American Journal of Emergency Medicine 33 (2015) 478.e1–478.e2
Contents lists available at ScienceDirect
American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajem
Case Report
Fluorescein-related extensive jaundice Abstract Fluorescein is a chemical dye frequently used in eye diseases to assess blood flow in the retina, choroid tissue, and iris. Although it has many known adverse effects, it has not previously been reported to lead to jaundice. The purpose of this case report was to emphasize that for patients presenting at the emergency department with jaundice symptoms, it should not be forgotten by emergency physicians that jaundice can develop after fluorescein angiography. Case: A 65-year-old woman presented at the emergency department with extensive jaundice that had developed on her entire body a few hours after fluorescein angiography applied because of vision impairment. The test results for all the diseases considered to cause jaundice were normal, and fluorescein-related jaundice was diagnosed. Conclusion: A detailed anamnesis should be taken when jaundice is seen in patients who have undergone fluorescein angiography, and it should not be forgotten that fluorescein dye is a rare cause of jaundice. Fluorescein angiography has been used for approximately 40 years in the diagnosis of chorioretinal diseases. Several adverse effects associated with fluorescein have been reported in the ophthalmic literature. These may be classified as mild, moderate, and severe. Mild adverse effects are those that do not generally require treatment, such as nausea, vomiting, itching, and subcutaneous leakage. Moderate adverse effects are those requiring treatment such as urticaria, fainting, thrombophlebitis, and local tissue necrosis. Edema of the larynx, anaphylactic shock, tonic-clonic seizure, and myocardial infarct are severe adverse effects. Mild adverse effects are common, whereas severe adverse effects are rare [1–5]. A case of systemic jaundice caused by fluorescein is reported here. A 65-year-old woman presented at the emergency department with extensive jaundice over her entire body. There was nothing significant in her medical history apart from fluorescein angiography performed a few hours previously. Physical examination revealed jaundice in the sclera and over the entire body. Other system examination results were normal. Hemogram values were hemoglobin 14.5 g/dL, leukocyte 8000 U/L, and thrombocyte 265 000/dL. In the biochemical tests, blood urea nitrogen was 12 mg/dL, creatinine was 0.7 mg/dL, alanine aminotransferase was 11 U/L, aspartate aminotransferase was 14 U/L, total bilirubin was 0.4 mg/dL (N = 0.2-1.2), and direct bilirubin was 0.2 mg/dL (N = 0-0.5). No pathology was determined on the hepatobiliary system ultrasonography performed for obstructive icterus (Figure). No medication was administered. Tests and examination results were normal, and the jaundice was attributed to fluorescein material. Checkups at the clinic were advised, and the patient was discharged. The jaundice had completely resolved at checkup at the emergency department 4 days later. Jaundice may develop in association with many diseases. Hematological diseases, and particularly biliary tract pathologies, which
0735-6757/© 2014 Elsevier Inc. All rights reserved.
may cause obstructive icterus, may lead to jaundice [6]. Emergency service physicians have a responsibility to investigate the cause of jaundice. Several tests must therefore be performed. These range from simple blood count to abdominal computerized tomography. Several tests for jaundice were performed in the current case, and all results were normal. As the patient did not immediately report that she had received fluorescein angiography and because we had no previous experience of fluorescein being capable of causing jaundice, several tests were performed, which represented a loss of time for both the patient and physician. Fluorescein angiography plays an important role in illuminating retinal and choroidal diseases. Macular edema and vascular leakage can be evaluated qualitatively with fluorescein angiography, and the presence of ischemia can be detected on angiography [7]. Fluorescein, which is a weak dibasic acid, is an organic dye with a molecular weight of 376.67. The sodium salt of this acid is generally used. Fluorescein sodium, which has the same molecular weight, is crystalline in nature and assumes a reddish-yellow color in aqueous solution. This dye exhibits fluorescent properties and converts 100% of the light it absorbs into fluorescent light. The molecular weight is low, whereas diffusion in
Figure. Hepatobiliary system ultrasonography performed for obstructive icterus.
478.e2
A. Kalkan et al. / American Journal of Emergency Medicine 33 (2015) 478.e1–478.e2
body fluids is very rapid. When administered intravenously, 60% to 80% of fluorescein binds to plasma proteins, particularly albumin; and 20% circulates freely in the plasma. Fluorescein does not normally pass through the retinal artery endothelium and retinal pigment endothelium. The purpose of fluorescein angiography is to observe the material inside and outside the vasculature [8]. Allergic events underlie the commonly seen adverse effects. Fluorescein administered rapidly and intravenously creates a hapten effect in the body by binding to plasma proteins, thus enabling contact with antibodies. This gives rise to immunoglobulin E–mediated mast cell activation. The activation of mast cells increases vascular permeability by causing histamine release. Increased vascular permeability causes subcutaneous jaundice by enabling dye material in the blood vessels to enter the interstitial space [9]. Although local jaundice caused by fluorescein leaking beneath the skin is a known condition [10], extensive jaundice across the entire body may also be attributed to this mechanism. The jaundice developing within a few hours in the patient reported here may be attributed to the same cause. Jaundice is generally temporary, resolving spontaneously in 3 to 5 days. A detailed anamnesis should be taken when jaundice is observed, particularly in patients who have received fluorescein angiography. Fluorescein dye should not be forgotten as a rare cause of jaundice. This report can be considered of value as the first case of systemic jaundice caused by fluorescein dye.
Asim Kalkan, MD Recep Tayyip Erdogan University Faculty of Medicine Department of Emergency Medicine, Rize, Turkey Tel.: +90 464 217 0366 E-mail addresses: [email protected], [email protected]
Suleyman Turedi, MD KTU University Faculty of Medicine Department of Emergency Medicine Trabzon, Turkey Ibrahim Aydin, MD Recep Tayyip Erdogan University Faculty of Medicine Department of General Surgery, Rize, Turkey http://dx.doi.org/10.1016/j.ajem.2014.08.053
References [1] Stein MR, Parker CW. Reactions following intravenous fluorescein. Am J Ophthalmol 1971;72:861–8. [2] Kwiterovich KA, Maguire MG, Murphy RP, Schachat AP, Bressler NM, Bressler SB, et al. Frequency of adverse systemic reactions after fluorescein angiography: results of a prospective study. Ophthalmology 1991;98:1139–42. [3] Fluorescein angiography complication survey. Ophthalmology 1986;93:611–7. [4] Berkow JW, Flower RW, Orth DH, Kelley JS. Fluorescein and ındocyanine green angiography: techniques and interpretation. 2nd ed. San Francisco: The Foundation of the American Academy of Ophthalmology; 1997. [5] Kwan AS, Barry C, McAllister IL, Constable I. Fluorescein angiography and adverse drug reactions revisited: the Lions Eye experience. Clin Experiment Ophthalmol 2006;34:33–8. [6] Sticova E, Jirsa M. New insights in bilirubin metabolism and their clinical implications. World J Gastroenterol 2013;19:6398–407. [7] Sonmez A, Erbil HH, Yaylali SA, Akçakaya AA, Acar H, Karakurt Y, et al. The correlation of fluorescein angiografic and optical coherence tomographic features in diabetic macular edema. J Ret-Vit 2007;15:165–9. [8] Tewari H, Verma L, Venkatesh P. Fluorescein angiography—a user’s manual. 2nd ed. Jaypee Publications; 2003. [9] Akbulut A, Akman A, Yılmaz G. Ardışık floresein ve indosiyanin yeşili anjiografi sırasında görülen atipik komplikasyonlar. J Ret-Vit 2001;9:266–9. [10] Kalogeromitros DC, Makris MP, Aggelides XS, Mellios AI, Giannoula FC, Sideri KA, et al. Allergy skin testing in predicting adverse reactions to fluorescein: a prospective clinical study. Acta Ophthalmol 2011;89:480–3.
Contents lists available at ScienceDirect
American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajem
Case Report
Fluorescein-related extensive jaundice Abstract Fluorescein is a chemical dye frequently used in eye diseases to assess blood flow in the retina, choroid tissue, and iris. Although it has many known adverse effects, it has not previously been reported to lead to jaundice. The purpose of this case report was to emphasize that for patients presenting at the emergency department with jaundice symptoms, it should not be forgotten by emergency physicians that jaundice can develop after fluorescein angiography. Case: A 65-year-old woman presented at the emergency department with extensive jaundice that had developed on her entire body a few hours after fluorescein angiography applied because of vision impairment. The test results for all the diseases considered to cause jaundice were normal, and fluorescein-related jaundice was diagnosed. Conclusion: A detailed anamnesis should be taken when jaundice is seen in patients who have undergone fluorescein angiography, and it should not be forgotten that fluorescein dye is a rare cause of jaundice. Fluorescein angiography has been used for approximately 40 years in the diagnosis of chorioretinal diseases. Several adverse effects associated with fluorescein have been reported in the ophthalmic literature. These may be classified as mild, moderate, and severe. Mild adverse effects are those that do not generally require treatment, such as nausea, vomiting, itching, and subcutaneous leakage. Moderate adverse effects are those requiring treatment such as urticaria, fainting, thrombophlebitis, and local tissue necrosis. Edema of the larynx, anaphylactic shock, tonic-clonic seizure, and myocardial infarct are severe adverse effects. Mild adverse effects are common, whereas severe adverse effects are rare [1–5]. A case of systemic jaundice caused by fluorescein is reported here. A 65-year-old woman presented at the emergency department with extensive jaundice over her entire body. There was nothing significant in her medical history apart from fluorescein angiography performed a few hours previously. Physical examination revealed jaundice in the sclera and over the entire body. Other system examination results were normal. Hemogram values were hemoglobin 14.5 g/dL, leukocyte 8000 U/L, and thrombocyte 265 000/dL. In the biochemical tests, blood urea nitrogen was 12 mg/dL, creatinine was 0.7 mg/dL, alanine aminotransferase was 11 U/L, aspartate aminotransferase was 14 U/L, total bilirubin was 0.4 mg/dL (N = 0.2-1.2), and direct bilirubin was 0.2 mg/dL (N = 0-0.5). No pathology was determined on the hepatobiliary system ultrasonography performed for obstructive icterus (Figure). No medication was administered. Tests and examination results were normal, and the jaundice was attributed to fluorescein material. Checkups at the clinic were advised, and the patient was discharged. The jaundice had completely resolved at checkup at the emergency department 4 days later. Jaundice may develop in association with many diseases. Hematological diseases, and particularly biliary tract pathologies, which
0735-6757/© 2014 Elsevier Inc. All rights reserved.
may cause obstructive icterus, may lead to jaundice [6]. Emergency service physicians have a responsibility to investigate the cause of jaundice. Several tests must therefore be performed. These range from simple blood count to abdominal computerized tomography. Several tests for jaundice were performed in the current case, and all results were normal. As the patient did not immediately report that she had received fluorescein angiography and because we had no previous experience of fluorescein being capable of causing jaundice, several tests were performed, which represented a loss of time for both the patient and physician. Fluorescein angiography plays an important role in illuminating retinal and choroidal diseases. Macular edema and vascular leakage can be evaluated qualitatively with fluorescein angiography, and the presence of ischemia can be detected on angiography [7]. Fluorescein, which is a weak dibasic acid, is an organic dye with a molecular weight of 376.67. The sodium salt of this acid is generally used. Fluorescein sodium, which has the same molecular weight, is crystalline in nature and assumes a reddish-yellow color in aqueous solution. This dye exhibits fluorescent properties and converts 100% of the light it absorbs into fluorescent light. The molecular weight is low, whereas diffusion in
Figure. Hepatobiliary system ultrasonography performed for obstructive icterus.
478.e2
A. Kalkan et al. / American Journal of Emergency Medicine 33 (2015) 478.e1–478.e2
body fluids is very rapid. When administered intravenously, 60% to 80% of fluorescein binds to plasma proteins, particularly albumin; and 20% circulates freely in the plasma. Fluorescein does not normally pass through the retinal artery endothelium and retinal pigment endothelium. The purpose of fluorescein angiography is to observe the material inside and outside the vasculature [8]. Allergic events underlie the commonly seen adverse effects. Fluorescein administered rapidly and intravenously creates a hapten effect in the body by binding to plasma proteins, thus enabling contact with antibodies. This gives rise to immunoglobulin E–mediated mast cell activation. The activation of mast cells increases vascular permeability by causing histamine release. Increased vascular permeability causes subcutaneous jaundice by enabling dye material in the blood vessels to enter the interstitial space [9]. Although local jaundice caused by fluorescein leaking beneath the skin is a known condition [10], extensive jaundice across the entire body may also be attributed to this mechanism. The jaundice developing within a few hours in the patient reported here may be attributed to the same cause. Jaundice is generally temporary, resolving spontaneously in 3 to 5 days. A detailed anamnesis should be taken when jaundice is observed, particularly in patients who have received fluorescein angiography. Fluorescein dye should not be forgotten as a rare cause of jaundice. This report can be considered of value as the first case of systemic jaundice caused by fluorescein dye.
Asim Kalkan, MD Recep Tayyip Erdogan University Faculty of Medicine Department of Emergency Medicine, Rize, Turkey Tel.: +90 464 217 0366 E-mail addresses: [email protected], [email protected]
Suleyman Turedi, MD KTU University Faculty of Medicine Department of Emergency Medicine Trabzon, Turkey Ibrahim Aydin, MD Recep Tayyip Erdogan University Faculty of Medicine Department of General Surgery, Rize, Turkey http://dx.doi.org/10.1016/j.ajem.2014.08.053
References [1] Stein MR, Parker CW. Reactions following intravenous fluorescein. Am J Ophthalmol 1971;72:861–8. [2] Kwiterovich KA, Maguire MG, Murphy RP, Schachat AP, Bressler NM, Bressler SB, et al. Frequency of adverse systemic reactions after fluorescein angiography: results of a prospective study. Ophthalmology 1991;98:1139–42. [3] Fluorescein angiography complication survey. Ophthalmology 1986;93:611–7. [4] Berkow JW, Flower RW, Orth DH, Kelley JS. Fluorescein and ındocyanine green angiography: techniques and interpretation. 2nd ed. San Francisco: The Foundation of the American Academy of Ophthalmology; 1997. [5] Kwan AS, Barry C, McAllister IL, Constable I. Fluorescein angiography and adverse drug reactions revisited: the Lions Eye experience. Clin Experiment Ophthalmol 2006;34:33–8. [6] Sticova E, Jirsa M. New insights in bilirubin metabolism and their clinical implications. World J Gastroenterol 2013;19:6398–407. [7] Sonmez A, Erbil HH, Yaylali SA, Akçakaya AA, Acar H, Karakurt Y, et al. The correlation of fluorescein angiografic and optical coherence tomographic features in diabetic macular edema. J Ret-Vit 2007;15:165–9. [8] Tewari H, Verma L, Venkatesh P. Fluorescein angiography—a user’s manual. 2nd ed. Jaypee Publications; 2003. [9] Akbulut A, Akman A, Yılmaz G. Ardışık floresein ve indosiyanin yeşili anjiografi sırasında görülen atipik komplikasyonlar. J Ret-Vit 2001;9:266–9. [10] Kalogeromitros DC, Makris MP, Aggelides XS, Mellios AI, Giannoula FC, Sideri KA, et al. Allergy skin testing in predicting adverse reactions to fluorescein: a prospective clinical study. Acta Ophthalmol 2011;89:480–3.
