Clinical Rheumatology

, Volume 24, Issue 5, pp 476–479

Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome: ultrasonography as a diagnostic tool

Authors

    • Department of Clinical ImmunologySGPGIMS
    • Department of MedicineGovernment Medical College and Hospital
  • Ajay Kumar Dabra
    • Department of RadiodiagnosisGovernment Medical College and Hospital
  • Ravinder Kaur
    • Department of RadiodiagnosisGovernment Medical College and Hospital
  • Atul Sachdev
    • Department of MedicineGovernment Medical College and Hospital
  • Ram Singh
    • Department of MedicineGovernment Medical College and Hospital
Original Article

DOI: 10.1007/s10067-004-1061-x

Cite this article as:
Agarwal, V., Dabra, A.K., Kaur, R. et al. Clin Rheumatol (2005) 24: 476. doi:10.1007/s10067-004-1061-x

Abstract

Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome is characterized by symmetrical synovitis and swelling of both the upper and lower extremities. The anatomical determinant of RS3PE is predominantly extensor tenosynovitis as revealed by magnetic resonance imaging (MRI). Given the cost constraints, time, and expertise required in carrying out MRI and ease in diagnosing tenosynovitis by ultrasound, we utilized high-frequency ultrasonography (USG) for evidence of tenosynovitis of the distal tendons in patients with RS3PE. Diagnosis of tenosynovitis was made on the basis of anechoic or hypoechoic signals around the tendon sheaths in both transverse and longitudinal planes. Flexor and extensor tendons at the wrist and metacarpal heads and extensor digitorum longus (EDL) tendons at the ankle were evaluated with a 7.5–10-MHz linear probe. There were ten patients (seven males) with a mean age of 59.5 years (range: 52–78 years) and mean disease duration of 6.1 months (range: 1.5–12 months). Disease onset was acute in all of the cases. Pitting edema of the hands was present in all except two patients whereas four patients, in addition, had edema of the feet. Edema was symmetrical in seven patients. Inability to make a complete fist was noted in all. Tenosynovitis of extensor and flexor tendons at the wrist and the metacarpal heads was documented in all patients with edema of the hands. In seven cases extensor tendon tenosynovitis was more prominent compared to the flexor tendons. Tenosynovitis of EDL tendons was detected in six cases. Dramatic relief with low-dose prednisolone was noted in all patients within 6 weeks of therapy. At a mean follow-up of 10.1 months all patients had marked relief in edema of extremities and improvement in the grip strength. Our study confirms that tenosynovitis of both flexor and extensor tendons at the wrist and extensor tendons of the feet is the hallmark of RS3PE syndrome. USG is a reliable and cost-effective modality for evaluation of patients with suspected RS3PE.

Keywords

PolymyalgiaRheumatoidSarcoidosisTenosynovitis

Introduction

In 1985 McCarty et al. [1] noticed a subset of elderly, seronegative rheumatoid arthritis patients presenting with symmetrical synovitis and distal pitting edema of the extremities. The clinical picture of these patients resembled polymyalgia rheumatica and they showed dramatic and lasting response to low-dose glucocorticoid therapy. Of these patients, 59% had HLA-B7 positivity in contrast to 24% in the general population [2]. The term applied to this clinically distinct subset of patients was “remitting seronegative symmetrical synovitis with pitting edema” (RS3PE) syndrome. Since then a number of centers have reported their experiences with similar cases [26].

Distal pitting edema in these patients was postulated to be due to venous obstruction, increase in capillary permeability, lymphatic obstruction, or vigorous distal tenosynovitis. McCarty et al. [1, 2] reported tenosynovitis of the flexor tendons at the wrist joint. However, later studies documented tenosynovitis of the extensor digitorum tendons at the wrist [3, 4]. Recently, Cantini et al. [3] reported predominant involvement of the extensor tendons in RS3PE syndrome as evidenced on magnetic resonance imaging (MRI). MRI is a sensitive technique but is limited by availability and cost efficacy. Ultrasonography (USG) on the other hand is easily available, accessible, reliable, and cheaper in diagnosing inflammatory conditions of the tendons.

We took up this study with the aim of describing the clinical and laboratory features and outcome of North Indian patients with RS3PE and evaluating the efficacy of USG in diagnosing tenosynovitis in patients with RS3PE.

Methods

Patients attending the rheumatology and geriatric outpatient clinic at the Government Medical College Hospital, Chandigarh, fulfilling the criteria for diagnosis of RS3PE as proposed by Olive et al. [4], were enrolled in the study. Flexor and extensor tendons at the wrist joint, flexor tendons at the metacarpal heads, and extensor digitorum longus (EDL) tendons were evaluated with a B-mode, 7.5–10-MHz linear transducer on a Hewlett-Packard Image Point machine. Diagnosis of tenosynovitis was made on the basis of hypoechogenicity or anechogenicity around the tendon sheaths in both transverse and longitudinal planes. Serial USG was carried out at intervals of 6–8 weeks. Fifteen age- and sex-matched healthy controls were also studied. None of the controls demonstrated circumferential hypoechogenicity around any of the tendons examined. Patients below 50 years of age and fulfilling criteria for diagnoses of polymyalgia rheumatica, seropositive rheumatoid arthritis, spondyloarthropathy, and having erosions on roentgenograms of the joints and demonstrating crystals on synovial fluid examination were excluded from the study.

There were ten patients, seven males, with a mean age of 59.5 years (range: 52–78 years) and mean disease duration of 6.1 months (range: 1–12 months) (Table 1). All patients had acute onset of disease. Pitting edema of hands was present in eight cases whereas pitting edema of both hands and feet was present in four cases. In two cases there was pitting edema of the feet only. Edema was symmetrical in seven cases. Seven patients had symmetrical arthritis with hand joints (wrist, metacarpophalangeal, and proximal interphalangeal), ankle, elbow, and shoulders being involved in 8, 7, 5, and 4 cases, respectively. None of the patients had constitutional symptoms (fever, weight loss), subcutaneous nodules, or positivity for rheumatoid factor (RF). The duration of morning stiffness varied from 10 min to a whole day. The mean erythrocyte sedimentation rate was 43 mm/h (range: 20–62 mm/h). Roentgenograms of the hands and feet were normal in all except three cases, where mild juxta-articular osteopenia was noted.
Table 1

Demographic and clinical profile. EMS early morning stiffness

 

Case 1

Case 2

Case 3

Case 4

Case 5

Case 6

Case 7

Case 8

Case 9

Case 10

Age (years)

78

54

60

52

65

56

56

56

58

60

Sex

M

M

F

F

M

M

F

M

M

M

Duration (months)

7

12

1

12

3

1

1

12

6

5

Inability to make fist

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

No

Pitting edema

Hands

Hands, feet

Hands

Hands, feet

Hands

Hands

Hands, feet

Hands, feet

Feet

Feet

Symmetrical edema

Yes

Yes

No

Yes

No

No

Yes

Yes

Yes

Yes

EMS (min)

300

60

20

120

10

Whole day

120

60

60

30

Results

Ultrasonographic evaluation revealed tenosynovitis of extensor (Figs. 1, 2) and flexor digitorum tendons (Fig. 3) of hands in eight cases whereas tenosynovitis of EDL (Fig. 4) was detected in six cases. Tenosynovitis of the extensor tendons was more prominent compared to the flexor tendons in all eight cases. Nine patients continued to exhibit characteristics like pure RS3PE whereas one was later diagnosed to have sarcoidosis. She had ankle arthritis and mediastinal lymphadenopathy and raised serum angiotensin-converting enzyme level with negative Mantoux test. Follow-up ultrasound in all cases at 6 weeks revealed marked decrease in edema around the tendons.
Fig. 1

Ultrasonography of the hand. Transverse view through the right wrist extensor compartment showing diffuse edema of the subcutaneous tissue and tenosynovitis of the extensor tendons.

Fig. 2

Ultrasonography of the hand. Longitudinal view of the wrist extensor aspect shows tenosynovitis of one of the extensor digitorum tendon slips along with subcutaneous edema.

Fig. 3

Ultrasonography of both hands. Transverse view through both wrist flexor aspects shows diffuse subcutaneous edema and tenosynovitis of the flexor tendons.

Fig. 4

Ultrasonography of the ankle. Transverse view through the left ankle shows diffuse subcutaneous edema and tenosynovitis of the EDL tendon.

All patients had almost complete relief with low-dose prednisolone within the first 6 weeks of therapy (Table 2). Two patients had minor episodes of increased edema over the hands and feet during the first 3 months of therapy. One patient who discontinued prednisolone after 14 months of therapy relapsed 5 months after discontinuation. He, however, responded to a low dose of corticosteroid (10 mg/day) on reinstitution. At last follow-up, all patients had marked relief of edema of the hands and feet and increase in grip strength. Three of our patients had type II diabetes mellitus whereas one was detected to have hypothyroidism.
Table 2

Laboratory and treatment profile of patients. ESR erythrocyte sedimentation rate, JAO juxta-articular osteopenia

 

Case 1

Case 2

Case 3

Case 4

Case 5

Case 6

Case 7

Case 8

Case 9

Case 10

ESR (mm/h)

41

53

44

20

52

62

34

35

58

31

X-ray hands/feet

JAO

JAO

Normal

JAO

Normal

Normal

Normal

Normal

Normal

Normal

Response to prednisolone

Dramatic

Dramatic

Dramatic

75% relief at 4 weeks

80% at 6 weeks

80% at 6 weeks

Dramatic

Dramatic

Dramatic

Dramatic

Prednisolone (mg/day)

10

15

15

20

15

15

15

10

10

10

Follow-up (months)

26

16

10

7

8

12

8

7

8

6

Grip strength (mmHg)

 Baseline

48

96

40

36

28

10

40

62

104

68

 After 3 months of therapy

152

230

264

300

230

220

300

300

300

282

Discussion

The clinical and demographic profile of the cases in the present study were similar to earlier reports [1, 46], i.e., male predominance, elderly age, explosive onset, seronegativity for RF, and dramatic response to low-dose corticosteroids. McCarty et al. [1] had empirically selected patients with both upper and lower limb symmetrical involvement. However, as experienced by others [7] and us, the spectrum of RS3PE includes patients with unilateral findings. We included patients with unilateral or lower extremity involvement.

McCarty et al. [1, 2] in their initial description had reported predominant involvement of the flexor tendons of the hands in RS3PE. However, since the pitting edema of the dorsum of hands was the most conspicuous and prominent manifestation and given the anatomical setting, extensor tenosynovitis is more likely to cause swelling of the dorsum of hands. This discrepancy might have arisen due to difficulty in assessing extensor tenosynovitis at clinical examination in a patient with edema of the dorsum of hands. Cantini et al. [3] have suggested that pitting edema of hands is a manifestation of distal vigorous tenosynovitis and reported predominant involvement of the extensor tendons in RS3PE as evidenced on MRI. However, MRI has its own limitations: availability, claustrophobia, cost efficacy, and expertise required to interpret the findings.

Tendons are formed of type I collagen surrounded by a sheath of loose areolar tissue, paratendon, or synovial sheath which is adherent to the epitendineum. Normal tendon has homogeneous thickness, uniform fibrillar echotexture, and sharply defined echogenic margins as visualized on USG [8]. The paratendon appears as undefined hyperechoic tissue in continuity with subcutaneous fat. The synovial layer appears as a thin hypoechoic rim on the anterior and posterior surfaces of the tendon due to a thin film of synovial fluid between the two layers of the synovial sheath. The fluid can be hypoechoic or anechoic or echogenic. Inflamed tendons appear as thick nonhomogeneous echoic shadows with diffuse circumferential hypoechogenicity around the tendons. Simple fluid visualized by USG appears anechoic, demonstrating enhanced soft tissue echoes posterior to the fluid collection [9]. Tenosynovitis is documented when there is anechoic or hypoechoic fluid seen surrounding the tendon [10]. In our study, tenosynovitis of both the flexor and extensor tendons at the wrist and the hands was seen in all cases. However, anechogenicity was greater around the extensor tendons. The tenosynovitis not only paralleled the disease activity, it also paralleled the response to prednisolone therapy. It appeared that USG is useful not only as a diagnostic tool in evaluation of tenosynovitis in patients with RS3PE syndrome but also in follow-up.

The clinical findings of RS3PE have also been described in other rheumatic diseases such as polymyalgia rheumatica, spondylarthropathies, psoriatic arthritis, rheumatoid arthritis, and acute sarcoidosis as part of the paraneoplastic presentation [6]. One of our patients had RS3PE as the presenting manifestation of acute sarcoidosis as has been reported earlier [11]. Three of the patients in our series had diabetes and one had hypothyroidism. The association between diabetes mellitus and hypothyroidism and RS3PE seemed coincidental.

Take home message

Ultrasonography is a reliable and cost-effective modality for diagnosing tenosynovitis in RS3PE.

Copyright information

© Clinical Rheumatology 2005