Book Review

Cutaneous Allergy

N Engl J Med 1997; 337:504August 14, 1997

Article

Cutaneous Allergy
Edited by Ernest N. Charlesworth. 363 pp., illustrated. Cambridge, Mass., Blackwell Science, 1996. $150. ISBN: 0-86542-370-9

The skin has a love–hate relationship with T cells. Usually, the liaison works well, protecting the body's outer sheath from invading organisms and incipient cancers. When it sours, the range of destructive autoreactive, inflammatory, and allergic disorders is daunting.

As the interface between our internal and external environments, the integument is constantly challenged by a wide range of insults, from physical injury to invasion by infectious agents. The capacity for rapid mobilization of armies of defensive T lymphocytes to sites of cutaneous injury, presumably a prerequisite for mammalian evolution, depends on elaborate homing mechanisms that bring T cells into the skin.

For example, the adhesion molecule cutaneous lymphocyte-associated antigen, which fits in lock-and-key fashion with the E-selectin induced on dermal endothelial cells by interferon-γ, is displayed preferentially by T cells that abound in a wide variety of dermatologic inflammatory infiltrates. It is thought that cutaneous lymphocyte-associated antigen, displayed by less than 20 percent of blood T cells and 5 percent of lymph-node T cells but found on most T cells in inflammatory skin lesions, may have a central role in the egress of cutaneous T cells from blood vessels. Neoplastic conversion of the CD4 subgroup of this population of “cutaneous lymphocytes” is manifest as the relatively common cancer cutaneous T-cell lymphoma.

The intricate developmental kinship between the T cell and the epidermis is perhaps best revealed by the nude mouse. Nude mice lack not only terminal hair, but also a thymus and most mature T cells. The latter feature makes them useful in studies of transplantation and tumor immunology, and it has led to countless attempts to manipulate their genes. Remarkably, it has never been possible to separate the aberrations in thymic and epidermal development, suggesting that they may have the same genetic origin.

We now recognize that the epidermis is a diverse mix of cells, flooded by a multitude of cytokines and other mediators, all contributing to well-orchestrated immunologic homeostasis. Indeed, over the past two decades, much information has accumulated to suggest that the skin may even contribute to some aspects of post-thymic T-cell maturation through hormones such as thymopoietin.

In disease states, this fine music becomes cacophony, with the armies of T cells inadvertently turning on the skin's own cellular citizens. Cutaneous allergies and autoimmune diseases result from an inappropriate attack by the immune system on innocuous chemicals or normal tissue constituents. The incidence of contact dermatitis is staggering; it apparently accounts for 80 percent of occupational skin diseases and costs roughly $300 million for treatment and perhaps $1 billion in lost work output in the United States alone. The central role of T cells in defending against incipient cancers of keratinocytes, the major cellular component of the epidermis, is highlighted by the tremendously increased frequency of skin cancer in organ-transplant recipients who undergo long-term immunosuppressive therapy.

Cutaneous Allergy effectively covers major segments of this enormous clinical and scientific front. Written with the help of numerous authors, several of whom have shaped our knowledge of the disorders they discuss, this readable compendium is directed mainly at interested practitioners, both dermatologists and primary care physicians.

The introductory chapter about the immunobiology of skin is comprehensive, with the understandable limitation that a hard-bound book cannot contain the very latest information. It is particularly strong in the area of T-cell homing to skin, but there is no mention of exogenous or endogenous processing of peptide antigens for presentation to T cells. This lack is explicable, since most citations are from 1994 or earlier. Yet so much of our knowledge of antigen presentation and allergic reactions of the skin derives from our comprehension of the role of major histocompatibility complex (MHC) proteins in antigen presentation to T cells that this deficit should be corrected in the next edition. For example, contact allergic reactions to common agents, such as nickel or formaldehyde, appear to depend on promiscuous binding to endogenous proteins that, after digestion into small peptides and transport to the cell surface by MHC class II glycoproteins, are recognized by CD4 T cells. This process is central to understanding the basis of contact allergic dermatitis and perhaps atopic dermatitis as well.

The book is particularly strong on blistering autoimmune disorders, including pemphigus vulgaris and bullous pemphigoid, highlighting the roles of well-characterized autoantigens. The excellent overview of contact dermatitis lists the most common culprits, but with an understanding that the detective work required to identify the offending agents is often complex. Other strengths are the detailed chapters on hypersensitivity to the ubiquitous natural-latex products and the role of the human immunodeficiency virus in several common skin diseases, the practical discussion of the management of atopic dermatitis, and the high-quality clinical photographs.

Richard L. Edelson, M.D.
Yale University School of Medicine, New Haven, CT 06510

Citing Articles (1)

Citing Articles

1. 1

   Vijay Shreedhar, Angus M Moodycliffe, Stephen E Ullrich, Corazon Bucana, Margaret L Kripke, Leopoldo Flores-Romo. (1999) Dendritic Cells Require T Cells for Functional Maturation In Vivo. Immunity 11:5, 625-636
   CrossRef