Seth R. Stevens

Consensus conference on pediatric atopic dermatitis

C urrent information identifying risk factors for cutaneous diseases such as atopic dermatitis in childhood is limited. Cutaneous disease prevention programs and health promotion strategies in children and adolescents have not been addressed in a concerted way by government agencies or relevant medical societies. Disease-based interventions often emphasize adult disease, but many diseases may be prevented or minimized by intervention during childhood years. Research may be more effectively coordinated and carried out with the establishment of consensus on how best to diagnose and treat diseases such as atopic dermatitis (AD) in children and identify the most critical issues related to this condition. A consensus conference was convened by the American Academy of Dermatology on January 1921, 2001 to (1) define the core dermatologic issues related to AD in children and adolescents that can influence their dermatologic health over a lifetime and (2) prioritize future research efforts on epidemiology, pathogenesis, prevention, and management of AD. The following focus questions were addressed and responses/recommendations were developed:

Topical application of green and white tea extracts provides protection from solar-simulated ultraviolet light in human skin

Background:  Tea polyphenols have been found to exert beneficial effects on the skin via their antioxidant properties.

Apoptosis mechanisms related to the increased sensitivity of Jurkat T-cells vs A431 epidermoid cells to photodynamic therapy with the phthalocyanine Pc 4.

To examine the clinical applicability of Pc 4, a promising second‐generation photosensitizer, for the photodynamic treatment of lymphocyte‐mediated skin diseases, we studied the A431 and Jurkat cell lines, commonly used as surrogates for human keratinocyte‐derived carcinomas and lymphocytes, respectively. As revealed by ethyl acetate extraction and absorption spectrophotometry, uptake of Pc 4 into the two cell lines was linear with Pc 4 concentration and similar on a per cell basis but greater in Jurkat cells on a per mass basis. Flow cytometry showed that uptake was linear at low doses; variations in the dose–response for uptake measured by fluorescence supported differential aggregation of Pc 4 in the two cell types. As detected by confocal microscopy, Pc 4 localized to mitochondria and endoplasmic reticulum in both cell lines. Jurkat cells were much more sensitive to the lethal effects of phthalocyanine photodynamic therapy (Pc 4‐PDT) than were A431 cells, as measured by a tetrazolium dye reduction assay, and more readily underwent morphological apoptosis. In a search for molecular factors to explain the greater photosensitivity of Jurkat cells, the fate of important Bcl‐2 family members was monitored. Jurkat cells were more sensitive to the induction of immediate photodamage to Bcl‐2, but the difference was insufficient to account fully for their greater sensitivity. The antiapoptotic protein Mcl‐1 was extensively cleaved in a dose‐ and caspase‐dependent manner in Jurkat, but not in A431, cells exposed to Pc 4‐PDT. Thus, the greater killing by Pc 4‐PDT in Jurkat compared with A431 cells correlated with greater Bcl‐2 photodamage and more strongly to the more extensive Mcl‐1 degradation. Pc 4‐PDT may offer therapeutic advantages in targeting inflammatory cells over normal keratinocytes in the treatment of T‐cell‐mediated skin diseases, such as cutaneous lymphomas, dermatitis, lichenoid tissue reactions and psoriasis, and it will be instructive to evaluate the role of Bcl‐2 family proteins, especially Mcl‐1, in the therapeutic response.

A clinical and histologic mycosis fungoides simulant occurring as a T-cell infiltrate coexisting with B-cell leukemia cutis.

One year after the onset of chronic lymphocytic leukemia, an elderly man had scaly cutaneous plaques on the thighs that clinically and histologically resembled the mycosis fungoides type of cutaneous T-cell lymphoma. Two years later the patient had indurated, red dermal nodules on the face that clinically and histologically were characteristic of cutaneous chronic lymphocytic leukemia. Immunophenotyping results from a facial nodule confirmed the presence of a B-cell infiltrate (CD20+). Immunophenotyping of a lesion on the right thigh showed that half the cells were composed of a CD2+, CD45RO+ (UCHL-1+) upper dermal and focally epidermotropic population of T cells consistent with mycosis fungoides; however, these T cells coexisted with an equal number of CD20+ B cells arranged in distinct clusters. DNA from the thigh lesion exhibited a B-cell immunoglobulin gene rearrangement, but the T-cell receptor gene rearrangements were germline. In this case, the evidence favors a mycosis fungoides simulant occurring as a reactive T-cell infiltrate to an underlying B-cell chronic lymphocytic leukemia.

Relapsing livedo reticularis in the setting of chronic pancreatitis

Livedo reticularis (LR) is a characteristic netlike violaceous discoloration caused by a physiologic or pathologic cutaneous blood flow disturbance. Cutaneous vasculature consists of cones of arterioles whose margins have diminished arterial but prominent venous flow. Therefore, impeded blood flow through the skin can increase deoxyhemoglobin concentration, producing livid coloration in marginal zone venous areas.1 Benign causes include cutis marmorata and asymptomatic idiopathic LR. Diseases associated with LR include vessel wall disease, intravascular obstruction, and endocrine diseases.1-3 Rare clinical reports of LR associated with pancreatitis “Walzel’s Sign” exist.4 We describe a patient with asymmetric relapsing LR of the flank temporally associated with painful flares of her chronic pancreatitis.

Diagnosis of Sézary syndrome in a patient with generalized pruritus based on early molecular study and flow cytometry

2. Schmidt JB, Lindmaier A, Spona J. Endocrine parameters in acne vulgaris. Endocrinol Exp 1990,24:457-64. 3. Van der Meeren HLM, Thissen JHH. Circulating androgens in male acne. Br J Dermatol 1984;110:60911. 4. Rosenfield RL. Hyperandrogenism in peripubertal girls. Pediatr Clin North Am 1990;37:1333-58. 5. Forest MG. Differentiation and development of the male. Clin Endocrinol Metab 1975;4:569-96. 6. Duke EMC. Infantile acne associated with transient increases in plasma concentrations of luteinising hormone, follicle-stimulating hormone, and testosterone. Br Med J 1981;282: 1275-6. 7. Winter JSD, Faiman C, Hobson WC, et al. pituitarygonadal relations in infancy: I. patterns of serum gonadotropin concentrations f?om birth to four years of age in man and chimpanzee. J Clin Endocrinol Metab 1975;40:545-5 1. 8. Forest MG, Cathiard AM. Pattern of plasma testosterone and A4-androstenedione in normal newborns: evidence for testicular activity at birth. J Clin Endocrinol Metab 1975; 41:977-80. 9. Forest MG, Catbiard AM, Bertrand JA. Evidence of testicular activity in early infancy. J Clin Endocrinol Metab 1973;37:148-51. 10. Plewig G, Kligman AM. Acne neonatorum. In: Plewig G, Kligman AM, eds. Acne morphogenesis and tseatment. Berlin-Heidelberg: Springer-Verlag, 1975:213-5. 11. Forest MG, Cathiard AM, Bertrand JA. Total and unbound testosterone levels in the newborn and in normal and hypogonadal children: use of a sensitive radioimmunoassay for testosterone. J Clin Endocrinol Metab 1972; 15: 113242.

Atopic dermatitis: Current trends and future directions

Abstract Increasing knowledge regarding the pathogenesis of AD has emerged in the past two decades. We have presented 3 major lines of research that we believe have been particularly fruitful. These are elevated PDE levels, FceRI, IgE-mediated antigen focusing, and imbalanced cytokine expression. Additionally, basic elements of immune activation, such as T-cell activation and leukocyte adhesion, are nonspecific, yet important in the development of AD lesions. We have provided examples of actual and potential therapies for AD that target these important pathways. We recognize that for various reasons, such as cost, adverse effects, and inconvenience, some of these agents are less practical for use in AD. However, we hope to have given the reader a panoramic view of potential therapeutic strategies that take advantage of emerging concepts of AD pathophysiology.

Apoptosis mechanisms related to the increased sensitivity of Jurkat T-cells versus A431 epidermoid cells to photodynamic therapy with the phthalocyanine Pc 4 (Photochemistry and Photobiology (2008) 84, 2, (407-411))

Figure 4. Sensitivity to Pc 4-PDT. (a) Example of a cell cytotoxicity study using the MTT assay. Cells of each line were plated in 96-well plates, exposed to a series of Pc 4 concentrations followed by red light at 200 mJ ⁄ cm, and returned to the 37 C incubator for 24 hours. Cytotoxicity was assayed with MTT, and the LD50 determined (in this case, 20 nM for Jurkat cells and 140 nM for A431 cells). (b) Plot of LD50 of Pc 4 plotted versus fluence, for experiments on A431 (diamonds) and Jurkat (squares) cell lines. Solid and dashed lines are least-squares regression lines obtained by regressing Ln(LD50) vs Ln(Fluence) for A431 and Jurkat cells, respectively. (c) Quantification of Pc 4-PDT induced apoptosis. A431 cells (left) and Jurkat cells (right) were incubated with Pc 4-loaded growth medium for two h, followed by irradiation with 200 mJ ⁄ cm red light. After further incubation for 4 (open bars) or 18 (hatched bars) h, cells were fixed in 3.7% formaldehyde for 30 min at room temperature, followed by staining with Hoechst 33342 (Molecular Probes, Eugene, OR) for 30 min at room temperature. Slides were viewed under a fluorescence microscope. Cells displaying morphological apoptosis were quantified and normalized to untreated control cells. Data represent an average of 2–3 independent experiments ± standard error or range, except for A431 cells at 100 nM Pc 4, which are from single experiments.