RESUMO
BACKGROUND: Melkersson-Rosenthal syndrome is a rare disease characterized by the triad of recurrent orofacial swelling with facial paralysis and fissured dorsal tongue. Histologically, noncaseating granulomatous inflammation occurs that confirms the diagnosis. Overlaps between granulomatous diseases such as sarcoidosis and Crohn's disease are described. Systemic corticosteroid therapy is the treatment of choice for acute attacks. CASE PRESENTATION: We here present a case of a 59-year-old White woman suffering from Melkersson-Rosenthal syndrome with a past history of sarcoidosis on therapy with leflunomide in combination with low-dose tacrolimus successfully treated with the anti-leprosy drug clofazimine after failure of systemic steroid therapy. CONCLUSIONS: We propose clofazimine as an alternative treatment in steroid-refractory cases.
Assuntos
Doença de Crohn , Paralisia Facial , Síndrome de Melkersson-Rosenthal , Sarcoidose , Terapia Comportamental , Feminino , Humanos , Síndrome de Melkersson-Rosenthal/complicações , Síndrome de Melkersson-Rosenthal/diagnóstico , Síndrome de Melkersson-Rosenthal/tratamento farmacológico , Pessoa de Meia-Idade , Sarcoidose/complicações , Sarcoidose/diagnóstico , Sarcoidose/tratamento farmacológicoAssuntos
Sarcoidose , Corticosteroides/uso terapêutico , Infecções Bacterianas/complicações , Síndrome de Behçet/complicações , Colite/complicações , Doenças do Tecido Conjuntivo/complicações , Diagnóstico Diferencial , Progressão da Doença , Erisipela/diagnóstico , Eritema Nodoso/etiologia , Eritema Nodoso/patologia , Neoplasias Hematológicas/complicações , Humanos , Hanseníase/diagnóstico , Prognóstico , Sarcoidose/induzido quimicamente , Sarcoidose/diagnóstico , Sarcoidose/tratamento farmacológico , Sarcoidose/etiologia , Sarcoidose/patologia , Pele/patologiaAssuntos
Diabetes Mellitus Tipo 1/complicações , Sarcoidose/patologia , Dermatopatias/patologia , Adulto , Anti-Inflamatórios/uso terapêutico , Antirreumáticos/uso terapêutico , Humanos , Hidroxicloroquina/uso terapêutico , Masculino , Prednisolona/uso terapêutico , Sarcoidose/complicações , Sarcoidose/tratamento farmacológico , Sarcoidose Pulmonar/complicações , Sarcoidose Pulmonar/tratamento farmacológico , Dermatopatias/complicações , Dermatopatias/tratamento farmacológico , Vitiligo/complicações , Vitiligo/patologiaRESUMO
Thalidomide was developed in the 1950s as a sedative drug and withdrawn in 1961 because of its teratogenic effects, but has been rediscovered as an immuno-modulatory drug. It has been administered successfully for the treatment of erythema nodosum leprosum, aphthous ulceration and cachexia in HIV disease, inflammatory bowel diseases, and several malignant diseases. The suppressive effect of thalidomide on the activation of the nuclear transcription factor NF-κB may explain these effects of thalidomide. NF-κB is retained in the cytoplasm with IκBα, and is activated by a wide variety of inflammatory stimuli including TNF, IL-1 and endotoxin followed by its translocation to the nucleus. Angiogenesis and organogenesis also require gene transcription and signal translocation. The findings shed new light on the anti-inflammatory properties of thalidomide and suggest pharmaceutical actions of thalidomide via interference of transcription mechanism. I reviewed the effects of thalidomide on auto-inflammatory diseases of childhood.
Assuntos
Fatores Imunológicos/farmacologia , Talidomida/farmacologia , Síndrome de Behçet/tratamento farmacológico , Criança , Feminino , Humanos , Masculino , NF-kappa B/fisiologia , Sarcoidose/tratamento farmacológico , Talidomida/uso terapêuticoRESUMO
Thalidomide and analogues are a class of immunomodulatory drugs or IMiDS. Thalidomide was initially approved by the U.S. Food and Drug Administation for treatment of erythema nodosum in leprosy and is now approved for multiple myeloma as well. A second generation IMiD, lenalidomide, is also approved for multiple myeloma and refractory myelodysplastic syndrome. Discovery of this class of drugs has been serendipitous and empirical, as the drug targets have been unknown. In this review, the authors integrate recent identification of drug targets of IMiDS, which include the inducible form of nitric oxide synthase (iNOS), Rho GTPase and caspase-1, with the developments in the understanding of the molecular biology of human inflammatory, infectious and neoplastic skin disorders. Because thalidomide reemerged through leprosy, the original disease classified by the T cell, the authors have also emphasized advances in the understanding of T-cell subsets in human skin disorders.
Assuntos
Dermatite/tratamento farmacológico , Imunomodulação , Neoplasias Cutâneas/tratamento farmacológico , Talidomida/análogos & derivados , Talidomida/uso terapêutico , Síndrome de Behçet/tratamento farmacológico , Dermatite/imunologia , Eritema Nodoso/tratamento farmacológico , Eritema Nodoso/imunologia , Humanos , Lúpus Eritematoso Cutâneo/tratamento farmacológico , Lúpus Eritematoso Cutâneo/imunologia , Linfoma Cutâneo de Células T/tratamento farmacológico , Linfoma Cutâneo de Células T/imunologia , Sarcoidose/tratamento farmacológico , Sarcoidose/imunologia , Neoplasias Cutâneas/imunologia , Talidomida/farmacologiaRESUMO
Pentoxifylline (PTX) is a methylxanthine derivative with a variety of anti-inflammatory effects. Currently, PTX is approved by the Food and Drug Administration for the treatment of intermittent claudication, but studies have shown that it has a variety of physiological effects at the cellular level, which may be important in treating a diverse group of diseases.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Pentoxifilina/uso terapêutico , Adulto , Animais , Anti-Inflamatórios não Esteroides/farmacocinética , Anti-Inflamatórios não Esteroides/farmacologia , Antifibrinolíticos/farmacocinética , Antifibrinolíticos/farmacologia , Antifibrinolíticos/uso terapêutico , Síndrome de Behçet/tratamento farmacológico , Criança , Pré-Escolar , Doença Enxerto-Hospedeiro/tratamento farmacológico , Infecções por HIV/tratamento farmacológico , Hemorreologia/efeitos dos fármacos , Humanos , Lactente , Leishmaniose Cutânea/tratamento farmacológico , Hanseníase/tratamento farmacológico , Camundongos , Camundongos Nus , Pentoxifilina/farmacocinética , Pentoxifilina/farmacologia , Inibidores de Fosfodiesterase/farmacocinética , Inibidores de Fosfodiesterase/farmacologia , Inibidores de Fosfodiesterase/uso terapêutico , Sarcoidose/tratamento farmacológico , Dermatopatias/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Doenças Vasculares/tratamento farmacológicoRESUMO
A 34-year-old Thai man presented with a two years history of progressively enlarged lepromatous leprosy like nodules and plaques on his back, chest, and scalp. Skin biopsy showed diffuse nonnecrotizing granulomatous inflammation with numerous multinucleated giant cells, lymphocytes, and plasma cells infiltration. The missed diagnosis of leprosy was made and was treated with antilepromatous drugs for one year. After repeated skin biopsy, the diagnosis was compatible with sarcoidosis. He was treated with prednisolone 40 mg per day for two weeks. The lesions gradually decreased in size and were controlled with prednisolone 10 mg per day.
Assuntos
Hanseníase Virchowiana/diagnóstico , Sarcoidose/diagnóstico , Dermatopatias/diagnóstico , Adulto , Glucocorticoides/efeitos adversos , Humanos , Masculino , Prednisolona/efeitos adversos , Sarcoidose/tratamento farmacológico , Dermatopatias/tratamento farmacológicoRESUMO
Thalidomide was first introduced in the 1950s as a sedative but was quickly removed from the market after it was linked to cases of severe birth defects. However, it has since made a remarkable comeback for the U.S. Food and Drug Administration-approved use in the treatment of erythema nodosum leprosum. Further, it has shown its effectiveness in unresponsive dermatological conditions such as actinic prurigo, adult Langerhans cell histiocytosis, aphthous stomatitis, Behçet's syndrome, graft-versus-host disease, cutaneous sarcoidosis, erythema multiforme, Jessner-Kanof lymphocytic infiltration of the skin, Kaposi sarcoma, lichen planus, lupus erythematosus, melanoma, prurigo nodularis, pyoderma gangrenosum and uraemic pruritus. This article reviews the history, pharmacology, mechanism of action, clinical uses and adverse effects of thalidomide.
Assuntos
Fármacos Dermatológicos/uso terapêutico , Dermatopatias/tratamento farmacológico , Talidomida/uso terapêutico , Adulto , Síndrome de Behçet/tratamento farmacológico , Fármacos Dermatológicos/efeitos adversos , Eritema/tratamento farmacológico , Doença Enxerto-Hospedeiro/tratamento farmacológico , Histiocitose de Células de Langerhans/tratamento farmacológico , Humanos , Líquen Plano/tratamento farmacológico , Lúpus Eritematoso Cutâneo/tratamento farmacológico , Melanoma/tratamento farmacológico , Prurigo/tratamento farmacológico , Sarcoidose/tratamento farmacológico , Sarcoma de Kaposi/tratamento farmacológico , Estomatite Aftosa/tratamento farmacológico , Talidomida/efeitos adversosRESUMO
STUDY OBJECTIVES: Thalidomide therapy has been shown to modify granulomatous diseases, such as tuberculosis and leprosy. Lupus pernio is a skin manifestation of sarcoidosis that does not remit spontaneously, and was used as a marker of efficacy of thalidomide for sarcoidosis. DESIGN: An open-label, dose-escalation trial of thalidomide. SETTING: Patients were seen at one of four specialized sarcoidosis clinics in the United States. PATIENTS: Fifteen patients with lupus pernio and other manifestations of sarcoidosis unresponsive to prior therapy were enrolled. INTERVENTIONS: Skin lesions were assessed with visual examination by the treating physician, and photographic evaluation by a blinded panel of physicians reviewing photographs of the lesions before and after therapy. MEASUREMENTS AND RESULTS: Fourteen patients completed 4 months of therapy. All patients experienced some improvement in their skin lesions subjectively, and 10 of 12 evaluable patients showed improvement using photograph scoring. Five patients were better after 1 month (treated with 50 mg/d of thalidomide), seven more patients improved after 2 months (treated with 100 mg/d of thalidomide in the second month), and two patients required an additional month of 200 mg of thalidomide to achieve a response. Patients reported increased somnolence (n = 9), numbness (n = 7), dizziness (n = 2), constipation (n = 6), rash (n = 1), and increasing shortness of breath (n = 1). One patient discontinued therapy because of new-onset dyspnea, due to probably unrelated new-onset congestive heart failure. CONCLUSION: Thalidomide was an effective form of treatment for chronic cutaneous sarcoidosis. The drug was well tolerated and may be a useful alternative to systemic corticosteroids.
Assuntos
Imunossupressores/uso terapêutico , Sarcoidose/tratamento farmacológico , Dermatopatias/tratamento farmacológico , Talidomida/uso terapêutico , Adulto , Doença Crônica , Relação Dose-Resposta a Droga , Feminino , Humanos , Imunossupressores/efeitos adversos , Masculino , Pessoa de Meia-Idade , Fotografação , Sarcoidose/patologia , Dermatopatias/patologia , Talidomida/efeitos adversos , Resultado do Tratamento , Estados UnidosAssuntos
Dermatopatias/tratamento farmacológico , Doença Crônica , Fotografia , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Relação Dose-Resposta a Droga , Sarcoidose/patologia , Sarcoidose/tratamento farmacológico , Talidomida/efeitos adversos , Talidomida/uso terapêuticoRESUMO
Sarcoidosis, a chronic granulomatous disease of unknown etiology, is treated with immune suppressive drugs such as corticosteroids. Sarcoidosis patients have been reported to benefit clinically from treatment with thalidomide. We administered thalidomide for 16 weeks to eight patients with chronic skin sarcoidosis and evaluated the drug's effects before and with treatment. After thalidomide treatment, all skin biopsies showed decreases in granuloma size and reduction in epidermal thickness. We also observed extensive T cell recruitment into the granulomas, the appearance of multinucleated giant cells, and increased numbers of dermal Langerhans cells (CD1a(+)) and mature dendritic cells (CD83(+) or DC-LAMP(+)). Plasma IL-12 levels increased and remained elevated during the treatment period. We noted increased HLA-DR expression on peripheral blood lymphocytes and a corresponding drop in the naive T cell marker CD45RA. Our data suggest that thalidomide treatment of sarcoidosis results in granuloma differentiation to a Th1-type cellular immune response usually associated with protective immunity to tuberculosis and tuberculoid leprosy.
Assuntos
Fármacos Dermatológicos/imunologia , Fármacos Dermatológicos/uso terapêutico , Imunossupressores/uso terapêutico , Sarcoidose/tratamento farmacológico , Dermatopatias/tratamento farmacológico , Talidomida/imunologia , Talidomida/uso terapêutico , Adulto , Antígenos CD/efeitos dos fármacos , Células Dendríticas/efeitos dos fármacos , Feminino , Citometria de Fluxo , Antígenos HLA-DR/efeitos dos fármacos , Humanos , Imuno-Histoquímica , Interleucina-12/sangue , Interleucina-2/sangue , Células de Langerhans/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Sarcoidose/imunologia , Sarcoidose/patologia , Dermatopatias/imunologia , Dermatopatias/patologia , Linfócitos T/efeitos dos fármacos , Resultado do Tratamento , Fator de Necrose Tumoral alfa/efeitos dos fármacosAssuntos
Antígenos CD , Antígenos HLA-DR , Citometria de Fluxo , Células Dendríticas , Células de Langerhans , Dermatopatias/dietoterapia , Dermatopatias/imunologia , Dermatopatias/patologia , Fator de Necrose Tumoral alfa , Fármacos Dermatológicos/imunologia , Fármacos Dermatológicos/uso terapêutico , Imuno-Histoquímica , Imunossupressores/uso terapêutico , /sangue , /sangue , Linfócitos T , Resultado do Tratamento , Sarcoidose/imunologia , Sarcoidose/patologia , Sarcoidose/tratamento farmacológico , Talidomida/imunologia , Talidomida/uso terapêuticoRESUMO
Sarcoidosis is a chronic systemic granulomatous disease that occasionally affects the larynx. When the larynx is affected, the symptoms are frequently mild, but severe airway obstruction can occur. Although systemic corticosteroids are helpful, patients may become refractory to further drug administration. The current methods of treatment are here summarized, and the patient literature is reviewed. We also report a case of a young patient suffering from laryngeal sarcoidosis successfully treated by the antileprosy agent clofazimine and propose it as an alternative treatment of laryngeal sarcoidosis in patients refractory to corticosteroids.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Clofazimina/uso terapêutico , Doenças da Laringe/tratamento farmacológico , Hansenostáticos/uso terapêutico , Sarcoidose/tratamento farmacológico , Adulto , Obstrução das Vias Respiratórias/etiologia , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios não Esteroides/farmacologia , Biópsia , Clofazimina/farmacologia , Transtornos de Deglutição/etiologia , Dispneia/etiologia , Rouquidão/etiologia , Humanos , Doenças da Laringe/complicações , Doenças da Laringe/patologia , Laringoscopia , Hansenostáticos/farmacologia , Masculino , Prednisona/uso terapêutico , Sarcoidose/complicações , Sarcoidose/patologia , Síndromes da Apneia do Sono/etiologia , Resultado do TratamentoRESUMO
We report a rare case of concomitant Hansen's disease (HD) and sarcoidosis. Reticulin staining may be a helpful diagnostic tool in establishing the diagnosis of sarcoidosis in skin lesions. The diagnosis of HD can be established despite negative polymerase chain reaction results for the detection of Mycobacterium leprae DNA. Finally, a well-established diagnosis of sarcoidosis does not preclude the development of another granulomatous disorder. Hence, when new lesions developed in a patient with sarcoidosis despite appropriate therapy, other concurrent diagnoses should be pursued.
Assuntos
Hanseníase Tuberculoide/complicações , Sarcoidose/complicações , Anti-Inflamatórios/uso terapêutico , Biópsia , Clofazimina/uso terapêutico , Dapsona/uso terapêutico , Fármacos Dermatológicos/uso terapêutico , Eletromiografia , Feminino , Humanos , Hidroxicloroquina/uso terapêutico , Hansenostáticos/uso terapêutico , Hanseníase Tuberculoide/tratamento farmacológico , Hanseníase Tuberculoide/patologia , Linfadenite/patologia , Pessoa de Meia-Idade , Mycobacterium leprae/química , Mycobacterium leprae/genética , Mycobacterium leprae/isolamento & purificação , Peptidil Dipeptidase A/sangue , Reação em Cadeia da Polimerase , Prednisona/uso terapêutico , Reticulina/análise , Rifampina/uso terapêutico , Sarcoidose/tratamento farmacológico , Sarcoidose/patologia , Pele/química , Pele/patologia , Triancinolona/uso terapêuticoRESUMO
Realizamos uma revisäo sobre as principais doenças granulomatosas que podem acometer a laringe, devido à grande ocorrência dessas afecçöes no Brasil e em outros países de clima tropical e subtropical. Ressaltamos os aspectos histopatológicos para o seu diagnóstico, assim como o seu tratamento.
Assuntos
Humanos , Actinomicose/fisiopatologia , Amiloidose/fisiopatologia , Blastomicose/fisiopatologia , Doenças Faríngeas/fisiopatologia , Granulomatose com Poliangiite/fisiopatologia , Hanseníase/fisiopatologia , Histoplasmose/fisiopatologia , Leishmaniose/fisiopatologia , Rinoscleroma/fisiopatologia , Sarcoidose/fisiopatologia , Sífilis/fisiopatologia , Tuberculose/fisiopatologia , Actinomicose/diagnóstico , Actinomicose/tratamento farmacológico , Amiloidose/diagnóstico , Amiloidose/terapia , Blastomicose/diagnóstico , Blastomicose/tratamento farmacológico , Doenças Faríngeas/diagnóstico , Doenças Faríngeas/tratamento farmacológico , Doenças Faríngeas/terapia , Granulomatose com Poliangiite/diagnóstico , Granulomatose com Poliangiite/tratamento farmacológico , Hanseníase/diagnóstico , Hanseníase/tratamento farmacológico , Histoplasmose/diagnóstico , Histoplasmose/tratamento farmacológico , Leishmaniose/diagnóstico , Leishmaniose/tratamento farmacológico , Rinoscleroma/diagnóstico , Rinoscleroma/tratamento farmacológico , Sarcoidose/diagnóstico , Sarcoidose/tratamento farmacológico , Sífilis/diagnóstico , Sífilis/tratamento farmacológico , Tuberculose/diagnóstico , Tuberculose/tratamento farmacológicoAssuntos
Actinomicose/diagnóstico , Actinomicose/fisiopatologia , Actinomicose/tratamento farmacológico , Amiloidose/diagnóstico , Amiloidose/fisiopatologia , Amiloidose/tratamento farmacológico , Blastomicose/diagnóstico , Blastomicose/fisiopatologia , Blastomicose/tratamento farmacológico , Doenças Faríngeas/diagnóstico , Doenças Faríngeas/fisiopatologia , Doenças Faríngeas/terapia , Doenças Faríngeas/tratamento farmacológico , Granulomatose com Poliangiite/diagnóstico , Granulomatose com Poliangiite/fisiopatologia , Granulomatose com Poliangiite/tratamento farmacológico , Hanseníase/diagnóstico , Hanseníase/fisiopatologia , Hanseníase/tratamento farmacológico , Histoplasmose/diagnóstico , Histoplasmose/fisiopatologia , Histoplasmose/tratamento farmacológico , Leishmaniose/diagnóstico , Leishmaniose/fisiopatologia , Leishmaniose/tratamento farmacológico , Rinoscleroma/diagnóstico , Rinoscleroma/fisiopatologia , Rinoscleroma/tratamento farmacológico , Sarcoidose/diagnóstico , Sarcoidose/fisiopatologia , Sarcoidose/tratamento farmacológico , Sífilis/diagnóstico , Sífilis/fisiopatologia , Sífilis/tratamento farmacológico , Tuberculose/diagnóstico , Tuberculose/fisiopatologia , Tuberculose/tratamento farmacológicoAssuntos
Eritema Nodoso/tratamento farmacológico , Hanseníase/tratamento farmacológico , Dermatopatias/tratamento farmacológico , Talidomida/uso terapêutico , Humanos , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Paniculite Nodular não Supurativa/tratamento farmacológico , Prurigo/tratamento farmacológico , Sarcoidose/tratamento farmacológico , Estomatite Aftosa/tratamento farmacológico , Talidomida/efeitos adversos , Talidomida/farmacologiaRESUMO
A series of eight hundred and eighteen patients with histologically-confirmed multisystem sarcoidosis was analysed; within this series were 53 (6 per cent) patients with sarcoidosis of the upper respiratory tract (SURT). Two-thirds presented with predominantly upper respiratory tract symptoms when the systemic disorder was minimal or unrecognized. Women were affected twice as often as men. SURT is commonly associated with lupus pernio and other manifestations of chronic fibrotic sarcoidosis, and it follows the same indolent course. When granulomas are found on biopsy of the upper respiratory tract, there should be a management plan to determine whether they are due to multisystem sarcoidosis or other granulomatous disorders including tuberculosis, Wegener's granulomatosis and leprosy. About one-half of patients with SURT will need oral steroids, either alone or in combination with topical steroids or chloroquine.