Jurij R. Bilyk

BASICS

DESCRIPTION

• Idiopathic orbital inflammatory syndrome (IOIS) is a nonspecific inflammation of orbital tissue with no identifiable local or systemic cause.

• IOIS is a diagnosis of exclusion, made only after other entities have been ruled out.

• IOIS can involve any orbital tissue individually or in combination; often subcategorized based on anatomic location of inflammation:

– Myositis

– Dacryoadenitis

– Posterior scleritis

– Inflammation of the orbital fat

– Inflammation of the orbital apex

EPIDEMIOLOGY

Incidence

• Unknown

• Accounts for ∼5% of orbital disorders

• Peak incidence between 40 and 60 years of age, but may occur at any age

Prevalence

Unknown

RISK FACTORS

• No clear risk factors

• On occasion, patients with IOIS also have or develop other autoimmune diseases. This may simply be an epiphenomenon.

• IOIS never progresses to lymphoma.

Genetics

No known hereditary pattern

GENERAL PREVENTION

None known

PATHOPHYSIOLOGY

• The signs and symptoms of IOIS most likely represent the clinical manifestations of a variety of autoimmune and cell-mediated processes for which the trigger(s) has yet to be determined.

• There is no evidence that IOIS is part of the spectrum of lymphoproliferative diseases (see Ocular Adnexal Lymphoma chapter).

ETIOLOGY

See pathophysiology

COMMONLY ASSOCIATED CONDITIONS

• Idiopathic

• Possible associations have been reported with Crohn’s disease, systemic lupus erythematosus, rheumatoid arthritis, diabetes, and ankylosing spondylitis. This may be an epiphenomenon.

DIAGNOSIS

HISTORY

• The ‘classic’ presentation includes the abrupt onset of one or more of the following signs and symptoms:

– Periorbital pain. Absence of pain is an atypical feature of IOIS.

– Diplopia

– Visual changes

• There may be a history of autoimmune disease.

• Complete review of systems, including the presence of constitutional symptoms (particularly in children), history of malignancy, respiratory symptoms, autoimmune disease, or immunosuppression

PHYSICAL EXAM

• Complete ophthalmic and orbital exam. Some or all of the following may be seen:

– Boggy eyelid edema

– Erythema, which is usually more pink than red

– Conjunctival chemosis and/or injection

– Proptosis

– External ophthalmoplegia

– Choroidal detachment and optic disc swelling may be seen in cases of posterior scleritis.

• Children may present with bilateral findings, either simultaneously or sequentially.

DIAGNOSTIC TESTS & INTERPRETATION

Lab

Initial lab tests

• Baseline serologic work-up may include:

– CBC with differential, ACE, cANCA, ANA, SPEP, and serum lactate dehydrogenase

Follow-up & special considerations

• Follow-up with primary care doctor (± rheumato-logist) if lab studies reveal positive findings.

Imaging

• All cases of clinically suspected IOIS require orbital imaging. The diagnosis of IOIS should never be made on clinical grounds alone.

• CT

– Focal or diffuse mass, poorly demarcated, which enhances with contrast

– Bone erosion is highly atypical for IOIS.

• MRI

– T1: low signal intensity

– T2: increased signal intensity

– Gadolinium: + homogenous enhancement

• Echography

– Not widely used, but may be very useful for suspected posterior scleritis: scleral thickening with a squared-off optic nerve entry (T-sign) may be seen.

Diagnostic Procedures/Other

• Orbital biopsy may not be required for diagnosis:

– Should be attempted in patients who present in an atypical fashion, in patients who do not respond to corticosteroid treatment, and in patients with recurrent episodes of inflammation

– A low threshold for biopsy is also indicated in patients with a known history of local or distant malignancy.

– Some experts will also perform biopsy on all patients presenting with lacrimal gland inflammation, because this area is easily accessible and, on occasion, a malignancy can present with secondary inflammation.

Pathological Findings

Nonspecific paucicellular infiltrate of lymphocytes, plasma cells, and histiocytes, and varying degrees of fibrosis

DIFFERENTIAL DIAGNOSIS

• Acute bacterial cellulitis: This is especially important to rule out in children before beginning corticosteroid therapy.

• Sarcoidosis

• Wegener granulomatosis

• Lymphoproliferative disease, including lymphoma

• Tolosa–Hunt syndrome

• Benign neoplasm

• Malignancy: primary or metastatic

• Thyroid eye disease

TREATMENT

MEDICATION

First Line

• Oral corticosteroids:

– Starting dosage of 1.0–1.5 mg/kg/day

– A prompt and complete response is expected, and may be considered part of the diagnostic algorithm.

– Symptom rebound during steroid taper may occur and may respond to a slower taper.

– Inflammation not sensitive to the effects of steroids or an inability to taper off steroids is considered ‘atypical’, and alternative diagnoses should be sought.

– Note that a course of corticosteroids may mask the true diagnosis if biopsy is needed at a later date. This is particularly true for inflammatory (e.g., sarcoidosis) or lymphoproliferative lesions.

Second Line

• Parenteral corticosteroids

– Often reserved for cases of IOIS-related optic neuropathy

• Non-steroidal anti-inflammatory medications:

– Typically used as bridging therapy at the tail end of the corticosteroid taper in patients who re-flare at lower corticosteroid doses

– Some experts advocate the use of NSAIDs as first-line therapy.

• Local intralesional corticosteroid injections (off-label use of triamcinolone acetonide)

– May be used in cases of local inflammatory masses or dacryoadenitis.

– Use is controversial because of potential side effects and risks of injection.

ADDITIONAL TREATMENT

General Measures

• Observation:

– Inflammation often resolves slowly without treatment.

Issues for Referral

• Referral for orbital biopsy should be considered in cases that present in an atypical fashion, in patients with a history of malignancy, or in those treated empirically with corticosteroids if:

– Minimal or sub-total response to adequate corticosteroid treatment

– Relapse of symptoms

Additional Therapies

• Orbital radiotherapy

– May be used in steroid-resistant cases or those unable to tolerate corticosteroids

– Biopsy should be obtained prior to radiotherapy if the tissue is accessible without excessive morbidity.

• Immuno-modulating agents may be used in steroid-resistant cases, but it is preferable to obtain tissue biopsy first. All therapies listed below are off-label uses of the specific agent:

– Antimetabolites (e.g., methotrexate, azathioprine)

– Alkylating agents (e.g., cyclophosphamide, chlorambucil)

– T-cell inhibitors (e.g., cyclosporine, tacrolimus)

– Biologic agents (e.g., infliximab, enteracept)

SURGERY/OTHER PROCEDURES

• Tissue biopsy for confirmation should be performed in all atypical cases.

• The threshold for biopsy is lower in patients with a history of malignancy.

• Some experts will biopsy all cases of inflammatory dacryoadenitis.

• Complete excision is typically not needed and is, usually, technically not feasible without significant local morbidity.

IN-PATIENT CONSIDERATIONS

Admission Criteria

• Comorbidities (e.g., brittle diabetes) which preclude the use of corticosteroids on an outpatient basis

• Postoperative observation following deep orbital biopsy

IV Fluids

As needed for inpatient corticosteroid therapy.

Nursing

As needed for inpatient corticosteroid therapy or postoperative care

Discharge Criteria

Response to therapy and stability of comorbidities

ONGOING CARE

FOLLOW-UP RECOMMENDATIONS

Long-term follow-up is recommended after the resolution of a patient’s acute symptoms, as an episode of ‘idiopathic’ orbital inflammation may be a harbinger of systemic disease.

Patient Monitoring

• As required during the treatment period:

– Monitoring patient’s response to treatment and treatment-related side effects, including blood sugar elevation

• Bi-annual or annual follow-up after resolution to monitor for signs of recurrence

PATIENT EDUCATION

• IOIS is a diagnosis often made based on clinical grounds, without pathologic confirmation.

– Patients must understand that they need to be followed prospectively for the development of an alternate diagnosis.

PROGNOSIS

• Most patients respond well and completely to treatment.

– Patients with severe disease or multiple recurrences may, in rare cases, develop orbital scarring, permanent diplopia, or loss of vision.

COMPLICATIONS

• Treatment-related (see Treatment section)

• Permanent orbital scarring

• Complications related to tissue biopsy (e.g., visual loss, diplopia, hypesthesia, ptosis, infection)

ADDITIONAL READING

• Harris G. Idiopathic orbital inflammation: A pathogenetic construct and treatment strategy. Ophthal Plast Reconst Surg 2006;22:79–86.

• Yuen SJ, Rubin PA. Idiopathic orbital inflammation: Distributions, clinical features and treatment outcome. Arch Ophthalmol 2003;121:491–499.

• Rose GE. A personal view: Probability in medicine, levels of (un)certainty, and the diagnosis of orbital disease (with particular reference to orbital “pseudotumor”). Arch Ophthalmol 2007;125:1171–1172.

• Lane KA, Bilyk JR. Current concepts in the diagnosis and management of idiopathic orbital inflammation. In: Guthoff R, Katowtiz JA, eds. Essentials in ophthalmology: oculoplastics and orbit: Aesthetic and functional oculofacial plastic problem-solving in the 21st century. Berlin: Spring-Verlag, 2010:47–63.

See Also (Topic, Algorithm, Electronic Media Element)

• Idiopathic Orbital Inflammatory Syndrome, Typical and Atypical (algorithm)

CODES

ICD9

• 375.00 Dacryoadenitis, unspecified

• 376.00 Orbital inflammation, unspecified

• 376.11 Inflammatory orbital pseudotumor

CLINICAL PEARLS

• IOIS is a diagnosis of exclusion. The clinician should always maintain a degree of uneasiness with this diagnosis and follow the patient over the long term.

• Typical features of IOIS include sudden, painful onset; varying degrees of external signs of inflammation; orbital soft tissue infiltration with lack of bone erosion on imaging; and rapid, dramatic response to appropriate systemic corticosteroid therapy (algorithm).

• All other presentations should be considered atypical and lower the threshold for tissue biopsy (algorithm).

• A history of cancer lowers the threshold for tissue biopsy.

• Some experts advocate biopsy of all cases of suspected inflammatory dacryoadenitis.

• Systemic corticosteroid therapy may mask pathologic processes on subsequent tissue biopsy.

Stay updated, free articles. Join our Telegram channel

Join