Pyoderma gangrenosum and impact on quality of life: A narrative review.

Pyoderma gangrenosum (PG) is an autoinflammatory disorder typically characterized by progressive ulcers with dense neutrophilic infiltrates in the absence of infectious causes. The chronic nature of this disease significantly impacts the patients' quality of life (QoL). Yet there is currently a dearth of information in the literature regarding standardised treatment guidelines and the impact of PG on patients' QoL. We conducted a literature search on PubMed using the terms "pyoderma gangrenosum" AND "quality of life." We identified nine relevant articles that provide insight into which domains are affected and what treatment can improve QoL. The most common domains involved are physical, emotional, and psychological. Patients tend to feel depressed/anxious, isolated, and embarrassed secondary to PG manifestations. Comorbidities such as Crohn's disease, monoclonal gammopathy of dermatologic significance, and ulcerative colitis can worsen the impact on these patients' QoL. Pain is also a significant contributor to decreasing patients' QoL. Treatments such as topical steroids, adalimumab, and canakinumab may help improve QoL scores. We believe this information can help clinicians guide the care of patients with PG and highlight the need for more studies and clinical trials focusing on PG treatments' impact on QoL.

Novel assessment of lip redness and microcirculation using optical coherence tomography after dermal filler injection.

OBJECTIVES: Lip filler injections are one of the most popular procedures in esthetic dermatology. In this study, we used three-dimensional colorimetric photography to assess lip color and optical coherence tomography-angiography (OCT-A), a noninvasive alternative to histopathology, to evaluate microcirculation after hyaluronic acid (HA) injection. The pain of the injection procedure was also assessed. METHODS: An average of 0.85cc of the total volume of HA with lidocaine was injected into the upper and lower lip of eighteen young (<30yo) and nine postmenopausal healthy women. OCT-A, two-dimensional, and three-dimensional images were acquired immediately before (visit 1) and 15 days after injection (visit 2). Custom-made software was used to analyze the imaging data to detect vessel morphology and redness changes. The Wong-Baker FACES pain rating scale (0-10) was used to score the subject procedural pain. RESULTS: For young and old subjects, three-dimensional lip volume was greater than the injected volume. OCT-A images of the lips showed higher vessel density and thickness, reaching statistical significance in the younger cohort. The overall trend of increased redness assessed by three-dimensional colorimetric imaging and increased vascularity evaluated by OCT-A imaging were similar. However, the correlation was not statistically significant for standard two-dimensional digital photography. The average pain score after the first needle insertion and overall procedure were 2.9 and 3.5, respectively. CONCLUSIONS: The results suggest an increased microvasculature network observed in OCT-A images in young females. The increased blood vessel density and thickness observed by OCT-A after HA lip filler injection is associated with increased lip redness and volume as assessed by colorimetric three-dimensional photography; however, more research is needed to confirm these findings. This study presents OCT-A as a novel noninvasive tool to investigate changes in lip microvascularity after HA filler injection and indicates that HA filler procedures may affect lip vascularity.

Inhibition of dipeptidyl-peptidase 4 induces upregulation of the late cornified envelope cluster in keratinocytes.

Dipeptidyl-peptidase 4 (DPP4) is a multifunctional type II transmembrane glycoprotein that is expressed on various cell surfaces. While DPP4 inhibitors have a therapeutic role in the treatment of diabetes mellitus, they are an independent risk factor in the development of bullous pemphigoid. Contrarily, there are reports of improvement in psoriasis with DPP4 inhibition. We investigated the effect of DPP4 inhibition on primary human keratinocytes to determine whether DPP4 modulates keratinocyte inflammatory signaling and keratinocyte homeostasis. We performed RNA sequencing of primary adult human keratinocytes treated with DPP4 inhibitor, identifying 424 differentially expressed genes. Gene ontology analysis revealed significant enrichment of epidermal differentiation and cornified envelope genes. Using three-dimensional organotypic cultures and a pan-late cornified envelope 2 (LCE2) antibody, we demonstrate a dose dependent relationship between DPP4 inhibition and increased expression of LCE2 during epidermal development. The late cornified envelope gene clusters are expressed at the late stages of epithelial development, responding to stimuli such as calcium and ultraviolet light. While its biologic function is not fully understood, mutations in LCE3B/LCE3C confer a 40% increased risk in the development of plaque psoriasis. While we did not identify significant modulation of keratinocyte inflammatory markers, DPP4 inhibition increased expression of the late cornified envelope may offer a potential alternative therapeutic mechanism in psoriasis.

Dermatologic manifestations of pediatric cardiovascular diseases: Skin as a reflection of the heart.

Cutaneous disease can often be an initial clue of an underlying cardiovascular disease. Many congenital conditions (ie, Noonan syndrome with multiple lentigines, Carney complex, and Fabry disease) and acquired conditions may present initially with specific cutaneous features that should prompt clinicians to conduct a full cardiac workup. Given the extensive number of conditions with both cardiovascular and cutaneous findings, this review will focus on diseases with cardiocutaneous pathology with hopes of raising clinician awareness of these associations to decrease morbidity and mortality, as several of these diseases often result in fatal outcomes.

Treatment of Pain in Keloids Using Only a Long-Pulsed 1064 nm Nd:YAG Laser.

BACKGROUND AND OBJECTIVE: Keloids are benign lesions arising from overproduction of the extracellular matrix and abnormal collagen deposition by dermal fibroblasts. This altered wound healing typically occurs in response to dermal trauma. Keloid treatment poses a challenge due to the variable nature of treatment response, which can be affected by the size, appearance, and associated symptoms of erythema, pruritus, and pain. Recently, successful treatment of keloids has been reported using the Nd:YAG laser in conjunction with 5-fluorouracil and intralesional corticosteroids. We present a series of patients with symptomatic keloids, who we treated with only a 1064 nm Nd:YAG laser. STUDY DESIGN/MATERIALS AND METHODS: Eight patients of Fitzpatrick skin types I-VI presented for treatment of keloids with associated symptoms of pain. The keloids were most commonly located on the trunk, and seven patients had intralesional steroid injections prior to presentation with persistence of symptoms. Patient treatment consisted of two passes under a long-pulsed 1064 nm Nd:YAG laser with a 10 mm spot size, a fluence of 18-19 J/cm2 , and 60 ms pulse duration every 3-8 weeks. Patient-reported pain scores were collected before and after treatment. RESULTS: Following treatment, transient erythema and mild edema were noted at the treatment site. All patients reported improvement in the symptoms of pain, with an average of a 5-point reduction using a 10-point scale (R: 2-10). Five out of eight patients had total resolution of their pain. An average of 3.25 treatments (R:1-5) were needed for patients to first notice an improvement in the pain. A Wilcoxon signed-rank test showed that treatment with a 1064 nm laser elicited a statistically significant improvement in pain in individuals with keloids (Z = 2.46, P = 0.01). No patients in our study suffered any scarring or pigment changes as a result of these treatments. CONCLUSION: Keloids are a common condition with variable rates of treatment satisfaction. Lasers have been used in an attempt to improve clinical appearance and associated symptoms. We report a significant reduction in pain for patients treated exclusively with a 1064 nm Nd:YAG laser. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.

The role of Dipeptidyl Peptidase-4 in cutaneous disease.

Dipeptidyl peptidase-4 (DPP4) is a multifunctional, transmembrane glycoprotein present on the cell surface of various tissues. It is present in multiple molecular forms including cell surface and soluble. The role of DPP4 and its inhibition in cutaneous dermatoses have been a recent point of investigation. DPP4 exerts a notable influence on T-cell biology, the induction of skin-specific lymphocytes, and the homeostasis between regulatory and effector T cells. Moreover, DPP4 interacts with a broad range of molecules, including adenosine deaminase, caveolin-1, CXCR4 receptor, M6P/insulin-like growth factor II-receptor and fibroblast activation protein-α, triggering downstream effects that modulate the immune response, cell adhesion and chemokine activity. DPP4 expression on melanocytes, keratinocytes and fibroblasts further alters cell function and, thus, has crucial implications in cutaneous pathology. As a result, DPP4 plays a significant role in bullous pemphigoid, T helper type 1-like reactions, cutaneous lymphoma, melanoma, wound healing and fibrotic disorders. This review illustrates the multifactorial role of DPP4 expression, regulation, and inhibition in cutaneous diseases.

Evaluation of Abbott anti-SARS-CoV-2 CMIA IgG and Euroimmun ELISA IgG/IgA assays in a clinical lab.

BACKGROUND: We report our findings of test performance especially specificity of a fully automated Abbott Architect anti-SARS-CoV-2 CMIA IgG and Euroimmun anti-SARS-CoV-2 ELISA IgA/IgG in human plasma. METHODS: We used positive cohort of 97 samples from Covid-19 patients or healthcare workers, collected at late time points from symptom onsets. We also included another cohort of 215 samples as negative controls, 78 of which had positive serology test results of other infectious diseases or autoimmunity. Assay specificity was assessed by using a total of 847 anonymized samples which were collected before the Covid-19 pandemic from local patient populations seeking clinical care for rheumatoid diseases, thyroid cancer, and therapeutic drug monitoring. RESULTS: Abbott IgG, Euroimmun IgG/IgA had high precision, demonstrated by both intra- and inter-day CVs of <2%. There was no Abbott or Euroimmun IgG assay cross reactivity in the 78 samples with positive serology of non-SARS-CoV-2 infectious diseases and positive autoimmune antibodies. The Abbott IgG has specificity of 99.6%, while Euroimmun IgG and IgA were as high as 91.5% and 71.5%, respectively. CONCLUSIONS: Our evaluation confirmed high specificity of the Abbott IgG assay, while it was lower for Euroimmun IgG. Euroimmun IgA has suboptimal specificity which may limit its clinical use. Assay sensitivity was high for both Abbott and Euroimmun IgG assays.

The Role of Collagen XVII in Cancer: Squamous Cell Carcinoma and Beyond.

Alterations in the extracellular matrix (ECM) likely facilitate the first steps of cancer cell metastasis and supports tumor progression. Recent data has demonstrated that alterations in collagen XVII (BP180), a transmembrane protein and structural component of the ECM, can have profound effects on cancer invasiveness. Collagen XVII is a homotrimer of three α1 (XVII) chains. Its intracellular domain contains binding sites for plectin, integrin ß4, and BP230, while the extracellular domain facilitates interactions between the cell and the ECM. Collagen XVII and its shed ectodomain have been implicated in cell motility and adhesion and are believed to promote tumor development and invasion. A strong association of collagen XVII ectodomain shedding and tumor invasiveness occurs in squamous cell carcinoma (SCC). Aberrant expression of collagen XVII has been reported in many epithelial cancers, ranging from squamous cell carcinoma to colon, pancreatic, mammary, and ovarian carcinoma. Thus, in this review, we focus on collagen XVII's role in neoplasia and tumorigenesis. Lastly, we discuss the importance of targeting collagen XVII and its ectodomain shedding as a novel strategy to curb tumor growth and reduce metastatic potential.

Successful Mastectomy and Chemotherapy in a Patient with Breast Cancer and Active Generalized Pyoderma Gangrenosum.

INTRODUCTION: Pyoderma gangrenosum (PG) is a rare, ulcerating neutrophilic dermatosis often associated with inflammatory bowel disease, rheumatoid arthritis, and myeloproliferative disorders. The classic description of PG includes irregularly shaped ulcers with undermined edges with a gun-metal gray or violaceous hue. The etiology remains unclear but appears to be related to genetically predisposed dysregulation of the innate immune system. Diagnosis of PG can be difficult as it can present with symptoms similar to cutaneous infections including erythema, edema, ulceration, fever and leukocytosis. Surgical procedures are generally contraindicated in patients with PG due to the risk of pathergy, excessive cutaneous injury, or ulceration in response to trauma. CASE REPORT: The authors report the development of PG with the initiation of chemotherapy in a 46-year-old woman with breast cancer. The patient had a complicated clinical course after multiple surgical debridements due to an initial misdiagnosis of necrotizing fasciitis. The patient's rapid onset of post-procedural ulceration was consistent with the pathergy of PG. The diagnosis of PG was confirmed by skin biopsy, which revealed a diffuse neutrophilic infiltrate, and with the patient's negative cultures and response to steroids. The patient was treated with perioperative prednisone and intravenous immunoglobulin prior to a mastectomy for her breast cancer. The surgery was not complicated by pathergy. CONCLUSIONS: This unique case highlights the challenging aspects in the medical and perioperative management of active PG in a patient with breast cancer.

Hidradenitis suppurativa and pemphigus: a cross-sectional study.

A recent study of comorbidities in hospitalized pemphigus patients in the United States has demonstrated a significant association of hidradenitis suppurativa (HS) and pemphigus, but this association has not been firmly established in other populations. A retrospective, cross-sectional study was undertaken to determine the prevalence of HS in patients with pemphigus and compare with control subjects. Regression analysis was performed to obtain ORs, and 95% CIs, to evaluate the prevalence between pemphigus patients and controls matched by age, sex, and ethnicity. Among the patients included in the study, 1985 patients had pemphigus and 9874 were control subjects. The average age of presentation of pemphigus was 72.1 ± 18.5 and the group was comprised of 59.8% females. Overall, the pemphigus group had lower rates of smoking (25.7% vs. 27.9%; P = 0.045). The prevalence of HS was greater in patients with pemphigus than in control subjects (OR 4.98; 95% CI 1.01-24.69; P < 0.001), with an even more prominent association among patients who have been prescribed "pemphigus-related treatments" (OR 6.30; 95% CI 1.27-31.22; P < 0.001). The study detected a significant association between HS and pemphigus in an Israeli population. Future prospective studies are needed to establish a temporal order of appearance and the mechanistic relationship between these entities.

Aesthetic Outcomes of Nasal Burow's Grafts With Interdomal Sutures After Mohs Micrographic Surgery.

BACKGROUND: Post-Mohs reconstruction of distal nasal defects is challenging. Many repair options exist, each with advantages and disadvantages. Utilization of a Burow's graft in combination with manipulation of the underlying nasal cartilages with interdomal sutures is an underreported yet effective repair option. OBJECTIVE: To present the authors' experience with Burow's grafts facilitated by interdomal sutures for repair of nasal defects after Mohs micrographic surgery (MMS). MATERIALS AND METHODS: Patients who underwent repair with Burow's grafts and interdomal sutures from 2013 to 2017 at a single university were identified. Demographics, follow-up, and complications were recorded. Two independent, board-certified dermatologists evaluated photographs for cosmesis and alar symmetry. RESULTS: Thirty-one patients were identified. A total of 5/31 patients (16.1%) experienced minor complications without permanent sequelae. A total of 4/31 (12.9%) patients underwent cosmetic revision. No incidences of pincushioning, nasal valve dysfunction, or graft necrosis occurred. Aesthetic ratings were good to excellent with mean visual analog score of 80.8. Alar symmetry was excellent. CONCLUSION: A Burow's full-thickness skin graft facilitated by an interdomal suture to maintain nasal tip orientation and projection is an elegant repair technique for distal nasal oncologic defects with good to excellent aesthetic outcomes. It should be considered in the armamentarium for repair of distal nasal defects after MMS.

Combination of Melolabial Interpolation Flap and Nasal Sidewall and Cheek Advancement Flaps Allows for Repair of Complex Compound Defects.

BACKGROUND: The paramedian forehead flap (PMFF) is the repair of choice for large nasal defects involving multiple cosmetic subunits. However, the PMFF may not be optimal for all patients. The combination of a melolabial interpolation flap (MLIF) and a nasal sidewall flap may serve as an alternative. OBJECTIVE: To present the surgical technique and aesthetic outcomes of the alternative reconstruction for surgical defects of the lower nose. MATERIALS AND METHODS: Fourteen patients with multisubunit nasal Mohs defects reconstructed alternatively were identified from 2 academic centers in this retrospective case series. Illustrations and photographs were used to demonstrate surgical technique and outcomes. Final aesthetic results were analyzed using the Patient and Observer Scar Assessment Scale. RESULTS: The physician observer rated the scar outcome a mean score of 10.9 ± 3.3. Patients rated their results as a mean of 9.1 ± 4.7. The mean "Patient" Overall Opinion score was 2.3 ± 2.6 and the mean "Observer" Overall Opinion score was 1.9 ± 0.9. No patients reported problems with nasal airflow or obstruction, and cosmetic complications such as pincushioning or alar buckling were not observed. CONCLUSION: The combined MLIF and nasal sidewall flap is an alternative repair for complex distal nasal defects.