Prevention of corneal-graft failure with the immunosuppressive drug azathioprine

Mackay, Ian R.; Bignell, John L.; Smith, P. H.; Crawford, B. A.

doi:10.1097/00007890-196805000-00047

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“…13 There exist only sporadic reports of the use of topical AZA in oral diseases such as aphthous stomatitis and periodontosis 14,15 and as immunosuppressive therapy in the prevention of corneal graft rejection. 16,17 The role of systemic AZA in the management and prevention of inflammatory bowel disease (IBD) has been well characterized, 18,19 and shows AZA to be efficacious in the long- term management of inflammatory bowel diseases such as Crohn's disease, with less long-term toxicity than that associated with corticosteroids. 20 Recent studies of the pharmacokinetics of alternative formulations of azathioprine in the treatment of inflammatory bowel diseases have been undertaken with the goal of offering methods of local drug delivery in the lower intestine that reduce both systemic bioavailability and resultant toxicity.…”

Section: Discussionmentioning

confidence: 99%

Topical azathioprine in the combined treatment of chronic oral graft-versus-host disease

Epstein

Nantel

Sheoltch

2000

Bone Marrow Transplant

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Summary:This paper presents the first report of the use of topical azathioprine in the management of persistent symptomatic chronic oral graft-versus-host disease (GVHD). Topical azathioprine suspension was used as an oral rinse and was swallowed, maintaining the previously prescribed systemic dose of azathioprine, and resulted in improvement in a case of oral GVHD that was resistant to other approaches to management. Topical azathioprine may provide additional therapy in the management of immune-mediated oral mucosal disease. Clinical trials appear warranted based upon the results of topical azathioprine use as presented in this case report. Bone Marrow Transplantation (2000) 25, 683-687. Keywords: oral graft-versus-host disease; bone marrow transplant; azathioprine Bone marrow transplant (BMT) is a common treatment for many hematologic malignancies and immune deficiency states, and is used with increasing frequency for salvage therapy of many solid malignancies. Oral involvement with graft-versus-host disease (GVHD) may occur in 25-70% of patients, 1 despite GVHD prophylaxis. The oral findings of acute GVHD include painful desquamative, erythematous, and ulcerative mucosal lesions. 1,2 Chronic oral GVHD can display lichenoid, erythematous, and ulcerative lesions, manifestations of systemic sclerosis and a sicca syndrome consisting of xerostomia and salivary gland atrophy. 1-3 Oral complications include pain due to the mucosal changes and altered or reduced taste, and may potentially have an impact on speech, deglutition, and use of oral prostheses. Oral infection, particularly due to candida species, and dental demineralization and caries may also occur.The management of chronic oral GVHD consists of appropriate systemic therapy combined with proper oral hygiene and use of topical steroids. cannot be effectively managed, the complications of persisting xerostomia, including candidosis and caries risk, must require treatment.We report a severe case of chronic oral GVHD refractory to systemic and topical therapies, which was managed successfully with the addition of a topically applied liquid formulation of the immunosuppressive drug azathioprine (AZA). Case reportA 34-year-old male presented with pancytopenia in late October 1994, and was diagnosed with aplastic anemia. He received a matched sibling donor bone marrow transplant on 1 November 1994, and was seen monthly following transplant. He had continuing difficulties with GVHD, including oral involvement. This case report focuses on the progress of the oral complications. His oral status was evaluated at day 100 post BMT in March 1995. Oral findings were consistent with pseudomembranous candidiasis, and ulceration on the left cheek was consistent with minor trauma. There were no clinical findings suggestive of oral GVHD, and saliva volumes were not decreased. Acute (grade II) GVHD (skin and liver) was treated with systemic corticosteroids. Therapy with systemic cyclosporin (3 mg/kg twice a day) and prednisone (1 mg/kg/day) was commenced in May 1995.Persistin...

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