A 50-year-old man with diabetes, coronary artery disease, and hepatitis C presented to the ED after being discharged from another facility three days earlier for an episode of diabetic ketoacidosis possibly precipitated by an infection.
The patient said he started having urinary and penile pain even before he was discharged. Since then, he developed mouth sores and a rash on his buttocks. He was not discharged on any new medications and had no history of anything similar.
His vital signs were a blood pressure of 150/100 mm Hg, heart rate of 100 bpm, respiratory rate of 16 bpm, and temperature of 36.7°C. The sores in his mouth are shown in the photo. What is on your differential diagnosis, and what is the treatment?
Find the diagnosis and case discussion on next page.
Diagnosis: Stevens-Johnson Syndrome
Stevens-Johnson syndrome (SJS) is a mucocutaneous reaction caused by a type IV or T-cell-mediated hypersensitivity reaction, most commonly to a drug. Other agents, however, have been associated with SJS. Necrosis of the epidermis and blistering are followed by detachment of the epidermis. The exact pathophysiology is not clear, but is said to involve T-cell-mediated apoptosis of the keratinocytes, which leads to bullae formation and sluffing of detached skin.
SJS, an epidermal necrosis involving less than 10 percent of the total body surface, is part of a disease continuum with toxic epidermal necrolysis (TEN). TEN is diagnosed when more than 30 percent of the body is involved. Between 10 and 30 percent is called SJS/TEN overlap, and risk factors are HIV, lupus, underlying malignancy, and certain HLA alleles. Patients have a low probability of developing the disease even when a specific HLA allele strongly associated with SJS is present. (Curr Allergy Asthma Rep 2018;18:26.)
The incidence of SJS/TEN varies by region, and is estimated to occur in nine per one million people in the United States. (Clin Rev Allergy Immunol 2018;54:147.) The mortality for SJS worldwide is around 10 percent and 30-40 percent for TEN but 19 percent in the United States. (Curr Allergy Asthma Rep 2018;18:26.) SJS/TEN can affect patients of any age, and has a slightly higher incidence in women. SJS/TEN mortality is mostly associated with sepsis, organ dysfunction, and other sequela of the disease rather than the disease itself.
Symptoms can be subtle or obvious depending on when patients present. A prodrome of fever (up to 102°F), myalgias, and flu-like symptoms often precedes the skin eruption. The first skin symptoms are frequently mucosal surfaces—the mouth, eye, and urogenital tract. Ninety percent of patients with SJS/TEN have mucosal surface involvement at some point (Orphanet J Rare Dis 2010;5:39; http://bit.ly/2DDAkTL), and it can be the only initial symptom.
The hallmark skin lesions start out as dark purple or erythematous lesions with purpuric centers. They progress to bullae; the skin adjacent to the lesion will easily detach from the dermis with gentle pressure, called a positive Nikolsky sign. (Curr Allergy Asthma Rep 2018;18:26.) The first bulla appeared on our patient three hours after presentation. (See photo.) As the disease progresses, the mucosal surfaces of the GI tract, lungs, and other organs can also become involved, leading to immediate and long-term complications. Important differential diagnoses include staphylococcal scalded skin syndrome, other autoimmune bullous diseases, and bullous fixed drug eruption. Many of these are differentiated only on biopsy.
Diagnosis in the ED is primarily clinical. Identifying the bullae on the skin, especially those with associated mucosal involvement, should cause the emergency physician to suspect SJS/TEN. Suspicion should be even higher if the patient was recently or is currently on agents classically associated with SJS/TEN. Common medications most strongly associated with SJS/TEN are phenytoin, carbamazepine, lamotrigine, sulfas, and allopurinol. (J Clin Diagn Res 2016;10: FD01; http://bit.ly/2DFPeJf.)
No blood tests can diagnose SJS/TEN, but a complete blood count, basic metabolic panel, and liver function tests should be obtained to aid in prognosis and assess disease severity. The SCORTEN score can help predict the severity and identify patients who would benefit from ICU or specialty center care. One point is given for age over 40, current diagnosis of malignancy, more than 30 percent of body surface area affected, tachycardia greater than 120 bpm, BUN of more than 28 mg/dL, glucose of more than 240 mg/dL, and serum bicarbonate of less than 20 mg/dL. The total possible score is 7. Patients with a score of 2 or higher should be managed in an ICU. Diagnosis is confirmed through a skin biopsy by dermatology.
The most important initial management of SJS/TEN is identifying and stopping the offending agent. The hypersensitivity reaction can develop one to four weeks after exposure, so a detailed history is needed. (Curr Allergy Asthma Rep 2018;18:26.) The offending agents can be medications or prior infection or can remain unknown. Other initial interventions are similar to those for a burn patient. Fluid administration should be guided by total body surface area affected. Wound care and pain control are also important. Supportive care is the mainstay treatment, especially initially, and adjunct therapies studied included steroids, IVIG, cyclosporine, and plasmapheresis, to name a few. Most studies were small and retrospective, and many looked at a combination of drugs. Cyclosporin A seems to be the most promising treatment, but initiation can wait until the ICU. (Clin Rev Allergy Immunol 2018;54:147.)
Patients may need multiple consultants. Ophthalmology should be a high priority to evaluate the extent of ocular involvement. Treatment with steroid drops or special films may prevent delayed complications and loss of vision. Other consultants to consider early include gynecology and urology to prevent strictures and contractures.
Our patient was evaluated by dermatology in the ED and was subsequently transferred to a burn center and given steroids only. He had a total body surface involvement of six percent. He was later seen for poor wound healing with associated cellulitis, resulting in a few short admissions.
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Dr. Barrettis an assistant professor of emergency medicine at the University of Colorado School of Medicine in Aurora and an attending physician at Denver Health Medical Center. She is also an associate medical director for the Denver Health Paramedic Division and the medical director for the paramedic school.