Metastatic Merkel Cell Carcinoma After Simultaneous Pancreas-Kidney Transplantation: Fatal Outcomes.

Merkel cell carcinoma (MCC) is a rare, highly aggressive cutaneous malignancy. Immunosuppression increases the risk of MCC and is associated with poor prognosis. Organ transplant recipients (OTR) have worse overall survival (OS) than patients with immunosuppression due to other causes. Treating MCC after organ transplantation is challenging, as checkpoint inhibitor immunotherapy, the standard of care for treating MCC, increases the risk of transplant rejection. This paper reviews the cases of two simultaneous pancreas-kidney transplant (SPKT) recipients with MCC and explores the role of immunosuppression in the development of MCC. Immunosuppression was discontinued and checkpoint inhibitor therapy was initiated in the first patient and considered by the second patient. In both cases, treatment failed, and the patients died shortly after developing metastatic MCC. These cases illustrate the need for improved multidisciplinary treatment regimens for MCC in OTRs. J Drugs Dermatol. 2024;23(5):376-377.     doi:10.36849/JDD.8234  .

Therapeutic Response to Treatment of a Papillomatous Ocular Surface Squamous Neoplasia With Intramuscular Human Papillomavirus Vaccine.

PURPOSE: The purpose of this study was to describe the response of a papillomatous ocular surface squamous neoplasia (OSSN) to the intramuscular (IM) 9-valent human papillomavirus (HPV) vaccine after failed medical and surgical interventions. METHODS: A 79-year-old White man with a conjunctival lesion underwent a biopsy which revealed OSSN and positivity for high-risk HPV. Initially treated with medical therapy and surgical excisions, the patient developed a recurrence and refused further surgery. He was given 4 doses of IM HPV vaccine at the 6-week interval. RESULTS: A dramatic reduction in lesion size and reduced epithelial thickening and hyperreflectivity was noted on slitlamp examination and high-resolution anterior segment optical coherence tomography after receiving the IM HPV vaccine. Although lesion size was markedly reduced, the therapy did not achieve total resolution, resulting in further treatment with topical 1% 5-fluorouracil (5-FU) eye drops and later 0.04% mitomycin C eye drops. The patient then elected to discontinue further treatment and solely observe. CONCLUSIONS: This case report adds to the growing literature demonstrating the potential therapeutic use of vaccines in cancer treatment. Although HPV vaccination is currently approved for prophylaxis, the use of HPV vaccines as a therapeutic option for various HPV-mediated diseases, including OSSN, should be further explored. The HPV vaccine yielded significant initial improvement in this patient who refused further surgical interventions. The use of IM HPV vaccine as an adjunctive treatment of papillomatous OSSN may represent a potential therapeutic option in cases refractory to standard treatment modalities.

Approach to diagnosis, evaluation, and treatment of generalized and nonlocal dysesthesia: A review.

Dysesthesia is an abnormal sensation in the skin that occurs in the absence of any extraordinary stimulus or other primary cutaneous disorders, excluding any delusions or tactile hallucinations. Clinicians have characterized dysesthesias to include sensations such as burning, tingling, pruritus, allodynia, hyperesthesia, or anesthesia. The etiology and pathogenesis of various generalized dysesthesias is largely unknown, though many dysesthesias have been associated with systemic pathologies including malignancy, infection, autoimmune disorders, and neuropathies. Dermatologists are often the first-line clinicians for patients presenting with such cutaneous findings, thus it is crucial for these physicians to be able to methodically work-up generalized dysesthesias to build a working differential diagnosis, follow up with key labs and/or imaging, and offer patients evidence-based treatment to relieve their symptoms. This broad literature review is an attempt to centralize key studies, cases, and series to help guide dermatologists in their assessment and evaluation of complaints of abnormal cutaneous sensations.

Keratinocyte Carcinoma Chemoprevention With a Combination of Imiquimod, 5-Fluorouracil, and Tretinoin.

BACKGROUND: The incidence of keratinocyte carcinomas (KCs), comprising basal and squamous cell carcinomas, is rising in the United States. Chemoprevention is one modality by which patients can reduce the incidence of KCs. METHODS: We performed a retrospective review of 327 patients who employed a combination of imiquimod 5% cream, 5-fluorouracil 2% solution, and tretinoin 0.1% cream in a field therapy regimen over the face/ears or scalp for chemoprevention. RESULTS: Patients had dramatically lower odds of having KCs in the treatment location (face/ears or scalp) in the one-year period after field treatment than in the one-year period preceding field treatment (OR=0.06, 95% CI: [0.02, 0.15]). Patients were also at lower odds of having KCs in non-treated areas the year after field treatment than in the year preceding it (OR=0.25, 95% CI: [0.14, 0.42]). Additionally, fewer cryotherapy sessions were performed for actinic keratoses in the treatment areas in the year after treatment (mean=1.5, SD=1.21) than the year preceding treatment (mean=2.3, SD=0.99; t=11.68, P<0.001). CONCLUSIONS: A combination of imiquimod 5% cream, 5-fluorouracil 2% solution, and tretinoin 0.1% cream were effective at reducing the incidence of new KCs for at least one year. Individualized treatment application frequency allowed for increased patient adherence. Prospective studies evaluating combination topical treatments for chemoprevention of KCs are needed to further assess the treatment effects found in this study. J Drugs Dermatol. 2023;22(5): doi:10.36849/JDD.7334.

Keratinocyte Carcinomas in Immunocompromised Patients Are Reduced After Administration of the Nonavalent Human Papillomavirus Vaccine.

Immunosuppression, as seen in solid organ transplant recipients, is highly associated with the development of keratinocyte carcinomas (KCs). Reducing the level of immunosuppression lowers the incidence of KCs but at the cost of increased potential morbidity and mortality. Recent studies have revealed a greater prevalence of HPV DNA, especially that of β-HPV, in KCs of immunocompromised patients compared to KCs of immunocompetent individuals. A prior report demonstrated that the HPV vaccine was associated with reducing KC incidence in immunocompetent patients. The nonavalent HPV vaccine was administered to two immunosuppressed individuals with histories of multiple prior KCs. Both patients are male, with Patient 1 being a liver transplant recipient who was on tacrolimus for an extended period and Patient 2 having Crohn’s disease and currently being treated with mercaptopurine. The treatment was well tolerated without adverse events and was associated with dramatic reductions in average incidence of KCs/year in both patients. Patient 1 demonstrated an 88% reduction in new KCs/year (87% squamous cell carcinomas (SCCs); 100% basal cell carcinomas (BCCs) post-injection of the intramuscular vaccine and Patient 2 demonstrated a 63% reduction in incidence of KCs/year (30% SCCs; 100% BCCs). Evidence links the β-HPV genera to the development of SCCs and actinic keratoses. The nonavalent HPV vaccine, containing antigens of the α-HPV genera, may also induce humoral immunity to β-HPV due to shared expression of L1 and L2 capsid proteins. The HPV vaccine may be an effective tool in the prevention of KCs in immunosuppressed patients. J Drugs Dermatol. 2022;21(5):526-528. doi:10.36849/JDD.6536.

An Update on CFTR Modulators as New Therapies for Cystic Fibrosis.

Over the past decade there have been significant developments in the field of Cystic Fibrosis Transmembrane Regulator modulator drugs. Following treatment in patients with cystic fibrosis with common gating mutations using the potentiator drug ivacaftor, successive development of corrector drugs used in combination has led to highly effective modulator therapy being available to more than 85% of the cystic fibrosis population over 12 years of age in the form of elexacaftor/tezacaftor/ivacaftor. In this article, we review the evidence from clinical trials and mounting real-world observational and registry data that demonstrates the impact highly effective modulators have on both pulmonary and extra-pulmonary manifestations of cystic fibrosis. As clinical trials progress to younger patient groups, we discuss the challenges to demonstrating drug efficacy in early life, and also consider practicalities of drug development in an ever-shrinking modulator-naïve population. Drug-drug interactions are an important consideration in people with cystic fibrosis, where polypharmacy is commonplace, but also as the modulated population look to remain healthier for longer, we identify trials that aim to address treatment burden too. Inequity of care, through drug cost or ineligibility for modulators by genotype, is widening without apparent strategies to address this; however, we present evidence of hopeful early-stage drug development for non-modulatable genes and summarise the current state of gene-therapy development.

Skin cancer: Primary, secondary, and tertiary prevention. Part II.

Skin cancer is the most commonly diagnosed cancer worldwide. Understanding the natural history of skin cancer will provide a framework for the creation of prevention and control strategies that aim to reduce skin cancer burden. The strategies include health promotion, primary prevention, secondary prevention, and tertiary prevention. Health promotion and primary prevention were covered in the first part of this 2-part review. The second part covers the secondary and tertiary prevention of skin cancer. In particular, preventive strategies centered on the early detection of skin cancer, the prevention of disease progression, clinical surveillance, and educational and behavioral interventions are highlighted. The summaries of existing recommendations, challenges, opportunities, and future directions are discussed.

COVID-19 and delivery of difficult asthma services.

The COVID-19 pandemic necessitated an urgent reconfiguration of our difficult asthma (DA) service. We rapidly switched to virtual clinics and rolled out home spirometry based on clinical need. From March to August 2020, 110 patients with DA (68% virtually) were seen in clinic, compared with March-August 2019 when 88 patients were seen face-to-face. There was DA clinic cancellation/non-attendance (16% vs 43%; p<0.0003). In patients with home spirometers, acute hospital admissions (6 vs 26; p<0.01) from March to August 2020 were significantly lower compared with the same period in 2019. There was no difference in the number of courses of oral corticosteroids or antibiotics prescribed (47 vs 53; p=0.81). From April to August 2020, 50 patients with DA performed 253 home spirometry measurements, of which 39 demonstrated >20% decrease in forced expiratory volume in 1 s, resulting in new action plans in 87% of these episodes. In our DA cohort, we demonstrate better attendance rates at virtual multidisciplinary team consultations and reduced hospital admission rates when augmented with home spirometry monitoring.

A Non-Surgical and Cost-Effective Treatment Approach Employing Topical Imiquimod, 5-Fluorouracil, and Tretinoin for Primary Non-Melanoma Skin Cancers.

BACKGROUND: Minimally invasive alternative approaches to treat non-melanoma skin cancers remain limited and unproven. OBJECTIVE: We aim to assess the efficacy of varying combinations of anti-tumor agents—imiquimod 5% cream, 5-fluorouracil 2% solution, and tretinoin 0.1% cream—with brief cryotherapy in treating non-melanoma skin cancers. METHODS: This retrospective study included 690 cases of non-melanoma skin cancers in 480 patients who received a diagnosis of a basal cell carcinoma or squamous cell carcinoma during a ten-year period. During treatment period, patients applied 30 applications of one of three combinations (imiquimod/tretinoin, 5-fluorouracil/tretinoin, or imiquimod/5-fluorouracil/tretinoin) and had cryotherapy every 2 weeks. Each patient had a clinical examination at least three years post-treatment or documented treatment failure. Clearance was defined by a lack of persistence or recurrence for 3 years following the completion of treatment. The likelihood of lesion clearance was evaluated using multivariable logistic regression analysis. RESULTS: A total of 186 cases (97; basal cell carcinoma and 89; squamous cell carcinoma) in 133 patients [37% women and 63% men; median (interquartile range) age, 77 (69, 83) years] met the inclusion criteria. Multivariable logistic regression analysis adjusting for clinical and lesion variables demonstrated that, relative to the imiquimod/5-fluorouracil/tretinoin treatment approach, imiquimod/ tretinoin (odds ratio, 0.05; 95% confidence interval, 0.00-0.99) and 5-fluorouracil/tretinoin (0.02; 0.00–0.45) were associated with lower likelihoods of lesion clearance. Likewise, morpheaform basal cell carcinoma had a lower probability of clearance (0.05; 0.00–0.72). CONCLUSIONS: The combination of imiquimod/5-fluorouracil/tretinoin with cryotherapy had high clearance rates and was the most effective treatment regimen. J Drugs Dermatol. 2021;20(3):260-267. doi:10.36849/JDD.5427.

Treating Melanoma in Situ During a Pandemic with Telemedicine and a Combination of Imiquimod, 5-Fluorouracil, and Tretinoin.

The recent coronavirus disease 2019 (COVID-19) pandemic has created a quandary for the physician in terms of evaluating and treating cutaneous skin cancers, particularly melanomas. At the onset of the pandemic, many planned medical and surgical visits for skin cancers were postponed. Physicians and patients have had to balance the risk of exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with that of worsening morbidity and mortality due to delays in skin cancer treatments. We present a male patient who had two melanoma-in-situs (MISs) that were treated during the COVID-19 pandemic with a combination of topical imiquimod 5% cream, 5-fluorouracil 2% solution, and tretinoin 0.1% cream. The successful treatments occurred without in-person visits and with the aid of telemedicine. Although surgery is the standard for the treatment of melanoma in situ, this case demonstrates an effective viable treatment modality for MIS during a pandemic situation.

Combination Topical Chemotherapy for the Treatment of an Invasive Cutaneous Squamous Cell Carcinoma

Introduction: Standard of care for squamous cell carcinoma (SCC) is usually surgical, with either excision or Mohs micrographic surgery. However, surgery may not be ideal for elderly patients with numerous lesions, who are poor surgical candidates or who refuse surgery. Topical 5-fluorouracil (5-FU) and imiquimod have been studied off-label as monotherapies in the treatment of SCC in situ with promising results. However, long-term tumor-free survival rates are still less than with surgical management. Methods: We report a case of biopsy-proven invasive SCC in an 86-year-old Caucasian male with history of multiple actinic keratoses and no previous skin cancers. The patient declined surgical treatment due to concerns about cosmetic outcomes. A combination of topical 5% imiquimod cream, 2% 5-FU solution, and 0.1% tretinoin cream was used five nights per week under occlusion for a treatment goal of 30 total applications. The patient was evaluated in clinic every 2 weeks during which the site was treated with cryotherapy. The patient reported burning pain associated with treatment and only completed 24 of the 30 applications. Results: Follow-up biopsy 15 months after completing topical treatment revealed dermal scar with no evidence of residual carcinoma. Conclusion: Topical combination therapy with imiquimod, 5-FU, and tretinoin with intermittent, brief cryotherapy effectively treated a small, invasive SCC in this select patient who deferred surgery. Prospective randomized-controlled clinical trials to assess the role of combination topical treatment for invasive SCCs are warranted. J Drugs Dermatol. 2020;19(2)202-204. doi:10.36849/JDD.2020.2228