04.05.2016
Case Ties Alemtuzumab to Nocardia Brain Infection
Female patient had
A patient developed a cerebral Nocardia infection while taking the immunosuppressive agent alemtuzumab (Lemtrada) for relapsing-remitting multiple sclerosis, adding to
A patient developed a cerebral Nocardia infection while taking the immunosuppressive agent alemtuzumab (Lemtrada) for relapsing-remitting multiple sclerosis, adding to a list of opportunistic infections seen with the drug, researchers said.
The woman, in her late 40s, developed the infection 5 months after an initial course of alemtuzumab. Her history of anorexia may have contributed to the problem, Thomas Korn, MD, of Technische Universitat Munchen in Germany, and colleagues reported online in JAMA Neurology.
"Physicians should be cautious when considering alemtuzumab in patients with MS and suspected altered cellular immunity of any origin, including a low body mass index," they wrote.
Alemtuzumab is a humanized monoclonal IgG1 antibody against the protein CD52 that is expressed in many types of immune cells, and it depletes circulating T cells, B cells, natural killer cells, and some monocytes.
In clinical trials, herpes virus infections seen among those on the drug led to a recommendation of prophylactic anti-herpes virus treatment with acyclovir during the first month of therapy.
Mild-to-moderate infections associated with the drug have mostly been respiratory and urinary, and more severe infections include reports of spirochetal gingivitis, pyogenic granuloma, esophageal candidiasis, tuberculosis, and listeria meningitis.
Cancers have been reported, but the numbers are too small for assessing statistical significance, researchers said. But about 30% to 40% of alemtuzumab-treated patients develop autoimmune thyroid disease, and 1% to 3% develop immune thrombocytopenia.
Korn and colleagues said that cases of pulmonary and disseminated nocardiosis associated with alemtuzumab have been reported only in patients with pre-existing conditions that compromise immunity, including non-Hodgkin lymphoma, B-cell lymphocytic leukemia, and organ transplant.
The woman in the present case had been diagnosed in 2007 and started on interferon beta 1-a, then switched to natalizumab (Tysabri) but was taken off because of conversion to JC virus positivity. She started taking alemtuzumab in February 2015.
In June 2015, she was admitted to the hospital for reduced ambulation and a personality change in the previous 3 weeks.
Empiric antibiotic therapy had no effect and a search for specific infectious agents and foci was initially inconclusive. At that point, the team performed intracranial biopsy and saw infection with Nocardia farcinica. This bacterium infects the lungs and spreads via the bloodstream, and it has the potential to damage the central nervous system when intraepithelial and systemic cellular immunity fail, the researchers wrote.
The patient was treated with imipenem, co-trimoxazole, and amikacin plus dexamethasone. She also needed transient noradrenaline infusion and mechanical ventilation for 10 days before discharge to rehabilitation. At the time of writing, she was again able to walk but blood counts and other indicators had not fully normalized.
Korn and colleagues said that cases of pulmonary and disseminated nocardiosis associated with alemtuzumab have been reported only in patients with pre-existing conditions that compromise immunity, including non-Hodgkin lymphoma, B-cell lymphocytic leukemia, and organ transplant.
The woman in the present case had been diagnosed in 2007 and started on interferon beta 1-a, then switched to natalizumab (Tysabri) but was taken off because of conversion to JC virus positivity. She started taking alemtuzumab in February 2015.
In June 2015, she was admitted to the hospital for reduced ambulation and a personality change in the previous 3 weeks.
Empiric antibiotic therapy had no effect and a search for specific infectious agents and foci was initially inconclusive. At that point, the team performed intracranial biopsy and saw infection with Nocardia farcinica. This bacterium infects the lungs and spreads via the bloodstream, and it has the potential to damage the central nervous system when intraepithelial and systemic cellular immunity fail, the researchers wrote.
The patient was treated with imipenem, co-trimoxazole, and amikacin plus dexamethasone. She also needed transient noradrenaline infusion and mechanical ventilation for 10 days before discharge to rehabilitation. At the time of writing, she was again able to walk but blood counts and other indicators had not fully normalized.
Korn and colleagues acknowledged that antibiotic treatment after nocardiosis of the central nervous system is recommended for a year, but it may be continued even longer in this patient depending on the reconstitution of her mononuclear cell compartment.
They added that in this case, besides eliminating circulating mononuclear cell subsets, alemtuzumab might have depleted lymphocytes in compartments that are normally spared -- and the patient's low body mass index given her history of anorexia may have contributed to a pre-existing immunodeficient state.
It was also unlikely that the infection was related to the natalizumab treatment because the patient's mononuclear cells were normal when she started alemtuzumab, they said.
Korn and colleagues suggested that the case is particularly concerning because there is currently no test prior to beginning alemtuzumab treatment to identify patients at high risk for developing profound immunodeficiency.
In an accompanying editorial, Reinhard Hohlfeld, MD, and Tania Kumpfel, MD, of Klinikum Grosshadern in Munich, noted that of all the immunotherapies available for MS, alemtuzumab has the longest lasting effects on the immune system, and that it takes the various cells different times to recover: for instance, CD8+ populations take 3 years and CD4+ populations may take even longer, they wrote.
"Cerebral nocardiosis should be added to the list of differential diagnoses when neurologic complications arise during alemtuzumab treatment," they wrote. "This case report serves as an important note of caution. It should raise vigilance against alemtuzumab-associated opportunistic infections, which will undoubtedly continue."
http://www.medpagetoday.com/clinical...clerosis/57171
Case Ties Alemtuzumab to Nocardia Brain Infection
Female patient had
A patient developed a cerebral Nocardia infection while taking the immunosuppressive agent alemtuzumab (Lemtrada) for relapsing-remitting multiple sclerosis, adding to
A patient developed a cerebral Nocardia infection while taking the immunosuppressive agent alemtuzumab (Lemtrada) for relapsing-remitting multiple sclerosis, adding to a list of opportunistic infections seen with the drug, researchers said.
The woman, in her late 40s, developed the infection 5 months after an initial course of alemtuzumab. Her history of anorexia may have contributed to the problem, Thomas Korn, MD, of Technische Universitat Munchen in Germany, and colleagues reported online in JAMA Neurology.
"Physicians should be cautious when considering alemtuzumab in patients with MS and suspected altered cellular immunity of any origin, including a low body mass index," they wrote.
Alemtuzumab is a humanized monoclonal IgG1 antibody against the protein CD52 that is expressed in many types of immune cells, and it depletes circulating T cells, B cells, natural killer cells, and some monocytes.
In clinical trials, herpes virus infections seen among those on the drug led to a recommendation of prophylactic anti-herpes virus treatment with acyclovir during the first month of therapy.
Mild-to-moderate infections associated with the drug have mostly been respiratory and urinary, and more severe infections include reports of spirochetal gingivitis, pyogenic granuloma, esophageal candidiasis, tuberculosis, and listeria meningitis.
Cancers have been reported, but the numbers are too small for assessing statistical significance, researchers said. But about 30% to 40% of alemtuzumab-treated patients develop autoimmune thyroid disease, and 1% to 3% develop immune thrombocytopenia.
Korn and colleagues said that cases of pulmonary and disseminated nocardiosis associated with alemtuzumab have been reported only in patients with pre-existing conditions that compromise immunity, including non-Hodgkin lymphoma, B-cell lymphocytic leukemia, and organ transplant.
The woman in the present case had been diagnosed in 2007 and started on interferon beta 1-a, then switched to natalizumab (Tysabri) but was taken off because of conversion to JC virus positivity. She started taking alemtuzumab in February 2015.
In June 2015, she was admitted to the hospital for reduced ambulation and a personality change in the previous 3 weeks.
Empiric antibiotic therapy had no effect and a search for specific infectious agents and foci was initially inconclusive. At that point, the team performed intracranial biopsy and saw infection with Nocardia farcinica. This bacterium infects the lungs and spreads via the bloodstream, and it has the potential to damage the central nervous system when intraepithelial and systemic cellular immunity fail, the researchers wrote.
The patient was treated with imipenem, co-trimoxazole, and amikacin plus dexamethasone. She also needed transient noradrenaline infusion and mechanical ventilation for 10 days before discharge to rehabilitation. At the time of writing, she was again able to walk but blood counts and other indicators had not fully normalized.
Korn and colleagues said that cases of pulmonary and disseminated nocardiosis associated with alemtuzumab have been reported only in patients with pre-existing conditions that compromise immunity, including non-Hodgkin lymphoma, B-cell lymphocytic leukemia, and organ transplant.
The woman in the present case had been diagnosed in 2007 and started on interferon beta 1-a, then switched to natalizumab (Tysabri) but was taken off because of conversion to JC virus positivity. She started taking alemtuzumab in February 2015.
In June 2015, she was admitted to the hospital for reduced ambulation and a personality change in the previous 3 weeks.
Empiric antibiotic therapy had no effect and a search for specific infectious agents and foci was initially inconclusive. At that point, the team performed intracranial biopsy and saw infection with Nocardia farcinica. This bacterium infects the lungs and spreads via the bloodstream, and it has the potential to damage the central nervous system when intraepithelial and systemic cellular immunity fail, the researchers wrote.
The patient was treated with imipenem, co-trimoxazole, and amikacin plus dexamethasone. She also needed transient noradrenaline infusion and mechanical ventilation for 10 days before discharge to rehabilitation. At the time of writing, she was again able to walk but blood counts and other indicators had not fully normalized.
Korn and colleagues acknowledged that antibiotic treatment after nocardiosis of the central nervous system is recommended for a year, but it may be continued even longer in this patient depending on the reconstitution of her mononuclear cell compartment.
They added that in this case, besides eliminating circulating mononuclear cell subsets, alemtuzumab might have depleted lymphocytes in compartments that are normally spared -- and the patient's low body mass index given her history of anorexia may have contributed to a pre-existing immunodeficient state.
It was also unlikely that the infection was related to the natalizumab treatment because the patient's mononuclear cells were normal when she started alemtuzumab, they said.
Korn and colleagues suggested that the case is particularly concerning because there is currently no test prior to beginning alemtuzumab treatment to identify patients at high risk for developing profound immunodeficiency.
In an accompanying editorial, Reinhard Hohlfeld, MD, and Tania Kumpfel, MD, of Klinikum Grosshadern in Munich, noted that of all the immunotherapies available for MS, alemtuzumab has the longest lasting effects on the immune system, and that it takes the various cells different times to recover: for instance, CD8+ populations take 3 years and CD4+ populations may take even longer, they wrote.
"Cerebral nocardiosis should be added to the list of differential diagnoses when neurologic complications arise during alemtuzumab treatment," they wrote. "This case report serves as an important note of caution. It should raise vigilance against alemtuzumab-associated opportunistic infections, which will undoubtedly continue."
http://www.medpagetoday.com/clinical...clerosis/57171
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