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Background: Phase 3 PRIME/PRIME2 trials independently demonstrated efficacy and an acceptable safety profile of dupilumab adults with moderate-to-severe prurigo nodularis. Objective: To obtain a more precise estimate of onset and magnitude of treatment effect using PRIME/PRIME2 pooled data. Methods: In PRIME/PRIME2, patients were randomized to dupilumab or placebo for 24 weeks. Pooled analysis assessed proportion of patients achieving clinically meaningful improvement in itch, clear/almost-clear skin, or both; at weeks 12 and 24; overall and by demographic subgroups and changes from baseline to week 24 in symptoms, signs, and quality of life. Results: Patients receiving dupilumab (n = 153) vs placebo (n = 158) experienced significant improvements in all tested endpoints. At week 24, 90 (58.8%) dupilumab-treated vs 30 (19.0%) placebo-treated patients achieved clinically meaningful improvement in itch, 71 (46.4%) vs 27 (17.1%) clear/almost clear skin, and 54 (35.3%) vs 14 (8.9%) achieved both (P < .0001 for all). Treatment benefits were independent of baseline demographics. Safety to week 36 was generally consistent with the known dupilumab safety profile. Limitations: On-treatment data limited to 24 weeks. Conclusions: Pooled analysis confirmed improvements reported in individual trials and revealed earlier effect onset in itch and skin pain. Dupilumab treatment showed benefits across demographics.
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Importance: Chronic pruritus, defined as itch experienced for 6 weeks or longer, affects approximately 22% of people in their lifetime. Approximately 1% of physician visits are for the chief concern of chronic pruritus. Chronic pruritus is associated with adverse outcomes, including impaired sleep and reduced quality of life. Observations: Chronic pruritus can be categorized by etiology into inflammatory, neuropathic, or a combination of inflammatory and neuropathic pruritus. Chronic pruritus is due to inflammation in approximately 60% of patients and may be caused by eczema, psoriasis, or seborrheic dermatitis. Chronic pruritus is due to a neuropathic or mixed etiology in approximately 25% of patients. Neuropathic causes of chronic pruritus include postherpetic neuralgia and notalgia paresthetica and are typically due to localized or generalized nerve dysregulation. Approximately 15% of people with chronic pruritus have other causes including systemic diseases with secondary itch, such as uremic pruritus and cholestatic pruritus, medication-induced pruritus such as pruritus due to immunotherapy, and infectious etiologies such as tinea corporis and scabies. When few primary changes are present, a thorough history, review of symptoms, and laboratory evaluation should be performed, particularly for people with chronic pruritus lasting less than 1 year. Clinicians should consider the following tests: complete blood cell count, complete metabolic panel, and thyroid function testing to evaluate for hematologic malignancy, liver disease, kidney disease, or thyroid disease. First-line treatment for inflammatory chronic pruritus includes topical anti-inflammatory therapies such as hydrocortisone (2.5%), triamcinolone (0.1%), or tacrolimus ointment. Approximately 10% of patients do not respond to topical therapies. In these patients, referral to dermatology and systemic oral or injectable treatments such as dupilumab or methotrexate may be considered. When no underlying systemic disease associated with pruritus is identified, patients are likely to have neuropathic chronic pruritus or mixed etiology such as chronic pruritus of unknown origin. In these patients, neuropathic topical treatments such as menthol, pramoxine, or lidocaine can be used either alone or in combination with immunomodulatory agents such as topical steroids. Other effective therapies for neuropathic pruritus include gabapentin, antidepressants such as sertraline or doxepin, or opioid receptor agonist/antagonists such as naltrexone or butorphanol. Conclusions and Relevance: Chronic pruritus can adversely affect quality of life and can be categorized into inflammatory, neuropathic, or a combined etiology. First-line therapies are topical steroids for inflammatory causes, such as hydrocortisone (2.5%) or triamcinolone (0.1%); topical neuropathic agents for neuropathic causes, such as menthol or pramoxine; and combinations of these therapies for mixed etiologies of chronic pruritus.
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Antipruriginosos , Prurito , Humanos , Enfermedad Crónica , Prurito/etiología , Prurito/tratamiento farmacológico , Antipruriginosos/uso terapéuticoRESUMEN
BACKGROUND: Prurigo Nodularis (PN) is a relatively rare chronic inflammatory skin disease characterized by firm pruritic nodules. PN is associated with significantly increased rates of many systemic and non-systemic comorbidities. This results in a higher burden of disease and utilization of specialty care compared to non-PN United States (US) adults. Psychiatric comorbidities associated with PN include depression and anxiety. In this article, we describe the burden of comorbidities. sequelae of disease, inflammatory disease signatures, and the impact of PN in African American and Asian patients. Furthermore, we explore challenges in the recognition and diagnosis of PN and describe methods to increase awareness of PN among dermatologists. J Drugs Dermatol. 2023;22:12(Suppl 2):s12-14.
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Prurigo , Adulto , Humanos , Prurigo/diagnóstico , Prurigo/epidemiología , Piel , Comorbilidad , Progresión de la Enfermedad , Enfermedad CrónicaRESUMEN
Prurigo nodularis (PN) is a chronic inflammatory skin disease with intensely pruritic nodules. The LIBERTY-PN PRIME and PRIME2 phase 3 trials enrolled adults with PN with ≥20 nodules and severe itch uncontrolled with topical therapies. Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin (IL)-4 and IL-13. Patients were randomized 1:1 to 300 mg dupilumab or placebo subcutaneously every 2 weeks for 24 weeks. The primary endpoint was pruritus improvement, measured by proportion of patients with a ≥4-point reduction in Worst Itch Numeric Rating Scale (WI-NRS) from baseline at week 24 (PRIME) or week 12 (PRIME2). Key secondary endpoints included nodule number reduction to ≤5 at week 24. PRIME and PRIME2 enrolled 151 and 160 patients, respectively. Both trials met all the pre-specified primary and key secondary endpoints. A ≥4-point WI-NRS reduction at week 24 in the dupilumab and placebo arms was achieved by 60.0% and 18.4% of patients, respectively, in PRIME (95% confidence interval (CI), 27.8-57.7 for the difference, P < 0.001) and at week 12 by 37.2% and 22.0% of patients, respectively, in PRIME2 (95% CI, 2.3-31.2; P = 0.022). Dupilumab demonstrated clinically meaningful and statistically significant improvements in itch and skin lesions versus placebo in PN. Safety was consistent with the known dupilumab safety profile.ClinicalTrials.gov identifiers: NCT04183335 and NCT04202679 .
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Prurigo , Adulto , Humanos , Prurigo/tratamiento farmacológico , Índice de Severidad de la Enfermedad , Inyecciones Subcutáneas , Resultado del Tratamiento , Prurito/tratamiento farmacológico , Método Doble Ciego , Enfermedad CrónicaAsunto(s)
Dermatología , Servicios Farmacéuticos , Farmacia , Estados Unidos , Humanos , Medicaid , Autorización PreviaRESUMEN
Orofacial granulomatosis is a rare disorder that is heterogeneously defined in the published literature. Herein, we describe a patient with orofacial granulomatosis with clinical and histologic evidence, discuss differential diagnoses, and offer clinical pearls for diagnosing and assessing this disorder. Our case provides support that orofacial granulomatosis is a distinct disorder as opposed to a sequela of other systemic granulomatous diseases. This information will aid dermatologists in decision making and diagnosing the disorder.
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Granulomatosis Orofacial , Humanos , Granulomatosis Orofacial/diagnóstico , Granulomatosis Orofacial/patología , Diagnóstico Diferencial , Progresión de la Enfermedad , Enfermedades RarasRESUMEN
BACKGROUND: Programmed cell death protein (PD-1) and programmed death-ligand 1 (PD-L1) inhibition checkpoint blockade leads to various cutaneous adverse reactions, including bullous pemphigoid and lichen-planus-like reactions. However, lichen planus pemphigoides (LPP), manifesting histopathologic features of both lichen planus and bullous pemphigoid, has more rarely been associated with immunotherapy. METHODS: The clinical and histopathologic findings of three patients were examined, and a review of cases of LPP and bullous lichen planus secondary to PD-1 inhibitor therapy was performed. RESULTS: Three patients (two with advanced non-small-cell lung adenocarcinoma and the third with metastatic breast cancer) presented with both lichenoid eruptions and bullae. Biopsy of the lesions revealed lichenoid tissue reactions in all three patients. Together with the histopathologic findings, direct immunofluorescence (DIF) showing linear C3 and IgG deposition and positive enzyme-linked immunosorbent assay (ELISA) showing BP180 positivity supported a diagnosis of LPP in two patients. The third patient in our series also showed confirmatory ELISA testing supporting LPP. CONCLUSIONS: Lichen planus pemphigoides is a distinct cutaneous toxicity to checkpoint inhibitor therapy illustrates a possible pathogenic mechanism and the importance of dermatopathology recognition to render an accurate diagnosis.
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Carcinoma de Pulmón de Células no Pequeñas , Liquen Plano , Neoplasias Pulmonares , Penfigoide Ampolloso , Proteínas Reguladoras de la Apoptosis/uso terapéutico , Antígeno B7-H1 , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Humanos , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Inmunoglobulina G , Liquen Plano/diagnóstico , Neoplasias Pulmonares/tratamiento farmacológico , Penfigoide Ampolloso/diagnóstico , Receptor de Muerte Celular Programada 1RESUMEN
There is currently no standardized algorithm for the treatment of chronic pruritus (CP), or itch lasting more than 6 weeks, in adults aged ≥ 65 years. The antiepileptic agents gabapentin and pregabalin, however, are gaining popularity in the dermatologic community for their efficacy in treating CP of neuropathic origin. Yet the lack of literature specifically looking at the safety and efficacy of these medications in older adults results in limited guidance for providers in the safe use of gabapentinoids. In this paper we discuss special considerations and recommendations for treating older adults with gabapentin and pregabalin and explore the possibility for these drugs to ameliorate CP of multiple etiologies.
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BACKGROUND: Prurigo nodularis (PN) is a chronic disease characterized by intensely pruritic, raised, nodular lesions. Because there are currently no United States Food and Drug Administration-approved therapies specifically for PN, management is highly variable, and no consensus exists on treatment regimens. OBJECTIVE: To provide practical guidance to help United States dermatologists diagnose and effectively treat patients with PN. METHODS: We participated in a roundtable discussion to develop consensus recommendations on diagnosis and treatment of PN from a United States perspective. RESULTS: The core findings in PN are the presence of firm, nodular lesions; pruritus lasting at least 6 weeks; and a history or signs, or both, of repeated scratching, picking, or rubbing. The diagnostic workup involves a complete review of systems, considering potential systemic diseases, and assessment of disease severity, including disease burden and pruritus intensity. Treatment should be selected based on a patient's clinical presentation, comorbidities, and response to prior treatments and should address both neural and immunologic components of pruritus. LIMITATIONS: Data on PN are from anecdotal or small clinical trials, and all treatments are currently used off-label. CONCLUSION: An effective treatment approach for patients with PN should be based on clinical judgment and tailored to the individual needs of the patient.
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Consenso , Fármacos Dermatológicos/uso terapéutico , Guías de Práctica Clínica como Asunto , Prurigo/diagnóstico , Enfermedad Crónica/tratamiento farmacológico , Dermatología/normas , Diagnóstico Diferencial , Quimioterapia Combinada/métodos , Quimioterapia Combinada/normas , Humanos , Uso Fuera de lo Indicado , Prurigo/tratamiento farmacológico , Prurigo/etiología , Resultado del Tratamiento , Estados UnidosRESUMEN
Cutaneous T-cell lymphoma (CTCL) represents a diagnostic challenge because of its large symptomatic overlap with other common skin conditions such as atopic dermatitis (AD) and psoriasis. Dupilumab has offered promising results in AD treatment; however, concerns exist that its use may exacerbate undiagnosed CTCL. We present a patient with CTCL and concomitant AD who experienced improvement in both CTCL blood involvement and AD following the addition of dupilumab therapy.