- Email: [email protected]
Ocular tuberculosis
CORRESPONDENCE
scotomas, and red-green colour blindness. The visual symptoms precede a measurable loss of visual acuity. This complication is dose-related and occurs in less than 1% of patients given a daily dose of 15 mg/kg, and increases with a daily dose of 25 mg/kg.3 Ocular toxicity induced by antituberculosis treatment should have been an important consideration when starting drugs. Grosse and colleagues, having enucleated one eye, could have chosen a more appropriate drug than ethambutol, given its known ocular toxicity. Thus, the aim should have been to preserve the remaining healthy eye from an iatrogenic insult leading to irreversible loss of vision. Lastly, Grosse and colleagues mention that they excluded other causes of generalised lymphadenopathy, including toxoplasmosis, brucellosis, yersiniosis, and syphilis by serological tests. Such elaborate and costly serological investigations might not be possible and economically viable in a developing country like India, which bears 28·4% of the entire world’s burden of tuberculosis, and where every second an individual older than 20 years is infected with M tuberculosis.5 A simple biopsy of an easily accessible cervical lymph node would have been more appropriate. Abraham Kuruvilla Department of Neurology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum 695 011, India (e-mail: [email protected]) 1
2
3
4 5
Grosse V, Bange FC, Tischendorf J, Schmidt RE, Manns MP. A mass in the eye. Lancet 2002; 360: 922. Haas DW, Des Prez RM. Mycobacterium tuberculosis. In: Mandell GL, Bennett JE, Dolan R, eds. Principles and practices of infectious diseases, 4th edn. New York: Churchill Livingston, 1995: 2213–43. Garg SP, Venkatesh P. Ocular tuberculosis. In: Sharma SK, Mohan A, eds. Tuberculosis. New Delhi: Jaypee Brothers, 2001: 294–303. Vanscoy RE, Willowske CJ. Antituberculous agents. Mayo Clinic Proc 1992; 67: 179–87. Sharma SK. Introduction. In: Sharma SK, Mohan A, eds. Tuberculosis. New Delhi: Jaypee Brothers, 2001: 1–4.
Histopathological results showed an eyeball full of necrotic tissue extending to the iris and ciliary body. Kuruvilla also argues that ethambutol is associated with optic neuritis and therefore should be used with caution in a patient who has lost already one eye. We were aware of this possible ocular toxicity, but thought it to be a problem only with higher doses.1 However, we acknowledge that there have been reports of serious visual impairment on conventional doses, with permanent blindness in some cases, and painfully slow recovery in others.2 Our treatment was guided by the current recommendation that, unless the rate of resistance to isoniazid is less than 4%, the initial antituberculosis treatment regimen should consist of isoniazid, rifampicin, pyrazinamide, and ethambutol or streptomycin.3 Optic neuritis due to ethambutol usually resolves after the drug is stopped.4 In this case, the patient was monitored closely for the development of symptoms and signs related to ocular toxicity. He developed no optic neuritis. We agree that, in a country like India, with relatively low income levels and high incidence of tuberculosis (184 cases per 100 000 people),5 serological investigations to exclude other causes of generalised lymphadenopathy might not be economically sound. In Germany, however, the incidence of tuberculosis is low (11 per 100 000). Therefore, while the diagnosis of tuberculosis was pending, other possible causes for generalised lymphadenopathy were excluded, which included serological tests for syphilis, toxoplasmosis, and brucellosis. *V Grosse, F C Bange, J Tischendorf, R E Schmidt, M P Manns Divisions of *Clinical Immunology (VG, RES), and Gastroenterology and Hepatology (JT, MPM), Department of Medicine, and Department of Microbiology (FCB), Hannover Medical School, 30625 Hannover, Germany (e-mail: [email protected]) 1
Authors’ reply 2
Sir—Abraham Kuruvilla is right that avoidance of ocular biopsy or enucleation is preferable if possible. Early diagnosis and treatment is essential for saving the sight of patients with ocular manifestations of tuberculosis. Yet in this case, the patient presented when infection was already far advanced and the eye could not be saved. Enucleation was done because of acute panophthalmitis and complete destruction of the overlying retina, and not exclusively for diagnostic reasons.
3
4
5
American Thoracic Society. Treatment of tuberculosis and tuberculosis infection in adults and children. Am J Respir Crit Care Med 1994; 149: 1359–74. Russo PA, Chaglasian MA. Toxic optic neuropathy associated with ethambutol: implications for current therapy. J Am Optom Assoc 1994; 65: 332–38. Small PM, Fujiwara PI. Management of tuberculosis in the United States. N Engl J Med 2001; 345: 189–200. Friedberg DN, Lorenzo-Latkany M. Ocular complications of tuberculosis. In: Rom WN, Garay SM, eds. Tuberculosis. Boston: Little, Brown and Company, 1996: 557–66. World Health Organization. Global tuberculosis control: surveillance, planning, financing. WHO Report 2002. Geneva: WHO, 2002. http://www.who.int/gtb/ publications/globrep02/index.html (accessed Jan 8, 2003).
THE LANCET • Vol 361 • January 18, 2003 • www.thelancet.com
Avoidance of bioflavonoid supplements during pregnancy Sir—On July 28, 2002, the Italian Health Ministry published a statement in the Gazzetta Ufficiale, ordering that all dietary supplements containing bioflavonoids should be labelled: “Not to be taken during pregnancy”. This precautionary decision was taken because of the possibility of an increased risk of severe diseases during the first year of life due to prenatal exposure to bioflavonoids. The scientific basis for this association was provided by reports that suggested a relation between dietary flavonoids and infant leukaemia.1,2 However, the discussion sections of these reports highlighted a large number of questions (epidemiological, molecular, and medical) that should be addressed and that make the relation between bioflavonoids and infant leukaemia very weak. Moreover, there is evidence that dietary bioflavonoids afford protection from cancer owing to their antioxidant properties.3–5 Supplements containing bioflavonoids and marketed in Italy provide a median of 50–60 mg/day (range 2–500) bioflavonoids. The average daily quantity of bioflavonoids in a Mediterranean diet is more than 2000 mg. Thus, although the supplements are probably not necessary, their average bioflavonoid content corresponds to 3–5% of the dietary intake in Italian pregnant women. Although the evidence provided by the above cited reports suggests that precautions could be taken, there are no scientific grounds for such a decision, nor for unduly alarming the public. In fact, the decision to label the supplements is now having a striking effect, and women who were taking supplements or who took them in pregnancy are becoming anxious about the possible effects of these tablets on their children. Furthermore, supplements contain other ingredients, such as folic acid, proteins, and minerals, which could be beneficial for pregnant women. To add to the confusion, no adequate information has been issued to physicians and health operators to allow risk-benefit analysis and risk communication. No other countries, to our knowledge, have forbidden these compounds in pregnancy. We believe that decisions concerning public health should not be taken without a proper strategy for risk assessment and risk communication,
261
For personal use. Only reproduce with permission from The Lancet Publishing Group.
scotomas, and red-green colour blindness. The visual symptoms precede a measurable loss of visual acuity. This complication is dose-related and occurs in less than 1% of patients given a daily dose of 15 mg/kg, and increases with a daily dose of 25 mg/kg.3 Ocular toxicity induced by antituberculosis treatment should have been an important consideration when starting drugs. Grosse and colleagues, having enucleated one eye, could have chosen a more appropriate drug than ethambutol, given its known ocular toxicity. Thus, the aim should have been to preserve the remaining healthy eye from an iatrogenic insult leading to irreversible loss of vision. Lastly, Grosse and colleagues mention that they excluded other causes of generalised lymphadenopathy, including toxoplasmosis, brucellosis, yersiniosis, and syphilis by serological tests. Such elaborate and costly serological investigations might not be possible and economically viable in a developing country like India, which bears 28·4% of the entire world’s burden of tuberculosis, and where every second an individual older than 20 years is infected with M tuberculosis.5 A simple biopsy of an easily accessible cervical lymph node would have been more appropriate. Abraham Kuruvilla Department of Neurology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum 695 011, India (e-mail: [email protected]) 1
2
3
4 5
Grosse V, Bange FC, Tischendorf J, Schmidt RE, Manns MP. A mass in the eye. Lancet 2002; 360: 922. Haas DW, Des Prez RM. Mycobacterium tuberculosis. In: Mandell GL, Bennett JE, Dolan R, eds. Principles and practices of infectious diseases, 4th edn. New York: Churchill Livingston, 1995: 2213–43. Garg SP, Venkatesh P. Ocular tuberculosis. In: Sharma SK, Mohan A, eds. Tuberculosis. New Delhi: Jaypee Brothers, 2001: 294–303. Vanscoy RE, Willowske CJ. Antituberculous agents. Mayo Clinic Proc 1992; 67: 179–87. Sharma SK. Introduction. In: Sharma SK, Mohan A, eds. Tuberculosis. New Delhi: Jaypee Brothers, 2001: 1–4.
Histopathological results showed an eyeball full of necrotic tissue extending to the iris and ciliary body. Kuruvilla also argues that ethambutol is associated with optic neuritis and therefore should be used with caution in a patient who has lost already one eye. We were aware of this possible ocular toxicity, but thought it to be a problem only with higher doses.1 However, we acknowledge that there have been reports of serious visual impairment on conventional doses, with permanent blindness in some cases, and painfully slow recovery in others.2 Our treatment was guided by the current recommendation that, unless the rate of resistance to isoniazid is less than 4%, the initial antituberculosis treatment regimen should consist of isoniazid, rifampicin, pyrazinamide, and ethambutol or streptomycin.3 Optic neuritis due to ethambutol usually resolves after the drug is stopped.4 In this case, the patient was monitored closely for the development of symptoms and signs related to ocular toxicity. He developed no optic neuritis. We agree that, in a country like India, with relatively low income levels and high incidence of tuberculosis (184 cases per 100 000 people),5 serological investigations to exclude other causes of generalised lymphadenopathy might not be economically sound. In Germany, however, the incidence of tuberculosis is low (11 per 100 000). Therefore, while the diagnosis of tuberculosis was pending, other possible causes for generalised lymphadenopathy were excluded, which included serological tests for syphilis, toxoplasmosis, and brucellosis. *V Grosse, F C Bange, J Tischendorf, R E Schmidt, M P Manns Divisions of *Clinical Immunology (VG, RES), and Gastroenterology and Hepatology (JT, MPM), Department of Medicine, and Department of Microbiology (FCB), Hannover Medical School, 30625 Hannover, Germany (e-mail: [email protected]) 1
Authors’ reply 2
Sir—Abraham Kuruvilla is right that avoidance of ocular biopsy or enucleation is preferable if possible. Early diagnosis and treatment is essential for saving the sight of patients with ocular manifestations of tuberculosis. Yet in this case, the patient presented when infection was already far advanced and the eye could not be saved. Enucleation was done because of acute panophthalmitis and complete destruction of the overlying retina, and not exclusively for diagnostic reasons.
3
4
5
American Thoracic Society. Treatment of tuberculosis and tuberculosis infection in adults and children. Am J Respir Crit Care Med 1994; 149: 1359–74. Russo PA, Chaglasian MA. Toxic optic neuropathy associated with ethambutol: implications for current therapy. J Am Optom Assoc 1994; 65: 332–38. Small PM, Fujiwara PI. Management of tuberculosis in the United States. N Engl J Med 2001; 345: 189–200. Friedberg DN, Lorenzo-Latkany M. Ocular complications of tuberculosis. In: Rom WN, Garay SM, eds. Tuberculosis. Boston: Little, Brown and Company, 1996: 557–66. World Health Organization. Global tuberculosis control: surveillance, planning, financing. WHO Report 2002. Geneva: WHO, 2002. http://www.who.int/gtb/ publications/globrep02/index.html (accessed Jan 8, 2003).
THE LANCET • Vol 361 • January 18, 2003 • www.thelancet.com
Avoidance of bioflavonoid supplements during pregnancy Sir—On July 28, 2002, the Italian Health Ministry published a statement in the Gazzetta Ufficiale, ordering that all dietary supplements containing bioflavonoids should be labelled: “Not to be taken during pregnancy”. This precautionary decision was taken because of the possibility of an increased risk of severe diseases during the first year of life due to prenatal exposure to bioflavonoids. The scientific basis for this association was provided by reports that suggested a relation between dietary flavonoids and infant leukaemia.1,2 However, the discussion sections of these reports highlighted a large number of questions (epidemiological, molecular, and medical) that should be addressed and that make the relation between bioflavonoids and infant leukaemia very weak. Moreover, there is evidence that dietary bioflavonoids afford protection from cancer owing to their antioxidant properties.3–5 Supplements containing bioflavonoids and marketed in Italy provide a median of 50–60 mg/day (range 2–500) bioflavonoids. The average daily quantity of bioflavonoids in a Mediterranean diet is more than 2000 mg. Thus, although the supplements are probably not necessary, their average bioflavonoid content corresponds to 3–5% of the dietary intake in Italian pregnant women. Although the evidence provided by the above cited reports suggests that precautions could be taken, there are no scientific grounds for such a decision, nor for unduly alarming the public. In fact, the decision to label the supplements is now having a striking effect, and women who were taking supplements or who took them in pregnancy are becoming anxious about the possible effects of these tablets on their children. Furthermore, supplements contain other ingredients, such as folic acid, proteins, and minerals, which could be beneficial for pregnant women. To add to the confusion, no adequate information has been issued to physicians and health operators to allow risk-benefit analysis and risk communication. No other countries, to our knowledge, have forbidden these compounds in pregnancy. We believe that decisions concerning public health should not be taken without a proper strategy for risk assessment and risk communication,
261
For personal use. Only reproduce with permission from The Lancet Publishing Group.