From the Guidelines
I recommend initiating ganciclovir 5 mg/kg IV twice daily for treatment of CMV infection while continuing high-dose prednisone and azathioprine for immune checkpoint inhibitor (ICI) hepatitis. The patient's clinical picture suggests multiple overlapping issues: ICI-related hepatitis and colitis, possible infectious colitis (ETEC positive), and CMV viremia. The CMV viral load of 2,344 IU/ml in an immunocompromised patient warrants antiviral therapy, especially given the patient's age and multiple comorbidities, as suggested by 1. After 2-3 weeks of IV therapy and clinical improvement, transition to oral valganciclovir 900 mg twice daily. Monitor CMV viral load weekly until undetectable, then continue treatment for at least 2 additional weeks. For the ICI-related toxicities, continue prednisone with a slow taper over 4-6 weeks once symptoms improve and liver enzymes normalize, as recommended by 1. The azathioprine should be continued as a steroid-sparing agent. Also, obtain C. difficile testing to rule out concurrent infection, and consider flexible sigmoidoscopy with biopsies to evaluate for CMV colitis if diarrhea persists despite treatment. Regular monitoring of liver function tests, complete blood count, and renal function is essential during treatment, as emphasized by 1 and 1. Key considerations in management include:
- Excluding infectious causes of diarrhea before treating suspected ICI colitis, as stated in Best Practice Advice 1 by 1
- Using high-dose systemic glucocorticoids for ICI colitis, with doses of 0.5–2 mg/kg prednisone equivalent daily and a taper of 4–6 weeks, as recommended by 1
- Considering infliximab and vedolizumab as options for treatment of glucocorticoid refractory colitis, as suggested by 1 and 1
From the Research
Management of Immune Checkpoint Inhibitor Hepatitis
- The patient has been diagnosed with immune checkpoint inhibitor (ICI) hepatitis, which is a known side effect of ipilimumab and nivolumab treatment 2.
- High-dose corticosteroids (1-2 mg/kg/day methylprednisolone equivalents) are recommended for treating grade ≥3 ICI hepatitis, but a study suggests that initial treatment with 1 mg/kg/day methylprednisolone equivalents provides similar hepatitis outcomes with reduced risk of steroid-related complications 2.
- The patient has been started on high-dose prednisone, which is a common treatment for ICI hepatitis.
Use of Azathioprine
- Azathioprine is an immunosuppressant that is often used in combination with prednisone to treat autoimmune hepatitis 3, 4.
- A study found that the combination of prednisone and azathioprine is effective in improving symptoms, resolving laboratory and histologic features, and prolonging survival in patients with autoimmune hepatitis 3.
- The patient has been started on azathioprine, which may help to reduce the risk of steroid-related complications and improve treatment outcomes.
Management of CMV Infection
- The patient has a high CMV viral load (2,344 IU/ml), which may require antiviral treatment.
- However, there is no direct evidence in the provided studies to guide the management of CMV infection in this patient.
Treatment of Proctitis
- The patient has been diagnosed with proctitis, which is a known side effect of ipilimumab and nivolumab treatment.
- The treatment of proctitis typically involves the use of corticosteroids and/or immunosuppressants, but the optimal treatment approach is not clearly defined in the provided studies.
GI Pathogen Panel Results
- The patient's GI pathogen panel results showed the presence of ETEC, but C. diff was not performed.
- The treatment of ETEC infection typically involves the use of antibiotics, but the optimal treatment approach is not clearly defined in the provided studies.