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Immunosuppression is a well-documented risk factor for skin cancer, as exemplified by the 65- to 250-fold higher squamous cell carcinoma risk, 10-fold higher basal cell carcinoma risk, and 0 to 8-fold higher melanoma risk in solid organ transplant recipients (SOTRs) receiving potent, prolonged courses of immunosuppressive therapies. Numerous immune system components have been shown to either suppress or promote tumor growth, and immunosuppressive drugs may have additional effects on proliferative pathways independent of the immune system. Thus, evaluation of the specific regimen by the dermatologist is key for assessing skin cancer risk in each patient. In the present manuscript, the immune-mediated mechanisms of skin cancer development and regression are first reviewed. Next, a synthesis of the evidence shows the differing effects of immunosuppressive agents commonly used in SOTRs on melanoma and nonmelanoma skin cancer risk. These include systemic calcineurin inhibitors, thiopurines, IMDH (inosine monophosphate dehydrogenase) inhibitors, mTOR (mammalian target of rapamycin) inhibitors, and systemic corticosteroids. Finally, recommendations for skin cancer screening in SOTRs are discussed. We further offer recommendations for select nontransplant patients who may benefit from routine skin cancer screening due to risks associated with specific immunosuppressant exposure, and we propose evidence-based strategies for minimizing high-risk immunosuppressant use in clinical practice.

In solid organ transplant recipients, skin cancer risk associated with post-transplant immunosuppression has been well-described, and screening practices generally reflect these risks. In addition to agents used post-transplant, other classes of immunosuppressants also have the potential to raise the risk of nonmelanoma skin cancer (NMSC) or melanoma. In the present manuscript, the evidence for melanoma and NMSC risk associated with methotrexate, cyclophosphamide, biologic cytokine inhibitors including TNF-alpha and interleukin inhibitors, costimulation blockers such as abatacept, integrin inhibitors such as natalizumab, targeted B-cell and T-cell inhibitors including CD20, CD52, and BTK inhibitors, and JAK inhibitors is reviewed. Based on the available data, we recommend regular skin cancer screening for select non-transplant patients receiving immunosuppressive regimens shown to raise the risk of NMSC or melanoma. We also offer suggestions for conscientious use of these therapies in high-risk patients. Finally, a comprehensive summary of the relative risk associated with each immunosuppressant class and associated recommendations is presented.

It is important for the dermatopathologist to be adept in differentiating tissue artifacts from normal tissue variants and pathologies. Numerous tissue artifacts have been described to date; however, once we are familiar with the common artifacts that appear in our practice, we may not immediately recognize other confounders. For example, dermatopathologists in more temperate regions of the country may not be familiar with freezing artifact. In this case series, we present three common diagnoses in dermatopathology that were obscured by the extreme winter weather that severely impacted the Southern United States in February 2021 and discuss methods to prevent these artifacts.

Hidradenitis suppurativa (HS) is an inflammatory skin disorder typically affecting the groin, inframammary folds, and axillae. HS is characterized by the development of boils, abscesses, fistulas, and sinus tracts. Due to the inflammatory destruction of lymph vessels, patients with long-standing HS may develop lymphedema. Most commonly reported in the literature is lymphedema involvement of the genital and anal regions. In this case report, we describe unilateral breast skin changes in a patient with HS. The patient was extensively worked up for inflammatory breast cancer, and eventually underwent stereotactic biopsies. Subsequently, these biopsies were consistent with lymphedema due to her chronic HS. Although rare, there is a paucity of literature describing breast lymphedema associated with HS. As breast lymphedema due to HS may mimic inflammatory breast cancer, it is important for providers to firstly rule out malignancy and place lymphedema high on the differential when examining and treating these patients.

AIMS Lentigo maligna (LM), the most common type of melanoma in situ, is a diagnostically challenging lesion for pathologists due to abundant background melanocytic hyperplasia in sun-damaged skin. Currently, no laboratory methods reliably distinguish benign from malignant melanocytes. However, preferentially expressed antigen in melanoma (PRAME) has shown promise in this regard, and could potentially be applied to diagnosis and margin assessment in difficult cases of LM. METHODS AND RESULTS Ninety-six cases with a diagnosis of LM (n = 77) or no residual LM (n = 19) following initial biopsy were identified and stained with an antibody directed towards PRAME. Immunohistochemistry (IHC) was scored as positive or negative, and measurement of histological margins by PRAME was performed and compared to the measurement of histological margins using conventional methods [haematoxylin and eosin (H&E) and/or sex-determining region Y-box 10 (SOX10) and/or Melan-A]. Of cases with LM, 93.5% (72 of 77) were PRAME+ and 94.7% (18 of 19) of cases with no residual LM were PRAME- . Of the 35 cases with no margin involvement by PRAME or conventional assessment, 14 cases (40.0%) had no difference in measurement, 17 (48.6%) had a difference of 1 mm or less and four (11.4%) differed by between 1 and 3.5 mm. There was a high correlation between margin assessment methods (r = 0.97, P

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A distinct Darier phenotype presenting with confetti-like hypopigmented macules was first described in 1965. Designated as "guttate leukoderma," this skin finding is a rarely-reported presentation of Darier disease. It has been theorized that the mutation in ATP2A2 causes defective E-cadherin, which in turn disrupts the adhesion of melanocytes to keratinocytes, thus leading to impaired dendrite formation, hindered melanin transfer, and ultimately to melanocyte apoptosis. Herein, we contribute a case of a 56-year old woman who presented with the rarely-described guttate leukoderma of Darier disease and acrokeratosis verruciformis of Hopf.

Background: The aim of this study was to validate the English version of the Itch Cognition Questionnaire in a sample of patients with chronic itch due to psoriasis or atopic dermatitis. An English-language version of an instrument assessing itch-related cognitions is needed since cognitions can contribute to a worsening of itch, and chronic itch is prevalent in English-speaking counties and internationally. Methods: The German Itch Cognitions Questionnaire was translated into English, and cognitive interviewing was conducted to finalize item wording. Internal and test-retest reliability, item discrimination, responsiveness to change, and construct, convergent, and discriminant validity were assessed in a national sample of 137 individuals with chronic itch due to atopic dermatitis or psoriasis recruited online. Results: Internal reliability was high with Cronbach’s alphas of 0.93 for the Catastrophizing subscale and 0.88–0.90 for Coping. The Pearson’s correlation assessing 1-month test-retest reliability for the Catastrophizing subscale was r = 0.62 and for the Coping subscale was r = 0.61. The corrected item-total correlation revealed that items were relatively consistent with the scores for the subscales (with correlations ranging from 0.58 to 0.79), indicating very good item discrimination. Results of factor analysis, convergent and discriminant, and responsiveness to change analyses provided evidence for validity. Conclusions: This study showed good psychometric characteristics of the English version of the Itch Cognitions Questionnaire. We suggest that future studies investigate the use of the measure in clinical practice to assist with treatment planning and outcome assessment related to itch as well as address study limitations such as sampling and replication.

A distinct Darier phenotype presenting with confetti-like hypopigmented macules was first described in 1965. Designated as "guttate leukoderma," this skin finding is a rarely-reported presentation of Darier disease. It has been theorized that the mutation in ATP2A2 causes defective E-cadherin, which in turn disrupts the adhesion of melanocytes to keratinocytes, thus leading to impaired dendrite formation, hindered melanin transfer, and ultimately to melanocyte apoptosis. Herein, we contribute a case of a 56-year old woman who presented with the rarely-described guttate leukoderma of Darier disease and acrokeratosis verruciformis of Hopf.

is missing (Short communication)

Drug-induced chronic cutaneous lupus erythematosus, or drug-induced discoid lupus erythematosus, is a rare cutaneous phenomenon. Various medications have been associated with drug-induced discoid lupus erythematosus including fluorouracile agents, especially tegafur and uraciltegafur, and TNF-α antagonists such as infliximab or etanercept. Recent literature has described a case series of six patients receiving IgG immunoglobulin for chronic inflammatory demyelinating polyneuropathy with subsequent presentations of discoid lupus erythematosus. We present a patient with chronic inflammatory demyelinating polyneuropathy who developed discoid lupus erythematosus secondary to IgG immunoglobulin.

Self-report measures are needed to better understand the relationships among sleep, itching, scratching, and chronic itch conditions and their associations with disease severity, QOL, health, and functioning. Two scales related to sleep and/or scratch were recently developed and assessed in 137 patients with chronic itch and atopic dermatitis or psoriasis. The Scratch Intensity and Impact Scale consisted of two factors (scratching intensity and impact of scratching on QOL) that accounted for 64.59% of the variance with a total of 13 items, overall Cronbach's α of 0.93, and test-retest reliability of 0.66. The Sleep-Related Itch and Scratch Scale consisted of one factor that accounted for 63.01% of the variance with a total of 16 items, overall Cronbach's α of 0.98, and test-retest reliability of 0.66. Both measures demonstrated significant correlations with each other as well as other itch-related measures and nonsignificant correlations with scales hypothesized to be unrelated. The final measures demonstrated adequate preliminary psychometric characteristics. It is hoped that these scales will be used for future research and clinical purposes to help fill recognized gaps in understanding about sleep, itch, scratching, atopic dermatitis, and psoriasis.

Patient education programs are beneficial in the treatment of chronic diseases. In Germany, France, and other countries worldwide, educating children, adolescents, and adults plus the parents of children with atopic dermatitis (AD) leads to better coping with the skin disease, as well as to a reduction in the severity of the skin symptoms and signs. The results in Europe led to the idea to also establish an eczema school in the United States. In the style of the German eczema school, an eczema school was founded in 2014 at Temple University, Philadelphia, PA. Since then, a team consisting of a dermatologist, psychologist, nutritionist, and nurse practitioner has offered an eczema school to interested patients with AD and their families three times a year. This patient education program consists of three weekly 2-hour sessions, which address proper skin care, the itch-scratch cycle, healthy nutrition, and the role of stress in AD. The current review summarizes the first experiences with the education program in the United States.

Clinical trials have shown the positive effects of local insulin therapy in the formation of new vessels and fibrosis in acute and chronic diabetic wounds without major adverse effects.The aim of this study was to investigate the effects of local insulin use on wound healing in non-diabetic patients.A randomized, split-plot, double-blind, placebo-controlled trial was conducted. Ten non-diabetic patients with full-thickness acute wounds were recruited (5 due to trauma, 3 to burns, and 2 to pressure). All wounds received standard bedside treatment. Each wound was divided into 2 zones. One side received a standard care plus insulin, while the other received standard care plus injection of saline solution. A biopsy specimen was taken from both sites on days 0 and 14. The amount of blood vessel growth and the percentage of fibrosis were evaluated.A significant difference in the number of new vessels was observed on the insulin-treated site (70.6 [29.21]) compared to saline only (26.5 [34.3];We suggest that local insulin administration is a safe therapeutic option for angiogenesis in wounds of non-diabetic patients.Les essais cliniques démontrent les effets positifs de l’insulinothérapie localisée pour former de nouveaux vaisseaux ou une fibrose en cas de plaies aiguës ou chroniques causées par le diabète, sans entraîner de réactions indésirables majeures.La présente étude visait à évaluer les effets de l’utilisation localisée d’insuline chez des patients non diabétiques.Les chercheurs ont réalisé un essai aléatoire et contrôlé contre placebo, en parcelles divisées et à double insu. Ils ont recruté dix patients non diabétiques ayant des plaies aiguës de pleine épaisseur (cinq à cause d’un traumatisme, trois à cause de brûlures et deux à cause de pression). Toutes les plaies ont fait l’objet de soins standards au chevet du patient et chacune a été divisée en deux zones. Une zone faisait l’objet de soins standards avec l’ajout d’insuline et l’autre zone, de soins standards avec l’injection de soluté physiologique. Les chercheurs ont prélevé une biopsie dans chaque zone les jours 0 et 14. Ils ont évalué la croissance des vaisseaux sanguins et le pourcentage de fibrose.Les chercheurs ont observé une différence significative dans le nombre de nouveaux vaisseaux de la zone traitée à l’insuline (70,6 ± 29,21) par rapport à celle traitée à l’aide de soluté physiologique (26,5 ± 34,3;Selon les chercheurs, l’administration localisée d’insuline serait sécuritaire pour l’angiogenèse des plaies des patients non diabétiques.

Chronic itch is a common and debilitating health condition in the elderly. There are several common causes of itch in the mature population, such as skin xerosis, immunosenescence, and neuropathic changes. In addition, skin diseases, such as seborrheic dermatitis and stasis dermatitis, systemic conditions (end-stage renal disease and diabetes), or psychogenic derailments, such as depression, anxiety, and dementia, can all serve as triggers of pruritus. Polypharmacy, a common occurrence among the elderly population, may also serve as a cause of itch that may or may not be accompanied by dermatitis. Such medications as μ opioids and calcium channel blockers have been found to have a connection with pruritus in the advanced aging population. Determining the exact trigger for pruritus in the elderly may be especially challenging, because itch can be idiopathic in many cases. The role of treatments should not only take into account elimination of various underlying cutaneous, systemic, or psychogenic conditions associated with itch but also focus on the skin changes that are characteristic of the aging process. Development of such treatment options can be guided by elucidation of the mechanisms underlying the pathophysiology of itch in the geriatric population.

A cross-sectional study of geriatric patients was performed to provide a comprehensive description of the prevalence and clinical characteristics of chronic itch affecting Hispanic geriatric subjects in Mexico. Participants were recruited from both nursing homes and geriatric ambulatory care centers. Patients without dementia were evaluated using an itch intensity and characteristic questionnaire and were assessed for itch-related dermatoses (n = 302). Data on medications and underlying systemic diseases were obtained from medical records. The prevalence of chronic itch was 25% in this population. Of those with chronic itch, 69% had xerosis, 28% had itch-related dermatoses, and 96% had documented comorbidities. The most common comorbidities were diabetes mellitus (OR = 2.3, 95% CI 1.3-3.9, p = 0.003) and chronic venous insufficiency (OR = 4.4, 95% CI 1.6-12.2, p = 0.002). The most common areas where patients experienced itch were legs (54%), back (45%), scalp (28%) and arms (27%). Patients experienced the greatest amount of itch in the winter (77%) and during the night (65%). Chronic itch is a common problem in the studied Hispanic geriatric population, and its presence significantly correlates with xerosis, diabetes, and venous insufficiency.

Skin is the most exposed organ of the body, and military personnel face many external skin threats. As a result, skin disease is an important source of morbidity among military personnel deployed on combat or peacekeeping operations. This article reviews the most common conditions seen by deployed military dermatologists. A PubMed search was used to identify articles in English, written between 1965 and 2014, using medical subject headings "military medicine" AND "skin disease" or "military personnel" AND "skin disease." The five most common reasons for physician consultation for skin conditions in wartime since the Vietnam War were warts (10.7%), fungal infections (10.4%), acne (9.0%), nonspecific eczematous conditions (7.1%), and sexually transmitted diseases (6.1%). There was a significant difference in the skin conditions seen in the hot and humid climates of Vietnam and East Timor, where bacterial and fungal infections were more common reasons for consultation, and the dry climates of Bosnia and Iraq, where eczematous conditions made up a larger part of the dermatologic caseload.

Atopic dermatitis is a chronic skin condition which has significant psychosocial and quality of life impact. The condition causes physical discomfort, emotional distress, embarrassment, social stigma and daily activity limitation. In an effort to assess these aspects of disease burden, quality of life measurement tools were developed. Through use of these tools, we have expanded our knowledge of the psychosocial and quality of life burden of this condition. A variety of quality of life assessment tools exist, yet there is no consensus on which tool is best suited to assess the quality of life impact of atopic dermatitis. Research studies assessing quality of life in atopic dermatitis patients utilize a variety of quality of life measurement tools; this complicates comparisons across research studies. Though comparison across studies is difficult, the data echoes tremendous overall burden of disease, especially pertaining to psychosocial status and life quality.

Melanoma is the leading cause of skin cancer deaths in the United States, and its incidence has been rising steadily for the past 30 years (Aftab, Dinger, & Perera, 2014). A more complete understanding of the molecular mechanisms that drive melanomagenesis is crucial to improve diagnosis, prognostication, and treatment of this disease. Given that melanoma survival rates are better when the disease is detected early, precise diagnostic tests for early melanoma detection would be extremely useful. In addition, as survival rates decrease drastically when the disease becomes metastatic, improved tools to more precisely identify high-risk patients as well as to predict treatment response are necessary. The role of microRNAs (miRNAs) in melanoma biology could be the key. miRNA expression profiling has identified several miRNAs that play a crucial role in melanoma cell proliferation, migration, and invasion, as well as miRNAs involved in apoptosis and in the immune response. Here we review the most current data on the miRNAs involved in melanoma as well as their potential roles as diagnostic and prognostic biomarkers of this disease.

To identify itch-related mediators and receptors that are differentially expressed in pruritic skin, we used RNA sequencing to analyze the complete transcriptome in skin from paired itchy, lesional and nonitchy, nonlesional skin biopsies from 25 patients with atopic dermatitis and 25 patients with psoriasis and site-matched biopsies from 30 healthy controls. This analysis identified 18,000 differentially expressed genes common between itchy atopic and psoriatic skin compared with healthy skin. Of those, almost 2,000 genes were differentially expressed between itchy and nonitchy skin in atopic and psoriatic subjects. Overexpression of several genes, such as phospholipase A2 IVD, substance P, voltage-gated sodium channel 1.7, and transient receptor potential (TRP) vanilloid 1, in itchy skin was positively correlated with itch intensity ratings in both atopic dermatitis and psoriasis. Cytokines such as IL-17A, IL-23A, and IL-31 had elevated gene transcript levels in both itchy atopic and psoriatic skin. However, expression of genes for TRP vanilloid 2, TRP ankyrin 1, protease-activated receptor 2, protease-activated receptor 4, and IL-10 was found to be increased only in pruritic atopic skin, whereas expression of genes for TRP melastatin 8, TRP vanilloid 3, phospholipase C, and IL-36α/γ was elevated only in pruritic psoriatic skin. This "itchscriptome" analysis will lead to an increased understanding of the molecular mechanisms of chronic pruritus and provide targets for itch treatment irrespective of disease state.

Atopic dermatitis is a chronic skin condition which has significant psychosocial and quality of life impact. The condition causes physical discomfort, emotional distress, embarrassment, social stigma and daily activity limitation. In an effort to assess these aspects of disease burden, quality of life measurement tools were developed. Through use of these tools, we have expanded our knowledge of the psychosocial and quality of life burden of this condition. A variety of quality of life assessment tools exist, yet there is no consensus on which tool is best suited to assess the quality of life impact of atopic dermatitis. Research studies assessing quality of life in atopic dermatitis patients utilize a variety of quality of life measurement tools; this complicates comparisons across research studies. Though comparison across studies is difficult, the data echoes tremendous overall burden of disease, especially pertaining to psychosocial status and life quality.

Objective The presence in the brain of α-synuclein containing Lewy neurites, or bodies, is the histological hallmark of Parkinson's disease (PD). The discovery of α-synuclein aggregates in nerve endings of the heart, digestive tract, and skin has lent support to the concept of PD as a systemic disease. Our goals were, first, to demonstrate the presence of α-synuclein inclusions in the skin and, second, to detect quantitative differences between patients with PD and atypical parkinsonism (AP). Methods Skin biopsies were taken from 67 patients and 20 controls. The biopsies underwent immunohistochemistry (IHC) and immunofluorescence (IF) testing for α-synuclein, whereupon its presence was quantified as the percentage of positive cells. Patients were divided into those with PD and those with AP. AP patients included AP with neurodegenerative disease (proteinopathies) and secondary AP. Results Sixty-seven patients (34 with PD) and 20 controls were recruited. In the PD group, α-synuclein was detected in 58% of the cells in the spinous cell layer (SCL), 62% in the pilosebaceous unit (PSU), and 58% in the eccrine glands (EG). The AP-proteinopathies group showed 7%, 7%, and 0% expression of α-synuclein, respectively. No expression was found in the skin of the control group. Conclusions The expression of α-synuclein in the skin was relatively high in the PD group, scarce in AP, and null for the individuals in the control group. While these findings require further confirmation, this minimally invasive technique may aid in the improvement of the accuracy of PD diagnoses.

BACKGROUND Clinical trials have shown the effectiveness of systemic and local insulin therapy in improving wound healing. Diabetic wounds remain a challenge for healthcare providers. Impaired angiogenesis and reduced granulation tissue formation contribute to inadequate wound healing. The aim of this study was to investigate the effect of local insulin administration in acute and chronic diabetic wounds. METHODS Eight diabetic patients presenting with full-thickness wounds, of different causes, were included in this study. Five wounds were due to necrobiosis, one to trauma, and two to postneoplasm resection. All wounds were treated with regular bedside treatment. In addition, half of the wound surface was treated with insulin and the other half did not receive insulin. Thermographic and biopsy specimens of the two sides were obtained on days 0 and 14. The presence of fibrosis, change in temperature, and amount of blood were evaluated. RESULTS Significant differences in the number of vessels were observed on the insulin-treated side (96 ± 47) when compared with the no-insulin side (32.88 ± 45) (p < 0.026). The percentage of fibrosis (insulin: 44.42 ± 30.42 percent versus no insulin: 12.38 ± 36.17 percent; p < 0.047) and the mean temperature (insulin: 1.27 ± 1.12°C versus no-insulin: 0.13 ± 1.22°C; p < 0.001) were also significantly different between sides. No adverse events related to the study occurred. CONCLUSION The use of local insulin improves the formation of new blood vessels, increases fibrosis, and correlates with increased temperature. CLINICAL QUESTION/LEVEL OF EVIDENCE Therapeutic, II.

Supplemental Digital Content is available in the text., Itch can be suppressed by scratching. At the same time, scratching evokes a pleasurable sensation. In the present study, we investigated the peripheral mechanism of scratching-induced pleasurability and its association with itch relief using compression nerve block. We found that myelinated nerve fibers (Aβ-fibers and possibly Aδ-fibers), are involved in transmission of scratching-induced pleasurability. We observed that itch relief effect was the same regardless of whether the pleasurable sensation was evoked by scratching an itch, indicating that pleasure is not a necessary component to induce itch relief. This is the first study to investigate the peripheral mechanism of scratching-induced pleasurability and itch relief.

Chronic itch is a common skin manifestation in many connective tissue diseases. However, the cause of chronic itch in these diseases is still not fully understood. The complex, and in some cases incomplete understanding of, pathogenesis in each condition makes it difficult to target specific mediators of chronic itch. It is important to better understand the pathophysiology of chronic itch in these conditions, as this information might provide a fuller understanding of the pathogenesis of the diseases in general and lead to the development of more specific treatments for connective tissue diseases in patients with chronic itch. We present a review of the literature on what is known about the prevalence, possible pathophysiology, and effect on quality of life of chronic itch in patients with scleroderma, Sjogren's syndrome, dermatomyositis, systemic lupus erythematosus, cutaneous lupus erythematosus, and mixed connective tissue disease.

A 66-year-old woman presented with a 3 cm black, ulcerated nodule located on the skin of the upper abdomen, just below the breast. The lesion was painful to the touch, but the patient reported no other associated symptoms and was otherwise healthy. A 4-mm punch biopsy of the affected skin was obtained and the histological diagnosis was cutaneous metastatic pigmented breast carcinoma.