In Patients With Acute Mono/Oligoarthritis, a Targeted Ultrasound Scanning Protocol Shows Great Accuracy for the Diagnosis of Gout and CPPD

Edoardo Cipolletta; Emilio Filippucci; Abhishek Abhishek; Jacopo Di Battista; Gianluca Smerilli; Marco Di Carlo; Ferdinando Silveri; Rossella De Angelis; Fausto Salaffi; Walter Grassi; Andrea Di Matteo

Disclosures

Rheumatology. 2023;62(4):1493-1500.

Abstract and Introduction

Abstract

Objectives: To determine an US scanning protocol with the best accuracy for the diagnosis of gout and CPPD in patients with acute mono/oligo-arthritis of unknown origin.

Methods: Patients with acute mono/oligo-arthritis in whom a joint aspiration at the most clinically involved joint (target joint) was requested were consecutively enrolled. US was performed in each patient before the arthrocentesis. The accuracy of different US findings and scanning protocols for the diagnosis of gout and CPPD was calculated.

Results: A total of 161 subjects were included (32 gout patients, 30 CPPD patients and 99 disease-controls). US findings had a high specificity for gout (0.92–0.96) and CPPD (0.90–0.97), while the sensitivity ranged from 0.73 to 0.85 in gout (double contour sign and tophi, respectively) and from 0.60 to 0.90 in CPPD (hyaline and fibrocartilage deposits, respectively). The US assessment of two joints bilaterally (gout: knees, MTP1 joints; CPPD: knees, wrists) plus the target joint had an excellent diagnostic sensitivity (gout: 0.91, CPPD: 0.93) and specificity (gout: 0.91, CPPD: 0.89). This targeted US scanning protocol yielded to higher diagnostic accuracy compared with the US evaluation of the target joint [gout area under the curve (AUC) 0.91 vs 0.84, P = 0.03; CPPD AUC 0.93 vs 0.84, P = 0.04] unless the target joint was the knee or the MTP1 joint in gout and the knee or the wrist in CPPD.

Conclusions: A targeted US scanning protocol of two joints bilaterally plus the target joint showed an excellent accuracy (>90%) for the diagnosis of crystal arthritis in patients with acute mono/oligoarthritis.

Introduction

Acute mono and oligoarthritis are common clinical presentations in primary care services, rheumatology outpatients and hospital emergency departments.^[1–4] Common causes of acute mono and oligoarthritis are crystal arthritis, inflammatory flares of OA, acute flares of autoimmune inflammatory arthritis, reactive arthritis and septic arthritis.^[3] In patients with arthritis of unknown aetiology, synovial fluid analysis (SFA) is of utmost importance, especially for the diagnosis of crystal arthritis and to rule out septic arthritis. Reaching a definite diagnosis of crystal arthritis on clinical grounds alone may be challenging^[5] and alternative diagnostic tests when SFA is not possible have been proposed.^[6–9] Ultrasonography (US) has been validated and standardized in gout and calcium pyrophosphate deposition disease (CPPD) and it plays a growing role in the diagnosis and management of these conditions.^[9–15]

The OMERACT Working Groups have developed definitions for the US findings of gout and CPPD.^[16,17] The diagnostic accuracy of these definitions in patients with acute mono/oligoarthritis has been scarcely explored^[18–21] and the optimum scanning protocol (i.e. which and how many joints need to be scanned) for the diagnosis of gout and CPPD in such clinical scenario has not been established. Therefore the aim of this study was to identify the US scanning protocol with the best performance in the diagnosis of gout and CPPD in patients with acute mono/oligoarthritis.

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Abstract and Introduction
Methods
Results
Discussion
Conclusion
References
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Table 1. US scanning protocol
Joint	US findings	Indicative for
Shoulder	CPP deposits within the humeral condyle's HC	CPPD
	CPP deposits in the glenoid FC	CPPD
	DC at the humeral condyle's HC	Gout
Elbow	CPP deposits within the elbow's HC	CPPD
	DC at the elbow's HC	Gout
	Tophi in the olecranon bursa	Gout
Wrist	CPP deposits in the TFCC	CPPD
	CPP deposits in the SLL	CPPD
	Tophi in the wrist joint	Gout
MCP2	CPP deposits within the MCP2's HC	CPPD
	DC at the MCP2 joint's HC	CPPD
	Tophi in the MCP2 joint	Gout
Hip	CPP deposits within the femoral head's HC	CPPD
	CPP deposits in the acetabular FC	CPPD
	DC at the femoral head's HC	Gout
	Tophi in the hip joint	Gout
Knee	CPP deposits within the femoral condyle's HC	CPPD
	CPP deposits in the meniscal FC	CPPD
	CPP deposits in the patellar tendon	CPPD
	DC at the femoral condyle's HC	Gout
	Tophi in the popliteal groove	Gout
	Tophi in the patellar tendon	Gout
Ankle	CPP deposits within the talar HC	CPPD
	CPP deposits in the Achilles tendon	CPPD
	DC at the talar HC	Gout
	Tophi in the Achilles tendon	Gout
MTP1	CPP deposits within the MTP1j's HC	CPPD
	DC at the MTP1j's HC	Gout
	Tophi in the MTP1j	Gout

FC: fibrocartilage; HC: hyaline cartilage; SLL: scapholunate ligament; TFCC: triangular fibrocartilage complex.

Table 2. Baseline demographic, clinical and laboratory data
Demographic data	Age, years, mean (S.D.)	58.9 (15.1)
	Female, n (%)	65 (40.4)
	BMI, kg/m², mean (S.D.)	26.3 (5.1)
Clinical data	Oligoarthritis, n (%)	49 (30.4)
	Monoarthritis, n (%)	112 (69.6)
	Number of joints in the oligoarthritis group, median (IQR)	2.0 (2.0–3.0)
	First episode of arthritis, n (%)	101 (62.7)
	Number of previous episodes of arthritis, median (IQR)^a	1.0 (1.0–2.0)
	Subcutaneous tophi, n (%)	4 (2.5)
	Site of joint aspiration/injection, n (%)	Knee	96 (59.6)
		Ankle	19 (11.8)
		Shoulder	10 (6.2)
		Hip	9 (5.6)
		Elbow	9 (5.6)
		Wrist	8 (5.0)
		MTP1	8 (5.0)
		MCP2	2 (1.2)
Laboratory data	CRP, mg/dl, mean (S.D.)	2.0 (2.1)
	SU, mg/dl, mean (S.D.)	6.7 (3.4)
	Crystals in the SFA, n (%)	60 (37.3)

IQR: interquartile range.
^aThe median and IQR were calculated on the number of patients with one or more episodes of arthritis before the enrolment (n = 61).

Table 3. Accuracy of different US scanning protocols in the diagnosis of gout and CPPD
Disease	Protocol	US finding	SE (95% CI)	SP (95% CI)	PPV (95% CI)	NPV (95% CI)
Gout	Target joint^a	MSU deposits ≥1	0.75 (0.57, 0.89)	0.91 (0.85, 0.96)	0.69 (0.55, 0.80)	0.94 (0.89, 0.96)
	Extended scanning protocol^b	MSU deposits ≥1	0.91 (0.75, 0.98)	0.83 (0.75, 0.89)	0.57 (0.47, 0.66)	0.97 (0.92, 0.99)
		MSU deposits ≥2	0.88 (0.71, 0.96)	0.95 (0.89, 0.98)	0.80 (0.66, 0.89)	0.97 (0.92, 0.99)
		MSU deposits ≥3	0.81 (0.64, 0.93)	1.0 (0.97, 1.0)	1.0 (0.87, 1.0)	0.96 (0.91, 0.98)
	Reduced scanning protocol^c	MSU deposits ≥1	0.91 (0.75, 0.98)	0.91 (0.84, 0.95)	0.71 (0.58, 0.81)	0.98 (0.93, 0.99)
CPPD	Target joint^a	CPP deposits ≥1	0.73 (0.54, 0.88)	0.95 (0.89, 0.98)	0.76 (0.60, 0.87)	0.94 (0.90, 0.97)
	Extended scanning protocol^b	CPP deposits ≥1	0.97 (0.83, 1.0)	0.82 (0.74, 0.88)	0.55 (0.46, 0.64)	0.99 (0.94, 1.0)
		CPP deposits ≥2	0.93 (0.78, 0.99)	0.95 (0.89, 0.98)	0.80 (0.66, 0.89)	0.98 (0.94, 1.0)
		CPP deposits ≥3	0.90 (0.74, 0.98)	0.98 (0.93, 1.0)	0.90 (0.75, 0.97)	0.98 (0.94, 1.0)
		CPP deposits ≥4	0.63 (0.44, 0.80)	1.0 (0.97, 1.0)	1.0 (0.82, 1.0)	0.92 (0.88, 0.95)
	Reduced scanning protocol^d	CPP deposits ≥1	0.93 (0.78, 0.99)	0.89 (0.83, 0.94)	0.67 (0.55, 0.77)	0.98 (0.94, 1.0)

FC: fibrocartilage; HC: hyaline cartilage; SLL: scapholunate ligament; TFCC: triangular fibrocartilage complex.
^aThe US assessment of the target joint included all the US findings reported in Table 1.
^bThe extended scanning protocol included all the US findings reported in Supplementary Table S3.
^cThe reduced scanning protocol in gout included the knees (DC sign and tophi), the MTP1 joints (DC sign and tophi) plus the target joint (unless this was the knee or the MTP1 joint).
^dThe reduced scanning protocol in CPPD included the knees (deposits within the HC and deposits in the meniscal FCs), the wrists (deposits in the TFCC and in the SLL) plus the target joint (unless this was the knee or the wrist).

Table 4. Subanalyses of the diagnostic accuracy (95% CI) of the US scanning protocol by confounding factors
Confounding factors	Target joint	P-value	Extended scanning protocol	P-value	Reduced scanning protocol	P- value
Gout
Knee was the target joint	0.88 (0.79, 0.97)	0.27	0.94 (0.86, 1.0)	0.73	0.96 (0.89, 1.0)	0.14
Knee was not the target joint	0.79 (0.66, 0.97)	0.27	0.91 (0.82, 1.0)	0.73	0.87 (0.78, 0.96)	0.14
Either knee or MTP1 was the target joint	0.90 (0.84, 0.97)	<0.01	0.93 (0.87, 1.0)	0.78	0.90 (0.83, 0.96)	0.80
Neither knee nor MTP1 was the target joint	0.56 (0.42, 0.70)	<0.01	0.91 (0.74, 1.0)	0.78	0.92 (0.77, 1.0)	0.80
First episode of arthritis	0.82 (0.70, 0.93)	0.04	0.92 (0.78, 1.0)	0.78	0.90 (0.81, 0.98)	0.37
More than one episode of arthritis	0.94 (0.90, 0.98)	0.04	0.95 (0.88, 1.0)	0.78	0.95 (0.88, 1.0)	0.37
CPPD
Knee was the target joint	0.90 (0.82, 0.99)	0.03	0.98 (0.96, 1.0)	0.07	0.95 (0.92, 0.97)	0.08
Knee was not the target joint	0.71 (0.55, 0.87)	0.03	0.90 (0.82, 0.99)	0.07	0.90 (0.82, 0.97)	0.08
Either knee or wrist was the target joint	0.94 (0.87, 1.0)	<0.01	0.94 (0.86, 1.0)	0.96	0.92 (0.84, 1.0)	0.58
Neither knee nor wrist was the target joint	0.71 (0.56, 0.85)	<0.01	0.94 (0.87, 1.0)	0.96	0.89 (0.82, 0.96)	0.58
First episode of arthritis	0.78 (0.66, 0.89)	0.02	0.92 (0.82, 1.0)	0.60	0.91 (0.81, 1.0)	0.61
More than one episode of arthritis	0.96 (0.87, 1.0)	0.02	0.95 (0.90, 1.0)	0.60	0.93 (0.90, 0.97)	0.61