Acrokeratosis paraneoplastica (Basex syndrome) with trachyonychia preceding the diagnosis of squamous cell carcinoma of the lung.

Acrokeratosis paraneoplastica (Basex syndrome) is a rare paraneoplastic condition hallmarked by psoriasiform lesion development on acral surfaces, most often related to an underlying squamous cell carcinoma. Patients may also present with nail plate changes. Successful management of this condition can be accomplished by treating the underlying malignancy.

Rubella virus-associated necrotizing neutrophilic granuloma in a patient with common variable immunodeficiency.

Patients with inborn errors of immunity (IEI) may develop granulomas in multiple organ systems including the skin. Vaccine strain rubella virus (RuV), part of the live attenuated measles, mumps, and rubella (MMR) vaccine, has been identified within these granulomas. RuV is typically found in macrophages; however, recently neutrophils have been identified as a novel cell type infected. Here, we present a case of RuV-associated cutaneous granuloma with RuV localized to neutrophils. A 46-year-old female with common variable immunodeficiency presented with verrucous papules and crusted plaques from the right knee to the distal shin of 20 years duration, associated with prior physical trauma. Biopsy specimen showed palisaded granulomas surrounding central necrosis with scattered aggregates of neutrophils. Vaccine-derived RuV was detected by molecular sequencing in lesional skin. Fluorescent immunohistochemistry with CD206, myeloperoxidase (MPO), and RV capsid (RVC) antibodies demonstrated that RuV localized to neutrophils but not macrophages. The clinical presentation, cutaneous findings, and likely presence of RVC-positive granulocytes in bone marrow provide potential support to the evolving hypothesis of persistent RuV within neutrophils contributing to chronic granulomatous inflammation in a milieu of immune dysregulation.

Intralesional 5-Fluorouracil for Treatment of Non-Melanoma Skin Cancer: A Systematic Review.

BACKGROUND: Surgical excision is the paradigm treatment option for non-melanoma skin cancer (NMSC), however intralesional fluorouracil (IL 5-FU) is an efficacious alternative and superior to other chemotherapy agents in NMSC. Yet, little summative data exists on the topic. OBJECTIVE: To assess the efficacy of IL 5-FU in the treatment of NMSC. METHODS AND MATERIALS: A systematic review was performed using PubMed, Embase and Web of Science databases. 19 studies were included. ANOVA test was used to compare the duration of lesion prior to therapy and resolution time following IL 5-FU treatment. A two-way proportion test was performed to compare the clearance rate between squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and keratoacanthoma (KA). RESULTS: There was no significant difference between the clearance rate of SCC and BCC after IL 5-FU therapy (87 % vs 91.4%, respectively; P=0.2); however, the clearance rate of both SCC and BCC was significantly greater than that of KA (74.5%; P<0.007); 95% CI [2.56%–19.1%]. Lesion duration and resolution time did not significantly differ across SCC, BCC, and KA (P>0.3). CONCLUSION: While majority of data is derived from individual cases, IL 5-FU achieved higher clearance rate in SCC and BCC groups than in KA group. J Drugs Dermatol. 2021;20(2):192-198. doi:10.36849/JDD.5518.

Discrepancies by dermatology resident gender in diagnostic confidence and management of female and male genital lichen sclerosus.

Physician gender may impact their exposure to genital dermatoses during residency. The purpose of this study was to survey current dermatology residents regarding their comfort in diagnosing and managing lichen sclerosus. As residents progress through training, confidence improves in diagnosing and managing both male and female lichen sclerosus. However, residents overall feel less comfortable with male genital lichen sclerosus, with female residents displaying the greatest confidence discrepancy. This study highlights gender discrepancies with dermatology resident confidence and practice habits and may serve to further guide curricula to address these disparities.

Morbihan disease: a case report and differentiation from Melkersson-Rosenthal syndrome.

We present a 32-year old woman with a 9-year history of upper facial swelling. A workup by the ophthalmology department led to the diagnosis of Melkersson-Rosenthal syndrome. Re-evaluation in our dermatology clinic confirmed a diagnosis of Morbihan disease. Herein, we review case reports and case series of upper facial swelling in the dermatologic and ophthalmologic literature. Although the two entities share histopathological changes, they tend to have different clinical presentations. Melkersson-Rosenthal syndrome appears to be more likely diagnosed in the ophthalmologic literature when the clinical presentation and histopathology may be more consistent with Morbihan disease. In a patient with upper facial swelling, an absence of orolabial swelling, and lack of facial neuropathy, we argue for a diagnosis of Morbihan disease over Melkersson-Rosenthal syndrome, especially if the patient has a history of rosacea.

Functionalization of soft materials for cardiac repair and regeneration.

Coronary artery disease is a leading cause of death in developed nations. As the disease progresses, myocardial infarction can occur leaving areas of dead tissue in the heart. To compensate, the body initiates its own repair/regenerative response in an attempt to restore function to the heart. These efforts serve as inspiration to researchers who attempt to capitalize on the natural regenerative processes to further augment repair. Thus far, researchers are exploiting these repair mechanisms in the functionalization of soft materials using a variety of growth factor-, ligand- and peptide-incorporating approaches. The goal of functionalizing soft materials is to best promote and direct the regenerative responses that are needed to restore the heart. This review summarizes the opportunities for the use of functionalized soft materials for cardiac repair and regeneration, and some of the different strategies being developed.

Human blood and cardiac stem cells synergize to enhance cardiac repair when cotransplanted into ischemic myocardium.

BACKGROUND: Blood-derived circulatory angiogenic cells (CACs) and resident cardiac stem cells (CSCs) have both been shown to improve cardiac function after myocardial infarction. The superiority of either cell type has long been an area of speculation with no definitive head-to-head trial. In this study, we compared the effect of human CACs and CSCs, alone or in combination, on myocardial function in an immunodeficient mouse model of myocardial infarction. METHODS AND RESULTS: CACs and CSCs were cultured from left atrial appendages and blood samples obtained from patients undergoing clinically indicated heart surgery. CACs expressed a broader cytokine profile than CSCs, with 3 cytokines in common. Coculture of CACs and CSCs further enhanced the production of stromal cell-derived factor-1α and vascular endothelial growth factor (P ≤ 0.05). Conditioned media promoted equivalent vascular networks and CAC recruitment with superior effects using cocultured conditioned media. Intramyocardial injection of CACs or CSCs alone improved myocardial function and reduced scar burdens when injected 1 week after myocardial infarction (P ≤ 0.05 versus negative controls). Cotransplantation of CACs and CSCs together improved myocardial function and reduced scar burdens to a greater extent than either stem cell therapy alone (P ≤ 0.05 versus CAC or CSC injection alone). CONCLUSIONS: CACs and CSCs provide unique paracrine repertoires with equivalent effects on angiogenesis, stem cell migration, and myocardial repair. Combination therapy with both cell types synergistically improves postinfarct myocardial function greater than either therapy alone. This synergy is likely mediated by the complimentary paracrine signatures that promote revascularization and the growth of new myocardium.

Squamous Cell Carcinoma Arising in Chronic Inflammatory Dermatoses.

Squamous cell carcinoma (SCC) is a known sequela of chronic inflammatory conditions of the skin. Labial discoid lupus erythema-tosus (DLE), oral lichen planus (OLP), and lichen sclerosus have a relatively short lag time from dermatosis onset to manifestation of malignancy; cutaneous DLE, hypertrophic lichen planus, chronic wounds, hidradenitis suppurativa (HS), and necrobiosis lipoidica can be present for decades before an associated malignancy is observed. Vigilant monitoring is essential for orolabial DLE, chronic HS, and chronic wounds because malignancies in these settings are particularly aggressive and often fatal. We summarize what is known about the nature and demographics of SCC arising within chronic inflammatory dermatoses, emphasizing lag time from dermatosis diagnosis to malignancy onset of common inflammatory conditions.

Utility of hydroxychloroquine laboratory monitoring in dermatologic and rheumatologic patients.

Hydroxychloroquine (HCQ) is an immunomodulator used in dermatology and rheumatology. Side effects may be observed on routine monitoring studies before they become clinically apparent. The goal of this retrospective chart review was to assess laboratory abnormalities in dermatologic and rheumatologic patients taking HCQ. Medical records of patients prescribed HCQ were retrospectively reviewed. Demographics, reported side effects, and parameters on baseline and follow-up complete blood count (CBC) and comprehensive metabolic panel (CMP) were recorded and graded. Laboratory abnormalities were considered severe if they were grade 3 or greater according to Common Terminology Criteria for Adverse Events v3.0 and persistent if they continued beyond subsequent laboratory testing. Of 646 eligible charts, 289 had monitoring studies for review. There were 35 severe (grade 3 or 4, 35/289; 12%) adverse events that developed, as noted on CBC or CMP. Of these 35 severe adverse events, 25 self-corrected on subsequent testing, and 10 (10/289, 3%) across 9 patients were persistent, including glomerular filtration rate, alanine transferase, alkaline phosphatase, glucose, hemoglobin and lymphopenia abnormalities. Of these 10 abnormalities, 7/10 (70%) were unlikely due to hydroxychloroquine use according to the calculated Naranjo score for each patient. Severe laboratory abnormalities while taking hydroxychloroquine are rare, even in a population with a high rate of comorbidities. Among the abnormalities observed, the majority of them (70%) were likely due to disease progression or a medication other than hydroxychloroquine. CBC and CMP monitoring for the reason of observing abnormalities while on HCQ should be at the discretion of the prescribing physician.

Healthcare Provider Experience in Diagnosing and Treating Cutaneous T-Cell Lymphoma.

INTRODUCTION: Cutaneous T-cell lymphoma (CTCL) is a rare, heterogeneous group of non-Hodgkin lymphomas characterized by various clinical, molecular, and histopathologic features of the skin. Variants of CTCL share many clinical features with common inflammatory skin diseases such as atopic dermatitis and psoriasis, making accurate and early diagnosis challenging in clinical settings. Inappropriate treatment or a delay in diagnosis can lead to increased morbidity and mortality. Here, we report findings from an online survey that investigated dermatology community practice, knowledge, and education surrounding CTCL. METHODS: An electronic survey of ten questions was developed and approved by physician experts in CTCL to assess experiences in diagnosing and treating CTCL among healthcare providers (HCPs). The survey was deployed to 10,600 US dermatology HCPs, including medical doctors (MDs), doctors of osteopathic medicine (DOs), nurse practitioners (NPs), and physician assistants (PAs) and excluding HCPs associated with CTCL centers of excellence. RESULTS: Among 44 HCPs who responded and were eligible for inclusion, 82% had diagnosed between one and ten CTCL cases in the last 5 years. Most respondents (91%) reported that they include CTCL in their differential diagnoses after patients do not respond to treatment of more common conditions. Patients with CTCL were frequently diagnosed with other inflammatory dermatoses-most commonly dermatitis and psoriasis-before a CTCL diagnosis, and many were treated with ineffective therapies for years. The most common length of time before a CTCL diagnosis was made was between 1 and 3 years, though 16% of HCPs reported that patients were treated for other diseases or skin conditions for ≥ 5 years. Two-thirds of HCPs agreed that further education surrounding CTCL is needed. CONCLUSIONS: Given the infrequency of CTCL and its similar presentation to other common dermatologic conditions, increased education of CTCL is needed in the dermatology community to improve patient outcomes.

Macrophages in dermatology: pathogenic roles and targeted therapeutics.

The field of macrophage biology is rapidly growing. Recent studies have shifted focus from classic wound healing roles to newly identified roles in dermatologic pathology. These studies have identified pathogenic roles of macrophages in relatively common conditions, such as psoriasis, skin cancer, and cutaneous T-cell lymphoma. Selective depletion of these cells or their associated cytokines leads to improved clinical outcome. Herein, we review recent animal and human studies that have elucidated novel pathogenic roles of macrophages in conditions frequently encountered by dermatologists and discuss clinically relevant macrophage-targeted therapies.

Ex vivo generation of a highly potent population of circulating angiogenic cells using a collagen matrix.

Biomaterials that have the ability to augment angiogenesis are highly sought-after for applications in regenerative medicine, particularly for revascularization of ischemic and infarcted tissue. We evaluated the culture of human circulating angiogenic cells (CAC) on collagen type I-based matrices, and compared this to traditional selective-adhesion cultures on fibronectin. Culture on a collagen matrix supported the proliferation of CD133(+) and CD34(+)CD133(+) CACs. When subjected to serum starvation, the matrix conferred a resistance to cell death for CD34(+) and CD133(+) progenitors and increased phosphorylation of Akt. After 4days of culture, phenotypically enriched populations of endothelial cells (CD31(+)CD144(+)) and progenitor cells (CD34(+)CD133(+)) emerged. Culture on matrix upregulated the phosphorylation and activation of ERK1/2 pathway members, and matrix-cultured cells also had an enhanced functional capacity for adhesion and invasion. These functional improvements were abrogated when cultured in the presence of ERK inhibitors. The formation of vessel-like structures in an angiogenesis assay was augmented with matrix-cultured cells, which were also more likely to physically associate with such structures compared to CACs taken from culture on fibronectin. In vivo, treatment with matrix-cultured cells increased the size and density of arterioles, and was superior at restoring perfusion in a mouse model of hindlimb ischemia, compared to fibronectin-cultured cell treatment. This work suggests that a collagen-based matrix, as a novel substrate for CAC culture, possesses the ability to enrich endothelial and angiogenic populations and lead to clinically relevant functional enhancements.

Use of monocyte/endothelial cell co-cultures (in vitro) and a subcutaneous implant mouse model (in vivo) to evaluate a degradable polar hydrophobic ionic polyurethane.

Potential benefits of co-culturing monocytes (MC) with vascular smooth muscle cells have been reported on for tissue engineering applications with a degradable, polar, hydrophobic, and ionic polyurethane (D-PHI). Since the interaction of MC and endothelial cells (EC) within the blood vessel endothelium is also a process of wound repair it was of interest to investigate their function when cultured on the synthetic D-PHI materials, prior to considering the materials' use in vascular engineering. The co-culture (MC/EC) in vitro studies were carried out on films in 96 well plates and porous scaffold disks were prepared for implant studies in an in vivo subcutaneous mouse model. After 7 days in culture, the MC/EC condition was equal to EC growth but had lower esterase activity (a measure of degradative potential), no pro-inflammatory TNF-α and a relatively high anti-inflammatory IL-10 release while the ECs maintained their functional marker CD31. After explantation of the porous scaffolds, a live/dead stain showed that the cells infiltrating the scaffolds were viable and histological stains (May-Grunwald, Trichrome) demonstrated tissue in growth and extracellular matrix synthesis. Lysates from the implant scaffolds analyzed with a cytokine antibody array showed decreased pro-inflammatory cytokines (IL-6, TNF-α, GM-CSF), increased anti-inflammatory cytokines (IL-10, IL-13, TNF-RI), and increased chemotactic cytokines (MCP-1, MCP-5, RANTES). The low foreign body response elicited by D-PHI when implanted in vivo supported the in vitro studies (EC and MC co-culture), demonstrating that D-PHI promoted EC growth along with an anti-inflammatory MC, further demonstrating its potential as a tissue engineering scaffold for vascular applications.