J Oral Maxillofac Surg 69:2508-2512, 2011 A Series of Complications After Third Molar Osteotomy in a Pancytopenia Patient and Spontaneous Healing After Bone Marrow Transplantation Jan C. Klatt, MD, DMD,* Alexander Gröbe, MD, DMD,† Rainer Schmelzle, MD, DMD, PhD,‡ Artun Atac, MD,§ Max Heiland, MD, DMD, PhD, Marco Blessmann, MD, DMD, PhD,¶ and Philipp Pohlenz, MD, DMD, PhD# Complications can result from the surgical removal of third molars, and the complication rate is expected to be higher in immunosuppressed patients. However, such cases are rare. Leflunomide is a slow-acting antirheumatic agent used in the treatment of rheumatoid arthritis and psoriatic arthritis. It inhibits dihydroorotate dehydro- genase, a key enzyme in pyrimidine metabolism that is particularly significant in the cell division of T lymphocytes, and suppresses leukocyte migration. In the intestinal wall and the liver, leflunomide is con- verted into its active metabolite, A771726, which is further metabolized into additional active substances. The half-life of these active leflunomide metabolites is between 1 and 4 weeks. Known side effects of le- flunomide are itching, mucous membrane lesions, hair loss (alopecia), diarrhea, and very rarely, agranu- locytosis and fatal liver necrosis. Combination therapies with leflunomide and other basic antirheumatic drugs such as methotrexate and chloroquine are more effective than monotherapy and are widely used in nonsurgical rheumatology. However, the combination of leflunomide and meth- otrexate is associated with the risk of severe liver damage (eg, granulomatous hepatitis) and/or life- threatening infections. Furthermore, the risks of long- term treatment with such a combination therapy are not yet well-known. We report for the first time a case of life-threatening complications after surgical removal of the infected mandibular third molar in a patient with leflunomide- induced pancytopenia. Case Report In late March 2008, a 32-year-old woman presented to our clinic with a third molar infection. She had experienced pain at the mandibular third molar for 3 to 4 weeks, and the pain had worsened considerably over the last 3 to 4 days. The patient had experienced pain at the mandibular third molar several times in the previous year; at that time, how- ever, the pain regressed with intensive oral hygiene. The patient was diagnosed with rheumatoid arthritis (of the hands, knees, and spine) in October 2007 and has been treated with the disease-modifying antirheumatic drug le- flunomide, 20 mg (Arava; Sanofi-Aventis, North Ryde, Aus- tralia), since that time. In the subsequent 4 weeks, the patient increasingly had sore throat, fever, chills, and diar- rhea. Distinctive hematomas also appeared after minor trauma. At the beginning of 2008, the patient was admitted in deteriorating general condition to a Hamburg hospital; she was diagnosed with pancytopenia (leukocyte count, 1.17/nanoliter [nL]; platelet count, 13/nL; hemoglobin *Resident, Department of Oral and Maxillofacial Surgery, Univer- sity Medical Center Hamburg-Eppendorf, Hamburg, Germany. †Resident, Department of Oral and Maxillofacial Surgery, Univer- sity Medical Center Hamburg-Eppendorf, Hamburg, Germany. ‡Professor and Head, Department of Oral and Maxillofacial Sur- gery, University Medical Center Hamburg-Eppendorf, Hamburg Germany. §Resident, Department of Oral and Maxillofacial Surgery, Univer- sity Medical Center Hamburg-Eppendorf, Hamburg, Germany. Professor and Head, Department of Oral and Maxillofacial Sur- gery, Medical Center Bremerhaven-Reinkenheide, Bremerhaven, Germany. ¶Senior Resident, Department of Oral and Maxillofacial Surgery, University Medical Center Hamburg-Eppendorf, Hamburg Ger- many. #Senior Resident, Department of Oral and Maxillofacial Surgery, University Medical Center Hamburg-Eppendorf, Hamburg Germany. Address correspondence and reprint requests to Dr Klatt: De- partment of Oral and Maxillofacial Surgery, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany; e-mail: j.klatt@uke.uni-hamburg.de © 2011 American Association of Oral and Maxillofacial Surgeons 0278-2391/11/6910-0011$36.00/0 doi:10.1016/j.joms.2011.02.032 2508