Alezzandrini Syndrome 

Updated: Apr 20, 2020
Author: Camila K Janniger, MD; Chief Editor: William D James, MD 

Overview

Background

In 1959, Casala and Alezzandrini[1] 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, Alezzandrini[2] 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, Vogt[4] reported a patient with nontraumatic uveitis, poliosis, and alopecia. He hypothesized that the uveitis and poliosis were due to a single disease process. In 1910, Gilbert[5] described a patient who had generalized vitiligo followed by bilateral uveitis and optic neuritis. In 1926, Harada[6] 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, Koyanagi[7] 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, as exemplified by a patient with progressive depigmentation, uveitis and meningitis.[9, 10]

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.[11] A study from China found TNFAIP3 gene polymorphisms in a Chinese Han population with Vogt-Koyanagi-Harada syndrome.[12]

Etiology

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

Epidemiology

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 Dudley[13] 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 associates[14] described bilateral retinal detachment in a patient with Alezzandrini syndrome.

International

Alezzandrini syndrome, in its classic description, is extremely rare. Vogt-Koyanagi-Harada syndrome tends to occur in those with darker skin pigmentation. Asians, Native Americans, and Hispanics are most often affected.[15]

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.

Prognosis

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

Prognostic factors for Vogt-Koyanagi-Harada disease in Singapore were analyzed.[16] Early high-dose systemic corticosteroid therapy reduced inflammation, and, like a younger age at onset, was also associated with a better outcome.

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.

Patient Education

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

 

Presentation

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. This disorder may be first evident with unilateral vitiligo on the cheek and partial loss of hearing and vision on the same side.[17]

Alopecia areata is a common disorder that has been described in association with Vogt-Koyanagi-Harada syndrome.[18] One should delineate the alopecia and poliosis linked with Vogt-Koyanagi-Harada syndrome from alopecia areata. Vogt-Koyanagi-Harada disease may be first evident as a headache.[19, 20]

Physical Examination

Alezzandrini syndrome is characterized by unilateral tapetoretinal (retinal pigmented epithelia) degeneration with the ipsilateral appearance of facial vitiligo and poliosis, as shown in the image below.

Gray forelock and vitiligo on the forehead in a pa Gray forelock and vitiligo on the forehead in a patient with Alezzandrini syndrome.

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. Lorincz[21] 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. Two most highly specific, at least in those with Vogt-Koyanagi-Harada disease, are exudative retinal detachment during acute disease and sunset glow fundus during the chronic phase of the disease.[22]

Congenital leukoderma suggests the need for evaluation of ocular, auditory, and/or neurologic abnormalities.[23] Poliosis may be acquired in vitiligo, Vogt-Koyanagi-Harada syndrome, Alezzandrini syndrome, and sarcoidosis. However, vitiligo patients have more lenticular and retinal changes than one should anticipate.[24]

A patient was described with a large hyperpigmented macule suggestive of an ipsilateral café-au-lait spot on the neck.[25]

 

DDx

Diagnostic Considerations

Vitiligo with Alezzandrini syndrome may be confused with other systemic disorders and disorders of depigmentation, including tuberous sclerosis, progressive systemic sclerosis (scleroderma), and, in endemic regions, leprosy.[26, 27]  Also consider choroidal lymphoma.[28]

Differential Diagnoses

 

Workup

Laboratory Studies

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

Other Tests

Fundus examination is indicated. Fundus autofluorescence and spectral domain-optical coherence tomography imaging may facilitate improved assessment of retinal pigment epithelium and the outer retina.[29] Visual acuity test may be performed.

Audiometry may be required.

For Vogt-Koyanagi-Harada syndrome and other entities associated with uveitis, the positive predictive value of routinely applied HLA typing as a diagnostic test was judged to be of limited usefulness.[30]

 

Treatment

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. As for uveitis in this syndrome, interleukin 6 therapy may be an option.[31]

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. Intravitreal bevacizumab injection has been reported.[32]

Limited experience suggests that infliximab as adjunctive therapy may be of benefit in reducing systemic corticosteroid dosage, at least in those with Vogt-Koyanagi-Harada syndrome.[33] A study comparing cyclosporine/mycophenolate mofetil and cyclosporine/azathioprine in Vogt-Koyanagi-Harada patients delineated no statistically significant difference in efficacy or safety.[34, 35] When untreated from early stages, severe iris depigmentation and ocular hypotony may develop.[36]

Consultations

Consultation with the following specialists may be needed:

  • Dermatologist

  • Ophthalmologist

  • Otolaryngologist

Complications

A gradual loss of vision may occur. Deafness may occur. Retinal detachment is a possible complication. Patients with diabetes mellitus should be closely monitored because they have an increased risk of retinal detachment, as Hoffman and Dudley observed.[13]

Prevention

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

Long-Term Monitoring

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.