Rituximab induced acute respiratory distress syndrome (ARDS) reversed with plasmapheresis: case report

¹Department of Anesthesiology and Intensive Care, Military Hospital Mohammed V, Faculty of Medicine and Pharmacy of Rabat, Mohammed V University, Rabat, Morocco

^&Corresponding author
Bouaiyda Ayoub, Department of Anesthesiology and Intensive Care, Military Hospital Mohammed V, Faculty of Medicine and Pharmacy of Rabat, Mohammed V University, Rabat, Morocco

Introduction    

Rituximab is a chimeric Anti-CD20 anti-body initially used in the treatment of non-Hodgkin´s B-cell lymphoma. Currently, the field of use has become wider, particularly in rheumatoid arthritis and cryoglobulinemia [1]. Despite the results in terms of therapeutic efficiency, rituximab has been implicated in numerous adverse events [2]. We´re here to report the case of a female patient with post-viral C cryoglobulinemia who developed ARDS following rituximab infusion.

Patient and observation     

A 69-year-old female patient was admitted to the intensive care unit for respiratory distress. In her antecedents we find a viral hepatitis C treated 10 years ago complicated by cryoglobulinemia, put on anti-CD20, which last cure was 5 days before her admission to the hospital. The history of the disease goes back to 3 days after the last infusion, following the appearance of dyspnea with a cough. Initially, the patient was treated as acute bronchitis put under symptomatic treatment by her attending physician without improvement. The evolution was marked by the appearance of respiratory distress which led to her admission to the emergency room and then to the intensive care unit. The patient was conscious, hemodynamically stable with signs of respiratory distress. Blood gas analysis showed hypoxia and hypocapnia, which led to a thoracic angio-scan that showed a bilateral diffuse interstitial syndrome involving all 2 pulmonary fields with bilateral pleurisy of low abundance without signs of pulmonary embolism (Figure 1). The patient received iterative sessions of non-invasive ventilation and was placed on broad-spectrum antibiotics, antiviral drugs, and corticosteroids. The check-ups performed showed deep hypogammaglobulinemia at 2.6 g/l, white blood cells at 29,000 elements/mm³, CRP at 32 mg/l, procalcitonin at 0.7 and acute renal failure at 1.50 g/l urea and creatinine at 10 mg/l and hemoglobin at 10 g/dl. Several etiological hypotheses have been evoked: notably the infectious cause, but the virologic research by FilmArray came back negative including CMV serology and the research for urine-soluble antigens. The cardiac origin was also evoked, but a cardiac ultrasound scan showed a defective left ventricle with left ventricular ejection fraction (LVEF) at 30-40%. But the filling pressures were low which eliminated a cardiac pulmonary overload.

The patient received a polyvalent immunoglobulin cure in front of the hypogammaglobulinemia, always without improvement. In front of the deterioration of her clinical state, we decided to intubate the patient. Following the intubation, the patient showed a decrease in the need for oxygen and positive end expiration pressure (PEEP). In view of this clinical presentation, the most plausible diagnosis remains a side effect of the treatment. Thus, after a multi-disciplinary consultation, it was decided to put the patient on boluses of 500mg of methylprednisolone for 3 days and discussion of plasmapheresis. In the absence of improvement with corticosteroids, plasmapheresis was initiated, the patient underwent 2 sessions, the evolution was marked by an improvement of her hematosis with a radiological cleaning allowing the patient to be extubated (Figure 2). The patient was conscious but very hypotonic with difficulties to cough and expectorate which required non-invasive ventilation and respiratory kinesitherapy, 24 hours later. The patient's exhaustion was resolved by reintubation. The patient subsequently developed hemodynamic instability with anuria requiring the introduction of vasoactive drugs. An echocardiogram was carried out, showing signs of hypovolemia, a filling was carried out under ultrasound control, still without improvement, with major metabolic acidosis on blood gas analysis. an attempt to connect the patient to the hemodialysis machine was not tolerated. the patient is subsequently deceased in a hypoxic state with refractory shock and multi-visceral failure.

Discussion     

Rituximab is a human/mouse anti-CD20 chimeric antibody that appeared in the 2000s as a treatment for Hodgkin´s lymphoma, nowadays its spectrum of use has become wider, especially for other types of hematological malignancies as well as for autoimmune diseases such as rheumatoid arthritis and cryoglobulinemia. It binds to the CD 20 antigen expressed on the surface of most malignant B cells but also on the surfaces of normal B lymphocytes and its precursors while sparing other elements of the plasma. In spite of its therapeutic efficacy, its involvement in numerous undesirable effects has been demonstrated, ranging in severity from a simple skin rash to serious systemic damage [2]. Pulmonary impairment of Rituximab (RTX) has been reported in the literature since the beginning of its use [3], the respiratory manifestations ranged from simple transient manifestations to true respiratory distress with the need for mechanical ventilation. Acute respiratory distress syndrome is one of the fatal complications described, and to the best of our knowledge, it has been poorly reported in the literature [4-6]. The exact pathophysiology of lung involvement is still unclear, but immunological involvement is clearly demonstrated. it is probably due to immune complex deposition on the alveolar-capillary membrane responsible for inflammation with capillary leakage, or it is secondary to an inflammatory reaction following repeated RTX infusions [7].

Plasmapheresis is an extracorporeal technique that allows for to subtract pathogenic macromolecules from the blood. it has become a frequently used and relatively safe technique. Recognized indications for plasmapheresis include neurological, renal, hematological pathologies as well as systemic diseases. It is based on the separation of whole blood into plasma and cellular elements, the oldest technique is unfractionated plasmapheresis, which consists of removing the plasma obtained or replacing it with fresh frozen plasma (FFP) or albumin. Currently, technological progress has led to the development of a technique that allows the extraction only of the macromolecules involved in the pathology in question, known as fractionated plasmapheresis, the separation process can be done in two ways: either by centrifugation or by highly permeable filters [8]. To the best of our knowledge, the use of plasmapheresis in RTX-linked ARDS was reported to have resulted in a spectacular improvement in the patient's hematosis with radiological cleaning, allowing ventilatory withdrawal and extubation of the patient. However, the type of plasmapheresis was not specified [9]. Other treatments have been described for the management of ARDS related to RTX, notably extra corporeal membrane oxygenation (ECMO), which according to the authors, allowed a rapid regression of lesions and an improvement of oxygenation [6], in the case of our patient we did not have this possibility given the unavailability of the device. As for our patient, the plasmapheresis sessions allowed a notable improvement of her gasometric parameters with an improvement of the radiological images, unfortunately, her hypotonia with her altered cardiac function probably prevented her improvement.

Conclusion     

Acute respiratory distress syndrome (ARDS) related to RTX infusion is a rare pathology and the treatment modalities of this entity are poorly described, we think that plasmapheresis should be among the pioneer arms in its treatment, the rarity of similar cases makes it difficult to carry out studies to prove its effectiveness and its possible undesirable effects.

Competing interests     

The authors declare no competing interests.

Authors' contributions     

AB and AJ examined the patient and drafted the manuscript. HB evaluated the findings and gave important clinical opinions. CC and MK participated in the design of the case report and helped to draft the manuscript. All authors read and approved the final manuscript.

Acknowledgments     

We would like to thank the cooperation from the patient's family.

Figures     

Figure 1: thoracic CT scan that show a bilateral diffuse interstitial syndrome involving all 2 pulmonary fields with bilateral pleurisy of low abundance

Figure 2: the evolution of the radiological images which show an improvement after plasmapheresis sessions; A) after the first session; B) after the second session

References