The clinical picture initially pointed firmly toward rheumatology. The man had inflammatory polyarthritis involving the wrists, metacarpophalangeal joints, proximal interphalangeal joints, elbows, shoulders, knees and feet, together with fatigue, anorexia, weight loss, evening chills and sweating after warming. He needed water to swallow dry food because of dry mouth, and he reported dry eyes and nocturia.

Outside testing before admission had already shown an erythrocyte sedimentation rate of 54 mm/h and a C-reactive protein level of 106.8 mg/L, while rheumatoid factor and anti-cyclic citrullinated peptide antibody were not elevated. On admission, C-reactive protein had climbed to 205.88 mg/L and the sedimentation rate to 75 mm/h. This combination of seronegative inflammatory arthritis, sicca symptoms, weight loss and generalized lymphadenopathy can overlap with seronegative rheumatoid arthritis, a Sjogren-like syndrome, sarcoidosis, lymphoma and tuberculosis, and the admitting team considered all of them.

The diagnostic workup was extensive and deliberately multidisciplinary. A full autoimmune panel, including antinuclear antibodies, anti-SSA/Ro60 and Ro52, anti-SSB/La, antineutrophil cytoplasmic antibodies, anti-myeloperoxidase, anti-proteinase 3, anti-glomerular basement membrane antibodies, autoimmune liver antibodies and anti-endothelial cell antibodies, was negative, and serum IgG4 was not elevated. Tuberculosis screening was similarly unrevealing: the patient had no respiratory or gastrointestinal symptoms, T-SPOT testing was negative, chest CT showed no typical pulmonary tuberculosis lesion, and cytomegalovirus and Epstein-Barr virus DNA were negative.

Musculoskeletal ultrasonography did confirm genuine inflammatory changes, demonstrating synovial hyperplasia and flexor tenosynovitis of the bilateral metacarpophalangeal and selected interphalangeal joints, which lent objective support to the arthritis rather than leaving it a purely subjective complaint. Imaging then widened the puzzle rather than narrowing it. 18F-FDG PET/CT showed increased uptake around the bilateral shoulders, hips and sternoclavicular joints, with uptake at several rib-vertebral and facet joints, the L4 posterior elements and the right sacroiliac region interpreted as more likely degenerative.

More consequentially, the scan revealed multiple FDG-avid lymph nodes in the cervical, supraclavicular, axillary, anterior chest wall, iliac and inguinal regions, plus focal uptake in the C5 vertebral body. Cervical MRI showed mild C5 marrow edema alongside multilevel degenerative changes and disc protrusions, and cervical spondylitis was suspected clinically. An ultrasound-guided core biopsy of a right inguinal lymph node showed preserved architecture with tissue edema, scattered non-necrotizing granulomatous nodules, locally increased plasma cells and scattered or focal eosinophilic infiltration.

Acid-fast and periodic acid-Schiff stains were negative, and the pathology report described reactive lymphoid hyperplasia with granulomatous inflammation, recommending further evaluation for special infection. The decisive clue came from targeted infectious testing informed by the patient's history. He had long-term occupational exposure to cattle, the classic reservoir of Brucella species.

A Rose Bengal plate agglutination test and a Brucella IgG assay were both positive, and a standard tube agglutination test was reported positive at a titer of 1:100. On that basis, together with the systemic illness and multisite inflammation, the team arrived at a discharge diagnosis of systemic brucellosis with inflammatory arthritis, granulomatous lymphadenitis and suspected cervical spondylitis. The authors are careful, however, to frame this as a working diagnosis of probable systemic brucellosis rather than microbiologically confirmed disease.

Both final blood and bone marrow cultures were negative, Brucella IgM and quantitative IgG values were not documented, and no short-interval confirmatory serum sample was obtained. That caution matters because brucellosis serology is context-dependent in ways that are easy to overlook. Cross-reactivity, assay variability and previous exposure can all produce positive results without active infection, and IgG positivity in a repeatedly exposed farmer may reflect remote contact with the organism rather than current disease.

Chinese guidance recognizes an agglutination endpoint titer of 1:100, whereas 1:160 is commonly used internationally, a difference that helps explain the original clinical interpretation but does not by itself prove active infection. A single 1:100 result, without a paired follow-up sample or a demonstrated fourfold rise in titer, cannot resolve this uncertainty. The diagnosis therefore rests on the convergence of exposure, constitutional illness, multisite inflammation and serology, not on a definitive microbiological anchor.

Treatment followed infectious-disease consultation. During the inpatient stay the patient received rifampicin 750 mg once daily plus a tetracycline-class agent, documented locally as minocycline 100 mg twice daily, along with ceftriaxone 2 g once daily during the early phase for suspected spinal involvement. The planned approach was prolonged oral combination therapy for at least 12 weeks, with ceftriaxone for approximately four to six weeks, reflecting the longer courses generally required for spinal brucellosis.

At telephone follow-up, however, the patient reported that outpatient treatment had consisted of oral rifampicin and doxycycline for two years, extended because symptoms had not completely resolved. That duration substantially exceeds usual regimens, including most spinal regimens described in contemporary reviews, and the authors stress it should not be interpreted as a recommended duration. No adverse effects requiring intervention were reported, but systematic safety-monitoring records were unavailable.

The follow-up story is where the report becomes most instructive about the limits of inference. The patient reported near-disappearance of cervical pain after roughly three months of anti-Brucella treatment, and later normalization of ESR and CRP with hemoglobin recovery to the normal range after more than six months. His daughter reported a negative local agglutination result at about three months, but the original report, assay type, numerical titer and laboratory cutoff were all unavailable.

Because antibodies often persist for months or years after treatment, and because a low starting titer or a change of assay could influence whether a result is called negative, this unverified result cannot establish true seroreversion, microbiological cure, or retrospective confirmation of the diagnosis. Moreover, tetracyclines, particularly minocycline, have shown anti-inflammatory effects in rheumatoid arthritis trials, so improvement during antibiotics may partly reflect drug anti-inflammatory activity rather than bacterial clearance. The most sobering element is the long-term outcome.

From 2023 onward the patient had intermittent bilateral hip and knee pain requiring as-needed etoricoxib, and at the most recent follow-up he needed a walking aid, though he could not recall when that dependence began. Degenerative right hip changes were documented at admission and offer one possible contributor, but they do not explain bilateral symptoms or the severity of disability. Structural joint damage, mechanical disease, deconditioning, persistent or relapsing infection, and coexisting seronegative inflammatory arthritis all remain alternatives, as does an infection-triggered inflammatory arthropathy that is possible but unproven.

Persistent pain alone cannot diagnose chronic active brucellosis, and earlier normalization of inflammatory markers cannot establish current infection status. In-person joint and neurological examination, updated inflammatory markers and targeted hip, knee or spinal imaging would help distinguish these possibilities, but none were available. The authors also weigh competing diagnoses that were never definitively excluded.

Brucellar endocarditis is uncommon but accounts for a substantial proportion of brucellosis-related mortality, and while no vegetation or murmur was documented, transesophageal echocardiography was not recorded, so endocarditis was neither demonstrated nor ruled out. Negative T-SPOT testing, absence of typical pulmonary lesions and negative tissue acid-fast staining do not exclude extrapulmonary tuberculosis. The non-necrotizing granulomas in the lymph node are not Brucella-specific, sarcoidosis remains a noninfectious alternative, and a limited core biopsy cannot definitively exclude unsampled lymphoma.

The report's strength lies in its multidisciplinary diagnostic trajectory, from rheumatologic presentation through multimodal imaging, lymph-node pathology and targeted infectious testing. Its message for clinicians is one of sustained vigilance: in exposed patients with seronegative inflammatory arthritis, sicca symptoms and granulomatous lymphadenopathy, treatable infection deserves evaluation before immunosuppressive therapy is escalated, and both the original diagnosis and any persistent disability warrant critical reassessment rather than assumption.

Subject of Research: A case report of probable systemic brucellosis mimicking seronegative inflammatory arthritis with sicca symptoms and suspected cervical spondylitis

Article Title: Case Report: When infection wears a rheumatic mask: probable systemic brucellosis mimicking seronegative inflammatory arthritis with sicca symptoms and suspected cervical spondylitis

Article References: Zou, Y., Zhang, J., Zhang, X., Zhang, Q., Zhang, L., Yu, R., Long, T., Li, J., Zhang, Y., & Li, S.-G. (2026). Case Report: When infection wears a rheumatic mask: probable systemic brucellosis mimicking seronegative inflammatory arthritis with sicca symptoms and suspected cervical spondylitis. Frontiers in Medicine, 13, 1996243. https://doi.org/10.3389/fmed.2026.1996243

Image Credits: AI Generated

DOI: 10.3389/fmed.2026.1996243

Keywords: brucellosis, seronegative inflammatory arthritis, sicca symptoms, cervical spondylitis, granulomatous lymphadenitis, zoonotic infection, rheumatology, case report, PET/CT, antibiotic therapy, occupational exposure, diagnostic uncertainty