Laryngeal involvement in toxic epidermal necrolysis DAVID WAHLE, MD, DAVID J. BESTE, MD, and STEPHEN F. CONLEY, MD, Milwaukee, Wisconsin
Toxic epidermal necrolysis (TEN) represents the most severe form of Stevens-Johnson syndrome (SJS), a mucocutaneous reaction most frequently related to medication use. Mucosal involvement of the oral cavity is a diagnostic criterion of SJS, and involvement of the tracheobronchial mucosa has also been well-documented. To our knowledge, epiglottitis associated with TEN has been reported only once previously. I We report a case of an 8-year-old boy in whom epiglottitis in progression from SJS to TEN developed; we also provide a brief discussion of this clinical entity. CASE REPORT
A previously healthy 8-year-old boy was taken to a community emergency room with a history of two episodes of tonic clonic activity on February 21, 1990. His evaluation, including an electroencephalogram and intracranial CT scan, 'did not reveal any contributing factors. Treatment with phenytoin was begun on February 23, 1990, and the patient was' discharged. On March 4, 1990, a morbilliform rash developed on his face and chest, with no associated fever. The treatment with phenytoin was discontinued and phenobarbital was initiated, with resolution of the rash over 4 days. On March 14, 1990, the patient returned with a fine erythematous maculopapular rash on the face, chest, and extremities. The phenobarbital was discontinued and, on the following day, a lowgrade fever developed, with an associated cough and mild respiratory distress. The patient was admitted to the community hospital for Ii high fever on March 16, 1990, and was treated with intravenous cefuroxime and erythromycin. On March 17, 1990, the patient was transferred to Children's Hospital of Wisconsin with severe odynophagia, persistent fevers to 40° C, coalescence of his facial rash, and bilaterally injected sclerae. Mild respiratory distress developed over 2 to 3 hours, with increased facial swelling and dysphagia. Initial otolaryngologicevaluation revealed a drooling, febrile boy, sitting in the tripod position, with no stridor, present. The oral cavity contained a diffuse severe mucositis.
From the Department of Otolaryngology and Human Communication, Medical College of Wisconsin. Received for publication Jan. 10, 1992; revision received Aug. 14, 1992; accepted Aug. 24, 1992. Reprint requests: Stephen F. Conley, MD, 8701 West Watertown Plank Rd., MACC Building, Room 3017, Milwaukee, WI 53226.
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A lateral neck roentgenogram demonstrated enlargement of the epiglottis (Fig. 1). The impression was progressive severe mucositis involving the pharynx and supraglottis. The patient was taken to the operating room for controlled nasotracheal intubation and direct laryngoscopy. The findings included multiple areas of erythema and exudate in the hypopharynx, with moderate edema of the epiglottis, arytenoids, and aryepiglottic folds. The true and false cords were uninvolved. Swab cultures of the supraglottis subsequently grew mixed oral flora. The boy was transferred to the intensive care unit for respiratory support. Stevens-Johnson syndrome was diagnosed and intravenous steroids and diphenhydramine were administered. Later that day, a dermatology consult was obtained when the patient developedfrank vesicular eruptions across the face, body, and extremities (Fig. 2). In addition, the scleral injection progressed to a severe conjunctivitis. The diagnosis of SJS was confirmed, with the addition of phenobarbital as the inciting cause. In subsequent days, the cutaneous involvement progressed to cover more than 20% of the body surface area. The final diagnosis of TEN was then established. The patient was extubated after 3 weeks, when a leak developed around the nasotracheal tube, and there was no subsequent respiratory compromise. The cutaneous lesions healed and there were no permanent ocular sequelae. He was discharged on a regimen oflorazepam as anti-seizure therapy. DISCUSSION
Drug-induced erythema multiform minor (EM), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN) probably represent variants of the same disorder." Each is a point on the continuum of extent and severity of the mucocutaneous involvement. EM primarily involves the skin, with no significant systemic symptoms. When mucous membrane and conjunctival involvement occur, the diagnosis of Stevens-Johnson syndrome (Muco-cutaneo-ocular syndrome) is made. SJS is an acute febrile illness characterized by generalized exanthems, purulent conjunctivitis, and mucositis that primarily involve the mouth and oropharynx. This is rapidly followed by the development of vesiculobullous lesions with desquamation. Immune complex deposition and complement fixation with subsequent neutrophil lysosomal release have been implicated as part of the pathophysiologic mechanism in the development of the skin and mucous membrane'Te-
sions.'
Volume 107 Number 6 Part1 December 1992
Case Reports 797
Fig. 1. Lateral neck roentgenogram demonstrates epiglottis enlargement,
The differentiation between SJS and TEN is made primarily on the basis of the size of the individual cutaneous lesions and on the percentage of body surface area involved.Y" The criteria for: diagnosing TEN is shown in Table I. TEN represents the most severe variant with the highest mortality 'rate, depending on the percentage body surface area used for differentiation between TEN and SJS. 1,2,4-7 The overall reported mortality with EM is nearly 0%, whereas SJS has a mortality of 5% to 15% and TEN has a mortality of 25% to 30%.3,8 The origin of SJS is not fully understood; however, an idiosyncratic reaction to numerous drugs has been strongly implicated as a major cause. 2,4,6,9,10 The balance of cases are either idiopathic or related to prodromal infections, such as upper respiratory infection, nonspecific viral illness, and pneumonitis resulting from Mycoplasma pneumoniae. EM and SJS tend to have similar ratios of inciting causes; however, TEN has a much higher percentage of association with antecedent drug therapy. A 5-year nationwide retrospective study from
France of 333 cases of TEN reported only 11 patients (4.5%) with no previous drug therapy." The case described is a classic presentation of druginduced SJS with progression to TEN. Both phenytoin and phenobarbital have previously been implicated in SJS and TEN. 6•12.13 The onset is typically 1 to 3 weeks after initiation of drug therapy. In many cases, there are prodromal features, consisting of a burning sensation of the conjunctiva, skin tenderness, fever, and malaise. These symptoms are followed in 1 to 2 days by a morbilliform rash on the face, trunk, and extremities. The rash then coalesces, leading to diffuse erythema of the involved skin. Vesiculation of macular lesions may occur before or during the coalescent phase. Confluence of vesicles leads to large flaccid bullae that rupture easily and leave huge denuded areas on the trunk, shoulders, and face. Minimal pressure on intact skin in the erythematous areas easily produces further separation of the epidermis from the dermis (Nikolsky's sign).' Mucous membrane involvement can be severe; it can involve the lips, oral mucosa, conjunctiva, urethra,
OtolaryngologyHead and Neck Surgery
798 Case Reports
Fig. 2. Vesicular eruption of lower extremity skin.
Table 1. Diagnostic criteria Erythema muillforme
Stevens·Johnsonsyndrome
Toxic epidermal necrolysls
- Classic target lesions - Individual lesions
Toxic epidermal necrolysis (TEN) represents the most severe form of Stevens-Johnson syndrome (SJS), a mucocutaneous reaction most frequently related to medication use. Mucosal involvement of the oral cavity is a diagnostic criterion of SJS, and involvement of the tracheobronchial mucosa has also been well-documented. To our knowledge, epiglottitis associated with TEN has been reported only once previously. I We report a case of an 8-year-old boy in whom epiglottitis in progression from SJS to TEN developed; we also provide a brief discussion of this clinical entity. CASE REPORT
A previously healthy 8-year-old boy was taken to a community emergency room with a history of two episodes of tonic clonic activity on February 21, 1990. His evaluation, including an electroencephalogram and intracranial CT scan, 'did not reveal any contributing factors. Treatment with phenytoin was begun on February 23, 1990, and the patient was' discharged. On March 4, 1990, a morbilliform rash developed on his face and chest, with no associated fever. The treatment with phenytoin was discontinued and phenobarbital was initiated, with resolution of the rash over 4 days. On March 14, 1990, the patient returned with a fine erythematous maculopapular rash on the face, chest, and extremities. The phenobarbital was discontinued and, on the following day, a lowgrade fever developed, with an associated cough and mild respiratory distress. The patient was admitted to the community hospital for Ii high fever on March 16, 1990, and was treated with intravenous cefuroxime and erythromycin. On March 17, 1990, the patient was transferred to Children's Hospital of Wisconsin with severe odynophagia, persistent fevers to 40° C, coalescence of his facial rash, and bilaterally injected sclerae. Mild respiratory distress developed over 2 to 3 hours, with increased facial swelling and dysphagia. Initial otolaryngologicevaluation revealed a drooling, febrile boy, sitting in the tripod position, with no stridor, present. The oral cavity contained a diffuse severe mucositis.
From the Department of Otolaryngology and Human Communication, Medical College of Wisconsin. Received for publication Jan. 10, 1992; revision received Aug. 14, 1992; accepted Aug. 24, 1992. Reprint requests: Stephen F. Conley, MD, 8701 West Watertown Plank Rd., MACC Building, Room 3017, Milwaukee, WI 53226.
23/4/42751
796
A lateral neck roentgenogram demonstrated enlargement of the epiglottis (Fig. 1). The impression was progressive severe mucositis involving the pharynx and supraglottis. The patient was taken to the operating room for controlled nasotracheal intubation and direct laryngoscopy. The findings included multiple areas of erythema and exudate in the hypopharynx, with moderate edema of the epiglottis, arytenoids, and aryepiglottic folds. The true and false cords were uninvolved. Swab cultures of the supraglottis subsequently grew mixed oral flora. The boy was transferred to the intensive care unit for respiratory support. Stevens-Johnson syndrome was diagnosed and intravenous steroids and diphenhydramine were administered. Later that day, a dermatology consult was obtained when the patient developedfrank vesicular eruptions across the face, body, and extremities (Fig. 2). In addition, the scleral injection progressed to a severe conjunctivitis. The diagnosis of SJS was confirmed, with the addition of phenobarbital as the inciting cause. In subsequent days, the cutaneous involvement progressed to cover more than 20% of the body surface area. The final diagnosis of TEN was then established. The patient was extubated after 3 weeks, when a leak developed around the nasotracheal tube, and there was no subsequent respiratory compromise. The cutaneous lesions healed and there were no permanent ocular sequelae. He was discharged on a regimen oflorazepam as anti-seizure therapy. DISCUSSION
Drug-induced erythema multiform minor (EM), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN) probably represent variants of the same disorder." Each is a point on the continuum of extent and severity of the mucocutaneous involvement. EM primarily involves the skin, with no significant systemic symptoms. When mucous membrane and conjunctival involvement occur, the diagnosis of Stevens-Johnson syndrome (Muco-cutaneo-ocular syndrome) is made. SJS is an acute febrile illness characterized by generalized exanthems, purulent conjunctivitis, and mucositis that primarily involve the mouth and oropharynx. This is rapidly followed by the development of vesiculobullous lesions with desquamation. Immune complex deposition and complement fixation with subsequent neutrophil lysosomal release have been implicated as part of the pathophysiologic mechanism in the development of the skin and mucous membrane'Te-
sions.'
Volume 107 Number 6 Part1 December 1992
Case Reports 797
Fig. 1. Lateral neck roentgenogram demonstrates epiglottis enlargement,
The differentiation between SJS and TEN is made primarily on the basis of the size of the individual cutaneous lesions and on the percentage of body surface area involved.Y" The criteria for: diagnosing TEN is shown in Table I. TEN represents the most severe variant with the highest mortality 'rate, depending on the percentage body surface area used for differentiation between TEN and SJS. 1,2,4-7 The overall reported mortality with EM is nearly 0%, whereas SJS has a mortality of 5% to 15% and TEN has a mortality of 25% to 30%.3,8 The origin of SJS is not fully understood; however, an idiosyncratic reaction to numerous drugs has been strongly implicated as a major cause. 2,4,6,9,10 The balance of cases are either idiopathic or related to prodromal infections, such as upper respiratory infection, nonspecific viral illness, and pneumonitis resulting from Mycoplasma pneumoniae. EM and SJS tend to have similar ratios of inciting causes; however, TEN has a much higher percentage of association with antecedent drug therapy. A 5-year nationwide retrospective study from
France of 333 cases of TEN reported only 11 patients (4.5%) with no previous drug therapy." The case described is a classic presentation of druginduced SJS with progression to TEN. Both phenytoin and phenobarbital have previously been implicated in SJS and TEN. 6•12.13 The onset is typically 1 to 3 weeks after initiation of drug therapy. In many cases, there are prodromal features, consisting of a burning sensation of the conjunctiva, skin tenderness, fever, and malaise. These symptoms are followed in 1 to 2 days by a morbilliform rash on the face, trunk, and extremities. The rash then coalesces, leading to diffuse erythema of the involved skin. Vesiculation of macular lesions may occur before or during the coalescent phase. Confluence of vesicles leads to large flaccid bullae that rupture easily and leave huge denuded areas on the trunk, shoulders, and face. Minimal pressure on intact skin in the erythematous areas easily produces further separation of the epidermis from the dermis (Nikolsky's sign).' Mucous membrane involvement can be severe; it can involve the lips, oral mucosa, conjunctiva, urethra,
OtolaryngologyHead and Neck Surgery
798 Case Reports
Fig. 2. Vesicular eruption of lower extremity skin.
Table 1. Diagnostic criteria Erythema muillforme
Stevens·Johnsonsyndrome
Toxic epidermal necrolysls
- Classic target lesions - Individual lesions
