Eosinophilia, Edema, and Nail Dystrophy: Harbingers of Severe Chronic Graft Versus Host Disease of the Skin in Children

Abstract

            Skin involvement has been shown to be predictive of poor prognosis in patients with chronic graft-versus-host disease (cGVHD).  However, cGVHD of the skin has not been well described in children.  The purpose of this study was to characterize distribution, type, and extent of skin cGVHD and correlate findings with laboratory markers, severity of disease, and multi-organ involvement in a cohort of pediatric hematopoietic stem cell transplant recipients.  12 consecutive pediatric patients with skin cGVHD seen at Dana-Farber Cancer Institute and Boston Children's Hospital were evaluated over a 2-year period.  6 (50%) patients had de novo, 4 had progressive, and 2 had quiescent onset cGVHD.  Type of skin GVHD included sclerotic (9), eczematous (2), and ichthyosiform (1).  8 of 9 (89%) patients with sclerotic cGVHD had multi-organ involvement; 1 of 3 (33%) patients with nonsclerotic disease had multi-organ involvement. All patients with sclerotic cGVHD had steroid resistant disease while all patients with non-sclerotic cGVHD responded either to topical therapy or prednisone alone.  Peripheral eosinophil counts > 300 cells/uL was identified in 10 patients prior to onset of cGVHD, of whom only one could be attributed to drug hypersensitivity.  Mean peak peripheral eosinophil count of those with myofascial sclerotic cGVHD was significantly higher than that of remaining patients (1962 cells/uL vs. 525 cells/uL, p=0.03).  Mean time of onset of eosinophilia for patients with myofascial sclerotic cGVHD was 79 days (range 21-182) prior to onset of cGVHD.  6 patients were noted to have otherwise unexplained edema of the lower ± upper limbs prior to onset of skin cGVHD.  Patients with myofascial sclerotic cGVHD were significantly more likely than those with other types of skin cGVHD to have preceding peripheral edema (6/6 vs. 0/4, p=0.005).   In addition, patients with severe cGVHD were significantly more likely than those with mild or moderate cGVHD to have preceding peripheral edema (5/5 vs. 1/5, p=0.05).  Nail dystrophy was present in 7/12 (58%) patients in our cohort, and was significantly more likely to occur in patients with myofascial sclerotic cGVHD than those with other forms of skin cGVHD (7/7 vs. 1/5, p=0.01).  Pterygium inversum inguis, a specific form of nail dystrophy, was present in 4 of 12 patients, and was significantly more likely to occur in patients awaiting lung transplantation (3/4 vs. 0/8, p=0.02).  This study represents the largest cohort of pediatric patients with skin cGVHD reported in the literature and suggests that peripheral eosinophilia, edema, and nail dystrophy are harbingers of severe cGVHD of the skin in children.