A 26-year-old man is brought to the emergency department due to fever and lethargy. His girlfriend says the patient abruptly began experiencing fever, chills, vomiting, and diarrhea several hours ago, which were quickly followed by lightheadedness and lethargy. He has no prior medical conditions other than an episode of epistaxis after a bar fight 3 days ago. The patient does not smoke cigarettes or use injection drugs. There is no history of exposure to sick contacts, and he has not eaten anything out of the ordinary. Temperature is 38.9 C (102 F), blood pressure is 90/60 mm Hg, and pulse is 120/min. Physical examination shows a diffuse, erythematous rash. There is an anterior nasal packing in the left nostril, removal of which shows mild mucosal erythema with a purulent discharge. Cardiopulmonary and abdominal examinations reveal no abnormalities, and signs of meningeal irritation are absent. Which of the following processes is most essential in pathogenesis of this patient's current condition?

Question

A 26-year-old man is brought to the emergency department due to fever and lethargy.  His girlfriend says the patient abruptly began experiencing fever, chills, vomiting, and diarrhea several hours ago, which were quickly followed by lightheadedness and lethargy.  He has no prior medical conditions other than an episode of epistaxis after a bar fight 3 days ago.  The patient does not smoke cigarettes or use injection drugs.  There is no history of exposure to sick contacts, and he has not eaten anything out of the ordinary.  Temperature is 38.9 C (102 F), blood pressure is 90/60 mm Hg, and pulse is 120/min.  Physical examination shows a diffuse, erythematous rash.  There is an anterior nasal packing in the left nostril, removal of which shows mild mucosal erythema with a purulent discharge.  Cardiopulmonary and abdominal examinations reveal no abnormalities, and signs of meningeal irritation are absent.  Which of the following processes is most essential in pathogenesis of this patient's current condition?

Quizplus · Accepted Answer

11ec160b_37d7_bf69_9249_db39437cc47f_MD0001_00 Staphylococcal toxic shock syndrome (TSS) is an exotoxin-mediated disease associated with rapid-onset high fever, hypotension, multiorgan failure, and a diffuse, erythematous rash. Most cases are linked to prolonged tampon use or nasal wound packing, which provides a medium for localized Staphylococcus aureus proliferation and the elaboration of pyrogenic toxin superantigens (eg, toxic shock syndrome toxin-1 [TSST-1]) into the bloodstream. Pyrogenic toxin superantigens are generated by strains of S aureus (and Streptococcus pyogenes) that have acquired an underlying mobile genetic element via bacteriophage or plasmid. These exotoxins are called superantigens because they bind to the invariant region of the MHC-II complex of antigen-presenting cells without first being internalized and processed (MHC-II antigens are normally processed by the phagolysosome) (Choice E). The superantigen/MHC-II complex subsequently interacts with the variable part of the T-cell receptor beta chain, which results in the nonspecific stimulation of a large percentage (>20%) of total T cells and the massive release of inflammatory cytokines (eg, IL-1, IL-2, TNF-alpha & beta, interferon-gamma). Cytokine release mediates the major manifestations of TSS including fever, increased capillary permeability, and hypotension. (Choice A) Endotoxin in the cell membrane of gram-negative bacteria can cause rapid-onset fever and hypotension due to activation of toll-like receptors on cells of the innate immune system. However, in this case, the presence of nasal packing and a diffuse, erythematous rash make TSS far more likely than gram-negative sepsis. (Choice C) Anaphylactic shock occurs due to antigen-stimulated cross-linking of IgE that is bound to basophils or mast cells, which activates the cell and releases massive amounts of inflammatory mediators. Anaphylactic shock is typically characterized by hypotension, bronchospasm, and shortness of breath; most cases are triggered by insect stings, food, or medications, and manifestations occur shortly after exposure. (Choice D) Patients who develop TSS usually have a noninvasive infection in the vaginal canal or area of wound packing. TSS is mediated by the absorption of superantigens into the blood, not the invasion of bacteria. Educational objective: Toxic shock syndrome is typically associated with the prolonged use of tampons or wound packing, which allows Staphylococcus aureus to replicate locally and release pyrogenic toxic superantigens (eg, toxic shock syndrome toxin-1) into the blood. Superantigens bind to the MHC-II complex of antigen-presenting cells without processing and nonspecifically activate T cells. This leads to a dramatic release of inflammatory cytokines, which causes the manifestations of the disease (eg, hypotension; high fever; organ failure; diffuse, erythematous rash). __________ References: Exotoxins of Staphylococcus aureus (http://www.ncbi.nlm.nih.gov/pubmed/10627489)

A 26-Year-Old Man Is Brought to the Emergency Department Due