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Clinicopathologic Reports, Case Reports, and Small Case Series
October 2004

Juvenile Xanthogranuloma With Presumed Involvement of the Optic Discand Retina

Arch Ophthalmol. 2004;122(10):1551-1555. doi:10.1001/archopht.122.10.1551

Juvenile xanthogranuloma (JXG) is a rare idiopathic granulomatous disorderof early childhood. Ocular involvement of the anterior segment, notably theiris, is well recognized. Involvement of the optic nerve disc is exceptionallyrare and is associated with loss of vision. We are aware of only 2 previouslypublished reports of optic disc involvement, one proven on histologic examination1 and the other presumed.2 Wedescribe herein a third child who was initially identified by screening andin whom it was possible to detect early optic disc involvement. As far aswe know, we describe for the first time the prospective clinical managementof this vision-threatening condition during more than 2 years of follow-up.This case illustrates the natural history of this condition and demonstratesthat vision can be partly preserved with early detection and treatment.

Report of a Case

A previously healthy 11-month-old white girl was referred to the pediatricdermatology department with a 5-month history of a progressive yellowish papularrash on her face and eyelids (Figure 1 and Figure 2). A skin biopsy at age 12 monthsconfirmed classic JXG composed of plump histiocytic cells intermingled withspindle cells and numerous multinucleate Touton giant cells, the histopathologichallmark of JXG (Figure 3). Immunostainingfor factor XIIIa was positive, while CD1a staining was negative and S100 stainingshowed occasional positive staining of dendritic cells. A diagnosis of JXGwas made. It was decided to observe the skin lesions because of no systemicinvolvement and because cutaneous JXG frequently resolves spontaneously. Becauseof "blank spells," a referral was made at age 13 months to a pediatric neurologistwho did not find any neurological abnormality. Results of a brain magneticresonance imaging scan with gadolinium and an electroencephalogram were alsofound to be normal.

Figure 1.
Facial distribution of the yellowishpapular rash involving the eyelids at 11 months of age.

Facial distribution of the yellowishpapular rash involving the eyelids at 11 months of age.

Figure 2.
Close-up view of a juvenile xanthogranulomapapule.

Close-up view of a juvenile xanthogranulomapapule.

Figure 3.
Typical Touton-type giant cellsshowing the classic multinucleate cell with nuclei in a circumferential arrangementsurrounded by small fat droplets are seen on an eyelid skin biopsy specimen(hematoxylin-eosin, original magnification approximately ×160).

Typical Touton-type giant cellsshowing the classic multinucleate cell with nuclei in a circumferential arrangementsurrounded by small fat droplets are seen on an eyelid skin biopsy specimen(hematoxylin-eosin, original magnification approximately ×160).

Initial routine screening in the pediatric ophthalmology clinic at age17 months revealed hypermetropia (4.50–diopter spheres [DS] OU) butotherwise healthy-looking eyes with a visual acuity of 20/32 OU, no squint,and unremarkable optic nerve discs. Between 17 and 24 months of age, she developedanisohypermetropia (4.00 DS OD and 7.50 DS OS) and intermittent exotropiain her left eye. Her left optic disc margin was noted to be slightly blurredat 21 months of age. However, pattern reversal visual evoked potentials showedno significant interocular difference. Patching was initiated and glassesprescribed. On review at age 27 months, an infiltrating mass of the left opticnerve papilla was seen, which extended to the macula (Figure 4). Within 6 days, her visual acuity deteriorated from 20/60to 20/400 OS.

Figure 4.
Evolution of the yellowish-whitelesion extending from the left optic disc to the macula at age 27 months (A),39 months (B), and 47 months (C).

Evolution of the yellowish-whitelesion extending from the left optic disc to the macula at age 27 months (A),39 months (B), and 47 months (C).

She had had chickenpox at age 19 months but was otherwise healthy. Noother ocular abnormalities, including the anterior segment, were seen. Herphysical examination findings were unremarkable, and she has remained otherwisehealthy throughout her follow-up. No axillary freckling or café-au-laitspots were found. A chest radiograph showed no abnormality.

Pretreatment laboratory values (followed by reference ranges) includedthe following: white blood cells, 9.9 × 103/µL (5.0-15.0× 103/µL); lymphocytes, 6.5 × 103/µL(2.0-9.5 × 103/µL); monocytes, 0.7 × 103/µL (0.3-1.5 × 103/µL); eosinophils, 0.2× 103/µL (0.3-0.8 × 103/µL);basophils, 0.1 × 103/µL (0-0.2 × 103/µL);red blood cells, 5.0 × 106/µL (3.7-5.3 × 106/µL); hemoglobin, 13.2 g/dL (10.5-13.5 g/dL); platelets, 701× 103/µL (150-450 × 103/µL);erythrocyte sedimentation rate, 5 mm/h (0-10 mm/h); C-reactive protein, 0.9mg/dL (0-2.0 mg/dL); glucose, 92 mg/dL (5.1 mmol/L) (63-99 mg/dL [3.5-5.5mmol/L]); sodium, 142 mEq/L (135-145 mEq/L); potassium, 4.4 mEq/L (3.5-5.5mEq/L); serum urea nitrogen, 12 mg/dL (4.4 mmol/L) (9-19 mg/dL [3.3-6.6 mmol/L]);creatinine, 0.4 mg/dL (32 µmol/L) (0-0.6 mg/dL [0-56 µmol/L]);calcium, 10.4 mg/dL (2.60 mmol/L) (9.1-10.6 mg/dL [2.28-2.64 mmol/L]); magnesium,2.1 mg/dL (0.88 mmol/L) (1.8-2.4 mg/dL [0.74-1.00 mmol/L]); phosphate, 5.9mg/dL (1.89 mmol/L) (4.0-5.5 mg/dL [1.29-1.78 mmol/L]); albumin, 4.5 g/dL(3.5-5.5 g/dL); total bilirubin, 0.5 mg/dL (9 µmol/L) (0-1.1 mg/dL [0-18µmol/L]); alkaline phosphatase, 210 U/L (110-350 U/L); and alanine transaminase,19 U/L (5-45 U/L). Further serologic test results were positive for IgG antibodiesagainst varicella zoster virus and measles virus and were negative for cytomegalovirusantibody, Epstein-Barr virus IgG, and herpes simplex viruses 1 and 2 IgG.The angiotensin-converting enzyme level was 11 U/L (20-90 U/L), and the Toxocara antibody test result was negative at age 2 years8 months.

B-mode ultrasound of her left globe revealed a raised solid lesion overlyingthe optic disc and adjacent macula. Magnetic resonance imaging demonstratedan optic disc lesion without further optic nerve, orbital, or intracranialextension. Electrophysiologic findings are shown in Figure 5.

Figure 5.
Serial pattern reversal visualevoked potentials (VEPs) demonstrate the episodes of deterioration and recoveryof the VEP in the left eye (A). Part B (inset) are flash electroretinograms(ERGs) show the 6-ms relative delay in B-wave latency in the left eye, indicatinginvolvement of the left inner retina as well. The increased latency of theB-wave in the left eye was especially conspicuous under cone-mediated conditions.C (inset), Pattern ERGs to 100' reversing checks. The abnormal left patternERGs are consistent with macular pathway dysfunction of the left eye.

Serial pattern reversal visualevoked potentials (VEPs) demonstrate the episodes of deterioration and recoveryof the VEP in the left eye (A). Part B (inset) are flash electroretinograms(ERGs) show the 6-ms relative delay in B-wave latency in the left eye, indicatinginvolvement of the left inner retina as well. The increased latency of theB-wave in the left eye was especially conspicuous under cone-mediated conditions.C (inset), Pattern ERGs to 100' reversing checks. The abnormal left patternERGs are consistent with macular pathway dysfunction of the left eye.

She received 2 once-daily pulses of intravenous methylprednisolone succinate(500 mg/d, or 30 mg/kg of body weight at each pulse) followed by oral prednisolonesodium phosphate at a dosage of up to 3 mg/kg per day. Corticosteroid treatmentwas well tolerated, and her visual acuity rapidly recovered from 20/400 OSto 20/80 OS. Her corticosteroid dosage was therefore slowly tapered for 3months. Within 2 weeks of stopping the corticosteroid treatment, however,her left vision deteriorated again owing to vitritis and progression of theoptic disc lesion. Oral prednisolone treatment was restarted at 3 mg/kg. Shedid well for the subsequent 16 months on a slow corticosteroid taper. Withpatching and glasses, vision in the left eye improved to as much as 20/50.

Twenty months into her treatment, she developed a large peripapillarytractional retinal detachment with vitreous hemorrhage. No clinical evidenceof rebound inflammation was seen. Despite vitrectomy and membrane delamination,the macula remained severely puckered because of persistent or recurrent traction.Intraoperative biopsy of the vitreous and posterior hyaloid confirmed an inflammatorymembrane but showed no evidence of active xanthogranuloma. Her vision 3½months following her surgery was 20/200 OS and 20/20 OD while receiving 1.5mg/d of maintenance prednisolone. The relationship between visual acuity,corticosteroid treatment, and patching is shown in Figure 6.

Figure 6.
Relationship between visual acuity,corticosteroid dosage (in milligrams per day), and amblyopia treatment overtime (in months). Reported compliance with patching was graded as full (asinstructed), partial, or none. Refraction was regularly checked and glassesadjusted as required throughout follow-up.

Relationship between visual acuity,corticosteroid dosage (in milligrams per day), and amblyopia treatment overtime (in months). Reported compliance with patching was graded as full (asinstructed), partial, or none. Refraction was regularly checked and glassesadjusted as required throughout follow-up.

Comment

Involvement of the optic disc is a rare complication of JXG. In the2 cases reported previously,1,2 theaffected eyes were already blind at initial examination. It is therefore notknown how best to treat optic disc and macular involvement. To our knowledge,we herein report for the first time the prospective long-term response toearly treatment and the electrophysiologic findings in such a case.

Loss of vision may be due to different mechanisms. Serial pattern reversalvisual evoked potentials demonstrated attenuation and increased latency inthe left eye of our patient. Attenuation was also found in the left patternelectroretinogram, indicating left macular pathway dysfunction. Moreover,the left flash electroretinogram showed a persistent relative delay in B-wavelatency to all intensities compared with the right eye, indicating additionalinvolvement of the inner retina, probably due to early retinal vascular compromiseor the direct effect of infiltration. We observed tractional retinal detachmentof the macula due to fibrosis as a late complication and as a further mechanismof visual loss in posterior segment disease. We emphasize that, apart fromthe direct pathologic effects of JXG disease and its treatment, special considerationshould be given to the recognition of amblyopia and its management to maximizethe remaining visual potential in the affected eye.

We believe that corticosteroid treatment was effective in treating theoptic disc and macular lesion during the inflammatory phase, as shown by themarked initial improvement of inflammatory activity and vision while receivingsystemic corticosteroids, the clinical deterioration on stopping treatment,and the clinical improvement on starting corticosteroid regimens again. Oncethe inflammation was controlled, vision improved further with treatment foramblyopia (Figure 6). Glasses were prescribed and updated throughout follow-up.Visual acuities were usually obtained by the same senior orthoptist (C.T.)who also supervised the occlusion therapy. The final visual deteriorationat age 3 years 11 months followed 20 months of systemic corticosteroid treatmentand was caused by tractional retinal detachment thought to be due to fibrosisrather than rebound inflammatory activity.

Should children with cutaneous JXG routinely be screened by ophthalmologists?Ocular involvement subsequent to initial cutaneous presentation is potentiallyvision threatening but uncommon. Chang et al3 reporteda survey incidence of ocular complications in children with cutaneous JXGof 0.3% and a literature incidence of 0.4%. Children with newly diagnosedJXG, multiple skin lesions, and onset at 2 years or younger were found tobe at greatest risk and should therefore be targeted for surveillance.3 Chang4 suggestedannual or semiannual ophthalmic screening in these high-risk groups. As aminimum, all parents should be instructed to seek immediate specialist ophthalmologicaladvice in case of any new eye pain, redness, squint, or visual complaint ina child with recognized cutaneous JXG. If intraocular involvement is found,we recommend close follow-up and early intervention, as clinical deteriorationmay be precipitous and difficult to control.

Correspondence: Dr Taylor, Department of Paediatric Ophthalmology,Great Ormond Street Hospital for Children, London WC1N 3JH, England (DSIT@btinternet.com).

This study was presented at the 26th European Paediatric OphthalmologyGroup Meeting, September 9, 2000; Cambridge, England.

We thank Nick Geddes for taking the fundal photographs.

The authors have no relevant financial interest in this article.

References
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Chang  MWFrieden  IJGood  W The risk of intraocular juvenile xanthogranuloma: survey of currentpractices and assessment of risk. J Am Acad Dermatol. 1996;34445- 449
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