Cutaneous Chronic GVHD: Sclerodermatous and Morpheic Variants

Abstract

Patients with cutaneous chronic GVHD (cGVHD) often undergo a progression to a sclerodermatous phase. This occurs in three pathways following a generalized lichenoid inflammatory state, less commonly out of a morpheic state or as eosinophilic fasciitis. The changes include fibrous remodeling of the dermal collagen, which eventually leads to dense dermal fibrosis and fibrosis within the underlying subcutaneous fat, resulting in contractures and frozen joints. The evolution from an inflammatory to sclerotic phase is a continuum. The pandermal sclerosis may be modified by immunosuppression, and there is variability from different sites. Evaluation of sclerodermatous chronic GVHD requires a full-thickness biopsy. However, because it is difficult to distinguish static from active changes, the diagnosis often relies on clinical evaluation. A framework for evaluating fibrosis after clinical intervention is proposed. Sclerodermatous cGVHD phenotypically resembles progressive systemic sclerosis (PSS). Pathobiological studies of the microvasculature’s role in the genesis of sclerosis indicate normal dermal capillary architecture and endothelial phenotype in cGVHD in contrast to PSS. Studies regarding a reduction of dermal vessels in patients with cGVHD are discordant. The current thinking is that the sclerosis evolves from a combination of cytokines and B-cell hyper-reactivity, leading to prolonged stimulation of fibrosis.