Rheumatology‎ > ‎

Seronegative Arthritis


  • 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
        • 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