Teaching Case

A 63-year-old patient presented at the emergency department with progressive dyspnea over the last week and fever (38.5 ^o C). There was also mild non-productive cough. The patient was under treatment of a follicular B-cell lymphoma, receiving chemotherapy according to the CHOP scheme including rituximab (CHOP-R).

A 63-year-old man presented at the emergency department with progressive dyspnoea over the last week and fever (38.5 ^o C). There was also mild non-productive cough. The patient was under treatment of a follicular B-cell lymphoma, having been diagnosed 5 months prior to the admission. He actually received chemotherapy with CHOP-R, the last time about three weeks before admission. The patient showed elevated C-reactive protein and an elevated white cell count. On admission an ECG was recorded, which showed signs of right heart dysfunction and sinus tachycardia. A standard chest radiograph showed diffuse reticular densities with an area of beginning consolidation in the right upper lobe (Figure 1). In a chest CT scan pulmonary embolism could be ruled out, but an interstitial disease pattern with patchy areas with ground glass attenuation and reticular densities and some areas of consolidation was found. There were no signs of pulmonary fibrosis and no pleural effusions (Fig. 2). Given the clinical picture the diagnosis of an atypical pneumonia was made and a therapy with antibiotics and corticosteroids was initiated. Bronchoalveolar lavage was performed, but all bacterial, viral and fungal cultures were negative. Because of the negative microbiological cultures the observed good response to the applied corticosteroids the diagnosis of a rituximab induced pneumonitis was made. The control scan two weeks after the initiation of therapy showed a marked improvement and the patient could leave the hospital soon thereafter (Fig. 3).

Rituximab is a chimeric antibody, directed against the CD20-antigen of lymhocytes. It has been first approved in 1997 and is now part of the standard therapy of CD20+ non- Hodgkin’s lymphomas and is also used in a wide variety of autoimmune diseases, for example rheumatoid arthritis or idiopathic thrombocytopenic purpura [1]. Common side effects are fever, chills, headache and vomiting at the time of application. These infusion related reaction can be diminished with the use of paracetamol and antihistaminergics. Rituximab is considered to be a safe treatment and pulmonary drug reactions after rituximab have been considered a rare event [2]. About 10 years after the approval of rituximab Heresi et al. reported about 21 cases in the literature [3]. In contrast, pulmonary drug reactions have been reported in 9% of patients in a recently published series of 108 patients undergoing treatment with rituximab [4]. This data warrants confirmation, but it could be that rituximab induced lung damage is more common than previously reported. Pathogenesis is unclear, however a dysregulation of the immune system is proposed. In most cases bilateral areas of alveolar or interstitial infiltrations with a patchy appearance on imaging is reported, but also the picture of cryptogen organizing pneumonia has been reported [1, 3]. The clinical picture is not uniform and lethal cases due to ARDS are reported [1]. Diagnosis is not straight forward because a wide range of differential diagnosis has to be considered, specifically opportunistic infections. In clinical practice the diagnosis is usually made using exclusion. Therapy consists of corticosteroids and the response to them is prognostically important [1, 3].
In conclusion, pulmonary drug reactions following the use of rituximab are a rare entity in clinical practice. But as its prevalence may be underestimated and its use increases, radiologists should be aware of this side effect and consider it in their differential diagnosis in the proper clinical context.