What is reactive arthritis?
Reactive arthritis is a chronic form of inflammatory arthritis featuring the following three conditions: (1) inflamed joints, (2) inflammation of the eyes (conjunctivitis), and (3) inflammation of the genital, urinary, or gastrointestinal systems.
This form of joint inflammation is called "reactive arthritis" because it is felt to involve an immune system that is "reacting" to the presence of bacterial infections in the genital, urinary, or gastrointestinal systems. Accordingly, certain people's immune systems are genetically primed to react aberrantly when these areas are exposed to certain bacteria. The aberrant reaction of the immune system leads to spontaneous inflammation in the joints and eyes. This can be confounding to the patient and the doctor when the infection has long passed at the time of presentation with arthritis or eye inflammation.
Reactive arthritis has, in the past, been referred to as Reiter syndrome (a term that has lost favor because of Dr. Hans Reiter's dubious past, one of enthusiastically embracing Nazi politics and medical abominations). In addition, Reiter syndrome would refer to a specific type of reactive arthritis limiting inflammation to the eyes, urethra, and joints.
Reactive arthritis most frequently occurs in patients in their 30s or 40s, but it can occur at any age. The form of reactive arthritis that occurs after genital infection (venereal) occurs more frequently in males. The form that develops after bowel infection (dysentery) occurs in equal frequency in males and females.
Reactive arthritis is considered a systemic rheumatic disease. This means it can affect other organs than the joints, causing inflammation in tissues such as the eyes, mouth, skin, kidneys, heart, and lungs. Reactive arthritis shares many features with several other arthritic conditions, such as psoriatic arthritis, ankylosing spondylitis, and arthritis associated with Crohn's disease and ulcerative colitis. Each of these arthritic conditions can cause similar disease and inflammation in the spine and other joints, eyes, skin, mouth, and various organs. In view of their similarities and tendency to inflame the spine, these conditions are collectively referred to as "spondyloarthropathies."
What causes reactive arthritis?
As mentioned, reactive arthritis is felt in part to be genetic. There are certain genetic markers that are far more frequent in patients with reactive arthritis than in the normal population. For example, the HLA-B27 gene is commonly seen in patients with reactive arthritis. Even in patients who have the genetic background that predisposes them to developing reactive arthritis, however, exposure to certain infections seems to be required to trigger the onset of the disease.
Reactive arthritis can occur after venereal infections. The most common bacterium that has been associated with this post-venereal form of reactive arthritis is an organism called Chlamydia trachomatis. Reactive arthritis also occurs after infectious dysentery, with bacterial organisms in the bowel, such as Salmonella, Shigella, Yersinia, Campylobacter, and Clostridium difficile. Typically, the arthritis develops one to three weeks after the onset of the bacterial infection. Reactive arthritis has also been reported associated with bladder infusions of BCG used for treating bladder cancer.
What are the risk factors for reactive arthritis?
- Gender: Reactive arthritis is more frequent in men.
- Age: It is most frequent in people 20-40 years of age.
- Hereditary factors: There are inherited genes, such as HLA-B27, that increase the risk for developing reactive arthritis.
SLIDESHOW
See SlideshowWhat are the symptoms of reactive arthritis?
The symptoms of reactive arthritis can be divided into those that affect the joints and those that affect the non-joint areas.
The classic joints that can become inflamed in reactive arthritis are the knees, ankles, and feet. The particular joints involved are usually asymmetric, that is, one side of the body or the other is affected with signs and symptoms, rather than both sides simultaneously. The inflammation leads to joint pain, stiffness, swelling, warmth, and redness. Patients may develop inflammation of entire fingers or toes which can give the appearance of a "sausage digit." This feature is also seen in patients with another type of arthritis called psoriatic arthritis that is associated with skin inflammation of psoriasis. The arthritis of reactive arthritis can be associated with fever and inflammation of the spine, leading to stiffness and joint pain in the back or neck (characteristic of all of the spondyloarthropathies, including ankylosing spondylitis and psoriatic arthritis).
Cartilage can also become inflamed, especially around the breastbone where the ribs meet in the front of the chest; this condition is called costochondritis. Muscles attach to the bones by tendons. In reactive arthritis, the tendon insertion points can become inflamed (enthesitis), tender, and painful when exercised. Achilles tendinitis is common with reactive arthritis.
Non-joint areas that become inflamed and cause symptoms of pain and irritation in patients with reactive arthritis include the eyes (conjunctivitis), genitals, urinary tract (urethra, bladder and prostate gland), skin, mouth lining, large bowel, and the aorta.
Inflammation of the white portion of the eye (conjunctivitis) and the iris of the eye (iritis) is frequently seen early in reactive arthritis and may be intermittent. When the whites of the eye are inflamed causing conjunctivitis, there may be no pain. When the colored part of the eye (iris) is inflamed, causing iritis and uveitis, it can be very painful and especially worse when looking into bright lights (medically referred to as photophobia).
Urinary tract inflammation commonly involves the urethra, the tube that drains urine from the bladder. This inflammation (urethritis) can be associated with burning on urination and/or pus drainage from the end of the penis. The skin around the penis can become inflamed and peel. The bladder and prostate gland can also become inflamed, leading to an urge to urinate from cystitis and prostatitis respectively.
The skin of the palms of the hands and/or the soles of the feet can develop tiny fluid-filled blisters that sometimes are filled with old blood. The affected skin can peel and may mimic psoriasis. The classic appearance is medically referred to as keratoderma blennorrhagica. Similar inflammation of the tip of the penis can cause irritating rash in males, referred to as circinate balanitis.
The mouth can develop open sores (ulcerations) on the hard and soft palate and even on the tongue. These may go unnoticed by the patient, as they are often painless. Inflammation of the large bowel (colitis) can cause diarrhea or pus or blood in the stool. Inflammation of the aorta (aortitis) can be seen in a small percentage of patients who have reactive arthritis. It can lead to failure of the aortic valve of the heart, which can cause heart failure. The electrical conducting pathway of the heart can also become scarred in reactive arthritis, leading to irregular heartbeats (arrhythmias) that may require placement of a pacemaker to regulate the heartbeat.
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Reactive arthritis diagnosis and testing
There is no single lab test used to diagnose reactive arthritis. Reactive arthritis is diagnosed based upon recognition of the combination of arthritis with symptoms such as inflammation of the eyes, and the genital, urinary, and/or gastrointestinal systems. The health care professional obtains a medical history to note the time course of possible infection in the genital or urinary tracts, or the bowel. Stiffness and pain are monitored. Inflammatory types of joint problems typically cause more stiffness in the morning. Blood tests such as a sedimentation rate may be obtained to document the presence of inflammation in the body. The rheumatoid factor, which is typically present in rheumatoid arthritis, is usually negative in reactive arthritis. The HLA-B27 gene marker blood test can be helpful, especially in the diagnosis of patients with spine disease. Other tests may be ordered to eliminate other possible diseases with similar symptoms.
X-rays of the spine or other joints can reveal typical changes of inflammation in these areas but generally not until later in the disease. Occasionally, there are areas of unusual calcifications at the points where the tendons attach to the bones, indicating past inflammation in these areas. Those patients with eye inflammation may require ophthalmology evaluation to document the degree of inflammation in the iris. Stool cultures might be obtained to detect the presence of infections in the bowel. Similarly, urinalysis and culture of the urine may be necessary to detect bacterial infection in the urinary tract. The prostate gland, which can also be inflamed in a patient with reactive arthritis, may be examined for tenderness.
Sometimes the fluid of the inflamed joint needs to be examined. In this case, a health care professional will use a needle to withdraw fluid from the joint in sterile fashion. The joint fluid will be examined for white blood cells, bacteria (to check for infection), and crystals (to eliminate gout as a diagnosis).
What are the treatments and medications for reactive arthritis?
Treatment of reactive arthritis is based on where it has become manifest in the body. For joint inflammation, patients are generally initially treated with nonsteroidal anti-inflammatory drugs (NSAIDs). These NSAIDs include aspirin, indomethacin (Indocin), tolmetin (Tolectin), sulindac (Clinoril), piroxicam (Feldene), and others. Among their potential side effects are gastrointestinal irritation, including ulceration and bleeding. Non-steroidal anti-inflammatory drugs should be taken with food to minimize this risk. Corticosteroids, such as prednisone, can be helpful to reduce inflammation and are used in the short-term treatment of inflammation in reactive arthritis. They can be given by mouth or by local injection into the joint. Corticosteroids are also used to decrease tendon inflammation in some forms of tendinitis.
Antibiotics may be prescribed if one still has the infection that triggered reactive arthritis.
Sulfasalazine (Azulfidine) has been shown to be effective in some patients with persistent reactive arthritis. Potential side effects of this sulfa-based medication include sulfa rash reaction and suppression of the bone marrow. Therefore, blood counts are monitored when Azulfidine is used long-term.
For the aggressive inflammation of chronic joint inflammation in reactive arthritis, medications that suppress the immune system, including the disease-modifying anti-rheumatic drug (DMARD) methotrexate (Rheumatrex, Trexall), are used. Methotrexate can be given orally by injection. It is given on a weekly basis and requires regular monitoring of blood counts and blood liver tests because of potential toxicity to the bone marrow and liver.
Tumor necrosis factor blockers (TNF): The cell protein TNF acts as an inflammatory agent in rheumatoid arthritis. There is some evidence that TNF blockers can also be helpful in reactive arthritis.
Reactive arthritis has been reported in association with HIV infection (AIDS virus). In this context, immune-suppression medicine is generally avoided because of the potential for worsening the HIV disease.
Eye inflammation can be alleviated with anti-inflammatory drops. Some patients with severe iritis require local injections of cortisone to prevent damaging inflammation to the eye, which can lead to blindness.
The inflammation around the penis can be helped by cortisone creams (such as Topicort). When bacteria are discovered in the bowel or urine, antibiotics specific for those bacteria are given.
Exercise has shown to help people with arthritis. You should have a physical therapist show you specific exercises for your joints.
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What is the prognosis of reactive arthritis?
The outlook for reactive arthritis is generally very good. Today, there are many effective treatments. The outlook is best when the disease is diagnosed and treated aggressively early on. When a specific cause is identified and eradicated, it is sometimes possible to completely cure reactive arthritis. Complications, such as eye, skin, or prostate disease, can require comanagement with appropriate specialists, including ophthalmologists, dermatologists, and urologists as well as rheumatologists.
Is it possible to prevent reactive arthritis?
Yes. Reactive arthritis can be prevented, to some extent, by avoiding sexual infection and by storing food properly and cooking it properly.
Fauci, A.S., and C.A. Langford. Harrison's Rheumatology. New York: McGraw-Hill Medical Publishing, 2006.
Gaston, J.S.H. "Immunological basis of chlamydia induced reactive arthritis." BMJ 76.3 (2000): 156-161.
Hannum T., L. Mattila, H. Rautelin, P. Pelkonen, P. Lahdenne, A. Siitonen, M. Leirisalo-Repo. "Campylobacter-triggered reactive arthritis: a population-based study." Rheumatology 41.3 Mar. 1, 2002: 312-318.
Hughes, R.A., and A.C. Keat. "Reiter's Syndrome and Reactive Arthritis: A Current View." Semin Arthritis Rheum 24.3 Dec. 1994: 190-210.
Koopman, William, et al., eds. Clinical Primer of Rheumatology. Philadelphia: Lippincott Williams & Wilkins, 2003.
Ruddy, Shaun, et al., eds. Kelley's Textbook of Rheumatology. Philadelphia: W.B. Saunders Co., 2000.
United States. National Center for Advancing Translational Sciences. Genetic and Rare Diseases Information Center. "Reactive Arthritis." May 1, 2018. <https://rarediseases.info.nih.gov/diseases/5693/reactive-arthritis>.
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