Clinical Review & Education
JAMA Pediatrics Clinical Challenge
Adolescent With Right Orbital Swelling and Proptosis Tiffany S. Chang, BA; Savitha M. Sunkara, MD; Anthony S. Cooley, MD
B
A
C
Figure. Adolescent boy with eyelid swelling, redness, and pain. A, Swelling of the right orbital (white arrowhead) and periorbital (black arrowhead) tissues and proptosis, with mild swelling of the left upper eyelid (blue arrowhead). B, Maxillofacial computed tomography with intravenous contrast showed severe right proptosis with stretching of the right optic nerve (white arrowhead) and thickening of the rectus muscles and soft tissues (black arrowhead). Mild
enlargement of the lacrimal gland on the left side can also be seen (blue arrowhead). C, Maxillofacial magnetic resonance imaging with intravenous contrast. Coronal (left) and axial (right) views showed inflammation involving the intraconal fat and perineural soft tissues (white arrowhead), as well as the inferior and lateral extraocular muscles, on the right side. The black arrowheads indicate the muscles in the coronal and axial views.
An adolescent boy presented to our hospital with a 5-day history of right eyelid swelling and redness accompanied by blurred vision and pain with ocular movement. This was his third hospitalization for these symptoms; the previous admissions were 2 and 4 months earlier, with no symptoms in the intervals. During the prior admissions, treatment included antibiotics for orbital cellulitis and corticosteroids for suspected antibiotic allergies. Physical examination was notable for right upper and lower eyelid edema and erythema, conjunctival hyperemia, chemosis, and proptosis (Figure, A). The left eye appeared normal at admission. However, within 24 hours after admission, our patient developed left chemosis with eyelid edema and erythema. His vision and pupillary responses were normal. Fundus exQuiz at jamapediatrics.com amination revealed mild blurring of the disc margins only on the right side. Slitlamp examination identified numerous cells in the right anterior chamber. Extraocular movements were limited in all directions in both eyes, with a larger deficit in the right eye. Computed tomography (Figure, B) and magnetic resonance imaging (MRI) (Figure, C) of the orbit were performed. The results of these examinations, in conjunction with the patient’s history, prompted biopsy.
jamapediatrics.com
WHAT IS YOUR DIAGNOSIS?
A. Orbital cellulitis B. Rhabdomyosarcoma of the extraocular muscles C. Idiopathic orbital inflammatory syndrome D. Thyroid ophthalmopathy
JAMA Pediatrics July 2014 Volume 168, Number 7
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://archpedi.jamanetwork.com/ by a Rutgers University Libraries User on 06/01/2015
677
Clinical Review & Education JAMA Pediatrics Clinical Challenge
Diagnosis C. Idiopathic orbital inflammatory syndrome
Discussion Computed tomography showed stretching of the optic nerve and inflammation of the extraocular muscles and lacrimal gland and MRI, inflammation of the intraconal tissues and rectus muscles. The results of a biopsy of the right lacrimal gland confirmed chronic inflammatory changes. Evaluation for an infectious cause was unrevealing, with negative rapid plasma reagin, treponemal antibody, Bartonella henselae IgG and IgM, and Lyme borreliosis IgG. Results of a complete blood cell count were unremarkable, including a leukocyte count that was within the reference range. Rheumatologic workup showed levels within the reference ranges for antinuclear antibody, rheumatoid factor, angiotensin-converting enzyme, and HLA-antigen B27. The erythrocyte sedimentation rate and Creactive protein level were mildly elevated. Peripheral flow cytometry performed using the biopsy sample was negative. With an angiotensin-converting enzyme level within the reference range and no abnormal pulmonary findings or rash, rheumatologists excluded sarcoidosis. With the exclusion of infection, malignant disease, and rheumatologic disease, bilateral idiopathic orbital inflammatory syndrome (IOIS) was diagnosed. After a 4-day course of corticosteroids, the patient’s condition improved, and the therapy was transitioned to a 1-month tapering regimen at discharge. To provide better control for refractory disease, corticosteroid-sparing therapy was initiated with methotrexate sodium, 15 mg per week. Our patient remained symptom free at follow-up 4 months after discharge. Idiopathic orbital inflammatory syndrome, also known as orbital pseudotumor, was first described by Birch-Hirschfield in 1905.1 Although characterized by inflammation of the tissues surrounding the orbit, IOIS is neither infectious nor neoplastic.2 Idiopathic orbital inflammatory syndrome usually occurs in adults, but up to 17% of the cases have been reported in children.2,3 Typically, the extraocular muscles, lacrimal glands, and orbital fat are affected.4 When inflammation is localized to one structure, it is termed myositis or dacryoadenitis, accordingly.5 Idiopathic orbital inflammatory syndrome can present as a palpable mass (ie, pseudotumor). DifferenARTICLE INFORMATION Author Affiliations: Student, School of Medicine, Emory University, Atlanta, Georgia (Chang); Department of Family and Preventive Medicine, Emory University, Atlanta, Georgia (Sunkara); Division of General Pediatric Hospitalists, Department of Pediatrics, School of Medicine, Emory University, and Children’s Healthcare of Atlanta, Atlanta, Georgia (Cooley). Corresponding Author: Anthony S. Cooley, MD, Division of General Pediatric Hospitalists, Department of Pediatrics, School of Medicine, Emory University, 1405 Clifton Rd, Atlanta, GA 30322. Section Editor: Samir S. Shah, MD, MSCE Conflict of Interest Disclosures: None reported. REFERENCES 1. Stevens JL, Rychwalski PJ, Baker RS, Kielar RS. Pseudotumor of the orbit in early childhood. JAAPOS. 1998;2(2):120-123. 678
tial diagnoses include malignant diseases (eg, rhabdomyosarcoma, retinoblastoma, and lymphoma), infections (orbital cellulitis), and autoimmune conditions (eg, thyroid ophthalmopathy, juvenile idiopathic arthritis, and sarcoidosis).6,7 A 1978 case series2 identified clinical characteristics found in 29 childhood cases of IOIS, the most common being pain, swelling, ptosis, photophobia, and proptosis. Unlike adults, children were more likely to have bilateral disease, with bilateral cases reported in 45% of the children. Pediatric cases were more often associated with trauma. Children with bilateral disease were more likely to have corticosteroid-dependent refractory disease. Children frequently had systemic symptoms, such as headache, anorexia, fever, and malaise.2,5 The diagnosis of IOIS is one of exclusion. The complete blood cell count and inflammatory markers usually are within normal limits. However, mild elevation of the leukocyte count and erythrocyte sedimentation rate, as well as eosinophilia, may be seen.8 Computed tomography or MRI may identify enlargement of periorbital tissues, including muscles and tendons. Dacryoadenitis and myositis are common findings in IOIS. Any bone involvement argues against IOIS and suggests infection or malignant disease. Biopsy can be used to diagnose IOIS and exclude malignant disease.4 The biopsy specimen typically shows a mixture of inflammatory cells, especially lymphocytes. 3 The Mottow and Jakobiec 2 study reported increased residua of disease in patients with IOIS who underwent biopsy. Thus, biopsy is advised only for atypical presentation, poor response to corticosteroids, or suspected malignant disease.3 Corticosteroids are the cornerstone of therapy for IOIS.6 Many patients improve with short courses of corticosteroids and do not require long-term immunosuppression. In cases that recur or are resistant to corticosteroid treatment, immunomodulatory agents can be used for long-term management.9 In one case report,7 IOIS in a 14-year-old girl was treated successfully with a regimen of azathioprine sodium, cyclosporine, and low-dose prednisone. Another report10 described the use of methotrexate and infliximab to treat refractory IOIS in a 15-year-old boy. Although immunomodulatory agents may produce adverse effects, they can be therapeutic for refractory disease and avoid the complications associated with extended use of corticosteroids.
2. Mottow LS, Jakobiec FA. Idiopathic inflammatory orbital pseudotumor in childhood, I: clinical characteristics. Arch Ophthalmol. 1978;96 (8):1410-1417.
7. Guerriero S, Di Leo E, Piscitelli D, et al. Orbital pseudotumor in a child. Clin Exp Med. 2011;11(1):6163.
3. Belanger C, Zhang KS, Reddy AK, Yen MT, Yen KG. Inflammatory disorders of the orbit in childhood. Am J Ophthalmol. 2010;150(4):460-463.
8. Mottow-Lippa L, Jakobiec FA, Smith M. Idiopathic inflammatory orbital pseudotumor in childhood, II: results of diagnostic tests and biopsies. Ophthalmology. 1981;88(6):565-574.
4. Browne MA, O’Keefe M, Twomey E, Donoghue V, Ryan S. A case of relapsing flitting bilateral idiopathic orbital inflammation. Pediatr Radiol. 2009;39(12):1361-1364.
9. Carruth BP, Wladis EJ. Inflammatory modulators and biologic agents in the treatment of idiopathic orbital inflammation. Curr Opin Ophthalmol. 2012; 23(5):420-426.
5. Foley MR, Moshfeghi DM, Wilson MW, Haik BG, Pappo AS, Hill DA. Orbital inflammatory syndromes with systemic involvement may mimic metastatic disease. Ophthal Plast Reconstr Surg. 2003;19(4): 324-327.
10. Wilson MW, Shergy WJ, Haik BG. Infliximab in the treatment of recalcitrant idiopathic orbital inflammation. Ophthal Plast Reconstr Surg. 2004; 20(5):381-383.
6. Berger JW, Rubin PA, Jakobiec FA. Pediatric orbital pseudotumor. Int Ophthalmol Clin. 1996;36 (1):161-177.
JAMA Pediatrics July 2014 Volume 168, Number 7
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://archpedi.jamanetwork.com/ by a Rutgers University Libraries User on 06/01/2015
jamapediatrics.com
JAMA Pediatrics Clinical Challenge
Adolescent With Right Orbital Swelling and Proptosis Tiffany S. Chang, BA; Savitha M. Sunkara, MD; Anthony S. Cooley, MD
B
A
C
Figure. Adolescent boy with eyelid swelling, redness, and pain. A, Swelling of the right orbital (white arrowhead) and periorbital (black arrowhead) tissues and proptosis, with mild swelling of the left upper eyelid (blue arrowhead). B, Maxillofacial computed tomography with intravenous contrast showed severe right proptosis with stretching of the right optic nerve (white arrowhead) and thickening of the rectus muscles and soft tissues (black arrowhead). Mild
enlargement of the lacrimal gland on the left side can also be seen (blue arrowhead). C, Maxillofacial magnetic resonance imaging with intravenous contrast. Coronal (left) and axial (right) views showed inflammation involving the intraconal fat and perineural soft tissues (white arrowhead), as well as the inferior and lateral extraocular muscles, on the right side. The black arrowheads indicate the muscles in the coronal and axial views.
An adolescent boy presented to our hospital with a 5-day history of right eyelid swelling and redness accompanied by blurred vision and pain with ocular movement. This was his third hospitalization for these symptoms; the previous admissions were 2 and 4 months earlier, with no symptoms in the intervals. During the prior admissions, treatment included antibiotics for orbital cellulitis and corticosteroids for suspected antibiotic allergies. Physical examination was notable for right upper and lower eyelid edema and erythema, conjunctival hyperemia, chemosis, and proptosis (Figure, A). The left eye appeared normal at admission. However, within 24 hours after admission, our patient developed left chemosis with eyelid edema and erythema. His vision and pupillary responses were normal. Fundus exQuiz at jamapediatrics.com amination revealed mild blurring of the disc margins only on the right side. Slitlamp examination identified numerous cells in the right anterior chamber. Extraocular movements were limited in all directions in both eyes, with a larger deficit in the right eye. Computed tomography (Figure, B) and magnetic resonance imaging (MRI) (Figure, C) of the orbit were performed. The results of these examinations, in conjunction with the patient’s history, prompted biopsy.
jamapediatrics.com
WHAT IS YOUR DIAGNOSIS?
A. Orbital cellulitis B. Rhabdomyosarcoma of the extraocular muscles C. Idiopathic orbital inflammatory syndrome D. Thyroid ophthalmopathy
JAMA Pediatrics July 2014 Volume 168, Number 7
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://archpedi.jamanetwork.com/ by a Rutgers University Libraries User on 06/01/2015
677
Clinical Review & Education JAMA Pediatrics Clinical Challenge
Diagnosis C. Idiopathic orbital inflammatory syndrome
Discussion Computed tomography showed stretching of the optic nerve and inflammation of the extraocular muscles and lacrimal gland and MRI, inflammation of the intraconal tissues and rectus muscles. The results of a biopsy of the right lacrimal gland confirmed chronic inflammatory changes. Evaluation for an infectious cause was unrevealing, with negative rapid plasma reagin, treponemal antibody, Bartonella henselae IgG and IgM, and Lyme borreliosis IgG. Results of a complete blood cell count were unremarkable, including a leukocyte count that was within the reference range. Rheumatologic workup showed levels within the reference ranges for antinuclear antibody, rheumatoid factor, angiotensin-converting enzyme, and HLA-antigen B27. The erythrocyte sedimentation rate and Creactive protein level were mildly elevated. Peripheral flow cytometry performed using the biopsy sample was negative. With an angiotensin-converting enzyme level within the reference range and no abnormal pulmonary findings or rash, rheumatologists excluded sarcoidosis. With the exclusion of infection, malignant disease, and rheumatologic disease, bilateral idiopathic orbital inflammatory syndrome (IOIS) was diagnosed. After a 4-day course of corticosteroids, the patient’s condition improved, and the therapy was transitioned to a 1-month tapering regimen at discharge. To provide better control for refractory disease, corticosteroid-sparing therapy was initiated with methotrexate sodium, 15 mg per week. Our patient remained symptom free at follow-up 4 months after discharge. Idiopathic orbital inflammatory syndrome, also known as orbital pseudotumor, was first described by Birch-Hirschfield in 1905.1 Although characterized by inflammation of the tissues surrounding the orbit, IOIS is neither infectious nor neoplastic.2 Idiopathic orbital inflammatory syndrome usually occurs in adults, but up to 17% of the cases have been reported in children.2,3 Typically, the extraocular muscles, lacrimal glands, and orbital fat are affected.4 When inflammation is localized to one structure, it is termed myositis or dacryoadenitis, accordingly.5 Idiopathic orbital inflammatory syndrome can present as a palpable mass (ie, pseudotumor). DifferenARTICLE INFORMATION Author Affiliations: Student, School of Medicine, Emory University, Atlanta, Georgia (Chang); Department of Family and Preventive Medicine, Emory University, Atlanta, Georgia (Sunkara); Division of General Pediatric Hospitalists, Department of Pediatrics, School of Medicine, Emory University, and Children’s Healthcare of Atlanta, Atlanta, Georgia (Cooley). Corresponding Author: Anthony S. Cooley, MD, Division of General Pediatric Hospitalists, Department of Pediatrics, School of Medicine, Emory University, 1405 Clifton Rd, Atlanta, GA 30322. Section Editor: Samir S. Shah, MD, MSCE Conflict of Interest Disclosures: None reported. REFERENCES 1. Stevens JL, Rychwalski PJ, Baker RS, Kielar RS. Pseudotumor of the orbit in early childhood. JAAPOS. 1998;2(2):120-123. 678
tial diagnoses include malignant diseases (eg, rhabdomyosarcoma, retinoblastoma, and lymphoma), infections (orbital cellulitis), and autoimmune conditions (eg, thyroid ophthalmopathy, juvenile idiopathic arthritis, and sarcoidosis).6,7 A 1978 case series2 identified clinical characteristics found in 29 childhood cases of IOIS, the most common being pain, swelling, ptosis, photophobia, and proptosis. Unlike adults, children were more likely to have bilateral disease, with bilateral cases reported in 45% of the children. Pediatric cases were more often associated with trauma. Children with bilateral disease were more likely to have corticosteroid-dependent refractory disease. Children frequently had systemic symptoms, such as headache, anorexia, fever, and malaise.2,5 The diagnosis of IOIS is one of exclusion. The complete blood cell count and inflammatory markers usually are within normal limits. However, mild elevation of the leukocyte count and erythrocyte sedimentation rate, as well as eosinophilia, may be seen.8 Computed tomography or MRI may identify enlargement of periorbital tissues, including muscles and tendons. Dacryoadenitis and myositis are common findings in IOIS. Any bone involvement argues against IOIS and suggests infection or malignant disease. Biopsy can be used to diagnose IOIS and exclude malignant disease.4 The biopsy specimen typically shows a mixture of inflammatory cells, especially lymphocytes. 3 The Mottow and Jakobiec 2 study reported increased residua of disease in patients with IOIS who underwent biopsy. Thus, biopsy is advised only for atypical presentation, poor response to corticosteroids, or suspected malignant disease.3 Corticosteroids are the cornerstone of therapy for IOIS.6 Many patients improve with short courses of corticosteroids and do not require long-term immunosuppression. In cases that recur or are resistant to corticosteroid treatment, immunomodulatory agents can be used for long-term management.9 In one case report,7 IOIS in a 14-year-old girl was treated successfully with a regimen of azathioprine sodium, cyclosporine, and low-dose prednisone. Another report10 described the use of methotrexate and infliximab to treat refractory IOIS in a 15-year-old boy. Although immunomodulatory agents may produce adverse effects, they can be therapeutic for refractory disease and avoid the complications associated with extended use of corticosteroids.
2. Mottow LS, Jakobiec FA. Idiopathic inflammatory orbital pseudotumor in childhood, I: clinical characteristics. Arch Ophthalmol. 1978;96 (8):1410-1417.
7. Guerriero S, Di Leo E, Piscitelli D, et al. Orbital pseudotumor in a child. Clin Exp Med. 2011;11(1):6163.
3. Belanger C, Zhang KS, Reddy AK, Yen MT, Yen KG. Inflammatory disorders of the orbit in childhood. Am J Ophthalmol. 2010;150(4):460-463.
8. Mottow-Lippa L, Jakobiec FA, Smith M. Idiopathic inflammatory orbital pseudotumor in childhood, II: results of diagnostic tests and biopsies. Ophthalmology. 1981;88(6):565-574.
4. Browne MA, O’Keefe M, Twomey E, Donoghue V, Ryan S. A case of relapsing flitting bilateral idiopathic orbital inflammation. Pediatr Radiol. 2009;39(12):1361-1364.
9. Carruth BP, Wladis EJ. Inflammatory modulators and biologic agents in the treatment of idiopathic orbital inflammation. Curr Opin Ophthalmol. 2012; 23(5):420-426.
5. Foley MR, Moshfeghi DM, Wilson MW, Haik BG, Pappo AS, Hill DA. Orbital inflammatory syndromes with systemic involvement may mimic metastatic disease. Ophthal Plast Reconstr Surg. 2003;19(4): 324-327.
10. Wilson MW, Shergy WJ, Haik BG. Infliximab in the treatment of recalcitrant idiopathic orbital inflammation. Ophthal Plast Reconstr Surg. 2004; 20(5):381-383.
6. Berger JW, Rubin PA, Jakobiec FA. Pediatric orbital pseudotumor. Int Ophthalmol Clin. 1996;36 (1):161-177.
JAMA Pediatrics July 2014 Volume 168, Number 7
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://archpedi.jamanetwork.com/ by a Rutgers University Libraries User on 06/01/2015
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