305
Australian Dental Journal, August, 1978
Volume 23 : : Number 4
AUGUST, 1978
Acute stoma4itis medicamentosa. Two case reports
Neville Smith, M.D.S., F.R.A.C.D.S.
Senior Lecturer, Department of Oral Medicine arid Oral Surgery, The University of Sydney
ABSTRACT-TWO cases of acute drug reaction with oral mucosal lesions and problems of diagnosis in the absence of specific clinical and histopathological findings are presented.
(Received for publication Iiitie, 1977)
Introduction
Stomatitis medicamentosa describes an inflammatory, ulcerative or bullous response seen in the oral mucosa as the consequence of the systemic administration of a chemical compound, usually a drug but sometimes an excipient such as a colouring or preservative agent'. The skin is peculiarly liable to respond t o drugs in a variety of ways. Dermal drug reactions may simulate a spectrum of inflammatory dermatological disease, a fact long recognized by dermatologists.
1
McCarthy, P. L., and Shklar, G.-Diseases of the oral mucosa. New York. McGraw-Hill Book Company, 1964 (P. 142).
The oral musoca may be affected a t the same time as the skin but experience has shown that it is unusual for lesions to be restricted to the mouth while the skin remains clear?. 3,4. I n instances where only the oral mucosa is affected diagnosis is frequently dificult because of the varied appearance of the lesions and the absence of specific featuresl. When mild there may be little more than
Pindborg. J. J.-Texthook of dermatology. Edits., Rook, A., Wilkinson. D. S., and Ehling, F. J . G. Oxford, Blackwell Scientific Publications, Vol. 2. 1968 (p. 1472). :'Scopp. I. W.-Oral medicine. St. Louis, The C. V. Mosby Co., 2nd ed., 1973 (p. 199). 4 Shafer, W. G., Hine, M. K.. and Levy, B. M.-A textbook of oral pathology. Philadelphia, W. B. Saunders Co., 3rd ed., 1974 (pp. 532-534).
2
306
Australian Dental Journal, August, 1978
erythema, in some the response may mimic lichen planus, while, in others, more severe, blistering and ulceration may be seen%6 - 7 . It is worth noting that any drug is potentially capable of inducing a mild to severe response which is not necessarily doserelated and, in a susceptible individual, an
When examined, a number of irregularly shaped ulcers four to eight miilimetres in diameter. each covered by a creamy-white sero-fibrinous membrane were seen on the soft palate and the buccal and labial mucosa (Fig. 1). A biopsy specimen was examined by immunofluorescence and light micro-
Fig. 1 . A e r c 1. Irregularly shaped ulcer covered by a serc-fibrinous membrane located on the soft palate.
Fig. ? . - C a s e I . Immunofluorescence showing complement in a m a l l blood vessel of the lamina propria. Orig., x 280.
ordinarily insignificant amount of a drug may induce a full scale reactionl. Contact sensitivity, or stomatitis venenata, resulting from the direct contact of skin or mucosa with a sensitizing agent is a different phenomenon and will not be considered here. The following two cases are reported as illustrations of stomatitis medicamentosa. Case reports Case I A 53-year-old woman, an insulin dependent diabetic, complained of a sore throat for two months and oral ulceration of three weeks duration. At age 16 years, duodenal ulceration had been diagnosed, and she was currently being treated for hyperthyroidism. Apart from insulin, the following medication was taken daily: carbimazole, ibuprofen, Veracolate”, Mucaine‘:*, an oral contraceptive, and multi-vitamins.
scopy and serum taken for indirect immunofluorescence examination. Complement deposits were found in the smaller blood vessels of the lamina propria (Fig. 2). There was n o evidence of antibody to epithelial intercellular substance or basement membrane thus excluding pemphigus and mucosal pemphigoid. Examination by transmitted light showed patchy necrosis of the epithelium with an extensive inflammatory infiltrate which included numerous plasma cells. One week later the oral ulceration became more severe, necessitating hospitalization to maintain the patient’s control of her diabetic state. Shortly after admission an extensive skin rash developed and all drugs other than insulin were withdrawn. Subsequently, the oral lesions and then the rash healed. When seen again five weeks after the initial consultation the mouth was normal although healing lessions were still present on the skin. Skin rash, sore throat and fever are known to be signs of toxic reaction to the antithyroid drug carbimazole.
* William
** Wyeth
R . Warren and Company Pty. Ltd. Pharmaceutical Pty. Ltd.
Gardner, A. F.-Pathology of oral manifestations of systemic diseases. New York, Hefner Publishing Co. Inc., 1972 (p. 19). 0 Kennett, S.-Stomatitis medicamentosa due to barbiturates. Oral Surg., 25:3, 351-356 (Mar.) 1968. ‘Dinsdale, R. C. W., and Walker Anne, E.-Amiphenazole sensitivity with oral ulciration. Brit. D. J ., 121:lO. 460-462 (Nov. 15) 1966. 5
Case 2 An otherwise healthy woman, 41 years old, complained of a painful ulceration of the hard palate and lower lip of four days duration. She stated that a blister had formed on the hard palate, lasted about nine hours and then burst, leaving a painful ulcer. A similar lesion had developed on the
3 07
Australian Dental Journal, August, 1978 mucosa of the lower lip (Fig. 3 ) . The decongestants Demazin: and SudafedV were taken regularly for chronic sinusitis, nasal drops occasionally, and sometimes diazepam to relieve premenstrual tension. On examination two irregularly shaped ulcers
Fig. 3.--Cose 2. Mucosal surface of lower lip with an irregularly shaped ulcer surrounded by an erythematous border.
were present, each covered by a creamy-coloured sero-fibrinous plaque and surrounded by an erythematous border. A diagnosis could not be made from the appearance of the lesion. A biopsy specimen examined by immunofluorescence, revealed deposits of complement around a few blood vessels in the lamina propria consistent with a diagnosis of drug reaction. Viewed with transmitted light, sections showed ulceration and a chronic inflammatory infiltrate in the lamina propria. When seen three days later, the ulcers had almost healed. At this visit the patient recalled having taken chlorthalidone to relieve premenstrual oedema shortly before the appearance of the oral lesions. The patient was advised to avoid its further use.
t Schering Corporation, U.S.A.
i t Burroughs
Wellcome and Company.
RCopemnn. P. W. M.-Drug
ill effects on the skin. Brit.
On occasion, this drug has been known to cause hypersensitivity resulting in skin rashes and, more rarely, blood changes such a s ngranulocytosis, neutropenia or thrombocytopenia. Discussion
Diagnosis of stomatitis medicamentosa is often difficult. It frequently rests on the suspicion of a reaction to a drug and, where possible, the effect of withdrawal of the suspected agent. Where such a course is not feasible because medication is essential, chemically unrelated drugs might be substituted in the patient's regimen. Difficulties arise from exposure to unsuspected sources of drugs or chemicals, for example quinine in soft drinks or phenolphthalein in laxatives#. Furthermore, drugs may have been taken for years and may appear innocuous but eventually cause a pathological responseg. The mere fact that a medication has been taken for some time without untoward effect does not necessarily exclude it as a causative agent. Another problem is that lesions of similar appearance may be produced by a variety of drugsl. 8. Whilst there are n o histological changes absolutely diagnostic of drug reaction, biopsy is valuable in excluding otber diseases such as pemphigus or pemphigoid and in demonstrating features consistent with drug reactionlo. Typical changes seen in the lamina propria are dilatation of the blood vessels and an inflammatory infiltrates. Immunofluorescence, both direct using fresh, unfixed biopsy tissue, and indirect with patient's serum, may assist diagnosis. The finding of complement in vessel walls is consistent with a diagnosis of stomatitis medicamentosa. Prognosis is usually excellent following withdrawal of the offending drug, although widespread skin involvement carries with it the risk of far more serious consequences1 1. The only way to confirm a drug's culpability is to again challenge the patient with a test dose. This is a hazardous procedure because severe hypersensitivity reactions may occur with attendant risk for the patientlz. 1.1. Where a diagnosis of drug sensitivity is established, it is important that the patient be fully informed in writing of the name of the drug, given an appropriate warning, and advised t o avoid strictly its future use. Acknowledgement
Vaughan. J . H. Ncw York, McGraw-Hill I 1971 (p. 1307). '"ibid, p. 1304. ' I ibid. p. 1313. Rook. A,. and Rowell, N . R.-Textbook of dermatology. Edits., Rook A., Wilkinson, D. S., and Ebling, F. J . G . Oxford, Blackwell Scientific Publication 1968 (pp. 394395). I n Kantor. F. S.-Textbook of medicine. Edits., Beeson, P. B.. and McDermott, W . Philadelphia, W. B. Saunders Co., 13th ed., 1971 (p. 806).
I am indebted to D r C. S. Lauer, Royal Prince Alfred Hospital, for the photomicrograph. Faculty of Dentistry, The University of Sydney, 2 Chalmers Street, Surry Hills, N.S.W., 2010.
Australian Dental Journal, August, 1978
Volume 23 : : Number 4
AUGUST, 1978
Acute stoma4itis medicamentosa. Two case reports
Neville Smith, M.D.S., F.R.A.C.D.S.
Senior Lecturer, Department of Oral Medicine arid Oral Surgery, The University of Sydney
ABSTRACT-TWO cases of acute drug reaction with oral mucosal lesions and problems of diagnosis in the absence of specific clinical and histopathological findings are presented.
(Received for publication Iiitie, 1977)
Introduction
Stomatitis medicamentosa describes an inflammatory, ulcerative or bullous response seen in the oral mucosa as the consequence of the systemic administration of a chemical compound, usually a drug but sometimes an excipient such as a colouring or preservative agent'. The skin is peculiarly liable to respond t o drugs in a variety of ways. Dermal drug reactions may simulate a spectrum of inflammatory dermatological disease, a fact long recognized by dermatologists.
1
McCarthy, P. L., and Shklar, G.-Diseases of the oral mucosa. New York. McGraw-Hill Book Company, 1964 (P. 142).
The oral musoca may be affected a t the same time as the skin but experience has shown that it is unusual for lesions to be restricted to the mouth while the skin remains clear?. 3,4. I n instances where only the oral mucosa is affected diagnosis is frequently dificult because of the varied appearance of the lesions and the absence of specific featuresl. When mild there may be little more than
Pindborg. J. J.-Texthook of dermatology. Edits., Rook, A., Wilkinson. D. S., and Ehling, F. J . G. Oxford, Blackwell Scientific Publications, Vol. 2. 1968 (p. 1472). :'Scopp. I. W.-Oral medicine. St. Louis, The C. V. Mosby Co., 2nd ed., 1973 (p. 199). 4 Shafer, W. G., Hine, M. K.. and Levy, B. M.-A textbook of oral pathology. Philadelphia, W. B. Saunders Co., 3rd ed., 1974 (pp. 532-534).
2
306
Australian Dental Journal, August, 1978
erythema, in some the response may mimic lichen planus, while, in others, more severe, blistering and ulceration may be seen%6 - 7 . It is worth noting that any drug is potentially capable of inducing a mild to severe response which is not necessarily doserelated and, in a susceptible individual, an
When examined, a number of irregularly shaped ulcers four to eight miilimetres in diameter. each covered by a creamy-white sero-fibrinous membrane were seen on the soft palate and the buccal and labial mucosa (Fig. 1). A biopsy specimen was examined by immunofluorescence and light micro-
Fig. 1 . A e r c 1. Irregularly shaped ulcer covered by a serc-fibrinous membrane located on the soft palate.
Fig. ? . - C a s e I . Immunofluorescence showing complement in a m a l l blood vessel of the lamina propria. Orig., x 280.
ordinarily insignificant amount of a drug may induce a full scale reactionl. Contact sensitivity, or stomatitis venenata, resulting from the direct contact of skin or mucosa with a sensitizing agent is a different phenomenon and will not be considered here. The following two cases are reported as illustrations of stomatitis medicamentosa. Case reports Case I A 53-year-old woman, an insulin dependent diabetic, complained of a sore throat for two months and oral ulceration of three weeks duration. At age 16 years, duodenal ulceration had been diagnosed, and she was currently being treated for hyperthyroidism. Apart from insulin, the following medication was taken daily: carbimazole, ibuprofen, Veracolate”, Mucaine‘:*, an oral contraceptive, and multi-vitamins.
scopy and serum taken for indirect immunofluorescence examination. Complement deposits were found in the smaller blood vessels of the lamina propria (Fig. 2). There was n o evidence of antibody to epithelial intercellular substance or basement membrane thus excluding pemphigus and mucosal pemphigoid. Examination by transmitted light showed patchy necrosis of the epithelium with an extensive inflammatory infiltrate which included numerous plasma cells. One week later the oral ulceration became more severe, necessitating hospitalization to maintain the patient’s control of her diabetic state. Shortly after admission an extensive skin rash developed and all drugs other than insulin were withdrawn. Subsequently, the oral lesions and then the rash healed. When seen again five weeks after the initial consultation the mouth was normal although healing lessions were still present on the skin. Skin rash, sore throat and fever are known to be signs of toxic reaction to the antithyroid drug carbimazole.
* William
** Wyeth
R . Warren and Company Pty. Ltd. Pharmaceutical Pty. Ltd.
Gardner, A. F.-Pathology of oral manifestations of systemic diseases. New York, Hefner Publishing Co. Inc., 1972 (p. 19). 0 Kennett, S.-Stomatitis medicamentosa due to barbiturates. Oral Surg., 25:3, 351-356 (Mar.) 1968. ‘Dinsdale, R. C. W., and Walker Anne, E.-Amiphenazole sensitivity with oral ulciration. Brit. D. J ., 121:lO. 460-462 (Nov. 15) 1966. 5
Case 2 An otherwise healthy woman, 41 years old, complained of a painful ulceration of the hard palate and lower lip of four days duration. She stated that a blister had formed on the hard palate, lasted about nine hours and then burst, leaving a painful ulcer. A similar lesion had developed on the
3 07
Australian Dental Journal, August, 1978 mucosa of the lower lip (Fig. 3 ) . The decongestants Demazin: and SudafedV were taken regularly for chronic sinusitis, nasal drops occasionally, and sometimes diazepam to relieve premenstrual tension. On examination two irregularly shaped ulcers
Fig. 3.--Cose 2. Mucosal surface of lower lip with an irregularly shaped ulcer surrounded by an erythematous border.
were present, each covered by a creamy-coloured sero-fibrinous plaque and surrounded by an erythematous border. A diagnosis could not be made from the appearance of the lesion. A biopsy specimen examined by immunofluorescence, revealed deposits of complement around a few blood vessels in the lamina propria consistent with a diagnosis of drug reaction. Viewed with transmitted light, sections showed ulceration and a chronic inflammatory infiltrate in the lamina propria. When seen three days later, the ulcers had almost healed. At this visit the patient recalled having taken chlorthalidone to relieve premenstrual oedema shortly before the appearance of the oral lesions. The patient was advised to avoid its further use.
t Schering Corporation, U.S.A.
i t Burroughs
Wellcome and Company.
RCopemnn. P. W. M.-Drug
ill effects on the skin. Brit.
On occasion, this drug has been known to cause hypersensitivity resulting in skin rashes and, more rarely, blood changes such a s ngranulocytosis, neutropenia or thrombocytopenia. Discussion
Diagnosis of stomatitis medicamentosa is often difficult. It frequently rests on the suspicion of a reaction to a drug and, where possible, the effect of withdrawal of the suspected agent. Where such a course is not feasible because medication is essential, chemically unrelated drugs might be substituted in the patient's regimen. Difficulties arise from exposure to unsuspected sources of drugs or chemicals, for example quinine in soft drinks or phenolphthalein in laxatives#. Furthermore, drugs may have been taken for years and may appear innocuous but eventually cause a pathological responseg. The mere fact that a medication has been taken for some time without untoward effect does not necessarily exclude it as a causative agent. Another problem is that lesions of similar appearance may be produced by a variety of drugsl. 8. Whilst there are n o histological changes absolutely diagnostic of drug reaction, biopsy is valuable in excluding otber diseases such as pemphigus or pemphigoid and in demonstrating features consistent with drug reactionlo. Typical changes seen in the lamina propria are dilatation of the blood vessels and an inflammatory infiltrates. Immunofluorescence, both direct using fresh, unfixed biopsy tissue, and indirect with patient's serum, may assist diagnosis. The finding of complement in vessel walls is consistent with a diagnosis of stomatitis medicamentosa. Prognosis is usually excellent following withdrawal of the offending drug, although widespread skin involvement carries with it the risk of far more serious consequences1 1. The only way to confirm a drug's culpability is to again challenge the patient with a test dose. This is a hazardous procedure because severe hypersensitivity reactions may occur with attendant risk for the patientlz. 1.1. Where a diagnosis of drug sensitivity is established, it is important that the patient be fully informed in writing of the name of the drug, given an appropriate warning, and advised t o avoid strictly its future use. Acknowledgement
Vaughan. J . H. Ncw York, McGraw-Hill I 1971 (p. 1307). '"ibid, p. 1304. ' I ibid. p. 1313. Rook. A,. and Rowell, N . R.-Textbook of dermatology. Edits., Rook A., Wilkinson, D. S., and Ebling, F. J . G . Oxford, Blackwell Scientific Publication 1968 (pp. 394395). I n Kantor. F. S.-Textbook of medicine. Edits., Beeson, P. B.. and McDermott, W . Philadelphia, W. B. Saunders Co., 13th ed., 1971 (p. 806).
I am indebted to D r C. S. Lauer, Royal Prince Alfred Hospital, for the photomicrograph. Faculty of Dentistry, The University of Sydney, 2 Chalmers Street, Surry Hills, N.S.W., 2010.
