http://informahealthcare.com/cot ISSN: 1556-9527 (print), 1556-9535 (electronic) Cutan Ocul Toxicol, Early Online: 1–3 ! 2014 Informa Healthcare USA, Inc. DOI: 10.3109/15569527.2014.918139 CASE REPORT The efficiency of granulocyte colony-stimulating factor in hemorrhagic mucositis and febrile neutropenia resulted from methotrexate toxicity Hatice Uce Ozkol 1 , Tayfur Toptas 2 , and Omer Calka 1 , Necmettin Akdeniz 3 1 Department of Dermatology, Yuzuncu Yil University, Faculty of Medicine, Van, Turkey, 2 Department of Hematology, Van Regional Training and Research Hospital, Van, Turkey, and 3 Department of Dermatology, Faculty of Medicine, Medeniyet University, Istanbul, Turkey Abstract Methotrexate (MTX) remains one of the most frequently used anti-metabolite agents in dermatology. MTX is an analog of folate that competitively and irreversibly inhibits dihydrofolate reductase. Oral mucositis is a common side effect of chemotherapy drugs and is characterized by erythema, pain, poor oral intake, pseudomembranous destruction, open ulceration and hemorrhage of the oral mucosa. In this paper, we report a 32-year-old female with a case of mucositis due to MTX intoxication that resulted from an overdose for rheumatoid arthritis. The patient had abdominal pain, vomiting, and nausea. During follow-up, the patient’s white blood cell count was found to be 0.9  10 9 /L (4–10  10 9 /L). The patient developed fever exceeding 40  C. The patient was consulted to the hematology service. They suggested using granulocyte colony-stimulating factor for febrile neutropenia. On the fifth day of treatment, the white blood cell count reached 5.3  10 9 /L and the patient’s fever and mucositis started to resolve. Here, we presented a case of hemorrhagic mucositis and febrile neutropenia resulted from high-dose MTX that responded very well to granulocyte colony-stimulating factor treatment and we reviewed the literature. Keywords Febrile neutropenia, granulocyte colony-stimulating factor, mucositis History Received 31 March 2014 Revised 11 April 2014 Accepted 17 April 2014 Published online 19 June 2014 Introduction Methotrexate (MTX) is a commonly used drug in daily practice and has anti-neoplastic and anti-inflammatory properties. One of the most common indications is rheuma- toid arthritis. Its usual recommended dose ranges from 12.5 to 20 mg per week for this indication 1 . However, overdose is a commonly encountered problem in these patients. Language barriers, time constraints in a busy outpatient clinic, and several other causes may facilitate this potentially fatal condition. MTX most strongly affects rapidly proliferating tissues, including bone morrow precursor cells and the mucosal tissues lining the gastrointestinal and genitourinary tracts 2 . Usually, mucositis resolves following neutrophil recovery, which takes approximately 2–3 weeks. Supportive care together with granulocyte or granulocyte-monocyte colony-stimulating factor (G-CSF or GM-CSF) transfusions, parenteral antibiotics, and symptomatic rinses forms the alternatives of the treatment 3 . However, preventive measures consisting of a careful description of MTX use and informing patients about the potential dangers and alarm symptoms of drug overdose/misuse are the key components of management for these patients 4 . We present this patient because of the severe mucositis that accompanied febrile neutropenia due to high-dose MTX and the fact her condition responded very well to treatment with G-CSF. Case A 32-year-old female was seen in our clinic complaining of sore throat and severe mucositis. Her medical history included rheumatoid arthritis for a year. She was receiving oral prednisone 10mg a day and MTX. Additionally, MTX was prescribed at a dose of 20 mg/week. However, she had been erroneously taking MTX 20 mg/d for the past 10 d. On dermatological examination, markedly active bleeding and hemorrhagic necrotic crusts on the lips were noted (Figure 1). Her laboratory tests revealed profound pancytopenia with a neutrophil count 5 1.0  109/L, Hb 5 7.0 g/dL, and platelet count 5 20 000/mL. She was referred to a hematologist. A peripheral blood smear revealed pancytopenia with no atypical mononuclear cells. G-CSF, 5 MU/kg (300 MU/d), was started. The daily hematological findings for the patient were noted (Table 1). Blood components were replaced to maintain a Hb 4 7.0 g/dL and platelet count 4 20 000/as needed. She developed a fever that exceeded 39.7  C (Table 1). Piperacillin/tazobactam was started according to the febrile neutropenia protocol from the hospital’s infectious disease committee. An oral rinse, including 4 mL of lidocaine 2%, 120 mL of benzydamine hydrochloride 0.15%, was given to Address for correspondence: Hatice Uce Ozkol, Department of Dermatology, Faculty of Medicine, Yuzuncu Yil University, Van, Turkey. E-mail: drhaticeuce@mynet.com Cutaneous and Ocular Toxicology Downloaded from informahealthcare.com by Mrs Claire Summerfield on 06/30/14 For personal use only.