Rare Case of MG and Bone Marrow Disorders Reported

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by Vanda Pinto, PhD |

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An extremely rare case of myasthenia gravis (MG) associated with paroxysmal nocturnal hemoglobinuria (PNH) and aplastic anemia (AA), two bone marrow failure conditions in which the immune system mistakenly attacks developing red blood cells, was reported recently.

The report, “Myasthenia gravis and paroxysmal nocturnal hemoglobinuria after thymectomy: A rare association,” was published in the journal eJHaem.

In MG, the immune system produces self-reactive antibodies that erroneously attack acetylcholine receptors (AChRs) and other proteins involved in nerve-muscle communication, causing muscles to become weaker.

The thymus, an organ that is part of the immune system, has been reported to contribute to the development of the self-reactive antibodies driving MG.

This report describes the case of a 56-year-old man in France who had been diagnosed in 1992 with MG, which was thought to be associated with thymus hyperplasia, a condition in which the thymus becomes enlarged.

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He had undergone a thymectomy (thymus removal surgery) and was taking steroids, as well as an anticholinesterase, which is a medication that enables acetylcholine, a signaling molecule that promotes muscle contraction, to last longer after being released. Despite treatment, he still had sporadic flares.

In 2011, he complained of weakness and his lab tests revealed low levels of neutrophils (a type of white blood cell), and platelets, as well has high levels of lactate dehydrogenase, a marker of tissue damage. He also had hemolytic anemia, a condition in which red blood cells are destroyed faster than they are made.

A bone marrow biopsy showed he was lacking precursor cells that later turn into neutrophils, and his red blood cells were developing in an abnormal way.

Collectively, these features were consistent with AA, a type of autoimmune cytopenia — a group of disorders in which the immune system attacks blood cell precursors, causing one or more blood cell types to be lower than it should be.

In addition, a PNH clone was detected. Of note, PNH is caused by mutations in the PIGA gene in blood stem cells in the bone marrow. These mutations are passed down each time an abnormal stem cell makes clones, or copies, of itself. When abnormal stem cells eventually grow into other blood cell types, these newly-formed blood cells are attacked by the complement, a part of the immune system.

The patient received the diagnosis of AA with PNH, and was monitored closely until November 2013, when the destruction of his red blood cells worsened. He received a blood transfusion and in January of the following year he started treatment with Soliris (eculizumab), a complement inhibitor marketed by Alexion Pharmaceuticals.

“In the first 6 months, two red blood cell transfusions were required, most likely due to the underlying AA,” the authors wrote.

However, his levels of reticulocytes (immature red blood cells), neutrophils, and platelets spontaneously rose by the end of 2014. Authors reported that his MG stabilized following treatment with Soliris together with the corticosteroid prednisone, and anticholinesterase medication.

“In conclusion, we report the first case of PNH associated with MG and safely treated by [Soliris]. Although extremely rare, we believe that these conditions are not coincidental, since thymic abnormalities and thymectomy could be linked to autoimmune cytopenia, including AA, with the latter sharing a common [mechanism] with PNH,” the researchers wrote.

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