Severe Delayed Reactions Resource Page
| Acute Generalized Exanthematous Pustulosis VisualDx Images in Children (CMH users) |
AGEP is a severe cutaneous adverse reaction that appears rapidly, often within 2-3 days of exposure. The reaction is characterized by the sudden appearance of numerous small, non-follicular, sterile pustules surrounded by a red, inflamed base (erythema). Some patients may also experience fever, leukocytosis, or other systemic symptoms (De et al., 2018; Parisi et al., 2023). |
| Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) VisualDx Images in Children (CMH users) |
DRESS syndrome is a potentially life-threatening, delayed hypersensitivity reaction. Symptoms may appear 2-6 weeks after starting a medication, or sooner upon re-exposure. Clinical manifestations may include morbilliform rash, fever, facial edema, lymphadenopathy, blood dyscrasias and end organ damage (including liver, kidney, heart, and lungs)(Calle et al., 2023). Mortality is estimated to be 3.8 - 10% (Chen et al., 2010; Hiransuthikul et al., 2016). Due to the delayed onset and diverse presentation, diagnosis is challenging and requires extensive investigation (Calle et al., 2023; Wolfson et al., 2019). Link to calculate RegiSCAR Score |
| Eosinophilic granulomatosis with polyangiitis (EGPA) VisualDx Images (CMH users) |
EGPA (formerly Churg-Strauss syndrome) is a rare autoimmune condition characterized by inflammation of small blood vessels which may lead to end organ damage, particularly in the lungs. The onset is slow, typically over months to years. Early symptoms include adult-onset asthma, chronic hay fever, chronic sinusitis, nasal polyps, generalized joint/muscle pain, fever, malaise and fatigue. If left untreated, EGPA can cause serious damage to other organs and tissues including the heart and kidneys (Cleveland Clinic, 2024). |
| Febrile neutrophilic dermatosis (Sweet Syndrome) VisualDx Images in Children (CMH users) |
Sweet syndrome is a rare skin reaction characterized by the abrupt onset of tender, red or purplish lesions, often accompanied by fever, fatigue, joint pain, or headaches. Other symptoms may include ocular inflammation or oral or genital lesions (Cleveland Clinic, 2024; Vashisht et al, 2022). |
| Serum sickness-like reaction (SSLR) VisualDx Images in Children (CMH users) |
Serum sickness is a type III immune complex-mediated hypersensitivity reaction due to administration of serum from a different species. Symptoms include rash, joint inflammation, fever, renal/ hepatic dysfunction, and hypocomplementemia. Serum sickness-like reaction (SSLR) can occur from other medications but the mechanism underlying SSLR is not clear. SSLR typically occurs 1 - 2 weeks after administration of the drug. Symptoms include urticaria, erythema multiforme, joint pain/inflammation, with or without fever (Delli Colli et al., 2021; Khan et al., 2022; Schiavino et al., 2006). |
| Stevens-Johnson syndrome (SJS) AND Toxic Epidermal necrosis (TEN) VisualDx Images in Children (CMH users) |
SJS is a serious condition affecting the skin and mucous membranes. Patients may present with flu-like symptoms such as fever, body aches, and fatigue, followed by a painful rash that will begin to blister and peel. Mucous membranes in the eyes, mouth, and genitalia are often involved. TEN is a more severe form of the condition, involving > 30% of the skin surface and mucous membranes. Both conditions are potentially life-threatening and should be considered medical emergencies. Hospitalization is generally required for supportive care focusing on pain management, wound healing, and avoidance of complications (Cleveland Clinic, 2020; Mayo Clinic, 2025). |
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References: Calle, A. M., Aguirre, N., Ardila, J. C., & Cardona Villa, R. (2023). DRESS syndrome: A literature review and treatment algorithm. World Allergy Organ J, 16(3), 100673. https://doi.org/10.1016/j.waojou.2022.100673 Chen, Y. C., Chiu, H. C., & Chu, C. Y. (2010). Drug reaction with eosinophilia and systemic symptoms: a retrospective study of 60 cases. Arch Dermatol, 146(12), 1373-1379. https://doi.org/10.1001/archdermatol.2010.198 De, A., Das, S., Sarda, A., Pal, D., & Biswas, P. (2018). Acute Generalised Exanthematous Pustulosis: An Update. Indian J Dermatol, 63(1), 22-29. https://doi.org/10.4103/ijd.IJD_581_17 Delli Colli, L., Gabrielli, S., Abrams, E. M., O'Keefe, A., Protudjer, J. L. P., Lavine, E., Pitt, T., Atkinson, A., Eiwegger, T., McCusker, C., & Ben-Shoshan, M. (2021). Differentiating Between β-Lactam-Induced Serum Sickness-Like Reactions and Viral Exanthem in Children Using a Graded Oral Challenge. J Allergy Clin Immunol Pract, 9(2), 916-921. https://doi.org/10.1016/j.jaip.2020.08.047 Cleveland Clinic. (2024, July 25). Eosinophilic Granulomatosis With Polyangiitis (EGPA, formerly Churg-Strauss Syndrome). https://my.clevelandclinic.org/health/diseases/churg-strauss-syndrome-eosinophilic-granulomatosis-with-polyangiitis-egpa Cleveland Clinic. (2020, Dec 18). Stevens-Johnson Syndrome. https://my.clevelandclinic.org/health/diseases/17656-stevens-johnson-syndrome Hiransuthikul, A., Rattananupong, T., Klaewsongkram, J., Rerknimitr, P., Pongprutthipan, M., & Ruxrungtham, K. (2016). Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DIHS/DRESS): 11 years retrospective study in Thailand. Allergol Int, 65(4), 432-438. https://doi.org/10.1016/j.alit.2016.04.001 Khan, D. A., Banerji, A., Blumenthal, K. G., Phillips, E. J., Solensky, R., White, A. A., Bernstein, J. A., Chu, D. K., Ellis, A. K., Golden, D. B. K., Greenhawt, M. J., Horner, C. C., Ledford, D., Lieberman, J. A., Oppenheimer, J., Rank, M. A., Shaker, M. S., Stukus, D. R., Wallace, D.,…Wang, J. (2022). Drug allergy: A 2022 practice parameter update. J Allergy Clin Immunol, 150(6), 1333-1393. https://doi.org/10.1016/j.jaci.2022.08.028 Mayo Clinic. (2025, Apr 30). Stevens-Johnson Syndrome. https://www.mayoclinic.org/diseases-conditions/stevens-johnson-syndrome/symptoms-causes/syc-20355936 Parisi, R., Shah, H., Navarini, A. A., Muehleisen, B., Ziv, M., Shear, N. H., & Dodiuk-Gad, R. P. (2023). Acute Generalized Exanthematous Pustulosis: Clinical Features, Differential Diagnosis, and Management. Am J Clin Dermatol, 24(4), 557-575. https://doi.org/10.1007/s40257-023-00779-3 Schiavino, D., Nucera, E., De Pasquale, T., Roncallo, C., Pollastrini, E., Lombardo, C., Giuliani, L., Larocca, L. M., Buonomo, A., & Patriarca, G. (2006). Delayed allergy to aminopenicillins: clinical and immunological findings. Int J Immunopathol Pharmacol, 19(4), 831-840. https://doi.org/10.1177/039463200601900412 Vashisht, P., Goyal, A., Hearth Holmes, M.P. (2022, Sep 12). Sweet Syndrome. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK431050/ Wolfson, A. R., Zhou, L., Li, Y., Phadke, N. A., Chow, O. A., & Blumenthal, K. G. (2019). Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome Identified in the Electronic Health Record Allergy Module. J Allergy Clin Immunol Pract, 7(2), 633-640. https://doi.org/10.1016/j.jaip.2018.08.013 |
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These pathways do not establish a standard of care to be followed in every case. It is recognized that each case is different, and those individuals involved in providing health care are expected to use their judgment in determining what is in the best interests of the patient based on the circumstances existing at the time. It is impossible to anticipate all possible situations that may exist and to prepare a pathway for each. Accordingly, these pathways should guide care with the understanding that departures from them may be required at times.