Published on 18/03/2015 by admin
Filed under Dermatology
Last modified 22/04/2025
This article have been viewed 1862 times
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.
Three patients, ages 6, 8, and 12, are described presenting with fever, arthritis and an elevated ASO titer. One did not have evidence of signs or symptoms consistent with acute rheumatic fever including erythema marginatum, chorea, subcutaneous nodules or cardiac murmurs. A diagnosis of post-streptococcal ReA can be made in the setting of an acute non-migratory arthritis, antecedent strep infection, and failure to fulfill the Jones criteria. While antibiotic prophylaxis is crucial in the setting of acute rheumatic fever, its use in post-streptococcal ReA is not as well defined.
Carter JD, Valeriano J, Vasey FB. J Rheumatol 2004; 31: 1973–80.
A prospective randomized study of 30 patients with chronic inflammatory arthritis without evidence of preceding inflammatory bowel disease, psoriasis, ankylosing spondylitis or dysentery. Patients received either doxycycline 100 mg twice daily or doxycycline 100 mg twice daily plus rifampin 600 mg daily. Patients in the combination group reported greater improvement in joint symptoms and swelling of joints.
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.
Rothe MJ, Kerdel FA. Int J Dermatol 1991; 30: 173–80.
Mucocutaneous lesions may necessitate only local care for mucosal erosions and topical steroids for psoriasiform lesions.
As treatment in ReA is typically directed towards the musculoskeletal component and urethritis, there is a paucity of studies designed for the treatment of cutaneous disease. However, despite the lack of controlled studies, topical steroids are accepted as first-line therapy for mild cutaneous lesions.
Volden G. Acta Derm Venereol 1992; 72: 69–71.
Two patients with skin lesions of reactive arthritis and 19 patients with palmoplantar pustulosis responded to clobetasol propionate lotion once weekly under occlusion. The mean interval to remission was 3 weeks for the skin lesions of ReA and 2.2 weeks for palmoplantar pustulosis.
Vaughan Jones SA, McGibbon DH. Clin Exp Dermatol 1994; 19: 430–3.
A case report of a 32-year-old male with AIDS whose psoriasiform lesions improved following 2 weeks of topical corticosteroids and a course of flucloxacillin.
Herrera-Esparza R, Medina F, Avalos-Diaz E. J Clin Rheumatol 2009; 15: 377–9.
A report of three patients with evidence of circinate balanitis refractory to systemic therapy with corticosteroids and sulfasalazine, but responsive to treatment with topical tacrolimus 0.1%.
Arora S, Arora G. Indian J Dermatol Venereol Leprol 2005; 71: 285–6.
A case report of a 6-year-old child with ReA whose primary keratoderma blennorrhagicum lesions were treated with topical salicylic acid and hydrocortisone with complete resolution in 3 weeks.
Thiers BH. J Am Acad Dermatol 1997; 37: S69–71.
A 47-year-old man with relapsing ReA, with pustules and hyperkeratotic plaques on his palms and soles, as well as circinate balanitis, responded to 14 days of doxycycline (100 mg twice a day) and topical calcipotriene.
Lewis A, Nigro M, Rosen T. J Am Acad Dermatol 2000; 43: 400–2.
A case report of a 64-year-old man with ReA who responded to daily application of tazarotene gel 0.1% to his soles.
Blanche P. Clin Exp Rheum 1999; 17: 105–6.
A case report of a 46-year-old patient with AIDs and ReA whose arthritis and skin lesions responded to 2 weeks of acitretin (25 mg daily). Therapy was continued for 5 months; a recurrence occurred several months after the acitretin was stopped despite maintenance on antiretroviral therapy. Acitretin was resumed resulting in prompt resolution of disease, and continued for 6 months. No recurrence was observed after 13 months.
Romani J, Puig L, Baselga E, De Moragas JM. Int J Dermatol 1996; 35: 484–8.
A retrospective review of seven HIV positive patients with Reiter’s like psoriasiform dermatitis. Etretinate alone and RePUVA (etretinate 1 mg/kg daily, 8-methoxypsoralen 0.6 mg/kg followed by UVA) were safe and effective in controlling skin disease. Methotrexate (15 mg weekly in three divided doses) was effective, but was complicated by hematologic toxicity in two patients. Cyclosporine (2.5 mg/kg daily) was moderately effective and was not associated with progression of AIDS.
Report of 2 cases. Louthrenoo W. J Rheumatol 1993; 20: 1243–6.
A report of two cases of HIV related ReA responding dramatically to 4 weeks of etretinate (0.5–1.0 mg/kg daily).
McGonagle D, Reade S, Emery P. Ann Rheum Dis 2001; 60(7): 696–8.
Case report of a 31-year-old HIV positive man with ReA with extensive polyenthesitis and osteitis. Patient’s arthritis worsened despite treatment including indomethacin, tramadol, and sulfasalazine but improved dramatically after antiretroviral treatment (lamivudine, ritonavir, and stavudine). Improvement was accompanied by a significant rise in CD4 T-lymphocyte counts.
Fischer T, Ramadori G. AIDS 1999; 13: 628–9.
Case report of a 38-year-old HIV positive male with viremia and psoriasis. Patient was started on multiple antiretroviral agents in addition to topical steroids and vitamin D3 analogs. Despite antiretroviral therapy, his viral load remained high and his psoriasis persisted. It was not until his viral load decreased below 400 that his skin lesions started to improve.
Lally EV, Ho G Jr. Semin Arthritis Rheum 1985; 15: 139–45.
A case report and review of the literature. Eighteen of 20 patients noted dramatic improvement in skin lesions within 2 weeks of receiving methotrexate; 15 of 20 patients had significant improvement in arthritis, although the response was generally slower. Methotrexate was generally well tolerated, but the drug had to be discontinued in three cases due to adverse effects. Methotrexate was used for exacerbations and then was discontinued after clinical improvement. The usual dosage was 10–50 mg/week administered either orally or parenterally.
Berenbaum F, Duvivier C, Prier A, Kaplan G. Br J Rheumatol 1996; 35: 295.
A case report of a 37-year-old man with AIDS and severe ReA who responded to prednisone 20 mg daily and methotrexate 20 mg/week. This was combined with antiretroviral therapy, chemoprophylaxis of infection, and aggressive therapy of Kaposi’s sarcoma without exacerbation of his AIDS.
Kiyohara A, Ogawa H. J Am Acad Dermatol 1997; 36: 482–3.
A case report of a 48-year-old man with post-chlamydia ReA not responsive to topical steroids and etretinate treated successfully with 5 mg/kg daily cyclosporine therapy that was slowly tapered. No recurrence of the disease noted at 18 months.
Gaylis N. J Rheumatol 2003; 30: 2.
A case report of a 41-year-old man with ReA who responded to infliximab, methotrexate, and systemic corticosteroid treatment regimens. During therapy his arthritis resolved, as did the onycholysis and keratoderma blennorrhagica of the soles. The patient was able to discontinue systemic corticosteroids and was maintained on intravenous infliximab at a dose of 300 mg (3 mg/kg) every 6 to 7 weeks and intramuscular methotrexate at a dose of 15 mg/week for 18 months without a decrease in his CD4 cells or a rise in his viral load.
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.
Gill H, Majithia V. Clin Rheumatol 2008; 27: 121–3.
A case report of a 28-year-old man with HIV with ReA complicated by circinate balanitis and arthritis, as well as onycholysis and keratoderma blennorrhagica who did not respond to aggressive treatment with NSAIDs, prednisone (60–20 mg/day), and methotrexate (15 mg/week) for 3 months. He was treated with infliximab 200 mg (3 mg/kg) intravenously with rapid improvement of skin lesions and arthritis. This regimen was well tolerated. Patient was subsequently lost to follow-up.
Sanchez-Cano, D, Callejas-Rubio, JL, Ortego-Centeno, N. J Clin Rheum 2007; 13: 176.
A case report describing a 21-year-old female with oligoarthritis affecting the lower extremities after pharyngitis 2 weeks before the onset of arthritis. NSAIDs, prednisone (1 mg/kg/day), hydroxychloroquine (6 mg/kg/day), and methotrexate (25 mg/weekly) were not effective. Clinical response was achieved 8 weeks after introduction of adalimumab (40 mg subcutaneously every 2 weeks) and was maintained. Steroids and methotrexate were discontinued; no side effects were observed after 1 year of treatment with adalimumab.
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.
Wechalekar M, Rischmueller M, Whittle S, Burnet S, Hill C. J Clin Rheumatol 2010; 16: 79–80.
A case report of a 25-year-old female with an 11-month history of progressive oligoarthritis and increasing CRP after Chlamydia trachomatis infection. She failed treatment with azithromycin, NSAIDs, corticosteroid injections, methotrexate, sulfasalazine, and hydroxychloroquine. Subsequently, infliximab at a dose of 6 mg/kg was given. After the first two doses her symptoms resolved with normalization of her CRP. Methotrexate, sulfasalazine, and hydroxychloroquine were tapered without evidence of recurrent disease.
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.
Thomas-Pohl M, Tissot A, Banal F, Lechevalier D. Joint Bone Spine 2012; 79: 524.
A case report describing a 32-year-old male with acute febrile polyarthritis 1 month after gastrointestinal infection. After failing NSAIDs, ofloxacin (200 mg twice daily for 16 days), rifampin 300 mg twice daily for 4 days), and methylprednisone, he was given infliximab (5 mg/kg). Immediately after the infusion, he reported a decrease in pain with improvement of inflammatory markers.
Treatment of Skin Disease Comprehensive Therapeutic Strategies 4e
WhatsApp us
Topical steroids
Calcipotriene (calcipotriol)
Tazarotene
Tacrolimus
Systemic retinoids
UVB/PUVA
Antiretroviral therapy
Methotrexate
Cyclosporine
TNF inhibitors
