Resolution of acne following therapy with an oral contraceptive in a patient with Apert syndrome

Abstract

To the Editor: Apert syndrome is a genetic disorder characterized by irregular craniosynostosis, midfacial hypoplasia, syndactyly, and severe, difficult-to-control widespread acne, usually requiring isotretinoin treatment.1Jones K.L. Smith D.W. Smith's recognizable patterns of human malformation. W.B. Saunders Company, Philadelphia1996Google Scholar To our knowledge, our patient represents the first reported case of Apert syndrome whose severe acne resolved dramatically following therapy with an oral contraceptive. A female patient with Apert syndrome was first seen in the dermatology clinic at 15 years of age with a history of severe acne for 2 years, involving her face, chest, back, abdomen, and arms (Fig 1, A). She had tried various topical medications and oral erythromycin without good response. Oral isotretinoin was recommended as first line. However, given her family's concerns with the side effects, oral minocycline, and adapalene cream were started with mild improvement. At 17 years of age, she was started on a triphasic oral contraceptive (norgestimate/ethinyl estradiol) for a large ovarian cyst. Consequently, she saw dramatic improvement in her acne. The improvement was maintained as she continued on the oral contraceptive one year later with no adjunctive therapies (Fig 1, B). Apert syndrome is inherited in an autosomal dominant fashion; however, the vast majority of the cases are sporadic. The prevalence is approximately 15.5/1,000,000 births, and it affects both sexes in the same ratio. There is a significant association with advanced paternal age, and mutations occur on the paternal chromosome. Mutations in the fibroblast growth factor receptor 2 gene (FGFR2), which maps to chromosome 10q25-10q26, cause Apert syndrome. Specific missense substitutions involving adjacent amino acids (Ser252Trp and Pro253Arg) in the linker between the second and third extracellular immunoglobulin domains of the FGFR2 (exon IIIa) cause the majority of cases.1Jones K.L. Smith D.W. Smith's recognizable patterns of human malformation. W.B. Saunders Company, Philadelphia1996Google Scholar, 2Munro C.S. Wilkie A.O. Epidermal mosaicism producing localized acne: somatic mutation in FGFR2.Lancet. 1998; 352: 704-705Abstract Full Text Full Text PDF PubMed Scopus (110) Google Scholar The dermatologic hallmark of Apert syndrome is severe inflammatory and comedonal acne, involving the face, chest, back, and also unusual areas such as the forearms, buttocks, and thighs.3Cohen M.M. Kreiborg S. Cutaneous manifestations of Apert syndrome.Am J Med Genet. 1995; 58: 94-96Crossref PubMed Scopus (44) Google Scholar FGFR2 is hypothesized to be involved in its pathogenesis.2Munro C.S. Wilkie A.O. Epidermal mosaicism producing localized acne: somatic mutation in FGFR2.Lancet. 1998; 352: 704-705Abstract Full Text Full Text PDF PubMed Scopus (110) Google Scholar This acne is often resistant to conventional therapies. Five previous case reports have reported isotretinoin to be useful in controlling acne in Apert syndrome, though high doses and repeated or prolonged courses were required.4Parker T.L. Roth J.G. Esterly N.B. Isotretinoin for acne in Apert syndrome.Pediatr Dermatol. 1992; 9: 298-300Crossref PubMed Scopus (15) Google Scholar The efficacy of oral contraceptives to improve acne in healthy adolescents has been reported in many studies, including recent multicenter, randomized, placebo-controlled trials. Oral hormonal contraceptives affect acne in several ways. Estrogen improves acne by increasing levels of sex hormone-binding globulin (SHBG), thus decreasing free testosterone, and by suppressing gonadotropin secretion, thus reducing ovarian androgen production.5Lucky A.W. Henderson T.A. Olson W.H. Robisch D.M. Lebwohl M. Swinyer L.J. Effectiveness of norgestimate and ethinyl estradiol in treating moderate acne vulgaris.J Am Acad Dermatol. 1997; 37: 746-754Abstract Full Text Full Text PDF PubMed Scopus (185) Google Scholar The progestin norgestimate used in this case has a low binding affinity for androgen receptors and SHBG. Patients with Apert syndrome are found to have an abnormal sensitivity to normal circulating levels of androgens. Thus, the antiandrogenic action of oral contraceptives would plausibly explain the underlying mechanism in controlling acne in Apert syndrome.