Case Presentation: A 25-year-old female with a history of End Stage Renal Disease (ESRD) due to Focal Segmental Glomerulosclerosis (FSGS) status post cadaveric kidney transplant one year ago presented with acute rejection of the transplanted kidney, likely due to medication non-compliance. Renal biopsy demonstrated that the kidney was no longer salvageable, and she was started on hemodialysis (HD). During this admission, she was also found to have an ectopic pregnancy. After discussion of risks and benefits, Methotrexate (MTX) was chosen for abortive therapy over surgical intervention, despite her renal failure and dependence on HD. She was given a single dose of intramuscular MTX 50mg/m2 and discharged two days later. The plan was for her to receive outpatient HD two days post-discharge, but she was unable to follow through with this to due logistical difficulties. She was admitted five days after discharge to a community hospital with MTX toxicity and was treated with leucovorin and sodium bicarbonate as well as intermittent HD (iHD). Upon transfer back to our referral center, she was febrile and tachycardic, and physical exam revealed sloughing of the lips and oral mucosa, decreased breath sounds in the left lower lung field, and tender, bleeding genital lesions. Labwork was notable for WBC of 0.13 K/mm3, ANC of 0.01 K/mm3, hemoglobin of 7.5 g/dL, platelets of 4 K/mm3, and MTX level of 0.07 µmol/L. Chest X-ray showed a left lower lung consolidation as well as a hazy right lower lung opacity. Despite empiric treatment for pneumonia with Vancomycin, Meropenem, and Micafungin, she continued to worsen and developed acute hypoxic respiratory failure requiring intubation. Bronchoalveolar lavage was performed, and a sample sent for HSV-1 PCR returned positive, leading to a diagnosis of HSV-1 pneumonia. After treatment with intravenous acyclovir she was successfully extubated and transferred out of the ICU.
Discussion: This case illustrates an interesting presentation of acute MTX toxicity leading to HSV-1 pneumonia requiring ICU admission and intubation. The use of MTX in ESRD patients on HD is very controversial. MTX is primarily eliminated through the kidneys, and it has been found that even low doses of MTX can lead to serious morbidity and mortality in HD patients. In this case, shared medical decision-making resulted in the choice of MTX treatment over surgery, but perhaps further consideration should have been given to the patient’s social factors and history of non-compliance. These often overlooked factors appear to have led to failure of the discharge plan as the patient missed her planned outpatient HD. Lastly, the patient was also affected by a delayed diagnosis of HSV-1 pneumonia, which, although an uncommon illness, can be relatively common in immunocompromised patients in the ICU and should be considered in an immunosuppressed patient with respiratory failure not responding to antibiotics.
Conclusions: MTX should be avoided in HD patients, if at all possible, given the high risk of toxicity, but shared medical decision-making can be complex. Anticipation of possible outpatient problems is a crucial component of forming a successful treatment plan which can sometimes be neglected in Hospital Medicine. The unfortunate series of events that led to this patient being intubated due to HSV-1 pneumonia highlights the importance of several themes, including social determinants of health, shared medical decision-making in the hospital, and delayed diagnosis due to rare disease.