Where has SARA gone? Prof. David Kane Consultant Rheumatologist Beacon & Tallaght Hospitals Clinical Professor in Rheumatology Trinity College Dublin 1
Reactive Arthritis Seronegative Asymmetrical Arthritis following Urethritis / Cervicitis or Infectious Diarrhoea Specifically associated with Inflammatory Eye Disease Balanitis, Oral Ulceration, Keratoderma Enthesopathy Sacroiliitis Tetrad: Arthritis, Urethritis, Conjunctivitis, Mucocutaneous Disease
Reactive Arthritis
Infectious life cycle of Chlamydia trachomatis 2014 by BMJ Publishing Group Ltd and European League Against Rheumatism Henning Zeidler, and Alan P Hudson Ann Rheum Dis 2014;73:637-644
Reactive Arthritis Incidence 1-2% of males with urethritis 95% + males 1-6 weeks after infection Knee, Tarsus, SIJ involved Now considered a subset of SpA ASAS Two thirds resolve with 6-12 weeks Must screen and treat infections Treating infection - unclear impact on arthritis Kvein et al Ann Rheum Dis 2005
Conjunctivitis (50%)
Iritis (<5%)
Circinate Balanitis Genital Ulcers
Tongue Erosions & Mouth Ulcers
Pustules in Reactive Arthritis
Keratoderma Blennorrhagica Keratoderma Blennorrhagica
Gonococcal Arthritis Tenosynovitis, dermatitis, polyarthralgia syndrome Incidence 2.8 cases per 100,000 person years Acute illness with fever, chills, malaise. Tenosynovitis Mono/Oligoarticular Knees, wrists, ankles Dermatitis: pustular or vesicopustular
Hepatitis B Acute Hepatitis B Acute polyarthritis, Hands & knees, precedes jaundice, urticarial rash Chronic Hepatitis B Transient arthralgia / arthritis Cryoglobulinaemia Polyarteritis nodosa
HIV Arthralgia Reactive Arthritis: 5-10% Psoriatic Arthritis: 1-6% Undifferentiated Spondyloarthropathy 3-11% HIV associated arthritis: symmetric non-erosive Aseptic Necrosis Septic Arthritis Sjogren s-like Syndrome (DI Inflammatory and non-inflammatory myopathy Systemic Vasculitis Lupus-like Syndrome
Inflammatory arthritis Rheumatoid Arthritis Seronegative Spondyloarthritis Psoriatic Arthritis, Reactive Arthritis, Enteropathic Arthritis, Ankylosing Spondylitis, Undifferentiated Viral Parvovirus B19, Rubella, Hepatitis B, C, EBV, CMV Infection Sepsis, Gonococcus, Lyme Disease, Rheumatic Fever, Post streptococcal Other 15 Osteoarthritis, Sarcoidosis, SLE, Gout, Henoch Schonlein purpura, Neoplasia.
Rheumatology Specialty evolved from need for therapy of autoimmune inflammatory arthritis Prevalence of diseases Rheumatoid Arthritis 1-2% Seronegative Arthritis 1-2% SLE, scleroderma, sjogrens0.2% Vasculitis <0.1% PMR 0.5% Symptomatic Osteoarthritis 10% Gout 4% Hyperuricaemia 21% of US adults
44% 5 year survival of severe RA Pincus T, Callahan LF. Scand J Rheumatol Suppl. 1989;79:67-96.
RA has high mortality / morbidity if un(der)treated (The Pre-Biologic Age) 40,000 people in Ireland with RA Average life expectancy shortened by 5-15 years. Twice as likely to have MI or CVA Increased risk of infection Risk of lymphoma 3 times greater than general population Average lifetime earnings loss = 50% 40%-85% unable to work within 8-10 years of disease onset Brown SL, et al. Arthritis Rheum. 2002;46:3151 3158; Bjornadal L, et al. J Rheumatol. 2002;29:906 912; Wolfe F, et al. J Rheumatol. 2003;30:36 40; Doran MF, et al. Arthritis Rheum. 2002;46:2287 2293; Asten P, et al. J Rheumatol. 1999;26:1705 1714; Jones M, et al. Br J Rheumatol. 1996;35:738 745; Baecklund E, et al. BMJ. 1998;317:180 181; Isomaki HA, et al. J Chronic Dis. 1978;31:691 696; Solomon DH, et al. Circulation. 2003;107:1303 1307.
Early Treatment Prevents Joint Damage on X- ray 1 Treating 15 Days After First Visit Resulted in Better Radiographic Outcomes at 2 Years 1 Median Sharp Score 14 12 10 8 6 4 2 0 0 6 12 18 24 Months * Delayed treatment (median 123 days after first visit) (n=109) Early treatment (median 15 days after first visit) (n=97) *p<0.05 vs. the delayed treatment group 19 Reference: 1. Reprinted from: Lard LR, et al. Am J Med. 2001;111:446-451 with permission from Excerpta Medica, Inc.
How to recognise Early IA 1 3 Swollen Joints and/or MCP or MTP Involvement and/or Morning Stiffness 30 Minutes 20 Soft tissue swelling, Redness & Warmth, Pain Improvement with anti-inflammatory Rx
How to recognise Early IA 1 Psoriasis and/or Inflammatory Back Pain and/or Uveitis Inflam BD 21 Rapid loss of function in short space of time CT features: rash, photosensitivity, alopecia, raynauds, skin tightening, general malaise
National Early Inflammatory Arthritis Referral Form Irish Society for Rheumatology & ICGP 29 Rheumatologists 650 GPs
First assessment 30-45 minutes Rheumatoid Arthritis Seronegative Spondyloarthritis Psoriatic Arthritis, Reactive Arthritis, Enteropathic Arthritis, Ankylosing Spondylitis, Undifferentiated Viral Parvovirus B19, Rubella, Hepatitis B, C, EBV, CMV Infection Sepsis, Gonococcus, Lyme Disease, Rheumatic Fever, Post streptococcal Other 24 Osteoarthritis, Sarcoidosis, SLE, Gout, Henoch Schonlein purpura, Neoplasia.
Initial tests for IA ESR CRP Rheumatoid Factor ACPA } 80-90% of patients } 80-90% of patients } 70% of RA } 70% of RA FBC, R/L/B, Urate } Useful ANA } Only if CT disease suspected 25
Inflammatory Joint Disease X-ray US MRI CT NM Negative Positive Prognosis Diagnosis Intervention Therapy target / Disease monitoring / Remission
Ultrasound and MRI are gold standard for synovitis in RA 27
Score: 0 Score: 1 28 Score: 2 Score: 3 Hand. II MCP joint. Longitudinal dorsal scan. Power Doppler score 0-3. 0 = no signal; 1 = mild; 2 = moderate; 3 = severe.
Epidemiology ReA 1.2-1.4% of patients with SpA. Rheumatol Clin. 2012 May;8(3):107-13 ReA in Chlamydia 1-2% ReA in Campylobacter, Salmonella, and Shigella, was estimated as 9, 12, and 12 per 1,000 patients..j Health Popul Nutr. 2013 Sep;31(3):299-307
Chlamydia Ireland 2012 6162 (48.4%) Chlamydia trachomatis notifications in 2012..6696 in 2014 134 per 100,000 population in 2012 HSE East 212 per 100,000 population Women (53.6%), men (44.0%) Estimated 30-120 cases SARA p.a.
Where has SARA gone?? Underdiagnosed in Rheumatology clinic? More prompt treatment with antibiotics? Change in pathogenicity of Chlamydia
Asymptomatic infections are Underdiagnosed in clinical rheumatology practice Chlamydia commonly asymptomatic Two studies of oligoarthritis patients noted asymptomatic CT in 36% and 17% of patients Weyand CM, Goronzy JJ. Clinically silent infections in patients with oligoarthritis:results of a prospective study. Ann Rheum Dis 1992;51:253 8. Schnarr S, Putschky N, Jendro MC, et al. Chlamydia and Borrelia DNA in synovial fluid of patients with early undifferentiated oligoarthritis: results of a prospective study. Arthritis Rheum 2001;44:2679 85. 35
Treatment of Reactive Arthritis NSAID Corticosteroids oral / intra-articular Intensive physiotherapy Intensive hydrotherapy Occasionally needs DMARD (Sulfasalazine, Methotrexate, Anti-TNF)??Antibiotics
Combination antibiotics as a treatment for chronic Chlamydia-induced ReA: a double-blind, placebo-controlled, prospective trial. (Carter JD et al. Arthritis Rheum 2010;62:1298 307) SpA patients with positive culture 6-month course of combination therapy with rifampicin (300 mg/day) plus doxycycline (200 mg/day) or plus azithromycin (500 mg/day followed by 5 days of 2 500 mg once/week) 63% versus 22% clinical response 20% versus 0% complete remission
ReA at the Sydney Sexual Health Centre 1992-2012: declining despite increasing chlamydia diagnoses Case control study 85 ReA cases (1992-2012) 23 (1992-1996) 1 (2007-2011) and 0 (2012) Chlamydia diagnoses increased 770 (1992-1996) 2257 (2007-2011). Male sex OR = 3.27 95% CI 1.04-10.32; p = 0.043 Int J STD AIDS. 2015 Sep 16. pii
IFN- Dendritic Cell IL-12, IL-23 chemokines ECM ±? T 1 cell cell contact macrophage IL-17 IL-22 TNF- IL-1 IL-15 IL-18 IL-6 IL-10 IL-1Ra IL-18BP fibroblast endothelial cell Kelley 2003, adapted courtesy Iain McInnes. B cell tissue cell C H R O N I C I N F L A M M A T I O N
Is it all Reactive Arthritis? Psoriatic Arthritis Streptococcus species in psoriatic plaques Ankylosing Spondylitis Klebsiella in Large bowel Rheumatoid Arthritis Increased frequency of infections in newly diagnosed Porphyromonas gingivalis (Periodontitis)