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Orbital Proptosis and Sinusitis in a Middle-aged Woman

Educational Objective
Based on this clinical scenario and the accompanying image, understand how to arrive at a correct diagnosis.
1 Credit CME

A 48-year-old woman presented with 3 days of worsening right orbital swelling, eye pain, blurry vision, and 3 months of bilateral photophobia. She also reported bilateral rhinorrhea, congestion, and right frontal and temporal headaches. Active medical issues included hypertension, very poorly controlled type 2 diabetes, hyperlipidemia, tobacco use, and asthma. Her brother and father both had a history of chronic orbital swelling. Vital signs were unremarkable, and examination of the right eye showed moderate chemosis, injected conjunctiva, and periorbital edema. Both eyes were proptotic, right worse than left. She had normal bilateral extraocular movements, pupillary light reflexes, and gross vision. Computed tomography with contrast revealed bilateral ethmoid and frontal sinus opacification and right worse than left orbital fat stranding (Figure 1A). Magnetic resonance imaging with contrast demonstrated both enlargement and enhancement of bilateral extraocular muscles, especially the right superior rectus (Figure 1B). Initially she was started on antibiotic therapy. Right nasal biopsy, right endoscopic sinus surgery, and right anterior superior orbital tissue biopsy were performed. Intraoperatively, the sinus mucosa demonstrated only edema and mild secretions, but there was no necrosis or purulence. Both orbital and nasal cultures grew methicillin-resistant Staphylococcus aureus. Orbital biopsy showed nodular lymphoplasmacytic infiltrates without evidence of fungal infection or necrosis (Figure 1C). Further workup revealed elevated erythrocyte sedimentation rate, C-reactive protein, total IgG, and IgG4 levels and normal white blood cell count, thyroid-stimulating hormone, angiotensin-converting enzyme, lysozyme, antinuclear antibody, and antineutrophil cytoplasmic antibody (ANCA) levels.

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C. IgG4-related disease

Further immunohistochemical staining demonstrated focally increased immunoglobulin G4 (IgG4)-positive staining plasma cells at approximately 80 to 100 per high-power field (HPF) (Figure 2). Steroid therapy was initiated, antibiotic therapy was discontinued, and orbital symptoms improved to baseline over 3 to 4 days.

Immunoglobulin G4-related disease (IgG4-RD) is a systemic autoimmune disease first described in 2003.1 Though the precise details remain unclear, pathogenesis involves antigen presentation by B cells to T cells, which triggers class switching to IgG4-producing plasma cells.2,3 While increased levels of serum IgG4 and tissue infiltration of IgG4-positive plasma cells are hallmarks of the disease, it is still unclear what role IgG4 plays in pathogenesis.

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Article Information

Corresponding Author: Jeffrey W. Yu, MD, Department of Otolaryngology–Head and Neck Surgery, University of Illinois at Chicago, 1855 W Taylor St, MC 648, Chicago, IL 60612 (jeffwyu@uic.edu).

Published Online: January 5, 2023. doi:10.1001/jamaoto.2022.4366

Conflict of Interest Disclosures: None reported.

Additional Contributions: We thank the patient for granting permission to publish this information. We also would like to acknowledge John Frederiksen, MD, PhD, from the Department of Pathology at University of Illinois at Chicago for providing the pathological figures and descriptions. He was not compensated for this contribution.

References
1.
Kamisawa  T , Funata  N , Hayashi  Y ,  et al.  A new clinicopathological entity of IgG4-related autoimmune disease.   J Gastroenterol. 2003;38(10):982-984. doi:10.1007/s00535-003-1175-yPubMedGoogle ScholarCrossref
2.
Kubo  S , Nakayamada  S , Zhao  J ,  et al.  Correlation of T follicular helper cells and plasmablasts with the development of organ involvement in patients with IgG4-related disease.   Rheumatology (Oxford). 2018;57(3):514-524. doi:10.1093/rheumatology/kex455PubMedGoogle ScholarCrossref
3.
Perugino  CA , Stone  JH .  IgG4-related disease: an update on pathophysiology and implications for clinical care.   Nat Rev Rheumatol. 2020;16(12):702-714. doi:10.1038/s41584-020-0500-7PubMedGoogle ScholarCrossref
4.
Katz  G , Stone  JH .  Clinical perspectives on IgG4-related disease and its classification.   Annu Rev Med. 2022;73:545-562. doi:10.1146/annurev-med-050219-034449PubMedGoogle ScholarCrossref
5.
Wallace  ZS , Naden  RP , Chari  S ,  et al; Members of the ACR/EULAR IgG4-RD Classification Criteria Working Group.  The 2019 American College of Rheumatology/European League Against Rheumatism classification criteria for IgG4-related disease.   Ann Rheum Dis. 2020;79(1):77-87. doi:10.1136/annrheumdis-2019-216561PubMedGoogle ScholarCrossref
6.
Ueno  M , Nakano  K , Miyagawa  I , Tanaka  Y .  Five cases of IgG4-related disease with nasal mucosa and sinus involvement.   Intern Med. 2020;59(15):1905-1911. doi:10.2169/internalmedicine.4127-19PubMedGoogle ScholarCrossref
7.
Lanzillotta  M , Mancuso  G , Della-Torre  E .  Advances in the diagnosis and management of IgG4 related disease.   BMJ. 2020;369:m1067. doi:10.1136/bmj.m1067PubMedGoogle ScholarCrossref
8.
Lanzillotta  M , Fernàndez-Codina  A , Culver  E ,  et al.  Emerging therapy options for IgG4-related disease.   Expert Rev Clin Immunol. 2021;17(5):471-483. doi:10.1080/1744666X.2021.1902310PubMedGoogle ScholarCrossref
9.
Campochiaro  C , Della-Torre  E , Lanzillotta  M ,  et al.  Long-term efficacy of maintenance therapy with rituximab for IgG4-related disease.   Eur J Intern Med. 2020;74:92-98. doi:10.1016/j.ejim.2019.12.029PubMedGoogle ScholarCrossref
AMA CME Accreditation Information

Credit Designation Statement: The American Medical Association designates this Journal-based CME activity activity for a maximum of 1.00  AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to:

  • 1.00 Medical Knowledge MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program;;
  • 1.00 Self-Assessment points in the American Board of Otolaryngology – Head and Neck Surgery’s (ABOHNS) Continuing Certification program;
  • 1.00 MOC points in the American Board of Pediatrics’ (ABP) Maintenance of Certification (MOC) program;
  • 1.00 Lifelong Learning points in the American Board of Pathology’s (ABPath) Continuing Certification program; and
  • 1.00 CME points in the American Board of Surgery’s (ABS) Continuing Certification program

It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting MOC credit.

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