Reviewer: Dr. Nicolas Richard
Assistant Professor (Adjunct), Department of Medicine, Division of Rheumatology
McMaster University
Dr. Nicholas Richard, MD FRCPC
Professeur adjoint de clinique, Département de médecin, Université de Montréal, et
Division de rhumatologie, Hôpital Maisonneuve-Rosemont, Montréal, Québec
Topic last updated: February 2025
Topic last reviewed: February 2025
BOTTOM LINE
Spondyloarthropathies (SpA) are a family of related diseases that can affect skin/nails (psoriasis), eyes (uveitis), GI tract (Crohn’s/ulcerative colitis), and joints (inflammatory arthritis). Joint manifestations include axial disease with inflammatory back pain, sacroiliitis, syndesmophytosis, and ankylosis; peripheral joint disease manifests as peripheral inflammatory arthritis, enthesitis, and dactylitis.
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OVERVIEW
- Spondyloarthropathy (SpA) is an umbrella term referring to a family of related diseases which can occur alone or together as a spectrum within a single patient.
- SpA can manifest in various tissues:
- Joint:
- Axial arthritis, peripheral arthritis, enthesitis, dactylitis
- Bone:
- CNO (Chronic non-bacterial osteomyelitis); encompasses CRMO (Chronic Recurrent Multifocal Osteomyelitis)
- SAPHO (Synovitis Acne Pustolosis Hyperostosis Osteitis)
- Gastrointestinal:
- Inflammatory bowel disease (Crohn’s, Ulcerative Colitis)
- Skin/nails:
- Cutaneous psoriasis, Nail psoriasis, Hidradenitis suppurativa
- Eye:
- Uveitis
- Joint:
DEFINITIONS
| Term | Definition |
|---|---|
| Seronegative | Not associated with positive antibodies (ex: negative RF, ACPA, ANA, etc.) |
| Axial Arthritis | Arthritis affecting vertebral column, sternoclavicular, costochondral, sacroiliac joints |
| Peripheral Arthritis | Arthritis affecting hands, wrists, elbows, shoulders, hips, knees, ankles, feet |
| Enthesitis | Inflammation at insertion of tendon/ligament to bone (ex: elbow epicondylitis, Achilles enthesitis, plantar fasciitis, patellar tendon, iliac crest, supraspinatus insertions, greater trochanters). Enthesitis can occur individuals without SpA, but happen more frequently in patients with SpA. |
| Dactylitis | Relatively uniform swelling of entire finger or toe (“sausage digit”). Due to synovitis, osteitis, and flexor tenosynovitis. |
IMPLICATIONS
- Clinically:
- A thorough clinical assessment for SpA includes a review, exam, and investigations to detect evidence of SpA manifestations in the tissues above (joint, bone, GI tract, skin, nails, and eye)
- Therapeutically:
- Several of the above diseases may respond to the similar DMARD therapies
- Treatment challenges occur when one tissue domain responds to a DMARD, but another tissue domain worsens
- Immunologically:
Different cytokines appear to play a more important pathogenic role in different tissues (no particular order):- Skin: IL-17, IL-23p19, IL-12/23p40, TNF
- Peripheral joints: TNF, IL-17, IL-23p19, IL-12/23p40
- Axial joints: TNF, IL-17, (?IL23)
- Enthesitis: IL-17, IL-12/23p40, TNF, IL-23p19
- Gut: TNF, IL-12/23p40, IL-23p19
- Thus, targeted DMARD therapy in SpA may include PDE-4 inhibitors (downregulates TNF and IL23 production), TNF-inhibitors, IL-17 inhibitors, IL-23 inhibitors, IL-12/23 inhibitors, JAK inhibitors (IL-23 signals though the JAK-STAT pathway to increase IL-17 production)
Choosing therapy in a SpA patient often depends on which dominant tissue domain (and therefore which cytokine targets) are involved in the patient’s disease
TREATMENTS
REFERENCES
Li, H., & Tsokos, G. C. (2021). IL-23/IL-17 Axis in Inflammatory Rheumatic Diseases. Clinical reviews in allergy & immunology, 60(1), 31–45. https://doi.org/10.1007/s12016-020-08823-4
Robinson, P. C., van der Linden, S., Khan, M. A., & Taylor, W. J. (2021). Axial spondyloarthritis: concept, construct, classification and implications for therapy. Nature reviews. Rheumatology, 17(2), 109–118. https://doi.org/10.1038/s41584-020-00552-4
Siebert, S., Millar, N. L., & McInnes, I. B. (2019). Why did IL-23p19 inhibition fail in AS: a tale of tissues, trials or translation?. Annals of the rheumatic diseases, 78(8), 1015–1018. https://doi.org/10.1136/annrheumdis-2018-213654