Legionella pneumophila pneumonia possibly due to ustekinumab therapy in a patient with Crohn's disease.

PURPOSE: A case report of Legionella pneumophila pneumonia associated with off-label use of ustekinumab in a patient with Crohn's disease (CD) is presented. SUMMARY: A 57-year-old man with longstanding CD was hospitalized with a four-day history of fever (38.5 °C), dyspnea, left pleuritic pain, and weight loss (more than 6 kg) about six weeks after beginning treatment with ustekinumab, a human monoclonal antibody approved in the United States for two indications (plaque psoriasis and psoriatic arthritis) and currently under investigation as a potential treatment for CD and other inflammatory disorders. During the preceding 25 years, the man had been treated for severe CD with a number of agents (e.g., infliximab, adalimumab, certolizumab); ultimately, off-label ustekinumab therapy (90 mg subcutaneously weekly) was initiated due to persistent severe CD symptoms. Chest x-ray studies at the time of admission demonstrated left upper lobar consolidation, and a urine antigen test was positive for L. pneumophila. The patient was treated with i.v. levofloxacin and methylprednisolone and discharged after two weeks. Ustekinumab was reintroduced (45 mg subcutaneously every two weeks), and the patient continued to receive the drug for 16 months, with clinical remission of CD symptoms and no further adverse events. A literature search identified two case reports of pneumonia associated with ustekinumab use, but neither case involved L. pneumophila. CONCLUSION: Pneumonia caused by L. pneumophila developed in a patient with CD treated with ustekinumab. Pneumonia symptoms resolved after ustekinumab was discontinued.

Pneumonia por Legionella após uso de Infliximabe em paciente com Artrite Reumatoide / Legionella pneumonia after infliximab in a patient with Rheumatoid Arthritis

Os antagonistas do fator de necrose tumoral (anti-TNF) têm sido utilizados com sucesso em várias doenças inflamatórias crônicas, como artrite reumatoide (AR), mas alguns estudos observaram a ocorrência de infecções por patógenos intracelulares em pacientes medicados com anti-TNF. Relatamos um caso de paciente mulher com diagnóstico prévio de AR durante 16 anos e que estava sendo medicada com várias drogas antirreumáticas modificadoras de doença (DARMDs), tendo como resultado o insucesso terapêutico, sendo em seguida tratada com infliximab. Depois de transcorridos 15 dias da segunda dose, a paciente foi acome- tida por dor torácica ventilatório-dependente, tosse seca e dispneia. Foi hospitalizada, e o diagnóstico de pneumonia por Legionella pneumophila foi confirmado pela presença do antí- geno de Legionella na urina. TNF é uma citocina inflamatória que também promove inibição do crescimento bacteriano de patógenos intracelulares, e sua inibição parece aumentar a sensibilidade a essas infecções em alguns pacientes.

The antagonists of tumour necrosis factor (anti-TNF) have been successfully used in several chronic inflammatory diseases such as Rheumatoid Arthritis (RA), but some studies have observed the development of infections by intracellular pathogens in patients using anti-TNF. We report a case of a female patient with previous diagnosis of RA for 16 years that used several disease-modifying anti-rheumatic drugs (DMARDs) that resulted in treatment failure, and then was treated with infliximab. After fifteen days of the second dose, the patient developed ventilatory-dependent chest pain, dry cough and dyspnea. She was hospitalized, and the diagnosis of pneumonia by Legionella pneumophila was confirmed by the presence of Legionella antigen in an urine test. TNF is an inflammatory cytokine that also acts inhibiting the bacterial growth of intracellular pathogens, and its inhibition seems to increase susceptibility to these infections in some patients.

[Legionella pneumonia after infliximab in a patient with rheumatoid arthritis]. / Pneumonia por Legionella após uso de Infliximabe em paciente com Artrite Reumatoide.

The antagonists of tumour necrosis factor (anti-TNF) have been successfully used in several chronic inflammatory diseases such as Rheumatoid Arthritis (RA), but some studies have observed the development of infections by intracellular pathogens in patients using anti-TNF. We report a case of a female patient with previous diagnosis of RA for 16 years that used several disease-modifying anti-rheumatic drugs (DMARDs) that resulted in treatment failure, and then was treated with infliximab. After fifteen days of the second dose, the patient developed ventilatory-dependent chest pain, dry cough and dyspnea. She was hospitalized, and the diagnosis of pneumonia by Legionella pneumophila was confirmed by the presence of Legionella antigen in an urine test. TNF is an inflammatory cytokine that also acts inhibiting the bacterial growth of intracellular pathogens, and its inhibition seems to increase susceptibility to these infections in some patients.

A severe complication of anti-TNF alfa treatment.

The antitumor necrosis factor (TNF-alpha) drugs are increasingly used in treating skin diseases such as psoriasis. TNF-alpha is a proinflammatory cytokine with a key role in the pathogenesis of psoriasis but also in host defence against bacterial pathogens, especially against those that multiply inside host cells. The effectiveness of anti-TNF-alpha in the treatment of psoriasis is now widely recognized and has led to their increasingly wide use. Although these drugs are considered relatively safe, their use is associated with an increased incidence of serious infections even in patients treated. Have been described above numerous cases of tuberculosis but has also observed an increased incidence of granulomatous infections by intracellular bacteria such as Legionella pneumophila required. Infections due to this biotic agent, if not diagnosed early, are potentially fatal. We report the case of a patient, heavy smoker, suffering from severe skin psoriasis who after starting treatment with infliximab developed a pneumonia caused by Legionella pneumophila. Our aim is to draw the attention of specialists on increasing risk of granulomatous infections by intracellular agents in patients being treated with anti TNF-alpha.

[Severe legionellosis after abuse of anti-inflammatory drugs--diagnostic and intensive care aspects based on a case report]. / Schwere Legionellose nach Antiphlogistika-Abusus--diagnostische und intensivtherapeutische Aspekte anhand einer Kasuistik.

Legionella infections are getting increasingly important as causes of severe pneumonias or of acute respiratory insufficiency. Consumptive or immunosuppressive underlying diseases such as diabetes mellitus, cardiac insufficiency, alcohol-induced liver damage, malignant tumours or drug-induced immunosuppression after organ transplantation, are among the risk factors. Diagnosis is based on direct identification of the pathogen from body secretions by means of direct immunofluorescence. The serological immunoresponse often takes place long after outbreak of the disease or fails entirely to appear and is therefore only suitable for retrospective confirmation. Therapy of choice is an intravenous administration of erythromycin. There are now increasing pointers to the efficiency of fluoroquinolone antibiotics, such as ciprofloxacin. We report on the course of a severe case of legionnaire's disease with multiple organ failure occurring in a patient after bone marrow depression induced by anti-inflammatory drugs. Treatment erythromycin resulted in a marked cholestasis, so that antibiotic treatment was changed to ciprofloxacin. This therapy as well as the supportive intensive-care treatment eventually led to the patient's complete recovery. Based on the case report, fundamental aspects of diagnostics, antibiotic treatment, intensive-care treatment and prognosis of severe cases of legionellosis are discussed.