Journal Of Investigative Dermatology

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878 Investigating T cell phenotype and function in delayed-type drug hypersensitivity reactions

Wed, 2020-07-01 00:00
Delayed-type drug hypersensitivity reactions (DHR) range in severity from mild rash to severe sloughing of skin and mucosal surfaces, with or without internal organ involvement. Pathobiology is poorly understood including the phenotype and function of T cells mediating DHR. We performed transcript analysis of 186 genes using Nanostring on FFPE skin samples from adult and pediatric patients with morbilliform drug eruption (MDE) (n=7), Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) (n=6), and Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN) (n=14).

877 Quality of life among family members of patients with atopic dermatitis and psoriasis

Wed, 2020-07-01 00:00
Chronic inflammatory skin diseases like psoriasis (PsO) and atopic dermatitis (AD) severely impact the quality of life (QoL) of patients. However, the effect of these diseases can extend beyond the affected patients and diminish their families’ QoL as well. We held focus groups and interviews with 23 family members–most commonly significant others–twelve had a family member with AD and 11 had a family member with psoriasis to understand these impacts. After two researchers independently coded the transcripts, we conducted a thematic analysis using a grounded-theory approach to arrive at a consensus on the major themes.

876 When itchiness is not enough: Understanding the impact of pain on experiences with atopic dermatitis

Wed, 2020-07-01 00:00
Pain, separate from pruritus, is a relatively unappreciated, and poorly understood, symptom of atopic dermatitis (AD) that can affect patients’ health-related quality of life (HRQoL). This qualitative study involved 24 patients with AD and 12 family members who participated in focus groups and interviews aimed at understanding the impact of pain on AD patients and their family members to capture how this symptom affects HRQoL. Thematic analysis was conducted using grounded theory approach. Two researchers independently coded the transcripts and reached a consensus on major themes.

875 Insights into the far-reaching effects of the itchiness of atopic dermatitis

Wed, 2020-07-01 00:00
Atopic dermatitis (AD) is a chronic inflammatory skin condition characterized by xerotic and eczematous lesions. Severe itchiness is the cardinal symptom of this disease and significantly impacts individuals' health-related quality of life. This study aimed to qualitatively explore the experiences of participants with AD and their family members who live with the itchiness of AD. Twenty-four participants with AD and 12 of their family members participated in focus groups and interviews. After two researchers independently coded the narratives, we conducted a thematic analysis using a grounded theory approach to arrive at a consensus on the major themes.

874 Understanding the triggers and consequences of atopic dermatitis

Wed, 2020-07-01 00:00
Atopic dermatitis (AD) is a common skin condition that can affect many aspects of a patient’s health-related quality of life (HRQoL). However, during the time-constrained clinical visit, clinicians rarely capture a complete picture of the impact of AD on the daily home lives of our patients. This study aims to understand triggers and consequences of AD to help clinicians better grasp the full implications of living with AD on an individual and their family members. For this qualitative study, 24 patients with AD and 12 family members participated in focus groups and interviews with questions on how AD affects all aspects of their lives and relationships.

873 A computational method to automate acne lesion counting

Wed, 2020-07-01 00:00
Counting primary acne lesions such as comedones, pustules/papules, or nodules is a first necessary step to measuring acne severity both for patient monitoring and for clinical trials. While clinicians quickly estimate the number of lesions upon a visual inspection, a precise count of all lesions present can be time consuming, and, additionally, for clinical trials, many hours of training are often needed to decrease inter-rater variability. The task becomes even more difficult when working with photographs, as in addition to the multifaceted appearance of acne lesions, challenges are posed by varying illumination and skin color.

872 IL-1β is a potential central mediator to Papulopustular Rosacea pathology as determined by paired transcriptomic and proteomic analysis

Wed, 2020-07-01 00:00
Papulopustular rosacea (PPR) is a chronic inflammatory skin disease characterized by redness, sensitive skin, and inflammatory lesions. Multiple inflammatory pathways have been described to be upregulated in PPR; however, a complete mechanistic understanding of the central mediators of PPR lesions requires further study. To this end, we quantitatively evaluated both the transcriptomic (RNAseq) and proteomic (OLINK® and MSD®) signature of paired non-lesional (NLS) and lesional (LS) PPR biopsy explants (n=5 patients).

871 Continuous hair density differentiation to score extent of alopecia areas automatically

Wed, 2020-07-01 00:00
Commonly used alopecia severity scales usually rely on having clinicians individuate areas of hair loss and compare their locations and/or sizes in order to map the hair loss appearance to a score, such as overall percent alopecia (e.g., Severity of Alopecia Tool, SALT, score) or hair loss top extent score (e.g., Central Scalp Alopecia Photographic, CSAP, scale). To automate this process, we developed a computational tool that takes standardized photographs of patients’ scalps and returns an overall percent hair loss as well as a top extent alopecia shape score as output without any user input.

870 Clinical and histopathologic characteristics of metastatic and locally aggressive basal cell carcinomas

Wed, 2020-07-01 00:00
Due to the rarity of metastatic or locally advanced basal cell carcinoma (mBCC, laBCC), most of the data regarding their characteristics come from single case reports and small series. None have performed a thorough evaluation of the histologic parameters of mBCC. To address this gap, we searched the entire medical record at Vanderbilt University Medical Center to identify potential cases of locally advanced or metastatic BCC occurring between 1984 and January 2019. A retrospective chart review was performed of all identified patients to determine case status.

869 Establishment of a model of ras oncogene induced senescence in endothelial cells

Wed, 2020-07-01 00:00
Oncogene induced senescence underlies many processes in dermatology, such as driver mutation induced vascular malformations, nevi, and seborrheic keratoses. These processes are difficult to study given that cells with driver oncogenes rapidly senescence in culture, whether the cells are transduced with a driver oncogene or cultured from a primary lesion. In order to provide a model easily accessible to the research community, we have established a model of oncogene induced senescence through the sequential introduction of a temperature sensitive large T oncogene followed by oncogenic H-ras into microvascular endothelial cells.

868 Pathogenesis based therapy improves cutaneous abnormalities in porokeratosis- A pilot study

Wed, 2020-07-01 00:00
Porokeratosis is a heterogenous group of keratinization disorders associated with mevalonate pathway gene mutations. Treatments options for the disease are few and often ineffective. On the basis of the possible pathogenic role of pathway end-product deficiency (cholesterol) and accumulation of toxic precursors, we studied the efficacy of topical lovastatin/cholesterol in different variants of porokeratosis. We recruited 1 patient with disseminated superficial actinic porokeratosis (DSAP), 2 patients with porokeratosis palmaris et plantaris disseminate (PPPD) and 2 patients with linear porokeratosis (LP).

867 Direct mechanical measurements of skin to quantify evolution of sclerotic disease

Wed, 2020-07-01 00:00
There is an unmet need for objective cutaneous measurements to track the progression of sclerosing diseases, such as chronic graft-versus-host disease (cGVHD). The handheld Myoton device extracts biomechanical parameters of stiffness, frequency, and relaxation time characterizing soft tissue through its damped oscillation response to a mechanical micro-impulse. Cutaneous measurements using Myoton have differentiated sclerotic cGVHD patients from post-transplant controls. In a prospective longitudinal pilot study, we assessed Myoton’s ability to numerically monitor sclerosis over time.

866 Baseline differences in circulation between early vs late responder patients with vitiligo treated with ruxolitinib cream

Wed, 2020-07-01 00:00
Vitiligo is a chronic, inflammatory skin disease characterized by increased interferon-gamma signaling through Janus kinase (JAK) 1 and JAK2 and subsequent activation of CD8+ T cells, which target melanocytes resulting in areas of depigmentation. Ruxolitinib cream, a JAK1/JAK2 inhibitor, is under investigation for vitiligo treatment in a 52-week, randomized, double-blind, phase 2 study (NCT03099304). Significantly more patients treated with ruxolitinib cream vs vehicle achieved ≥50% improvement in facial Vitiligo Area Scoring Index (F-VASI50) at Week 24 (primary endpoint); at Week 52, patients treated with ruxolitinib cream 1.5% twice daily (BID) attained the highest F-VASI50 response (57.6%).

865 Immunotherapy in advanced Merkel cell carcinoma: Frequent responses but a potentially concerning recurrence rate after therapy discontinuation

Wed, 2020-07-01 00:00
Merkel cell carcinoma (MCC) is an aggressive skin cancer that often recurs. MCC tumors can respond to PD-1 pathway inhibitors rapidly, however, it is unclear how often these responses persist after discontinuation of therapy. We retrospectively assessed 159 persons with advanced MCC treated with first-line anti-PD-(L)1 agents. Non-responders were defined as those with progressive disease (PD) or stable disease (SD), while responders had partial response (PR), or complete response (CR), based on clinician assessment.

864 Lesional immune cells in cutaneous acute graft-versus-host disease: A prospective cohort study

Wed, 2020-07-01 00:00
Hematopoietic stem cell transplant (HSCT) is an intricate process that carries a risk of similarly convoluted complications, including graft-versus-host-disease (GVHD). Acute and chronic GVHD are distinct entities, defined by a combination of historical, clinical and pathologic data, but both are generally thought to stem from self-propagating aberrantly activated immune cells inflicting end organ damage, with the potential to cause significant morbidity and mortality. Survival rates after HSCT have improved significantly over the past few decades, but GVHD remains a major hurdle in improving the efficacy and safety of transplant.

863 Role of STAT6 in advanced-stage cutaneous T-cell lymphoma

Wed, 2020-07-01 00:00
Cutaneous T-cell lymphomas (CTCL) are a heterogeneous group of lymphoproliferative disorders derived from skin-homing memory T cells. Mycosis fungoides (MF) and Sezary syndrome (SS) are the most common subtypes. Aberrant cytokine expression in the MF/SS tumor microenvironment (TME) is a major factor in disease pathogenesis and progression. We have previously shown that MF/SS malignant lymphocytes produce high levels of IL-13, which acts as an autocrine factor for tumor cells and suppresses tumor-cell immunosurveillance.

862 Thioredoxin regenerates elastic fibers in the dermis

Wed, 2020-07-01 00:00
Wrinkles and sagging occurring with aging affect the human physical appearance, resulting in poor quality of life. Therefore, care methods for these need to be improved. Wrinkles and sagging are thought to be caused by alterations in the internal skin structure; however, the specific morphological alterations and molecular mechanisms remain unclear. Previously, we observed the three-dimensional (3D) structure of the elastic fibers in the dermis by using tissue decolorization technology, and established a novel computational method to analyze its structural characteristics (volume, surface area, blanch numbers, length, diameter, and straightness).

861 Intravenous gentamicin therapy for junctional epidermolysis bullosa patients harboring nonsense mutations

Wed, 2020-07-01 00:00
Generalized severe junctional epidermolysis bullosa (GS-JEB) is an incurable and fatal inherited blistering skin disease most commonly caused by nonsense mutations in LAMA3, LAMB3, or LAMC2 genes. These mutations impair the ability to produce functional laminin 332, needed for epidermal-dermal adherence. Previously, we showed that topical gentamicin therapy generated new, functional laminin 332 and improved wound healing in GS-JEB patients. Although effective, topical administration of gentamicin to the entire skin surface is cumbersome and would not treat mucosal sites, including the upper respiratory tract.

860 Microbiome therapy of atopic dermatitis by application of rationally selected human commensal skin bacteria

Wed, 2020-07-01 00:00
Disease severity in atopic dermatitis (AD) is negatively influenced by S. aureus (SA). SA can be inhibited by antimicrobial molecules made by some strains of coagulase-negative Staphylococcus (AM+CoNS). A lack of AM+CoNS correlates with SA abundance and disease severity in AD. A previous clinical trial showed autologous AM+CoNS could reduce SA on AD skin within 24 hrs. Recently, some CoNS were also found to inhibit expression of SA toxins by blocking quorum sensing through production of autoinducing peptides (AIPs).

859 Molecular characterization of mucosal lichen planus

Wed, 2020-07-01 00:00
Lichen planus (LP) is an inflammatory mucocutaneous disease. The precise pathogenesis remains elusive. A critical event in the initiation of immune responses in LP lesions is for memory T cells to migrate from the circulation into the skin leading to cytokine/chemokine release (i.e. IFN-γ, IL-1β, IL-6, IL-8, IL-17, JAK3 and TNF-α). We sought to quantitatively examine the differential expression of various molecular mediators in idiopathic mucosal lichen planus and to test if the expression pattern is anatomic site-specific.

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