Plantar Skin Exhibits Altered Physiology, Constitutive Activation of Wound-Associated Phenotypes, and Inherently Delayed Healing.

Wound research has typically been performed without regard for where the wounds are located on the body, despite well-known heterogeneities in physical and biological properties between different skin areas. The skin covering the palms and soles is highly specialized, and plantar ulcers are one of the most challenging and costly wound types to manage. Using primarily the porcine model, we show that plantar skin is molecularly and functionally more distinct from nonplantar skin than previously recognized, with unique gene and protein expression profiles, broad alterations in cellular functions, constitutive activation of many wound-associated phenotypes, and inherently delayed healing. This unusual physiology is likely to play a significant but underappreciated role in the pathogenesis of plantar ulcers as well as the last 25+ years of futility in therapy development efforts. By revealing this critical yet unrecognized pitfall, we hope to contribute to the development of more effective therapies for these devastating nonhealing wounds.

Epidermolysis Bullosa Acquisita: A Case Report.

BACKGROUND Epidermolysis bullosa acquisita is a rare, subepithelial bullous disorder, which is distinguished from other autoimmune blistering diseases by the production of antibodies against type VII collagen. CASE REPORT Here, we describe the case of a 79-year-old male resident of the Northern Mariana Islands who presented to the clinic with multiple blistering skin lesions. CONCLUSIONS The primary focus of treatment is to prevent disease progression and serious complications of scarring (including blindness and respiratory obstruction) by avoiding physical trauma and suppressing the immune systems with agents, including corticosteroids, colchicine, dapsone, methotrexate, and cyclophosphamide. Successful treatment of the condition should involve a multidisciplinary team of medical professionals with regular monthly follow-ups during periods of active disease.

Targeted therapy guided by single-cell transcriptomic analysis in drug-induced hypersensitivity syndrome: a case report.

Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DiHS/DRESS) is a potentially fatal multiorgan inflammatory disease associated with herpesvirus reactivation and subsequent onset of autoimmune diseases1-4. Pathophysiology remains elusive and therapeutic options are limited. Cases refractory to corticosteroid therapy pose a clinical challenge1,5 and approximately 30% of patients with DiHS/DRESS develop complications, including infections and inflammatory and autoimmune diseases1,2,5. Progress in single-cell RNA sequencing (scRNA-seq) provides an opportunity to dissect human disease pathophysiology at unprecedented resolutions6, particularly in diseases lacking animal models, such as DiHS/DRESS. We performed scRNA-seq on skin and blood from a patient with refractory DiHS/DRESS, identifying the JAK-STAT signaling pathway as a potential target. We further showed that central memory CD4+ T cells were enriched with DNA from human herpesvirus 6b. Intervention via tofacitinib enabled disease control and tapering of other immunosuppressive agents. Tofacitinib, as well as antiviral agents, suppressed culprit-induced T cell proliferation in vitro, further supporting the roles of the JAK-STAT pathway and herpesviruses in mediating the adverse drug reaction. Thus, scRNA-seq analyses guided successful therapeutic intervention in the patient with refractory DiHS/DRESS. scRNA-seq may improve our understanding of complicated human disease pathophysiology and provide an alternative approach in personalized medicine.

Heparin-induced bullous hemorrhagic dermatosis confined to the oral mucosa.

Unfractionated heparin (UFH) is frequently used in the treatment of venous thromboembolism and acute coronary syndrome. There are many common cutaneous adverse reactions to this medication. We present a unique case of hemorrhagic bullae limited to the oral mucosa that developed within 6 hours of a patient receiving UFH.

Bullous systemic lupus erythematosus successfully treated with rituximab.

Bullous systemic lupus erythematosus (BSLE) is a rare complication of systemic lupus erythematosus (SLE) characterized by cutaneous vesicles and bullae with a primarily neutrophilic infiltrate on histopathology. Bullous SLE is a heterogeneous disease without pathognomonic clinical features, making the diagnosis and differentiation from other blistering diseases challenging. We present the case of a single patient with SLE in whom 3 different clinical appearances of BSLE manifested over 5 years. The cutaneous eruption dramatically improved with rituximab at the initial presentation and continued to respond to rituximab during subsequent flares over the subsequent 5 years.

The Burden of Skin Disease on Deployed Servicemembers.

INTRODUCTION: Skin diseases have had a significant impact on the health of deployed military service members throughout history. Given the high prevalence historically of cutaneous disease among United States deployed servicemembers, we review the burden of skin disease on the modern military by analyzing the most common dermatologic diagnoses made in deployed settings from 2008 to 2015. Furthermore, we compare the most common dermatologic diagnoses made in the deployed setting with those made by dermatologists and nondermatologists in the civilian healthcare system to highlight the differences between the civilian and deployed military practice environment. METHODS: This study queried the Theater Medical Data Store for International Classification of Diseases, Ninth Revision (ICD-9) codes to determine the total number of dermatologic encounters as part of all medical encounters from 2008 to 2015 in a deployed setting. These data were provided by the Armed Forces Health Surveillance Branch. For all statistical tests, analyses were conducted using R statistical software, with type I error controlled at 5%. RESULTS: From 2008 to 2015, 92 dermatology-specific ICD-9 codes accounted for 429,837 dermatologic diagnoses that were made in a deployed setting, equating to 10% of all diagnoses. The top 20 dermatologic diagnoses were identified, and the percentage of total medical diagnoses (TMD) was calculated. Once the individual diagnoses were categorized, a direct comparison was made between the top 20 most prevalent disease categories among deployed military servicemembers and those of the United States (US) population as a whole, based on claims. The most prevalent diagnoses were compared amongst four different settings: Deployed military, military teledermatology, civilian dermatologists, and civilian nondermatologists. Overall comparison of the prevalence between each of these groups showed an association between setting and diagnosis prevalence. CONCLUSIONS: The total burden of disease based on diagnostic codes from 2008 to 2015 is 429,837 diagnoses. This accounts for 10% of TMD from 2008 to 2015 in the deployed setting. Diagnoses most prevalent in the deployed military setting had more in common with those made by civilian nondermatologists compared with military teledermatology and civilian dermatologists. At 10% of diagnoses made in the deployed military setting in this timeframe, skin disease accounts for a substantial burden on deployed servicemembers. Deployed servicemembers with skin disease should be supported through use of teledermatology resources and improved dermatology education for primary care and deployed medical personnel.

The dermatologist's role in amputee skin care.

Amputees face many challenges associated with residual limbs. Overall, amputees have an increased risk for skin disease occurring at residual limb sites. Although prosthetists and primary care physicians often accomplish routine care, the dermatologist plays a very important role within the multidisciplinary team. Many military dermatologists have unique clinical experience treating amputees, as a portion of their practice consists of providing care to soldiers with traumatic amputations from complex and dramatic blast injuries. Although current therapies and preventative treatments are for the most part successful, future research involving advanced technology is promising.

Amantadine-induced livedo reticularis in a child treated off label for neurobehavioral disorders.

We report the case of an 8-year-old boy who was taking amantadine off label for multiple childhood neurobehavioral disorders and subsequently developed livedo reticularis. Although this side effect is well-described in adult patients taking amantadine for Parkinson disease, it is now being seen in children as the off-label use of amantadine is expanded to this population.

Diffuse vesiculobullous eruption with systemic findings.

Drug induced linear IgA bullous dermatosis (LABD) is a rare blistering disease that has been shown to be associated with the use of various medications. Although rarely seen together, some of the medications associated with LABD can lead to the syndrome drug reaction with eosinophilia and systemic symptoms (DRESS), which presents with fever, cutaneous eruption, and multi-organ involvement. We present a patient who developed fever and a generalized vesiculobullous eruption after recently starting amlodipine and meloxicam. Initial laboratory tests demonstrated elevated liver function tests, leukocystosis, and eosinophilia. Histopathologic examination of the punch biopsy revealed a bulla with sub-epidermal split and numerous neutrophils. Direct immunofluorescence demonstrated broad deposition of IgA along the dermal-epidermal junction. These findings were consistent with an overlap between LABD and DRESS. Drug induced LABD and DRESS are independently both rare diseases. It is even more uncommon to see the two concurrently in the same patient. In this patient, these two conditions were thought to be triggered by either amlodipine or meloxicam. Given the high mortality rate associated with DRESS, it is important to recognize the presentation and initiate the appropriate treatment plan as soon as possible.

Melanoma in an Active Duty Marine.

Given that the majority of active duty service members are young and healthy, potentially malignant diagnoses such as skin cancer may be overlooked. Although melanoma accounts for only approximately 1% of skin cancers, it causes the greatest majority of skin cancer deaths. We present the case of a 27-year-old active duty Marine who presented with a hyperpigmented macule at his lateral neck that was a malignant melanoma in situ. This article reviews risk factors for the development of melanoma, offers guidelines for primary care providers, reviews resources for providers in a deployed or austere environment, offers recommendations for prevention and early diagnosis, and discusses follow up.

Total-body photography in skin cancer screening: the clinical utility of standardized imaging.

Early detection of skin cancer is essential to reducing morbidity and mortality from both melanoma and nonmelanoma skin cancers. Total-body skin examinations (TBSEs) may improve early detection of malignant melanomas (MMs) but are controversial due to the poor quality of data available to establish a mortality benefit from skin cancer screening. Total-body photography (TBP) promises to provide a way forward by lowering the costs of dermatologic screening while simultaneously leveraging technology to increase patient access to dermatologic care. Standardized TBP also offers the ability for dermatologists to work synergistically with modern computer technology involving algorithms capable of analyzing high-quality images to flag concerning lesions that may require closer evaluation. On a population level, inexpensive TBP has the potential to increase access to skin cancer screening and it has several specific applications in a military population. The utility of standardized TBP is reviewed in the context of skin cancer screening and teledermatology.

Exploration of modern military research resources.

This article outlines the unique resources available in the US Military to investigate epidemiologic trends, disease pathology, and clinical outcomes. These resources are available to military researchers and civilian collaborators and provide an invaluable research platform.

How to teach the potassium hydroxide preparation: a disappearing clinical art form.

Using potassium hydroxide (KOH) preparations in the diagnosis of superficial fungal infections is a technique that has been handed down from teacher to apprentice for more than 100 years. The technique is simple, accurate, and inexpensive; however, there is reason to believe it is falling to the wayside in favor of empiric treatment, especially in primary care settings. To continue the use of this valuable diagnostic aid, a system of teaching the KOH preparation to the next generation of physicians (ie, medical students, residents) is proposed with emphasis on facilitating the process by storing viable skin samples infected with dermatophytes for long periods of time. This technique obviates the need to find suitably infected patients before each teaching laboratory. This technique also is appropriate to refresh the skills of practicing physicians as they prepare for point-of-care testing assessments.

Treatment of Psoriasis in the Deployed Setting.

Psoriasis is a chronic immune-mediated disorder that can be triggered by environmental changes, illness, smoking, or medications. This case describes a 25-year-old, active-duty Marine Corps Sergeant with a severe perideployment psoriatic flare, and illustrates treatment limitations, restricted access to specialized care, and the importance of mitigating triggers in the deployed setting.

Utilization of telemedicine in the U.S. military in a deployed setting.

BACKGROUND: A retrospective evaluation of the Department of Defense teledermatology consultation program from 2004 to 2012 was performed, focusing on clinical application and outcome measures such as consult volume, response time, and medical evacuation status. METHODS: A retrospective review of the teledermatology program between 2004 and 2012 was evaluated based on defined outcome measures. In addition, 658 teledermatology cases were reviewed to assess how the program was utilized by health care providers from 2011 to 2012. RESULTS: As high as 98% of the teledermatology consults were answered within 24 hours, and 23% of consults within 1 hour. The most common final diagnoses included eczematous dermatitis, contact dermatitis, and evaluation for nonmelanoma skin cancer. The most common medications recommended included topical corticosteroids, oral antibiotics, antihistamines, and emollients. Biopsy was most commonly recommended for further evaluation. Following teleconsultation, 46 dermatologic evacuations were "avoided" as the patient was not evacuated based on the consultants' recommendation. Consultants' recommendations to the referring provider "facilitated" 41 evacuations. CONCLUSION: Telemedicine in the U.S. military has provided valuable dermatology support to providers in remote locations by delivering appropriate and timely consultation for military service members and coalition partners. In addition to avoiding unnecessary medical evacuations, the program facilitated appropriate evacuations that may otherwise have been delayed.

Bullous systemic lupus erythematosus: a review and update to diagnosis and treatment.

Bullous systemic lupus erythematosus (BSLE) is a rare cutaneous complication of systemic lupus erythematosus (SLE). It is a heterogeneous disease that is caused by autoantibodies to the dermoepidermal junction, mainly type VII collagen. Similarities in histology and immunopathology exist between BSLE and other primary bullous dermatoses, namely dermatitis herpetiformis (DH) and epidermolysis bullosa acquisita (EBA), respectively. EBA and BSLE commonly share the same autoantibody to type VII collagen and heterogeneous clinical presentations, creating a diagnostic challenge. However, clinical presentation combined with histology, immunological testing, and concomitant diagnosis of SLE distinguish this entity from other similar dermatoses. Diagnosis of this disease is important given its coexistence with SLE and its many complications. New developments in IgG subtyping have shown subtle variations in IgG subtypes between EBA and BSLE. In addition, rituximab was recently found to be efficacious in recalcitrant cases of BSLE that do not respond to dapsone and immunosuppressants. We review the topic of BSLE with emphasis on clinical, histologic, and immunopathologic features, as well as new methods of diagnosis and treatment.

Amputation stump: Privileged harbor for infections, tumors, and immune disorders.

The stump site of amputees presents a fragile cutaneous landscape that is prone to skin disease due to many factors. Amputations damage cutaneous, nervous, musculoskeletal, and vascular structures, and alter lymphatic drainage. This altered skin, when placed in the socket of a prosthesis, must adapt to a humid environment and withstand the compressive and frictional forces for which it is poorly adapted. These factors and any history of vascular disease, diabetes, or malignancy make stump skin more vulnerable to immunologic and tissue breakdown, leading to an area of local immune dysregulation called an immunocompromised district. This term encompasses the idea that stump skin is more prone to dermatologic conditions, such as inflammation, infection, and malignancies. Unlike the volar skin found on the palms and soles, the stump skin is not adapted to withstand the compressive forces generated from the prosthesis during movement, particularly during ambulation. In some cases, skin disease and pain at the stump lead to prosthesis abandonment, which has a negative impact on amputees' quality of life. Researchers are looking into ways to increase the adaptation and durability of stump skin, thereby decreasing skin breakdown, infections, tumors, and malignancies commonly seen on this vulnerable site. Skin disease continues to be a vexing problem for amputees and those who care for them. This contribution reviews skin disease at the stump site and explores the broader context of the amputee stump as an immunocompromised district.

Survey of medical student preference for simulation models for basic dermatologic surgery skills: simulation platforms in medical education.

BACKGROUND: The authors investigated the use of simulator platforms in fourth-year medical student education. OBJECTIVE: To evaluate which simulation platform students preferred for learning dermatologic procedures and to assess the effectiveness of the exercise in terms of the change in confidence that the students had performing dermatologic procedures. MATERIALS AND METHODS: After medical students were instructed on how to perform a punch biopsy and then assisted in executing the task, they were surveyed to determine their preferred simulation platform and simulator properties. Students were surveyed at the beginning and completion of the teaching block. RESULTS: One hundred fifty-seven students completed the skills laboratory, and 78 completed the preference questionnaire. Of the 11 surveyed categories, students preferred the pig foot in eight categories. Seventy students responded to a surgical skills questionnaire that assessed their overall confidence in planning and executing the procedure before and after the skills laboratory. The students had a statistically significant increase in confidence in dermatologic procedural skills as a result of the activity. CONCLUSION: Preference data show that the pig foot model is preferred for teaching dermatologic surgical skills. These results re-affirm that the pig foot model is an effective, low-cost solution for training.