We report the first case of a liver transplant in a patient with epidermolysis bullosa acquisita and associated hepatitis B virus-hepatitis D virus cirrhosis and its inherent technical issues. Epidermolysis bullosa acquisita is an autoimmune multisystem disorder involving skin and mucosa characterized by the appearing of blisters and erosions. The more severe forms may result in nutritional compromise, anemia, osteopenia, dilated cardiomyopathy, laryn­geal mucosal involvement, esophageal strictures, bladder, and kidney involvement requiring surgical intervention. Epidermolysis bullosa acquisita has become recognized as a multisystem disorder that poses several surgical challenges. This case shows that liver transplant is a feasible procedure in patients affected by epidermolysis bullosa acquisita. Patients with epidermolysis bullosa acquisita require a particular pretransplant assessment and a dedicated intra- and postoperative management of every invasive procedure that can traumatize the skin and mucosal epithelium to achieve an uneventful liver transplant. Epidermolysis bullosa acquisita does not represent a contraindication to liver transplant, and immunosuppression after transplant may favor a good systemic control of this immunologic disorder.

Key words : Liver transplant, Acquired epidermolysis bullosa, Immunosuppression, Tacrolimus, Hepatitis B

Introduction

Epidermolysis bullosa acquisita (EBA) is an autoimmune multisystem disorder involving the skin and the mucosae, characterized by the appearance of blisters and erosions and secondary infections that result from the effects of IgG autoantibodies directed against the 145-kDa non-collagenous aminoterminal (NC-1) domain of collagen VII, a major component of anchoring fibrils. Clinical and laboratory features of EBA overlap with those of other bullous dermatoses, making diagnosis challenging.

The more severe form of EBA may result in cutaneous and mucosal scarring that could lead to blindness, oesophageal strictures, joint contractures, nutritional compromise, anaemia, osteopenia, and laryngeal mucosal involvement.^1,2 Moreover, EBA may be associated with other conditions (eg, inflammatory bowel disease, amyloidosis, lymphoma, and systemic lupus erythematosus).² The involvement of gastrointestinal and respiratory mucosa is particularly concerning because during intubation manoeuvres, some lesions may occur and esophageal membranes or ulcers also may appear.² Furthermore, EBA has been reported infrequently in association with chronic liver disease. Treatment consists of systemic glucocorticoids or other immunosuppressive drugs (eg, azathioprine or mycophenolate mofetil).^1,2 More recently, rituximab has been tested in refractory cases.³

For the aforementioned reasons, EBA is a multisystem disorder that poses several surgical challenges. We report the first case of liver transplant for hepatitis B virus-hepatitis D virus (HBV-HDV) cirrhosis in a patient with this dermatologic disease, including all the aforementioned technical issues.

Case Report

A 54-year-old woman with HBV-HDV cirrhosis was assessed for liver transplant. She was HBsAg-positive, HBeAg-positive, with a fluctuating HBV-DNA and with HDV-RNA positivity. Since 1994, she had been diagnosed as having EBA, presenting with large blisters on the skin and skin erosions that were treated with oral steroids. The disease forced her to sleep always with special linen sheets, being careful to avoid potential wounds or chafing. The patient had had multiple episodes of liver failure with ascites during the previous 2 years. Total bilirubin was 3.9 mg/dL and international normalized ratio was 1.4. Child Pugh score was B9 with a Model for End-Stage Liver Disease of 17. Her medical history was unremarkable for bullous diseases, and her family history was negative for blistering disease. Examination of a skin biopsy specimen revealed a cell-poor subepidermal vesicle. Direct immuno­fluorescence analysis showed typical IgG deposition in the dermal-epidermal interface at immuno­fluorescence.

She was assessed by a multidisciplinary team for hematologic, cardiac, skeletal, gastrointestinal, nutritional, and metabolic issues in addition to a careful airway assessment. She had a history of surgery for kidney stones under total anaesthesia and orotracheal intubation without complications. An orthotopic liver transplant from a deceased donor was finally performed. At the time of admission for orthotopic liver transplant, physical examination did not show any skin lesions. During the procedure, attention was placed on patient mobilization and positioning on the operative table to reduce the risk of inadvertent shearing of the skin; the operative table was padded. Special care was taken with airway intubation, using a smaller endotracheal tube. All equipment was well lubricated and all invasive devices (eg, the central venous catheter, Swan-Ganz catheter, nasogastric tube, and radial cannula) were fixed with stitches to the skin avoiding the use of adhesive tapes. All wounds were covered by nonadhesive dressing.

The patient had no complications during surgery or during her time in the intensive care unit. The automatic respirator was removed 6 hours after surgery without blistering of her mouth and airway. Daily postoperative wound care and pain management was taken during dressing changes. However, during hospitalization she developed some blisters skin along the nonadhesive dressing application site, but thanks to proper wound care, she had no infective complications (Figures 1 - 2 - 3). Immunosuppression was accomplished with tacro-limus, mycophenolate acid, and steroids. Three months after transplant, she developed dysphagia and had some difficulty in taking her medications; an upper gastrointestinal endoscopy showed linear ulcers of the distal oesophagus. This was resolved with proton pump inhibitors. At 48 months of follow-up, the patient has a good liver function, and controls the HBV with lamivudine.

Discussion

Epidermolysis bullosa acquisita is a subepidermal bullous disease whose pathogenesis is autoantibody mediated. These patients produce IgG against type VII collagen, a major component of anchoring fibrils. At immunofluorescence, this can be seen as a deposit of IgG along the dermal-epidermal junction. Because of this alteration, the epidermal layer may detach from the derma and vesicles, and bullae are formed. Autoantibodies also may be present in the patient’s serum.¹ Involvement of the gastrointestinal and respiratory mucosa is especially frightening because during the intubation maneuvers, some lesions can be procured and esophageal membranes or ulcers may develop.² Treatment for this disease consists of systemic glucocorticoids, sometimes in combination with other immunosuppressive drugs (eg, azathio-prine or mycophenolate mofetil).² More recently rituximab, an anti-CD20 monoclonal antibody used for treatment of non-Hodgkin’s lymphomas, has been tested in refractory cases of EBA.³

Epidermolysis bullosa acquisita is known to be a multisystem disorder that poses several surgical challenges. This case shows that liver transplant may be a feasible procedure in patients affected by advanced liver cirrhosis and EBA. It requires careful pretransplant assessment, and a dedicated intra- and postoperative management of every invasive procedure has the potential of traumatizing the skin and mucosal epithelium to achieve an uneventful liver transplant. We think that the association of EBA with liver cirrhosis does not represent a contraindication to liver transplant and a tacrolimus-based immunosuppression after transplant may favor a good systemic control of this immunologic disorder.

References:

1. Mayuzumi M, Akiyama M, Nishie W, et al. Childhood epidermolysis bullosa acquisita with autoantibodies against the noncollagenous 1 and 2 domains of type VII collagen: case report and review of the literature. Br J Dermatol. 2006;155(5):1048-1052.
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2. Goldschneider K, Lucky AW, Mellerio JE, et al. Perioperative care of patients with epidermolysis bullosa: proceedings of the 5th international symposium on epidermolysis bullosa, Santiago Chile, December 4-6, 2008. Paediatr Anaesth. 2010;20(9):797-804.
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3. Crichlow SM, Mortimer NJ, Harman KE. A successful therapeutic trial of rituximab in the treatment of a patient with recalcitrant, high-titre epidermolysis bullosa acquisita. Br J Dermatol. 2007;156(1):194-196.
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