Are apoptosis‐determining techniques useful to establish an early diagnosis of acute graft‐vs‐host disease in pediatric patients under treatment with multiple drugs?

Background There are no pathognomonic histopathological features to distinguish acute graft‐vs‐host disease (aGVHD) from skin drug reactions (SDRs) in pediatric patients with multiple drug regimens that have received blood transfusions and/or transplants. We aimed to determine if the addition of apoptosis markers is helpful to distinguish aGVHD from SDRs in these patients. Methods Skin biopsy specimens from patients with a clinical diagnosis of aGVHD or SDRs were evaluated for the presence of apoptotic bodies, satellitosis, interface damage, vasculitis, and inflammatory infiltrate on H&E stain. Information was completed with apoptotic markers (transferase‐mediated dUTP nick end‐labeling [TUNEL], bcl‐2, and caspase‐3). Results The skin biopsy specimens of 32 patients with aGVHD and 11 with SDRs were included for study. Only the number of apoptotic keratinocytes per 10 high‐power fields (hpf) showed a significant difference between both groups ( P = 0.02); the presence of ≥4 apoptotic keratinocytes per 10 hpf was identified as the optimal cut‐off point to discriminate aGVHD from SDRs. No SDRs cases had follicular apoptotic cells. TUNEL, bcl‐2, and caspase‐3 determination showed no difference between both groups. Conclusions The presence of ≥4 apoptotic keratinocytes per 10 hpf (in aGVHD) and the absence of follicular apoptotic cells (in SDRs) might be a useful marker to distinguish between them.