Itch intensity in prurigo nodularis is closely related to dermal interleukin-31, oncostatin M, IL-31 receptor alpha and oncostatin M receptor beta.

Prurigo nodularis (PN) is a chronic skin dermatosis with hyperkeratotic and intensely pruritic nodules. Managing PN-associated itch is difficult because its aetiology is still unknown. This study aimed to investigate the correlation between itch intensity in PN and the expression of a pruritogenic cytokine interleukin (IL)-31, its receptor complex components IL-31 receptor α (IL-31RA) and oncostatin M receptor ß (OSMRß), and oncostatin M (OSM), which is a ligand of OSMR ß, through immunofluorescence staining examination. Itch intensity in PN was closely correlated with the number of dermal IL-31(+) cells (Spearman's r = 0.551, p < 0.05), dermal IL-31RA(+) cells (r = 0.475, p < 0.05) and dermal OSM(+) cells (r = 0.505, p < 0.05). In addition, the number of dermal OSMRß (+) cells was increased in PN (t test, p < 0.05), despite not being correlated with itch intensity (Spearman's r = 0.375, p > 0.05). Major cellular sources of dermal IL-31 were T cells (27.0% of total IL-31-expressing cells) and macrophages (35.0%), while those of OSM were mainly T cells (49.8%) and mast cells (26.8%). IL-31RA-expressing dermal cells were mostly mast cells (49.3%) and macrophages (36.6%), and OSMRß was mainly expressed by macrophages (51.8%) in the dermis. These findings indicate that IL-31 (mainly from macrophages and T cells) and OSM (principally from T cells and mast cells) stimulate dermal cells expressing IL-31RA and OSMRß (e.g. macrophages), which may further promote itch and inflammation in PN. This complex dermal milieu of cell/cytokine/receptor network can be a therapeutic target for PN-associated itch.

The Potential Impact of Social Genomics on Wound Healing.

Significance: Human skin wounds carry an immense epidemiologic and financial burden, and their impact will continue to grow with an aging population and rising incidence of comorbid conditions known to affect wound healing. To comprehensively address this growing clinical issue, physicians should also be aware of how conditions of the human social environment may affect wound healing. Here we provide a review of the emerging field of social genomics and its potential impact on the wound healing. Recent Advances: Multiple studies using human and animal models have correlated social influences and their contributing effects to acute and chronic stress with delays in wound healing. Furthermore, observations between nongenetic factors such as nutrition, socioeconomic, and educational status have also shown to have a direct or indirect impact on clinical outcomes of wound healing. Critical Issues: Nutrition, financial burden, socioeconomic and education status, and acute and chronic stress are variables that have either direct (epigenetic) or indirect impact on wound healing and patients' quality of life. Wound care is costly and remains a challenge placing economic burden on patients. Furthermore, poor clinical outcomes and complications including loss of mobility and disability may lead to job loss, further contributing to socioeconomic related stress. Thus, the economic burden and inadequate wound healing are intertwined, making each other worse. Future Directions: Although some evidence regarding the specific changes in genetic pathways imparted by conditions of the social environment exists, further studies are warranted to identify potential mechanisms, interventions, and prevention approaches.

Evolving management of positive regional lymph nodes in melanoma: Past, present and future directions.

Sentinel lymph node (SLN) biopsy has become the standard of care for lymph node staging in melanoma and the most important predictor of survival in clinically node-negative disease. Previous guidelines recommend completion lymph node dissection (CLND) in cases of positive SLN; however, the lymph nodes recovered during CLND are only positive in a minority of these cases. Recent evidence suggests that conservative management (i.e. observation) has similar outcomes compared to CLND. We sought to review the most current literature regarding the management of SLN in metastatic melanoma and to discuss potential future directions.

The Role of Completion Lymphadenectomy in Positive Regional Lymph Nodes in Melanoma: A Meta-analysis.

BACKGROUND: The optimal management of melanoma with positive sentinel lymph node (SLN) remains unclear. Completion lymph node dissection (CLND) only yields additional positive non-SLN in 20% of cases and its benefits on survival remains debatable. METHODS: An online database search of Medline was performed; key bibliographies were reviewed. Studies comparing outcomes after CLND versus observation were included. Odds ratios (ORs) with the corresponding 95% confidence intervals (CIs) by random fixed effects models of pooled data were calculated. The primary endpoints were disease-free survival (DFS), melanoma-specific survival (MSS), and overall survival (OS). RESULTS: Search strategy yielded 117 publications. Twelve studies were selected for inclusion, comprising 7966 SLN-positive patients. Among these patients, 5306 (66.6%) subjects underwent CLND and 2660 (33.4%) patients were observed. Median Breslow thickness and ulceration were similar between groups (2.8 ± 0.6 mm versus 2.5 ± 0.8 mm, P = 0.721; and 38.8% versus 37.2%, P = 0.136, CLND versus observation, respectively). CLND was associated with statistically significant improved 3-y (71.0% versus 66.2%, OR 0.82, 95% CI 0.69-0.97, P = 0.02) and 5-y DFS (48.3% versus 47.8%, OR 0.75, 95% CI 0.59-0.96, P = 0.02) compared with observation. However, no difference was demonstrated in 3-y MSS (83.7% versus 84.7%, OR 1.09, 95% CI 0.88-1.35, P = 0.41), 5-y MSS (68.4% versus 69.8%, OR 1.02, 95% CI 0.88-1.19, P = 0.78), or OS (68.2% versus 78.9%, OR 0.93, 95% CI 0.55-1.57, P = 0.78). CONCLUSIONS: Based on this large-scale analysis, CLND improved both 3- and 5-y DFS, possibly because of increased rates of local control; however, this did not translate in improved MSS or OS. Efforts toward the identification of molecular markers associated with poor outcomes in SLN-positive patients who undergo observation are warranted.

Laser and Light Treatments for Hair Reduction in Fitzpatrick Skin Types IV-VI: A Comprehensive Review of the Literature.

Unwanted facial and body hair presents as a common finding in many patients, such as females with hirsutism. With advances in laser and light technology, a clinically significant reduction in hair can be achieved in patients with light skin. However, in patients with darker skin, Fitzpatrick skin types (FST) IV-VI, the higher melanin content of the skin interferes with the proposed mechanism of laser-induced selective photothermolysis, which is to target the melanin in the hair follicle to cause permanent destruction of hair bulge stem cells. Many prospective and retrospective studies have been conducted with laser and light hair-removal devices, but most exclude patients with darkly pigmented skin, considering them a high-risk group for unwanted side effects, including pigmentation changes, blisters, and crust formation. We reviewed the published literature to obtain studies that focused on hair reduction for darker skin types. The existing literature for this patient population identifies longer wavelengths as a key element of the treatment protocol and indicates neodymium-doped yttrium aluminum garnet (Nd:YAG), diode, alexandrite, and ruby lasers as well as certain intense pulsed light sources for safe hair reduction with minimal side effects in patients with FST IV-VI, so long as energy settings and wavelengths are appropriate. Based on the findings in this review, safe and effective hair reduction for patients with FST IV-VI is achievable under proper treatment protocols and energy settings.

Efficacy of fractional lasers in treating alopecia: a literature review.

Hair loss stemming from different types of alopecia, such as androgenic alopecia and alopecia areata, negatively affects over half the population and, in many circumstances, causes serious psychosocial distress. Current treatment options for alopecia, such as minoxidil, anthralin, and intralesional corticosteroids, vary efficacy and side effect profiles. It is known that low-level laser/light therapies (LLLT), or photobiomodulations, such as the US FDA-cleared HairMax Lasercomb®, He-Ne laser, and excimer laser, are relatively affordable, user-friendly, safe, and effective forms of treatment for hair loss. While less is known about the effectiveness of fractional lasers for combating hair loss, research suggests that by creating microscopic thermal injury zones, fractional lasers may cause an increase in hair growth from a wound healing process, making them potential therapeutic options for alopecia. A literature review was performed to evaluate the effectiveness of fractional lasers on hair regrowth. The specific fractional laser therapies include the 1550-nm nonablative fractional erbium-glass laser, the ablative fractional 2940-nm erbium:YAG laser, and the ablative fractional CO2 fractional laser. Additional randomized controlled trials are necessary to further evaluate the effectiveness of the lasers, as well as to establish appropriate parameters and treatment intervals.