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2.
Clin Dermatol ; 38(2): 193-207, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32513399

RESUMO

Drug eruptions are among the great masqueraders that sometimes cause diagnostic challenges in clinical practice. Pharmacologic agents may induce skin changes, sharing the same pathophysiologic mechanisms of specific dermatoses, or inducing drug eruptions with different pathologic mechanisms that have similar clinical presentations. The former conditions are usually called drug-induced skin diseases, whereas the latter conditions are termed "dermatosis-like drug eruptions." Both types are great imitators in dermatologic practice and can be easily misdiagnosed as other diseases or lead to unrecognized causative agents.


Assuntos
Erupção por Droga/diagnóstico , Erupção por Droga/etiologia , Pele/patologia , Diagnóstico Diferencial , Erupção por Droga/patologia , Humanos
3.
Clin Dermatol ; 38(2): 208-215, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32513400

RESUMO

Many studies have investigated cutaneous reactions to antitumor drugs and found them to be quite numerous. We describe drug eruptions that may be associated with different therapies by class: antimetabolite chemotherapeutics, genotoxic agents, spindle inhibitors, signal transduction inhibitors, and immunotherapies. Methotrexate is most often associated with mucocutaneous reactions, alkylating antimetabolite agents with hyperpigmentation, and platinum antimetabolite agents with type I IgE-mediated hypersensitivity reactions. Anthracycline derivatives can induce the hand-foot syndrome in patients, and bleomycin is associated with a bleomycin-induced flagellate erythema. Taxane spindle inhibitors can result in acneiform eruptions, which may also be seen with use of epidermal growth factor receptor inhibitors. Imatinib and its derivatives can cause a truncal maculopapular eruption, whereas multikinase inhibitors can produce a hand-foot-skin reaction. Vemurafenib can result in squamous cell carcinomas and photosensitivity. First-generation mammalian target of rapamycin inhibitors may cause a maculopapular eruption initially involving the face and neck. Programmed death (PD)-1-ligand and receptor inhibitors are associated with bullous pemphigoid. Ipilimumab, targeting Cytotoxic -T- Lymphocyte- associated (CTLA-4) receptors, can cause a morbilliform reaction, whereas Interleukin -2 (IL-2) analogs can create the capillary leak syndrome. Chemotherapeutic drug eruptions classically can manifest in the aforementioned ways; however, it is important to understand that they are associated with myriad cutaneous adverse effects, which may be mistaken for organic skin disease. Oncologists prescribing these medications should be familiar with the cutaneous side effects of these medications, and so they may counsel patients to be on the lookout for them.


Assuntos
Antineoplásicos/efeitos adversos , Erupção por Droga/diagnóstico , Erupção por Droga/etiologia , Pele/patologia , Antimetabólitos Antineoplásicos/efeitos adversos , Diagnóstico Diferencial , Erupção por Droga/patologia , Humanos , Mutagênicos/efeitos adversos
4.
Clin Dermatol ; 38(1): 52-62, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32197749

RESUMO

Immunosuppressed patients frequently have skin diseases of mild to moderate intensity. Diagnosis as well as treatment should be performed early to avoid important complications for these patients. Skin eruptions are among these problems. Life-threatening eruptions in HIV and other types of immunosuppression range from acute retroviral syndrome to drug eruptions; immune reconstitution inflammatory syndrome; infection by virus, protozoan, bacteria, or fungi; inflammatory and immune dermatoses; and neoplasia. All of these are discussed in this group of patients.


Assuntos
Infecções por HIV/complicações , Hospedeiro Imunocomprometido , Dermatopatias/etiologia , Síndrome Retroviral Aguda/complicações , Infecções Bacterianas/complicações , Erupção por Droga/etiologia , Erupção por Droga/patologia , Humanos , Inflamação/complicações , Micoses/complicações , Neoplasias/complicações , Doenças Parasitárias/complicações , Dermatopatias/patologia
5.
Clin Dermatol ; 38(1): 63-78, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32197750

RESUMO

A red swollen face can be a skin sign of a potentially life-threatening condition. We present in detail the main clinical presentations, diagnostic tests, and management of some of the most severe conditions that can frequently present as a red and swollen face: acute or recurrent angioedema, mast cell-driven or bradykinin-mediated angioedema, nonhereditary and hereditary angioedema, allergic or photoallergic facial contact dermatitis, contact urticaria, severe adverse drug reactions (particularly drug reaction with eosinophilia and systemic symptoms [DRESS]), skin infections (erysipelas, cellulitis, necrotizing fasciitis), and autoimmune diseases (dermatomyositis). There are many other conditions that also have to be considered in the differential diagnosis of a red swollen face.


Assuntos
Dermatite/patologia , Exantema/etiologia , Exantema/patologia , Face/patologia , Angioedema/etiologia , Angioedema/patologia , Dermatite/etiologia , Dermatomicoses/etiologia , Dermatomicoses/patologia , Erupção por Droga/etiologia , Erupção por Droga/patologia , Humanos
6.
Clin Dermatol ; 38(1): 94-104, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32197753

RESUMO

Immune checkpoint inhibitors (ICPi) have emerged as a new frontier of cancer therapy. Although monoclonal antibodies to cytotoxic T-lymphocyte associated protein 4 (CTLA-4), programmed cell death 1 (PD-1), and programmed cell death ligand 1 (PD-L1) have revolutionized oncologic management, these agents may result in a spectrum of immune-related adverse events (irAE) of which dermatologic toxicities are among the most frequent. Prompt recognition and management of irAE is essential for dermatologists caring for the expanding population of cancer patients exposed to these drugs. Cutaneous toxicities range from mild cases to severe and life-threatening presentations that may cause significant morbidity and mortality. This review provides an overview of severe cutaneous adverse reactions (SCARs) that may develop during ICPi therapy, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP). In addition, immunobullous disorders, erythroderma, neutrophilic dermatoses, and cutaneous eruptions associated with systemic manifestations are discussed.


Assuntos
Anticorpos Monoclonais/efeitos adversos , Antineoplásicos/efeitos adversos , Erupção por Droga/etiologia , Erupção por Droga/patologia , Pustulose Exantematosa Aguda Generalizada/etiologia , Pustulose Exantematosa Aguda Generalizada/patologia , Antígeno B7-H1/imunologia , Antígeno CTLA-4/imunologia , Humanos , Receptor de Morte Celular Programada 1 , Síndrome de Stevens-Johnson/etiologia , Síndrome de Stevens-Johnson/patologia
9.
Phytomedicine ; 68: 153173, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31999977

RESUMO

BACKGROUND: Chrysoeriol is a flavone found in diverse dietary and medicinal herbs such as Lonicerae Japonicae Flos (the dried flower bud or newly bloomed flower of Lonicera japonica Thunb.). These herbs are commonly used for treating inflammatory diseases. Herbal extracts containing chrysoeriol have been shown to have anti-inflammatory effects and inhibit nuclear factor-kappa B (NF-κB) signaling. Some of these extracts can inhibit signal transducers and activators of transcription 3 (STAT3) signaling in cancer cells. PURPOSE: This study aimed to determine whether chrysoeriol has anti-inflammatory effects and whether NF-κB and STAT3 pathways are involved in the effects. STUDY DESIGN AND METHODS: A TPA (12-O-tetradecanoylphorbol-13-acetate)-induced ear edema mouse model and LPS-stimulated RAW264.7 cells were used to evaluate the effects of chrysoeriol. Griess reagent was used to measure the production of nitric oxide (NO). Western blot and enzyme-linked immunosorbent assays were employed to detect protein levels. RT-qPCR analyses were used to detect mRNA levels. Haematoxylin and eosin (H&E) staining was employed to examine the pathological conditions in animal tissues. RESULTS: In the mouse model, chrysoeriol ameliorated acute skin inflammation, evidenced by reduced ear thickness, ear weight and number of inflammatory cells in inflamed ear tissues. The compound lowered protein levels of phospho-p65 (Ser536), phospho-STAT3 (Tyr705), inducible nitric oxide synthases (iNOS), cyclooxygenase-2 (COX-2), interleukin 6 (IL-6), IL-1ß and tumor necrosis factor α (TNF-α) in mouse swollen ears. In LPS-stimulated RAW264.7 cells, chrysoeriol also lowered levels of these proteins. In addition, chrysoeriol decreased the production of NO and prostaglandin E2; inhibited the phosphorylation of inhibitor of κB (Ser32), p65 (Ser536) and Janus kinase 2 (Tyr1007/1008); decreased nuclear localization of p50, p65 and STAT3; and down-regulated mRNA levels of pro-inflammatory cytokines IL-6, IL-1ß and TNF-α that are transcriptionally regulated by NF-κB and STAT3 in the cell model. CONCLUSION: We for the first time demonstrated that chrysoeriol ameliorates TPA-induced ear edema in mice, and that inhibition of JAK2/STAT3 and IκB/p65 NF-κB pathways are involved in the anti-inflammatory effects of chrysoeriol. This study provides chemical and pharmacological justifications for the use of chrysoeriol-containing herbs in treating inflammatory diseases, and provides pharmacological groundwork for developing chrysoeriol as a novel anti-inflammatory agent.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Erupção por Droga/tratamento farmacológico , Flavonas/farmacologia , NF-kappa B/metabolismo , Fator de Transcrição STAT3/metabolismo , Animais , Citocinas/metabolismo , Modelos Animais de Doenças , Erupção por Droga/metabolismo , Erupção por Droga/patologia , Regulação da Expressão Gênica , Proteínas I-kappa B/metabolismo , Lipopolissacarídeos/toxicidade , Masculino , Camundongos , Camundongos Endogâmicos ICR , Óxido Nítrico Sintase Tipo II/metabolismo , Células RAW 264.7 , Acetato de Tetradecanoilforbol/análogos & derivados , Acetato de Tetradecanoilforbol/toxicidade
10.
Mol Cell Biochem ; 465(1-2): 175-185, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31853800

RESUMO

Cutaneous changes like rash and hair loss, as well as other neurogenic inflammation side effects, occur frequently during anticancer treatment with the epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), erlotinib. These adverse events may be so severe that they impair the patient's compliance with the treatment or even cause its discontinuation. In the current preclinical study, rats (9.2 weeks) were treated with erlotinib (10 mg/kg/day) ± aprepitant (2 mg/kg/day) for 12 weeks. Visual changes in the development of facial skin lesions/hair loss and SP-receptor expression (immunohistochemically) in facial skin tissue were assessed; also changes in plasma magnesium, 8-isoprostane, substance P (SP), neutrophil superoxide production, and cardiac function (echocardiography) were measured. Erlotinib lowered plasma magnesium 14%, elevated SP 65%, caused 3.7-fold higher basal superoxide production, 2.5-fold higher 8-isoprostane levels, 11.6% lower cardiac systolic, and 10.9% lower diastolic function. Facial dermatological changes (alopecia, skin reddening, scabbing, nose crusting) occurred by 4 weeks (± + to ++) in erlotinib-treated rats, and progressively worsened (±++ to +++) by week 12. Facial skin SP-receptor upregulation (78% higher) occurred in epidermal and hair follicle cells. All adverse effects were substantially and significantly mitigated by aprepitant, including a 62% lowering of skin SP-receptors (p < 0.05). Elevated SP levels mediated the side effects of erlotinib treatment, but aprepitant's significant prevention of the systemic and cutaneous adverse events indicates a novel potential therapy against the side effects of this anticancer treatment.


Assuntos
Aprepitanto/farmacologia , Erupção por Droga , Cloridrato de Erlotinib/efeitos adversos , Doenças do Sistema Nervoso , Antagonistas do Receptor de Neuroquinina-1/farmacologia , Animais , Erupção por Droga/tratamento farmacológico , Erupção por Droga/metabolismo , Erupção por Droga/patologia , Cloridrato de Erlotinib/farmacologia , Masculino , Doenças do Sistema Nervoso/induzido quimicamente , Doenças do Sistema Nervoso/tratamento farmacológico , Doenças do Sistema Nervoso/metabolismo , Doenças do Sistema Nervoso/patologia , Ratos , Ratos Sprague-Dawley
11.
J Cutan Pathol ; 47(1): 65-69, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31390071

RESUMO

Checkpoint inhibition has become an important target in the management of malignant melanoma. As anti-CTLA4 inhibitors and anti-PD1 antibodies are increasingly utilized, reports of immune-related adverse events (IRAEs) are becoming more frequent. Common noted cutaneous IRAEs are morbilliform, lichenoid, bullous, granulomatous, psoriasiform, and eczematous eruptions. We report a case of interstitial granulomatous dermatitis and granulomatous arteritis in the setting of nivolumab (anti-PD1) monotherapy for metastatic melanoma. There are many different causes for granulomatous vasculitis, such as herpes virus infection, lymphoproliferative disorders, systemic vasculitis, and inflammatory bowel disease. This report adds to the growing literature on granulomatous IRAEs due to checkpoint inhibition.


Assuntos
Erupção por Droga , Melanoma , Proteínas de Neoplasias/antagonistas & inibidores , Nivolumabe , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Neoplasias Cutâneas , Vasculite do Sistema Nervoso Central , Erupção por Droga/metabolismo , Erupção por Droga/patologia , Feminino , Humanos , Melanoma/tratamento farmacológico , Melanoma/metabolismo , Melanoma/patologia , Pessoa de Meia-Idade , Metástase Neoplásica , Nivolumabe/administração & dosagem , Nivolumabe/efeitos adversos , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia , Vasculite do Sistema Nervoso Central/induzido quimicamente , Vasculite do Sistema Nervoso Central/metabolismo , Vasculite do Sistema Nervoso Central/patologia
12.
Am J Dermatopathol ; 42(3): 215-217, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31855583

RESUMO

Lichen planus-like atopic dermatitis clinically mimics lichen planus and can pose a diagnostic challenge. We report a case of a 55-year-old African American woman who developed intensely pruritic papules and plaques on bilateral hands. Histological examination demonstrated acute spongiotic dermatitis with lymphocyte exocytosis into the epidermis. Taken together, a diagnosis of lichen planus-like atopic dermatitis was made. This case serves to highlight that lichen planus-like atopic dermatitis can develop on hands and that it presents as spongiotic dermatitis with lymphocyte exocytosis into the epidermis. Correlating the clinical presentation with histopathological findings will assist in establishing the diagnosis and guiding appropriate management.


Assuntos
Dermatite Atópica/diagnóstico , Inibidores da Captação Adrenérgica/efeitos adversos , Amitriptilina/efeitos adversos , Dermatite Atópica/induzido quimicamente , Diagnóstico Diferencial , Erupção por Droga/diagnóstico , Erupção por Droga/patologia , Feminino , Mãos , Humanos , Líquen Plano/diagnóstico , Pessoa de Meia-Idade
13.
J Am Acad Dermatol ; 82(2): 430-439, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31859047

RESUMO

BACKGROUND: T helper (Th) type 17 and Th2 cells mediate psoriasis and eczema, respectively. Some dermatoses exhibit overlapping clinicopathologic features, and their immunopathology is relatively unexplored. OBJECTIVE: To determine whether Th17 and Th2 subsets and interleukin (IL) 36 and ß-defensin 2 (BD-2) markers of IL-17 signaling expression can discriminate between biopsy samples of psoriasis and eczematous/spongiotic dermatitis and to use those markers to immunophenotype cases with clinicopathologic overlap. METHODS: A retrospective study was performed on biopsy samples of psoriasis, eczema/spongiotic dermatitis, sebopsoriasis, tumor necrosis factor α inhibitor-associated psoriasiform dermatitis, and ambiguous cases diagnosed as spongiotic psoriasiform dermatitis. Dual CD4/GATA3 and CD4/RORC, IL-36, and BD-2 immunohistochemistry was performed. RESULTS: IL-36 and BD-2 were strongly expressed in biopsy samples of psoriasis compared with eczema/spongiotic dermatitis. No significant differences were observed in the percentages of Th2 and Th17 cells between disease types. Strong expression of IL-36 and BD-2 was observed in a subset of spongiotic psoriasiform dermatitis, sebopsoriasis, and tumor necrosis factor α inhibitor-associated psoriasiform dermatitis biopsy samples. LIMITATIONS: This was an exploratory study with a small sample size. No multiple testing adjustment was done. Clinical follow-up was limited. CONCLUSIONS: In cases with clinicopathologic overlap between psoriasis and spongiotic dermatitis, IL-36, and to a lesser extent BD-2, may be used to assess for a psoriasis-like/IL-17 phenotype, which could inform therapeutic clinical decisions.


Assuntos
Erupção por Droga/sangue , Erupção por Droga/complicações , Eczema/sangue , Eczema/complicações , Interleucina-17/sangue , Interleucina-1/sangue , Psoríase/sangue , Psoríase/complicações , Células Th17 , Células Th2 , Fator de Necrose Tumoral alfa/antagonistas & inibidores , beta-Defensinas/sangue , Adolescente , Adulto , Idoso , Biópsia , Criança , Erupção por Droga/etiologia , Erupção por Droga/patologia , Eczema/imunologia , Eczema/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Psoríase/imunologia , Psoríase/patologia , Estudos Retrospectivos , Adulto Jovem
14.
Rheumatology (Oxford) ; 58(Suppl 7): vii17-vii28, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31816081

RESUMO

Immune check point inhibitor (CPI) therapy has revolutionized treatment paradigms for several cancers, but at the cost of triggering a diverse spectrum of immune-mediated injury to non-cancer tissues. The complex biology of these toxicities remains incompletely understood, partly because tissue acquisition from affected areas can be challenging to retrieve, thus hindering development of targeted therapy. Here, we review the literature describing pathology of immune-mediated tissue lesions including gastrointestinal, skin, rheumatic, pulmonary, cardiac, renal and hepatic lesions and highlight key immunological insights.


Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Fatores Imunológicos/efeitos adversos , Imunoterapia/efeitos adversos , Neoplasias/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/patologia , Erupção por Droga/etiologia , Erupção por Droga/patologia , Gastroenteropatias/induzido quimicamente , Gastroenteropatias/patologia , Humanos , Imunoterapia/métodos , Nefropatias/induzido quimicamente , Nefropatias/patologia , Pneumopatias/induzido quimicamente , Pneumopatias/patologia , Miocardite/induzido quimicamente , Miocardite/patologia , Doenças Reumáticas/induzido quimicamente , Doenças Reumáticas/patologia
15.
Skinmed ; 17(5): 306-309, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31782703

RESUMO

Bullous fixed drug eruption (FDE) is a severe reaction due to drug intake and requires specific management in dermatology. The sites of predilection are the lips, trunk, genitalia, and perineal area. The aim of our study was to assess the features and outcomes of bullous FDE with genital involvement through a retrospective study of 18 years (2000-2017) conducted in the Dermatology Department of Habib Thameur Hospital. Ten patients were included in the study. The ratio of men to women was 6.4. The mean age of the patients was 46.3 years. The most frequently affected genital site in men was the glans penis. Nonsteroidal anti-inflammatory drugs were the most frequent drugs associated with genital bullous FDE, followed by paracetamol and trimethoprim-sulfamethoxazole. Residual hyperpigmentation of the genitals was not observed in our patients. Genital involvement in bullous FDE is more frequent in men.


Assuntos
Vesícula/induzido quimicamente , Erupção por Droga/etiologia , Doenças dos Genitais Femininos/induzido quimicamente , Doenças dos Genitais Masculinos/induzido quimicamente , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/efeitos adversos , Anti-Inflamatórios não Esteroides/efeitos adversos , Criança , Pré-Escolar , Erupção por Droga/patologia , Feminino , Doenças dos Genitais Femininos/patologia , Doenças dos Genitais Masculinos/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Membrana Mucosa , Estudos Retrospectivos , Adulto Jovem
16.
Ann Dermatol Venereol ; 146(11): 740-755, 2019 Nov.
Artigo em Francês | MEDLINE | ID: mdl-31672325

RESUMO

Cutaneous drug reactions are a common reason for calls and visits. This term chiefly refers to hypersensitivity reactions ranging from benign rash without contraindication of treatment to severe life-threatening clinical pictures, such as anaphylactic shock and epidermal necrolysis. They should be carefully managed from the outset. Indeed, history taking and precise semiological description of the lesions are crucial to the formulation of recommendations for the patient. Allergological investigation of such reactions has developed greatly in recent decades and must now be carried out much more extensively. The arrival of new drug families such as biotherapies and the development of drug habituation protocols constitute the challenges of tomorrow for cutaneous drug reactions.


Assuntos
Erupção por Droga/patologia , Dermatite Fotoalérgica/patologia , Diagnóstico Diferencial , Erupção por Droga/etiologia , Humanos
19.
BMJ Case Rep ; 12(9)2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31570343

RESUMO

Dipeptidyl peptidase 4 (DPP-4) inhibitors are increasingly used these days in management of diabetes. There has been reported in a few case reports of increasing association between DPP-4 inhibitor use and bullous pemphigoid (BP). We report a case of association between linagliptin use and BP and subsequent treatment with rituximab.


Assuntos
Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Erupção por Droga/patologia , Linagliptina/efeitos adversos , Penfigoide Bolhoso/induzido quimicamente , Rituximab/uso terapêutico , Idoso , Antibacterianos/uso terapêutico , Clobetasol/uso terapêutico , Inibidores da Dipeptidil Peptidase IV/administração & dosagem , Erupção por Droga/tratamento farmacológico , Humanos , Linagliptina/administração & dosagem , Masculino , Minociclina/uso terapêutico , Penfigoide Bolhoso/patologia , Prednisona/uso terapêutico , Resultado do Tratamento
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