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

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? 1.Osteoarthritis 2.Reactive arthritis 3.Spondyloarthritis 4.Rheumatoid arthritis 5.Crystal-related arthritis 6.Septic arthritis

4 Answer Question 1 Which differential diagnosis should be considered in this patient? 1.Osteoarthritis 2.Reactive arthritis 3.Spondyloarthritis 4.Rheumatoid arthritis 5.Crystal-related arthritis 6.Septic arthritis

5 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] […] Recommandation 1 (beginning)

6 Diagnosis% RA50 OA33 Reactive arthritis32 Crystal27 Psoriatic arthritis21 trauma20 SpA18 AS15 CTD15 Septic15 SLE14 Sarcoidosis9 Soft-tissue disorders7.5 Polymyalgia rheumatica7.5 uSpA6 Diagnosis% Lyme disease4.5 Wegener3 Sjogren’s syndrome3 JIA3 Palindromic rheumatism3 Polymyositis3 Fibromyalgia3 Endocrinologic origin3 Systemic autoimmune diseases3 Malignancy-related3 Viral3 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) Differential diagnosis

7 Question 2 What are the minimal laboratory and imaging investigations necessary to identify most causes of arthritis? 1.Acute phase reactants 2.renal function, Urate 3.RF, anti-CCP antibodies 4.Synovial fluid analysis 5.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? 1.Acute phase reactants 2.renal function, Urate 3.RF, anti-CCP antibodies 4.Synovial fluid analysis 5.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 1 st 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? 1.Some genetic markers are highly specific for Ankylosing Spondylitis (AS) 2.In isolation, the genetic markers are not very informative for the diagnosis of AS 3.The negative predictive value of HLA B27 for AS is very high 4.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 1 st 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? 1.Some genetic marker are highly specific of AS 2.In isolation, the genetic markers are not very informative for the diagnosis of AS 3.the negative predictive value of HLA B27 for ankylosing spondylitis is very high 4.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? 1.Yes 2.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? 1.Yes 2.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)