Chronic graft versus host disease and skin

Abstract

In this issue, Selvaag et al . (p. 575) report an interesting new skin alteration in two young patients with graft vs host disease (GVHD). Both experienced rapid development of furrows and wrinkles on the skin of the face after a generalized rash with diffuse erythema and desquamation. The authors interpreted these skin manifestations as part of a general premature ageing process induced by GVHD, possibly related to the action of autoantibodies against collagen components. The spectrum of clinical expression of acute GVHD (aGVHD) and especially chronic GVHD (cGVHD) is wide. It is difficult to explain the pathophysiology of all signs and symptoms. The cases described by Selvaag et al . are peculiar in several aspects: the wrinkles developed in a short time after the generalized erythematous skin eruption; only the face was involved; and the clinical features resembled sun damage. It is not easy to understand how these skin changes take place, especially without a skin biopsy. As interleukins (ILs) are probably involved in the immunopathogenesis of cGVHD, these skin alterations may be related to autoreactive or alloreactive T cell production of IL4 and interferon γ (INF γ ) cytokines known to stimulate fibroblast production of collagen and perhaps also elastolytic protease and collagenase. A loss of balance between synthesis and degradation of dermal extracellular matrix, possibly influenced by other extrinsic or intrinsic factors, may theoretically lead to accumulation of elastotic material and the skin manifestations already mentioned.This paper underlines the intriguing aspects of the cutaneous manifestations and mechanisms involved in the development of GVHD. As grafts are increasingly used in the treatment of various disorders, haematological and otherwise, and as dermatological manifestations occur in more than 80% of transplant patients, it is essential for the dermatologist to be aware of the clinical spectrum of GVHD. Here we looked mainly at the clinical aspects and pathophysiology of cGVHD.

Eosinophilic pulmonary syndrome as a manifestation of GVHD following hematopoietic stem cell transplantation in three patients

“…9,10 Blood eosinophilia has also been associated with progression to chronic GVHD, and an increased probability of developing sclerodermatous GVHD. [11][12][13] Peripheral eosinophilia and eosinophilic infiltrates have also been described in the setting of solid organ transplantation, and are almost always associated with graft rejection. In liver 14 and lung 4 transplant recipients, graft infiltration by eosinophils is known to be a sensitive marker of rejection.…”

Kinetics of Th1/Th2 cytokines and lymphocyte subsets to predict chronic GVHD after allo-SCT: results of a prospective study

“…In fact, CD8 þ T cells and high levels of Th1 cytokines such as tumour necrosis factora (TNF-a), IFN-g and IL-1 were found in skin lesions and in the peripheral blood of patients with cGVHD. [9][10][11][12] In murine models of sclerodermatous GVHD, T lymphocytes and monocytes may induce skin fibrosis by the modulation of collagen production through IFN-g and transforming growth factor-beta. 13 Other data suggest that cGVHD could be mediated by Th2 immune response mechanisms.…”

Acute hepatic failure as onset of progressive sclerodermatous chronic graft-versus-host disease after donor lymphocyte infusion

“…6 A Th2 polarization with autoimmune aspects has been observed in some cases. [5][6][7][8] In our case, a Th2-type reaction could have been the trigger for hepatic and sclerodermic flare or a Th2 response could have been followed by the shift toward a Th1 response. The first immunosuppressive therapy could have stopped the Th2 reaction but not Th1 and/or the flow of cytokines and chemokines, which activated fibrosis through TGF-b.…”

“…There is no unique theory to explain the immunopathogenesis of chronic GVHD. [6][7][8] Clinical data and experimental models have demonstrated that chronic GVHD has an imbalance in the immune response toward Th1 type. 6 A Th2 polarization with autoimmune aspects has been observed in some cases.…”

“…[6][7][8] Clinical data and experimental models have demonstrated that chronic GVHD has an imbalance in the immune response toward Th1 type. 6 A Th2 polarization with autoimmune aspects has been observed in some cases. [5][6][7][8] In our case, a Th2-type reaction could have been the trigger for hepatic and sclerodermic flare or a Th2 response could have been followed by the shift toward a Th1 response.…”