Crowned dens syndrome, yet another rheumatic disease imposter

Clinical Rheumatology https://doi.org/10.1007/s10067-019-04822-9 ORIGINAL ARTICLE Crowned dens syndrome, yet another rheumatic disease imposter Abid Awisat 1 & Itzhak Rosner 1,2 & Doron Rimar 1,2 & Michael Rozenbaum 1 & Nina Boulman 1 & Lisa Kaly 1 & Amal Silawy 1 & Nizar Jiries 3 & Shira Ginsberg 3 & Haya Hussein 1 & Gleb Slobodin 1,2 Received: 8 May 2019 / Revised: 17 September 2019 / Accepted: 17 October 2019 # International League of Associations for Rheumatology (ILAR) 2019 Abstract Objective Crowned dens syndrome (CDS) is defined as acute cervical or occipital pain due to a local inflammatory reaction related to calcifications in the ligaments surrounding the odontoid process. Virtually, all previous descriptions of CDS have related to calcium pyrophosphate dehydrate (CPPD) arthropathy. Methods We prospectively identified a total of twenty-four consecutive inpatients with Crowned dens syndrome from January 2016 to December 2017 in our institution. Results All patients (age range 54 to 87 years, 67% females) presented with acute onset pain in the upper neck and/or occiput accompanied with extreme neck stiffness. Most patients (79%) had elevated inflammatory markers. Four patients underwent temporal artery biopsy, which was negative for arteritis in all cases, and one was subjected to lumbar puncture, which was noncontributory. Seventeen patients (71%) had known rheumatic disease on presentation: 10 patients had the diagnosis of calcium pyrophosphate dehydrate arthropathy, 3 patients had ankylosing spondylitis, 2 patients had rheumatoid arthritis, 1 patient had Behcet’s disease, and 1 suffered from Familial Mediterranean Fever. In 4 more patients, crowned dens syndrome was the presenting symptom of calcium pyrophosphate dehydrate disease. All patients were treated with glucocorticoids as 0.5 mg/kg prednisone plus colchicine 0.5 mg bid resulting in dramatic improvement in both clinical (head/neck pain alleviated and cervical spinal mobility regained) and laboratory measures. Conclusions Crowned dens syndrome should be considered, and craniocervical junction imaged in the context of acute cervical or occipital pain with stiffness and elevated inflammation markers not only in patients previously diagnosed with calcium pyrophosphate dehydrate arthropathy but also in diverse clinical settings. Key Points • This report highlights that crowned dens syndrome should be considered in various clinical setting besides calcium pyrophosphate dehydrate (CPPD) arthropathy. • Vigilance to this syndrome allows rapid treatment and may spare the patient unnecessary invasive procedures (i.e., temporal artery biopsy or lumbar puncture). Keywords Calcium pyrophosphate dehydrate arthropathy . Craniocervical junction . Crowned dens syndrome . Rheumatic disease imposter The current article was presented as an abstract in the 2018 EULAR meeting (https://ard.bmj.com/content/77/Suppl_2/656.2). * Abid Awisat [email protected] 1 Rheumatology Unit, Bnai Zion Medical Center, 47 Elyahu Golumb St, 3339419 Haifa, Israel 2 Ruth and Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel 3 Internal medicine B, Bnai Zion Medical Center, 3339419 Haifa, Israel Introduction The term crowned dens syndrome (CDS) was first described in 1985 by Bouvet et al. [1], defined as acute neck pain and elevated C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR) due to calcification in ligaments and structures surrounding the odontoid process caused by crystal deposition [2]. A new onset of occipital or neck tenderness, elevated inflammatory markers, and shoulder pain in patients > 50 years old can potentially be misinterpreted as the manifestation of polymyalgia rheumatica, ankylosing spondylitis, infectious Clin Rheumatol spondylitis, or meningitis. When investigating the etiology of these symptoms, the craniocervical, i.e., C1-C2 region, is often overlooked. In recent years, several reports of CDS were published by rheumatologists, orthopedic surgeons [3], and neurosurgeons [4] indicating growing multidisciplinary interest and awareness to this phenomenon and highlighting the versatile presentations of this phenomenon, e.g., fever of unknown origin [5], odontogenic infection and osteomyelitis [6], and meningitis-like [7]. In this report, we present 24 cases of CDS which were not exclusively confined to calcium pyrophosphate dehydrate (CPPD) arthropathy patients but rather to patients with heterogeneous rheumatic diseases. Methods We prospectively identified a total of twenty-four consecutive inpatients with CDS from January 2016 to December 2017 in our institution. As a part of the workup, all patients diagnosed with CDS in this study underwent pelvic and peripheral joint imaging in search of radiographic calcifications and chondrocalcinosis consistent with CPPD in addition to the diagnostic cervical spine computerized tomography performed initially for diagnosis. Blood levels of magnesium, thyroid hormone, parathyroid hormone, phosphate, and ferritin were performed in all patients to rule out secondary CPPD. Results All patients (age range 54 to 87 years, 67% females) presented with acute onset pain in the upper neck and/or occiput accompanied with neck stiffness. Nineteen of 24 patients (79%) had elevated erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP). Five patients (21%) complained of concomitant severe diffuse headache. Four of those underwent temporal artery biopsy, which was negative for arteritis in all cases. Symptoms were associated with fever in one patient who was subjected to lumbar puncture, which was non-contributory. The diagnosis of CDS was confirmed on cervical spine computed tomography imaging in all patients, with precipitations of calcium deposits seen most often in the transverse ligament in 15 patients (Fig. 1) or alar ligaments in 9 patients (Fig. 2). Secondary pyrophosphate calcium deposition workup was negative in all patients. Uric acid levels were elevated only in one patient (7.9 mg/dl) with no antecedent episodes of gout. Seventeen patients (71%) had a known rheumatic disease on presentation: 10 patients had antecedent diagnosis of CPPD arthropathy, 3 patients had ankylosing spondylitis, 2 patients had rheumatoid arthritis, 1 patient had Behcet’s disease, and Fig. 1 Axial CT image showing calcifications (arrow) in transverse ligament in a patient with crowned dens syndrome one patient suffered from Familial Mediterranean Fever (Table 1). In 4 more patients, CDS was the presenting symptom of CPPD disease, which was the final diagnosis during hospitalization after peripheral joint imaging was completed. In total, fourteen patients had peripheral joint imaging findings consistent with CPPD arthropathy. Eight patients had knee chondrocalcinosis, three patients had radiocarpal chondrocalcinosis, and the remaining three patients had both knee and wrist radiographic evidence of CPPD arthropathy. All patients were treated with glucocorticoids as 0.5 mg/kg prednisone plus colchicine 0.5 mg bid resulting in dramatic improvement in both clinical (head/neck pain alleviated and cervical spinal mobility regained) and laboratory measures. Glucocorticoids dose was tapered gradually throughout several weeks to months until stopped. Fig. 2 Calcifications (arrow) in alar ligament Clin Rheumatol Table 1 Clinical and laboratory feature of 24 patients with crowned dens Age, years, and median (range) 71 (54–87) Females (ratio) Presenting symptoms: Neck pain Neck stiffness Headache Fever Antecedent rheumatologic diagnosis: Calcium pyrophosphate dehydrate Ankylosing spondylitis Rheumatoid arthritis Bechet’s disease Familial Mediterranean Fever Elevated inflammatory markers, (mean) Patients underwent temporal artery biopsy 16/24 (66% females) No. (%) 24 (100%) 24 (100%) 5 (20.6%) 1 (4%) No. (%) 14 (58%) 3 (12.5%) 2 (8.3%) 1 (4%) 1 (4%) 19 (79%) 4 (16.6%) Discussion In the current report, we prospectively overviewed twentyfour consecutive patients with CDS, one of the largest series in the literature, to evaluate their full clinical context. Overall, and since CDS was first described [1], 194 patients with CDS were reported, mainly as case reports or in a retrospective manner. The gold standard for diagnosis of CDS is the combination of acute neck or occipital pain and stiffness accompanied by elevated inflammatory markers and typical findings in cervical spine CT. In several reported cases of CDS, patients were subjected to invasive procedures to exclude urgent or life-threatening conditions as meningitis and giant cell arteritis [7–9]. In our series, CDS was diagnosed in patients with heterogeneous rheumatic diseases, four of which underwent unnecessary and ultimately normal temporal artery biopsy, and one patient was submitted to lumbar puncture with no findings suggestive of infection or inflammation. Differentiating CDS from giant cell arteritis (GCA) or polymyalgia rheumatica (PMR) can be quite challenging since these disorders share numerous epidemiologic and clinical features: age, new headache, and shoulder pain. Furthermore, CDS patients may fulfill classification criteria for GCA and PMR [10, 11]. Nevertheless, absence of temporal tenderness, ophthalmic complains, and jaw claudication combined with limited neck movement and peripheral radiologic evidence of CPPD should prompt further exploration, e.g., CT of cervical spine, even in patients with no history of CPPD or those with other rheumatic diseases prior to invasive procedures or initiation of prolonged treatment with high dose glucocorticosteroids. High level of suspicion is mandatory since CDS presentation can be challenging and atypical as in recent reports in which it manifested as FUO [5] and osteomyelitis [6]. While some researchers have gone a step further and developed a semi-quantitative method to measure calcium deposits in ligaments surrounding the dens and demonstrated a significantly strong and linear correlation with CRP levels [12], others have shown that calcifications around the odontoid are not synonymous with CDS as in a retrospective study by Sano et al. [4], in which odontoid calcifications were found in 88 out of 554 patients (15.9%) undergoing CT scans upon admission to neurosurgical ward, but as few as eleven (12.5%) of the 88 patients with odontoid calcification were diagnosed with CDS. In previously published cases of CDS, patients were treated with NSAIDS, colchicine or, steroids [8–10, 13]. We chose to treat with a combination of prednisone and colchicine targeting rapid and eminent relief due to the acute and disabling nature of CDS symptoms and in an attempt to achieve treatment homogeneity. The uniqueness of our series, beside the large number of patients, is the variety of rheumatic diseases in which CDS was diagnosed which should further raise the awareness of this phenomenon regardless of the background rheumatic diagnosis. While generally believed to be a rare phenomenon, CDS was seen in 24 patients in a 400-bed general hospital within 2 years and is probably underdiagnosed. Furthermore, early diagnosis and vigilance to this rarely reported phenomenon can lead to rapid treatment and resolution of symptoms while avoiding long-term steroid treatment and preventing unnecessary invasive medical procedures, i.e., temporal artery biopsy or lumbar puncture. We believe that clinical and radiographic follow-up (preferably by computerized tomography) is mandatory for patient with CDS in order to further understand the natural history of this disorder and to determine whether longterm treatment is required to prevent exacerbations and damage. Conclusions CDS should be considered and craniocervical junction imaged in the context of acute cervical or occipital pain with stiffness and elevated inflammation markers not only in patients previously diagnosed with CPPD but also in diverse clinical settings. Particularly, CDS should be recognized as a possible alternative diagnosis in older patients referred with suspicion for giant cell arteritis because of new headache and elevated ESR/CRP with neck stiffness underlined as a clear differentiating sign. Clin Rheumatol Compliance with ethical standards Disclosures None. Ethical approval All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. References 1. 2. 3. 4. 5. 6. Bouvet JP, le Parc JM, Michalski B, Benlahrache C, Auquier L (1985) Acute neck pain due to calcifications surrounding the odontoid process: the crowned dens syndrome. Arthritis Rheum 28(12):1417–1420 Constantin A, Bouteiller G (1998) Acute neck pain and fever as the first manifestation of chondrocalcinosis with calcification of the transverse ligament of the atlas. 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