Quantitative Analysis of Eosinophils in Acute Graft-Versus-Host Disease Compared With Drug Hypersensitivity Reactions

Abstract

Acute graft-versus-host disease (aGVHD), if not detected and treated early, is a common cause of morbidity and mortality. Drug hypersensitivity reactions (DHRs), the most frequent clinical and histopathological mimickers of early aGVHD, are often still distinguished from aGVHD by the presence of eosinophils within the inflammatory infiltrate on skin biopsy. Distinguishing these entities is important because the delay of appropriate treatment of aGVHD may lead to advanced stages of the disease process with a poor prognosis. To determine whether the existence or amount of eosinophilic infiltrate could be used to differentiate these entities, we employed a quantitative method of analyzing eosinophils in skin biopsies of rashes from patients with aGVHD and DHR. Eosinophils were counted in 50 high-power fields (HPFs) in skin biopsies of patients with clinical grade >or=2 aGVHD (+aGVHD), with clinical grade <2 aGVHD (-aGVHD), and those with clinical DHR (+DHR). The average number of eosinophils per 10 HPFs (ave. eos/10 HPFs) increased throughout each group. The ave. eos/10 HPFs in +DHR was significantly different from both aGVHD groups (P < 0.001). The specificity to completely rule out aGVHD did not reach 100% until 16.0 ave. eos/10 HPFs was observed. There is a significant difference between the numbers of eosinophils found in differentiating DHR from aGVHD, but a very high number (>16.0 ave. eos/10 HPFs) is necessary to rule out aGVHD completely. Therefore, a quantitative analysis of eosinophils in all biopsies to rule out aGVHD would be of limited value and should only be considered in those biopsies with significant eosinophilia.

Histopathologic Features of Cutaneous Acute Graft-Versus-Host Disease in T-Cell–Depleted Peripheral Blood Stem Cell Transplant Recipients

“…For example, eosinophils were common to both groups post TCD transplantation, but slightly less frequent in aGVHD. As with other studies 12,13 , we observed the presence of necrotic keratinocytes, including some within skin adnexal structures, in TCD non-aGVHD skin rashes, confirming that this feature alone cannot be used to make a diagnosis of GVHD.…”

“…11–13 For example, one study in allogeneic BMT recipients reported that early histopathologic evaluation provided little value, and that clinical assessment was more useful in determining prognosis. 14 Contradictory conclusions were drawn by a separate multicenter retrospective study of patients after reduced-intensity conditioning regimens, who reported that histopathologic diagnosis influenced clinical management and correlated with survival, ultimately recommending the continued use of skin biopsies in assessing patients for GVHD.…”

Workshop report from the National Institutes of Health Taskforce on the Research Needs of Eosinophil-Associated Diseases (TREAD)

“…Yet, even when intact eosinophils are not observed in tissues, the deposition of their toxic granule proteins, revealed by immunofluorescence testing, supports the premise of their involvement. 40 …”

Graft-versus-host disease

“…25 A recent review found that a very high number of eosinophils (average 16 eosinophils/10 high power fields) was needed to rule out the possibility of GHVD with 100% specificity. 26 Dyskeratotic epidermal cells, which may be contiguous to a ''satellite lymphocyte,'' are characteristic of more advanced GVHD, but are also not specific to GVHD. 27,28 Disease progression results in clefts at the dermoepidermal junction followed by complete epidermal separation (Table III).…”