Autoimmune Disorders During Pregnancy

WHAT ARE THE EFFECTS OF PREGNANCY ON RHEUMATIC DISEASES?

During pregnancy, the effects of inflammation when rheumatic disease becomes active, and medications used to treat it, can cause problems.

The effects of pregnancy on rheumatic diseases vary by condition. Rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and APS typically are modified by pregnancy. For instance, symptoms of RA often improve in pregnant patients, frequently resulting in a reduced need for medication, but may flare up after delivery.

The relationship between lupus activity and pregnancy is more debated. In general, there is a tendency for mild to moderate flares, especially during the second half of pregnancy and the post-partum period. However, most of these flares do not endanger the mother's or the baby's life, nor do they substantially alter the long term prognosis of lupus. A prolonged period of clinical remission before conception decreases the chance of a flare during pregnancy.

Antiphospholipid syndrome (APS), increases the risk of clots in veins and arteries as well as obstetric complications such as miscarriage, prematurity or hypertension (high blood pressure) during pregnancy. When combined with kidney disease, the possibility exists for pre-eclampsia. Pre-eclampsia and eclampsia are conditions that may damage the mother’s kidneys and liver and also increase the risk of prematurity or death of the fetus. Thus, for women with APS, pregnancy—especially the time around delivery—is a particularly dangerous period and dictates special care.

Pulmonary hypertension, which complicates some rheumatic diseases (SLE, APS, Sjögren’s and, particularly, scleroderma), also warrants mention. Because this severe disease frequently is worsened during pregnancy—especially in the post-partum period—pregnancy isconsidered inadvisable. 

Other diseases such as scleroderma (in the absence of pulmonary hypertension or lung fibrosis), polymyositis, dermatomyositis and vasculitis do not seem to be particularly influenced by pregnancy. However, it is still recommended that you consider pregnancy only when these diseases are under control and with the care of your rheumatologist.

What are the effects of rheumatic diseases on pregnancy?

During pregnancy, the effects of inflammation when rheumatic disease becomes active as well as the then necessary anti-inflammatory and/or immunosuppressive drugs can cause problems. Those diseases with the potential to affect the kidney and, especially, APS are more likely to affect pregnancy outcome than others.

Patients who have or have had kidney disease, due to vasculitis, scleroderma or, more frequently, lupus, in general are at increased risk of severe hypertension and pre-eclampsia. If renal function and blood pressure prior to pregnancy are normal and the disease is inactive at the time of conception for a period of at least six months, the outcome is likely to be good. Conversely, women with severely impaired renal function, uncontrolled hypertension and/or active kidney involvement usually are advised against getting pregnant.

APS probably has the greatest impact on pregnancy. It is related to both early and late miscarriage, prematurity and low-weight babies, as well as thrombosis and pre-eclampsia. Thus, pregnancy in women with APS should always be considered as high risk, and be the subject of close medical and obstetric monitoring. Therapy is based on low-dose aspirin and heparin.

Finally, a rare condition named congenital heart block can occur in 2% of children born to mothers with anti-Ro antibodies (most frequently seen in patients with LUPUS and Sjögren's syndrome). Anti-Ro antibodies can gain access to the fetal circulation and produce disturbances in the baby's heart, which result in a slow heart rate. These babies may need a permanent pacemaker. Thus, women with anti-Ro antibodies also should be closely monitored including fetal heart scans during pregnancy. 

USE OF RHEUMATIC DRUGS DURING PREGNANCY AND LACTATION

Information regarding the safety of many drugs in pregnant women is incomplete and difficult to obtain. Recently, however, a group of obstetricians, rheumatologists and internists with experience in the management of pregnancy in women with rheumatic diseases reached consensus on the use of antirheumatic drugs during pregnancy and lactation. A summary of these conclusions is shown in Table 1.

	Pregnancy	Lactation
NSAID	Yes (avoid after 32 weeks)	Yes
Sulfasalazine	Yes	Yes
Antimalarials	Yes	Yes
Corticosteroids	Yes	Yes
Cyclosporin	Yes	probably yes
Azathioprine	Yes	probably yes
Mycophenolate	No	No
Methotrexate	No	No
Cyclophosphamide	No	No
Anti-tumor necrosis factor (TNF)	Yes	Yes
Rituximab	No	No
Warfarin	No (with caution, only after first trimester)	Yes
Heparin	Yes	Yes

Ideally, women should take no medication during pregnancy and nursing. However, the consequences of not being on medicine and risking flare up of the rheumatic illness are important considerations and this should be discussed with both the rheumatologist and obstetrician.

Several drugs (particularly methotrexate and cyclophosphamide) have effects on sperm cells. It is recommended that these medications be stopped for 3 months before a man fathers a child.

MANAGEMENT OF PREGNANCY IN WOMEN WITH RHEUMATIC DISEASES

All women with rheumatic disease should undergo counseling before conception for their specific risk. During that discussion with your doctor, you can review specific concerns of pregnancy and possible of pregnancy complications (Table 2).

Table 2: What makes a pregnancy “high risk”?

• Previous pregnancy with complications
• Underlying kidney disease
• Underlying heart disease
• Underlying lung disease (including pulmonary hypertension)
• Flare of rheumatic illness
• A history of previous blood clot
• the presence of SSA and SSB antibodies
• IVF (in vitro fertilization)
• pregnancy with twins, triplets, etc
• Maternal age over 40 years

Each woman’s rheumatic disease should be well under control for a period of at least 3-6 months before attempting pregnancy. As long as your medicines are not harmful to the fetus, you should remain on your medicines to prevent risk of a disease flare. Prednisone should be used at doses below 10 mg/d whenever possible, due to the risk of associated complications such as high blood pressure, diabetes, excessive weight gain, risk of infections and premature rupture of membranes. Hydroxychloroquine, is an extremely safe drug for both the mother and the fetus, and should not be stopped before, during or after pregnancy. High blood pressure should be managed using medicines that are safe during pregnancyCCaptopril and enalapril are safe drugs during breast feeding.

Women with APS must receive low-dose aspirin, with or without heparin depending on the previous obstetric and thrombotic history. In some women with antiphospholipid antibody syndrome or previous history of blood clots, prevention of blood clots using heparin following delivery is recommended for 4-6 weeks. Those with previous blood clot should re-start warfarin as soon as possible after delivery, since this drug is safe during lactation (Table 1).

Women with a low-risk profile should include in their usual treatment plan regular visits to the rheumatologist, as a precaution. However, those with a high risk profile should be managed by both the rheumatologist and obstetric team with experience in high-risk pregnancies. Visits should be more frequent as pregnancy advances, and include monitoring of fetal and maternal well-being. Doppler studies of the placenta are highly recommended. Blood-pressure measurements and urine dipstick should be performed frequently to assure the early detection and treatment of pre-eclampsia.

POINTS TO REMEMBER

All women should undergo counseling before conception for their specific risk profile and subsequent design of a management plan.

• All women should undergo counselling before conception for their specific risk, depending on their rheumatic condition and the medications they are taking.
• Each woman’s rheumatic disease should be well under control for a period of at least 3-6 months before attempting pregnancy. As long as your medicines are not harmful to the fetus, you should remain on your medicines to prevent risk of a disease flare. In particular, hydroxychloroquine is a very safe drug during pregnancy and lactation.
• Women with a low-risk profile can be managed with usual visits to the rheumatologist as a precaution. Those with a high-risk profile should be managed by both the rheumatologist and obstetric team with experience in high-risk pregnancies.

Low back Ache

WHAT IS SPINAL STENOSIS?

Spinal stenosis is a narrowing of one or more areas of the spine. This narrowing, which occurs most often in the lower back or neck, can put pressure on the spinal cord or nerves that branch out from the squeezed areas. Typically, a person with this condition complains of severe pain in the legs, calves or lower back when standing or walking. Pain may come on more quickly when walking up or down a hill, a ramp or steps. Usually, it is relieved by sitting down or leaning over.

However, not all patients with spinal narrowing develop symptoms—and we still don't understand why. Because of this, the term "spinal stenosis" actually refers to the symptoms of pain and not to the narrowing itself.

WHAT CAUSES SPINAL STENOSIS?

The image above shows the narrowing of the spinal canal.

Some people are born with a small spinal canal. This is called "congenital stenosis". However, spinal narrowing is most often due to age-related changes that take place over time. This is called "acquired spinal stenosis."

WHO GETS SPINAL STENOSIS?

The risk of developing spinal stenosis increases if:

• You were born with a narrow spinal canal
• You are female
• You are 50 years old or older
• You've had a previous injury or surgery of the spine

Some medical conditions can cause spinal stenosis. These include:

• Osteoarthritis and bony spurs that form as we age
• Inflammatory spondyloarthritis (e.g., ankylosing spondylitis)
• Spinal tumors
• Paget's Disease

HOW IS SPINAL STENOSIS DIAGNOSED?

A rheumatologist will ask about your symptoms and medical history. If he suspects spinal stenosis, he will do a physical exam. Some symptoms he will look for include:

• Numbness, weakness, cramping or pain in the legs, thighs or feet that makes it hard to walk
• Pain that goes down the leg
• Abnormal bowel/and or bladder function
• Loss of sexual function
• In severe cases, partial or complete leg paralysis. This is considered a medical emergency and you should get to an emergency room as quickly as possible.

A rheumatologist will also consider other conditions that can cause similar symptoms, such as arthritis of the hips or knees; disorders of the nervous system; or disorders of the heart and blood vessels.

A rheumatologist may also order other tests to confirm the diagnosis and determine the seriousness of your condition.

These include:

• An X-ray of the spine to check for osteoarthritis, bone spurs and narrowing of the spinal canal
• A computed tomography (CT) scan, which takes more detailed images of the back and spinal canal
• A magnetic resonance imaging (MRI) scan of the spine to take pictures of the spinal cord and nerves
• An EMG (electromyogram) to check the nerves going to your legs
• X-rays of the hips or knees, blood tests, as well as tests to check the circulation in your legs and to rule out other diseases with similar symptoms

HOW IS SPINAL STENOSIS TREATED?

Although there is no cure for spinal stenosis, regular exercise, medication and in some cases surgery can provide relief.

Exercise. Regular exercise can help you build and maintain strength in the muscles of your arms and upper legs (the hip adductors and abductors, quadriceps and hamstrings). This will improve your balance, ability to walk, bend and move about, as well as control pain. A physical therapist can show you which exercises are right for you.

Medications. Over-the-counter medications such as acetaminophen (Tylenol), or nonsteroidal anti-inflammatories (commonly called NSAIDS) such as ibuprofen (Advil, Motrin) or naproxen (Aleve, Anaprox), may also relieve pain. In addition, a rheumatologist may prescribe other medications to help with pain and/or muscle spasm.

Cortisone injections. Injections directly into the area around the spinal cord (known as epidural injections) may provide a great deal of temporary, sometimes permanent, relief. These injections are usually given on an outpatient basis in a hospital or clinic setting.

Surgery. Some patients with severe or worsening symptoms (but who are otherwise healthy) may be candidates for a "decompression laminectomy." This surgery removes the bony spurs and buildup of bone in the spinal canal, freeing space for the nerves and spinal cord. Afterwards, doctors often perform a spinal fusion to connect two or more vertebrae and better support for the spine.

Several recent studies have found that surgery produces better results than non-surgical treatment in the short term. However, results vary and, like all surgeries, this one also carries risks. These risks include blood clots in the brain and/or the legs; tears in the tissue around the spinal cord; infection; and injury to the nerve root. While surgery may bring some relief, it will not cure spinal stenosis or osteoarthritis and symptoms may recur.

BROADER HEALTH IMPACTS

Spinal stenosis can lead to the slow but steady loss of strength in the legs. The severe pain caused by this condition can be quite disabling, even if you have no muscle weakness, since it greatly affects your ability to work and enjoy life.

LIVING WITH SPINAL STENOSIS

There is no cure for this condition but there are steps you can take to feel better. For example:

• Get moving. Regular exercise is very important, so do it often – at least three times a week for about 30 minutes. Start slowly with flexion-based (forward-bending) exercises. As you begin to feel stronger, add walking or swimming to your plan.
• Modify activity. Don't do anything that can trigger or worsen pain and disability such as lifting heavy objects or walking long distances.
• Talk to your physician about pain medications, as well as alternative therapies such as acupuncture or massage that can ease pain.
• Explore non-surgical options first except in rare cases when pain, weakness and numbness comes on quickly.

Reactive Arthritis

WHAT IS REACTIVE ARTHRITIS?

Reactive arthritis is a painful form of inflammatory arthritis (joint disease due to inflammation). It occurs in reaction to an infection by certain bacteria. Most often, these bacteria are in the genitals (Chlamydia trachomatis) or the bowel (Campylobacter, Salmonella, Shigella and Yersinia). Chlamydia most often transmits by sex. It often has no symptoms, but can cause a pus-like or watery discharge from the genitals. The bowel bacteria can cause diarrhea.

Reactive arthritis can have any or all of these features:

• Pain and swelling of certain joints, often the knees and/or ankles
• Swelling and pain at the heels
• Extensive swelling of the toes or fingers
• Persistent low back pain, which tends to be worse at night or in the morning

Some patients with this type of arthritis also have eye redness and irritation. Still other signs and symptoms include burning with urination and a rash on the palms or the soles of the feet.

WHAT CAUSES REACTIVE ARTHRITIS?

The bacteria induce (cause) arthritis by distorting your body's defense against infections, as well as your genetic environment.

How exactly each of these factors plays a role in the disease likely varies from patient to patient. This is a focus of research.

WHO GETS REACTIVE ARTHRITIS?

The bacteria that cause reactive arthritis are very common. In theory, anyone who becomes infected with these germs might develop reactive arthritis. Yet very few people with bacterial diarrhea actually go on to have serious reactive arthritis. What remains unclear is the role of Chlamydia infection that has no symptoms. It is possible that some cases of arthritis of unknown cause are due to Chlamydia.

Reactive arthritis tends to occur most often in men between ages 20 and 50.

Some patients with reactive arthritis carry a gene called HLA-B27. Patients who test positive for HLA-B27 often have a more sudden and severe onset of symptoms. They also are more likely to have chronic (long-lasting) symptoms. Yet, patients who are HLA-B27 negative (do not have the gene) can still get reactive arthritis after exposure to an organism that causes it.

Although immunodeficient, patients who have the AIDS virus HIV can also develop reactive arthritis.

HOW IS REACTIVE ARTHRITIS DIAGNOSED?

Diagnosis is largely based on symptoms of the inducing infections and appearance of typical musculoskeletal (joint and muscle) involvement. If indicated, doctors might order a test for Chlamydia infection or test for the HLA-B27 gene.

The test for Chlamydia uses a urine sample or a swab of the genitals.

HOW IS REACTIVE ARTHRITIS TREATED?

The type of treatment depends on the stage of reactive arthritis.

Treatment for early stage. The acute (early) inflammation can be treated with nonsteroidal anti-inflammatory drugs (often referred to as NSAIDs). These drugs, which suppress swelling and pain, include naproxen (Aleve), diclofenac (Voltaren), indomethacin (Indocin) or celecoxib (Celebrex). The exact effective dose varies from patient to patient.

The risk of side effects of these drugs, such as gastrointestinal (often called GI) bleeding, also varies. Your doctor will consider your risk of GI bleeding in suggesting an NSAID.

Treatment for late stage. Chronic reactive arthritis may require treatment with a disease-modifying antirheumatic drug (sometimes called a DMARD) such as sulfasalazine or methotrexate. Sulfasalazine may be more useful when the reactive arthritis is triggered by a GI infection. In some cases, very inflamed joints may benefit from corticosteroid injections (cortisone shots).

New research suggests that a prolonged course of two or more antibiotics might be effective in patients with chronic Chlamydia-induced reactive arthritis. However, more studies are needed.

Talk to your physician about what to expect from treatment with NSAIDs and DMARDs.

Gout

WHAT IS GOUT?

Gout is a painful and potentially disabling form of arthritis that has been around since ancient times. The first symptoms usually are intense episodes of painful swelling in single joints, most often in the feet, especially the big toe. The swollen site may be red and warm.

Treatments are available to control most cases of gout. However, diagnosing gout can be hard, and treatment plans often must be tailored for each person.

WHAT CAUSES GOUT?

Gout occurs when excess uric acid (a normal waste product) collects in the body, and needle‐like urate crystals deposit in the joints. This may happen because either uric acid production increases or, more often, the kidneys cannot remove uric acid from the body well enough. Certain foods and drugs may raise uric acid levels and lead to gout attacks. These include the following:

• Foods such as shellfish and red meats
• Alcohol in excess
• Sugary drinks and foods that are high in fructose
• Some medications
  • low-dose aspirin (but because it can help protect against heart attacks and strokes, we do not recommend that people with gout stop taking low-dose aspirin)
  • certain diuretics (“water pills”) such as hydrochlorothiazide (Esidrix, Hydro‐D)
  • immunosuppressants used in organ transplants such as cyclosporine (Neoral, Sandimmune) and tacrolimus (Prograf)
   

Over time, increased uric acid levels in the blood may lead to deposits of urate crystals in and around the joints. These crystals can attract white blood cells, leading to severe, painful gout attacks and chronic arthritis. Uric acid also can deposit in the urinary tract, causing kidney stones.

WHO GETS GOUT?

Gout affects more than 3 million Americans. This condition and its complications occur more often in men, women after menopause, and people with kidney disease. Gout is strongly linked to obesity, hypertension (high blood pressure), hyperlipidemia (high cholesterol and triglycerides) and diabetes. Because of genetic factors, gout tends to run in some families. Gout rarely affects children.

In patients with chronic undertreated gout crystals can be found in deposits (called tophi) that can damage joints & can appear under the skin.

HOW IS GOUT DIAGNOSED?

Some other kinds of arthritis can mimic gout, so proper diagnosis (detection) is key. Health care providers suspect gout when a patient has joint swelling and intense pain in one or two joints at first, followed by pain‐free times between attacks. Early gout attacks often start at night.

Diagnosis depends on finding the distinguishing crystals. The physician may use a needle to extract fluid from an affected joint and will study that fluid under a microscope to find whether urate crystals are present. Crystals also can be found in deposits (called tophi) that can appear under the skin. These tophi occur in advanced gout. Uric acid levels in the blood are important to measure but can sometimes be misleading, especially if measured at the time of an acute attack. Levels may be normal for a short time or even low during attacks. Even people who do not have gout can have increased uric acid levels.

X-rays may show joint damage in gout of long duration. Ultrasound and dual energy computed tomography (commonly called dual energy CT) can show early features of gouty joint involvement. These imaging techniques also can help suggest the diagnosis.

HOW IS GOUT TREATED?

Treatment of acute attacks. One treatment for active flares of gout is colchicine. This medicine can be effective if given early in the attack. However, colchicine can cause nausea, vomiting, diarrhea and other side effects. Side effects may be less frequent with low doses. Patients with kidney or liver disease, or who take drugs that interact (interfere) with colchicine, must take lower doses or use other medicines. Colchicine also has an important role in preventing gout attacks (see below).

Nonsteroidal anti‐inflammatory drugs—commonly called NSAIDs—are aspirin‐like medications that can decrease inflammation and pain in joints and other tissues. NSAIDs, such as indomethacin (Indocin) and naproxen (Naprosyn), have become the treatment choice for most acute attacks of gout. (The fact sheet on NSAIDslists the types of patients who cannot take NSAIDs.) There is no proof that any one NSAID is better than others. High doses of short‐acting NSAIDs give the fastest relief of symptoms. These medicines may cause stomach upset, ulcers or diarrhea but, if used for the short term, are well tolerated by most people.

Some people cannot take NSAIDs because of health conditions such as ulcer disease or impaired kidney function or the use of blood thinners. Corticosteroids such as prednisone and triamcinolone are useful options for patients who cannot take NSAIDs. Given orally (by mouth) or by injection (shot) into the muscle, these medicines can be very effective in treating gout attacks. If only one or two joints are involved, your doctor can inject a corticosteroid directly into your joint.

Health care providers may prescribe anakinra (Kineret), an “interleukin 1 beta antagonist,” for very severe attacks of gout. Though this rheumatoid arthritis drug is not approved by the Food and Drug Administration (commonly referred to as the FDA), for gout treatment, it can quickly relieve gout symptoms for some patients.

Some home remedies may help ease gout pain. Rest the affected joint and apply ice packs or cold compresses (cloths soaked in ice water and wrung out) to that spot.

Treatment to remove excess uric acid. Patients who have repeated gout attacks, abnormally high levels of blood uric acid, or tophi or kidney stones should strongly consider medicines to lower blood uric acid levels. These medications do not help the painful flares of acute gout, so most patients should start taking them after acute attacks subside. The drug most often used to return blood levels of uric acid to normal is allopurinol (Lopurin, Zyloprim). It blocks production of uric acid. A recent option, febuxostat (Uloric), also acts by blocking uric acid production.

Probenecid (Benemid) helps the kidneys remove uric acid. Only patients with good kidney function who do not overproduce uric acid should take probenecid.

Pegloticase (Krystexxa) is given by injection and breaks down uric acid. This drug is for patients who do not respond to other treatments or cannot tolerate them. New drugs to lower uric acid levels and to treat gouty inflammation are under development.

If you are taking a uric acid-lowering drug, your doctor should slowly raise the dose and keep checking your blood uric acid levels. Once your uric acid levels drop below 6 mg/dL (normal), crystals tend to dissolve and new deposits of crystals can be prevented. You probably will have to stay on this medicine long term to prevent gout attacks.

What works well for one person may not work as well for another. Therefore, decisions about when to start treatment and what drugs to use should be tailored for each patient. Treatment choices depend on kidney function, other health problems, personal preferences and other factors.

What you eat can increase uric acid levels. Limit the amount of high-fructose drinks, such as nondiet soda. Also, do not drink alcohol, especially beer. Restrict eating foods that are rich in purines, compounds that break down into uric acid. These compounds are high in meat and certain types of seafood. Purines in vegetables appear to be safe, new research has found. Low‐fat dairy products may help lower uric acid levels.

In almost all cases, it is possible to successfully treat gout and bring a gradual end to attacks. Treatment also can decrease the number and size of tophi.

Lifestyle changes such as controlling weight, limiting alcohol consumption, and limiting meals with meats and fish rich in purines, can be helpful in controlling gout.

BROADER HEALTH IMPACTS OF GOUT

Gout often is associated with high blood pressure, heart and kidney disease, or the use of medications that increase uric acid levels. Therefore, health care providers should test for these related health problems. Researchers are studying whether lowering blood uric acid levels can help heart disease and kidney disease.

LIVING WITH GOUT

Gout affects quality of life by both the intermittent attacks and the potential for chronic (lasting) arthritis. Compliance with your treatment plan is critical.

Lifestyle changes may make it easier to manage this lifelong disease. Suggestions include gradual weight loss, avoidance of alcohol and reduced consumption of fructose‐containing drinks and foods high in purines.

Scleroderma

WHAT IS SCLERODERMA?

Scleroderma (also known as systemic sclerosis) is a chronic disease that causes the skin to become thick and hard; a buildup of scar tissue; and damage to internal organs such as the heart and blood vessels, lungs, stomach and kidneys. The effects of scleroderma vary widely and range from minor to life-threatening, depending on how widespread the disease is and which parts of the body are affected.

The two main types of scleroderma are:

• Localized scleroderma, which usually affects only the skin, although it can spread to the muscles, joints and bones. It does not affect other organs. Symptoms include discolored patches on the skin (a condition called morphea); or streaks or bands of thick, hard skin on the arms and legs (called linear scleroderma). When linear scleroderma occurs on the face and forehead, it is called en coup de sabre.
• Systemic scleroderma, which is the most serious form of the disease, affects the skin, muscles, joints, blood vessels, lungs, kidneys, heart and other organs.

WHAT CAUSES SCLERODERMA?

The cause of scleroderma is not known. Genetic factors (different genes) appear be important in the disease. Although exposure to certain chemicals may play a role in some people having scleroderma, the vast majority of patients with scleroderma do not have a history of exposure to any suspicious toxins. The cause of scleroderma is likely quite complicated.

WHO GETS SCLERODERMA?

Scleroderma is relatively rare. About 75,000 to 100,000 people in the U.S. have this disease; most are women between the ages of 30 and 50. Twins and family members of those with scleroderma or other autoimmune connective tissue diseases, such as lupus, may have a slightly higher risk of getting scleroderma. Children can also develop scleroderma, but the disease is different in children than in adults.

This image shows diffuse soft-tissue swelling of the digits, characteristic of the early edematous phase of scleroderma.

HOW IS SCLERODERMA DIAGNOSED?

Diagnosis can be tricky because symptoms may be similar to those of other diseases. There is no one blood test or X-ray that can say for sure that you have scleroderma.

To make a diagnosis, a doctor will ask about the patient's medical history, do a physical exam and possibly order lab tests and X-rays. Some symptoms he or she will look for include:

• Raynaud's phenomenon. This term refers to color changes (blue, white and red) that occur in fingers (and sometimes toes), often after exposure to cold temperatures. It occurs when blood flow to the hands and fingers is temporarily reduced. This is one of the earliest signs of the disease; more than 90 percent of patients with scleroderma have Raynaud's. Raynaud's can lead to finger swelling, color changes, numbness, pain, skin ulcers and gangrene on the fingers and toes. People with other diseases can also have Raynaud's and some people with Raynaud's do not have any other disease.
• Skin thickening, swelling and tightening. This is the problem that leads to the name "scleroderma" ("Sclera" means hard and "derma" means skin). The skin may also become glossy or unusually dark or light in places. The disease can sometimes result in changes is personal appearance, especially in the face. When the skin becomes extremely tight, the function of the area affected can be reduced (for example, fingers).
• Enlarged red blood vessels on the hands, face and around nail beds (called "telangiectasias").
• Calcium deposits in the skin or other areas.
• High blood pressure from kidney problems.
• Heartburn; this is an extremely common problem in scleroderma.
• Other problems of the digestive tract such as difficulty swallowing food, bloating and constipation, or problems absorbing food leading to weight loss.
• Shortness of breath.
• Joint pain.

HOW IS SCLERODERMA TREATED?

While some treatments are effective in treating some aspects of this disease, there is no drug that has been clearly proven to stop, or reverse, the key symptom of skin thickening and hardening. Medications that have proven helpful in treating other autoimmune diseases, such as rheumatoid arthritis and lupus, usually don't work for people with scleroderma. Doctors aim to curb individual symptoms and prevent further complications with a combination of drugs and self-care. For example:

Raynaud's phenomenon can be treated with drugs such as calcium channel blockers or drugs called PDE-5 inhibors - sildenafil (Viagra®), tadalafil (Cialis®) - which open up narrowed blood vessels and improve circulation. To prevent further damage, it's important to keep the whole body warm, especially fingers and toes. It's also important to protect fingertips and other skin areas from injury, which can happen even during normal daily activities.

Heartburn (acid reflux) can be treated with antacid drugs, especially proton-pump inhibitors (omeprazole and others). These medications ease gastro-esophageal reflux disease (known as GERD).

Scleroderma kidney disease can be treated with blood pressure medications called "angiotensin converting enzyme inhibitors" (ACE inhibitors). These can often effectively control kidney damage if started early and use of these drugs has been a major advance for treating scleroderma.

Muscle pain and weakness can be treated with anti-inflammatory drugs such as glucocorticoids (prednisone), intravenous immunoglobin (IVIg), and/or immunosuppressive medications. Physical therapy may be useful to maintain joint and skin flexibility.

Lung damage. There are two types of lung disease that patients with scleroderma may develop. The first type is called interstitial lung disease (scarring). There is evidence that cyclophosphamide is somewhat effective in treating the interstitial lung disease in scleroderma. Clinical trials are underway assessing the effectiveness of several other drugs for this problem.

The second type of lung disease seen in scleroderma is pulmonary arterial hypertension (high blood pressure in the arteries in the lungs). In the last 10 years, a number of drugs have become available to treat this condition, including prostacyclin-like drugs (epoprostenol, treprostinol, iloprost), the endothelin receptor antagonists (bosentan, ambrisentan), and PDE-5 inhibitors (sildenafil, vardenafil, tadalafil).

Much research is ongoing into new treatments for scleroderma. Patients and their families should know that experts remain optimistic and take comfort in the fact that work towards a cure will continue.

BROADER HEALTH IMPACT OF SCLERODERMA

Scleroderma can involve almost every organ system in the body. Although symptoms vary greatly from patient to patient, it can dramatically impact someone's life.

Patients should consult a rheumatologist—or a team of specialists---who are experienced in dealing with this complicated disease. Several other diseases that affect the skin are sometimes confused with scleroderma.

LIVING WITH SCLERODERMA

Living with scleroderma is quite challenging. Everyday activities can sometimes be difficult due to physical limitations and pain. Problems with digestion may require changes in diet; patients often have to eat several small meals rather than fewer large meals. Patients must also keep the skin well-moisturized to lessen stiffness and be careful during activities such as gardening, cooking—even opening envelopes---to avoid finger injuries. To keep the body warm, patients should dress in layers; wear socks, boots and gloves; and avoid very cold rooms. Unfortunately, moving to a warmer climate does not necessarily lead to dramatic improvement. Exercise and/or physical therapy may ease stiffness in the joints.

Patients must also deal with the psychological setbacks that come from living with a disease that is chronic, uncommon and currently incurable. Because scleroderma can cause significant changes in appearance, a patient's self-esteem and self-image are almost always affected. The support of family and friends is vital in helping to maintain a good quality of life.

Arthritis in Children

WHAT IS JUVENILE IDIOPATHIC ARTHRITIS (JIA)?

There are many terms used to describe a child with chronic arthritis. These include juvenile rheumatoid arthritis, juvenile chronic arthritis and juvenile idiopathic arthritis. While

JIA is used most by specialists in pediatric rheumatology, JRA is commonly used in the United States. 

Several types of arthritis, all involving chronic (long-term) joint inflammation, fall under the JIA heading. This inflammation begins before patients reach the age of 16, and symptoms last from 6 weeks to 3 months to be called chronic. JIA may involve one or many joints, and cause other symptoms such as fevers, rash and/or eye inflammation.

Systemic onset JIA affects about 10 percent of children with arthritis. It begins with repeating fevers that can be 103°F or higher, often accompanied by a salmon-colored rash that comes and goes. Systemic onset JIA may cause inflammation of the internal organs as well as the joints, though joint swelling may not appear until months or even years after the fevers begin. Anemia (a low red blood cell count) and elevated white blood cell counts are also typical findings in blood tests ordered to evaluate the fevers and ongoing symptoms. Arthritis may persist even after the fevers and other symptoms have disappeared.

Oligoarticular JIA, which involves fewer than five joints in its first stages, affects about half of all children with arthritis. Girls are more at risk than boys. Older children with oligoarticular JIA may develop “extended” arthritis that involves multiple joints and lasts into adulthood. Children who develop the oligoarticular form of JIA when they are younger than 7 years old have the best chance of having their joint disease subside with time. They are, however, at increased risk of developing an inflammatory eye problem (iritis or uveitis). Eye inflammation may persist independently of the arthritis. Because iritis usually does not cause symptoms, regular exams by an ophthalmologist (eye doctor) are essential to detect these conditions and identify treatment to prevent vision loss.

Polyarticular JIAaffects five or more joints and can begin at any age. Children diagnosed with polyarticular JIA in their teens may actually have the adult form of rheumatoid arthritis at an earlier-than-usual age.

With Psoriatic Arthritis, children have both arthritis and a skin disease called psoriasis or a family history of psoriasis in a parent or sibling. Typical signs of psoriatic arthritis include nail changes and widespread swelling of a toe or finger called dactylitis.

Enthesitis-Related Arthritis is a form of JIA that often involves attachments of ligaments as well as the spine. This form is sometimes called a spondyloarthropathy. These children may have joint pain without obvious swelling and may complain of back pain and stiffness.

Some children with arthritis develop uveitis, an inflammation of the eye.

WHAT CAUSES JIA?

Malfunctioning of the immune system in JIA targets the lining of the joint, known as the synovial membrane. This causes inflammation. When the inflammation persists, joint damage may occur. (See diagram of normal joint versus inflamed joint below.)

It is not known what causes the immune system to malfunction in JIA. These conditions are not considered hereditary and rarely involve more than one family member. Research suggests that some individuals may have a genetic tendency to develop JIA, but develop the condition only after exposure to an infection or other unknown trigger. Dietary and emotional factors do not appear to play a role in the development of JIA.

WHO GETS JIA?

About 1 child in every 1,000 develops some type of juvenile arthritis. These disorders can affect children at any age, although rarely in the first six months of life. It is estimated that around 300,000 children in the United States have been diagnosed with JIA.

HOW IS JIA DIAGNOSED?

JIA may be difficult to diagnose because some children may not complain of pain at first, and joint swelling may not be obvious. There is no blood test that can be used to diagnose the condition and adults with rheumatoid arthritis typically have a positive rheumatoid factor blood test, but children with JIA typically have a negative rheumatoid factor blood test. As a result, diagnosis of JIA depends on physical findings, medical history and the exclusion of other diagnoses. Typical symptoms include:

• limping
• stiffness when awakening
• reluctance to use an arm or leg
• reduced activity level
• persistent fever
• joint swelling
• difficulty with fine motor activities

Other conditions that can look like JIA, including infections, childhood cancer, bone disorders, Lyme disease and lupus also must be ruled out before a diagnosis of JIA can be confirmed.

HOW IS JIA TREATED?

Optimal care is tailored for each child with JIA and provided by an experienced team of health care providers that should include a pediatric rheumatologist, physical and occupational therapist, social worker and nurse specialist. This core team can coordinate efforts with the child's pediatrician, adult rheumatologists, other physicians (such as an ophthalmologist or orthopedic surgeon) and other health professionals (dentist, nutritionist or psychologist) as well as reach out to schools and additional community resources as necessary to ensure that the child receives the best care possible.

The overall treatment goal is to control symptoms, prevent joint damage and maintain function.
The first line of treatment involves a non-steroidal anti-inflammatory drug or NSAID. Examples of NSAIDs, such as ibuprofen (such as Motrin or Advil) or naproxen (Naprosyn), administered in a dose appropriate for the child’s weight. Younger children may be given liquid preparations or medications that require less frequent use. Because NSAIDs can cause gastrointestinal distress, such as stomachaches, they should be taken with food.

Disease modifying drugs—commonly called DMARDs—are added as a second-line treatment when arthritis does not respond to NSAIDs. DMARDs include methotrexate (Rheumatrex), leflunamide (Arava) and more recently developed medications known as biologics. The biologics include anti-tumor necrosis factor agents such as etanercept (Enbrel); infliximab (Remicade); adalimumab (Humira); abatacept (Orencia); anakinra (Kineret;); canakinumab (Ilaris) and tocilizumab (Actemra). Each of these medications can cause side effects that need to be monitored and discussed with the pediatric rheumatologist treating your child. Most of these treatments are approved for use in children as well as adults. In addition, researchers are developing new treatments.
When only a single joint is involved, a steroid can be injected into the joint before any additional medications are given. Oral steroids such as prednisone (Deltasone, Orasone, Prelone, Orapred) may be used in certain situations, but only for as short a time and at the lowest dose possible. The long-term use of steroids is associated with unacceptable side effects such as weight gain, poor growth, osteoporosis, cataracts, avascular necrosis, hypertension, and risk of infection.

PREVENTION

Because the causes of JIA are unknown, no one knows how to prevent these conditions.

CHILDREN LIVING WITH ARTHRITIS

Children with JIA should attend school, participate in extra-curricular and family activities, and live life as normally as possible. To foster a healthy transition to adulthood, adolescents with JIA should be allowed to enjoy independent activities, such as taking a part-time job and learning to drive.

A positive outlook and continued physical activity will help. Physical and occupational therapy can increase joint motion, reduce pain, improve function, and increase strength and endurance. Therapists may construct splints to prevent permanent joint tightening or deformities, and work with school-based therapists to address issues at school.

Glucocorticoid-Induced Osteoporosis

WHAT IS GLUCOCORTICOID-INDUCED OSTEOPOROSIS?

Glucocorticoid-induced osteoporosis is a form of osteoporosis—sometimes called OP—that is caused by taking glucocorticoid medicines. These drugs include prednisone (Deltasone, Orasone, etc.), prednisolone (Prelone), dexamethasone (Decadron, Hexadrol), and cortisone (Cortone). They are common treatments of many rheumatic (joint and muscle) diseases, includingrheumatoid arthritis, lupus, myositis (muscle inflammation) and polymyalgia rheumatica.

WHAT CAUSES GLUCOCORTICOID-INDUCED OSTEOPOROSIS?

Glucocorticoid medicines have both direct and indirect effects on bone tissue that lead to bone loss. These drugs have a direct negative effect on bone cells, resulting in a reduced rate of forming new bone. Also, they can interfere with the body's handling of calcium and affect levels of sex hormones. Either of these problems can lead to increased bone loss.

Anyone who is taking glucocorticoid medications and has other risk factors for OP is at increased risk of getting glucocorticoid-induced OP and breaking a bone (fracture). You can change some of these risk factors, but not others.

Major risk factors that you cannot change include:

• Older age (children are at risk too)
• Non-Hispanic white or Asian ethnic background
• Small bone structure
• Family history of OP or an OP-related fracture in a parent or sibling
• Prior fracture due to a low-level injury, particularly after age 50

Risk factors that you may be able to change include:

• Low levels of sex hormone, mainly estrogen in women (e.g., menopause) and men
• The eating disorder anorexia nervosa
• Cigarette smoking
• Alcohol abuse
• Low calcium and vitamin D, by low dietary intake or poor absorption in your gut
• Sedentary (inactive) lifestyle or immobility
• Certain medications besides glucocorticoids, including the following:
  • excess thyroid hormone replacement
  • the blood thinner heparin
  • some treatments of breast cancer (Arimidex, Femara, etc.) or prostate cancer (e.g., Lupron) that deplete sex hormones
   
• A disease that can affect bones
  • endocrine (hormone) diseases (hyperthyroidism, hyperparathyroidism, Cushing's disease, etc.)
  • inflammatory arthritis (rheumatoid arthritis, ankylosing spondylitis, etc.)
   

WHO GETS GLUCOCORTICOID-INDUCED OSTEOPOROSIS?

Anyone who needs to take glucocorticoid medicine is at risk of developing OP and fractures.

HOW IS GLUCOCORTICOID-INDUCED OSTEOPOROSIS DIAGNOSED?

You can learn if you have OP by having a simple test that measures bone mineral density—sometimes called BMD. BMD—the amount of bone you have in a given area—is measured at different parts of your body. Often the measurements are at your spine and your hip, including a part of the hip called the femoral neck, at the top of the thighbone (femur). Dual energy X-ray absorptiometry (referred to as DXA and pronounced "dex-uh") is the best current test to measure BMD.

The test is quick and painless. It is similar to an X-ray, but uses much less radiation. Even so, pregnant women should not have this test, to avoid any risk of harming the fetus.

DXA test results are scored compared with the BMD of young, healthy people. This results in a measure called a T-score. The scoring is as follows:

DXA T-Score	Bone Mineral Density (BMD)
Not lower than –1.0	Normal
Between –1.0 and –2.5	Osteopenia (mild BMD loss)
–2.5 or lower	Osteoporosis

The risk of fracture most often is lower in people with osteopenia than those with OP. But, if bone loss continues, the risk of fracture increases. Yet, people taking glucocorticoids seem to be at an increased risk of fracture at higher bone densities than would be expected.

HOW IS GLUCOCORTICOID-INDUCED OSTEOPOROSIS TREATED?

Osteoporosis is a condition of weak bone caused by a loss of bone mass as well as a change in bone structure. The first picture is normal bone and the second shows osteoporotic bone.

Anyone taking glucocorticoid medicine must get enough calcium and vitamin D. The American College of Rheumatology recommends you should take at least 1,200 to 1,500 milligrams (shortened as mg) of calcium and 800 to 1,000 International Units (called IU) of vitamin D supplements each day. Your doctor may measure the vitamin D level in your blood to find out if you need more vitamin D supplementation.

Some people also will need medication. The decision to start prescription medications will depend on your other risk factors, the dose of glucocorticoid medication you are taking and how long you may be on it, as well as your BMD results by DXA.

The US Food and Drug Administration (better known as the FDA) has approved certain drugs to prevent and treat glucocorticoid-induced OP. In a drug class called bisphosphonates, risedronate (Actonel) and zoledronic acid (Reclast) are FDA approved for both the prevention and treatment of glucocorticoid-induced OP. Another drug in this class, alendronate (Fosamax), is approved for the treatment of this type of OP.

Teriparatide (Forteo), a different type of drug, also is approved for treatment of glucocorticoid-induced OP. This manmade form of parathyroid hormone helps stimulate bone formation. You can find more information about these drugs in the "Osteoporosis" fact sheet, under the section "How is osteoporosis treated?"

Women planning a pregnancy should talk to their doctor about the pros and cons of using a bisphosphonate or teriparatide. None of the prescription drugs for managing OP has enough safety data available to recommend using them in women who are pregnant or breastfeeding. (For more information, see the section "Young women and pregnancy" in the patient fact sheet aboutOP.

PREVENTION

If you take glucocorticoid medicine for any length of time, you should start taking calcium and vitamin D supplements at the doses recommended in the prior section. Work with your doctor to help use the smallest dose of glucocorticoid for the shortest duration possible that will still keep your disease under control.

Patients taking glucocorticoid medicine should:

• Be physically active and do weight-bearing exercises, like walking, most days each week.
• Change lifestyle choices that raise your risk of OP, such as quitting smoking.
• Implement strategies to help decrease your risk of falling, which raises the risk of fractures. (See "Living with osteoporosis" in the "Osteoporosis" fact sheet.)
• Get DXA testing of your BMD.

If you have low bone density and a high risk of breaking a bone, your doctor may suggest medicine to prevent your bones from getting weaker. (See the section "How is osteoporosis treated?") Health care providers now have a tool for estimating the risk of a patient having an osteoporotic fracture in the next 10 years. This fracture risk assessment tool, from the World Health Organization, is called FRAX. It can help guide treatment decisions.

BROADER HEALTH IMPACT OF GLUCOCORTICOID-INDUCED OSTEOPOROSIS

The most serious health consequence of any type of OP is a fracture. Spine and hip fractures especially may lead to chronic pain, long-term disability and even death. The main goal of treating glucocorticoid-induced OP is to prevent fractures.

POINTS TO REMEMBER

Weight-bearing exercise is a key part of prevention.

• A bone density test can safely measure changes in bone density during glucocorticoid treatment.
• Both men and women can decrease bone loss from glucocorticoid treatment by using calcium and vitamin D supplements.

THE RHEUMATOLOGIST'S ROLE IN THE TREATMENT OF GLUCOCORTICOID-INDUCED OSTEOPOROSIS

As doctors who are experts in diagnosing and treating diseases of the joints, muscles and bones, rheumatologists can help find the cause of OP. They can provide and monitor the best treatments for this condition.