Seronegative spondyloarthropathy Flashcards

Question

Predictive markers for radiographic progression

Answer 1

Elevated ESR/CRP Syndesmophytes at baseline Smoking

Answer 2

Spectrum of same disease • Evolution of nr-axSpA to AS is time dependent ○ 10% will develop AS over 2 years ○ 20% will develop AS over 2 years if CRP elevated, or baseline MRI is +ve ○ 85% will develop AS over 20 years ○ 10-15% never develop plain film changes that define AS * In AS, male > female; in nr-axSpA, male = female. * Management - Australian PBS now funds golimumab for non-readiographic axial spondyloarthritis

Answer 3

* ~40% of psoriatic arthritis present concurrently with onset of skin disease. ~60% develop arthritis after onset of skin psoriasis. 10% of patients develop psoriatic arthritis with no skin disease. * ~15% of psoriasis patients develop psoriatic arthritis.

Answer 4

• Men = women. However, earlier disease onset is observed in males, whereas women peak in 6th decade.

Answer 5

• Strong genetic influences: ○ HLA genotype § HLAB27 as it falls under spondyloarthropathy. However, other HLA genes important. § HLA-C Cw0606 strongest genetic marker for psoriasis, and contributes to type 1 phenotype of severe psoriasis which usually occurs early <40 years, but has delayed appearance of arthritis § HLAB27 and HLAB39 have associations with simultaneous onset of skin and arthritis disease. ○ Parental imprinting phenomenon ○ Family history - increased risk of first degree relative has psoriasis or psoriatic arthritis. • Trauma to joints or tendons implicated in triggering psoriatic arthritis, as well as infections (especially HIV). • Compared to RA, the synovium of psoriatic arthritis is characterised by hypervascularity and morphologically tortuous vessels. Importance of VEGF and TGF-b over-expression which contribute to the vascular but also characteristic bone changes of psoriatic arthritis. New bone formation leads to fluffly periostitis. • RANKL important in osteoclast proliferation and activation, leading to bony erosions and osteolysis. This clinically results in arthritis mutilans, including pencil-in-cup deformities. • IL-23 also identified as being important in the skin manifestations of psoriasis, and in promoting entheseal inflammation • DIP joint involvement & dactylitis, uniquely distinguishes psoriatic arthritis from RA. ○ DIP joint involvement is due to extensor tendon enthesitis at the nail bed ○ Dactylitis is due to flexor tenosynovitis of the entire digit. • Much of the inflammation in psoriatic arthritis is not intra-articular, but due to enthesitis rather than articular synovitis. However, synovitis can be present.

Answer 6

• Moll and Wright classification - 5 patterns of psoriatic arthritis ○ Distal interphalangeal joint (DIP) arthritis - typically associated with nail changes. ○ Asymmetric oligoarthritis (most common) ○ Symmetric polyarthritis ○ Arthritis mutilans - complete destruction and resorption of joints. Uncommon but characteristic. You can get telescoping digits where you can pull in/out the joints. ○ Psoriatic spondylitis with sacroiliac and spinal involvement. Very uncommon as isolated presentation, may occur years after peripheral arthritis. Over time, disease pattern also changes with a tendency to become polyarticular in the majority of patients. CASPAR classification - higher sensitivity (91.4%) and specificity (98.7%), but used in established disease. If used in recent-onset psoriatic arthritis, sensitivity is lower as they may lack radiographical changes of periostitis. You need inflammatory articular disease (joint, spine, entheseal) with 3 or more points from following 5 categories: ○ Current psoriasis (2 points), personal history of psoriasis (1 point), or family history of psoriasis (1 point) ○ Typical psoriatic nail dystrophy (1 point) ○ A negative test for RF (1 point) ○ Current or history of dactylitis (1 point) ○ Radiographic evidence of juxta-articular new bone formation appearing as ill-defined ossification near joint margins (periostitis) on plain film in hands/feet (1 point)

Answer 7

Risk factors • Psoriasis - most significant risk factor. • Family history of psoriasis or psoriatic arthritis, especially first degree relatives. • History of joint or tendon trauma - can be present prior to onset of arthritis, equivalent to Koebner phenomenon observed in skin. • HIV infection - in the HIV population, risk of psoriatic disease appears much higher than the general population.

Answer 8

Clinical presentation • Typically young or middle-aged • Joint symptoms ○ Inflammatory joint pain. See Moll and Wright classification for different kinds of joint presentations. ○ Typically monoarticular or asymmetric oligoarticular joint involvement, usually lower joints (eg, knees). Polyarticular joint or dactylitis are high risk presentations with significant progression and poorer outcomes. ○ Spinal stiffness may be present with axial involvement. Assess spine and mobility - tragus-to-wall distance, modified Schober's. When it does involve the spine, typically affects cervical spine most severely. • Enthesitis eg, heel pain (plantar fascia, Achilles), elbow pain, lateral hip pain related to entheseal inflammation • Dactylitis - common. Uniform swelling of an entire digit. Majority of swelling is in the flexor tenosynovium and will lead to limited motion. Dacylitis is associated with poor outcomes and significant progression, as is polyarticular joint as initial presentation. • Psoriasis ○ Disease typically occurs in established psoriasis. 10% of patients present with arthritis compatible with psoriatic arthritis, but no skin disease. Some of these patients have family history or develop psoriasis later on. ○ Inspect scalp, intergluteal fold, perineum, periumbilical regions ○ There is no close correlation between extent of skin disease and joint involvement, except for association of DIP joint arthritis and nail disease. • Nail changes ○ Pitting ○ Onycholysis ○ Subungual hyperkeratosis ○ Oil drop or salmon patch (translucent yellow-red discolouration in the nail bed proximal to onycholysis, reflecting inflammation and can be tender) ○ There is no close correlation between extent of skin disease and joint involvement, except for association of DIP joint arthritis and nail disease. Assess BMI and blood pressure due to increased risk of metabolic syndrome and CV disease.

Answer 9

§ Soft tissue swelling may be only radiographic finding seen in early disease. § Erosion, if present, in DIP joint suggestive of psoriatic arthritis § Fluffy periostitis reflecting periarticular new bone formation suggestive of psoriatic arthritis § Osteolysis leading to arthritis mutilans or pencil-in-cup deformity only in advanced disease. Pencil in cup deformity where there is bony resorption of distal tuft of proximal phalanx, and new bone formation of proximal end of distal phalanx. § Unlike RA, periarticular osteopenia is not a manifestation of early psoriatic arthritis. Erosions are seen in less than a quarter of early disease cases. § Asymmetric sacroiliitis is characteristic of psoriatic arthritis and may be asymptomatic. SIJ plain film usually normal in early disease but develop later on. Not routine, but MRI of SIJ can be used to detect early disease. § Spinal changes tend to be spotty, preferentially affecting the cervical spine > lumbar spine. Typically normal in early disease, in advanced disease may see syndesmophytes predominantly in the cervical spine.

Answer 10

* RF and anti-CCP. If -ve, can be helpful to distinguish from RA * ESR and CRP - if elevated, can be associated with polyarticular psoriatic arthritis & progressive arthritis. * Metabolic screening - increased risk of metabolic syndrome * Joint US for entheseal involvement.

Answer 11

DDx: • RA ○ Polyarticular psoriatic arthritis can be DDx for RA. However, distinguished by presence of dactylitis, DIP joint involvement, absence of RF/anti-CCF. ○ RA typically involves 'rows' or digits, whereas psoriatic arthritis involves individual whole digits. ○ RA does not affect the lumbar spine or SIJ ○ Dactylitis is not a feature of RA. ○ Hand x-rays in RA typically have marginal erosions affecting the subchondral bone first and later progressing to cause joint space narrowing. In psoriatic arthritis, erosions are uncommon in early disease, seen in less than quarter of early disease. ○ Periarticular osteopenia/osteoporosis is a feature of RA, but not in psoriatic arthritis ○ Fluffy periostitis is a feature of psoriatic arthritis, but not RA. • Gout ○ Gout is typically monoarticular, or oligoarticular. Can be polyarticular affecting multiple joints in the hands and feet especially in elderly people. ○ Synovial fluid examination reveals negatively birefringent, needle shaped crystals ○ Erosions in gout are typically 'rat bite' erosions with overhanging edges • Erosive osteoarthritis ○ Predominantly middle aged women ○ Affects DIP and PIP ○ Plain film shows changes typical of OA involving DIP and PIP, with marginal or central bone erosions, resulting in characteristic gull-wing deformity. • Reactive arthritis ○ Recent exposure to certain GIT and GUT infections (Chlamydia, Salmonella, Campylobacter, Yersinia). ○ Typically oligoarthritis of weightbearing joints, enthesitis, dactylitis. ○ Has other extra-articular manifestations eg, conjunctivitis, urethritis, stomatitis. • Mycobacterial tenosynovitis - dactylitis like swelling of single digit may be observed • Sarcoid dactylitis - dactylitis observed in some patients with chronic sarcoid.

Answer 12

• Peripheral arthritis ○ 1st line: NSAIDs, physiotherapy, +/- intra-articular corticosteroid injection. May suffice if limited disease (monoarthritis/oligoarthritis, no joint erosions). If using intra-articular corticosteroid injection, avoid long-acting agents such as triamcinolone in superficial joints as it may cause subcutaneous atrophy, use methylprednisolone acetate instead. ○ 2nd line: DMARD if refractory. § Primary option: Methotrexate is first agent or ciclosporin. No additional benefit with combined with sulfasalazine or leflunomide. No benefit in axial/spinal disease. § Secondary option: sulfasalazine or leflunomide monotherapy. These reduce peripheral joint involvement, but do not slow radiographic progression. § Tertiary option: methotrexate + ciclosporin. If failing single agent DMARD, combination treatment may improve joint and skin symptoms, and reduce radiographic progression compared to MTX/ciclosporin monotherapy. ○ 3rd line: TNF-a inhibitor, or monoclonal antibody, or apremilast § TNF-a inhibitor eg, infliximab, adalimumab, etancercept, certolizumab pegol, golimumab. Used if failed conventional DMARD. Slow radiographic progression. Additional of TNF-a inhibitor to MTX therapy is no more effective than TNF-a inhibitor alone. § Monoclonal antibody: ustekinumab (anti IL12 and IL23), secukinumab (anti IL17), ixekizumab (anti IL17). Slows radiographic progression, enthesitis and dactylitis may respond. § Apremilast: PO phosphodiesterase inhibitor. Significant improvement in symptoms. However, if not responsive to TNF-a inhibitor therapy, will not respond to apremilast. ○ Avoid systemic corticosteroids as it can cause post-exposure psoriasis flare • Dacylitis ○ 1st line: NSAIDS, physiotherapy + DMARDS § DMARD as similar to peripheral arthritis. Primary DMARD choice is MTX or ciclosporin, secondary choice is sulfasalazine or leflunomide, tertiary choice is MTX + ciclosporin. § RACP lecture does not recommend DMARDS for dactylitis. ○ 2nd line: TNF-a inhibitor, or monoclonal antibody. Not apremilast. § TNF-a inhibitor § Monoclonal antibody: ustekinumab or secukinumab. § Apremilast not likely to be effective. • Spondylitis and/or enthesitis ○ 1st line: NSAID ○ 2nd line: TNF-a inhibitor or monoclonal antibody, or apremilast § TNF-a inihibitor, mAbs, apremilast as per peripheral arthritis and dactylitis treatment. § As per ankylosing spondylitis trials, TNF-a inhibitor therapy has not been demonstrated to inhibit radiographic progression. • If hip involvement, and severe, consider hip arthroplasty Hip involvement is feature of psoriatic arthritis, frequently bilateral. Joint deterioration may be rapidly progressive, resulting in arthroplasty within 5 years of onset of symptoms.

Answer 13

* 30-50% of patients develop chronic reactive arthritis. Defined as chronic reactive arthritis when joint symptoms present for >6 months. The other 50% resolve within 6 months. * Classic triad is 'Reiter's syndrome' of post-infectious arthritis, conjunctivitis, non-gonococcal urethritis. However, full triad only found in minority of cases and not required for diagnosis.

Answer 14

• Bacteria associated with reactive arthritis are typically Gram -ve organisms with lipopolysaccharide (LPS). The bacteria and bacterial components have been found in synovial tissues. • Most commonly implicated organisms: ○ Most common: Chlamydia trachomatis and Chlamydia pneumoniae, but trachomatis > pneumoniae. ○ Campylobacter jejuni - most important cause of post-dysenteric reactive arthritis ○ Salmonella enteritidis ○ Shigella ○ Yersinia • HLA-B27 plays important role. Present in 30-50% of patients with reactive arthritis. Not required for diagnosis.

Answer 15

* Male > female (9:1) for Chlamydia induced reactive arthritis. Male = female for post-dysentery reactive arthritis. * HLAB27, present in 30-50% * Preceding GUT or GIT infection (Chlamydia, Campylobacter, Shigella, Salmonella, Yersinia).

Answer 16

Clinical presentation • Typically asymmetric oligoarthritis of lower extremity larger joints (eg, knees) 1-4 weeks after onset of infection ○ Polyarthritis and monoarthritis can occur ○ Inflammatory joint pain. • Axial arthritis ○ SIJ and lumbosacral spine involvement is common. ○ Thoracic and cervical spine involvement can be seen in chronic reactive arthritis • Dactylitis • Enthesitis ○ Heel tenderness is common (Achilles' tendon and plantar fascia at insertion into calcaneus) • Constitutional symptoms: fever, anorexia, weight loss, lethargy • Mucus membrane involvement: painless oral ulcers • Urethritis leading to sterile dysuria. Cystitis, prostatitis, cervicitis can also occur. • Skin involvement: ○ Keratoderma blennorrhagicum - hyperkeratotic skin in the soles or palms. Typically starts as vesicular lesion that becomes plaque-like or pustular, and microscopically indistinguishable from pustular psoriasis ○ Circinate balanitis - painless ulcers and plaque-like lesions in shaft or glans penis. • Ocular involvement ○ Conjunctivitis with sterile purulent discharge ○ Anterior uveitis (iritis), associated with HLA positivity. • Cardiac manifestations ○ Can lead to aortitis, which can lead to aortic regurgitation, heart failure, and arrhythmias.

Answer 17

• ESR and CRP - often elevated, but tend to normalise when chronic. • RF and anti-CCF - typically negative • HLAB27 - found in 30-50% of reactive arthritis, not required for diagnosis, but can be suggestive of diagnosis. May predict more severe chronic disease. • Microbiology to identify triggering infection & rule out other infectious processes eg, gonorrhoea: ○ Urogenital § First pass urine PCR, urine culture § Urethral swab (if discharge present) for PCR and culture § Endocervical or high vaginal swab for PCR and culture § Other sites depending on sexual behaviour: rectal swab, throat swab ○ Stool MCS ○ However, cultures usually negative after onset of arthritis. • Synovial fluid analysis to rule out other causes eg, septic arthritis, crystal arthropathy • Plain x-ray: ○ Soft tissue swelling may be only finding in early disease ○ In chronic form of disease: § Erosions and joint space narrowing in small joints of hands and feet. § Periostitis reflecting fluffy periosteal new bone formation, due to enthesitis at sites of tendon and ligamentous insertions. § Calcification of Achilles' tendon & exuberant bony spurs in calcaneus reflecting chronic enthesitis § Asymmetric sacroiliitis in 1/3rd of patients. § Non-marginal syndesmophytes as a result of chronic enthesitis of paraspinal ligaments. Cf. marginal syndesmophytes in AS, which can result in Bamboo spine in late disease.

Answer 18

Differential diagnosis • Ankylosing spondylitis ○ Shows similar spinal involvement to reactive arthritis, but is more symmetrical in the sacroiliac joints. ○ Also the syndesmophytes tend to be marginal rather than non-marginal that are seen in reactive arthritis. ○ Bamboo spine is also indicative of AS > reactive arthritis. ○ AS also has less prominent peripheral joint involvement than reactive arthritis. • Psoriatic arthritis ○ Difficult to distinguish from reactive arthritis especially if no psoriasis present in the psoriatic arthritis. In psoriatic arthritis, the DIP joints more commonly affected. • Rheumatoid arthritis ○ Typically symmetrical polyarthritis affecting hands and feet. RA does not affect the SIJ and lumbar spine. Also RF and anti-CCP may be +ve. Hand x-rays reveal typical erosive changes and periarticular osteopenia. • Rheumatic fever ○ Typically URTI/pharyngitis preceding arthritis. ○ Typically migratory arthritis involving both upper and lower limb extremities, with no axial involvement. ○ You can get post-streptococcal reactive arthritis, which will not fulfil Jones criteria for acute rheumatic fever, and will have a lower limb predominance. • Adult-onset Still's disease ○ Double quotidian fever (2 fevers per day), characteristic evanescent salmon coloured rash at same time as fevers. ○ Hand X-rays show intercarpal and carpometacarpal joint space narrowing without erosions. • Enteropathic arthritis ○ Presence of IBD can distinguish from reactive arthritis. ○ Enteropathic arthritis tend to have bilateral symmetric sacroiliitis, whereas reactive arthritis tends to be asymmetrical. ○ Enteropathic arthritis typically as marginal syndesmophytes vs. non-marginal in reactive arthritis. • Gout - typically more DIP joint involvement and uric acid tophi eg, in pinna of ear. • Post-viral arthritis - preceded by influenza like illness, has rheumatoid distribution of joint involvement (symmetrical small joint), maculopapular rash.

Answer 19

Management • Acute reactive arthritis: ○ 1st line: NSAIDS ○ 2nd line: corticosteroids (eg, PO prednisolone) only in severe/polyarticular disease, eye disease. Effective for peripheral arthritis, but not for axial disease. • Chronic or persistent reactive arthritis: ○ DMARD: primary option is sulfasalazine. Only DMARD to have been evaluated in RCT for reactive arthritis. MTX is another option. • Skin disease ○ Topical steroids for circinate balanitis and keratoderma blennorrhagicum. • Emerging: ○ TNF-a inhibitors - no RCT assessing efficacy in reactive arthritis, but case reports have suggested clinical benefit.

Answer 20

Spondyloarthritis ~10% of AS have IBD, and about ~10% of IBD have AS.

Answer 21

• Arthritis can occur with or after onset of IBD. However, can also occur before onset of IBD especially axial arthritis.

Answer 22

• Crohn's disease or Ulcerative colitis Can also occur in Whipple disease, Coeliac disease, or gastrointestinal bypass surgery Risk factors • Crohn's disease or Ulcerative colitis • Can also occur in Whipple disease, Coeliac disease, or gastrointestinal bypass surgery • Peripheral arthritis more common in women; axial arthritis more common in men • Smoking • Several HLA associations. HLAB27 associated with axial arthropathy. • Family history of spondyloarthropathy

Answer 23

Pathogenesis • GIT bacteria may play role in development of both IBD and arthritis. Klebsiella pneumoniae may be contributing organism. • Increased intestinal permeability in IBD may increase immune response to gastrointestinal bacteria. • Innate and adaptive immune cells may migrate from GIT to synovium.

Answer 24

Types of enteropathic arthritis • Peripheral arthritis ○ Type 1 § Non-deforming, non-erosive § Correlates with IBD activity § Asymmetric oligoarthritis, typically lower limb large joints ○ Type 2 § Same clinical presentation as ankylosing spondylitis § May be erosive § Independent of IBD activity § Symmetric polyarthritis, typically upper limbs both large and small joints • Axial arthritis ○ Independent of IBD activity ○ Has similar course to ankylosing spondylitis. ○ Can be sacroiliitis, or ankylosing spondylitis. Can lead to progressive ankylosis of vertebrae and SIJ. Clinical presentation • Types of enteropathic arthritis as described above. ○ Sacroiliitis is most common manifestation. ○ Arthritis symptoms occur with or after onset of IBD, but axial arthritis may occur before IBD. • Enthesitis • Dactylitis • Extra-articular and extra-gastrointestinal manifestations ○ Uveitis ○ Skin: erythema nodosum, pyoderma gangrenosum

Answer 25

Investigations • ESR, CRP may be elevated. However, may be normal. • HLA typing does not aid in diagnosis • RF and anti-CCP usually -ve • Faecal calprotectin to detect IBD • Plain X-ray ○ Similar to other spondyloarthropathies ○ Axial arthritis may be seen on plain film in established advanced disease, not often see on early disease. • MRI to detect early sacroiliitis

Answer 26

Management • Treat the IBD to resolve both the GIT and joint symptoms. • Use NSAIDS with caution. • Glucocorticoids are effective, but most patients have recurrence of joint symptoms with tapering. • Limited data for DMARDS for arthropathy symptoms, but consider methotrexate in Crohn's, and 5-aminosalicylic acid compounds for UC. ○ Hydroxychloroquine and azathioprine do not effectively treat arthritis in IBD • TNF-a inhibitors if refractory to NSAIDS, DMARDS, or steroid dependent. Other biologics that can be used is ustekinumab. Avoid IL-17 blockers as it can make IBD/enteropathic arthritis worse.

Seronegative spondyloarthropathy Flashcards

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