Cholangiocarcinoma Presenting with Bone and Skeletal Muscle Metastases Mimicking a Relapse of Adult-Onset Still’s Disease: A Case Report ()
1. Introduction
Adult-onset Still’s disease (AOSD) is a rare systemic autoinflammatory disorder with an etiology that remains poorly elucidated. First described by Bywaters in 1971 as the adult equivalent of pediatric Still’s disease, it is clinically characterized by prolonged high fever, arthritic manifestations, and an evanescent rash. Biologically, it features an inflammatory syndrome, hyperleukocytosis predominantly neutrophilic, often marked hyperferritinemia, and low glycosylated ferritin levels. These abnormalities serve as orienting elements. Diagnosis relies on clinico-biological criteria (particularly those of Fautrel), but above all remains a diagnosis of exclusion. It is crucial to rigorously rule out infectious, autoimmune, and neoplastic causes.
The association between AOSD and malignant disorders remains exceptional. Reported cases primarily involve hematologic malignancies, especially lymphomas and leukemias. Solid tumors are more rarely reported, dominated by breast, lung, and digestive (stomach, colon, and rectum) cancers [1].
Cholangiocarcinoma is a rare malignant tumor of the biliary tract, accounting for less than 3% of digestive cancers. Its clinical presentation is often insidious, associating altered general condition, cholestatic jaundice, and right hypochondriac pain. Diagnosis is frequently late and unfavorable.
To date, the association between AOSD and cholangiocarcinoma remains extremely rare and poorly documented in the literature. The observation we report concerns the occurrence of cholangiocarcinoma in a patient with AOSD whose symptoms were mistaken for a relapse.
2. Case Presentation
2.1. First Rheumatology Admission—29/09/2024
A 37-year-old man with a history of chronic smoking was admitted to the rheumatology department with a one-week history of acute febrile migratory polyarthritis involving the shoulders, wrists, knees, and ankles, with no axial involvement. He also reported odynophagia and a transient maculopapular rash. His general condition was preserved. On admission, physical examination revealed a temperature of 39˚C, arthritis of the left wrist, painful limitation of movement of the large joints, pharyngitis and a skin rash.
Laboratory investigations demonstrated a marked inflammatory syndrome. Leukocytosis was 16,000/mm3, with 83% neutrophils. C-reactive protein was 188 mg/L [normal < 5], and the erythrocyte sedimentation rate was 85 mm/1st hour [normal < 15]. Serum protein electrophoresis was normal. There was hyperferritinaemia at 2880 µg/L [normal < 300] associated with a low glycosylated ferritin fraction of 19% [normal > 50%]. Infectious work-up, including procalcitonin, urine cytobacteriological analysis, blood cultures, antistreptolysin O titres and viral and bacterial serologies (viral hepatitis, syphilis, HIV, brucellosis, Lyme disease), was negative. Radiographs of the chest and of the painful joints showed no abnormalities. Transthoracic echocardiography did not reveal any vegetations. Liver function tests and renal function were normal. Immunological tests (antinuclear antibodies, rheumatoid factor, anti-CCP antibodies) were negative. There were no constitutional symptoms or clinical findings suggestive of an underlying malignancy, and no dedicated malignancy screening was performed at this stage.
A diagnosis of adult-onset Still’s disease was established according to Fautrel’s criteria, based on six criteria: five major criteria (fever, arthritis, pharyngitis, neutrophils ≥ 80%, and a glycosylated ferritin fraction ≤ 20%) and one minor criterion (maculopapular rash).
The patient received intravenous methylprednisolone pulses at a dose of 500 mg/day for three consecutive days. Oral therapy was then switched to prednisone 40 mg/day. Background therapy with methotrexate was initiated at a dose of 15 mg/week. The subsequent course was marked by clinical and biological improvement, with resolution of fever and arthralgia, a C-reactive protein level of 5.07 mg/L and an erythrocyte sedimentation rate of 2 mm/h at three months. Corticosteroid therapy was progressively tapered by 10 mg/month, achieving a prednisone dose of 20 mg/day after three months. As his condition improved, the patient was then lost to follow-up nine months after treatment initiation. He continued to take prednisone in a non-supervised, self-medicated manner at doses ranging from 20 to 40 mg/day, and he discontinued methotrexate.
2.2. Second Rheumatology Admission—10/09/2025
One year after the initial diagnosis, he was readmitted for inflammatory low back pain and left buttock pain, with severe pain rated at 9/10 on a visual analogue scale, associated with asymmetric polyarthralgia involving the large joints. The patient reported a weight loss of 15 kg, deterioration of his general condition, night sweats and intermittent dry cough. Examination found a lumbar spinal pain syndrome with stiffness (fingertip-to-floor distance 30 cm; Schober test 10 + 3 cm) and tenderness on palpation of the sacroiliac joints. Hepatomegaly was also noted (liver span 13 cm). At this stage, two diagnoses were considered: a relapse of adult-onset Still’s disease and spondyloarthritis.
Laboratory tests showed: C-reactive protein 293 mg/L; erythrocyte sedimentation rate 80 mm/h, with a normal complete blood count. Serum protein electrophoresis showed an inflammatory pattern associated with hypogammaglobulinaemia at 6 g/L [normal: 8 - 13]. Hyperferritinaemia at 3186 ng/mL was observed. Radiographs of the lumbar spine, sacroiliac joints and symptomatic joints were unremarkable. Chest radiography demonstrated bilateral micronodular opacities suggestive of miliary tuberculosis. Liver and renal function tests remained normal. Infectious investigations, including the tuberculosis work-up (sputum examination for acid-fast bacilli, GeneXpert and Quantiferon®), were negative.
Cervico-thoraco-abdomino-pelvic computed tomography showed bronchial micronodules, intraparenchymal pulmonary nodules, and poorly enhancing hypodense hepatic lesions after contrast injection, as well as subcentimetric mediastinal lymph nodes. Abdominal ultrasonography revealed suspicious hepatic nodular lesions. At this stage, and pending completion of further investigations, a trial anti-tuberculous regimen was initiated in consultation with infectious disease specialists, but without clinical improvement.
Spinal MRI (Figure 1) revealed multifocal STIR hyperintense lesions involving the vertebral bodies D2, D5, D12, L1, L4 and L5, with contrast enhancement after gadolinium injection. At the sacroiliac level: multiple enhancing nodular lesions after contrast injection, the largest involving the various bony segments of the pelvis, without evidence of sacroiliitis. Contrast enhancement of the paravertebral muscles and paravertebral soft tissues, also involving the peri-aponeurotic and peri-tendinous regions at the lumbosacral level. Multiple foci of enhancement of the subcutaneous adipose tissue, the largest opposite S1, measuring 9 mm in its greatest diameter.
Figure 1. MRI of the lumbar spine and sacroiliac joints showing nodular and patchy signal abnormalities of the axial skeleton, together with muscular and subcutaneous lesions suspicious for malignancy.
The bone marrow aspirate was unremarkable. Creatine kinase levels were within the normal range at 57 U/L (normal < 200), whereas LDH was elevated at 433 U/L (normal < 225). Tumour markers showed a marked increase in CA 19-9 above 1200 U/mL (normal < 37), with a normal PSA and a CEA level of 14 ng/mL (normal < 10).
Magnetic resonance cholangiopancreatography revealed a non-characterisable nodular lesion in hepatic segment VIII. Ultrasound-guided liver needle biopsy performed on 17/09/2025 concluded, after immunohistochemical analysis, that there was a poorly differentiated infiltrating adenocarcinoma of biliary origin, consistent with cholangiocarcinoma. Oesophagogastroduodenoscopy and colonoscopy were normal.
During his 3-week hospital stay, the patient received analgesic treatment with prolonged-release morphine (Mostin 40 mg) twice daily and immediate-release morphine (Sevredol 10 mg) twice daily.
2.3. Transfer to Oncology—28/09/2025
Whole-body 18F-FDG PET-CT (Figure 2) demonstrated hepatic involvement and radiologically presumed metastatic lesions in the bones, skeletal muscles, skin, and lungs, associated with hypermetabolic supradiaphragmatic lymphadenopathy.
Figure 2. 18F-FDG PET-CT showing hepatic involvement with radiologically presumed osseous, musculo-cutaneous, and pulmonary metastatic lesions, with hypermetabolic supradiaphragmatic lymphadenopathy.
The final diagnosis was adult-onset Still’s disease associated with stage IV metastatic cholangiocarcinoma. The clinical course was rapidly unfavorable, leading to the patient’s death one month after hospitalization.
3. Discussion
Adult-onset Still’s disease (AOSD) is a rare systemic autoinflammatory disorder, and its diagnosis relies on a constellation of clinical and laboratory features after rigorous exclusion of infectious, autoimmune and neoplastic causes. Malignancies represent a major differential diagnosis of AOSD because of the potential overlap in systemic and biological manifestations, and systematic screening for an underlying neoplasm is an integral part of the initial work-up and of any subsequent reassessment during the disease course. The presence of an active tumour process is classically considered an argument against the diagnosis of AOSD [2].
However, true associations between AOSD and malignancy have been reported, although they remain rare and poorly documented, suggesting that a neoplastic process may be discovered during follow-up without necessarily invalidating the initial diagnosis, particularly when the initial presentation is typical and the therapeutic response is as expected [3]. These situations highlight the need for prolonged vigilance and systematic reassessment in the event of an atypical disease course.
Associations between AOSD and solid tumours remain exceptional and mainly involve breast, bronchopulmonary and digestive cancers [4]-[7]. In such cases, the inflammatory presentation may mimic or overlap that of AOSD (high fever, arthralgia/arthritis, evanescent rash, pharyngitis), with highly suggestive laboratory abnormalities, particularly hyperferritinaemia and decreased glycosylated ferritin, which may transiently fulfil the Yamaguchi or Fautrel diagnostic criteria [2] [8]. This close semiological overlap mandates careful chronological assessment and close re-evaluation in the event of atypical evolution or treatment resistance.
In our patient, readmission was marked by several atypical features for an AOSD relapse: deterioration of general condition with weight loss and night sweats, dry cough, newly appearing lymphadenopathy and diffuse bone pain. These alarm signs prompted an extensive search for a disseminated infectious or neoplastic cause. The lack of response to empirical anti-tuberculous therapy further reinforced the need for an in-depth aetiological reassessment.
A hypothetical pathophysiological explanation may involve a convergence of cytokine signatures. Flares of AOSD are characterised by activation of innate immunity, driven predominantly by interleukin (IL)-1β, IL-18 and IL-6, which contribute to fever, hyperferritinaemia and the systemic inflammatory response [9]. Conversely, some cancers, particularly at an advanced stage, can induce a major inflammatory state through increased production of pro-inflammatory cytokines, thereby mimicking an AOSD flare.
The temporal proximity between the inflammatory flare and the diagnosis of cholangiocarcinoma may reflect a shared inflammatory profile, raising the possibility of common immuno-inflammatory mechanisms. However, this remains hypothetical, as no cytokine measurements or mechanistic evidence were obtained in this patient. Cholangiocarcinoma is a rare malignant tumour of the biliary tract, accounting for less than 3% of digestive cancers. Its diagnosis may be delayed because early clinical manifestations are often non-specific [10].
In our case, the marked elevation of CA 19-9 suggested an underlying neoplastic process; this marker, mainly used in pancreatic and biliary malignancies, is highly suggestive of a tumoural origin when markedly increased [11]. It is also important to underline the unusual radiologically presumed metastatic spread, with osseous, musculocutaneous and nodal involvement, a pattern that remains infrequent in cholangiocarcinoma.
To the best of our knowledge, no published report to date has described an association between adult-onset Still’s disease and cholangiocarcinoma, making this coexistence exceptional and reinforcing the value of prolonged surveillance and publication of original cases to broaden understanding of possible links between AOSD and malignancy. Corticosteroid therapy and methotrexate may transiently modulate the inflammatory response and attenuate systemic manifestations, potentially complicating the distinction between an AOSD flare and an underlying neoplastic process [12]. However, their contribution to the diagnostic course in our patient remains uncertain.
Thus, although rare, an underlying malignancy should be reconsidered in patients with AOSD who develop an atypical disease course, new constitutional symptoms, or treatment resistance. Prolonged surveillance and regular reassessment are essential to facilitate early detection of an underlying neoplasm and avoid diagnostic delay with potentially significant prognostic consequences.
4. Conclusions
Adult-onset Still’s disease is a rare autoinflammatory disorder whose diagnosis relies on the exclusion of infectious, autoimmune and neoplastic causes. While the presence of a tumour is classically viewed as an argument against this diagnosis, our case illustrates that AOSD may coexist with metastatic cholangiocarcinoma, an exceptional and rarely reported association.
This coexistence highlights the need for sustained diagnostic vigilance and systematic reassessment in the event of an atypical course or treatment resistance, in order to detect an underlying neoplasm early and adapt management accordingly.
Patient Consent
Consent was obtained from the patient’s legal representatives.
Author Contributions
Patient management: Ilyass Chergaoui, Anass Kherrab, Mirieme Ghazi; data collection: Hayat Ali, Maria Adel, Anass Chbihi-Kaddouri; manuscript drafting: Hayat Ali; critical revision of the manuscript: Imane El Bouchti, Redouane Niamane; supervision and final approval: Redouane Niamane. All authors have read and approved the final version of the manuscript.