3.4Special Circumstances

3.4.1Pediatric IOIS

3Pediatric IOIS comprises between 6% and 16% of all IOIS in published series [5, 7, 34, 60]. While the signs and symptoms of IOIS are generally consistent across all age groups, a number of large studies have ascribed several features of pediatric IOIS that are thought to be atypical in the adult population: (1) the presence of constitutional symptoms; (2) accompanying anterior chamber reaction; and (3) the presence of bilateral disease [34, 36].

The differential diagnosis of IOIS in children includes orbital cellulitis and trauma as well as such potentially lethal entities as rhabdomyosarcoma and neuroblastoma, among others. While “classic” IOIS in a child may be approached in a manner similar to that used in adults, a high degree of suspicion should be maintained. As in the adult population, any patient with atypical presentation or recurrent disease should undergo orbital biopsy of the involved tissue.

The treatment algorithm for pediatric IOIS is also similar to that of the adult population. However, certain aspects deserve mention. Corticosteroids should be administered based on a weight-based formula, typically at a dosage of 1 mg/kg/day for oral prednisone. Steroidrelated side effects, such as increased appetite, weight gain, gastritis, headache, and mood swings are common in children, and the classic cushingoid appearance may develop quickly. Corticosteroids also have an effect on linear growth, especially with prolonged therapy [8]. Fortunately, corticosteroids also inhibit closure of epiphyseal plates [22]. Once the steroids are tapered, children often experience rebound growth, allowing them to rejoin previous growth curves and attain normal adult height. Other known complications of steroid use, such as hypertension, diabetes, glaucoma, and cataract, are rare in the pediatric population [8, 22].

The data with regard to other treatment modalities are sparse for pediatric IOIS. Radiation therapy is generally avoided in children due to fears of inducing bony hypoplasia, soft tissue deformities, and secondary tumors, such as are seen in children receiving radiation for retinoblastoma and rhabdomyosarcoma. Although the dosages in the treatment are much lower (2,000 cGy vs. 5,000– 6,000 cGy), there are no studies in the literature documenting a “safe” dosage. Anecdotally, we have treated two patients, ages 11 and 15, with orbital radiation. Both have been followed for more than 4 years, and neither has experienced any treatment-related side effects.

Methotrexate, cyclosporine, and etanercept have been used with much success in the treatment of pediatric

uveitis [54] and rheumatologic diseases [38]. These agents may also be employed in the treatment of children with refractory IOIS or in those who become intolerant of steroid-related side effects, although there is very little published to support this use. Consultation and comanagement with a pediatric rheumatologist familiar with the use of these steroid-sparing and immunomodulating agents are recommended.

Summary for the Clinician

■The signs and symptoms of IOIS in the pediatric population are similar to those of adults. The presence of bilateral disease, constitutional symptoms, and an accompanying anterior chamber reaction may be more common in children. Peripheral eosinophilia may also be present.

■Corticosteroid dosages for treatment of IOIS should be calculated based on the child’s weight (1 mg/kg/day).

■Therapeutic management of pediatric IOIS should be managed in conjunction with pediatricians or pediatric rheumatologists familiar with the dosages and side effects of treatment regimens.

3.4.2Sclerosing Pseudotumor

Idiopathic sclerosing orbital inflammation (ISOI) is a rare cause of orbital inflammation that some consider a distinct clinicopathological entity [48]. It is characterized by a chronic, slowly progressive course and lacks the acute onset frequently associated with IOIS. Common signs and symptoms of ISOI include a dull pain, proptosis, EOM restriction with diplopia, and mild-to-moder- ate inflammation [21, 48]. Within the orbit, the superior and lateral portions, particularly the lacrimal gland, tend to be affected more often; however, up to 50% of patients may present with an apical mass [21, 48]. The disease is often unilateral but may be bilateral and asymmetric (Fig. 3.14).

On imaging, ISOS is characterized by a homogeneously enhancing mass with irregular margins, which may obliterate adjacent structures such as EOMs, the lacrimal gland, or bone. The masses are deeply hypointense on T2-weighted sequences. Histopathologically, normal anatomic structures are replaced by broad areas of fibrosis with a sparse inflammatory infiltrate of lymphocytes, plasma cells, histiocytes, eosinophils, and neutrophils [21, 48]. This characteristic picture is also seen in retroperitoneal fibrosis, a condition with which ISOI may be associated [31]. Calcification may also be present [61].

Summary for the Clinician

■IOSI may be a distinct clinicopathological entity characterized by broad areas of fibrosis with a sparse inflammatory infiltrate of lymphocytes, plasma cells, histiocytes, eosinophils, and neutrophils, which replace normal anatomic structures.

■Common signs and symptoms include a dull pain, proptosis, EOM restriction with diplopia, and mild-to-moderate inflammation

■ISOI is usually less responsive to corticosteroids than IOIS. Surgical debulking combined with immunomodulating agents may slow the course of this chronic, often progressive, disease.

In contrast to IOIS, which shows a dramatic response to corticosteroid treatment, a more aggressive regimen is often required to control the progression of ISOI. Hsuan et al [21] reviewed the largest series of patients in the literature (n = 31) from five regional centers. While the majority of patients received oral prednisolone, only nine had a “good” response with marked improvement. Eleven patients had a “partial” response with significant but limited improvement, and seven had minimal or no benefit. The authors noted a trend toward greater improvement in patientswithshorterdurationofdisease.Cyclophosphamide and azithioprine were used with some success in patients who did not respond well to steroids or those who experienced steroid intolerance. Radiotherapy was ineffective; however, surgical debulking did result in symptomatic relief in three of four patients.

3.4.3 Tolosa–Hunt Syndrome

Tolosa–Hunt syndrome (THS) is an idiopathic, painful ophthalmoplegia characterized by one or more episodes of

3periorbital or hemicranial pain and variably combined with ipsilateral cranial nerve palsies, oculosympathetic paralysis, or sensory loss in the distribution of the ophthalmic and occasionally the maxillary division of the trigeminal nerve. In 2004, the International Headache Society redefined the diagnostic criteria of THS specifying that granuloma, as demonstrated by magnetic resonance imaging (MRI) or biopsy, is required for diagnosis [56]. Some may argue that this change makes the inclusion of the THS in a discussion of IOIS more controversial. The histopathology, however, is no different from that of idiopathic orbital granulomatous inflammation dubbed “orbital sarcoid,” as discussed. In addition, like IOIS, the symptoms of THS are extremely sensitive to treatment with corticosteroids. The resolution of pain and paresis within 72 hours of starting corticosteroid therapy is, in fact, part of the new diagnostic criteria for the syndrome [56].

The characteristic findings of THS on MRI include lesions that enlarge the cavernous sinus, are isointense on T1-weighted images, and enhance markedly with contrast. In a literature review based on the new 2004 inclusion criteria, MRI detected a lesions in 7 (47%) of 15 patients with a normal computed tomographic (CT) scan,

demonstrating the importance of proper imaging in patients with suspected THS. These lesions diminished or disappeared during follow-up (range 1 week to 1 year) [27]. In our experience, the pain associated with THS responds rapidly to corticosteroids, but the cranial neuropathy has a distinct lag in resolution, usually taking several weeks. In addition, THS anecdotally appears to recur with greater frequency than IOIS and may be sequentially bilateral (Fig. 3.15). This atypical behavior of THS understandably produces a necessary underlying clinical trepidation in the treating physician and should always result in close follow-up over the long term with serial imaging.

With improvements in modern imaging, a tissue biopsy is rarely sought to establish the diagnosis of THS. Neurosurgical biopsy of the dural wall of the cavernous sinus is a technically difficult operation and exposes the patient to significant iatrogenic risks. Therefore, the procedure is generally considered one of “last resort” in patients with rapidly progressive neurological deficits, lack of steroid responsiveness, or persistent abnormalities on neuroimaging studies [26].

As is the case with IOIS, the differential diagnosis of cavernous sinus inflammation is long and includes many potentially serious conditions. While the updated inclusion criteria may help to rule out painful ophthalmoplegia caused by intracranial tumors and vascular anomalies that would be visible on MRI, signal