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.

More on Juvenile Xanthogranuloma

Overview: Juvenile Xanthogranuloma
Differential Diagnoses & Workup: Juvenile Xanthogranuloma
Treatment & Medication: Juvenile Xanthogranuloma
Follow-up: Juvenile Xanthogranuloma
References

References

  1. Cypel TK, Zuker RM. Juvenile xanthogranuloma: Case report and review of the literature. Can J Plast Surg. Fall 2008;16(3):175-7. [Medline][Full Text].

  2. Liang S, Liu YH, Fang K. Juvenile xanthogranuloma with ocular involvement. Pediatr Dermatol. Mar-Apr 2009;26(2):232-4. [Medline].

  3. Karcioglu ZA, Mullaney PB. Diagnosis and management of iris juvenile xanthogranuloma. J Pediatr Ophthalmol Strabismus. Jan-Feb 1997;34(1):44-51. [Medline].

  4. Vendal Z, Walton D, Chen T. Glaucoma in juvenile xanthogranuloma. Semin Ophthalmol. Jul-Sep 2006;21(3):191-4. [Medline].

  5. Cambiaghi S, Restano L, Caputo R. Juvenile xanthogranuloma associated wiht neurofibromatosis 1: patients without evidence of hematologic malignancies. Pediatr Dermatol. 2004;21(2):97-101. [Medline].

  6. Cadera W, Silver MM, Burt L. Juvenile xanthogranuloma. Can J Ophthalmol. Jun 1983;18(4):169-74. [Medline].

  7. Chang MW. Update on juvenile xanthogranuloma: unusual cutaneous and systemic variants. Semin Cutan Med Surg. Sep 1999;18(3):195-205. [Medline].

  8. DeBarge LR, Chan CC, Greenberg SC, et al. Chorioretinal, iris, and ciliary body infiltration by juvenile xanthogranuloma masquerading as uveitis. Surv Ophthalmol. Jul-Aug 1994;39(1):65-71. [Medline].

  9. Harley RD, Romayananda N, Chan GH. Juvenile xanthogranuloma. J Pediatr Ophthalmol Strabismus. Jan-Feb 1982;19(1):33-9. [Medline].

  10. Hernandez-Martin A, Baselga E, Drolet BA, Esterly NB. Juvenile xanthogranuloma. J Am Acad Dermatol. Mar 1997;36(3 Pt 1):355-67; quiz 368-9. [Medline].

  11. Kaur H, Cameron JD, Mohney BG. Severe astigmatic amblyopia secondary to subcutaneous juvenile xanthogranuloma of the eyelid. J AAPOS. Jun 2006;10(3):277-8. [Medline].

  12. Miszkiel KA, Sohaib SA, Rose GE, et al. Radiological and clinicopathological features of orbital xanthogranuloma. Br J Ophthalmol. Mar 2000;84(3):251-8. [Medline].

  13. Shields JA, Shields CL. Clinical spectrum of histiocytic tumors of the orbit. Trans Pa Acad Ophthalmol Otolaryngol. 1990;42:931-7. [Medline].

  14. Tanz WS, Schwartz RA, Janniger CK. Juvenile xanthogranuloma. Cutis. Oct 1994;54(4):241-5. [Medline].

  15. Weitzman S, Jaffe R. Uncommon histiocytic disorders: The non-Langerhans cell histiocytoses. Pediatr Blood Cancer. 2005;44:1-9. [Medline].

  16. Zvulunov A, Barak Y, Metzker A. Juvenile xanthogranuloma, neurofibromatosis, and juvenile chronic myelogenous leukemia. World statistical analysis. Arch Dermatol. Aug 1995;131(8):904-8. [Medline].

Further Reading

Keywords

juvenile xanthogranuloma, JXG, Langerhans cell histiocytosis, uvea, hyphema, glaucoma, amblyopia, vision loss, blindness

Contributor Information and Disclosures

Author

Theodore Curtis, MD, Assistant Professor, Department of Ophthalmology, University of Colorado; Consulting Staff, Rocky Mountain Lions Eye Institute
Theodore Curtis, MD is a member of the following medical societies: American Academy of Ophthalmology and American Association for Pediatric Ophthalmology and Strabismus
Disclosure: Nothing to disclose.

Coauthor(s)

David T Wheeler, MD, Associate Professor, Departments of Ophthalmology and Pediatrics, Oregon Health & Science University
David T Wheeler, MD is a member of the following medical societies: American Academy of Ophthalmology, American Association for Pediatric Ophthalmology and Strabismus, and Phi Beta Kappa
Disclosure: Nothing to disclose.

Medical Editor

Gerhard W Cibis, MD, Clinical Professor, Director of Pediatric Ophthalmology Service, Department of Ophthalmology, University of Kansas, Kansas City
Gerhard W Cibis, MD is a member of the following medical societies: American Academy of Ophthalmology, American Association for Pediatric Ophthalmology and Strabismus, and American Ophthalmological Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Simon K Law, MD, PharmD, Assistant Professor of Ophthalmology, Jules Stein Eye Institute; Chief of Section of Ophthalmology Surgical Services, Department of Veterans Affairs Healthcare Center, West Los Angeles
Simon K Law, MD, PharmD is a member of the following medical societies: American Academy of Ophthalmology, American Glaucoma Society, and Association for Research in Vision and Ophthalmology
Disclosure: Nothing to disclose.

Managing Editor

J James Rowsey, MD, Former Director of Corneal Services, St Luke's Cataract and Laser Institute, Florida
J James Rowsey, MD is a member of the following medical societies: American Academy of Ophthalmology, American Association for the Advancement of Science, American Medical Association, Association for Research in Vision and Ophthalmology, Florida Medical Association, Pan-American Association of Ophthalmology, Sigma Xi, and Southern Medical Association
Disclosure: Nothing to disclose.

CME Editor

Lance L Brown, OD, MD, Ophthalmologist, Affiliated With Freeman Hospital and St John's Hospital, Regional Eye Center, Joplin, Missouri
Disclosure: Nothing to disclose.

Chief Editor

Hampton Roy Sr, MD, Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences
Hampton Roy Sr, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, and Pan-American Association of Ophthalmology
Disclosure: Nothing to disclose.

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