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Seronegative Arthritis


SpA features (11). Note: Inflammatory back pain has 8 subquestions to ask to. 

Following SpA features were negative unless otherwise stated 
Inflammatory back pain (age <45yr, duration > 3 months, insidious onset, stiffness > 30 min, improvement with exercise, no improvement with rest, awakening from pain especially in the second half of the night with improvement on arising, alternating buttock pain) (2 or more suspicious; 4 or more considered diagnostic for Inflammatory back pain)
Arthritis 
Enthesitis (heel) 
Uveitis
Dactylitis 
Psoriasis
Crohn’s disease/ulcerative colitis 
Good response to NSAIDs 
Family history for SpA
HLA-B27
Elevated CRP


25 yo with 2 yr history of suspicious inflammatory low back pain (3/8 features), uveitis, psoriasis, elevated CRP, positive HLA-B27
X ray negative 
MRI negative

Applying ASAS criteria: Given age < 45, duration > 3 months, with HLA B27+, and has > 2 SpA features (Uveitis, Psoriasis, elevated CRP) meets classification criteria for SpA.

But this criterion is 83 % sensitive and only 84% specific. Hence, a false positive is included as AS if we were to use this for diagnosis. 

Hence, instead, if we use the NEJM paper algorithm, 

Does not have definitive radiographic SI, next 
Fulfills 3 SpA features (Uveitis, Psoriasis, elevated CRP), because it is 2-3 SpA features
Check for HLAB27 - which is positive, 
Yet does not have compelling features, hence consider MRI (note, if had compelling clinical features, will have SpA) (note: if had 0,1 SpA features, even with compelling clinical features, one will need MRI) (if the 4 or more SpA features were present, then even in the absence of compelling clinical features, we will diagnose with AS even without the need of MRI given HLA B27 is positive)
MRI done does not show any SI 
-hence his disease is not consistent with a diagnosis of AS 

Hence, this would have been a false positive case of a SpA using ASAS criteria if used for diagnosis. 





Spondyloarthopathies

  • Current classification 
    • Axial Spondyloarthritis
      • With radiographic sacroileitis
      • Without radiographic sacroiletis 
        • MRI positive 
        • HLA B27 positive 
    • Peripheral sondyloarthritis (PIPI without PIPI)
      • With Psoriasis 
      • With IBD
      • With preceding infection
      • Without IBD, Psoriasis, or Preceding infection 




  • 4 Major Groups (classic classification) 
    1. Reactive Arthritis 
    2. Ankylosing Spondylitis 
    3. Psoriatic Arthritis 
    4. Enteropathic Arthritis (IBD associated)


Common C/F
  • Both Axial or Peripheral Arthritis can occur
  • Enthesitis
  • Dactylitis


1. Reactive Arthritis 
  • Skin Manifestations: 
    • Keratoderma Blenorrhagica


2. Ankylosing Spondylitis 


3. Psoriatic Arthritis 
  • Epidemiology: similar M:F prevalence in the world.
  • Pathogenesis: 



        1. Pencil in Cup 
        2. coexistence of erosive changes and new bone formation which may occur within the same joint or in different joints
        3. fluffy periostitis, as well as new bone formation, at the site of enthesitis
        4. gross destruction of isolated joints; and 
        5. the occurrence of both joint lysis and ankylosis in the same patient
    • Nonpharmacological Treatment:
      • Exercise, PT, OT
      • Weight reduction
    • Pharmacological Treatment: 
      • NSAIDs: Naproxone: 375-500 mg BID; Celecoxib 200 mg BID; Ibuprofen, Diclofenac
      • Glucocorticoids
      • csDMARD
        • MTX
        • SFS
        • LFL
        • Cyclosporin
      • Anti-TNF - AVOID IN MALIGNANCY
        • 5 FDA approved Anti-TNF medications

        • Etanercept– 50 mg as a subcutaneous injection once weekly. Etanercept is a dimeric p75 TNF-alpha receptor Fc fragment fusion protein that binds TNF. An initial dose of 50 mg twice weekly for the first three months of therapy may be used in patients requiring treatment for moderate to severe psoriatic skin disease.

          Infliximab– 5 mg/kg administered by intravenous infusion at zero, two, and six weeks, followed by 5 mg/kg every eight weeks thereafter. It may be given either with or without MTX. Infliximab is a human / mouse chimeric anti-TNF-alpha antibody.

          Adalimumab 40 mg subcutaneously once every two weeks. Adalimumab is a human monoclonal anti-TNF antibody.

          ●Golimumab 50 mg subcutaneously once monthly. Golimumab is a human monoclonal anti-TNF antibody.

          ●Certolizumab pegol: nitial dose of 400 mg (administered as two 200 mg injections subcutaneously), with this dose repeated two and four weeks after the initial dose; maintenance with 200 mg once every other week, but may alternatively treat with 400 mg every four weeks. Certolizumab pegol is a pegylated Fab fragment of a humanized anti-TNF monoclonal antibody.


      • IL - 17 antibody: - AVOID IN BOWEL STMPTOMS 
        • Secukinumab (Cosentyx™) - monoclonal antibody against 17 A
        • Ixecukinumab 
      • Anti IL-12/23: 
        • Ustekinumab (Stelara) : PSUMMIT 1 and PSUMMIT 2 
          • IL-12 leads to Th1 pathway 
          • IL-23 leads to Th17 pathway 
          • Ustekinumab (UST), an mAb directed against the p40 subunit of IL-12 and IL-23
      • Anti-IL23
        • Guselkokumab
      • JAKi
        • Tofacitinib: JAK1/3: OPAL Broaden, and OPAL Beyond  
        • Filgotinib: JAK1
        • Baricitinib: 
      • CTLA4-Ig
        • Abatacept 
      • PDE-4 (Phosphodiesterase 4) Inhibitor: Apremilast 
        • Downstream in the TNF pathway
        • Increases expression of IL-10 
      • EULAR
        1. T2T: Remission or LDA. How to define LDA or Remission in PsA?
        2. NSAIDs for MSK s/s +- local steroid injection (1 month for Peripheral, Incase of axial ds, up to 2 months)
        3. Local steroid injection
        4. Polyarthritis - csDMARD (MTX preferred), LFL / SFS alternatives 
        5. Mono/Oligoarthritis with poor features - csDMARD . What are poor features findings - structural damage, high erythrocyte sedimentation rate/c reactive protein, dactylitis or nail involvement? All of the findings of Ms. S (4SW3)
        6. csDMARD not improved, or T2T in 6 months - bDMARD (if skin involvement IL-17i or 1L-12/23 i)
        7. csDMARD + bDMARD not adequate  or bDMARD not appropriate- tsDMARD (JAKi) (Tofacitinib) - similar to adalimumab for PsA but less good for skin involvement. When is bDMARD not appropriate? 
        8. When 7 not enough or not appropriate - then PDE4 i  (apremilast) can be used. When is JAKi not appropriate? 
        9. enthesitis not responding to NSAIDs -+ local steroid, start bDMARD (HERE ONLY TNFi or IL17 if has skin findings i) NOT - IL12/23 or JAKi. What bDMARD can be used for Ax PsA or enthesitis? 
        10. Ax PsA not responding to NSAIDs +- local GC, start bDMARD as in 9
        11. Not responding to bDMARD or not tolerating, okay to switch to another of the same class for 1 time ... if no other option, can try abatacept, lower efficacy in PsA 
        12. Sustained remission - cautious remission should be initiated 
      • ACR 

4. Enteropathic Arthritis (IBD associated)


Clinical Trials on 

Psoriatic arthritis
  • ACR20
  • ACR50
  • ACR70
  • Health Assessment Questionnaire Disability Index (HAQ-DI
Ankylosing Spondylitis 
  • Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), — if patient has high comorbidities can drive the BASDAI higher 
  • Functional ability measured by the Bath Ankylosing Spondylitis Functional Index (BASFI), and 
  • mobility of the spine measured by the Bath Ankylosing Spondylitis Metrology Index (BASMI)
  • Assessment in Ankylosing Spondylitis (ASAS) criteria 
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