A Comparative Analysis of Local Anesthetics: Injection Associated Pain and Duration of Anesthesia.

BACKGROUND: Local anesthesia administration is frequently the most painful step of dermatologic surgery. Identification of an anesthetic that minimizes infiltration pain and toxicity while maximizing duration of action would improve both patient satisfaction and procedural safety. This study compared eight local anesthetic solutions to identify the composition that minimizes infiltration pain, maximizes duration of effect, and minimizes amount of local anesthetic needed. METHODS: In a double-blinded study, thirty subjects were injected with eight local anesthetic solutions of varied concentrations of lidocaine, epinephrine, benzyl alcohol, and sodium bicarbonate. Infiltration pain was rated by subjects using a visual analog scale and duration of anesthesia was assessed by needle prick sensation every 15 minutes. RESULTS: Solutions 2, 7, and 8, were significantly less painful (P<0.001), though not statistically different from each other. Two of the three solutions were buffered 10:1 with sodium bicarbonate. Additionally, two of the three contained notably decreased concentrations of lidocaine, 0.091% and 0.083%, than traditionally used in practice. The use of benzyl alcohol did not result in a reduction of reported pain. The duration of action was equal among the solutions regardless of anesthetic concentration. CONCLUSIONS: A solution of 0.091% lidocaine with epinephrine 1:1,100,000 and 0.82% benzyl alcohol reduces medication dose while ensuring maximum patient comfort and, theoretically, increases shelf life. While considered off-label, clinically effective dermal anesthesia may be obtained at a lower concentration of lidocaine and epinephrine than is commonly used, aiding conservative use of local anesthetic, particularly during times of national shortage. J Drugs Dermatol. 2023;22(4): doi:10.36849/JDD.5183 Citation: Moses A, Klager S, Weinstein A, et al. A comparative analysis of local anesthetics: Injection associated pain and duration of anesthesia. J Drugs Dermatol. 2023;22(4):364-368. doi:10.36849/JDD.5183.

Successful systemic treatment outcomes of lichen planus: A single-center retrospective review.

Lichen planus (LP) affects up to 4% of adults and can cause significant distress and morbidity, especially to those with persistent disease. As many as 20% of patients with LP may exhibit widespread or recalcitrant disease necessitating systemic treatment options. We sought to evaluate the effectiveness of systemic treatments for severe and recalcitrant LP not responsive to topical corticosteroids or calcineurin inhibitors. Over a 10-year period, 374 patients with cutaneous and mucosal LP were evaluated at a major regional tertiary medical center; 94 qualified for inclusion in the study. In all, 26 (28%) patients achieved remission, 52 (55%) experienced stable disease control, and 16 (17%) failed all attempted treatments. Among medications most trialed, intramuscular triamcinolone (IM TAC), hydroxychloroquine, and methotrexate were most successful with 79%, 61%, and 42% respective response rates. In contrast, oral corticosteroids and dapsone were less frequently successful at rates of 24% and 20%. IM TAC represented the highest level of treatment success and was statistically significant compared to other systemic treatments (P < .01). Among adjuvant therapies, intralesional triamcinolone (IL TAC) demonstrated higher success (71%) than oral corticosteroids (29%). Based on this multi-year evaluation, we recommend that clinicians consider IM TAC as a first-line systemic option for severe or refractory LP, with hydroxychloroquine as the steroid-sparing treatment of choice. For patients requiring adjuvant therapy, IL TAC should be considered to hasten response and symptom relief. Patients with severe or widespread disease may benefit from earlier initiation of systemic therapy to prevent significant morbidity and impact on daily function.

Treatment of pruritus with botulinum toxin in a pediatric patient with Fox-Fordyce disease.

Fox-Fordyce disease is a chronic pruritic disorder of apocrine sweat glands that is often associated with significantly decreased quality of life. With no definitive cure, affected patients are often treated with topical corticosteroids as first-line therapy, but evidence for treatment of refractory cases is limited. We present an adolescent with Fox-Fordyce disease successfully treated for symptomatic relief with botulinum toxin type A injections. While previously reported in an adult patient, we detail the efficacy of this therapy in a pediatric patient.

Drugs as a Frequent Cause of Acute Rash in Patients after CD34+-Selected Peripheral Blood Stem Cell Transplantation.

Although histopathological differences have been reported between acute graft-versus-host disease (aGVHD) rash and non-aGVHD rash in CD34+-selected peripheral blood stem cell transplantation (PBSCT) recipients, skin biopsy alone is usually insufficient to determine rash etiology. As such, distinguishing inflammatory non-aGVHD rashes, such as drug eruptions, from cutaneous aGVHD after CD34+-selected PBSCT remains challenging and relies on clinical presentation. This study aimed to identify etiologies of skin rash in the first year after CD34+-selected PBSCT and to assess whether laboratory serologic markers, transplant characteristics, and rash morphology and symptomatology aid in differentiation of cutaneous aGVHD rash versus non-aGVHD rash. We conducted a retrospective study of 243 adult patients who underwent CD34+-selected PBSCT at Memorial Sloan Kettering Cancer Center between 2008 and 2011. Among this cohort of transplant recipients, only 43 patients (17.7%) developed cutaneous aGVHD. A total of 152 patients (63%) were identified with rash within 1 year after PBSCT. The proportion of patients who experienced peripheral eosinophilia was not different between those with an aGVHD versus non-aGVHD rash (P ≥ .90), nor when stratified by CD34+ selection method (Isolex, P = .70; CliniMACS, P≥ .90). The proportion of patients with pruritus was also not different between those with an aGVHD rash versus non-aGVHD rash (P= .20), or when stratified by CD34+ selection modality (Isolex, P = .20; CliniMACS, P = .50). The most common cause of non-aGVHD rash among those with a clear etiology was drug (39% of Isolex; 26% of CliniMACS). Single drug culprits were identified in 51% of drug rashes. The most commonly reported offending agents included antibiotics, keratinocyte growth factor, chemotherapy, and recombinant glycosylated human IL-7.

Flavoring Chemicals and Aldehydes in E-Cigarette Emissions.

Regulations on e-cigarettes in the U.S. do not provide guidelines on the chemical content of e-cigarette liquids. We evaluated emissions of aldehydes and flavoring chemicals in e-cigarette vapor under typical usage conditions. We selected 24 e-cigarette flavors from the top selling disposable e-cigarette brands. E-cigarettes were connected to a pump drawing air for two second puffs with sixty-second intervals between puffs. The vapor was analyzed for the presence of aldehydes using high-performance liquid chromatography-ultraviolet detector and for the presence of flavoring chemicals with gas chromatography and an electron capture detector. All e-cigarette emissions tested contained at least one aldehyde and/or flavoring chemical on either the FEMA "High Priority Chemicals" or FDA Harmful and Potentially Harmful Constituents lists when sampled at typical usage conditions. Diacetyl, a known respiratory hazard, along with acetoin, were the most prevalent of the flavoring chemicals in e-cigarette vapor, being found in more than 60% of samples. The presence of propionaldehyde, acetaldehyde and formaldehyde were correlated, corroborating previous work suggesting thermal degradation as a pathway for aldehyde generation in e-cigarette vapors. Median formaldehyde concentrations of 626 µg/m3 in e-cigarette vapor exceed the ACGIH maximum concentrations allowable for workers of 370 µg/m3.

Update in Diagnosis and Management of Primary Cutaneous B-Cell Lymphomas.

Primary cutaneous lymphomas are a rare group of diseases, with an estimated incidence of 0.5-1 case per 100,000 people per year. Primary cutaneous B-cell lymphomas (pCBCLs) represent 25-30% of all primary cutaneous lymphomas. There are three main subtypes of pCBCL: primary cutaneous marginal zone lymphoma, primary cutaneous follicle center lymphoma, and primary cutaneous diffuse large B-cell lymphoma, leg type. Cutaneous B-cell lymphomas have a broad spectrum of clinical presentations, which makes diagnostic and therapeutic strategies challenging. To date, treatment recommendations for cutaneous B-cell lymphomas have been largely based on small retrospective studies and institutional experience. Recently, the pharmacotherapeutic landscape has expanded to include drugs that may modify the underlying disease pathology of pCBCLs, representing new therapeutic modalities for this rare group of diseases. Novel therapies used for other systemic B-cell lymphomas show promise for the treatment of pCBCLs and are being increasingly considered. These new therapies are divided into five main groups: monoclonal antibodies, immune checkpoint inhibitors, small-molecule inhibitors, bispecific T-cell engaging, and chimeric antigen receptor T cell. In this review, we discuss the clinical, histopathological, molecular, and cytogenetic features of the most common pCBCL subtypes with a focus on current and innovative therapeutic developments in their management. These emerging treatment strategies for B-cell lymphomas and cutaneous B-cell lymphomas may represent novel first-line options for the management of these rare diseases.

Efficacy of intralesional sodium thiosulfate for the treatment of dystrophic calcinosis cutis: A double-blind, placebo-controlled pilot study.

BACKGROUND: Intralesional injection of sodium thiosulfate has emerged as a promising therapy for calcinosis cutis, but to our knowledge there are no randomized controlled trials evaluating its efficacy as a treatment. OBJECTIVE: Conduct a prospective, double-blinded investigation of intralesional sodium thiosulfate versus normal saline in the treatment of dystrophic calcinosis cutis. METHODS: This prospective pilot study injected normal saline or sodium thiosulfate at 0.1 mL/cm2 into lesions at baseline and at 1- and 2-month follow-up. Subjects were followed for a total of 12 weeks. An in-person Physician Global Assessment score was assigned by the injecting physician at each visit and was repeated by an independent observer. RESULTS: Of 4 subjects who completed the study, only 1 experienced improvement in the size and Physician Global Assessment score of the lesion. By 3-month follow-up, there was no difference between the average size of the treatment and control lesions (P = .39). LIMITATIONS: This was a small single-center study with limited demographic diversity and a short follow-up period. Only dystrophic calcinosis cutis subjects were included, and subjects received only 3 monthly injections of sodium thiosulfate. CONCLUSIONS: With only 1 positive response, our results highlight the need for further study of sodium thiosulfate treatment for dystrophic calcinosis.

New insights into fetal mammary gland morphogenesis: differential effects of natural and environmental estrogens.

An increased breast cancer risk during adulthood has been linked to estrogen exposure during fetal life. However, the impossibility of removing estrogens from the feto-maternal unit has hindered the testing of estrogen's direct effect on mammary gland organogenesis. To overcome this limitation, we developed an ex vivo culture method of the mammary gland where the direct action of estrogens can be tested during embryonic days (E)14 to 19. Mouse mammary buds dissected at E14 and cultured for 5 days showed that estrogens directly altered fetal mammary gland development. Exposure to 0.1 pM, 10 pM, and 1 nM 17 ß-estradiol (E2) resulted in monotonic inhibition of mammary buds ductal growth. In contrast, Bisphenol-A (BPA) elicited a non-monotonic response. At environmentally relevant doses (1 nM), BPA significantly increased ductal growth, as previously observed in vivo, while 1 µM BPA significantly inhibited ductal growth. Ductal branching followed the same pattern. This effect of BPA was blocked by Fulvestrant, a full estrogen antagonist, while the effect of estradiol was not. This method may be used to study the hormonal regulation of mammary gland development, and to test newly synthesized chemicals that are released into the environment without proper assessment of their hormonal action on critical targets like the mammary gland.

Mix it and fix it: functions of composite olfactory signals in ring-tailed lemurs.

Animals communicating via scent often deposit composite signals that incorporate odorants from multiple sources; however, the function of mixing chemical signals remains understudied. We tested both a 'multiple-messages' and a 'fixative' hypothesis of composite olfactory signalling, which, respectively, posit that mixing scents functions to increase information content or prolong signal longevity. Our subjects-adult, male ring-tailed lemurs (Lemur catta)-have a complex scent-marking repertoire, involving volatile antebrachial (A) secretions, deposited pure or after being mixed with a squalene-rich paste exuded from brachial (B) glands. Using behavioural bioassays, we examined recipient responses to odorants collected from conspecific strangers. We concurrently presented pure A, pure B and mixed A + B secretions, in fresh or decayed conditions. Lemurs preferentially responded to mixed over pure secretions, their interest increasing and shifting over time, from sniffing and countermarking fresh mixtures, to licking and countermarking decayed mixtures. Substituting synthetic squalene (S)-a well-known fixative-for B secretions did not replicate prior results: B secretions, which contain additional chemicals that probably encode salient information, were preferred over pure S. Whereas support for the 'multiple-messages' hypothesis underscores the unique contribution from each of an animal's various secretions, support for the 'fixative' hypothesis highlights the synergistic benefits of composite signals.