Tuberculosis miliar en pacientes en tratamiento con adalimumab, una asociación no tan frecuente en pediatría / Miliary tuberculosis in patients treated with adalimumab, an association not so frequent in pediatrics

Los antagonistas del Factor de Necrosis Tumoral-α, son medicamentos que en los últimos años han tenido un incremento de su uso en pacientes con condiciones inflamatorias inmunomediadas en pediatría, como la Artritis Idiopática Juvenil y la Enfermedad Inflamatoria Intestinal. El uso de estos medicamentos en adultos tiene una fuerte asociación con la primoinfección o reactivación por Mycobacterium tuberculosis, pero en niños la evidencia es limitada. Se presentan 2 casos de pacientes tratados con adalimumab, quienes, a pesar de un buen control de su enfermedad y una prueba de tuberculina negativa al inicio de la terapia, desarrollaron tuberculosis miliar en el seguimiento, con importantes implicaciones para su salud. El tamizaje de tuberculosis latente con tuberculina/IGRAS (Interferón-γ release assays, por sus siglas en inglés) y un alto índice de sospecha de tuberculosis, son las herramientas disponibles para una adecuada identificación de la tuberculosis en pacientes que reciben crónicamente estas terapias.

Tumor Necrosis Factor-α antagonists are drugs that in recent years have seen an increase in their use in patients with immune-mediated inflammatory conditions in pediatrics such as Juvenile Idiopathic Arthritis and Inflammatory Bowel Disease. The use of these drugs in adults has a strong association with primary infection or reactivation by mycobacterium tuberculosis, but in children the evidence is limited. We present 2 cases of patients treated with adalimumab who, despite good control of their disease and a negative tuberculin test at the beginning of therapy, developed miliary tuberculosis during follow-up with important implications for their health. Screening for latent tuberculosis with tuberculin / IGRAS (Interferón-γ release assays) and a high index of suspicion for tuberculosis are the tools available for an adequate identification of tuberculosis in patients who receive these therapies chronically.

Herpetic whitlow in a child with AIDS: the importance of Tzanck test in the diagnosis

Abstract Herpetic whitlow is a viral infection of the fingers caused by the herpes simplex virus. The disease has a bimodal age distribution, affecting children under 10 years of age and young adults between 20 and 30 years old. It can be easily mistaken for panaritium or bacterial cellulitis. In patients with AIDS, atypical, chronic and recurrent ulcerated lesions occur. The Tzanck test allows a quick and low-cost diagnosis of herpes simplex virus infection. The authors report the case of a child with AIDS with painful finger ulcers in which the diagnosis was confirmed by the Tzanck test.

Interstitial lung disease due to anti-TNF use in the treatment of psoriasis

Abstract Psoriasis is a chronic inflammatory disease that affects the skin variably, according to genetic and environmental factors. Some patients may benefit from systemic treatment with immunobiological agents, drugs that can be accompanied by several adverse effects. A case of a 58-year-old patient undergoing treatment for psoriasis with adalimumab for five years is reported. Alterations compatible with interstitial pneumonia were detected with important regression after adalimumab discontinuation. This case is relevant due to the scarcity of reports on late pulmonary adverse effect of anti-TNF treatment of psoriasis.

Psoriasis paradójica palmoplantar secundaria al tratamiento de la colitis ulcerosa con adalimumab / Paradoxical psoriasis of the palms and soles due to treatment of ulcerative colitis with adalimumab

Los anticuerpos anti-TNF-a (tumor necrosis factor alpha) se utilizan para tratar tanto la psoriasis como la enfermedad inflamatoria intestinal (EII). Sin embargo, estos fármacos han sido implicados en la ocurrencia de la psoriasis paradójica en los pacientes sin antecedentes de psoriasis que reciben tratamiento por una colitis ulcerosa (CU) y otras enfermedades autoinmunes. Se presenta el caso de un paciente de 29 años, sin antecedentes de dermatosis, que desarrolló una psoriasis palmoplantar paradójica por el uso del adalimumab que recibía por un diagnóstico de CU. El cuadro remitió al suspender el medicamento y recurrió al reiniciarlo, motivo por el cual se rotó al ustekinumab. La CU respondió satisfactoriamente, sin nuevas lesiones dermatológicas.

Anti TNF-a (tumor necrosis factor alpha) antibodies are used to treat both psoriasis and inflammatory bowel disease (IBD). However, these drugs have been implicated in the occurrence of the so-called paradoxical psoriasis in patients with no previous history of psoriasis, who receive treatment for ulcerative colitis and other autoimmune diseases. We present a 29-year-old male patient, with no previous history of dermatosis, who developed paradoxical palmar-plantar psoriasis due to the use of adalimumab that he was receiving for a diagnosis of ulcerative colitis. The condition remitted when the drug was suspended and recurred when it was restarted, and for that reason, treatment was rotated to ustekinumab. Ulcerative colitis responded satisfactorily, with no new dermatological lesions.

Three cases of anti-TNF induced myositis and literature review / Três casos de miosite induzida pelo anti-TNF e revisão da literatura

Abstract Anti-tumor necrosis factor drugs are frequently preferred in the treatment of rheumatologic diseases and other inflammatory diseases. The development of myositis after using anti-tumor necrosis factor drugs is a rare clinical condition. Here we aimed to report cases who developed myositis after using anti-tumor necrosis factor drugs and review the current literature. We report two cases of rheumatoid arthritis and a case of ankylosing spondylitis developed idiopathic inflammatory myopathy following anti-tumor necrosis factor therapy. In conclusion, myositis could develop during anti-tumor necrosis factor therapy, so these patients should be evaluated carefully initially for myositis and should be closely monitored due to the potential for developing myositis in treatment process.

Resumo Os fármacos antifator de necrose tumoral (anti-TNF) são frequentemente preferidos no tratamento de doenças reumatológicas e outras doenças inflamatórias. O desenvolvimento de miosite após o uso de anti-FNT é uma condição clínica rara. Este estudo objetivou descrever casos de pacientes que desenvolveram miosite após o uso de anti-TNF e fazer uma revisão da literatura atual. Descrevem-se dois casos de artrite reumatoide (AR) e um caso de espondilite anquilosante (EA) que desenvolveram miopatia inflamatória idiopática após o tratamento com anti-TNF. Em conclusão, pode haver desenvolvimento de miosite durante o tratamento com anti-TNF, de modo que esses pacientes devem ser cuidadosamente avaliados inicialmente à procura de miosite e devem ser cuidadosamente monitorados em razão do potencial de desenvolvimento de miosite no processo de tratamento

Perfil de segurança da terapia anti-TNF na doença de Crohn: um estudo observacional brasileiro comparativo entre infliximabe e adalimumabe / Safety profile of anti-tnf therapy in crohn's disease management: a brazilian single-center direct retrospective comparison between infliximab and adalimumab

ABSTRACT BACKGROUND: Infliximab and adalimumab are considered effective drugs in the management of Crohn's disease. However, due to significant immunossupression, they can cause important adverse events, mostly infections. OBJECTIVE: The aim of this study was to quantify and describe adverse events derived from adalimumab and infliximab use in Crohn's disease patients, and to compare the safety profile between these two agents. METHODS: This was an observational, single-center, longitudinal, retrospective study with Crohn's disease patients under infliximab or adalimumab therapy. Variables analyzed: demographic characteristics (including the Montreal classification), type of agent used, concomitant immunomodulators, presence and types of adverse events observed. Patients were allocated in two groups (infliximab and adalimumab) and had their adverse events accessed and subsequently compared. RESULTS: A total of 130 patients were included (68 in infliximab and 62 in adalimumab groups, respectively). The groups were fully homogeneous in all baseline characteristics, with a median follow-up of 47.21±36.52 months in the infliximab group and 47.79±35.09 in the adalimumab group (P=0.512). Adverse events were found in 43/68 (63.2%) and 40/62 (64.5%) in each group, respectively (P=0.879). There were no differences between the groups regarding infections (P=0.094) or treatment interruption (P=0.091). There were higher rates of infusion reactions in the infliximab group (P=0.016). Cephalea and injection site reactions were more prevalent in adalimumab patients. CONCLUSION: Adverse events were found in approximately two thirds of Crohn's disease patients under anti-TNF therapy, and there were no significant differences between infliximab or adalimumab.

RESUMO CONTEXTO: A utilização de inibidores do fator de necrose tumoral (TNF) alfa no manejo da doença de Crohn é cada vez mais frequente. Tanto o infliximabe quanto o adalimumabe são considerados medicamentos efetivos no controle da doença. Entretanto, por serem potentes imunossupressores, podem causar efeitos adversos importantes, principalmente infecções. OBJETIVO: O objetivo primário deste estudo foi analisar a presença de efeitos adversos dos anti-TNFs em portadores de doença de Crohn, comparando-se infliximabe e adalimumabe e individualizando-se o perfil de segurança de cada droga. MÉTODOS: Estudo observacional, longitudinal e retrospectivo, que incluiu portadores de doença de Crohn com uso de infliximabe ou adalimumabe de uma coorte de pacientes tratados em um único centro. Analisou-se características demográficas (incluindo-se a classificação de Montreal), tipo de agente utilizado, presença e tipo dos eventos adversos observados, entre outras variáveis. Os pacientes foram alocados em dois grupos (infliximabe e adalimumabe) e tiveram os efeitos adversos anotados e posteriormente comparados. RESULTADOS: Um total de 130 pacientes foram incluídos (68 com infliximabe e 62 com adalimumabe). Os grupos foram homogêneos em todas as variáveis analisadas, com tempo de seguimento médio de 47,21±36,52 meses no grupo infliximabe e 47,79±35,09 no grupo adalimumabe (P=0,512). Efeitos adversos foram encontrados em 43/68 (63,2%) e 40/62 (64,5%) nos dois grupos, respectivamente (P=0,879). Não houve diferença entre os grupos em relação a infecções (P=0,094) ou interrupção do tratamento (P=0,091). Houve maiores índices de reações infusionais no grupo infliximabe (P=0,016). Cefaleia e reações no local das injeções foram mais frequentes no grupo adalimumabe. CONCLUSÃO: Efeitos adversos foram encontrados em cerca de dois terços dos pacientes com doença de Crohn em uso de anti-TNF, não havendo maiores diferenças em relação ao uso de infliximabe ou adalimumabe.

Guillain-Barré syndrome in a patient on adalimumab for the treatment of psoriasis

Abstract The use of TNF-α inhibitors for the treatment of moderate to severe psoriasis and psoriatic arthritis is increasingly more frequent. The authors report a case of Guillain-Barré syndrome as a late manifestation of the treatment with adalimumab. Although unusual, this is relevant for professionals who prescribe biologic drugs. We also stress the importance of investigating the past and family medical history regarding demyelinating diseases before starting treatment.

Paradoxical psoriasis after the use of anti-TNF in a patient with rheumatoid arthritis

Abstract The use of tumor necrosis factor antagonists (anti-TNF) has become a usual practice to treat various inflammatory diseases. Although indicated for the treatment of psoriasis, anti-TNF may paradoxically trigger a psoriasiform condition. We present a case of a female patient who, during the use of infliximab for rheumatoid arthritis, developed psoriasis. In an attempt to switch anti-TNF class, we observed a cumulative worsening of the lesions requiring suspension of the immunobiological agent and the introduction of other drugs for clinical control. The therapeutic challenge of this paradoxical form of psoriasis is the focus of our discussion. The use of another anti-TNF in these patients is a matter of debate among experts.

Drug-induced lupus with leukocytoclastic vasculitis: a rare expression associated with adalimumab

TNF alpha antagonist-induced lupus-like syndrome is a rare condition which predominantly affects women (4:1). The average age of onset is 46-51 years. It occurs after exposure to TNF alpha antagonist and disappears after discontinuation of such agents. The pathogenic mechanism for development of the TNF alpha antagonist-induced lupus-like syndrome is not fully defined. It is believed that the medication induces apoptosis, leading to an accumulation of nucleosomal antigens of apoptotic cells. This would cause autoantibodies to be produced by susceptible individuals. The most common cutaneous manifestations include maculopapular exanthem, malar rash, alopecia, photosensitivity and, more rarely, vasculitis. Extracutaneous manifestations include: fever, weight loss, arthritis or arthralgia, myositis and hematological abnormalities. Antinuclear antibody may be positive in 80% of cases and anti-histone antibody is considered a disease marker for TNF alpha antagonist-induced lupus-like syndrome. Treatment corresponds to drug discontinuation. We report a rare case of sub-acute cutaneous lupus erythematosus with leukocytoclastic vasculitis induced by adalimumab in a 42-year-old patient.

Perfuração do colo por colite amebiana invasiva durante terapia anti-TNF para espondiloartrite / Colonic perforation due to invasive amebic colitis during anti-TNF therapy for spondyloarthritis

O bloqueio do TNF tem tido sucesso no tratamento de algumas doenças reumáticas, como a espondiloartrite. Relatam-se muitas complicações infecciosas com a terapia anti-TNF, principalmente infecções bacterianas, micobacterianas, virais e fúngicas. A Entamoeba histolytica é um protozoário extracelular que causa principalmente colite e abscesso hepático, sendo que a perfuração intestinal é uma complicação rara, com alta mortalidade. O TNF é considerado o principal mediador da imunidade celular contra a amebíase. Inicialmente, é quimiotático para a E. histolytica, potencializando sua adesão ao enterócito por meio da lectina galactose-inibível, e depois ativando os macrófagos para matarem a ameba pela liberação de NO; assim, o bloqueio do TNF poderia ser prejudicial, aumentando a virulência amebiana. Descreve-se o caso de uma mulher de 46 anos com espondiloartrite que apresentou uma perfuração do colo por colite amebiana invasiva durante uso de anti-TNF.

TNF blockade has been successful in the treatment of some rheumatic diseases such as spondyloarthritis. Many infectious complications have been reported with anti-TNF therapy, mainly bacterial, mycobacterial, viral and fungal infections. Entamoeba histolytica is an extracellular protozoan parasite that mainly causes colitis and hepatic abscess; bowel perforation is an uncommon complication with high mortality. TNF is considered the principal mediator of cell immunity against amebiasis. Initially, it is chemotactic to E. histolytica, enhancing its adherence to enterocyte via galactose inhibitable lectin, and then activating macrophages to kill ameba though the release of NO, so that TNF blocking could be harmful, increasing amebic virulence. We describe the case of a 46-year-old woman with spondyloarthritis who presented a colonic perforation due to invasive amebic colitis during anti-TNF use.

Comparative analysis of adverse events between infliximab and adalimumab in Crohn's disease management: a Brazilian single-centre experience / Análise comparativa dos eventos adversos entre infliximabe e adalimumabe no tratamento da doença de Crohn: experiência em um centro brasileiro

INTRODUCTION: Data is scarce regarding adverse events (AE) of biological therapy used in the management of Crohn's Disease (CD) among Brazilian patients. OBJECTIVES: To analyse AE prevalence and profile in patients with CD treated with Infliximab (IFX) or Adalimumab (ADA) and to verify whether there are differences between the two drugs. METHOD: Retrospective observational single-centre study of CD patients on biological therapy. Variables analysed: Demographic data, Montreal classification, biological agent administered, treatment duration, presence and type of AE and the need for treatment interruption. RESULTS: Forty-nine patients were analysed, 25 treated with ADA and 24 with IFX. The groups were homogeneous in relation to the variables studied. The average follow-up period for the group treated with ADA was 19.3 months and 21.8 months for the IFX group (p = 0.585). Overall, 40% (n = 10) of patients taking ADA had AE compared with 50% (n = 12) of IFX users (p = 0.571). There was a tendency towards higher incidence of cutaneous and infusion reactions in the IFX group and higher incidence of infections in the ADA treated group, although without significant difference. CONCLUSIONS: No difference was found in the AE prevalence and profile between ADA and IFX CD patients in the population studied. (AU)

INTRODUÇÃO: Há poucos dados sobre os eventos adversos (EA) da terapia biológica usada no tratamento da doença de Crohn (DC) entre os pacientes brasileiros. OBJETIVOS: Analisar a prevalência dos EA e o perfil dos pacientes com DC tratados com Infliximabe (IFX) ou Adalimumabe (ADA) e verificar se há diferenças entre esses dois fármacos. MÉTODO: Estudo observacional e retrospectivo de pacientes com DC em terapia biológica, realizado em centro único. As variáveis analisadas foram: dados demográficos, classificação de Montreal, agente biológico administrado, duração do tratamento, presença e tipo de EA e necessidade de interrupção do tratamento. RESULTADOS: Quarenta e nove pacientes foram analisados, 25 tratados com ADA e 24 com IFX. Os grupos eram homogêneos em relação às variáveis estudadas. O período médio de acompanhamento foi de 19,3 meses para o grupo tratado com ADA e de 21,8 meses para o grupo tratado com IFX (p = 0,585). No total, 40% dos pacientes (n = 10) que receberam ADA tiveram AE, em comparação com 50% dos pacientes (n = 12) que receberam IFX (p = 0,571). Houve uma maior incidência de reação cutânea e à infusão no grupo IFX e de infecções no grupo ADA, embora sem diferença significativa. CONCLUSÃO: Não houve diferença na prevalência de EA e no perfil dos pacientes com DC que receberam ADA e IFX. (AU)