it is a recombinant - dna - engineered fusion protein consisting of an extracellular ligand protein domain for tumor necrosis factor- ( tnf- ) and the constant portion of the human igg molecule1 ) . etanercept has demonstrable clinical benefits in several inflammatory arthropathies , including ra and psoriatic arthritis2 ) . despite trials indicating their safety , the wider use of tnf--blocking drugs in patients with ra has led to reports of serious infectious complications . in one study , 5 of 180 patients with rheumatic disease developed the following serious infections while taking etanercept3 ) . acute cholecystitis , septic wrist caused by staphylococcus aureus , arthroplastic hip infection caused by methicillin - resistant staphylococcus aureus , psoas abscess caused by mycobacterium avium - intracellulare , and bacteremia following colonoscopy . we report the first case of severe adenovirus pneumonia with myocarditis that developed in a patient during etanercept therapy . she had worked as a car saleswoman in pennsylvania and had arrived in seoul the day before admission . she had suffered from ra for about 20 years and had been treated with a regimen including prednisolone , methotrexate , and etanercept for 2 years . she had noticed progressive fatigue , malaise , anorexia , oral bleeding , and a weight loss of 10 kg within the previous 3 months . upon admission , her body temperature was 37.5 , blood pressure was 120/80 mmhg , pulse rate was 104 beats per minute , and respiratory rate was 18 breaths per minute . on physical examination , she appeared chronically ill with a pale conjunctiva , oral ulcer , and advanced multiple symmetrical joint deformities of both hands . her chest examination was notable for fine rales on both lower lung fields , but no murmur was noted . laboratory findings revealed hemoglobin at 7.7 g / dl , a platelet count of 40,000/mm , and a white blood cell count of 3,000/mm with 65% granulocytes , 26% lymphocytes , and 18.3% monocytes . l , alanine aminotransferase at 113 iu / l , and albumin at 2.4 g / dl . her rheumatoid factor was 2,180 iu / ml . chest radiography showed poorly - defined nodular opacities in both lower lung zones ( figure 1a ) . a ct scan of the abdomen revealed enlarged lymph nodes in the para - aortic area ( figure 1b ) . on hospital day 4 , she complained of dyspnea , and her oxygen saturation dropped below 80% while she was breathing 100% oxygen . pulmonary hemorrhage was suspected , and chest radiography showed diffuse bilateral pulmonary consolidation in both lungs ( figure 2a ) . a ct scan of the chest obtained at the same time showed diffuse consolidation that was strongly suspicious for pulmonary hemorrhage combined with pneumonia ( figure 2b ) . transthoracic echocardiography revealed minimal pericardial effusion with diffuse hypokinesia and a left ventricular ( lv ) ejection fraction of 36% . we performed a bronchoscopy that showed mucosal injection and fold thickening , but could not find a definite focus of bleeding . intravenous immunoglobulin ( 35 g / day ) was given for sepsis , and solucortef ( 50 mg / day ) was maintained for ra . treatment with azithromycin , ceftriaxone and amikacin was started , but because her condition deteriorated , these were changed to meropenem and ciprofloxacin on hospital day 10 . her condition improved , with chest radiograph showing complete resolution of previous lesions by hospital day 40 ( figure 3 ) . follow - up echocardiography showed normal lv systolic function with an ejection fraction of 70% without hypokinesia . the result of endotracheal aspiration for viruses was positive for adenovirus , which was confirmed by pcr . after discharge , she maintained oral medication including prednisolone at 10 mg per day , celecoxib at 200 mg per day , hydroxychloroquine sulfate at 300 mg per day and methotrexate at 7.5 mg per week through an outpatient clinic without complications . tnf- is a cytokine that plays a critical role in the regulation of inflammatory processes due to infection5 ) . early in the infectious process , tnf- promotes the influx of cells to the injured area to counter the inciting agent , while it subsequently helps to limit the extent of damage by inducing apoptosis and maintaining granuloma formation . these essential functions may be compromised by inhibition of tnf- via anti - tnf- blockers , so that patients who receive anti - tnf- blocking therapy are vulnerable to new or latent infection6 ) . the spectrum of pathogens causing invasive disease in patients receiving tnf- blockade therapy ranges from bacteria to more opportunistic organisms such as mycobacterium tuberculosis , cryptococcus and aspergillus6 ) . a recent review of reports from 1998 to 2002 revealed that the incidence of granulomatous infections was 74 per 100,000 using etanercept7 ) . m. tuberculosis is the most frequently reported infection in patients treated with etanercept , with a rate of 35 per 100,000 . this is much lower than the rate of 144 per 100,000 in infliximab - treated7 ) . the median time to develop the infection of m. tuberculosis was reportedly 12 weeks in patients treated with infliximab , whereas it was 46 weeks in those treated with etanercept5 ) . in clinical trials involving etanercept treatment in ra , infections of the upper respiratory tract were the most commonly reported , whereas serious infections requiring hospitalization were rare and did not increase in frequency during treatment8 ) . however , in a more recent study , serious and non - serious respiratory tract infections were significantly more common in patients receiving etanercept than in patients treated with conventional disease - modifying antirheumatic drugs ( 7.04 versus 1.75 per 100 patient - years)9 ) . as for viral infections , tnf is integral to the immune response to many pathogens , including respiratory viruses . binding of tnf cytokines to their receptors initiates several signaling pathways culminating in the activation of transcription factors , cysteine proteases , which results in apoptosis , and cytosolic phospholipase a2 , an enzyme responsible for the production of inflammatory mediators , which are involved in cytolysis by tnf10 ) . adenoviruses are non - enveloped , icosahedral dna viruses that cause a variety of clinical syndromes . the majority of these infections are self - limited , with disseminated disease occurring rarely in immunocompetent patients11 ) . involvement of the lung , liver , pancreas , heart , colon and central nervous system has been reported . possible risk factors in these disseminated cases include the underlying medical condition , prolonged hospitalization , invasive procedures , broad - spectrum antibiotics and immunosuppressive drugs11 ) . four ( 1.3% ) of 317 korean adult patients with community- acquired pneumonia were diagnosed with adenoviral pneumonia by indirect immunofluorescence staining or culture12 ) . adenoviruses can also infect the mucosal endothelium , as well as the epithelium11 ) , which can lead to life - threatening hemorrhage , as was observed in this case . furthermore , sudden decreased myocardial function without identifiable precipitating factors also developed during hospitalization , and function fully recovered without sequelae . this can be attributed to adenoviral myocarditis . since tnf- exerts widespread biological effects on immune cells , it is not surprising that tnf inhibition results in a decreased ability to control infection in both animal models and humans . in this case , we conclude that all patients should be thoroughly assessed for the presence of any possible risk factors for infection prior to commencement of etanercept therapy . we recommend close monitoring for any infections during the etanercept treatment and suggest that discontinuation of therapy may be indicated during the development of infection7 ) . further study of the relationship between etanercept therapy and respiratory viral infections may be warranted .
inhibitors of tumor necrosis factor - alpha ( tnf- ) have been approved for treating rheumatoid arthritis . 
 as one of the biological response modifiers , etanercept has also been used in the treatment of psoriatic arthritis and inflammatory bowel disease . while etanercept is effective , certain infectious complications , such as tuberculosis , fungus , and cytomegalovirus , have been reported . 
 we report the first korean case of adenoviral pneumonia in a 55-year - old female who developed disseminated adenoviral infection following etanercept treatment , which resolved after anti - tnf- discontinuation .