1. Corresponding Author: rjhavar@kingsbrook.org No financial disclosures apply to authors Table 1: Pertinent Laboratory Values for Selected Dates Date Prior to AdmissionDay 1Day 2Day 3Day 4Day 6Day 7Day 8Day 9Day 10Day 11 Day 22 WBC (x10 3 )52.70.60.70.60.52.47.112.613.617.410.6 Hgb (g/dl)10.37.18.278.37.610 10.711.210.69.7 Platelets (x10 3 )14928397557419482109114128208 WBC = white blood count; Hgb = hemoglobin; Hct = hematocrit Case Description Laboratory Data Discussion  An 85 year old African American female presented to the Emergency Room with history of oral ulcers, dark colored loose stools and myalgias. She had been in her usual health until 3 days prior to admission and had been on 7.5 mg of MTX weekly, without side effects. Her hematologic laboratory values had been stable for 6 years.  Past Medical History: seropositive Rheumatoid arthritis (RA), chronic renal insufficiency (GFR 48), hypertension and diabetes mellitus.  Medications: MTX started in Oct 2009, low dose aspirin, Ibuprofen, folic acid, carvedilol, valsartan, gabapentin.  Social history/ family history : not significant  Hospital Course: Triage vitals: BP: 144/100 mmHg, pulse: 101 bpm, resp: 22 bpm, T: 99 0 F, 99% oxygen saturation on room air, 8/10 on pain scale.  On examination she appeared ill and had generalized pain, she had oral mucosal ulcerations which had bled recently. The abdomen was soft, mildly tender without organomegaly. She had mild synovitis of her knees and hands with limitation of movement.  Initial hematologic blood work compared to her usual baseline (Table1) showed a drastic change with pancytopenia with an absolute neutrophil count of 0.5 and acute on chronic renal failure.  A chest radiograph and Electrocardiogram were normal. Blood, urine and respiratory cultures sent on admission and proved to be negative. Cat scan of abdomen showed possible colitis.  Aggressive intravenous hydration and 2 units of packed red cells were given.  Empiric antibiotics(Levofloxacin and metronidazole) were started for pancytopenia and possible colitis.  Although a provisional diagnosis of MTX induced pancytopenia was made, MDS/leukemia/malignancy had to be ruled out. Patient was started on granulocyte colony stimulating factor injections.  Day 3: Since the pancytopenia persisted, a bone marrow biopsy was done and it showed no evidence of abnormal myeloid maturation, no evidence of lympho-proliferative disorder or increased blast population.  Clinical improvement was seen on Day 4 after starting pulse doses of intravenous Solumederol 80 mg and folinic acid (leucovorin) 5mg every 8 hours.(see Table 1 lab trends)  By Day 6, the patient was clinically improving and transferred to a general medical floor.  Day 7-9: Patient continued to improve-she started oral feeds, underwent physical therapy and returned to her baseline functional status to be discharged home, shortly after.  Low dose MTX is usually well tolerated and efficacious in RA.  The prevalence of hematological toxicity, including leucopenia, thrombocytopenia, and megaloblastic anemia and pancytopenia, is estimated to be 3%.The extent of pancytopenia, a serious and unpredictable adverse effect of low- dose MTX, may be underestimated.  The mortality rate of severe pancytopenia is about 28%. Deaths are frequently due to sepsis. When it occurs within 1- 2 months of starting treatment it is likely an idiosyncratic reaction.  With long-term use of MTX, it is important that patients be monitored for hematological side-effects, as pancytopenia can be a late manifestation of cumulative toxicity.  Associated factors which increase the chances of this adverse effect are listed above.  Although there are numerous associated factors, the exact pathogenesis and likely time of occurrence of severe pancytopenia are unknown. Pharmacogenomics may hold the answer to predicting who is at risk of this potentially fatal complication of MTX.  Our case illustrates the potential for severe morbidity with low dose MTX therapy in RA and the importance of a prompt diagnosis and timely management in averting a potential catastrophe.  This patient did have chronic renal insufficiency and was using ibuprofen as an analgesic.  Complacency, while a patient is on long term MTX, is to be avoided and education of physicians as well as the patients, in general, is crucial. Mechanism Introduction Dihydrofolate DNA Synthesis Methotrexate Folinic Acid Tetrahydrofolate Predisposing FactorsDispensing Practice 20mg/week 2.5mg/day x8 d  Methotrexate (MTX) is an anti-metabolite.  Low dose MTX is now used as the standard disease modifying agent in the treatment of Rheumatoid Arthritis (RA).  Bone marrow suppression causing severe pancytopenia is a rare side-effect of low dose MTX but known to occur especially in the presence of co-morbid conditions such as renal insufficiency. References  1. Lim AYN, et al. Methotrexate-induced pancytopenia: serious and under reported? Our experience of 25 cases in 5 years. Rheumatology 2005; 44:1051-1055  2. Kuitunen T, et al Pancytopenia induced by low-dose methotrexate. A study of the cases reported to the Finnish Adverse Drug Reaction Register from 1991 to 1999 Scand J Rheumat. 2005; 34:238-241  3. Sosin M, et al Low dose methotrexate and bone marrow suppression. BMJ 2003; 326 Raagsudha Jhavar, MD; Karishma Patel, MD; Kyaw Thein, MD; Jitendra Patel, MD; Rajat Mukherji, MD.  Kingsbrook Jewish Medical Center Brooklyn, New York An Unusual Case: Low-Dose Methotrexate Induced Pancytopenia In Rheumatoid Arthritis