New York University Department of Dermatology
This 51-year-old man presented to the Charles C. Harris Skin and Cancer Pavilion for treatment of warts on the face. During the physical examination, yellow, indurated plaques with a peau d'orange surface were scattered on the arms. There were no lesions on the neck or torso. He denied pruritus, pain, or any symptoms at the sites. The patient was referred to an ophthalmologist.
Past medical history includes end-stage renal failure of unknown etiology that required hemodialysis. He underwent a cadaveric renal transplantation that failed and was subsequently removed. Medications include prednisone 5 mg. every other day, hydroxychloroquine, simvastatin, famotidine, calcium acetate, erythropoietin, and calcitriol. He had no known drug allergies.
Yellow, indurated plaques with a peau d'orange surface, some with erythema, were scattered on the arms.
A blood chemistry profile showed a sodium of 134 meq/L, chlorine 90 meg/L , blood urea nitrogen 71 mg/dl, creatinine 14.6 mg/dl, and a hematocrit 35.6% with a normal white-cell and platelet counts. Liver function tests were normal. Amylase was elevated at 178 U/L and lipase was 545 U/L. Echocardiography demonstrated a normal left ventricular ejection fraction with mild left ventricular hypertrophy.
Irregular aggregates of clumped, thickened, elastic fibers are present in the papillary and reticular dermis. A von Kossa stain demonstrates calcification of these fibers.
Electron microscopy demonstrates aggregates of granular, amorphous electron-dense material, which is consistent with calcium deposits in bundles of elastic fibers. In longitudinal sections, elastic fibers are seen to be encrusted and/or impregnated with calcific deposits and are surrounded by finely granular and filamentous material.
Pseudoxanthoma elasticum, or Gronblad-Strandberg syndrome, is a systemic, genetic disorder of connective tissue that is characterized by progressive calcification of abnormal elastic fibers in the skin, blood vessels, and Bruch's membrane in the eye. Prevalence has been estimated to range from 1 in 100,000 to 160,000. All races are affected, and the female-to-male ratio is 2:1. The inheritance is usually autosomal recessive but may be autosomal dominant or sporadic. At least three recessive and two dominant subtypes have been described. Cutaneous lesions occur in the second or third decade of life; the average age of onset of skin findings is 13.5 years. Signs of vascular disease may be noted by age 30. Ocular signs may not present early in life but are found in nearly all affected adults.
Clinically, yellow papules that coalesce into plaques with a plucked chicken skin or cobblestone appearance occur in flexural regions, most commonly the neck and axillae. Other areas of involvement include the antecubital fossae, popliteal fossae, inguinal regions, and periumbilical regions as well as the oral, rectal and vaginal mucosae. The disorder may progress to involve the entire integument. Later in the course of the disease, redundant folds of skin may develop, especially of the neck, axillae, and groin.
Vascular complications include intermittent claudication, angina pectoris, abdominal angina, hypertension, and gastrointestinal hemorrhage. Angioid streaks, which are red-to-brown, curvilinear bands that radiate from the optic disk, occur in 85% of patients. Complications from the damage to Bruch's membrane include retinal hemorrhage, retinal detachment, and visual impairment. Other ocular findings include a yellow mottling of the posterior pole (leopard spotting), drusen, and a reticular pigmentary pattern in the retina. There may be an increased risk of miscarriage in the first trimester in women.
The locus of pseudoxanthoma elasticum has been mapped to an approximately 500-kb interval on chromosome 16p13.1. Pathogenetic mutations in MRP6, which is a member of the MRP (multiple drug resistance associated protein) family of the ABC (ATP-binding casette) transmembrane transporters, has been reported in kindreds with pseudoxanthoma elasticum.
The most important aspect of management of patients with pseudoxanthoma elasticum is evaluation for cardiovascular and ophthalmologic sequelae. Genetic counseling is indicated for the patient's relatives.
ReferencesLebwohl M, et al. Classification of pseudoxanthoma elasticum: report of a consensus conference. J Am Acad Dermatol 30:103, 1994
Sherer DW, et al. Pseudoxanthoma elasticum: an update. Dermatology 199:3, 1999
Cai L, et al. A 500-kb region on chromosome 16p13.1 contains the pseudoxanthoma elasticum locus: high-resolution mapping and genomic structure. J Mol Med 78:36, 2000
Ringpfeil F, et al. Pseudoxanthoma elasticum: mutations in the MRP6 gene encoding a transmembrane ATP-binding cassette (ABC) transporter. Proc Natl Acad Sci (USA) 97:6001, 2000
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