Reactive Arthritis

Reactive arthritis REF: Harrison’s Principles of Internal Medicine 17′ ed-chapter 318

Reactive Arthritis:

Associated with HLA-B27

• Etiology and Pathogenesis:

Of the four Shigella species S. sonnei, S. boydii, S. flexneri, and S. dysenteriae, S. flexneri has most often been implicated. Other bacteria identified definitively as triggers of ReA include several Salmonella spp., Yersinia enterocolitica, pseudotuberculosis, Campylobacter jejuni, and Chlamydia trachomatis.

• Clinical Features

The clinical manifestations of ReA constitute a spectrum that ranges from an isolated, transient monarthritis to severe multisystem disease. The joints of the lower extremities, especially the knee, ankle, and subtalar, metatarsophalangeal, and toe interphalangeal joints, are the most common sites of involvement, Dactylitis, or “sausage digit,” a diffuse swelling of a solitary finger or toe, is a distinctive feature of ReA. Tendinitis and fasciitis are particularly characteristic lesions

Urogenital lesions: In males: urethritis may be marked or relatively asymptomatic. Prostatitis is also common. In Females: cervicitis or salpingitis

Ocular: transient, asymptomatic conjunctivitis, anterior uveitis

Mucocutaneous lesions: Oral ulcers, the characteristic skin lesions- keratoderma blenorrhagica, consist of vesicles that become hyperkeratotic, ultimately forming a crust before disappearing. They are most common on the palms and soles, Lesions on the glans penis, termed circinate balanitis, are common

• Management:

Most patients with ReA benefit to some degree from NSAIDs, although acute symptoms are rarely completely ameliorated, and some patients fail to respond at all. Indomethacin, 75-150 mg/d in divided doses, is the initial treatment of choice, but other NSAIDs may be tried.

Prompt, appropriate antibiotic treatment of acute chlamydial urethritis or enteric infection may prevent the emergence of ReA. However, several controlled trials have failed to demonstrate any benefit for antibiotic therapy that is initiated after onset of arthritis

Chlamydia [Ref: Harrison 17/e p2113; http://www.emedicine.com/derm/TOPIC207.HTM; http://www.entedicine.com/med/TOPIC1998.11TM%5D

• Reactive arthritis is a systemic disorder of unknown etiology that is defined by the development of conjunctivitis, urethritis, arthritis, and mucocutaneous lesions following an episode of infection elsewhere in the body.
• In 1916, Hans Reiter described the triad of nongonococcal urethritis, conjunctivitis, and arthritis in a young German officer with bloody dysentery.The classic triad of the disease, namely urethritis, arthritis, and conjunctivitis, is present in only one third of the patients.
• Reactive arthritis is frequently associated with the human leukocyte antigen B27 (1-ILA-B27) haplotype.
• The etiology of reactive arthritis remains uncertain. The most accepted theory about the pathophysiology of reactive arthritis involves initial activation by a microbial antigen, followed by an autoimmune reaction that involves the skin, eyes, and joints.
• Two forms are recognized: a sexually transmitted form and a dysenteric form. Gastrointestinal infections with Shigella, Salmonella, and Campylobacter species and other microorganisms, and genitourinary infections especially with Chlamydia trachomatis have been found to trigger reactive arthritis.
• Young children tend to have the post dysenteric form, whereas adolescents and young men are most likely to acquire reactive arthritis after they have urethritis.
• It’s not clear which organism is most commonly associated with reactive arthritis. Both Shigella and Chlamydia appear to he most common. After going through many articles from journals on the net, Chlamydia appears to he the most common. We would prefer to go with Chlamydia. (However if any one finds a reliable reference documenting the most common organism, please mail us at our email id.
• The article on Reactive Arthritis in the journal “Best Practice & Research Clinical Rheumatology” Vol. 20, No. 6, pp. 1119e1137, 2006 writes- “The prevalence is estimated to be 30-40 cases per 100,000 adults; the annual incidence is estimated to be 4.6/100,000 _.for Chlamydia-induced arthritis and 5/100,000 _.for enterobacteria-induced reactive arthritis.4,5 However, real numbers may be significantly higher^?
• The following article “Frequency of triggering bacteria in patients with reactive arthritis and undifferentiated oligoarthritis and the relative importance of the tests used for diagnosis” in Ann Rheum Dis. 2001 April; 60(4): 337­343 at the following website- http://www.pubmedcentralmih.gov/articlerenderfcgi?artid=1753604 writes its conclusion as:

“CONCLUSIONS—Chlamydia trachomatis, yersinia, and salmonella can be identified as the causative pathogen in about 50% of patients with probable or possible ReA if the appropriate tests are used.”

Ureaplasma urealyticum

Agents responsible for Reiter’s syndrome:

• Salmonella enteritidis
• S. typhimurium
• S. heidelberg
• Yersinia enterocolitica
• Y. pseudotuberculosis
• Campylobacter fetus
• Shigella flexneri
• Genitourinary pathogens (such as Chlamydia or Ureaplasma urealyticum)

Reactive arthritis is most common among young men (except after Yersinia infection) and has been linked to the HLA-B27 locus as a potential genetic predisposing factor. Patients report painful, asymmetric oligoarthritis that affects mainly the knees, ankles, and feet.

Low-back pain is common, and radiographic evidence of sacroiliitis is found in patients with long-standing disease. Most patients recover within 6 months, but prolonged recurrent disease is more common in cases that follow chlamydial urethritis.

Migratory polyarthritis and fever constitute the usual presentation of acute rheumatic fever in adults. This presentation is distinct from that of post-streptococcal reactive arthritis, which also follows infections with group A Streptococcus but is not migratory, lasts beyond the typical 3-week maximum of acute rheumatic fever, and responds poorly to aspirin.

Ref: Madoff L.C. (2012). Chapter 334. Infectious Arthritis. In D.L. Longo, A.S. Fauci, D.L. Kasper, S.L. Hauser, J.L. Jameson, J. Loscalzo (Eds), Harrison’s Principles of Internal Medicine, 18e.

“The prevalence of ractive arthritis is estimated to be 30-40 cases per 100,000 adults; the annual, incidence is estimated to be 4.6/100,000 for Chlamydia-induced arthritis and 5/100,000for enterobacteria-induced reactive arthritis.”;From  Reactive Arthritis in the journal “Best Practice & Research Clinical Rheumatology” Chlamydia appears to be the most common.

Think Detail:

Reactive arthritis is a systemic disorder ,defined by the development of conjunctivitis, urethritis, arthritis, and mucocutaneous lesions following an episode of infection elsewhere in the body.

In 1916, Hans Reiter described the triad of nongonococcal urethritis, conjunctivitis, and arthritis in a young German officer with bloody dysentery.

Triad: The classic triad of the disease, namely

• Arthritis

• Urethritis

• Conjunctivitis

Pathophysiology:The etiology of reactive arthritis remains uncertain. The most accepted theory is, initial activation by a microbial antigen, followed by an autoimmune reaction that involves the skin, eyes, and joints. Human leukocyte antigen B27 (HLA-B27) haplotype is frequently associated.

Two forms are recognized: a sexually transmitted form and a dysenteric form.

• Gastrointestinal infections with Shigella, Salmonella, and Campylobacter species and other microorganisms.Young children tend to have the post dysenteric form.

• Genitourinary infections especially with Chlamydia trachomatis have been found to trigger reactive arthritis.Adolescents and young men are most likely to acquire reactive arthritis after they have urethritis.

Clinical features: The arthritis is most commonly asymmetric and frequently involves the large weight-bearing joints (chiefly the knee and ankle); Systemic symptoms including  fever and weight loss are common at the onset of disease. The mucocutaneous lesions may include balanitis, stomatitis, and keratoderma blennorrhagicum, indistinguishable from pustular psoriasis. Signs of the disease disappear within days or weeks, the arthritis may persist for several months or become chronic.

Investigations:

Sacroiliac as well as the peripheral joints may show progressive joint disease in radiograph.Synovial fluid from affected joints is culture-negative.

Treatment:

NSAIDs have been the mainstay of therapy. Antibiotics do not alleviate symptoms. Patients who do not respond to NSAIDs may respond to sulfasalazine, 1000 mg orally twice daily, or to methotrexate, 7.5–20 mg orally per week.

Reference:

Cleveland Clinic, Intensive Review of Internal Medicine, edited by James K. Stoller,5th Edition,Page 345

D i.e. Chlamydia

• Reactive arthritis (ReA) is most commonly triggered by Shigella (usually flexneriQ > sonnei, boydii, dysenteriae) > Chlamydia trachomatisQ> Salmonell, Yersinia (enterocolitica, pseudotuberculosis), Campylobacter jejuni > Clostridium difficile, Campylobacter coli, toxic E.coli > Ureoplasma ureallyticum, Mycoplasma genitalium > Chlamydia pneumoniae URTI
• Most common cause of ReA are Shigella flexneri (enteric) and Chlamydia trachomatis (genito urinary /venereal) infectionsQ

C. Keratoderma mostly on glans

Answer is D (Chlamydia):

Amongst the options provided Chlamydia is the most commonly implicated agent in Reactive arthritis.

`Chlamydia Trachomatis is by far the most common cause of urethritis and of reactive arthritis following urethritis.

Answer is C (Reactive Arthritis):

Keratoderma Blenorrhagica is the charachteristic skin lesion seen in patients with Reactive Arthritis.

‘The charachteristic skin lesions in Reactive Arthritis, Keratoderma Blenorrha2ica, consist of vesicles that become hyperkeratotic, ultimately forming a crust before disappearing. In patients with HIV infection, these lesions are often extremely severe and extensive sometimes dominating the clinical picture ‘-

Ans. D: All of the above

Ans:C.)Reactive Arthritis.

The given image shows the presence of Keratoderma Blenorrhagica.

Keratoderma Blenorrhagica is the charachteristic skin lesion seen in patients with Reactive Arthritis.

‘The characteristic skin lesions in Reactive Arthritis, Keratoderma Blenorrhagica, consist of vesicles that become hyperkeratotic, ultimately forming a crust before disappearing. In patients with HIV infection, these lesions are often extremely severe and extensive sometimes dominating the clinical picture ‘-