NANOS Rare Orbital Inflammations

Steven Feldon MD MBAProfessor amp Chair Department of Ophthalmology

University of Rochester School of Medicine amp Dentistry

Relevant Financial Disclosures

bull I do not have any financial interests or relationships to disclose

Differential Diagnosis of Non-idiopathic Orbital Inflammatory Disease

bull Sarcoidosisbull Churg-Strauss Syndromebull Wegenerrsquos Granulomatosis Granulomatosis with Polyangiitis (GPA)bull Giant Cell Arteritisbull Adult Xanthogranulomatous Diseasesbull Rosai-Dorfman

Sarcoidosis

bull Demographics 3rd and 6th decade M=Fbull Incidence 60100K Scandinavia 35100K in AArsquos and 11100K in US for

Caucasiansbull Post-911 the incidence of sarcoid lung disease in NYFDrsquos responders was

86100K (primarily pulmonary) suggesting environmental triggerbull Systemic findings pulmonarygtskingtneuroaxisbull Ocular findings uveitis of any type lid granulomasbull Orbit bilateral disease in 50 systemic manifestations in 70 lacrimal

gland involvement in 55 discrete mass in 20 nerve sheath in 20bull Pathology non-caseating granulomas giant cells Schumann body inclusions

background fibrosisbull Test ACE lysozyme imaging enhancesbull Treatment steroids cyclosporine azothioprine systemically may benefit

some patient with steroid injection locally into lesion

Am J Ophthalmol 2007 Nov144(5)769-775 Diverse clinical presentations of orbital sarcoid Mavrikakis I1 Rootman J

Relevant Financial Disclosures

bull I do not have any financial interests or relationships to disclose

Differential Diagnosis of Non-idiopathic Orbital Inflammatory Disease

bull Sarcoidosisbull Churg-Strauss Syndromebull Wegenerrsquos Granulomatosis Granulomatosis with Polyangiitis (GPA)bull Giant Cell Arteritisbull Adult Xanthogranulomatous Diseasesbull Rosai-Dorfman

Sarcoidosis

bull Demographics 3rd and 6th decade M=Fbull Incidence 60100K Scandinavia 35100K in AArsquos and 11100K in US for

Caucasiansbull Post-911 the incidence of sarcoid lung disease in NYFDrsquos responders was

86100K (primarily pulmonary) suggesting environmental triggerbull Systemic findings pulmonarygtskingtneuroaxisbull Ocular findings uveitis of any type lid granulomasbull Orbit bilateral disease in 50 systemic manifestations in 70 lacrimal

gland involvement in 55 discrete mass in 20 nerve sheath in 20bull Pathology non-caseating granulomas giant cells Schumann body inclusions

background fibrosisbull Test ACE lysozyme imaging enhancesbull Treatment steroids cyclosporine azothioprine systemically may benefit

some patient with steroid injection locally into lesion

Am J Ophthalmol 2007 Nov144(5)769-775 Diverse clinical presentations of orbital sarcoid Mavrikakis I1 Rootman J

Differential Diagnosis of Non-idiopathic Orbital Inflammatory Disease

bull Sarcoidosisbull Churg-Strauss Syndromebull Wegenerrsquos Granulomatosis Granulomatosis with Polyangiitis (GPA)bull Giant Cell Arteritisbull Adult Xanthogranulomatous Diseasesbull Rosai-Dorfman

Sarcoidosis

bull Demographics 3rd and 6th decade M=Fbull Incidence 60100K Scandinavia 35100K in AArsquos and 11100K in US for

Caucasiansbull Post-911 the incidence of sarcoid lung disease in NYFDrsquos responders was

86100K (primarily pulmonary) suggesting environmental triggerbull Systemic findings pulmonarygtskingtneuroaxisbull Ocular findings uveitis of any type lid granulomasbull Orbit bilateral disease in 50 systemic manifestations in 70 lacrimal

gland involvement in 55 discrete mass in 20 nerve sheath in 20bull Pathology non-caseating granulomas giant cells Schumann body inclusions

background fibrosisbull Test ACE lysozyme imaging enhancesbull Treatment steroids cyclosporine azothioprine systemically may benefit

some patient with steroid injection locally into lesion

Am J Ophthalmol 2007 Nov144(5)769-775 Diverse clinical presentations of orbital sarcoid Mavrikakis I1 Rootman J

Sarcoidosis

bull Demographics 3rd and 6th decade M=Fbull Incidence 60100K Scandinavia 35100K in AArsquos and 11100K in US for

Caucasiansbull Post-911 the incidence of sarcoid lung disease in NYFDrsquos responders was

86100K (primarily pulmonary) suggesting environmental triggerbull Systemic findings pulmonarygtskingtneuroaxisbull Ocular findings uveitis of any type lid granulomasbull Orbit bilateral disease in 50 systemic manifestations in 70 lacrimal

gland involvement in 55 discrete mass in 20 nerve sheath in 20bull Pathology non-caseating granulomas giant cells Schumann body inclusions

background fibrosisbull Test ACE lysozyme imaging enhancesbull Treatment steroids cyclosporine azothioprine systemically may benefit

some patient with steroid injection locally into lesion

Am J Ophthalmol 2007 Nov144(5)769-775 Diverse clinical presentations of orbital sarcoid Mavrikakis I1 Rootman J

Am J Ophthalmol 2007 Nov144(5)769-775 Diverse clinical presentations of orbital sarcoid Mavrikakis I1 Rootman J

Churg-Strauss Syndrome

bull Demographics 5th decade peakbull Incidence bull Systemic findings Asthma rash painnumbness in extremities malaise night

sweats bleeding bull Ocular findings

bull Ischemic presentation amaurosis ION BRAO or CRAObull Infiltrative presentation lid swelling episcleritis periscleritis

conjunctival granulomas dacryoadenitis thickened optic nerve sheathsbull Pathology eosinophilic infiltration of granulomatous inflammation

vasculitisbull Test B scan choroidal thickening in macula weak + ANCAbull Treatment steroids methotrexate cytotoxic drugs for refractory states

Ophthalmology 2001 Jun108(6)1129-33Orbital inflammatory pseudotumor and ischemic vasculitis in Churg-Strauss syndrome report of two cases and review of the literature Takanashi T1 Uchida S AritaM Okada M Kashii S

Ophthalmology 2001 Jun108(6)1129-33Orbital inflammatory pseudotumor and ischemic vasculitis in Churg-Strauss syndrome report of two cases and review of the literature Takanashi T1 Uchida S AritaM Okada M Kashii S

Granulomatosis with Polyangiitis (GPA)

bull Demographics peak 5th-8th decade M=F Caucasionsbull Incidence 4-8100Kbull Systemic findings upper airway including sinus involvement in 90

classical nasal septal perforation frequent lung and renal involvementbull Ocular findings episcleritis scleritis keratitis retinal vasculitisbull Orbit bilateral dacryoadenitis orbital fibrosisbull Pathology fat necrosis with giant cells free vacuoles fibrosisbull Test cANCA + in gt90bull Treatment corticosteroids plus cyclophosphomide methotrexate or

azathioprine some anti TNF and anti CD20 monoclonals may be helpful

Semin Arthritis Rheum 2006 Apr35(5)284-92 Wegeners granulomatosis ophthalmic manifestations and managementPakrou N1 Selva D Leibovitch I

Semin Arthritis Rheum 2006 Apr35(5)284-92 Wegeners granulomatosis ophthalmic manifestations and managementPakrou N1 Selva D Leibovitch I

Am J Med 2004 Jul 1117(1)39-50The antineutrophil cytoplasmic antibody-associated vasculitidesSeo P1 Stone JH

Giant Cell Arteritis

bull Demographics peak 8th decade Caucasian MF = 12bull Incidence rare orbital involvementbull Systemic findings headache neck pain jaw claudication scalp tenderness

polymyalgia weight loss bull Ocular findings AION in 20 CRAO amaurosis fugax diplopiabull Orbit diffuse orbital inflammation bull Pathology epithelioid cells giant cells round cell infiltrationbull Test CRP sed rate biopsybull Treatment hi dose corticosteroids methotrexate azathioprine cyclosporine

immunomodulatory drugs (tocilizumab abatacep ustakinumab)

bull

Graefes Arch Clin Exp Ophthalmol2001 Jul239(7)509-13Orbital presentations of giant cell arteritis Lee AG1 Tang RA Feldon SE Pless M Schiffman JS Rubin RM Rao N

Graefes Arch Clin Exp Ophthalmol2001 Jul239(7)509-13Orbital presentations of giant cell arteritis Lee AG1 Tang RA Feldon SE Pless M Schiffman JS Rubin RM Rao N

Adult Xanthogranulomatous Disease(AOX AAPOX NBX ECD)

bull Demographics peak in 6th decade M=Fbull Systemic findings bull AAPOX is associated with asthma and lymphadenopathy bull NBX is associated with paraproteinemiamyelomabull ECD is characterized by pulmonary cardiac and retroperitoneal fibrosis

as well as bone involvementbull Ocular findings eyelid massesbull Orbit dacryoadenitis diffuse infiltrative processbull Pathology foamy histiocytes (CD68+) Touton giant cells spindle cells

mononuclear infiltratebull Test paraproteins lymph node biopsybull Treatment multi-agent chemo with or without radiation combo

cyclosporine and cyclophosphamide

Dermatol Clin 2015 Jul33(3)457-63 doi 101016jdet201503010 Epub2015 May 8 Adult Orbital Xanthogranulomatous Disease A Review with Emphasis on Etiology Systemic Associations Diagnostic Tools and Treatment Kerstetter J1 Wang J2

Dermatol Clin 2015 Jul33(3)457-63 doi 101016jdet201503010 Epub2015 May 8 Adult Orbital Xanthogranulomatous Disease A Review with Emphasis on Etiology Systemic Associations Diagnostic Tools and Treatment Kerstetter J1 Wang J2

Rosai-Dorfman

bull Demographics MgtF 80 are lt21 years oldbull Incidence rarebull Systemic findings lymphadenopathy of head and neck respiratory tract

salivary glands skin bone meninges CNS testes bull Ocular findings rare scleritis uveitis marginal corneal ulcers choroidal

mass lid lesionsbull Orbit often sinus involvement bilateral dacryadenitis enhancing

homogeneous mass on T1 MRI and only rare bony destructionbull Pathology Emperipolesis (lymphoctyes found phagocytized by large

histiocytes lymph node architecture in extranodal locations scattered mixed inflammatory reaction

bull Test anemia polyclonal hypergammaglobulinemiabull Treatment Excision or debulking of masses Spontaneous remission possible

Radiation steroids and chemo for recurrent or unresponsive cases

Ophthal Plast Reconstr Surg 2016 NovDec32(6)458-461 Extranodal Rosai-Dorfman Disease of the Orbit Clinical Features of 8 Cases Tan JJ1 Narang S Purewal B Langer PD Blaydon S Schwarcz RM McCormick SA Kim JY Walrath JD Burt BO Shinder R

Ophthal Plast Reconstr Surg 2016 NovDec32(6)458-461 Extranodal Rosai-Dorfman Disease of the Orbit Clinical Features of 8 Cases Tan JJ1 Narang S Purewal B Langer PD Blaydon S Schwarcz RM McCormick SA Kim JY Walrath JD Burt BO Shinder R

Ocular Disease Truth Table

Disease Uveitis Scleritis Epi-

scleritis

Keratitis Choroid Retinal

Vasculitis

ION CRAO or

BRAO

Lid Mass

Sarcoid X X X

Churg-

StraussX X X X X (conj)

GPA X X X X

GCA X X

AAPOX X

NBX X

Rosai-

DorfmanX X X X X

Systemic Disease Truth Table

Disease Asthm

a

Sinus Skin CNS Lung Other

organs

Bone cANC

A

Para-

proteins

Sarcoid X X X

Churg-

Strauss

X X X

GPA X X X X

GCA

AAPOX X

NBX X

ECD X X X X

Rosai-

Dorfman

X X X X X X X

SUMMARY

Non-idiopathic orbital inflammation should be suspected when

bull The inflammation is bilateral

bull There is ocular involvement

bull There are systemic symptoms or signs

bull There is a characteristic biopsy

Treatment consists of

1 Biopsy of orbit skin or other involved organ

2 Corticosteroids (localized or systemic)

3 Immune suppression

4 Targeted biologicals

Systemic Disease Truth Table

Disease Asthm

a

Sinus Skin CNS Lung Other

organs

Bone cANC

A

Para-

proteins

Sarcoid X X X

Churg-

Strauss

X X X

GPA X X X X

GCA

AAPOX X

NBX X

ECD X X X X

Rosai-

Dorfman

X X X X X X X

SUMMARY

Non-idiopathic orbital inflammation should be suspected when

bull The inflammation is bilateral

bull There is ocular involvement

bull There are systemic symptoms or signs

bull There is a characteristic biopsy

Treatment consists of

1 Biopsy of orbit skin or other involved organ

2 Corticosteroids (localized or systemic)

3 Immune suppression

4 Targeted biologicals

SUMMARY

Non-idiopathic orbital inflammation should be suspected when

bull The inflammation is bilateral

bull There is ocular involvement

bull There are systemic symptoms or signs

bull There is a characteristic biopsy

Treatment consists of

1 Biopsy of orbit skin or other involved organ

2 Corticosteroids (localized or systemic)

3 Immune suppression

4 Targeted biologicals