Aplastic anemia secondary to propylthiouracil: A rare and life-threatening adverse effect

Abstract

Background Propylthiouracil has been in use for more than half a century for the treatment of hyperthyroidism. While it is largely known to cause agranulocytosis, its association with aplastic anemia is rarely heard of. Our case will be the third in literature to suggest aplastic anemia as a manifestation of propylthiouracil, which unfortunately culminated in the death of the patient. Case A 67-year-old female, with recently diagnosed metastatic adenocarcinoma of the lung, developed hyperthyroidism after being started on Nivolumab and Iplimumab. After she developed atrial fibrillation, she was started on propylthiouracil to control the thyroid activity. Soon after that, she was admitted with severe neutropenia, which progressed to pancytopenia confirmed as aplastic anemia on a bone marrow biopsy. Despite discontinuation of propylthiouracil and aggressive treatment, she developed septic shock and multi-organ failure, leading to her death. Conclusion Aplastic anemia has been sparingly reported as an extremely rare complication of propylthiouracil. Further adding to the ambiguity is the unknown etiology and lack of specific therapy for the complication when attributed to propylthiouracil. The disease can carry an extremely poor prognosis if untreated, as proven by our case. Due to the same reasons, we recommend that further investigations be done to elucidate the pathogenesis and assist with treatment of the disease when caused by propylthiouracil.

Letters about Published Papers

“…Third, the AA described by Shaikh et al. 1 is brutal and severe, i.e. quite different from the AA due to PTU already published.…”

“…Finally, the patient described by Shaikh et al. 1 displayed rapidly an irAE (hyperthyroidism), just after the very first line of Nivolumab+Ipilimumab treatment, suggesting that she was probably predisposed to these sort of drug-induced autoimmune complications.…”

“…In a recent article, Shaikh et al. 1 described a patient with a metastatic adenocarcinoma of the lung who died during a second course of regimen combining two immune checkpoint inhibitors (ICI), i.e. Nivolumab and Ipilimumab.…”

“…The authors consider this life-threatening AA as a secondary rare adverse effects of PTU; in our opinion, the accountability of PTU in this AA onset is largely excessive and must be challenged for several reasons: First, concomitant treatment with PTU and ICI makes it difficult to unambiguously attribute this complication to anti-thyroid drug. Second, like the authors indicate, AA as a side effect of PTU has been extremely rarely described (only twice), 2,3 whereas this drug has been very widely used for almost 50 years, for very common pathologies in the general population. Third, the AA described by Shaikh et al. 1 is brutal and severe, i.e. quite different from the AA due to PTU already published.…”

A response to the letter to the editor on Shaikh et al. Aplastic anemia secondary to propylthiouracil: A rare and life-threatening adverse effect

“…We thank Xavier Lafarge for the response to our article, Aplastic anemia secondary to propylthiouracil: A rare and life-threatening adverse effect, 1 and for opening up the discussion.…”