lodochiorhydroxyquin and optic nerve damage To the editor: Oral administration of iodochlorhydroxyquin (Entero-Vioform), or related halogenated hydroxyquinolines, is well reported as therapy for acrodermatitis enteropathica, an uncommon hereditary disease characterized by alopecia, apathy, diarrhea and a distinctive dermatitis of the oral and mucocutaneous areas. More commonly this agent is used to treat travellers' diarrhea or nonspecific diarrhea of infancy. However, reports of serious side effects such as optic neuropathy are increasing in number. The following case is an example. A 4-year-old boy was seen because of increasing visual difficulties. Visual acuity was 20/80 for the right eye and 20/200 for the left but no appreciable refractive error was found. Temporal pallor of both optic discs was noted and bilateral optic atrophy diagnosed. The remainder of his examination, which included full neurologic assessment and appropriate laboratory, radiologic and electroencephalographic studies, yielded results within normal limits. At 6 weeks of age he had been weaned from breast to cow's milk; shortly irritability, diarrhea, abdominal cramps and non-
specific dermatitis developed. Subsequent skin biopsy revealed features compatible with acrodermatitis enteropathica. (A sibling had died at age 11 months of malnutrition secondary to acrodermatitis enteropathica.) Therapy with Entero-Vioform, 1200 mg daily, was begun at age 2 months and continued for 2 years, after which the daily dose was tapered to 600 mg with no adverse effects. He continued to take 400 to 600 mg daily until the diagnosis of bilateral optic atrophy was made. His therapy was then changed to 30 mg of zinc sulfate daily with no untoward symptoms. He has since been symptom free. There have been many cases of neurologic syndromes associated with the use of halogenated hydroxyquinolines.'6 A dose-toxicity relationship has been established as follows:7 * 750 mg daily for 4 weeks or less has little risk of reaction. * 750 to 1500 mg daily for 2 weeks or less produces neurologic symptoms in 1% of patients but if taken in excess of 2 weeks produces symptoms in up to 35%. * 1800 mg daily can cause symptoms as early as the 5th day. Our case demonstrates toxicity from prolonged use of Entero-Vioform in a
daily dose ranging from 200 to 1200 mg over 6 years. It also demonstrates that acrodermatitis enteropathica can be controlled with low doses of zinc sulfate. This drug and similar agents were available over the counter but are now available only by prescription. Physicians prescribing these medications and pharmacists recommending their use for either travellers' diarrhea or nonspecific diarrhea of infancy should be aware of their toxicity and avoid their use except in life-threatening situations. W.G.L. CARR, MD P0 Box 512 Nanaimo, BC R.A. BOWEN, MD, FRCS[C] 235 Bastion St. Nanaimo, BC FA. HORNER, MD, FRCP[C] 1525 Dufferin Cres. Nanaimo, BC
References 1. SPILLANE JD: S.M.O.N. (C). Lancet 2: 1371, 1971 2. Idem: S.M.O.N. (C). Lancet 1: 154, 1972 3. MCEWAN LM: Neuropathy after dioquinol (C). Br Med J 4: 169, 1971 4. SELBY G: Subacute myelo-optic neuropathy in Australia. Lancet 1: 123, 1972 5. KAE5ER HE, WUTHRICH R: Zur Frage der Neurotoxizitat der Oxychinoline. Dtsch Med Wochenschr 95: 1685, 1970 6. OSTERMAN OP: Myelopathy after clioquinol treatment (C). Lancet 2: 544, 1971 7. OAKLEY GP Ja: The neurotoxicity of the halogenated hydroxyquinolines. JAMA 225: 395, 1973
7.
Gravergol has the answer. Gravergol. is a member of the Gravol family designed to relieve migraine and similar vascular headache attacks. Each Gravergol capsule contains 1 mg ergotamine tartrate and 100 mg caffeine to relieve the attack by vasoconstnctive action on distended cranial arteries plus 50 mg dimenhydrinate to treat the accompanying nausea Gravol (dimenhydrinate) is available in the following forms: 50 mg tablets. 75 mg long-acting capsules. 100 mg adult suppositories. 15 mgI5 ml liquid in 75 ml plastic containers. 50 mg pediatric suppositories. 50 mglml llm ampoules: 1 and 2 ml; and lIm vials: 5 ml. 10 mglml Iv ampoules: 5 ml.
D.D.
Gravol*
Canada's most widely Montr6al,Cariada
used antinsuseant. Reg. T.M.
. .ppl.
CMA JOURNAL/FEBRUARY 5, 1977/VOL. 116 251
specific dermatitis developed. Subsequent skin biopsy revealed features compatible with acrodermatitis enteropathica. (A sibling had died at age 11 months of malnutrition secondary to acrodermatitis enteropathica.) Therapy with Entero-Vioform, 1200 mg daily, was begun at age 2 months and continued for 2 years, after which the daily dose was tapered to 600 mg with no adverse effects. He continued to take 400 to 600 mg daily until the diagnosis of bilateral optic atrophy was made. His therapy was then changed to 30 mg of zinc sulfate daily with no untoward symptoms. He has since been symptom free. There have been many cases of neurologic syndromes associated with the use of halogenated hydroxyquinolines.'6 A dose-toxicity relationship has been established as follows:7 * 750 mg daily for 4 weeks or less has little risk of reaction. * 750 to 1500 mg daily for 2 weeks or less produces neurologic symptoms in 1% of patients but if taken in excess of 2 weeks produces symptoms in up to 35%. * 1800 mg daily can cause symptoms as early as the 5th day. Our case demonstrates toxicity from prolonged use of Entero-Vioform in a
daily dose ranging from 200 to 1200 mg over 6 years. It also demonstrates that acrodermatitis enteropathica can be controlled with low doses of zinc sulfate. This drug and similar agents were available over the counter but are now available only by prescription. Physicians prescribing these medications and pharmacists recommending their use for either travellers' diarrhea or nonspecific diarrhea of infancy should be aware of their toxicity and avoid their use except in life-threatening situations. W.G.L. CARR, MD P0 Box 512 Nanaimo, BC R.A. BOWEN, MD, FRCS[C] 235 Bastion St. Nanaimo, BC FA. HORNER, MD, FRCP[C] 1525 Dufferin Cres. Nanaimo, BC
References 1. SPILLANE JD: S.M.O.N. (C). Lancet 2: 1371, 1971 2. Idem: S.M.O.N. (C). Lancet 1: 154, 1972 3. MCEWAN LM: Neuropathy after dioquinol (C). Br Med J 4: 169, 1971 4. SELBY G: Subacute myelo-optic neuropathy in Australia. Lancet 1: 123, 1972 5. KAE5ER HE, WUTHRICH R: Zur Frage der Neurotoxizitat der Oxychinoline. Dtsch Med Wochenschr 95: 1685, 1970 6. OSTERMAN OP: Myelopathy after clioquinol treatment (C). Lancet 2: 544, 1971 7. OAKLEY GP Ja: The neurotoxicity of the halogenated hydroxyquinolines. JAMA 225: 395, 1973
7.
Gravergol has the answer. Gravergol. is a member of the Gravol family designed to relieve migraine and similar vascular headache attacks. Each Gravergol capsule contains 1 mg ergotamine tartrate and 100 mg caffeine to relieve the attack by vasoconstnctive action on distended cranial arteries plus 50 mg dimenhydrinate to treat the accompanying nausea Gravol (dimenhydrinate) is available in the following forms: 50 mg tablets. 75 mg long-acting capsules. 100 mg adult suppositories. 15 mgI5 ml liquid in 75 ml plastic containers. 50 mg pediatric suppositories. 50 mglml llm ampoules: 1 and 2 ml; and lIm vials: 5 ml. 10 mglml Iv ampoules: 5 ml.
D.D.
Gravol*
Canada's most widely Montr6al,Cariada
used antinsuseant. Reg. T.M.
. .ppl.
CMA JOURNAL/FEBRUARY 5, 1977/VOL. 116 251
