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

ABSTRACT Background Reflectance confocal microscopy (RCM) allows noninvasive, real-time evaluation of the skin at resolution akin to histopathology (HP), but its application in cutaneous graft-versus-host disease (GvHD) has not been extensively assessed. Objective 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. Study Design Thirty-two adult and pediatric allogeneic hematopoietic cell transplant (allo-HCT) recipients with cutaneous GvHD received RCM imaging of ≥1 lesions (n=44), 13 of which required skin biopsy. RCM images were de-identified and assessed by 2 RCM experts blinded to clinical and HP findings to reach consensus on features and patterns of inflammatory dermatoses. Major RCM features (present in ≥65% of lesional sites) and patterns were reported. To determine 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 (PABAK). Results Seven early and late aGvHD patients (7 lesions) had irregular honeycombing, spongiosis, dermoepidermal (DEJ) and dermal inflammation, and melanophages; early aGvHD also had hyperkeratosis, dilated vessels, and coarse connective tissue. Both had an interface dermatitis pattern. Eighteen nonsclerotic cGvHD patients (24 lesions) had irregular honeycombing, spongiosis, DEJ and dermal inflammation, dilated vessels, coarse connective tissue and interface and spongiotic dermatitis patterns. Three sclerotic cGvHD patients (7 lesions) had irregular honeycombing, DEJ and dermal inflammation, with an interface dermatitis pattern. Four inactive GvHD patients (6 lesions) showed minimal inflammation. RCM and HP had similar detection for 6 of 13 features and overall patterns important in diagnosis for 2 late aGvHD (2 lesions; 15%) and 10 nonsclerotic cGvHD patients (11 lesions; 85%) requiring skin biopsy. Conclusion RCM can detect features commonly reported in cutaneous GvHD and is comparable to HP. Additional characterization of cutaneous GvHD on RCM may enable future use to diagnose, monitor, or predict disease in real time.