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8/13/2019 2.7 Staining of Children's Teeth by Tetracycline, Ronald p. Benson, m.b., Ch.b. (Cape Town), m.r.

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8 Februarie 1964 S TYDSKR I F V IR G EN EESK UN DE 115injection. She received no further tetracycline during her firstyear of life. Other antibiotics used in the neonatal period totreat a lung infection were streptomycin, chloramphenicol, andampicillin ( penbritin ). She developed mild physiological jaundice. She received 35 ml of blood by scalp vein for mildanaemia at the age of 2 months. Her subsequent progress wassatisfactory, and she was discharged from hospital 2t monthsafter birth weighing 5 lb. 1t oz. She cut her first tooth at theage of 1 months. At 13 months there were 7 teeth whichwere well formed and showed no apparent signs of enamelhypoplasia, but they were ll uniformly canary yellow colour. There was no evidence of pigment staining of herskin, sclerae or nails. At the age of 15 months she weighed25 lb. Her milestones were normal, and 8 teeth were present.The cutting edges of the teeth were sharp and thin. They weredull yellow in colour with irregular brown mottling of theenamel. Under ultraviolet light the teeth gave a yellowfluorescence which was especially noticeable in the distal halfof the teeth.CaseE.E. was the first of twins who were born prematurely.Birth weight was 4 lb. 4t oz The infant was blue and limpat first. He slowly improved, but 3 hours after birth respiratorydistress developed. Physical signs showed cyanosis andmoderate sternal recession and poor ir entry over the lowerzone of the r ight lung. Treatment included a total of 225 mg.of tetracycline phosphate (tetrex) intramuscularly over a periodof 3t days. The baby improved and was discharged 22 dayslater weighing 5t lb. Only slight icterus neonatorum wasobserved.He was breast fed for 6 months. The first tooth erupted at5 months. He was seen at 16 months for acute bronchiolitis.He weighed 26 lb. He had 12 teeth which were yellow incolour. The anterior molars were noticeably yellow, but therewas no evidence of enamel hypoplasia. The teeth fluorescedunder ultraviolet light. n iron-deficiency anaemia (Hb=65 )was treated at the same time as the chest.

CaseE.E. was the second twin and brother of Case 2 He weighed4 lb. 14t oz at birth and he also showed signs of respiratorydistress. He received 275 mg. of tetracycline phosphate(tetrex), 75 mg of which was given intramuscularly and 200mg orally. He made an uneventful recovery. At 16 monthshe had 12 teeth which were bright yellow in colour, slightlyhypoplastic, and they also fluoresced under UVL.Case 4T.T. was a full-term infant born after a perfectly normaldelivery. Several hours after birth he became cyanosed anddistressed, and atelectasis was diagnosed. Treatment included6 days of intramuscular and oral tetracycline phosphate compound (tetrex).The parents noticed that the infant s teeth were yellow whenthey first erupted. At the age of 4 years the child had 20teeth. All the teeth were discoloured brown, particular ly attheir distal ends. The enamel of the bicuspids was hypoplasticso tha t the cusps appeared sharp and saw-like. The canineswere narrow, sharp and hypoplastic. Several dental caries werealso present. The teeth gave a slight yellow fluorescence underUVL In comparison, the teeth of his 2 older sisters werewell-formed, unstained, and relatively free of caries.

DISCUSSIONDiscolouration of teeth was reported several years ago inchildren who suffered from mucoviscidosis and who wereon long-term tetracycline therapy.3. is now known thattetracycline can be deposited in bone and in the dentineand enamel of teeth, possibly by forming complexes withcalcium ions. Yellow-staining of bones caused by tetracycline and cWortetracycline has been shown to develop inanimals; and stunting and malformation of bones in chickembryos have been demonstrated when tetracycline was

adrninistered : However, there is no evidence of teratogenic e ffect in the human embryo.Enamel hypoplasia, pitting of the enamel, and mal

formed cusps may go hand-in-hand with yellow or browndiscolouration of childrens teeth after tetracycline therapy(Case 4). This usua lly follows in t ee th where the yellowstaining is at first intense. Whether tetracycline depositioncauses enamel hypoplasia in every instance is uncertain,since enamel hypoplasia without discolouration may beobserved in premature infants who have never receivedtetracycline Proved tetracycline-stained teeth may showno evidence of enamel hypoplasia, as in Case 2.According to Wallman and Hilton the severity of pig

ment discolouration of t he te eth is related to the hightotal dosage of tetracycline rather than to the durationof therapy. Another observation is that the more premature the baby, the greater is the extent of enamel involvement. The colour of the teeth varies according to the ageof the child. The younger the child, the brighter the yellowpigment, while in older children the pigment is morebrownish. The teeth change f rom yellow to brown withthe passage of time, and eventually pa rts or the whole ofthe brown-discoloured teeth may lose their fluorescence.This change in colour is probably brought about by theoxidation process of the tetracycline compound in theteeth.Tetracycline is slowly removed from teeth and bones

of affected children, and any ill-effects of prolonged retention of the drug in these and in other o rgans a re asye t unknown. Teratogenic effects, which are r epor ted tooccur in the chick embryo: should nevertheless not beoverlooked in humans.The permanent teeth are unlikely to be affected by tetracycline administered during the newborn period or later

in infancy, since th e evidence is that the chief risk oftetracycline pigment deposition occurs during th e periodof rapid development of the tooth bud . Once the enamelis l aid down and the teeth ar e mature, there is l it tle likelihood of significant tetracycline deposition. Tetracyclineis thus unlikely to damage the teeth of chi ld ren ove r theage of 6 months. On the othe r hand , the more immaturethe infant, the greater the chances of tetracycline deposition in growing teeth and bones. is unlikely that thepoor glomerular filtration rate of the immature kidney ofthe premature baby causes higher blood levels of tetracycline and consequently greater tissue penetration.Administration of tetracycline during pregnancy has notdefinitely been shown to affect the teeth of th e foetus,

bu t if given during the last trimester of pregnancy in bigdoses and for long periods, that possibility ca n arise.Tetracycline passes freely through the placental barrier tothe foetus.Great care should be taken in the choice of antibiotics

fo r prophylactic and curative therapy in premature as wellas full-term infants. The number of ide-effects of antibiotics is increasing, and alarming results are seen fromtime to time. Chloramphenicol, fo r instance, may causethe grey syndrome owing to th e inability of th e immature l iver to metabolize and detoxicate the drug as rapidlyas th e matu re liver. Novobiocin may give r ise to yellowpigmentation of the skin and eyes and occasionally to liver

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116 S M E D I C L J O U R N L 8 February 1964damage. The sulphonamides, e.g. sulphafurazole ('gantrisin') are not without dangers in premature infants sincethey elevate the unconjuga ted form of bil irubin in theblood, and this in turn may lead to kernicterus in susceptible babies.Tetracycline is normally a bright yel low compound. Itstains the skin when handled and it turns the urine yellow.We can now add to these minor drawbacks the moreserious ones of staining the teeth, hypoplasia of theenamel, and the staining of bones and certain other organs,e.g. the eye, particularly in premature infants. Othereffects, such as malformat ion of bones and stunting ofgrowth, are not cer ta in , but Bevelander' reports thatwhen newborn infants are given tetracycline in doses of100 mg. / kg. for 1 days, the result is a decrease of up to40 in the linear growth of the f ibula as compared to thenormal growth rate. After cessation of drug the rapy therate of growth returns to normal. He also attributes anumber of cases of dental caries in children to tetracyclineadministration during infancy which has led to enamelhypoplasia.Tetracycline is otherwise safe and popular and it hasa wide antibiotic spect rum. It s use should no t be lightlydiscarded in the newborn period, but before prescribingany antibiotic in this age group, the dosage and side-effectsof this antibiotic preparation should be carefully considered. Wallman and Hilton pointed out that oxytetracycline did not produce staining of teeth in their cases.While chlortetracycline is known to stain the bones ofanimals; there is no reliable evidence to date that thisdrug and related demethylchlortetracycline can affect theteeth and bones of infants. Demethylchlortetracycline isnormal ly broken down in the body with the release ofchlortetracycline or free base.

The soluble salts of penicillin, streptomycin, erythromycin, and the newer penicillins, e.g. ampicillin, methicillin

and cloxacillin, are well tried and relatively safe antibioticsand few infections of the neonatal pe riod fail to respondrapidly and completely when these antibiotics, singly orin combination, are given.SUMMARY

The case histories of 4 children are presented whoseprimary teeth were discoloured yellow from past tetracycline therapy in the newborn period.Their tee th frequently show enamel hypoplasia whichmay be an important factor in the development of dentalcaries later on in childhood.Antibiotics are often needed for the t reatment and prevention of infections in the neonatal period. Great careshould e exercised in the choice of an antibiotic for infants of this age group. Side-effects may be harmful, whilethe correct dosage of the antibiotic should be ascertainedbefore prescribing the drug.Tetracycline-stained teeth are not only unsightly butthey may also be costly because of the dental attentionrequired later. would appear that tetracycline should begiven with great circumspection to infants under the ageof 6 months, considering the complications of tetracycline.

REFERENCESI Wallman. I S. a nd Hil ton, H. B (1962): Lancet. I, 827.2 . Dav ies. P. A., Little, K an d Ah erne. W. (1962): Ibid I, 742.3. Zegarelli, E. V. , Denning, C. R. , Kut sche r, A . H. , Ju ot i, F . and DiSant Agnese, P. A. (1960): Pediatrics, 26 , 1050.4. Shwachman, H. , Fekete. E. , Kulozycki. L L an d Foley. G. E.(1958 - 59): Antibiot ics Annual p. 502. New York: Medical Encyclopaedia Inc5. Buyske. D. A., Eisner, H. J. and Kelley, R. G. (1960): J. Pharmacol.,no, 150.6. Bevelander, G. , Nakahara, H. and Rolle, G. K. (1959): Nature (Lond.),184, 728.7. Bevelander, G. (1963): Brit. Med. J. , I, 54.8. Rendle-Short, J . (1962): Lancet, I, 1188.9. Miller, J. (1962): Ibid I, 1072.

10. Hargreaves, T. a nd Hol ton, J. B. (1962): Ibid I, 839.I . Leading article (1962): Ibid I, 847.12. Stewart, G. T. a nd Hol t, R. J. (1963): Bri t. Med . J. , I 308.

A CASE OF SELF-MUTILATION YMEANS OF PINSB. PARKER, M.B., CH.B., Oranje Hospital Bloemfontein

Elizabeth B is a 37-year-old White imbecile, an inmateof Witrand Ins ti tu tion, Potchefst room. She has contractures of her knees and a pareti c left upper limb.

From 1952 onwards, her folder contains frequent notesabout superficial areas of inflammation, e.g. 'mult ipleboils', 'cellulitis', 'furunculosis', etc. As witnessto this, she has numerous scars on many parts of herbody. In December 1962 she developed an inflammatoryswelling of her lef t forearm.

On X-ray examination her forearm was seen to contain21 pins (Fig. 1). Subsequently, the rest of her body wasX-rayed, revealing 202 foreign bodies in her tissues. Mostappea red to be pins, of which the heads had been brokenoff, bu t sewing-machine needles, darning needles, andpieces of wire were also present. These objects were seenPreviously of Witrand Institution, Potchefstroom

in both lower limbs, buttocks, left upper l imb, neck,face, breasts, and within the thoracic cavity (Fig. 2).The patient herself, on account of her partial paralysis,

is unable to search for pins where they are likely to befound. has been discovered that several other imbecilepatients have made a practice of collecting sharp objectsand presenting these to the patient. One was discoveredin the act of taking a cigare tte-box to her filled with rustynails.

There is no doubt that the patient herself introduced thepins, since she is well able to defend herse lf agains t a ttackby others , and her sound arm is conspicuously free ofpins.When accused of having pushed pins through her skin,the patient denied it and was quite unruffled. She becamevery angry when a superficial ly situated pin was removed

under local anaesthesia. She reacts normal ly to pain fulstimuli administered by other people.