Haitsma, Iain

Karim, A. Faiz

Li, Jiawei

Monserez, Dominiek A.

Oei, Edwin H. G.

Oei, Ling

Ten Cate, David

van Laar, Jan A. M.

Verdijk, Robert M.

Zillikens, M. Carola

English

EUR Research Repository

Letter to the Editor (Case report)A dens fracture case solvedLing Oei1, Jiawei Li 1, A. Faiz Karim2, Robert M. Verdijk3, Edwin H. G. Oei4, Jan A. M. van Laar1,5,David Ten Cate6,7, Iain Haitsma8, Dominiek A. Monserez9, M. Carola Zillikens1,*1Department of Internal Medicine, Erasmus MC, University Medical Center, Rotterdam, The Netherlands2Department of Internal Medicine, Groene Hart Hospital, Gouda, The Netherlands3Department of Pathology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands4Department of Radiology and Nuclear Medicine, Erasmus MC, University Medical Center, Rotterdam, The Netherlands5Department of Immunology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands6Department of Rheumatology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands7Department of Rheumatology, Sint Maartenskliniek, Nijmegen, The Netherlands8Department of Neurosurgery, Erasmus MC, University Medical Center, Rotterdam, The Netherlands9Department of Otolaryngology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands*Correspondence to: M. Carola Zillikens, Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, PO Box 2040-Rg-528, 3000 CARotterdam, The Netherlands. E-mail: m.c.zillikens@erasmusmc.nlGraphical AbstractAccepted: 27 November 2023VC The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology.This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), whichpermits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.Rheumatology, 2024, 00, 1–3https://doi.org/10.1093/rheumatology/keae026Advance access publication 8 February 2024Letter to the EditorRheumatologyDownloaded from https://academic.oup.com/rheumatology/advance-article/doi/10.1093/rheumatology/keae026/7603980 by Erasmus University Rotterdam user on 27 February 2024DEAR EDITOR, IgG4-related disease (IgG4-RD) is a fibroinflam-matory condition [1] characterized by dense lymphoplasmo-cytic infiltration rich in IgG4-positive plasma cells, storiformfibrosis and prompt response to corticosteroids. IgG4-RDcommonly presents as salivary and lacrimal gland enlarge-ment, orbital disease, autoimmune pancreatitis, retroperito-neal fibrosis and tubulointerstitial nephritis [2]. It sometimesmimics malignancy by inflammatory pseudotumors, compli-cating correct diagnosis and treatment. Rarely IgG4-RDcauses lytic bone lesions, which is known for an aggressivecourse [3, 4]. Nonetheless, the involvement of the dens hasnot yet been reported. This case is the first report of osteolysisof the dens due to IgG4-RD, which should be added to thedifferential diagnosis of lytic bone lesions.The patient was a 50-year-old male with a non-united densfracture. He presented with sudden severe pain in the neck,limited and painful mobility of the neck and fever. Past medi-cal history included type 2 diabetes, ulcerative colitis, primarysclerosing cholangitis and bisphosphonate use for 3 years forosteoporosis. He was not on immunosuppressive therapy. Nofocal neurologic deficits were found. CRP was 67 mg/l andESR was 62 mm/h. Serum calcium, phosphorus, creatinine,anti-CCP, angiotensin-converting enzyme, 25-hydroxyvita-min D and 1,25-dihydroxyvitamin D were normal, alkalinephosphatase was slightly increased and IgG4 was within thereference range. Infectious meningitis was ruled out by lum-bar puncture. Imaging showed calcification around the densand inflammation of soft tissue. Therefore, a working diagno-sis of crowned dens syndrome (CDS) was initially made.NSAID (celecoxib) and prednisolone treatments initiallyresulted in a biochemically good response. However, withinweeks, destructive and expansive osteolysis of the dens andanterior arch of the atlas arose. Although inflammatorymarkers decreased, a non-united fracture remained (Fig. 1I).CDS was deemed unlikely, as there were no improvementsof the neck symptoms and osteolysis after 2 months of pred-nisolone treatment. Also, the aggressive course did not fit andthe radiologist had doubts about CDS because there wereonly some small calcifications and no typical ‘crown’ or ‘halo’configuration. X-rays of the hand, knees and feet were alsonormal. Biopsy of the dens and surrounding soft tissuesshowed localized crystalline material, scattered moderate in-filtration of bone with lymphocytes, plasma cells and focalcrystalline birefringent material, but no clear calcium pyro-phosphate crystals. Immunohistochemistry showed CD3-positive T cells and CD79a- and CD138-positive plasma cells(Fig. 1II) and no evidence of malignancy, lymphoma or multi-ple myeloma. 18F-fluorodeoxyglucose (18F-FDG) PET underprednisolone showed no abnormalities.Despite normal serum IgG4, pathology revision demon-strated dense lymphocytic fibrosing infiltrate with >100IgG4-positive plasma cells/HPF and an IgG4:IgG ratio of50%, highly suspicious of IgG4-RD (Fig. 1II). Another 18F-FDG PET/CT without prednisolone showed increased radio-tracer activity in the dens and additionally in the right medialrectus eye muscle, supporting the diagnosis of IgG4-RD(Fig. 1III). Further, an enlargement of the pituitary gland wasfound without PET avidity and was judged as an incidentallydetected microadenoma. After multidisciplinary discussion,the working diagnosis of CDS was changed to IgG4-RD.CDS, a condition in which the atlanto-occipital joint is af-fected by calcium pyrophosphate deposition disease [5], thesecond most common crystal-induced arthritis [6], presentswith acute cervico-occipital pain and inflammation.Radiologically, CDS is characterized by peri-odontoid calcifi-cations of the transverse ligament of the atlas.In clinical practice, elevated serum IgG4 represents the onlyvalidated non-invasive biomarker for IgG4-RD. The associa-tion of serum IgG4 with diagnosis, prognosis, response totreatment and disease activity of IgG4-RD has beenFigure 1. Imaging and histopathological results of the dens and surrounding tissues. I. CT scans of the dens. (A) Initial CT shows degenerative changes ofthe C1–C2 joint with small calcifications. (B) Low-dose CT shows lucency of the dens as a first sign of osteolysis. (C) Destructive and expansiveosteolysis of the dens and anterior atlas arose. (D) With 2months of prednisolone treatments, a radiological improvement with more ossification wasseen. Yet the non-union fracture remained. II. 18F-FDG PET/CT. (A) 18F-FDG PET/CT without prednisolone treatment showed avid FDG uptake in andaround the dens. (B) PET/CT without prednisolone additionally showed avidity in the medial rectus eye muscle. (C) MRI showed an enlargement of thepituitary. III. Histopathology results of the dens and surrounding tissues. (A) Haematoxylin and eosin staining showed scattered moderate infiltration ofbone with lymphocytes and plasma cells. (B) IgG immunostaining showed IgG-positive plasma cells. (C) IgG4 immunostaining showed IgG4-positiveplasma cells within the tissuesRheumatology key message• IgG4-RD should be included in the differential diagnosis oflytic bone lesions.2 Letter to the EditorDownloaded from https://academic.oup.com/rheumatology/advance-article/doi/10.1093/rheumatology/keae026/7603980 by Erasmus University Rotterdam user on 27 February 2024investigated. However, serum IgG4 is normal in approxi-mately half of the patients with IgG4-RD [2].Imaging may contribute to the diagnosis by means of 18F-FDG PET, which shows increased FDG uptake in the involvedtissues. On MRI, homogeneous enhancement after gadolin-ium contrast administration also suggests the existence ofIgG4-RD. However, some cases did not show enhancementafter gadolinium on MRI and showed no enhancement onPET/CT, probably due to relatively low disease activity underuse of immunosuppressors [3]. Most importantly, osteolyticlesions may not emerge during the early stages of IgG4-RD,as was the case in our patient. Once impairment of the odon-toid process occurs, reversal by medical therapy is difficult.To diagnose IgG4-RD, histopathology remains the gold stan-dard and requires careful examination of the tissue, includingimmunohistochemical analysis with anti-IgG4 and anti-IgG anti-bodies. We recommend histopathological examination by tissuebiopsy when IgG4-related bone lesions are highly suspected.Our patient was followed up with repeat imaging and labora-tory investigations by our multidisciplinary team. He received aneck collar for 8 months in total as a conservative treatment andhe has been doing quite well except for persisting limited rangeof motion of the neck and neck pain. No progression or relapseof IgG4-RD has been observed to date. Our case adds to thespectrum of known manifestations of IgG4-RD.Data availabilityThe data that has been used is confidential.Authors’ contributionsLing Oei, Jiawei Li and M. Carola Zillikens: conceptualiza-tion, writing original draft. All authors reviewed and revisedthe manuscript to improve its intellectual and technicalcontent.FundingNo specific funding was received from any bodies in the pub-lic, commercial or not-for-profit sectors to carry out the workdescribed in this article.Disclosure statement: The authors have declared no conflictsof interest. Informed consent was obtained from the patientfor research and publication.References1. Wallace ZS, Naden RP, Chari S et al.; American College ofRheumatology/European League Against Rheumatism IgG4-Related Disease Classification Criteria Working Group. The 2019American College of Rheumatology/European League AgainstRheumatism Classification Criteria for IgG4-related disease.Arthritis Rheumatol 2020;72:7–19.2. Johnston J, Allen JE. IgG4-related disease in the head and neck. CurrOpin Otolaryngol Head Neck Surg 2018;26:403–8.3. Detiger SE, Karim F, Monserez D et al. IgG4-related disease of skullbase: case series of 3 patients with headache. World Neurosurg2020;134:536–9.4. Park BJ, Starks R, Kirby P, Menezes AH, Dlouhy BJ. IgG4-relateddisease of the craniovertebral junction. World Neurosurg 2020;134:264–71.5. Ferrone C, Andracco R, Cimmino MA. Calcium pyrophosphate de-position disease: clinical manifestations. Reumatismo 2012;63:246–52.6. Haikal A, Everist BM, Jetanalin P, Maz M. Cervical CT-dependentdiagnosis of crowned dens syndrome in calcium pyrophosphatedihydrate crystal deposition disease. Am J Med 2020;133:e32–7.Letter to the Editor 3Downloaded from https://academic.oup.com/rheumatology/advance-article/doi/10.1093/rheumatology/keae026/7603980 by Erasmus University Rotterdam user on 27 February 2024

A dens fracture case solved

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A dens fracture case solved

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