Where has SARA gone? Prof. David Kane Consultant Rheumatologist Beacon & Tallaght Hospitals. Clinical Professor in Rheumatology Trinity College Dublin

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1 Where has SARA gone? Prof. David Kane Consultant Rheumatologist Beacon & Tallaght Hospitals Clinical Professor in Rheumatology Trinity College Dublin 1

2 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

3 Reactive Arthritis

4 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:

5 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

6 Conjunctivitis (50%)

7 Iritis (<5%)

8 Circinate Balanitis Genital Ulcers

9 Tongue Erosions & Mouth Ulcers

10 Pustules in Reactive Arthritis

11 Keratoderma Blennorrhagica Keratoderma Blennorrhagica

12 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

13 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

14 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

15 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.

16 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

17 44% 5 year survival of severe RA Pincus T, Callahan LF. Scand J Rheumatol Suppl. 1989;79:67-96.

18 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: ; Bjornadal L, et al. J Rheumatol. 2002;29: ; Wolfe F, et al. J Rheumatol. 2003;30:36 40; Doran MF, et al. Arthritis Rheum. 2002;46: ; Asten P, et al. J Rheumatol. 1999;26: ; Jones M, et al. Br J Rheumatol. 1996;35: ; Baecklund E, et al. BMJ. 1998;317: ; Isomaki HA, et al. J Chronic Dis. 1978;31: ; Solomon DH, et al. Circulation. 2003;107:

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 *

19 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 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: with permission from Excerpta Medica, Inc.

20 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

21 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

22 National Early Inflammatory Arthritis Referral Form Irish Society for Rheumatology & ICGP 29 Rheumatologists 650 GPs

24 First assessment 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.

25 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

26 Inflammatory Joint Disease X-ray US MRI CT NM Negative Positive Prognosis Diagnosis Intervention Therapy target / Disease monitoring / Remission

27 Ultrasound and MRI are gold standard for synovitis in RA 27

28 Score: 0 Score: 1 28 Score: 2 Score: 3 Hand. II MCP joint. Longitudinal dorsal scan. Power Doppler score = no signal; 1 = mild; 2 = moderate; 3 = severe.

32 Epidemiology ReA % of patients with SpA. Rheumatol Clin May;8(3): 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 Sep;31(3):

33 Chlamydia Ireland (48.4%) Chlamydia trachomatis notifications in in per 100,000 population in 2012 HSE East 212 per 100,000 population Women (53.6%), men (44.0%) Estimated cases SARA p.a.

34 Where has SARA gone?? Underdiagnosed in Rheumatology clinic? More prompt treatment with antibiotics? Change in pathogenicity of Chlamydia

35 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: 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:

36 Treatment of Reactive Arthritis NSAID Corticosteroids oral / intra-articular Intensive physiotherapy Intensive hydrotherapy Occasionally needs DMARD (Sulfasalazine, Methotrexate, Anti-TNF)??Antibiotics

37 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: ) 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 mg once/week) 63% versus 22% clinical response 20% versus 0% complete remission

38 ReA at the Sydney Sexual Health Centre : declining despite increasing chlamydia diagnoses Case control study 85 ReA cases ( ) 23 ( ) 1 ( ) and 0 (2012) Chlamydia diagnoses increased 770 ( ) 2257 ( ). Male sex OR = % CI ; p = Int J STD AIDS Sep 16. pii

IFN- Dendritic Cell IL-12, IL-23 chemokines

IL-18BP fibroblast endothelial cell Kelley

39 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

40 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)

First Presentation of Joint Pain

First Presentation of Joint Pain Andrew Harrison Rheumatologist Wellington Regional Rheumatology Unit, HVDHB Bowen Centre, Crofton Downs, Wellington Assoc. Prof. in Medicine, University of Otago Wellington