Accelerated healing of pyoderma gangrenosum treated with bioengineered skin and concomitant immunosuppression.

Pyoderma gangrenosum is a rare, destructive, neutrophilic dermatosis, the origin of which remains largely obscure. The ulcerative variant of this inflammatory disorder causes painful, necrotic, rapidly enlarging ulcers. Because of pathergy, many clinicians avoid managing these nonhealing ulcers with aggressive surgical debridement and autologous grafts. This article proposes that the application of an allogeneic cultured human skin equivalent (Graftskin) not only circumvents this problem, but also hastens re-epithelialization of the ulcer bed. An added benefit of the possible improvement of the cosmetic appearance of the final scar by preventing severe wound contracture is also postulated. We report a newly diagnosed case of ulcerative pyoderma gangrenosum; the use of bioengineered skin as an adjunct to concurrent immunosuppressive therapy with cyclosporine hastened the healing and diminished pain in a rapidly enlarging leg ulcer. Within 2 weeks, the ulcer was 30% to 40% healed, achieving 100% re-epithelialization within 6 weeks.

Preschoolers' understanding of pretense and presumption of congruity between action and representation.

In a series of 4 studies, A. S. Lillard's (1993) paradigm for studying preschoolers' understanding of pretense was replicated and systematically examined. The design varied the extent of the contradiction built into Lillard's format. Decreases in contradictory information yielded increases in the incidence of correct judgments indicative of an implicitly representational understanding of pretense. The findings present a challenge to A. S. Lillard's (1993) conceptual analysis of pretense and suggest that methods adopted from the classic false-belief paradigm of H. Wimmer and J. Perner (1983) may be inappropriate for assessing preschoolers' understanding of pretense.

Neurilemmomatosis, NF2, and juvenile xanthogranuloma.

The gene locus for neurilemmomatosis has been reported to lie within the neurofibromatosis type 2 gene region, suggesting that these 2 diseases may be identical. We describe an adolescent girl with multiple neurilemmomas and juvenile xanthogranulomas, who was found to have bilateral acoustic neuromas and multiple central nervous tissue tumors as seen in patients with a diagnosis of neurofibromatosis type 2. This case and recent genetic studies suggest that neurilemmomatosis and neurofibromatosis type 2 are the same disease.

Suppressive and enhancing effects of ultraviolet B radiation on expression of contact hypersensitivity in man.

Ultraviolet B (UVB) radiation has multiple effects on the immune system, and these effects contribute to the development of UVB-induced skin cancers in mice, and probably man. Depending upon dose and duration of UVB exposure, the resultant immune aberrations may be strictly local (at the irradiated skin site) or systemic. One important local effect of acute, low-dose UVB regimens is impaired induction of contact hypersensitivity (CH). Because a significant proportion of humans who develop CH when hapten is painted on UVB-exposed skin fall to display a primary allergic reaction at that site, we inquired into the effects of UVB radiation on the expression of CH in man. A high proportion of individuals who were first exposed to a sensitizing dose of hapten via UVB-exposed skin displayed CH when challenged on unirradiated (normal) skin 11 d later. However, only 50% of these subjects developed CH when challenged simultaneously on skin that had been exposed to UVB radiation 11 d previously. Because the density of epidermal antigen-presenting cells was comparable in both responders and non-responders, we interpret these findings to mean that UVB radiation can create a sustained immunosuppressive microenvironment that inhibits the expression of CH. In separate experiments, when normal volunteers were sensitized with hapten via unirradiated (normal) skin, expression of CH at UVB-exposed challenge sites 11 d later was found to be enhanced, at least in some individuals, compared to expression of CH at unirradiated challenge sites. Thus, the local effects of UVB radiation on expression of CH in man may be enhancing or inhibitory, depending upon whether initial sensitization occurred through normal or through UVB-exposed skin.

Relationship between ultraviolet radiation-induced immunosuppression and carcinogenesis.

The capacity of ultraviolet B (UVB) radiation to damage the cutaneous immune system has been extensively documented, and there is good reason to believe that UVB-induced damage is a critical, albeit permissive, factor in the development of sunlight-induced skin cancers. A summary of the evidence shows that acute, low-dose UVB protocols, which resemble quantitatively and qualitatively the manner in which human beings typically experience sun exposure, alter the cutaneous immune system in at least two important ways: they impair the induction of contact hypersensitivity to cutaneous antigens, and induce antigen-specific tolerance. In mice there is compelling evidence that immunogenetic factors dictate whether UVB radiation will impair contact hypersensitivity induction or not. The genetic loci that contain the relevant polymorphic alleles include tumor necrosis factor-alpha and lipopolysaccharide. Because the effects of UVB radiation on contact hypersensitivity induction are mimicked by intracutaneous injections of subinflammatory doses of tumor necrosis factor-alpha or cis-urocanic acid, the favored hypothesis to explain the mechanism of action of UVB radiation in UVB-susceptible individuals is that UVB-dependent transformation of trans- to cis-urocanic acid in the epidermis triggers the intracutaneous release of excess amounts of tumor necrosis factor-alpha. By transiently immobilizing Langerhans cells and other local antigen-presenting cells within the skin, the requirement that hapten be brought to the draining lymph node to sensitive naive hapten-specific T cells is not met, and contact hypersensitivity fails to develop. Because the UVB-susceptibility and UVB-resistance traits have also been demonstrated in human beings, the hypothesis is advanced that these traits are similarly under control of immunogenetic factors, and that a constellation of immune susceptibility genes contributes to the risk of developing sunlight-induced skin cancer. The cellular and molecular basis of UVB-induced tolerance is not as well described, but current evidence suggests that different mechanisms, and presumably different polymorphic genes, dictate whether tolerance will emerge after UVB exposure in mice. Because acute, low-dose UVB also induces tolerance in human beings, the immunogenetic factors that dictate tolerance of this type may also contribute to the risk of developing sunlight-induced skin cancer.

Immune surveillance and sunlight-induced skin cancer.

Immune surveillance poses the existence of a recirculating pool of lymphocytes that migrate randomly through somatic tissues. Upon recognition of neoantigens on malignantly transformed cells, lymphocytes proceed to attack and destroy degenerate cells before a tumor emerges. Here, J. Wayne Streilein and colleagues review the effects of ultraviolet B irradiation on the induction of cutaneous immunity in the skin of mice and humans. Furthermore, they discuss the possibility of a genetic predisposition to skin cancer, mediated by a defect in the normal process by which contact hypersensitivity, and therefore immunogenicity, is elicited.

Representational development of the human figure in familial retardates.

Representational development of the human figure of normal and familially retarded children was examined. Five tasks were employed: Drawing a Person, Figure Completion, two Form Puzzles, and Drawing on Dictation. Ss included 34 normal children, ages 3-0 to 5-10, and 34 familially retarded children, ages 4-4 to 13-1. The two groups were matched for mental age, socioeconomic status, public school attendance, and intact family structure. Results indicate that familial retardates performed as well as normals and at times surpassed them. Performance on these representational tasks is, predominantly, a function of mental age which lends support to a "developmental" theory of familial retardation and refutes the "defect" hypothesis.