- Email: [email protected]
Choroidal Vitiligo Masquerading as Large Choroidal Nevus: A Report of Four Cases
Choroidal Vitiligo Masquerading as Large Choroidal Nevus: A Report of Four Cases Carol L. Shields, MD,1 Aparna Ramasubramanian, MD,1 W. Benjamin Kunz, MD,1 Ekta Aggarwal, MD,1 Jerry A. Shields, MD1 Purpose: To describe 4 patients with choroidal vitiligo masquerading as large choroidal nevus. Design: Retrospective chart review. Participants: Observational case series of 4 patients. Methods: Retrospective chart review. Main Outcome Measures: Clinical features. Results: Four patients referred with the diagnosis of large choroidal nevus were found to have unilateral (n ⫽ 1) or bilateral (n ⫽ 3) extensive patchy choroidal depigmentation classified as choroidal vitiligo. There was no evidence of choroidal nevus, and the pigmented “lesion” proved to be normal choroidal pigment surrounded by a region of pigment absence (vitiligo). There was no evidence of ocular inflammation or related retinal or retinal pigment epithelial changes. The choroidal vitiligo was clinically flat and measured 12 to 24 mm diameter, involving the post-equatorial fundus in all cases. There were no related anterior segment abnormalities. Cutaneous vitiligo was present in all cases. There was no documented progression of the choroidal or cutaneous vitiligo over a maximum 2-year follow-up. Conclusions: Choroidal vitiligo is an idiopathic benign process that can involve large segments of the posterior choroid, leaving only patches of residual choroidal pigment, simulating, in reverse, a large choroidal nevus. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Ophthalmology 2010;117:109 –113 © 2010 by the American Academy of Ophthalmology.
Vitiligo is an acquired disorder characterized by flat, cutaneous depigmented macules. Several hypotheses have been proposed for this condition, including autoimmunity, viral infection, chemical exposure, neurohumoral mechanism, or autocytotoxicity, but the exact pathogenesis remains obscure. According to a dermatopathology textbook, the “essential process in vitiligo is the destruction of melanocytes.”1 Antibodies to melanocytes have been found in the sera of patients with vitiligo but not in normal sera.2 Furthermore, patients with vitiligo can show antibodies to adrenal and thyroid cells, thyroglobulin, gastric parietal cells, and pancreatic islet cells.1 Early lesions show few melanocytes and melanin granules in the basal epithelial layer.3 Long-standing lesions demonstrate no melanocytes. The occasional presence of a lymphocytic infiltrate, often in contact with cutaneous melanocytes or Langerhans cells, suggests an immunologic cause.1 Most patients with cutaneous vitiligo have no underlying disease. However, vitiligo has been reported with autoimmune conditions, including alopecia areata, hypothyroidism, Graves’ disease, Addison’s disease, pernicious anemia, insulin-dependent diabetes mellitus, polyglandular autoimmune syndromes, melanoma, and uveitis, notably VogtKoyanagi-Harada (VKH) syndrome.4 Choroidal vitiligo is an acquired condition manifesting as flat depigmentation of the normally pigmented choroid. This condition can occur as a primary or secondary process. Primary choroidal vitiligo occurs as an idiopathic process © 2010 by the American Academy of Ophthalmology Published by Elsevier Inc.
without preceding inflammation, toxin, or trauma. Secondary choroidal vitiligo is generally postinflammatory and found most often with VKH syndrome. Vogt-KoyanagiHarada syndrome is an autoimmune reaction to epidermal, cochleal, meningeal, and uveal melanin resulting in destruction of melanin-producing cells and producing cutaneous vitiligo, tinnitus, headache, and choroidal depigmentation (vitiligo) and atrophy, classically with extensive overlying retinal pigment epithelial (RPE) changes.5,6 This report describes 4 cases of primary choroidal vitiligo associated with cutaneous vitiligo but no evidence of VKH.
Case Reports The cases are summarized in Table 1 (available at http://aaojournal. org). Institutional review board approval was obtained.
Case 1 A 65-year-old asymptomatic African American woman with a 25-year history of diabetes mellitus and a 4-year history of cutaneous vitiligo of the eyebrows, eyelids, nose, nares, philtrum neck, hands, and feet was referred with a newly diagnosed choroidal nevus. There was no history of ocular medication use. Confluent panretinal photocoagulation for diabetic retinopathy had been performed in both eyes. On examination, visual acuity was 6/24 in the right eye and 6/12 in the left eye. The anterior segment and intraocular pressures were normal in both eyes. Posterior examination disclosed a unilateral solitary patch of choroidal pigmentary ISSN 0161-6420/10/$–see front matter doi:10.1016/j.ophtha.2009.11.018
109
Ophthalmology Volume 117, Number 1, January 2010 loss (vitiligo) encircling the optic disc and measuring 12 mm in diameter and 1.4 mm in thickness (Fig 1; available at http:// aaojournal.org). There were no related retinal or RPE alterations and no sign of inflammation. There was no follow-up.
Case 2 A 57-year-old asymptomatic Caucasian woman with hypothyroidism and fibromyalgia and an 18-year history of cutaneous vitiligo of the eyebrows, cheeks, nose, perioral region, elbows, and hands was referred with multifocal choroidal nevi. There was no history of ocular medication use. On examination, visual acuity was 6/6 in the right eye and 6/7.5 in the left eye. The anterior segment and intraocular pressures were normal in both eyes. Posterior examination disclosed bilateral patchy choroidal vitiligo throughout the entire fundus without overlying retinal or RPE alterations (Fig 2). There was no sign of inflammation. The retinal layers were intact on optical coherence tomography (OCT). There was slight choroidal hyperfluorescence at the site of vitiligo on fluorescein angiography. Autofluorescence disclosed striking transmission of scleral hyperautofluorescence through the areas of vitiligo. The fundus was stable at 2-year follow-up.
Case 3 A 59-year-old asymptomatic African American woman with diabetes mellitus and cutaneous vitiligo of the eyebrow, perioral region, and knee was referred with a choroidal nevus. There was no history of ocular medication use. On examination, visual acuity was 6/6 in both eyes. The anterior segment and intraocular pressures were normal in both eyes. Posterior examination disclosed bilateral patchy post-equatorial choroidal vitiligo measuring 6 mm diameter (2 sites) in the right eye and 25 mm in the left eye with 1.6 mm thickness in both eyes (Fig 3). There were no overlying retinal or RPE alterations. There was no sign of inflammation. The retinal layers were intact on OCT. The fundus was stable at 1-year follow-up.
Case 4 A 73-year-old asymptomatic Hispanic woman with diabetes mellitus and faint cutaneous vitiligo of the cheeks, perioral region, arms, and hands, and a family history of cutaneous vitiligo in her father, son, and 2 nieces, was referred with bilateral choroidal nevi. There was no ocular medication use. On examination, visual acuity was 6/15 in both eyes. The anterior segment disclosed trabeculectomy blebs and posterior chamber intraocular lens. Intraocular pressures were normal in both eyes. Posterior examination disclosed bilateral post-equatorial patchy choroidal vitiligo measuring 6 mm in diameter in the right eye and 18 mm in the left eye with 1.4-mm thickness. There were no overlying retinal or RPE alterations (Fig 4; available at http://aaojournal.org). There was no sign of inflammation. The retinal layers were intact on OCT. There was slight choroidal hyperfluorescence at the site of vitiligo on fluorescein angiography. Autofluorescence disclosed striking transmission of scleral hyperautofluorescence transmission through the areas of vitiligo. The fundus was stable at 2-year follow-up.
Discussion Primary acquired choroidal vitiligo is a rare condition with only few reported cases in the literature.7,8 Vingerling et al7 observed 2 Chinese patients, a 59-year-old man and a 48-
110
year-old woman, with extensive choroidal vitiligo and cutaneous vitiligo. In both cases, there was no evidence of past or present ocular inflammation and the overlying RPE was intact. Visual fields and electrodiagnostic test results were normal. They speculated that the similar derivation of cutaneous and choroidal melanocytes from neural crest cells, differing from RPE cellular derivation from neuroectoderm, could account for the exclusionary depigmentation of skin and choroid without RPE abnormality.9 Ciardella et al8 described a 43-year-old Hispanic woman with diabetes mellitus, cutaneous vitiligo, and striking bilateral asymptomatic choroidal vitiligo with no signs of inflammation or RPE alterations.8 Other authors have evaluated patients with cutaneous vitiligo for eye findings but have been less descriptive of the exact ocular features or have included a potpourri of diseases in their analyses. In the dermatology literature, Cowan et al10 evaluated 156 patients with cutaneous vitiligo for ocular abnormalities and reported sketchy detail of “pigment clumps, focal hypopigmented spots, and choroidal nevi,” but stated that the findings were similar to those in patients without vitiligo.10 Bulbul Baskan et al11 evaluated 45 patients with cutaneous vitiligo and found that periorbital cutaneous vitiligo was significantly (P⬍0.001) related to ocular findings.11 The ocular findings included a conglomeration of “iris involvement (feature not specified), peripapillary atrophy (tissue not specified), RPE atrophy, focal hypopigmented spots on the retina, and diffuse hypopigmentation (tissue not specified).” The described ocular features were scanty, and illustrations showed peripapillary RPE and choroidal atrophy in 2 cases, congenital hypertrophy of RPE in 1 case, and macular choroidal vitiligo in 1 case. They found that periorbital cutaneous vitiligo promoted a 58-fold risk for this assortment of ocular findings. In the ophthalmology literature, Albert et al12,13 studied ocular findings in patients with cutaneous vitiligo noting the prominence of RPE alterations; however, these reports included a spectrum of diseases, such as uveitis, particularly VKH, and retinitis pigmentosa. Our report is different from the above publications in which the eye was studied after cutaneous vitiligo was found. In our analysis, we studied the skin and systemic features after choroidal vitiligo was detected. The patients and findings in our series were different in that none of our patients had uveitis, tinnitus, headache, meningismus, progressive vitiligo, or rheumatologic symptoms. There were no features of Waardenburg’s syndrome, VKH syndrome, or other uveal inflammatory conditions. All patients had cutaneous vitiligo, but it was subtle in some instances with faint depigmentation in the eyebrow, periocular, and perioral region. The ocular features involved only choroidal vitiligo without RPE abnormalities. Our series represents primary acquired choroidal vitiligo. In our series, all 4 patients were referred with the diagnosis of suspicious choroidal nevus rule out melanoma. All patients were of dark complexion, and the choroidal vitiligo contrasted with the residual normal choroidal pigment, simulating a pigmented choroidal tumor. In the reverse, the abnormality was the surrounding depigmentation. Other conditions in the differential diagnosis included sectoral choroidal melanocytosis, giant choroidal nevus, and diffuse choroidal melanoma.
Shields et al 䡠 Choroidal Vitiligo
Figure 2. Case 2: A 57-year-old woman with cutaneous vitiligo of the eyebrow skin (A), cheeks, nose, lips, elbows, and hands (B, C) manifested choroidal vitiligo (D, E). The vitiligo showed corresponding transmission of scleral autofluorescence (F, G). The vitiligo displayed slightly more choroidal hyperfluorescence on angiography (H, I). The vitiligo showed slightly greater light transmission deep into the choroid on spectral-domain OCT (horizontal orientation through the fovea) (J, K), but no overlying retinal anatomic disturbance.
This is the first report to analyze the OCT and autofluorescence features of choroidal vitiligo. By OCT, the overlying retina was intact without photoreceptor degeneration, concurring with the observed preservation of visual acuity and electrodiagnostic tests, even when there was subfoveolar vitiligo. In the areas of vitiligo, there was increased optical transmission of OCT deep into the choroid. By
autofluorescence, the patches of vitiligo allowed for a 1-to-1 correlation of bright transmission of underlying scleral hyperautofluorescence. There was no evidence of RPE or lipofuscin abnormality on autofluorescence. Fluorescein angiography revealed slight choroidal hyperfluorescence in the region of vitiligo relative to the normal pigmented choroid, but without leakage or staining.
111
Ophthalmology Volume 117, Number 1, January 2010
Figure 3. Case 3: A 59-year-old woman with cutaneous vitiligo of the right eyebrow skin (A), lips, elbows, and knee (B) manifested choroidal vitiligo (C, D). Compared with the normally pigmented fovea of the right eye (E), the vitiligo in the left eye (F) showed slightly greater light transmission deep into the choroid on spectral-domain optical coherence tomography (OCT), but no overlying retinal anatomic disturbance. (OCT orientation vertical through the fovea in the right eye and horizontal left eye to encompass regions of vitiligo.)
In conclusion, we present a series of 4 patients who were referred with the diagnosis of suspicious choroidal nevus rule out melanoma and found to have, in reverse, asymptomatic choroidal vitiligo. All 4 patients displayed cutaneous vitiligo. This asymptomatic condition of choroidal vitiligo allows for normal visual acuity and fields, and normal retinal and RPE anatomy, but increased optical transmission into the choroid on OCT, normal RPE features on autofluorescence, and 1-to-1 correlation of bright transmission of scleral autofluorescence.
References 1. Spielvogel RL, Kantor GR. Vitiligo. In: Elder D, Elenitsas R, Jaworksky C, Johnson B Jr, eds. Lever’s Histopathology of the Skin.8th ed. Philadelphia, PA: Lippincott; 1997;620 –1.
112
2. Naughton GK, Eisinger M, Bystryn JC. Detection of antibodies to melanocytes in vitiligo by specific immunoprecipitation. J Invest Dermatol 1983;81:540 –2. 3. Brown J, Winkelmann RK, Wolff K. Langerhans cells in vitiligo: a qualitative study. J Invest Dermatol 1967;49: 386 –90. 4. Bolognia JL, Pawelek JM. Biology of hypopigmentation. J Am Acad Dermatol 1988;19:217–55. 5. Nordlund JJ, Taylor NT, Albert DM, et al. The prevalence of vitiligo and poliosis in patients with uveitis. J Am Acad Dermatol 1981;4:528 –36. 6. da Silva FT, Damico FM, Marin ML, et al. Revised diagnostic criteria for Vogy-Koyanagi-Harada disease: considerations on the different disease categories. Am J Ophthalmol 2009;147: 339 – 45. 7. Vingerling JR, Owens S, van der Maijden WI, et al. Cutaneous vitiligo associated with choroidal hypopigmentation [letter]. Eye 2004;18:939 – 40.
Shields et al 䡠 Choroidal Vitiligo 8. Ciardella AP, Horsley MB, Brown DM. Hypopigmentary fundus changes seen with cutaneous vitiligo. Arch Ophthalmol 2007;125:576. 9. Vingerling JR, Owens S, van der Meijden WI, et al. Hypopigmentary fundus changes with cutaneous vitiligo [letter]. Arch Ophthalmol 2008;126:439. 10. Cowan CL Jr, Halder RM, Grimes PE, et al. Ocular disturbances in vitiligo. J Am Acad Dermatol 1986;15:17–24.
11. Bulbul Baskan E, Baykara M, Ercan I, et al. Vitiligo and ocular findings: a study on possible associations. J Eur Acad Dermatol Venereol 2006;20:829 –33. 12. Albert DM, Nordlund JJ, Lerner AB. Ocular abnormalities occurring with vitiligo. Ophthalmology 1979;86:1145– 60. 13. Albert DM, Wagoner MD, Pruett RC, et al. Vitiligo and disorders of the retinal pigment epithelium. Br J Ophthalmol 1983;67:153– 6.
Footnotes and Financial Disclosures Originally received: July 19, 2009. Final revision: November 11, 2009. Accepted: November 11, 2009. Available online: November 24, 2009. 1
Manuscript no. 2009-966.
Ocular Oncology Service, Wills Eye Institute, Thomas Jefferson University, Philadelphia, Pennsylvania. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Support provided by the Retina Research Foundation of the Retina Society in Capetown, South Africa (CLS); the Paul Kayser International Award of
Merit in Retina Research, Houston, Texas (JAS); a donation from Michael, Bruce, and Ellen Ratner, New York, New York (JAS, CLS); Mellon Charitable Giving from the Martha W. Rogers Charitable Trust, Philadelphia, Pennsylvania (CLS); the LuEsther Mertz Retina Research Foundation, New York, New York (CLS); and the Eye Tumor Research Foundation, Philadelphia, Pennsylvania (CLS, JAS). Correspondence: Carol L. Shields, MD, Ocular Oncology Service, Suite 1440, Wills Eye Institute, 840 Walnut Street, Philadelphia, PA 19107. E-mail: carol. [email protected].
113
Ophthalmology Volume 117, Number 1, January 2010 Table 1. Summary of Four Cases of Choroidal Vitiligo Patient Findings
Eye Findings Overlying Changes
4
73 HF 6/15 OU
DM
Nevus
OD
Post-equatorial
12
1.4
NA
NA
NA
None
None*
None
Nevus
OU
Entire
24
1.3
Intact
Slight increased choroidal fluorescence
Yes
None
None
Stable (2)
Nevus
OU
Post-equatorial
24
1.6
Intact
NA
NA
None
None
Stable (1)
Nevus
OU
Post-equatorial
18
1.4
Intact
Slight increased choroidal fluorescence
Yes
None
None
None
FA
RPE
DM
Retina
59 AAF 6/6 OU
Autofluorescence Scleral Transmission
3
OCT Photoreceptors
HT FM
Thickness mm
57 CF 6/6 OD 6/7.5 OS
Largest Base mm
2
Brows Lids Nose Nares Philtrum Neck Hands Feet (4) Brows Cheeks Nose Lips Elbows Hands (18) Brow Lip Knee (50) Cheeks Lips Arms Hands (NA)
Fundus Location
DM
Laterality
65 AAF 6/24 OD 6/12 OS
Ocular Referral Diagnosis
1
Skin Vitiligo (Duration in Years)
Autoimmune Syndromes
Age Race Gender Visual Acuity
Case
Choroidal Vitiligo
Follow-up (yrs)
AA ⫽ African American; Brows ⫽ eyebrows; C ⫽ Caucasian; DM ⫽ diabetes mellitus; F ⫽ female; FA ⫽ fluorescein angiography; FM ⫽ fibromyalgia; H ⫽ Hispanic; HT ⫽ hypothyroidism; lids ⫽ eyelids; lips ⫽ perioral region; NA ⫽ not available (test not performed); OCT ⫽ optical coherence tomography; OD ⫽ right eye; OS ⫽ left eye; OU ⫽ both eyes; RPE ⫽ retinal pigment epithelium. *Confluent peripheral panretinal photocoagulation for diabetes mellitus led to peripheral RPE changes.
113.e1
Shields et al 䡠 Choroidal Vitiligo
Figure 1. Case 1: A 65-year-old woman with cutaneous vitiligo of the eyebrow skin, eyelids, nose, nares (A), neck, hands (B, C), and feet manifested unilateral choroidal vitiligo (D). Note the panretinal photocoagulation scars for treatment of diabetic retinopathy.
113.e2
Ophthalmology Volume 117, Number 1, January 2010
Figure 4. Case 4: A 73-year-old woman with cutaneous vitiligo of the cheeks (A), lips, arms (B, C), and hands manifested choroidal vitiligo (D, E). The vitiligo showed corresponding transmission of scleral autofluorescence (F, G). The vitiligo displayed slightly more choroidal hyperfluorescence on angiography (H, I). The vitiligo showed slightly deeper light transmission into the choroid on spectral-domain optical coherence tomography (OCT) (J, K), but no overlying retinal anatomic disturbance. (OCT orientation vertical through the nasal juxtapapillary vitiligo in the right eye and horizontal through the fovea left eye to encompass regions of vitiligo.)
113.e3
Vitiligo is an acquired disorder characterized by flat, cutaneous depigmented macules. Several hypotheses have been proposed for this condition, including autoimmunity, viral infection, chemical exposure, neurohumoral mechanism, or autocytotoxicity, but the exact pathogenesis remains obscure. According to a dermatopathology textbook, the “essential process in vitiligo is the destruction of melanocytes.”1 Antibodies to melanocytes have been found in the sera of patients with vitiligo but not in normal sera.2 Furthermore, patients with vitiligo can show antibodies to adrenal and thyroid cells, thyroglobulin, gastric parietal cells, and pancreatic islet cells.1 Early lesions show few melanocytes and melanin granules in the basal epithelial layer.3 Long-standing lesions demonstrate no melanocytes. The occasional presence of a lymphocytic infiltrate, often in contact with cutaneous melanocytes or Langerhans cells, suggests an immunologic cause.1 Most patients with cutaneous vitiligo have no underlying disease. However, vitiligo has been reported with autoimmune conditions, including alopecia areata, hypothyroidism, Graves’ disease, Addison’s disease, pernicious anemia, insulin-dependent diabetes mellitus, polyglandular autoimmune syndromes, melanoma, and uveitis, notably VogtKoyanagi-Harada (VKH) syndrome.4 Choroidal vitiligo is an acquired condition manifesting as flat depigmentation of the normally pigmented choroid. This condition can occur as a primary or secondary process. Primary choroidal vitiligo occurs as an idiopathic process © 2010 by the American Academy of Ophthalmology Published by Elsevier Inc.
without preceding inflammation, toxin, or trauma. Secondary choroidal vitiligo is generally postinflammatory and found most often with VKH syndrome. Vogt-KoyanagiHarada syndrome is an autoimmune reaction to epidermal, cochleal, meningeal, and uveal melanin resulting in destruction of melanin-producing cells and producing cutaneous vitiligo, tinnitus, headache, and choroidal depigmentation (vitiligo) and atrophy, classically with extensive overlying retinal pigment epithelial (RPE) changes.5,6 This report describes 4 cases of primary choroidal vitiligo associated with cutaneous vitiligo but no evidence of VKH.
Case Reports The cases are summarized in Table 1 (available at http://aaojournal. org). Institutional review board approval was obtained.
Case 1 A 65-year-old asymptomatic African American woman with a 25-year history of diabetes mellitus and a 4-year history of cutaneous vitiligo of the eyebrows, eyelids, nose, nares, philtrum neck, hands, and feet was referred with a newly diagnosed choroidal nevus. There was no history of ocular medication use. Confluent panretinal photocoagulation for diabetic retinopathy had been performed in both eyes. On examination, visual acuity was 6/24 in the right eye and 6/12 in the left eye. The anterior segment and intraocular pressures were normal in both eyes. Posterior examination disclosed a unilateral solitary patch of choroidal pigmentary ISSN 0161-6420/10/$–see front matter doi:10.1016/j.ophtha.2009.11.018
109
Ophthalmology Volume 117, Number 1, January 2010 loss (vitiligo) encircling the optic disc and measuring 12 mm in diameter and 1.4 mm in thickness (Fig 1; available at http:// aaojournal.org). There were no related retinal or RPE alterations and no sign of inflammation. There was no follow-up.
Case 2 A 57-year-old asymptomatic Caucasian woman with hypothyroidism and fibromyalgia and an 18-year history of cutaneous vitiligo of the eyebrows, cheeks, nose, perioral region, elbows, and hands was referred with multifocal choroidal nevi. There was no history of ocular medication use. On examination, visual acuity was 6/6 in the right eye and 6/7.5 in the left eye. The anterior segment and intraocular pressures were normal in both eyes. Posterior examination disclosed bilateral patchy choroidal vitiligo throughout the entire fundus without overlying retinal or RPE alterations (Fig 2). There was no sign of inflammation. The retinal layers were intact on optical coherence tomography (OCT). There was slight choroidal hyperfluorescence at the site of vitiligo on fluorescein angiography. Autofluorescence disclosed striking transmission of scleral hyperautofluorescence through the areas of vitiligo. The fundus was stable at 2-year follow-up.
Case 3 A 59-year-old asymptomatic African American woman with diabetes mellitus and cutaneous vitiligo of the eyebrow, perioral region, and knee was referred with a choroidal nevus. There was no history of ocular medication use. On examination, visual acuity was 6/6 in both eyes. The anterior segment and intraocular pressures were normal in both eyes. Posterior examination disclosed bilateral patchy post-equatorial choroidal vitiligo measuring 6 mm diameter (2 sites) in the right eye and 25 mm in the left eye with 1.6 mm thickness in both eyes (Fig 3). There were no overlying retinal or RPE alterations. There was no sign of inflammation. The retinal layers were intact on OCT. The fundus was stable at 1-year follow-up.
Case 4 A 73-year-old asymptomatic Hispanic woman with diabetes mellitus and faint cutaneous vitiligo of the cheeks, perioral region, arms, and hands, and a family history of cutaneous vitiligo in her father, son, and 2 nieces, was referred with bilateral choroidal nevi. There was no ocular medication use. On examination, visual acuity was 6/15 in both eyes. The anterior segment disclosed trabeculectomy blebs and posterior chamber intraocular lens. Intraocular pressures were normal in both eyes. Posterior examination disclosed bilateral post-equatorial patchy choroidal vitiligo measuring 6 mm in diameter in the right eye and 18 mm in the left eye with 1.4-mm thickness. There were no overlying retinal or RPE alterations (Fig 4; available at http://aaojournal.org). There was no sign of inflammation. The retinal layers were intact on OCT. There was slight choroidal hyperfluorescence at the site of vitiligo on fluorescein angiography. Autofluorescence disclosed striking transmission of scleral hyperautofluorescence transmission through the areas of vitiligo. The fundus was stable at 2-year follow-up.
Discussion Primary acquired choroidal vitiligo is a rare condition with only few reported cases in the literature.7,8 Vingerling et al7 observed 2 Chinese patients, a 59-year-old man and a 48-
110
year-old woman, with extensive choroidal vitiligo and cutaneous vitiligo. In both cases, there was no evidence of past or present ocular inflammation and the overlying RPE was intact. Visual fields and electrodiagnostic test results were normal. They speculated that the similar derivation of cutaneous and choroidal melanocytes from neural crest cells, differing from RPE cellular derivation from neuroectoderm, could account for the exclusionary depigmentation of skin and choroid without RPE abnormality.9 Ciardella et al8 described a 43-year-old Hispanic woman with diabetes mellitus, cutaneous vitiligo, and striking bilateral asymptomatic choroidal vitiligo with no signs of inflammation or RPE alterations.8 Other authors have evaluated patients with cutaneous vitiligo for eye findings but have been less descriptive of the exact ocular features or have included a potpourri of diseases in their analyses. In the dermatology literature, Cowan et al10 evaluated 156 patients with cutaneous vitiligo for ocular abnormalities and reported sketchy detail of “pigment clumps, focal hypopigmented spots, and choroidal nevi,” but stated that the findings were similar to those in patients without vitiligo.10 Bulbul Baskan et al11 evaluated 45 patients with cutaneous vitiligo and found that periorbital cutaneous vitiligo was significantly (P⬍0.001) related to ocular findings.11 The ocular findings included a conglomeration of “iris involvement (feature not specified), peripapillary atrophy (tissue not specified), RPE atrophy, focal hypopigmented spots on the retina, and diffuse hypopigmentation (tissue not specified).” The described ocular features were scanty, and illustrations showed peripapillary RPE and choroidal atrophy in 2 cases, congenital hypertrophy of RPE in 1 case, and macular choroidal vitiligo in 1 case. They found that periorbital cutaneous vitiligo promoted a 58-fold risk for this assortment of ocular findings. In the ophthalmology literature, Albert et al12,13 studied ocular findings in patients with cutaneous vitiligo noting the prominence of RPE alterations; however, these reports included a spectrum of diseases, such as uveitis, particularly VKH, and retinitis pigmentosa. Our report is different from the above publications in which the eye was studied after cutaneous vitiligo was found. In our analysis, we studied the skin and systemic features after choroidal vitiligo was detected. The patients and findings in our series were different in that none of our patients had uveitis, tinnitus, headache, meningismus, progressive vitiligo, or rheumatologic symptoms. There were no features of Waardenburg’s syndrome, VKH syndrome, or other uveal inflammatory conditions. All patients had cutaneous vitiligo, but it was subtle in some instances with faint depigmentation in the eyebrow, periocular, and perioral region. The ocular features involved only choroidal vitiligo without RPE abnormalities. Our series represents primary acquired choroidal vitiligo. In our series, all 4 patients were referred with the diagnosis of suspicious choroidal nevus rule out melanoma. All patients were of dark complexion, and the choroidal vitiligo contrasted with the residual normal choroidal pigment, simulating a pigmented choroidal tumor. In the reverse, the abnormality was the surrounding depigmentation. Other conditions in the differential diagnosis included sectoral choroidal melanocytosis, giant choroidal nevus, and diffuse choroidal melanoma.
Shields et al 䡠 Choroidal Vitiligo
Figure 2. Case 2: A 57-year-old woman with cutaneous vitiligo of the eyebrow skin (A), cheeks, nose, lips, elbows, and hands (B, C) manifested choroidal vitiligo (D, E). The vitiligo showed corresponding transmission of scleral autofluorescence (F, G). The vitiligo displayed slightly more choroidal hyperfluorescence on angiography (H, I). The vitiligo showed slightly greater light transmission deep into the choroid on spectral-domain OCT (horizontal orientation through the fovea) (J, K), but no overlying retinal anatomic disturbance.
This is the first report to analyze the OCT and autofluorescence features of choroidal vitiligo. By OCT, the overlying retina was intact without photoreceptor degeneration, concurring with the observed preservation of visual acuity and electrodiagnostic tests, even when there was subfoveolar vitiligo. In the areas of vitiligo, there was increased optical transmission of OCT deep into the choroid. By
autofluorescence, the patches of vitiligo allowed for a 1-to-1 correlation of bright transmission of underlying scleral hyperautofluorescence. There was no evidence of RPE or lipofuscin abnormality on autofluorescence. Fluorescein angiography revealed slight choroidal hyperfluorescence in the region of vitiligo relative to the normal pigmented choroid, but without leakage or staining.
111
Ophthalmology Volume 117, Number 1, January 2010
Figure 3. Case 3: A 59-year-old woman with cutaneous vitiligo of the right eyebrow skin (A), lips, elbows, and knee (B) manifested choroidal vitiligo (C, D). Compared with the normally pigmented fovea of the right eye (E), the vitiligo in the left eye (F) showed slightly greater light transmission deep into the choroid on spectral-domain optical coherence tomography (OCT), but no overlying retinal anatomic disturbance. (OCT orientation vertical through the fovea in the right eye and horizontal left eye to encompass regions of vitiligo.)
In conclusion, we present a series of 4 patients who were referred with the diagnosis of suspicious choroidal nevus rule out melanoma and found to have, in reverse, asymptomatic choroidal vitiligo. All 4 patients displayed cutaneous vitiligo. This asymptomatic condition of choroidal vitiligo allows for normal visual acuity and fields, and normal retinal and RPE anatomy, but increased optical transmission into the choroid on OCT, normal RPE features on autofluorescence, and 1-to-1 correlation of bright transmission of scleral autofluorescence.
References 1. Spielvogel RL, Kantor GR. Vitiligo. In: Elder D, Elenitsas R, Jaworksky C, Johnson B Jr, eds. Lever’s Histopathology of the Skin.8th ed. Philadelphia, PA: Lippincott; 1997;620 –1.
112
2. Naughton GK, Eisinger M, Bystryn JC. Detection of antibodies to melanocytes in vitiligo by specific immunoprecipitation. J Invest Dermatol 1983;81:540 –2. 3. Brown J, Winkelmann RK, Wolff K. Langerhans cells in vitiligo: a qualitative study. J Invest Dermatol 1967;49: 386 –90. 4. Bolognia JL, Pawelek JM. Biology of hypopigmentation. J Am Acad Dermatol 1988;19:217–55. 5. Nordlund JJ, Taylor NT, Albert DM, et al. The prevalence of vitiligo and poliosis in patients with uveitis. J Am Acad Dermatol 1981;4:528 –36. 6. da Silva FT, Damico FM, Marin ML, et al. Revised diagnostic criteria for Vogy-Koyanagi-Harada disease: considerations on the different disease categories. Am J Ophthalmol 2009;147: 339 – 45. 7. Vingerling JR, Owens S, van der Maijden WI, et al. Cutaneous vitiligo associated with choroidal hypopigmentation [letter]. Eye 2004;18:939 – 40.
Shields et al 䡠 Choroidal Vitiligo 8. Ciardella AP, Horsley MB, Brown DM. Hypopigmentary fundus changes seen with cutaneous vitiligo. Arch Ophthalmol 2007;125:576. 9. Vingerling JR, Owens S, van der Meijden WI, et al. Hypopigmentary fundus changes with cutaneous vitiligo [letter]. Arch Ophthalmol 2008;126:439. 10. Cowan CL Jr, Halder RM, Grimes PE, et al. Ocular disturbances in vitiligo. J Am Acad Dermatol 1986;15:17–24.
11. Bulbul Baskan E, Baykara M, Ercan I, et al. Vitiligo and ocular findings: a study on possible associations. J Eur Acad Dermatol Venereol 2006;20:829 –33. 12. Albert DM, Nordlund JJ, Lerner AB. Ocular abnormalities occurring with vitiligo. Ophthalmology 1979;86:1145– 60. 13. Albert DM, Wagoner MD, Pruett RC, et al. Vitiligo and disorders of the retinal pigment epithelium. Br J Ophthalmol 1983;67:153– 6.
Footnotes and Financial Disclosures Originally received: July 19, 2009. Final revision: November 11, 2009. Accepted: November 11, 2009. Available online: November 24, 2009. 1
Manuscript no. 2009-966.
Ocular Oncology Service, Wills Eye Institute, Thomas Jefferson University, Philadelphia, Pennsylvania. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Support provided by the Retina Research Foundation of the Retina Society in Capetown, South Africa (CLS); the Paul Kayser International Award of
Merit in Retina Research, Houston, Texas (JAS); a donation from Michael, Bruce, and Ellen Ratner, New York, New York (JAS, CLS); Mellon Charitable Giving from the Martha W. Rogers Charitable Trust, Philadelphia, Pennsylvania (CLS); the LuEsther Mertz Retina Research Foundation, New York, New York (CLS); and the Eye Tumor Research Foundation, Philadelphia, Pennsylvania (CLS, JAS). Correspondence: Carol L. Shields, MD, Ocular Oncology Service, Suite 1440, Wills Eye Institute, 840 Walnut Street, Philadelphia, PA 19107. E-mail: carol. [email protected].
113
Ophthalmology Volume 117, Number 1, January 2010 Table 1. Summary of Four Cases of Choroidal Vitiligo Patient Findings
Eye Findings Overlying Changes
4
73 HF 6/15 OU
DM
Nevus
OD
Post-equatorial
12
1.4
NA
NA
NA
None
None*
None
Nevus
OU
Entire
24
1.3
Intact
Slight increased choroidal fluorescence
Yes
None
None
Stable (2)
Nevus
OU
Post-equatorial
24
1.6
Intact
NA
NA
None
None
Stable (1)
Nevus
OU
Post-equatorial
18
1.4
Intact
Slight increased choroidal fluorescence
Yes
None
None
None
FA
RPE
DM
Retina
59 AAF 6/6 OU
Autofluorescence Scleral Transmission
3
OCT Photoreceptors
HT FM
Thickness mm
57 CF 6/6 OD 6/7.5 OS
Largest Base mm
2
Brows Lids Nose Nares Philtrum Neck Hands Feet (4) Brows Cheeks Nose Lips Elbows Hands (18) Brow Lip Knee (50) Cheeks Lips Arms Hands (NA)
Fundus Location
DM
Laterality
65 AAF 6/24 OD 6/12 OS
Ocular Referral Diagnosis
1
Skin Vitiligo (Duration in Years)
Autoimmune Syndromes
Age Race Gender Visual Acuity
Case
Choroidal Vitiligo
Follow-up (yrs)
AA ⫽ African American; Brows ⫽ eyebrows; C ⫽ Caucasian; DM ⫽ diabetes mellitus; F ⫽ female; FA ⫽ fluorescein angiography; FM ⫽ fibromyalgia; H ⫽ Hispanic; HT ⫽ hypothyroidism; lids ⫽ eyelids; lips ⫽ perioral region; NA ⫽ not available (test not performed); OCT ⫽ optical coherence tomography; OD ⫽ right eye; OS ⫽ left eye; OU ⫽ both eyes; RPE ⫽ retinal pigment epithelium. *Confluent peripheral panretinal photocoagulation for diabetes mellitus led to peripheral RPE changes.
113.e1
Shields et al 䡠 Choroidal Vitiligo
Figure 1. Case 1: A 65-year-old woman with cutaneous vitiligo of the eyebrow skin, eyelids, nose, nares (A), neck, hands (B, C), and feet manifested unilateral choroidal vitiligo (D). Note the panretinal photocoagulation scars for treatment of diabetic retinopathy.
113.e2
Ophthalmology Volume 117, Number 1, January 2010
Figure 4. Case 4: A 73-year-old woman with cutaneous vitiligo of the cheeks (A), lips, arms (B, C), and hands manifested choroidal vitiligo (D, E). The vitiligo showed corresponding transmission of scleral autofluorescence (F, G). The vitiligo displayed slightly more choroidal hyperfluorescence on angiography (H, I). The vitiligo showed slightly deeper light transmission into the choroid on spectral-domain optical coherence tomography (OCT) (J, K), but no overlying retinal anatomic disturbance. (OCT orientation vertical through the nasal juxtapapillary vitiligo in the right eye and horizontal through the fovea left eye to encompass regions of vitiligo.)
113.e3