eMedicine Specialties > Ophthalmology > Iris & Ciliary Body

Juvenile Xanthogranuloma

Author: Theodore Curtis, MD, Assistant Professor, Department of Ophthalmology, University of Colorado; Consulting Staff, Rocky Mountain Lions Eye Institute
Coauthor(s): David T Wheeler, MD, Associate Professor, Departments of Ophthalmology and Pediatrics, Oregon Health & Science University
Contributor Information and Disclosures

Updated: Jan 26, 2010

Introduction

Background

Juvenile xanthogranuloma (JXG) primarily is a self-limited dermatologic disorder that is associated rarely with systemic manifestations. Infants and small children are mainly affected.

JXG consists of lesions that may be single or multiple and appear as firm, slightly raised papulonodules several millimeters in diameter. They are tan-orange in color and occur frequently on the head and neck, but many extracutaneous sites have been reported.

The eye, particularly the uveal tract, is the most frequent site of extracutaneous involvement. Approximately one half of patients with ocular involvement have skin lesions. JXG is the most frequent cause of spontaneous hyphema in children and can result in secondary glaucoma and eventual blindness.

Pathophysiology

The etiology of JXG is unknown. JXG is believed to result from a disordered macrophage response to a nonspecific tissue injury, resulting in a granulomatous reaction. JXG is on a spectrum of histiocytic disorders that includes benign cephalic histiocytosis, generalized eruptive histiocytosis, adult xanthogranuloma, and progressive nodular histiocytosis. These diseases are less common than the related Langerhans cell histiocytoses.

Frequency

United States

The frequency is unknown, but it may be higher than reported, since lesions occur early in life, may be misdiagnosed, and spontaneously regress. In those affected, 92% of ocular involvement occurs before age 2 years.¹

Mortality/Morbidity

Cutaneous lesions generally are self-limited and rarely require treatment. The risk of morbidity is high with ocular involvement and can include hyphema, glaucoma, corneal blood staining, cataract, vascular occlusion, and retinal detachment, all of which can lead to amblyopia in childhood. Rarely, death has been reported among children with visceral JXG.

Race

No reported predilection of race exists in JXG, although few African American patients have been described.

Sex

Cutaneous JXG is reported 1.5 times more in male children, but no sex predilection exists in adults. Both sexes are equally at risk for ocular involvement.

Age

JXG may be present at birth (in about 10%) but most often arises in infancy. Children younger than 6 months are more likely to have multiple lesions.¹ Zimmerman reported 64% of cutaneous lesions to be present by age 7 months and 85% before 1 year. Adult onset is reported infrequently.

Clinical

History

• Most patients with juvenile xanthogranuloma (JXG) are asymptomatic.
• Ocular lesions usually are discovered incidentally or following spontaneous hyphema. They may be noted by observant parents or primary care physicians.
• Screening for ocular involvement generally is not performed because of its low incidence. The eye probably is affected in only about 0.5% of patients with cutaneous JXG,² although some early studies found an incidence as high as 10%.^3,4
• Those at greatest risk are children younger than 2 years with multiple skin lesions.¹
• The most common ocular presentation involves the iris. Iris tumors may be diffuse or localized and lead to heterochromia, uveitis, spontaneous hyphema, and secondary glaucoma.
• Other ocular tissues are involved much less frequently, and orbital tumors are rare.
• Nearly all cases are unilateral, and spontaneous regression of lesions is uncommon.
• An association with neurofibromatosis type 1 (NF-1) and juvenile chronic myelogenous leukemia (JCML) has been reported. A recent retrospective review by Cambiaghi of 77 patients younger than 3 years with NF-1 yielded 17 (22%) with JXG, but none developed JCML or other hematologic abnormalities.⁵

Physical

• Skin lesions are well demarcated, rubbery, tan-orange papulonodules ranging from 1-20 mm in size. They may be single or multiple and usually occur on the head and neck, but they may appear at any site on the body surface.
• Extracutaneous involvement occurs in 4% of children and in 5-10% overall. Extracutaneous involvement has been reported in every organ system in the body, including central nervous system, eye, salivary glands, larynx, lung, pericardium, myocardium, liver, spleen, colon, retroperitoneum, kidney, adrenal gland, gonads, bone, periosteum, muscle, and mucous membranes.
• Ocular lesions usually involve the iris, but they may occasionally be seen in the eyelids, conjunctiva, cornea, limbal tissue, sclera, retina, choroid, optic nerve, and orbit. Cases are usually unilateral, but bilateral cases have been reported.
• Iris lesions most often resemble isolated cutaneous lesions in color and appearance. They may be single or multiple and localized or diffuse. Tumors have been described to increase in thickness and lighten in color with maturation.
• Iris JXG also may present as diffuse conjunctival injection with uveitis, congenital or acquired heterochromia iridis, spontaneous hyphema, or secondary glaucoma. Involvement of other uveal tissue is very uncommon.
• The second most commonly affected ocular site is the eyelid. Lesions appear as typical cutaneous tumors. Subcutaneous forms are rare, but they can mimic a recurrent/nonresolving chalazion. They can cause deprivational amblyopia or refractive amblyopia if they induce significant astigmatism.
• Intraocular lesions rarely have been reported in the posterior pole.
• Orbital lesions are extremely uncommon. They usually appear as infiltrative soft tissue tumors and often cause proptosis of the globe. At least one case has been described as a locally aggressive lesion causing bony destruction with intracranial extension.

Causes

• The etiology of JXG is unknown, but a genetic basis has been suggested given the multiple sites of occurrence. However, familial cases have not been observed.
• The transformation of benign cephalic histiocytosis (a related disorder) into JXG has been reported infrequently. A recent report postulated this progression could be virally mediated.

• Search for CME/CE on This Topic »

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