Liver Transplantation in an Adult With Sclerosing Cholangitis due to Multisystem Langerhans Cell Histiocytosis

Abstract

To the Editor: Langerhans cell histiocytosis (LCH) is a rare hematopoietic disorder characterized by proliferation of CD1a+ dendritic cells. An association between LCH and sclerosing cholangitis (SC) has rarely been reported in adults with only four cases of liver transplantation for LCH associated SC in the literature (1). We have recently managed such a patient with SC secondary to LCH who eventually required liver transplantation, and feel the case adds to the evidence that liver transplantation can be efficacious in treating some rare diseases, such as LCH, and that posttransplant immunosuppression can prevent recurrence. Furthermore, it highlights the ethical implications of using valuable organs when evidence for transplant is scarce. The patient was diagnosed with SC in 2006, aged 39, following previous gallstone pancreatitis and chronically abnormal liver function with intermittent pruritis. He was then independently diagnosed with LCH in 2007 after a symptomatic scapula mass was biopsied. His SC progressed despite repeated biliary duct dilatations and by 2008 he was being considered for liver transplant with a Model for End-stage Liver Disease (MELD) score of 15. Pretransplant liver biopsy revealed immunostaining diagnostic of LCH (Figure 1). He underwent successful orthotopic liver transplantation in March 2009 and was immunosuppressed postoperatively with tacrolimus and prednisolone. Due to subsequent hyperglycemia this was changed to cyclosporine and mycofenolate mofetil. At present, he is well with normalized liver function and no signs of transplant rejection in two subsequent liver biopsies. Liver biopsy: (A) portion of a segmental bile duct (BD) infiltrated by Langerhans cells (arrows), CD1a [panel (B)] and S100 immunoreactive [panel (D)]. High-power view of mass of Langerhans cells with eosinophils (Eos) [panel (C)]. Liver transplantation has been shown to be the only successful treatment of end-stage biliary cirrhosis in patients with LCH (1). Chemotherapy in this group may actually cause deterioration in liver function. Our decision to transplant was precipitated by the patient's liver failure and rising MELD score. A recent study of 1130 patients demonstrated survival benefit at 1 year posttransplant once a patient's MELD score reached 15 irrespective of pathogenesis (2). In rare diseases where evidence of efficacy is limited to a few case reports, deterioration in liver function may therefore best guide a decision to consider transplantation. Due to the systemic nature of LCH, there is the additional concern of disease recurrence posttransplant. Reassuringly, only one recurrence within an adult graft has previously been described (3). Immunosuppression posttransplant could reduce recurrence rates and this may suggest an immune mechanism in the pathogenesis of LCH. In liver transplantation secondary to LCH the ideal immunosuppressant would prevent graft rejection and LCH recurrence. There is currently no convincing evidence which agent most effectively achieves this. Cyclosporine has been the most extensively documented immunosuppressant used to treat LCH. However evidence of its efficacy is mainly in the form of case series and these have demonstrated widely varying results (4, 5). To our knowledge there is no literature on the use of other immunosuppressants such as mycophenolate mofetil, mammalian target of rapamycin (mTOR) inhibitors or calcineurin inhibitors as anti-LCH agents. Of note Jorden et al. have shown that pathological Langerhans cells aberrantly express CD52, whereas normal Langerhans cells do not (6). Therefore alemtuzumab, an anti-CD52 monoclonal antibody previously shown to be efficacious in preventing graft rejection (7), may also have activity against LCH. The immunological mechanisms involved in this disease, although as yet poorly understood, provide the opportunity for posttransplant immunosuppression to have a dual role in preventing graft rejection and disease recurrence. The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation.