Asunto(s)
Melanocitos/efectos de los fármacos , Enfermedades Profesionales/inmunología , Fenoles/toxicidad , Linfocitos T/inmunología , Vitíligo/inmunología , Apoptosis/efectos de los fármacos , Apoptosis/inmunología , Células Cultivadas , Humanos , Masculino , Melaninas/biosíntesis , Melanocitos/inmunología , Melanocitos/metabolismo , Persona de Mediana Edad , Enfermedades Profesionales/inducido químicamente , Exposición Profesional/efectos adversos , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/inmunología , Cultivo Primario de Células , Piel/citología , Piel/inmunología , Piel/patología , Pigmentación de la Piel/efectos de los fármacos , Pigmentación de la Piel/inmunología , Vitíligo/inducido químicamente , Vitíligo/patologíaRESUMEN
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are both part of a spectrum of serious mucocutaneous disorders, most often caused by drugs, with a high morbidity and mortality. In the acute stage, serious skin and mucocutaneous lesions with painful blistering, erosions and systemic involvement present the main focus of attention. The severity of skin manifestations in the acute stage, however, does not necessarily correlate with that of the mucosal lesions. Most feared are long-term sequelae, especially chronic eye involvement, which can be highly disabling. Here, we illustrate the importance of daily evaluation, early recognition and treatment of eye involvement in the acute stage of SJS/TEN, even when skin manifestations and/or initial eye involvement are relatively mild. Timely performed amniotic membrane transplantation in the acute stage can limit irreversible damage, caused by chronic inflammation, and therefore prevent cicatrisation at a later stage.
Asunto(s)
Oftalmopatías/etiología , Oftalmopatías/terapia , Síndrome de Stevens-Johnson/complicaciones , Humanos , MasculinoRESUMEN
Acute generalised exanthematous pustulosis (AGEP) is a rare but serious cutaneous adverse drug reaction, often related to antibiotics such as beta-lactams or macrolides. However, it is rarely associated with clindamycin which belongs to the lincosamide antibiotics. The Netherlands Pharmacovigilance Centre Lareb received five reports of AGEP associated with the use of clindamycin. We present these five cases and provide support for this association from the Lareb database, the database of the WHO Collaborating Centre for International Drug Monitoring (Vigibase™), the database of the European Medicine Agency (Eudravigilance), and from a mini review of the literature.
Asunto(s)
Pustulosis Exantematosa Generalizada Aguda/etiología , Antibacterianos/efectos adversos , Clindamicina/efectos adversos , Absceso/tratamiento farmacológico , Adulto , Anciano , Erupciones por Medicamentos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Paroniquia/tratamiento farmacológico , Sepsis/tratamiento farmacológico , Sinusitis/tratamiento farmacológico , Tonsilitis/tratamiento farmacológicoRESUMEN
BACKGROUND: Cutaneous adverse drug reactions frequently present as a benign maculopapular exanthema (MPE) with a rapid healing. Sometimes systemic signs are present, which could represent a more severe or systemic MPE (sMPE) or even be the initial phase of a drug reaction with eosinophilia and systemic symptoms (DRESS). Histopathology associated with MPE, sMPE and DRESS has not been well characterized. OBJECTIVES: To study the cutaneous histopathological changes associated with MPE, sMPE and DRESS. METHODS: A retrospective clinicopathological analysis of 13 cases of MPE, 13 of sMPE and 45 of DRESS, collected in one centre from 2005 to 2013. RESULTS: The number of histopathological changes per section increased gradually from MPE to sMPE and DRESS. Prevalence of spongiosis, dermal lymphocytes, eosinophils and neutrophils did not differ between MPE, sMPE and DRESS. Keratinocyte damage, rare in MPE, was regularly found in sMPE and frequent in DRESS. The density of the inflammatory infiltrate increased progressively from MPE to sMPE and DRESS. Atypical lymphocytes were absent in MPE, present in sMPE and more frequent in DRESS. Deep dermal involvement and leukocytoclastic vasculitis were only observed in DRESS. LIMITATIONS: This was a retrospective study. CONCLUSIONS: Numerous histopathological changes per section in drug-induced exanthema should alert for a more severe form of cutaneous adverse drug reactions, i.e. DRESS.
Asunto(s)
Síndrome de Hipersensibilidad a Medicamentos/patología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Exantema/patología , Anciano , Anciano de 80 o más Años , Síndrome de Hipersensibilidad a Medicamentos/etiología , Exantema/inducido químicamente , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
BACKGROUND: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare and severe adverse drug reaction. Large detailed studies of histopathological features of DRESS are sparse and suggest an association between keratinocyte damage and the severity of visceral involvement. OBJECTIVES: To describe the dermatopathological features in a large series of DRESS and their possible association with clinical features and the severity of the disease. METHODS: A retrospective analysis of the clinicobiological and dermatopathological features in a monocentric cohort of patients with DRESS. RESULTS: From January 2005 to January 2013, 45 patients were validated as probable or definite cases of DRESS. The median age was 64 years (range 3-87). The most frequent clinical and biological features included: fever ≥38.5°C (95%), facial oedema (72%), enlarged lymph nodes (51%), visceral involvement (75%), blood eosinophilia (97%) and atypical lymphocytes (82%). Severe DRESS occurred in 24% and a fatal outcome in 6% of patients. Histopathological analysis showed that no specific histopathological pattern was characteristic for DRESS. However, several changes in different cutaneous compartments were observed in 2 of 3 of cases. Spongiosis (55%) and keratinocyte damage (53%) were the most common epidermal changes. Spongiosis was associated with non-severe DRESS (P = 0.041) whereas confluent keratinocyte necrosis correlated with severe DRESS (P = 0.011). Vascular changes were frequent (88%). A moderate dermal perivascular lymphocytic infiltrate was invariably present, containing eosinophils, neutrophils and/or atypical lymphocytes in 57% of cases. CONCLUSIONS: Epidermal changes are indicative for the severity of DRESS.
Asunto(s)
Síndrome de Hipersensibilidad a Medicamentos/patología , Edema/etiología , Epidermis/patología , Cara , Queratinocitos/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Síndrome de Hipersensibilidad a Medicamentos/complicaciones , Femenino , Fiebre/etiología , Humanos , Enfermedades Linfáticas/etiología , Linfocitos/patología , Masculino , Persona de Mediana Edad , Necrosis , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
Acute generalized exanthematous pustulosis (AGEP) and Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) are rare but severe cutaneous adverse drug reactions. Especially in TEN, large areas of the skin and mucosae may become detached. Although AGEP and SJS/TEN are distinct entities with a different clinical picture, pathogenesis, prognosis and treatment, they may share some features, raising the hypothesis of overlap between both entities. We present a severe case of AGEP, caused by flucloxacillin, clinically presenting with TEN-like features and pronounced systemic symptoms with haemodynamic and respiratory instability. Furthermore, we present a review of the literature on cases of AGEP with features resembling SJS/TEN or a supposed overlap with SJS/TEN.
Asunto(s)
Pustulosis Exantematosa Generalizada Aguda/etiología , Antibacterianos/efectos adversos , Floxacilina/efectos adversos , Síndrome de Stevens-Johnson/etiología , Pustulosis Exantematosa Generalizada Aguda/patología , Adulto , Erisipela/tratamiento farmacológico , Femenino , Humanos , Síndrome de Stevens-Johnson/patologíaRESUMEN
Patients who use immunosuppressive agents, in particular medication that blocks tumour necrosis factor-a, are at risk for mycobacterial infections. Besides the typical Mycobacterium tuberculosis infection, a lso a typical mycobacterial disease may occur. Here we demonstrate two patients with such atypical mycobacterial infection due to swimming and fishing water contact. We propose that patients, before starting with immunosuppressive therapy, are counselled about risk factors for mycobacterial disease.
Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Pasatiempos , Inmunosupresores/uso terapéutico , Infecciones por Mycobacterium no Tuberculosas/microbiología , Mycobacterium marinum , Enfermedades Cutáneas Bacterianas/microbiología , Adalimumab , Anciano , Animales , Antibacterianos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Peces , Humanos , Masculino , Persona de Mediana Edad , Infecciones por Mycobacterium no Tuberculosas/tratamiento farmacológico , Natación , Tuberculosis Cutánea , Factor de Necrosis Tumoral alfa/antagonistas & inhibidoresRESUMEN
BACKGROUND: Cases of severe drug hypersensitivity, demonstrating a variable spectrum of cutaneous and systemic involvement, are reported under various names, especially drug reaction with eosinophilia and systemic symptoms (DRESS). Case definition and overlap with other severe cutaneous adverse reactions (SCAR) are debated. OBJECTIVES: To analyse the spectrum of signs and symptoms of DRESS and distribution of causative drugs in a large multicentre series. PATIENTS AND METHODS: RegiSCAR, a multinational registry of SCAR, prospectively enrolled 201 potential cases from 2003 to mid-2009. Using a standardized scoring system, 117 cases were validated as showing probable or definite DRESS. RESULTS: The male/female ratio was 0.80; females were borderline significantly younger than males. Next to the ubiquitous exanthema, the main features were eosinophilia (95%), visceral involvement (91%), high fever (90%), atypical lymphocytes (67%), mild mucosal involvement (56%) and lymphadenopathy (54%). The reaction was protracted in all but two patients; two patients died during the acute phase. Drug causality was plausible in 88% of cases. Antiepileptic drugs were involved in 35%, allopurinol in 18%, antimicrobial sulfonamides and dapsone in 12% and other antibiotics in 11%. The median time interval after drug intake was 22 days (interquartile range 17-31) for all drugs with (very) probable causality, with differences between drugs. CONCLUSION: This prospective observational study supports the hypothesis that DRESS is an original phenotype among SCAR in terms of clinical and biological characteristics, causative drugs, and time relation. The diversity of causative drugs was rather limited, and mortality was lower than that suggested by prior publications.
Asunto(s)
Síndrome de Hipersensibilidad a Medicamentos/diagnóstico , Adulto , Anciano , Erupciones por Medicamentos/diagnóstico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Sistema de RegistrosRESUMEN
BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe cutaneous adverse reactions with high morbidity and mortality. Some expressions of lupus erythematosus (LE) may cause enormous difficulties in differentiating them from SJS and TEN by showing large areas of sheet-like epidermal necrosis. OBJECTIVE: To evaluate clinically and histopathologically probable or definite cases of SJS/TEN with a history of systemic or other LE [(S)LE]. METHODS: This was a retrospective analysis of validated cases of SJS/TEN with a history of (S)LE, based on a large population-based national registry. RESULTS: Among 1366 patients with SJS/TEN, 17 with a sufficiently documented history of (S)LE and representative histological material could be identified, suggesting a considerable over-representation of LE in patients with SJS/TEN. Eight of these showed clinically and/or histopathologically some LE-characteristic features interfering with the diagnosis of SJS/TEN. Differentiation could be elaborated on clinical and histopathological grounds: four patients were classified as SJS/TEN with a preceding (S)LE exacerbation and/or LE-typical histopathological features, and four as 'TEN-like' (S)LE. CONCLUSION: Most patients with SJS/TEN and a history of (S)LE demonstrate clinical and histopathological properties allowing clear differentiation. However, occasionally acute cutaneous manifestations of (S)LE and SJS/TEN can be phenotypically similar, caused by extensive epidermal necrosis. Although no feature by itself is conclusive, a combination of recent (S)LE exacerbation, evident photodistribution, annular lesions and absent or only mild focal erosive mucosal involvement may favour LE over SJS/TEN clinically. Histopathologically, in particular, junctional vacuolar alteration, and the presence of solitary necrotic keratinocytes at lower epidermal levels, combined with moderate to dense periadnexal and perivascular lymphocytic infiltrates with a variable presence of melanophages, and mucin point to a LE-related origin.
Asunto(s)
Lupus Eritematoso Sistémico/patología , Síndrome de Stevens-Johnson/patología , Adulto , Anciano , Anciano de 80 o más Años , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sistema de Registros , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND: Acute generalized exanthematous pustulosis (AGEP) is a rare severe pustular reaction pattern with a typical clinical picture. OBJECTIVES: To characterize the histopathological features of AGEP in a large series of cases with a validated diagnosis. METHODS; A multinational retrospective histopathological study was conducted. It included 102 hospitalized patients (recruited within the EuroSCAR and RegiSCAR studies) with a validated diagnosis of probable or definite AGEP. A systematic description of the histopathological features in AGEP was done based on a standardized grading system. RESULTS: Sub/intracorneal pustules (41%), intraepidermal pustules (20%) or combinations of them (38%) were observed in 102 cases. The pustules were usually large (> 15 keratinocytes) (82% and 89%, respectively) and regularly contained eosinophils (36% and 32%, respectively). Spongiform features were less prominent in the sub/intracorneal pustules compared with the intraepidermal pustules (44% and 95%, respectively). The main epidermal features were necrotic keratinocytes (67%), including incidental segmental necrosis (7%), and spongiosis (80%) with neutrophil exocytosis (77%). The main dermal features were papillary oedema (88%) and mixed superficial (100%), interstitial (93%), and mid/deep-dermal infiltrates (95%) containing neutrophils (100%) and eosinophils (81%). Follicular pustules were also seen (23%), but vasculitis generally was absent. Classical features of plaque-type psoriasis were infrequent and usually mild. No significant differences were observed between a subgroup of 16 cases with and 86 cases without psoriasis. CONCLUSIONS: The present histopathological study concerns a large series of cases with a validated diagnosis of AGEP. It provides diagnostic clues in favour of AGEP in patients with a pustular eruption.
Asunto(s)
Exantema/patología , Enfermedad Aguda , Epidermis/patología , Femenino , Humanos , Masculino , Estudios RetrospectivosAsunto(s)
Antiinfecciosos/efectos adversos , Desensibilización Inmunológica/efectos adversos , Erupciones por Medicamentos/prevención & control , Infecciones por VIH/inmunología , Pruebas del Parche , Combinación Trimetoprim y Sulfametoxazol/efectos adversos , Adulto , Antiinfecciosos/administración & dosificación , Erupciones por Medicamentos/etiología , Erupciones por Medicamentos/inmunología , Humanos , Masculino , Neumonía por Pneumocystis/prevención & control , Combinación Trimetoprim y Sulfametoxazol/administración & dosificaciónRESUMEN
BACKGROUND: Drug-induced photosensitivity is difficult to predict and remains a challenge for both the dermatological clinical practice and pharmacovigilance. PURPOSE: To assess the association between spectroscopic and molecular characteristics and the occurrence of photosensitivity reactions. METHODS: For 143 well-known photosensitisers (e.g. tetracyclines, diuretics), we retrieved information on spectroscopic and molecular parameters, including: absorption maximum lambda(max), molar absorption coefficient epsilon, area under the absorption curve (AUC), molecular weight and configuration, hetero and aromatic halogen atoms, lipophilicity (log P) and acid/base status (pKa). In the WHO-ADR database, all reports with suspected adverse drug reactions of the study drugs were selected. We identified all reports on photosensitivity reactions and defined them as cases. All other reports were selected as non-cases. A case-non-case approach was performed to assess the spectroscopic and molecular exposure variables as a factor for photosensitivity reactions. Logistic regression was used to calculate odds ratios (OR) with 95% confidence intervals (CI). RESULTS: A lambda(max) between 290 and 320 nm (OR 3.74, 95% CI 3.45-4.06), and an epsilon > 20,000 M(-1) cm(-1) (OR 5.49, 95% CI 5.10-5.92) were highly associated with the reporting of photosensitivity reactions. Risk of the photosensitivity reactions was significantly increased among intermediate or high AUCs compared to low AUC. Low molecular weight and aromatic halogen atoms were associated with photosensitivity reactions (OR 2.37, 95% CI 2.07-2.71 resp. OR 3.37, 95% CI 3.15-3.61) as were log p < 1 and pKa < 7. CONCLUSION: The reporting of photosensitivity reactions to established phototoxic drug classes is strongly influenced by spectroscopic and physicochemical characteristics of individual drugs.
Asunto(s)
Trastornos por Fotosensibilidad/inducido químicamente , Trastornos por Fotosensibilidad/epidemiología , Medicamentos bajo Prescripción/efectos adversos , Medicamentos bajo Prescripción/química , Análisis Espectral/estadística & datos numéricos , Bases de Datos Factuales/estadística & datos numéricos , Humanos , Medicamentos bajo Prescripción/análisis , Factores de Riesgo , Estaciones del Año , Rayos Ultravioleta/efectos adversos , Organización Mundial de la SaludRESUMEN
Imatinib, a synthetic tyrosine kinase inhibitor, is used as first-line therapy for chronic myeloid leukaemia. Imatinib treatment is associated with a variety of adverse effects, most of which are mild to moderate and generally abate after the first months of treatment. Cutaneous adverse reactions are often encountered in patients using imatinib. Pseudoporphyria is regularly associated with the use of medication, especially naproxen and other nonsteroidal anti-inflammatory drugs, but the list of culprits is expanding. We present a patient with imatinib-induced pseudoporphyria. Taking into account the rapidly growing use of imatinib, physicians should be aware of the possibility of imatinib-induced pseudoporphyria. Adequate photoprotection can improve treatment compliance.
Asunto(s)
Antineoplásicos/efectos adversos , Leucemia Mieloide/tratamiento farmacológico , Piperazinas/efectos adversos , Porfirias/inducido químicamente , Pirimidinas/efectos adversos , Adulto , Antineoplásicos/administración & dosificación , Benzamidas , Citarabina/administración & dosificación , Erupciones por Medicamentos/etiología , Quimioterapia Combinada , Humanos , Mesilato de Imatinib , Masculino , Piperazinas/administración & dosificación , Porfirias/patología , Pirimidinas/administración & dosificaciónRESUMEN
Erlotinib (Tarceva) is an epidermal growth factor receptor (EGFR) inhibitor, a member of a new group of molecular targeted drugs that combine high efficacy against tumours with less, often self-limiting, toxicity, compared with traditional chemotherapeutics. It is used for treatment of solid-organ tumours, especially as second- or third-line therapy for non-small-cell lung cancer. Dose-related cutaneous side-effects and diarrhoea may be a significant obstacle to treatment compliance. We present two cases with long-lasting acneiform eruptions, complicated by significant impetiginization, resulting in hospitalization in one case. The other patient suffered from sleep-disturbing, itching crusts on the scalp. As the use of EGFR inhibitors is increasing, clinicians should be aware of their side-effects. Early and timely dermatological intervention may diminish adverse events for patients treated with these agents and improve quality of life.
Asunto(s)
Antibacterianos/uso terapéutico , Erupciones por Medicamentos/etiología , Minociclina/uso terapéutico , Inhibidores de Proteínas Quinasas/efectos adversos , Quinazolinas/efectos adversos , Anciano , Diarrea/inducido químicamente , Relación Dosis-Respuesta a Droga , Erupciones por Medicamentos/tratamiento farmacológico , Emolientes/uso terapéutico , Clorhidrato de Erlotinib , Humanos , Masculino , Persona de Mediana Edad , Prurito/inducido químicamenteAsunto(s)
Muñones de Amputación , Enfermedad de Darier , Folículo Piloso/ultraestructura , Adulto , Muñones de Amputación/patología , Enfermedad de Darier/complicaciones , Enfermedad de Darier/patología , Femenino , Enfermedades del Cabello/complicaciones , Enfermedades del Cabello/patología , Humanos , PiernaRESUMEN
A 61-year-old man presented with visual problems due to a marked two-sided periorbital swelling that had started three years earlier. There was no obvious underlying cause and he had persistent rhinoconjunctival symptoms. At the time the swelling started he was already suffering from xanthelasmata palpebrarum and chronic obstructive pulmonary disease. He had been taking simvastatin and salmeterol-fluticason for a year and carbasalate calcium for two years. There was marked periorbital swelling accompanied by xanthelasmata palpebrarum and slight chemosis and erythema of the eyelids. After exclusion of other potential causes for the swelling, acenocoumarol was prescribed in place of carbasalate calcium. This resulted in a quick recovery from the swelling and rhinoconjunctival symptoms. Provocation with acetyl salicylic acid led to renewed swelling of both eyelids. Periorbital angio-oedema, a relatively uncommonly reported side effect of acetyl salicylic acid and its derivates, can occur even after previous long-term medication use.
Asunto(s)
Aspirina/análogos & derivados , Aspirina/efectos adversos , Edema/inducido químicamente , Enfermedades de los Párpados/inducido químicamente , Urea/análogos & derivados , Urea/efectos adversos , Aspirina/administración & dosificación , Diagnóstico Diferencial , Edema/diagnóstico , Edema/patología , Enfermedades de los Párpados/diagnóstico , Enfermedades de los Párpados/patología , Párpados/patología , Humanos , Masculino , Persona de Mediana Edad , Inhibidores de Agregación Plaquetaria/efectos adversos , Urea/administración & dosificación , Campos VisualesRESUMEN
A 62-year-old female patient is described who developed toxic epidermal necrolysis (TEN) after medication with phenytoin and oxazepam. Initially phenytoin was discontinued and dexamethasone pulse therapy (1.5 mg/kg on 3 consecutive days) was initiated on the tenth day of skin disease. This resulted in clinical improvement. Histologically re-epithelialization could be demonstrated below the necrotic epidermis. However, on the eighteenth day of skin disease (10 days after discontinuation of phenytoin and 8 days after the start of dexamethasone pulse therapy), a histologically verified rebound-TEN developed with a detachment of 95%. Oxazepam was stopped and a second series of dexamethasone pulse therapy was given. Re-epithelialization began within 24 h of the start of the second series of dexamethasone pulse therapy, and continued to almost complete recovery within 1 week.