mitte’s sign, herpes zoster infection, hypothyroidism and infertility.

Radiation therapy-induced complications with ocular impact include lid edema, loss of lid lashes, insufficient or excessive tearing, keratitis, conjunctivitis, iritis, lens edema, cataract, retinopathy, optic neuropathy and trigeminal sensory neuropathy.

Chemotherapeutic toxicities vary with the regimen and dose and include fatigue, hair loss, nausea, myelosuppression, pulmonary impairment, peripheral neuropathy and infertility.

Ocular complications of chemotherapy used in Hodgkin’s disease include keratitis, conjunctivitis, uveitis, retinal hemorrhage, neuroretinitis, ocular motor nerve palsies, cortical visual loss and possibly optic neuropathy.

The most serious complication of radiation or chemotherapy is the development of a second malignancy. Secondary malignancies include acute leukemia or other myelodysplasias, which usually occur within 1 to 2 years after treatment, and a variety of solid carcinomas of the lung (the most common second malignancy), breast, thyroid, head, neck and stomach, sarcomas and melanoma, which may develop after a latency period of many years.

COMMENTS

The treatment of Hodgkin’s disease is continuously progressing. A clear understanding of the pathogenesis remains a challenge. When ocular complications occur, close cooperation is required among the ophthalmologist, pathologist, medical oncologist and radiation oncologist to achieve the best result for the patient.

REFERENCES

Barkana Y, Zadok D, Herbert M, et al: Granulomatous kerato-conjunctivi- tis as a manifestation of Hodgkin lymphoma. Am J Ophthalmol 131:796–797, 2001.

Connors JM: State-of-the-art therapeutics: Hodgkin’s lymphoma. J Clin Oncol 23:6400–6408, 2005.

Diehl V, Thomas RK, Re D: Part II: Hodgkin’s lymphoma-diagnosis and treatment. Lancet Oncol 5:19–26, 2004.

Kasner SE, Galetta SL, Vaughn DJ: Cavernous sinus syndrome in Hodgkin’s disease. J Neuroophthalmol 16:204–207, 1996.

Klapper SR, Jordan DR, McLeish W, et al: Unilateral proptosis in an immunocompetant man as the initial clinical manifestation of systemic Hodgkin disease. Ophthalmology 106:338–341, 1999.

Nasir MA, Jeffe GJ: Cytomegalovirus retinitis associated with Hodgkin’s disease. Retina 16:324–327, 1996.

Thakker MM, Perez VL, Moulin A, et al: Multifocal nodular episcleritis and scleritis with undiagnosed Hodgkin’s lymphoma. Ophthalmology 110:1057–1060, 2003.

To TW, Rankin GA, Jakobiec FA, Hidayat AA: Intraocular lymphoproliferations simulating uveitis. In: Albert DM, Jakobiec FA, eds. Principles and practices of ophthalmology. 2nd edn. WB. Saunders, 2000:2(98): 1315–1338.

Yung L, Linch D: Hodgkin’s lymphoma. Lancet 361:943–951, 2003.

130 JUVENILE XANTHOGRANULOMA

224.0

(JXG)

Theodore H. Curtis, MD

Portland, Oregon

David T. Wheeler, MD

Portland, Oregon

Juvenile xanthogranuloma (JXG) is a rare, generally benign, skin disorder of uncertain etiology that typically affects infants and young children, and very rarely presents in adults. It was first described by Adamson in 1905 as ‘congenital xanthoma multiplex’ and the first case with intraocular involvement was a child reported by Blank in 1949. It is characterized by single or multiple discreet, firm, rubbery, yellowish-pink to tan papulonodules several millimeters in diameter, preferentially occurring on the head and neck but also seen on the trunk and extremities. Skin lesions often regress spontaneously and are not usually associated with systemic manifestations.

Extracutaneous manifestations have been described in eye, lung, liver, pericardium, myocardium, spleen, colon, retroperitoneum, kidney, adrenal gland, gonads, central nervous system, bone, periostium, muscle, mucous membranes, salivary glands and larynx. The eye is the most frequently affected extracutaneous site, with an incidence of 0.3% to 0.5% in cutaneous JXG. Approximately 40% of patients with ocular involvement have cutaneous lesions, usually multiple. In patients with visceral involvement, cutaneous lesions are always multiple and ocular involvement is rare.

Ocular involvement occurs most often during the first two years of life. Uveal JXG is the most common presentation and can include a localized or diffuse iris tumor (heterochromia iridis), spontaneous hyphema, secondary glaucoma, erythema and uveitis. Additional sites of ocular involvement are much less common and include eyelids, cornea, limbus, conjunctiva, sclera, orbit, retina, choroid and optic nerve. Epibulbar lesions have been known to extend into the anterior chamber. Orbital lesions are rare and may occur with or without bony destruction; most present in the perinatal period. Most cases are unilateral, but bilateral involvement has been reported. Spontaneous regression of ocular lesions without medical intervention has been described rarely. Skin lesions develop after those in the eye or orbit in up to 45% of affected patients.

Associations have been noted with neurofibromatosis, epilepsy, Niemann–Pick disease, urticaria pigmentosa, insulindependent diabetes mellitus, leukemic disorders and cytomegalovirus infections. All but the association with neurofibromatosis and some leukemias are probably coincidental. A triple association with neurofibromatosis (type 1), juvenile chronic myelogenous leukemia and JXG has been well described. No lipid abnormality or other metabolic disturbances have been reported.

Langerhans-dendritic (antigen-presenting) pathways. JXG is thought to be a disorder of macrophages. Other benign proliferative macrophage disorders such as benign cephalic histiocytosis, papular xanthoma and progressive nodular histiocytosis are probably clinical variants of the same underlying process. These tumors usually do not stain with S100 and lack Birbeck granules, which are typical of the ‘histiocytosis X’ group of diseases such as Hand–Schuller–Christian, Letterer–Siwe and eosinophilic granuloma. JXG is a clinically distinct entity and not a member of this family of diseases, which have vastly different clinical and pathologic findings.

The incidence of JXG is unknown but may be higher than reported as it often occurs early in life, may be mistaken for a ‘mole’ and may spontaneously regress. In cutaneous JXG, a male predominance (1.5 : 1) has been noted in childhood but there is no reported sex predilection in adults. There is no known ethnic predisposition. Tumors are present at birth in 5% to 17% and occur during the first year of life in 40% to 70%. Adult onset is infrequent with a peak incidence in late twenties and early thirties. Familial cases have not been observed.

COURSE/PROGNOSIS

Spontaneous regression of skin lesions is well documented but the natural history of ocular lesions is less well understood. JXG is an important cause of spontaneous hyphema in childhood. Secondary glaucoma and blindness can occur. Visual prognosis of anterior uveal involvement depends on prompt recognition of the disease and early resolution of the lesion. With orbital lesions, prognosis varies with the extent of orbital and optic nerve involvement and the degree of secondary fibrosis.

that cause iris neovascularization (such as juvenile retinoschisis) or diseases characterized by pupillary or retrolental membranes (like retinopathy of prematurity or persistent fetal vasculature).

TREATMENT

Ocular

●For patients with skin lesions only, careful ophthalmic follow-up but no active intervention is indicated.

●Ocular involvement limited to eyelids or epibulbar tissue also does not require specific treatment but close observation for uveal lesions is necessary.

●Topical, intralesional and systemic corticosteroids have been used successfully for intraocular and orbital JXG. Diffuse or localized uveal lesions should probably be treated initially with topical medication but systemic treatment should be added if there is no response in several weeks. Intralesional steroids may be effective in orbital lesions (dexamethasone 4 mg and betamethasone 6 mg).

●Radiotherapy is recommended for diffuse uveal lesions or those associated with glaucoma, and for any lesions that fail to respond to corticosteroids. Dramatic response can occur to low doses of 250 to 400 cGy, usually 100 to 200 cGy per dose spread over 2 or 3 weeks. Total dose of greater than 500 cGy may increase the risk of radiation damage to normal structures.

●Surgery is reserved for well-localized iris lesions less than one quadrant in size. The benefit of tissue diagnosis must be weighed against the risks of hyphema and lens damage, particularly as these lesions are often extremely sensitive to steroids and radiation.

taining densely packed polyhedral histiocytes with abundant cytoplasm that exhibits varying degrees of vacuolization, occasional Touton multinucleated giant cells and a prominent network of thin-walled vessels.

●Perivascular edema, duplication of capillary basement membranes, and endothelial cell swelling and degeneration suggest an inflammatory process.

Differential diagnosis

●Many dermatologic diseases can be confused with JXG on clinical examination (see Tanz for a comprehensive listing).

●The ocular lesions of JXG must be differentiated from dermoid, dermolipoma, neurofibroma, fibrous histiocytoma, Langerhans’ granulomatoses and xanthoma disseminatum (see Yanoff for a more complete listing).

●Spontaneous hyphema in infancy may also be caused by unsuspected or unreported trauma, any intraocular tumor involving the anterior segment (including retinoblastoma, medulloepithelioma, leukemia and lymphoma), diseases

detachment leading to blindness.

COMMENTS

Screening for ocular involvement is controversial due to its relatively low incidence; however, over half the patients with both ocular and cutaneous involvement have skin lesions first. In addition, these patients nearly always have multiple skin lesions and are usually younger than 2 years of age (92%). It would therefore be reasonable and cost-effective to refer only this subgroup of higher risk patients, i.e. patients less than 2 years old with multiple cutaneous lesions, to an ophthalmologist.

REFERENCES

Blank H, Eglick P, Beerman H: Nevoxanthoendothelioma with ocular involvement. Pediatrics 4:349–354, 1949.

These chemotherapeutic regimens are associated with a dismal prognosis, but the introduction of highly active antiretroviral therapy has changed the course of the disease.

Topical

Drugs suggested for intralesional chemotherapy are bleomycin, vinblastine, interferon and inteleukine 2.

132 KERATOACANTHOMA 238.2

F. Hampton Roy, MD, FACS

Little Rock, Arkansas

Surgical

Smaller lesions may be treated by electrodessication and curettage or surgical excision.

Cryotherapy

This technique is indicated in cases of palpebral lesions less than 1 cm in diameter.

Radiation

The KS lesions are generally radio-sensitive. Radiotherapy is likely to lead to a cicatrizing course of the external eye (external beam radiation) and lacrimal outflow system. The total dose is between 2000 cGy to 3000 cGy divided into 200–300 cGy a time for 3 weeks.

COMPLICATIONS

The major complicating factor in local treatment of KS is the relatively high rate of tumor recurrence – 29%–66% cases. The most frequent complication of the systemic treatment is the aggravation of the immunodepression for the worse.

COMMENTS

The evolution of disease depends on the epidemiological-clini- cal type of KS and its clinical extent in general. It is a very slowly developing disease, and the treatment should aim first at correcting a potential functional or aesthetic gene. The treatment should avoid the development of dangerous immunosuppression in patients.

REFERENCES

Christopher DM, Fletcher K, Krishnan U, Fredrik M: Pathology and genetics of tumors of soft tissue and bone. International agency for research of cancer IARC Press, Lyon, 2002.

Collaco L, Goncalves M, Gomes L, Miranda R: Orbital Kaposi’s sarcoma in acquired immunodeficiency syndrome. Eur J Ophthalmol 10(1):88– 90, 2000.

Corti M, Solari R, de Carolis L, Corraro R: Eye involvement in AIDS-related Kaposi sarcoma. Enferm Infec Microbiol Clin 19(1):3–6, 2001.

Heimann H, Kreusel KM, Foerster MH, et al: Regression of conjunctival Kaposi’s sarcoma under chemotherapy with bleomycin. Br J Ophthalmol 81(11):1019–1020, 1997.

Munteanu G, Munteanu M, Giuri S: Conjunctival-palpebral Kaposi’s angiosarcoma: report of a case. J Fr Ophtalmol 26(10):1059–1062, 2003.

Schmid K, Wild T, Bolz M, et al: Kaposi’s sarcoma of the conjunctiva leads to a diagnosis of acquired immunodeficiency syndrome. Acta Ophthalmol Scand 81(4):411–413, 2003.

Souhail H, Albouzidi A, Laktaoui A, et al: Orbital location of Kaposi’s sarcoma. J Fr Ophtalmol 26(10):1071–1074, 2003.

ETIOLOGY/INCIDENCE

Keratoacanthoma is a benign epithelial tumor that arises in hair follicles in exposed skin of white patients. The majority of these tumors are solitary, occur on the face (including the eyelids and rarely the conjunctiva), where they may become unusually aggressive.

Keratoacanthomas occur in several different subtypes.

●The Ferguson Smith type consists of multiple self-healing keratoacanthomas of the skin and may appear in childhood or early adolescence.

●The Grzybowski-type keratoacanthomas are smaller (2 to 3 mm in diameter) and do not appear until adulthood.

●The Witten Zak variant combines characteristics of both the larger self-healing Ferguson Smith type and the multiple miliary Grzybowski keratoacanthomas.

●A giant, massive, or confluent keratoacanthoma is believed to result from the fusion of small, closely spaced tumors.

●In keratoacanthoma centrifugum marginatum, multiple keratoacanthomas appear at the periphery of a progressively expanding lesion with central scar formation; unlike solitary keratoacanthomas, this variant has no tendency to involute spontaneously.

●Muir–Torre syndrome is an autosomal dominant genodermatosis consisting of multiple keratoacanthomas and sebaceous skin tumors associated with up to 40% incidence rate of internal malignancies, especially adenocarcinoma of the colon.

The etiology of keratoacanthoma is unknown. Most lesions occur on sun-exposed areas of light-skinned individuals. Keratoacanthomas may occur:

1.In patients with xeroderma pigmentosa;

2.In immunologically compromised patients (e.g. transplant recipients and patients with metastatic cancer, leukemia, lymphoma or acquired immune deficiency syndrome);

3.In industrial workers exposed to mineral oils, pitch or tar; and

4.In patients treated with psoralen plus ultraviolet A light therapy.

Exposure to chemical carcinogens, immunologic depression and a hereditary component have been suggested as possible causes in some patients.

DIAGNOSIS

Clinical signs and symptoms

The usual solitary keratoacanthoma has the following manifestations.

●The onset is sudden.

●Growth is rapid, possibly reaching 1 to 2 or more cm in diameter in 6 to 8 weeks.