Year : 1953 | Volume
: 1 | Issue : 3 | Page : 89--93
A case of arsenical amaurosis treated successfully with BAL
BK Das Gupta
Sir Nilaratan Sircar Medical College, Calcutta, India
B K Das Gupta
Sir Nilaratan Sircar Medical College, Calcutta
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Das Gupta B K. A case of arsenical amaurosis treated successfully with BAL.Indian J Ophthalmol 1953;1:89-93
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Das Gupta B K. A case of arsenical amaurosis treated successfully with BAL. Indian J Ophthalmol [serial online] 1953 [cited 2013 May 25 ];1:89-93
Available from: http://www.ijo.in/text.asp?1953/1/3/89/40763
Of all the preparations of arsenic, inorganic and organic, inorganic salts are supposed to be innocuous for the eyes. Cases in the literature causing amblyopic symptoms by inorganic salts are rare. Reynolds (1900) reported that in a masspoisoning due to drinking of arsenic-contaminated beer in Manchester, which affected about 1,000 people, not a single case of amblyopia was seen nor a single case with affection of the retina or the optic nerve occurred. de Haas ( 1919 ), however, reported occurrence of neuro-retinitis with development of bilateral central scotoma from poisoning by inorganic arsenic salts.
In contrast, organic arsenical preparations show a high degree of toxicity for the visual elements. It has been found that the penta-valent compounds are particularly injurious to the eyes, as compared with the tri-valent compounds, which are relatively non-toxic. The first compounds which showed marked toxicity were atoxyl and soamin, which were given in large doses for trypanosomiasis and syphilis. They rapidly produced a large number of cases of permanent blindness. Several other preparations of organic arsenic have shown similar results. Even relatively non-toxic acetylarsan or tryparsamide have caused permanent blindness, though in less numbers. But it is considered that acetylarsan and tryparsamide are relatively much safer than atoxyl and soamin, if they are given carefully and if a sharp watch is kept on the peripheral field.
There are certain factors which should be taken into consideration before arsenical treatment is begun : old people show comparatively lesser tolerance to arsenicals than younger age groups; marked arteriosclerosis or advanced diseased conditions of the kidneys or liver are definite contraindications; in diseased condition of the optic nerve it should never be administered.
The symptoms usually appear weeks or months after the injections of arsenicals or they may make their appearance in a sudden and dramatic way. In those cases, which appear weeks or months after, usually the visual symptoms precede signs of general arsenical poisoning, such as, headache, vomiting, colic, labyrinthine disturbances, ataxy, incontinence etc. Cases which start with dramatic suddenness show complete bilateral amaurosis from which no recovery results (Tessot-Daquette, 1934). Usually, however, the clinical picture takes the form of a rapidly developing extreme concentric contraction of the peripheral fields with a central depression, which is soon followed by pallor of the optic discs developing into optic atrophy with no tendency to recovery. There may be progressive deterioration until even perception of light is abolished. No treatment seems to do any good, although Veil ( 1935 ) reported improvement after immediate injection of acetyl-choline.
Experimental research on animals have shown gross non-inflammatory degenerative changes in the ganglionic cell layer of the retina and the optic nerve. The earliest changes are, however, found in the proximal portion of the optic nerve. In the human subjects also, similar histological changes are found in the retina and the optic nerve.
The purpose of this paper is to show the efficacy of BAL in arsenical total amaurosis, which affected both the eyes.
It has been found that the body-tissues require the help of -SH or thiol groups for carrying out their normal activities. These -SH groups are found in the tissue-protein. It has been shown that arsenicals possess a high degree of affinity for -SH groups and it was suggested that the combination of arsenicals with -SH groups caused blocking of the normal tissue-activity and this accounted for the toxic action of various arsenicals--Voegtlin, Dyer and Leonard ( 1923 ).
At the beginning of the second world war Peters, Stocken and Thomson (1945) started work to find out an antidote for arsenical war gas lewisite. Stocken and Thomson ( 1946 ) studied the effect of kerateine, a thiol-rich protein, on lewisite. They showed that it only combined with lewisite when it was in the reduced form (-SH), but, when oxidised to -S-S form, it had no affinity for lewisite. It appeared that each atom of arsenic combined with two adjacent -SH groups and formed a stable ring.
It was thought that organic dithiols would form similar stable rings with arsenicals and for this reason, one of the compounds tried in the earlier stages of experiment was 2,3-dimercaptopropanol. It was found that this substance was much more effective than any known monothiols. It formed a complex with lewisite much more stable than kerateine-lewisite complex. It not only protected but even reversed the poisoning process by lewisite.
The name "British Anti-Lewisite" or "BAL" was given to this substance 2,3-dimercaptopropanol. The ability- to form complexes with thiols is not only confined to arsenicals, but has been extended to poisoning by heavy metals and metalloids.
The action of BAL lies in its ability to form a stable compound with arsenic and other metals. Being ineffective by mouth, BAL is administered by intramuscular injections when it is distributed throughout the body. It is concentrated in the kidneys and excreted in the urine. The effect of a single dose largely disappears within four hours after injection and, therefore, this should be the interval between doses in acute poisoning. It is presumed that in acute poisoning BAL transfers the toxic element from the tissue-cells to the tissue-fluids, particularly the plasma and thence to the urine.
So far the papers which have appeared in which BAL has been found to be effective deal with various manifestations of arsenical poisoning occurring mostly during anti-syphilitic treatment with arsenicals, and local and systemic poisoning by arsenical war gas-lewisite, such as, exfoliative dermatitis, arsenical encephalopathy and agranulocytosis following arsenical therapy. It has also been found effective in acute mercuric chloride poisoning and in exfoliative dermatitis following gold therapy.
Favourable results have been obtained in 50 to 80 per cent of cases suffering from exfoliative dermatitis ( Eagle and Magnuson, 1946 ). If relapses occur, they respond to a further course of BAL. Less data is available to assess the effectivity of BAL in other toxic reactions of arsenicals. Clinical improvement and much reduction of mortality has been reported in arsenical encephalopathy when treatment with BAL was initiated less than six hours from the onset of cerebral symptoms (Eagle and Magnuson, 1946). In agranulocytosis or leucopenia following treatment by arsenicals, recovery is probably accelerated by BAL ( Holley, 1947).
Until now, to my knowledge, no case of complete blindness following arsenical therapy treated with BAL has been reported in the literature. The purpose of this paper is to report such a case which has responded extremely favourably to " British Anti-Lewisite ".
Peters, Stocken and Thomson (1947) recommend the following dosage for BAL for intramuscular injections in the thigh or gluteal region.
First day: four injections, each of 2 c.c. of 5 per cent BAL at four hourly intervals.
Second, third and fourth days: 2 c.c. twice daily. Fifth and six days: 2 c.c. daily.
There are certain risks which should be borne in mind when BAL is being administered. In the presence of liver damage, it should not be given as it enhances the toxicity (Cameron et al. 1947). In poisoning by other metals, where the efficiency of BAL has not been established, it is very risky to start treatment with this drug, as it might form a complex with the metal which might prove more toxic than the original metal itself.
Mrs. D. G., 35 years, female, of Rewa state, came for consultation on 20-11-52 for hazy vision of both the eyes--duration 7 days.
Past history. Has been sulfering from asthma for the last 7 years. Was being treated with soamin injections. Developed optic neuritis of the right eye 2 years back. On that occasion she recovered the lost vision completely on Vitamin B, injections and B-complex by mouth, but the right optic disc remained pale. She was strongly advised not to take any more injections containing arsenic.
Present history. For the last 2 years she was keeping fairly well and did not have any severe attack of asthma. About 3 weeks back she had a very bad attack of asthma and she did not get any relief from ordinary medicines. She was given Acetyl-arsan 1 c.c. every 3 days. Five such injections were given. Three days after the last injection she developed hazy vision in both the eyes.
This time the patient entered the consultation room with such reduction of vision that she had to be carried by four people.
Examination. Right eye: conjunctiva and cornea were normal, pupil reacted activiely to light, tension was normal, vision was reduced to 1/60. Optic disc was pale, but the margins were not indistinct. No other abnormality was seen in the fundus.
Left eye: conjunctiva and cornea were normal, pupil was widely dilated, direct reaction to light being totally absent, tension was normal. She had no perception of light. Disc margins were hazy, and the disc was hyperemic. No other abnormality was seen in the fundus.
Treatment : While in Rewa, as soon as she developed hazy vision, she was given 200 m.-m. of Vitamin B, injection with Sodium Thio-sulphate with no effect.
She was advised intramuscular injections of BAL (5 per cent of BAL with 10 per cent of benzyl benzoate in arachis oil-Boots) deep into the gluteal region, 3 injections daily every 4 hours-first dose 4 cc., second dose 2 cc. and third dose 4 cc.-for 7 days. Along with this, intravenous injection of Vitamin C 300 mg. daily was advised.
26-11-52, that is, 7 days later, she was seen again. In the right eye vision improved to 6/ 18. But, in the left eye, vision was only appreciation of hand movement. The pupil was slightly smaller than before and was very feebly reacting to light. She was advised to continue BAL 2 cc, twice daily with 300 mg. of Vitamin C daily intravenously.
2-12-52. Right eye vision improved to 6/12. In the left eye vision was now finger counting at 8 inches. Left pupil was now smaller and almost of the same size as that of the right one. Direct reaction to light was brisk. She was advised to continue BAL in doses of 2 c.c. intravenously every day with 400 mg. of Vitamin C daily by mouth.
9-12-52. No further improvement in her condition was noticed. BAL stopped. Vitamin C and & were ordered by mouth.
16-12-52. Condition same as above. Treatment continued as above.
23-12-52. Vision in left eye improved to finger counting at 12 inches.
On 7-1-53 she reported that the left eye, which was progressing very slowly, started improving very quickly and now she could see better with the left eye compared with the right. But a fresh complication had developed in the meantime. The day she left Calcutta (25-12-52) she had a feeling of tingling in both the feet. The sensation extended up to the waist on the left side, but it remained confined to the foot on the right side. Two days later she had a feeling of numbness in the left leg extending up to the region where BAL was injected. On the right side there was no feeling of numbness only tingling sensation was there up to the ankle. On 28-2-53 she reported that all the numbness and tingling had practically disappeared. She had her eyes tested by an eye-specialist and the vision was 6/6 in each eye.
She came down to Calcutta again on 12-6-53. Vision was 6/6 in each eye. Both pupils were equal and normal and were briskly active to light. Left optic disc was pinker than the right.
The field of vision was taken of each eye with 3 mm. white and 5 mm. red objects at 333 mm. distance on 13-6-53. The extent of the field of vision of the left eye was constricted as compared with that of the right eye with white object. The field of vision of both the eyes with red object was very much smaller than normal.
Certain points have emerged from the study of this interesting case, which are at variance with the views previously held. It has been held that a damaged optic nerve is more likely to suffer in arsenical poisoning in a severer form than a healthy optic nerve. In this case the healthy eye was affected more severely than the previously damaged eye. It is, therfore, quite justifiable to assume that, in arsenical poisoning, both optic nerves are likely to be affected but one may be affected in a severer form than the other.
It has also been held that cases which start with dramatic suddenness with complete bilateral amaurosis, do not show any recovery, but, in this case, almost complete restoration of sight was attained within three months.
The field changes in organic arsenical poisoning take the form of a rapidly developing concentric contraction of the peripheral fields with a central depression, which is followed by optic atrophy with no subsequent tendency to recovery. In this case, on recovery, the improvement of the field of vision for white objects was considerable, but, the extent of the field for red objects remained markedly contracted. The restoration of sight after complete bilateral amaurosis and the recovery of the visual field for white objects show that there occurred a temporary blockage of the normal tissue-activity due to combination of arsenicals with -SH groups and that this combination could he dissociated if BAL is administered early in the diseased process.
One puzzling feature of the treatment was the development of numbness and tingling in the lower extremities about a month after commencement of treatment and lasting for about a month.
1. A case of bilateral arsenical amaurosis, following injections of acetylarsan, is described, which responded marvellously to BAL.
2. The mechanism of arsenical tissue-toxicity is discussed and the introduction of BAL, its mechanism of action and dosage are reviewed. The effectivity of BAL in various heavy metal poisonings is discussed.
3. As far as could be ascertained, this is the first case reported on the efficacy of BAL in total bilateral arsenical amaurosis.
|1||Cameron. G. R., Burgess, F and Trenwith. V. S. (1947) Brit. J. Pharmacology, 2, 59.|
|2||de Hass (1919) Arch. fur Ophth. 99, 16.|
|3||Eagle, H. and Magnuson, H. J. ( 1946) Am. J. Syph. 30, 420. |
|4||Holley, H. L. (1947) Ann. Int. Med. 27, 231.|
|5||Peters, R. A., Stocken, L. A. and Thompson, R. H. S. ( 1945) Nature, 156, 616.|
|6||Report from the BAL conference, Medical Research Council. signed by Peters, R. A. (Chairman) and 13 others. ( 1947) Lancet, ii, 497. |
|7||Reynolds ( 1900) Brit. Med. Jour. ii, 1492. |
|8||Stocken, L. A. and Thompson, R. H. S. (1946) Biochem. J. 40, 529. |
|9||Tissot-Daquette (1934 ). Arch. d'Ophth. 51, 17. |
|10||Veil ( 1935) Bull. Soc. d'Ophth. Paris, 47, 71.|
|11||Voegtlin. C., Dyer. H. A. and Leonard, C. S. ( 1923) Pub. Hlth. Rep. Wash, 83, 182. as quoted by M. Weatherall ( 1948) The Practitioner, 160, 239.|