Systemic hypersensitivity

Anaphylactic shock. A systemic hypersensitivity response resulting in dramatic decrease in blood pressure. 

Local or systemic hypersensitivity reactions may occur in some patients receiving vasopressin. Tremor, sweating, vertigo, nausea, vomiting, abdominal cramps, and water intoxication (overdosage, toxicity) may also be seen. 

Much of the methods development and validation efforts in the past have been focused on evaluation of immunosuppression and contact or dermal sensitization. Currently available animal models and assays are not valid to assess the potential for systemic hypersensitivity and, at this time, reliable models to assess autoimmunity are not available. 

There are no established assays that reliably assess potential for autoimmunity and acute systemic hypersensitivity. The popliteal lymph node assay (PLNA) has only a relatively small database available for assessing its usefulness for drug regulatory purposes. 

Shock, similar to that of anaphylaxis, may occur as a third form of a delayed systemic hypersensitivity response. However, unlike anaphylaxis, IgE antibodies are not involved. This type of response may occur 5-8 h after systemic exposure and can result in fatality within 24 h following intravenous or intraperitoneal injection. 

Urist, M. R. Induced systemic hypersensitivity Selye s theory. Science 137,120—121 (1962). 

Mozelsio, N.B. et ah, Immediate systemic hypersensitivity reaction associated with topical application of Australian tea tree oil. Allergy Asthma Proc. 24, 73-75, 2003. 

Weaver, J.L., Staten, D., Swarm, J., Armstrong, G., Bates, M., Hastings, K.L. (2003). Detection of systemic hypersensitivity to drugs using standard guinea pig assays. Toxicology 193 209-17. 

Dorzolamide is administered topically but can be absorbed systemically. Although there is risk of systemic hypersensitivity reactions to dorzolamide, a nonantibiotic sulfonamide, in patients allergic to sulfonamide antibiotics, the risk appears to be low. 

Ocular complications are rare with systemic use of this class of drugs. Lid edema, conjunctivitis, chemosis, anterior uveitis, and scleral reactions have been reported with high-dose administration of sulfenilamide. The observed reactions appear to be analogous to systemic hypersensitivity reactions, such as urticaria and edema, seen in some patients who are allergic to sulfonamides. Several cases of Stevens-Johnson syndrome have been reported in patients of Japanese or Korean descent who were given oral metha-zolamide, a sulfonamide used to decrease lOP. Stevens-Johnson syndrome tends to show acute ocular involvement in 69% of affected individuals.This is stratified into mild ocular involvement in 40%, moderate in 25%, and severe in 4%. Late complications can occin and are usually in the form of severe ocular surfece disease and trichiasis. 

Although anaphylactic reactions without any documented immune-mediated mechanism have been reported in about 8% of patients with testicular cancer given GM-CSF (48), GM-CSF has only otherwise rarely been associated with allergic reactions. Of two patients who had possible immune-mediated reactions (SEDA-19, 342) one had an immediate recurrent local reaction followed by systemic hypersensitivity reaction after sargramostim, and the other had a maculopapular pruritic eruption after molgramostim. Cross-reaction between the two recombinant forms of GM-CSF was suggested by the results of skin prick tests in one patient, but both patients thereafter tolerated filgrastim uneventfully. 

Mandell BE, Raps EC. Severe systemic hypersensitivity reaction to ibuprofen occrrrring after prolonged therapy. Am J Med 1987 82(4) 817-20. 

Postmarketing surveillance data of adverse events after Japanese encephalitis immunization in Japan and the USA have been compared (7). The rates of total reported adverse events were 2.8 per 100 000 doses in Japan and 15.0 per 100 000 doses in the USA. In Japan, 17 neurological disorders were reported from April 1996 to October 1998 (0.2 per 100 000 doses), whereas in the USA there were no serious neurological adverse events temporally associated with Japanese encephalitis vaccine from January 1993 to June 1999. Rates for systemic hypersensitivity reactions were 0.8 and 6.3 per 100 000 doses in Japan and the USA respectively. 

Systemic hypersensitivity reactions are not a frequent problem in local anesthesia. Systemic toxicity or allergy to additives (hyaluronidase, bisulfate, parabens) has sometimes been mistakenly classified as hypersensitivity to local anesthetics (SEDA-17,135) (29). WeU-documented case reports are very few, relating particularly to the older aminoesters this appears to be because these agents have the highly antigenic para-aminobenzoic acid as a metabolite (SEDA-13, 98). The incidence of true allergy is actually very low, probably less than 1% of all the adverse effects attributable to these substances (SEDA-20, 123). 

There are various types of NSAID-induced rashes. The main morphological patterns are urticarial, maculo-papular, vesicular, and exfoliative. Skin reactions to NSAIDs are probably of phototoxic origin and can be associated with systemic hypersensitivity or other allergic reactions. More rarely, NSAIDs can exacerbate... 

Grussendorf M, Andrassy K, Waldherr R, Ritz E. Systemic hypersensitivity to allopurinol with acute interstitial nephritis. Am J Nephrol 1981 1 195-109. 

The organic alkylmercury compound thimerosal (sodium ethyl-mercury thiosalicylate) is another modem facet of mercury. Rare cases of systemic hypersensitivity with skin (Zenarola et al., 1995) and respiratory (Maibach, 1975) manifestations as well as acrodynia (Matheson et al., 1980) have been reported. Thimerosal in vaccines is discussed more in chapter 9. 

---