Abstract
Steven-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) are life-threatening dermatologic conditions hallmarked by extensive exanthematous eruption, epidermal necrolysis, and peripheral lymphadenopathy.1 These conditions pose significant diagnostic and clinical challenges and have limited therapeutic options. While the inpatient management of these reactions is well documented in the literature, there is a gap in knowledge and guidance in the prehospital domain.
We present the case of a medically complex, 58-year-old woman suffering from a severe, drug hypersensitivity reaction comorbid with rapidly progressive amyotrophic lateral sclerosis (ALS). Key tenets of management include early recognition, prompt cessation of the offending agent, and initiation of supportive care measures.1
Prehospital providers should be vigilant in gathering detailed patient history, conducting a thorough physical examination, and considering early and aggressive interventions to optimize patient outcomes. This case underscores the challenges faced by prehospital providers in managing such complex scenarios and highlights the need for improved knowledge and guidance in the prehospital domain.
Case
EMS was dispatched by county 911 to the residence of a 58-year-old female complaining of vomiting and fever. Upon arrival, the patient’s family reports a past medical history significant for advanced amyotrophic lateral sclerosis (ALS), resulting in bed confinement. She was recently diagnosed with a urinary tract infection (UTI) and was prescribed a course of a beta-lactam antibiotic. Around 1 a.m. on the day prior, the patient’s husband noticed a rash developing on her trunk and extremities and administered diphenhydramine (Benadryl).
She presented to the emergency department later that day for evaluation of her rash, which continued to spread throughout the evening. Hospital staff noted the presence of a nonpruritic morbilliform rash across the patient’s trunk and extremities, thought to be related to amoxicillin/clavulanate (Augmentin) use. The suspected causative agent was discontinued (Augmentin), and the patient was given an empiric dose of Fosfomycin for continued coverage of her UTI. She was discharged with a course of prednisone and was encouraged to follow up closely with her primary care provider.
Over the next 12 hours, the patient’s husband reported a significant decline in her status, citing the continued spread of the rash with concern for peritoneal skin sloughing, multiple episodes of vomiting, diaphoresis, an increased work of breathing, fever, and a decreased level of responsiveness. The patient’s husband ultimately decided to summon EMS after consultation with the patient’s primary care provider. The patient presented to EMS with a toxic appearance, significant for a decreased level of responsiveness, tachycardia, borderline hypotension, high fever, and respiratory distress. An extensive, pruritic, morbilliform rash was appreciated on the patient’s trunk, face, and extremities.
Background
Steven-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) are life-threatening dermatologic conditions hallmarked by extensive exanthematous eruption, epidermal necrolysis, and peripheral lymphadenopathy.1 These spectra of conditions are unique in their percentage of affected total body surface area (TBSA) and other histological deviations.1
Although the etiology remains poorly characterized, these conditions are thought to be T-cell mediated hypersensitivity reactions to certain medications.1 Prodromal symptoms appear one to three weeks following the onset of exposure, including fever, malaise, and a cough. Later phases include the appearance of an erythematous maculopapular rash on the trunk, pruritus, epidermal detachment, and systemic manifestations.2
Mucosal involvement is common, occurring in more than 90% of patients and predominantly affecting the mouth, ocular mucosa, and genitals.1 Long-term sequelae are often pervasive, leaving survivors with lifelong challenges related to scarring, adhesion formation, chronic pain, and psychosocial stress.3 With an estimated mortality of 4.8% (SJS), 10% (DRESS), and 14.8% (TEN), these conditions present considerable risk with limited therapeutic options.4,5 Timely recognition, appropriate management, and specialized care are crucial in improving outcomes for patients affected by these life-threatening dermatological conditions.
Case Cont.
Medical command was contacted early regarding concern for anaphylaxis versus drug-induced systemic hypersensitivity reaction. Given the history of present illness and concern for aspiration pneumonia and reduced respiratory reserve in the setting of ALS, command advised continued supportive care and to withhold epinephrine or corticosteroids unless the patient’s condition deteriorated further.
Transport to a burn center was considered but not initially advised. The patient’s prehospital management included airway management, high-flow oxygen, nebulized bronchodilators, antipyretics, intravenous crystalloids, and diphenhydramine. Initial steps were also taken to address the patient’s dermatologic needs, including basic wound care and temperature management.
These interventions were successful in reversing the patient’s hypoxia, however, the patient remained borderline hypotensive and febrile despite aggressive fluid resuscitation.
Upon presentation to the emergency department, the patient was initially treated for anaphylaxis without marked improvement. Initial laboratory studies revealed lactic acidosis without electrolyte derangements or leukocytosis. Given concern for sepsis versus an evolving systemic drug reaction, empiric cefepime was given for broad-spectrum UTI coverage and the patient was admitted to the medical intensive care unit.
Over the course of her admission, a multidisciplinary team was consulted including dermatology and ophthalmology to address the patient’s worsening erythroderma and facial edema. Histopathological studies confirmed a drug rash with eosinophilia and systemic symptoms (DRESS) with evolving concern for Steven-Johnson Syndrome (SJS)/toxic epidermal necrolysis (TEN) with appropriate clinical correlation.
The offending agent was ultimately believed to be sodium phenylbutyrate and taurursodiol (Relyvrio), a medication used to slow the progression of ALS, that the patient had begun taking approximately two weeks prior to presentation of her symptoms. With cessation of this medication and supportive care including corticosteroids and intravenous immunoglobulin (IVIG), the patient’s symptoms improved. Despite improvement in dermatologic condition, she was discharged to home palliative care given her rapidly progressive ALS.
Discussion
DRESS, SJS, and TEN are rare, life-threatening, dermatologic emergencies that pose significant diagnostic and clinical challenges for prehospital and inpatient providers alike. While the inpatient management of severe, adverse drug reactions is well documented in the literature, there is a gap in knowledge and guidance available in the prehospital domain.
As demonstrated in this case review, there are multiple ways in which prehospital providers can acutely manage and contribute to reducing the morbidity and mortality associated with these conditions.
History and Physical
The prompt recognition of drug-induced systemic hypersensitivity reactions is crucial, as immediate cessation of the offending agent is necessary to mitigate the progression and severity of the condition.2 Early identification by prehospital providers facilitates the timely initiation of appropriate management strategies, leading to improved patient outcomes.
Gathering a detailed patient history, including recent medication use/changes and any associated symptoms, can provide vital clues to help identify the causative agent and help differentiate between acute anaphylactic reactions and other types of medication-triggered reactions. This is even more important when patients are not able to provide history themselves. Physical examination findings, such as an extensive rash, epidermal or mucosal sloughing or blistering, and signs of shock, should stand out as “red flags” for hypersensitivity reactions.6
While certain medications have been implicated in the pathogenesis of these reactions, most commonly antiepileptics, non-steroidal anti-inflammatory drugs (NSAID), antibiotics, allopurinol, and immune checkpoint inhibitors, there is growing evidence to support that infection by mycoplasma pneumoniae and genetic predisposition can play a role in occurrence.6
Airway Management
Patients suffering from systemic drug hypersensitivity reactions are often afflicted with mucosal edema and sloughing of the conjunctiva, oropharynx, esophagus, and genitalia.2 This involvement can easily lead to airway emergencies including partial or full obstruction, excessive airway secretions, and respiratory distress.
While there are limited guidelines available regarding indications for early intubation in patients with severe, systemic drug reactions, recent evidence suggests that inpatients with total body surface area (TBSA) greater than 30% require intubation for either wound management or primary airway involvement,7 as well as concurrent bacteremia and multisystem organ failure.8
Similar to findings in patients with inhalation injuries, exam findings that should increase suspicion of airway compromise include perioral or facial involvement, dyspnea, stridor, wheezing, excessive coughing or inability to control secretions, and a decreased level of responsiveness.7 Prehospital providers should consider early and aggressive airway management as guided by their local protocols and with direction from medical command.
Supportive Care
Hypoperfusion, or shock, is a common complication of severe drug hypersensitivity reactions, resulting from an inflammatory cascade and comorbidities including septicemia, HIV infection, mycoplasma infection, and a variety of malignancies.4 While there is little to no available guidance for the prehospital management of DRESS, SJS, and TEN, shock management is a mainstay of prehospital care.
Prehospital providers are encouraged to manage shock with attention to local protocols, most appropriately including administration of crystalloids, judicious use of vasopressors, temperature management, and oxygen administration. In fact, supportive care should mirror burn management in relation to fluid resuscitation and wound care.9 Inpatient fluid replacement and electrolyte management with electrolyte solution and albumin is titrated to a urine output of 0.5 -1 mL/kg/hr, consistent with burn management guidelines.9 In the absence of output monitoring in the prehospital setting, initial fluid replacement should be guided by the maintenance of adequate tissue perfusion through achieving a mean arterial pressure (MAP) >65 mmHg, referencing local protocols regarding shock management.
In addition to shock management, supportive care should include both wound care and pain management. Inpatient pain management strategies can easily be mirrored in the field and include a variety of oral and intravenous medications.
Ranging from acetaminophen for mild pain and opioids for moderate to severe pain, standard prehospital analgesics are appropriate and should be used judiciously as mucocutaneous pain is a primary symptom. According to local protocols, low-dose ketamine can also be an efficacious option, especially over the course of long-term transport and in pediatric populations.10
Wound care guidelines generally echo burn management, however, are somewhat more conservative in preservation of detached epidermis. As such, anti-shear therapies are recommended, including non-adherent dressings and caution when performing extrication and other movements.10 To achieve these goals, admission to an intensive care or burn specialized unit can be useful.10
Conclusion
We present the case of a medically complex, 58-year-old woman suffering from a severe, drug hypersensitivity reaction comorbid with rapidly progressive amyotrophic lateral sclerosis (ALS).
Emphasizing the importance of early recognition, prompt cessation of the offending agent, and initiation of supportive care measures, prehospital providers should be vigilant in gathering detailed patient history, conducting a thorough physical examination, and considering early and aggressive prehospital interventions to optimize patient outcomes.
This case underscores the challenges faced by prehospital providers in managing such complex scenarios and highlights the need for improved knowledge and guidance in the prehospital domain.
References
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