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Rash and fever
The Journal of Emergency Medicine, Vol. 31, No. 3, pp. 293–297, 2006 Copyright © 2006 Elsevier Inc. Printed in the USA. All rights reserved 0736-4679/06 $–see front matter
Case Presentations of the Harvard Emergency Medicine Residency
RASH AND FEVER David J. McCann,
MD*,
Eric S. Nadel,
MD,†‡
and David F. M. Brown,
MD‡
*Division of Emergency Medicine, Harvard Medical School, Boston, Massachusetts, †Department of Emergency Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, and ‡Department of Emergency Medicine, Massachusetts General Hospital, Boston, Massachusetts Reprint Address: Eric S. Nadel, MD, Department of Emergency Medicine, Brigham and Women’s Hospital, 75 Francis Street, Boston, MA 02115
Dr. David McCann: Today’s case is that of a 20-yearold woman who presented to the Emergency Department (ED) with complaint of an allergic reaction. The patient was in her usual state of health until 2 days prior, when she presented to an outside ED complaining of redness and watery discharge of the eyes, swelling and pain of the lips, and sore throat. At that time, she was diagnosed with an “allergic reaction” and was treated with acetaminophen and oxycodone for pain and sent home. Since that time, her symptoms worsened, and she developed sloughing of the lips, purulent appearing discharge of the eyes, mild cough, shortness of breath, fever to 38.3°C (101°F), and a rash. Review of systems was otherwise negative. Dr. Eric Nadel: Are there any questions about the patient’s history of present illness? Dr. Derek Barclay: Where did the rash start and was it pruritic or painful? Dr. McCann: The rash was first noted distally on the hands and arms, and then spread centripetally to the chest and back. The rash was mildly pruritic and painless, although the sloughing on the lips was painful. Dr. Todd Listwa: Did the patient have any other medical history, any recent new medications, any sick contacts, or any travel history? Dr. McCann: The patient reported that 3 weeks prior to the onset of symptoms, she had started to take an over-the-counter diet pill. Additionally, she had her first intra-muscular injection of medroxyprogesterone acetate
(Depo provera) 3 months prior to her presentation. She denied any other new medications prior to onset of her symptoms. She lived in a college dormitory but had no sick contacts or recent travel. Her only other medical history was chickenpox at age 4 years. Upon arrival in the ED, vital signs were: temperature 38.7°C, blood pressure 124/60 mm Hg, heart rate 124 beats/min, respiratory rate 16 breaths/min, and oxygen saturation 99% on room air. In general, the patient was alert, uncomfortable but in no acute distress. The head and neck examination revealed scattered erythematous papules and small pustules on the face consistent with acne. There was a bilateral mucopurulent discharge of the eyes with conjunctival erythema (Figure 1). The patient had full thickness desquamation of the lips with mucosal edema (Figure 2), cobblestone-like papules, and scattered 3–5-mm oral ulcers of the hard palate and buccal mucosa. Examination of the chest revealed clear lungs bilaterally, and the heart examination revealed tachycardia without murmurs, rubs, or gallops. The abdomen was soft and benign. The skin examination revealed 2– 4-mm erythematous, blanching papules on the chest (Figure 3) and upper back, some of which had a darker center. On the upper extremities were scattered 2–3-mm erythematous, non-targetlike, blanching macules on the palms bilaterally (Figure 4). The neurological examination was normal. Dr. Robert Miller: What was your differential diagnosis and initial diagnostic workup?
Case Presentations of the Harvard Emergency Medicine Residency are coordinated by David F. M. Brown, MD, and Eric S. Nadel, MD, of Harvard University Medical School, Boston, Massachusetts 293
294
D. McCann et al.
Figure 2. Reveals desquamation of the lips with mucosal edema.
Erythema multiforme (EM) is a dermatosis that derives its name from its characteristic target-shaped lesions. The classification of EM and its relation to SJS and TEN is in flux, and for that reason differentiating them can be a challenge. Historically, EM has been divided into EM minor and EM major. EM minor is a localized skin eruption with characteristic target lesions. EM major includes these lesions, but may include inflammatory lesions of mucosal surfaces. Oral mucosal surfaces are the most common, including hemorrhagic crusting of lips and ulceration of the non-keratinized mucosa. Ocular mucosal inflammation may include conjunctivitis, lacrimation, photophobia, and purulent eye discharge. Uro-
Figure 1. Reveals mucopurulent discharge of the eye with conjunctival erythema.
Dr. McCann: Given the patient’s dermatologic complaints, our differential diagnosis included erythema multiforme major (EMM), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN).
Figure 3. Reveals erythematous, blanching papules on the chest.
Rash and Fever
Figure 4. Reveals erythematous, blanching macules on the palms.
genital mucosa involvement can cause itching or burning. EM major is often preceded 1–14 days by a clinical prodrome of fever, malaise, cough, pharyngitis, chest pain, gastrointestinal discomfort, nausea and vomiting. Erythema multiforme has historically been considered to exist on a spectrum of disease with Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). In the past, EM major was considered synonymous with SJS; SJS and TEN also have been labeled as variants of the same disease (1,2). However, the most current clinical classification scheme differentiates EM, SJS, and TEN based on the percent of body area affected by desquamation, and the type of lesions identified (typical target lesions, atypical flat target lesions, macules, or large epidermal sheets) (3,4) (Table 1). The appearance and distribution of the patient’s rash was most consistent with EM. Our initial diagnostic workup included a complete blood count, which revealed a white blood cell count 13 K/mm3, hematocrit of 38%, and platelets 226 K/mm3. Electrolytes and liver function tests were normal. Urinalysis was normal, and pregnancy test was negative. The initial workup also included chest X-ray study and blood cultures. Serologies were sent to investigate the possibility of occult mycoplasma infection (IgG and IgM). Additionally, herpes simplex virus (HSV) oral mucosa swabs, and IgG and IgM serologies were sent. Culture and Gram’s stain of the eye discharge was sent. Dr. Barclay: What are the causative agents for EM, and did you identify a causative agent for this patient?
295
Dr. McCann: Infection and drugs have been implicated in EM. HSV antigens have been demonstrated to occur with much greater frequency in EM lesions (5). EM minor can be attributed in almost 100% of cases to Herpes simplex virus infection. EM major can be attributed in approximately 55% of cases to HSV, with the next most common cause being Mycoplasma infection. Prior association of EM with certain medications is confounded by the fact that until recently there was thought to be little distinction between SJS and EM major. The most common drugs implicated in EM, TEN, and SJS include antibiotics (sulfonamides, penicillins), anticonvulsants (carbamazepine, phenytoin), and aspirin. It has been proposed also that drug-virus interactions may be a cause of some cases of EM (6). The patient had no history of HSV. As for medications, the diet pill that the patient began 3 weeks prior was never identified. Erythema multiforme has been linked to oral contraceptive use in the past, but it has not been linked to use of medroxyprogesterone acetate, which the patient had started 3 months prior (7,8). Dr. Listwa: Is there any role for dermatology consultation or biopsy to confirm the diagnosis? Dr. McCann: For the emergency physician, acute tissue diagnosis is typically unavailable. History and physical examination are sufficient to make the diagnosis of EM. However, if biopsy is performed, EM typically shows partial thickness T-cell rich lymphocytic infiltration of the dermal-epidermal junction, whereas more advanced lesions may show full thickness epidermal necrosis, subepidermal blistering, and (particularly in drug-related cases) eosinophilic inflammation. SJS typically shows mononuclear and eosinophilic infiltration, and sometimes blister formation. TEN is characterized early by infiltration of the papillary dermis with T lymphocytes, and later by full thickness epidermal necrosis, which has been described as both eosinophilic and cellpoor (9). Although there is overlap in the types and patterns of inflammation and necrosis demonstrated in EM, SJS, and TEN, studies have demonstrated significant variation between patients clinically diagnosed with each (10).
Table 1. Classification Summary EM
SJS
TEN
% BSA ⬍ 10 ⬍ 10 10–30 Lesions Target lesions Erythematous or Macules, flat or raised purpuric macules; atypical targets, atypical or flat atypical or large target target lesions epidermal lesions sheets. EM ⫽ erythema multiforme; SJS ⫽ Stevens-Johnson syndrome; TEN ⫽ toxic epidermal necrolysis; BSA ⫽ body surface area.
296
Dr. David Peak: How common is erythema multiforme and which patients are at risk? Dr. McCann: EM is common, and has been reported as the chief complaint for up to 1% of dermatologic outpatient visits. Estimates of its annual incidence are variable, and have been reported between 0.1% and 1% (11). Males are affected slightly more often than females. The highest incidence occurs in patients in their teens to 30s. Dr. Mariah McNamara: What is the initial Emergency Department treatment? Dr. McCann: The mainstay of treatment of EM is diagnosis and withdrawal of any presumed causative agent, treating potential underlying infection, symptomatic treatment, and appropriate admission and consultation. Our initial therapy was symptomatic and supportive: fluid resuscitation for dehydration, acetaminophen for fever, and viscous lidocaine for odynophagia. We started empiric treatment with acyclovir for a possible viral etiology. Because of her fever and respiratory complaints we empirically started ceftriaxone and doxycycline for possible atypical pneumonia. Additionally, we treated her for possible purulent conjunctivitis with erythromycin ophthalmic ointment. At the recommendation of dermatology, the patient was also treated with intravenous steroids. The level of evidence for these treatments is variable. Empiric treatment with acyclovir and valcyclovir has shown benefit in small series and case reports for patients with recurrent EM (12–14). One placebo-controlled study demonstrated its efficacy at suppressing recurrent EM (15). For this reason, it is recommended as a prophylactic medication for patients with recurrent EM, although its role for acute EM is not defined. Steroids for EM are controversial. Although one randomized trial showed symptomatic improvement in children, there is no evidence for improved morbidity or mortality in any population (16,17). There is no evidence for empiric treatment of mycoplasma in the absence of a concurrent mycoplasma infection. Dr. Benjamin White: What is the prognosis for patient with EM, and from what complications can they suffer? Dr. McCann: The prognosis for these patients is excellent, though there is infrequent morbidity and mortality. EM usually takes a benign and self-limited course and resolves over 3– 6 weeks. Skin lesions heal, though hyper- or hypopigmentation of the healed skin is common. Mortality for EM has been reported as high as 5%, although more recent distinctions between EM major and SJS suggest that these fatalities were patients with SJS. Complications from ocular mucosal inflammation also can cause morbidity. Superinfection of inflamed conjunctiva can cause a purulent conjunctivitis to develop.
D. McCann et al.
Blindness can occur in severe cases. Urethral and vaginal stenoses can occur but are rare (18). Urinary retention due to dysuria and phimosis also has been reported. Recurrence of EM is relatively common, occurring in up to 30% of cases, whereas recurrence of SJS and TEN is rare and typically occurs only upon exposure to the offending medication (19). The patient was admitted to the dermatology service, with consultations from ophthalmology and infectious disease. Blood cultures and serologic testing showed no evidence of acute infection. The immunoglobulin serologies for Epstein-Barr virus and Varicella Zoster virus suggested prior infection. Notably, the patient had a monospot done at the original institution where she presented, which was positive. Culture discharge from the right eye was polymicrobial with coagulase negative staphylococcus and alpha hemolytic streptococcus, both likely contaminants of skin flora. Culture of oral mucosa for HSV was negative. Urine culture revealed ⬎ 100,000 CFU of gardnerella vaginallis. On recommendation of the infectious disease consultants, ceftriaxone and doxycycline were discontinued. Ophthalmologic consultation was also obtained, and corneal inspection revealed small corneal abrasions, which were treated with artificial tears and erythromycin ointment. The patient was maintained on oral prednisone and discharged on a prednisone taper for a total duration of therapy of 3 weeks. Her other discharge medications included valcyclovir for empiric HSV treatment; erythromycin ophthalmologic ointment and artificial tears for conjunctivitis; and viscous lidocaine and nystatin suspension for odynophagia. At last report the patient had a full recovery of her rash and was feeling well. REFERENCES 1. Roujeau JC. Stevens-Johnson syndrome and toxic epidermal necrolysis are severity variants of the same disease which differs from erythema multiforme. J Dermatol 1997;24:726 –9. 2. Roujeau JC, Stern RS. Severe adverse cutaneous reactions to drugs. N Engl J Med 1994;331:1272– 85. 3. Assier H, Bastuji-Garin S, Revuz J, Roujeau JC. Erythema multiforme with mucous membrane involvement and Stevens-Johnson syndrome are clinically different disorders with distinct causes. Arch Dermatol 1995;131:539 – 43. 4. Bastuji-Garin S, Rzany B, Stern RS, Shear NH, Naldi L, Roujeau JC. Clinical classification of cases of toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme. Arch Dermatol 1993;129:92– 6. 5. Orton PW, Huff JC, Tonnesen MG, Weston WL. Detection of a herpes simplex viral antigen in skin lesions of erythema multiforme. Ann Intern Med 1984;101:48 –50. 6. Carducci M, Latini A, Acierno F, Amantea A, Capitanio B, Santucci B. Erythema multiforme during cytomegalovirus infection and oral therapy with terbinafine: a virus-drug interaction. J Eur Acad Dermatol Venereol 2004;18:201–3. 7. Krueger GG, Mcquarrie HG, Swinyer LJ. Desirable and undesirable cutaneous effects of oral contraceptives. Drug Ther (NY) 1977;7:46 – 8.
Rash and Fever 8. Suzuki R, Matsumura Y, Kambe N, Fujii H, Tachibana T, Miyachi Y. Erythema multiforme due to progesterone in a low-dose oral contraceptive pill. Br J Dermatol 2005;152:370 –1. 9. Paquet P, Pierard GE. Erythema multiforme and toxic epidermal necrolysis: a comparative study. Am J Dermatopathol 1997;19:127–32. 10. Cote B, Wechsler J, Bastuji-Garin S, Assier H, Revuz J, Roujeau JC. Clinicopathologic correlation in erythema multiforme and Stevens-Johnson syndrome. Arch Dermatol 1995;131:1268 –72. 11. Huff JC, Weston WL, Tonnesen MG. Erythema multiforme: a critical review of characteristics, diagnostic criteria, and causes. J Am Acad Dermatol 1983;8:763–5. 12. Schofield JK, Tatnall FM, Leigh IM. Recurrent erythema multiforme: clinical features and treatment in a large series of patients. Br J Dermatol 1993;128:542–5. 13. Kerob D, Assier-Bonnet H, Esnault-Gelly P, Blanc F, Saiag P. Recurrent erythema multiforme unresponsive to acyclovir prophylaxis and responsive to valacyclovir continuous therapy. Arch Dermatol 1998;134:876 –7.
297 14. Lynn WA, Davidson RN, Wansbrough-Jones MH. Successful use of oral acyclovir to prevent herpes simplex-associated erythema multiforme. J Infect 1987;15:192–3. 15. Tatnall FM, Schofield JK, Leigh IM. A double-blind, placebocontrolled trial of continuous acyclovir therapy in recurrent erythema multiforme. Br J Dermatol 1995;132:267–70. 16. Kakourou T, Klontza D, Soteropoulou F, Kattamis C. Corticosteroid treatment of erythema multiforme major in children. Eur J Pediatr 1997;156:90 –3. 17. Rasmussen JE. Erythema multiforme in children. Response to treatment with systemic corticosteroids. Br J Dermatol 1976;95: 181– 6. 18. Graham-Brown PA. Vaginal stenosis due to bullous erythema multiforme (Stevens-Johnson syndrome). Case report. Br J Obstet Gynaecol 1981;88:1156 –7. 19. Bachot N, Roujeau JC. Differential diagnosis of severe cutaneous drug eruptions. Am J Clin Dermatol 2003;4:561–72.
Case Presentations of the Harvard Emergency Medicine Residency
RASH AND FEVER David J. McCann,
MD*,
Eric S. Nadel,
MD,†‡
and David F. M. Brown,
MD‡
*Division of Emergency Medicine, Harvard Medical School, Boston, Massachusetts, †Department of Emergency Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, and ‡Department of Emergency Medicine, Massachusetts General Hospital, Boston, Massachusetts Reprint Address: Eric S. Nadel, MD, Department of Emergency Medicine, Brigham and Women’s Hospital, 75 Francis Street, Boston, MA 02115
Dr. David McCann: Today’s case is that of a 20-yearold woman who presented to the Emergency Department (ED) with complaint of an allergic reaction. The patient was in her usual state of health until 2 days prior, when she presented to an outside ED complaining of redness and watery discharge of the eyes, swelling and pain of the lips, and sore throat. At that time, she was diagnosed with an “allergic reaction” and was treated with acetaminophen and oxycodone for pain and sent home. Since that time, her symptoms worsened, and she developed sloughing of the lips, purulent appearing discharge of the eyes, mild cough, shortness of breath, fever to 38.3°C (101°F), and a rash. Review of systems was otherwise negative. Dr. Eric Nadel: Are there any questions about the patient’s history of present illness? Dr. Derek Barclay: Where did the rash start and was it pruritic or painful? Dr. McCann: The rash was first noted distally on the hands and arms, and then spread centripetally to the chest and back. The rash was mildly pruritic and painless, although the sloughing on the lips was painful. Dr. Todd Listwa: Did the patient have any other medical history, any recent new medications, any sick contacts, or any travel history? Dr. McCann: The patient reported that 3 weeks prior to the onset of symptoms, she had started to take an over-the-counter diet pill. Additionally, she had her first intra-muscular injection of medroxyprogesterone acetate
(Depo provera) 3 months prior to her presentation. She denied any other new medications prior to onset of her symptoms. She lived in a college dormitory but had no sick contacts or recent travel. Her only other medical history was chickenpox at age 4 years. Upon arrival in the ED, vital signs were: temperature 38.7°C, blood pressure 124/60 mm Hg, heart rate 124 beats/min, respiratory rate 16 breaths/min, and oxygen saturation 99% on room air. In general, the patient was alert, uncomfortable but in no acute distress. The head and neck examination revealed scattered erythematous papules and small pustules on the face consistent with acne. There was a bilateral mucopurulent discharge of the eyes with conjunctival erythema (Figure 1). The patient had full thickness desquamation of the lips with mucosal edema (Figure 2), cobblestone-like papules, and scattered 3–5-mm oral ulcers of the hard palate and buccal mucosa. Examination of the chest revealed clear lungs bilaterally, and the heart examination revealed tachycardia without murmurs, rubs, or gallops. The abdomen was soft and benign. The skin examination revealed 2– 4-mm erythematous, blanching papules on the chest (Figure 3) and upper back, some of which had a darker center. On the upper extremities were scattered 2–3-mm erythematous, non-targetlike, blanching macules on the palms bilaterally (Figure 4). The neurological examination was normal. Dr. Robert Miller: What was your differential diagnosis and initial diagnostic workup?
Case Presentations of the Harvard Emergency Medicine Residency are coordinated by David F. M. Brown, MD, and Eric S. Nadel, MD, of Harvard University Medical School, Boston, Massachusetts 293
294
D. McCann et al.
Figure 2. Reveals desquamation of the lips with mucosal edema.
Erythema multiforme (EM) is a dermatosis that derives its name from its characteristic target-shaped lesions. The classification of EM and its relation to SJS and TEN is in flux, and for that reason differentiating them can be a challenge. Historically, EM has been divided into EM minor and EM major. EM minor is a localized skin eruption with characteristic target lesions. EM major includes these lesions, but may include inflammatory lesions of mucosal surfaces. Oral mucosal surfaces are the most common, including hemorrhagic crusting of lips and ulceration of the non-keratinized mucosa. Ocular mucosal inflammation may include conjunctivitis, lacrimation, photophobia, and purulent eye discharge. Uro-
Figure 1. Reveals mucopurulent discharge of the eye with conjunctival erythema.
Dr. McCann: Given the patient’s dermatologic complaints, our differential diagnosis included erythema multiforme major (EMM), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN).
Figure 3. Reveals erythematous, blanching papules on the chest.
Rash and Fever
Figure 4. Reveals erythematous, blanching macules on the palms.
genital mucosa involvement can cause itching or burning. EM major is often preceded 1–14 days by a clinical prodrome of fever, malaise, cough, pharyngitis, chest pain, gastrointestinal discomfort, nausea and vomiting. Erythema multiforme has historically been considered to exist on a spectrum of disease with Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). In the past, EM major was considered synonymous with SJS; SJS and TEN also have been labeled as variants of the same disease (1,2). However, the most current clinical classification scheme differentiates EM, SJS, and TEN based on the percent of body area affected by desquamation, and the type of lesions identified (typical target lesions, atypical flat target lesions, macules, or large epidermal sheets) (3,4) (Table 1). The appearance and distribution of the patient’s rash was most consistent with EM. Our initial diagnostic workup included a complete blood count, which revealed a white blood cell count 13 K/mm3, hematocrit of 38%, and platelets 226 K/mm3. Electrolytes and liver function tests were normal. Urinalysis was normal, and pregnancy test was negative. The initial workup also included chest X-ray study and blood cultures. Serologies were sent to investigate the possibility of occult mycoplasma infection (IgG and IgM). Additionally, herpes simplex virus (HSV) oral mucosa swabs, and IgG and IgM serologies were sent. Culture and Gram’s stain of the eye discharge was sent. Dr. Barclay: What are the causative agents for EM, and did you identify a causative agent for this patient?
295
Dr. McCann: Infection and drugs have been implicated in EM. HSV antigens have been demonstrated to occur with much greater frequency in EM lesions (5). EM minor can be attributed in almost 100% of cases to Herpes simplex virus infection. EM major can be attributed in approximately 55% of cases to HSV, with the next most common cause being Mycoplasma infection. Prior association of EM with certain medications is confounded by the fact that until recently there was thought to be little distinction between SJS and EM major. The most common drugs implicated in EM, TEN, and SJS include antibiotics (sulfonamides, penicillins), anticonvulsants (carbamazepine, phenytoin), and aspirin. It has been proposed also that drug-virus interactions may be a cause of some cases of EM (6). The patient had no history of HSV. As for medications, the diet pill that the patient began 3 weeks prior was never identified. Erythema multiforme has been linked to oral contraceptive use in the past, but it has not been linked to use of medroxyprogesterone acetate, which the patient had started 3 months prior (7,8). Dr. Listwa: Is there any role for dermatology consultation or biopsy to confirm the diagnosis? Dr. McCann: For the emergency physician, acute tissue diagnosis is typically unavailable. History and physical examination are sufficient to make the diagnosis of EM. However, if biopsy is performed, EM typically shows partial thickness T-cell rich lymphocytic infiltration of the dermal-epidermal junction, whereas more advanced lesions may show full thickness epidermal necrosis, subepidermal blistering, and (particularly in drug-related cases) eosinophilic inflammation. SJS typically shows mononuclear and eosinophilic infiltration, and sometimes blister formation. TEN is characterized early by infiltration of the papillary dermis with T lymphocytes, and later by full thickness epidermal necrosis, which has been described as both eosinophilic and cellpoor (9). Although there is overlap in the types and patterns of inflammation and necrosis demonstrated in EM, SJS, and TEN, studies have demonstrated significant variation between patients clinically diagnosed with each (10).
Table 1. Classification Summary EM
SJS
TEN
% BSA ⬍ 10 ⬍ 10 10–30 Lesions Target lesions Erythematous or Macules, flat or raised purpuric macules; atypical targets, atypical or flat atypical or large target target lesions epidermal lesions sheets. EM ⫽ erythema multiforme; SJS ⫽ Stevens-Johnson syndrome; TEN ⫽ toxic epidermal necrolysis; BSA ⫽ body surface area.
296
Dr. David Peak: How common is erythema multiforme and which patients are at risk? Dr. McCann: EM is common, and has been reported as the chief complaint for up to 1% of dermatologic outpatient visits. Estimates of its annual incidence are variable, and have been reported between 0.1% and 1% (11). Males are affected slightly more often than females. The highest incidence occurs in patients in their teens to 30s. Dr. Mariah McNamara: What is the initial Emergency Department treatment? Dr. McCann: The mainstay of treatment of EM is diagnosis and withdrawal of any presumed causative agent, treating potential underlying infection, symptomatic treatment, and appropriate admission and consultation. Our initial therapy was symptomatic and supportive: fluid resuscitation for dehydration, acetaminophen for fever, and viscous lidocaine for odynophagia. We started empiric treatment with acyclovir for a possible viral etiology. Because of her fever and respiratory complaints we empirically started ceftriaxone and doxycycline for possible atypical pneumonia. Additionally, we treated her for possible purulent conjunctivitis with erythromycin ophthalmic ointment. At the recommendation of dermatology, the patient was also treated with intravenous steroids. The level of evidence for these treatments is variable. Empiric treatment with acyclovir and valcyclovir has shown benefit in small series and case reports for patients with recurrent EM (12–14). One placebo-controlled study demonstrated its efficacy at suppressing recurrent EM (15). For this reason, it is recommended as a prophylactic medication for patients with recurrent EM, although its role for acute EM is not defined. Steroids for EM are controversial. Although one randomized trial showed symptomatic improvement in children, there is no evidence for improved morbidity or mortality in any population (16,17). There is no evidence for empiric treatment of mycoplasma in the absence of a concurrent mycoplasma infection. Dr. Benjamin White: What is the prognosis for patient with EM, and from what complications can they suffer? Dr. McCann: The prognosis for these patients is excellent, though there is infrequent morbidity and mortality. EM usually takes a benign and self-limited course and resolves over 3– 6 weeks. Skin lesions heal, though hyper- or hypopigmentation of the healed skin is common. Mortality for EM has been reported as high as 5%, although more recent distinctions between EM major and SJS suggest that these fatalities were patients with SJS. Complications from ocular mucosal inflammation also can cause morbidity. Superinfection of inflamed conjunctiva can cause a purulent conjunctivitis to develop.
D. McCann et al.
Blindness can occur in severe cases. Urethral and vaginal stenoses can occur but are rare (18). Urinary retention due to dysuria and phimosis also has been reported. Recurrence of EM is relatively common, occurring in up to 30% of cases, whereas recurrence of SJS and TEN is rare and typically occurs only upon exposure to the offending medication (19). The patient was admitted to the dermatology service, with consultations from ophthalmology and infectious disease. Blood cultures and serologic testing showed no evidence of acute infection. The immunoglobulin serologies for Epstein-Barr virus and Varicella Zoster virus suggested prior infection. Notably, the patient had a monospot done at the original institution where she presented, which was positive. Culture discharge from the right eye was polymicrobial with coagulase negative staphylococcus and alpha hemolytic streptococcus, both likely contaminants of skin flora. Culture of oral mucosa for HSV was negative. Urine culture revealed ⬎ 100,000 CFU of gardnerella vaginallis. On recommendation of the infectious disease consultants, ceftriaxone and doxycycline were discontinued. Ophthalmologic consultation was also obtained, and corneal inspection revealed small corneal abrasions, which were treated with artificial tears and erythromycin ointment. The patient was maintained on oral prednisone and discharged on a prednisone taper for a total duration of therapy of 3 weeks. Her other discharge medications included valcyclovir for empiric HSV treatment; erythromycin ophthalmologic ointment and artificial tears for conjunctivitis; and viscous lidocaine and nystatin suspension for odynophagia. At last report the patient had a full recovery of her rash and was feeling well. REFERENCES 1. Roujeau JC. Stevens-Johnson syndrome and toxic epidermal necrolysis are severity variants of the same disease which differs from erythema multiforme. J Dermatol 1997;24:726 –9. 2. Roujeau JC, Stern RS. Severe adverse cutaneous reactions to drugs. N Engl J Med 1994;331:1272– 85. 3. Assier H, Bastuji-Garin S, Revuz J, Roujeau JC. Erythema multiforme with mucous membrane involvement and Stevens-Johnson syndrome are clinically different disorders with distinct causes. Arch Dermatol 1995;131:539 – 43. 4. Bastuji-Garin S, Rzany B, Stern RS, Shear NH, Naldi L, Roujeau JC. Clinical classification of cases of toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme. Arch Dermatol 1993;129:92– 6. 5. Orton PW, Huff JC, Tonnesen MG, Weston WL. Detection of a herpes simplex viral antigen in skin lesions of erythema multiforme. Ann Intern Med 1984;101:48 –50. 6. Carducci M, Latini A, Acierno F, Amantea A, Capitanio B, Santucci B. Erythema multiforme during cytomegalovirus infection and oral therapy with terbinafine: a virus-drug interaction. J Eur Acad Dermatol Venereol 2004;18:201–3. 7. Krueger GG, Mcquarrie HG, Swinyer LJ. Desirable and undesirable cutaneous effects of oral contraceptives. Drug Ther (NY) 1977;7:46 – 8.
Rash and Fever 8. Suzuki R, Matsumura Y, Kambe N, Fujii H, Tachibana T, Miyachi Y. Erythema multiforme due to progesterone in a low-dose oral contraceptive pill. Br J Dermatol 2005;152:370 –1. 9. Paquet P, Pierard GE. Erythema multiforme and toxic epidermal necrolysis: a comparative study. Am J Dermatopathol 1997;19:127–32. 10. Cote B, Wechsler J, Bastuji-Garin S, Assier H, Revuz J, Roujeau JC. Clinicopathologic correlation in erythema multiforme and Stevens-Johnson syndrome. Arch Dermatol 1995;131:1268 –72. 11. Huff JC, Weston WL, Tonnesen MG. Erythema multiforme: a critical review of characteristics, diagnostic criteria, and causes. J Am Acad Dermatol 1983;8:763–5. 12. Schofield JK, Tatnall FM, Leigh IM. Recurrent erythema multiforme: clinical features and treatment in a large series of patients. Br J Dermatol 1993;128:542–5. 13. Kerob D, Assier-Bonnet H, Esnault-Gelly P, Blanc F, Saiag P. Recurrent erythema multiforme unresponsive to acyclovir prophylaxis and responsive to valacyclovir continuous therapy. Arch Dermatol 1998;134:876 –7.
297 14. Lynn WA, Davidson RN, Wansbrough-Jones MH. Successful use of oral acyclovir to prevent herpes simplex-associated erythema multiforme. J Infect 1987;15:192–3. 15. Tatnall FM, Schofield JK, Leigh IM. A double-blind, placebocontrolled trial of continuous acyclovir therapy in recurrent erythema multiforme. Br J Dermatol 1995;132:267–70. 16. Kakourou T, Klontza D, Soteropoulou F, Kattamis C. Corticosteroid treatment of erythema multiforme major in children. Eur J Pediatr 1997;156:90 –3. 17. Rasmussen JE. Erythema multiforme in children. Response to treatment with systemic corticosteroids. Br J Dermatol 1976;95: 181– 6. 18. Graham-Brown PA. Vaginal stenosis due to bullous erythema multiforme (Stevens-Johnson syndrome). Case report. Br J Obstet Gynaecol 1981;88:1156 –7. 19. Bachot N, Roujeau JC. Differential diagnosis of severe cutaneous drug eruptions. Am J Clin Dermatol 2003;4:561–72.