Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Adult orbital xanthogranuloma: long-term follow-up of treated cases

Eye volume 37, pages 2475–2481 (2023)Cite this article

Subjects

Abstract

Background

Adult orbital xanthogranulomatous disease (AOXGD) is a group of rare disorders. Four subtypes are identified: adult-onset xanthogranuloma (AOX), adult-onset asthma and periocular xanthogranuloma (AAPOX), necrobiotic xanthogranuloma (NBX), and Erdheim-Chester disease (ECD). Therapy options vary and little is known about the long-term effect of the treatment. In this study, we will describe the clinical behaviour, effect of treatment, and long-term outcome in a consecutive series of patients with AOXGD.

Methods

This is a descriptive, retrospective study with a long follow-up term of 21 patients with histologically proven AOXGD, treated between 1989 and 2021 in the Rotterdam Eye Hospital and Erasmus MC University Medical Center.

Results

Twenty-one patients with histologically proven AOXGD were included. The follow-up ranged from 2–260 months (median of 67 months). Six of the nine patients with AOX were treated with surgery alone, with recurrence in two. Three received systemic therapy, with recurrence in one. All four patients with AAPOX received systemic treatment, the disease recurred in two. Two patients with NBX were treated with surgery alone, with recurrence in one. Four required additional therapy with recurrence in two. Both patients with ECD required systemic therapy.

Conclusions

Recognition of AOXGD is important, in particular, because of the potential severe systemic locations in the different subtypes. Surgical excision might be a sufficient therapy for patients with AOX. Patients with AAPOX, NBX, and ECD warrant systemic therapy. Currently, there is no conclusive evidence for a superior treatment strategy, but further studies are necessary to investigate treatment options.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Kaplan-Meier curve of the proportion of patients with recurrence-free survival.
Fig. 2: Ophthalmic soft tissue signs before and after treatment.

Similar content being viewed by others

Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

References

  1. Guo J, Wang J. Adult orbital xanthogranulomatous disease: review of the literature. Arch Pathol Lab Med. 2009;133:1994–7.

    Article  PubMed  Google Scholar 

  2. Baykal C, Polat Ekinci A, Yazganoglu KD, Buyukbabani N. The clinical spectrum of xanthomatous lesions of the eyelids. Int J Dermatol. 2017;56:981–92.

    Article  PubMed  Google Scholar 

  3. Kiratli H, Kilic M, Tarlan B, Soylemezoglu F. Adult orbital xanthogranulomas: clinical features and management. Eur J Ophthalmol. 2015;25:288–92.

    Article  PubMed  Google Scholar 

  4. Sivak-Callcott JA, Rootman J, Rasmussen SL, Nugent RA, White VA, Paridaens D, et al. Adult xanthogranulomatous disease of the orbit and ocular adnexa: new immunohistochemical findings and clinical review. Br J Ophthalmol. 2006;90:602–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Asproudis I, Kanari M, Ntountas I, Ragos V, Goussia A, Batistatou A, et al. Successful treatment with rituximab of IgG4-related disease coexisting with adult-onset asthma and periocular xanthogranuloma. Rheumatol Int. 2020;40:671–7.

    Article  CAS  PubMed  Google Scholar 

  6. Honda Y, Nakamizo S, Dainichi T, Sasai R, Mimori T, Hirata M, et al. Adult-onset asthma and periocular xanthogranuloma associated with IgG4-related disease with infiltration of regulatory T cells. J Eur Acad Dermatol Venereol. 2017;31:e124–e5.

    Article  CAS  PubMed  Google Scholar 

  7. London J, Martin A, Soussan M, Badelon I, Gille T, Uzunhan Y, et al. Adult Onset Asthma and Periocular Xanthogranuloma (AAPOX), a rare entity with a strong link to IgG4-related disease: an observational case report study. Medicine. 2015;94:e1916.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Pomponio G, Olivari D, Mattioli M, Angeletti A, Rossetti G, Goteri G, et al. Sustained clinical response after single course of rituximab as first-line monotherapy in adult-onset asthma and periocular xanthogranulomas syndrome associated with IgG4-related disease: A case report. Medicine. 2018;97:e11143.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Stelmach-Goldys A, Garus B, Skowronek M, Kopczynski J, Trzpiot S, Pasiarski M. Periocular xanthogranuloma with adult-onset asthma: a rare disorder associated with elevated IgG4 levels. Pol Arch Intern Med. 2019;129:827–9.

    PubMed  Google Scholar 

  10. Efebera Y, Blanchard E, Allam C, Han A, Lee S, Munshi N. Complete response to thalidomide and dexamethasone in a patient with necrobiotic xanthogranuloma associated with monoclonal gammopathy: a case report and review of the literature. Clin Lymphoma Myeloma Leuk. 2011;11:298–302.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Finan MC, Winkelmann RK. Necrobiotic xanthogranuloma with paraproteinemia. A review of 22 cases. Medicine. 1986;65:376–88.

    Article  CAS  PubMed  Google Scholar 

  12. Fink C, Schneiderbauer R, Hartschuh W, Enk A, Toberer F. Necrobiotic xanthogranuloma associated with chronic lymphocytic leukemia. Int J Dermatol. 2018;57:719–20.

    Article  PubMed  Google Scholar 

  13. Hilal T, DiCaudo DJ, Connolly SM, Reeder CB. Necrobiotic xanthogranuloma: a 30-year single-center experience. Ann Hematol. 2018;97:1471–9.

    Article  CAS  PubMed  Google Scholar 

  14. Mello RB, Vale E. Necrobiotic xanthogranuloma associated with smoldering multiple myeloma: satisfactory response to cyclophosphamide, dexamethasone, and thalidomide. Bras Dermatol. 2019;94:337–40.

    Article  Google Scholar 

  15. Merritt H, Pfeiffer ML, Richani K, Phillips ME. Erdheim-Chester disease with orbital involvement: Case report and ophthalmic literature review. Orbit 2016;35:221–6.

    Article  PubMed  Google Scholar 

  16. Davies MJ, Whitehead K, Quagliotto G, Wood D, Patheja RS, Sullivan TJ. Adult orbital and adnexal xanthogranulomatous disease. Asia Pac J Ophthalmol (Philos). 2017;6:435–43.

    CAS  Google Scholar 

  17. Jakobiec FA, Mills MD, Hidayat AA, Dallow RL, Townsend DJ, Brinker EA, et al. Periocular xanthogranulomas associated with severe adult-onset asthma. Trans Am Ophthalmol Soc. 1993;91:99–125.

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Wang TT, Lin TT, Liu X, He YJ. Clinical analysis of adult onset orbital xanthogranuloma. Zhonghua Yan Ke Za Zhi. 2019;55:381–6.

    CAS  PubMed  Google Scholar 

  19. Cavallazzi R, Hirani A, Vasu TS, Sergott RC, Bilyk JR, Eagle RC, et al. Clinical manifestations and treatment of adult-onset asthma and periocular xanthogranuloma. Can Respir J. 2009;16:159–62.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Hayden A, Wilson DJ, Rosenbaum JT. Management of orbital xanthogranuloma with methotrexate. Br J Ophthalmol. 2007;91:434–6.

    Article  PubMed  Google Scholar 

  21. Elner VM, Mintz R, Demirci H, Hassan AS. Local corticosteroid treatment of eyelid and orbital xanthogranuloma. Trans Am Ophthalmol Soc. 2005;103:69–73.

    PubMed  PubMed Central  Google Scholar 

  22. Rose GE, Patel BC, Garner A, Wright JE. Orbital xanthogranuloma in adults. Br J Ophthalmol. 1991;75:680–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Bijlsma WR, van den Bosch WA, van Daele PL, Paridaens D. Azathioprine and prednisolone combination treatment for adult periocular and orbital xanthogranulomatous disease. Acta Ophthalmol. 2011;89:e278–82.

    Article  PubMed  Google Scholar 

  24. Verdijk RM, Heidari P, Verschooten R, van Daele PL, Simonsz HJ, Paridaens D. Raised numbers of IgG4-positive plasma cells are a common histopathological finding in orbital xanthogranulomatous disease. Orbit 2014;33:17–22.

    Article  PubMed  Google Scholar 

  25. Maeng MM, Godfrey KJ, Jalaj S, Kazim M. Adult xanthogranulomatous disease of the orbit: case report of spontaneous regression and review of treatment modalities. Orbit 2020;39:31–7.

    Article  PubMed  Google Scholar 

  26. Andron AA, Nair AG, Della Rocca D, Della Rocca RC, Reddy HS. Concomitant adult onset xanthogranuloma and IgG4-related orbital disease: a rare occurrence. Orbit. 2022;41:108–11.

  27. McKelvie P, McNab AA, Hardy T, Rathi V. Comparative study of clinical, pathological, radiological, and genetic features of patients with adult ocular adnexal xanthogranulomatous disease, Erdheim-Chester Disease, and IgG4-related disease of the orbit/ocular adnexa. Ophthalmic Plast Reconstr Surg. 2017;33:112–9.

    Article  PubMed  Google Scholar 

  28. Mudhar HS, Bhatt R, Sandramouli S. Xanthogranulomatous variant of immunoglobulin G4 sclerosing disease presenting as ptosis, proptosis and eyelid skin plaques. Int Ophthalmol. 2011;31:245–8.

    Article  PubMed  Google Scholar 

  29. Khosroshahi A, Wallace ZS, Crowe JL, Akamizu T, Azumi A, Carruthers MN, et al. International Consensus Guidance Statement on the Management and Treatment of IgG4-Related Disease. Arthritis Rheumatol. 2015;67:1688–99.

    Article  CAS  PubMed  Google Scholar 

  30. Papa BM, Prince HM, McNab AA, McKelvie P. IgG4-related ophthalmic disease in association with adult-onset asthma and periocular xanthogranuloma: a case report. Orbit. 2021;7:1–6.

  31. Sahu K, Sethy M, Sirka CS, Rout AN. Adult-Onset Asthma with Periocular Xanthogranuloma (AAPOX), a variant of periorbital xanthogranulomatous disease: an uncommon entity. Indian Dermatol Online J. 2020;11:792–5.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Hammond MD, Niemi EW, Ward TP, Eiseman AS. Adult orbital xanthogranuloma with associated adult-onset asthma. Ophthalmic Plast Reconstr Surg. 2004;20:329–32.

    Article  PubMed  Google Scholar 

  33. Elner VM, Mintz R, Demirci H, Hassan AS. Local corticosteroid treatment of eyelid and orbital xanthogranuloma. Ophthalmic Plast Reconstr Surg. 2006;22:36–40.

    Article  PubMed  Google Scholar 

  34. Ugurlu S, Bartley GB, Gibson LE. Necrobiotic xanthogranuloma: long-term outcome of ocular and systemic involvement. Am J Ophthalmol. 2000;129:651–7.

    Article  CAS  PubMed  Google Scholar 

  35. Meyer S, Szeimies RM, Landthaler M, Hohenleutner S. Cyclophosphamide-dexamethasone pulsed therapy for treatment of recalcitrant necrobiotic xanthogranuloma with paraproteinemia and ocular involvement. Br J Dermatol. 2005;153:443–5.

    Article  CAS  PubMed  Google Scholar 

  36. Chave TA, Chowdhury MM, Holt PJ. Recalcitrant necrobiotic xanthogranuloma responding to pulsed high-dose oral dexamethasone plus maintenance therapy with oral prednisolone. Br J Dermatol. 2001;144:158–61.

    Article  CAS  PubMed  Google Scholar 

  37. Kerstetter J, Wang J. Adult orbital xanthogranulomatous disease: a review with emphasis on etiology, systemic associations, diagnostic tools, and treatment. Dermatol Clin. 2015;33:457–63.

    Article  CAS  PubMed  Google Scholar 

  38. Rubinstein TJ, Mehta MP, Schoenfield L, Perry JD. Orbital xanthogranuloma in an adult patient with xanthelasma palpebrarum and hypercholesterolemia. Ophthalmic Plast Reconstr Surg. 2014;30:e6–8.

    Article  PubMed  Google Scholar 

  39. Beeram M, Patnaik A, Rowinsky EK. Raf: a strategic target for therapeutic development against cancer. J Clin Oncol. 2005;23:6771–90.

    Article  CAS  PubMed  Google Scholar 

  40. Badalian-Very G, Vergilio JA, Degar BA, MacConaill LE, Brandner B, Calicchio ML, et al. Recurrent BRAF mutations in Langerhans cell histiocytosis. Blood 2010;116:1919–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Haroche J, Charlotte F, Arnaud L, von Deimling A, Helias-Rodzewicz Z, Hervier B, et al. High prevalence of BRAF V600E mutations in Erdheim-Chester disease but not in other non-Langerhans cell histiocytoses. Blood 2012;120:2700–3.

    Article  CAS  PubMed  Google Scholar 

  42. Techavichit P, Sosothikul D, Chaichana T, Teerapakpinyo C, Thorner PS, Shuangshoti S. BRAF V600E mutation in pediatric intracranial and cranial juvenile xanthogranuloma. Hum Pathol. 2017;69:118–22.

    Article  CAS  PubMed  Google Scholar 

  43. Zhang C, Feng ZX, Solarte CE, Li L. Ocular juvenile xanthogranuloma with BRAF V600E mutation in a child. J Pediatr Ophthalmol Strabismus. 2021;58:e19–e21.

    Article  PubMed  Google Scholar 

  44. Chakraborty R, Hampton OA, Abhyankar H, Zinn DJ, Grimes A, Skull B, et al. Activating MAPK1 (ERK2) mutation in an aggressive case of disseminated juvenile xanthogranuloma. Oncotarget 2017;8:46065–70.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Ozkaya N, Rosenblum MK, Durham BH, Pichardo JD, Abdel-Wahab O, Hameed MR, et al. The histopathology of Erdheim-Chester disease: a comprehensive review of a molecularly characterized cohort. Mod Pathol. 2018;31:581–97.

    Article  CAS  PubMed  Google Scholar 

  46. Milman T, Eiger-Moscovich M, Henry RK, Ida CM, Ruben M, Shields CL, et al. Cyclin D1 Expression and Molecular Genetic Findings in Periocular Histiocytoses and Neoplasms of Macrophage-Dendritic Cell Lineage. Am J Ophthalmol. 2022;242:36–51.

Download references

Author information

Authors and Affiliations

  1. The Rotterdam Eye Hospital, Rotterdam, The Netherlands

    S. E. Detiger & R. M. Verdijk

  2. The Rotterdam Eye Hospital, Department of Oculoplastic, Orbital and Lacrimal Surgery, Rotterdam, The Netherlands

    G. J. Hötte, R. O. B. de Keizer & D. Paridaens

  3. Department of Pathology, Section of Ophthalmic Pathology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands

    R. M. Verdijk

  4. Department of Ophthalmology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands

    R. O. B. de Keizer & D. Paridaens

  5. Departments of Internal Medicine and Immunology, section Clinical Immunology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands

    P. M. van Hagen & J. A. M. van Laar

Authors
  1. S. E. Detiger
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. G. J. Hötte
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. R. M. Verdijk
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. R. O. B. de Keizer
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. P. M. van Hagen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. J. A. M. van Laar
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. D. Paridaens
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors were involved in the design of the study. RV evaluated all haematoxylin and eosin slides for the correct histopathological diagnosis. SD, GH, and DP performed the analyses. SD wrote the manuscript. DP, JvL, RM, GH, RdK, and PvH advised and reviewed the manuscript. All authors conform that neither this manuscript nor part of it has been published and is not under consideration for publication elsewhere.

Corresponding author

Correspondence to S. E. Detiger.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Detiger, S.E., Hötte, G.J., Verdijk, R.M. et al. Adult orbital xanthogranuloma: long-term follow-up of treated cases. Eye 37, 2475–2481 (2023). https://doi.org/10.1038/s41433-022-02357-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41433-022-02357-z

Search

Advanced search

Quick links