7/12/12. Orbital Inflammatory Syndrome. What s in a title? Why orbital pseudotumor is no longer a useful concept. orbital pseudotumor
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1 Orbital Inflammatory Syndrome Daniel R. Lefebvre, MD Ophthalmic Plastic Surgery What s in a title? orbital pseudotumor Idiopathic Orbital Inflammatory Syndrome Idiopathic Orbital Inflammatory Disease Non- specific Orbital Inflammatory Syndrome pseudotumor confused with pseudotumor cerebri i.e. Idiopathic Intracranial Hypertension (IIH) Why orbital pseudotumor is no longer a useful concept. Jack Rootman: orbital pseudotumor its definition is of such diverse character that it no longer serves a useful purpose. In fact, its use contributes to intellectual laxity in clinical analysis and may have significant negative consequences as a result of delay and confusion in diagnosis and management of patients. Rootman, J. Why orbital pseudotumor is no longer a useful concept. Br J Ophthalmol 1998;82:
2 Specifically Dacryoadenitis (lacrimal gland) Myositis (extra- ocular muscle and/or levator) Posterior Scleritis Tolosa- Hunt Syndrome (cavernous sinus inflammation) Orbital apex inflammation Diffuse orbital inflammation Sclerosing orbital inflammation 2
3 Nonspecific Orbital Inflammation Benign inflammatory process of the orbit Polymorphous lymphoid infiltrate Varying degrees of fibrosis Diagnosis of exclusion i.e. without known, identifiable cause NSOI Immune- mediated Can be a/w systemic immunologic disease Crohn disease Systemic lupus erythematosis Rheumatoid arthritis Diabetes mellitus Myasthenia gravis Ankylosing spondylitis NSOI Rapid response to corticosteroids / immunosuppressives E.g. 1 mg/kg/day prednisone Suggests a cell- mediated pathophysiology 3
4 Affected orbital tissues Extraocular muscles myositis (most common) Lacrimal gland dacryoadenitis Anterior orbit / scleritis Orbital apex Diffuse inflammation throughout the orbit Symptoms / Signs Pain is an important feature (generally) Usually boring and deep within the orbit Motility limitation Proptosis Conjunctival injection / chemosis Eyelid erythema / edema Symptoms / Signs Pain with movement myositis Decreased vision scleritis / optic nerve involvement Diffuse enlargement of lacrimal gland dacryoadenitis 4
5 Myositis vs. Thyroid Orbitopathy NSOI myositis often includes inflammation of EOM tendons Thyroid Eye Disease typically spares tendons Thyroid vs. NSOI Thyroid EOM frequency Inferior rectus Medial rectus Superior rectus Lateral rectus I am Simmons Lessell Thyroid Orbitopathy 5
6 Orbital Myositis Dacryoadenitis Potential causes: Viral: EBV, CMV, Mumps Bacterial: Staph, Strep, Gonoccal, TB Neoplastic: lymphoid, epithelial (pleomorphic adenoma, adenoid cystic carcinoma) Other: sarcoidosis, Wegener s, inflammatory bowel disease, Sjogren s, ruptured dermoid cyst Dacryoadenitis 6
7 Lacrimal Gland Biopsy Orbital Apex Inflammation Orbital Apex Syndrome External and Internal Ophthalmoplegia Decreased Vision Possible orbital / facial pain Possible Venous Engorgement Differential Dx Orbital Apex Sx Inflammatory 1. Sarcoidosis 2.Systemic lupus erythematosus 3. Churg Strauss syndrome 4.Wegener granulomatosis 5. Tolosa- Hunt Syndrome (Idiopathic orbital apex inflammation) 6.Giant cell arteritis 7.Thyroid orbitopathy 7
8 Differential Dx Orbital Apex Sx Infectious 1.Fungi: Aspergillosis, Mucormycosis (diabetic, sinus dz) 2.Bacteria: various 3. Viruses: Herpes zoster Differential Dx Orbital Apex Sx Neoplastic Adenoid cystic carcinoma nasopharyngeal carcinoma meningioma, schwannoma metatstatic lesion (lung, breast, renal cell, malignant melanoma), lymphoma / leukemia Differential Dx Orbital Apex Sx Other Post- surgical (iatrogenic) Trauma (apical fracture, hematoma, foreign body) Cavernous sinus fistula / thrombosis Mucocele 8
9 Orbital Apex Syndrome Need prompt evaluation Imaging (CT with contrast) Look for adjacent sinus disease Mucormycosis (?immunocompromised / diabetic,?recent steroids) Tumor infiltration (?bony destruction from sphenoid sinus)?fracture / foreign body May need MRI / MRV (?cavernous sinus thrombosis, sphenoid sinus disease) Orbital Inflammation: Random Points Simultatneous bilateral orbital inflammation in adults: Think possible systemic vasculitis Note: 33% of pediatric cases NSOI are bilateral and idiopathic Orbital Inflammation: Random Points Histology Pleomorphic cellular infiltrate Lymphocytes (separate from distinct lymphoid proliferations) Plasma cells Eosinophils Variable degrees of reactive fibrosis Sclerosing subtypes demonstrate predominance of fibrosis 9
10 Risk Factors Idiopathic Orbital Inflammation (IOI) Case- control study 69 adults with first episode IOI 296 control adults with rheg. retinal detachment 6- page questionnaire to all patients Social and medical history at time of Dx and 2 years prior Bijlsma WR, van Gils CH, Paridaens D, Mourits MP, Kalmann. Risk factors for idiopathic orbital inflammation: a case- control study. Br J Oophthalmol 2011;95: Risk Factors Idiopathic Orbital Inflammation (IOI) IOI Average age 52.6 years Male:Female = 2:3 Isolated Myositis 25% (17/69) Isolated Dacryoadenitis 28% (19/69) Diffuse Orbital Inflammation 48% (33/69) Classic Inflammation 68% (21/31) Sclerosing Inflammation 26% (8/31) Granulomatous Inflammation 6% (2/31) Bijlsma WR, van Gils CH, Paridaens D, Mourits MP, Kalmann. Risk factors for idiopathic orbital inflammation: a case- control study. Br J Oophthalmol 2011;95: Risk Factors Idiopathic Orbital Inflammation (IOI) Increased risk for IOI: Higher BMI (OR 2.88, 95% CI 1.32 to 6.32) Bisphosphonates (OR 8.68, 95% CI 1.16 to 65.0)?autoimmune disease (OR 2.56, 95% CI 0.93 to 7.05) Decreased risk for IOI: Higher socioeconomic status (OR 0.38, 95% CI 0.17 to 0.84) Women older at first childbirth (OR 0.14, 95% CI 0.03 to 0.64) Bijlsma WR, van Gils CH, Paridaens D, Mourits MP, Kalmann. Risk factors for idiopathic orbital inflammation: a case- control study. Br J Oophthalmol 2011;95:
11 Workup / Treatment Physical examination Full orbital examination Visual acuity, color vision, possibly HVF Motility, pupils External exam (erythema, globe dystopia, ptosis) Palpation of orbits (?masses,?orbital resistance) Cranial Nerve Exam IOP Prism Exophthalmometry SLE, DFE Workup / Treatment Imaging CT Orbits with contrast Sometimes MRI with gadolinium of orbits Labs CBC with diff (sometimes eosinophilia) Glucose (r/o DM?mucormycosis) Consider: ANCA ANA ACE Lyme Thyroid (TSH, T3, FT4, TPO, TSI, anti- Thyroglobulin Ab) Workup / Treatment Prednisone 1 mg / kg / day (e.g. 80 mg per day) Expect rapid response (~2 days) Note, many entities can temporarily improve from prednisone metastases ruptured dermoid cyst infections lymphoid infiltrates (e.g. lymphoma) 11
12 22 y/o female 2 day h/o pain, diplopia Limitation of abduction OD 12
13 13
14 85 y/o male h/o CLL and Diabetes 3 days ago diplopia Now: VA OD = HM Ophthalmoplegia OD Except MRD1 1mm Trace supraduction OD w/q, no proptosis, no pain 14
15 85 y/o male, CLL/DM2, Ophthalmoplegia Endoscopic sphenoid sinus and pterygopalatine fossa biopsy Aspergillus fungus ball, NOT invasive Lymphoplasmacytic infiltrate 85 y/o male, CLL/DM2 Orbital Apex Syndrome No one could agree on diagnosis?leukemic infiltrate?invasive fungal infection?systemic vasculitis (e.g. Wegener s)? pseudotumor i.e. NSOI Repeat biopsy: Endonasal endoscopic biopsy of orbital apex Lymphoplasmacytic infiltrate Flow Cytometry: non- revealing (baseline CLL monoclonality) 15
16 VA Light Perception (over 1 week) 80 mg prednisone initiated (under coverage of voriconazole) VA up to 20/200 within ~ 3 days Motility significantly improved galactomannan Component of cell- wall of the mold Aspergillus Released during growth Detectable in blood in patients with invasive disease (ELISA) 55 F, Metastatic Lung CA 1 day history of redness / pain / decreased motility OS VA 20/25 OU 16
17 Zoledronic acid Intravenous bisphosphenate (e.g. for Paget s disease or to combat osteoporosis) Our patient received infusion 2 days previously A number of documented cases of orbital inflammation following zoledronic acid infusion (w/in 48 hours) Pt improved over the course of ~10 days without steroids Idiopathic Sclerosing Orbital Inflammation Unique clinicopathological entity Represents ~7.8% of all orbital inflammatory lesions Clinically: Aggressive, insidious, chronic, progressive sclerosis Histologically: Dense fibrotic tissue, paucicellular (T lymphs, eosinophils, plasma cells, histiocytes) 17
18 Idiopathic Sclerosing Orbital Inflammation Typically 4 th decade Proptosis Pain Normal vision No ethnic / gender / comorbidity predilections Idiopathic Sclerosing Orbital Inflammation May be part of idiopathic multifocal sclerosis Retroperitoneal fibrosis Sclerosing cholangiitis Mediastinal fibrosis Riedel s thyroiditis (thyroid replaced by rock- hard fibrosis) Idiopathic Sclerosing Orbital Inflammation IgG4 related systemic disease Elevated levels of IgG4 in serum and tissue biopsy ISOI Autoimmune pancreatitis Mediastinal fibrosis Retroperitoneal fibrosis Reidel s thyroiditis Mikulicz Syndrome (bilat lacrimal / parotid) Kuttner s tumor (benign inflammatory submandibular gland) 18
19 Idiopathic Sclerosing Orbital Inflammation Treatment Biopsy Aggressive anti- inflammatory (e.g. steroids)?rituxan?radiation therapy References American Academy of Ophthalmology BCSC Section 7 Rootman, J. Why orbital pseudotumor is no longer a useful concept. Br J Ophthalmol 1998;82: Espinoza GM. Orbital Inflammatory Pseudotumors: Etiology, Differential Diagnosis, and Management. Curr Rheumatol Rep 2010;12: Harris GJ. Idiopathic Orbital Inflammation: A Pathogenetic Construct and Treatment Strategy. Ophthalm Plast Reconst Surg 2006;22(2): Ortiz- Perez S, Fernandez E, Molina JJ, et al. Two Cases of Drug- Induced Orbital Inflammatory Disease. Orbit 2011;30(1): Bijlsma WR, van Gils CH, Paridaens D, Mourits MP, Kalmann. Risk factors for idiopathic orbital inflammation: a case- control study. Br J Oophthalmol 2011;95: Pemberton JD, Fay A. Idiopathic Sclerosing Orbital Inflammation: A Review of Demographics, Clinical Presentation, Imaging, Pathology, Treatment, and Outcome. Ophthal Plast Reconstr Surg 2012;28(1): Rootman J, McCarthy M, White V, et al. Idiopathic sclerosing inflammation of the orbit. A distinct clinicopathological entity. Ophthalmology 1994;101: Khosroshahi A, Stone JH. A clinical overview of IgG4- related systemic disease. Curr Opin Rheumatol 2011; 23 (1):
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