Diffuse alveolar hemorrhage during alemtuzumab infusion in a patient with multiple sclerosis: a case report

Abstract

BackgroundDiffuse alveolar bleeding is a potentially life-threatening condition that can be induced by several drugs. Whereas fatal cases have been reported in patients treated for other indications, no report have so far been published in a patient with multiple sclerosis treated with alemtuzumab.Case presentationWe report a case of alemtuzumab-induced diffuse alveolar bleeding in a 29 year old woman with relapsing remitting multiple sclerosis. The patient developed acute shortness of breath, chest pain on inspiration and haemoptysis following the second infusion of alemtuzumab during the first treatment cycle. Computed tomography showed bilateral alveolar opacities. Bronchoscopy and broncho-alveolar lavage showed persistently bloody return with no evidence of infection. The symptoms resolved completely without treatment and control computed tomography performed one week later showed total resolution of pulmonary infiltrates.ConclusionThis is the first published report of diffuse alveolar bleeding in a patient with multiple sclerosis treated with alemtuzumab. Four similar cases in patients treated for multiple sclerosis and several fatal cases in patients treated for other conditions are registered at the World Health Organization database of suspected adverse events (VIgiBase©), underscoring that this is a serious and possibly under-recognized complication of alemtuzumab which can also occur in the treatment of multiple sclerosis. The clinician should consider the possibility of diffuse pulmonary haemorrhage in patients with sudden onset of respiratory distress and haemoptysis following administration of alemtuzumab for multiple sclerosis.

Alemtuzumab-induced simultaneous onset of autoimmune haemolytic anaemia, alveolar haemorrhage, nephropathy, and stroke: A case report

“…CT scan was performed and showed ground-glass opacities suggesting DAH that was confirmed with bronchoscopy. Alemtuzumab was reported in several cases to be the probable cause of DAH, particularly, five cases were associated with this phenomenon during MS therapy (Myro et al, 2018). DAH was reported to present within days of infusion initiation and even after a few sessions in others.…”

“…Here, we report the second possible complication, alemtuzumabinduced diffuse alveolar haemorrhage. Diffuse alveolar haemorrhage (DAH) is a life-threatening condition due to injury of the pulmonary vascular microcirculation that can be caused by multiple aetiologies such as coagulopathy, infections, and drugs (Myro et al, 2018). DAH commonly presents as cough, dyspnoea, and haemoptysis in nearly 30% of patients.…”

Alemtuzumab-associated diffuse alveolar damage – a case report

“…The mechanism underlying alemtuzumab induced DAD is unknown. In diffuse alveolar hemorrhage after alemtuzumab treatment, it has been speculated that alemtuzumab induced effector mechanisms lead to acute inflammation that may damage membranes and cells not expressing CD52 [ 2 ].…”

“…Well-known side effects include an increased infection rate including respiratory tract infections and secondary autoimmune reactions mainly consisting of thyroid disorders, immune thrombocytopenia, anti-glomerular basement membrane (GBM) disease and membranous glomerulonephritis, which may occur after years of first treatment. Since its approval by the European Medicines Agency (EMA) in 2013, non-infective respiratory tract side effects causing dyspnea have been reported in patients treated with alemtuzumab including diffuse alveolar hemorrhage [ 2 ], pneumonitis [ 3 ], anti-GBM antibody disease [ 4 ] and acute respiratory distress syndrome (ARDS) [ 5 ]. Five cases of diffuse alveolar damage (DAD) associated with alemtuzumab have been reported to VigiBase©, the World Health Organization’s international database for suspected adverse drug reactions [ 6 ], without providing further details on treated disorders or other potentially confounding factors.…”

Adverse events with fatal outcome associated with alemtuzumab treatment in multiple sclerosis

“…Even though alemtuzumab is generally considered safe, serious adverse reactions have been identified, including infections, immune-mediated thrombocytopenia and thyroiditis [3] Following regulatory approval of alemtuzumab for relapsing remitting MS in 2013 by the European Medicines Agency (EMA) and in 2014 by the U.S. Food and Drug Administration (FDA), there have been reports of severe and even fatal suspected adverse effects. These include listeriosis [4,5], alveolar hemorrhage [6], neutropenia with staphylococcus infection [7], autoimmune hemolytic anemia with necrotizing leukoencephalopathy [8], and hemofagocytic lymphohistocytosis [9]. These concerns led us to perform a systematic search for information on fatal cases following treatment with alemtuzumab in MS, retrieving data from the European database of suspected adverse drug reaction reports (EudraVigilance).…”