In the management of patients experiencing cervical pain, it is imperative to discern among various underlying conditions. Conventionally, attention is given to mechanical pain associated with shoulder discomfort or cervical radiculopathy, characterized by pain radiating into the arms or hands. Nevertheless, C1-2 (atlantoaxial joint) issues are sporadically documented and can arise from a spectrum of conditions, ranging from degenerative arthritis to bone metastasis. The importance of an accurate and thorough differential diagnosis cannot be overstated. This case series elucidates three inflammatory diseases originating from the atlantoaxial joint that contribute to cervical pain.

The initial case analyzes calcium pyrophosphate dihydrate disease (CPPD) occurring within the atlantoaxial joint, commonly referred to as crowned dens syndrome (CDS).^1,2 The second case underscores septic arthritis arising from infection of the atlantoaxial joint, necessitating meticulous differentiation for precise antibiotic intervention.^3,4 The concluding case examines rheumatoid arthritis affecting the cervical spine, accentuating the varied manifestations of inflammatory conditions within the atlantoaxial joint.⁵

1. Case #1

A 64-year-old woman presented with persistent and severe neck pain lasting two months, rated at a numeric rating scale of 9. The pain was accompanied by a restricted range of motion (ROM) in her cervical spine. With a history of bilateral knee arthroplasty and recent hospitalization for neck pain, she tested positive for human leukocyte antigen (HLA) B-27, without further clinical correlation. Initially diagnosed with cervical disc-related pain, the ongoing limited ROM prompted a reevaluation. The initial examination revealed no apparent neurological deficits, sensory impairments, or muscle weaknesses. Cervical rotation and flexion were restricted to less than 5 degrees in all directions, and the patient complained of pain in both shoulders and hip joints.

Laboratory examinations indicated an elevated erythrocyte sedimentation rate (ESR) of 72 mm/hr and a C-reactive protein level (CRP) of 1.86 mg/dL. Notably, serum uric acid levels were within normal limits. Tests for connective tissue diseases and vasculitis, including rheumatoid factor, anti-neutrophil cytoplasmic antibody perinuclear, anti-double-strand-DNA antibodies, and anti-cyclic citrullinated peptide antibodies, were negative.

Admitted for further assessment, the patient’s presentation aligned with the EULAR criteria suggestive of polymyalgia rheumatica. Criteria included bilateral shoulder pain, age over 50, elevated ESR and CRP levels, and morning stiffness lasting more than 45 minutes. The patient showed mildly decreased hip mobility, rendering squatting difficult, and tested negative for rheumatoid factor.

A positron emission tomography (PET) scan revealed increased uptake in the left atlantoaxial joint, prompting consideration of a steroid injection. However, due to proximity to the vertebral artery and associated risks, this intervention was not attempted. Cervical CT confirmed calcifications in the atlantoaxial joint, consistent with CDS (Fig. 1-A∼1-C). Findings included narrowing of the left atlantoaxial joint space, intraarticular calcific deposition, subchondral cysts, and sclerosis. Given the suspected polymyalgia rheumatica diagnosis, a PET scan showed an active inflammatory lesion within the atlantoaxial joint, suggesting CPPD arthropathy (Fig. 1-D, 1-E).

Figure 1. Cervical CT in sagittal (A), axial (B), and coronal (C) views, there is evident left atlantoaxial joint space narrowing (green arrowhead) along with subchondral cysts and sclerosis. Within the joint space, there is the presence of amorphous radiopaque material (green arrows), raising the possibility of CPPD arthropathy. PET imaging (D) and (E) of the atlantoaxial joint reveal an active inflammatory lesion (large green arrows) with a standardized uptake value (SUVmax) of 5.6, confirming the likelihood of inflammation. 

The patient, having previously taken non-steroidal anti-inflammatory drugs (NSAIDs) without significant pain improvement, was discharged with a prescription for prednisolone 30 mg. After three weeks of daily prednisolone intake, the patient’s pain level decreased to a numeric rating scale of 5 points, accompanied by improved ROM. Steroid treatment was gradually tapered, and NSAIDs were continued. At the 8-week follow-up, the patient exhibited further improvement, with a numeric rating scale score of 2 points and increased ROM.

In summary, this case underscores the complexity of the diagnostic process in the context of severe neck pain, emphasizing the importance of considering various conditions during clinical evaluations. The deviations from conventional expectations highlight the necessity of a comprehensive approach to diagnosis and treatment.

2. Case #2

An 82-year-old female presented with acute focal tenderness in the right paracervical area and a limited ROM, specifically a right laterocolis of 30 degrees. Even during passive rotation to a neutral position, the patient reported significant pain. Despite the absence of fever or systemic symptoms, the prescribing of Cetamadol (tramadol and acetaminophen) and aceclofenac (NSAID) 200 mg aimed at symptom control.

Physical examination, including a Cervical CT and MRI on October 11th, 2023, revealed inflammatory arthropathy involving the atlanto-axial joint, specifically the right C1-2 joint (Fig. 2). Elevated inflammatory markers, CRP (12.41 mg/dL) and ESR (69 mm/hr), prompted a referral to the rheumatology department. Despite an initial prescription of oral steroids (prednisolone 30 mg for 1 day, followed by 20 mg for 3 days) on October 23, 2023, there was no observed improvement. Persistent increases in CRP (10.5 mg/dL) and white blood cell (WBC) (13K) raised concerns about a potential of cervical abscess, leading to consultation with the infectious disease department. A subsequent blood culture confirmed the presence of methicillin-sensitive staphylococcus aureus bacteria, diagnosing the patient with bacteremia. This necessitated admission for intravenous antibiotic treatment.

Figure 2. On October 11, 2023, cervical MRI was conducted, revealing the presence of joint effusion (green arrows) in the right C1-2 facet joint and atlantoaxial joint on the enhanced T2 sagittal (A) and axial (B) images. Additionally, there is enhancement of the adjacent bone marrow, indicative of inflammation disease. On October 26, 2023, Cervical CT sagittal (C) and axial (D) imaging indicated a progression of arthritis in C1 and C2 compared to the MRI conducted on October 11, 2023 (green arrows). 

Upon admission, a physical examination revealed grade 4 finger flexor strength bilaterally, with no other neurological symptoms. Pathologic reflexes were negative, deep tendon reflexes were normal, and there were no abnormalities in urination or defecation. A follow-up MRI on November 1, 2023, disclosed infectious spondylitis involving the atlanto-occipital and atlanto-axial joints, coupled with an anterior epidural abscess causing cord compression (Fig. 3-A, 3-B). Initiation of cefazolin 2 g was crucial for treatment. Subsequent December 2023 spine MRI exhibited improved lesions, prompting the transition from intravenous to oral antibiotics (ciprofloxacin 500 mg bid/cefadroxil 500 mg bid) (Fig. 3-C, 3-D). The patient’s current status reflects normalized CRP/WBC, continuous normal neurological symptoms, a substantial reduction in pain from a numeric rating scale 9 to 3∼4, and improved neck ROM.

Figure 3. A follow-up MRI conducted on November 1, 2023, revealed, on the sagittal (A) and axial (B) images with T1 contrast fat-saturated sequences, the presence of fluid exhibiting rim enhancement in the anterior epidural space extending to the C0-3 body level (green arrows). These findings are indicative of an epidural abscess. In the most recent cervical MRI conducted on December 7, 2023, sagittal (C) and axial (D) images with T1 contrast fat-saturated sequences revealed a reduction in the size of joint effusion and anterior epidural abscess compared to the previous examination (green arrows). Additionally, there is improvement in spinal cord compression. A slight decrease in infiltrative enhancement in the prevertebral space suggests a positive response to antibiotic therapy, indicative of resolving inflammation.

3. Case #3

A 69-year-old male, who underwent a hepatectomy for hepatocellular carcinoma in 2020, reported experiencing warmth in both elbow joints, neck pain, and discomfort in both wrists, the right acromioclavicular joint, and the right index finger since August 2023. Tenderness was noted during the physical examination at the right acromioclavicular joint, both wrists, and the right index finger proximal interphalangeal (PIP) joint. While suboccipital tenderness was absent, ROM testing indicated no limitation in neck movement, with confirmed shoulder ROM (flexion > 135º, abduction > 135º). Limited elbow flexion was noted due to a previous injury, and each wrist’s volarflexion was limited to 15º/30º, with intact ROM of finger joints.

Laboratory tests revealed positive anti-cyclic citrullinated peptide (CCP), HLA-B27, and rheumatoid factor, alongside elevated ESR and CRP, necessitating the differentiation of systemic inflammatory diseases. An October 2023 spine MRI detected a suspicious lesion at the T11 level, confirmed as a spine metastasis of hepatocellular carcinoma through biopsy. The MRI also revealed enhancement of the C1-2 facet joint and atlanto-odontoid joint, with high signal intensity in the atlanto-axial joint transverse ligament, suggesting degenerative changes in the atlantoaxial joint (Fig. 4-A, 4-B). A PET scan in the same month indicated fluorodeoxyglucose uptake between the C1-2 spine, suggesting a benign condition such as arthritis, with no additional metastasis lesions observed (Fig. 4-D).

Figure 4. In the cervical MRI conducted in October 2023, sagittal T1 enhanced (A) and T1 (B) images revealed contrast enhancement in the odontoid process and the bodies of C5, C6, and C7. No evidence of surrounding phlegmon or abscess was observed, confirming findings associated with degeneration and suggesting a benign inflammatory disease. In the cervical flexion x-ray taken in November 2023 (C), an increase in the anterior atlanto-dental interval of 4 mm or more was observed (green arrows), confirming Atlantoaxial subluxation. Furthermore, the PET scan revealed fluorodeoxyglucose uptake between the C1-2 spine (D), indicative of a benign condition such as arthritis.

Following consultation with the rheumatology department, the patient received a diagnosis of RA based on diagnostic criteria, including joint involvement, elevated CRP/ESR over six weeks, and a positive rheumatoid factor. A conference with the radiology department confirmed inflammatory lesions in the C1-2 joint consistent with RA manifestations. However, the immunosuppressive therapy for RA was constrained by on-going cancer treatment for bone metastasis. Currently, the patient is under observation while taking prednisolone 5 mg bid and hydroxychloroquine 200 mg daily.

The analysis of three patients uncovered distinct benign inflammatory and infectious conditions that may originate in the atlantoaxial joint, with each case exhibiting unique clinical characteristics. In the case of CDS, the presentation was marked by sudden and intense pain, resulting in a restricted ROM. Laboratory findings revealed a mild elevation in ESR and CRP, while cervical CT confirmed the characteristic calcification associated with CPPD, commonly referred to as CDS. In instances where CPPD is suspected, opting for a neck CT emerges as the preferred diagnostic approach.⁶ Despite procedural risks, reports indicate the effectiveness of C1-2 steroid injections in cases of persistent symptoms, complementing the positive outcomes of oral steroids.⁷ In this patient’s case, it was confirmed that oral steroids provided sufficient therapeutic effect.

In cases where cervical symptoms arise from infection and abscess in the atlantoaxial joint, careful consideration must be given to the differential diagnosis. Although steroids are frequently employed for treating inflammatory conditions, their use can have poor consequences in instances of infection. Our experience underscores the importance of recognizing that patients with septic arthritis can manifest sudden neck pain and limited ROM, resembling the clinical presentation of CPPD, despite having distinct prognoses.^8,9 Suspicions of an abscess are heightened by persistently elevated ESR and CRP levels, and the confirmation of bacterial presence through blood culture is instrumental in the diagnostic process. Differential diagnosis is validated through cervical MRI, where the abscess typically exhibits T2 hyperintensity and rim enhancement. This imaging characteristic serves as a crucial distinction from the presentation of CPPD, enhancing the accuracy of diagnostic differentiation.¹⁰ Although not observed in our specific case, exploring procedures like cervical epidural steroid injection is recommneded as part of the comprehensive history-taking process. The treatment protocol involves a prolonged course of antibiotics tailored to the cultured bacteria, with intravenous administration continued until clinical improvement is evident. Subsequently, a transition to oral antibiotics is made in tandem with radiological improvement noted in MRI follow-up, highlighting the prognosis’s dependence on the timely initiation of antibiotic therapy.

In the case of the patient with RA, distinctive features included persistent neck pain over several months, accompanied by pain in various joints. The RA diagnosis, based on the ACR/EULAR 2010 criteria, confirmed prolonged pain lasting over 6 weeks in wrist and finger PIP joints, mild elevation in ESR and CRP, and positive RA factor and anti-CCP.¹¹ Imaging characteristics of RA at the C1-2 level include atlanto-axial subluxation instability, evident in cervical full flexion x-rays where the distance from C1 anterior arch to the dens exceeds 4 mm, indicative of instability (Fig. 4-C).¹² A PET scan showed localized fluorodeoxyglucose uptake in the C1-2 joint, characteristic of benign inflammation.¹³ In contrast to the other conditions, RA showed only marginal improvement with NSAIDs. This series of cases highlights that, despite their conventional association with other anatomical areas, these inflammatory and infectious conditions can manifest specifically at the C1-2 region. This underscores the crucial significance of recognizing their distinct features for effective differentiation and management in patients reporting neck pain.

In conclusion, for patients presenting with severe neck pain and restricted joint mobility, evaluating the atlantoaxial joint is recommended. Using three-dimensional CT to assess crystal deposition proves beneficial in diagnosing CPPD. Confirming blood lab results against RA diagnostic criteria is crucial, especially when accompanied by pain in other joints. Cases displaying persistent high ESR and CRP, with or without fever, may necessitate excluding septic conditions through enhanced MRI. In such scenarios, differentiation among these inflammatory diseases becomes essential for effective diagnosis and treatment. 

We appreciated to three patients for permission on clinical research.

JC (Jihong Choi) and YN (Yoonju Na) had full access to all data in the study. Drafting of the manuscript, SK (Sungwon Kim) and YN; Medical Image Editing, JC; Critical manuscript revision for important intellectual content, YN and DHS (Duk Hyun Sung).

The authors confirm that there is no conflict of interest related to the manuscript.