Bullous Pemphigoid Associated With Acute Renal Allograft Rejection

Abstract

Bullous pemphigoid (BP) can occur rarely with renal allograft rejection. Three cases have been reported in the literature, and all of them occurred during chronic rejection of transplanted kidneys. We report a case of acute renal allograft rejection presenting with bullous pemphigoid. A 46-year-old man was admitted to our hospital for a generalized bullous skin eruption. This was associated with mild decrease in urine output. He denied any history of pruritus, eye lesions, and photosensitivity. His other significant medical history included hypertension, hepatitis-C, and type-1 diabetes mellitus with end-stage renal disease. He received a cadaveric renal transplant in 2002. He was on tacrolimus and mycophenolate mofetil, the later medication was discontinued a few weeks before onset of his symptoms. He denied taking any other medication. Physical examination revealed an oral temperature of 99.6 and a heart rate of 106. Cutaneous examination revealed widespread tense bullae over his face, trunk, and all four extremities. The remainder of the systemic examination was normal. At admission, serum creatinine was 2.4 with a blood urea nitrogen of 40 mg/dL. His baseline creatinine had been 1.0 mg/dL. Urinalysis revealed proteinuria without any evidence of infection. He had no eosinophiluria. Complete blood count, liver function test, chest X-ray, electrocardiography, renal ultrasound, polymerase chain reaction for cytomegalovirus, herpes simplex virus, and Epstein-Barr virus, 24-hour total urinary protoporphyrins, Wood's lamp screen for protoporphyria, and cultures of blister fluid were all normal. Autoimmune screen performed after admission revealed antinuclear antibody positive in a titer of 1:80; C-ANCA, P-ANCA, complement-C3, C4, total complement, and serum electrophoresis were all normal. Histopathology of renal graft biopsy revealed chronic inflammatory infiltrate rich in polyclonal plasma cells (kappa and lambda positive) occupying 30% of interstitium. There were foci of moderate tubulitis. A predominance of CD-3 lymphocytes over CD-20 lymphocytes and occasional eosinophils were seen. CD4 was negative in peritubular capillaries on direct immunofluorescence of kidney biopsy. This was consistent with the diagnosis of acute T-cell-mediated renal graft rejection (BANFF score-1). Histology of skin biopsy showed subepidermal separation with minimal lymphocytic infiltrate. Direct immunofluorescence examination was positive for IgG and C-3 linear deposits along dermal-epidermal junction and negative for IgA (Fig. 1). This confirmed the diagnosis of BP versus other bullous disorders. Antibodies to BP antigen were strongly positive with titers of 1:2560. He was treated with high-dose steroids and mycophenolate was restarted. His renal functions improved,—serum creatinine decreased from 2.4 to 1.2 mg/dL, and skin lesions began to resolve. BP is idiopathic in most of the cases. Several drugs are associated with BP (1). BP could also be associated with some glomerulopathies (2, 3). BP is considered to have an autoimmune etiopathology. Autoantibodies directed against certain molecules in hemidesmosomes of basal keratinocytes, called BP antigen-180 and BP antigen-240, results in complement activation followed by chemotaxis of neutrophils and eosinophils (4). There have been only a few cases of BP associated with chronic renal allograft rejection reported in literature (5–7). Acute allograft rejection presenting with BP, although not reported previously, was a strong possibility in our patient. Temporal relationship between cessation of mycophenolate medication and acute graft rejection along with appearance of skin lesions suggests a common immune injury producing this clinical picture. The immune mechanism producing skin lesions during renal graft rejection is not clear so far. Cross-reactivity between epidermal and glomerular basement membrane antigen has been suggested in some of the reported cases of BP occurring in association with renal graft rejection (8). The alpha-5 chain of type-IV collagen present in renal and epidermal basement membrane has been suggested to be the target antigen for autoantibodies (9). Because all the three reported cases of chronic graft rejection with BP had resolution of skin lesions after graft nephrectomy (5, 7) or graft atrophy (6), the possibility of immunological activity within the renal graft triggering the skin lesions by some yet unidentified immune mechanism has been suggested to explain this association (7). Our patient was not taking any drug associated with BP. Because BP did not appear immediately on cessation of mycophenolate, we feel that it was related to renal rejection. In addition to this, the resolution of acute renal allograft rejection followed by clearing of bullous skin lesions on reinitiating immunosuppressive therapy in our patient supports the argument that immune mechanisms involved with graft rejection could be triggering the skin lesions. To the best of our knowledge, this is the first case report of acute renal allograft rejection manifesting with BP. Aijaz A. Sofi Department of Medicine University of Toledo Medical Centre Toledo, OH Lorrie Gottwald Department of Dermatology University of Toledo Medical Centre Toledo, OH Keith Bohman Department of Pathology University of Toledo Medical Centre Toledo, OH Dinkar Kaw Division of Nephrology Department of Medicine University of Toledo Medical Centre Toledo, OH