Journal of Pediatric Ophthalmology and Strabismus

Original Article 

Idiopathic Orbital Pseudotumor Preceding Systemic Inflammatory Disease in Children

Mai Tsukikawa, MD; Sara E. Lally, MD; Carol L. Shields, MD; Ralph C. Eagle Jr., MD; Forrest J. Ellis, MD; Barry N. Wasserman, MD

Abstract

Purpose:

To describe four pediatric cases in which isolated orbital pseudotumor preceded the development of a systemic inflammatory disease by months to years.

Methods:

The medical records of all patients with the clinical diagnosis of orbital pseudotumor seen at the Ocular Oncology Service of Wills Eye Hospital and Northern Virginia Ophthalmology Associates from 2010 to 2015 were reviewed retrospectively, and those associated with systemic inflammatory disease were selected for further study. Data were retrospectively collected from medical record review regarding patient demographics and clinical features, time to development of systemic inflammatory disease, and medical management.

Results:

In four pediatric patients, isolated orbital pseudotumor preceded the development of a systemic inflammatory disease, including pauciarticular juvenile idiopathic arthritis, eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome), granulomatosis with polyangiitis (Wegener's granulomatosis), and Crohn's disease.

Conclusions:

Orbital pseudotumor may be an antecedent to systemic inflammatory disease in children. Because this was a small case series, the authors are not ready to suggest that a full systemic work-up for systemic inflammatory disease is warranted for every patient with orbital pseudotumor. However, close observation and suspicion for systemic inflammatory conditions may be reasonable in children who present with idiopathic orbital pseudotumor.

[J Pediatr Ophthalmol Strabismus. 2019;56(6):373–377.]

Abstract

Purpose:

To describe four pediatric cases in which isolated orbital pseudotumor preceded the development of a systemic inflammatory disease by months to years.

Methods:

The medical records of all patients with the clinical diagnosis of orbital pseudotumor seen at the Ocular Oncology Service of Wills Eye Hospital and Northern Virginia Ophthalmology Associates from 2010 to 2015 were reviewed retrospectively, and those associated with systemic inflammatory disease were selected for further study. Data were retrospectively collected from medical record review regarding patient demographics and clinical features, time to development of systemic inflammatory disease, and medical management.

Results:

In four pediatric patients, isolated orbital pseudotumor preceded the development of a systemic inflammatory disease, including pauciarticular juvenile idiopathic arthritis, eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome), granulomatosis with polyangiitis (Wegener's granulomatosis), and Crohn's disease.

Conclusions:

Orbital pseudotumor may be an antecedent to systemic inflammatory disease in children. Because this was a small case series, the authors are not ready to suggest that a full systemic work-up for systemic inflammatory disease is warranted for every patient with orbital pseudotumor. However, close observation and suspicion for systemic inflammatory conditions may be reasonable in children who present with idiopathic orbital pseudotumor.

[J Pediatr Ophthalmol Strabismus. 2019;56(6):373–377.]

Introduction

Idiopathic orbital pseudotumor, also termed idiopathic orbital inflammation, is a non-infectious and non-neoplastic clinical syndrome characterized by the presence of an inflammatory mass within the orbit. The etiology of orbital pseudotumor is unknown. Although orbital pseudotumor has been observed in association with systemic inflammatory diseases,1 there are no recommendations on evaluating children who present with idiopathic orbital pseudotumor for future development of systemic inflammatory diseases. We describe four pediatric patients in whom idiopathic orbital pseudotumor was the initial solitary finding, with systemic inflammatory disease developing much later.

Patients and Methods

The medical records of all patients with the clinical diagnosis of orbital pseudotumor seen at the Ocular Oncology Service of Wills Eye Hospital and Northern Virginia Ophthalmology Associates from 2010 to 2015 were reviewed retrospectively, and those associated with systemic inflammatory disease were selected for further study. Institutional review board approval was obtained. Data were retrospectively collected from medical record review regarding patient demographics including age at initial presentation (in years), age at diagnosis of orbital pseudotumor (in years), race (white, African American, Hispanic, or Asian), sex (male or female), medical history, and ocular history. The clinical data included visual acuity, laterality (unilateral or bilateral), involvement of lacrimal gland and muscles, recurrence, treatment for orbital pseudotumor, type of systemic inflammatory disease and time to diagnosis (in months), treatment for systemic inflammatory disease, and length of follow-up (in years).

Results

Over a 5-year period, four cases of pediatric patients with orbital pseudotumor preceding systemic inflammatory disease were found. The demographic and clinical features of the patients are shown in Table 1. The mean patient age was 9.75 years (median: 11.5 years; range: 2 to 14 years). There were three white patients and one Hispanic patient; three of the patients were female and one was male. Orbital pseudotumor was present in the right eye for three patients (Figure 1) and in both eyes for one patient. Radiologic imaging showed that the lesion involved the lacrimal gland and orbital soft tissue in all four cases and additional extraocular muscle involvement in three cases (Figure 2). Systemic management of orbital pseudotumor for all four cases included oral prednisone.

Clinical Features at Initial Examination

Table 1:

Clinical Features at Initial Examination

Orbital pseudotumor in children preceding systemic inflammatory conditions. (A) Case 1: A 2-year-old girl presented with right upper eyelid swelling, 1 mm ptosis, and a full lacrimal gland. Juvenile idiopathic arthritis was diagnosed 12 months later. (B) Case 2: An 11-year-old girl presented with right upper eyelid swelling, 2 mm ptosis, and an enlarged lacrimal gland with no palpable mass. She developed eosinophilic granulomatosis with polyangiitis 9 months after orbital pseudotumor. (C) Case 3: A 12-year-old girl presented with swelling of the right eye and a palpable fixed nodule on the superotemporal rim of the right eye, and presented with granulomatosis with polyangiitis 4 months later.

Figure 1.

Orbital pseudotumor in children preceding systemic inflammatory conditions. (A) Case 1: A 2-year-old girl presented with right upper eyelid swelling, 1 mm ptosis, and a full lacrimal gland. Juvenile idiopathic arthritis was diagnosed 12 months later. (B) Case 2: An 11-year-old girl presented with right upper eyelid swelling, 2 mm ptosis, and an enlarged lacrimal gland with no palpable mass. She developed eosinophilic granulomatosis with polyangiitis 9 months after orbital pseudotumor. (C) Case 3: A 12-year-old girl presented with swelling of the right eye and a palpable fixed nodule on the superotemporal rim of the right eye, and presented with granulomatosis with polyangiitis 4 months later.

Radiologic imaging of orbital pseudotumor in children. (A) Case 1: Magnetic resonance imaging revealed a mass-like region of enhancement involving the right lacrimal gland contacting the lateral and superior rectus muscles, with thickening and inflammation in the overlying right periorbital soft tissues and preseptal soft tissues. (B) Case 2: Magnetic resonance imaging disclosed a right superolateral orbital lesion extending posteriorly close to the orbital apex, inseparable from the lacrimal gland, with a mass effect on superior and lateral rectus muscles. (C) Case 3: Magnetic resonance imaging revealed enhancing soft tissue in the right lateral extraconal space between a mildly thickened right lateral rectus muscle and sclerotic right lateral orbital wall. (D) Case 4: Computed tomography scan revealed diffuse enlargement of the extraocular muscles consistent with orbital pseudotumor.

Figure 2.

Radiologic imaging of orbital pseudotumor in children. (A) Case 1: Magnetic resonance imaging revealed a mass-like region of enhancement involving the right lacrimal gland contacting the lateral and superior rectus muscles, with thickening and inflammation in the overlying right periorbital soft tissues and preseptal soft tissues. (B) Case 2: Magnetic resonance imaging disclosed a right superolateral orbital lesion extending posteriorly close to the orbital apex, inseparable from the lacrimal gland, with a mass effect on superior and lateral rectus muscles. (C) Case 3: Magnetic resonance imaging revealed enhancing soft tissue in the right lateral extraconal space between a mildly thickened right lateral rectus muscle and sclerotic right lateral orbital wall. (D) Case 4: Computed tomography scan revealed diffuse enlargement of the extraocular muscles consistent with orbital pseudotumor.

Histopathology was available in two cases (cases 2 and 3) and revealed non-specific inflammation (Figure 3). In case 2, there was chronic non-granulomatous dacryoadenitis with fibrosis and mild eosinophilia. In case 3, there was chronic nongranulomatous dacryoadenitis with atrophy and fibrosis.

Histopathologic findings of orbital pseudotumor in children. (A) Case 2: Microscopic examination shows chronically inflamed, atrophic, scarred lacrimal gland tissue (hematoxylin–esosin stain, original magnification ×10). (B) Case 2: High magnification discloses an inflammatory infiltrate of lymphocytes, plasma cells, and rare eosinophils (hematoxylin–eosin stain, original magnification ×100). (C) Case 3: Microscopic examination shows chronic dacryoadenitis (hematoxylin–eosin stain, original magnification ×10). (D) Case 3: High magnification discloses acinar atrophy, fibrosis, and patchy chronic inflammation including a germinal center (hematoxylin–eosin stain, original magnification ×25).

Figure 3.

Histopathologic findings of orbital pseudotumor in children. (A) Case 2: Microscopic examination shows chronically inflamed, atrophic, scarred lacrimal gland tissue (hematoxylin–esosin stain, original magnification ×10). (B) Case 2: High magnification discloses an inflammatory infiltrate of lymphocytes, plasma cells, and rare eosinophils (hematoxylin–eosin stain, original magnification ×100). (C) Case 3: Microscopic examination shows chronic dacryoadenitis (hematoxylin–eosin stain, original magnification ×10). (D) Case 3: High magnification discloses acinar atrophy, fibrosis, and patchy chronic inflammation including a germinal center (hematoxylin–eosin stain, original magnification ×25).

The clinical course is detailed in Table 1. In the months following the diagnosis of orbital pseudotumor, all four patients developed systemic inflammatory disease, including pauciarticular juvenile idiopathic arthritis (case 1), eosinophilic granulomatosis with polyangiitis (also known as Churg-Strauss syndrome) (case 2), granulomatosis with polyangiitis (formerly known as Wegener's granulomatosis) (case 3), and Crohn's disease (case 4). The medical treatment for each case is listed in Table 2.

Management and Clinical Course

Table 2:

Management and Clinical Course

Discussion

Orbital pseudotumor has been observed in association with systemic inflammatory diseases, such as Crohn's disease, systemic lupus erythematosus, inflammatory arthritis, and granulomatous vasculitis.1 The four cases in this study are unique because each patient initially presented with idiopathic orbital pseudotumor, at which time there were no signs of systemic disease. The clinical features of systemic inflammatory disease appeared months to years after the original diagnosis of idiopathic orbital pseudotumor.

Orbital pseudotumor is a common cause of unilateral proptosis in adults and accounts for approximately 10% of orbital mass lesions,2 but is rarely seen in children.3 In an analysis of 30 children with orbital pseudotumor, the main findings included periorbital edema (67%), blepharoptosis (57%), periorbital pain (40%), decreased extraocular movements (37%), proptosis (23%), and conjunctival injection (20%).4 This disease is a diagnosis of exclusion because many neoplastic, infectious, or systemic conditions mimic its symptoms. These include orbital cellulitis, thyroid ophthalmopathy, sarcoidosis, lymphoproliferative disorders, and metastatic carcinoma.5 Orbital pseudotumor is distinguished by its rapid response to high-dose corticosteroids, but inflammatory symptoms may return once steroid therapy is terminated.

Case 1 was a 2-year-old girl with pauciarticular juvenile idiopathic arthritis with associated anterior uveitis. Mahdaviani et al.6 described a patient with juvenile idiopathic arthritis and simultaneous orbital pseudotumor, but our case demonstrated orbital pseudotumor as an antecedent to juvenile idiopathic arthritis. Case 2 was an 11-year-old girl with eosinophilic granulomatosis with polyangiitis, also known as Churg-Strauss syndrome. Takanashi et al.7 reviewed 17 reported cases of Churg-Strauss syndrome with ocular manifestations, but a search of the literature suggests that our patient is the first case of orbital pseudotumor preceding eosinophilic granulomatosis with polyangiitis. Case 3 was a 12-year-old girl with granulomatosis with polyangiitis. Approximately 40% of patients with granulomatosis with polyangiitis demonstrate inflammatory eye involvement.8 Several studies have found orbital pseudotumor to be the initial presentation of childhood granulomatosis with polyangiitis.9 Case 4 was a 14-year-old boy with Crohn's disease. Orbital pseudotumor is a rare extraintestinal manifestation of inflammatory bowel disease.10

Orbital pseudotumor may be an antecedent to systemic inflammatory disease in children. We do not know the incidence of orbital pseudotumor in the general population, or specifically in the pediatric population. We believe that early diagnosis of systemic inflammatory disease in our four cases may have been possible if systemic screening had been performed at the initial presentation of orbital pseudotumor. With systemic diseases such as juvenile idiopathic arthritis, early diagnosis can potentially save a patient from significant ocular complications, as well as rheumatologic discomfort. Because this is a small case series, we are not ready to suggest that a full systemic work-up for systemic inflammatory disease is warranted for every patient with orbital pseudotumor. However, close observation and suspicion for systemic inflammatory conditions may be reasonable in children who present with idiopathic orbital pseudotumor.

References

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Clinical Features at Initial Examination

CaseAge at Initial Presentation (years)Age at Diagnosis of Orbital Pseudotumor (years)Race/SexEye(s)Visual AcuityGland/Muscle Involvement
122W/FOD20/20 OULacrimal gland and lateral and superior rectus muscles
21011H/FOD20/25 OULacrimal gland
3712W/FOD20/20 OULacrimal gland and lateral rectus muscle
41415W/MOU20/20 OULacrimal gland and all rectus muscles

Management and Clinical Course

CaseTreatment for Orbital PseudotumorRecurrenceTime to Presentation of Systemic Inflammatory Disease (months)Systemic Inflammatory DiseaseTreatment for Systemic Inflammatory DiseaseFollow-up (years)
1Oral prednisoneN12Juvenile idiopathic arthritisNaproxen and methotrexate4
2Oral prednisone and excisional biopsyY9Churg-Strauss syndromeCyclophosphamide and prednisone3
3Oral prednisone and subtotal excisional biopsyN4Granulomatosis with polyangiitisMethotrexate and sulfamethoxazole/trimethoprim5
4Oral prednisoneY10Crohn's disease6-mercaptopurine and mesalamine2
Authors

From Pediatric Ophthalmology and Ocular Genetics (MT, BNW), Ocular Oncology Service (SEL, CLS), and Ocular Pathology (RCE), Wills Eye Hospital, Philadelphia, Pennsylvania; and Northern Virginia Ophthalmology Associates, Falls Church, Virginia (FJE).

The authors have no financial or proprietary interest in the materials presented herein.

Correspondence: Barry N. Wasserman, MD, Wills Eye Hospital, 840 Walnut Street, Suite 1210, Philadelphia, PA 19107. E-mail: bnwass27@aol.com

Received: November 13, 2018
Accepted: August 30, 2019

10.3928/01913913-20190923-02

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