Determining early referral criteria for patients with suspected inflammatory arthritis presenting to primary care physicians: a cross-sectional study

Figures & data

Figure 1 Study design.

Abbreviations: CPR, C-reactive protein; RF, rheumatoid factor; ESR, erythrocyte sedimentation rate; Hep, hepatitis; ANA, antinuclear antibody; AST, aspartate aminotransferase; ALT, alanine aminotransferase; ACPA, anti-citrullinated protein antibodies; US, ultrasonography.

Figure 2 Standardized musculoskeletal examination procedures.

Note: The described techniques for physical examination should be performed by a trained clinician.
Abbreviations: MCP, metacarpophalangeal; PIP, proximal inter-phalangeal.

Table 1 Demographic and patient-reported variables with their association to positive diagnosis of inflammatory arthritis

	N	Disease status		p-value*
		Yes	No
Demographics
Sex
Male	37	24	13	0.496
Female	165	104	61
Age
<40 years	74	52	22	0.081
≥40 years	128	76	52
Patient-reported
Loss of appetite
Yes	31	25	6	0.04
No	171	103	68
Stiffness
Yes	93	51	42	0.02
No	109	77	32
Family history of uveitis
Yes	7	1	6	0.01
No	195	127	68

Note:

* Chi-square test.

Table 2 Musculoskeletal parameters significantly associated with a positive diagnosis of inflammatory arthritis

	N	Disease status		p-value
		Yes	No
Metacarpophalangeal joints
Swelling of MCP 2 (right)
Yes	26	21	5	0.048
No	176	107	69
Swelling of MCP 2 (left)
Yes	27	23	4	0.008
No	175	105	70
Swelling of MCP 5 (right)
Yes	7	7	0	0.036
No	195	121	74
Swelling of MCP 3 (left)
Yes	26	21	5	0.036
No	176	107	69
Tenderness of MCP 1 (right)
Yes	57	42	15	0.038
No	145	86	59
Tenderness of MCP 1 (left)
Yes	61	47	14	0.006
No	141	81	60
Tenderness of MCP 2 (left)
Yes	73	53	20	0.028
No	129	75	54
Proximal inter-phalangeal joints
Swelling of PIP 2 (right)
Yes	29	25	4	0.006
No	173	103	70
Swelling of PIP 2 (left)
Yes	29	25	4	0.006
No	173	103	70
Swelling of PIP 3 (right)
Yes	34	28	6	0.011
No	168	100	68
Swelling of PIP 3 (left)
Yes	32	26	6	0.027
No	170	102	68
Swelling of PIP 5 (right)
Yes	12	11	1	0.036*
No	190	117	73
Wrist
Swelling of the wrist (right)
Yes	42	37	5	0.001
No	160	91	69
Tenderness of the wrist (right)
Yes	42	36	6	0.001
No	160	92	68

Note: p-values calculated using the chi-square test, except *Fisher’s exact test.

Abbreviations: MCP, metacarpophalangeal; PIP, proximal inter-phalangeal.

Table 3 Blood parameters significantly associated with a positive diagnosis of inflammatory arthritis

	N	Disease status		p-value
		Yes	No
CRP
Positive	26	21	5	0.048
Negative	176	107	69
RF
Positive	28	24	4	0.008
Negative	166	99	67
ACPA
Positive	30	28	2	0.001
Negative	160	91	69

Abbreviations: CRP, C-reactive protein; RF, rheumatoid factor; ACPA, anti-citrullinated protein antibodies.

Table 4 Analysis of variables showing an association with a positive diagnosis of inflammatory arthritis

	Sensitivity	Specificity	PPV	NPV	Diagnostic accuracy	Likelihood ratio (positive)	Likelihood ratio (negative)
Loss of appetite	19.5% (13.6–27.2)	89.47% (80.6–94.6)	75.8% (59.0–87.2)	39.8% (32.7–47.3)	45.6% (39.0–52.4)	1.9 (1.1–3.3)	0.90 (0.88–0.92)
Swelling of MCP 2 (right)	16.4% (11.0–23.8)	93.2% (85.1–97.1)	80.8% (62.1–91.5)	39.2% (32.3–46.6)	44.6% (37.9–51.5)	2.5 (1.0–5.8)	0.9 (0.9–0.9)
Swelling of MCP 2 (left)	18.0% (12.3–25.5)	94.6% (86.9–97.9)	85.2% (67.5–94.1)	40.0% (33.0–47.4)	46.0% (39.3–52.9)	3.3 (1.4–8.0)	0.9 (0.8–0.9)
Swelling of MCP 5 (right)	5.5% (2.7–10.9)	100.0% (95.1–100.0)	100.0% (64.6–100.0)	38.0% (31.4–44.9)	40.1% (33.6–47.0)	undefined	1.0 (0.9–1.0)
Swelling of PIP 2 (right)	19.5% (13.6–27.2)	94.6% (86.9–97.9)	86.2% (69.4–94.5)	40.5% (33.4–47.9)	47.0% (40.3–53.9)	3.6 (1.6–8.1)	0.9 (0.8–0.9)
Swelling of PIP 2 (left)	18.0% (12.3–25.5)	91.9% (83.4–96.2)	79.3% (61.6–90.2)	39.3% (32.3–46.7)	45.1% (38.3–51.9)	2.2 (1.1–4.5)	0.9 (0.9–0.9)
Swelling of PIP 3 (right)	21.9% (15.6–29.8)	91.9% (83.4–96.2)	82.4% (66.5–91.7)	40.5% (33.4–48.0)	47.5% (40.8–54.4)	2.7 (1.5–4.8)	0.9 (0.8–0.9)
Swelling of PIP 3 (left)	20.3% (14.3–28.1)	91.9% (83.4–96.2)	81.3% (64.7–91.1)	40.0% (32.9–47.5)	46.5% (39.8–53.4)	2.5 (1.3–4.7)	0.9 (0.8–0.9)
Swelling of PIP 5 (right)	8.6% (4.9–14.7)	98.7% (92.7–99.8)	91.7% (64.6–98.5)	38.4% (31.8–45.5)	41.6% (35.0–48.5)	6.4 (0.1–300.4)	0.9 (0.9–0.9)
Swelling of wrist (right)	28.9% (21.8–37.3)	93.2% (85.1–97.1)	88.1% (75.0–94.8)	43.1% (35.7–50.9)	52.5% (45.6–59.3)	4.3 (2.5–7.2)	0.8 (0.7–0.8)
Tenderness of wrist (right)	28.1% (21.1–36.5)	91.9% (83.4–96.2)	85.7% (72.2–93.3)	42.5% (35.1–50.3)	51.5% (44.6–58.3)	3.5 (2.2–5.5)	0.8 (0.8–0.8)
RF positive	19.5% (13.5–27.4)	94.4% (86.4–97.8)	85.7% (68.5–94.3)	40.4% (33.2–48.0)	46.9% (40.0–53.9)	3.5 (1.5–7.9)	0.9 (0.8–0.9)
ACPA positive	23.5% (16.8–31.9)	97.2% (90.3–99.2)	93.3% (78.7–98.2)	43.1% (35.7–50.9)	51.1% (44.0–58.1)	8.5 (2.5–27.9)	0.8 (0.8–0.8)

Note: 95% confidence intervals correspond to Wilson’s score intervals.

Abbreviations: PPV, positive predictive value; NPV, negative predictive value; MCP, metacarpophalangeal; PIP, proximal inter-phalangeal; RF, rheumatoid factor; ACPA, anti-citrullinated protein antibodies.

Table 5 Suggested variables that should be included in a referral criteria (based on variables that showed >90% specificity and good positive predictive value and likelihood ratio)

No.	Criteria	How to assess
1	Loss of appetite	History taking
2	MCP 2 swelling either in right and/or left hand	MCP scissor technique: The examiner should make a scissor-like shape with his/her fingers, joining the index and middle fingers together while joining the ring and little finger together, making a space in between. Then, the patient’s hand is held from the sides at the MCP level and the MCPs are flexed to 90 degrees. Then, two free thumbs from both hands are used to palpate the joint line for every MCP joint. One thumb is pressed firmly for a power causing whitening of the distal thumb nail, while the other thumb is pushed intermittently in and out to assess for swelling (fluctuation of fluid).
3	MCP 5 swelling either in right and/or left hand	MCP scissor technique: The examiner should make a scissor-like shape with his/her fingers, joining the index and middle fingers together while joining the ring and little finger together, making a space in between. Then, the patient’s hand is held from the sides at the MCP level and the MCPs are flexed to 90 degrees. Then, two free thumbs from both hands are used to palpate the joint line for every MCP joint. One thumb is pressed firmly for a power causing whitening of the distal thumb nail, while the other thumb is pushed intermittently in and out to assess for swelling (fluctuation of fluid).
4	PIP 2 swelling either in right and/or left hand	PIP 4-finger: The examiner’s thumb and index finger of one hand should hold each PIP from the side and press firmly until the whitening of distal fingers from low blood supply is clear. With the thumb and index finger of the other hand, the examiner should hold the same PIP-joint from anteroposterior direction and push intermittently in and out to look for swelling (fluctuation of fluid).
5	PIP 3 swelling either in right and/or left hand	PIP 4-finger: The examiner’s thumb and index finger of one hand should hold each PIP from the side and press firmly until the whitening of distal fingers from low blood supply is clear. With the thumb and index finger of the other hand, the examiner should hold the same PIP-joint from anteroposterior direction and push intermittently in and out to look for swelling (fluctuation of fluid).
6	Wrist swelling either in right and/or left hand	Wrist 2-thumbs: The examiner thumb should follow the third metacarpal bone on the dorsal aspect of the hand until reaching a dimple at the capitate level. This thumb should exert a firm, continuous pressure on this point until the whitening of the distal thumb nail is clear, with the examiner’s other thumb pushing intermittently in and out just half an inch away from the other thumb on wrist joint line looking for swelling (fluctuation of fluid).
7	Wrist tenderness either in right and/or left hand	Wrist 2-thumbs: The examiner thumb should follow the third metacarpal bone on the dorsal aspect of the hand until reaching a dimple at the capitate level. This thumb should exert a firm, continuous pressure on this point until the whitening of the distal thumb nail is clear, with the examiner’s other thumb pushing intermittently in and out just half an inch away from the other thumb on wrist joint line looking for tenderness (pain felt by the patient).
8	ACPA positivity	Laboratory finding
9	Rheumatoid factor positivity	Laboratory finding

Notes: In adult patients ≥18 years of age who present with small joint pain to PCPs, these variables correlated with the final diagnosis of arthritis. Further research work is needed to determine how to use these variables in clinical practice.

Abbreviations: MCP, metacarpophalangeal; PIP, proximal inter-phalangeal; ACPA, anti-citrullinated protein antibodies; PCPs, primary care physicians.