A 50-year-old male was referred to our academic bone center because of a non-union dens fracture. Past medical history included type 2 diabetes, ulcerative colitis, primary sclerosing cholangitis, and bisphosphonates for 3 years for osteoporosis (low bone mineral density and a traumatic clavicle fracture). Eight months prior, the patient had presented with a sudden inability to move his head, fever and increased C-reactive protein. Infectious meningitis was excluded. Initially, head and neck CT only showed periodontoid ligament calcifications judged as crowned dens syndrome. However, in ensuing weeks destructive and expansive osteolysis of the dens arose. Myeloma screen revealed no abnormal monoclonal protein. Trans-oral bone biopsy of the dens showed plasma cells and crystals with negative microbiological tests. Under a work diagnosis of calcium pyrophosphate dihydrate crystal deposition disease, the most frequent cause of crowned dens syndrome, prednisone treatment was started. Inflammatory markers decreased, but a non-union fracture remained.

Although serum immunoglobulin G4 (IgG4) was within references, pathologic revision of the dens material demonstrated dense lymphocytic fibrosing infiltrate with >100 IgG4-positive plasma cells/HPF and an IgG4/IgG ratio of 50%, fitting IgG4-related disease (IgG4-RD). After radiological revision crowned dens syndrome was discarded. PET-CT showed avidity in the medial rectus eye muscle and in the dens.

Crowned dens syndrome is characterized by ligament calcifications, and often resolves spontaneously or requires only short anti-inflammatory treatment. Contrariwise, IgG4-RD, which has been reported in virtually every organ system, is a rare cause of lytic bone lesions and is known for a more aggressive course. Histopathology is key to IgG4-RD diagnosis. A diagnostic caveat is that serum IgG4 is normal in half of cases.

In conclusion, critical re-appraisal may alter the working diagnosis at any stage and may draw upon the expertise of a multi-disciplinary review board, resulting in clinically relevant insights.