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JAMA Clinical Challenge
March 29, 2019

A Man With Headache, Fever, and Neck Stiffness

Author Affiliations
  • 1Lifespan/Rhode Island Hospital, Providence
  • 2Warren Alpert Medical School of Brown University, Providence, Rhode Island
JAMA. 2019;321(16):1624-1625. doi:10.1001/jama.2019.1772
Case

A 53-year-old man presented with 2 weeks of back pain, stiff neck, headache, and fevers. He also reported 3 days of right knee pain and swelling. He had a history of pseudogout and kidney transplant 13 years ago. He was taking sirolimus and prednisone, with excellent graft function. His temperature on presentation was 102°F (38.9°C). He had nuchal rigidity and positive Kernig sign. There were no focal neurologic deficits and no spinal tenderness. He had a right knee effusion without erythema and with full range of motion. Laboratory workup of serum showed a white blood cell (WBC) count of 10 200/μL (neutrophils, 63.8%; lymphocytes, 19.6%; monocytes, 15.1%) and erythrocyte sedimentation rate, 63 mm/h; workup of cerebrospinal fluid showed a WBC count of 0/μL; red blood cell count, 32/μL; total protein level, 109 mg/dL; and glucose level, 59 mg/dL (3.3 mmol/L). Magnetic resonance imaging (MRI) of the spine showed cervical degenerative changes with reactive marrow (Figure 1). He was prescribed intravenous vancomycin and cefepime. Blood and cerebrospinal fluid (CSF) cultures were negative.

Figure 1.
Magnetic resonance imaging of the cervical spine.

Magnetic resonance imaging of the cervical spine.

Box Section Ref ID

What Would You Do Next?

  1. Continue intravenous antibiotics

  2. Obtain additional imaging with computed tomography (CT)

  3. Start gabapentin

  4. Start high-dose ibuprofen

Discussion
Diagnosis

Crowned dens syndrome

What to Do Next

B. Obtain additional imaging with computed tomography (CT)

The key to the correct diagnosis is the presence on a CT scan of synovial crown- or halo-like calcific densities of the atlantoaxial (C1/C2) joint, surrounding the odontoid process, in a patient with history of peripheral acute calcium pyrophosphate (CPP) crystal arthritis (“pseudogout”) (Figure 2). This patient had crowned dens syndrome (CDS), ie, deposition of CPP or, less frequently, basic calcium phosphate (BCP) crystals in the atlantoaxial joint, causing symptoms and signs of cervical spine inflammation. Continuation of antibiotics was not indicated, since CSF and MRI findings were not consistent with infection. Gabapentin is effective against neuropathic but not acute inflammatory pain. Like other forms of crystal deposition disease, CDS can be treated with corticosteroids or colchicine when there is a relative contraindication to use of nonsteroidal anti-inflammatory drugs (NSAIDs, eg, ibuprofen), such as renal transplant in this patient.

Figure 2.
Axial (A), coronal (B), and sagittal (C) computed tomography scan of C1/C2 showing periodontoid calcifications.

Axial (A), coronal (B), and sagittal (C) computed tomography scan of C1/C2 showing periodontoid calcifications.

CDS was first described in 19801 and is defined as otherwise unexplained neck pain in the presence of radiographic atlantoaxial (C1/C2) calcifications. Fever, headache, meningismus, and elevated levels of inflammatory markers are common.2-6

The prevalence of CDS is not clearly established. In 1 US series of 513 consecutive CT scans obtained for acute trauma,7 the prevalence of atlantoaxial calcific depositions was 12.9% overall and was 34% after age 60 years. In 2 other recent reports, 12.5%8 to 36%9 of patients with atlantoaxial calcifications had neck pain.

CDS is most commonly associated with osteoarthritis but can also be observed in patients with rheumatoid arthritis and metabolic disorders such as hyperparathyroidism or hemochromatosis, which are linked to acute CPP crystal arthritis.3,6,9,10 Synovial fluid analysis from a peripheral joint aspirate can show CPP crystals, with negative or weakly positive birefringence under polarized light microscopy. The absence of crystals does not rule out CPP crystal disease, since the sensitivity of microscopic examination for CPP crystal detection ranges from 12% to 83%.6 Radiographic imaging of the knees and wrists at the time of presentation is a noninvasive way to infer diagnosis of CDS, by visualizing peripheral chondrocalcinosis.3,5

The gold standard for diagnosis is CT scan of the cervical spine, focusing on C1/2 (Figure 2). CT has greater sensitivity than MRI in demonstrating the characteristic calcifications surrounding the odontoid process3-6,9 and should be performed first when CDS is likely (eg, in patients with history of acute CPP crystal arthritis). MRI can also show signs of inflammatory arthropathy suggestive of CDS in the appropriate clinical context (degenerative changes with reactive marrow) (Figure 1). However, MRI is usually ordered when there is clinical suspicion of cord compression, osteomyelitis, or malignancy.6

The differential diagnosis of CDS includes infectious meningitis, retropharyngeal abscess, and diskitis-osteomyelitis of the cervical spine.3-5 Importantly, CPP calcifications, including the C1/C2 joint, are often observed in asymptomatic individuals.5,7-10 Thus, radiographic findings suggestive of CDS can coexist with infectious causes of neck pain. Therefore, even when CDS is suspected, some patients should still undergo evaluation for infection (lumbar puncture, MRI) and receive antibiotics until infection is ruled out. Unremarkable CSF studies and MRI results favor noninfectious etiologies, prompting discontinuation of antibiotics. Other considerations are tension headache, occipital neuralgia, cervicobrachial syndrome, BCP calcific longus colli tendinitis,6 polymyalgia rheumatica/giant cell arteritis when neck stiffness is associated with shoulder pain or jaw claudication,3-6 and vertebral metastases in patients with cancer.3

Treatment of CDS is similar to that of peripheral acute crystal arthritis and typically consists of a short course of high-dose NSAIDs.10 Colchicine and oral corticosteroids are effective alternatives.10 Anti-inflammatory treatment results in rapid resolution of symptoms, within days to weeks.1,4,5,10

Patient Outcome

Before obtaining CT of the cervical spine, knee arthrocentesis was performed to rule out septic arthritis. Synovial fluid was consistent with aseptic inflammatory arthritis, although crystals were not seen. Three-view radiographs of the hands showed bilateral chondrocalcinosis. All antibiotics were stopped. On discharge, the patient was prescribed prednisone (40 mg daily) for 5 days with rapid clinical improvement and then resumed low-dose prednisone (5 mg daily). He has not had recurrence of his symptoms after 12 months.

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Article Information

Corresponding Author: Dimitrios Farmakiotis, MD, Rhode Island Hospital, 593 Eddy St, Gerry House 111, Providence, RI 02903 (Dimitrios.Farmakiotis@lifespan.org).

Published Online: March 29, 2019. doi:10.1001/jama.2019.1772

Conflict of Interest Disclosures: None reported.

Additional Contributions: We thank the patient for providing permission to share his information.

Section Editor: Mary McGrae McDermott, MD, Senior Editor.
Submissions: We encourage authors to submit papers for consideration as a JAMA Clinical Challenge. Please contact Dr McDermott at mdm608@northwestern.edu.
References
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