- Email: [email protected]
Aureomycin in the Therapy of Herpes Simplex Labialis and Recurrent Oral Aphthae
A U R EO M Y C IN IN THE THERAPY OF HERPES SIMPLEX LABIALIS A N D RECURRENT O RAL APH TH AE
Frank G . Everett, D.M.D., M.D., Portland, Ore.
oral aphthae (canker sores) and herpes simplex labialis (cold sores) are two bothersome condi tions frequently encountered in dental practice. T he primary lesions in both pathoses are vesicles. In herpes labialis these can be seen clearly as single or multiple small blisters filled with a serous exudate, occurring at the mucocutaneous border of the lip. A fter one to several days these vesicles break and a yellowish or dark red crust is formed. In recurrent oral aphthae the vesicles can only rarely be demonstrated as the oral fluid quickly macerates the epithelial covering. The second stage of this pathosis then appears as a grayish-yellow shallow ulcer. O ral aphthae may recur almost continuously and are oftentimes intensely painful ex cept when the lesion is located in areas of the oral mucosa where nerve endings transmitting the modality of pain are few or absent.1 W hile herpes labialis does not usually cause pain, considerable discomfort may be experienced prior to and during the early vesicular stage of the eruption. If this condition recurs fre quently, however, it presents a serious cosmetic problem for the patient, and also interferes with further dental work. For an excellent review of the bacteri ology, mode of infection, incidence, symptomatology, histopathology and fur ther differential diagnosis of herpes la bialis and recurrent oral aphthae, the reader is referred to the outstanding ar ticle on this subject by Cahn and Bar tels.2
R
Etiology
e c u r r e n t
555
The etiology of these two common le sions has baffled researchers for many years.3-7 Herpes Labialis. — Overwhelming evi dence, however, has been produced in the last thirty-five years to establish the etiologic agent of herpes labialis as a filtrable virus.8’9’10 T h e proof of the role of the virus in the causation of herpes simplex rests on the demonstration of the direct transmissibility of the vims from the content of the herpetic vesicle to the corneal conjunctiva of the rabbit,8’9’10
From the Division of Oral Pathology of the University of Oregon Dental School and the Department of Phar macology of the University of Oregon Medical School. 1. Bard, P., M a c L e o d ’s Physiology in M odern M e d i cine, ed. 9, St. Louis: C. V . Mosby Co., 1941. 2.
Cahn, L . R ., and Bartels, H . A., Aphthae and
Herpetic Gingivostomatitis. A m . J. O rthodont. & Oral Surg. (Oral Surg. Sect.) 28:140 (March) 1942; correc tion 28:242 (April) 1942. 3. Goeckerman, W. H ., and Wilhelm, L. F. X ., Herpes Zoster and Herpes Simplex. A rch. D erm al. & Syph . 3 5 :8 6 8 (May) 1937. 4. Alvarez, W. C ., Canker Sores. Minnesota M e d . 20:602 (Sept.) 1937. 5. Beecher, W. L., Canker Sores in the Mouth. C lin. M e d . & Surg., 35:903 (Dec.) 1928. 6. Burket, L . W ., and Hickman, G. C ., Oral Herpes (Simplex) Manifestations: Treatment with Vitamin B Complex. J .A .D .A . 29:411 (March) 1942. 7. Strauss, K ., Vitamin Bi Therapy in Cyclic Habit ual Aphthous Stomatitis in Women. Brit. £>. J. 8 3 :7 7 (Aug.) 1947. 8. Grueter, W .. Das Herpesvirus, seine aetiologische und klinische Bedeutung. M u ench en. med. Wchnschr. 71:1058 (Aug.) 1924. 9. Loewenstein, A., Aetiologische Untersuchungen ueber den fieberhaften Herpes. M u en ch en . med. Wchnschr. 66:769 (July) 1919. 10. Goodpasture, E. W ., Herpetic Infection, ■with Especial Reference to Involvement of the Nervous System. M edicin e 8:223 (May) 1929.
556
the demonstration of the virus in the sa liva10’11 and in the desquamated epithe lial cells of the oral mucosa,12 the de termination of high herpes simplex anti body titers in the blood of patients affect ed by herpes simplex13’14’15 and, finally, in the demonstration of the typical his topathologic findings2 including, espe cially, the presence of intranuclear acido philic inclusion bodies16 in the experi mentally infected tissues. Apparently the original invasion with the virus of herpes simplex occurs in childhood in form of a gingivostomati tis13’14’17' 22 of varying degrees of sever ity.14 Following this initial attack, repeat ed eruptions of herpes labialis may be brought about throughout life in suscep tible individuals and, indeed, in the greater part of the population23 by any agent which may temporarily lower the particular local or systemic defensive mechanism protecting against erup tion.13'14’15 Oral Aphthae.— T he etiology of recur rent oral aphthae is not so well estab lished. Writers of modem textbooks on virus diseases24’25 have stated that recur rent oral aphthae are caused by the virus of herpes simplex. Neither the evidence in support of this contention26' 30 nor that contradicting it20’31 is fully convincing. In festation with the virus of herpes simplex is nearly universal10’13"15’23 and saliva con tains the virus at odd intervals.10’11 Therefore transmissibility to the rabbit cornea from recurrent oral aphthae does not with certainty prove causation of this lesion by any virus, especially also be cause methods for such transfer from oral aphthae are crude.26’31 It can only be assumed that the etiologic agent of re current oral aphthae is a filtrable virus possibly related to, but not necessarily identical with the virus of herpes simplex. In some respects the lesions of herpes labialis and recurrent oral aphthae cer tainly resemble each other grossly; like wise they show similar duration and re
The Journal of the Am erican Dental Association
sponse to medication.27 Their histopathology also is quite similar except that no inclusion bodies have been demonstrated in recurrent oral aphthae.28 In herpetic gingivostomatitis, the original infection with the virus of herpes simplex, the pri mary lesions are vesicles of the oral mucosa.13 T h e fact that these turn quickly into aphthous ulcers17’18’21’22 resembling recurrent oral aphthae also points to a close relationship of the two conditions under discussion. 11. Levaditi, C ., Ectodermoses Neurotropes. Mono graphies de l’Institut Pasteur, Paris: Masson et Cie., 1922. 12. Levaditi, C .; Harvier, P., and Nicolau, S., Etude Expérimentale de l’Encephalite dite “ Lethargique.” A n n . de V Institut Pasteur 36:105 (Feb.) 1922. 13. Burnet, F. M ., and Lush, D ., Herpes Simplex. Lancet 1:629 (M arch), 1939. 14. Burnet, F. M ., and Williams, S. W ., Herpes Simplex; A New Point of View. M e d . J . Australia 1:037 (April) 193915. Rose, H. M ., and Molloy, E., Cutaneous Re actions With the Virus of Herpes Simplex. J. Im m unol. 56:287 (July) 1947. 16. Lipschuetz, B., Ueber Chlamydozoa-Strongyloplasmen. Zur Kenntnis des Herpes febrilis. W ien. m ed. Wchnschr. 71:231 (Jan.) 1921. 17. Dodd, K.,* Johnston, L . M ., and Buddingh, G. J., Herpetic Stomatitis. / . Pediat. 12:95 (Jan.) 1938. 18. Gans, O ., Zur Aetiologie der Stomatitis aphthosa. K lin. Wchnschr. 3:447 (March) 1924. 19. Youmans, J. B., Herpetic Fever with Stomatitis* South M . J . 25:228 (March) 1932. 20. Black, W. C ., The Etiology of Acute Infectious Gingivostomatitis (Vincent’s Stomatitis). J . Pediat. 20:145 (Feb.) 1942. 21. Ziskin, D . E ., and Holden, M ., Acute Herpetic Gingivostomatitis: Report of 15 Cases. J .A .D .A ., 30:1697 (Nov.) 1943. 22. " Chilton, N. W., Herpetic Stomatitis: A Report of Six Cases Occurring in One Family. A m . J . O rth odont. & Oral Surg. (Oral Surg. Sect) 30:335 (June) 1944. 23. Keddie, F. M .; Rees, R . B., Jr., and Epstein, N. N., Herpes Simplex Following Artificial Fever Ther apy. J .A .M .A . 117 :13 2 7 (Oct.) 1941. 24. Rooyen, C . E., and Rhodes, A. J., Virus D is eases of M a n , ed. 2. New York: Thomas Nelson, 1948. 25. Rivers, T . M ., Viral and Rickettsial Infections of M a n , Philadelphia: Lippincott, 1948. 26. Scott, T . F. M .; Steigman, A. J .2 and Convey, J. H ., Acute Infectious Gingivo-Stomatitis. J .A .M .A . 1 1 7 :9 9 9 (Sept.) 1941. 27. Woodburne, A. R ., Herpetic Stomatitis. A rch. D erm at. & Syph. 43:543 (March) 1941. 28. Steinmaurer, H., Virus Observations on Aph thous Stomatitis. M edizin . K lin . 3 6 :100, 1940, quoted from Cahn K L . R ., and Bartels, H . A ., Aphthae and Herpetic Gingivostomatitis. A m . J. O rthodont. & Oral Surg. (Oral Surg. Sect.) 28:140 (March) 1942. 29. Curth, H . O ., Recurrent Genito-Oral Aphthosis and Uveitis with Hypopyon (Behcet’s Syndrome). A rch . D erm at. < 2? Syph. 54:179 (Aug.) 1946. 30. Franceschetti, A .; Valerio, M ., and Babel, J., Recurrent Aphthous Uveitis with Muco-Cutaneous L e sions. A r c h . O p h th . 35:469 (May) 1946. 31. Templeton, H. J., Is Aphthous Stomatitis due to> the Virus of Herpes Simplex? A rch. D erm at. & Syph,. 1 4 :4 3 9 (Oct.) 1926.
Everett
M any different local and systemic causes may initiate the eruption of herpes labialis. Exposure to sunlight, extreme cold, and mechanical irritation15 as in shaving are some of the local exciting circumstances. Intoxications,10 colds, fever during any disease and fever ther apy23 are some of the common systemic exciting causes for an eruption. Similarly in recurrent oral aphthae a m ultiplicity of factors may bring on an attack. Eating of walnuts, chocolate, salted foods may act as local exciting causes. M an y women suffer from these lesions before or during menstruation.7 Vitam in deficiencies6’ 7 and food aller gies4’5 have also been mentioned as systemic exciting factors. T h e dentist is especially interested in these two lesions, because the application of the rubber-dam, even with the best precautions, may bring on an eruption of herpes labialis; or these lesions m ay be provoked by stretching of the lips in pro cedures o f oral surgery, prosthodontia, periodontia and operative dentistry. In some patients aphthous ulcers develop from the use of cotton rolls, injections with anesthetic solutions2 or from any other routine dental manipulation. It w ould appear that these various secondary causes, serving to precipitate the attack in the susceptible, act only as a trigger mechanism to lower the resistance of the host locally, generally, or both locally and generally, at that time. This would explain the variety both of etiologic factors implicated and of treatments recommended for these conditions in the past. Review of Medication Used in the Past
L ocal therapy has been used by the practitioner primarily. Customarily the aphthous lesions have been treated with silver nitrate io per cent, chromic acid 5 per cent,2 phenol or other caustics and astringents in order to coagulate and numb the superficial exposed nerve end
J.A.D.A., Vol. 40, M a y 1950
557
ings, thereby providing symptomatic but uncertain relief. Similarly, the local treatment of herpes labialis has been nonspecific and sympto m atic.32 Topical applications with Campho-Phenique, spirit of camphor, mentholated ointments, aluminum ace tate 0.2 per cent, and with other drugs, have been used with similar mildly pal liative results.2’ 33 U ltraviolet irradiation34 and roentgenotherapy35 of the lesions have also been advocated. Systemic treatment with thiamin chlo ride has been used with a certain measure of success in recurrent oral aphthae,6’7 but such therapy has never become popular with the dentist. Repeated vac cination with smallpox vaccine27 has also been recommended. T he systemic treatment used for herpes labialis has included such therapy as vac cination with fluid from the patient’s own herpes vesicle,36 with smallpox vaccine,37 injection with formolized, inactivated, herpes virus38 and intradermal injection of moccasin snake venom.39 Although some of these therapies have been used with fair to good results, none of them has acquired a permanent place in the therapeutic armamentarium of the practicing dentist. Pharmacology of Aureomycin
Am ong the more than 100 antibiotic substances introduced into medicine in
32. Shulman, B. H., Recurrent Herpes Labialis, Naval Med. Bull. 4 5 : i 6 i (July) 1945. 33. Thoma, K . H ., Oral Pathology, ed. 2. St. Louis: C . V. Mosby Co., 1944. 34. Weinbren. M ., Ultraviolet Radiation in Treat ment of Herpes Labialis. Lancet 2:865 (Oct.) 1927. 35. Hall, W. C ., Radiation Treatment of Herpes Simplex. Am. J. Roentgenol. 39:393 (March) 1938. 36. Schmidt, F. R ., Vaccination for Herpes. Arch. Dermat. & Syph. 3 2 :io 6 (July) 1935. 37. Foster, P. D ., and Abshier, A. B., Smallpox Vaccine in the Treatment of Recurrent Herpes Simplex. Arch. Dermat. & Syp. 36:294 (Aug.) 1937. 38. Frank, S. B., Formolized Herpes Virus Therapy and the Neutralizing Substance in Herpes Simplex. /. Invest. Dermat. 1:267 (Aug.) 1938. 39. Kelly, R. J., Treatment of Herpes Simplex with Moccasin Venom. Arch. Derma\ Syph. 38:599 (Oct.) 1938.
The Journal of the A m erican Dental Association
558
the last few years,40 aureomycin occupies an interesting position therapeutically. This new drug has considerable effect not only upon certain bacterial forms, but also upon rickettsiae which are organisms of a size smaller than bacteria, and on some of the yet smaller invisible filtrable viruses.41 Aureomycin is effective at small dosage42’43 and is of low toxicity.44’45’46 Recent reports call attention to the effectiveness of the topical application of aureomycin in the treatment of herpes simplex corneae and of virus-caused in clusion conjunctivitis.47’48 Based on this work, it was decided to test the drug by local administration in the prevention and treatment of herpes labialis and in the treatment of recurrent oral aphthae.
not involving the use of the rubber-dam. Tw o hundred and thirty-three patients received 460 such dental treatments. In a few cases of very extensive manipulation, the patients were handed also a one dram tube of the 5 per cent aureomycin oint ment with instructions to apply it to the lips for three days after each meal and cach time after washing the face. Female patients were requested not to use lip stick during this period. A total of 3 lesions of herpes labialis resulted within the two day period after dental treat ment. In a control series involving iden tical use of petrolatum ointment base not containing aureomycin, 227 patients re ceived 534 dental treatments. Thirteen lesions appeared in the two day period following the dental appointment (Table
Clinical Data
0In a compilation of all patients receiv ing aureomycin ointment prophylaxis against herpes labialis, obtained by add ing the results of the two preceding groups, it is seen that 289 patients49 re ceived 902 dental appointments; 59 of these appointments were in patients with
Prophylaxis Against Herpes Labialis. ■ — In the first clinical series, aureomycin hydrochloride ointment 5 per cent in a base of petrolatum was used for the pre vention of lesions of herpes labialis in patients where the rubber-dam was to be applied in the course of routine dental operative procedures. T he patient’s lips were coated lightly with the ointment both before the application of the rubberdam and at the time the dam was re moved at the end of the operation. One hundred and seventy-eight patients re ceived 442 applications of the dam. Only one lesion of herpes labialis resulted within two days after treatment. In a control group involving the use of identi cal petrolatum ointment base not con taining aureomycin and following the same method of application, 221 patients received 730 applications of the dam. In these patients 15 lesions developed within two days after dental treatment (Table 0 A second group of patients were treated similarly with the aureomycin ointment, but received minor oral sur gery, extensive periodontal or prosthodontic treatment or operative dentistry
40. Duggar, B. M ., Aureomycin: A Product of the Continuing Research for New Antibiotics. A n n . N ew York A cad. Sc. 5 1 :1 7 7 (Nov.) 1948. 41. Wong, S. C ., and Cox, H. R ., Action of Aureo mycin Against Experimental Rickettsial and Viral In fections. A n n . N e w York A cad . S c. 51:290 (Nov.) 1948. 42. Schneierson, S. S., and Toharsky, B., A Method for the Determination of Aureomycin in the Blood. /. B a d . 57:483 (May) 1949. 43. Dowling, H . F .; Lepper, M . H .; Sweet, L . K ., and Brickhouse, R . L ., Studies on Serum Concentra tions in Humans and Preliminary Observations on the Treatment of Human Infections with Aureomycin. A nn. N ew York A cad. Sc. 51:1241 (Nov.) 1948. 44. Harned, B. K .; Cunningham, R. W .; Clark, M. C .; Cosgrove, R .; Hine. C . H .; McCauley, W. J.; Stokey, E.; Vessey, R. E .; Yuda, N. N ., and Subbarow. Y ., The Pharmacology of Duomycin. A n n . N ew York A cad. Sc. 5 1:18 2 (Nov.) 1948. 45. Schoenbach, E. B .; Bryer, M . S., and Long, P. H., The Pharmacology and Clinical Trial of Aureo mycin: A Preliminary Report. A n n . N e w York A cad. Sc. 51:267 (Nov.) 1948. 46. Dowling, H. F .; Lepper, M . H .; Caldwell, Jr., E. R .; Whelton, R. L ., and Sweet, L . K ., Aureomycin in Various Infections: Report of One Hundred and Eighty Cases and Review of the Clinical Literature. M e d . Annals. 18:335 (July) J94947. Braley, A . E., and Sanders, M .. Aureomycin in Ocular Infections. J .A . M . A . 138:426 (Oct.) 1948. 48. Braley, A. E., and Sanders, M ., Aureomycin in Ocular Infections. A nn. N ew York A cad. Sc. 51:280 (Nov.) 1948.
Everett
J.A.D.A., Vol. 40, M a y 1950 . . . 559
Table I.— Effect of aureomycin in the prevention of herpes labialis following extensive dental procedures
Treatment
Patients
Appointments
Mean length of appoint ment
Lesions seen within two days after treatment
1. Rubber-dam used Aureomycin prophylaxis................. Petrolatum prophylaxis...................
178
221
442 730
38.5 40.1
15
2. No rubber-dam used...................... Aureomycin prophylaxis................. Petrolatum prophylaxis..................
233 227
460 534
32.4 32.6
3 13
3. Total cases* Aureomycin prophylaxis............... Petrolatum prophylaxis..................
289 311
902 1264
35.4 36.9
4 28
1
*Some of these patients received dental treatment involving the use of the rubber-dam as well as other exten sive dental work not involving application of the dam; therefore the totals are smaller than simple addition of the preceding groups would show.
a known past history of herpes labialis following dental treatment. Four lesions developed within two days after treat ment. T he control group of 311 patients49 received 1,264 dental treatments accom panied by prophylaxis with petrolatum ointment base which did not contain aureomycin; 74 of these appointments were in patients with a known past history of herpes labialis following dental treat ment. Twenty-eight lesions developed within the two day period following treat ment. T able 1 summarizes these clinical data and gives also the mean length of a single appointment. Treatment of Herpes Labialis.— In a sec
ond series the therapeutic properties of the aureomycin ointment 5 per cent in existing lesions of herpes labialis were tested, whether the lesions occurred from other exciting causes or following dental treatment. Patients received a one dram tube o f the salve and were instructed to apply a thin coat of the material after each meal and each time after washing the face. Fifty-two lesions in 44 patients were thus treated. T h e duration (arithmetic mean) of the lesions when left untreated
or treated with the usual local palliatives, as obtained from the past history of each patient, had been 10.1 days. Duration (arithmetic mean) for lesions in these same patients treated with the aureomy cin ointment was 6.1 days. Thus aureo mycin ointment therapy resulted in a 39.9 per cent reduction (arithmetic mean) of the duration of the lesions (Table 2 ). In 6 lesions the duration was not reduced. In 3 lesions no relief from discomfort was experienced. A total of 8 patients were not benefited by the treatment objec tively, subjectively, or both (Table 2). Further analysis of the above data shows that the time of the institution of therapy is important. W hen treatment had been started during the first 24 hours after eruption, the reduction (arithmetic mean) in duration amounted to 58.1 per cent of the time usually taken by the le sion to heal without medication. When treatment started during the second 24
49. It should be noted that some of these patients received dental treatment involving the use of the rubber-dam as well as other extensive dental work not involving application of the dam; therefore the totals are smaller than simple addition of the preceding groups would show.
560
T a b le 2.— T re atm e n t o f h e rp e s la b ia lis with a u re o m ycin o in tm e n t
Number of patien ts...................................... 44 Number of lesions treated.......................... 52 Duration of untreated lesion (arithmetic m e a n ) ................................... 10.1 Duration of treated lesion (arithmetic mean) . ............................... 6.1 Reduction in duration in % (arithmetic mean) ................................... 39.9 Number of treated lesions leading to no reduction of duration............................... 6 Number of treated lesions leading to no relief from discomfort ............................ 3 Number of patients not benefited by treat ment, subjectively, objectively or both 8
hours, the reduction amounted to 38.5 per cent, and when it started during or after the third day the reduction amounted to only 13.7 per cent (F ig u re). Treatment of Recurrent Oral Aphthae.— For the treatment of recurrent oral aph thae, troches containing 15 mg. of aureo mycin hydrochloride were prescribed. The patients were instructed to let each troche melt slowly in the mouth and to use one every two waking hours for three days. Forty-four crops of lesions in 38 patients were treated. T he duration (arithmetic mean) of the lesions, as obtained from past history, had been 10.2 days, when untreated or treated with the usual local palliatives. Duration (arithmetic mean) of the aphthous lesions treated with aureomycin troches was 6.5 days. In other words, treatment of the recurrent oral aphthae with aureomycin troches resulted in a reduction (arithmetic m ean) of the duration of the lesions of 36.1 per cent. In 4 lesions the duration could not be reduced by the treatment. In 3 lesions no relief from discomfort could be ob tained. In 2 cases mild nausea was ob served, a symptom rarely seen in oral medication with aureomycin.42’ 45’ 46 A to tal of 5 patients were not benefited by the treatment subjectively, objectively, or both (Table 3).
The Journal of the A m erica n Dental A ssociation
Here, too, the time of the institution of therapy is important. W hen the treat ment started during the first 24 hours after eruption, the reduction (arithmetic mean) in duration amounted to 57.6 per cent of the time usually taken by the le sion to heal when no or indifferent medi cation was used. W hen treatment started during the second 24 hours the reduction amounted to 53.3 per cent, and when it started on or after the third day to 23.1 per cent (illustration). Discussion
In the clinical data presented the note worthy prophylactic effect of aureomycin hydrochloride ointment in the prevention of lesions of herpes labialis is shown. The controls showed more than four times as many lesions of herpes labialis per ap pointment following dental treatment as patients who had received prophylactic aureomycin inunction. Considerable improvement has also been demonstrated in the subjective and objective symptoms by the treatment of existing lesions of herpes labialis with
Reduction of duration of lesions of herpes labialis and recurrent oral aphthae in relation to the time of the institution of topical aureo mycin therapy
Everett
this ointment and by the treatment of recurrent oral aphthae with aureomycin troches. Especially, the duration of these lesions has been reduced by better than one-third. These results seem to show that in aureomycin the dentist and the phy sician have available a specific medica tion for these two conditions. Comparison of T able 2 and Table 3 shows the interesting fact that the dura tion (arithmetic mean) of the untreated lesions of herpes labialis and that of re current oral aphthae are practically the same, namely 10.1 and 10.2 days, which speaks for a relationship of the etiology of the two pathoses. Study of T able 3 shows that the reduction in duration (arithmetic mean) is best, and practically the same for the two lesions, when treat ment starts during the first 24 hours.47 W hen medication begins during the sec ond and third day a considerable differ ence develops. Recurrent oral aphthae re spond well to medication on the second and even fairly well on the third day, while herpes labialis shows by far the best result when treated on the first day after eruption. It m ay be assumed that once a crust is formed in the course of the eruption of herpes labialis, the virus is protected by it from the influence of the medication, while in recurrent oral aph thae the shallow ulcer remains accessible to the drug. T h e similarity in response to medication also lends weight to the argu ment of the similarity in etiology of these two lesions.27 T h e prompt relief from pain in the treatment of recurrent oral aphthae was pronounced in the great majority of these cases. No attempt was made to measure pain relief objectively because of the vari ations of the pain threshold in different persons, different areas of the oral mu cosa1 and the difficulty per se of measur ing pain.50 Part of the beneficial effect of the treatment of recurrent oral aphthae with the aureomycin troches accrues undoubt edly to the effect of the drug on secon-
J.A.D.A., Vol. 40, M a y 1950 . . . 561
T a b le
3.— T re a tm e n t of recurre nt oral t w ith a u re o m y c in tro ch e s
a p h th a e
N um ber of patients ..................................... 38 N um ber of lesions t r e a t e d .......................... 44 D u ration of u ntreated lesion (arithm etic m e a n ) .................................... 10.2 D u ratio n of treated lesion (arithm etic m ean) .................................... 6.5 R ed u ction in duration in % (arithm etic m ean) ................................. 36.1 N u m ber of treated lesions lead ing to no reduction in duration. . 4 N u m ber of treated lesions lead ing to no relief of discom fort. . . 3 N um ber of treated lesions lead in g to' m ild n a u s e a ............................. 2 N um ber of patients not benefited by treat m ent subjectively, ob jectively or both 5
dary invaders; how great that part is, we do not know. It is true that in many cases the aph thous and herpetic lesions recurred at a later time. No m ajor systemic effect, eliminating the entire infestation o f the host, can be expected from such topical medication. T h e ointment and troches served well, however, in the treatment of the lesions of herpes labialis and recur rent oral aphthae. T h e success in the pre vention of herpes labialis by this simple procedure was especially gratifying. It is felt that topical medication with aureo mycin hydrochloride is a useful and spe cific therapy in the prevention and treat ment of herpes labialis and in the treat ment of recurrent oral aphthae. Summary
1. The etiologies of herpes labialis and recurrent oral aphthae are reviewed. It is noted that a filtrable virus is the causa tive agent responsible for the former and probably also for the latter pathosis.
50. Everett, F. G ., A Comparison of Depth of A n esthesia and Toxicity of 2 and 4 per cent Procaine Hydrochloride Solutions. J. D. Kes. 28:204 (June) «949-
562
2. Consideration is given to local and systemic medication used previously in the treatment of these conditions; the pharmacology of aureomycin is discussed briefly, mentioning its viricidal proper ties. 3. Prophylactic treatment .with 5 per cent aureomycin ointment applied to the lips before and after dental procedures showed a marked reduction in the inci dence of herpes labialis. O nly 4 lesions of herpes labialis developed in 289 pa tients receiving 902 dental treatments when aureomycin ointment was used prophylactically; 28 lesions were observed in a control group of 311 patients receiv ing 1,264 treatments accompanied by lip protection with plain petrolatum oint ment only. Prophylactic use of aureo mycin ointment thus reduced the inci dence of herpes labialis by more than 75 per cent. 4. Treatm ent of existing lesions of herpes labialis (52, lesions in 44 patients) with repeated application of aureomy cin ointment over the time of the du ration of the lesion showed a reduction of 39.9 per cent as compared with the du ration previously experienced by the pa
The Journal of the A m erican Dental A ssociation
tients when indifferent or no therapy was used. 5. Treatm ent of the lesions of recurrent oral aphthae (44 lesions in 38 patients) by the oral administration of 25 aureo mycin troches, 15 mg. each, given at two hour intervals over a period of three days was found effective. A reduction of 36.1 per cent in the duration of the lesions, as compared with the duration previously experienced by the patient, was noted. 6. T h e data offered indicate that topi cal medication with aureomycin is a use ful and specific therapy in the preven tion of herpes labialis, and in the treat ment of already existing lesions of this pathosis and of recurrent oral aphthae. The best response to this treatment was noted in these conditions when medica tion started within the first 24 hours after eruption. 7. The finding of almost equal dura tion of the untreated lesions of herpes labialis and of recurrent oral aphthae, as well as that of their similar response to topical aureomycin therapy, afford cir cumstantial support to the theory o f a close etiologic relationship of these two pathoses.— 8og Northeast Sixth Avenue.
A W h en the beneficiaries of a trust becom e its adm inistrators, the essen tial prin cip le of trusteeship is destroyed. In com pulsory social security, the people w ho are the beneficiaries elect from am ong them selves the people w ho fram e the program of benefits, exact the m oney to m eet it, and adm inister the details of the plan. I t differs from the principle of private m u tu al insurance in th at the means to m eet the costs are not volu ntarily subscribed by the beneficiaries but are taken from all taxpayers. I t w ould be difficu lt to im agine a more dan gerous situation. T h e citizen w h o accepts the largess of governm ent can n ot preserve individual freedom , fo r he w h o pays the p iper calls the tun e.— Raym ond M oley, “ Illusions of Security,’ ’ Newsweek, August 29, 1949, p. 76. T ru st e e sh ip a n d F r e e d o m .—
Frank G . Everett, D.M.D., M.D., Portland, Ore.
oral aphthae (canker sores) and herpes simplex labialis (cold sores) are two bothersome condi tions frequently encountered in dental practice. T he primary lesions in both pathoses are vesicles. In herpes labialis these can be seen clearly as single or multiple small blisters filled with a serous exudate, occurring at the mucocutaneous border of the lip. A fter one to several days these vesicles break and a yellowish or dark red crust is formed. In recurrent oral aphthae the vesicles can only rarely be demonstrated as the oral fluid quickly macerates the epithelial covering. The second stage of this pathosis then appears as a grayish-yellow shallow ulcer. O ral aphthae may recur almost continuously and are oftentimes intensely painful ex cept when the lesion is located in areas of the oral mucosa where nerve endings transmitting the modality of pain are few or absent.1 W hile herpes labialis does not usually cause pain, considerable discomfort may be experienced prior to and during the early vesicular stage of the eruption. If this condition recurs fre quently, however, it presents a serious cosmetic problem for the patient, and also interferes with further dental work. For an excellent review of the bacteri ology, mode of infection, incidence, symptomatology, histopathology and fur ther differential diagnosis of herpes la bialis and recurrent oral aphthae, the reader is referred to the outstanding ar ticle on this subject by Cahn and Bar tels.2
R
Etiology
e c u r r e n t
555
The etiology of these two common le sions has baffled researchers for many years.3-7 Herpes Labialis. — Overwhelming evi dence, however, has been produced in the last thirty-five years to establish the etiologic agent of herpes labialis as a filtrable virus.8’9’10 T h e proof of the role of the virus in the causation of herpes simplex rests on the demonstration of the direct transmissibility of the vims from the content of the herpetic vesicle to the corneal conjunctiva of the rabbit,8’9’10
From the Division of Oral Pathology of the University of Oregon Dental School and the Department of Phar macology of the University of Oregon Medical School. 1. Bard, P., M a c L e o d ’s Physiology in M odern M e d i cine, ed. 9, St. Louis: C. V . Mosby Co., 1941. 2.
Cahn, L . R ., and Bartels, H . A., Aphthae and
Herpetic Gingivostomatitis. A m . J. O rthodont. & Oral Surg. (Oral Surg. Sect.) 28:140 (March) 1942; correc tion 28:242 (April) 1942. 3. Goeckerman, W. H ., and Wilhelm, L. F. X ., Herpes Zoster and Herpes Simplex. A rch. D erm al. & Syph . 3 5 :8 6 8 (May) 1937. 4. Alvarez, W. C ., Canker Sores. Minnesota M e d . 20:602 (Sept.) 1937. 5. Beecher, W. L., Canker Sores in the Mouth. C lin. M e d . & Surg., 35:903 (Dec.) 1928. 6. Burket, L . W ., and Hickman, G. C ., Oral Herpes (Simplex) Manifestations: Treatment with Vitamin B Complex. J .A .D .A . 29:411 (March) 1942. 7. Strauss, K ., Vitamin Bi Therapy in Cyclic Habit ual Aphthous Stomatitis in Women. Brit. £>. J. 8 3 :7 7 (Aug.) 1947. 8. Grueter, W .. Das Herpesvirus, seine aetiologische und klinische Bedeutung. M u ench en. med. Wchnschr. 71:1058 (Aug.) 1924. 9. Loewenstein, A., Aetiologische Untersuchungen ueber den fieberhaften Herpes. M u en ch en . med. Wchnschr. 66:769 (July) 1919. 10. Goodpasture, E. W ., Herpetic Infection, ■with Especial Reference to Involvement of the Nervous System. M edicin e 8:223 (May) 1929.
556
the demonstration of the virus in the sa liva10’11 and in the desquamated epithe lial cells of the oral mucosa,12 the de termination of high herpes simplex anti body titers in the blood of patients affect ed by herpes simplex13’14’15 and, finally, in the demonstration of the typical his topathologic findings2 including, espe cially, the presence of intranuclear acido philic inclusion bodies16 in the experi mentally infected tissues. Apparently the original invasion with the virus of herpes simplex occurs in childhood in form of a gingivostomati tis13’14’17' 22 of varying degrees of sever ity.14 Following this initial attack, repeat ed eruptions of herpes labialis may be brought about throughout life in suscep tible individuals and, indeed, in the greater part of the population23 by any agent which may temporarily lower the particular local or systemic defensive mechanism protecting against erup tion.13'14’15 Oral Aphthae.— T he etiology of recur rent oral aphthae is not so well estab lished. Writers of modem textbooks on virus diseases24’25 have stated that recur rent oral aphthae are caused by the virus of herpes simplex. Neither the evidence in support of this contention26' 30 nor that contradicting it20’31 is fully convincing. In festation with the virus of herpes simplex is nearly universal10’13"15’23 and saliva con tains the virus at odd intervals.10’11 Therefore transmissibility to the rabbit cornea from recurrent oral aphthae does not with certainty prove causation of this lesion by any virus, especially also be cause methods for such transfer from oral aphthae are crude.26’31 It can only be assumed that the etiologic agent of re current oral aphthae is a filtrable virus possibly related to, but not necessarily identical with the virus of herpes simplex. In some respects the lesions of herpes labialis and recurrent oral aphthae cer tainly resemble each other grossly; like wise they show similar duration and re
The Journal of the Am erican Dental Association
sponse to medication.27 Their histopathology also is quite similar except that no inclusion bodies have been demonstrated in recurrent oral aphthae.28 In herpetic gingivostomatitis, the original infection with the virus of herpes simplex, the pri mary lesions are vesicles of the oral mucosa.13 T h e fact that these turn quickly into aphthous ulcers17’18’21’22 resembling recurrent oral aphthae also points to a close relationship of the two conditions under discussion. 11. Levaditi, C ., Ectodermoses Neurotropes. Mono graphies de l’Institut Pasteur, Paris: Masson et Cie., 1922. 12. Levaditi, C .; Harvier, P., and Nicolau, S., Etude Expérimentale de l’Encephalite dite “ Lethargique.” A n n . de V Institut Pasteur 36:105 (Feb.) 1922. 13. Burnet, F. M ., and Lush, D ., Herpes Simplex. Lancet 1:629 (M arch), 1939. 14. Burnet, F. M ., and Williams, S. W ., Herpes Simplex; A New Point of View. M e d . J . Australia 1:037 (April) 193915. Rose, H. M ., and Molloy, E., Cutaneous Re actions With the Virus of Herpes Simplex. J. Im m unol. 56:287 (July) 1947. 16. Lipschuetz, B., Ueber Chlamydozoa-Strongyloplasmen. Zur Kenntnis des Herpes febrilis. W ien. m ed. Wchnschr. 71:231 (Jan.) 1921. 17. Dodd, K.,* Johnston, L . M ., and Buddingh, G. J., Herpetic Stomatitis. / . Pediat. 12:95 (Jan.) 1938. 18. Gans, O ., Zur Aetiologie der Stomatitis aphthosa. K lin. Wchnschr. 3:447 (March) 1924. 19. Youmans, J. B., Herpetic Fever with Stomatitis* South M . J . 25:228 (March) 1932. 20. Black, W. C ., The Etiology of Acute Infectious Gingivostomatitis (Vincent’s Stomatitis). J . Pediat. 20:145 (Feb.) 1942. 21. Ziskin, D . E ., and Holden, M ., Acute Herpetic Gingivostomatitis: Report of 15 Cases. J .A .D .A ., 30:1697 (Nov.) 1943. 22. " Chilton, N. W., Herpetic Stomatitis: A Report of Six Cases Occurring in One Family. A m . J . O rth odont. & Oral Surg. (Oral Surg. Sect) 30:335 (June) 1944. 23. Keddie, F. M .; Rees, R . B., Jr., and Epstein, N. N., Herpes Simplex Following Artificial Fever Ther apy. J .A .M .A . 117 :13 2 7 (Oct.) 1941. 24. Rooyen, C . E., and Rhodes, A. J., Virus D is eases of M a n , ed. 2. New York: Thomas Nelson, 1948. 25. Rivers, T . M ., Viral and Rickettsial Infections of M a n , Philadelphia: Lippincott, 1948. 26. Scott, T . F. M .; Steigman, A. J .2 and Convey, J. H ., Acute Infectious Gingivo-Stomatitis. J .A .M .A . 1 1 7 :9 9 9 (Sept.) 1941. 27. Woodburne, A. R ., Herpetic Stomatitis. A rch. D erm at. & Syph. 43:543 (March) 1941. 28. Steinmaurer, H., Virus Observations on Aph thous Stomatitis. M edizin . K lin . 3 6 :100, 1940, quoted from Cahn K L . R ., and Bartels, H . A ., Aphthae and Herpetic Gingivostomatitis. A m . J. O rthodont. & Oral Surg. (Oral Surg. Sect.) 28:140 (March) 1942. 29. Curth, H . O ., Recurrent Genito-Oral Aphthosis and Uveitis with Hypopyon (Behcet’s Syndrome). A rch . D erm at. < 2? Syph. 54:179 (Aug.) 1946. 30. Franceschetti, A .; Valerio, M ., and Babel, J., Recurrent Aphthous Uveitis with Muco-Cutaneous L e sions. A r c h . O p h th . 35:469 (May) 1946. 31. Templeton, H. J., Is Aphthous Stomatitis due to> the Virus of Herpes Simplex? A rch. D erm at. & Syph,. 1 4 :4 3 9 (Oct.) 1926.
Everett
M any different local and systemic causes may initiate the eruption of herpes labialis. Exposure to sunlight, extreme cold, and mechanical irritation15 as in shaving are some of the local exciting circumstances. Intoxications,10 colds, fever during any disease and fever ther apy23 are some of the common systemic exciting causes for an eruption. Similarly in recurrent oral aphthae a m ultiplicity of factors may bring on an attack. Eating of walnuts, chocolate, salted foods may act as local exciting causes. M an y women suffer from these lesions before or during menstruation.7 Vitam in deficiencies6’ 7 and food aller gies4’5 have also been mentioned as systemic exciting factors. T h e dentist is especially interested in these two lesions, because the application of the rubber-dam, even with the best precautions, may bring on an eruption of herpes labialis; or these lesions m ay be provoked by stretching of the lips in pro cedures o f oral surgery, prosthodontia, periodontia and operative dentistry. In some patients aphthous ulcers develop from the use of cotton rolls, injections with anesthetic solutions2 or from any other routine dental manipulation. It w ould appear that these various secondary causes, serving to precipitate the attack in the susceptible, act only as a trigger mechanism to lower the resistance of the host locally, generally, or both locally and generally, at that time. This would explain the variety both of etiologic factors implicated and of treatments recommended for these conditions in the past. Review of Medication Used in the Past
L ocal therapy has been used by the practitioner primarily. Customarily the aphthous lesions have been treated with silver nitrate io per cent, chromic acid 5 per cent,2 phenol or other caustics and astringents in order to coagulate and numb the superficial exposed nerve end
J.A.D.A., Vol. 40, M a y 1950
557
ings, thereby providing symptomatic but uncertain relief. Similarly, the local treatment of herpes labialis has been nonspecific and sympto m atic.32 Topical applications with Campho-Phenique, spirit of camphor, mentholated ointments, aluminum ace tate 0.2 per cent, and with other drugs, have been used with similar mildly pal liative results.2’ 33 U ltraviolet irradiation34 and roentgenotherapy35 of the lesions have also been advocated. Systemic treatment with thiamin chlo ride has been used with a certain measure of success in recurrent oral aphthae,6’7 but such therapy has never become popular with the dentist. Repeated vac cination with smallpox vaccine27 has also been recommended. T he systemic treatment used for herpes labialis has included such therapy as vac cination with fluid from the patient’s own herpes vesicle,36 with smallpox vaccine,37 injection with formolized, inactivated, herpes virus38 and intradermal injection of moccasin snake venom.39 Although some of these therapies have been used with fair to good results, none of them has acquired a permanent place in the therapeutic armamentarium of the practicing dentist. Pharmacology of Aureomycin
Am ong the more than 100 antibiotic substances introduced into medicine in
32. Shulman, B. H., Recurrent Herpes Labialis, Naval Med. Bull. 4 5 : i 6 i (July) 1945. 33. Thoma, K . H ., Oral Pathology, ed. 2. St. Louis: C . V. Mosby Co., 1944. 34. Weinbren. M ., Ultraviolet Radiation in Treat ment of Herpes Labialis. Lancet 2:865 (Oct.) 1927. 35. Hall, W. C ., Radiation Treatment of Herpes Simplex. Am. J. Roentgenol. 39:393 (March) 1938. 36. Schmidt, F. R ., Vaccination for Herpes. Arch. Dermat. & Syph. 3 2 :io 6 (July) 1935. 37. Foster, P. D ., and Abshier, A. B., Smallpox Vaccine in the Treatment of Recurrent Herpes Simplex. Arch. Dermat. & Syp. 36:294 (Aug.) 1937. 38. Frank, S. B., Formolized Herpes Virus Therapy and the Neutralizing Substance in Herpes Simplex. /. Invest. Dermat. 1:267 (Aug.) 1938. 39. Kelly, R. J., Treatment of Herpes Simplex with Moccasin Venom. Arch. Derma\ Syph. 38:599 (Oct.) 1938.
The Journal of the A m erican Dental Association
558
the last few years,40 aureomycin occupies an interesting position therapeutically. This new drug has considerable effect not only upon certain bacterial forms, but also upon rickettsiae which are organisms of a size smaller than bacteria, and on some of the yet smaller invisible filtrable viruses.41 Aureomycin is effective at small dosage42’43 and is of low toxicity.44’45’46 Recent reports call attention to the effectiveness of the topical application of aureomycin in the treatment of herpes simplex corneae and of virus-caused in clusion conjunctivitis.47’48 Based on this work, it was decided to test the drug by local administration in the prevention and treatment of herpes labialis and in the treatment of recurrent oral aphthae.
not involving the use of the rubber-dam. Tw o hundred and thirty-three patients received 460 such dental treatments. In a few cases of very extensive manipulation, the patients were handed also a one dram tube of the 5 per cent aureomycin oint ment with instructions to apply it to the lips for three days after each meal and cach time after washing the face. Female patients were requested not to use lip stick during this period. A total of 3 lesions of herpes labialis resulted within the two day period after dental treat ment. In a control series involving iden tical use of petrolatum ointment base not containing aureomycin, 227 patients re ceived 534 dental treatments. Thirteen lesions appeared in the two day period following the dental appointment (Table
Clinical Data
0In a compilation of all patients receiv ing aureomycin ointment prophylaxis against herpes labialis, obtained by add ing the results of the two preceding groups, it is seen that 289 patients49 re ceived 902 dental appointments; 59 of these appointments were in patients with
Prophylaxis Against Herpes Labialis. ■ — In the first clinical series, aureomycin hydrochloride ointment 5 per cent in a base of petrolatum was used for the pre vention of lesions of herpes labialis in patients where the rubber-dam was to be applied in the course of routine dental operative procedures. T he patient’s lips were coated lightly with the ointment both before the application of the rubberdam and at the time the dam was re moved at the end of the operation. One hundred and seventy-eight patients re ceived 442 applications of the dam. Only one lesion of herpes labialis resulted within two days after treatment. In a control group involving the use of identi cal petrolatum ointment base not con taining aureomycin and following the same method of application, 221 patients received 730 applications of the dam. In these patients 15 lesions developed within two days after dental treatment (Table 0 A second group of patients were treated similarly with the aureomycin ointment, but received minor oral sur gery, extensive periodontal or prosthodontic treatment or operative dentistry
40. Duggar, B. M ., Aureomycin: A Product of the Continuing Research for New Antibiotics. A n n . N ew York A cad. Sc. 5 1 :1 7 7 (Nov.) 1948. 41. Wong, S. C ., and Cox, H. R ., Action of Aureo mycin Against Experimental Rickettsial and Viral In fections. A n n . N e w York A cad . S c. 51:290 (Nov.) 1948. 42. Schneierson, S. S., and Toharsky, B., A Method for the Determination of Aureomycin in the Blood. /. B a d . 57:483 (May) 1949. 43. Dowling, H . F .; Lepper, M . H .; Sweet, L . K ., and Brickhouse, R . L ., Studies on Serum Concentra tions in Humans and Preliminary Observations on the Treatment of Human Infections with Aureomycin. A nn. N ew York A cad. Sc. 51:1241 (Nov.) 1948. 44. Harned, B. K .; Cunningham, R. W .; Clark, M. C .; Cosgrove, R .; Hine. C . H .; McCauley, W. J.; Stokey, E.; Vessey, R. E .; Yuda, N. N ., and Subbarow. Y ., The Pharmacology of Duomycin. A n n . N ew York A cad. Sc. 5 1:18 2 (Nov.) 1948. 45. Schoenbach, E. B .; Bryer, M . S., and Long, P. H., The Pharmacology and Clinical Trial of Aureo mycin: A Preliminary Report. A n n . N e w York A cad. Sc. 51:267 (Nov.) 1948. 46. Dowling, H. F .; Lepper, M . H .; Caldwell, Jr., E. R .; Whelton, R. L ., and Sweet, L . K ., Aureomycin in Various Infections: Report of One Hundred and Eighty Cases and Review of the Clinical Literature. M e d . Annals. 18:335 (July) J94947. Braley, A . E., and Sanders, M .. Aureomycin in Ocular Infections. J .A . M . A . 138:426 (Oct.) 1948. 48. Braley, A. E., and Sanders, M ., Aureomycin in Ocular Infections. A nn. N ew York A cad. Sc. 51:280 (Nov.) 1948.
Everett
J.A.D.A., Vol. 40, M a y 1950 . . . 559
Table I.— Effect of aureomycin in the prevention of herpes labialis following extensive dental procedures
Treatment
Patients
Appointments
Mean length of appoint ment
Lesions seen within two days after treatment
1. Rubber-dam used Aureomycin prophylaxis................. Petrolatum prophylaxis...................
178
221
442 730
38.5 40.1
15
2. No rubber-dam used...................... Aureomycin prophylaxis................. Petrolatum prophylaxis..................
233 227
460 534
32.4 32.6
3 13
3. Total cases* Aureomycin prophylaxis............... Petrolatum prophylaxis..................
289 311
902 1264
35.4 36.9
4 28
1
*Some of these patients received dental treatment involving the use of the rubber-dam as well as other exten sive dental work not involving application of the dam; therefore the totals are smaller than simple addition of the preceding groups would show.
a known past history of herpes labialis following dental treatment. Four lesions developed within two days after treat ment. T he control group of 311 patients49 received 1,264 dental treatments accom panied by prophylaxis with petrolatum ointment base which did not contain aureomycin; 74 of these appointments were in patients with a known past history of herpes labialis following dental treat ment. Twenty-eight lesions developed within the two day period following treat ment. T able 1 summarizes these clinical data and gives also the mean length of a single appointment. Treatment of Herpes Labialis.— In a sec
ond series the therapeutic properties of the aureomycin ointment 5 per cent in existing lesions of herpes labialis were tested, whether the lesions occurred from other exciting causes or following dental treatment. Patients received a one dram tube o f the salve and were instructed to apply a thin coat of the material after each meal and each time after washing the face. Fifty-two lesions in 44 patients were thus treated. T h e duration (arithmetic mean) of the lesions when left untreated
or treated with the usual local palliatives, as obtained from the past history of each patient, had been 10.1 days. Duration (arithmetic mean) for lesions in these same patients treated with the aureomy cin ointment was 6.1 days. Thus aureo mycin ointment therapy resulted in a 39.9 per cent reduction (arithmetic mean) of the duration of the lesions (Table 2 ). In 6 lesions the duration was not reduced. In 3 lesions no relief from discomfort was experienced. A total of 8 patients were not benefited by the treatment objec tively, subjectively, or both (Table 2). Further analysis of the above data shows that the time of the institution of therapy is important. W hen treatment had been started during the first 24 hours after eruption, the reduction (arithmetic mean) in duration amounted to 58.1 per cent of the time usually taken by the le sion to heal without medication. When treatment started during the second 24
49. It should be noted that some of these patients received dental treatment involving the use of the rubber-dam as well as other extensive dental work not involving application of the dam; therefore the totals are smaller than simple addition of the preceding groups would show.
560
T a b le 2.— T re atm e n t o f h e rp e s la b ia lis with a u re o m ycin o in tm e n t
Number of patien ts...................................... 44 Number of lesions treated.......................... 52 Duration of untreated lesion (arithmetic m e a n ) ................................... 10.1 Duration of treated lesion (arithmetic mean) . ............................... 6.1 Reduction in duration in % (arithmetic mean) ................................... 39.9 Number of treated lesions leading to no reduction of duration............................... 6 Number of treated lesions leading to no relief from discomfort ............................ 3 Number of patients not benefited by treat ment, subjectively, objectively or both 8
hours, the reduction amounted to 38.5 per cent, and when it started during or after the third day the reduction amounted to only 13.7 per cent (F ig u re). Treatment of Recurrent Oral Aphthae.— For the treatment of recurrent oral aph thae, troches containing 15 mg. of aureo mycin hydrochloride were prescribed. The patients were instructed to let each troche melt slowly in the mouth and to use one every two waking hours for three days. Forty-four crops of lesions in 38 patients were treated. T he duration (arithmetic mean) of the lesions, as obtained from past history, had been 10.2 days, when untreated or treated with the usual local palliatives. Duration (arithmetic mean) of the aphthous lesions treated with aureomycin troches was 6.5 days. In other words, treatment of the recurrent oral aphthae with aureomycin troches resulted in a reduction (arithmetic m ean) of the duration of the lesions of 36.1 per cent. In 4 lesions the duration could not be reduced by the treatment. In 3 lesions no relief from discomfort could be ob tained. In 2 cases mild nausea was ob served, a symptom rarely seen in oral medication with aureomycin.42’ 45’ 46 A to tal of 5 patients were not benefited by the treatment subjectively, objectively, or both (Table 3).
The Journal of the A m erica n Dental A ssociation
Here, too, the time of the institution of therapy is important. W hen the treat ment started during the first 24 hours after eruption, the reduction (arithmetic mean) in duration amounted to 57.6 per cent of the time usually taken by the le sion to heal when no or indifferent medi cation was used. W hen treatment started during the second 24 hours the reduction amounted to 53.3 per cent, and when it started on or after the third day to 23.1 per cent (illustration). Discussion
In the clinical data presented the note worthy prophylactic effect of aureomycin hydrochloride ointment in the prevention of lesions of herpes labialis is shown. The controls showed more than four times as many lesions of herpes labialis per ap pointment following dental treatment as patients who had received prophylactic aureomycin inunction. Considerable improvement has also been demonstrated in the subjective and objective symptoms by the treatment of existing lesions of herpes labialis with
Reduction of duration of lesions of herpes labialis and recurrent oral aphthae in relation to the time of the institution of topical aureo mycin therapy
Everett
this ointment and by the treatment of recurrent oral aphthae with aureomycin troches. Especially, the duration of these lesions has been reduced by better than one-third. These results seem to show that in aureomycin the dentist and the phy sician have available a specific medica tion for these two conditions. Comparison of T able 2 and Table 3 shows the interesting fact that the dura tion (arithmetic mean) of the untreated lesions of herpes labialis and that of re current oral aphthae are practically the same, namely 10.1 and 10.2 days, which speaks for a relationship of the etiology of the two pathoses. Study of T able 3 shows that the reduction in duration (arithmetic mean) is best, and practically the same for the two lesions, when treat ment starts during the first 24 hours.47 W hen medication begins during the sec ond and third day a considerable differ ence develops. Recurrent oral aphthae re spond well to medication on the second and even fairly well on the third day, while herpes labialis shows by far the best result when treated on the first day after eruption. It m ay be assumed that once a crust is formed in the course of the eruption of herpes labialis, the virus is protected by it from the influence of the medication, while in recurrent oral aph thae the shallow ulcer remains accessible to the drug. T h e similarity in response to medication also lends weight to the argu ment of the similarity in etiology of these two lesions.27 T h e prompt relief from pain in the treatment of recurrent oral aphthae was pronounced in the great majority of these cases. No attempt was made to measure pain relief objectively because of the vari ations of the pain threshold in different persons, different areas of the oral mu cosa1 and the difficulty per se of measur ing pain.50 Part of the beneficial effect of the treatment of recurrent oral aphthae with the aureomycin troches accrues undoubt edly to the effect of the drug on secon-
J.A.D.A., Vol. 40, M a y 1950 . . . 561
T a b le
3.— T re a tm e n t of recurre nt oral t w ith a u re o m y c in tro ch e s
a p h th a e
N um ber of patients ..................................... 38 N um ber of lesions t r e a t e d .......................... 44 D u ration of u ntreated lesion (arithm etic m e a n ) .................................... 10.2 D u ratio n of treated lesion (arithm etic m ean) .................................... 6.5 R ed u ction in duration in % (arithm etic m ean) ................................. 36.1 N u m ber of treated lesions lead ing to no reduction in duration. . 4 N u m ber of treated lesions lead ing to no relief of discom fort. . . 3 N um ber of treated lesions lead in g to' m ild n a u s e a ............................. 2 N um ber of patients not benefited by treat m ent subjectively, ob jectively or both 5
dary invaders; how great that part is, we do not know. It is true that in many cases the aph thous and herpetic lesions recurred at a later time. No m ajor systemic effect, eliminating the entire infestation o f the host, can be expected from such topical medication. T h e ointment and troches served well, however, in the treatment of the lesions of herpes labialis and recur rent oral aphthae. T h e success in the pre vention of herpes labialis by this simple procedure was especially gratifying. It is felt that topical medication with aureo mycin hydrochloride is a useful and spe cific therapy in the prevention and treat ment of herpes labialis and in the treat ment of recurrent oral aphthae. Summary
1. The etiologies of herpes labialis and recurrent oral aphthae are reviewed. It is noted that a filtrable virus is the causa tive agent responsible for the former and probably also for the latter pathosis.
50. Everett, F. G ., A Comparison of Depth of A n esthesia and Toxicity of 2 and 4 per cent Procaine Hydrochloride Solutions. J. D. Kes. 28:204 (June) «949-
562
2. Consideration is given to local and systemic medication used previously in the treatment of these conditions; the pharmacology of aureomycin is discussed briefly, mentioning its viricidal proper ties. 3. Prophylactic treatment .with 5 per cent aureomycin ointment applied to the lips before and after dental procedures showed a marked reduction in the inci dence of herpes labialis. O nly 4 lesions of herpes labialis developed in 289 pa tients receiving 902 dental treatments when aureomycin ointment was used prophylactically; 28 lesions were observed in a control group of 311 patients receiv ing 1,264 treatments accompanied by lip protection with plain petrolatum oint ment only. Prophylactic use of aureo mycin ointment thus reduced the inci dence of herpes labialis by more than 75 per cent. 4. Treatm ent of existing lesions of herpes labialis (52, lesions in 44 patients) with repeated application of aureomy cin ointment over the time of the du ration of the lesion showed a reduction of 39.9 per cent as compared with the du ration previously experienced by the pa
The Journal of the A m erican Dental A ssociation
tients when indifferent or no therapy was used. 5. Treatm ent of the lesions of recurrent oral aphthae (44 lesions in 38 patients) by the oral administration of 25 aureo mycin troches, 15 mg. each, given at two hour intervals over a period of three days was found effective. A reduction of 36.1 per cent in the duration of the lesions, as compared with the duration previously experienced by the patient, was noted. 6. T h e data offered indicate that topi cal medication with aureomycin is a use ful and specific therapy in the preven tion of herpes labialis, and in the treat ment of already existing lesions of this pathosis and of recurrent oral aphthae. The best response to this treatment was noted in these conditions when medica tion started within the first 24 hours after eruption. 7. The finding of almost equal dura tion of the untreated lesions of herpes labialis and of recurrent oral aphthae, as well as that of their similar response to topical aureomycin therapy, afford cir cumstantial support to the theory o f a close etiologic relationship of these two pathoses.— 8og Northeast Sixth Avenue.
A W h en the beneficiaries of a trust becom e its adm inistrators, the essen tial prin cip le of trusteeship is destroyed. In com pulsory social security, the people w ho are the beneficiaries elect from am ong them selves the people w ho fram e the program of benefits, exact the m oney to m eet it, and adm inister the details of the plan. I t differs from the principle of private m u tu al insurance in th at the means to m eet the costs are not volu ntarily subscribed by the beneficiaries but are taken from all taxpayers. I t w ould be difficu lt to im agine a more dan gerous situation. T h e citizen w h o accepts the largess of governm ent can n ot preserve individual freedom , fo r he w h o pays the p iper calls the tun e.— Raym ond M oley, “ Illusions of Security,’ ’ Newsweek, August 29, 1949, p. 76. T ru st e e sh ip a n d F r e e d o m .—