other SpAs, especially for peripheral joint

involvement.

Toxicities include rash,

nausea, diarrhea, and agranulocytosis (rarely).

Other medications

Anecdotal reports suggest that

other medications are helpful in the treatment of AS, including

methotrexate, azathioprine, cyclophosphamide, and cyclosporine.

Methotrexate shows the most

promise, although reports regarding the efficacy of this agent in AS

conflict.

Because of the role of

TNF-alpha in the inflammatory process of AS, thalidomide, etanercept, and

infliximab may be useful therapeutic agents. Several case reports show

improvement with these agents, but no controlled trials have been

reported.

Corticosteroids

Oral corticosteroids

occasionally are helpful in controlling symptoms; however, use them only

for short-term management. No evidence exists that corticosteroids alter

the outcome of the disease, and they increase the tendency towards spinal

osteoporosis.

Local corticosteroid

injections are useful for symptomatic sacroiliitis, peripheral

enthesitis, and arthritis, although the response typically is not as

rapid as in patients with rheumatoid arthritis.

Treatment of extraarticular manifestations

Treat extraarticular

manifestations as dictated by the clinical setting.

Acute anterior uveitis

presents as a painful red eye that is associated with photophobia and

often recurs. Untreated uveitis may lead to vision loss.

Deliver evaluation and

treatment under the guidance of an ophthalmologist. Generally, patients

respond well to topical corticosteroids, mydriatics, and artificial

tears, with resolution of the attack over 2-3 months. Treatment

occasionally may require topical NSAIDs, retrobulbar corticosteroid

injections, or immunosuppressive drugs. TNF antagonists may be helpful in

selected cases.

Surgical Care:

Surgery occasionally is useful to correct spinal

deformities or repair damaged peripheral joints.

Vertebral osteotomy may be performed to correct

spinal deformities, but significant morbidity is related to neurologic

complications of this procedure. This procedure should be performed only

by surgeons specializing in spine surgery who have experience with this

procedure.

Patients may need total hip replacement and,

occasionally, total shoulder replacement. These procedures may be very

useful to reduce pain and improve function when the hip and shoulder

joints become severely damaged. Heterotopic bone formation may occur after

total joint replacement, especially around the hip. Heterotopic bone

formation can be reduced by using postoperative NSAIDs (eg, indomethacin).

In general, outcomes of total joint replacement in patients have been

satisfactory.

Activity:

Physical therapy

Physical therapy, including an

exercise program and postural training, is important to maintain

function.

Spinal extension and

deep-breathing exercises help maintain spinal mobility, encourage erect

posture, and promote chest expansion. Maintaining an erect posture during

daily activities and sleeping on a firm mattress with a thin pillow also

tend to reduce the tendency towards thoracic kyphosis.

Water therapy and swimming are

excellent activities to maintain mobility and fitness.

The goal of pharmacotherapy is to reduce morbidity

and prevent complications.

Drug

Name

Indomethacin (Indocin, Indochron) -- Thought to be

the most effective NSAID for the treatment of AS, although no scientific

evidence supports this claim. The most common toxicities include nausea,

dyspepsia, peptic ulcer disease, central nervous system toxicity, and renal

toxicity.

Adult

Dose

100-150 mg/d PO

divided in bid/tid

Pediatric

Dose

1.5-3 mg/kg/d PO

divided in bid/tid

Contraindications

Documented hypersensitivity; history of peptic ulcer

disease (unless prophylaxis is adequate); renal insufficiency,

anticoagulation, and coagulopathy

Interactions

Coadministration with ACE inhibitors, angiotensin-II

receptor blockers, and potassium-sparing diuretics may result in

hyperkalemia; coadministration with warfarin may increase PT due to

displacement of warfarin from plasma proteins and may aggravate bleeding

tendency due to antiplatelet effect of NSAIDs; may decrease effect of

diuretics

Pregnancy

C - Safety for use during pregnancy has not been

established.

Precautions

Most common toxicities include gastrointestinal

manifestations such as nausea, abdominal pain, peptic ulcer disease, and

renal insufficiency; may cause increased blood pressure in patients with

hypertension due to blunting of effects of antihypertensive medications;

patients with congestive heart failure may have exacerbations due to fluid

and sodium retention; patients with diabetes mellitus should have close

monitoring of renal function

Drug

Name

Ibuprofen (Ibuprin, Motrin) -- For relief of mild to

moderate pain; inhibits inflammatory reactions and pain by decreasing

activity of cyclooxygenase, which results in a decrease of prostaglandin

synthesis.

Adult

Dose

600-800 mg PO

tid/qid

Pediatric

Dose

30-40 mg/kg/d divided tid/qid

Contraindications

Documented hypersensitivity; history of peptic ulcer

disease (unless prophylaxis is adequate); renal insufficiency,

anticoagulation, and coagulopathy

Interactions

Coadministration with ACE inhibitors, angiotensin-II

receptor blockers, and potassium-sparing diuretics may result in

hyperkalemia; coadministration with warfarin may increase PT due to

displacement of warfarin from plasma proteins and may aggravate bleeding

tendency due to antiplatelet effect of NSAIDs; may decrease the effect of

diuretics

Pregnancy

C - Safety for use during pregnancy has not been

established.

Precautions

Most common toxicities include gastrointestinal

manifestations such as nausea, abdominal pain, peptic ulcer disease, and

renal insufficiency; may cause increased blood pressure in patients with

hypertension due to blunting of effects of antihypertensive medications;

patients with congestive heart failure may have exacerbations due to fluid

and sodium retention; patients with diabetes mellitus should have close

monitoring of renal function

Drug

Name

Naproxen (Naprosyn, Naprelan, Aleve, Anaprox) -- For

relief of mild to moderate pain; inhibits inflammatory reactions and pain by

decreasing activity of cyclooxygenase, which results in a decrease of

prostaglandin synthesis.

Adult

Dose

500 mg PO bid/tid

Pediatric

Dose

10-20 mg/kg/d divided bid/tid

Contraindications

Documented hypersensitivity; history of peptic ulcer

disease (unless prophylaxis is adequate); renal insufficiency,

anticoagulation, and coagulopathy

Interactions

Coadministration with ACE inhibitors, angiotensin-II

receptor blockers, and potassium-sparing diuretics may result in

hyperkalemia; coadministration with warfarin may increase PT due to

displacement of warfarin from plasma proteins and may aggravate bleeding

tendency due to antiplatelet effect of NSAIDs; may decrease the effect of

diuretics

Pregnancy

C - Safety for use during pregnancy has not been

established.

Precautions

Most common toxicities include gastrointestinal

manifestations such as nausea, abdominal pain, peptic ulcer disease, and

renal insufficiency; may cause increased blood pressure in patients with

hypertension due to blunting of effects of antihypertensive medications;

patients with congestive heart failure may have exacerbations due to fluid

and sodium retention; patients with diabetes mellitus should have close

monitoring of renal function

Drug

Name

Sulfasalazine (Azulfidine, EN-tabs) -- Shown to

reduce inflammatory symptoms of AS in controlled studies; most common

toxicities include nausea, diarrhea, and hypersensitivity reactions (rash).

Adult

Dose

2000-3000 mg/d PO

divided bid/tid

Pediatric

Dose

40-60 mg/kg/d PO

divided bid/tid

Contraindications

Documented hypersensitivity; porphyria (may

precipitate acute exacerbations)

Interactions

Absorption may be reduced by coadministration of

oral iron

Pregnancy

B - Usually safe but benefits must outweigh the

risks.

Precautions

Most common toxicities include nausea, diarrhea, and

hypersensitivity; caution in renal or hepatic impairment, blood dyscrasias,

or urinary obstruction; rarely, patients may develop blood dyscrasias,

especially leukopenia, which may progress to agranulocytosis or

hepatotoxicity

[Guest guest]

Thank you, Michele, for reposting these articles..these are "new" articles for us."Tepper, Michele" <MTepper@...> wrote: From: Georgina [mailto:gmckingte (DOT) net] Sent: Thursday, November 14, 2002 9:39 PM * JRA News & Views Subject: [JRAnewsandviews] SEA Syndrome (Seronegativity, Enthesopathy, Arthropathy) Juvenile Spondyloarthopathy http://www.arthritis.org/conditions/DiseaseCenter/juvenilespondyloarthopathy.asp What is It? Some types of arthritis involve the spine as well as tendons, especially at the spots where the tendons attach to the bone (enthesis or enthesopathy). This family of disorders is called seronegative spondyloarthropathies. When seen in children, they are referred to a Juvenile Spondyloarthropathies (JSp). Terminology of Juvenile Spondyloarthropathy It is important to determine if your child has arthritis or one of the arthritis-related conditions that affect children because treatments vary for each type. Early diagnosis and treatment are keys to slowing or preventing joint and tissue damage. There are several kinds of JSp. They include: Juvenile Ankylosing Spondylitis, Juvenile Psoriatic arthritis, the arthritis associated with Inflammatory Bowel Disease (Enteropathogenic arthritis), reactive arthritis, (Reiter's syndrome is one type of reactive arthritis), and the SEA syndrome (seronegativity, enthesopathy, arthropathy). There are similar features that are often found in people with these diseases that make them a "family" of conditions. The JSp tend to: 1). involve the spine and especially the sacroiliac joints; 2). affect a particular joint on one side of the body rather than both sides at the same time (both sides involved is called "symmetrical arthritis"); 3) affect mostly large joints; 4). cause eye

inflammation; 5). involve the entheses; 6). be found in people with a certain genetic tissue type, HLA-B27. There is no single test to diagnose JSp. The diagnosis is made when there have been persistent symptoms for at least 6 weeks after other possible illnesses have been ruled out. Sometimes, a variety of tests may be necessary to come to a firm diagnosis. Once your child's physician suspects or makes this diagnosis, your child may be referred to a pediatric rheumatologist. This is a physician who specializes in the diagnosis and treatment of children with arthritis and arthritis-related conditions. SEA Syndrome (Seronegativity, Enthesopathy, Arthropathy) Children who appear to have one of the juvenile spondyloarthropathies, but whose illness cannot be classified specifically into one of the more clear-cut categories, can be diagnosed with SEA syndrome. Signs and Symptoms Negative rheumatoid factor (seronegativity) Affects large joints, such as the hips, knees and ankles

Joints are affected on one side of the body only (arthropathy) Inflammation and tenderness where the tendons meet the bones (enthesopathy) Long-Term Effects Some children's condition will never progress from the SEA syndrome stage. Others, however, will go on to develop juvenile psoriatic arthritis, juvenile enteropathic arthritis or juvenile ankylosing spondylitis. Your doctor will review any new symptoms or problems at each visit to determine if your child has any of these diseases. ************************************************************************* http://www.arthritis.org/conditions/DiseaseCenter/Spondyloarthropathy/treatment_meds.asp The following medications may be used to treat children with arthritis and related conditions. NSAIDs Nonsteroidal anti-inflammatory drugs (NSAIDs) are the first line of medication used in juvenile arthritis and are the mainstay of the initial therapy. NSAIDs must be taken for at least three to four weeks to tell whether they are helping control pain and inflammation. Laboratory tests may be done a few times a year to monitor medication side effects. These medications come in liquid or pill form and are taken from one to four times per day, depending on the drug prescribed.

Some common NSAIDs on the market approved for children include: ibuprofen, naproxen, tolmentin, aspirin, choline magnesium trisalicylate and indomethacin. Indomethacin is often one of the first NSAIDs tried for children with JSp since it seems to work very well for these types of arthritis. Children with JEA may be harder to treat with these drugs due to the problems with colitis that the child already has. Possible side effects of NSAIDs include: occasional stomach pain, nausea and vomiting; anemia; headache; and uncommonly, blood in the urine; fluid retention; thinning and scarring of the skin (especially with naproxen); difficulty concentrating; and rarely, stomach ulcer. Slow-Acting Anti-Inflammatory

Drugs These drugs do not relieve pain or inflammation right away; instead, they are given to change the progress of joint disease (such as joint erosions or cartilage and bone destruction) weeks to months after therapy is begun. Therefore, they are referred to as slow-acting anti-rheumatic drugs (SAARDs) or disease modifying anti-rheumatic drugs (DMARDs). These drugs are often used in combination with NSAIDs. Because they are more powerful medications, children will need to have more frequent laboratory tests for monitoring of possible side effects. Some of these medications are described below Sulfasalazine Sulfasalazine (Azulfadine) is one of the most commonly used SAARDs for the JSp. It is given in pill form. This medication helps the joint pain, stiffness and swelling. In cases with JEA, it can also help the symptoms of colitis. It has a sulfa antibiotic component in it, so cannot be used by people with sulfa allergies. It takes 6-12 weeks to work. Side effects may include stomach upset, achiness, diarrhea, dizziness, headache, light sensitivity, itching, appetite loss, liver abnormalities, lowered blood count, nausea, vomiting or rash. Blood work is checked within a few weeks of starting this medication then every few months to check for these changes. Doxycyline and Antibiotic Therapy With the strong association of the JSp and infections, especially JReA, antibiotics play an important role in the treatment of some of these children. Tetracycline antibiotics, most often doxycycline, have been shown to help some of these children. These antibiotics must not be given to children under 8 years old due to bone and teeth side effects. The medication is taken twice a day and may cause nausea and sun sensitivity of the skin. It may take 2-3 months for these medications to be effective. Doxycycline may be taken as the sole SAARD or in conjunction with other agents. Immune System Medications Methotrexate Methotrexate (Rbeumatrex) is given weekly either orally as a liquid or in pill form, or by injection. It is one of the most commonly prescribed SAARDs for children with the JSp. It works best for JPsA, JEA and less so for JAS. It can help control eye inflammation (uveitis, scleritis) in more severe cases. It takes 4-8 weeks to work. Few side effects are typically reported at the low doses at which methotrexate is usually prescribed (typically 7.5 to 25 mg a week), but regular laboratory monitoring is still important. Blood tests are usually checked every month at first then every 6-8

weeks later on. This is also a cancer chemotherapy drug but the dosages used in children with JRA are much lower. Therefore, the side effects are less frequent. Side effects may include nausea, mouth sores, moodiness, diarrhea, low white blood cell count, lung irritation, infections and liver irritation. Avoid all alcohol intake and smoking while on this medication. Etanercept and Other Biologic Agents Biological agents are a new class of medications made of synthetic proteins. These drugs may be made of

antibodies that block high levels of inflammatory proteins in patients with arthritis. The drugs available include etanercept (Enbrel) which blocks the protein TNF, and was approved in 1998 by the FDA for RA treatment in adults, and in 1999 for the treatment of JRA. Infliximab (Remicade) is another anti-TNF medication that is approved to treat RA and has begun testing in JRA. Both these agents have been studied in Europe and the United States for the spondyloarthropathies. They show great promise and will likely be approved to treat JPsA in the near future. Intravenous immunoglobulin (IVIG) is used to treat several childhood rheumatic diseases. It is usually given intravenously once a month. It is sometimes used as part of the treatment of

systemic JRA. Side effects include the risk of allergic reactions, headaches, stomachache and flu-like symptoms. Researchers are developing other experimental biologic therapies that are aimed at specific proteins to control a variety of different diseases. ************************************************************************* http://www.emedicine.com/med/topic2700.htm Medical Care:

Treatment of AS is divided into medical care, physical therapy, and surgical care. Patient education is important in the management of any chronic disease so that the patient is familiar with the symptoms, course, and treatment of the disease. No drugs modify the course of the disease. Nonsteroidal anti-inflammatory drugs NSAIDs improve the symptoms of the disease. Indomethacin may be more effective than other NSAIDs, although this has not been proven. Salicylates seldom give adequate relief. Cyclooxygenase-2 (COX-2) inhibitors probably are as effective as nonselective NSAIDs but have not been studied. Give NSAIDs in full anti-inflammatory doses. Common toxicities involve the gastrointestinal (nausea, dyspepsia, ulceration, bleeding), renal, and central nervous systems. Sulfasalazine Sulfasalazine is an effective treatment in AS and other SpAs, especially for peripheral joint involvement. Toxicities include rash, nausea, diarrhea, and agranulocytosis (rarely). Other medications Anecdotal reports suggest that other medications are helpful in the treatment of AS, including methotrexate, azathioprine, cyclophosphamide, and cyclosporine. Methotrexate shows the most promise, although reports regarding the efficacy of this agent in AS conflict. Because of the role of TNF-alpha in the inflammatory process of AS, thalidomide, etanercept, and infliximab may be useful therapeutic agents. Several case reports show improvement with these agents, but no controlled trials have been reported. Corticosteroids Oral corticosteroids occasionally are helpful in controlling symptoms; however, use them only for short-term management. No evidence exists that corticosteroids alter the outcome of the disease, and they increase the tendency towards spinal osteoporosis. Local corticosteroid injections are useful for symptomatic sacroiliitis, peripheral enthesitis, and arthritis, although the response typically is not as rapid as in patients with rheumatoid arthritis. Treatment of extraarticular manifestations Treat extraarticular manifestations as dictated by the clinical setting. Acute anterior uveitis presents as a painful red eye that is associated with photophobia and often recurs. Untreated uveitis may lead to vision loss. Deliver evaluation and treatment under the guidance of an ophthalmologist. Generally, patients respond well to topical corticosteroids, mydriatics, and artificial tears, with resolution of the attack over 2-3 months. Treatment occasionally may require topical NSAIDs, retrobulbar corticosteroid injections, or immunosuppressive drugs. TNF antagonists may be helpful in selected cases. Surgical Care: Surgery occasionally is useful to correct spinal deformities or repair damaged peripheral joints. Vertebral osteotomy may be performed to correct spinal deformities, but significant morbidity is related to neurologic complications of this procedure. This procedure should be performed only by surgeons specializing in spine surgery who have experience with this procedure. Patients may need total hip replacement and, occasionally, total shoulder replacement. These procedures may be very useful to reduce pain and improve function when the hip and

shoulder joints become severely damaged. Heterotopic bone formation may occur after total joint replacement, especially around the hip. Heterotopic bone formation can be reduced by using postoperative NSAIDs (eg, indomethacin). In general, outcomes of total joint replacement in patients have been satisfactory. Activity: Physical therapy Physical therapy, including an exercise program and

postural training, is important to maintain function. Spinal extension and deep-breathing exercises help maintain spinal mobility, encourage erect posture, and promote chest expansion. Maintaining an erect posture during daily activities and sleeping on a firm mattress with a thin pillow also tend to reduce the tendency towards thoracic kyphosis. Water therapy and swimming are excellent activities to maintain mobility and fitness. The goal of pharmacotherapy is to reduce morbidity and prevent complications. Drug Name Indomethacin (Indocin, Indochron) -- Thought to be the most effective NSAID for the treatment of AS, although no scientific evidence supports this claim. The most common toxicities include nausea, dyspepsia, peptic ulcer disease, central nervous system toxicity, and renal toxicity. Adult Dose 100-150 mg/d PO divided in bid/tid Pediatric Dose 1.5-3 mg/kg/d PO divided in bid/tid Contraindications Documented hypersensitivity; history of peptic ulcer disease (unless prophylaxis is adequate); renal insufficiency, anticoagulation, and coagulopathy Interactions Coadministration with ACE

inhibitors, angiotensin-II receptor blockers, and potassium-sparing diuretics may result in hyperkalemia; coadministration with warfarin may increase PT due to displacement of warfarin from plasma proteins and may aggravate bleeding tendency due to antiplatelet effect of NSAIDs; may decrease effect of diuretics Pregnancy C - Safety for use during pregnancy has not been established. Precautions Most common toxicities include gastrointestinal manifestations such as nausea, abdominal pain, peptic ulcer disease, and renal insufficiency; may cause increased blood pressure in patients with hypertension due to blunting of effects of antihypertensive medications; patients with congestive heart failure may have exacerbations due to fluid and sodium retention; patients with diabetes mellitus should have close monitoring of renal

function Drug Name Ibuprofen

(Ibuprin, Motrin) -- For relief of mild to moderate pain; inhibits inflammatory reactions and pain by decreasing activity of cyclooxygenase, which results in a decrease of prostaglandin synthesis. Adult Dose 600-800 mg PO tid/qid Pediatric Dose 30-40 mg/kg/d divided tid/qid Contraindications Documented hypersensitivity; history of

peptic ulcer disease (unless prophylaxis is adequate); renal insufficiency, anticoagulation, and coagulopathy Interactions Coadministration with ACE inhibitors, angiotensin-II receptor blockers, and potassium-sparing diuretics may result in hyperkalemia; coadministration with warfarin may increase PT due to displacement of warfarin from plasma proteins and may aggravate bleeding tendency due to antiplatelet effect of NSAIDs;

may decrease the effect of diuretics Pregnancy C - Safety for use during pregnancy has not been established. Precautions Most common toxicities include gastrointestinal manifestations such as nausea, abdominal pain, peptic ulcer disease, and renal insufficiency; may cause increased blood pressure in patients with hypertension due to blunting of effects of antihypertensive medications; patients with congestive heart failure may have exacerbations due to fluid and sodium retention; patients with diabetes mellitus should have close monitoring of renal function Drug Name Naproxen (Naprosyn, Naprelan, Aleve, Anaprox) -- For relief of mild to moderate pain; inhibits inflammatory reactions and pain by decreasing activity of cyclooxygenase, which results in a decrease of prostaglandin synthesis. Adult Dose 500 mg PO bid/tid Pediatric Dose 10-20 mg/kg/d divided bid/tid Contraindications Documented hypersensitivity; history of peptic ulcer disease (unless prophylaxis is adequate); renal insufficiency, anticoagulation, and coagulopathy Interactions Coadministration with ACE inhibitors, angiotensin-II receptor blockers, and potassium-sparing diuretics may result in hyperkalemia; coadministration with warfarin may increase PT due to displacement of warfarin from plasma proteins and may aggravate bleeding tendency due to antiplatelet effect of NSAIDs; may decrease the effect of diuretics Pregnancy C - Safety for use during pregnancy has not been established. Precautions Most common toxicities include

gastrointestinal manifestations such as nausea, abdominal pain, peptic ulcer disease, and renal insufficiency; may cause increased blood pressure in patients with hypertension due to blunting of effects of antihypertensive medications; patients with congestive heart failure may have exacerbations due to fluid and sodium retention; patients with diabetes mellitus should have close monitoring of renal function Drug Name Sulfasalazine (Azulfidine, EN-tabs) -- Shown to reduce inflammatory symptoms of AS in controlled studies; most common toxicities include nausea, diarrhea, and hypersensitivity reactions (rash). Adult Dose 2000-3000 mg/d PO divided bid/tid Pediatric Dose 40-60 mg/kg/d PO divided bid/tid Contraindications Documented hypersensitivity; porphyria (may precipitate acute exacerbations) Interactions Absorption may be reduced by coadministration of oral iron Pregnancy B - Usually safe but benefits must outweigh the risks. Precautions Most common toxicities include nausea, diarrhea, and hypersensitivity; caution in renal or hepatic impairment, blood dyscrasias, or urinary obstruction; rarely, patients may develop blood dyscrasias, especially leukopenia, which may progress to agranulocytosis or hepatotoxicity