This Month in Archives of Dermatology

THIS MONTH IN ARCHIVES OF DERMATOLOGY

SECTION EDITOR: ROBIN L. TRAVERS, MD

Heterozygosity for a Single X-Linked Ectodermal Dysplasia With Immunodeficiency Mutation in the ABCC6 Gene Caused by NEMO Mutation May Closely Mimic PXE -linked ectodermal dysplasia with immu- seudoxanthoma elasticum X nodeficiency (XL-EDA-ID) is character- P (PXE) is an inherited connec- ized by hypohidrosis, dental anomalies, alope- tive tissue disorder characterized his- cia, and immunodeficiency and is associated with tologically by fragmented elastic fi- hypomorphic mutations in IKBKG, which codes bers. Homozygous mutations in for NEMO (nuclear factor-␬B essential modu- ABCC6 have been identified as caus- lator). Male patients with NEMO mutations are ative for PXE, and characterization of difficult to diagnose in infancy. In this case re- these mutations has allowed clarifi- port, Mancini et al describe a male infant with cation of the various PXE subtypes. XL-EDA-ID whose mother reported a history of In this case series, Martin et al de- incontinentia pigmenti with mild expressivity. scribe individuals with heterozy- The authors describe the relationship of hetero- gous ABCC6 mutations who demon- zygous large-scale deletions of IKBKG mutation to incontinentia pigmenti, strate symptoms of PXE, suggesting as opposed to the hypomorphic mutations in IKBKG in which some NEMO a phenotype overlap between hetero- function is preserved resulting in the XL-EDA-ID phenotype in affected males. zygous carriers and some patients See page 342 with PXE. Heterozygous individuals may rarely demonstrate the severe A Human Papillomavirus–Associated Disease With ophthalmologic and cardiovascular Disseminated Warts, Depressed Cell-Mediated Immunity, manifestations of PXE. Such hetero- Primary Lymphedema, and Anogenital Dysplasia: zygous patients should be consid- WILD Syndrome ered to have PXE by definition, and physicians should initiate appropri- pidermodysplasia verruciformis (EV) is a rare genodermatosis charac- ate clinical follow-up of heterozy- terized by a generalized infection with human Betapapillomavirus spe- gous ABCC6 mutation carriers. E cies and an increased risk of squamous cell carcinomas in sun-exposed areas. See page 301 In this case report, Kreuter et al describe a 37-year-old woman with primary lymphedema; depressed, cell-mediated immunity; and persistent, generalized warts other than the EV-defining Betapapillomavirus species. In addi- “Nagashima-Type” tion, the typical histologic features of EV were missing. This combination of Keratosis as a Novel Entity clinical findings was sufficiently similar to that of a 1987 report to suggest that it might be representative of a previously undescribed syndrome, dis- he palmoplantar keratoses tinct from EV and characterized by warts, depressed immunity, lymph- T (PPKs) include a heteroge- edema, and anogenital dysplasia (WILD syndrome). neous group of disorders difficult to See page 366 classify because of interindividual and intraindividual variations and A Romanian Population Isolate With High Frequency differences in nomenclature. Based of Vitiligo and Associated Autoimmune Diseases on accepted classification schemes, the diffuse autosomal recessive itiligo is an acquired disorder of patchy skin depigmentation, several sub- hereditary PPKs include mal de V types of which may be distinguished clinically. Melanocyte destruction Meleda, Gamborg-Nielsen type, in this disorder seems to have an autoimmune basis, and a major goal in vitiligo “Nagashima type,” and acral kera- research remains the identification of key disease processes and pathways that toderma. Almost 20 cases of Na- might present novel therapeutic targets. In this prospective and retrospective gashima-type PPK have been re- study, Birlea et al describe a population of 51 patients with vitiligo and their close ported from Japan, but this disease relatives from a geographically isolated and inbred community in the moun- remains poorly recognized else- tains of northern Romania in which there is a greatly elevated frequency of viti- where in the world. In this case re- ligo. The age at onset of vitiligo is relatively delayed, suggesting that the cause port, Kabashima et al describe a 17- of vitiligo may be somewhat atypical in this community. Genetic segregation year-old with Nagashima-type PPK analysis was consistent with a single major locus recessive model, although in- and carefully differentiate the clini- complete reentrance and heritability suggest that other genes and environmen- cal and genetic findings from those tal factors may influence the disease phenotype. of mal de Meleda PPK. See page 310 See page 375

(REPRINTED) ARCH DERMATOL/ VOL 144 (NO. 3), MAR 2008 WWW.ARCHDERMATOL.COM 296