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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 β (OSMRβ), and oncostatin M (OSM), which is a ligand of OSMR β, 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 OSMRβ (+) 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 OSMRβ 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 OSMRβ (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.

Background One of the hallmarks of bullous pemphigoid (BP) is moderate to severe chronic itch. Managing this is difficult because little is known about the mechanisms of itch in BP. Objective We sought to elucidate the pathophysiologic mechanisms of itch in BP. Methods The expression of itch mediators in lesions of 24 patients with BP and 6 healthy individuals were examined through immunofluorescence staining. Furthermore, the expression of itch mediators and itch severity was correlated. Results Itch severity was correlated with eosinophils, substance P, neurokinin 1R, interleukin (IL) 31 receptor A, oncostatin M receptor-β, IL-13, periostin, and basophils. There was also a trend between itch severity and IL-31 expression. Most of the cells expressing IL-31 or neurokinin 1R were identified as eosinophils. Intraepidermal nerve fiber density was decreased. Other itch mediators, including mast cells, IL-4, thymic stromal lymphopoietin, transient receptor potential vanilloid 1 and ankyrin 1, and protease activated receptor 2 were not significantly correlated with itch severity. Limitations The relatively small sample size, the examination of protein expression exclusively through immunofluorescent analysis, and lack of functional assays in patients are the limitations. Conclusions Multiple factors are involved in BP-associated itch, including eosinophils, substance P, neurokinin 1R, IL-31, IL-31 receptor A, oncostatin M receptor-β, IL-13, periostin, and basophils. They could be useful therapeutic targets.

BACKGROUND Dermatology consultations in the inpatient hospital setting can improve diagnostic accuracy and management. OBJECTIVE Characterize dermatologic diagnostic and treatment trends in the hospital setting and identify variables that may affect patient care. METHODS Retrospective chart review from 1 January 2012 to 31 December 2017 at Jackson Memorial Hospital (JMH) (Miami, Florida, USA), an academic non-profit tertiary care centre affiliated with University of Miami Miller School of Medicine, was performed. Patients who received dermatology consultations in the emergency department (ED) or inpatient settings were included. Patient demographics, admission information, provisional diagnosis and management plans by primary teams, final diagnosis, management plans and testing recommendations by the dermatology consults team, and follow-up information were collected. Analysis using Microsoft Excel of how time to consultation, admission length, inpatient versus ED setting and primary team affected diagnostic accuracy was also performed. RESULTS The 1004 consultations for 812 patients (n = 812) were reviewed (359 women, 453 men). Most patients were Hispanic (n = 359; 44.2%) or African American (n = 273; 33.6%). Mean admission length was 20.6 days (range 0-439; median 6). The most common consulting service was internal medicine (n = 452). In 387 cases (47.6%), primary teams did not give a provisional diagnosis. The most common provisional diagnoses were bacterial infection (n = 93), viral infection (n = 49) and drug reaction (n = 44). The most common diagnoses by dermatology were viral infection (n = 93), bacterial infection (n = 90) and drug reaction (n = 80). Dermatology consultation changed the provisional diagnosis in 55.7% of cases, more often in cases where consultation took place ≥2 days after admission (P

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.

Introduction: Standard of care for squamous cell carcinoma (SCC) is usually surgical, with either excision or Mohs micrographic surgery. However, surgery may not be ideal for elderly patients with numerous lesions, who are poor surgical candidates or who refuse surgery. Topical 5-fluorouracil (5-FU) and imiquimod have been studied off-label as monotherapies in the treatment of SCC in situ with promising results. However, long-term tumor-free survival rates are still less than with surgical management. Methods: We report a case of biopsy-proven invasive SCC in an 86-year-old Caucasian male with history of multiple actinic keratoses and no previous skin cancers. The patient declined surgical treatment due to concerns about cosmetic outcomes. A combination of topical 5% imiquimod cream, 2% 5-FU solution, and 0.1% tretinoin cream was used five nights per week under occlusion for a treatment goal of 30 total applications. The patient was evaluated in clinic every 2 weeks during which the site was treated with cryotherapy. The patient reported burning pain associated with treatment and only completed 24 of the 30 applications. Results: Follow-up biopsy 15 months after completing topical treatment revealed dermal scar with no evidence of residual carcinoma. Conclusion: Topical combination therapy with imiquimod, 5-FU, and tretinoin with intermittent, brief cryotherapy effectively treated a small, invasive SCC in this select patient who deferred surgery. Prospective randomized-controlled clinical trials to assess the role of combination topical treatment for invasive SCCs are warranted. J Drugs Dermatol. 2020;19(2)202-204. doi:10.36849/JDD.2020.2228

The dermatologic manifestations of Waldenstrom macroglobulinemia (WM) are typically categorized as disease specific or non–disease specific.1 Non–disease-specific findings are related to hyperviscosity or cryoglobulinemia, including mucosal bleeding, purpura, livedo reticularis, and Raynaud phenomenon. Two rare types of specific skin findings have been identified: cutaneous infiltrates of mature B-cell neoplasms, specifically heavy-chain or malignant immunoproliferative diseases, and deposits of monoclonal immunoglobulin (Ig) M, referred to as cutaneous macroglobulinosis (CM). Although classically described in patients with WM, cutaneous deposition could develop in any condition associated with IgM paraproteinemia. First documented in 1978 by Tichenor et al,2 CM is remarkable for its association with underlying plasma cell dyscrasias and its ability to mimic other depositional disorders. Here, we report a patient initially diagnosed with lymphoplasmacytic lymphoma (LPL) whose subsequent development of neuropathy and hyperviscosity syndrome due to elevated serum IgM led to a diagnosis of WM. The patient then developed a disseminated cutaneous presentation of CM, with minimal residual WM disease and cryoglobulinemia.

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.

Activated charcoal has become popular in the cosmetic industry and is found in a variety of products, including facial cleansers and soaps. For centuries, charcoal has been used as an antidote for poisonings, but now companies claim that charcoal-containing products can treat acne, dandruff, and others; however, clinical evidence does not support these claims. Patients should be counseled that the use of activated charcoal is generally safe but advised that there is a lack of evidence to support its exfoliative or anti-aging abilities.

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.

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.

Introduction: Non-melanoma skin cancers (NMSCs) are the most common malignancies in humans. When treating NMSC, quality-of-life (QOL) is an important consideration. The purpose of this study was to measure and compare QOL outcomes of two common therapies for NMSC: Mohs micrographic surgery and excision, using a disease-specific QOL instrument, the Skin Cancer Index (SCI).Methods: The University of Miami Institutional Review Board approved this retrospective chart review of patients diagnosed with NMSC from 2016 through 2019 at a private dermatology clinic (Deerfield Beach, FL, USA). Disease-specific QOL before and after surgery was measured with the SCI.Results: Pre- and post-surgery surveys were completed by 208 patients undergoing Mohs surgery and 30 patients undergoing excisional surgery. All patients were similar in age, gender, and race, and most patients undergoing either procedure had a history of additional prior skin cancers. For the Mohs cohort, the total SCI scores and each of the subscales were significantly higher post-surgery when compared with the baseline scores. In contrast, in the excision cohort, the social subscale was significantly lower post-surgery when compared with the baseline scores.Conclusion: There is limited data in the literature describing the specific effects of Mohs or excision for NMSC on QOL using a disease-specific QOL instrument. Our data supports increased QOL at 2-week follow up for patients with NMSC treated with Mohs, but no improvement in QOL was noted for patients treated with excision. This data is limited by the fact there were far more patients that underwent Mohs as opposed to excision, which gave the Mohs cohort greater statistical power when analyzing the difference in SCI.

Laser and light-based therapies including low-level laser and light therapy, fractional, excimer, and other lasers are increasingly well-regarded treatment options for patients with hair loss.

Stasis dermatitis (SD) is a common disease in the elderly population, with pruritus being one of the troublesome symptoms. However, there are few therapeutic modalities available for SD-associated itch because little is known about its pathophysiological mechanism. Therefore, we sought to investigate the mediators of itch in SD using an immunofluorescence study on patient lesions focusing on IL-31. Ex vivo stimulation studies using murine peritoneal macrophages were also used to elucidate the pathological mechanisms of the generation of IL-31. In SD lesions, dermal infiltrating IL-31(+) cells were increased in number compared with the healthy controls, and the majority of IL-31(+) cells were CD68(+) macrophages. The presence of itch in SD was significantly associated with the amount of CD68(+)/IL-31(+) macrophages and CD68(+)/CD163(+) M2 macrophages. The number of CD68(+)/IL-31(+) macrophages was correlated with the number of dermal C-C chemokine receptor type 4(+) T helper type 2 cells, IL-17(+) cells, basophils, substance P(+) cells, and dermal deposition of periostin and hemosiderin. Furthermore, murine peritoneal macrophages expressed an M2 marker arginase-1 and generated IL-31 when stimulated with a combination of substance P, periostin, and red blood cell lysate (representing hemosiderin). IL-31 from macrophages may play a role in itch in SD.

Primary cutaneous Rosai-Dorfman disease is a rare form of Rosai-Dorfman disease limited to the skin. The diagnosis of primary cutaneous disease is based on a combination of clinical presentation, histopathology, and the detection of S100+, CD68+, and CD1a- histiocytic immunophenotyping. However, the diagnosis of primary cutaneous disease is often difficult and significantly delayed due to the non-specific nature of its histologic and clinical features. In this review, we describe four cases in order to familiarize pathologists and dermatopathologists with the clinicopathologic correlation of primary cutaneous Rosai-Dorfman disease and to help facilitate early diagnosis. In addition, we discuss the proposed pathophysiology and molecular etiology of this tumor, and its relationship with IgG4 sclerosing disease.

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.

Melasma is a common acquired pigmentary disorder marked by irregular hyperpigmented macules or patches and most commonly occurs in women of darker skin color. It is a chronic often-relapsing condition that causes negative psychosocial effects in those affected. Current treatments such as hydroquinone, kojic acid, and retinoids, among others, demonstrate variable efficacy and side-effect profiles. We conducted a comprehensive literature review examining the use of tranexamic acid (TA), a well-known anti-fibrinolytic agent, in the treatment of melasma. TA delivered orally, topically, and through physical methods works via the inhibition of ultraviolet (UV)-induced plasmin activity in keratinocytes. Predefined search terms were entered into PubMed. Articles were then independently screened by two authors to include only those written in the English language and relating to human subjects with at least mild melasma. The search identified 28 articles, 15 of which met the criteria for full review. The review revealed that TA treatment for melasma is equally effective or more effective than other standard therapies and may induce fewer side effects. Our comprehensive review suggests that TA may be a promising treatment option for melasma because of its demonstrated effectiveness alone and in combination with other modalities as well as its limited side-effect profile.