AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Multimedia
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Multimedia
• References

Background

In 1959, Casala and Alezzandrini¹ described a patient with vitiligo, poliosis, and unilateral pigmentary retinitis with hyperacusis. During the next 4 years, they observed 2 more patients with similar presentations and were convinced that the condition was a distinct clinical syndrome. In 1964, Alezzandrini² described 3 patients with unilateral tapetoretinal degeneration of the eye associated with ipsilateral facial vitiligo and poliosis. Two of these patients had hypoacusis.

The relationship between Alezzandrini syndrome and other syndromes involving vitiligo and eye pathology is uncertain. Among the most well-defined syndromes combining eye pathology and vitiligo is Vogt-Koyanagi-Harada syndrome.³ The relationship of this syndrome to Alezzandrini syndrome is uncertain. In order to best describe Alezzandrini syndrome, a discussion of Vogt-Koyanagi-Harada syndrome is necessary.

In 1906, Vogt⁴ reported a patient with non-traumatic uveitis, poliosis, and alopecia. He hypothesized that the uveitis and poliosis were due to a single disease process. In 1910, Gilbert⁵ described a patient who had generalized vitiligo followed by bilateral uveitis and optic neuritis. In 1926, Harada⁶ described 5 patients with a condition called acute diffuse choroiditis. These 5 patients had posterior uveitis that frequently resulted in retinal separation, severe headaches, fever, and confusion. In 1929, Koyanagi⁷ reported 16 cases of a syndrome with findings of idiopathic bilateral anterior uveitis, dysacusis, vitiligo, poliosis, and alopecia, as well as a prodromal phase of headache, fever, and confusion. These entities have significant overlap and are considered to be one syndrome called Vogt-Koyanagi-Harada syndrome.

A patient was described with uveomeningitic disease with bilateral intermediate uveitis and macular edema, which could be interpreted as an atypical form of Vogt-Koyanagi-Harada disease or a new uveomeningitic syndrome because the patient had no evidence of any other known disease.⁸ These disease categories can be complex.

For additional information, see eMedicine's Dermatology article Vogt-Koyanagi-Harada Syndrome and Ophthalmology article Vogt-Koyanagi-Harada Disease.

Pathophysiology

Although the etiology of Alezzandrini syndrome is unknown, several theories involving viral or autoimmune processes have been postulated.

Melanocytes originate in the neural crest then migrate to the skin, leptomeninges, retinas, uvea, cochleae, and vestibular labyrinths. Any disorder that destroys the melanocytes in the skin also affects other organs and systems such as the eye, ear, and central nervous system.

Evidence from 2008 suggests that CTLA-4 genetic polymorphisms may be associated with susceptibility to this syndrome.⁹

Frequency

United States

The condition is rare. In addition to Alezzandrini's original 3 cases, only 2 further cases of Alezzandrini syndrome have been reported. In 1992, Hoffman and Dudley¹⁰ described a case of suspected Alezzandrini syndrome in a diabetic patient with retinal detachment. The presence of tapetoretinal degeneration could not be confirmed because of the retinal detachment. In 1994, Shamsadini and associates¹¹ described bilateral retinal detachment in a patient with Alezzandrini syndrome.

International

This condition, in its classic description, is extremely rare.

Mortality/Morbidity

Alezzandrini syndrome is a rare disorder with an unknown mortality rate.

• Most patients have retinal detachment and subsequent blindness.
• Hypoacusis is also described, but not in all of the reported patients.

Race

Alezzandrini syndrome is not limited to a certain race.

Sex

Because Alezzandrini syndrome is a rare disorder, the sex prevalence is difficult to determine.

Age

Most patients initially presented when they were aged 12-30 years.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Multimedia
• References

History

• A gradual loss of visual acuity initially occurs, predominantly in one eye.
• The hair and skin in affected areas lose their pigmentation.
• In one patient, ipsilateral hypoacusis was a late finding.
• Bilateral deafness developed in one patient.

Physical

• Alezzandrini syndrome is characterized by unilateral tapetoretinal (retinal pigmented epithelia) degeneration with the ipsilateral appearance of facial vitiligo and poliosis.
• Ipsilateral perceptual deafness may be an additional finding.
• Unilateral cutaneous and retinal disease also characterize Alezzandrini syndrome.
• The symptom originally described was a gradual loss of visual acuity, which predominantly affected one eye.
• Lorincz¹² believes that the gradual loss of visual acuity on the ipsilateral side is the criterion that should be used to diagnosis Alezzandrini syndrome.
• After 3-13 years, vitiligo and poliosis develop on the head, on the side ipsilateral to the retinal lesions.

Causes

• The condition has an unknown etiology.
• Several theories, including those involving viral or autoimmune processes, are postulated.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Multimedia
• References

Other Problems to be Considered

Vitiligo with Alezzandrini syndrome may be confused with other systemic disorders, including tuberous sclerosis, progressive systemic sclerosis (scleroderma), and, in endemic regions, leprosy.¹³

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Multimedia
• References

Lab Studies

• No laboratory studies are required.
• Diagnosis is based on the clinical presentation.

Other Tests

• Fundus examination is indicated.
• Visual acuity test may be performed.
• Audiometry may be required.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Multimedia
• References

Medical Care

Medical care includes follow-up fundus examinations, visual acuity tests, and audiometry.

• In cases with widespread depigmentation, treatment with psoralen plus ultraviolet A (PUVA) can be provided. However, PUVA should be used with great caution in patients with anterior uveitis because phototherapy might aggravate the ocular inflammatory disorder.
• Topical steroids may be tried on localized areas of vitiligo. Patients with vitiligo should use sunscreen to prevent sunburn and subsequent skin cancer.
• See Vitiligo for more information about medical treatment.

Consultations

• Dermatologist
• Ophthalmologist
• Otolaryngologist

FOLLOW-UP

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Multimedia
• References

Further Outpatient Care

• Follow-up fundus examinations, visual acuity tests, and audiometry can be performed.
• These examinations may aid in the early detection of complications such as deafness and retinal detachment.

Deterrence/Prevention

• Because Alezzandrini syndrome is a rare disease of unknown etiology, no methods of prevention are yet known.

Complications

• A gradual loss of vision may occur.
• Deafness may occur.
• Retinal detachment is a possible complication.

Prognosis

• The prognosis currently is unclear because of the paucity of reports.
• Future clinical observations may help in elucidating this matter.

Patient Education

• Educate patients about this rare disease.
• Advise patients to use sunscreens to prevent sunburn and subsequent skin cancer.

MISCELLANEOUS

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Multimedia
• References

Medical/Legal Pitfalls

• The failure to perform a fundus examination may hinder appropriate diagnosis.
• The failure to routinely perform audiometry and fundus examinations may hamper the early detection of complications (eg deafness, retinal detachment).

Special Concerns

• Patients with diabetes mellitus should be closely monitored because they have an increased risk of retinal detachment as Hoffman and Dudley¹⁰ observed.

MULTIMEDIA

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Multimedia
• References

Media file 1:  Gray forelock and vitiligo on the forehead in a patient with Alezzandrini syndrome.
	View Full Size Image
Media type:  Photo

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Multimedia
• References

1. Casala AM, Alezzandrini AA. Vitiligo, poliosis unilateral con retinitis pigmentaria y hypoacusia. Arch Argent Dermatol. 1959;9:449.
2. Alezzandrini AA. [Unilateral manifestations of tapeto-retinal degeneration, vitiligo, poliosis, grey hair and hypoacousia]. Ophthalmologica. 1964;147:409-19. [Medline].
3. Barnes L. Vitiligo and the Vogt-Koyanagi-Harada syndrome. Dermatol Clin. Apr 1988;6(2):229-39. [Medline].
4. Vogt A. Fruhzeities ergraven der zilien und bemerkungen uber den sogenannten plotzlichen einendieser veranderugn. Klin Monatsbl Augenheilkd. 1906;44:228.
5. Gilbert W. Vitiligo und Auge, ein Beitrag zur Kenntnis der herpetischen augeenerkran kunger. Klin Monatsbl Augenheilkd. 1910;48:24.
6. Harada E. Clinical study of nonsuppurative choroiditis: A report of acute diffuse choroiditis. Acta Soc Opthalmol Jpn. 1926;30:356.
7. Koyanagi Y. Dysakusis, Alopecia, und Poliosis beschwerer Uveitis nicht traumatischen Ursprunge. Klin Monatsbl Augenheilkd. 1929;82:194.
8. Kodjikian L, Seve P, Le Hoang P, Garweg JG. Atypical Vogt-Koyanagi-Harada disease or new uveomeningitic syndrome?. Graefes Arch Clin Exp Ophthalmol. Mar 2005;243(3):263-5. [Medline].
9. Du L, Yang P, Hou S, Lin X, Zhou H, Huang X, et al. Association of the CTLA-4 gene with Vogt-Koyanagi-Harada syndrome. Clin Immunol. Apr 2008;127(1):43-8. [Medline].
10. Hoffman MD, Dudley C. Suspected Alezzandrini's syndrome in a diabetic patient with unilateral retinal detachment and ipsilateral vitiligo and poliosis. J Am Acad Dermatol. Mar 1992;26(3 Pt 2):496-7. [Medline].
11. Shamsadini S, Meshkat MR, Mozzafarinia K. Bilateral retinal detachment in Alezzandrini's syndrome. Int J Dermatol. Dec 1994;33(12):885-6. [Medline].
12. Lorincz AL. Disturbances of melanin pigmentation. In: Moschella SL, Hurley JH, eds. Dermatology. Philadelphia, Pa: WB Saunders; 1985.
13. Huggins RH, Janusz CA, Schwartz RA. Vitiligo: a sign of systemic disease. Indian J Dermatol Venereol Leprol. Jan-Feb 2006;72(1):68-71. [Medline].
14. Cremona AC, Alezzandrini AA, Casala AM. [Vitiligo, poliosis and unilateral macular degeneration.]. Arch Oftalmol B Aires. May 1961;36:102-6. [Medline].
15. Horie Y, Kitaichi N, Takemoto Y, Namba K, Yoshida K, Hirose S, et al. Polymorphism of IFN-gamma gene and Vogt-Koyanagi-Harada disease. Mol Vis. Dec 21 2007;13:2334-8. [Medline].
16. Horie Y, Namba K, Kitaichi N, Ohno S. Sister cases of Behcet's disease and Vogt-Koyanagi-Harada disease. Br J Ophthalmol. Mar 2008;92(3):433-4. [Medline].
17. Kawaguchi T, Yokota M, Sugita S, Mochizuki M. [Disc neovascularization in a patient with Vogt-Koyanagi-Harada disease and efficacy of steroid pulse therapy]. Nippon Ganka Gakkai Zasshi. Jan 2006;110(1):58-60. [Medline].
18. Kjeka O, Krohn J. [Vogt-Koyanagi-Harada disease]. Tidsskr Nor Laegeforen. Aug 25 2005;125(16):2195-7. [Medline].
19. Naughton GK, Eisinger M, Bystryn JC. Detection of antibodies to melanocytes in vitiligo by specific immunoprecipitation. J Invest Dermatol. Dec 1983;81(6):540-2. [Medline].

Article Last Updated: Apr 17, 2008