Dr Hannah Roomi (BMBS)
Reactive Arthritis (RA), formerly known as Reiter’s Syndrome, refers to non-septic joint inflammation that develops in reaction to an infection in another part of the body. RA is often characterized by a classic triad of symptoms: inflammation of multiple asymmetric joints usually in the lower limbs, inflammation of the eyes in the form of conjunctivitis or uveitis and urethritis in men or cervicitis in women. These three symptoms may occur separately, all at once or not at all.
Patients with RA can also present with mucocutaneous lesions such as keratoderma blennorrhagicum, most found on the soles of the feet, balanitis circinata and aphthous stomatitis. RA belongs to a group of diseases, known as autoimmune seronegative spondyloarthropathies, that are associated with a high incidence of HLA B27 antigen. The most common bacterial infections that are known to precede RA include urethritis due to Chlamydia and gastroenteritis due to Salmonella, Shigella, Yersinia, and Campylobacter. This article presents the case of a 22-year-old female patient that was diagnosed with RA after an initial presentation with acute anterior uveitis.
A 22-year-old female presented to Eye Casualty with a 3-day history of gradually increasing pain and redness of her left eye with associated blurred vision and photophobia. The patient denied any other symptoms and reported to be otherwise well within herself. The patient had no past medical history of note and was on no regular medication. Systemic review was unremarkable.
On examination, visual acuity and visual field tests were normal in both eyes. Slit-lamp examination of both eyes with dilated pupils revealed inflammatory cells and flare in the left anterior chamber with posterior synechiae but no evidence of seclusio pupillae. Intraocular pressure measurement was normal in both eyes.
Given that this was the patient’s first episode of unilateral symptoms with no systemic involvement, she was diagnosed with idiopathic anterior chamber uveitis. The patient was treated with topical Dexamethasone 0.1% eye drops, to be administered up to every hour of the waking day until symptoms settle, and Cyclopentolate 1% eye drops to be used three times daily for seven days. The patient was given tapering advice with her steroid prescription and was asked to return to the eye clinic in 4 weeks’ time, or earlier if her symptoms worsened.
The patient returned to the clinic 4 weeks later for review where she reported improvement of her eye symptoms but was now complaining of a one-week history of malaise, fever and pain in her lower back, knee and ankle joints with associated stiffness. A meticulous history was taken but the patient denied any abdominal, genito-urinary or respiratory symptoms and any new features within her history.
On examination, she had tenderness and swelling of both her sacroiliac joints, right knee and left ankle joints with associated reduced range of movement. On systemic examination, the patient had two painless, shiny aphthae on her palate and on the mucosa of her right cheek. Full exposure of the patient did not reveal any other skin changes. The patient was febrile with a low-grade temperature of 38.3 degrees but was otherwise haemodynamically stable. Ophthalmic examination showed improvement in existing signs with no new ocular features.
The patient was admitted under the medical team for further investigations including ESR, serum ACE, ANA, ANCA, anti-dsDNA, syphilis serology, HLA B27 and vulvovaginal swabs for nucleic acid amplification tests in addition to routine blood tests. Vulvovaginal swabs confirmed Chlamydia Trachomatis; HLA B27 was positive and she had raised inflammatory and infection markers. She was subsequently diagnosed with Reactive Arthritis with a background of asymptomatic Chlamydia infection and was referred to Rheumatology and Genito-Urinary Medicine for further investigation and follow-up. The patient was treated with doxycycline 100mg twice daily for 7 days and Ibuprofen 400mg three times daily for 3 weeks with appropriate gastric cover.
Acute anterior uveitis (AAU) is an intraocular inflammatory disease of the iris alone (iritis), anterior part of ciliary body (anterior cyclitis) or both structures (iridocyclitis) that is closely associated with autoimmune conditions and previous viral or bacterial infections. Patients with AAU will often complain of pain, redness, photophobia, blurred vision and watering of the eye. AAU, although less common than conjunctivitis, occurs in around 2-11% of patients with sexually acquired reactive arthritis (SARA)1 and approximately 50% of patients with AAU test positive for HLA B27 antigen.
AAU is one of the most common ocular manifestations of rheumatic disease and studies have shown that AAU is the first clinical sign in up to 40% of patients diagnosed with spondyloarthropathy.2 Furthermore, studies have shown that patients presenting with AAU who are HLA B27 positive have less favourable outcomes than HLA B27-negative patients and are more likely to develop long-term ocular complications such as secondary glaucoma or cataracts, vitritis and optic disc oedema.3 For this reason, all patients that present with recurring unilateral AAU without rheumatic symptoms require referral to a rheumatologist for further investigation and management.
AAU generally requires medical management, with surgical intervention only indicated if secondary complications such as cataract or glaucoma cause structural complications within the eye. The main goals of medical treatment for AAU are relief of pain and photophobia, elimination of inflammation, prevention of structural complications such as synechiae and preservation or restoration of vision. 4 First line treatment for AAU is topical corticosteroids to reduce inflammation with supportive use of cycloplegic agents to stabilize the blood-aqueous barrier and to prevent posterior synechiae that can lead to iris bombe and elevated intraocular pressure. Treatment response is monitored using visual acuity tests and grading of cells and flare in the anterior chamber and the initial follow-up schedule varies depending on the severity of the initial inflammation.
SARA refers to cases of RA that are caused by a sexually transmitted pathogen in the genital tract.5 SARA has an incidence of 3.0–8.1%6 and is most common in young adults aged between 20 and 40. Other predisposing factors for SARA include gender with men being affected ten times more frequently than women,7 HIV infection and HLA B27 gene, which is prevalent in 30% of RA cases and in up to 70% of severe RA cases that require inpatient admission.8 The most common pathogen associated with SARA is Chlamydia trachomatis, which primarily infects epithelial surfaces of the urogenital system or the ocular conjunctivae.Following the acute infection stage, C. trachomatis organisms can disseminate from their primary site of infection to distant anatomic locations where they go on to display aberrant morphological and transcriptional factors, which ultimately elicits an immuno-pathogenic response.9
According to The Office of Rare Diseases of the National Institutes of Health, RA is listed as a “rare disease”, however an increasing number of studies have suggested that RA is not as rare as initially believed, but rather a condition that is often misdiagnosed or missed entirely by clinicians. In SARA cases, for example, up to 20% of patients with Chlamydia infection are asymptomatic. Furthermore, Chlamydia infection can sometimes self-resolve, without the use of antibiotic treatment, before the development of any further symptoms that could suggest RA, rendering local culture for the organism unsuccessful and therefore a potentially missed diagnosis.10 This highlights the importance of clinicians taking thorough sexual histories that include specific details about sexual contacts and any genital symptoms to ascertain the risk of acquiring a sexually transmitted infection that may precede RA.
In this case, the patient presented with a first episode of AAU and despite a thorough sexual history being taken, the patient reported to have only had sexual intercourse with one long-term regular partner in the last twelve-month period. However, considering the patient’s age, presenting symptoms and absence of any infective symptoms, the likelihood of Chlamydia infection was relatively high.
- AAU is one of the most common ocular manifestations of rheumatic disease and forms part of the triad of symptoms that are associated with RA.
- AAU requires urgent management to prevent potential sight-threatening complications such as secondary glaucoma or cataracts, vitritis and optic disc oedema.
- HLA B27 gene is associated with more severe AAU disease and long-term complications.
- All patients that present with recurring unilateral AAU, with or without rheumatic symptoms, require referral to a rheumatologist for further investigation and management.
- Sexually transmitted bacterial infections, such as Chlamydia, are known to precede RA and therefore patients presenting with idiopathic AAU require a thorough sexual history to identify any risk factors.
- Carlin EM, Ziza JM, Keat A, Janier M. 2014 European Guideline on the management of sexually acquired reactive arthritis. International journal of STD & AIDS. 2014 Nov;25(13):901-12.
- Fernández-Melón J, Muñoz-Fernández S, Hidalgo V, Bonilla-Hernán G, Schlincker A, Fonseca A, Vieitez J, Martín-Mola E. Uveitis as the initial clinical manifestation in patients with spondyloarthropathies. The Journal of rheumatology. 2004 Mar 1;31(3):524-7
- Power WJ, Rodriguez A, Pedroza-Seres M, Foster CS. Outcomes in anterior uveitis associated with the HLA-B27 haplotype. Ophthalmology. 1998 Sep 1;105(9):1646-51
- Agrawal RV, Murthy S, Sangwan V, Biswas J. Current approach in diagnosis and management of anterior uveitis. Indian journal of ophthalmology. 2010 Jan;58(1):11
- Carlin E, Flew S. Sexually acquired reactive arthritis. Clinical Medicine. 2016 Apr;16(2):193.
- Denison HJ, Curtis EM, Clynes MA, Bromhead C, Dennison EM, Grainger R. The incidence of sexually acquired reactive arthritis: a systematic literature review. Clinical rheumatology. 2016 Nov;35(11):2639-48.
- Keat AC, Maini RN, Nkwazi GC, Pegrum GD, Ridgway GL, Scott JT. Role of Chlamydia trachomatis and HLA-B27 in sexually acquired reactive arthritis. Br Med J. 1978 Mar 11;1(6113):605-7
- Gaston JS. Immunological basis of Chlamydia induced reactive arthritis. Sexually transmitted infections. 2000 Jun 1;76(3):156-61
- Carter JD, Inman RD. Chlamydia-induced reactive arthritis: hidden in plain sight?. Best practice & research Clinical rheumatology. 2011 Jun 1;25(3):359-74.)
- Haller-Schober EM, El-Shabrawi Y. Chlamydial conjunctivitis (in adults), uveitis, and reactive arthritis, including SARA. Best Practice & Research Clinical Obstetrics & Gynaecology. 2002 Dec 1;16(6):815-28.