Reactive arthritis ( ReA ) is one of the seronegative spondyloarthropathies ( these include ankylosing spondylitis , psoriatic arthritis , Inflammatory bowel disease and undifferentiated SpA – closely linked with HLA-B27 gene ) It is a sterile inflammation of the synovial membranes , fascia and tendons triggered by an infection at a distal site ( BASH National Guideline on the Management of Sexually Acquired Reactive Arthritis 2019 )
Due to enteric infection with gastrointestinal pathogens as Salmonella , Shigella , Campylobacter
ReA is a group of conditions -associated with HLA-B27 gene – ie these conditions manifest some shared rheumatic features as enthesitis , sacroiliitis , peripheral arthritis and associated extra-articular lesions particularly psoriasis , uveitis and inflammatory bowel disease Previously described as Reiter’s disease with classic triad of arthritis , urethritis and conjunctivitis ReA is precipitated by an infection at a distant site and genetic susceptibility , marked by possession of the HLA B27 gene It is thought an aberrant immune response to the infectious pathogens leads to ReA ( proliferative T cell response targets autoantigens causing inflammation and tissue destruction ) Chlamydophila pneumoniae – is also an accepted cause of ReA , however it is less frequent than that caused by C.trachomatis Pathogenesis of ReA is not fully understood
Worldwide incidence of ReA is about 30- 200 cases per 1000,000 population ( this varies among different geographic locations ) True incidence is possibly underestimated as milder forms often go unrecognised More common in Caucasians ( possibly due to higher incidence of HLA-B27 gene ) Relatively rare occurrence , more common in adult males and in 2nd and 3 rd decades of life Most frequent age of onset is in early 20s , but it has also been recognised from childhood into the 6th decade
Gram negative bacilli members of the Enterobacteriaceae as Salmonella , Yersinia , Campylobacter , Shigella , Chlamydia trachomatis ( responsible for 35 % to 70 % ) of cases with SARA Chlamydia pneumoniae , Clostridium difficile , vibrio parahaemolyticus , Mycobacterium bovis , species of Mycoplasma e.g Ureaplasma urealyticum , Mycobacterium tuberculosis
diverse clinical manifestations which can involve the peripheral jt, spine , skin , eyes , digestive tract & other systems ReA can happen several weeks ( typically 1-6 ) after a gastrointestinal or urogenital infection Symptom severity and frequency is increased in patients who are HLA-B27 positive Patiens may also c/o constitutional symptoms as malaise , fatigue ,weight loss and fever ReA was classically recognised as ‘ Cant see ( ocular ) , cant pee ( genitourinary ) , cant climb a tree ( musculoskeletal ) Data has shown that ReA is often under-diagnosed or misdiagnosed Enquire if other family members have sufferred with other spondyloarthropathies
Symptoms develop several days to weeks after the initial infection Arthritis happens in about 95 % of cases pain , swelling , stiffness and redness can happen ologoarthritis which is asymmetric , affects the lower extremities ( large jts ) more including knees / ankles small joint polyarthritis in upper limbs can also happen axial involvement – of cervical , thoracic and lumbosacral spine sacroiliitis – can cause LBP which is worse at night and also alternating buttock pain enthesopathy ( inflammation of tendons ) at their insertion ( e,g Achilles tendon or plantar aponeurosis insertions into calcaneus – pain when walking ) dactylitis or sausage digits ( diffuse swelling of a whole toe or finger due to digital tendonitis , interphalangeal joint synovitis and multiple entheseal lesions ) of the can also happen
conjunctivitis ( most common 35 % ) can happen with all types of ReA , as an early symptom ( particularly in those caused by Chlamydia ) precedes arthritis by a few days usually settles within 1-4 weeks but in occasionally it may progress to episcleritis , keratitis and corneal ulceration conjunctivitis can relapse and take a severe course uveitis – 2nd most common episcleritis , scleritis , keratitis , optic neuritis , glaucoma and retinal vasculitis are also among the ophthalmological manifestations of ReA
less common Keratoderma blenrrhorhagicum -pustular lesions in plantar areas , they can coalesce and turn into psoriatic plaques ( affects 5 % to 10 % of patients ) Circinate balanitis – painless shallow psoriasiform lesions over glans or shaft of penis oral ulcerations , dystrophic nails may also be seen nail changes as in psoriasis
urethritis , prostatitis , haemorrhagic cystitis , cervicitis SARA is always associated with urethritis or cervicitis SARA – a h/o recent STI in the last 4-6 weeks is often noted (enquire about h/o sexual intercourse with a new partner in the preceding 3 months )
Oligoarthritis and h/o diarrhoea or genitourinary infection detailed hx physical examination any recent illnes ? diarrhoea , urethritis asymmetric oligoarthritis finger – sausage , toe , heel pain , spine , nails eye- conjunctivitis , iritis urethritis ? genital ulcers
Diagnosis – No consensus on diagnostic criteria & no single definitive diagnostic test Called as seronegative as historically patients tested negative for rheumatoid factor at the time of presentation the previous bacterial infection is often asymptomatic and identification of the triggering bacterium is difficult American College of Rheumatology ( ACR ) issued guidance for classifying and diagnosing ReA in 2009- called as Major and Minor criteria European criteria – 3rd International Workshop on Reactive Arthritis 1996
Non-specific findings CRP & ESR can be elevated in the acute phase Normal inflammatory markers does not r/o ReA FBC -Mild normocytic anaemia , neutrophilic leucocytosis Moderate neutrophilia Urinalysis – may detect aseptic pyuria Antinuclear antibodies ( ANA ) and rheumatoid factor are negative HLA B27 – not diagnostic and may not help clinically but correlates with severity of the disease ( + ve test increases the likelihood of ReA ) STI screening / testing Joint fluid aspiration & synovial tissue examination Blood / stool culture Imaging – XR usually normal or show non-specific changes as periarticular osteopenia and soft tissue swelling ( imaging may show changes consistent with enthesitis or arthritis )
other seronegative spondyloarthopathies septic arthritis infection related arthritis e,g Lyme disease , poststreptococcal arthritis , due to Brucella infection , viral arthritis , parasitic arthritis , sexually acquired arthritis ( gonococcal , HIV ) sarcoid arthritis gout ReA is very common in HIV individuals.
No cure for ReA – aim is to alleviate pain & inflammation , reduce long term complications and limit disease progression NSAIDs limited data but large breath of clinical experience ) for atleast 2-4 weeks ( first line pharmacological treatment ) Intra-articular corticosteroid injection Corticosteroids ( usage has shown to be beneficial but limited clinical data ) spontaneous resolution ( in weeks to months after infection ) in 2/3 rd it may become chronic ( ie > 6 months ) in about 30 % to 50 % of patients Antibiotic only if the infection is well established ( 2ary care ) and mainly for those with chlamydia Disease modifying anti rheumatic drugs ( DMARDs ) for e,g sulfasalazine particularly in those with peripheral manifestations TNF agents as etanercept in severe cases If SARA suspected seek opinion from genitourinary specialist
course of ReA , duration , frequency / severity of relapses are highly variable about 30 % to 60% may develop chronic ReA ( lasting > 6 months ) symptomatic relapses may happen ankylosing spondylitis recurrent exacerbation of urethritis , uveitis and arthralgias disability due to chronic destructive arthritis urethral stricture aortic root necrosis cataracts cystoid macular edema
- Lahu, Ali et al. “Modes of presentation of reactive arthritis based on the affected joints.” Medical archives (Sarajevo, Bosnia and Herzegovina) vol. 69,1 (2015): 42-5. doi:10.5455/medarh.2015.69.42-45
- Hannu T. Reactive arthritis. Best Pract Res Clin Rheumatol. 2011 Jun;25(3):347-57. doi: 10.1016/j.berh.2011.01.018. PMID: 22100285.
- Pennisi M, Perdue J, Roulston T, Nicholas J, Schmidt E, Rolfs J. An overview of reactive arthritis. JAAPA. 2019 Jul;32(7):25-28. doi: 10.1097/01.JAA.0000558320.47868.2f. PMID: 31169570.
- Kwiatkowska B, Filipowicz-Sosnowska A. Reactive arthritis. Pol Arch Med Wewn. 2009 Jan-Feb;119(1-2):60-5. PMID: 19341180. Reactive arthritis – PubMed (nih.gov)
- Hamdulay, S S et al. “When is arthritis reactive?.” Postgraduate medical journal vol. 82,969 (2006): 446-53. doi:10.1136/pgmj.2005.044057
- Nidavani, Ramesh & AM, Mahalakshmi & L, Krishna. (2015). Update on the diagnosis and management of Reactive arthritis (Reiter’s syndrome). Der Pharmacia Sinica. 6. 12-18.
- Cheeti A, Chakraborty RK, Ramphul K. Reactive Arthritis. [Updated 2022 Jan 4]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK499831/