Resolution of Severe Atopic Dermatitis after Tacrolimus Withdrawal

Abstract

Tacrolimus is an immunosuppressive agent used in solid organ and islet transplantation. Its topical form has shown benefit in the treatment of inflammatory skin conditions. Although tacrolimus has a wide spectrum of side effects, dermatological complications related to systemic tacrolimus therapy are limited in the literature. Atopic dermatitis (AD) is a chronic pruritic cutaneous condition that usually begins in infancy and is characterized by an increased Th2 response. We report the case of a patient with type 1 diabetes mellitus (T1DM) and history of AD latent for 10 years who developed severe dermatitis and alopecia 5 months after undergoing allogeneic islet transplantation and initiating a steroid-free immunosuppressive regimen with sirolimus and tacrolimus maintenance. After exclusion of other possible causes for the progression and exacerbation of the clinical presentation of AD, discontinuation of tacrolimus and introduction of mycophenolate mofetil resulted in full remission of the symptoms. The beneficial effects of tacrolimus withdrawal suggest a cause-effect relationship between this adverse event and the utilization of the drug. Islet graft function remained stable after modification of the therapeutic regimen (stable glycemic control and unchanged C-peptide).Key words: Atopic dermatitis; Alopecia areata; Diabetes; Immunosuppression; Islet transplantation; Tacrolimus INTRODUCTIONbetes quality of life (41) is commonly observed in patients with T1DM after islet transplantation, which is the direct consequence of improved glycemic control and Transplantation of allogeneic islets is currently limited to patients with type 1 diabetes mellitus (T1DM) reduced fear of hypoglycemia. The steady progress of the islet transplantation field with hypoglycemia unawareness and unstable glycemic control (8,24,34,40,45,47,48,52,56,57). The most remarkhas led to increased success both in islet cell processing and clinical outcome in recent years (37,45). Very promable benefits of islet transplantation include improved glycemic control (with normalization of glycated hemoising approaches are under development aiming at improving the efficiency of organ recovery and islet isolation globin A1c and reduction of glycemic excursion throughout the day) (20) and prevention of severe hypoglycemic techniques (6,15,19,50,54,59,63,67), enhancing engraftment through cytoprotection of islet grafts (27,28,35, episodes (1,40,51,53), even when exogenous insulin is required (i.e., marginal islet graft function) (8,24,34,40,38,68), islet implantation into alternative sites (7,23,39), implementation of immunomodulatory (38,43) and im-45,47,48,52,56,57 munoisolation (30,31) protocols to reduce the need for mated digestion method followed by density gradient purification was used (15,26,46). Islets were then transchronic immunosuppression (47). Meanwhile, increasing efforts have been focused toward the identification of planted intrahepatically by percutaneous catheterization of the portal vein using the bag technique (3,18). safe and unl...

Five-year follow-up of patients with type 1 diabetes transplanted with allogeneic islets: the UIC experience

“…Drug-related side effects of sirolimus and tacrolimus [34] were comparable to the rates reported by other centers [35]. Proteinuria secondary to sirolimus and reversal after discontinuation has been reported in both renal and islet transplant patients [36–40].…”

Paradoxic eczema in infants after heart transplantation

“…Refractory eczema has been reported in transplant recipients undergoing a variety of antirejection regimens, including tacrolimus monotherapy and combination therapy with sirolimus, mycophenolate mofetil, and prednisone alone or in combination . Our patients developed eczema after transitioning to maintenance regimens including tacrolimus with or without mycophenolate mofetil or azathioprine.…”

“…Systemic tacrolimus withdrawal was followed by skin clearance in one patient, and a second patient improved after dose reduction. Prior reports document similar improvement in atopic disease after oral tacrolimus dose reduction or a change in therapy, including 12 pediatric liver recipients with a history of recurrent food‐triggered angioedema or anaphylaxis whose tolerance, a 3‐year‐old heart recipient whose widespread eczema resolved, and an adult with type 1 diabetes who developed severe dermatitis after islet transplantation cleared . A theoretical risk of transplant rejection exists with discontinuation or dose reduction in immunosuppressant therapy for improvement of skin disease, although graft function remained stable in reports published to date …”

The use of selective Th2 blocker dupilumab for the treatment of atopic dermatitis in a heart transplant patient: Case report

“…Oral calcineurin inhibitors such as tacrolimus affect the Th1 response without significant effect on the Th2 pathway and notably decrease Tregs control over the Th2 pathway (Ponte et al, ; San Segundo et al, ; Weimer et al, ). Selective inhibition of the Th1 response likely shifts the immune response toward the Th2 pathway, predisposing transplant patients to the development or worsening of AD (Ponte et al, ; Weimer et al, ). Similar to immunosuppression, thymectomy at or around the time of HXT has been employed as a method toward the prevention of organ rejection, but it has been shown to accelerate premature aging of the immune system, leading to reduced TCR diversity, which is associated with AD (López‐Abente et al, ; Niemeier et al, ; Ponte et al, ).…”