Contraceptive counseling for iPLEDGE and its burden on dermatologists.

Since 2006, iPLEDGE, a risk evaluation and mitigation strategy (REMS), has attempted to prevent fetal exposures in people taking isotretinoin through contraceptive requirements and regular pregnancy testing. There has been criticism of iPLEDGE's requirements, results, and accessibility. iPLEDGE has placed significant burdens on physicians, patients, and administrative staff. Some level of burden is acceptable to prevent fetal exposures, but iPLEDGE burdens are so strenuous that physicians may choose not to prescribe isotretinoin because of them. There are several evidence-based adaptations that iPLEDGE and physicians can enact to improve the isotretinoin experience. First, physicians can practice shared-decision making in contraceptive counseling and educate patients on long-acting reversible contraceptives (LARCs) to improve the counseling process and outcomes. Second, physicians can take advantage of the reimbursed iPLEDGE contraceptive counseling sessions and refer patients accordingly. Finally, iPLEDGE should recognize the variation in efficacy among contraceptives. Specifically, LARCs and permanent surgical sterilization should be exempt from certain iPLEDGE requirements such as monthly pregnancy testing and attestations. iPLEDGE should work with dermatologists for the continual improvement of iPLEDGE. Communication, repetitive reassessment, and subsequent adaptations will result in better care for patients requiring isotretinoin.

Recrudescence of Severe Carbamazepine- Induced DRESS Syndrome after Initiation of Levetiracetam.

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a potentially fatal cutaneous hypersensitivity reaction commonly precipitated by antiepileptic drugs (AEDs). Cross-reactivity among aromatic AEDs is well-documented, but between aromatic and nonaromatic AEDs. We report a patient with severe DRESS syndrome precipitated by aromatic AED carbamazepine with recrudescence approximately 2 weeks after substitution with nonaromatic AED levetiracetam. The patient was treated with high-dose corticosteroids and switched to the benzodiazepine AED clobazam. At follow-up appointment several weeks later, the patient's rash, liver injury, and eosinophilia had resolved.

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.

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.

Hidradenitis Suppurativa: Host-Microbe and Immune Pathogenesis Underlie Important Future Directions.

Hidradenitis suppurativa (HS) is an inflammatory disease of the skin with a chronic, relapsing-remitting course. The pathogenesis of the disease is poorly understood and involves multiple factors, including genetics, environment, host-microbe interactions, and immune dysregulation. In particular, the composition of the cutaneous microbiome shifts as the disease progresses, although it is unclear whether this is a primary or secondary process. Trials with immunomodulatory therapy elucidate the role of specific immune pathways and cytokine signaling in disease mechanism, such as TNF-α, IL-1ß, IL-12, IL-17, IL-23, and complement. Future studies should continue examining the causes of and contributing factors to microbial changes and immune dysregulation in HS pathogenesis.

Single-Cell RNA Sequencing Reveals Cellular and Transcriptional Changes Associated With M1 Macrophage Polarization in Hidradenitis Suppurativa.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterized by recurrent abscesses, nodules, and sinus tracts in areas of high hair follicle and sweat gland density. These sinus tracts can present with purulent drainage and scar formation. Dysregulation of multiple immune pathways drives the complexity of HS pathogenesis and may account for the heterogeneity of treatment response in HS patients. Using transcriptomic approaches, including single-cell sequencing and protein analysis, we here characterize the innate inflammatory landscape of HS lesions. We identified a shared upregulation of genes involved in interferon (IFN) and antimicrobial defense signaling through transcriptomic overlap analysis of differentially expressed genes (DEGs) in datasets from HS skin, diabetic foot ulcers (DFUs), and the inflammatory stage of normal healing wounds. Overlap analysis between HS- and DFU-specific DEGs revealed an enrichment of gene signatures associated with monocyte/macrophage functions. Single-cell RNA sequencing further revealed monocytes/macrophages with polarization toward a pro-inflammatory M1-like phenotype and increased effector function, including antiviral immunity, phagocytosis, respiratory burst, and antibody-dependent cellular cytotoxicity. Specifically, we identified the STAT1/IFN-signaling axis and the associated IFN-stimulated genes as central players in monocyte/macrophage dysregulation. Our data indicate that monocytes/macrophages are a potential pivotal player in HS pathogenesis and their pathways may serve as therapeutic targets and biomarkers in HS treatment.

ENTPD1 (CD39) Expression Inhibits UVR-Induced DNA Damage Repair through Purinergic Signaling and Is Associated with Metastasis in Human Cutaneous Squamous Cell Carcinoma.

UVR and immunosuppression are major risk factors for cutaneous squamous cell carcinoma (cSCC). Regulatory T cells promote cSCC carcinogenesis, and in other solid tumors, infiltrating regulatory T cells and CD8+ T cells express ectonucleoside triphosphate diphosphohydrolase 1 (ENTPD1) (also known as CD39), an ectoenzyme that catalyzes the rate-limiting step in converting extracellular adenosine triphosphate (ATP) to extracellular adenosine (ADO). We previously showed that extracellular purine nucleotides influence DNA damage repair. In this study, we investigate whether DNA damage repair is modulated through purinergic signaling in cSCC. We found increased ENTPD1 expression on T cells within cSCCs when compared with the expression on T cells from blood or nonlesional skin, and accordingly, concentrations of derivative extracellular adenosine diphosphate (ADP), adenosine monophosphate (AMP), and ADO are increased in tumors compared with those in normal skin. Importantly, ENTPD1 expression is significantly higher in human cSCCs that metastasize than in those that are nonmetastatic. We also identify in a mouse model that ENTPD1 expression is induced by UVR in an IL-27-dependent manner. Finally, increased extracellular ADO is shown to downregulate the expression of NAP1L2, a nucleosome assembly protein we show to be important for DNA damage repair secondary to UVR. Together, these data suggest a role for ENTPD1 expression on skin-resident T cells to regulate DNA damage repair through purinergic signaling to promote skin carcinogenesis and metastasis.