Exp. Clin. Endocrino!. Vol. 97, No. 2/3, 1991, PP. 328-331
J. A. Barth, Leipzig
Hospita! Saint Pierre, University of Brussels, Department of Internal Medicine, Thyroid Investigation Clinic, Brussels/Belgium
The Role of Plasmapheresis in Graves' Ophthalmopathy
Introduction It is particularly appropriate that Graves' Ophthalmopathy (GO) has been included
in the programme of an International Thyroid Symposium, commemorating the "150th Anniversary of Basedow's Disease", because GO still constitutes today one of the most extraordinary, difficult and challenging aspect of this common endocrine disorder. It is also appropriate to discuss the role of plasmapheresis (PP) in an anniversary meeting, since the first case with severe GO was treated using this procedure ap-
proximately 10 years ago by Dandona et al. (1979). I therefore wish to thank the organizers for giving me the opportunity to present my views on this important problem, even though little progress has been made over the last years to evaluate more completely the usefulness of this therapeutic approach. Hence, my presentation today will be largely based on the conferences presented in September 1988 in Montreal (First
International Symposium on Graves' Ophthalmopathy; Glinoer et al., 1990) and May 1989 in Helsinki (Advances in Endocrine Ophthalmopathy of Graves' Disease; Glinoer and Schrooyen, 1990).
Procedure and Rationale Plasma exchange therapy is based on the likely assumption that GO is of autoimmune origin, and hence that extraction of detrimental substances from the blood might be beneficial. This hypothesis
was confirmed in the origina! reports of Dandona et al. (1979) where the authors showed that plasmapheresis was inactive in chronic non-progressive GO, but was quite effective in more acute forms. The authors also observed that a rebound occurred if plasmapheresis was not followed by immunosuppression. Our own experience encompasses a total of 15 patients, 12 of whom are regularly followed in our institution. The current procedure used consists in 4 plasmapheresis sessions performed over a period of 5-8 days, with a total of 10 liters of plasma removed (replaced by stable solutions of plasma proteins). To avoid recurrences, immunosuppressive therapy with prednisolone (40 mg/day) and azathioprine (100mg/day) is administered to all patients after the last plasmapheresis session. The treatment is main-
tained for 3-6 months and prednisolone is usually rapidly tapered (after 3-4 weeks) to between 15 and 7.5 mg/day. In most patients, steroids can be stopped after 3 months, owing to the rapid improvement in ocular findings. Our view is not that plasmapheresis is effective in all severe cases, nor that it should be considered as the sole form of medical therapy. In addition, PP is an expensive technique,
Downloaded by: Universite Laval. Copyrighted material.
D. GLINOER
329
D. GLINOER, Plasmapheresis in Ophthalmopathy
requiring hospitalization, and it is not automatically reimbursed by the social security systems in every European country. Plasma exchange therapy has, however, 3 main advantages: the ocular improvement is quite rapid, sometimes dramatic. It is effective even in patients in whom other treatments have failed, and it allows for a striking decrease in the adverse reactions to adjuvant high-dose prolonged steroid administration.
Results
läble 1 lists the results obtained by comparing a modified Donaldson, ophthalmopathy index score before and after plasmapheresis, that is before adjuvant immunosuppressive therapy was started. In the scoring system used, maximal severity for one given item is "3". The patients had been selected for plasmapheresis because of extraocular pressure, and ocular mobility). It should be emphasized that a "1" point difference in the score for sight loss may be of crucial importance for the patient's vision. This actually represents one of the difficulties with the use of scoring systems, which frequently underevaluate the clinical reality. The mean reduction in scores reached 4OWo and clinical improvement was evident in almost all patients. Two additional features deserve a comment. First, extraocular muscle changes (measured by CT scan) were impressive, with a 10-25% decrease in transverse
muscle thickness (which represents up to 50% reduction in volume), and a 40-60% decrease in muscle density, presumably representing the decrease in órbita! accumulation of glycosaminoglycans (GAG). Second, in most patients GAG excretion was initially markedly elevated (up to 10-fold the normal values) and decreased by 60% after plasma exchange therapy.
Our present conclusions are therefore that plasmapheresis is quite effective, but should be reserved as a first line of treatment for severe and rapidly progressive GO. After withdrawal of immunosuppressive therapy, recurrence was observed after about 6 months
in 1/3 of the patients. With a second course of PP followed by a shorter immunosuppressive treatment, all patients have remained stabilized since then and are doing well. Thble 1
Short-term effects of plasmapheresis ) Before plasmapheresis
Ophthalmopathy index Soft tissue Proptosis Intraocular pressure Extraocular muscle Cornea Visual acuity Urinary excretion of GAG Total GAG, mg/day Uronic acid (mg/d)
After plasmapheresis
2.0 2.0 2.0
0.9
1.8 2.5
1.2 1.0 1.6
2.6
1.3 1.1
0.005 0.005 0.001 0.05 0.10 0.10
b)
35
15
3
1
')Reproduced from Horm. Res. 26 (1987) 287. b)
p
J. A. Barth, Leipzig
Hospita! Saint Pierre, University of Brussels, Department of Internal Medicine, Thyroid Investigation Clinic, Brussels/Belgium
The Role of Plasmapheresis in Graves' Ophthalmopathy
Introduction It is particularly appropriate that Graves' Ophthalmopathy (GO) has been included
in the programme of an International Thyroid Symposium, commemorating the "150th Anniversary of Basedow's Disease", because GO still constitutes today one of the most extraordinary, difficult and challenging aspect of this common endocrine disorder. It is also appropriate to discuss the role of plasmapheresis (PP) in an anniversary meeting, since the first case with severe GO was treated using this procedure ap-
proximately 10 years ago by Dandona et al. (1979). I therefore wish to thank the organizers for giving me the opportunity to present my views on this important problem, even though little progress has been made over the last years to evaluate more completely the usefulness of this therapeutic approach. Hence, my presentation today will be largely based on the conferences presented in September 1988 in Montreal (First
International Symposium on Graves' Ophthalmopathy; Glinoer et al., 1990) and May 1989 in Helsinki (Advances in Endocrine Ophthalmopathy of Graves' Disease; Glinoer and Schrooyen, 1990).
Procedure and Rationale Plasma exchange therapy is based on the likely assumption that GO is of autoimmune origin, and hence that extraction of detrimental substances from the blood might be beneficial. This hypothesis
was confirmed in the origina! reports of Dandona et al. (1979) where the authors showed that plasmapheresis was inactive in chronic non-progressive GO, but was quite effective in more acute forms. The authors also observed that a rebound occurred if plasmapheresis was not followed by immunosuppression. Our own experience encompasses a total of 15 patients, 12 of whom are regularly followed in our institution. The current procedure used consists in 4 plasmapheresis sessions performed over a period of 5-8 days, with a total of 10 liters of plasma removed (replaced by stable solutions of plasma proteins). To avoid recurrences, immunosuppressive therapy with prednisolone (40 mg/day) and azathioprine (100mg/day) is administered to all patients after the last plasmapheresis session. The treatment is main-
tained for 3-6 months and prednisolone is usually rapidly tapered (after 3-4 weeks) to between 15 and 7.5 mg/day. In most patients, steroids can be stopped after 3 months, owing to the rapid improvement in ocular findings. Our view is not that plasmapheresis is effective in all severe cases, nor that it should be considered as the sole form of medical therapy. In addition, PP is an expensive technique,
Downloaded by: Universite Laval. Copyrighted material.
D. GLINOER
329
D. GLINOER, Plasmapheresis in Ophthalmopathy
requiring hospitalization, and it is not automatically reimbursed by the social security systems in every European country. Plasma exchange therapy has, however, 3 main advantages: the ocular improvement is quite rapid, sometimes dramatic. It is effective even in patients in whom other treatments have failed, and it allows for a striking decrease in the adverse reactions to adjuvant high-dose prolonged steroid administration.
Results
läble 1 lists the results obtained by comparing a modified Donaldson, ophthalmopathy index score before and after plasmapheresis, that is before adjuvant immunosuppressive therapy was started. In the scoring system used, maximal severity for one given item is "3". The patients had been selected for plasmapheresis because of extraocular pressure, and ocular mobility). It should be emphasized that a "1" point difference in the score for sight loss may be of crucial importance for the patient's vision. This actually represents one of the difficulties with the use of scoring systems, which frequently underevaluate the clinical reality. The mean reduction in scores reached 4OWo and clinical improvement was evident in almost all patients. Two additional features deserve a comment. First, extraocular muscle changes (measured by CT scan) were impressive, with a 10-25% decrease in transverse
muscle thickness (which represents up to 50% reduction in volume), and a 40-60% decrease in muscle density, presumably representing the decrease in órbita! accumulation of glycosaminoglycans (GAG). Second, in most patients GAG excretion was initially markedly elevated (up to 10-fold the normal values) and decreased by 60% after plasma exchange therapy.
Our present conclusions are therefore that plasmapheresis is quite effective, but should be reserved as a first line of treatment for severe and rapidly progressive GO. After withdrawal of immunosuppressive therapy, recurrence was observed after about 6 months
in 1/3 of the patients. With a second course of PP followed by a shorter immunosuppressive treatment, all patients have remained stabilized since then and are doing well. Thble 1
Short-term effects of plasmapheresis ) Before plasmapheresis
Ophthalmopathy index Soft tissue Proptosis Intraocular pressure Extraocular muscle Cornea Visual acuity Urinary excretion of GAG Total GAG, mg/day Uronic acid (mg/d)
After plasmapheresis
2.0 2.0 2.0
0.9
1.8 2.5
1.2 1.0 1.6
2.6
1.3 1.1
0.005 0.005 0.001 0.05 0.10 0.10
b)
35
15
3
1
')Reproduced from Horm. Res. 26 (1987) 287. b)
p
