Bacterial antimicrobial resistance and dermatological ramifications.

The spread of COVID-19 serves as a reminder of the might of microbes in the era of modern medicine. For years, another threat has preoccupied infectious disease experts and public health officials alike: rising antimicrobial resistance (AMR). Resistance is exceeding stewardship efforts as well as the rates of new drug development and approval in the market. A dry antimicrobial pipeline is threatening regression to a preantibiotic era. While the consequences of resistance may seem far removed from daily clinical practice, awareness of AMR is essential to dermatological care given that dermatologists prescribe more antibiotics per physician than other providers. Antibiotics in dermatology are often used for prolonged courses, with significant potential for microbiome alteration and antibiotic-related adverse effects. Through this review we hope to contribute to efforts of bringing the crisis of AMR to the forefront of daily dermatological practice.

Antimicrobials and resistance part II: Antifungals, antivirals, and antiparasitics.

The available antifungal armamentarium consists of only a few drug classes, many limited in their use by significant toxicities and dangerous drug interactions. Rising opportunistic multidrug-resistant pathogens in the last few decades are further limiting available treatment options in life-threatening invasive fungal diseases. Similarly, antiviral resistance, although uncommon in healthy hosts, remains a challenge in immunocompromised patients with a risk for dissemination and severe disease. As evidenced by a dry pipeline, the gravity of antifungal, antiviral, and antiparasitic resistance has yet to draw the same attention as antibacterial resistance. Resistance disproportionately affects immunocompromised and vulnerable hosts, underscoring the urgent need to develop novel therapeutics. Antifungals, antiparasitics, and antivirals of main significance will be reviewed here, along with resistance concerns and some therapeutic agents under investigation.

Part I Antimicrobial resistance: Bacterial pathogens of dermatologic significance and implications of rising resistance.

Although the COVID-19 pandemic has been the defining global health crisis of our time, public health officials have been sounding the alarm of another ominous threat for years: an impending antimicrobial resistance crisis. In dermatology, antibiotics are often used for prolonged courses in the treatment of skin and soft tissue infections and common inflammatory skin conditions, increasing the risk of microbiome alteration and antibiotic-related adverse effects, all while exerting consequential selective pressures on both pathogenic and bystander bacteria. In this review, we hope to raise awareness of the crisis of antimicrobial resistance and review resistance concerns related to dermatology-relevant bacterial pathogens.

Tuberculosis: Common Questions and Answers.

Approximately 10 million people worldwide were infected with tuberculosis (TB) in 2019, resulting in 1.4 million deaths. In the United States that same year, there were nearly 9,000 reported cases of TB disease and up to 13 million people were living with latent TB infection (LTBI), which is an asymptomatic, noncommunicable infection caused by Mycobacterium tuberculosis. Without treatment, LTBI will progress to active TB disease in approximately 5% to 10% of affected people. Individuals with symptoms of TB disease warrant testing. The U.S. Preventive Services Task Force recommends testing individuals at increased risk of LTBI with an interferon-gamma release assay or tuberculin skin testing. Because the incidence of LTBI in health care professionals is similar to that of the general population, periodic retesting is not recommended. After a positive test result, chest radiography should be performed and, in patients with suspected pulmonary TB disease, sputum collected for diagnosis. Both suspected and confirmed cases of LTBI and TB disease must be reported to local or state health departments. Preferred treatment regimens for LTBI include isoniazid in combination with rifapentine or rifampin, or rifampin alone for a duration of three and four months, respectively. Treatment of drug-susceptible TB disease includes an eight-week intensive phase with four drugs (isoniazid, rifampin, pyrazinamide, and ethambutol), followed by a continuation phase lasting 18 weeks or more, with two drugs based on susceptibility testing results. Consultation with a TB expert is necessary if there is suspicion or confirmation of drug-resistant TB.

Gene expression profiling of lichenoid dermatitis immune-related adverse event from immune checkpoint inhibitors reveals increased CD14+ and CD16+ monocytes driving an innate immune response.

BACKGROUND: Cancer patients receiving antibodies abrogating immune checkpoint pathways may develop a diverse array of immune-related adverse events (irAEs), of which lichenoid dermatitis (LD) is the most common. The mechanism driving the emergence of these irAEs remain understudied, underscoring a critical need to determine the unique gene expression profiles and immune composition in LD-irAE. METHODS: LD-irAE (n = 3) and benign lichenoid keratosis (BLK) control (n = 3) were profiled with NanoString nCounter PanCancer Immune Profiling Panel interrogating the mRNA levels of 770 genes. Immunohistochemical (IHC) studies (n = 14 samples) for CD14, CD16, T-Bet, Gata-3, and FoxP3 were further evaluated using Aperio digital image analysis. RESULTS: The LD-irAE showed downregulation of 93 mRNA transcripts (P < 0.05) and upregulation of 74 mRNA transcripts (P < 0.04) including toll-like receptor (TLR) 2 and TLR4 (P < 0.05). CD14+ and CD16+ monocytes quantified by IHC (H-score) were higher in LD-irAE than in the BLK control (P < 0.05). The immune composition of LD-irAE exhibited higher numbers of T-Bet+ (Th1) cells compared with Gata-3+ (Th2) cells (P = 0.016) and lower numbers of FoxP3 (T regulatory) cells (P = 0.008). CONCLUSIONS: LD-irAE exhibited activation of CD14/TLR innate immune response with increased CD14+ and CD16+ monocytes compared with BLK control. CD14/TLR signaling may drive the development of LD-irAE.

Evaluation and endodontic management of a patient with 6 single-rooted molars: a case report.

This case report describes a patient with unusual tooth morphology involving the bilateral presence of 6 maxillary and mandibular first and second molars with a single root and a single canal. The article also discusses the endodontic management of a single-rooted maxillary molar and the use of cone beam computed tomography for evaluation and diagnosis of these anatomical variations.

Periorbital edema associated with alpelisib.

Alpelisib is an alpha isoform-specific phosphatidylinositol 3-kinase (PI3K) inhibitor approved for use in the treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor (HER2)-negative metastatic breast cancer in combination with fulvestrant. Hyperglycemia, rash, and gastrointestinal upset are the most commonly reported adverse events associated with alpelisib. Although rash is a known on-target effect of alpelisib, patients typically present with a morbilliform rash. We describe two cases of periorbital edema associated with alpelisib. We discuss the clinical findings, management, and prognosis of this unique reaction. These cases highlight the importance of early involvement of dermatology to manage adverse cutaneous events associated with alpelisib.

Granuloma annulare of the palms.

Granuloma annulare (GA) is a common, benign skin condition, which was first described over a century ago, but still remains an enigma with respect to etiology, associated systemic diseases, and treatment. A number of clinical variants have been classified. We report an atypical presentation of GA localized to the palms.

Effect of root dentin conditioning using different chelating agents on pushout bond strength of MTA-fillapex and bioroot RCS: An in vitro study.

CONTEXT: The success of endodontic therapy depends on proper biomechanical preparation and obturation. AIM: To evaluate and compare the pushout bond strength (POBS) of MTA Fillapex (MF) and BioRoot RCS (BRCS) sealers in endodontically treated teeth with different irrigants-5.25% Sodium hypochlorite (NaOCl), 17% ethylenediaminetetraacetic acid (EDTA) and 0.2% Chitosan. MATERIALS AND METHODS: 60 premolars were divided into three groups. Each group was then subdivided into A and B. The three groups were Group 1A: 17% EDTA + 5.25% NaOCl with MF sealer (n = 10); Group 1B: 17% EDTA + 5.25% NaOCl with BRCS sealer (n = 10); Group 2A: 0.2% Chitosan + 5.25% NaOCl with MF sealer (n = 10); Group 2B: 0.2% Chitosan + 5.25%NaOCl with BRCS sealer (n = 10); Group 3A: 5.25% NaOCl + MF sealer (n = 10); and Group 3B: 5.25% NaOCl + BRCS sealer (n = 10). After obturation, they were sectioned horizontally (1.5 mm thick). The POBS was studied using a universal testing machine (Autograph AG-1). The sample size was calculated using the statistical package G * Power (3.1.5). RESULTS: It was found that the POBS of BRCS was higher when the root canal was irrigated with 0.2% Chitosan + 5.25% NaOCl. Thus, Group 2B showed significantly higher POBS than Group 2A. CONCLUSION: The irrigation regimen of Chitosan with NaOCl was found to have better debriding effect on the root canal. Of the two sealers, BRCS showed the higher bond strength values than MF.

Disseminated cutaneous nocardiosis mimicking cellulitis and erythema nodosum.

Infection with Nocardia asteroides is a rare, life-threatening infection, which is most commonly encountered in immunocompromised patients. Cutaneous involvement is usually seen with disseminated infection but may also occur as primary cutaneous nocardiosis. We present a case of an immunocompromised patient who presented with cellulitis of the right hand and disseminated subcutaneous nodules of the lower extremities resembling erythema nodosum. Cultures from both a skin biopsy of a subcutaneous nodule on the leg as well as a surgical specimen from the debridement of her hand grew Nocardia asteroides. The patient was treated successfully with trimethoprim-sulfamethoxazole. This case likely represents primary cutaneous nocardiosis with secondary dissemination, which has been rarely reported. It also emphasizes that nocardial infection should be considered in the differential diagnosis of lesions suggestive of cellulitis or erythema nodosum in the severely immunocompromised patient.

Segmental neurofibromatosis in association with a large congenital nevus and malignant melanoma.

We describe a patient with segmental neurofibromatosis and a large congenital nevus who developed malignant melanoma in the same anatomic distribution. The overlapping presentation suggests a common etiologic link between neurofibromatosis and large congenital nevi and the possibility that neurofibromatosis increases the risk of melanoma with large congenital nevi.

Up-regulation of Flotillin-2 is associated with melanoma progression and modulates expression of the thrombin receptor protease activated receptor 1.

Flotillin 2 (flot-2) is a highly conserved protein isolated from caveolae/lipid raft domains that tether growth factor receptors linked to signal transduction pathways. Flot-2 protein and mRNA were increased in tumorigenic and metastatic melanoma cell lines in vitro, and the immunostaining intensity increased substantially across a tissue array of melanocytic lesions. Flot-2 transfection transformed SB2 melanoma cells from nontumorigenic, nonmetastatic to highly tumorigenic and metastatic in a nude mouse xenograft model. SB2 cells stably transfected with the flot-2 cDNA (SB2-flot)-2 cells proliferated faster in the absence of serum, and their migration through Matrigel was additionally enhanced by thrombin. When SB2-flot-2 cells were compared with SB2-vector-control cells on a cancer gene pathway array, SB2-flot-2 cells had increased expression of protease activated receptor 1 (PAR-1) mRNA, a transmembrane, G-protein-coupled receptor involved in melanoma progression. PAR-1 and flot-2 were coimmunoprecipitated from SB2-flot-2 cells. Up-regulation of PAR-1 was additionally confirmed in SB2-flot-2 cells and melanoma cell lines. SB2-flot-2 cells transfected with flot-2-specific small-interfering RNAs made substantially less flot-2 and PAR-1 mRNA. In conclusion, flot-2 overexpression is associated with melanoma progression, with increased PAR-1 expression, and with transformation of SB2 melanoma cells to a highly metastatic line. Flot-2 binds to PAR-1, a known upstream mediator of major signal transduction pathways implicated in cell growth and metastasis, and may thereby influence tumor progression.

Distal lower extremity paresthesia and foot drop developing during adalimumab therapy.

The development of tumor necrosis factor inhibitor biologic therapy is arguably one of the most significant achievements in the treatment of rheumatic diseases to date. Neurologic events suggestive of demyelination have been reported for patients receiving treatment with the antitumor necrosis factor agents etanercept and infliximab. We describe the onset of lower extremity paresthesia and foot drop in a patient who was receiving adalimumab for the treatment of psoriasis and examine the relationship of tumor necrosis factor antagonism and demyelinating disease.

Clinical manifestations of varicella-zoster virus infection.

Infections by VZV, the virus that causes chickenpox and herpes zoster, usually are diagnosed by the classic clinical presentations. In immunocompromised patients, however, the atypical presentation can make the diagnosis more challenging. Although varicella typically follows an uncomplicated course in children, adults and immunocompromised patients can develop complications involving several organs; some complications may be fatal. Prevention of disease with the vaccine is ideal. When varicella or zoster infection does occur, proper treatment should be initiated, depending on the age and immune status of the patient.

Dentine microhardness changes following conventional and alternate irrigation regimens: An in vitro study.

AIM: To compare the changes in microhardness of root dentin caused by two novel irrigation regimens with conventional irrigation. MATERIALS AND METHODS: Forty extracted human permanent incisor teeth were selected. Decoronated roots were separated longitudinally to get 80 specimens that were embedded in autopolymerizing acrylic resin and grounded flat with silicon carbide abrasive papers. Of these, 60 root segments without any cracks or defects were selected and divided into four groups according to the irrigation regimen used (n = 15). Group I: 5% sodium hypochlorite (NaOCl) + 17% ethylenediaminetetraacetic acid (EDTA) + 0.2% chlorhexidine digluconate (CHX) (conventional). Group II: 6% Morinda Citrifolia Juice + 17% EDTA (MCJ). Group III: 5% NaOCl + Q Mix 2 in 1 (QMix). Group IV: Distilled water (control). Irrigation regimens were performed for 5 minutes. Dentin microhardness was measured with a Vickers indenter under a 200-g load and a 20-s dwell time at the midroot level of root dentin. The data were analyzed using Kruskal Wallis test and Dunn's multiple comparison tests. RESULTS: A significant difference was seen in the median values of the four groups. The control group showed the least reduction in microhardness when comparison with the other groups. Except for Group III (Q Mix), the other groups that were tested (MCJ and conventional regimens) showed statistically significant difference from the control group. CONCLUSION: Within the limitation of this study, it was concluded that NaOCl + Q Mix were least detrimental to root dentin microhardness when compared with MCJ and conventional irrigation regimens.

A permanent mandibular second molar with seven root canal systems.

This case report illustrates the nonsurgical endodontic management of a seven-canaled mandibular second molar. The root canal configuration presented as four mesial and three distal canals. Identification of the canal system was made with the aid of magnification, ultrasonics, and multiple angulated radiographs. Postoperative examination at 18 months showed a clinically asymptomatic tooth with resolution of the periapical pathology.