History

• 66-year-old Caucasian male
• Sudden onset swelling, irritation, redness, pain with extraocular movement OS for three weeks
• Took augmentin for 10 days prescribed by referring ophthalmologist for preseptal cellulitis and amoxicillin for five more days, with no improvement
• Referred to LAC + USC Medical Center for further management
• Denies any prior episodes, trauma, sick contact, URI, skin infection, recent dental procedure, fever, chills

Exam Findings

• Pupils equal round reactive, no RAPD
• VA 20/20 OU
• IOP 10, 17mmHg
• EOM: -1 limitation in abduction OS
• Ishihara color plate 8/8 OU, subjective brightness 100% OU, no red desaturation
• Hertel exophthalmometer: 14>121<15
• Dilated fundus exam normal OU

Differential Diagnosis

• Orbital cellulitis
• Infectious dacryoadenitis
• Thyroid eye disease
• Idiopathic orbital inflammatory syndrome
• IgG4 related disease
• Sarcoidosis
• Lymphoproliferative disease
• Pleomorphic adenoma
• Adenoid cystic carcinoma

Additional Investigations

• CBC with mild neutrophil predominant leukocytosis
• Quantiferon Gold, RPR/FTA-ABS, HIV negative
• TSH/FT4 WNL
• CRP elevated, ESR WNL
• RF negative
• ACE WNL, lysozyme WNL
• ANA negative
• ANCA negative
• IgG4 WNL
• CXR WNL

Diagnosis

• Idiopathic orbital inflammatory syndrome/dacryoadenitis

Management of our Patient

• IV Solumedrol once a day with improvement in symptoms and signs
• Switched to PO prednisone
• Slowly tapered over two months with no recurrence
• No side effects from PO prednisone

Pathophysiology

• The classic histopathologic pattern consists of a paucicellular infiltrate of lymphocytes, plasma cells, and histiocytes.
• The pathogenesis remains elusive

Treatment – General Principles

• Observation and NSAIDs may be used in mild cases but oral prednisone is the mainstay of treatment
• IV steroids used with apical involvement and vision loss
• Low dose radiation may be used in steroid-intolerant cases
• Immunosuppressants in patients who do not fully respond to steroids, do not tolerate steroids, or cannot be weaned off of steroids

Prognosis and Future Directions

• Recurrence has been described in the literature. As much as 52% of the patients treated with systemic steroids recurred in a study done by Mombaerts et al.
• A 2005 ASOPRS Foundation Lecture has recommended beginning with oral prednisone at 1.0 to 1.5mg/kg/d for one to two weeks and then taper dosage to zero over six to 12 weeks.
• If there is inadequate response by one to two weeks or there is recurrence during taper, a biopsy is indicated which may lead to an alternative diagnosis of neoplasm, systemic autoimmune disease, or “nonspecific” chronic inflammation that may otherwise respond to steroids-sparing immunosuppressants.
• Novel treatments are being studied, including but not limited to low dose intralesional Rituximab which has been described to be effective by Savino et al, intralesional steroids, and tocilizumab, a novel IL-6R inhibitor, which has been trialed however has yet to show significant benefits.

References

• Andrew NH, Kearney D, Sladden N, Mckelvie P, Wu A, Sun MT, McNab A, Selva D. Idiopathic Dacryoadenitis: Clinical Features, Histopathology, and Treatment Outcomes. Am J Ophthalmol 2016; 163:148-153.
• Cytryn AS, Putterman AM, Schneck GL, et al. Predictability of Magnetic Resonance Imaging in Differentiation of Orbital Lymphoma from Orbital Inflammatory Syndrome. Ophthalmic Plastic and Reconstructive Surgery. Vol. 13. No. 2, pp 129-134.
• Dagi Glass LR, Freitag S. Orbital Inflammation: Corticosteroids First. Survey of Ophthalmology 61 (2016)670-673.
• Harris GJ. Idiopathic Orbital Inflammation: A Pathogenetic Construct and Treatment Strategy. The 2005 ASOPRS foundation Lecture. Ophthalmic Plastic and Reconstructive Surgery. Vol. 22. No. 2, pp 79-86.
• Jacobs D, Galetta S. Diagnosis and management of orbital pseudotumor. Current Opinion in Ophthalmology 2002, 13:347-351
• Luemsamran P, Rootman J, White VA, Nassiri N, Heran MKS. The Role of Biopsy in Lacrimal Gland Inflammation: A Clinicopathologic Study. Orbit 2017 1744-5108.
• Mombaerts I. The Many Facets of Dacryoadenitis: Curr Opin Ophthalmol 2015, 26:399-407.
• Mombaerts I, Bilyk J, Rose G, McNab A, Fay A, Dolman P, Allen R, Devoto M, Harris G. Consensus on Diagnostic Criteria of Idiopathic Orbital Inflammation Using a Modified Delphi Approach. JAMA Ophthalmol. 2017; 135(7):769-776.
• Mombaerts I, Goldschmeding R, Schlingemann RO, et al. What is Orbital Pseudotumor? Survey of Ophthalmology. Volume 41. Number 1. Jul-Aug 1996.
• Mombaerts I, Rose G, Garrity J. Orbital Inflammation: Biopsy First. Survey of Ophthalmology 61 (2016)664-669.
• Mombaerts I, Schlingemann RO, Goldschmeding R, et al. Are systemic corticosteroids useful in the management of orbital pseudotumors? Ophthalmology. 1996 Mar; 103(3):521-8.
• Savino G, Battendieri R, Siniscalco A, et al. Intraorbital injection of Rituximab in idiopathic orbital inflammatory syndrome: case reports. Rheumatol Int. 2015 Jan; 35(1):183-8.
• Silpa-Archa S, Oray M, Preble JM, et al. Outcome of tocilizumab treatment in refractory ocular inflammatory diseases. Acta Ophthalmol. 2016 Sep;94(6):e400-6.
• Swamy BN, McCluskey P, Nemet A, et al. Idiopathic orbital inflammatory syndrome: Clinical features and treatment outcomes. Br J Ophthalmol 2007;91:1667-1670

Contact

• Youning Zhang, MD, PGY-2 Ophthalmology resident, youning.zhang@med.usc.edu
• Jessica R. Chang, MD, Assistant Professor of Clinical Ophthalmology, jessica.chang@med.usc.edu

Section Editors

• Vivek Patel, MD, Associate Professor of Clinical Ophthalmology, Program Director, vivek.patel@med.usc.edu
• Jesse Berry, MD, Assistant Professor of Clinical Ophthalmology, Associate Program Director, jesse.berry@med.usc.edu

Produced by: Monica Chavez, John Daniel, Mellissa Linton and Dr. Vivek Patel