Ethosuximide-induced drug reaction with eosinophilia and systemic symptoms with mediastinal lymphadenopathy.

Lymphadenopathy is a common sign for drug reaction and eosinophilia with systemic symptoms (DRESS) syndrome, but hilar and mediastinal lymphadenopathy may be underreported. We describe a 7-year-old boy who started taking ethosuximide for absence seizures and presented with diffuse rash, fever, elevated transaminases, facial swelling, and hilar and mediastinal lymphadenopathy. His mediastinal lymphadenopathy was concerning for lymphoma, which led to more invasive testing to rule out malignancy. This report highlights an unusual and likely underreported presenting sign of DRESS syndrome in children.

Lipocalin 2: A New Antimicrobial in Mast Cells.

Mast cells (MCs) play a significant role in the innate immune defense against bacterial infection through the release of cytokines and antimicrobial peptides. However, their antimicrobial function is still only partially described. We therefore hypothesized that MCs express additional antimicrobial peptides. In this study, we used FANTOM 5 transcriptome data to identify for the first time that MCs express lipocalin 2 (LCN2), a known inhibitor of bacterial growth. Using MCs derived from mice which were deficient in LCN2, we showed that this antimicrobial peptide is an important component of the MCs' antimicrobial activity against Escherichia coli (E. coli). Since sphingosine-1-phosphate receptors (S1PRs) on MCs are known to regulate their function during infections, we hypothesized that S1P could activate LCN2 production in MCs. Using an in vitro assay, we demonstrated that S1P enhances MCs antimicrobial peptide production and increases the capacity of MCs to directly kill S. aureus and E. coli via an LCN2 release. In conclusion, we showed that LCN2 is expressed by MCs and plays a role in their capacity to inhibit bacterial growth.

Scabies presenting as cutaneous nodules or malar erythema: reports of patients with scabies surrepticius masquerading as prurigo nodularis or systemic lupus erythematosus.

Scabies surrepticius is a unifying term that represents non-classical presentations of scabies mite infestation. A patient with scabies surrepticius is described: a man with scabies masquerading as prurigo nodularis. The 91-year-old man had metastatic prostate cancer and presented with diffuse pruritic nodules. Prurigo nodularis was suspected; however, the biopsy revealed scabies mites in the stratum corneum. He was successfully treated with topical permethrin 5% cream and oral ivermectin. In addition, the features of a woman with scabies mimicking systemic lupus erythematosus are summarized. The 47-year-old woman had idiopathic thrombocytopenic purpura and presented with malar erythema and a positive antinuclear antibody (titer 1:320). A diagnosis of systemic lupus erythematous was entertained until skin scraping and mineral oil preparation revealed scabies mites; she was successfully treated with oral ivermectin. In conclusion, Sarcoptes scabiei infestation can present with atypical clinical morphology and an absence of classical lesions such as burrows conventionally distributed in the interdigital web spaces, volar wrists, periumbilical area, or genitalia. Scabies surrepticius is a term that has been designated to describe these unusual presentations. Prurigo nodularis and systemic lupus erythematosus can be added to the litany of conditions masquerading as scabies and are included amongst the guises of scabies surrepticius.

Reducing Legal Risks and Social Media Issues for Cosmetic Surgery.

It is important to understand the legal malpractice risks and strategies to reduce them in facial plastic surgery. Cosmetic procedures and the use of social media introduces additional risks that should be considered by practicing facial plastic surgeons. Strategies should be implemented to protect yourself and your patients, which include an emphasis on informed consent as it relates to using photos on social media platforms, removing photos from social media, and addressing online reviews. By understanding the risks and using adequate strategies, facial plastic surgeons can minimize the risk of litigation when performing cosmetic procedures.

Tumor Necrosis Factor Inhibitor-Induced Eczematous Eruption: A Report of Two Cases and Review of the Literature.

Tumor necrosis factor-alpha (TNF-α) inhibitors are frequently used for the management of type 1 helper T-cell (Th1) immune-mediated chronic inflammatory conditions such as psoriasis and Crohn's disease. Although TNF-α inhibitors are usually well-tolerated, various cutaneous side effects are frequently observed, including eczematous or atopic dermatitis-like eruptions. It is postulated that the attenuation of the Th1 immune pathway with TNF-α inhibition causes a shift towards a type 2 helper T-cell (Th2) immune response, leading to the development of skin lesions grossly and histologically consistent with the Th2 mediated disease atopic dermatitis. Herein, we describe the development of an eczematous eruption in two patients with a history of Th1-mediated disease after months of therapy with a TNF-α inhibitor.

The Relationship Between Epidermal Mitotic Density, Atypical Mitotic Figure Density, Breslow Depth, Ulceration, and Dermal Mitotic Rate in Cutaneous Melanoma: A Retrospective Cohort Study.

Prognostic factors for melanoma include Breslow depth (BD), ulceration, and dermal mitotic rate (DMR). No studies have queried the effect of epidermal mitotic density (EMD) or atypical mitotic figure density (AMD) in an outcome-based assessment. Our objective was to determine if there is a relationship between EMD, AMD, BD, DMR, and ulceration and patient outcomes. This was a retrospective cohort study of 185 cases of thick and thin melanomas. Univariate and multivariate cause-specific regression analysis was performed. There was a positive correlation between EMD and BD (P = .0001). The difference between AMD in thick and thin melanomas was statistically significant. For every unit increase in EMD, patients had a 2.8-fold increase in the risk of distant metastasis; however, statistical significance was lost in the multivariate analysis. In adjusted analyses, ulceration, DMR, and BD were associated with outcomes. There were no statistically significant correlations between AMD and outcomes. This study is limited by its small sample size, diminution of the epidermis in some thick melanomas preventing EMD estimates, and reproducibility of mitotic figure counting. EMD and AMD do not seem to have any independent value in multivariate analyses for melanoma. Ulceration, BD, and DMR were significantly associated with outcomes and further solidify these known predictors of prognosis.

Botulinum toxin blocks mast cells and prevents rosacea like inflammation.

BACKGROUND: Rosacea is a chronic inflammatory skin condition whose etiology has been linked to mast cells and the antimicrobial peptide cathelicidin LL-37. Individuals with refractory disease have demonstrated clinical benefit with periodic injections of onabotulinum toxin, but the mechanism of action is unknown. OBJECTIVES: To investigate the molecular mechanism by which botulinum toxin improves rosacea lesions. METHODS: Primary human and murine mast cells were pretreated with onabotulinum toxin A or B or control. Mast cell degranulation was evaluated by ß-hexosaminidase activity. Expression of botulinum toxin receptor Sv2 was measured by qPCR. The presence of SNAP-25 and VAMP2 was established by immunofluorescence. In vivo rosacea model was established by intradermally injecting LL-37 with or without onabotulinum toxin A pretreatment. Mast cell degranulation was assessed in vivo by histologic counts. Rosacea biomarkers were analyzed by qPCR of mouse skin sections. RESULTS: Onabotulinum toxin A and B inhibited compound 48/80-induced degranulation of both human and murine mast cells. Expression of Sv2 was established in mouse mast cells. Onabotulinum toxin A and B increased cleaved SNAP-25 and decreased VAMP2 staining in mast cells respectively. In mice, injection of onabotulinum toxin A significantly reduced LL-37-induced skin erythema, mast cell degranulation, and mRNA expression of rosacea biomarkers. CONCLUSIONS: These findings suggest that onabotulinum toxin reduces rosacea-associated skin inflammation by directly inhibiting mast cell degranulation. Periodic applications of onabotulinum toxin may be an effective therapy for refractory rosacea and deserves further study.

Human Keratinocytes Use Sphingosine 1-Phosphate and its Receptors to Communicate Staphylococcus aureus Invasion and Activate Host Defense.

Sphingosine 1-phosphate (S1P) is a bioactive lipid mediator generated when a cell membrane or its components are damaged by various factors. S1P regulates diverse cell activities via S1P receptors (S1PRs). Keratinocytes express S1PR1-5. Although it is known that S1PRs control keratinocyte differentiation, apoptosis, and wound healing, S1PR functions in keratinocyte infections have not been fully elucidated. We propose that the S1P-S1PR axis in keratinocytes works as a biosensor for bacterial invasion. Indeed, in human impetigo infection, we found high epidermal expression of S1PR1 and S1PR2 in the skin. Furthermore, in normal human epidermal keratinocytes in vitro, treatment with Staphylococcus aureus bacterial supernatant not only induced S1P production but also increased the transcription of S1PR2, confirming our in vivo observation, as well as increased the levels of TNFA, IL36G, IL6, and IL8 mRNAs. However, direct treatment of normal human epidermal keratinocytes with S1P increased the expressions of IL36G, TNFA, and IL8, but not IL6. In both S1P- and S. aureus bacterial supernatant-treated normal human epidermal keratinocytes, S1PR1 knockdown reduced IL36G, TNFA, and IL8 transcription, and the S1PR2 antagonist JTE013 blocked the secretion of these cytokines. Overall, we have proven that during infections, keratinocytes communicate damage by using S1P release and tight control of S1PR1 and 2.

Persistent Alopecia in a Breast Cancer Patient Following Taxane Chemotherapy and Adjuvant Endocrine Therapy: Case Report and Review of Post-treatment Hair Loss in Oncology Patients with Breast Cancer.

Taxane chemotherapy and adjuvant endocrine therapy are commonly used in breast cancer patients following surgery. We describe a 59-year-old woman with a triple-positive invasive right breast cancer that was treated with surgery, radiation, chemotherapy, and adjuvant hormonal therapy. She subsequently developed scalp alopecia, with histopathological features of both androgenetic alopecia and alopecia areata; the hair loss did not resolve after completion of her chemotherapy. Significant clinical improvement was observed with topical minoxidil therapy. PubMed was searched for the following terms: alopecia, breast, cancer, chemotherapy, endocrine, hair, loss, minoxidil, permanent, and taxane. The papers containing these terms and their references were reviewed. Temporary hair loss is frequently observed following taxane chemotherapy; however, albeit uncommon, persistent or permanent alopecia may occur in women with breast cancer who have been treated with taxane chemotherapy and endocrine therapy. It may be reasonable to initiate therapy with topical minoxidil in breast cancer patients who develop alopecia after treatment with either taxane chemotherapy or endocrine therapy alone or both.

Pagetoid Dyskeratosis of the Male Genitalia: Case Report and Review.

Pagetoid dyskeratosis is a benign incidental pathologic finding that has been reported in many distinct skin lesions on various locations of the body. A man who had pagetoid dyskeratosis within lesions of the penile shaft is described and similar cases of pagetoid dyskeratosis in lesions of the male genitalia are reviewed. The patient was a 26-year-old healthy man who developed several asymptomatic penile papules that were refractory to topical imiquimod 5% cream and cryotherapy. Snip biopsies were performed and microscopic examination revealed pagetoid dyskeratosis. PubMed was searched for the following terms: cell, clear, dyskeratosis, genitalia, pagetoid, penile, penis, prepuce, scrotum, and shaft. The papers containing these terms and their references were reviewed. Pagetoid dyskeratosis has been observed in lesions on the prepuce and scrotum; this case report now expands the distribution of this finding to the penile shaft. Clinicians and pathologists should be aware of this intriguing potential incidental finding within skin lesions of the male genitalia.

Topical Application of 5-Fluorouracil Associated with Distant Seborrheic Dermatitis-like Eruption: Case Report and Review of Seborrheic Dermatitis Cutaneous Reactions after Systemic or Topical Treatment with 5-Fluorouracil.

INTRODUCTION: 5-Fluorouracil is a fluoropyrimidine antineoplastic medication that is used to topically treat actinic keratoses. Although local adverse effects to the drug are common and anticipated, distant skin reactions are rare and unexpected. In this case report, we describe a patient who developed seborrheic dermatitis-like eruption at a distant site after topical application of 5-fluorouracil to his arms. CASE REPORT: A 63-year-old man with actinic keratoses on his arms developed a facial seborrheic dermatitis-like reaction after topically applying 5-fluorouracil 5% cream twice daily to actinic keratoses on his forearms for 7 days. The facial dermatosis resolved shortly after discontinuation of the 5-fluorouracil; upon rechallenge of topical 5-fluorouracil on his arms, the facial seborrheic dermatitis recurred. DISCUSSION: Several case reports have been published which describe exacerbations of preexisting seborrheic dermatitis with local topical 5-fluorouracil. Additionally, one case series describes the development of scrotal dermatitis in two patients after distant treatment with 5-fluorouracil. The pathogenesis that causes this distant reaction is unclear. CONCLUSION: We describe a patient with a seborrheic dermatitis eruption after topical application of 5-fluorouracil at a distant site. The etiologic association between the drug and adverse effect was confirmed with multiple cycles of application and discontinuation of the offending agent.

Ranitidine-Associated Sleep Disturbance: Case Report and Review of H2 Antihistamine-Related Central Nervous System Adverse Effects.

Ranitidine is an H2 antihistamine used as an off-label therapy for recalcitrant verruca vulgaris. We describe a man who developed a sleep disturbance after initiating therapy with ranitidine and review similar adverse effects associated with other drugs in this class. The patient was a 40-year-old man with an eight-year history of a wart on his right plantar foot that was recalcitrant to several topical therapies. Adjunctive treatment with ranitidine 150 mg twice daily was initiated. He developed sleep disturbance with bizarre dreams and gastrointestinal symptoms. All symptoms resolved after discontinuation of the medication and recurred when he restarted the drug. PubMed was searched for the following terms: disturbance, dream, ranitidine, verruca, wart, and Zantac. The papers containing these terms and their references were reviewed. Sleep disturbance caused by ranitidine is an uncommon adverse event in patients receiving the drug. However, similar reactions have been observed with other H2 antihistamines such as cimetidine and famotidine. Clinicians should be aware that sleep disturbance secondary to ranitidine is a potential side effect of this medication.

Benign Familial Pemphigus in Skin of Color.

This case report describes friable erythematous plaques on the neck, inguinal folds, buttocks, bilateral axillae, and bilateral antecubital fossae.

Potent antigen-specific immune response induced by infusion of spleen cells coupled with succinimidyl-4-(N-maleimidomethyl cyclohexane)-1-carboxylate (SMCC) conjugated antigens.

In the present study, we report our recently developed new approach to inducing antigen-specific immune response. We use two nucleophilic substitution "click" chemistry processes to successfully couple protein antigens or peptides to mouse spleen cells or T cells by a heterobifunctional crosslinker, succinimidyl-4-(N-maleimidomethyl cyclohexane)-1-carboxylate (SMCC) or sulfo-SMCC. SMCC and its water-soluble analog sulfo-SMCC contain N-hydroxysuccinimide (NHS) ester and maleimide groups, which allow stable covalent conjugation of amine- and sulfhydryl-containing molecules in trans. Protein coupling to cells relies on the free sulfhydryls (thiols) on cell surfaces and the free amines on protein antigens. Although the amount of protein coupled to cells is limited due to the limited number of cell surface thiols, the injection of spleen cells coupled with antigenic proteins, such as keyhole limpet hemocyanin (KLH) or ovalbumin (OVA), induces a potent antigen-specific immune response in vivo, which is even stronger than that induced by the injection of a large dose of protein plus adjuvants. In addition, short peptides coupled to purified splenic T cells also potently elicit peptide-specific T cell proliferation in vivo after injection. Further studies show that antigen-coupled spleen cell treatment leads to augmented IFN-γ-producing T cells. Our study provides a unique antigen delivery method that efficiently distributes antigen to the entire immune system, subsequently eliciting a potent antigen-specific immune response with enhanced IFN-γ production. The findings in the present study suggest that this antigen-cell coupling strategy could be employed in immunotherapy for cancers, infectious diseases as well as immune-mediated disorders.