A Rare Case of Stevens-Johnson Syndrome in a Young Patient Presenting With Odynophagia Following Antibiotic Use

Introduction

Stevens-Johnson syndrome (SJS) is a rare but life-threatening mucocutaneous hypersensitivity reaction characterized by extensive keratinocyte apoptosis, epidermal detachment, and mucosal involvement affecting the oral, ocular, and genital regions. It involves less than 10% of the body surface area and carries a high risk of morbidity and mortality if not promptly diagnosed and managed. The annual incidence of SJS in the United States is approximately 1 to 5 cases per million, underscoring its rarity in the general population [1].

The pathogenesis of SJS is primarily immune-mediated, with growing evidence pointing to a delayed-type hypersensitivity reaction that is both HLA class I-restricted and CD8+ T-cell driven [2]. This understanding has led to preventive strategies, such as screening for the HLA-B*15: 02 allele in certain populations prior to prescribing high-risk medications like carbamazepine [3].

Drug exposure is the most common trigger, with anticonvulsants, sulfonamides, and antibiotics such as cephalosporins being among the most frequently implicated [4]. Other etiologies include infections, notably Mycoplasma pneumoniae, and malignancies. Idiopathic causes account for 5% to 20% of cases [5]. Onset of symptoms typically occurs 4 to 28 days after initial exposure to the causative agent, but re-exposure can precipitate a much more rapid reaction [5].

Clinically, SJS presents with a prodrome of fever, malaise, pharyngitis, and conjunctivitis, followed by the appearance of painful, erythematous macules that evolve into vesicles and erosions [6]. The mucosa is affected in over 85% of cases involving oral and genital mucosa, as well as the conjunctiva [2].

Despite the robust documentation of SJS in adults, its presentation in pediatric and adolescent populations is significantly less common [7]. Even more rare are cases that present with isolated oropharyngeal symptoms, particularly odynophagia (painful swallowing) as the initial or predominant concern. Compared with more typical manifestations involving skin and mucosal involvement [8], such atypical presentations can complicate the diagnostic process and delay definitive management, especially when cutaneous lesions are absent or emerge later in the disease course. Differential diagnoses for early or atypical SJS presenting with isolated oropharyngeal involvement may include herpes simplex virus (HSV), Bechet disease, recurrent aphthous stomatitis, herpangina (Coxsackievirus A), hand, foot, and mouth disease (HFMD), Mycoplasma pneumoniae-associated mucositis (MPAM), and infectious mononucleosis (EBV).

In this report, we describe a diagnostically challenging and clinically significant case of SJS in an otherwise healthy adolescent male. This case highlights the novelty of a mucosal-predominant presentation and underscores the importance of maintaining a high index of suspicion for SJS in the differential diagnosis of oropharyngeal pain – particularly in the setting of recent drug exposure – and contributes to the limited literature on atypical pediatric presentations.

Case Report

An 18-year-old male with no significant past medical history presented to the emergency department with a 2-day history of sore throat with odynophagia, a burning sensation intraorally, and poor oral intake. He reported 2 episodes of emesis and subjective fever. Additionally, he had dry, pruritic eyes and pain on urination. Four days prior to the hospital visit, he developed symptoms of nasal congestion, sinus pain, and mild sore throat. He was examined by a general practitioner and was diagnosed with post-nasal drip for which he was prescribed cefdinir and fexofenadine. After a week, symptoms had not resolved and progressively worsened, which prompted the visit to the emergency department. Initially, he was treated for an allergic reaction, nausea, and vomiting with epinephrine, famotidine, ondansetron, and pain medication. He was afebrile and denied any respiratory, chest, or abdominal symptoms. A CT neck soft tissue with contrast showed non-specific patchy subcutaneous/soft tissue edema. Laboratory studies were suspicious for an infectious process as white blood cell count and C-reactive protein were elevated at 12.1×103/mm3 and 11.4 mg/dL, respectively; complete metabolic panel revealed hyponatremia; respiratory viral panel and strep test were both negative. An STI panel came back negative. Throat and urine cultures were collected.

Upon physical examination, the patient appeared distressed. Vital signs were as follows: temperature 36.8°C, heart rate 62 beats per minute, blood pressure 135/64 mmHg, respiratory rate 18 beats per minute, and oxygen saturation 99% on room air. Pertinent findings on the head and neck examination included bilateral conjunctival injection with dry-appearing eyes and mild chemosis. Sialorrhea was present. The upper and lower lips were edematous and erythematous with hemorrhagic crusting and exudate. Intraorally, there were generalized, ulcerative, and erosive lesions noted on the buccal and labial mucosa, floor of mouth, ventral and dorsal tongue, and hard palate. Gingival desquamation was present with positive Nikolsky’s sign. The oropharynx was difficult to examine due to pain and severe gag reflex; however, erythema and edema were appreciable, with enlarged bilateral tonsils. Cranial nerves V and VII were found to be grossly intact.

The patient was admitted to the pediatric floor with a working diagnosis of Stevens-Johnson syndrome secondary to cefdinir use. Given the recent exposure to a cephalosporin temporally associated with symptom onset, cefdinir was initially suspected as the inciting agent and was discontinued. The patient was started on aggressive intravenous (IV) fluids, methylprednisolone 4 mg/kg/day, and clindamycin for antimicrobial coverage during wound healing. Acetaminophen, ketorolac, magic mouthwash (numbing agent, antacid, diphenhydramine, corticosteroid, antifungal), and triamcinolone acetonide 0.1% were ordered for pain control. Per ophthalmology recommendations, prednisolone acetate eye drops, erythromycin ophthalmic ointment, and artificial tears were ordered.

Early in his hospital course, he became progressively worse with increased intensity of symptoms, including multiple episodes of fever and development of an erythematous, macular rash on the palms and soles of the hands and feet, without pruritus (Figures 1, 2). The eyes and mouth showed increased erythema, edema, and crusting (Figure 3). New-onset pain during inspiration through the nose developed, which was attributed to sloughing of nasal mucosa. The skin overlying the scrotum became extremely sensitive and irritated along with mucosal sloughing around the urethra. On hospital day 3, throat swabs were again collected and sent for PCR, which were positive for M. pneumoniae antibody immunoglobulin G and immunoglobulin M. These values were elevated (1559 and 1716, respectively), and the patient was started on an intravenous (IV) IG infusion. Azithromycin was also added to the medication regimen due to positive Mycoplasma IgM. At this time, the diagnosis was modified to SJS secondary to M. pneumoniae infection.

Towards the end of his 2-week hospital course, he showed significant improvement, with almost complete resolution of symptoms. He was able to tolerate oral intake, with a normal diet. The genital and ocular symptoms had resolved, as did the cutaneous rash. Methylprednisolone dosing was gradually reduced and the patient was discharged with a 3-day steroid taper, pain medication, and prednisolone ophthalmic ointment.

After discharge, he remained clinically stable and had full resolution of the mucosal and skin lesions. He was seen for a 2-month follow up at the infectious disease clinic, where he was symptom-free and no longer using any mediations. There were no notable findings other than geographic tongue. He was able to return to his daily life, including attendance at his high school senior prom and graduation.

Discussion

SJS is a rare mucocutaneous disorder characterized by erosions and epidermal detachment. It is widely regarded as a dermatologic and medical emergency, typically triggered by medications or infections. SJS involves <10% of total body surface area, and frequently affects multiple mucosal sites, including the oral, ocular, and genital mucosa [9]. One to 5% of patients with SJS will succumb to this condition. It is similar to but less severe than toxic epidermal necrolysis (TEN), which involves over 30% of total body surface area and has a mortality rate of 25% to 30% [10]. Our patient initially presented with odynophagia and mucosal ulceration in the absence of skin involvement – a presentation that differs from classic descriptions and emphasizes the novelty of this mucosal-predominant variant, particularly in children and adolescents.

While the classic presentation of SJS involves a prodrome of fever and malaise, followed by widespread erythematous macules or targetoid lesions and mucosal ulceration, several reports have documented mucosal-predominant or mucosal-only variants [11]. A retrospective analysis by Frantz et al found that mucosal involvement can precede skin findings by several days, particularly in younger patients or those with Mycoplasma pneumoniae-associated SJS (MP-SJS) [12].

Our patient’s primary concern of odynophagia, with subsequent development of oral and genital ulceration, is an example of a mucosal-predominant variant. Such cases have been historically misdiagnosed as viral pharyngitis, aphthous ulcers, or herpetic stomatitis, often delaying appropriate treatment [13]. A positive Nikolsky’s sign and rapid spread of mucosal desquamation should prompt clinicians to consider SJS, even in the absence of classic cutaneous signs.

Antibiotics are the medications most frequently associated with the onset of SJS, particularly sulfonamides, beta-lactam agents, and cephalosporins; however, infection-associated SJS, particularly with Mycoplasma pneumoniae, is also well-documented in adolescents and young adults [14]. Although this case was initially suspected to be cefdinir-induced based on recent exposure and symptom onset, it was later reclassified as MP-SJS after serologic confirmation of elevated IgM and IgG titers. MP-SJS has been shown to present more frequently with atypical features, including limited skin involvement and more severe mucositis [15]. As highlighted by Canavan et al, MP-SJS can have a more insidious onset, requiring clinical suspicion and laboratory confirmation for diagnosis [16]. It is important to note that drug- and infection-induced SJS can coexist, and the challenge of differentiating between these highlights the need for a comprehensive history of recent infections and drug exposures, as emphasized by the RegiSCAR criteria [17].

The use of systemic corticosteroids in SJS remains controversial. While some studies suggest increased risk of infection and delayed healing, others have demonstrated potential benefit when administered early in the disease course [18]. In our case, methylprednisolone was initiated empirically and tapered with clinical improvement, consistent with data supporting short-term corticosteroids in selected cases, particularly MP-SJS [19]. Additionally, the use of IVIG was guided by the presumed immunologic etiology. Although randomized controlled data are limited, IVIG has shown variable benefit in SJS, potentially by blocking Fas-FasL-mediated keratinocyte apoptosis [20]. A 2019 meta-analysis by Zimmermann et al found that high-dose IVIG combined with corticosteroids can reduce mortality, particularly in pediatric populations [21].

Optimal management of SJS requires a multidisciplinary approach – including dermatology, ophthalmology, infectious disease, ENT, or oral and maxillofacial surgery – and critical care, as well as rigorous supportive therapy. Our patient received comprehensive management involving pain control, maintenance of hydration, ocular lubrication, and meticulous mucosal wound care. Ophthalmologic involvement is critical, as up to 50% of SJS/TEN survivors develop long-term ocular complications, including symblepharon and corneal scarring, and, in severe cases, blindness.

This case illustrates the need for clinical vigilance in recognizing early SJS, particularly in adolescents presenting with mucosal concerns and recent antibiotic exposure or respiratory illness. Mucosal-predominant SJS is likely under-recognized, and delays in diagnosis can lead to unnecessary morbidity. Prompt withdrawal of the offending agent, targeted antimicrobial therapy (in cases of MP-SJS), and aggressive supportive care remain the cornerstones of treatment. This case also reinforces the utility of repeating diagnostic tests, including PCR and serologies for atypical pathogens, when the clinical course does not improve as expected.

Conclusions

SJS should be considered in patients with acute-onset painful mucositis, odynophagia, and ocular or genital symptoms, even in the absence of skin involvement. This case adds to the limited reports of mucosal-predominant MP-SJS in adolescents and demonstrates how the initial presentation can mimic benign oropharyngeal disease. Mycoplasma pneumoniae-associated SJS can present atypically and requires a high index of suspicion. Future studies are needed to establish best practices for immunomodulatory therapy in MP-SJS and to define standardized treatment protocols in atypical cases.