Reactive arthritis [archaic eponym: Reiter’s syndrome] systemic, seronegative spondyloarthropathy secondary to a precipitating infection.
Clinical manifestations include the classic triad of arthritis, urethritis and conjunctivitis. Symptoms of arthritis, range from arthralgia to debilitating polyarthritis and usually begin 2-4 weeks (but potentially up to 12 weeks) following an infection. Large joints such as the knees and ankles are most often affected. Inflammation at bony insertion sites of ligaments and tendons (enesthitis) is common.
- Ocular involvement (5-30%): Ranges from asymptomatic conjunctivitis to anterior uveitis or amnio conjunctivitis with severe ocular pain, redness, photophobia, and visual impairment (5%).
- Skin lesions (5-30%): Papulosquamous, psoriasiform lesions are more common in disease initiated by urogenital rather than enteric infections. Circinate balanitis (penis) and keratoderma blennorrhagica (soles of the feet and palms). Up to 30% of patients (usually following urogenital infection) will have superficial mucosal ulcers (buccal mucosa, palate, lips, or tongue).
- Risk: HLA-B27+ve individuals are at increased risk of sudden onset; severe symptoms and chronic persisting symptoms (though HLA-B27-ve individuals may still be affected). Immunosupression secondary to HIV and AIDS
- Common causative organisms: Chlamydia trachomatis, Campylobacter, Salmonella, Shigella and Yersinia
- Incidence: most common in men between ages 20 and 50.
1494 – DJ Allison postulated in 1980 that Christopher Columbus was the first European patient to develop reactive arthritis. After arriving in the New World, Columbus became ‘lame‘, potentially from an infection such as shigella flexneri, common in the tropics during this time. Traveling between Puerto Rico and Santa Domingo in September of 1494 he presented with a picture of fever, confusion, and severe arthritis of the lower extremities. In 1498, he had a relapse with fevers and acute articular symptoms. Six weeks thereafter, he developed articular inflammation and eye pain:
I have never had such affliction of my eyes with hemorrhage and pain as in this timeAllison, 1980
1776 – Stoll provided a good description of an association between arthritis, conjunctivitis, and urethritis following a diarrheic illness.
1818 – Sir Benjamin Collins Brodie (1783-1862) reported case histories of five patients with the symptom complex of urethral discharge, arthritis, and inflammation of the eyes. Further case descriptions were added in the 1836 4th edition of his textbook. Brodie clearly describes a disease pattern of recurrent episodes of acute urethritis, arthritis, and conjunctivitis. The arthritis affected the knees, ankles, and feet predominantly, but one patient had ‘swelling of nearly all the joints‘.
Brodie description of reactive arthritis 1818
Case 1: In a man aged 45, arthritis and conjunctivitis developed about a week after a urethral discharge. The joints of the feet and knees were first involved and later the right elbow and shoulder were painful but without “any perceptible swelling”. The attack lasted 6 to 7 weeks; 6 months later he had “another attack of the same complaint” lasting about 6 weeks, and after 3 months iritis occurred. He subsequently had a second attack of iritis 4 years later. [Brodie, 1818 p54-60][Cases 2-6: 1836:61-63]
1858 – Alfred Jean Fournier (1832-1914) described rhumatisme blenorrhagique, and presented evidence to differentiate between this form of arthritis from rheumatic fever. He presented case reports of 21 male patients; 10 with recurrent attacks, and thirteen with involvement of the eyes. [1868;1(1):120]
1904 – Markwald described a patient with both urethritis and conjunctivitis complicating dysenteric infection.
During World War I evidence was presented to establish the non-gonococcal origin of some of these cases and for the first time the triad of urethritis, arthritis, and conjunctivitis was separated into the venereal and the post-dysenteric forms.
1916 – Ludwig Waelsch (1867-1924) presented 44 cases of patients with abacterial urethritis of venereal origin, one with rheumatic pains of the knees and ankles, and one with conjunctivitis. [1916;123(5):1089-1105]
1916 – Noël Fiessinger and Emile Leroy presented 4 patients with conjunctivitis, urethritis and arthritis. They noted the triad of symptoms following bacillary dysentery. This report appeared eight days prior to the report of Reiter. Fiessinger and LeRoy called it the ‘conjunctival, urethral, synovial syndrome.‘
1916 – Whilst on the Balkan front, Reiter treated a German army officer with the triad of symptoms – conjunctivitis, urethritis and arthritis following dysentery. He originally deemed the disease to be casued by a spirochetal infection and suggested the name ‘Spirochetosis arthritica‘
Reiter Original description 1916
On Oct 14,1916, Lt N was admitted to the reserve hospital with a history of becoming ill with abdominal cramps, diarrhea, and bloody stools on the 21st of Aug. A discharge from the urethra and purulent conjunctival catarrh developed on the 29th of Aug. Rheumatic complaints appeared the following day. On the 31st of Aug the patient was admitted to a field hospital.
The findings on admission included: a red urethral meatus, purulent urethral discharge, dysuria, intense injection of purulent secretion of the conjunctivae, edema of the eyelids, swelling of the right knee with no active movement possible, passive movement produced severe pain. On the 2nd of Sept the evening temperature exceeded 39 C; both knees were swollen and very painful, no active motion was possible, discharge was diminishing. On the 10th of Sept the urethral secretions contained no gonococci. The following day the left foot was swollen. On the 15th of Sept the right elbow and the left hand were swollen, and while the conjunctivitis had disappeared, minute corneal opacities remained. On the 18th of Sept it was necessary to feed the patient because of severe limitation of joint function.
A pure culture of spirochaeta was obtained in the blood from venous puncture on the 21st of Oct. An injection of 0.3 gm of neosalvarsan was made on Nov 3 and Nov 6.
Characteristic of this disease, which I propose to call spirochetosis arthritica, is the course of fever which, if not influenced by aspirin, periodically fluctuated between 37 C in the morning and 39 C at night and is accompanied by regular night sweats. Outstanding clinical symptoms are the severe joint involvement, cystitis and conjunctivitis. For 13 weeks the clinical course remained unchanged, his condition was serious, patient being bedfast, debilitated, with decubiti, and completely unable to take care of himself, even needing assistance in eating. The skin was pale and the hemoglobin content was decreased to 60% to 70%. Salvarsan exerted no influence on the course of the illness. [Reiter, 1916] [/DDET]
1942 – Bauer and Engleman first used the term ‘Reiter’s syndrome‘, [Trans Assoc Am Physicians 1942;57:307–13.] leading to the terms subsequent widespread adoption.
2003 – Rheumatology journal editors agreed to expunge the term ‘Reiter’s syndrome‘ from the literature, substituting the term ‘reactive arthritis‘
- Sir Benjamin Collins Brodie (1783 – 1862)
- Alfred Jean Fournier (1832 – 1914)
- Hans Conrad Julius Reiter (1881–1969)
- Spirochetosis arthritica – original proposed term (Reiter, 1916)
- Fiessinger-Leroy syndrome (Fiessinger-Leroy, 1916)
- Stoll-Brodie-Fiessinger-LeRoy syndrome (Iglesias-Gammara, 2005)
- Archaic: Reiter’s disease (English literature); Reiter’s Syndrome (North America/Latin America) – (rescinded 2003)
- Stoll M. De l’arthrite dysenterique. [Recount par Huette] Archives générales de médecine. 1869;14:129-130.
- Brodie B. Pathological and Surgical Observations on Diseases of the Joints. Longman. 1818 [Case 1: 54-60][Case 2-5: 60-63] and [Case 6: 1836:61-63]
- Fournier A. Le rhumatisme blenorrhagique. Annales de dermatologie et de syphiligraphie (Paris). 1868;1(1):120, 161, 289, 319.
- Markwald B. Ueber seltene Complicationen der Ruhr. Zeitschrift für klinische Medizin. 1904;53:321
- Waelsch L. Über chronische nicht gonorrhoische Urethritis. Archiv für Dermatologie und Syphilis (Berlin) 1916;123(5):1089-1105.
- Reiter H. Ueber eine bisher unerkannte Spirochäteninfektion (Spirochaetosis arthritica) [About an as yet unrecognized spirochete infection] Deutsche medizinische Wochenschrift. 1916;42(50):1535-1536.
- Fiessinger N, Leroy E. Contribution à l’étude d’une épidémie de dysenterie dans la Somme. Bulletins et mémoires de la Société Médicale des Hôpitaux de Paris. 1916;40:2030-2069.
- Allison DJ. Christopher Columbus: first case of Reiter’s disease in the old world? Lancet. 1980;2(8207):1309. [PMID 6108485]
- Iglesias-Gammara A, Restrepo JF, Valle R, Matteson EL. A Brief History of Stoll-Brodie-Fiessinger-Leroy Syndrome (Reiter’s Syndrome) and Reactive Arthritis with a Translation of Reiter’s Original 1916 Article into English. Cur Rheumatol Rev 2005;1:71–79
- Wu IB, Schwartz RA. Reiter’s syndrome: the classic triad and more. J Am Acad Dermatol. 2008 Jul;59(1):113-21 [PMID 18436339]