Severe Bone Marrow Suppression Accompanying Pulmonary Infection and Hemorrhage of the Digestive Tract Associated with Leflunomide and Low-dose Methotrexate Combination Therapy

Abstract

A 60-year-old male patient developed hyperpyrexia, cough, expectoration with blood-stained sputum, mouth ulcers, and suppurative tonsillitis after receiving 35 days of combination treatment with leflunomide (LEF) and low-dose methotrexate (MTX) for active rheumatoid arthritis. On admission, routine blood tests showed severe thrombocytopenia, agranulocytosis, and decreased hemoglobin concentration compared with the relatively normal results of 1 month previously during the first hospitalization. Chest radiography revealed inflammation in both lungs, and a fecal occult blood test was positive. Given this presentation, severe bone marrow suppression accompanying pulmonary infection and hemorrhage of the digestive tract associated with LEF and MTX combination therapy was diagnosed. After 28 days of symptomatic treatment, the patient's complications subsided gradually. This case highlighted that bone marrow suppression associated with MTX and LEF combination therapy could be very serious, even at a normal dose or especially at the beginning of treatment. MTX and LEF combination therapy should be used with caution or be limited in those with a history of pulmonary disease, hemorrhage of the digestive tract, or other relevant diseases.

Impacts of Low-Dose Total Glycosides of Tripterygium wilfordii plus Methotrexate on Immunological Function and Inflammation Level in Patients with Rheumatoid Arthritis

“…On the other hand, MTX, when used alone, brings many side effects and has a poor effect on lymphocyte proliferation of the immune system. Therefore, it is necessary to combine with other drugs to inhibit lymphocyte proliferation and finally improve the abnormal immune response of RA patients [20][21][22]. As an extract of Chinese herbal medicine, total GTW is effective in the treatment of various systemic diseases [23].…”

The Incidence, Prevalence, and Associated Costs of Anemia, Malignancy, Venous Thromboembolism, Major Adverse Cardiovascular Events, and Infections in Rheumatoid Arthritis Patients by Treatment History in the United States

“…The emergence of JAKi for the treatment of RA stimulated discussions around assessing risk of venous thromboembolisms (VTEs), anemia, and infections such as herpes zoster (HZ) ( 2 , 3 , 4 , 5 ). Estimates for comorbidities frequently associated with DMARD therapies exist for malignancies ( 6 , 7 ), VTE (deep‐vein thrombosis [DVT] or pulmonary embolism [PE]) ( 8 , 9 , 10 ), major adverse cardiovascular events (MACE) ( 11 , 12 ), infections ( 2 , 3 , 4 , 5 , 13 , 14 ), and anemia ( 15 , 16 , 17 , 18 ). However, contemporary estimates are lacking by treatment history.…”