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The patient was diagnosed with group A streptococcus (strep) pharyngitis, also known as strep throat, after complaining of a sore throat for three days and a positive rapid strep test. A physical exam revealed a reddened posterior pharynx, white exudate on the tonsils, tonsils enlarged to 3+, and cervical adenopathy.
Strep throat is a bacterial infection caused by streptococcus pyogenes, gram-positive cocci that grow in chains in the throat and tonsils (Centers for Disease Control and Prevention, 2022). Streptococcus pyogenes are called group A streptococcus (Centers for Disease Control and Prevention, 2022).

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Group A streptococcus is contagious and spreads through respiratory droplets or direct contact (Centers for Disease Control and Prevention, 2022). It usually takes two to five days for someone exposed to group A streptococcus bacteria to become ill with strep throat (Centers for Disease Control and Prevention, 2022).

Acute pharyngitis commonly presents with a sore throat, painful swallowing, fever, pharyngeal and tonsillar erythema, tonsillar hypertrophy with or without exudate, palate petechiae, and cervical lymphadenopathy due to colonization in the throat and tonsils (Centers for Disease Control and Prevention, 2022).

Strep throat is more common in children 5 to 15 years old, rare in children less than three-year-old, and most common during the winter and spring in the United States (Centers for Disease Control and Prevention, 2022).

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Adults are at increased risk for strep if they have school-aged children or are in frequent contact with children (Centers for Disease Control and Prevention, 2022). Close contact with infected individuals is the most common risk factor for illness (Centers for Disease Control and Prevention, 2022).

Infection typically spreads in large groups of people, such as schools, daycares, or military facilities (Centers for Disease Control and Prevention, 2022). Since this patient is 16 years old, he likely attends school, and this is likely where he contracted the illness.

If this were an adult that works from home with grown children, he would be less susceptible to contracting the infection. There appears to be no genetic component to strep throat; however, conditions associated with recurrent strep susceptibility run in families, suggesting a genetic component (Dan et al., 2019).

Dan et al. (2019) found that children with recurrent tonsillitis had smaller germinal centers and reduced antibacterial antibodies revealing that altered adaptive immune responses to group A streptococcus may make an individual susceptible to recurrent infection (Dan et al., 2019).

Since this patient denies a history of recurrent colds, influenza, ear infections, or pneumonia, we can presume this is an isolated occurrence.

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Because the patient reported no know drug allergies, amoxicillin was ordered. However, the patient quickly complained of swollen lips and tongue, difficulty breathing, and wheezing. These symptoms signify a type I immediate hypersensitivity reaction to amoxicillin.

Hypersensitivity reactions are exaggerated immune responses to an antigen or allergen (Justiz-Vaillant & Zito, 2019). Immediate hypersensitivity reactions are types I, II, and III, and they occur within 24 hours of exposure (Justiz-Vaillant & Zito, 2019).

Type I hypersensitivity reactions exhibit a response mediated by immunoglobulin E (IgE) antibodies produced by the immune system in response to allergens and typically occur within 15 to 30 minutes of exposure to the antigen (Justiz-Vaillant & Zito, 2019; Soo, 2018).

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Anaphylaxis is the most rapid and severe immediate hypersensitivity reaction occurring within minutes of re-exposure to the allergen; symptoms of generalized anaphylaxis include breathing problems, gastrointestinal upset, headaches, erythema, bronchial constriction, laryngeal edema, vascular collapse, hypotension, and itching (McCance & Huether, 2019).

This response occurred because this patient likely had a previous exposure to amoxicillin. With the first exposure, the allergen binds to B cells which stimulate the production of IgE antibodies against this allergen; the IgE antibodies bind to Fc receptors on mast cells (Soo, 2018).

When exposed to the allergen again, the allergen binds to the antibodies attached to the mast cells causing the mast cells to degranulate and release chemicals that are proinflammatory mediators (Soo, 2018). These histamines include prostaglandins, interleukins, and leukotrienes (Soo, 2018). This is a form of adaptive immunity.

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Adaptive immunity attacks specific antigens with a slow initial response but a more rapid response with the second exposure (Soo, 2018). Mediators include histamine and lipid mediators such as PAF, LTC4, and PGD2, causing bronchoconstriction, inflammation, vascular leak, and intestinal hypermotility (Justiz-Vaillant & Zito, 2019).

Tumor necrosis factor causes inflammation (Justiz-Vaillant & Zito, 2019). Basophils can be found in the nose, lungs, skin, or gut during a hypersensitivity reaction, and mast cells are found in the mucosa and connective tissue (Justiz-Vaillant & Zito, 2019).

This causes symptoms including wheezing, airway inflammation, tachycardia, tachypnea, itchy eyes and nose, sneezing, dermatitis, gastrointestinal upset, increased vascular permeability, vasodilation, hypotension, hives, bronchoconstriction, and increased mucous secretions (Justiz-Vaillant & Zito, 2019; Soo, 2018).

This allergic response is why this patient presents with wheezing, difficulty breathing, and swelling of the lips and tongue. IgE initiates inflammatory and allergic reactions (Soo, 2018).

In type I hypersensitivity reactions, the allergens are proteins with a molecular weight of 10 to 40 kDa; allergens include drugs, plants, fungi, rats, grass, German cockroaches, dust mites, and cats (Justiz-Vaillant & Zito, 2019).

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β-lactam antibiotics, including penicillin and amoxicillin, are associated with various immune-mediated or hypersensitivity reactions, including immediate type I reactions (Nicoletti et al., 2021).

Hypersensitivity reactions are common, affecting 15% of the world’s population at some point (Justiz-Vaillant & Zito, 2019). Type I hypersensitivity reactions have a strong genetic or hereditary linkage regarding IgE response to the antigen or allergens (Soo, 2018).

Risk factors for immediate hypersensitivity reactions to β-lactam antibiotics are family history, concurrent virus infections, and the route of administration (Nicoletti et al., 2021). An analysis of single nucleotide polymorphisms identified that the HLA-DRA locus might protect against penicillin-induced immediate hypersensitivity reactions (Nicoletti et al., 2021).

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Wong et al. (2019) conducted a study that found that females account for most hypersensitivity reactions. The study also revealed that white patients accounted for most immediate and delayed hypersensitivity reactions (Wong et al., 2019).

Penicillin also accounted for one of the most significant proportions of drug hypersensitivity reactions (Wong et al., 2019).

References

Centers for Disease Control and Prevention. (2022, June 27). Group A streptococcus: Information for clinicians. Centers for Disease Control and Prevention. Retrieved November 28, 2022, from https://www.cdc.gov/groupastrep/diseases-hcp/index.html

Dan, J. M., Havenar-Daughton, C., Kendric, K., Al-kolla, R., Kaushik, K., Rosales, S. L., Anderson, E. L., LaRock, C. N., Vijayanand, P., Seumois, G., Layfield, D., Cutress, R. I., Ottensmeier, C. H., Lindestam Arlehamn, C. S., Sette, A., Nizet, V., Bothwell, M., Brigger, M., & Crotty, S. (2019). Recurrent group A Streptococcus tonsillitis is an immunosusceptibility disease involving antibody deficiency and aberrant TFH cells. Science Translational Medicine, 11(478). https://doi.org/10.1126/scitranslmed.aau3776

Justiz-Vaillant, A. A., & Zito, P. M. (2019). Immediate hypersensitivity reactions. In StatPearls. Treasure Island, FL: StatPearls Publishing. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK513315/

McCance, K. L. & Huether, S. E. (2019). Pathophysiology: The biologic basis for disease in adults and children (8th ed.). St. Louis, MO: Mosby/Elsevier.

Nicoletti, P., Carr, D. F., Barrett, S., McEvoy, L., Friedmann, P. S., Shear, N. H., Nelson, M. R., Chiriac, A. M., Blanca-López, N., Cornejo-García, J. A., Gaeta, F., Nakonechna, A., Torres, M. J., Caruso, C., Valluzzi, R. L., Floratos, A., Shen, Y., Pavlos, R. K., Phillips, E. J., … Pirmohamed, M. (2021). Beta-lactam-induced immediate hypersensitivity reactions: A genome-wide association study of a deeply phenotyped cohort. The Journal of Allergy and Clinical Immunology, 147(5), 1830–1837. https://doi.org/10.1016/j.jaci.2020.10.004

Soo, P. (2018, July 28). Pathophysiology Ch 10 alterations in immune function [Video file]. Retrieved from

Wong, A., Seger, D. L., Lai, K. H., Goss, F. R., Blumenthal, K. G., & Zhou, L. (2019). Drug Hypersensitivity Reactions Documented in Electronic Health Records within a Large Health System. The Journal of Allergy and Clinical Immunology: In Practice, 7(4), 1253–1260. https://doi.org/10.1016/j.jaip.2018.11.023

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