compared patients with IOIS to those with lymphoma and found that more patients with lymphoid tumors had a palpable mass than did patients with IOIS (90% vs. 65%, p < .0001). They also noted that patients with IOIS were

3more likely to present with lid swelling (55% vs. 40%, p =

.014); eyelid or conjunctival congestion (42% vs. 24%, p =

.001); and pain (24% and 1%, p < .0001), among others. Two entities that may mimic IOIS in the pediatric population need to stressed. Rhabdomyosarcoma presents with rapidly progressive orbital signs (proptosis, globe malposition) in the absence of acute inflammation (pain, erythema, etc.), but on occasion, inflammation may also be present [53]. Conversely, a ruptured dermoid cyst presents with an intense inflammatory orbital reaction that may mimic cellulitis or IOIS [53].

Tumors metastatic to the orbit are rare, representing 7–10% of all orbital neoplasms [47, 53]. Similar to IOIS, diplopia, ocular motility limitation, proptosis, or globe dystopia and the presence of a palpable mass are common signs and symptoms of metastasis to the orbit [14, 16]. However, the tempo of onset tends to be less acute than in IOIS (Fig. 3.9). Common primary sites include breast, prostate, lung, and kidney. Of note, orbital metastasis may be the presenting sign of systemic cancer in as many as 25–30% [14, 53] of patients. Certainly, in any patient with a known history of cancer, the diagnosis of IOIS should be made with extreme caution. Even if biopsy of the involved tissue may appear inflammatory, the possibility of an acute or chronic inflammatory reaction surrounding a metastatic lesion should also be considered.

3.2.2A Diagnostic Corticosteroid Trial?

Despite patient age, duration of symptoms, or tissue type involved, one of the most consistent findings in patients with IOIS is an exquisite sensitivity to corticosteroids. It is common to observe near-complete resolution of a patient’s signs and symptoms after the first dose or two of oral or intravenous steroids (Fig. 3.10). Some have advocated that such a rapid and significant response to corticosteroids be considered diagnostic of IOIS [29]. Others counter that any type of reactive inflammation, be it due to tumor, infection, systemic vasculitis, or hematological malignancy, will demonstrate clinical improvement with systemic steroids, and that therefore a “steroid response” cannot be used as a diagnostic test for IOIS [34, 49]. There are also numerous examples in the literature of patients with IOIS who “fail” corticosteroid therapy. Care must be taken in interpreting these steroid failures, however, as steroid resistance may be multifactorial. For example, inadequate dosage may result in incomplete resolution of

Summary for the Clinician

■IOIS is a diagnosis of exclusion.

■Patients with TED may present with periorbital pain, proptosis, and diplopia that is slow in onset and accompanied by characteristic eyelid findings, such as upper eyelid retraction and lateral flare.

■Acute bacterial cellulitis has an abrupt onset, is painful, and is often associated with a prior history of sinusitis, dental disease, or trauma. Patients are often febrile with an elevated white blood cell count. Orbital imaging usually distinguishes infection from IOIS.

■Sarcoidosis is a chronic systemic disease characterized by noncaseating granulomatous inflammation involving at least two organ systems. Within the orbit, sarcoidosis can involve the lacrimal gland, the EOMs and other soft tissues, and the optic nerve. On occasion, isolated orbital sarcoid may occur with no serologic or chest abnormality.

■WG is a chronic systemic disease characterized by necrotizing granulomatous inflammation of the upper or lower respiratory tract; necrotizing granulomatous vasculitis, usually affecting small vessels; and focal segmental glomerulonephritis. Cases involving the orbit may be part of a more limited form of the disease and may present with sinusitis, proptosis, nasolacrimal duct obstruction, conjunctival granulomas, or dacryoadenitis. cANCA may be negative in the limited form of WG.

■Primary orbital tumors often present with the insidious onset of proptosis, orbital congestion, or diplopia.

■Tumors metastatic to the orbit are rare but may present in a manner similar to IOIS. Orbital biopsy should be strongly considered in any patient with a knownhistoryofcancerwhopresentswithsuspected IOIS.

a patient’s symptoms and thus may be interpreted as treatment failure. The standard oral dose for suspected IOIS is between 1.0 and 1.5 mg/kg/day or approximately 80 mg of prednisone a day for a 70-kg adult. In addition, corticosteroids that are tapered too rapidly may predispose a patient to significant symptomatic flares, which may also be misconstrued as “steroid failures.”

The literature addressing the use of corticosteroids in the diagnosis of IOIS is limited. Mombaerts et al examined the efficacy of systemic corticosteroids in a group

of patients with IOIS that excluded all patients with inflammatory myositis or dacryoadenitis [34]. Of the 27 patients in this study who were initially treated with corticosteroids, only 78% of patients demonstrated an initial response to a single course of oral corticosteroids. With this relatively low sensitivity rate and the low specificity of corticosteroids, they concluded that the response to corticosteroids should not be used as a diagnostic test of IOIS. However, when the same group examined patients with the myositis variant of IOIS, all patients responded to oral corticosteroids. However, 50% of initial responders experienced symptomatic recurrence, and all of these cases were defined as a steroid failure [33].

Certainly, in a patient who presents in a manner classic for IOIS, an immediate and near-complete response to systemic corticosteroids may allow the clinician to feel more comfortable with the presumptive diagnosis. This adequate response to empiric therapy does not mean that continued vigilance is not necessary, however. In addition, one cannot conclude that an initially successful corticosteroid regimen is diagnostic of IOIS if the patient cannot be easily tapered off of the steroids, or if he or she experienced a recurrence of symptoms. Such a case would be considered “atypical,” and alternative diagnoses should be sought, be it through a biopsy of the involved tissue or through further systemic workup.