Photoactivated rose bengal mitigates a fibrotic phenotype and improves cutaneous wound healing in full-thickness injuries.

Healing of deep cutaneous wounds often results in detrimental sequelae, including painful and debilitating scars. Current therapies for full-thickness injuries that target specific phases of wound healing have moderate success; however, full resolution remains incomplete and negative consequences persist if skin homeostasis is not achieved. Photoactivated molecules can modulate cellular responses by generating reactive oxygen species and may provide a novel therapeutic option to improve wound healing. In the current study, we investigated the effects of Rose bengal (RB) dye in a preclinical model of full-thickness cutaneous injury. Monochromatic green light activates RB to generate ROS in the presence of oxygen, subsequently crosslinking collagen fibrils. In in vitro studies, we show that photoactivated RB is well tolerated by epidermal keratinocytes and dermal fibroblasts and can mitigate fibrotic signalling by downregulating collagen production. In a murine model of full-thickness injury, topically-applied and photoactivated RB closed wounds faster than control and vehicle treatments and showed significantly improved wound healing outcomes, including enhanced early granulation, better collagen organisation and increased vascularity in the presence of protracted tissue ROS. These data support an overall improved cutaneous wound healing profile after RB phototherapy and warrant further investigations into this versatile molecule.

Cutaneous nontuberculous mycobacteria infections: A retrospective case series of 78 patients from the Texas Gulf Coast region.

BACKGROUND: The incidence of cutaneous nontuberculous mycobacteria (NTM) infections is increasing. These infections are a diagnostic and therapeutic challenge. OBJECTIVE: We investigated the clinical features, diagnosis, and management of cutaneous NTM infections. METHODS: A retrospective case series studied 78 patients from a Gulf Coast tertiary referral center diagnosed with cutaneous NTM infection by culture or stain of a skin biopsy specimen. RESULTS: A history of trauma, procedure, or environmental exposure was common. The mean time between the initial evaluation and diagnosis was 12 weeks. Only 15% of acid-fast bacillus-positive cultures had a positive acid-fast bacillus smear, and only 43% of those accompanied by skin biopsy specimen had a positive Fite stain. Immunosuppressed patients were more likely to have a positive Fite stain. Treatment included surgery and multiple antibiotics. Immunosuppressed patients and Mycobacterium abscessus group infections were more likely to have persistent disease. LIMITATIONS: M chelonae and M abscessus isolates were indistinguishable and therefore were reported together. Five cases were not confirmed by culture. CONCLUSIONS: Even with clinical suspicion, the diagnosis of NTM infection can be difficult. Results of acid-fast bacillus smears and special stains are frequently negative. Antibiotic resistance is common. Multidrug treatment is often required, and surgical therapy may be needed.

A case of erythema multiforme major following administration of ciprofloxacin ophthalmic drops.

A 49-year old woman was hospitalized for generalized rash and pruritus following the administration of ophthalmic drops containing ciprofloxacin to treat conjunctivitis. Physical examination demonstrated diffuse erythematous papules and plaques with a targetoid appearance, injected sclera, and multiple erosions in the oropharynx. Skin biopsy confirmed a diagnosis of erythema multiforme major. The eye drops were discontinued and supportive treatment was initiated; the patient recovered in four weeks and was discharged from the hospital. Although cases such as this are rare, it is important that physicians take a thorough medication history from all patients with suspected erythema multiforme, including topical and ophthalmic medications. Prompt discontinuation of the offending agent can hasten patient recovery and optimize outcomes.

Pentoxifylline and cyclosporine in the treatment of febrile ulceronecrotic Mucha-Habermann disease.

We describe two pediatric cases of febrile ulceronecrotic Mucha-Habermann disease (FUMHD) with response to pentoxifylline and cyclosporine therapies. Based on our review of the literature, we are presenting the first case of FUMHD treated with pentoxifylline and the third case of FUMHD successfully treated with cyclosporine. These agents may be of therapeutic benefit in the treatment of FUMHD, in part by suppressing tumor necrosis factor-alpha, which we believe may mediate the disease process.

Mycobacterium fortuitum infection arising in a new tattoo.

We report an uncommon case of a cutaneous infection with Mycobacterium fortuitum arising in a new tattoo. A 29-year-old man presented with a several month history of a non-pruritic papular eruption within a tattoo; the papules developed 1-to-2 weeks after the tattoo procedure. He denied similar symptoms with previous tattoos. He had been treated unsuccessfully with cephalexin. Histopathologic examination revealed perifollicular chronic and granulomatous inflammation, consistent with chronic folliculitis. Acid-fast bacilli culture identified Mycobacterium fortuitum complex. The patient was treated with a 2-month course of oral trimethoprim-sulfamethoxazole (160mg/800mg twice daily) and ciprofloxacin (250 mg twice daily), with clinical improvement at follow up after three weeks of the antibiotic regimen. Rapidly growing mycobacteria have emerged as a cause of tattoo-associated cutaneous infection in recent years. Diagnosis and treatment can be difficult without clinical suspicion. M. fortuitum and other rapidly growing mycobacteria should be considered in the differential diagnosis of tattoo-associated dermatologic complications.

Screening for HPV-Related Oropharyngeal Cancer in Gay and Bisexual Men: Acceptability and Predicting Possible Use of "Oral Selfies" by Smartphone as a Secondary Prevention Approach.

Oropharyngeal cancers (OPCa) caused by HPV have emerged as one of the leading causes of malignancies caused by HPV infection. They are also significantly more likely to occur in males and in people with a history of oral sex with multiple partners. Gay and bisexual men are disproportionately affected by HPV-positive oropharyngeal cancers. We studied 1699 gay and bisexual men on 2 major dating sites in the US to assess their knowledge about HPV-related OPCa, attitudes toward screening for it, beliefs about oropharyngeal cancer screening based on the Health Belief Model, and attitudes toward possible screening approaches for OPCa. Knowledge on a 12-item scale was low, with a median of 5 items correct: 72% knew of the benefits of HPV vaccination. Significant predictors of needing OPCa screening included perception of risk for OPCa, seeing it as severe, having lower barriers, fewer reasons to avoid screening, higher knowledge, and being HPV vaccinated were significant predictors, explaining half the total variance. Most participants would accept routine, virtual/online doctor or dental appointments, and over half would accept an in-person screening. Nearly two-thirds stated that they would accept getting checked for OPCa if they could do self-screening at home, and half were prepared to use an online screening tool or app, where they could take an "oral selfie" and send it to a healthcare provider for examination. One-third stated that they would trust the results of a home screening completed by themselves and posted to a website equally as cancer screening completed online by a healthcare provider. Data indicate that despite low OPCA knowledge levels, the risk of HPV-associated OPCa was known. Being at personal risk and having knowledge of disease severity had 70% of the sample thinking about, or preparing to get, screening. Self-screening by a smartphone "oral selfie" transmitted to a screening website was acceptable to many gay and bisexual men, and online screening by a doctor or dentist was acceptable to most. OPCa screening in this population using electronic technology, together with the increasing incidence of HPV-associated OPCa in gay and bisexual men, brings together an opportunity to detect OPCa early.

Role of oligomers in the amyloidogenesis of primary cutaneous amyloidosis.

BACKGROUND: Primary cutaneous amyloidosis (PCA) describes a heterogeneous group of cutaneous diseases characterized by amyloid deposition; this may manifest as macules, papules, or nodules, depending on the subtype involved. To date, relatively little is known about the process of amyloidogenesis in the skin; however, investigators recently have identified small amyloid species, known as oligomers, which give rise to large amyloid fibrillar aggregates. OBJECTIVE: The purpose of the current study was to identify small oligomers in patients with PCA using novel immunohistochemical techniques and to examine our findings in light of previous hypotheses of amyloid formation in these diseases. METHODS: Six cases of PCA were analyzed using Congo red, thioflavin S, and hematoxylin-eosin. We also analyzed these samples with the novel oligomer-specific conformational antibody I-11 to detect the small, misfolded protein oligomers. Semiquantitative analysis was performed on these samples to grade the amount of amyloid aggregates and oligomers detected in the skin samples with light and polarized microscopy. RESULTS: In the cases examined, we detected intracellular oligomers in the basal cell layer of the epidermis and the surrounding cells in the dermis. We also were able to detect large aggregates of amyloid in our samples and to correlate the relationship of oligomers to amyloid aggregates in accordance with previous studies on cutaneous amyloidosis and other amyloid-related diseases. LIMITATIONS: Small sample size is a limitation. CONCLUSIONS: PCA is an amyloid-related disease that likely follows a similar mechanism as other more intensively studied amyloid diseases.

Dermatologic rituximab dosing: treatment of refractory pemphigus vulgaris in an adolescent male.

Rituximab is a chimeric monoclonal antibody against CD20 that mediates B-cell depletion. It has been shown to be effective in a variety of autoimmune-related diseases, including pemphigus vulgaris. Most reports of pemphigus treatment utilize the weekly dosing regimen designed for the treatment of B-cell malignancy. The authors report a case of successful treatment of refractory pemphigus vulgaris in an adolescent male using three infusions of rituximab spread over a four-month period of time. The authors also discuss recent updates in rituximab's mechanism of action in autoimmune disease. Rituximab acts to destroy auto-reactive B-cells prior to their development into auto-antibody producing plasma cells. More recent reports have shown that rituximab also indirectly leads to a decrease of autoreactive CD4+ T cells via depletion of B-cells that are necessary for antigen presentation. Monthly to bi-monthly rituximab infusion dosing may be a more appropriate dosing strategy for autoimmune disease that minimizes potential side effects while generating remission of disease. Dermatology continues to see an increase in use of medications designed for treatment of rheumatologic disease and malignancy. Additional studies should focus on the appropriate dosing of these medications for dermatologic conditions that limit the risk of adverse effects while preserving therapeutic benefit.

High blood pressure arising from a defect in vascular function.

Hypertension, a major cardiovascular risk factor and cause of mortality worldwide, is thought to arise from primary renal abnormalities. However, the etiology of most cases of hypertension remains unexplained. Vascular tone, an important determinant of blood pressure, is regulated by nitric oxide, which causes vascular relaxation by increasing intracellular cGMP and activating cGMP-dependent protein kinase I (PKGI). Here we show that mice with a selective mutation in the N-terminal protein interaction domain of PKGIalpha display inherited vascular smooth muscle cell abnormalities of contraction, abnormal relaxation of large and resistance blood vessels, and increased systemic blood pressure. Renal function studies and responses to changes in dietary sodium in the PKGIalpha mutant mice are normal. These data reveal that PKGIalpha is required for normal VSMC physiology and support the idea that high blood pressure can arise from a primary abnormality of vascular smooth muscle cell contractile regulation, suggesting a new approach to the diagnosis and therapy of hypertension and cardiovascular diseases.

Keloid Scars: An Updated Review of Combination Therapies.

Keloid scars are a common yet poorly understood complication of wound healing that can cause a diminished quality of life. Currently, there is little agreement amongst the medical community regarding the best treatment modality for keloids. For this reason, we have created an updated review of the most successful combination therapies for keloid scars and compared their efficacy based on rates of recurrence following treatment. Additionally, these combination therapies have been compared with intralesional triamcinolone acetonide corticosteroid (TAC), which is considered the mainstay monotherapy for keloids. All combination therapies included in our review were shown to produce superior outcomes than TAC monotherapy. We have also found that certain combination therapies are known to produce superior results when used in specific anatomic locations. Intralesional TAC plus intralesional cryotherapy appeared to have the most promising results for non-auricular keloids, and the authors suggest considering this as a first-line treatment. Additionally, the use of surgical excision plus compression therapy achieved superior results for auricular keloids and should be considered first-line for keloids in these locations.

A Case of Lansoprazole-Induced Bullous Pemphigoid After Zantac Recall.

Proton pump inhibitors (PPIs) are the mainstay of treatment for many gastric acid-related diseases with a relatively safe drug profile. One of the rare side effects is PPI-induced bullous pemphigoid. We describe a case of new-onset bullous pemphigoid on initiation of lansoprazole for esophagitis after a nationwide Zantac recall. This condition can improve with the cessation of PPI and the use of corticosteroids. However, it poses a significant challenge to the management of gastroesophageal reflux disease by limiting available pharmacologic options. In addition, this case highlights the negative effects of a drug recall.

A comparison of risk factors for atypical squamous cells and squamous intraepithelial lesions in a sample of US- and African-born HIV-positive women.

Previous research conducted in the USA and Africa has identified human immunodeficiency virus (HIV) infection as a risk factor for women developing squamous intraepithelial lesion (SIL) diagnosis. This study was conducted to compare the odds of a diagnosis of atypical squamous cells (ASCUS) or SIL in a sample of mostly African-born and US-born women (n=275). A greater proportion of US-born women had an ASCUS (68.9%) or SIL (81.3%) diagnosis than African-born women (29.5% ASCUS, 15.6% SIL). After adjusting for age, smoking status, absolute CD4, and a prescription for HIV-antiviral medications, the US-born women had a greater odds of a SIL diagnosis than the African-born women (OR=0.22, 95% CI: 0.06-0.79); no significant differences in ASCUS remained after adjustment. In this sample, proportionately more African-American (55.3%) and white American (51.1%) women smoke tobacco than African-born women (1.9%), explaining, perhaps, some of the difference. We found that an absolute CD4 less than 200, when compared to an absolute CD4 above 500, was highly predictive of a SIL diagnosis (OR=6.31, 95% CI: 2.10-18.93, p-trend <0.01). A prescription for HIV-antiviral medications was not a significant predictor of an ASCUS or SIL diagnosis.

Transitional cell neoplasm of the nasolacrimal duct associated with human papillomavirus type 11.

BACKGROUND: Tumors of the lacrimal sac are rare but noteworthy because of their significant potential to become malignant or life-threatening if treatment is delayed. Dermatologists may be the first to encounter such neoplasms. OBSERVATIONS: We report a case of a 53-year-old Caucasian woman who presented with a seven-year history of an asymptomatic, subcutaneous nodule near her right medial canthus. Histology of the lesion revealed transitional epithelium in a papillary growth pattern with numerous goblet cells, scattered mitoses and focal full-thickness atypia. The patient was diagnosed with transitional cell neoplasm (inverted papilloma-type) of the nasolacrimal duct. PCR evaluation identified HPV type 11 in the lesion. CONCLUSION: Our report is one of a growing number of case reports and series detecting HPV DNA in these tumors which further supports HPV as an etiologic agent in epithelial lacrimal sac tumors. We believe that dermatopathologists need to be aware of this entity, as dermatologists may be the first to encounter these neoplasms. LIMITATIONS: The association of HPV with this tumor does not prove causality.