RESUMEN
BACKGROUND: Since the beginning of the coronavirus disease 2019 pandemic, the most common skin lesions observed due to infection with the severe acute respiratory syndrome coronavirus 2 are pseudochilblains (or coronavirus disease toes). However, this pathology remains infrequent and difficult to diagnose, as no specific test exists. CASE PRESENTATION: Two Caucasian women, 30 and 22 years old, presented to our General Medicine Unit with perniosis lesions on the feet during the first two waves of the coronavirus disease 2019 pandemic. They did not have respiratory or general symptoms of severe acute respiratory syndrome coronavirus 2 infection, the reverse transcription polymerase chain reaction on nasopharyngeal swabs was negative, and the serology was positive only in the first case. The clinical presentation differed for the two cases, as the second patient suffered from swelling and burning after cold application. The diagnosis was based on clinical presentation, temporality, exclusion of other differential diagnoses, and blood test results (positive serology in the first case and high level of CXCL13 and VEGF in the second), supported by current literature. Lesions resolved spontaneously in the first patient. The second case was hospitalized for pain management and received corticosteroid therapy with resolution of the symptoms. CONCLUSION: These two cases with different clinical presentations illustrate the diagnostic approach to coronavirus disease 2019, a challenging disease with diverse manifestations, including, in some cases, coronavirus disease toes. We present a literature review that illustrates the progression of scientific research. Skin lesions associated with coronavirus disease 2019 infection could be the expression of an important interferon type 1 response and should be considered in the differential diagnosis in a primary care setting.
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COVID-19 , Dedos del Pie , Humanos , COVID-19/complicaciones , COVID-19/diagnóstico , COVID-19/terapia , Femenino , Adulto , SARS-CoV-2 , Eritema Pernio/diagnóstico , Eritema Pernio/tratamiento farmacológico , Adulto Joven , Diagnóstico Diferencial , Pacientes AmbulatoriosRESUMEN
During SARS-CoV-2 pandemic, an outbreak of chilblain-like lesions has been developed, even if the relationship with the virus infection is still debated. We report the good results obtained in 12 patients with chilblain lesions and the use of oral cinnarizine, a piperazine derivative with many pharmacological properties among whom antihistaminic and calcium channel blocking activities.
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Tratamiento Farmacológico de COVID-19 , Eritema Pernio , Cinarizina , Eritema Pernio/diagnóstico , Eritema Pernio/tratamiento farmacológico , Eritema Pernio/epidemiología , Humanos , Pandemias , SARS-CoV-2Asunto(s)
Eritema Pernio , Lupus Eritematoso Cutáneo , Lupus Eritematoso Sistémico , Eritema Pernio/diagnóstico , Eritema Pernio/tratamiento farmacológico , Humanos , Lupus Eritematoso Cutáneo/diagnóstico , Lupus Eritematoso Cutáneo/tratamiento farmacológico , Piperidinas , Pirimidinas/uso terapéuticoRESUMEN
Idiopathic chilblains is a cold-induced inflammatory condition that causes significant morbidity. When preventative measures alone are inadequate, oral nifedipine is generally recommended as first-line pharmacologic therapy. Given the natural course of this spontaneously remitting/relapsing condition, controls are needed to critically appraise studies and determine the value of treatments. We report a systematic review of placebo-controlled or comparative therapeutic trials for the treatment of idiopathic chilblains. Our search of PubMed, Embase, and Cochrane databases, identified 11 studies that met our inclusion criteria for a combined study population n = 576. Therapies included nifedipine, pentoxifylline, tadalafil, topical glyceryl trinitrate (GTN), topical minoxidil, diltiazem, corticosteroids, and vitamin D. There was moderate evidence to support the use of nifedipine and pentoxifylline in the treatment of severe or refractory cases of idiopathic chilblains, while other therapies had inadequate evidence or nonsignificant results compared to placebo.
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Eritema Pernio/tratamiento farmacológico , Humanos , Nifedipino/uso terapéutico , Pentoxifilina/uso terapéutico , Vasodilatadores/uso terapéuticoAsunto(s)
Eritema Pernio , Clobetasol/administración & dosificación , Frío/efectos adversos , Lupus Eritematoso Cutáneo , Lupus Eritematoso Discoide/complicaciones , Lupus Eritematoso Sistémico/complicaciones , Piel/patología , Administración Tópica , Adulto , Biopsia/métodos , Eritema Pernio/diagnóstico , Eritema Pernio/tratamiento farmacológico , Eritema Pernio/etiología , Eritema Pernio/prevención & control , Femenino , Glucocorticoides/administración & dosificación , Humanos , Lupus Eritematoso Cutáneo/diagnóstico , Lupus Eritematoso Cutáneo/tratamiento farmacológico , Lupus Eritematoso Cutáneo/etiología , Lupus Eritematoso Cutáneo/prevención & control , Lupus Eritematoso Discoide/diagnóstico , Lupus Eritematoso Discoide/inmunología , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/inmunología , Resultado del TratamientoRESUMEN
AIM: In addition to its respiratory impact of SARS-CoV2, skin lesions of probable vascular origin have been described. This study intends to quantify the incidence of acro-ischemic lesions in COVID-19 infected adult subjects in our population, describing clinical patterns and associated findings. METHODS: All adult confirmed cases of COVID-19 infection who presented with acro-ischemic lesions and received care in our institution were prospectively enrolled up to May 15th, 2020. The variables included demographics, comorbidities, analytical parameters, clinical presentations and COVID-19 treatment. RESULTS: We enrolled 24 patients. The overall rate of acro-ischemic findings in COVID-19 patients was 1.2% [0.6% for outpatients and 2.9% for hospitalized (ICU and non-ICU patients)], but the observed incidence for acro-ischemia in ICU patients was remarkably higher (23.0%, p<0.001). We have described four different clinical patterns of acroischemia: atypical Raynaud´s phenomenon (ARP), (4); pseudo-pernio (PP), (5); severe microcirculatory ischemia with preserved pulse (SMI), (6); and dry gangrene with arteriosclerosis obliterans (AO), (9). Kendall´s τ correlation with lung disease severity was 0.877 (95% CI, 0.756 to 0.968); p<0.01). ARP individuals were predominantly female, while SMI appeared lately in elderly hospitalized subjects with better prognosis. AO occurred in patients with more comorbidity and younger than those with SMI. We observed other associated lesions of suggestive ischemic nature in other organs in all groups (15 patients of total sample). Plasma procalcitonin was significantly higher in patients who developed SMI (median and interquartile range: 9.99 (4.2, 12.3) mg/mL vs 0.26 (0.11, 0.89) mg/mL; p<0.001), and D-dimer level at hospital admission was significantly higher in AO patients (median and interquartile range: 1166 (1050, 2111) mg/L vs 502 (448, 777) mg/L; p<0.001). CONCLUSION: The observed risk for acroischemia in COVID-19 is high in ICU patients (23%). We have described four different clinical patterns of acroischemia (ARP, PP, SMI and AO) associated with lung disease severity. Authors have communicated various lesions of suggestive ischemic nature in other organs. Raynaud-like pattern is reported as a "novelty".
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COVID-19/epidemiología , Eritema Pernio/epidemiología , Isquemia/epidemiología , Enfermedad de Raynaud/epidemiología , Piel/irrigación sanguínea , Adulto , Anciano , Anciano de 80 o más Años , COVID-19/diagnóstico , Eritema Pernio/diagnóstico , Eritema Pernio/tratamiento farmacológico , Comorbilidad , Femenino , Gangrena , Humanos , Incidencia , Isquemia/diagnóstico , Isquemia/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Enfermedad de Raynaud/diagnóstico , Enfermedad de Raynaud/tratamiento farmacológico , Factores de Riesgo , Piel/patología , España/epidemiología , Tratamiento Farmacológico de COVID-19Asunto(s)
Anticoagulantes/administración & dosificación , Eritema Pernio/tratamiento farmacológico , Infecciones por Coronavirus/complicaciones , Nitroglicerina/administración & dosificación , Neumonía Viral/complicaciones , Administración Cutánea , Betacoronavirus/patogenicidad , COVID-19 , Eritema Pernio/etiología , Infecciones por Coronavirus/virología , Quimioterapia Combinada/métodos , Enoxaparina/administración & dosificación , Dedos , Humanos , Masculino , Persona de Mediana Edad , Pomadas , Pandemias , Neumonía Viral/virología , SARS-CoV-2 , Piel/efectos de los fármacos , Resultado del TratamientoAsunto(s)
Betacoronavirus , Eritema Pernio/tratamiento farmacológico , Infecciones por Coronavirus/complicaciones , Eritema/complicaciones , Heparina/administración & dosificación , Furoato de Mometasona/administración & dosificación , Neumonía Viral/complicaciones , Administración Tópica , Adolescente , Antiinflamatorios/administración & dosificación , Anticoagulantes/administración & dosificación , COVID-19 , Eritema Pernio/diagnóstico , Eritema Pernio/etiología , Infecciones por Coronavirus/epidemiología , Quimioterapia Combinada , Eritema/diagnóstico , Eritema/tratamiento farmacológico , Femenino , Geles , Humanos , Pomadas/administración & dosificación , Pandemias , Neumonía Viral/epidemiología , SARS-CoV-2RESUMEN
Sarcoidosis is a systemic granulomatous disease of unknown cause. Skin involvement may be specific lesions in which granulomas are detected on biopsy or nonspecific lesions without granulomatous inflammation on biopsy. Lupus pernio (LP) occurs in the form of smooth, bright nodules and plaques on the nose, ear, lips, and cheeks. Although presence of skin involvement is frequent, lupus perio is reported as a rare form of extrapulmonary sarcoidosis. A 57-year-old female patient applied to the dermatology outpatient clinic with a lesion on the nose. We report a case of chronic sarcoidosis presenting with lupus pernio with clinical and radiological improvement.
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Eritema Pernio , Hidroxicloroquina/administración & dosificación , Pulmón/diagnóstico por imagen , Metilprednisolona/administración & dosificación , Sarcoidosis Pulmonar , Piel/patología , Antirreumáticos/administración & dosificación , Biopsia/métodos , Eritema Pernio/tratamiento farmacológico , Eritema Pernio/etiología , Eritema Pernio/patología , Diagnóstico Diferencial , Femenino , Humanos , Inflamación , Persona de Mediana Edad , Pruebas de Función Respiratoria/métodos , Sarcoidosis Pulmonar/diagnóstico , Sarcoidosis Pulmonar/tratamiento farmacológico , Sarcoidosis Pulmonar/fisiopatología , Tomografía Computarizada por Rayos X/métodos , Resultado del TratamientoAsunto(s)
Eritema Pernio/tratamiento farmacológico , Eritema/inducido químicamente , Hidroxicloroquina/efectos adversos , Lupus Eritematoso Cutáneo/tratamiento farmacológico , Eosinofilia Pulmonar/inducido químicamente , Administración Cutánea , Administración Oral , Anciano , Betametasona/administración & dosificación , Quimioterapia Combinada/efectos adversos , Quimioterapia Combinada/métodos , Eosinófilos , Eritema/sangre , Eritema/diagnóstico , Eritema/tratamiento farmacológico , Femenino , Humanos , Hidroxicloroquina/administración & dosificación , Recuento de Leucocitos , Pulmón/diagnóstico por imagen , Prednisolona/uso terapéutico , Eosinofilia Pulmonar/sangre , Eosinofilia Pulmonar/diagnóstico , Eosinofilia Pulmonar/tratamiento farmacológico , Piel/efectos de los fármacos , Piel/patología , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
Janus kinase (JAK)/signal transducers and activators of transcription (STATs) are a group of molecules associated with one of the major pathways through which many cytokines exert and integrate their function, and as such they are increasingly recognized as playing critical role in the pathogenesis subserving various immune-mediated diseases, including RA, PsA, SpAs, IBD, skin disorders (e.g. alopecia areata, atopic dermatitis), single-gene disorders like interferonopathies, and others. JAKs are the key initiating players of the JAK/STAT pathway. Upon binding of their respective effector molecules (cytokines, IFNs, growth factors and others) to type I and type II receptors, JAKs are activated, and through phosphorylation of themselves and of other molecules (including STATs), they mediate signal transduction to the nucleus. A class of drugs-called JAK inhibitors or JAKinibs-that block one or more JAKs has been developed in the last decade, and now numbers >20 members. Although, so far, JAK inhibitors have been marketed only for RA and PsA, these drugs have been tested in phase 2 and phase 3 clinical trials for other inflammatory conditions and beyond. In this review, we summarize the clinical data, including efficacy and safety, available for JAK inhibitors used in some immune-mediated conditions other than RA.
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Artritis Psoriásica/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Inhibidores de las Cinasas Janus/uso terapéutico , Espondiloartropatías/tratamiento farmacológico , Alopecia Areata/tratamiento farmacológico , Enfermedades de la Aorta/tratamiento farmacológico , Artritis Reumatoide/tratamiento farmacológico , Enfermedades Autoinmunes/tratamiento farmacológico , Enfermedades Autoinmunes del Sistema Nervioso/tratamiento farmacológico , Eritema Pernio/tratamiento farmacológico , Citocinas , Hipoplasia del Esmalte Dental/tratamiento farmacológico , Dermatitis Atópica/tratamiento farmacológico , Arteritis de Células Gigantes/tratamiento farmacológico , Humanos , Síndromes de Inmunodeficiencia , Lupus Eritematoso Cutáneo/tratamiento farmacológico , Metacarpo/anomalías , Enfermedades Musculares/tratamiento farmacológico , Malformaciones del Sistema Nervioso/tratamiento farmacológico , Odontodisplasia/tratamiento farmacológico , Osteoporosis/tratamiento farmacológico , Psoriasis/tratamiento farmacológico , Uveítis/tratamiento farmacológico , Calcificación Vascular/tratamiento farmacológicoRESUMEN
Importance: Familial chilblain lupus is a monogenic autosomal dominant form of cutaneous lupus erythematosus that in most cases is caused by mutations in the 3 prime repair exonuclease 1 (TREX1). Familial chilblain lupus presents in early childhood with cold-induced painful erythematous infiltrates leading to mutilation and is associated with systemic involvement illustrated by an elevated type I interferon (IFN) signature in the skin and blood. Effective treatment is currently not available. Objectives: To evaluate the clinical response to the Janus kinase inhibitor baricitinib in familial chilblain lupus and assess the effect of cold on patient fibroblasts. Design, Setting, and Participants: In this case series, 3 patients with familial chilblain lupus due to TREX1 mutation underwent treatment with baricitinib for 3 months. Interventions: Doses of baricitinib, 4 mg, were administered daily for 3 months. Main Outcomes and Measures: Reduction of cutaneous lupus lesions was measured by the revised cutaneous lupus area and severity index, pain due to skin and joint involvement was assessed by visual analog scale, type I IFN signature in blood was determined by polymerase chain reaction, and the in vitro response of fibroblasts to cold exposure was analyzed. Results: All 3 patients (2 women and 1 man; mean [SD] age, 51 [24] years) showed a significant improvement of cutaneous lupus lesions with suppression of systemic type I IFN activation. One patient had a complete remission regarding pain and, in 2 patients, pain associated with joint inflammation was partially reduced. No severe adverse reactions were reported. Exposure of patient fibroblasts to cold induced a stress response and enhanced senescence along with induction of IFN-stimulated gene in vitro. Conclusions and Relevance: These findings demonstrate the therapeutic efficacy of Janus kinase inhibition in a monogenic form of lupus among 3 patients and provide mechanistic insight into the process of disease exacerbation by cold in TREX1-deficient cells. This finding may be relevant to other type I IFN-mediated disorders and implicates Janus kinase inhibition as a potential therapeutic option also for multifactorial cutaneous lupus erythematosus.
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Azetidinas/uso terapéutico , Eritema Pernio/tratamiento farmacológico , Eritema Pernio/genética , Exodesoxirribonucleasas/genética , Inhibidores de las Cinasas Janus/uso terapéutico , Lupus Eritematoso Cutáneo/tratamiento farmacológico , Lupus Eritematoso Cutáneo/genética , Fosfoproteínas/genética , Sulfonamidas/uso terapéutico , Adulto , Eritema Pernio/diagnóstico , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Humanos , Lupus Eritematoso Cutáneo/diagnóstico , Masculino , Mutación , Linaje , Pronóstico , Purinas , Pirazoles , Medición de Riesgo , Muestreo , Resultado del TratamientoAsunto(s)
Enfermedades Autoinmunes del Sistema Nervioso/inmunología , Azetidinas/uso terapéutico , Eritema Pernio/tratamiento farmacológico , Interferón Tipo I/inmunología , Inhibidores de las Cinasas Janus/uso terapéutico , Malformaciones del Sistema Nervioso/inmunología , Sulfonamidas/uso terapéutico , Antígenos/genética , Antígenos/inmunología , Antígenos de Superficie/genética , Antígenos de Superficie/inmunología , Enfermedades Autoinmunes del Sistema Nervioso/complicaciones , Enfermedades Autoinmunes del Sistema Nervioso/genética , Eritema Pernio/etiología , Proteínas del Citoesqueleto/genética , Proteínas del Citoesqueleto/inmunología , Femenino , Proteínas Ligadas a GPI/genética , Proteínas Ligadas a GPI/inmunología , Humanos , Péptidos y Proteínas de Señalización Intracelular/genética , Péptidos y Proteínas de Señalización Intracelular/inmunología , Monocitos/inmunología , Mutación , Proteínas de Resistencia a Mixovirus/genética , Proteínas de Resistencia a Mixovirus/inmunología , Malformaciones del Sistema Nervioso/complicaciones , Malformaciones del Sistema Nervioso/genética , Purinas , Pirazoles , Proteína 1 que Contiene Dominios SAM y HD/genética , Factor de Transcripción STAT1/metabolismo , Linfocitos T/inmunología , Linfocitos T/metabolismo , Proteínas Supresoras de Tumor/genética , Proteínas Supresoras de Tumor/inmunología , Adulto JovenAsunto(s)
Eritema Pernio/tratamiento farmacológico , Exodesoxirribonucleasas/deficiencia , Inhibidores de las Cinasas Janus/uso terapéutico , Lupus Eritematoso Cutáneo/tratamiento farmacológico , Fosfoproteínas/deficiencia , Eritema Pernio/genética , Preescolar , Femenino , Humanos , Lactante , Janus Quinasa 1/antagonistas & inhibidores , Janus Quinasa 2/antagonistas & inhibidores , Lupus Eritematoso Cutáneo/genética , Resultado del TratamientoAsunto(s)
Eritema Pernio/complicaciones , Eritema Pernio/diagnóstico , Clobetasol/uso terapéutico , Leucemia Mielomonocítica Crónica/complicaciones , Administración Cutánea , Anciano de 80 o más Años , Biopsia con Aguja , Eritema Pernio/tratamiento farmacológico , Técnica del Anticuerpo Fluorescente Directa , Estudios de Seguimiento , Humanos , Inmunohistoquímica , Leucemia Mielomonocítica Crónica/diagnóstico , Leucemia Mielomonocítica Crónica/tratamiento farmacológico , Masculino , Medición de Riesgo , Resultado del TratamientoRESUMEN
BACKGROUND: GPs prescribe topical corticosteroids to patients with chronic chilblains despite poor evidence for their effectiveness. The authors of the current study therefore decided to assess the effectiveness of topical steroids in a primary care setting. AIM: To assess the effectiveness of topical application of betamethasone valerate 0.1% cream in patients with chronic chilblains. DESIGN AND SETTING: A placebo-controlled, double-blind, crossover, randomised clinical trial in a Dutch primary care setting. METHOD: The study population consisted of 34 participants suffering from chronic chilblains. Intervention was topical application of betamethasone valerate 0.1% cream twice a day for 6 weeks compared with placebo. Primary outcome was the visual analogue scale on complaints (VOC). Secondary outcome was the visual analogue scale on disability (VOD). Both were assessed with a diary of daily scores on a 100 mm visual analogue scale. The authors took ambient temperatures into account, checked for a carry-over effect, performed additional analysis, and monitored adverse effects. RESULTS: On the primary outcome mean VOC, there was a difference of 0.56 mm (95% confidence interval [CI] = -2.88 to 3.99 mm) in favour of placebo (P = 0.744). On the secondary outcome mean VOD, there was a difference of 0.88 mm (95% CI = -2.22 to 3.98 mm) in favour of placebo (P = 0.567). This study found no carry-over effect and no adverse effects. CONCLUSION: In this study, topical betamethasone was not superior to placebo in the treatment of chronic chilblains. Topical betamethasone should not be used for chronic chilblains without new evidence.
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Betametasona/administración & dosificación , Betametasona/uso terapéutico , Eritema Pernio/tratamiento farmacológico , Fármacos Dermatológicos/administración & dosificación , Fármacos Dermatológicos/uso terapéutico , Atención Primaria de Salud , Administración Tópica , Eritema Pernio/patología , Estudios Cruzados , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Países Bajos , Calidad de Vida , Resultado del TratamientoRESUMEN
OBJECTIVES: Familial chilblain lupus is a monogenic form of cutaneous lupus erythematosus caused by loss-of-function mutations in the nucleases TREX1 or SAMHD1. In a family without TREX1 or SAMHD1 mutation, we sought to determine the causative gene and the underlying disease pathology. METHODS: Exome sequencing was used for disease gene identification. Structural analysis was performed by homology modelling and docking simulations. Type I interferon (IFN) activation was assessed in cells transfected with STING cDNA using an IFN-ß reporter and Western blotting. IFN signatures in patient blood in response to tofacitinib treatment were measured by RT-PCR of IFN-stimulated genes. RESULTS: In a multigenerational family with five members affected with chilblain lupus, we identified a heterozygous mutation of STING, a signalling molecule in the cytosolic DNA sensing pathway. Structural and functional analyses indicate that mutant STING enhances homodimerisation in the absence of its ligand cGAMP resulting in constitutive type I IFN activation. Treatment of two affected family members with the Janus kinase (JAK) inhibitor tofacitinib led to a marked suppression of the IFN signature. CONCLUSIONS: A heterozygous gain-of-function mutation in STING can cause familial chilblain lupus. These findings expand the genetic spectrum of type I IFN-dependent disorders and suggest that JAK inhibition may be of therapeutic value.
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Eritema Pernio/genética , Lupus Eritematoso Cutáneo/genética , Proteínas de la Membrana/genética , Adulto , Western Blotting , Eritema Pernio/tratamiento farmacológico , Eritema Pernio/inmunología , Eritema Pernio/patología , Familia , Femenino , Grecia , Humanos , Interferón Tipo I/inmunología , Interferón beta/inmunología , Lupus Eritematoso Cutáneo/tratamiento farmacológico , Lupus Eritematoso Cutáneo/inmunología , Lupus Eritematoso Cutáneo/patología , Masculino , Angioscopía Microscópica , Simulación del Acoplamiento Molecular , Mutación , Linaje , Piperidinas/uso terapéutico , Inhibidores de Proteínas Quinasas/uso terapéutico , Pirimidinas/uso terapéutico , Pirroles/uso terapéutico , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Piel/patologíaRESUMEN
Pernio (chilblains) is an inflammatory condition classically characterized by localized erythema and swelling of acral sites upon exposure to cool and damp conditions. It is reported a case of a 59-year-old otherwise healthy woman with acute primary perniosis. She had a 3-day history of lesions on the toes brought on by cold, damp weather. On initial presentation, a biopsy sample was taken of a hallux lesion, and the patient was given a trial course of oral pentoxifylline, topical corticoid and nifedipine therapy. Follow-up at 2 weeks showed complete relief of symptoms and the biopsy results confirmed the diagnosis. Pentoxifylline therapy has been shown to be effective and should be considered the standard of care in the treatment of perniosis along with conservative environmental measures.The etiology and pathogenesis of perniosis are reviewed and discussed, as well as differential diagnoses and treatment options. (AU)