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

  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]

  […] enteritis caused by salmonella, shigella, campylobacter, or yersinia; - urogenital infection (Chlamydia trachomatis) may also be involved; - yersiniosis: - more likely to have atypical presentation w/ pharyngitis & cervical adenopathy resembling rheumatic fever [wheelessonline.com]

• 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]

  Some affected individuals may develop headaches, hiccupping, and a general feeling of poor health (malaise). [rarediseases.org]

  Despite regular treatment, his joints became deformed and painful, and the whole course was punctuated with recurrences of skin lesions associated with fever, chills, malaise, headache etc. [ijdvl.com]

• Sausage Toe

  Clinical features Patients present with asymmetric oligoarthritis Articular and extra-articular manifestations are similar regardless of organisms causing this disorder Synovitis of digital tendon sheath produces sausage fingers or toes, causes spurs [pathologyoutlines.com]

  toes Associated with antecedent Genitourinary and GI infections. [masterofmedicine.com]

  Swollen “sausage” toe (top) and inflamed ankle (bottom) in a patient with postdysentery reactive arthritis on initial presentation. FIGURE 1. [aafp.org]

• Relapsing Polychondritis

  We describe a case of relapsing polychondritis associated with Reiter's Syndrome in a 46-year-old white man. [ncbi.nlm.nih.gov]

  영문 국문 regulatory T cell 조절 T 세포 rehabilitation-therapy 재활치료 Reiter’s syndrome 라이터증후군 relapse 재발 relapsing polychondritis 재발다발연골염 remission 관해 remodelling 리모델링 removal of loose bodies 유리체제거술 renal crisis 콩팥위기 renal tubular acidosis 신세관산증(콩팥요세관산증) resection [rheum.or.kr]

• Upper Abdominal Pain

  Some affected individuals may have symptoms associated with pelvic inflammatory disease including fever, vaginal discharge, and lower abdominal pain. Lower abdominal pain may precede, follow, or occur simultaneously with upper abdominal pain. [rarediseases.org]

• Tachycardia

  Apart from tachycardia of 114 beats / min, other systemic examinations were normal. Cardiac auscultation was normal. [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.[14] Some patients suffer serious gastrointestinal problems similar to those of [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]

  Reiter syndrome and keratosis blennorrhagica.-AMA Arch. Dermatol., 81 4. 551-555, 1959. La queratosis blenorrágica no se distingue del síndrome de Reiter con queratosis más que por la presencia de gonococo en la secreción uretral. [efdal.org]

  Skin rashes on the soles of the feet and, less often, on the palms of the hands or elsewhere may also occur; these rashes are called keratoderma blennorrhagicum (or keratosis blennorrhagica) and are similar to psoriasis. [foodpoisonjournal.com]

• Eczema

  We report the case of an HIV-positive patient with secondary syphilis, scaling palmoplantar keratoderma, scrotal eczema, balanitis and urethritis mimicking Reiter's syndrome. [ncbi.nlm.nih.gov]

• Arthritis

  […] the onset of arthritis; - urethritis is usually mild and painless with frequent nonpurulent urethral discharge; - severity of inciting infection does not correlate w/ intensity of arthritis which tends to appears one or two weeks later; - viable organisms [wheelessonline.com]

  Definition/Description Reiter’s Syndrome (now known as Reactive Arthritis) develops in response to an infection and characterized by a triad of arthritis, conjunctivitis, and nonspecific urethritis. [physio-pedia.com]

  Gonococcal arthritis. Gout. Inflammatory bowel disease. Psoriatic arthritis. Rheumatic fever. Rheumatoid arthritis. Septic arthritis. [patient.info]

  Although the triad of urethritis, conjunctivitis and arthritis is now rather well known, the high incidence of mucocutaneous lesions is not generally appreciated. [annals.org]

  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]

• 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]

  The doctor will look for skin rashes, gastrointestinal or urinary problems, eye inflammation, mouth sores, and involvement of joints of the arms or legs, in addition to back pain. [hss.edu]

  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]

• Heel Pain

  Heel pain was a prominent symptom in 10, with periostitis of other sites in 5, and "sausage digits" in 8. Mucocutaneous lesions occurred in 1 and significant weight loss in 6. Only 2 had sacro-illiitis. Chronicity has characterized the course in 12. [annals.org]

  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]

  Enthesitis can involve the Achilles tendon resulting in heel pain. Not all affected persons have all the manifestations. [pharmatutor.org]

  […] worse with rest; occasionally heel pain, red eyes, low grade fever; rarely high fever, weight loss, severe malaise, fatigue History of Present Illness (HPI): typically acute onset 1-4 weeks after venereal infection or gastroenteritis, venereal infection [enotes.tripod.com]

  Remember that in test examinations, they may test on Achilles tendon pain (Achilles tendonitis) with heel pain (plantar fasciitis) and its association with Reiter’s syndrome. [youtube.com]

• Low Back Pain

  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]

  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]

  Low back pain. The pain tends to be worse at night or in the morning. When to see a doctor If you develop joint pain within a month of having diarrhea or a genital infection, contact your doctor. [mayoclinic.org]

  Pain, inflammation and swelling affect the joints in the low back, pelvis, fingers, feet and toes. Psoriatic arthritis. [laserspineinstitute.com]

• Arthralgia

  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]

• 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]

  An ophthalmologist confirmed that the left eye pain resulted from iritis and episcleritis. [wwwnc.cdc.gov]

  He states he has also had some white discharge from his penis with pruritis and pain during urination. His history is significant for use of eye drops because he states his eye has been red and painful over the last week. [medbullets.com]

• Anterior Uveitis

  Plus Two of the following Recurrent Genital Ulceration Ocular lesions-Anterior uveitis,Posterior Uveitis,cells in vitreous,Retinal Vasculitis Skin Lesions [masterofmedicine.com]

  Review of case records of a patient presenting with incomplete Reiter's syndrome which included a reactive arthritis with keratoconjunctivitis and anterior uveitis. [ncbi.nlm.nih.gov]

• 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 In men: Burning sensation when passing [lahey.org]

  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]

• Photophobia

  Ophthalmologic problems include conjunctivitis with erythema, burning, tearing, and photophobia. Iritis and uveitis are less common. [orpha.net]

  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]

  Photophobia may be a symptom resulting from the pupillary and iris abnormalities. The most commonly recognized clinical manifestations of ARS are the iris correctopia/atrophy, and posterior embryotoxon.(figures 1,2). [eyewiki.aao.org]

• Blepharitis

  Squamous blepharitis and mild angular conjunctivitis were present. Circinate balanitis and oral lesions were conspicuous by their absence. [ijdvl.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]

  His diarrhea and dysuria resolved, but intra‐articular steroid injections were required for relief of his shoulder symptoms. [academic.oup.com]

  Urinary symptoms (polyuria and dysuria) are often the first manifestation. Prostatitis in men, and cervicitis, salpingitis and/or vulvovaginitis in women are frequent findings. [orpha.net]

  The eldest had dysuria and a history suggesting keratoderma blennorrhagica. All had HLA-B27 antigen. Inclusions indicative of chlamydial infection were seen in assays from the two youngest boys. [jamanetwork.com]

  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]

• Urethral Discharge

  […] the onset of arthritis; - urethritis is usually mild and painless with frequent nonpurulent urethral discharge; - severity of inciting infection does not correlate w/ intensity of arthritis which tends to appears one or two weeks later; - viable organisms [wheelessonline.com]

  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]

  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]

• Penile Lesion

  His penile lesion was treated with a topical steroid. His diarrhea and dysuria resolved, but intra‐articular steroid injections were required for relief of his shoulder symptoms. [academic.oup.com]

  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]

• Pelvic Pain

  Dermatologic manifestations; : skin lesions of the glans resembling psoriasis (balanitis circinata; ); hyperkeratinization of the palms and soles (keratoderma blenorrhagicum) Symptoms from preceding infection Diarrhea Urogenital tract symptoms (dysuria, pelvic [amboss.com]

  Prostate-specific antigen test in diagnostic evaluation of chronic prostatitis/chronic pelvic pain syndrome. Urology. 2006;67:337–342. [PubMed] [Google Scholar] 21. Hochreiter WW. [ncbi.nlm.nih.gov]

  However, urethritis, whether infectious or reactive, may cause significant pelvic pain or dysuria, and complications include prostatitis in men, and vaginitis, cervicitis, salpingitis, and pelvic inflammatory disease in women. [dermatologyadvisor.com]

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.

• 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 prevalence of ReA may be relatively high among patients with AIDS, especially men who are seropositive for HLA-B27. ReA develops in almost 75% of HIV-positive men with HLA-B27. [emedicine.com]

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.

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).

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:

• Shigella flexneri which may present as bacillary dysentery.
• Neisseria gonorrhoeae that causes venereal gonorrhea.
• Ureaplasma urealyicum found in urinary tract infections.
• Chlamydia trachomatis which is one of the main cause of sexually transmitted disease, where the L2b serotype predispose to Reiter’s syndrome [2].
• Salmonellosis with Salmonella enteritica with serovars typhimurium and entiritidis are primary gut infection that initiates the immune response in reactive arthritis [3].
• Mycobacteria tuberculosis
• Cyclospora
• Yersinia enterocolytica causing dysentery.
• Clostridium defficile that cause pseudomembranous colitis.
• Beta-hemolytic Streptococcal veridans (A group) which possesses the highest immune response [4].

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].

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).

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.

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.

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.

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