RESUMO
We report a patient with bullous pemphigoid (BP) who was successfully treated with dupilumab monotherapy. To clarify the underlying mechanism of this effective treatment, we investigated the dynamics of a variety of cytokine-producing T cells before and after treatment in the circulation and in blister fluid using flow cytometry. The patient was a 72-year-old woman who had a pruritic eruption consisting of erythema and tense blisters on the whole body. The skin biopsy and direct immunofluorescence of the skin were typical for BP. The serum level of anti-BP180NC16a antibodies was 111 U/ml. Flow cytometric analyses revealed that the proportions of circulating interleukin (IL)-4-, IL-13-, and IL-31-producing CD4+ and CD8+ T cells were substantially higher in our BP patient than in healthy subjects. Moreover, IL-4- and IL-13-producing CD4+ and CD8+ T cells were much higher in the blister fluids than in the circulation, whereas IL-31-producing CD4+ and CD8+ T cells were only slightly higher in the blister fluids. The proportions of circulating interferon (IFN)-γ-producing CD4+ and CD8+ T cells in the circulation were slightly lower in the patient than in healthy subjects. There was no significant difference in the circulating IL-17-producing CD4+ and CD8+ T cells between the patient and healthy subjects, although IL-17-producing CD4+ and CD8+ T cells were slightly higher in the blister fluids. Treatment with dupilumab promptly improved the pruritus and skin lesions, and anti-BP180 antibodies became negative. After treatment with dupilumab, the proportions of circulating IL-4- and IL-13-producing CD4+ T cells mainly decreased and IL-17- and IL-31-producing CD4+ T cells slightly decreased. There were no significant differences in the proportions of circulating IFN-γ-producing CD4+ and CD8+ T cells between before and after treatment. These results suggest that T-helper (Th)2 cells are involved in the pathogenesis of BP, and dupilumab exerts its effect mainly by suppressing Th2 cytokines.
Assuntos
Interleucina-4 , Penfigoide Bolhoso , Idoso , Anticorpos Monoclonais Humanizados , Vesícula/tratamento farmacológico , Linfócitos T CD4-Positivos , Linfócitos T CD8-Positivos , Citocinas , Feminino , Humanos , Interleucina-13 , Interleucina-17 , Penfigoide Bolhoso/tratamento farmacológicoRESUMO
Papuloerythroderma (PEO) is a representative form of senile erythroderma with an unclear pathogenesis. This study aimed to characterize the T-cell phenotypes responsible for the pathogenesis of PEO. Cytokine profiles and cutaneous lymphocyte antigen (CLA) expression on circulating T lymphocytes in patients with PEO were simultaneously analyzed using flow cytometry. The patients with PEO showed significantly higher circulating interleukin (IL)-4-, IL-13-, IL-22-, and IL-31-producing CD4+ and CD8+ T-cell levels than healthy subjects. However, their levels significantly decreased after remission of PEO. No difference was observed in the proportions of circulating interferon (IFN)-γ- and IL-17-producing CD4+ and CD8+ T cells between the patients with PEO and healthy subjects. In particular, the proportion of circulating IL-4-, IL-13-, IL-22-, and IL-31-producing CD4+ and CD8+ T cells was much higher in the CLA+ subset than in the CLA- subset. There was a positive correlation between IL-13-, IL-22-, and IL-31-producing CD4+ T cells and the disease severity score of PEO. Moreover, a positive correlation was also observed between the proportion of IL-22- or IL-31-producing cells and circulating IL-13-producing cells in both CD4+ and CD8+ T cells, and approximately 50% of both IL-22- and IL-31-producing CD4+ and CD8+ T cells coproduced IL-13. IL-13/IL-22/IL-31 skewing within the skin-homing T-cell population may be involved in the pathogenesis of PEO.
Assuntos
Antígenos de Diferenciação de Linfócitos T , Linfócitos T CD8-Positivos , Interleucinas , Parapsoríase/imunologia , Pele/imunologia , Linfócitos T CD4-Positivos , Citometria de Fluxo , Humanos , Interleucina-13 , Interleucina 22RESUMO
BACKGROUND: Although tetracycline has been used to treat cutaneous sarcoidosis, the mechanism of action for this treatment remains unclear. This study evaluated the efficacy of minocycline treatment on cutaneous sarcoidosis and the relationship between its efficacy and the presence of Propionibacterium acnes in skin sarcoid lesions. METHODS: We retrospectively reviewed results in 13 patients with cutaneous sarcoidosis treated with minocycline at Saitama Medical Center between 2010 and 2017. To demonstrate the presence of P. acnes in the skin lesions, skin biopsy specimens from 11 of the 13 patients were evaluated with immunohistochemistry using a specific monoclonal antibody against P. acnes (PAB antibody). RESULTS: Of the 13 patients treated with minocycline, six patients (46%) achieved a complete response (CR) and seven (54%) had a partial response (PR). The skin lesions regressed in 1.5-5 months (average, 3.2 months) after treatment with minocycline. No relapse had occurred during the minocycline therapy. Elevated serum angiotensin-converting enzyme levels were observed in five of the patients, and the levels reduced after treatment with minocycline. P. acnes, identified as round bodies that reacted with PAB antibody, were observed in the skin sarcoid granulomas in all patients tested. The number of PAB-positive round bodies was significantly higher in the skin lesions of patients who had CR than in those who had PR. CONCLUSIONS: These results suggest the effectiveness of minocycline for the treatment of cutaneous sarcoidosis and an association of P. acnes with the efficacy of minocycline therapy for cutaneous sarcoidosis.
Assuntos
Acne Vulgar/diagnóstico , Antibacterianos/uso terapêutico , Minociclina/uso terapêutico , Propionibacterium acnes/isolamento & purificação , Sarcoidose/tratamento farmacológico , Acne Vulgar/tratamento farmacológico , Acne Vulgar/microbiologia , Acne Vulgar/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Sarcoidose/microbiologia , Pele/microbiologia , Pele/patologia , Resultado do TratamentoRESUMO
The clinical classification of cutaneous adverse reactions by drugs should be clearly distinguished to avoid conceptual confusion and inconsistency. Although dermatologists appear to have established a roughly common consensus for cutaneous adverse reactions, some types are more rigorously defined than other, possibly misleading classifications. To assess the consensus on the clinical classifications, we investigated the concordance rate of diagnosis by Japanese experts through a snap visual inspection of various clinical pictures exhibiting erythema multiforme and maculopapular eruption types of cutaneous adverse reactions. The experts were shown images on a screen and were then asked to decide whether to classify cases as maculopapular eruption or erythema multiforme type, and the concordance rates were calculated. Overall, the mean concordance rate was 71.6% (standard deviation, 17.3%), and only 33.8% of cases had a 90% or more concordance rate. Our study shows that the determinations of erythema multiforme and maculopapular eruption types by the existing classification criteria were confusing even among experts, which prompted us to standardize the terminology. We propose clinically defining erythema multiforme type as generalized macules mainly of 1 cm or more with a tendency of elevation and coalescence, and maculopapular eruption type as generalized erythema other than erythema multiforme type. Currently, the clinical definitions of cutaneous adverse reactions are poorly described, which may be problematic upon analyzing large volumes of data. Our proposal for a new terminology will enhance the accuracy and consistency of information for the correct analysis of cutaneous adverse reactions.
Assuntos
Dermatologia/normas , Toxidermias/classificação , Eritema Multiforme/diagnóstico , Exantema/diagnóstico , Terminologia como Assunto , Toxidermias/diagnóstico , Eritema Multiforme/induzido quimicamente , Exantema/induzido quimicamente , Feminino , Humanos , MasculinoRESUMO
Biologics have been shown to constitute a highly effective treatment for patients with psoriasis. However, a significant number of patients treated with biologics will discontinue them due to loss of efficacy over time, a phenomenon known as biologic fatigue or secondary failure. Combination therapy of biologics with other agents can be considered as a treatment option in such cases. Information regarding the efficacy and safety of adding apremilast to biologic therapy in patients with psoriasis is limited. In the present study, we retrospectively evaluated the efficacy and safety of apremilast combined with biologics in 14 patients with psoriasis showing biologic fatigue at a single hospital. Before the addition of apremilast, the mean Psoriasis Area and Severity Index (PASI) score was 3.2 ± 0.4. At week 24 following the addition of apremilast, the mean PASI score decreased to 1.6 ± 0.3, and four (29%) and seven (50%) patients had achieved 75% and 50% reduction in PASI score, respectively. During the 24 weeks of treatment, diarrhea was observed in four patients, and diarrhea and nausea were observed in one patient. Weight loss of more than 5% bodyweight was observed in two patients. None of the patients discontinued therapy because of these side-effects. These results suggest that the combination therapy of apremilast and biologics could be a safe, effective option for the management of patients with psoriasis showing biologic fatigue.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Produtos Biológicos/uso terapêutico , Fármacos Dermatológicos/uso terapêutico , Psoríase/tratamento farmacológico , Talidomida/análogos & derivados , Adulto , Idoso , Anti-Inflamatórios não Esteroides/efeitos adversos , Produtos Biológicos/efeitos adversos , Fármacos Dermatológicos/efeitos adversos , Diarreia/induzido quimicamente , Quimioterapia Combinada/efeitos adversos , Tolerância a Medicamentos , Humanos , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Estudos Retrospectivos , Índice de Gravidade de Doença , Talidomida/efeitos adversos , Talidomida/uso terapêutico , Redução de PesoAssuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos/efeitos adversos , Leucemia-Linfoma de Células T do Adulto/tratamento farmacológico , Síndrome de Stevens-Johnson/imunologia , Linfócitos T/imunologia , Idoso , Biópsia , Feminino , Fatores de Transcrição Forkhead/metabolismo , Humanos , Prednisolona/administração & dosagem , Pele/patologia , Síndrome de Stevens-Johnson/tratamento farmacológico , Síndrome de Stevens-Johnson/patologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/metabolismoRESUMO
Treatment with tumor necrosis factor-α inhibitors has been reported to cause weight gain in patients with psoriasis; however, limited information is available in terms of the effects of interleukin (IL)-23 and IL-17A inhibitors on bodyweight (BW) in patients with psoriasis. This study aimed to investigate the effects of infliximab, ustekinumab and secukinumab on BW and body mass index (BMI) in patients with psoriasis. We retrospectively examined changes in BW and BMI among patients treated with these biologics at our hospital. At baseline, no significant differences in BW and BMI were observed among the patients treated with infliximab (n = 18), ustekinumab (n = 30) or secukinumab (n = 20). After 7 months of the therapy, significant increases in mean BW (from 71.4 to 74.3 kg) and mean BMI (from 24.7 to 25.7) were observed in the patients treated with infliximab, whereas no significant changes were observed in those treated with ustekinumab (BW, from 70.3 to 70.1 kg; BMI, from 25.4 to 25.3) or secukinumab (BW, from 69.0 to 68.9 kg; BMI, from 25.2 to 25.2). There were no differences in the proportion of the patients who showed 75% or more improvement in the Psoriasis Area and Severity Index among the three groups. These results suggest that infliximab increases BW in the patients with psoriasis, whereas ustekinumab and secukinumab do not affect the BW in these patients.
Assuntos
Produtos Biológicos/farmacologia , Índice de Massa Corporal , Peso Corporal/efeitos dos fármacos , Fármacos Dermatológicos/farmacologia , Psoríase/tratamento farmacológico , Adulto , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Produtos Biológicos/uso terapêutico , Fármacos Dermatológicos/uso terapêutico , Feminino , Humanos , Infliximab/farmacologia , Infliximab/uso terapêutico , Interleucina-17/antagonistas & inibidores , Subunidade p19 da Interleucina-23/antagonistas & inibidores , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do Tratamento , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Ustekinumab/farmacologia , Ustekinumab/uso terapêuticoAssuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais/efeitos adversos , Fármacos Dermatológicos/efeitos adversos , Toxidermias/etiologia , Doenças Palpebrais/induzido quimicamente , Dermatoses Faciais/induzido quimicamente , Interleucina-17/antagonistas & inibidores , Psoríase/tratamento farmacológico , Corticosteroides/uso terapêutico , Adulto , Idoso de 80 Anos ou mais , Toxidermias/diagnóstico , Toxidermias/tratamento farmacológico , Doenças Palpebrais/diagnóstico , Doenças Palpebrais/tratamento farmacológico , Dermatoses Faciais/diagnóstico , Dermatoses Faciais/tratamento farmacológico , Feminino , Humanos , Interleucina-17/imunologia , Masculino , Pessoa de Meia-Idade , Psoríase/diagnóstico , Psoríase/imunologia , Resultado do TratamentoRESUMO
BACKGROUND: Drug rash with eosinophilia and systemic symptoms (DRESS), also known as drug-induced hypersensitivity syndrome, is characterized by severe drug-induced reactions with extensive cutaneous lesions and visceral involvement. Although T cell-mediated hypersensitivity reactions to drugs may be involved in the pathogenesis of DRESS, there is limited data regarding the T-cell phenotypes responsible for the pathogenesis of DRESS. OBJECTIVE AND METHODS: Using flow cytometry, we investigated the cytokine profiles and cutaneous lymphocyte antigen (CLA) expression in circulating T cells in patients with DRESS. RESULTS: The proportions of circulating IL-4- and IL-13-producing CD4+ T cells, but not CD8+ T cells, were significantly higher in patients with DRESS during the active stage of the disease than in healthy subjects, and these proportions declined during the recovery stage. No differences in the proportions of circulating IFN-γ-, IL-17-, and IL-22-producing CD4+ and CD8+ T cells were observed between patients with DRESS and healthy subjects. A strong correlation between the proportion of IL-13-producing CD4+ T cells and serum levels of thymus and activation-regulated chemokine was observed. The proportion of CLA-expressing CD4+ T cells was significantly higher during the active stage of the disease. Moreover, the proportion of IL-13-producing CD4+ T cells was higher in the CLA+ subset than in the CLA- subset. CONCLUSIONS: Skin-homing IL-13-producing CD4+ T cells may be involved in the pathogenesis of DRESS.
Assuntos
Antígenos de Diferenciação de Linfócitos T/metabolismo , Linfócitos T CD4-Positivos/metabolismo , Síndrome de Hipersensibilidade a Medicamentos/sangue , Síndrome de Hipersensibilidade a Medicamentos/imunologia , Interleucina-13/metabolismo , Glicoproteínas de Membrana/metabolismo , Receptores de Retorno de Linfócitos/metabolismo , Adulto , Contagem de Linfócito CD4 , Relação CD4-CD8 , Linfócitos T CD8-Positivos/metabolismo , Quimiocina CCL17/sangue , Feminino , Humanos , Interleucina-4/metabolismo , Pessoa de Meia-IdadeAssuntos
Carcinoma de Células Escamosas/patologia , Segunda Neoplasia Primária/patologia , Nevo Sebáceo de Jadassohn/patologia , Neoplasias Cutâneas/patologia , Encéfalo/diagnóstico por imagem , Carcinoma de Células Escamosas/cirurgia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Segunda Neoplasia Primária/cirurgia , Nevo Sebáceo de Jadassohn/cirurgia , Neoplasias Cutâneas/cirurgia , TroncoRESUMO
We report a case of immunoglobulin G4-related disease (IgG4-RD) which presented with prurigo on the trunk and extremities. A 66-year-old man had a 2-month history of itchy erythematous papules on his trunk and extremities. Bilateral eyelid swelling and enlargement of the submandibular and parotid glands were also observed. Computed tomography revealed pleural thickening and diffuse pancreatic enlargement. Serum levels of IgG4 were markedly increased. A biopsy specimen obtained from an erythematous papule showed a perivascular inflammatory infiltrate of lymphocytes with eosinophils in the dermis, whereas a parotid gland biopsy revealed an infiltrate of abundant IgG4-positive plasma cells. Treatment with prednisolone resulted in improvement of the skin and other lesions along with a decrease in IgG4 serum levels. A flow cytometric assay revealed that percentages of interleukin (IL)-4- and IL-13-producing CD4(+) T cells were markedly higher in the circulation of the IgG4-RD patient than in that of healthy subjects. Moreover, those populations dramatically decreased after treatment. Thus, prurigo may be a skin manifestation of IgG4-RD and T-helper 2 cells may contribute to the pathogenesis.
Assuntos
Doenças Autoimunes/diagnóstico , Imunoglobulina G/imunologia , Prednisolona/uso terapêutico , Prurigo/imunologia , Células Th2/imunologia , Idoso , Doenças Autoimunes/sangue , Doenças Autoimunes/tratamento farmacológico , Doenças Autoimunes/patologia , Azatioprina/uso terapêutico , Biópsia , Linfócitos T CD4-Positivos/metabolismo , Quimiocina CCL17/sangue , Derme/citologia , Derme/patologia , Eosinófilos/patologia , Citometria de Fluxo , Humanos , Imunoglobulina E/sangue , Imunoglobulina G/sangue , Imunossupressores/uso terapêutico , Interleucina-13/metabolismo , Interleucina-4/metabolismo , Aparelho Lacrimal/diagnóstico por imagem , Imageamento por Ressonância Magnética , Masculino , Glândula Parótida/citologia , Glândula Parótida/patologia , Plasmócitos/metabolismo , Prurigo/tratamento farmacológico , Prurigo/patologia , Células Th2/metabolismo , Tomografia Computadorizada por Raios X , TroncoRESUMO
Eosinophilic pustular folliculitis (EPF) occurs in patients with hematological disorders. However, clinical information about hematological disorder-associated EPF is scarce. We report two cases of EPF associated with mantle cell lymphoma and reviewed the available published work on Japanese cases. We identified a total of 23 Japanese cases, including the two cases reported here, who had hematological disorder-associated EPF. Fourteen cases were associated with treatment for hematological malignancies (transplantation-related EPF) and nine cases were associated with hematological malignancies themselves (hematological malignancy-related EPF). Although the skin eruption was clinically indistinguishable between the two subtypes, transplantation-related EPF occurred on the face and trunk of young and middle-aged men and women, whereas hematological malignancy-related EPF occurred mostly on the face of older men. Peripheral blood eosinophilia was more frequently observed in transplantation-related EPF. These observations suggest variations among patients with EPF associated with hematological disorders.