Ординатура / Офтальмология / Английские материалы / Handbook of Pediatric Eye and Systemic Disease_Wright, Spiegel, Thompson_2006

22% had melanoma. The frequency of melanomas, resembling the frequency of nonmelanoma skin cancers, anterior eye cancers, and tongue cancers but not that of internal neoplasms, was increased 1000 fold or more in patients with XP who were younger than 20 years. The authors suggested that DNA repair plays a major role in the prevention of cutaneous cancers in the general population, and that sunlight exposure is responsible for the induction of melanoma as well as nonmelanoma skin cancers in patients with XP, although acting by different mechanisms for the two types of skin cancer.

About 20% of patients with XP have neurological abnormalities that may be more common in certain complementation subgroups of the disease. The neurological abnormalities include mental retardation in 80% of cases; microcephaly in 35%; progressive sensorineural deafness in 20%; spasticity and late onset of ataxia and choreoathetoid movements; abnormal electroencephalogram in 11%; and loss of neurons in the cerebral cortex or demyelination of the dorsal columns.

Ocular complications are limited to the anterior segment of the eye and occur in 40% to 80% of patients. The majority of patients have photophobia. Conjunctivitis, keratitis, and dryness of the ocular surface are common. Lid lesions with ectropion or entropion may occur. Squamous cell carcinoma develops in 13% of patients64 and tends to involve the limbus and interpalpebral fissure area and to spread over the cornea. Conjunctival melanosis and melanoma have been described, as well as an angiosarcoma of the limbal area that developed in a granulomatous mass.13

Management of patients with xeroderma pigmentosum consists of protection from ultraviolet light and chemical carcinogens. Regular skin and ocular examination with photography are required with excision of suspicious tumors. More extensive surgical management such as dermabrasion, dermatome shaving, and skin transplantation may be required in advanced cases. Corneal complications of this disorder may require penetrating keratoplasty for visual rehabilitation. Surgery is rarely undertaken in these eyes because of multiple associated problems involving the ocular surface and the lids. Jalali et al.125 reported three cases of successful penetrating keratoplasty in xeroderma pigmentosum and reviewed 9 cases reported earlier. Successful grafts were initially achieved in all 12 eyes. Graft failure occurred due to an untreated rejection episode in only 1 eye. Another eye was treated by exenteration for recurrent ocular

malignancies. The authors recommended penetrating keratoplasty in carefully selected patients.

Oral retinoids have been demonstrated to prevent new neoplasms but the dosage was toxic. Survival is reduced because of the development of malignant neoplasms. Early detection and prophylaxis from ultraviolet light has resulted in a reduction of malignant tumors and improvement of survival. There is a 70% chance of survival to age 40 years.

Ectodermal Dysplasia

The ectodermal dysplasias are characterized by abnormal hair, teeth, and nails and decreased or absent sweating. Ectodermal dysplasia occurs either as an isolated condition or in association with other systemic abnormalities. Freire-Maia83 has catalogued more than 100 types of ectodermal dysplasias.

One condition of interest to the ophthalmologist is the association of ectodermal dysplasia with ectrodactyly and cleft lip/palate (EEC). Ectrodactyly refers to the absence of one or more digits derived from the central ray of the hand or foot, resulting in a cleft or lobster-claw deformity (Fig. 5-14).

The EEC syndrome was first described by Eckholdt and Martens in 1804 and was further delineated and named by Rudiger and coworkers.240 Since then, numerous cases have been reported but the exact incidence of this disorder is unknown. The mode of inheritance is autosomal dominant with incomplete penetrance. Although frequent, ectrodactyly is not essential for the diagnosis, and patients without facial clefting have a characteristic facial appearance with maxillary hypoplasia, a short philtrum, and a broad nasal tip.85 Genitourinary abnormalities are also a component of the EEC syndrome.234 Tucker and Lipson290 observed choanal atresia and vesicoureteric reflux in one patient. It seems that no sign is obligatory for the diagnosis.85 Anneren and coworkers5 suggested that low birth weight and polysyndactyly (without ectrodactyly) may be features of the EEC syndrome.

Patients with EEC are photophobic and have a chronic blepharitis. There is a reduction or absence of meibomian gland orifices at the lid margins, which results in decreased secretion of the oily component of tears and instability of the tear film. The lacrimal puncta, canaliculi, and lacrimal sacs are absent. Despite normal production of tears, the absence of oily secretion and instability of the tear film lead to a relative dry eye syndrome

A

B

FIGURE 5-14A,B. Total madarosis (loss of lashes) in an adult with ectrodactyly–ectodermal dysplasia–clefting (EEC) syndrome (A). Note absent and fused fingers resulting in lobster-claw hand deformity (B).

with corneal vascularization and scarring. The corneal problems may, however, be due to the underlying ectodermal dysplasia. Treatment icludes surgical correction of the cleft and limb anomalies. Ocular lubricants are used to stabilize the tear film and reduce corneal scarring.

Another rare condition of interest to the ophthalmologist is the ectodermal dysplasia–ectrodactyly–macular dystrophy (EEM) syndrome. It is inherited in an autosomal recessive fashion and characterized by sparse hair, small and missing teeth, terminal transverse limb defects, and macular pigmentary changes.1,202

Juvenile Xanthogranuloma

Juvenile xanthogranuloma (JXG) is a benign histiocytic inflammatory condition affecting mostly infants and children in the first few years of life. JXG does not evolve into any of the histiocytosis-X group of conditions. Its etiology is unknown, although there is some evidence that it may represent a histioxanthomatous response to local tissue injury. JXG is present at birth in 30% of cases. Most cases, however, are detected in the first 2 years of life.

Cutaneous lesions may be as few as two or three in number (Fig. 5-15) or as many as several hundred. The lesions characteristically involve the scalp, face, neck, upper trunk, and proximal upper extremities. Varying in size from 1 to 20 mm, skin lesions may be relatively flat or may be elevated. Lesions thin with time and turn from orange-yellow to brown in color and then disappear, leaving a hypoor hyperpigmented scar. Histo-

FIGURE 5-15. Multiple unusually large xanthogranulomas in a 10-year- old girl.

FIGURE 5-16. Hyphema in a 1-year-old girl with juvenile xanthogranuloma. Tumor is partially masked by hemorrhage in superior aspect of the iris.

logically, skin lesions are composed of nodules of histiocytic proliferation with foam cell formation. Touton giant cells with circularly arranged nuclei are characteristic.

Cutaneous and ocular lesions spontaneously regress over 3 to 6 years. Rarely, xanthomatous lesions have involved other tissues such as muscle, salivary glands, kidneys, testes, periosteum, bone, colon, ovaries, pericardium, and myocardium. Metabolic and radiologic evaluations of patients with JXG have been consistently normal.

Ocular lesions may precede, follow, or occur simultaneously with the skin lesions. Occasional bilateral cases have been recorded. The iris and ciliary body are most commonly involved, but choroidal and retinal lesions have been reported. Other locations include the lids, orbit, and extraocular muscles, and rarely the cornea, conjunctiva, and sclera. Iris lesions may be nodular or diffusely infiltrating. Because of their vascularity, iris lesions can spontaneously bleed, and JXG is a leading cause of spontaneous hyphema in childhood (Fig. 5-16). This event may lead to glaucoma that may be relatively resistant to medical therapy. Infants with JXG may present with an irritated red eye or with corneal enlargement and clouding because of glaucoma. Rarely, patients may have an asymptomatic iris nodule or heterochromia irides.

Treatment of JXG is only indicated in the case of uveal involvement to prevent serious ocular complications. Topical steroids with or without systemic steroids are used. Radiation therapy may be of benefit in very selected cases if other therapeutic measures fail.

Erythema Multiforme and

Stevens–Johnson Syndrome

Erythema multiforme is characterized by target-shaped skin lesions with or without erythematous macules, papules, wheals, bullae, and ulcerations of mucous membranes. The Stevens– Johnson syndrome refers to the severe form of erythema multiforme with extensive skin and mucous membrane involvement along with fever and affection of the kidneys, gastrointestinal tract, and central nervous system.269 The mortality rate from the Stevens–Johnson syndrome ranges from 5% to 20%.38 Both conditions affect primarily children and young adults, and while males and females are equally affected in erythema multiforme, more males are affected in Stevens–Johnson syndrome.

The disease is precipitated by infections or medications, most notoriously by herpetic infections, Mycoplasma pneumoniae, and sulfonamides. In many cases it is uncertain whether the medications or the infection for which they were given are the culprits. Histologically, there is a vasculitis that involves the superficial dermal vessels. Helper/inducer T lymphocytes and Langerhans’ cells predominate in the dermis whereas cytotoxic/suppressor cells are found in the epidermis. In the conjunctiva there is an immune complex vasculitis with infiltration of the substantia propria by helper/inducer T cells.6 The lesions of erythema multiforme typically involve the abdomen, the extensor surfaces of the legs and arms, and the dorsal aspects of the hands and feet. There usually is severe pruritus. The lesions, which usually appear in crops, subside within 2 to 6 weeks. Mucosal involvement occurs in about one-third of patients and affects the conjunctiva and buccal surfaces. The nose, genitalia, and anal region are rarely involved, but when they are stenosis may occur. Tracheal lesions occur in about 50% of patients with Stevens–Johnson syndrome and may result in constriction and asphyxiation; death, however, usually ensues from renal and central nervous system complications. Ten percent to 15% of patients with erythema multiforme have recurrences that are usually precipitated by herpetic infections. Episodic con-

junctival inflammation may also follow the Stevens–Johnson syndrome.74

In the ocular surface, squamous metaplasia and conjunctival scarring lead to a dry eye state, trichiasis, corneal ulceration, scarring, and neovascularization.

The treatment of erythema multiforme and Stevens– Johnson syndrome consists of carrying patients over the period when the disease is most severe and managing the complications of systemic involvement. Antipruritic agents are helpful. Antibiotics are used to treat underlying or precipitating infections. High-dose systemic steroids may be used but their value is doubtful. Topical corticosteroid drops started early may prevent conjunctival scarring. Tear supplementation, lubricants, and bandage contact lenses are used to treat the ocular surface disorder. Topical retinoic acid may be of some value because of the squamous metaplasia. Oral acyclovir may be used in recurrent disease if a relation to recurrent herpetic infections is established.

SKELETAL DYSPLASIAS AND

RELATED DISORDERS

Oculo-dento-osseous Dysplasia

Oculo-dento-osseous dysplasia (ODOD) is a malformation syndrome involving the hair, face, eyes, teeth, and bones.97,183 The mode of inheritance generally autosomal dominant but a recessive variety probably exists.90,282 Patients with ODOD have a characteristic facies with scarce eyebrows, narrow and short palpebral fissures, microcornea or microphthalmia, and a small nose with hypoplastic alae nasae and a prominent columella (Fig. 5-17A). The dental enamel is dysplastic, and microdontia or hypodontia may be present. Skeletal abnormalities are most prominent in the distal parts of the extremities with camptodactyly (position of permanent flexion) or syndactyly of the ulnar two or three digits; the toes are short and frequently lack second metatarsals (Fig. 5-17B). Other skeletal abnormalities include calvarial hyperostosis, a heavy mandible with an obtuse angle between the body and rami, plump clavicles, thickened ribs, and poorly tubulated long bones. Generalized hair abnormalities are manifested by hypotrichosis, trichorrhexis, and dry hair. Less common abnormalities include cleft lip/palate,

conductive hearing loss, hip dislocation, and osteopetrosis. Intellect is generally normal.

Lid abnormalities in ODOD include telecanthus and epicanthal folds in the majority of cases. Hypotelorism is present in 40% of cases.66 Convergent strabismus is a frequent finding. There may be anterior segment dysgenesis, and the eye may be of low normal size or microphthalmic.130 Anterior segment dysgenesis may be more severe in the rarer presumed recessive form of ODOD.282 Remnants of the pupillary membrane are frequently present. Cataracts have been reported in two cases.12,103 Posterior segment abnormalities have included remnants of the hyaloid system103,282 and increased numbers of retinal vessels at the optic disc.130

Glaucoma has been reported in a total of 12 patients with ODOD.285 Glaucoma can develop in ODOD at different ages and is caused by a variety of mechanisms, the most important of which is anterior segment dysgenesis. In infancy, it is probably due to trabeculodysgenesis. The onset of glaucoma in the patients reported by Meyer-Schwikerath,183 Weintraub et al.,302 and Dudgeon and Chisholm58 was in childhood or early adulthood. An adult-onset open-angle type of glaucoma may occur, such as in one member of the family reported by Dudgeon and Chisholm.58 Finally, angle-closure glaucoma has been reported by Sugar273 in one eye of one patient who had infantile glaucoma in the other eye and in another patient he had previously reported274; the mechanism in this situation appears to be the presence of a lens of normal size in a small globe with a crowded anterior segment. Glaucoma is the most common cause of visual loss in patients with ODOD. Regular intraocular pressure measurements should be initiated as early as possible after diagnosis, especially in the presence of tearing, photophobia, and hazy or enlarged corneas. The management of glaucoma in ODOD patients is difficult, and multiple surgeries may be required.

Osteopetrosis (Albers–Schonberg Disease)

In osteopetrosis, failure of bone absorption occurs because of a defect in osteoclast function; this results in generalized bone sclerosis and the formation of bone that is more brittle than normal. There are characteristic radiologic findings, especially in the infantile form of the disease, with a sandwich appearance to the vertebral bodies and a masklike appearance to the skull. Two main categories are recognized: a more benign, autosomal dominant form, which is diagnosed in adulthood, and a severe,

autosomal recessive, “malignant” infantile category that is probably heterogeneous. Patients with the adult form are diagnosed when X-rays are taken for other reasons or when they present with fractures from minimal trauma. In the infantile form of malignant osteopetrosis, which occurs in about 0.5 to 1 per 100,000 live births, there is extramedullary hematopoiesis when bone marrow spaces are obliterated; this leads to hepatosplenomegaly, frontal bossing, anemia, thrombocytopenia, and their complications. Another form of recessive infantile osteopetrosis that results from a deficiency of the enzyme carbonic anhydrase II features renal tubular acidosis and cerebral calcifications with milder skeletal affection than the lethal type.150,263 A third and milder form of recessive osteopetrosis also exists with short stature, macrocephaly, disproportionate shortness of the limbs, recurrent fractures, and mild to moderate anemia.132

Deafness and optic atrophy occur secondary to a generalized thickening of calvarial bones that narrow the foramina transmitting cranial nerves, especially the third, fourth, and seventh nerves. Patients may have anosmia and facial palsy. A retinal dystrophy has also been reported in the recessive form of the disease, in addition to the compressive optic neuropathy may contribute to visual loss.139,239 Decreased vision leads to nystagmus and strabismus. Because of the bony abnormalities in the skull, patients with the infantile type of osteopetrosis have widely spaced eyes and may develop exophthalmos.

High doses of calcitriol and a low-calcium diet may increase osteoclast activity.140 Bone marrow transplantation has been used successfully in a few patients with the infantile form of the disease.39

Other Related Systemic and

Craniofacial Disorders

See Chapter 5 for discussion of mandibulofacial dysostosis (Treacher Collins syndrome), oculoauriculo-vertebral dysplasia (Goldenhar’s syndrome, hemifacial microsomia), Waardenburg syndrome, and Hallermann–Streiff–François syndrome (oculomandibulofacial syndrome, François’ dyscephalic syndrome).

References

1.Albrectsen B, Svendsen IB. Hypotrichosis, syndactyly, and retinal degeneration in two siblings. Acta Dermato-Venereol 1956;1:96–101.