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Multiple Oral and Skin Lesions Occurring after Treatment with Penicillin
J'AOA DIAGNOSING
ORAL
DISEASE
Multiple oral and skin lesions occurring after treatment with penicillin
Lauri R. Staretz, DDS Gayle Wallace DeBoom, DDS 28 -year-o ld m ale was r e fe r r e d to th e dental clinic fo r evaluation o f multiple, p a in fu l o ra l u lc e ra tio n s o f two d a y s ’ duration. Two weeks earlier, the patient had suf fe re d a b ee sting, w hich resu lted in localized c e llu litis o n the fo o t. F o r this p ro b le m , the patient has been taking penicillin, 250 mg, fou r tim es daily, as prescrib ed by a physician. T h e patient reported that he had developed sim ilar le s io n s o n o n e o th e r o c c a s io n , a n d h e h a d un d ergo n e a skin biopsy at an oth er hospital to establish a d efin itive d iagn osis. T h o se lesions had also o ccu rred after penicillin therapy.
A
b ra n e (F ig 1 ) . T h e v e rm ilio n b o rd e r o f the lower lip was ulcerated and partially covered by a hem orrh agic crust. Partially collapsed bullae and focal ulcerations w ere seen on the an terior part o f the tongue (Fig 2). A num ber o f skin lesions w ere also noted, dis tributed prim arily over the knees, elbows, and d o r s a l s u r fa c e s o f th e h a n d s . T h e le s io n s appeared as dusky purple-red papules and mac ules; m any showed a peripheral, pale red zone, surrou n ded by a darker red, m ore narrow ring (Fig 3).
Diagnosis Report of case At the time o f clinical exam ination, the patient was afebrile, and no regional lym phadenopathy was d etected . O ral exam in atio n d isclosed d if fuse m ucosal eryth em a and ed em a with large, irreg u larly shaped , shallow u lceration s on the b u cc al a n d la b ial m u cosa, an d gin giva. M ost such areas w ere overlaid by gray pseudom em
A lthough the previous biopsy was not available fo r review, the patient reported that it had been interpreted as erythem a m ultiform e (with clini cal correlatio n ). B ased on the cu rren t clinical findings and history o f recen t penicillin inges tion, cou pled with the history o f a sim ilar condi tion developing earlier after penicillin therapy, a diagnosis o f erythem a m ultiform e was m ade.
Fig 1 ■ Shallow, pseudomembrane-covered ulcer
Fig 2 ■ Ulcerated, crusted appearance o f vermil-
ations occurring on the edematous labial mucosa
ion border o f the lip.
and gingiva.
436 ■ JADA, Vol. 121, September 1990
T o p ical viscous lid o cain e an d a soft, bland d iet w ere prescribed to alleviate the p a tien t’s d is c o m fo r t . H e w as in s t r u c t e d to r e t u r n prom ptly if he did n o t im prove o r if symptoms b ecam e w orse. W hen the p atien t re tu rn e d 3 weeks later, all skin and oral lesions cleared.
Discussion E ryth em a m ultiform e (EM ) is an acute, often recurrent, inflam m atory disorder characterized in its m ildest fo rm by skin lesion s an d, in its m ost severe fo rm , as a life-th reaten in g con di tion (Stevens-Johnson syn drom e) that affects the skin, mouth, eyes, and gen italia.1-2 Erythem a m ultiform e may occur at any age, although the condition is reported to o ccu r in you ng males m ost com monly.2’3 T h e disease is characterized by rapidly devel oping lesions that usually heal without scarring, and the lesions are distributed in a symmetrical pattern over the skin, o cc u rrin g prim arily on the hands, feet, arms, legs, face, and neck. T he
Fig 3 ■ “Target” lesions o f skin (right and left),
D I A G N O S I N G
lesions appear as 1- to 2- cm, red or violet papules, macules, vesicles, and bullae, often with one or more peripheral concentric rings. T hese characteristic lesions are comm only referred to as “iris,” “target,” or “bull’s-eye” lesions. The lesions fade and eventually clear in 1 to 2 weeks.4 Mucous membranes characteristically show areas o f macular erythema, vésiculation, and edema. The oral bullae and vesicles rupture to form painful, shallow, pseudomembrane-covered ulcers. Hemorrhagic crusts may form on the lips.5 A prodromal period o f 1 to 14 days may occur, in which the patient experiences fever, malaise, sore throat, cough, and muscular aches (myalgias) .3 Patients may remain mildly febrile throughout the course o f the illness, or in severe cases, may be seriously ill. Erythema multiforme may have an acute or chronic pattern of occurrence. Lozada-Nur, Gorsky, and Silverman6 found that 73% of one series of patients had a noncyclic (chronic) pat tern o f occurrence. Those with self-limiting attacks experienced episodes o f 3 to 21 days duration. Interestingly, an increased incidence o f occurrence of erythema multiforme in the spring and fall seasons has been described among individuals experiencing recurrent, self limited attacks.2 The etiology o f erythem a m ultiform e is unclear. A significant number of cases exist in which the disease appears to be spontaneous, and the patients are unable to relate any spe cific agent or event to development of the dis ease. In som e cases, erythem a m ultiform e appears to represent a hypersensitivity reaction to a variety of causes including viruses, systemic diseases, neoplasms, radiation therapy, diseases o f connective tissue, severe emotional distur bances, prescription medications, and food preservatives.179 Pandi10 and Shelley11 consider herpes sim plex virus infection as the most common precip itating agent, usually preceding the onset of erythema multiforme by 1 to 3 weeks. Other researchers have proposed a defect in cellular immune reactivity as the cause o f erythema m u ltiform e, notin g a significantly lower response to delay hypersensitivity skin testing in affected patients.12 Histologic features of erythema multiforme include intracellular edema of the spinous layer of epithelium, intra- and subepithelial vesicle formation, and a primarily chronic inflamma tory cell infiltrate of varying intensity.4 These features are nonspecific, and Buchner and others13 have reported that the main value of performing a biopsy is to rule out other condi tions in the differential diagnosis. The differential diagnosis includes other
vesiculobullous and desquamative lesions. Ery them a m ultiform e-like lesio n s som etim es develop in patients who are receiving gold ther apy for rheumatoid arthritis.14 Staphylococcal scalded-skin syndrome, a disease of infants that occurs after staphylococcus infection, is charac terized by large bullae and skin lesions resem blin g erythem a m u ltiform e.15 R ecurrent aphthous stomatitis, bullous and mucous mem brane pemphigoid, herpetic gingivostomatitis, bullous and erosive lichen planus, pemphigus vulgaris, Behcet and Reiter syndromes, contact dermatitis, acute necrotizing ulcerative gingivi tis, dermatitis herpetiformis, chicken pox, and toxic epidermal necrolysis are other disease entities that may be included in the differential diagnosis.51617 Diagnosis of erythema multiforme is based on the sudden d evelop m en t o f skin and mucosal lesions showing a symmetrical distribu tion and the characteristic features of “target” lesions, coupled with a biopsy showing the pre viously described, nonspecific histologic fea tures that help to rule out other diseases.3 Treatment of the disease is related to severity. The conventional treatment is systemic and/or topical corticosteroids. Systemic antibiotics may be prescribed to control secondary infection. Prophylactic use o f acyclovir has been investi gated but has not significantly decreased the number of outbreaks of erythema multiforme in affected individuals.13 Fluid intake must be maintained, and a soft diet and nutritional supplements should be pre scribed. Topical anesthetics or an oral rinse con sisting of equal parts of diphenhydramine HCL and Koalin and Pectin oral suspension (Kaopectate, Upjohn) may also increase patient com fort.
Summary A case o f erythema multiforme has been pre sented. Erythema multiforme may be a self-limiting or chronic disease, of varying severity. The disease is of significance to dental practitioners who may be called on to establish a diagnosis and provide appropriate referral or treatment, especially when lesion s are lim ited to the m outh. The prognosis is generally good, although recurrence is common.
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q a
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The publication o f this series is coordinated by the Western Dental Education Center, West Los Angeles VA Medical Center, Los Angeles, and is supported by the Department o f Veterans Affairs and by the Ameri can Dental Association. The opinions and assertions contained herein are those o f the authors and are not to be construed as official or necessarily representing
O R A L
D I S E A S E
the views o f the Department o f Veterans Affairs. Dr. S taretz is c h ie f r e s id e n t in p e r io d o n t ic s, Wadsworth Division Dental Service, West Los Angeles VA Medical Center, Los Angeles. Dr. DeBoom is assis tant director, Western Dental Education Center (161), West Los A ngeles VA M edical Center, W ilshire and Sawtelle blvds, Los Angeles, CA 90073, and attending staff in oral pathology, Long Beach Va Medical Center, and a ssista n t c lin ic a l p r o fe sso r , d e p a r tm e n t o f medicine and surgery, University o f California School o f Medicine, Irving, CA. Address requests for reprints to Dr. DeBoom.
1. Bean SF, Quezada RK. Recurrent oral erythema m u ltiform e. C linical ex p e rien ce with 11 patients. JAMA 1983;249:2810. 2. Chanda JJ, Callen JR Erythema multiforme and th e S tev en s-J o h n so n S y n d ro m e. S o u th M ed J 1978;71:566. 3. Jensen JL. Acute episodic inflammatory lesions o f the mucous membrane and skin. JADA 1980;100:896. 4. Schafer WG, H ine MK, Levy BM. A textbook o f oral p ath ology. 4th e d . P h ila d e lp h ia : Saunders; 1983:817. 5. Rees T. Phenothiazine— another possible etiologic agent in erythema muldforme: report o f case. J Peri odontal 1985; 56:480. 6. Lozada-Nur F, Gorsky M, Silverman S. Oral ery them a multiform e: C linical observations and treat m ent o f 95 patients. Oral Surg Oral Med Oral Pathol 1989; 67:36. 7. Al-Ubaidy SS, Nally FF. Erythem a m ultiform e: review o f twenty-six cases. Oral Surg Oral Med Oral Pathol 1976;41:601. 8. Tonnesen M, Sorter N. Erythema multiforme. J Am Acad Dermatol 1979; 1:357-64. 9. Lewis MA, Lamey PJ, Forsyth A, Gall J. Recurrent erythema multiforme: a possible role o f food stuffs. Br D entJ 1989;166:371. 10. Pandi DN. H erpetic erythem a m ultiform e. Br MedJ 1964;1:746. 11. Shelley WB. Herpes simplex virus as a cause o f erythema multiforme. JAMA 1967;201:153. 12. Lozada F, Spitler L, Silverm an S. R esults o f im munologic testing in patients with erythema multi forme. J Dent Res 1980;59:567. 13. Buchner A, Lozada F, Silverman S. Histopatho logic spectrum o f oral erythem a m ultiform e. Oral Surg Oral Med Oral Pathol 1980;49:221. 14. Cameron AJ, Baron JH, Priestly BL. Erythema m ultiform e, drugs and ulcerative colitis. Br M ed J 1966;2:1125. 15. Ossoff R, GiuntaJL. The staphylococcal scaldedskin syndrome versus erythema multiforme. Oral Surg Oral Med Oral Pathol 1975;40:126. 16. Eversole LR. Clinical outline o f oral pathology, diagnosis and treatment. 2nd ed. Philadelphia: Lea & Febiger; 1984:36. 17. McKellar GM, Reade PC. Erythema multiforme and mycoplasma pneum oniae infection. Report and discussion o f a case presenting with stomatitis. Int J Oral Maxillo Surg 1986;15:342. 18. Kennedy CT, L eigh JM, Ridgeway HA, Wansbroughjones. Treatment o f erythema multiforme sec ondary to h erpes sim p lex by proph ylactic top ical acyclovir. Br Med J 1981; 283:1361.
JADA, Vol. 121, September 1990 ■ 437
ORAL
DISEASE
Multiple oral and skin lesions occurring after treatment with penicillin
Lauri R. Staretz, DDS Gayle Wallace DeBoom, DDS 28 -year-o ld m ale was r e fe r r e d to th e dental clinic fo r evaluation o f multiple, p a in fu l o ra l u lc e ra tio n s o f two d a y s ’ duration. Two weeks earlier, the patient had suf fe re d a b ee sting, w hich resu lted in localized c e llu litis o n the fo o t. F o r this p ro b le m , the patient has been taking penicillin, 250 mg, fou r tim es daily, as prescrib ed by a physician. T h e patient reported that he had developed sim ilar le s io n s o n o n e o th e r o c c a s io n , a n d h e h a d un d ergo n e a skin biopsy at an oth er hospital to establish a d efin itive d iagn osis. T h o se lesions had also o ccu rred after penicillin therapy.
A
b ra n e (F ig 1 ) . T h e v e rm ilio n b o rd e r o f the lower lip was ulcerated and partially covered by a hem orrh agic crust. Partially collapsed bullae and focal ulcerations w ere seen on the an terior part o f the tongue (Fig 2). A num ber o f skin lesions w ere also noted, dis tributed prim arily over the knees, elbows, and d o r s a l s u r fa c e s o f th e h a n d s . T h e le s io n s appeared as dusky purple-red papules and mac ules; m any showed a peripheral, pale red zone, surrou n ded by a darker red, m ore narrow ring (Fig 3).
Diagnosis Report of case At the time o f clinical exam ination, the patient was afebrile, and no regional lym phadenopathy was d etected . O ral exam in atio n d isclosed d if fuse m ucosal eryth em a and ed em a with large, irreg u larly shaped , shallow u lceration s on the b u cc al a n d la b ial m u cosa, an d gin giva. M ost such areas w ere overlaid by gray pseudom em
A lthough the previous biopsy was not available fo r review, the patient reported that it had been interpreted as erythem a m ultiform e (with clini cal correlatio n ). B ased on the cu rren t clinical findings and history o f recen t penicillin inges tion, cou pled with the history o f a sim ilar condi tion developing earlier after penicillin therapy, a diagnosis o f erythem a m ultiform e was m ade.
Fig 1 ■ Shallow, pseudomembrane-covered ulcer
Fig 2 ■ Ulcerated, crusted appearance o f vermil-
ations occurring on the edematous labial mucosa
ion border o f the lip.
and gingiva.
436 ■ JADA, Vol. 121, September 1990
T o p ical viscous lid o cain e an d a soft, bland d iet w ere prescribed to alleviate the p a tien t’s d is c o m fo r t . H e w as in s t r u c t e d to r e t u r n prom ptly if he did n o t im prove o r if symptoms b ecam e w orse. W hen the p atien t re tu rn e d 3 weeks later, all skin and oral lesions cleared.
Discussion E ryth em a m ultiform e (EM ) is an acute, often recurrent, inflam m atory disorder characterized in its m ildest fo rm by skin lesion s an d, in its m ost severe fo rm , as a life-th reaten in g con di tion (Stevens-Johnson syn drom e) that affects the skin, mouth, eyes, and gen italia.1-2 Erythem a m ultiform e may occur at any age, although the condition is reported to o ccu r in you ng males m ost com monly.2’3 T h e disease is characterized by rapidly devel oping lesions that usually heal without scarring, and the lesions are distributed in a symmetrical pattern over the skin, o cc u rrin g prim arily on the hands, feet, arms, legs, face, and neck. T he
Fig 3 ■ “Target” lesions o f skin (right and left),
D I A G N O S I N G
lesions appear as 1- to 2- cm, red or violet papules, macules, vesicles, and bullae, often with one or more peripheral concentric rings. T hese characteristic lesions are comm only referred to as “iris,” “target,” or “bull’s-eye” lesions. The lesions fade and eventually clear in 1 to 2 weeks.4 Mucous membranes characteristically show areas o f macular erythema, vésiculation, and edema. The oral bullae and vesicles rupture to form painful, shallow, pseudomembrane-covered ulcers. Hemorrhagic crusts may form on the lips.5 A prodromal period o f 1 to 14 days may occur, in which the patient experiences fever, malaise, sore throat, cough, and muscular aches (myalgias) .3 Patients may remain mildly febrile throughout the course o f the illness, or in severe cases, may be seriously ill. Erythema multiforme may have an acute or chronic pattern of occurrence. Lozada-Nur, Gorsky, and Silverman6 found that 73% of one series of patients had a noncyclic (chronic) pat tern o f occurrence. Those with self-limiting attacks experienced episodes o f 3 to 21 days duration. Interestingly, an increased incidence o f occurrence of erythema multiforme in the spring and fall seasons has been described among individuals experiencing recurrent, self limited attacks.2 The etiology o f erythem a m ultiform e is unclear. A significant number of cases exist in which the disease appears to be spontaneous, and the patients are unable to relate any spe cific agent or event to development of the dis ease. In som e cases, erythem a m ultiform e appears to represent a hypersensitivity reaction to a variety of causes including viruses, systemic diseases, neoplasms, radiation therapy, diseases o f connective tissue, severe emotional distur bances, prescription medications, and food preservatives.179 Pandi10 and Shelley11 consider herpes sim plex virus infection as the most common precip itating agent, usually preceding the onset of erythema multiforme by 1 to 3 weeks. Other researchers have proposed a defect in cellular immune reactivity as the cause o f erythema m u ltiform e, notin g a significantly lower response to delay hypersensitivity skin testing in affected patients.12 Histologic features of erythema multiforme include intracellular edema of the spinous layer of epithelium, intra- and subepithelial vesicle formation, and a primarily chronic inflamma tory cell infiltrate of varying intensity.4 These features are nonspecific, and Buchner and others13 have reported that the main value of performing a biopsy is to rule out other condi tions in the differential diagnosis. The differential diagnosis includes other
vesiculobullous and desquamative lesions. Ery them a m ultiform e-like lesio n s som etim es develop in patients who are receiving gold ther apy for rheumatoid arthritis.14 Staphylococcal scalded-skin syndrome, a disease of infants that occurs after staphylococcus infection, is charac terized by large bullae and skin lesions resem blin g erythem a m u ltiform e.15 R ecurrent aphthous stomatitis, bullous and mucous mem brane pemphigoid, herpetic gingivostomatitis, bullous and erosive lichen planus, pemphigus vulgaris, Behcet and Reiter syndromes, contact dermatitis, acute necrotizing ulcerative gingivi tis, dermatitis herpetiformis, chicken pox, and toxic epidermal necrolysis are other disease entities that may be included in the differential diagnosis.51617 Diagnosis of erythema multiforme is based on the sudden d evelop m en t o f skin and mucosal lesions showing a symmetrical distribu tion and the characteristic features of “target” lesions, coupled with a biopsy showing the pre viously described, nonspecific histologic fea tures that help to rule out other diseases.3 Treatment of the disease is related to severity. The conventional treatment is systemic and/or topical corticosteroids. Systemic antibiotics may be prescribed to control secondary infection. Prophylactic use o f acyclovir has been investi gated but has not significantly decreased the number of outbreaks of erythema multiforme in affected individuals.13 Fluid intake must be maintained, and a soft diet and nutritional supplements should be pre scribed. Topical anesthetics or an oral rinse con sisting of equal parts of diphenhydramine HCL and Koalin and Pectin oral suspension (Kaopectate, Upjohn) may also increase patient com fort.
Summary A case o f erythema multiforme has been pre sented. Erythema multiforme may be a self-limiting or chronic disease, of varying severity. The disease is of significance to dental practitioners who may be called on to establish a diagnosis and provide appropriate referral or treatment, especially when lesion s are lim ited to the m outh. The prognosis is generally good, although recurrence is common.
_ _ -------------- j a
q a
-----------------------
The publication o f this series is coordinated by the Western Dental Education Center, West Los Angeles VA Medical Center, Los Angeles, and is supported by the Department o f Veterans Affairs and by the Ameri can Dental Association. The opinions and assertions contained herein are those o f the authors and are not to be construed as official or necessarily representing
O R A L
D I S E A S E
the views o f the Department o f Veterans Affairs. Dr. S taretz is c h ie f r e s id e n t in p e r io d o n t ic s, Wadsworth Division Dental Service, West Los Angeles VA Medical Center, Los Angeles. Dr. DeBoom is assis tant director, Western Dental Education Center (161), West Los A ngeles VA M edical Center, W ilshire and Sawtelle blvds, Los Angeles, CA 90073, and attending staff in oral pathology, Long Beach Va Medical Center, and a ssista n t c lin ic a l p r o fe sso r , d e p a r tm e n t o f medicine and surgery, University o f California School o f Medicine, Irving, CA. Address requests for reprints to Dr. DeBoom.
1. Bean SF, Quezada RK. Recurrent oral erythema m u ltiform e. C linical ex p e rien ce with 11 patients. JAMA 1983;249:2810. 2. Chanda JJ, Callen JR Erythema multiforme and th e S tev en s-J o h n so n S y n d ro m e. S o u th M ed J 1978;71:566. 3. Jensen JL. Acute episodic inflammatory lesions o f the mucous membrane and skin. JADA 1980;100:896. 4. Schafer WG, H ine MK, Levy BM. A textbook o f oral p ath ology. 4th e d . P h ila d e lp h ia : Saunders; 1983:817. 5. Rees T. Phenothiazine— another possible etiologic agent in erythema muldforme: report o f case. J Peri odontal 1985; 56:480. 6. Lozada-Nur F, Gorsky M, Silverman S. Oral ery them a multiform e: C linical observations and treat m ent o f 95 patients. Oral Surg Oral Med Oral Pathol 1989; 67:36. 7. Al-Ubaidy SS, Nally FF. Erythem a m ultiform e: review o f twenty-six cases. Oral Surg Oral Med Oral Pathol 1976;41:601. 8. Tonnesen M, Sorter N. Erythema multiforme. J Am Acad Dermatol 1979; 1:357-64. 9. Lewis MA, Lamey PJ, Forsyth A, Gall J. Recurrent erythema multiforme: a possible role o f food stuffs. Br D entJ 1989;166:371. 10. Pandi DN. H erpetic erythem a m ultiform e. Br MedJ 1964;1:746. 11. Shelley WB. Herpes simplex virus as a cause o f erythema multiforme. JAMA 1967;201:153. 12. Lozada F, Spitler L, Silverm an S. R esults o f im munologic testing in patients with erythema multi forme. J Dent Res 1980;59:567. 13. Buchner A, Lozada F, Silverman S. Histopatho logic spectrum o f oral erythem a m ultiform e. Oral Surg Oral Med Oral Pathol 1980;49:221. 14. Cameron AJ, Baron JH, Priestly BL. Erythema m ultiform e, drugs and ulcerative colitis. Br M ed J 1966;2:1125. 15. Ossoff R, GiuntaJL. The staphylococcal scaldedskin syndrome versus erythema multiforme. Oral Surg Oral Med Oral Pathol 1975;40:126. 16. Eversole LR. Clinical outline o f oral pathology, diagnosis and treatment. 2nd ed. Philadelphia: Lea & Febiger; 1984:36. 17. McKellar GM, Reade PC. Erythema multiforme and mycoplasma pneum oniae infection. Report and discussion o f a case presenting with stomatitis. Int J Oral Maxillo Surg 1986;15:342. 18. Kennedy CT, L eigh JM, Ridgeway HA, Wansbroughjones. Treatment o f erythema multiforme sec ondary to h erpes sim p lex by proph ylactic top ical acyclovir. Br Med J 1981; 283:1361.
JADA, Vol. 121, September 1990 ■ 437