Bactrim and omeprazole were given for PCP and gastrointestinal prophylaxis, respectively. clinical trial protocols. pneumonia (PCP) and gastrointestinal prophylaxis, respectively. Unfortunately, during the steroid taper, he returned to the clinic with fever and headache when prednisone was decreased to 60 mg daily. Thyroid stimulating hormone (TSH), prolactin, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were below normal limits, although free T4 AKR1C3-IN-1 (thyroxine) and cortisol levels were normal at this time. The patient AKR1C3-IN-1 was started on methylprednisolone at 2 mg/kg/day IV. AKR1C3-IN-1 He was also started on antibiotics for empiric treatment of sepsis. Endocrinology and Rheumatology consultations were obtained. After 2 days of treatment, his headache Rabbit polyclonal to TP73 persisted. Therefore, oral mycophenolate 500 mg twice a day was started. Subsequently, after he was cleared for tuberculosis infection, infliximab 3 mg/kg IV was administered. He was also started on oral levothyroxine 50 g daily due to decrease of free T4. After 5 days of treatment, his headache improved significantly. He was discharged from the hospital and maintained on 100 mg of prednisone twice a day, which was tapered by 10 mg every week, and 500 mg of mycophenolate twice a day, which was discontinued after 3 weeks of treatment. At that time, oral azathioprine 50 mg twice a day was started in place of mycophenolate due AKR1C3-IN-1 to lack of insurance coverage of the latter. After another 7 weeks of treatment, prednisone was tapered to 5 mg daily, which was changed to hydrocortisone 20 mg in the morning and 10 mg in the evening. Azathioprine was discontinued at this time. The patient has remained on such doses of hydrocortisone and levothyroxine to date without other significant problems. Hepatotoxicity Hepatotoxicity includes elevation of serum liver transaminases and/or bilirubin. Hepatotoxicity of any grade occurred in about 2C9% of melanoma patients treated with ipilimumab [4, 14, 15]. Grade 2 hepatotoxicity (defined as 2.5 UNL [upper normal limit] AST/ALT 5 UNL; or 1.5 UNL total bilirubin 3 UNL) occurred in about 2.5% of patients treated with ipilimumab. Grade 3C5 hepatotoxicity (AST/ALT 5 UNL; or total bilirubin 3 UNL) occurred in 2% of ipilimumab-treated patients, with fatal hepatic failure in 0.2% [18]. Hepatotoxicity generally occurs between week 6 and week 14 after initiation of ipilimumab treatment [6]. In our experience with prostate cancer patients, grade 2 or less hepatotoxicity occurred in 18/44 (40.9%) patients, whereas grade 3C4 hepatotoxicity happened in 4/44 (9.1%) patients. Baseline and post-treatment AST, ALT, and total bilirubin levels should be obtained in all patients treated with ipilimumab. In patients who develop ipilimumab-induced hepatotoxicity, hepatology consultation should be obtained, and infectious and autoimmune hepatitis should be ruled out. For patients who develop hepatotoxicity of grade 2 or greater, ipilimumab should be withheld and methylprednisolone 1 mg/kg/day IV should be administered [18]. If patients require treatment with mycophenolate mofetil and/or infliximab, rheumatology consultation should be obtained to guide the use of the immune-suppressive medications. Ipilimumab should be permanently discontinued in patients with grade 3C5 hepatotoxicity. As an example of ipilimumab-induced hepatitis management, patient LS developed grade 3 transaminitis after receiving 4 doses of ipilimumab at 10 mg/kg every 3 weeks. He was immediately hospitalized and treated with 1 mg/kg/day methylprednisolone IV. After a week of treatment, transaminitis improved to grade 2. Steroid was changed to oral prednisone 100 mg daily with plan of tapering by 10 mg weekly. Bactrim and omeprazole were given for PCP and gastrointestinal prophylaxis, respectively. After about 3 months of treatment with slight fluctuations of transaminases, prednisone was eventually tapered to 30 mg daily. Unfortunately, the patient developed left foot drop, which was suspected due to ipilimumab-induced neuropathy. At this time, the patient was treated with oral mycophenolate 500 mg twice a day for a month. His prednisone was then completely tapered off with resolution of both transaminitis and neuropathy. Dermatitis Dermatitis is the most common irAE in melanoma patients treated with ipilimumab, occurring in as many as 44% treated patients [4, 11]. Grade 2 dermatitis occurred in about 12% of treated patients. Grade 3C5, life-threatening dermatitis, such as Stevens-Johnson syndrome, toxic epidermal necrolysis, or rash complicated by full thickness dermal ulceration/necrosis, occurred in only about 2.5% of ipilimumab-treated patients. The median time to onset of moderate or severe dermatitis was 3 weeks from the initiation of ipilimumab therapy, but the time to onset ranged up to 17 weeks [4, 11, 18]. In our clinical trials, grade 0C2 dermatitis occurred in 27/44 (61.4%) prostate cancer patients, whereas grade 3C4 dermatitis occurred in 3/44 (6.8%) patients. These toxicity rates are similar.