- Email: [email protected]
Reduction of allergic reactions in patients undergoing long-term hemodialysis
Barlan, Geha, and Schneider
J ALLERGY CLIN IMMUNOL VOLUME 92. NUMBER 2
responsible for the production of IgG3. Further studies are needed to clarify the relationship of the low IgG3 level and susceptibility to infection. In this study we report preliminary results of treatment of patients with recurrent infections and low IgG3 levels. Double-blind placebo-controlled trials are needed to conclusively demonstrate the efficacy of prophylactic antibiotics and/or IVIG therapy in this patient group. REFERENCES’
2. Skvaril F. IgG subclassesin viral infections. Monogr Allergy 1986;19:134-43. 3. Goldblatt D, Turner MW, Levinsky RL. Brunhamdu carurrhalis: antigenic determinants and the development of the IgG subclass response in childhood. J Infect Dis 1990; 1621128-35. 4. Grubb R, Hallberg T, Hammarstrom L, et al. Correlation between deficiency of irnmunoglobulin subclass G3 and Gm allotype. Acta Path Microbial Immunol Stand 1986;94:18791. 5. Hassan MS, Islam KB, Hammarffstrom L, Edward Smith CL Role of switch in the allotype-associated variation of human serum IgG3 levels. J Immunol 1992;148:2555-62.
1. Shapiro GG, Virant FS, Furukawa CI, Pierson WE, Bierman CW. Immunologic defects in patients with refractory sinusitis, Pediatr 1991:87:311-S.
Reduction of allergic reactions in patients undergoing long-term hemodialysis Jean-Marc Cavaillon, PhD,’ Jean-Louis Poignet, MD,” Catherine Fitting, Simone Delons, MD,b and Bernard David, MD” Park, France
Prevalence of pruritus and skin flush reaction can reach 50% in patients undergoing long-term hemodialysis. Specific IgE anti-ethylene oxide,’ specific IgE antidialysis bath-derived bacterial products,’ and generation of anaphylatoxins by complement activating membranes are among the parameters that might participate in the allergenic process. We decided to modify the conventional dialysis procedures by using y-irradiated membranes instead of ethylene oxide-treated membrane, “non-complement” activating membrane, and filtration of bicarbonate dialysates to avoid any :residual bacterial derived products. Patients have been followed up for 1 year, and comparisons of clinical status, antihistaminic medications intake, and levels of total and specific IgE From “Unite d’Immuno-Allergie, Institut Pasteur; and ‘Service d’hemodialyse, Centre Medical Edouard Rist, Paris. Reprint requests: Jean-Marc Cavaillon, Unite d’Immuno-Allergie, Institut Pasteur, 28 rue Dr. Roux, 75724 Paris Cedex 15, France. J ALLERGY CLIN IMMUNOL 1993;92:355-7 Copyright 0 1993 by Mosby-Year Book, Inc. 0091-6749/93$1.00 + .lO l/54/47123
I
I Abbreviation
used
SHR: Spontaneoushistamine release I
I
were performed. In addition, we studied the in vitro spontaneous histamine release (SHR), because a high SHR was frequently associated with the presence of symptoms.3 METHODS Patients Ten stablepatientswith end-stagerenal failure, who were undergoing hemodialysisthree times a week for more than 7 years, participated in the study. The patients were selectedbecausethey had experienced allergic reactions over the last 4 years. Multifactorial etiologies of pruritus (e.g., disturbanceof calcium and phosphorusmetabolism,xerotic and hypokerotic skin, chronic hepatitis) were excluded. In addition patients were chosenfor the presenceof IgE anti-ethyleneoxide and/or a high in vitro SHR. Skin flush reactions and pruritus were scaled according to the severity of symptoms“(0, no symptoms;1, mild; 2, moderate; 3, severe).
355
356 Cavaillon et al.
J ALLERGY
TABLE I. Clinical status, anti-H, automedication, antibodies
in vitro SHR, levels of total IgE and specific
CLIN IMMUNOL AUGUST 1993
IgE
of patients* Skin flusht Pruritus* Patient
No.
1
2 3 4 5 6 7 8 9 10 Wilcoxon signed-rank test
reaction
Anti-H, drug* intake/day
SHR (%)
TO
T+12
TO
T+12
TO
T+12
TO
T + 12
3 1 1 2 0 2 3 3 0 2
1 0 1 0 0 1 1 1 1 1
1 0 1 0 2 3 0 2 3 1
0 0 0 0 0 1 0 0 0 0
4 1 1 2 0 1 6 2 1 2
1 0 0 1 0 0 1 2 1 2
42 82 50 63 73 83 59 48 9 80
22 65 52 39 60 57 46 18 7 54
0.03
0.02
0.03
0.008
NS, Not significant. *Comparisons were made at the initiation of the study (To) and 12 months later (T + 12). tOz No symptoms; 1: mild; 2: moderate; 3: severe. SIntake on the day of the dialysis session.
Hemodialysis procedures Patients were transferred from “conventional” dialysis sessions (in which ethylene oxide-sterilized cuprophan, polyacrylonitrile, or polysulfone membranes were used) to new procedures in which non-complement activating membranes (CT110 [Baxter, Chicago, Ill.] and BKl-PMMA [Toray, Tokyo, Japan]), which were sterilized by -y-irradiation, were used. Dialysis was performed in the presence of a dialyzate filtration process for removal of bacteria and pyrogens.
investigate whether the suppression of putative allergic factors during the dialysis session could improve the clinical status of patients undergoing long-term hemodialysis who had allergic-like symptoms including skin flush reaction and pruritus. Instead of “conventional” sessions, patients were dialyzed over 1 year with y-irradiated, noncomplement activating membranes and filtered bicarbonate dialysates. Most of the improvements were observed within 3 months after introduction of the new dialysis conditions. Comparison between clinical status at the initiation of the study IgE antibodies and 12 months later shows a clear improvement of the patients’ symptoms (Table I). These clinical Total IgE was assessedwith the paper radioimmunosorbent test (Pharmacia, Uppsala, Sweden) findings were correlated with a lower self-adminand anti-ethylene oxide, anti-Demzatophczgoides istered intake of antihistamines by the patients. Each patient was re-exposed to conventional hepteronyssinus, and anti-cat allergens IgE were modialysis in another medical center, over a short measured with the CAP system (Pharmacia). period of time, during his or her vacation. All of SHR them reported the occurrence of allergic reactions and increased anti-H, intake during this period. SHR from isolated leukocytes was performed We have previously reported a high in vitro as previously described.3 SHR among numerous patients undergoing heRESULTS AND DISCUSSION modialysis who had allergic-like reactions.3 We addressed the question of whether the reduction Allergic reactions that occur in some patients of the encounter with putative allergens could undergoing long-term hemodialysis are a multiparametric phenomenon and might involve syner- also lead to a diminished SHR among the selected patients. Actually, a reduced SHR was observed, gistic actions. The purpose of this study was to
Cavaillon
J ALLERGY CLIN IMMUNOL VOLUME 92, NUMBER 2
Specific IgE anti-ethylene oxide (PRU/ml)
Total IgE (rig/ml) TO 64
2000 316 3442 6760 13000 94 588 3154 1830 0.02
Specific IgE anti-Dermafophagoides (PRU/ml)
et al.
Specific IgE anti-cat allergens (Pl?U/ml)
T + 12
TO
T + 12
TO
T + 12
TO
T + 12
78 1420 194 252 5746 9600 30 272 3394 1430
co.3 3.6 4.9 7.2 300 36.4 1.9 20 17 14.5
co.3 4.9 0.6 co.3 78.4 5.8 1.1 8.5 8.8 8.8
co.3 25.2 15.5 0.7 17.9 53.2 co.3 0.4 2 37
co.3 29.3 18.7 0.4 10.7 31.6 co.3 co.3 3.7 24.8
co.3 3.2 1.0 0.4 3.5 24.5 co.3 co.3 co.3 2.9
co.3 5.9 0.6 co.3 1.2 29.4 co.3 co.3 co.3 2.4
0.015
although none of the nine patients with high SHR recovered “normal” values (i.e., less than 10% of the total h.istamine content) (Table I). Finally, we have compared the levels of total IgE and specific IgE at the start of the study and 1 year later. Eight of nine patients with detectable specific anti-ethylene oxide IgE had a reduced level of IgE-specific antibodies (Table I). Although eight patients of 10 had a lowered level of total IgE, {thechange in dialysis conditions did not lead to a reduced level of specific antibodies directed against other allergens unrelevant to dialysis. Our observtion is in agreement with that of Bommer et al? who showed that patients with anaphylactoid reactions, who underwent dialysis with y-sterilized material experienced improvement and had a decreased in vitro protease release by leukocytes on incubation in the presence of ethylene oxide-bovine serum albumin complex. Altogether, our study indicates that eradication of some of the putative allergenic factors such as
NS
357
NS
ethylene oxide residues, bacterial derived products, and a limited release of circulating anaphylatoxins might together significantly improve the well-being of patients undergoing long-term hemodialysis who are subject to allergic-like symptoms.
Rumpf KW, Seubert A, Valentin R, et al. Association of ethylene oxide-induced IgE antibodies with symptoms in dialysis patients. Lancet 1985;2:1385-7. Cavaillon JM, Simard L, Poignet JL, et al. Allergenic&y of bacterial derived products in hemodialyzed patients [Abstract]. Allergy 1992;47(suppl):53. Cavaillon JM, Poignet JL, Fitting C, et al. High in vitro spontaneous histamine release in long-term hemodialysis patients. J ALLERGY CLIN ~MUNOL 1990;85:859-64. Riickel A, Klinke B, Hertel J, et al. Allergy to dialysis materials. Nephrol Dial Transplant 1989;4:646-52. Bommer J, Barth HP, Wifhems OM, Schinedele H, Ritz E. Anaphylactoid reactions in dialysis patients: role of ethylene oxide. Lancet 1985;2:1382-5.
J ALLERGY CLIN IMMUNOL VOLUME 92. NUMBER 2
responsible for the production of IgG3. Further studies are needed to clarify the relationship of the low IgG3 level and susceptibility to infection. In this study we report preliminary results of treatment of patients with recurrent infections and low IgG3 levels. Double-blind placebo-controlled trials are needed to conclusively demonstrate the efficacy of prophylactic antibiotics and/or IVIG therapy in this patient group. REFERENCES’
2. Skvaril F. IgG subclassesin viral infections. Monogr Allergy 1986;19:134-43. 3. Goldblatt D, Turner MW, Levinsky RL. Brunhamdu carurrhalis: antigenic determinants and the development of the IgG subclass response in childhood. J Infect Dis 1990; 1621128-35. 4. Grubb R, Hallberg T, Hammarstrom L, et al. Correlation between deficiency of irnmunoglobulin subclass G3 and Gm allotype. Acta Path Microbial Immunol Stand 1986;94:18791. 5. Hassan MS, Islam KB, Hammarffstrom L, Edward Smith CL Role of switch in the allotype-associated variation of human serum IgG3 levels. J Immunol 1992;148:2555-62.
1. Shapiro GG, Virant FS, Furukawa CI, Pierson WE, Bierman CW. Immunologic defects in patients with refractory sinusitis, Pediatr 1991:87:311-S.
Reduction of allergic reactions in patients undergoing long-term hemodialysis Jean-Marc Cavaillon, PhD,’ Jean-Louis Poignet, MD,” Catherine Fitting, Simone Delons, MD,b and Bernard David, MD” Park, France
Prevalence of pruritus and skin flush reaction can reach 50% in patients undergoing long-term hemodialysis. Specific IgE anti-ethylene oxide,’ specific IgE antidialysis bath-derived bacterial products,’ and generation of anaphylatoxins by complement activating membranes are among the parameters that might participate in the allergenic process. We decided to modify the conventional dialysis procedures by using y-irradiated membranes instead of ethylene oxide-treated membrane, “non-complement” activating membrane, and filtration of bicarbonate dialysates to avoid any :residual bacterial derived products. Patients have been followed up for 1 year, and comparisons of clinical status, antihistaminic medications intake, and levels of total and specific IgE From “Unite d’Immuno-Allergie, Institut Pasteur; and ‘Service d’hemodialyse, Centre Medical Edouard Rist, Paris. Reprint requests: Jean-Marc Cavaillon, Unite d’Immuno-Allergie, Institut Pasteur, 28 rue Dr. Roux, 75724 Paris Cedex 15, France. J ALLERGY CLIN IMMUNOL 1993;92:355-7 Copyright 0 1993 by Mosby-Year Book, Inc. 0091-6749/93$1.00 + .lO l/54/47123
I
I Abbreviation
used
SHR: Spontaneoushistamine release I
I
were performed. In addition, we studied the in vitro spontaneous histamine release (SHR), because a high SHR was frequently associated with the presence of symptoms.3 METHODS Patients Ten stablepatientswith end-stagerenal failure, who were undergoing hemodialysisthree times a week for more than 7 years, participated in the study. The patients were selectedbecausethey had experienced allergic reactions over the last 4 years. Multifactorial etiologies of pruritus (e.g., disturbanceof calcium and phosphorusmetabolism,xerotic and hypokerotic skin, chronic hepatitis) were excluded. In addition patients were chosenfor the presenceof IgE anti-ethyleneoxide and/or a high in vitro SHR. Skin flush reactions and pruritus were scaled according to the severity of symptoms“(0, no symptoms;1, mild; 2, moderate; 3, severe).
355
356 Cavaillon et al.
J ALLERGY
TABLE I. Clinical status, anti-H, automedication, antibodies
in vitro SHR, levels of total IgE and specific
CLIN IMMUNOL AUGUST 1993
IgE
of patients* Skin flusht Pruritus* Patient
No.
1
2 3 4 5 6 7 8 9 10 Wilcoxon signed-rank test
reaction
Anti-H, drug* intake/day
SHR (%)
TO
T+12
TO
T+12
TO
T+12
TO
T + 12
3 1 1 2 0 2 3 3 0 2
1 0 1 0 0 1 1 1 1 1
1 0 1 0 2 3 0 2 3 1
0 0 0 0 0 1 0 0 0 0
4 1 1 2 0 1 6 2 1 2
1 0 0 1 0 0 1 2 1 2
42 82 50 63 73 83 59 48 9 80
22 65 52 39 60 57 46 18 7 54
0.03
0.02
0.03
0.008
NS, Not significant. *Comparisons were made at the initiation of the study (To) and 12 months later (T + 12). tOz No symptoms; 1: mild; 2: moderate; 3: severe. SIntake on the day of the dialysis session.
Hemodialysis procedures Patients were transferred from “conventional” dialysis sessions (in which ethylene oxide-sterilized cuprophan, polyacrylonitrile, or polysulfone membranes were used) to new procedures in which non-complement activating membranes (CT110 [Baxter, Chicago, Ill.] and BKl-PMMA [Toray, Tokyo, Japan]), which were sterilized by -y-irradiation, were used. Dialysis was performed in the presence of a dialyzate filtration process for removal of bacteria and pyrogens.
investigate whether the suppression of putative allergic factors during the dialysis session could improve the clinical status of patients undergoing long-term hemodialysis who had allergic-like symptoms including skin flush reaction and pruritus. Instead of “conventional” sessions, patients were dialyzed over 1 year with y-irradiated, noncomplement activating membranes and filtered bicarbonate dialysates. Most of the improvements were observed within 3 months after introduction of the new dialysis conditions. Comparison between clinical status at the initiation of the study IgE antibodies and 12 months later shows a clear improvement of the patients’ symptoms (Table I). These clinical Total IgE was assessedwith the paper radioimmunosorbent test (Pharmacia, Uppsala, Sweden) findings were correlated with a lower self-adminand anti-ethylene oxide, anti-Demzatophczgoides istered intake of antihistamines by the patients. Each patient was re-exposed to conventional hepteronyssinus, and anti-cat allergens IgE were modialysis in another medical center, over a short measured with the CAP system (Pharmacia). period of time, during his or her vacation. All of SHR them reported the occurrence of allergic reactions and increased anti-H, intake during this period. SHR from isolated leukocytes was performed We have previously reported a high in vitro as previously described.3 SHR among numerous patients undergoing heRESULTS AND DISCUSSION modialysis who had allergic-like reactions.3 We addressed the question of whether the reduction Allergic reactions that occur in some patients of the encounter with putative allergens could undergoing long-term hemodialysis are a multiparametric phenomenon and might involve syner- also lead to a diminished SHR among the selected patients. Actually, a reduced SHR was observed, gistic actions. The purpose of this study was to
Cavaillon
J ALLERGY CLIN IMMUNOL VOLUME 92, NUMBER 2
Specific IgE anti-ethylene oxide (PRU/ml)
Total IgE (rig/ml) TO 64
2000 316 3442 6760 13000 94 588 3154 1830 0.02
Specific IgE anti-Dermafophagoides (PRU/ml)
et al.
Specific IgE anti-cat allergens (Pl?U/ml)
T + 12
TO
T + 12
TO
T + 12
TO
T + 12
78 1420 194 252 5746 9600 30 272 3394 1430
co.3 3.6 4.9 7.2 300 36.4 1.9 20 17 14.5
co.3 4.9 0.6 co.3 78.4 5.8 1.1 8.5 8.8 8.8
co.3 25.2 15.5 0.7 17.9 53.2 co.3 0.4 2 37
co.3 29.3 18.7 0.4 10.7 31.6 co.3 co.3 3.7 24.8
co.3 3.2 1.0 0.4 3.5 24.5 co.3 co.3 co.3 2.9
co.3 5.9 0.6 co.3 1.2 29.4 co.3 co.3 co.3 2.4
0.015
although none of the nine patients with high SHR recovered “normal” values (i.e., less than 10% of the total h.istamine content) (Table I). Finally, we have compared the levels of total IgE and specific IgE at the start of the study and 1 year later. Eight of nine patients with detectable specific anti-ethylene oxide IgE had a reduced level of IgE-specific antibodies (Table I). Although eight patients of 10 had a lowered level of total IgE, {thechange in dialysis conditions did not lead to a reduced level of specific antibodies directed against other allergens unrelevant to dialysis. Our observtion is in agreement with that of Bommer et al? who showed that patients with anaphylactoid reactions, who underwent dialysis with y-sterilized material experienced improvement and had a decreased in vitro protease release by leukocytes on incubation in the presence of ethylene oxide-bovine serum albumin complex. Altogether, our study indicates that eradication of some of the putative allergenic factors such as
NS
357
NS
ethylene oxide residues, bacterial derived products, and a limited release of circulating anaphylatoxins might together significantly improve the well-being of patients undergoing long-term hemodialysis who are subject to allergic-like symptoms.
Rumpf KW, Seubert A, Valentin R, et al. Association of ethylene oxide-induced IgE antibodies with symptoms in dialysis patients. Lancet 1985;2:1385-7. Cavaillon JM, Simard L, Poignet JL, et al. Allergenic&y of bacterial derived products in hemodialyzed patients [Abstract]. Allergy 1992;47(suppl):53. Cavaillon JM, Poignet JL, Fitting C, et al. High in vitro spontaneous histamine release in long-term hemodialysis patients. J ALLERGY CLIN ~MUNOL 1990;85:859-64. Riickel A, Klinke B, Hertel J, et al. Allergy to dialysis materials. Nephrol Dial Transplant 1989;4:646-52. Bommer J, Barth HP, Wifhems OM, Schinedele H, Ritz E. Anaphylactoid reactions in dialysis patients: role of ethylene oxide. Lancet 1985;2:1382-5.