Reactive arthritis

Published on 18/03/2015 by admin

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Reactive arthritis

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

image

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.

Management strategy

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.

Antibiotic use

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.

Other modalities

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.

Specific investigations

Antibiotic use

Combination antibiotics as a treatment for chronic Chlamydia-induced reactive arthritis: a double-blind, placebo controlled, prospective trial.

Carter JD, Espinoza LR, Inman RD, Sneed KB, Ricca LR, Vasey FB, et al. Arthritis Rheum 2010; 62: 1298–307.

A prospective randomized trial of 42 patients who had evidence of chronic post-chlamydial reactive arthritis. Patients were randomized to receive either doxycycline and rifampin (12 patients), azithromycin and rifampin (15 patients), or matching oral placebos (15 patients) for 6 months; 22% of subjects on combination antibiotic therapy achieved complete resolution of their symptoms in comparison to 0% of those receiving placebo. An increased number of patients in the antibiotic group became PCR negative for Chlamydia compared to the placebo group.

First–line therapies

Cutaneous disease
image Topical steroids C
image Calcipotriene (calcipotriol) E
image Tazarotene E
image Tacrolimus E

image

Second-line therapies

Cutaneous disease
image Systemic retinoids D
image UVB/PUVA D
image Antiretroviral therapy E

image

Third-line therapies

Cutaneous disease
image Methotrexate C
image Cyclosporine E
image TNF inhibitors C

image

Decreased pain and synovial inflammation after etanercept therapy in patients with reactive and undifferentiated arthritis: an open-label trial.

Flagg S, Meador R, Schumacher HR. Arthritis Rheum 2005; 53: 613–17.

Describes a 6-month open-label trial of 16 patients with undifferentiated or reactive arthritis treated with etanercept (25 mg subcutaneous twice weekly). Seven patients met the criteria for ReA and nine had a similar pattern of arthritis without evidence for infection. Ten patients completed the trial. Three patients tested positive for HLA-B27. All patients had been on NSAIDs and 11 had been treated with sulfasalazine and/or methotrexate. Of the 10 completers, nine were classified as responders with less tender joints and decreased swelling of joints. The tenth had improvement in pain but no change in the number of tender or swollen joints.

The use of anti-tumor necrosis factor therapy in HIV-positive individuals with rheumatic disease.

Cepeda E, William F, Ishimori M, Weisman M, Reveille J. Ann Rheum Dis 2008; 67: 710–12.

Eight HIV positive patients with rheumatic diseases (two with rheumatoid arthritis, three with psoriatic arthritis, one with ReA, one with undifferentiated spondyloarthritis, and one with ankylosing spondyloarthritis) refractory to disease modifying antirheumatic drugs who has a CD4 count >200 mm3 and a HIV viral load of <60 000 copies/mm3 and no active concurrent infections were treated with anti-TNF blockers. No significant clinical adverse effect was noted over 28 months. CD4 counts and HIV viral loads remained stable. Three patients on etanercept and two on infliximab had sustained improvement in their rheumatic disease.

Safety and efficacy of anti-tumor necrosis factor α therapy in ten patients with recent-onset refractory reactive arthritis.

Meyer A, Chatelus E, Wendling D, Berthelot JM, Dernis E, Houvenagel E, et al. Arthritis Rheum 2011; 63: 1274–80.

A retrospective review of anti-TNF-α therapy in 10 patients with evidence of new onset ReA. Five patients were given infliximab (four received 5 mg/kg and one received 3 mg/kg), four etanercept (50 mg/week), and one adalimumab (40 mg every 2 weeks). Concomitant therapies included NSAIDs (seven patients), oral corticosteroids (eight patients), methotrexate (seven patients), and sulfasalazine (three patients). No severe adverse events were reported during the median 20.6 months. Nine of 10 patients had improvement in their rheumatic symptoms with a median of 15 days for >30% improvement in their pain score and tender joint count, and a median of 33 days for >30% improvement in their swollen joint count. Improvement of anterior uveitis (in five patients after 6 months) and cutaneous manifestations were also noted.

[/level-membership-for-dermatology-category][not-level-membership-for-dermatology-category]

Reactive arthritis

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

image

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.

Management strategy

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.

Antibiotic use

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.

Other modalities

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.

Specific investigations