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Reiter's Syndrome

Reiter Syndrome

Reiter's syndrome (Reiter's arthritis, arthritis urethritica, venereal arthritis, reactive arthritis, polyarteritis enterica) is a triad of symptoms of unknown etiology comprising arthritis, urethritis and conjunctivitis. It is often triggered by earlier gastrointestinal infection or exposure to a sexually transmitted disease. It was first described by Hans Reiter, a German physician.


Presentation

In general, sign and symptoms of Reiter’s syndrome starts after 1 to 3 weeks from the initial primary infection. The following symptomatology are usually observed:

  • Arthritis in joints – most commonly on the ankles, knees, feet, heels and lower back spine. Pain and swelling may lead to stiffness and disability.
  • Conjunctivitis – Reactive arthritis is commonly associated with the inflammation of the conjunctiva.
  • Urinary complains – There is an increased frequency of urination with or without pain in a number of patients. The prostate and the cervix may also inflame in some cases.
  • Deformation of digits – In some cases of reactive arthritis, fingers and toes may swell and look deformed.
Fever
  • Abstract A 32-year-old Japanese man developed polyarthritis with mild fever and conjunctivitis. Clinical assessment indicated non-specific arthritis, aseptic pyuria induced by infection with Chlamydia, and conjunctivitis.[ncbi.nlm.nih.gov]
  • The patient presented with fever, conjunctivitis, dysentery, urethritis and arthralgia. The joint pains involved the left wrist (which was swollen), the right knee and ankle joints. The patient was managed conservatively.[ncbi.nlm.nih.gov]
  • Abstract A 40-year-old woman with Reiter's syndrome had low-grade fever, a psoriasislike eruption on feet and hands, and multiple esophageal ulcers.[ncbi.nlm.nih.gov]
  • However, case O.M required aggressive treatment for fever and arthralgia. These patients have recently shown no evidence of Reiter's syndrome; however, case T.M has had recurrent bowel hemorrhages due to ulcerative colitis.[ncbi.nlm.nih.gov]
  • Abstract A 50-year-old male with superficial bladder carcinoma developed fever, conjunctivitis, cystitis, and arthritis of the ankles and metatarsophalangeal and sacroiliac joints after the fourth course of intravesical Bacillus Calmette-Guerin (BCG)[ncbi.nlm.nih.gov]
Malaise
  • Nevertheless, significant side effects are associated with BCG instillations, including fever, myalgia, malaise, dysuria, hematuria, and irritable lower urinary tract symptoms.[ncbi.nlm.nih.gov]
  • The onset is most often acute, with malaise, fatigue, and fever. An asymmetrical, predominantly lower extremity, oligoarthritis (usually no more than six joints) is the major presenting symptom. [ 6 ] Low back pain often occurs.[patient.info]
  • Dactylitis or "sausage digit", plantar fasciitits, and achilles tendinitis are the most common sites. [1] [2] [3] [4] Skin lesions are very similar to those of psoriasis [2] [3] Constitutional symptoms include fatigue, malaise, fever, and weight loss[physio-pedia.com]
  • […] disabling enthesitis and extensive cutaneous manifestations Chief Concern (CC): mucocutaneous lesions, joint stiffness, myalgia, low back pain worse with rest; occasionally heel pain, red eyes, low grade fever; rarely high fever, weight loss, severe malaise[enotes.tripod.com]
Sausage Toe
  • toes Associated with antecedent Genitourinary and GI infections.[masterofmedicine.com]
  • " toe / inflamed ankle Radiograph: periosteal reaction at plantar fascia insertion Advertisement[pathologyoutlines.com]
  • Inflammation of the knee, sterno-clavicular joint and “sausagetoe occurred predominantly in males and finger involvements in females.[link.springer.com]
Relapsing Polychondritis
  • Abstract We describe a case of relapsing polychondritis associated with Reiter's Syndrome in a 46-year-old white man.[ncbi.nlm.nih.gov]
Aphthous Stomatitis
  • In the oral cavity, the patients may suffer from recurrent aphthous stomatitis, geographic tongue and migratory stomatitis in higher prevalence than the general population.[en.wikipedia.org]
Keratosis Blennorrhagica
  • Introduction The relationship of Reiter's syndrome and gonococcal keratosis blennorrhagica has intrigued us for a long time.[jamanetwork.com]
Eye Pain
  • He had developed intermittent arthralgia of the right knee for about 6 months and occasional bilateral eye pain for several months prior to admission.[ncbi.nlm.nih.gov]
  • The symptoms may include urethral discharge, frequency of passing urine, penile, mouth and tongue ulcers , fever, red eyes, painful joints and the scaly rash of psoriasis.[netdoctor.co.uk]
  • The symptoms may include urethral discharge, frequency of passing urine, penile, mouth and tongue ulcers, fever, red eyes, painful joints and the scaly rash of psoriasis.[netdoctor.co.uk]
  • Critical Essential Core Tested Community Questions (2) (M2.RH.4686) A 28-year-old man presents with one week of redness and discharge in his eyes, pain and swelling in his left second and third toes, and rash on the soles of his feet.[medbullets.com]
  • Redness of the eyes may be mild and not mentioned; if the iris becomes inflamed later in the course of the disease, eye pain and blurred vision may be reported. Individuals may have only a few of these symptoms.[nmihi.com]
Blurred Vision
  • Joints Swelling, pain, and redness, especially in the knees, ankles, and feet Heel pain Back pain and stiffness Eyes Redness Burning Irritation Blurred vision Tearing Discharge Urinary Tract and Reproductive System TOP In men: Burning sensation when passing[health.cvs.com]
  • Redness of the eyes may be mild and not mentioned; if the iris becomes inflamed later in the course of the disease, eye pain and blurred vision may be reported. Individuals may have only a few of these symptoms.[nmihi.com]
  • vision Skin and mucous membranes 1–2 months after the onset of arthritis, some patients develop keratoderma blennorrhagicum.[dermnetnz.org]
  • Possible symptoms are: Pain and swelling in joints, such as the knees, ankles, and feet Redness of the eyes, eye pain and irritation, blurred vision Signs of inflammation in the urinary tract, especially in men, such as an increased need to urinate, pain[summitmedicalgroup.com]
Photophobia
  • It usually causes mild eye redness and grittiness, but keratitis and anterior uveitis can develop also, causing eye pain, photophobia, and tearing.[merckmanuals.com]
  • The patient presented to the ophthalmic outpatient department (OPD) with diminished vision, photophobia, and a painful red right eye of 3-days duration.[jcor.in]
  • […] about crusting of eyelids, especially in the morning, which suggests subtle inflammation some patients develop bilateral obvious redness, burning sensation and exudation 20% acute anterior uveitis (iritis) may occur with severe ocular erythema, pain and photophobia[enotes.tripod.com]
Arthritis
  • Women with reactive arthritis often have milder symptoms than men. What are the symptoms? What are the symptoms of reactive arthritis? Symptoms of reactive arthritis may be so mild that you do not notice them.[niams.nih.gov]
  • Gonococcal arthritis. Gout. Inflammatory bowel disease. Psoriatic arthritis. Rheumatic fever. Rheumatoid arthritis. Septic arthritis.[patient.info]
  • Reiter's syndrome (Reiter's arthritis, arthritis urethritica, venereal arthritis, reactive arthritis, polyarteritis enterica) is a triad of symptoms of unknown etiology comprising arthritis, urethritis and conjunctivitis.[symptoma.com]
  • Patients with self-limiting arthritis without identified triggering agents (n 60, incidence 11.0/100,000) had a normal prevalence of HLA-B27 and a more heterogeneous pattern of arthritis.[ncbi.nlm.nih.gov]
  • Negative joint culture results from patients with reactive arthritis make it unlikely that bacteria in the joint are viable, although chlamydial DNA has been shown in the joints of patients with sexually acquired reactive arthritis using the polymerase[ncbi.nlm.nih.gov]
Back Pain
  • The patient was treated with nonsteroidal antiinflammatory drugs (for back pain) and eye ointment (for conjunctivitis) and his condition improved.[ncbi.nlm.nih.gov]
  • Abstract We report a case of atypical Reiter's syndrome occurring in a female patient who had severe, ulcerative vulvar disease develop in association with conjunctivitis, low back pain, stomatitis, and psoriasiform skin lesions.[ncbi.nlm.nih.gov]
  • The symptom of back pain was found in IdAS (78.8%), RS (38.2%) and PsA (21.4%); there was a significant difference (p 0.001) between IdAS and RS, and IdAS and PsA.[ncbi.nlm.nih.gov]
  • Almost 60% of patients have chronic relapses of peripheral arthritis when followed over a longer period and nearly 35% become disabled in some way; 50% have back pain and evidence of sacroidiitis.[myvmc.com]
Heel Pain
  • Other associated symptoms were similar, particularly evidence of enthesopathy (tendonitis, heel pain, plantar fasciitis), the polyarticular pattern was more common than the mono-articular pattern.[ncbi.nlm.nih.gov]
  • pain cause by enthesitis, an inflammation of the junction between tendons and bone Achilles tendonitis Inflammation of the glans penis ( balanitis circinata ) Swelling of the toes or fingers Those who have prolonged Reiter's syndrome may progress to[microbiologybook.org]
  • Usually urethritis precedes the symptoms of arthritis, which frequently presents as a red swollen toe or heel pain. There may also be characteristic skin lesions that may form on the palms of the hands and the bottom of the feet.[ahni.com]
  • Calcaneus is involved in more than 50% of patients, hence the name "lover's heel". Painful erosions and reactive spurs are very common at the attachment sites of Achilles tendon and plantar aponeurosis in calcaneus.[en.wikibooks.org]
  • Enthesitis can involve the Achilles tendon resulting in heel pain. Not all affected persons have all the manifestations.[en.wikipedia.org]
Low Back Pain
  • Abstract We report a case of atypical Reiter's syndrome occurring in a female patient who had severe, ulcerative vulvar disease develop in association with conjunctivitis, low back pain, stomatitis, and psoriasiform skin lesions.[ncbi.nlm.nih.gov]
  • Four weekly cycles of BCG were administered uneventfully; however, before the fifth instillation, the patient complained of urethral discharge, bilateral conjunctivitis, and low back pain.[ncbi.nlm.nih.gov]
  • All forms of spondylitis share common tendencies, including low back pain, fatigue and morning stiffness that improves during the course of the day, as well as after exercise.[laserspineinstitute.com]
  • Univariate logistic regression analysis revealed that ethnicity, HLA-B27, buttock pain, inflammatory low back pain, ankle involvement, grade I sacroiliitis at the beginning of the study, and the use of sulfasalazine were statistically associated with[doi.org]
  • 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[rheumatology.org]
Joint Swelling
  • Joints Swelling, pain, and redness, especially in the knees, ankles, and feet Heel pain Back pain and stiffness Eyes Redness Burning Irritation Blurred vision Tearing Discharge Urinary Tract and Reproductive System TOP In men: Burning sensation when passing[health.cvs.com]
  • Joint swelling, pain during urination, and changes in vision are signs of Reiter’s syndrome, more properly referred to in the medical community as reactive arthritis .[everydayhealth.com]
  • Medically Reviewed by Niya Jones, MD, MPH Joint swelling, pain during urination, and changes in vision are signs of Reiter’s syndrome, more properly referred to in the medical community as reactive arthritis.[everydayhealth.com]
  • The leading symptom is joint swelling. Arthritis is usually asymmetric. Lower extremities joints are swollen. The condition is aggravated in the morning and at night. When examining the skin, a patient can notice hyperemia and swelling.[brulanta.com]
Urethral Discharge
  • Four weekly cycles of BCG were administered uneventfully; however, before the fifth instillation, the patient complained of urethral discharge, bilateral conjunctivitis, and low back pain.[ncbi.nlm.nih.gov]
  • The symptoms may include urethral discharge, frequency of passing urine, penile, mouth and tongue ulcers , fever, red eyes, painful joints and the scaly rash of psoriasis.[netdoctor.co.uk]
  • The symptoms may include urethral discharge, frequency of passing urine, penile, mouth and tongue ulcers, fever, red eyes, painful joints and the scaly rash of psoriasis.[netdoctor.co.uk]
  • Urethral discharge Burning or stinging on urination. Pus filled sores. Rashes. Women are affected in the urogenital area, including the fallopian tubes, uterus, and vagina.[medigoo.com]
  • ), uveitis, skin lesions, & urethritis, however only a minority will have classic triad of symptoms; - conjunctivitis is observed early, usually before or at the onset of arthritis; - urethritis is usually mild and painless with frequent nonpurulent urethral[wheelessonline.com]
Dysuria
  • A 39-year-old Chinese man presented with a 3-week history of dysuria, suprapubic pain, and pain at the tip of the penis postmicturition.[ncbi.nlm.nih.gov]
  • In women, urethritis and cervicitis may be mild (with dysuria or slight vaginal discharge) or asymptomatic. Conjunctivitis is the most common eye lesion.[merckmanuals.com]
  • […] and mucopurulent urethral discharge, occasionally prostatitis or epididymitis women may have dysuria, vaginal discharge, purulent cervicitis or vaginitis asymptomatic patients often have sterile pyuria, especially on first-voided morning urine sample[enotes.tripod.com]
  • The patient denied dysuria and other urinary symptoms, and his ophthalmological exam was normal.[scielo.br]
  • The classical presentation of the syndrome starts with urinary symptoms such as burning pain on urination (dysuria) or an increased frequency of urination.[en.wikipedia.org]
Penile Lesion
  • Patient can have enthesitis presenting as heel pain, Achilles tendinitis or plantar fasciitis, along with balanitis circinata (circinate balanitis), which involves penile lesions present in roughly 20 to 40 percent of the men with the disease.[en.wikipedia.org]

Workup

A complete physical examination will reveal the swelling of the joints in foot, arms and the back. Eye examination may reveal conjunctivitis as a herald sign of Reiter’s disease. Blood test may be conducted to determine signs of previous and ongoing infection, signs of inflammation, presence of antibodies, and genetic markers that points to Reiter’s syndrome.

Arthrocentesis to acquire joint fluids elucidating the presence of inflammatory cells, presence of specific bacterial infections and pathologic joint crystals may also be necessary. Radiographs with x-ray of the joints, back and pelvis may show signs of reactive arthritis.

Chlamydia
  • In all patients standard laboratory analyses of the blood, urine and stool were made; antibody titer to Chlamydia trachomatis and Ureaplasma urealyticum was determined in synovial fluid and serum; isolation of Chlamydia trachomatis and Ureaplasma urealyticum[ncbi.nlm.nih.gov]
  • The laboratory examination showed significant elevation of serum IgG and IgA anti-Chlamydia antibodies.[ncbi.nlm.nih.gov]
  • Here we define the cellular location of chlamydia within the synovium via in situ hybridization.[ncbi.nlm.nih.gov]
  • Clinical assessment indicated non-specific arthritis, aseptic pyuria induced by infection with Chlamydia, and conjunctivitis. He was diagnosed with reactive arthritis (Reiter's syndrome).[ncbi.nlm.nih.gov]
  • Zeidler H, Hudson AP ; New insights into Chlamydia and arthritis. Promise of a cure? Ann Rheum Dis. 2014 Apr73(4):637-44. doi: 10.1136/annrheumdis-2013-204110. Epub 2013 Dec 2.[patient.info]
HLA-B27
  • METHODS: TAP1 and TAP2 alleles were determined for 34 patients with RS (28 HLA-B27 positive, 6 HLA-B27 negative), and their frequencies were compared with those observed for 52 HLA-B27 positive and 80 random disease-free control subjects.[ncbi.nlm.nih.gov]
  • The immunopathogenesis of Reiter's syndrome is linked to HLA-B27, which has been described as the disease susceptibility factor. The association of Reiter's syndrome and HLA-B27 positivity is 80%.[ncbi.nlm.nih.gov]
  • HLA B27 was present in 11 (61.1%) patients.[ncbi.nlm.nih.gov]
  • Although, he was negative for HLA-B27 or any other HLA-B27 cross-reactive MHC class I antigens, he was positive for HLA-B51. The laboratory examination showed significant elevation of serum IgG and IgA anti-Chlamydia antibodies.[ncbi.nlm.nih.gov]
  • We review the history of shipboard Reiter's syndrome, and discuss the pathogenic roles of HLA B27 and particular infectious agents.[ncbi.nlm.nih.gov]

Treatment

The main goal in the treatment of Reiter’s syndrome is to relieve symptoms and control underlying infections. Specific antibiotics for the bacterial causative agents that were identified in the laboratory can be given.

The use of the NSAID indomethacin may relieve mild pain symptoms in Reiter’s syndrome. Direct corticosteroid injections on the affected joints may address the debilitation instantly.

Evidences were mounted that some anti-arthritic drugs like sulfasalazine and methotrexate can help control the pain in Reiter’s syndrome.

Prognosis

The natural history of Reiter’s syndrome is self-limiting even in patients that are suffering from acute forms of debility in the early onset. Cases of untreated reactive arthritis culminates significantly within 3 to 12 months from onset of symptoms. Serious outcomes that results in mortality are very rare and are usually due to the adverse effects of treatment. Scientific literature confers that post-dysenteric arthritis has a better prognosis than their post-venereal counterparts. Recurrence of disease happens in 15-50% of cases especially those found positive with HLA-B27 marker.

Complications

The self-limiting nature of reactive arthritis confers limited complications to patients also. The most common complication is recurrence of the disease in almost half of the patients which are usually triggered by an immune deficient period or chronic stress.

Among the recurring cases, 15 to 30% of which leads to destructive arthritis and spondylitis which may have permanent debilitation consequences. Chronic Reiter’s syndrome may rarely occur especially those with the hip joint involvement. These chronic forms can be very severe that symptoms may no longer respond to classic non-steroidal anti-inflammatory drugs (NSAID).

Etiology

Reactive arthritis is a secondary reaction from a primary infection in the gastro-intestinal tract and genito-urinary tract. The primary infection are often caused by gram-negative, facultative, or obligate intracellular bacteria, and may present with very mild symptoms that may not be perceived by the patient [1].

Because of its usual origin in the gut and genitals, Reiter’s syndrome is sometimes classified as venereal or dysentery in nature. These are the most common etiologic agents that cause the primary disease in Reiter’s syndrome:

Epidemiology

The general incidence of Reiter’s syndrome is rare because its arthritic signs are often mistaken with the more common arthritis symptoms [5]. The cases in the US are estimated at 3.5 to 5 cases per 100,000 population. Reactive arthritis has a higher penetrance on patients with Acquired immune deficiency syndrome (AIDS).

A shigellosis outbreak (HLA-B27 positive type) in Oregon recorded an increased incidence of Reiter's syndrome reaching a penetrance of 29% among those who had Shigella dysentery. In European countries like Norway and Finland, primary infections of Yersinia enterocolyitca are most common.

Men at the third decade are more predisposed to reactive arthritis while children beyond 9 years of age may manifest after an enteric episode [6].

Sex distribution
Age distribution

Pathophysiology

The pathophysiology starts at the level of the primary infection with a bacteria in the level of the gastrointestinal tract (GIT) and the genitourinary tract (GUT). Respiratory infections like tonsillitis with streptococcal antigen may lead to Reiter’s syndrome but may be infrequent [7].

These bacterial antigen makes its way to the intrasynovial region where antibodies and the bacterial reactive T-cells causing an immune mediated synovitis and arthritis. In concert with the native T-cell response are various cytokines like the transforming growth factor (TGF-B) and Interleukin 6 and 17 (IL-6, IL-17) which mounts the antigen through time causing a more pronounced inflammation than the usual arthritis [8].

In AIDS patients, a severe immune response with generalized psoriasis-like rashes has been theorized to be mediated by the cytotoxic cells (CD4 and CD8).

Prevention

Preventing Reiter’s syndrome involves the examination of the family tree for possible hereditary links with reactive arthritis. Those with familial predispositions should prevent infections from bacteria that may cause Reiter’s syndrome.

Proper food sanitation must be in place to prevent shigellosis, salmonellosis and Camphylobacter infections of the gut which may lead to reactive arthritis [9]. Sexual precaution should always be observed to prevent sexually transmitted diseases.

Summary

Reiter’s syndromes or reactive arthritis is a clinical disease characterized by an autoimmune joint inflammation in reaction to an infection in another part of the body. Inflammation symptoms may also affect the eyes and urethra completing the syndrome triad of arthritis, genito-urinary tract signs and conjunctivitis.

The most common joints affected are those of the ankles and knees with primary infection from the intestines, urinary tract and genitals. Symptoms usually occur 1 to 3 weeks from the primary infection.

Reiter’s syndrome is the old name of reactive arthritis which is sometimes referred to as Fiessinger-Leroy disease. Reiter’s syndrome is a rare disease with benign symptoms that usually resolves within a year.

Patient Information

It must be remembered that Reiter’s syndrome occurs in patients with poor health-related quality of life; thus, efforts should be made to alleviate poor health conditions and maintain proper functional status with proper and good hygiene all the time [10].

Patients diagnosed with the disease should be educated on the possible complications of disease and the importance of long term compliance to medications. Regular exercise can modify sedentary lifestyles that are more prone to have the disease. Adolescents and young adults should be involved in the active control of the spread of sexually transmitted diseases by promoting safer sex practices.

References

Article

  1. Sahlberg AS, Granfors K, Penttinen MA . HLA-B27 and host-pathogen interaction Adv Exp Med Biol 2009; 649 235-44.
  2. El Karoui K, Mechai F, Ribadeau-Dumas F, Viard JP, Lecuit M, de Barbeyrac B, et al. Reactive arthritis associated with lymphogranuloma venereum proctitis L2b. Sex Transm Infect. June 2009, 85 (3): 180-1.
  3. Dworkin MS, Shoemaker PC, Goldoft MJ, Kobayashi JM. Reactive arthritis and Reiter's syndrome outbreak of gastroenteritis Following on Caused by Salmonella enteritidis. Clin Infect Dis. Oct 1 2001, 33 (7): 1010-4.
  4. van Bemmel JM, Delgado V, Holman ER, Allaart CF, Huizinga TW, Bax JJ, et al. Increased risk of valvular No heart disease in adult poststreptococcal reactive arthritis. Arthritis Rheum. April 2009, 60 (4): 987-93.
  5. Braun J, Kingsley G, van der Heijde D, Sieper J. On the Difficulties of Establishing a consensus on the definition of and diagnostic Investigations for reactive arthritis. Results and discussion of a questionnaire prepared for the 4th International Workshop on Reactive Arthritis, Berlin, Germany, July 3-6, 1999 J Rheumatol. September 2000, 27 (9) :. 2185-92 
  6. Macía Villa C, Sifuentes Giraldo W, Boteanu A, González Lanza M, Bachiller Corral J. Reactive arthritis after intravesical instillation of BCG the . Reumatol Clin Sep-Oct 2012, 8 (5): 284-6.
  7. Kobayashi S, Ichikawa G. Reactive arthritis induced by tonsillitis. a type of 'focal infection' Adv Otorhinolaryngol. 2011; 72: 79-82 (ISSN: 1662-2847)
  8. Singh AK, Misra R, Aggarwal A. Th-17 associated cytokines in patients with reactive arthritis / undifferentiated spondyloarthropathy. Clin Rheumatol. 2011; 30 (6): 771-6 (ISSN: 1434-9949)
  9. Ajene AN, Fischer Walker CL, Black RE. Enteric pathogens and reactive arthritis: a systematic review of campylobacter, salmonella and shigella-associated reactive arthritis. J Health Popul Nutr. , 2013, 31 (3): 299-307 (ISSN: 1606-0997)
  10. Inman RD . Innate immunity of spondyloarthritis: the role of toll-like receptors Adv Exp Med Biol 2009; 649 300-9

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Last updated: 2018-06-22 08:32