Published on 18/03/2015 by admin
Filed under Dermatology
Last modified 18/03/2015
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Sara Samimi, Leslie Castelo-Soccio and Abby S. Van Voorhees
Evidence Levels: A Double-blind study B Clinical trial ≥ 20 subjects C Clinical trial < 20 subjects D Series ≥ 5 subjects E Anecdotal case reports
Reactive arthritis (ReA) is one of the reactive forms of seronegative spondyloarthropathies. It is both a genetically determined and immune-mediated disease that primarily affects the skin and joints 2 to 4 weeks after an enteric or urogenital infection. Implicated gastrointestinal pathogens include Yersinia, Salmonella, Shigella, Campylobacter, and Clostridium difficile; implicated urogenital pathogens include Chlamydia trachomatis and Ureaplasma urealyticum. Rarely, ReA can manifest after a respiratory infection with Chlamydia pneumoniae or group A β-hemolytic Streptococcus.
ReA is characterized by a triad of urethritis, conjunctivitis, and oligoarthritis. The classic skin manifestations include keratoderma blennorrhagica and circinate balanitis. Erythema nodosum can also occur and is more common in the setting of a Yersinia infection. Additional extra-articular findings include enthesitis, tendinitis, bursitis, conjunctivitis, anterior uveitis, and keratitis. ReA was formerly known as Reiter syndrome, but was renamed when the Nazi war crime past of Hans Reiter was revisited.
The mucocutaneous lesions of uncomplicated ReA are usually self-limited and clear within a few months. Severe, extensive and chronic cutaneous presentations, which are more common in the setting of HIV infection, are generally treated in the same manner as pustular psoriasis. Initial therapy for limited skin disease includes topical steroids, topical vitamin D preparations, tacrolimus, and tazarotene. Second-line agents include UVB and systemic retinoids. Severe disease can be treated with psoralen plus UVA (PUVA) and immunosuppressive agents such as methotrexate and cyclosporine. Anti-tumor necrosis factor (TNF) agents have also been used successfully in patients with refractory disease as well as those with HIV.
The effects of short-term and long-term antibiotic therapy for reactive arthritis are controversial. While there is some evidence that antibiotics may be beneficial during the infectious phase before arthritis has developed, it is not clear whether the introduction of antibiotics after the development of arthritis will modify the disease course. One large double-blind, placebo-controlled study suggests no effect, but another small study reports a beneficial effect of combination treatment with doxycycline and rifampin for chronic spondyloarthritis. If the inciting organism is documented by culture or PCR, antibiotics are indicated. The true benefit of antibiotics, their dose and duration remains to be clarified. However, when evaluating a patient with reactive arthritis after a urogenital infection, it is also important to consider treatment of the patient’s partner for further disease prevention.
ReA in HIV-infected individuals may be more severe and progressive, being refractory to treatment. However, one report describes ReA as part of immune reconstitution syndrome that is rapidly responsive to a 2-week course of doxycycline.
The symptoms of arthritis and inflammation of the peripheral ligamentous or muscular attachments (enthesis) usually dictate the focus of treatment in most patients. Non-steroidal anti-inflammtory drugs (NSAIDs) are the first-line therapy. Corticosteroids injections can provide temporary relief of the pain caused by arthritis or bursitis while oral corticosteroids may also be beneficial when severe. Sulfasalazine and methotrexate have been shown to be effective and well tolerated in cases refractory to both NSAIDs and steroids. TNF inhibitors have also shown efficacy in treating severe disease.
Transient and mild conjunctivitis does not require specific therapeutic intervention. Symptoms of eye pain or blurry vision require immediate referral to ophthalmology to determine if these symptoms are due to conjunctivitis or a more serious eye problem such as uveitis, iritis or keratitis. Treatment often involves topical steriods and systemic corticosteriods as well other immunosuppressive medications such as methotrexate.
Recent history of gastrointestinal or genitourinary infection or symptoms
Skin biopsy
Urinalysis
Urethral, cervical and stool cultures
Serum antibodies to chlamydia
Erythroctye sedimenation rate and C-reactive protein
HIV testing/status
Rheumatoid factor and ANA- negative in reactive arthritis
Synovial fluid analysis
Radiographic imaging
HLA-B27 typing
Ophthalmological slit lamp exam
ECG in chronic disease – conduction abnormalities
Carlin EM, Keat AC. Int J STD AIDS 2001; 12(Suppl 3): 94–102.
A recent history of urethral discharge and/or dysuria is present in approximately 80% of men with sexually acquired ReA. Conjunctivitis occurs in 20–50% of patients and iritis is seen in 2–11%. Slit lamp exam is necessary to differentiate between them. Posterior uveitis and optic neuritis have also been described.
Leirisalo-Repo M.Scand J Rheum 2005; 34: 251–9.
Reactive arthritis was previously known as Reiter disease or Fiessinger–Leroy disease. Gram-negative microbes (Yersinia, Salmonella, Shigella, Campylobacter) are the most common enteric infections associated with ReA. Chlamydia trachomatis is the most common cause of ReA following urethritis. Sixty to 80% of patients with ReA are HLA-B27 positive; the presence of HLA-B27 predicts a more severe and prolonged form of the disease.
Penn H, Kaat A. Medicine 2006; 34: 413–16.
Laboratory tests such as erythroctye sedimenation rate (ESR) and C-reactive protein (CRP) can be helpful in establishing the diagnosis; however, ESR and CRP will return to normal after the initial inflammation subsides. A normal value can be consistent with the diagnosis. Rheumatoid factor and ANA (antinuclear antibody) will be negative in ReA. Radiographs of affected joints are initially normal. Radiography may demonstrate peripheral joint erosions or sacroiliitis in chronic cases. Synovial fluid and tissue cultures are negative.
Wu I, Schwartz R. J Am Acad Dermatol 2008; 59: 113–21.
ReA in patients with HIV/AIDS is more recalcitrant to therapy. Antiretroviral therapy may improve symptoms of ReA. Caution is advised with use of immunosuppressive drugs such as systemic corticosteroids, methotrexate, and cyclosporine. Acitretin appears safe for use in patients who are immunocompromised and can improve skin and joint symptoms.
Hannu T. Best Prac Res Clin Rheum 2011; 25: 347–57.
Though not universally agreed upon, a proposed classification is presented. Major criteria: (1) arthritis with two or three of the following: asymmetric, mono- or oligoarthritis affecting predominantly the lower limbs; (2) preceding symptomatic infection with one or two of the following: enteritis or urethritis. Minor criteria: (1) evidence of a triggering infection; (2) evidence of persistent synovial infection. A definite diagnosis requires both major criteria and a minor criterion.
Uziel Y, Perl L, Barash J, Hashkes PJ. Pediatr Rheumatol Online J 2011; 9: 32.
Treatment of Skin Disease Comprehensive Therapeutic Strategies 4e
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