Real-Time Reflectance Confocal Microscopy of Cutaneous Graft-versus-Host Disease Correlates with Histopathology

Abstract

Reflectance confocal microscopy (RCM) allows noninvasive, real-time evaluation of the skin at a resolution akin to histopathology (HP), but its application in cutaneous graft-versus-host disease (GVHD) has not been extensively assessed. We describe RCM features of cutaneous GVHD including acute (aGVHD), late acute, chronic (cGVHD; sclerotic and nonsclerotic subtypes), and inactive GVHD and correlate RCM with same-site HP for a subset of patients. Thirty-two adult and pediatric allogeneic hematopoietic cell transplantation (allo-HCT) recipients with cutaneous GVHD received RCM imaging of ≥1 lesions (n = 44), 13 of which necessitated skin biopsy. RCM images were deidentified and assessed by 2 RCM experts blinded to clinical and HP findings to reach a consensus on the features and patterns of the inflammatory dermatoses. Major RCM features (present in ≥65% of lesional sites) and patterns were reported. To determine the correlation between RCM and HP, detection of cellular features and patterns of inflammatory dermatoses were compared using percent agreement and prevalence-adjusted, bias-adjusted kappa estimates. Seven patients with early or late aGVHD (7 lesions) had irregular honeycombing, spongiosis, dermoepidermal junction (DEJ) and dermal inflammation, and melanophages; those with early aGVHD also had hyperkeratosis, dilated vessels, and coarse connective tissue. Both groups had an interface dermatitis pattern. Eighteen patients with nonsclerotic cGVHD (24 lesions) had irregular honeycombing, spongiosis, DEJ and dermal inflammation, dilated vessels, coarse connective tissue, and interface and spongiotic dermatitis patterns. Three sclerotic patients with cGVHD (7 lesions) had irregular honeycombing, DEJ and dermal inflammation with an interface dermatitis pattern. Four patients with inactive GVHD (6 lesions) showed minimal inflammation. RCM and HP had similar detection rates for 6 of 13 features and overall patterns important for diagnosis in 2 patients with late aGVHD (2 lesions; 15%) and 10 with nonsclerotic cGVHD (11 lesions; 85%) necessitating skin biopsy. RCM can detect features commonly reported in cutaneous GVHD and is comparable to HP. Additional characterization of cutaneous GVHD by RCM may enable future use in diagnosing, monitoring, or predicting disease in real time.