Case Presentation: A 78-year-old male with a past medical history of hypertension, primary hyperparathyroidism, hyperlipidemia, renal cell carcinoma with left nephrectomy, prostate cancer in remission, multiple skin cancers, and end-stage renal disease treated with transplant currently on immunosuppressants (sirolimus, azathioprine, and prednisone), who presented with one month of diffuse maculopapular pruritic skin rash and hair loss. The patient had reported that the rash started about two weeks after cyclosporine was stopped and sirolimus was started. Initial vitals were normal. Initial labs were remarkable of anemia at 10.2 g/dL and sirolimus level of 3.9 ng/mL Physical exam revealed minimal right lower quadrant tenderness and diffuse erythematous and scaly maculopapular rash involving the face, neck, upper extremities, and back. Transplant nephrology recommended holding sirolimus. Work-up (HSV IgG, CMV DNA, EBV PCR and BK PCR) was ordered to rule out transplant rejection and acute infection, which came back negative except for positive HSV 1 IgG. The patient was making adequate urine and his kidney function remained stable.Dermatology was consulted for skin biopsy which showed subacute pustular dermatitis with eosinophils and spongiosis consistent with a drug reaction. Given the temporal association between sirolimus initiation and rash occurrence, it was deduced that sirolimus was the likely causative agent. Dermatology recommended steroid topical cream and high dose oral prednisone with 8 days of taper to a daily home dose of 5mg daily. The patient’s body rash continued to improve significantly. Low dose tacrolimus was started. Azathioprine was stopped to prevent the recurrence of cancer. He was discharged in a stable condition with a close follow-up with dermatology and transplant nephrology.

Discussion: Sirolimus is an immunosuppressant medication, which is increasingly being used to prevent organ rejection in transplant patients. It also has potent anti-fungal and anti-tumor properties. Rash along with hypertriglyceridemia, hyperlipidemia, peripheral edema, thrombocytopenia, leukopenia, nausea, and constipation, etc are common side effects observed with sirolimus use. Most rash cases were mild-resembling localized, mild seborrheic dermatitis- and ranged from 6% to 20% in the analysis of phase 3 trials [1]. Severe diffuse rash resulting in sirolimus cessation has rarely been reported in the literature [2]. Our case is unique in this regard, as it presents the rare association of severe, diffuse rash with sirolimus use.

Conclusions: The mild rash is one of the common side effects of sirolimus use, but on rare occasions, it may result in severe, diffuse rash leading to its cessation.

IMAGE 1: The Sirolimus Induced Diffuse Maculopapular Rash