Clinical Manifestations and Genetic Influences in Sulfonamide-Induced Hypersensitivity

Figures & data

Figure 1 Sulfonamide metabolites that cause hypersensitivity.

Table 1 Summary of Clinical Manifestations of Sulfonamide Hypersensitivity Reactions

Clinical Manifestation	Mechanism	Type of Hypersensitivity	Number of Cases	References
Angioedema (Swelling around the eyes, lips, and tongue, shortness of breath and dizziness)	Increase in the permeability of the local or subcutaneous submucosal capillaries, which causes extravasation of plasma, eventually causing temporary swelling	Early-Type Hypersensitivity Reaction Type I hypersensitivity reaction	More than 25% of people in the US and 7.4% international occurrence	[19–23]
Uveitis (Redness, painful eyes, conjunctival injection, and total vision loss)	Unknown	Delayed-Type Hypersensitivity Reaction Type III hypersensitivity reaction	14 patients with bilateral anterior uveitis without hypopyon	[24–26]
Skin Rash (Redness, pain, swelling, itching, and irritation skin)	Involves Ig E and T cells and sometimes Ig G	Delayed-Type Hypersensitivity Reaction Type IV hypersensitivity reaction	Occurs in about 2–3% of hospitalized patients	[27–29]
SJS/TEN (Blisters, hemorrhagic erosion of mucous membranes, fever, and malaise)	Sulfonamides are metabolized by N-acetyltransferases, and associated with the formation of hydroxylamine, primarily via CYP2C9 that interact with cellular macromolecules which will initiate the formation of tissue damage	Delayed-Type Hypersensitivity Reaction Type IVc hypersensitivity reaction	1.8 and 9.0 per million person-years	[30–32]
Parotitis (Parotid swelling, tenderness, and erythema)	Unknown	Delayed-Type Hypersensitivity Reaction Type I hypersensitivity reaction	56 cases as salivary gland swelling with eosinophil-rich mucus	[33,34]
DRESS (fever, facial edema, papules on the buccal mucosa, and rash all over his body)	The mechanism has been seen in Figure 2	Delayed-Type Hypersensitivity Reaction Type IVb hypersensitivity reaction	17-year-old male and 23 cases	[35–37]
Pruritus (xerosis (dry skin) or eczema, and impair sleep, cause fatigue and irritability for chronic pruritus)	Basophilic leukocyte and mast cells have been activated by chemical, biology, or etc. Then, histamine has released and binds H1R. The activation of H1R by histamine causes activation of phospholipase Cβ3 (PLCβ3) and phospholipase A2 (PLA2) that increase the development of pruritus	Delayed-Type Hypersensitivity Reaction Type I hypersensitivity reaction	23% in 26 patients	[38–40]

Figure 2 Mechanism of sulfonamide hypersensitivity.

NIH. Rashes. Available from: https://medlineplus.gov/rashes.html. Accessed June 9, 2021.

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