Abstract
The 8th Annual Las Vegas Dermatology Seminar, as stated in its name, was held in Las Vegas, NV, USA on 8–11 November 2007. With an attendance of more than 300 people, this well-known event brought together prominent guest speakers from the USA, Italy, Mexico and the Czech Republic to present on numerous topics mostly related to medical dermatology. Additionally, the last day of the event was dedicated to cosmetic dermatology. The meeting had a strong clinical flavor with abundant and useful pearls for the practicing physician. The afternoon sessions focused on biologic therapy for psoriasis, and were targeted at third-year dermatology residents. The practical nature of the seminar was clearly revealed during the resident’s symposium, where most of the discussion time was devoted to the analysis of real-life cases/scenarios, preceded by a short and concise summary of biologics as individual drugs. This session concluded with an interesting discussion on optimal office effectiveness.
Nephrogenic systemic fibrosis
Whitney A High highlighted the most important details and latest developments on nephrogenic systemic fibrosis (NSF). Formerly known as nephrogenic fibrotic dermopathy, the first cases were described in 1997, as ‘scleromyxedema-like’ cutaneous disease in patients undergoing renal dialysis but, after noticing the prominent systemic findings in these patients, the terminology was changed to NSF.
Breakthrough came in January 2006, when five patients in Australia were diagnosed with this condition all of whom had previous history of magnetic resonance angiography with gadodiamide 2–4 weeks prior. In August of that same year, 13 patients were diagnosed in Denmark. They had no shared risk factor other than gadodiamide exposure 2–75 days prior to onset. Further studies have demonstrated that gadolinium can be detected in affected tissues (four out of seven patients) using a single thin histologic section.
High emphasized the need for a deep-punch biopsy of the involved skin for an accurate diagnosis. Another option could be the use of high-energy x-ray fluoroscopy, which, although is not readily available, represents a new alternative for diagnosis. There is no uniformly successful therapy to date, but some studies suggest that improvement may occur with restored kidney function, as well as extracorporeal photophoresis. UVA-1 light therapy and plasmapheresis are among other therapeutic modalities. Possible alternatives in the future, such as sodium thiosulfate, ethylenediaminetetraacetic acid, penicillamine, deferoxamine, anti-inflammatory drugs, TGF-2 inhibitors and endothelin inhibitors, were mentioned.
Stem cells in dermatology
Tissue homeostasis and injury repair depend upon adult stem cells. Stem cells are multipotent, self-renewing cells, flexible in their ability to reconstitute a variety of tissue lineages, since they can generate tissue for an extended period of time. Thus, there has been much recent interest to assess the therapeutic potential of different stem cell populations.
Ruby Ghadially explained the restrictions and differences between embryonic and adult stem cells. The embryonic stem cells are derived from the blastocyst, they are immortal in culture, but can have a teratoma potential. There are also ethical issues with them due to the way they are obtained. By contrast, the adult stem cells are derived from developing or adult organisms and have a restrictive replicative potential. Their use is restricted to some lineages, but there are no ethical issues. For example, epithelial cells have the particular advantages of being plentiful, easily accessible and the ability to be manipulated in tissue culture.
In some malignancies, it is now clear that only a small percentage of tumor cells have the ability to produce further cancer and those are now referred to as cancer stem cells or tumor-initiating cells (TICs). They share traits with normal stem cells, (i.e., they both have unlimited life span and capacity to produce a diverse range of cells). Current treatments focus on erradicating the greatest number of cancer cells, but a potential therapeutic target would be to identify the cancer stem cells in malignances, such as leukemia and melanoma, remove them and, thus, eradicate the tumors rather than shrink them.
Malignant melanoma
Due to the rising incidence of melanoma in the USA, the challenge to prevent and cure this malignancy continues to remain at the forefront of dermatologic and oncologic research, as discussed by Mark R Pittelkow. The principle etiologic determinants for development of melanoma, as well as molecular mechanisms inducing genetic alterations in the melanocytes, are actively being pursued by many research groups.
Various novel genetic and genomic approaches to identify the molecular pathogenesis of malignant melanoma were mentioned (i.e., Genome Wide Association Studies [GWAS] and Comparative Genome Hybridization [CGH]), which lever in genome mapping and gene probes to search for specific markers/associations in malignant melanoma. GWAS identifies genetic associations with the presence or absence of a disease or condition and, in healthy individuals, with observable traits. CGH surveys for regional differences in the content of a given subject’s DNA compared with control DNA (i.e., gains/losses), often in tumor cells. CGH will detect only unbalanced chromosome changes.
Pittelkow briefly mentioned the new concept of melanoma stem cells and the role of miRNA in the development of the condition, survival and propagation. The melanoma stem cells, or melanoma-initiating cells (MICs), refer to a small number of cells from melanomas that are capable of creating a new tumor. A new goal is to study the protein and gene expression of an enriched population of MIC’s to develop insights into the pathogenesis of this condition, and novel therapeutic targets.
Biologics
The prevalence of psoriasis is 2–3% in the US population. The estimated prevalence of psoriatic arthritis (PSA) in people with active psoriasis is estimated to be 6–42%. Increased mortality has been observed in a large ongoing case registry of patients with PSA.
Biologic therapy represents a valuable and effective therapeutic option for psoriasis. During the resident’s forum, a review of all biologics currently available was undertaken. Important information on etanercept, infliximab, efalizumab and alefacept was presented with new data on the anti-IL-12/23, the new biologics.
IL-12 and IL-23 are implicated in the pathophysiology of several immune-mediated diseases, including psoriasis and Crohn’s disease. The clinical picture of psoriasis results from infiltration of T cells into the skin and elaboration of inflammatory cytokines, such as IL-12 and IL-23. These two cytokines share the p40 subunit and have a distinct subunit (p35 and p19, respectively). An increased level of IL-12/23’s p40 protein is present in psoriatic lesions. Currently, breakthrough therapies for psoriasis are monoclonal antibodies that target these cytokines more specifically by inhibiting their p40 subunit.
During the resident’s seminar, preliminary data regarding the two anti-IL-12/23 drugs were presented. Centocor, Inc. has finished Phase III studies on the drug which is known as ustekinumab. Abbott has completed their Phase II trials and are ready to begin Phase III. Both drugs have shown great efficacy and the safety profile is good thus far.
Chimerism & graft-versus-host disease: role of the dermatologist
Rokea el-Azhary started her presentation by defining chimerism as the stable presence of foreign cells in an organism, citing one of the most common forms, fetomaternal microchimerism (or fetal chimerism), whereby cells from a fetus pass through into the mother. Fetal cells have been documented to persist in maternal circulation for as long as 38 years. Microchimerism had also been shown to exist after blood transfusions to a severely immunocompromised population of patients who have suffered trauma.
The long-term persistence of fetal cells, when considered together with clinical similarities to chronic graft-vesus-host disease (GVHD) and autoimmune diseases, led to the hypothesis that microchimerism is involved in some autoimmune processes. She also reviewed GVHD in solid-organ transplant recipients, stating that the skin, eyes and intestines are affected most often, and the presentation can range from mild to life threatening. Mixed chimerism portends a benefit to patients who received solid-organ transplants, because it may cause a state of induced tolerance, resulting in less GVHD.
el-Azhary also presented some clinical cases in which she emphasized the need to differentiate drug rashes from GVHD. She suggested that early testing of skin biopsy specimens using fluorescent in situ hybridization in sex-mismatched patients with solid-organ transplantation can serve as an early diagnostic tool for GVHD. This is due to the fact that a PCR-based chimerism assay may fail to identify donor DNA in peripheral blood.
Lifting the face with long-lasting fillers: a new paradigm
The American Society for Aesthetic Plastic Surgery (ASAPS) reported that, in the year 2006, 11.5 million nonsurgical cosmetic procedures were performed, accounting for 83% of the total surgical/nonsurgical procedures during that year. This represents an increase of 747% of the nonsurgical procedures since 1997. The top five procedures in this category in 2006 were: botox, hyaluronic acid, laser hair removal, microdermabrasion and laser skin resurfacing, respectively.
Rebecca Fitzgerald explained the hallmarks of facial aging, such as loss of volume as a consequence of dermal thinning, fat loss and redistribution, and skeletal remodeling (orbital expansion, maxillary flattening and mandibular shrinking). Therefore, the use of fillers represents a very good alternative to counteract facial aging.
Replacement fillers, such as collagen and hyaluronic acid, often achieve the desired correction in one treatment session, are cost effective for mild volume replacement and have a limited longevity (12–36 weeks). Stimulatory fillers (poly-l-lactide acid, poly[methyl methacrylate], ²TCap and CaHA) require multiple treatment sessions to achieve the desired correction, their optimal results are technique dependent, potentially useful in correcting significant volume loss and they have increased duration (12–36 months). They are, however, contraindicated for the lips, unlike the replacement fillers. Even distribution and proper placement are keys to an optimal outcome. Other recommendations are post-treatment massage, avoidance of superficial placement, avoidance of the placement in areas with hyperkinetic muscles and avoidance of overcorrection (i.e., too much, too soon).
Laboratory diagnosis of deep fungal & atypical mycobacterial infections
The identification of infectious agents has become a time-consuming task in dermopathology. Although conventional culture is still performed by many laboratories, there is a growing demand for simple, fast, cost effective and highly sensitive screening tools for the detection of microorganisms, as stated by Glenn D Roberts.
Many histochemical stains and increasing numbers of specific monoclonal antibodies, in conjunction with advanced molecular techniques, provide a huge armamentarium for the detection of microorganisms. Currently, commercially available probes are excellent for rapid identification of a limited number of mycobacteria and dimorphic fungi (in less than 1 h). PCR can be used for selected organisms, such as Aspergillus, Cryptococcus neoformans, Candida and dermatophytes, among others. Microarray screening/chip technology, although very expensive, has the advantage of being one test for hundreds of organisms.
Culture remains the ‘gold standard’ for detection of fungi and mycobacterium. However, owing to the fact that nucleic acid sequencing has played a major role in classifying mycobacteria (previously referred to as ‘atypical’), and can provide accurate identification of fungi (even those that are uncommon), it could become the new gold standard for identification of these organisms.
The best application for molecular methods is for slower growing organisms, and it is possible that, some day, they may replace many conventional methods if the complexity of the tests and costs are reasonable. Although presently available tests appear to be clinically useful when properly applied, further technical development and clinical studies are needed before these powerful diagnostic tools are able to achieve their full value.
Conclusion
This was a thoroughably enjoyable meeting with a strong clinical flavor. The meeting would be valuable for practicing dermatologists and third-year residents. Nurse practitioners and physician assistants would also gain considerable benefit by attending this meeting.