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Background: Managed care in the American health care system may limit access to health care specialists. Objective: We assessed primary care providers' abilities at diagnosing and treating patients with a previously undiagnosed skin disorder. Methods: Patients with previously undiagnosed skin disorders were seen and examined sequentially by three groups of physicians: (1) internal medicine residents, (2) board-certified internal medicine attending physicians and (3) dermatology faculty. The internal medicine residents and attending physicians' diagnoses were compared with the dermatologists'. Appropriateness of therapy ordered by the internal medicine residents and attending physicians was assessed. Results: Medical residents' diagnoses were correct in 43% of the patients whereas the attending physicians diagnosed 52% of cases correctly. Attending physicians and residents frequently ordered therapy inappropriate for the patient's diagnosis. Internal medicine residents and attending physicians were more likely to order skin biopsies than dermatologists. Conclusion: Our results confirm earlier studies that nondermatologists perform poorly in the diagnosis and treatment of skin disease. Primary care providers should receive more training in dermatology, or dermatologists should be permitted to act as primary caregivers to patients with skin disease.

The use of interferon (INF) is usually considered safe, the major side-effect being a flu-like syndrome. However, with its ability to alter immune responsiveness, INF has been associated with the induction of autoimmune diseases. We report a patient with Waldenstrom's macroglobulinaemia who developed a generalized blistering eruption after treatment with systemic INF-alpha 2A (INF) for multiple skin cancers. The patient's skin showed histological features, immunofluorescence findings, and immunoprecipitation diagnostic of paraneoplastic pemphigus. Despite aggressive treatment the patient died. In our patient, the use of INF was temporally related to the development of paraneoplastic pemphigus. Although interferon has been shown to induce other autoimmune diseases, to our knowledge this is only the second report of a patient treated with an interferon who subsequently developed a fatal autoimmune blistering disorder. Paraneoplastic pemphigus is a recently described autoimmune bullous disorder with a poor prognosis. The mechanism by which INF triggered the paraneoplastic pemphigus is not known.

Squamous cell carcinoma is a rare, but well documented complication of chronic osteomyelitis. Many authors have recommended amputation as the treatment of choice for locally invasive disease. Presented is a patient with squamous cell carcinoma arising in the draining sinus tract of chronic osteomyelitis of the lower extremity that was treated successfully with Mohs micrographic surgery (MMS). After ten year follow-up he remains tumor free and continues to enjoy use of his leg. We propose MMS as a therapeutic option to amputation for control of locally invasive disease.

T he treatment of chronic wounds with exposed tendons presents a clinical challenge. Establishment of a healthy base of granulation tissue is critical, and such a base can serve as either a bed for grafting or a substrate over which the patient’s own epithelial cells may migrate. Additionally, healthy granulation tissue is better able to effectively deliver host resistance factors to the wound bed and thus resists infection more readily than exposed tendons.1 For example, bacteria on exposed tendons have been reported to form adhesive colonies that are resistant to treatment, a phenomenon that may be similar to difficult-to-treat infections such as those found in catheters and artificial heart valves.2 Unfortunately, tendons are relatively avascular, and when a large area is exposed, this represents a poor substrate for coverage by granulation tissue. We describe a simple technique to accelerate the growth of granulation tissue over visible tendons. Using a 2-mm punch biopsy tool, we punch through the tendon to the underlying tissue after local anesthetic has been given (Figs 1 and 2). Depending on the size of the visible tendon, we stagger these spaces at 8to 10-mm intervals. Usually, 2 to 4 holes are placed. Care must be taken to avoiding weakening the tendon by removing too much of it. The

The skin has recently been found to produce cortisol and thereby serves as an extra-adrenal site of glucocorticoid synthesis, albeit in a tightly regulated manner, to simulate the hypothalamus–pituitary–adrenal axis (Vukelic et al., 2011). Therefore, investigation into whether the skin possesses other endocrinologic capabilities is both interesting and timely. It has been known for some time that the skin of amphibians, such as frogs, contains high amounts of thyrotropin-releasing hormone (TRH), which stimulates skin darkening in amphibians via centrally acting mechanisms (Jackson and Reichlin, 1977). Until recently, however, little was known about TRH in human skin and hair.

Objectives To determine the proportion of suspicious lesions referred by nondermatologists that are found to be malignant and the number of incidental skin cancers identified at the time of dermatology referral. Design Retrospective cohort study. Setting Veterans Affairs Connecticut Healthcare System. Patients Four hundred patients referred by nondermatologists for skin lesions suspected of being malignant between January 1, 2006, through December 31, 2009. Main Outcome Measures Data collected included the type of referring provider, the final diagnosis by the dermatologist, and the number and type of incidental lesions. Results Only 22.0% of the index lesions (ie, the lesions that prompted the referral) were found to be cancerous. In aggregate, 149 cancerous lesions were noted in 98 patients. However, only 88 (59.1%) were identified in the index lesion; 111 incidental lesions were biopsied by the consulting dermatologist, with 61 (55.0%) additional skin cancers identified. Twelve of the 61 incidental cancers (19.7%) were found in patients whose index lesion was clinically benign and was not biopsied. Conclusions Nondermatologists may benefit from focused educational initiatives on skin cancer detection, particularly the significance of the total body skin examination and the expectations for and limitations of teledermatology. A substantial proportion of malignant lesions was incidentally identified by the consulting dermatologist in addition to the primary lesion of concern. The use of teledermatology to assess a specific lesion of concern may be associated with underdiagnosis of clinically significant lesions that are not appreciated by the referring physician. Therefore, teledermatology must not be used as a substitute for a total body skin examination.

Deregulation of the AP1 family gene regulators have been implicated in a wide range of diseases, including cancer. Here, we report that c-Jun was activated in human squamous cell carcinoma (SCC) and coexpression of c-Jun with oncogenic Ras was sufficient to transform primary human epidermal cells into malignancy in a regenerated human skin grafting model. In contrast, JunB was not induced in a majority of human SCC cells. Moreover, exogenous expression of JunB inhibited tumorigenesis driven by Ras or spontaneous human SCC cells. Conversely, the dominant negative JunB mutant (DNJunB) promoted tumorigenesis, which is in contrast to the tumor suppressor function of the corresponding c-Jun mutant. At the cellular level, JunB induced epidermal cell senescence and slowed cell growth in a cell-autonomous manner. Consistently, coexpression of JunB and Ras induced premature epidermal differentiation concomitant with upregulation of p16 and filaggrin and downregulation of cyclinD1 and CDK4. These findings indicate that JunB and c-Jun differentially regulate cell growth and differentiation and induce opposite effects on epidermal neoplasia.

Not uncommonly, dermatologists are presented with the following scenario. A long-standing patient with atopic dermatitis informs you that she is pregnant. For the safety of her unborn child, you discontinue systemic medications but instruct her to continue using her topical steroids. Does use of topical steroids confer a risk to the fetus, and, if so, what is the risk? This clinical situation was, in part, the rationale behind the study by Chi and colleagues (2011, this issue), who utilized two clinical and administrative databases in the United Kingdom (the UK General Practice Research Database and a pregnancy-specific Mother–Baby Link data set) to address this question. Previous studies were limited by sample size and other data issues, leading to inconclusive results (Chi et al., 2010).

Dermal fibroblasts exposed to low oxygen tension show upregulated synthesis of transforming growth factor-beta 1 (TGF-beta 1), an established stimulatory peptide in the formation of extracellular matrix proteins. In this report, procollagen synthesis was measured in cultures of confluent adult human dermal fibroblasts exposed to either standard (20%) or low (2%) oxygen tension. By Northern blot analysis the steady state levels of alpha 1 (I) procollagen mRNA were increased by 75 to 150% of control (standard oxygen) as early as 12 hours and more than 200% 96 hours after exposure of cells to low oxygen. Similar increases in procollagen mRNA levels were obtained in hypoxic fibroblast cultures in a collagen lattice. The stimulatory effect of hypoxia on procollagen mRNA levels in fibroblast monolayers was diminished by antibodies to TGF-beta, and could not be augmented further by the addition of TGF-beta 1, evidence that hypoxic fibroblasts may already be maximally stimulated by TGF-beta 1. We conclude that low oxygen tension enhances Steady state mRNA levels of alpha 1 (I) procollagen, and that this effect is mediated at least in part by TGF-beta 1. © 1993 Wiley-Liss, Inc.

objective. To discuss the role of skin grafts in the functional repair of lower extremity ulcerations. methods. The indications, types of skin grafts, and the methods of harvesting grafts are described. results. Detailed description of our method of bedside split-thickness skin grafting with both pinch and mesh grafts in hospitalized patients is given. We also discuss post-operative care and complications seen with skin grafting. conclusion. Split-thickness skin grafting offers an important therapeutic option in the treatment of lower extremity ulcerations.

In standard tissue culture conditions (20% oxygen), single human dermal fibroblasts (one cell per well) do not proliferate. We now report that low oxygen tension is a potent stimulus for the proliferation and expansion of human adult and neonatal dermal fibroblasts seeded as single cells. This preferential single-cell proliferation in low oxygen is shown to be also a feature of human lung and dermal rodent fibroblasts, but not of human fibrosarcoma and immortalized 3T3 cells, which proliferate without difficulty in standard oxygen conditions. It is suggested that single-cell proliferation and its dramatic stimulation in low oxygen may represent a fundamental biologic process with an opportunity to better understand mammalian cell growth regulation.

Solitary morphoea profunda is a recently described morphological variant of localized scleroderma. Two of the five reported patients had a solitary fibrotic plaque in the paraspinal region. We report a 16-year-old boy with a solitary fibrotic paraspinal plaque which, on histological examination, showed dermal and subcutaneous sclerosis, with a polymorphous infiltrate including plasma cells and eosinophils. Laboratory tests were either negative or normal, except for mild peripheral blood eosinophilia. Antinuclear antibodies were not detected, and the patient had no evidence of Borrelia infection. Magnetic resonance imaging (MRI) showed that the process involved the subcutaneous tissue, but did not extend to the underlying bone. As half of the patients with this entity (three of six) now described have had a solitary fibrotic plaque in a paraspinal location, we suggest that it may be premature to classify all these cases as being a variant of morphoea. We propose the use of the descriptive term solitary fibrosing paraspinal plaque, until the aetiology or aetiologies of this condition are better understood.

To the Editors:—It was with great interest that we read the study by Scuffham et al.1 and the accompanying editorial by Larson2 about the use of n-of-1 trials. Traditional medical training often emphasizes large, randomized, controlled trials as being perched on the highest tier in the hierarchy of research, but as the authors clearly state, these studies’ findings may not be applicable to specific individuals. After reading these two articles, we came away both extremely impressed by their contents and this heretofore little known process, but extremely daunted by the prospect of employing it in most practitioners’ daily practice, especially with Scuffham’s definition of it being “multi-cycle within-patient, randomized, double-blind, cross-over comparisons of a drug and placebo (or another drug) using standardized measures of effect.” However, with additional reflection, we realize that busy general medicine clinicians geographically or psychologically far from academic centers have the opportunity to employ similar concepts, just as many dermatologists have been doing for years. This practical approach demonstrates particular utility in the setting of chronic inflammatory skin conditions, such as psoriasis or atopic dermatitis. For diffuse and often bilateral disease, one half of a patient’s body can serve as the control for the other half. In this way, patients can determine the relative efficacy of certain topical agents and individualize the long-term approach to their condition. In the case of psoriasis, patients may use a single agent (topical corticosteroids, vitamin D analogues, retinoids or even coal tar) on one side with comparison to another single agent or even combination therapy on the other side. Similarly, patients with atopic dermatitis often experience a chronic course of their disease with periods of variable severity. This approach may be utilized to determine individual patient response to treatment with topical steroids (which vary by medication, strength and vehicle) and/or the non-steroidal topical immunomodulators. For these patients, the efficacy of topical therapy is determined by a combination of the efficacy intrinsic to the medications, their individual response to therapy, and even more important the patients’ preference and subsequent adherence to regular application. These slightly inelegant, less than formal studies have proven invaluable in our own personal experience, and we encourage practitioners to consider this in some of their patients.

A middle-aged patient presents with multiple cafe-au-lait macules (CALMs), cutaneous neurofibromas, and axillary freckling. You ably make a diagnosis of neurofibromatosis-1 (NF-1) and explain to the patient the genetics involved and that further evaluation for ocular manifestations is warranted (Boyd et al., 2009). As you explain the risk of malignancy—particularly the risk of malignant peripheral nerve-sheath tumors (MPNST)—you ponder your patient's individual risk for developing this tumor and what precautions the patient should be taking (Rasmussen et al., 2001). Is Your Patient with Neurofibromatosis Likely to Develop a Malignancy?

Understanding the pathophysiology of various disease processes lends itself to a better understanding of the normal function of tissues. For example, studying autoimmune and infectious blistering diseases has led to significant advances in elucidating the structure and function of the epidermis and the epidermal basement membrane zone (Stanley and Amagai, 2006). Similarly, studies of diseases such as epidermolysis bullosa simplex and epidermolytic hyperkeratosis have helped herald the importance and function of keratin proteins (Leigh and Lane, 1993). Thus, probing the pathophysiology of skin diseases provides insights into the normal structure and function of skin. In a report published in this issue, physicians and investigators teamed together to examine the disease that caused the untimely death of a 14-year-old girl from Finland (Mahoney et al., 2010).

Endothelin-1 (ET-1) is the most potent vasoconstricting substance known, and is believed to have a fundamental role in the regulation of blood flow. It is a peptide produced and secreted by endothelial cells in response to hypoxia and injury, as well as by macrophages. These properties suggest that ET-1 may play a role during tissue repair. In this study, we have examined the effects of ET-1 on the growth and synthetic activity of human dermal fibroblasts. ET-1 stimulated DNA synthesis in serum-deprived cultures: this effect reached a mean value of 64% more than control (P < 0.01) at 2.5 ng/ml (10(-9) M) of ET-1. In contrast, the addition of ET-1 to fibroblasts at different densities and in 0, 3, or 10% fetal bovine serum (FBS) failed to increase cell counts. In 1% FBS, a 41% mean increase in cell counts compared to control values was observed in cultures treated with 2.5 ng/ml of ET-1 (P < 0.01). Incubation of dermal fibroblast cultures at 37 degrees C for 1 hr with increasing concentrations of 125I-ET-1 resulted in saturable binding and a half-maximal specific binding of 27.5 pM. Scatchard plot analysis of the binding showed a Kd of 224 pM and 11,400 high-affinity binding sites per cell. ET-1 had no effect on [14C]-glucosamine incorporation by fibroblasts and caused no increase in collagen synthesis, as measured by collagenase-sensitive [3H]proline incorporation and by salt precipitation of 3H-labeled collagen at acid and neutral pH successively.(ABSTRACT TRUNCATED AT 250 WORDS)

Background: The presence of tumor involving surgical margins after excision of basal cell carcinoma (BCC) presents a therapeutic dilemma. Some authors advocate a conservative policy whereas others recommend immediate reexcision. Objective: Our purpose was to evaluate residual tumor utilizing Mohs micrographic surgery (MMS) of those BCCs with margin involvement after primary excision. Methods: We retrospectively reviewed 77 patients with 78 tumors who underwent MMS because of margin involvement after primary excision of BCC to detect the presence or absence of residual tumor. Results: Residual tumor was found in 55% of the cases as defined by the need for two or more stages of MMS to achieve a tumor-free plane. Conclusion: We suggest reexcision of all BCCs that are found to have marginal involvement after primary excision because of the large percentage of cases found to have residual tumor.

Dermatomyositis is an uncommon inflammatory myopathy accompanied by characteristic cutaneous findings. Adult-onset dermatomyositis is often associated with internal malignancy. We report a case of dermatomyositis associated with an aggressive and fatal case of transitional cell carcinoma of the bladder.

Pemphigus foliaceus (PF), an autoimmune blistering disorder, is characterized by the development of superficial cutaneous blisters in a seborrheic distribution, without mucosal involvement. Autoantibodies target the desmoglein 1 (Dsg1) antigen expressed on the surface of keratinocytes located in the superficial levels of the epidermis (Mahoney et al., 1999), and both sporadic PF and endemic PF can occur. Endemic PF, referred to as fogo selvagem (FS), is endemic to specific areas of the world, most notably Brazil, although it has also been described in Tunisia and Colombia (Abreu-Velez et al., 2003). Both genetic and environmental factors appear to play a role in the development of FS. Certain human leukocyte antigen (HLA) types appear to be at greatest risk: the HLA-DRB1*0102, HLA-DRB1*0404, and HLA-DRB1*1402 alleles (P < 0.005, relative risk, 14; Moraes et al., 1997). It has been hypothesized that the disease may be triggered by a local environmental agent(s) such as Simulium (a hematophagous insect), causing a cross-reactive anti-Dsg1 antibody response that leads to FS (Diaz et al., 2004). Endemic PF is of special interest, beyond its clinical impact on those affected, because it can serve as a model for organ-specific immune disease with both genetic and environmental components. FS appears to be caused by isotyperestricted, pathogenic anti-Dsg1 autoantibodies that are predominantly IgG4 (Warren et al., 2003) and that increase in concentration in serum upon progression from preclinical to clinical disease. Development of a predictive test for PF would benefit those at high risk, and it could also serve as an investigative tool. In an effort to develop such a test, Qaqish et al. (2009, this issue) used Dsg1 enzyme-linked immunosorbent assay in a study of 214 patients with FS and 261 healthy controls, randomly divided into training (50%), validation (25%), and test (25%) sets. IgG4 was found to be the best predictor of FS, with a sensitivity of 92% and specificity of 97%. The positive predictive value of this test in the endemic region of Brazil (which has an FS prevalence of 3%) was 49%. This was then validated by testing 11 patients with FS before and after clinical disease onset, as well as 60 Japanese patients with PF. Through the following questions, we examine this paper in greater detail. For brief answers, please refer to http://

Objective To evaluate the relation of topical tretinoin, a commonly used retinoid cream, with all-cause mortality in the Veterans Affairs Topical Tretinoin Chemoprevention Trial (VATTC). The planned outcome of this trial was risk of keratinocyte carcinoma, and systemic administration of certain retinoid compounds has been shown to reduce risk of this cancer but has also been associated with increased mortality risk among smokers. Design The VATTC Trial was a blinded randomized chemoprevention trial, with 2- to 6-year follow-up. Oversight was provided by multiple independent committees. Setting US Department of Veterans Affairs medical centers. Patients A total of 1131 veterans were randomized. Their mean age was 71 years. Patients with a very high estimated short-term risk of death were excluded. Interventions Application of tretinoin, 0.1%, or vehicle control cream twice daily to the face and ears. Main Outcome Measures Death, which was not contemplated as an end point in the original study design. Results The intervention was terminated 6 months early because of an excessive number of deaths in the tretinoin-treated group. Post hoc analysis of this difference revealed minor imbalances in age, comorbidity, and smoking status, all of which were important predictors of death. After adjusting for these imbalances, the difference in mortality between the randomized groups remained statistically significant. Conclusions We observed an association of topical tretinoin therapy with death, but we do not infer a causal association that current evidence suggests is unlikely. Trial Registration clinicaltrials.gov Identifier:NCT00007631

One proposed mechanism for the beneficial effect of occlusive dressings on healing is the maintenance of contact between the wound bed and accumulated wound fluid, which is thought to contain growth stimulatory substances. We have examined the effect of human wound fluid on the in vitro growth of human dermal fibroblasts and umbilical vein endothelial cells. Acute wound fluid was collected from six patients undergoing split-thickness skin grafting. The acute wound fluid was sterilely collected daily from underneath a vapor-permeable membrane applied to the donor site and changed every 24 hours for 3 days postoperatively. After seeding in optimal growth media (control) on day 0, cultures of human dermal fibroblasts and umbilical vein endothelial cells were supplemented with or without acute wound fluid on the next day (day 1) and on day 3. As determined by cell counts, 2% acute wound fluid stimulated the growth of human dermal fibroblasts (p less than 0.05) and umbilical vein endothelial cells (p less than 0.01) when these cells were cultured in 2% fetal bovine serum and endothelial growth medium, respectively. Wound fluid from postoperative days 1 or 3 caused the same level of stimulation. The addition of an anti-platelet-derived growth factor antibody to wound fluid resulted in a 45% mean reduction in its stimulatory effect on fibroblast growth (p less than 0.02), suggesting that platelet-derived growth factor contributes to the observed effect.(ABSTRACT TRUNCATED AT 250 WORDS)

This patient was a 61-year-old white female who received several years of penicillamine therapy for the treatment of cystinuria. She subsequently developed penicillamine induced cutis laxa, elastosis perforans serpiginosa, and pseudoxanthoma elasticum like skin lesions. In addition, she suffered from numerous chronic bilateral lower extremity skin ulcerations. Her past medical history was also significant for end stage renal disease requiring hemodialysis and pulmonary fibrosis. She presented to the University of Miami Wound Care Center in 1/04 for treatment of her chronic ulcerations. On physical examination, the patient had multiple large hyperpigmented plaques with central ulcerations on her lower extremities. Some of the ulcers had overlying crust and others were covered with yellow fibrinous tissue. She also had generalized thickened, lax skin with multiple folds. On her neck, thighs, back and arms were violaceous, atrophic, serpiginous plaques with peripheral crusted erosions. A biopsy taken from the patients left thigh revealed dermal elastosis and the features of pseudo-pseudoxanthoma. Two additional biopsies taken from the left thigh demonstrated elastosis perforans serpiginosa. This case highlights multiple skin manifestations of penicillamine therapy.

Non-melanoma skin cancer (NMSC) has been associated with several other conditions, including melanoma and non-Hodgkin's lymphoma (Hjalgri et al., 2000; Hu et al., 2005). In addition, the risk of NMSC has been found to be greater in various chronic disease groups (Frisch and Melbye, 1995; Frisch et al., 1996). It is uncertain whether this association is related to the treatments for those chronic diseases (such as radiation therapy or immunosuppressant therapy) rather than the disease itself (Karagas et al., 2001; Saladi and Persaud, 2005). Moreover, using a Danish nationwide cohort of patients with NMSC, Jensen et al. (2006) found a lower mortality in basal cell carcinoma (BCC) patients compared with the general population, reflecting what the authors suggested to be a selection bias to that data set.

1Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA Antibodies against desmoglein proteins account for intraepidermal immunobullous disorders in the pemphigus family of diseases. Antibodies against desmoglein 3 are responsible for the blisters seen in patients with pemphigus vulgaris, whereas antibodies against desmoglein 1 lead to the more superficial separation seen in pemphigus foliaceus. Similar in both clinical and histologic features to pemphigus foliaceus (PF), an endemic form of the disease, fogo selvagem (FS) is found in high prevalence in certain regions of Brazil (Diaz et al., 1989). The endemic nature of the condition is thought to be precipitated by an immune response to an environmental antigen(s), currently not yet identified. This unique epidemiologic phenomenon provides researchers with an opportunity to study the differences between endemic and sporadic forms of this disease. In this issue of the Journal, Diaz et al. (2008) studied early immunologic responses among patients with FS to determine whether the IgM response differs from that seen in patients with the sporadic disease. In a comprehensive assessment of immune responses, they evaluated sera from patients with FS in rural endemic and urban areas of Brazil, patients with PF in the United States and Japan, and control subjects in these locations. Detection of desmoglein 1 IgM varied, with the highest levels (58%) in FS patients in endemic regions and control subjects (>50%) from the same areas. The desmoglein 1 IgM response was considerably lower (12–18%) in FS patients from urban areas of Brazil and still lower in patients from the United States (10%) and Japan (0%). Less variability was found in IgG responses in patients, with markedly lower responses in control subjects, apart from control subjects from rural areas of Brazil. The investigators hypothesize that an environmental agent responsible for the development of FS may cause an early IgM response that predates clinical disease. Through the following questions we will examine this paper in greater detail. For brief answers please refer to http:// network.nature.com/group/jidclub.

1Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA UV light is a major risk factor for skin cancer development (Essen and Klar, 2006). The mechanisms by which UV leads to cancer formation are complex and appear not to be limited solely to UV-induced DNA damage. UV induces immune suppression, which is associated with increased skin cancer formation, as evidenced by the increased cancer risk in immunosuppressed transplant patients (Bergstresser, 1983; Ulrich and Stockfleth, 2007). Therefore, protection against UV-induced immune suppression may have clinical benefits. In this issue, Damian et al. (2008) explore the potential role of topical nicotinamide in preventing UV immunosuppression in humans, based on animal models to prevent UV-induced immune suppression. Using volunteers with a positive Mantoux test (purified protein derivative positive from Bacille Calmette-Guerin vaccination), the authors studied the ability of topical nicotinamide to prevent UVB immune suppression and the mechanisms by which this occurred. They found that when nicotinamide was applied either before or after UV exposure (simulating normal sunlight exposure), the typically encountered immune suppression was reduced. Additionally, men were more sensitive to UV-light-induced immune suppression, which the investigators concluded may account, in part, for the greater incidence of skin cancer and skin cancer mortality in men. Nicotinamide did not work as a sunscreen but rather, as suggested by microarray analysis, as a mechanism that may include alterations in complement, energy metabolism, and apoptosis. Through the following questions we will delve into this paper in greater detail. For brief answers, please refer to http://network.nature.com/group/jidclub.

Darier's disease is an inherited condition of defective keratinization in which patients are predisposed to the development of severe viral infections and have an increased susceptibility to bacterial and mycotic infections. We describe a patient with Darier's disease who had a severe form of scabies infestation which responded to treatment with permethrin in combination with ivermectin. The tendency of patients with Darier's disease to develop severe forms of cutaneous infections and infestations may reflect a common underlying mechanism, and their management may require more aggressive therapeutic approaches.

Bacteria reside in various forms, including planktonic, or free-floating, or as biofilms, which are a tightly adherent, potentially more treatment-resistant form. Biofilms, composed in part as polysaccharide matrices, can act as protection for bacteria by shielding them from antimicrobials and the innate immune system. It is estimated that bacterial biofilm are responsible for 65–80% of all chronic infections and may be responsible in part for non-healing of chronic wounds. An advance in the treatment of non-healing wounds has lead to the development of human skin equivalents (HSE), which can successfully treat many non-healing wounds. Better understanding the interaction between bacteria and HSE might improve patient outcomes. Studies involving planktonic E. coli and HSE have demonstrated the growth of bacterial colonies only on the dermal surface. Growth was not seen on the epidermal layer of the HSE, possibly due in part to the expression of innate antimicrobial peptides called human β defensin-2 (hBD-2), which are expressed by HSE keratinocytes. The objective of this study was to determine if biofilm formation could occur on a bioengineered HSE. We used a commercially available HSE. Three (3) mm full-thickness incisions were made in a triangular section of HSE. Each section was inoculated on the epidermal aspect with 1.0 × 105CFU per gram of Pseudomonas aeruginosa at 35 degrees Celsius for specified time points. Sections of HSE were sampled in areas of injury at various time points. Biopsy sections were processed for histologic analysis with H&E and epifluorescent microscopy to visualize Pseudomonas aeruginosa. We found that biofilm formation occurred at multiple time points on HSE. Colonies of adherent bacteria were visualized within the injured area of the epidermal layer of HSE by H & E staining. Eplifluoresecnt microscopy using calcofluor white staining revealed the characteristic exopolysaccharide (EPS) matrix of biofilm. Visualization of the expression of human β defensin-2 (hBD-2) with HSE after biofilm formation is underway. This knowledge will help to understand the role of bacterial biofilms within HSE and their effect on subsequent healing.