D. I. Garcia1, P. Murty1, A. Fernandes1, D. N. Lewin3, K. E. Twombley2, S. N. Nadig1 1Medical University Of South Carolina,Surgery,Charleston, Sc, USA 2Medical University Of South Carolina,Pediatrics,Charleston, Sc, USA 3Medical University Of South Carolina,Pathology And Laboratory Medicine,Charleston, Sc, USA
Introduction:
Cystinosis is a rare autosomal recessive lysosomal storage disorder that results in the build up of cystine in multiple cell types. This disease particularly affects proximal tubule cells in the kidney resulting in development of Fanconi syndrome and subsequent renal failure. More than 90% of patients with this disease progress to end-stage by age 20 and require transplantation. Sirolimus is an anti-proliferative agent often used in post-transplantation immunosuppression regimens whose mechanism of action is to inhibit mammalian target of sirolimus (mTOR) thereby blocking cell cycle progression from G1 to S phase. It has fallen out of favor as a first-line reagent over the years due to its significant side effect profile resulting in discontinuation rates as high as 50%. Frequently reported adverse effects include hypercholesterolemia requiring lipid lowering agents, increased incidents of wound dehiscence and lymphoceles as well as a predisposition to development of focal segmental glomerulosclerosis. We describe the first reported case of pediatric sirolimus-induced colitis following renal transplant for nephropathic cystinosis.
Methods:
The patient underwent colonoscopy following onset of symptoms in which several colonic biopsies were taken. Histology with hemotoxylin and eosin staining was perfomed and evaluated by GI pathology fellowship board-certified pathologists at our institution. In addition to testing for inflammatory, autoimmune and infectious etiologies, donor-derived DNA and chimerism testing was run to assess for Graft Versus Host Disease (GVHD). Repeat colonic biopsies were performed following resolution of symptoms.
Results:
We describe the first reported case of pediatric sirolimus-induced colitis following renal transplant for nephropathic cystinosis. The patient was a twelve-year-old female who, three months post-transplant, developed symptoms of colitis following a change in immunosuppressive drug regimen to sirolimus and prednisone after adverse reactions to mycophenolate mofetil. Histology from colonic biopsies showed gland drop out with crypt atrophy and focal apoptosis initially concerning for a gastrointestinal manifestation of GVHD. Donor-derived DNA and chimerism testing, however, ruled out GVHD as a diagnosis. Following sirolimus discontinuation, the patient’s symptoms completely resolved and repeated colonic biopsy showed normal histology.
Conclusion:
Serologic and histologic testing proved to be negative for other etiologies of the patient's colitis symptoms. The temporal relationship of colitis symptoms following commencement of sirolimus as well as the resolution of symptoms following discontinuation of sirolimus led us to conclude that the patient's colitis was drug-related.
