The Clinical Picture

‘Boxing glove’ hands in a patient initially diagnosed with RS3PE syndrome

Hirokazu Takai, MD and Seiko Takai, MD
Cleveland Clinic Journal of Medicine March 2026, 93 (3) 135-137; DOI: https://doi.org/10.3949/ccjm.93a.25059

A 70-year-old man presented with acute-onset swelling, stiffness, and pain in both hands. Examination revealed swollen “boxing glove” hands with pitting edema and pressure marks (Figure 1A). The edema limited finger flexion, impairing daily tasks such as putting on socks.

Figure 1
Figure 1

(A) Marked pitting edema on the dorsum of both hands at initial presentation, creating the characteristic “boxing glove” appearance. Severe swelling limited finger flexion, and visible indentations remained after pressure. (B) Resolution of hand edema and restoration of the normal contours of both hands after oral prednisolone therapy.

Laboratory testing revealed markedly elevated inflammatory markers, with a C-reactive protein level of 12.8 mg/dL (reference range ≤ 0.8) and an erythrocyte sedimentation rate of 97 mm/hour (0–15). Serologic tests for rheumatoid factor and anti–cyclic citrullinated peptide antibody were negative. A diagnosis of remitting seronegative symmetrical synovitis with pitting edema (RS3PE) was made based on the presence of the characteristic clinical features of this syndrome.1

Comprehensive malignancy screening, including computed tomography of the chest and abdomen and upper and lower gastrointestinal endoscopy, showed no evidence of neoplasia.

Because RS3PE-specific guidelines have not been published, prednisolone was started and tapered with reference to general glucocorticoid management principles for inflammatory rheumatic diseases, including the 2016 European League Against Rheumatism rheumatoid arthritis management recommendations,2 recognizing that RS3PE is a distinct clinical entity and that this approach has inherent limitations. Oral prednisolone 15 mg/day led to rapid and marked improvement, with resolution of edema and restored hand function (Figure 1B). Symptoms recurred about 1 year after the final tapering dose of 2 mg/day was completed.

During reassessment, swelling of the wrists, metacarpophalangeal joints, and proximal interphalangeal joints was noted. Musculoskeletal ultrasonography revealed only minimal tenosynovial thickening, while plain radiography showed possible marginal erosions at the metacarpophalangeal joints. Contrast-enhanced computed tomography of the chest and abdomen showed no evidence of malignancy. Based on these findings, the rheumatologist diagnosed the patient with seronegative rheumatoid arthritis within the spectrum of elderly-onset rheumatoid arthritis. Methotrexate 6 mg/week was started, resulting in sustained symptom control.

RS3PE: ASSOCIATIONS AND OVERLAPS WITH OTHER CONDITIONS

RS3PE syndrome is a relatively rare inflammatory condition first described by McCarty et al1 in 1985. It is characterized by seronegative symmetrical synovitis that responds well to corticosteroids (remitting) and is associated with pitting edema.

RS3PE syndrome is often idiopathic. However, a systematic review of 331 published cases of RS3PE found that an association with malignancy was reported in about 16% of cases,3 suggesting that it may occur as a paraneoplastic syndrome; thus, careful cancer screening is crucial at initial diagnosis. Reported concurrent malignancies include prostate cancer in men and breast, ovarian, and endometrial cancers in women, as well as gastrointestinal, pancreatic, and hematologic malignancies.3 Indeed, diagnosing RS3PE can occasionally lead to the early detection of an underlying malignancy.

RS3PE syndrome generally responds well to corticosteroids, but symptom relapse has been reported in about 9% of patients during or after steroid tapering.3 In such situations, it may be necessary to revisit the initial diagnosis. Differential diagnoses such as elderly-onset rheumatoid arthritis and polymyalgia rheumatica should be considered, as these disorders share several clinical features with RS3PE syndrome.4,5

The patient’s initial presentation and steroid response were consistent with classic RS3PE syndrome. As such, his case serves as a reminder that such presentations may represent the early phase of other rheumatologic conditions. Because of these overlaps, differentiating RS3PE from elderly-onset rheumatoid arthritis or polymyalgia rheumatica at symptom onset can be challenging. Key clinical distinctions among these 3 conditions, including steroid responsiveness, radiographic findings, and typical treatment course, are summarized in Table 1.2–5 Accordingly, this patient’s case underscores the importance of continuous diagnostic reassessment and the potential need for disease-modifying antirheumatic drugs, even in patients initially diagnosed with RS3PE syndrome based on characteristic clinical findings.

View this table:
TABLE 1

Distinguishing features of remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome, elderly-onset rheumatoid arthritis (EORA), and polymyalgia rheumatica (PMR)

DISCLOSURES

The authors report no relevant financial relationships which, in the context of their contributions, could be perceived as a potential conflict of interest.

REFERENCES

  1. ↵
    1. McCarty DJ,
    2. O’Duffy JD,
    3. Pearson L,
    4. Hunter JB
    . Remitting seronegative symmetrical synovitis with pitting edema. RS3PE syndrome. JAMA 1985; 254(19):2763–2767. pmid:4057484
    OpenUrlCrossRefPubMed
  2. ↵
    1. Smolen JS,
    2. Landewé R,
    3. Bijlsma J, et al
    . EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. Ann Rheum Dis 2017; 76(6):960–977. doi:10.1136/annrheumdis-2016-210715
    OpenUrlAbstract/FREE Full Text
  3. ↵
    1. Karmacharya P,
    2. Donato AA,
    3. Aryal MR, et al
    . RS3PE revisited: a systematic review and meta-analysis of 331 cases. Clin Exp Rheumatol 2016; 34(3):404–415. pmid:27050250
    OpenUrlPubMed
  4. ↵
    1. Origuchi T,
    2. Umeda M,
    3. Koga T, et al
    . Comparison of complications during 1-year follow-up between remitting seronegative symmetrical synovitis with pitting edema syndrome and elderly-onset rheumatoid arthritis. Immunol Med 2022; 45(3):168–174. doi:10.1080/25785826.2022.2046307
    OpenUrlCrossRefPubMed
  5. ↵
    1. Lundberg IE,
    2. Sharma A,
    3. Turesson C,
    4. Mohammad AJ
    . An update on polymyalgia rheumatica. J Intern Med 2022; 292(5):717–732. doi:10.1111/joim.13525
    OpenUrlCrossRefPubMed
Back to top

In this issue

Print
Download PDF
Article Alerts
Email Article
Citation Tools

Jump to section

Related Articles

  • No related articles found.

Cited By...

  • No citing articles found.

More in this TOC Section

Similar Articles

Subjects