Stevens–Johnson Syndrome (SJS)/toxic epidermal necrolysis (TEN) is a severe mucocutaneous reaction often induced by medications. The co-occurrence of SJS/TEN and COVID-19 presents a unique challenge due to overlapping inflammatory pathways. This case study examined the cytokine profile of a patient with both TEN (triggered by lamotrigine) and COVID-19. The clinical history of the patient, including lamotrigine exposure and COVID-19 diagnosis, was documented. A 13-cytokine profile assessment was performed in peripheral blood mononuclear cells from the patient and their parents by using quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). A 6-year-old male patient developed lamotrigine-induced TEN with concomitant COVID-19 affecting 90% of the body surface area. Compared with their parents, who were positive for COVID-19, IL-6, IL-4, and IL-12 were modulated (downregulated) by TEN. The cytokine profile showed elevated levels of IL-1α, IL-1β, IL-5, IL-8, NF-κβ, and interferons (IFN; α, β, and γ), indicating a robust antiviral response. The immune profile suggested a hyperactivated immune state that contributed to the severity of the patient’s clinical manifestations, leading to death 18 days after hospitalization. Understanding the immune response is important for developing future targeted therapeutic strategies and improving patient outcomes. Further research is needed to explore the interaction between drug-induced SJS/TEN and infections.

Background: Kawasaki Disease (KD) is an acute vasculitis affecting children under five years of age, with atypical presentations posing diagnostic challenges and a higher risk of coronary complications when untreated. Methods: We report on a 2-year-old girl with persistent fever, limb edema, erythema, and non-purulent conjunctivitis, without cervical lymphadenopathy or the typical rash. Inflammatory markers were assessed, and a cytokine expression profile was obtained using qRT-PCR. Results: Laboratory analysis showed elevated C-reactive protein (11.1 mg/dL), high fibrinogen (468 mg/dL), borderline D-dimer (484 ng/mL), and a normal platelet count. The cytokine profile revealed marked upregulation of IFN-α, IFN-β, IFN-γ, IL-1α, IL-1β, IL-5, IL-8, and IL-12, with downregulation of IL-2 and IL-4, as well as low TNF-α levels. These findings, although not pathognomonic, were consistent with an inflammatory profile compatible with atypical KD, in which a preceding viral infection may have played a role, although causality cannot be established. Conclusions: This case highlights the diagnostic utility of cytokine profiling in suspected atypical KD, particularly when clinical criteria are incomplete. The integration of immunological data may aid in earlier recognition and therapeutic intervention, thereby helping to prevent cardiovascular sequelae. Cytokine analysis may serve as a promising adjunct for atypical KD diagnosis, although confirmation in larger cohorts is needed.