Investigating Undifferentiated Peripheral Inflammatory Arthritis: Case Study and Recommendations

1. 3e Initiative 2009How to investigate and follow-up Undifferentiated Peripheral Inflammatory Arthritis? Case 2

2. Case 2 John, 35 years old, is a computer scientist, athletic. He has developed a spontaneous swelling of the left knee for 15 days. He describes a family history of diabetes mellitus and psoriasis. He has a remote history of a left cruciate ligament tear after a skiing injury. Your exam confirms a monoarthritis. There is no evidence for synovitis any other joints or extra-articular manifestations.

3. Question 1 • Which differential diagnosis should be considered in this patient? • Osteoarthritis • Reactive arthritis • Spondyloarthritis • Rheumatoid arthritis • Crystal-related arthritis • Septic arthritis

4. Answer Question 1 • Which differential diagnosis should be considered in this patient? • Osteoarthritis • Reactive arthritis • Spondyloarthritis • Rheumatoid arthritis • Crystal-related arthritis • Septic arthritis

5. Recommandation 1 (beginning) • All possible causes of arthritis (idiopathic, autoimmune, degenerative, infectious, malignancy, traumatic, metabolic) should be considered in the differential diagnosis • Complete history and thorough physical examination will determine the ranking order of possible differential diagnoses [5, D] • […]

6. Differential diagnosis Mentioned* in the 66 studies analyzed with the % of times they were mentioned * (as exclusion criteria in studies including only UIPA patients and other diagnosis that were included in studies with a mixed population where a UIPA subset was defined)

7. Question 2 • What are the minimal laboratory and imaging investigations necessary to identify most causes of arthritis? • Acute phase reactants • renal function, Urate • RF, anti-CCP antibodies • Synovial fluid analysis • Left Knee, hands and feet X-ray

8. Answer Question 2 • What are the minimal laboratory and imaging investigations necessary to find possible causes of arthritis? • Acute phase reactants • renal function, Urate • RF, anti-CCP antibodies • Synovial fluid analysis • Left Knee, hands and feet X-ray

9. Recommendation 1 (continuation) • […] • Investigations should be based on the differential diagnosis of the patient [5, D]

10. Question 3 • The results of the lab tests and radiographs are as follows: • ESR: 12 mm at 1st hour, CRP: 5 mg/L • Creatinine 80Mmol/L, Urate 40mg/L • RF and Anti-CCP negative • Synovial fluid analysis: White cells 6000/mm3, sterile, without crystal • Normal X-ray.You will complete exams to classify this arthritis • On further history, you learn that his paternal aunt is treated by TNF-blockers for a B27+ spondyloarthritis. He asks you if his disease could be hereditary and if a genetic test could be useful to get ahead with a diagnosis. What is your answer? • Some genetic markers are highly specific for Ankylosing Spondylitis (AS) • In isolation, the genetic markers are not very informative for the diagnosis of AS • The negative predictive value of HLA B27 for AS is very high • In his case, HLA B27 testing may be useful

11. Answer Question 3 • The results of the lab tests and radiographs are the following: • ESR: 12 mm at 1st hour, CRP: 5 mg/L • Creatinine 80Mmol/L, Urate 40mg/L • RF and Anti-CCP negative • Synovial fluid analysis: White cells 6000/mm3, sterile, without crystal • Normal X-ray.You will complete exams to classify this arthritis • By questioning him another time, you learn that his paternal aunt is treated by TNF-blockers for a B27+ spondyloarthritis. He asks you if his disease could be hereditary and if a genetic test could be useful to get ahead with a diagnosis. What is your answer? • Some genetic marker are highly specific of AS • In isolation, the genetic markers are not very informative for the diagnosis of AS • the negative predictive value of HLA B27 for ankylosing spondylitis is very high • In his case, HLA B27 testing may be useful

12. Recommendation 7 • There is no genetic test that can be routinely recommended [3b, D], however HLA-B27 testing may be helpful in specific clinical settings [2b, C]

13. Question 4 • HLA B27 was tested and was negative. You perform 3 corticosteroid injections but arthritis reoccurs each time after 2 or 3 months. As you see him again for one year, he describes sometimes sudden high temperature. Physical exam is similar and there is no evidence for extra-articular manifestations. You are concerned that he may have a chronic infectious monoarthritis. Do you think that a synovial biopsy will give specific diagnostic information? • Yes • No

14. Answer Question 4 • HLA B27 was tested and was negative. You perform 3 corticosteroid injections but arthritis reoccurs each time after 2 or 3 months. As you see him again for one year, he describes sometimes sudden high temperature. Physical exam is similar and there is no evidence for extra-articular manifestations. You are concerned that he may have a chronic infectious monoarthritis. Do you think that a synovial biopsy can give information for differential diagnosis? • Yes • No

15. Recommendation 8 • Routine synovial biopsy is not recommended but can give information for differential diagnosis, especially in patients with persistent monoarthritis [2b, B]

16. Contribution of synovial biopsy in UPIA • Prognostic markers not yet identified • Vascular pattern can be of help in differentiating between different kinds of arthritides (Canete 2003) • CD22+ and CD38+ seem to help in differentiating RA and non-RA, whereas CD38+ and CD68+ can differentiate between RA – SpA, PsA, UA, ReA – OA, CA (Kraan 1999) • ACPA synovial staining not specific for RA (Vossenaar 2004, Baeten 2004)