RESUMEN
Generalized pustular psoriasis (GPP) is a chronic, rare, and potentially life-threatening inflammatory disease, characterized by the rapid and widespread eruption of small, sterile pustules with surrounding skin erythema. Abnormal signaling of the interleukin-36 (IL-36) pathway appears to have a central role in GPP immunopathology, and provides a rational therapeutic target. Spesolimab is a first-in-class humanized monoclonal antibody that binds specifically to the IL-36 receptor, and antagonizes IL-36 signaling. Spesolimab obtained regulatory approval in the United States (US) in September 2022 for use in the treatment of GPP flares in adults, and was subsequently approved for GPP flare treatment in many other countries across the world. Recently, regulatory approval was granted for subcutaneous dosing of spesolimab for treatment of GPP when not experiencing a flare. Here, we review data from two key clinical trials that supported the initial US regulatory approval; namely, the phase 1 proof-of-concept trial (ClinicalTrials.gov ID, NCT02978690), and Effisayil™ 1 (NCT03782792), which remains the largest and only randomized clinical trial in patients experiencing GPP flares published to date. In the phase 1 proof-of-concept trial, a Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) score of 0 or 1 (clear or almost clear skin) was attained in 5/7 (71%) patients by week 1 and in all 7 patients by week 4; and the mean percent improvement in the Generalized Pustular Psoriasis Area and Severity Index (GPPASI) score from baseline was 59.0% at week 1, 73.2% at week 2, and 79.8% at week 4. In Effisayil™ 1, a GPPGA pustulation subscore of 0 (no visible pustules) was achieved in 19/35 (54%) patients receiving spesolimab at the end of week 1, versus 1/18 (6%) receiving placebo (difference, 49 percentage points; 95% confidence interval [CI], 21 to 67; P<0.001); and a GPPGA total score of 0 or 1 was achieved by 15/35 (43%) patients in the spesolimab group, versus 2/18 (11%) patients in the placebo group (difference, 32 percentage points; 95% CI, 2 to 53; P = 0.02). Infections at week 1 were reported in 6/35 (17%) patients receiving spesolimab and in 1/18 (6%) patients receiving placebo. These data demonstrate the efficacy and safety of spesolimab in providing rapid and sustained clinical improvement for patients with GPP flares, which translates into improved quality of life, by offering a targeted therapy for GPP.
Asunto(s)
Anticuerpos Monoclonales Humanizados , Aprobación de Drogas , Psoriasis , Humanos , Psoriasis/tratamiento farmacológico , Estados Unidos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/efectos adversos , Adulto , Masculino , Femenino , Resultado del Tratamiento , Persona de Mediana Edad , United States Food and Drug Administration , InterleucinasRESUMEN
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  .
Asunto(s)
Carcinoma de Células de Merkel , Trasplante de Riñón , Trasplante de Páncreas , Neoplasias Cutáneas , Humanos , Carcinoma de Células de Merkel/terapia , Carcinoma de Células de Merkel/cirugía , Carcinoma de Células de Merkel/diagnóstico , Carcinoma de Células de Merkel/patología , Resultado Fatal , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Terapia de Inmunosupresión/efectos adversos , Inmunosupresores/efectos adversos , Inmunosupresores/uso terapéutico , Trasplante de Riñón/efectos adversos , Trasplante de Páncreas/efectos adversos , Neoplasias Cutáneas/patologíaAsunto(s)
Carcinoma de Células Escamosas , Infecciones por Papillomavirus , Vacunas contra Papillomavirus , Neoplasias Cutáneas , Humanos , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/prevención & control , Carcinoma de Células Escamosas/patología , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/prevención & control , Neoplasias Cutáneas/patología , Uñas/patología , Infecciones por Papillomavirus/prevención & control , ADN ViralRESUMEN
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.
Asunto(s)
Neoplasias de la Conjuntiva , Infecciones Virales del Ojo , Infecciones por Papillomavirus , Vacunas contra Papillomavirus , Tomografía de Coherencia Óptica , Humanos , Masculino , Anciano , Neoplasias de la Conjuntiva/tratamiento farmacológico , Neoplasias de la Conjuntiva/virología , Neoplasias de la Conjuntiva/terapia , Neoplasias de la Conjuntiva/patología , Infecciones por Papillomavirus/virología , Infecciones por Papillomavirus/prevención & control , Vacunas contra Papillomavirus/administración & dosificación , Infecciones Virales del Ojo/virología , Infecciones Virales del Ojo/tratamiento farmacológico , Infecciones Virales del Ojo/diagnóstico , Infecciones Virales del Ojo/prevención & control , Carcinoma de Células Escamosas/virología , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/terapia , Inyecciones Intramusculares , Fluorouracilo/uso terapéutico , Fluorouracilo/administración & dosificación , Antimetabolitos Antineoplásicos/uso terapéutico , Soluciones OftálmicasAsunto(s)
Carcinoma in Situ , Carcinoma de Células Escamosas , Infecciones por Papillomavirus , Vacunas contra Papillomavirus , Neoplasias del Pene , Masculino , Humanos , Recurrencia Local de Neoplasia/prevención & control , Recurrencia Local de Neoplasia/patología , Carcinoma de Células Escamosas/patología , Pene/patología , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/prevención & control , Infecciones por Papillomavirus/patología , Papillomaviridae , Neoplasias del Pene/patología , Carcinoma in Situ/patologíaRESUMEN
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.
Asunto(s)
Enfermedades del Sistema Nervioso Periférico , Enfermedades de la Piel , Humanos , Parestesia/diagnóstico , Parestesia/etiología , Parestesia/terapia , Piel , Prurito/diagnóstico , Prurito/etiología , Prurito/terapia , Enfermedades del Sistema Nervioso Periférico/complicaciones , Enfermedades de la Piel/complicacionesRESUMEN
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.
Asunto(s)
Carcinoma de Células Escamosas , Queratosis Actínica , Humanos , Imiquimod/uso terapéutico , Fluorouracilo , Tretinoina , Estudios Prospectivos , Queratosis Actínica/tratamiento farmacológico , Queratosis Actínica/prevención & control , Queratosis Actínica/patología , Queratinocitos , Carcinoma de Células Escamosas/prevención & control , Carcinoma de Células Escamosas/tratamiento farmacológico , Quimioprevención , Resultado del TratamientoRESUMEN
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.
Asunto(s)
Carcinoma Basocelular , Carcinoma de Células Escamosas , Infecciones por Papillomavirus , Vacunas contra Papillomavirus , Neoplasias Cutáneas , Carcinoma Basocelular/patología , Carcinoma de Células Escamosas/patología , Femenino , Humanos , Huésped Inmunocomprometido , Queratinocitos , Masculino , Infecciones por Papillomavirus/prevención & control , Vacunas contra Papillomavirus/efectos adversos , Neoplasias Cutáneas/patologíaRESUMEN
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.
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Fibrosis Quística , Aminofenoles/farmacología , Aminofenoles/uso terapéutico , Benzodioxoles/farmacología , Benzodioxoles/uso terapéutico , Fibrosis Quística/tratamiento farmacológico , Fibrosis Quística/genética , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Combinación de Medicamentos , Terapia Genética , Humanos , MutaciónAsunto(s)
Neoplasias de la Conjuntiva , Papiloma , Infecciones por Papillomavirus , Vacunas contra Papillomavirus , Conjuntiva , Neoplasias de la Conjuntiva/diagnóstico , Humanos , Papiloma/diagnóstico , Papiloma/tratamiento farmacológico , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/tratamiento farmacológico , Vacunas contra Papillomavirus/efectos adversosRESUMEN
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.
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Neoplasias Cutáneas , Promoción de la Salud , Humanos , Prevención Primaria , Prevención Secundaria , Piel , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/epidemiología , Neoplasias Cutáneas/prevención & control , Prevención TerciariaRESUMEN
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.
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Asma/terapia , COVID-19/epidemiología , Pandemias , Grupo de Atención al Paciente/organización & administración , Consulta Remota/organización & administración , Adolescente , Corticoesteroides/uso terapéutico , Antibacterianos/uso terapéutico , Asma/tratamiento farmacológico , Niño , Preescolar , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Monitoreo Fisiológico/métodos , SARS-CoV-2 , EspirometríaRESUMEN
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.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Carcinoma Basocelular/terapia , Carcinoma de Células Escamosas/terapia , Crioterapia/métodos , Recurrencia Local de Neoplasia/epidemiología , Neoplasias Cutáneas/terapia , Administración Cutánea , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/economía , Carcinoma Basocelular/economía , Carcinoma Basocelular/epidemiología , Carcinoma de Células Escamosas/economía , Carcinoma de Células Escamosas/epidemiología , Terapia Combinada/economía , Terapia Combinada/métodos , Análisis Costo-Beneficio , Crioterapia/economía , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/economía , Humanos , Imiquimod/administración & dosificación , Imiquimod/economía , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/economía , Recurrencia Local de Neoplasia/prevención & control , Estudios Retrospectivos , Neoplasias Cutáneas/economía , Neoplasias Cutáneas/epidemiología , Resultado del Tratamiento , Tretinoina/administración & dosificación , Tretinoina/economíaRESUMEN
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.