VOLUME 90 NUMBER 3, PAWfl
alterations in cell-mediated immunity in the already existing atopic disease derived from the onset o f JDMS may result in abnormally high levels o f serum IgE. Plans are being made to explore this matter further once enough patient data can be gathered for analysis. The occurrence of atopy in the general population is estimated at 30%. The prevalence of AD has also been increasing with estimates at 6.6%. 6 In our study coexistent atopic disease was found in nine (50%) of the 18 patients with J D M S , and coexistent A D was found in seven (39%). These figures a r e extremely high when compared with those mentioned above, especially for AD. A D is associated with impaired cell-mediated immunity, v On the other hand, a viral etiology, such as the Coxsackie B virus, s has been strongly postulated for JDMS. For these reasons, we deem that children with impaired cell-mediated immunity with such symptoms as A D may be more susceptible to JDMS than normal children, at least in Nagoya. Such susceptibility is believed to be unrelated to high dosages o f steroids, because no prior systemic steroid medication for AD was prescribed for any o f the patients with JDMS and A D in our series. Since A D states may vary from area to area because of such factors as changes in environment,9 a question remains as to whether our findings would hold true for A D in other localities. However, as speculative as this idea may be, it will no doubt be significant in elucidating the susceptibility to JDMS.
E l e v a t e d serurn tgE in J D M S
From our findings we conclude that, m general, children with impaired cell-mediated immunity with such symptoms as A D may have a higher tendency for developing DMS. We thank Professor Yoshiyuki Ohno of the Department of Preventive Medicine at Nagoya University ff~rtfis critical review of the manuscript.
REFERENCES 1. McKeon FD, Tuffanelli DL, Fukuyama K, Kirschner MW~ Autoirnmune response directed against conserved determinants of nuclear envelope proteins in a patient with linear scleroderma. Proc Natl Acad Sci U S A 1983;80:4374-8. 2. Cochrane CG, Koffler D. Immune complex disease in experimental animals and man. Adv Immunol 1973;I6:185-264. 3. Rebhun J, Quismorio F Jr, Dubois E, Heiner DC. Systemic lupus erythematosus activity and lgE. Ann Allergy 1983;50: 34-6. 4. Hiketa 3", Ohashi M. Juvenile dermatomyositis. Statistical observation of 105 patients with dermatomyositis Iin Japanese]. Jpn J Dermatol 1991;101:825-30 (in Japanese). 5. Bohan A, Peter JB. Polymyositis and dennatomyositis ( Fi.rstof two parts). N Engl J Med 1975;292:344-7. 6. Ueda H, Fujisawa Y. Is atopic dermatitis on the increase? !in Japanese]. Shoni Naika 1990;22:3t9-22. 7. Hanifin JM, Lobitz WC. Newer concepts ef atop~c dermatitis. Arch Dermatol 1977;113:663-70. 8. Christensen ML, Pachman LM, Schneidennan R, Patel DC, Friedman JM. Prevalence of Coxsackie B virus ~mtibodiesin patients with juvenile dermatomyosids. Arthritis Rheum 1986;29:1365-70. 9. Rajka G. Atopic dermatitis. Correlation of envir~)nmentalfactors with frequency. Int J Dermatol t986;25:301-4.
Prophylaxis against flu:ores in-induced anaphylactoid reactions Albert S. Rohr, MD, and Joseph E. Pappano, Jr., MD Bryn Mawr, Pa. Reactions to intravenous fluorescein are well described in the ophthalmology literature and include nausea and vomiting, flushing and urticaria, and anaphylactic shock. 1' 2 A 48.6% incidence of repeat reactions has been found in subjects with a history of a previous reaction to fluorescein.l Although most of these reactions consist o f nausea and vomiting, approximately 15% of these repeat reactions represent anaphylactoid reactions. We report a patient who experienced nausea and urticaria immediately after fluorescein injections on three occasions in the past, deFrom The Bryn Mawr Hospital, Bryn Mawr. Reprint requests: Albert S. Rohr, MD, Bryn Mawr Medical Bldg., South, Suite 107, Bryn Mawr, PA 19010. 1/ l/38531
spite premedication with diphenhydramine and prednisone before the last two studies and who required another fluorescein angiographic study.
CASE REPORT A 64-year-old man was referred in October of I987 because of previous reactions to intravenous fluorescein. In 1983, because of a fluid leak in his left retina caused by presumed ocular histoplasmosis syndrome, the patient received intravenous fluorescein (5 ml bolus of t0% Fluorescite), and within 15 minutes he had nausea and urticaria of his entire face. He was treated with diphenhydramine, and in l hour the hives resolved. Two months later he required another fluorescein study. Two days before th~s study he was started on diphenhydramine, 50 nag four times a day, and 60 mg prednisone daily. He was then given the intravenous fluorescein, and again within 15 minutes he had
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408 Rohr and Papano
J ALLERGYCLIN IMMUNOL SEPTEMBER 1992
nausea and facial hives of the same degree but no other systemic symptoms. The third fluorescein study was needed because of a hemorrhage in his right eye in 1987. Additional history obtained in 1987 showed a background of allergic rhinitis, hypertension (hydralazine 50 mg b.i.d, and hydrochlorothiazide 50 mg), but no history of any drug allergy problems, other than fluorescein. The patient was started on a regimen of 50 mg prednisone given 19 hours, 13 hours, 7 hours, and t hour before the fluorescein injection along with diphenhydramine 50 mg orally 1 hour before the injection. He had his intravenous fluorescein injection and again had facial urticaria and nausea, but no other allergic symptoms. The patient was not seen again until September of 1991 when because of a leak in the right eye another fluorescein study was required. Because of his previous reactions, the patient was started on 20 mg prednisone three times a day, 3 days and 2 days before the fluorescein injection. On the day before the study, he was given 20 mg of prednisone in the morning, 20 mg in the afternoon, and then 50 mg of prednisone 7 hours and again 1 hour before the fluorescein injection. One hour before the injection, he was also given 50 mg of diphenhydramine orally and 400 mg of cimetidine. The patient received his fluorescein injection and had his usual nausea, but 45 minutes later he had only a single urticarial lesion on the right temple, which lasted 20 minutes, and had no other symptoms. DISCUSSION There would appear to be several similarities between reactions to fluorescein and radiocontrast media. As with radiocontrast media, skin testing has not proved to be useful for the prediction o f fluoresceininduced reactions. 3 Anaphylactoid reactions to radiocontrast media are estimated at up to 1% of subjects receiving ionic agents, with a repeat reaction frequency of 16% to 33%. 4 Analogous statistics for fluorescein show a 0.5% initial incidence o f itching/urticaria, increasing to approximately 6% in subjects with prior reactions. ~ Approximately 200,000 fluorescein angiograms are done each year in the United States compared with 8 million radiocontrast
media studies per year. Deaths from fluorescein are estimated at 1 in 222,000 compared with 9 per 100,000 with hyperosmolar radiocontrast agents. 5 These statistics may explain why fluorescein has received little attention in the allergy and immunology literature. Despite the lower frequency o f severe reactions to fluorescein, it would seem prudent to develop an effective prophylactic regimen for subjects with a previous urticarial reaction to fluorescein. Ophthalmology reviews suggest pretreatment with 25 mg diphenhydramine in subjects with a previous urticarial reaction, but there appears to be little evidence to support the efficacy o f this regimen. 6 At the present time, a radiocontrast media type prophylactic regimen would seem most appropriate until controlled trials with fluorescein-induced urticarial/anaphylactoid reactions are published. In the case presented, perhaps the higher prednisone dosage or the use of an H2 blocker provided additional benefit during the fourth administration of fluorescein. This is only conjecture, and remains to be proved by controlled trials. We thank Alfred C, Lucier, MD, Senior Attending Ophthalmologist, Bryn Mawr Hospital. REFERENCES 1. Kwiterovich KA, Maguire MG, Murphy RP, et al. Frequency of adverse reactions after fluorescein angiography. Ophthalmology 1991;98:1139-42. 2. Lipson BK, Yannuzzi LA. Complications of intravenous fluorescein injections. Int Ophthalmol Clin 1989;29:200-5. 3. Stein MR, Parker CW. Reactions following intravenous fluorescein. Am J Ophthalmol 1971;72:861-8. 4. Marshall GD, Lieberman PL. Comparison of three pretreatment protocols to prevent anaphylactoid reactions to radiocontrast media. Ann Allergy 1991;67:70-3. 5. Lieberman PL. Anaphylactoid reactions to radiocontrast material. Ann Allergy 1991;67:91-9. 6. Ellis PP, Schoenberger M, Rendi MA. Antihistamines as prophylaxis against side reactions to intravenous fluorescein. Trans Am Ophthalmol Soc 1980;38:191-205.
alterations in cell-mediated immunity in the already existing atopic disease derived from the onset o f JDMS may result in abnormally high levels o f serum IgE. Plans are being made to explore this matter further once enough patient data can be gathered for analysis. The occurrence of atopy in the general population is estimated at 30%. The prevalence of AD has also been increasing with estimates at 6.6%. 6 In our study coexistent atopic disease was found in nine (50%) of the 18 patients with J D M S , and coexistent A D was found in seven (39%). These figures a r e extremely high when compared with those mentioned above, especially for AD. A D is associated with impaired cell-mediated immunity, v On the other hand, a viral etiology, such as the Coxsackie B virus, s has been strongly postulated for JDMS. For these reasons, we deem that children with impaired cell-mediated immunity with such symptoms as A D may be more susceptible to JDMS than normal children, at least in Nagoya. Such susceptibility is believed to be unrelated to high dosages o f steroids, because no prior systemic steroid medication for AD was prescribed for any o f the patients with JDMS and A D in our series. Since A D states may vary from area to area because of such factors as changes in environment,9 a question remains as to whether our findings would hold true for A D in other localities. However, as speculative as this idea may be, it will no doubt be significant in elucidating the susceptibility to JDMS.
E l e v a t e d serurn tgE in J D M S
From our findings we conclude that, m general, children with impaired cell-mediated immunity with such symptoms as A D may have a higher tendency for developing DMS. We thank Professor Yoshiyuki Ohno of the Department of Preventive Medicine at Nagoya University ff~rtfis critical review of the manuscript.
REFERENCES 1. McKeon FD, Tuffanelli DL, Fukuyama K, Kirschner MW~ Autoirnmune response directed against conserved determinants of nuclear envelope proteins in a patient with linear scleroderma. Proc Natl Acad Sci U S A 1983;80:4374-8. 2. Cochrane CG, Koffler D. Immune complex disease in experimental animals and man. Adv Immunol 1973;I6:185-264. 3. Rebhun J, Quismorio F Jr, Dubois E, Heiner DC. Systemic lupus erythematosus activity and lgE. Ann Allergy 1983;50: 34-6. 4. Hiketa 3", Ohashi M. Juvenile dermatomyositis. Statistical observation of 105 patients with dermatomyositis Iin Japanese]. Jpn J Dermatol 1991;101:825-30 (in Japanese). 5. Bohan A, Peter JB. Polymyositis and dennatomyositis ( Fi.rstof two parts). N Engl J Med 1975;292:344-7. 6. Ueda H, Fujisawa Y. Is atopic dermatitis on the increase? !in Japanese]. Shoni Naika 1990;22:3t9-22. 7. Hanifin JM, Lobitz WC. Newer concepts ef atop~c dermatitis. Arch Dermatol 1977;113:663-70. 8. Christensen ML, Pachman LM, Schneidennan R, Patel DC, Friedman JM. Prevalence of Coxsackie B virus ~mtibodiesin patients with juvenile dermatomyosids. Arthritis Rheum 1986;29:1365-70. 9. Rajka G. Atopic dermatitis. Correlation of envir~)nmentalfactors with frequency. Int J Dermatol t986;25:301-4.
Prophylaxis against flu:ores in-induced anaphylactoid reactions Albert S. Rohr, MD, and Joseph E. Pappano, Jr., MD Bryn Mawr, Pa. Reactions to intravenous fluorescein are well described in the ophthalmology literature and include nausea and vomiting, flushing and urticaria, and anaphylactic shock. 1' 2 A 48.6% incidence of repeat reactions has been found in subjects with a history of a previous reaction to fluorescein.l Although most of these reactions consist o f nausea and vomiting, approximately 15% of these repeat reactions represent anaphylactoid reactions. We report a patient who experienced nausea and urticaria immediately after fluorescein injections on three occasions in the past, deFrom The Bryn Mawr Hospital, Bryn Mawr. Reprint requests: Albert S. Rohr, MD, Bryn Mawr Medical Bldg., South, Suite 107, Bryn Mawr, PA 19010. 1/ l/38531
spite premedication with diphenhydramine and prednisone before the last two studies and who required another fluorescein angiographic study.
CASE REPORT A 64-year-old man was referred in October of I987 because of previous reactions to intravenous fluorescein. In 1983, because of a fluid leak in his left retina caused by presumed ocular histoplasmosis syndrome, the patient received intravenous fluorescein (5 ml bolus of t0% Fluorescite), and within 15 minutes he had nausea and urticaria of his entire face. He was treated with diphenhydramine, and in l hour the hives resolved. Two months later he required another fluorescein study. Two days before th~s study he was started on diphenhydramine, 50 nag four times a day, and 60 mg prednisone daily. He was then given the intravenous fluorescein, and again within 15 minutes he had
407
408 Rohr and Papano
J ALLERGYCLIN IMMUNOL SEPTEMBER 1992
nausea and facial hives of the same degree but no other systemic symptoms. The third fluorescein study was needed because of a hemorrhage in his right eye in 1987. Additional history obtained in 1987 showed a background of allergic rhinitis, hypertension (hydralazine 50 mg b.i.d, and hydrochlorothiazide 50 mg), but no history of any drug allergy problems, other than fluorescein. The patient was started on a regimen of 50 mg prednisone given 19 hours, 13 hours, 7 hours, and t hour before the fluorescein injection along with diphenhydramine 50 mg orally 1 hour before the injection. He had his intravenous fluorescein injection and again had facial urticaria and nausea, but no other allergic symptoms. The patient was not seen again until September of 1991 when because of a leak in the right eye another fluorescein study was required. Because of his previous reactions, the patient was started on 20 mg prednisone three times a day, 3 days and 2 days before the fluorescein injection. On the day before the study, he was given 20 mg of prednisone in the morning, 20 mg in the afternoon, and then 50 mg of prednisone 7 hours and again 1 hour before the fluorescein injection. One hour before the injection, he was also given 50 mg of diphenhydramine orally and 400 mg of cimetidine. The patient received his fluorescein injection and had his usual nausea, but 45 minutes later he had only a single urticarial lesion on the right temple, which lasted 20 minutes, and had no other symptoms. DISCUSSION There would appear to be several similarities between reactions to fluorescein and radiocontrast media. As with radiocontrast media, skin testing has not proved to be useful for the prediction o f fluoresceininduced reactions. 3 Anaphylactoid reactions to radiocontrast media are estimated at up to 1% of subjects receiving ionic agents, with a repeat reaction frequency of 16% to 33%. 4 Analogous statistics for fluorescein show a 0.5% initial incidence o f itching/urticaria, increasing to approximately 6% in subjects with prior reactions. ~ Approximately 200,000 fluorescein angiograms are done each year in the United States compared with 8 million radiocontrast
media studies per year. Deaths from fluorescein are estimated at 1 in 222,000 compared with 9 per 100,000 with hyperosmolar radiocontrast agents. 5 These statistics may explain why fluorescein has received little attention in the allergy and immunology literature. Despite the lower frequency o f severe reactions to fluorescein, it would seem prudent to develop an effective prophylactic regimen for subjects with a previous urticarial reaction to fluorescein. Ophthalmology reviews suggest pretreatment with 25 mg diphenhydramine in subjects with a previous urticarial reaction, but there appears to be little evidence to support the efficacy o f this regimen. 6 At the present time, a radiocontrast media type prophylactic regimen would seem most appropriate until controlled trials with fluorescein-induced urticarial/anaphylactoid reactions are published. In the case presented, perhaps the higher prednisone dosage or the use of an H2 blocker provided additional benefit during the fourth administration of fluorescein. This is only conjecture, and remains to be proved by controlled trials. We thank Alfred C, Lucier, MD, Senior Attending Ophthalmologist, Bryn Mawr Hospital. REFERENCES 1. Kwiterovich KA, Maguire MG, Murphy RP, et al. Frequency of adverse reactions after fluorescein angiography. Ophthalmology 1991;98:1139-42. 2. Lipson BK, Yannuzzi LA. Complications of intravenous fluorescein injections. Int Ophthalmol Clin 1989;29:200-5. 3. Stein MR, Parker CW. Reactions following intravenous fluorescein. Am J Ophthalmol 1971;72:861-8. 4. Marshall GD, Lieberman PL. Comparison of three pretreatment protocols to prevent anaphylactoid reactions to radiocontrast media. Ann Allergy 1991;67:70-3. 5. Lieberman PL. Anaphylactoid reactions to radiocontrast material. Ann Allergy 1991;67:91-9. 6. Ellis PP, Schoenberger M, Rendi MA. Antihistamines as prophylaxis against side reactions to intravenous fluorescein. Trans Am Ophthalmol Soc 1980;38:191-205.
