Amyopathic dermatomyositis with TIF1? positivity treated with IVIG.

Dermatomyositis is an inflammatory myopathy involving the skin that typically affects patients between 40-60 years of age and is more likely to be diagnosed in women. Around 10-20% of dermatomyositis cases present with subclinical or absent muscle involvement, termed "clinically amyopathic." Presence of anti-transcription intermediary factor 1? (TIF1?) antibodies is an important indicator of underlying malignancy. We present a patient with anti-TIF1? positive amyopathic dermatomyositis associated with bilateral breast cancer. The patient was safely treated with trastuzumab for breast cancer and intravenous immunoglobulin for dermatomyositis.

Store-and-Forward Images in Teledermatology: Narrative Literature Review.

Background: Store-and-forward (SAF) teledermatology uses electronically stored information, including patient photographs and demographic information, for clinical decision-making asynchronous to the patient encounter. The integration of SAF teledermatology into clinical practice has been increasing in recent years, especially during the COVID-19 pandemic. Despite this growth, data regarding the outcomes of SAF teledermatology are limited. A key distinction among current literature involves comparing the quality and utility of images obtained by patients and trained clinicians, as these metrics may vary by the clinical expertise of the photographer. Objective: This narrative literature review aimed to characterize the outcomes of SAF teledermatology through the lens of patient- versus clinician-initiated photography and highlight important future directions for and challenges of the field. Methods: A literature search of peer-reviewed research was performed between February and April 2021. Key search terms included patient-initiated, patient-submitted, clinician-initiated, clinician-submitted, store-and-forward, asynchronous, remote, image, photograph, and teledermatology. Only studies published after 2001 in English were included. In total, 47 studies were identified from the PubMed electronic database and Google Scholar after omitting duplicate articles. Results: Image quality and diagnostic concordance are generally lower and more variable with patient-submitted images, which may impact their decision-making utility. SAF teledermatology can improve the efficiency of and access to care when photographs are taken by either clinicians or patients. The clinical outcomes of clinician-submitted images are comparable to those of in-person visits in the few studies that have investigated these outcomes. Coinciding with the onset of the COVID-19 pandemic, asynchronous teledermatology helped minimize unnecessary in-person visits in the outpatient setting, as many uncomplicated conditions could be adequately managed remotely via images captured by patients and referring clinicians. For the inpatient setting, SAF teledermatology minimized unnecessary contact during dermatology consultations, although current studies are limited by the heterogeneity of their outcomes. Conclusions: In general, photographs taken by trained clinicians are higher quality and have better and more relevant diagnostic and clinical outcomes. SAF teledermatology helped clinicians avoid unnecessary physical contact with patients in the outpatient and inpatient settings during the COVID-19 pandemic. Asynchronous teledermatology will likely play a greater role in the future as SAF images become integrated into synchronous teledermatology workflows. However, the obstacles summarized in this review should be addressed before its widespread implementation into clinical practice.

Quality and Perceived Usefulness of Patient-Submitted Store-and-Forward Teledermatology Images.

Importance: Patient-submitted images vary considerably in quality and usefulness. Studies that characterize patient-submitted images in a real-life setting are lacking. Objective: To evaluate the quality and perceived usefulness of patient-submitted images as determined by dermatologists and characterize agreement of their responses. Design, Setting, and Participants: This survey study included patient images submitted to the Department of Dermatology at Duke University (Durham, North Carolina) between August 1, 2018, and December 31, 2019. From a total pool of 1200 images, 10 dermatologists evaluated 200 or 400 images each, with every image being evaluated by 3 dermatologists. Data analysis occurred during the year leading up to the article being written. Main Outcomes and Measures: The primary outcomes were the responses to 2 questions and were analyzed using frequency counts and interrater agreement (Fleiss κ) to assess image quality and perceived usefulness. We performed a random-effects logistic regression model to investigate factors associated with evaluators' decision-making comfort. We hypothesized that most images would be of low quality and perceived usefulness, and that interrater agreement would be poor. Results: A total of 259 of 2915 patient-submitted images (8.9%) did not depict a skin condition at all. The final analysis comprised 3600 unique image evaluations. Dermatologist evaluators indicated that 1985 images (55.1%) were useful for medical decision-making and 2239 (62.2%) were of sufficient quality. Interrater agreement for a given image's diagnostic categorization was fair to substantial (κ range, 0.36-0.64), while agreement on image quality (κ range, 0.35-0.47) and perceived usefulness (κ range, 0.29-0.38) were fair to moderate. Senior faculty had higher odds of feeling comfortable with medical decision-making than junior faculty (odds ratio [OR], 3.68; 95% CI, 2.9-4.66; P < .001) and residents (OR, 5.55; 95% CI, 4.38-7.04; P < .001). Images depicting wounds (OR, 1.75; 95% CI, 1.18-2.58; P = .01) compared with inflammatory skin conditions and that were in focus (OR, 5.56; 95% CI, 4.63-6.67; P < .001) had higher odds of being considered useful for decision-making. Conclusions and Relevance: In this survey study including 10 dermatologists, a slight majority of patient-submitted images were judged to be of adequate quality and perceived usefulness. Fair agreement between dermatologists was found regarding image quality and perceived usefulness, suggesting that store-and-forward teledermatology initiatives should consider a physician's individual experiences and comfort level. The study results suggest that images are most likely to be useful when they are in focus and reviewed by experienced attending physicians for wound surveillance, but dermatologists may be burdened by irrelevant or unsuitable images.

An Atypical Myelomonocytic Cell Infiltrate: Use of Next-Generation Sequencing to Diagnose Indeterminate Cell Histiocytosis.

ABSTRACT: Indeterminant cell histiocytosis (ICH) is a rare lymphoproliferative disorder that demonstrates features of Langerhans and non-Langerhans cell histiocytoses and diagnosis can be challenging. We present a case of a 62 year old woman with a generalized eruption of erythematous papules on the face, trunk and extremities. Skin biopsies demonstrated a dermal mononuclear cell infiltrate with monocytic (CD4, CD33), histiocytic (CD68, CD163), and dendritic cell (CD1a) immunophenotype but negative for Langerhans' cell marker (CD207). The differential diagnosis included leukemia cutis and ICH, and further workup revealed a normal bone marrow biopsy. To confirm the diagnosis of ICH, next generation sequencing with ETV3-NCOA2 gene fusion was performed and was positive. The patient's condition improved with methotrexate and narrow band UVB phototherapy. Our case adds to the existing literature supporting the use of next-generation sequencing to test for ETV3-NCOA2 gene fusion in suspected cases of ICH.

High-dose, high-frequency ustekinumab therapy for patients with severe hidradenitis suppurativa.

In this case series, ustekinumab therapy demonstrated efficacy in some patients with severe hidradenitis suppurativa previously treated with adalimumab and/or infliximab. Larger prospective studies are needed to evaluate ustekinumab as a treatment option for recalcitrant hidradenitis suppurativa.

Skin Injury Activates a Rapid TRPV1-Dependent Antiviral Protein Response.

The skin serves as the interface between the body and the environment and plays a fundamental role in innate antimicrobial host immunity. Antiviral proteins (AVPs) are part of the innate host defense system and provide protection against viral pathogens. How breach of the skin barrier influences innate AVP production remains largely unknown. In this study, we characterized the induction and regulation of AVPs after skin injury and identified a key role of TRPV1 in this process. Transcriptional and phenotypic profiling of cutaneous wounds revealed that skin injury induces high levels of AVPs in both mice and humans. Remarkably, pharmacologic and genetic ablation of TRPV1-mediated nociception abrogated the induction of AVPs, including Oas2, Oasl2, and Isg15 after skin injury in mice. Conversely, stimulation of TRPV1 nociceptors was sufficient to induce AVP production involving the CD301b+ cells‒IL-27‒mediated signaling pathway. Using IL-27 receptor‒knockout mice, we show that IL-27 signaling is required in the induction of AVPs after skin injury. Finally, loss of TRPV1 signaling leads to increased viral infectivity of herpes simplex virus. Together, our data indicate that TRPV1 signaling ensures skin antiviral competence on wounding.

IL-27 Derived From Macrophages Facilitates IL-15 Production and T Cell Maintenance Following Allergic Hypersensitivity Responses.

Crosstalk between T cells, dendritic cells, and macrophages in temporal leukocyte clusters within barrier tissues provides a new concept for T cell activation in the skin. Activated T cells from these leukocyte clusters play critical roles in the efferent phase of allergic contact hypersensitivity (CHS). However, the cytokines driving maintenance and survival of pathogenic T cells during and following CHS remain mostly unknown. Upon epicutaneous allergen challenge, we here report that macrophages produce IL-27 which then induces IL-15 production from epidermal keratinocytes and dermal myeloid cells within leukocyte clusters. In agreement with the known role of IL-15 as a T cell survival factor and growth cytokine, this signaling axis enhances BCL2 and survival of skin T cells. Genetic depletion or pharmacological blockade of IL-27 in CHS mice leads to abrogated epidermal IL-15 production resulting in a decrease in BCL2 expression in T cells and a decline in dermal CD8+ T cells and T cell cluster numbers. These findings suggest that the IL-27 pathway is an important cytokine for regulating cutaneous T cell immunity.

IL-27 signaling activates skin cells to induce innate antiviral proteins and protects against Zika virus infection.

In the skin, antiviral proteins and other immune molecules serve as the first line of innate antiviral defense. Here, we identify and characterize the induction of cutaneous innate antiviral proteins in response to IL-27 and its functional role during cutaneous defense against Zika virus infection. Transcriptional and phenotypic profiling of epidermal keratinocytes treated with IL-27 demonstrated activation of antiviral proteins OAS1, OAS2, OASL, and MX1 in the skin of both mice and humans. IL-27-mediated antiviral protein induction was found to occur in a STAT1- and IRF3-dependent but STAT2-independent manner. Moreover, using IL27ra mice, we demonstrate a significant role for IL-27 in inhibiting Zika virus morbidity and mortality following cutaneous, but not intravenous, inoculation. Together, our results demonstrate a critical and previously unrecognized role for IL-27 in cutaneous innate antiviral immunity against Zika virus.

Innate Antiviral Immunity in the Skin.

Barrier sites such as the skin play a critical role in immune defense. They must maintain homeostasis with commensals and rapidly detect and limit pathogen invasion. This is accomplished in part through the production of endogenous antimicrobial peptides and proteins, which can be either constitutive or inducible. Here, we focus particularly on the control of innate antiviral proteins and present the basic aspects of their regulation in the skin by interferons (IFNs), IFN-independent immunity, and environmental factors. We also discuss the activity and (dys-)function of antiviral proteins in the context of skin-tropic viruses and highlight the relevance of the innate antiviral pathway as a potential therapeutic avenue for vulnerable patient populations and skin diseases with high risk for virus infections.

A trichogenic tumor with aggressive features initially diagnosed as basal cell carcinoma.

Trichoblastic carcinoma is a rare carcinoma often arising in a pre-existing trichoblastoma. It may resemble basal cell carcinoma, posing a diagnostic challenge. Trichoblastic carcinoma is divided into low-grade and high-grade tumors. Low-grade tumors resemble basal cell carcinomas and are therefore synonymous in some classifications. High-grade tumors, which commonly present on the scalp in older individuals or in patients with Brooke-Spiegler syndrome, have been associated with a higher potential for distant metastasis and death. We present a case in which a 73-year-old female had a long-standing scalp nodule for over 30 years that rapidly increased in size. The patient's lesion was initially diagnosed as basal cell carcinoma on shave biopsy, but upon excision, revealed features concerning for trichoblastic carcinoma such as brisk mitotic activity and comedo-like necrosis. Sudden change in an atypical scalp lesion that has been present for many years should increase suspicion for an atypical trichogenic tumor, such as trichoblastic carcinoma.