Late-onset keratoconjunctivitis sicca syndrome after bone marrow transplantation: Incidence and risk factors

The incidence, time course and risk factors associated with late-onset keratoconjunctivitis sicca syndrome after bone marrow transplantation (BMT) was evaluated in a multicenter retrospective cohort study conducted by the European Group for Blood and Marrow Transplantation (EBMT) Working Party on Late Effects. Data were requested from participating European centers on all patients transplanted up to December 1980 and on all patients treated during the year of 1984. Twenty-eight centers reported data on 258 patients and 248 could be evaluated for keratoconjunctivitis. Forty-eight of the 248 (19%) patients developed a keratoconjunctivitis sicca syndrome between 3 and 127 months (13.8 months) after BMT. The actuarial probability of developing dry eyes was 21 ± 3% at 15 years. Thirty-three of the 48 (69%) patients with sicca syndrome had graft-versus-host disease (GVHD) compared to 60 of 200 (30%) patients without keratoconjunctivitis (P < 0.0001). The probability of developing keratoconjunctivitis sicca syndrome at 15 years was 38 ± 6% for patients with and 10 ± 3% (P < 0.0001) for those without chronic GVHD. Factors associated with an increased risk for late-onset of keratokonjunctivitis are chronic GVHD (relative risk 3.5; CI, 1.9-6.9), female patients (5.6; CI, 1.6-18.8), age older than 20 years (3.1; CI, 1.6-5.6), single dose irradiation for preparation to BMT (3.8; CI, 1.3-11.3) and methotrexate for prevention of GVHD (3.6, CI, 1.05-12.8). Late-onset keratoconjunctivitis is a frequent ocular complication of BMT. With adequate treatment, severe corneal defects can be avoided. It occurs more frequently in patients with chronic GVHD, but, independent of chronic GVHD, more frequently in older patients and in females as it is observed in de novo Sjogren's syndrome. These data support the current concept that chronic GVHD is a reaction of both, allo- and autoimmunity.