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Boric acid poisoning
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Boric acid poisoning Brent M. Schillinger, M . D . , Mindy Berstein, M . D . , Lisa A. Goldberg, M . D . , and Alan R. Shalita, M.D.
Brooklyn, NY The skin manifestations associated with boric acid intoxication are particularly striking. We present a case report of a 44-year-old black woman who, following a suicide attempt, demonstrated the classic features of acute boric acid poisoning. She developed generaIized erythema creating a "boiled lobster" appearance with massive areas of desquamation. A discussion of the history of the use of boric acid by the medical profession follows the patient presentation. (J AM ACAD DERM~,TOL7:667-673, 1982.)
Boric acid has been aptly called a " w o l f in s h e e p ' s clothing."1 Numerous studies have indic a t e d that the drug has relatively little therapeutic v a l u e , and its accidental use has resulted in significant morbidity and mortality. The toxic effects o f boric acid have been seen following both acute and chronic use of the s u b s t a n c e ) '~ The skin manifestations associated with boric acid intoxication are particularly striking. These have included extensive erythema with desquamation resembling a " b o i l e d lobster" following acute ingestion, and diffuse alopecia after chronic use. 2'4 We present a c a s e o f a patient who manifests the classic features o f acute boric acid intoxication following a suicidal attempt. CASE REPORT A 44-year-old black woman presented to the emergency room of Kings County Hospital Center with a widespread exfoliative dermatitis which had been present for 2 days. It started with an erythema which was first noted around the mouth and on the buttocks and perineum. The eruption spread within a 24-hour period to involve the trunk, followed by a similar eruption on the face and extremities. During the evolution of this
From the Department of Dermatology, State Unlvej'sity of New York Downstate Medical Center. Reprint requests to: Dr. Alan R. Shalita, Department of Dermatology, Downstate Medical Center, Brooklyn, NY 11203. 0190-9622/82/110667+07500.70/0 © 1982 Am Acad Dermatol
exanthem, the erythema was followed by exfoliation which, by the time of her admission, had progressed to large sheets of desquamation. The skin lesions were accompanied by a persistent sensation of nausea with multiple episodes of vomiting. The patient admitted to self-administration o f half a container of boric acid powder 3 days prior to admission to "scare her children." There was a prior psychiatric history of nervousness and depression for which she had been hospitalized on several occasions. At the time of admission the only medication the patient was using was hydrochlorothiazide, 50 m g daily, for hypertension. On physical examination, the patient was alert and oriented to time, place, and person. Blood pressure was 105/55 mm Hg without orthostatic changes; respirations, 20/min; pulse, 110 and regular; temperature, 37.8 ° C. She was grossly obese and weighed 109 kg. Examination of the skin revealed massive areas of desquamating necrotic tissue with concentration at the axillae, groin, and intertriginous areas (Fig. 1). There was generalized marked erythema creating a "boiled lobster" appearance. The palms and soles were markedly hyperemic. Hemorrhagic crusting was present in a perioral distribution extending to the mucocutaneous junction (Fig. 2). The conjunctiva and oral mucous membranes were also hyperemic. Her initial laboratory tests showed a hemoglobin of 11.3 gm and hematocrit of 33.6% without leukocytosis. Blood urea nitrogen (BUN) was 62 mg/dl; creatinine was 11.1 mg/dl. The calcium level on admission was 6.7 mg/dl; phosphorus was 1,6 mg/dl. Spot glu-
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Fig. 1. Erythema at denuded site of right axilla. A similar picture was seen below both breasts and in the perigenital area. Fig. 2. Boiled lobster appearance of face with hemorrhagic, necrotic involvement at lips, mucoeutaneous junction, and nasolabial fold.
Fig. 3. Sparse superficial perivascular infiltrate with markedly dilated blood vessels and focal vacuolar alteration at the derrnoepidermal interface. There is a stratum of parakeratosis forming a cleftlike space in the mid epidermis. (Hematoxylin-eosin stain; original magnification, ×40.) cose was 230 mg/dl. The following tests were either negative or normal: urinalysis, chest x-ray, sodium, potassium chloride, COz, iron, total iron binding capacity, B,2, folate, and VDRL. A culture taken from the macerated area above the groin grew Proteus mirabilis and Klebsiella pneumoniae. Multiple blood cultures were negative for pathogens. Bone marrow aspirate revealed hypercellularity, with an increase in
the myeloid series, decrease in the erytbroid series, adequate megakaryocytes, and iron present. Skin punch biopsies were taken from representative sites at the abdomen and right arm. Both sites showed an intraepidermal cleft with focal vacuolar changes at the dermoepidermal junction. Satellite cell necrosis was observed in the epidermis under high power (Figs. 3-5). Boric acid levels from blood and urine samples taken
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Fig. 4. There is satellite cell necrosis, vacuolar alteration of the basal layer, scattering of neutrophils and lymphocytes around blood vessels. (Hematoxylin-eosin stain; original magnification, x 400.)
Fig. 5. The superficial vessels have plump endothelial cells and a perivascular infiltrate of lymphocytes, neutrophils, and extravasated red blood cells. (Hematoxylin-eosin stain; original magnification, x 400.) at the time of admission were unfortunately lost in transit. Additional samples taken several days later were within normal limits as determined by the U.S. Borax Company Laboratory in Anaheim, CA. A family member did provide us with a half empty container of boric acid powder. The material was analyzed as being boric acid, and the exact amount missing from the container was determined to be 14 gm (analysis done at
Lederle Laboratories, Pearl River, NY). In light of this strong history and the consistency of physical findings with previously reported cases of boric acid toxicity, there seemed to be little or no doubt that this patient indeed had incurred boric acid intoxication. The patient responded well to supportive measures. Her renal function improved dramatically after one course of hemodialysis. The cutaneous lesions in-
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Fig. 6. Alopecia as observed on the thirteenth day following the ingestion of 14 gm of boric acid powder. Fig. 7. Sheetlike desquamation observed at palms and soles. This photograph depicts the involvement of the palms on the fifth day following intoxication. creased in severity and degree of involvement during the first few days of hospitalization. On the tenth day she developed a patchy alopecia of the scalp which progressed to alopecia totalis within a few days (Fig. 6). Skin care consisted of topical gentian violet applications at denuded areas and soaks four times daily with Burow's solution diluted 1:40. The patient received daily baths of KMnO4 diluted l : 80,000. As the lesions on the trunk were resolving, she developed marked desquamation in sheets at the palms and soles, which persisted for several days (Fig. 7). At this stage the cutaneous condition appeared to stabilize; she gradually became less erythematous and the desquamation subsided. Two days into the hospitalization the patient's mental status deteriorated and simultaneously she developed a fever of 39.0 ° C. The fever workup was completely negative: normal spinal tap, sterile blood cultures. With supportive therapy the fever lessened. One week into her hospital stay her hematocrit dropped to 19%, with a hemoglobin of 6.5 gm. There was no evidence of hemolysis on the peripheral blood smear. Coombs' direct and indirect tests were negative. Following bone marrow aspirate, the impression was bone marrow toxicity secondary to boric acid poisoning. The patient responded well to transfusion with three units of packed red cells. During the course of the hospitalization, she developed elevated liver function tests: serum glutamic oxatoacetic transaminase (SGOT), 107 U/liter; lactic dehydrogenase (LDH), 335 U/liter; alkaline phosphatase, 80. These leveled off without specific therapy by the time of her discharge. The initially elevated
blood sugar level came down to the normal range by her third day of hospitalization. The serum calcium levels remained low despite consistently normal serum albumin. The calcium spontaneously rose to "low normal" values by the end of her 2-week stay in the hospital. DISCUSSION Boric acid, or "boracic a c i d , " is a chemical substance which is stable in air, odorless, has a slightly acid bitter taste and a sweetish aftertaste, s Boric acid as a drug has been gradually dropped from official recognition in the United States. a Boric acid and its salts, including borax, are used widely outside o f medical applications. Boric acid is used in laundering, in fireproofing fabrics and wood, in the manufacture of leather, and in the production of glazes and enamels. Boric acid has also gained popularity in recent years as a good antiroach preparation. Joseph Lister 7 first introduced boric acid into surgery as an antiseptic solution applied to wounds. Lister was also the first to notice the toxic effect o f boric acid on human cells. H e observed experimentally that boric acid slowed down the rate o f epithelialization. 8 Nine years after Lister introduced boric acid as an antiseptic two deaths were reported from the use of boric acid as an irrigating fluid. T w o years later the first case of boric acid p o w d e r leading to a fatality was reported in the United States. -'1In fact
Volume 7 Number 5 November, 1982
there have been published accounts of deaths secondaiy to boric acid or borax poisoning in every decade from these early reports until the present day. Perhaps the most famous report is that of Wong et al 2 wherein boric acid poisoning of eleven infants as a result of accidental and inadvertent use of boric acid in the preparation of infant formula resulted in the deaths of five of the infants. A similar episode reported by Rubenstein and Musher ~° involved three out of four infants who were also given formula made up inadvertently with boric acid solution in place of distilled water. These three infants expired within a week o f ingestion of the boric acid mixture. The diagnosis of boric acid poisoning has to be based on symptomatology together with a history o f exposure. The toxic effects can be related to either acute or chronic exposure to the chemical. The minimal lethal dose of boric acid for man is not known. One report indicates that a man can take 4 gm a day orally without incident whereas a single dose of 18 to 20 gm is fatal. ~ Approximately 5 to 6 gm seems to be the lethal limit for infants and small children. Chronic intoxication has occurred after a daily ingestion of 4 to 5 gm per day for 3 to 4 weeks.'2 It was determined that our patient ingested approximately 14 gm of boric acid, which is consistent with the signs of acute toxicity she exhibited. Nausea, vomiting, and epigastric pain, often persistent, have been reported in numerous papers. 6 The present case is no exception. These gastrointestinal symptoms may be the only initial elements in the clinical picture. The skin lesions are typically the next symptoms to present. They are usually but not always present. It appears that in the severely poisoned individual death can actually occur before the onset of the skin manifestations. '~ Most commonly one observes erythema, desquamation, and exfoliation. The erythema may be very intense and is sometimes referred to as a "boiled lobster" appearance." The lesions may resemble those of scarlet fever or Ritter's disease. va,,4 In the most severe cases cyanosis may be present. Sites most commonly affected are the palms and soles, buttocks, and scrotum, although no surface is immune. Mucous membranes often share in the general erythema, and desquamation from the eyelids has been noted.
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Rubenstein and Musher '° indicate that boric acid poisoning, especially in the newborn, causes a picture clinically indistinguishable from staphylococcal scalded skin syndrome (SSSS). The features in common include fussiness, refusal to eat, vomiting, diarrhea, dehydration, and the characteristic exfoliative dermatitis. The mere presence of staphylococci should not be accepted as prima facie evidence of SSSS. Other skin signs of borate intoxication include psoriasiform lesions, bullae, and alopecia. 4 In infants the diaper ,area may show excoriations, desquamation, vesiculopustular lesions, edematous genitals, gangrene of the penis and scrotum, and m a c u l e s . :~
Since the greater amount of boron compounds accumulate in the brain, liver, and kidneys, injuries to these organs are expected in acute boric acid poisoning. Central nervous system manifestations are common and include signs of meningeal irritation, convulsions, delirium, and coma. :'3 Jaundice is sometimes present, and abnormal liver function tests are not unusual. In addition, oliguria and anuria may occur, with laboratory evidence of acute renal failure. In our patient central nervous system involvement was noted on the fifth day following ingestion of the boric acid. She showed a change in mental status, with loss of orientation to time and place. In terms of hepatic involvement, our patient developed elevated liver function tests at about the same time as the neurologic changes. Neither jaundice nor hyperbilirubinemia was appreciated during her hospital course. At the time of admission our patient was already in an oliguric state with sharply elevated BUN and serum creatinine. Chronic exposure to boric acid, as in the case of young children treated at home for diaper rash with a boric acid solution or medicated powder, can result in symptoms very similar to the acutely intoxicated. More often the symptoms are of a milder nature. ~2 Alopecia may be the most obvious presentation of chronic boric acid poisoning. Loss of hair occurred in one patient following the daily intake of 25 gm of boric acid tartrate for epilepsy. '~ Tan '~ reported on a factory worker who was exposed to a borax whitening solution for more than 6 years who also developed alopecia. Ingestion of a popu-
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Table 1. Common sources of boric acid*
Antiseptic agents Ammens Medicated Powder Cuticura Medicated Liquid Bluboro Powder Vaseline borated petroleum Denture adhesives Perma-Grip Powder Sodibor Detergents and starches Borateem Boraxo Breeze White Magic Liquid Starch
Foot powders Dr. Scholl's Bromidrosis Powder Quinsana Powder Mouthwashes Chloraseptic Listerine Pain-A-Lay Ophthalmic products Murine Visine eye drops Vaginal and douche preparations Massengill Lubricating Jelly Massengill Powder Ortho Creme
*Based on a list compiled by Dr. Kenneth M. Stein, Santa Rosa, CA.
lar mouthwash led to alopecia of a diffuse nature, which was reversed upon discontinuance of this occult source of boric acid. 4 Borates may be absorbed in solution or dry through intact skin, but more so through broken granulation tissue, serous cavities, or the gastrointestinal tract. Excretion is primarily through the kidneys, with approximately 50% excreted in the first 24 hours after exposure. One reason that boric acid poisoning, particularly the acute form, is so serious is that there is no effective antidote for it. Spontaneous or induced vomiting and diarrhea aid in emptying the intestinal tract of the substance. To speed up the removal of the boric acid before irreversible damage has been done, exchange blood transfusions have been utilized with success. ,6 Peritoneal dialysis has also proved effective. 17 Our patient responded well to hemodialysis. Most authorities recommended no more than symptomatic treatment for the skin exfoliation. It is critical to maintain a good fluid balance. Despite these measures, boric acid poisoning carries a high mortality rate, as high as 50% in children less than 1 year of age.* Boric acid has for years been a popular preparation for its alleged antiseptic activity. A survey conducted in the mid 1950s indicated that 94% of certified dermatologists used boric acid in their practice, TM yet there have never been conclusive *New York City Poison Control Center: Personal communication,
studies to support the antiseptic role. Early reports of in vitro testing indicate that boric acid has some activity against staphylococci and streptococci, but the action is primarily bacteriostatic and slow-acting at that. 19'2° One study demonstrated that boric acid is actually more toxic for human polymorphonuclear leukocytes than for various strains of Staphylococcus, thereby negating primary defense mechanisms of the body against bacteria. 2' Boric acid has also been shown to slow epithelialization of wounds and to retard the healing of burns. 6 .Some manufacturers incorporate boric acid into their products as a preservative. It appears that the efficacy here is more a matter of tradition than of scientific fact. In studying its preservative properties on urine specimens, boric acid was shown to be no more effective than hypertonic sodium chloride. 22 Pinto et a123 showed that acute ingestion of boric acid in adults and children is associated with excessive urinary excretion of riboflavin. This was not surprising as it is known that boric acid and riboflavin form a water-soluble complex .24 Further work has demonstrated in chickens that riboflavin supplementation protects against the toxicity of boric acid, particularly when boric acid is administered in large doses. 2'~ This may prove a future therapeutic tool for cases of boric acid poisoning. Boric acid intoxication will continue to remain a health hazard as long as the chemical is widely available as a medicinal product. Even the cautious
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consumer cannot avoid boric acid as it is incorporated into certain mouthwashes, skin ointments, hemorrhoidal suppositories, and processed food (Table I). The quantity o f boric acid found in these relatively frequently used preparations tends to be of low concentration. Chronic or excessive use in a susceptible individual, however, could lead to the manifestations associated with boric acid toxicity. 4'15 Bluboro powder, for example, contains a 3% concentration of boric acid in its dry form. W h e n diluted as directed, the amount o f boric acid b e c o m e s almost negligible. Yet there is still a potential for absorption. Both boric acid solution and borated talcum powder in low concentrations have been shown to be absorbed through intact as well as irritated skin. 26,27 The Food and Drug Administration O v e r the Counter Advisory Panel, in its last report, placed boric acid in Category II for safety and efficacy a m o n g O T C products. The panel r e c o m m e n d e d that the availability and use of boric acid be restricted. T h e y specifically suggested that boric acid ointment should carry a warning label that it is not to be used on inflamed skin, open wounds, and especially on large wounds such as burns. Despite these strong warnings against the use of what appears to be a potentially dangerous yet poorly effective substance, recent reports have suggested using boric acid for Vulvovaginal candidiasis and as a possible treatment for herpes simplex. 2s'29 Clearly one must consider these indications with utmost caution. We thank Dr. Edward Heilman and Dr. Albert E. Stanek, Jr. for review of the dermatopathology, and Dr. Thomas Lanzilotti for his medical management of this case and for his input in the preparation of this manuscript. REFERENCES 1. Halliday C: Boracic acid--the wolf in sheep's clothing. Can Nurse 55:1093-1094, 1959. 2. Wong LC, et al: Boric acid poisoning. Can Med Assoc J 90:1018-1023, 1964. 3. Valdes-Dapena MA, Arey JB: Boric acid poisoning. J Pediatr 61:531-546, 1962. 4. Stein DM, Odom RB, Justice GR, Rartin GC: Toxic alopecia from ingestion of boric acid. Arch Dermatol 108:95-97, 1973. 5. Martindale W: The extra pharmacopoeia, ed. 26, Amendments. London, 1973, The Pharmaceutical Press. 6. Morton HE: The over the counter miscellaneous external
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drug products. Review of the antimicrobial properties of acids: Boric acid. Washington, 1979, Food and Drug Administration Publications, pp. 22-105. 7. Lister J: Details of antiseptic surgery. Br Med J 2:10031006, 1882. 8. Lister J: Recent improvements in details of antiseptic surgery. Lancet 1:787-789, 1875. 9. Brose LD: Death following the external use of a powdered boracic acid. Med News 43: 1999-2000, 1883. 10. Rubenstein AD, Musher DM: Epidemic boric acid poisoning simulating staphylococcal toxic epidermal necrolysis of the newborn infant: Ritters disease. J Pediatr 77:884-887, 1970. 11. Dopfer H: Uber einen Todesfall nach Anwendung der Offizinetlen Borsalbe bei Einer Brandwunde. Mfinchen reed Wchnschr 52:763-770, t905. 12. Gordon AS, Prichard JS, Freedman MR: Seizure disorders and anemia associated with chronic borax acid intoxication. Can Med Assoc J 108:719-724, 1973. 13. Skipworth GN, Goldstein N, McBride WP: Boric acid intoxication from medicated talcum powder. Arch Dermatol 95:83-86, 1967. 14. Herren VC, Wyss F: Chronische Bors~iureverg.iftung. Schweiz Med Wochenscbr 94:1815-1818, 1964. 15. Tan TG: Occupational toxic alopecia due to borax. Acta Derm Venereol 50:55-58, 1970. 16. Boggs TF Jr, Anmde HG: Boric acid poisoning treated by exchange transfusion. Pediatrics 16:109-114, 1955. 17. Baliah T, MacLeish H, Drummond KN: Acute boric acid poisoning. Can Med Assoc J 101:166-168, 1969. 18. Fisher RS: The use of boric acid in dermatologic practice. Arch Dermatol 73:336-341, 1956. 19. Ochsner EH: The prevention and treatment of septic infections of the extremities. Medical Herald 30:30-36, 1911. 20. Ochsner EH: Biochemistry of topical applications: Use of boric acid in septic infections. JAMA 68:220-223, 1917. 21. Novak M, Taylor WI: Phagocyticidal and antibacterial action of boric acid. J Am Pharm Assoc (Scient Ed) 40:428-430, 1951. 22. Amies CR, Corpas A: A preservative for urine specimens in transit to the bacteriological laboratory. J Med Microbiol 4:362-365, 1971. 23. Pinto J, Huang YP, McConnell RJ, Rivlin RS: Increased urinary riboflavin excretion resulting from boric acid ingestion. J Lab Clin Med 92:126-134, 1978. 24. Zittle CA: Reaction of borate with substances of biological interest. Adv Enzymol 12:493-499, 1951. 25. Roe DA, McCormick DB, Lin RT: Effects of riboflavin on boric acid toxicity. J Pharm Sci 41:1081, 1972. 26. Draize JH, Delley EA: The urinary excretion of boric acid preparations following oral administration and topical applications to intact and damaged skin of rabbit. Toxicol Appl Pharmacol 1:267-276, 1969. 27. Fisher RS, Freimuth HC, O'Connor KA, Johns V: Boron absorption from borated talc. JAMA 157:503-505, 1955. 28. Weed JC: Vulvovaginal candidiasis. Obstet Gynecol 48:631-632, 1976. 29. Skinner GRB, Hartley CE: Possible treatment for cold sores. Br Med J 22:704, 1979.
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Boric acid poisoning Brent M. Schillinger, M . D . , Mindy Berstein, M . D . , Lisa A. Goldberg, M . D . , and Alan R. Shalita, M.D.
Brooklyn, NY The skin manifestations associated with boric acid intoxication are particularly striking. We present a case report of a 44-year-old black woman who, following a suicide attempt, demonstrated the classic features of acute boric acid poisoning. She developed generaIized erythema creating a "boiled lobster" appearance with massive areas of desquamation. A discussion of the history of the use of boric acid by the medical profession follows the patient presentation. (J AM ACAD DERM~,TOL7:667-673, 1982.)
Boric acid has been aptly called a " w o l f in s h e e p ' s clothing."1 Numerous studies have indic a t e d that the drug has relatively little therapeutic v a l u e , and its accidental use has resulted in significant morbidity and mortality. The toxic effects o f boric acid have been seen following both acute and chronic use of the s u b s t a n c e ) '~ The skin manifestations associated with boric acid intoxication are particularly striking. These have included extensive erythema with desquamation resembling a " b o i l e d lobster" following acute ingestion, and diffuse alopecia after chronic use. 2'4 We present a c a s e o f a patient who manifests the classic features o f acute boric acid intoxication following a suicidal attempt. CASE REPORT A 44-year-old black woman presented to the emergency room of Kings County Hospital Center with a widespread exfoliative dermatitis which had been present for 2 days. It started with an erythema which was first noted around the mouth and on the buttocks and perineum. The eruption spread within a 24-hour period to involve the trunk, followed by a similar eruption on the face and extremities. During the evolution of this
From the Department of Dermatology, State Unlvej'sity of New York Downstate Medical Center. Reprint requests to: Dr. Alan R. Shalita, Department of Dermatology, Downstate Medical Center, Brooklyn, NY 11203. 0190-9622/82/110667+07500.70/0 © 1982 Am Acad Dermatol
exanthem, the erythema was followed by exfoliation which, by the time of her admission, had progressed to large sheets of desquamation. The skin lesions were accompanied by a persistent sensation of nausea with multiple episodes of vomiting. The patient admitted to self-administration o f half a container of boric acid powder 3 days prior to admission to "scare her children." There was a prior psychiatric history of nervousness and depression for which she had been hospitalized on several occasions. At the time of admission the only medication the patient was using was hydrochlorothiazide, 50 m g daily, for hypertension. On physical examination, the patient was alert and oriented to time, place, and person. Blood pressure was 105/55 mm Hg without orthostatic changes; respirations, 20/min; pulse, 110 and regular; temperature, 37.8 ° C. She was grossly obese and weighed 109 kg. Examination of the skin revealed massive areas of desquamating necrotic tissue with concentration at the axillae, groin, and intertriginous areas (Fig. 1). There was generalized marked erythema creating a "boiled lobster" appearance. The palms and soles were markedly hyperemic. Hemorrhagic crusting was present in a perioral distribution extending to the mucocutaneous junction (Fig. 2). The conjunctiva and oral mucous membranes were also hyperemic. Her initial laboratory tests showed a hemoglobin of 11.3 gm and hematocrit of 33.6% without leukocytosis. Blood urea nitrogen (BUN) was 62 mg/dl; creatinine was 11.1 mg/dl. The calcium level on admission was 6.7 mg/dl; phosphorus was 1,6 mg/dl. Spot glu-
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Fig. 1. Erythema at denuded site of right axilla. A similar picture was seen below both breasts and in the perigenital area. Fig. 2. Boiled lobster appearance of face with hemorrhagic, necrotic involvement at lips, mucoeutaneous junction, and nasolabial fold.
Fig. 3. Sparse superficial perivascular infiltrate with markedly dilated blood vessels and focal vacuolar alteration at the derrnoepidermal interface. There is a stratum of parakeratosis forming a cleftlike space in the mid epidermis. (Hematoxylin-eosin stain; original magnification, ×40.) cose was 230 mg/dl. The following tests were either negative or normal: urinalysis, chest x-ray, sodium, potassium chloride, COz, iron, total iron binding capacity, B,2, folate, and VDRL. A culture taken from the macerated area above the groin grew Proteus mirabilis and Klebsiella pneumoniae. Multiple blood cultures were negative for pathogens. Bone marrow aspirate revealed hypercellularity, with an increase in
the myeloid series, decrease in the erytbroid series, adequate megakaryocytes, and iron present. Skin punch biopsies were taken from representative sites at the abdomen and right arm. Both sites showed an intraepidermal cleft with focal vacuolar changes at the dermoepidermal junction. Satellite cell necrosis was observed in the epidermis under high power (Figs. 3-5). Boric acid levels from blood and urine samples taken
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Fig. 4. There is satellite cell necrosis, vacuolar alteration of the basal layer, scattering of neutrophils and lymphocytes around blood vessels. (Hematoxylin-eosin stain; original magnification, x 400.)
Fig. 5. The superficial vessels have plump endothelial cells and a perivascular infiltrate of lymphocytes, neutrophils, and extravasated red blood cells. (Hematoxylin-eosin stain; original magnification, x 400.) at the time of admission were unfortunately lost in transit. Additional samples taken several days later were within normal limits as determined by the U.S. Borax Company Laboratory in Anaheim, CA. A family member did provide us with a half empty container of boric acid powder. The material was analyzed as being boric acid, and the exact amount missing from the container was determined to be 14 gm (analysis done at
Lederle Laboratories, Pearl River, NY). In light of this strong history and the consistency of physical findings with previously reported cases of boric acid toxicity, there seemed to be little or no doubt that this patient indeed had incurred boric acid intoxication. The patient responded well to supportive measures. Her renal function improved dramatically after one course of hemodialysis. The cutaneous lesions in-
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Fig. 6. Alopecia as observed on the thirteenth day following the ingestion of 14 gm of boric acid powder. Fig. 7. Sheetlike desquamation observed at palms and soles. This photograph depicts the involvement of the palms on the fifth day following intoxication. creased in severity and degree of involvement during the first few days of hospitalization. On the tenth day she developed a patchy alopecia of the scalp which progressed to alopecia totalis within a few days (Fig. 6). Skin care consisted of topical gentian violet applications at denuded areas and soaks four times daily with Burow's solution diluted 1:40. The patient received daily baths of KMnO4 diluted l : 80,000. As the lesions on the trunk were resolving, she developed marked desquamation in sheets at the palms and soles, which persisted for several days (Fig. 7). At this stage the cutaneous condition appeared to stabilize; she gradually became less erythematous and the desquamation subsided. Two days into the hospitalization the patient's mental status deteriorated and simultaneously she developed a fever of 39.0 ° C. The fever workup was completely negative: normal spinal tap, sterile blood cultures. With supportive therapy the fever lessened. One week into her hospital stay her hematocrit dropped to 19%, with a hemoglobin of 6.5 gm. There was no evidence of hemolysis on the peripheral blood smear. Coombs' direct and indirect tests were negative. Following bone marrow aspirate, the impression was bone marrow toxicity secondary to boric acid poisoning. The patient responded well to transfusion with three units of packed red cells. During the course of the hospitalization, she developed elevated liver function tests: serum glutamic oxatoacetic transaminase (SGOT), 107 U/liter; lactic dehydrogenase (LDH), 335 U/liter; alkaline phosphatase, 80. These leveled off without specific therapy by the time of her discharge. The initially elevated
blood sugar level came down to the normal range by her third day of hospitalization. The serum calcium levels remained low despite consistently normal serum albumin. The calcium spontaneously rose to "low normal" values by the end of her 2-week stay in the hospital. DISCUSSION Boric acid, or "boracic a c i d , " is a chemical substance which is stable in air, odorless, has a slightly acid bitter taste and a sweetish aftertaste, s Boric acid as a drug has been gradually dropped from official recognition in the United States. a Boric acid and its salts, including borax, are used widely outside o f medical applications. Boric acid is used in laundering, in fireproofing fabrics and wood, in the manufacture of leather, and in the production of glazes and enamels. Boric acid has also gained popularity in recent years as a good antiroach preparation. Joseph Lister 7 first introduced boric acid into surgery as an antiseptic solution applied to wounds. Lister was also the first to notice the toxic effect o f boric acid on human cells. H e observed experimentally that boric acid slowed down the rate o f epithelialization. 8 Nine years after Lister introduced boric acid as an antiseptic two deaths were reported from the use of boric acid as an irrigating fluid. T w o years later the first case of boric acid p o w d e r leading to a fatality was reported in the United States. -'1In fact
Volume 7 Number 5 November, 1982
there have been published accounts of deaths secondaiy to boric acid or borax poisoning in every decade from these early reports until the present day. Perhaps the most famous report is that of Wong et al 2 wherein boric acid poisoning of eleven infants as a result of accidental and inadvertent use of boric acid in the preparation of infant formula resulted in the deaths of five of the infants. A similar episode reported by Rubenstein and Musher ~° involved three out of four infants who were also given formula made up inadvertently with boric acid solution in place of distilled water. These three infants expired within a week o f ingestion of the boric acid mixture. The diagnosis of boric acid poisoning has to be based on symptomatology together with a history o f exposure. The toxic effects can be related to either acute or chronic exposure to the chemical. The minimal lethal dose of boric acid for man is not known. One report indicates that a man can take 4 gm a day orally without incident whereas a single dose of 18 to 20 gm is fatal. ~ Approximately 5 to 6 gm seems to be the lethal limit for infants and small children. Chronic intoxication has occurred after a daily ingestion of 4 to 5 gm per day for 3 to 4 weeks.'2 It was determined that our patient ingested approximately 14 gm of boric acid, which is consistent with the signs of acute toxicity she exhibited. Nausea, vomiting, and epigastric pain, often persistent, have been reported in numerous papers. 6 The present case is no exception. These gastrointestinal symptoms may be the only initial elements in the clinical picture. The skin lesions are typically the next symptoms to present. They are usually but not always present. It appears that in the severely poisoned individual death can actually occur before the onset of the skin manifestations. '~ Most commonly one observes erythema, desquamation, and exfoliation. The erythema may be very intense and is sometimes referred to as a "boiled lobster" appearance." The lesions may resemble those of scarlet fever or Ritter's disease. va,,4 In the most severe cases cyanosis may be present. Sites most commonly affected are the palms and soles, buttocks, and scrotum, although no surface is immune. Mucous membranes often share in the general erythema, and desquamation from the eyelids has been noted.
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Rubenstein and Musher '° indicate that boric acid poisoning, especially in the newborn, causes a picture clinically indistinguishable from staphylococcal scalded skin syndrome (SSSS). The features in common include fussiness, refusal to eat, vomiting, diarrhea, dehydration, and the characteristic exfoliative dermatitis. The mere presence of staphylococci should not be accepted as prima facie evidence of SSSS. Other skin signs of borate intoxication include psoriasiform lesions, bullae, and alopecia. 4 In infants the diaper ,area may show excoriations, desquamation, vesiculopustular lesions, edematous genitals, gangrene of the penis and scrotum, and m a c u l e s . :~
Since the greater amount of boron compounds accumulate in the brain, liver, and kidneys, injuries to these organs are expected in acute boric acid poisoning. Central nervous system manifestations are common and include signs of meningeal irritation, convulsions, delirium, and coma. :'3 Jaundice is sometimes present, and abnormal liver function tests are not unusual. In addition, oliguria and anuria may occur, with laboratory evidence of acute renal failure. In our patient central nervous system involvement was noted on the fifth day following ingestion of the boric acid. She showed a change in mental status, with loss of orientation to time and place. In terms of hepatic involvement, our patient developed elevated liver function tests at about the same time as the neurologic changes. Neither jaundice nor hyperbilirubinemia was appreciated during her hospital course. At the time of admission our patient was already in an oliguric state with sharply elevated BUN and serum creatinine. Chronic exposure to boric acid, as in the case of young children treated at home for diaper rash with a boric acid solution or medicated powder, can result in symptoms very similar to the acutely intoxicated. More often the symptoms are of a milder nature. ~2 Alopecia may be the most obvious presentation of chronic boric acid poisoning. Loss of hair occurred in one patient following the daily intake of 25 gm of boric acid tartrate for epilepsy. '~ Tan '~ reported on a factory worker who was exposed to a borax whitening solution for more than 6 years who also developed alopecia. Ingestion of a popu-
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Table 1. Common sources of boric acid*
Antiseptic agents Ammens Medicated Powder Cuticura Medicated Liquid Bluboro Powder Vaseline borated petroleum Denture adhesives Perma-Grip Powder Sodibor Detergents and starches Borateem Boraxo Breeze White Magic Liquid Starch
Foot powders Dr. Scholl's Bromidrosis Powder Quinsana Powder Mouthwashes Chloraseptic Listerine Pain-A-Lay Ophthalmic products Murine Visine eye drops Vaginal and douche preparations Massengill Lubricating Jelly Massengill Powder Ortho Creme
*Based on a list compiled by Dr. Kenneth M. Stein, Santa Rosa, CA.
lar mouthwash led to alopecia of a diffuse nature, which was reversed upon discontinuance of this occult source of boric acid. 4 Borates may be absorbed in solution or dry through intact skin, but more so through broken granulation tissue, serous cavities, or the gastrointestinal tract. Excretion is primarily through the kidneys, with approximately 50% excreted in the first 24 hours after exposure. One reason that boric acid poisoning, particularly the acute form, is so serious is that there is no effective antidote for it. Spontaneous or induced vomiting and diarrhea aid in emptying the intestinal tract of the substance. To speed up the removal of the boric acid before irreversible damage has been done, exchange blood transfusions have been utilized with success. ,6 Peritoneal dialysis has also proved effective. 17 Our patient responded well to hemodialysis. Most authorities recommended no more than symptomatic treatment for the skin exfoliation. It is critical to maintain a good fluid balance. Despite these measures, boric acid poisoning carries a high mortality rate, as high as 50% in children less than 1 year of age.* Boric acid has for years been a popular preparation for its alleged antiseptic activity. A survey conducted in the mid 1950s indicated that 94% of certified dermatologists used boric acid in their practice, TM yet there have never been conclusive *New York City Poison Control Center: Personal communication,
studies to support the antiseptic role. Early reports of in vitro testing indicate that boric acid has some activity against staphylococci and streptococci, but the action is primarily bacteriostatic and slow-acting at that. 19'2° One study demonstrated that boric acid is actually more toxic for human polymorphonuclear leukocytes than for various strains of Staphylococcus, thereby negating primary defense mechanisms of the body against bacteria. 2' Boric acid has also been shown to slow epithelialization of wounds and to retard the healing of burns. 6 .Some manufacturers incorporate boric acid into their products as a preservative. It appears that the efficacy here is more a matter of tradition than of scientific fact. In studying its preservative properties on urine specimens, boric acid was shown to be no more effective than hypertonic sodium chloride. 22 Pinto et a123 showed that acute ingestion of boric acid in adults and children is associated with excessive urinary excretion of riboflavin. This was not surprising as it is known that boric acid and riboflavin form a water-soluble complex .24 Further work has demonstrated in chickens that riboflavin supplementation protects against the toxicity of boric acid, particularly when boric acid is administered in large doses. 2'~ This may prove a future therapeutic tool for cases of boric acid poisoning. Boric acid intoxication will continue to remain a health hazard as long as the chemical is widely available as a medicinal product. Even the cautious
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consumer cannot avoid boric acid as it is incorporated into certain mouthwashes, skin ointments, hemorrhoidal suppositories, and processed food (Table I). The quantity o f boric acid found in these relatively frequently used preparations tends to be of low concentration. Chronic or excessive use in a susceptible individual, however, could lead to the manifestations associated with boric acid toxicity. 4'15 Bluboro powder, for example, contains a 3% concentration of boric acid in its dry form. W h e n diluted as directed, the amount o f boric acid b e c o m e s almost negligible. Yet there is still a potential for absorption. Both boric acid solution and borated talcum powder in low concentrations have been shown to be absorbed through intact as well as irritated skin. 26,27 The Food and Drug Administration O v e r the Counter Advisory Panel, in its last report, placed boric acid in Category II for safety and efficacy a m o n g O T C products. The panel r e c o m m e n d e d that the availability and use of boric acid be restricted. T h e y specifically suggested that boric acid ointment should carry a warning label that it is not to be used on inflamed skin, open wounds, and especially on large wounds such as burns. Despite these strong warnings against the use of what appears to be a potentially dangerous yet poorly effective substance, recent reports have suggested using boric acid for Vulvovaginal candidiasis and as a possible treatment for herpes simplex. 2s'29 Clearly one must consider these indications with utmost caution. We thank Dr. Edward Heilman and Dr. Albert E. Stanek, Jr. for review of the dermatopathology, and Dr. Thomas Lanzilotti for his medical management of this case and for his input in the preparation of this manuscript. REFERENCES 1. Halliday C: Boracic acid--the wolf in sheep's clothing. Can Nurse 55:1093-1094, 1959. 2. Wong LC, et al: Boric acid poisoning. Can Med Assoc J 90:1018-1023, 1964. 3. Valdes-Dapena MA, Arey JB: Boric acid poisoning. J Pediatr 61:531-546, 1962. 4. Stein DM, Odom RB, Justice GR, Rartin GC: Toxic alopecia from ingestion of boric acid. Arch Dermatol 108:95-97, 1973. 5. Martindale W: The extra pharmacopoeia, ed. 26, Amendments. London, 1973, The Pharmaceutical Press. 6. Morton HE: The over the counter miscellaneous external
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drug products. Review of the antimicrobial properties of acids: Boric acid. Washington, 1979, Food and Drug Administration Publications, pp. 22-105. 7. Lister J: Details of antiseptic surgery. Br Med J 2:10031006, 1882. 8. Lister J: Recent improvements in details of antiseptic surgery. Lancet 1:787-789, 1875. 9. Brose LD: Death following the external use of a powdered boracic acid. Med News 43: 1999-2000, 1883. 10. Rubenstein AD, Musher DM: Epidemic boric acid poisoning simulating staphylococcal toxic epidermal necrolysis of the newborn infant: Ritters disease. J Pediatr 77:884-887, 1970. 11. Dopfer H: Uber einen Todesfall nach Anwendung der Offizinetlen Borsalbe bei Einer Brandwunde. Mfinchen reed Wchnschr 52:763-770, t905. 12. Gordon AS, Prichard JS, Freedman MR: Seizure disorders and anemia associated with chronic borax acid intoxication. Can Med Assoc J 108:719-724, 1973. 13. Skipworth GN, Goldstein N, McBride WP: Boric acid intoxication from medicated talcum powder. Arch Dermatol 95:83-86, 1967. 14. Herren VC, Wyss F: Chronische Bors~iureverg.iftung. Schweiz Med Wochenscbr 94:1815-1818, 1964. 15. Tan TG: Occupational toxic alopecia due to borax. Acta Derm Venereol 50:55-58, 1970. 16. Boggs TF Jr, Anmde HG: Boric acid poisoning treated by exchange transfusion. Pediatrics 16:109-114, 1955. 17. Baliah T, MacLeish H, Drummond KN: Acute boric acid poisoning. Can Med Assoc J 101:166-168, 1969. 18. Fisher RS: The use of boric acid in dermatologic practice. Arch Dermatol 73:336-341, 1956. 19. Ochsner EH: The prevention and treatment of septic infections of the extremities. Medical Herald 30:30-36, 1911. 20. Ochsner EH: Biochemistry of topical applications: Use of boric acid in septic infections. JAMA 68:220-223, 1917. 21. Novak M, Taylor WI: Phagocyticidal and antibacterial action of boric acid. J Am Pharm Assoc (Scient Ed) 40:428-430, 1951. 22. Amies CR, Corpas A: A preservative for urine specimens in transit to the bacteriological laboratory. J Med Microbiol 4:362-365, 1971. 23. Pinto J, Huang YP, McConnell RJ, Rivlin RS: Increased urinary riboflavin excretion resulting from boric acid ingestion. J Lab Clin Med 92:126-134, 1978. 24. Zittle CA: Reaction of borate with substances of biological interest. Adv Enzymol 12:493-499, 1951. 25. Roe DA, McCormick DB, Lin RT: Effects of riboflavin on boric acid toxicity. J Pharm Sci 41:1081, 1972. 26. Draize JH, Delley EA: The urinary excretion of boric acid preparations following oral administration and topical applications to intact and damaged skin of rabbit. Toxicol Appl Pharmacol 1:267-276, 1969. 27. Fisher RS, Freimuth HC, O'Connor KA, Johns V: Boron absorption from borated talc. JAMA 157:503-505, 1955. 28. Weed JC: Vulvovaginal candidiasis. Obstet Gynecol 48:631-632, 1976. 29. Skinner GRB, Hartley CE: Possible treatment for cold sores. Br Med J 22:704, 1979.