Leflunomide/methotrexate

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An event is serious (based on the ICH definition) when the patient outcome is:

• * death

• * life-threatening

• * hospitalisation

• * disability

• * congenital anomaly

• * other medically important event

A 41-years-old woman developed visceral leishmaniasis and SARS-CoV-2 infection during treatment with methotrexate and leflunomide for rheumatoid arthritis, and unspecified corticosteroids for pemphigus vulgar [dosages and routes not stated].

The woman was presented to the hospital due to increased abdominal volume, skin, oral and vaginal bleeding. Her history was significant for rheumatoid arthritis for 20 years and for which she had regularly receiving methotrexate and leflunomide. Prior to 60 days, she was presented to the another hospital due to abdominal pain, skin and oral mucosa lesions. A diagnosis of pemphigus vulgar was made.

The woman started receiving unspecified corticosteroids for 2 months. However, her condition was declined. Approximately 50 days after the onset of treatment, she was hospitalised due to an increase in the abdominal volume associated with jaundice. Her examination revealed thrombocytopenia, anaemia and alterations in the hepatic profile. Her laboratory tests and clinical conditions worsened. An abdominal ultrasound revealed splenomegaly, mild hepatomegaly and ascites. On tenth day of hospitalisation, she experienced skin bleeding and bleeding from the oral and vaginal cavity with increased abdominal volume. Later, she was transferred to the current hospital. At the time of admission, she had ecchymosis on the upper limbs, jaundice, Glasgow was 14, active bleeding in the oral cavity, pulmonary auscultation with wheezing in the left hemithorax, semiglobular and flaccid abdomen, palpable liver at 4cm from the right costal margin and Traube's space occupied. She also had oedema of the lower limbs and circular lesion measuring 6cm in diameter of healing process on the left knee with delimited borders, fibrinous and shiny bottom. A chest CT revealed peripherally distributed ground-glass attenuation, mostly associated with thickening of the interlobular septa and subpleural lines, with a semiquantitative analysis of 75% of lung parenchyma involvement. She was transferred to the ICU. Later, a reverse transcription Polymerase chain reaction (RT-PCR) on nasopharyngeal swabs showed SARS-CoV-2 positive. Laboratory tests revealed changes in the liver function, blood glucose and blood cell count. Laboratory tests showed bilirubin direct 6.69 mg/dL, indirect bilirubin 1.44 mg/dL, ALP 150 kU/L, GGT 127 kU/L, AST 241 kU/L, ALT 104 kU/L, RBC count 2.99 million/µL, leucocyte count 13610/µL, myelocyte count 1%, metamyelocyte count 1%, band neutrophil count 15%, segmented neutrophil count 66%, eosinophil count 0%, basophils 0%, lymphocyte count 12%, monocyte count 5%, platelet count 19000/µL, blood glucose 16 mg/dL and CRP 135.5 mg/L. A blood smear revealed the presence of numerous free and intracellular amastigote forms of Leishmania spp. Subsequently, a rapid test for visceral leishmaniasis was positive and PCR revealed L. infantum chagasi and restriction fragment length polymorphism. The life threatening visceral leishmaniasis and SARS-CoV-2 infection were considered secondary to immunosuppression caused by methotrexate, leflunomide and unspecified corticosteroids [time to reaction onset not stated]. After 10 days of admission, her oxygen saturation significantly dropped with lowering of the consciousness level condition which required orotracheal intubation. After 2 days of hospitalisation, she had progressive clinical worsening and passed away.