Rheumatol Int DOI 10.1007/s00296-015-3376-0

Rheumatology INTERNATIONAL

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The prevalence of monosodium urate and calcium pyrophosphate crystals in synovial fluid from wrist and finger joints Paola Galozzi1 · Francesca Oliviero1 · Paola Frallonardo1 · Marta Favero1 · Ariela Hoxha1 · Anna Scanu1 · Mariagrazia Lorenzin1 · Augusta Ortolan1 · Leonardo Punzi1 · Roberta Ramonda1 

Received: 13 July 2015 / Accepted: 25 September 2015 © Springer-Verlag Berlin Heidelberg 2015

Abstract  The aim of this study was to assess the frequency of monosodium urate (MSU) and calcium pyrophosphate (CPP) crystals in synovial fluids (SFs) aspirated from wrist and finger joints of patients with previously diagnosed joint diseases. We reviewed the results of SF analysis of 1593 samples and identified 126 patients with effusions in the small joints of the hands and wrists. We reported from patients’ medical files data about sex, age, diagnosis, disease duration and the microscopic SF results. The prevalence of CPP crystals in SF was 85.71 % in CPPcrystals arthritis (CPP-CA), 19.35 % in rheumatoid arthritis (RA), 13.89 % in osteoarthritis (OA) and 0 % in psoriatic arthritis (PsA), spondyloarthritis (SpA), gout and miscellanea. The prevalence of MSU crystals in SF was 83.3 % in gout, 10 % in PsA, 2.8 % in OA and 0 % in RA, SpA, miscellanea and CPP-CA. Consistent with previously reported data concerning the big joints, microcrystals can be frequently found also in the small joints of patients with previous diagnosis. The finding underlines the importance of analyzing SF from the hand and wrist joints in the attempt to identify comorbidities associated with the presence of crystals and to develop targeted treatment strategies.

Introduction Synovial fluid (SF) analysis is an important tool for the diagnosis of joint diseases [1]. Examination of SFs is valuable for distinguishing inflammatory from non-inflammatory joint disorders, and it is required whenever septic or crystal-induced arthritis is suspected [2, 3]. Gout and calcium pyrophosphate (CPP)-related arthropathies are easy to diagnose when monosodium urate (MSU) and CPP crystals have been, respectively, identified in SF [4]. In a previous work [5], it has been stated that these crystals can be found also in SFs from patients with an established diagnosed joint disorder, such as rheumatoid arthritis (RA) and osteoarthritis (OA). SF is easier to obtain from large- or medium-sized joints, such as knees and shoulders, but small joints of hands and wrists are less frequent aspirated and rarely discussed in the literature [6]. This study aimed to examine the prevalence of CPP and MSU crystals in SFs obtained from wrist and finger joints of patients with previous diagnosis, by retrospectively evaluating the results of analyses carried out over the past 6 years in our Rheumatology Clinic.

Keywords  Synovial fluid · Monosodium urate crystals · Pyrophosphate crystals · Hand diseases

Methods

* Roberta Ramonda [email protected] 1



Rheumatology Unit, Department of Medicine ‑ DIMED, University of Padova, Via Giustiniani, 2, 35128 Padova, Italy

The results of SF analysis of 1593 samples collected from patients who were evaluated in our Rheumatology Unit for joint effusions between January 2008 and December 2014 were analyzed in this retrospective study. Among these results, we identified those referred to patients with articular swelling limited to hand and wrist joints and a well-defined diagnosis based on clinical and instrumental

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13 5 (1/4) 1 (0/1) 8 (5/3) 0 17 (9/8) 7460.71 ± 8186.23 48.57 ± 26.03 6 (19.35 %)

17 (4/13) 2 (1/1) 3 (0/3) 5 (0/5) 8 (5/3) 890 ± 1253.23 17.75 ± 19.05 5 (13.89 %)

1 (2.78 %)

MSU crystals (N, %)

2 (9.53 %)

12 (6/6) 2 (0/2) 3 (1/2) 1 (0/1) 3 (0/3) 25,418.75 ± 23,546.13 68.58 ± 14.77 0

21 8/13 55.5 ± 14.45 5.13 ± 4.26 0.51 ± 0.69

PsA

0

0 0 0 0 3 (1/2) 10,100 ± 6650.56 35 ± 20.22 0

3 1/2 55.67 ± 20.43 5.65 ± 7.56 0.3

SpA

5 (83.3 %)

0 1 (1/0) 2 (1/1) 0 3 (1/2) 1455 ± 1269.68 47.33 ± 31.26 0

6 5/1 72.33 ± 8.11 5.50 ± 10.37 1.44 ± 1.59

Gout

0

0 0 0 0 7 (4/3) 1050 ± 1343.50 28 6 (85.71 %)

7 1/6 73 ± 6.78 5.04 ± 7.01 0.32 ± 0.34

CPP-CA

  Joints: PIP proximal interphalangeal, DIP distal interphalangeal, MCP metacarpophalangeal, CMC carpometacarpal

b

  Diseases: OA osteoarthritis, RA rheumatoid arthritis, PsA psoriatic arthritis, SpA spondyloarthritis, CPP-CA acute calcium pyrophosphate crystal arthritis

a

Data are expressed as mean ± standard deviation

0

31 3/28 66.87 ± 17.85 12.25 ± 9.54 1.77 ± 2.30

36 4/32 65.4 ± 9 8.44 ± 6.42 0.74 ± 1.42

N M/F Age (years) Disease duration (years) Volume (mL) Jointsb, N (left/right)  PIP  DIP  MCP  CMC  Wrist WBC (N/mm3) PMN (%) CPP crystals (N, %)

RA

OA

Diseasesa

0

1 (0/1) 0 0 1 (0/1) 2 (2/0) 1350 ± 771.81 1.5 ± 0.71 0

4 3/1 62 0.25 ± 0.22 0.8 ± 0.4

Others

Table 1  Main features of the synovial fluids considered in this study, according to the disease and frequency of calcium phosphate (CPP) and monosodium urate (MSU) crystals

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examination. Moreover, multiple results from the same patient have been excluded. Data about the patients’ sex, age, diagnosis, disease duration and the microscopic characteristics of SF analysis were collected from their medical files. SF analysis was performed by trained operators according to conventional techniques. Total white blood cell (WBC) count was determined using a Bürker counting chamber, and differential cell counts were assessed with pre-stained slides for cell morphology (Testsimplets® Waldeck, Biosigma). Microcrystals were observed under a compensated polarized light microscope, which allows to identify their different morphology and birefringence. MSU crystals present the characteristic needle shape and intense birefringence with negative elongation. CPP crystals are instead recognized by their rod or rhomboidal shape and weak birefringence with positive elongation. All SFs data are expressed as mean ± standard deviation (SD).

Results Out of 1593 samples examined, 126 were collected from finger and wrist joints; 18 of these were further excluded due to missing data for diagnosis. The total number of samples included in this study was therefore 108; these referred to 23 males and 85 females with a mean age of 63.72 years (range 27–90 years). Overall, the aspirated joints were proximal interphalangeal (PIP) joints in 35 patients, distal interphalangeal (DIP) joints in 6 patients, metacarpophalangeal (MCP) joints in 16 patients, carpometacarpal (CMC) joints in 7 patients and wrist joints in 44 patients. Among the 108 patients, MSU crystals were found in 8 samples, whereas CPP crystals were found in 17. Table  1 outlines the breakdown of the results of this study, indicating the type of diseases affecting the patients studied: OA, RA, psoriatic arthritis (PsA), spondyloarthritis (SpA), gout, acute CPP crystal arthritis (CPP-CA) and other miscellanea disorders. The latter category included post-traumatic arthritis, polymyalgia rheumatica and tenosynovitis. The prevalence of CPP crystals in the SF was 85.71 % in CPP-CA, 19.35 % in RA, 13.89 % in OA and 0 % in PsA, SpA, gout and miscellanea, respectively. The prevalence of MSU crystals in the SF was 83.3 % in gout, 10 % in PsA, 2.8 % in OA and 0 % in RA, SpA, miscellanea and CPP-CA, respectively. Interestingly in our study, the identification of MSU or CPP crystals did not change the previous diagnosis; rather, it highlighted a possible additional association with crystalinduced arthritis.

Discussion Our study confirms the importance of analyzing SFs aspirated from swollen finger and wrist joints in indicating the prevalence of CPP and MSU crystals. As previously reported about SFs from big joints [5], the analysis of SFs from small joints allows to consider a possible association between CPP and MSU crystals and other well-established joint disorders. It is, nevertheless, true that aspirating synovial fluid from small hand joints even under ultrasound guidance represents a practice that is not so common in many rheumatologic clinics in view of its difficulty. With the exception of gout, MSU crystals were found in PsA (9.53 %) and OA (2.78 %). It is not unusual for uric acid to be elevated in acute phases of PsA, and coexistence with gout may occur in patients with PsA [7]. Controversial results have, instead, been reported with regard to MSU crystals in OA [8]. Some studies have suggested that crystal deposition may contribute to the onset or acceleration of OA joint damage, while others considered crystals as bystanders rather than causative factors of OA [9–11]. Remarkably, MSU crystals were not found in the SF of the RA patients, and, in fact, they are rarely described in the literature [12]. Excluding CPP-CA, CPP crystals were found in OA (13.89 %) and RA (19.35 %). These results are consistent with those reported for big joints, according to which CPP deposition is associated with distinct radiographic changes [5]. At the small joints, CPP crystal depositions could be identified by ultrasound imaging [1]. Concerning OA, some findings in the literature, such as the progression of patients with familial CPP to severe OA and the presence of CPP crystals in the SF of joints showing radiographic severity in OA patients, suggest an association with CPP disease [8, 13]. More interesting is the elevated percentage of CPP crystals in RA. Since data in the literature concerning the prevalence of CPP crystals in RA are conflicting [14, 15], our finding may support the hypothesis that there is an association between CPP deposition and RA. Another interesting finding uncovered by our study is the specific affected joints in connection to the different disease groups. Our data showed that PIP joints are more frequently involved in OA and PsA and wrists and MCP joints in RA. OA of the hand is known to mostly exhibit radiological changes at DIP and PIP joints [16]. The classic form of PsA typically affects DIP joints [17]; thus, the PIP joints involvement observed in our cases may be further evaluated. Concerning RA, it was already known that wrist and MCP joints are the most commonly involved regions in the upper limb in affected patients [18]. There are some limitations in our retrospective and observational study, including mainly the small number of

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the SFs included in the study. Other limitations are linked to the difficulty in aspirating, analyzing and interpreting the samples, especially when only small quantities of SF were obtained. These issues were obviated by employing trained specialists at all stages of the study. To conclude, as crystals can be detached more frequently than expected also in the small joints of patients with previous diagnosis of different other joint diseases, this marks the importance of SFs obtained from finger and wrist joints in identifying any possible comorbidities linked to the presence of crystals. Acknowledgments  The authors would like to express their appreciation to Linda Inverso Moretti for her help in preparing the English version of this manuscript.

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