BILATERAL OPTIC ATROPHY CAUSED BY CHRONIC ORAL INGESTIONAND TOPICAL APPLICATION OF HEXACHLOROPHENE

THOMAS L. SLAMOVITS, M.D., RONALD M. BURDE, M.D.,

AND TERENCE G. KLINGELE, M.D.

St. Louis, Missouri

Hexachlorophene has been shown tobe a neurotoxic agent in laboratory ani­mals and in children. We report a case ofoptic atrophy in a 31-year-old woman,which was probably caused by chronichexachlorophene ingestion.

CASE REPORT

In March 1975, a 31-year-old woman with visualloss was referred here. She and her family had nohistory of ocular problems. At age 29 years she had a"spell" of bilateral blindness with right-sided numb­ness and weakness lasting about five minutes withcomplete resolution and no recurrences. She under­went surgery in March 1974 to remove a growth fromher right ear. After this, she began taking anestimated 10 to 15 ml of hexachlorophene (pHiso­Hex) orally daily during the next ten to 11 months.She also applied large amounts of hexachlorophene toher face every day as self-treatment for pimples. Shewas depressed during this time. She noted noheadache, diplopia or dizziness, but may have hadintermittent numbness of her left foot.

In January 1975 she noted decreasing vision, firstin her right eye, described as a superior visual fieldloss that progressed inferiorly. She saw a physicianseveral days later. By that time her visual acuity waspoor in the right eye and also abnormal in the lefteye. She was told that she had optic atrophy and wasreferred to us for further examination. She was takingno medications with the exception of the hexachloro­phene. She reported no exposure to chemicals otherthan hexachlorophene.

Ophthalmic examination revealed a visual acuity ofRE.: hand motions and L.E.: 6/90 (20/300). Bothpupils were round and 6 mm in diameter. The leftpupil reacted more rapidly to light than the rightpupil, and there was no afferent pupillary defect onthe right. The near response was normal in botheyes. The patient could not detect the isochromaticcolor plates with her right eye; with the left eye she

could identify only the demonstration plate. Therewas an intermittent exotropia, but both versions andductions were full. Fine upbeat nystagmus waspresent on upgaze. The optokinetic response wasnormal in the left eye, but she could not see the tapewith the right eye.

Slit-lamp examination and intraocular pressures byapplanation were normal. Ophthalmoscopic examina­tion showed severe bilateral optic atrophy, which wasworse in the right eye than in the left eye. Nervefiber layer thinning was evident, but no other retinalabnormalities were noted. Visual fields showed asmall irregular island of vision near, but not includ­ing, fixation in the right eye and a superotemporalquadrantanopia in the left eye (Fig. 1). Electroreti­nography and visual-evoked response testing werenot done. The patient was admitted to the hospitalfor examination of a possible intracranial tumor.

During her hospitalization, a hypochromic, micro­cytic, iron deficiency anemia was uncovered. Electro­lytes, blood urea nitrogen, creatinine, and liverenzymes were normal. Lumbar puncture was normalwith cerebrospinal fluid and serum serology nonreac­tive. Chest x-ray, plain skull films, views of the opticforamina and computed axial tomography scan withand without contrast were all normal. A pneumoen­cephalogram showed thickening and widening of theoptic chiasm (Fig. 2).

The psychiatric consultant found hypochondriacalobsessions, perhaps delusions and occasional depres­sion, but she was not thought to be schizophrenic.Once or twice during her hospital stay, the patientingested hexachlorophene despite repeated advicenot to do so.

She was discharged with a diagnosis of hexa­chlorophene-induced optic atrophy and fol1owed upas an outpatient. During subsequent visits to ouroffice, the appearance of the fundus was not changed.Her visual fields improved and eventually stabilized(Fig. 3). Visual acuities also improved and stabilized.Four months after discharge visual acuity was R E.:6/120 (20/400) and L. E.; 6/12 (20/40). Fourteenmonths after discharge, visual acuity was R E.: 6/120(20/400) and L. E.: 617.5 (20/25) with no subsequentchanges.

From the Departments of Ophthalmology (Drs.Slamovits, Burde, and Klingele) and Neurology (Dr.Burde), Washington University School of Medicine,St. Louis, Missouri. This study was supported in partby a grant from Research To Prevent Blindness, Inc.,New York, New York. Dr. Slamovits was a HeedFoundation Fellow (1979-1980).

Reprint requests to Ronald M. Burde, M.D.,Department of Ophthalmology, Box 8096, 660 S.Euclid Ave., St. Louis, Mo 63110.

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DISCUSSION

Hexachlorophene is an effective anti­staphylococcal germicide used as soap ordetergent in a 2% (w/w) concentration.After oral or topical administration,neurotoxicity has been shown in animalssuch as rats,1,2 calves, sheep," monkeys."

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Fig. 1 (Slamovits, Burde, and Klingele). Visual fields obtained shortly after initial examination show a smallirregular island of vision near, but not including, fixation in the right eye and a superotemporal quadrantanopiain the left eye.

and tadpoles.! Human neurotoxicity hasbeen reported also after percutaneousapplication of hexachlorophene in pre­mature infants, full-term babies withnormal skin," patients with bums-" orichthyosis, as well as after ingestion. 8-10

Typical autopsy findings in both ani­mals!,2,5 and humans'v" include brainedema and myelin loss and vacuolation!(synonyms include honeycombing" orvacuolization'' or "aspec de dentelle'?')

of the myelin sheath. A number ofthese studies stress the extensive in­volvement and particular susceptibilityof the optic nerve and chiasm in bothanimals!-3,7 and humans.v"

Towfighi, Gonatas, and McCree! re­ported hind leg weakness or paralysisafter oral administration of hexachloro­phene to young adult rats. Findings

Fig. 2 (Slamovits, Burde, and Klingele). Suprasellar pneumopolytomography. Left, Frontal section shows asymmetrically widened and thickened chiasm (arrow), 24 x 9 mm in maximum dimensions (upper limits ofnormal being about 19 x 7 mm). Right, Lateral view again shows the enlarged chiasm (arrow). The sellaturcica is normal.

678 AMERICAN JOURNAL OF OPHTHALMOLOGY MAY, 1980

LEFT RIGHT

Fig. 3 (Slamovits, Burde, and Klingele). Visual fields obtained 28 months after initial examination showingimprovement (compare to Figure 1).

included vacuolation of myelinated fibersin the central nervous system and pe­ripheral nerves, which was more evidentin large than small fibers. Similarly,more vacuolation was found in centralthan in peripheral nerve myelin with themost severe changes seen in the opticnerve. They described cerebral and cere­bellar white matter softness and swellingas well as enlargement throughout theentire course of the optic nerves.

In rats given a diet containing hexa­chlorophene, Rose, Wisniewski, andCammer'' described intraperiod split­ting of myelin, which was visible on elec­tron microscopy. In one report'[ the ratretina was studied after a hexachloro­phene diet. Disruption of the disk mem­branes of the rod outer segments wasnoted together with photoreceptor loss.Towfighi, Gonatas, and McCree12 postu­lated the same mechanism for photore­ceptor disk and intramyelinic vacuola­tion, that is, hexachlorophene affinity forextracellular components of both recep­tor lamellae and myelin.

Coutieres and Aicardi" described au-

topsy findings after percutaneous hexa­chlorophene intoxication of children withnormal skin. Optic nerves and spinalcord were described as swollen, andmassive cystic spongiosis of the whitematter of the hemispheres was noted.They stated: "Oedema was most pro­nounced in the U fibres, internal cap­sule, white fasciculi coursing throughthe basal ganglia and optic nerves." Atautopsy of a boy who had died after acci­dental oral hexachlorophene ingestion,Martinez, Boehm, and Hadfield" founddiffuse white matter vacuolization and aselective optic pathway necrosis anteriorto the geniculate bodies.

The present case lends further clinicalsupport to laboratory observations. Ourpatient had significant visual impairmentcaused by anterior visual system damage.Possibly the apparent improvement invisual fields and visual acuity representssubsidence of optic nerve edema afterdiscontinuation of hexachlorophene use.The present stable visual acuity andvisual fields probably reflect the trueextent of the optic nerve damage induced

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by hexachlorophene. Clinical evaluationshowed bilateral optic neuropathy, andpneumoencephalography showed an en­larged chiasm. Results of neurologicexamination were normal except for theoptic atrophy. The patient denied symp­toms of gastrointestinal disease, althoughan iron-deficiency anemia was found.Laboratory studies disclosed no otherabnormalities.

Our patient, by conservative estimate,consumed an estimated 10 to 15 ml ofhexachlorophene daily during a period ofapproximately ten months, in addition tofrequent skin application. Some inges­tion took place in the hospital, despitewarnings not to take it. What oral dosesare likely to cause toxicity is unclearfrom published reports. For example,Martinez, Boehm, and Hadfield" reportedthe death of a 7-year-old boy after a45-ml dose was taken orally. Henry andDiMaio's" patient, a 46-year-old woman,died after taking 200 ml of hexachloro­phene orally. Lustig's13 patient, a 6­year-old, died after drinking 4 to 5ounces of hexachlorophene; yet, an in­fant who had a "spoonful" of hexachloro­phene with each feeding for several dayshad no residual effects."

It appears that adults tolerate greaterdoses than children, and susceptibility isvariable. Our case shows that anteriorvisual system damage can be presentwhen no other signs of poisoning arepresent.

SUMMARY

A 31-year-old woman ingested hexa­chlorophene (pHisoHex) over a ten­month period. She developed bilateraloptic atrophy with no other systemic

evidence of neurotoxicity. This case sup­ports pathologists' findings that the opticnerve and chiasm are particularly sensi­tive to the poisonous effects of hexachlo­rophene.

REFERENCES

1. Towfighi, J., Gonatas, N. K., and McCree, L.:Hexachlorophene induced changes in central andperipheral myelinated axons of developing and adultrats. Lab. Invest. 31:712, 1974.

2. Rose, A. L., Wisniewski, H. M., and Cammer,W.: Neurotoxicity of hexachlorophene. New patho­logical and biochemical observations. J. Neurol. Sci.24:425, 1975.

3. Udall, V., and Malone, J. C.: Optic nerveatrophy after drug treatment. Excerpta Medica11:244, 1970.

4. Hart, E. R.: Daily bathing of infant monkeys inpHisoHex. Toxiceffects and recovery status report. J.Clin. Pharmacol. 13:445, 1973.

5. de Webster, F. H., Ulsamer, A. G., andO'Connell, M.: Hexachlorophene induced myelinlesions in the developing nervous system of xenopustadpoles. Morphological and biochemical observa­tions. J. Neuropathol. Exp. Neurol. 33:144, 1973.

6. Coutieres, F., and Aicardi, J.: Accidental per­cutaneous hexachlorophene intoxication in children.Br. Med. J. 2:663, 1977.

7. Korlof, B., and Winsten, J.: The complicationsof pHisoHex. Scand. J. Plast. Reconstr. Surg. 1:78,1967. .

8. Mullick, F. G.: Hexachlorophene toxicity. Hu­man experience at the A.F.I.P. Pediatrics 51:395,1973.

9. Martinez, A. J., Boehm, R., and Hadfield,M. G.: Acute hexachlorophene encephalopathy. Clin­icc-neuropathological correlation. Acta Neuropathol.28:93, 1974.

10. Henry, L. D., and DiMaio, V. J. M.: A fatalcase of hexachlorophene poisoning. Milit. Med.139:41, 1974.

11. Lockhart, J. D.: Hexachlorophene and theFood and Drug Administration. J. Clin. Pharmacol.13:445, 1973.

12. Towfighi, J., Gonatas, N. K., and McCree, L.:Hexachlorophene retinopathy in rats. Lab. Invest.32:330, 1975.

13. Lustig, F. W.: A fatal case of hexachlorophene(pHisoHex) poisoning. Med. J. Aust. 1:737, 1963.

14. Pilapil, V. R.: Hexachlorophene toxicity in aninfant. Am. J. Dis. Child. 111:333, 1966.