Stevens-Johnson syndrome

Stevens-Johnson syndrome is a cutaneous reaction pattern that represents the progression of symptoms of erythema multiforme. These reactions can range from mild (EM minor) to severe (EM major) and even life-threatening (Stevens-Johnson syndrome or toxic epidermal necrolysis). The difference between Stevens.Johnson syndrome and toxic epidermal necrolysis is the percentage of body surface area involved; toxic epidermal necrolysis involves widespread skin necrosis and bullous formation with epidermal detachment resembling scalded skin. The three most common triggers for StevensJohnson syndrome are herpes simplex infection, Mycoplasma infection, and drug reactions. This is a case of StevensJohnson syndrome occurring after erythromycin treatment aboard an aircraft carrier while deployed at sea in the Persian Gulf.

Case Report

20-year-old black male presented to the medical clinic during normal sick-call hours aboard the USS Enterprise complaining of sore throat, dry cough, pain and swelling to his left lower eyelid, and fever. The patient had a temperature of 100.8F and slight edema and erythema to his left lower eyelid. Physical examination was otherwise normal. The patient was diagnosed with a viral upper respiratory infection (URI) and a hordeolum and was treated with acetaminophen and warm compresses. The patient returned the next morning complaining of body aches, productive cough, sore throat, fever, and right ear pain. He was febrile, with a temperature of 102.2F. Physical examination was otherwise normal, and the patient was diagnosed again with a URI and was placed on a decongestant, acetaminophen, and a 10-day course of erythromycin with 24 hours of bed rest. The patient followed up the next morning, stating that he felt better symptomatically, and was returned to full duty at this time.

The next day, however, the fourth day since his initial presentation and approximately 48 hours after starting on erythromycin, the patient presented to morning sick call complaining of blisters in his mouth but with resolution of his cough, ear pain, and fever. Physical examination showed multiple bullae throughout his oral pharynx. All medications were discontinued at this time, and the patient was diagnosed with stomatitis. He was given an oral rinse three times a day of lidocaine, Maalox, and Benadryl and placed on bed rest. The patient returned later that evening complaining of an inability to eat, drink, or speak without experiencing pain. Temperature at this time was 103.5F, and physical examination showed multiple erupted bullae throughout his oral mucosa. The patient was seen by the on-call physician and was admitted to the ward for observation and intravenous hydration because he showed an increasing inability to tolerate oral fluids. A sepsis workup was performed to rule out an occult bacterial infection as a cause for his fever. All laboratory tests (chest X-ray, complete blood count, urinalysis, sputum culture, and blood culture) were normal.

The patient was diagnosed with erythema multiforme major, and because this was recognized as a possible early presentation of Stevens-Johnson syndrome, the patient was started the next morning on intravenous Solu-Medrol, 60 mg/d. Throughout the day, the patient's mucous membranes began to dough off, in sequential order, his oral mucosa, lips, conjunctiva, urethra, glans of penis, and nasal mucosa. Twenty-four hours after the start of intravenous steroid treatment, the patient expressed considerable symptomatic improvement along with defervescence. On hospital day 3, the patient began to exhibit cutaneous lesions with a central vesicle surrounded by a ring of erythema, developing approximate 6 to 10 lesions on each extremity, chest, back, and scrotum. These were recognized as characteristic "target" lesions, and at this time the diagnosis of Stevens-Johnson syndrome was made.

Discussion

Stevens-Johnson syndrome is part of the continuing spectrum of the cutaneous reactions of erythema multiforme. The characteristic "target" or "iris" lesions, together with mucosal vesicle and bullae formation, are distinctive of this disorder. It mimics a graft-vs.-host reaction in which the patient rejects skin, mucous membranes, kidney, or liver cells to which the drug or virus has bound.' It typically involves less than 10% body surface area and carries a mortality of 5 to 15%.2-4 When there is extensive skin detachment (>30% body surface area) and the skin resembles scalded skin, it is referred to as toxic epidermal necrolysis and carries a 30 to 40% mortality.2'' Patients usually present with prodromal symptoms of fever, headache, malaise, cough, and sore throat 1 to 14 days before any lesions appear.2 Recent therapy has emphasized early corticosteroid administration in cases in which a drug reaction is suspected. Patterson et al. proposed that the survival of some patients with Stevens-Johnson syndrome may depend on this therapy.' The corticosteroids suppress the inflammatory rejection of skin and mucous membranes until the inciting agent (the virus, drug, or combination of the two) has been eliminated. Corticosteroid treatment may not be appropriate in cases caused by infection or in cases of toxic epidermal necrolysis because of the possibility of life-threatening sepsis.

The three most common causes of Stevens-Johnson syndrome are herpes simplex virus, Mycoplasma infection, and drug reactions.2 Treatment, therefore, should focus on these causes, and diagnostic means should be sought out if possible by culture of lesions for herpes simplex virus and cold agglutinin titers for Mycoplasma infection. In each test, however, a negative result does not rule out infection. Because of the limited laboratory capabilities on aircraft carriers, these tests could not be performed. As a result of the appearance of this patient's symptoms within 48 hours of erythromycin therapy, it is plausible to conclude that erythromycin was the trigger for his reaction. Whether or not it was a virus, the drug, or a combination of the two is impossible to determine with complete certainty. The role of erythromycin as a cause of Stevens-Johnson syndrome has not been well established or documented, but it is mentioned as a possible cause in several case studies.2,4

Operational Aspects of Stevens-Johnson Syndrome

Stevens-Johnson syndrome is a potentially life-threatening disorder that can result in renal tubular necrosis and overwhelming sepsis in the face of corticosteroid treatment. It can also result in ophthalmologic problems such as keratitis and corneal ulcerations.5 In the absence of any of these complications, however, Stevens-Johnson syndrome is a self limiting disorder that can be managed only with early corticosteroid treatment, as mentioned previously, and supportive therapy. Daily eye examinations, including the use of a slit lamp to assess any corneal involvement, and daily blood urea nitrogen and creatinine determinations to assess kidney function should be performed. Another aspect that should receive attention is nutritional intake, because this patient went several days with only intravenous fluids as a result of his inability to swallow and loss of appetite. This was resolved with a straw, several cans of Ensure, and encouragement. The question that should be posed on an aircraft carrier is should the patient be evacuated off the ship to a hospital or be monitored on board. Factors that should be considered are the ability to transport the patient in a timely manner if the need arises and the ongoing carrier and battle group operations. Evacuating a patient off an aircraft carrier involves considerable manpower, time, and coordination with the tower, and it poses a certain degree of danger to the aircrew and the patient, especially during combat flight operations. This decision should be carefully thought out and planned, and any such decision should be made in coordination with an accepting physician. With new technologies now available, however, we can obtain real-time consultations with specialists throughout the world via telemedicine. Indeed, the consulting physician can visually examine the patient through the video monitor in real time. This was done in this case with a dermatologist at the National Naval Medical Center in Bethesda, Maryland. The specialist agreed with the current diagnosis and treatment pending the development of any complication. The patient was monitored and discharged 10 days after hospital admission on a full diet with a 15-pound weight loss.

Conclusion

The case of Stevens-Johnson syndrome in this patient was most likely caused by erythromycin treatment, because his symptoms appeared in the first 48 hours after initiation of therapy. After infection was ruled out, he was started on intravenous corticosteroid treatment with daily eye examinations and laboratory tests to assess any corneal involvement and kidney function. No complications ensued, and a telemedicine consultation with a dermatologist led to agreement with the diagnosis of Stevens-Johnson syndrome and the current treatment. The patient was extremely ill in the first 48 hours but showed dramatic symptomatic improvement after corticosteroid therapy was initiated. The decision not to evacuate him off the ship was made in the absence of any complications, and the patient was discharged 10 days after admission on a full diet. Pending the development of a complication and in the absence of any other health problems, a patient with Stevens-Johnson syndrome can be safely monitored aboard an aircraft carrier with supportive treatment because he or she can receive what is needed most in a hospital on land as well as at sea: time.

References

1. Patterson R, Miller M, Kaplan M, et al: Effectiveness of early therapy with corticosteroids in Stevens-Johnson syndrome: experience with 41 cases and a hypothesis regarding pathogenesis. Ann Allergy 1994; 73: 274.

2. Lestico MR, Smith AD: Stevens-Johnson syndrome following erythromycin administration. Am J Health Syst Pharm 1995; 52: 1805-7.

3. Delattre JY, Safai B, Posner JB: Erythema multiforme and Stevens-Johnson syndrome in patients receiving cranial irradiation and phenytoin. Neurology 1988; 38: 194-8.

4. RouJeau JC, Kelly JP, Naldi L, et al: Medication use and the risk of StevensJohnson syndrome or toxic epidermal necrolysis. N Engl J Med 1995; 333: 1600-7.

5. Fitzpatrick TB, Johnson RA, Polano MK, et al: Color Atlas and Synopsis of Clinical Dermatology, Ed 2. Minneapolis, McGraw-Hill, 1994.

Guarantor: LT Dan Alen Williams, MC USN

Naval Hospital Branch Medical Clinic, Building 964, Naval Air Station, Jacksonville, FL 32214-5000.

This manuscript was received for review in August 1999 and was accepted for publication in October 1999.

Reprint & Copyright by Association of Military Surgeons of U.S., 2000.

Copyright Association of Military Surgeons of the United States Aug 2000
Provided by ProQuest Information and Learning Company. All rights Reserved