Arthus

Di-tert-butyl-4-hydroxyphenyl)-7//-triazolo [3,2-b][l, 2,4]triazin-7-one (HWA-131)is anon-immunosuppressive drug that effectively inhibited carrageenan-induced paw edema, attenuated the active Arthus reaction, and demonstrated antierythema as well as antipyretic activity. Part of the antiinflammatory effect of this new compound is most probably related to its antioxidative activity as well as inhibition of lipoxygenase... 

Hazenbos WL, Gessner JE, Hofhuis FM, Kuipers H, Meyer D, Heijnen lA, Schmidt RE, Sandor M, Capel PJ, Daeron M, van de Winkel JG, Verbeek JS Impaired IgG-dependent anaphylaxis and Arthus reaction in FcyRIII (CD16)-deficient mice. Immunity 1996 5 181-188. 

The Arthus reaction. The phenomenon is a local one and occurs if a soluble antigen is introduced into the body when there is a great excess of antibody. The union between the two results in an acute inflammatory reachon which may involve complement, polymorphs, lymphokines or platelet aggregation, all of which enhance the inflammatoiy response. 

Pain at the injection site is one of the most commonly reported adverse effects of vaccination. The reaction is usually mild with complaints of pain and tenderness at the injection site that may or may not be accompanied by erythema. Local reactions tend to be more frequent with repeated doses or booster doses of vaccine. The frequency and degree of the reactions appear to be related to the amount of preformed antibodies and rapid immunologic responses reflective of priming from previous doses. More serious Arthus reactions are infrequently reported. Arthus reactions are classified as type III hypersensitivity reactions, and are characterized by a massive local response involving the entire thigh or deltoid. Arthus reactions are also related to preformed antibody complexes that induce an inflammatory lesion.14... 

Arthus reaction Local inflammatory response due to deposition of immune complexes in tissues. 

Docebenone has shown anti-inflammatory effects in several animal models following local dosing phorbol ester-induced oedema and neutrophil influx in mouse skin [208,209], arachidonate-induced plasma extravasation in rabbit skin [210], the pleural reversed passive Arthus reaction in rats [211], and GPB [212], An oral dose of 80 mg/kg reduced infarct size, LTB4 levels and neutrophil infiltration in a rat myocardial infarction model [213,214], and in a rat brain ischaemia-reperfusion model oedema and LTC4 levels were reduced at 200 mg/kg [107]. Significant, but not dramatic, improvement in nasal symptoms was seen in humans following 150 mg of docebenone twice daily for 8 weeks [215], but there was no effect on bronchial hyperresponsiveness to acetylcholine in asthmatics [216]. 

One of the first compounds reported to inhibit 5-LO was the NSAID benox-aprofen (167) (reviewed in [405]). This drug (marketed by Lilly as Oraflex ) was effective in rheumatoid arthritis, but was withdrawn because of phototoxicity, liver toxicity and reports of drug-related deaths [406]. The typical NSAID anti-inflammatory profile of this compound was remarkable for its very weak seminal vesicle CO activity [407]. Additional in vivo activities were found for benoxaprofen which were not shared by other NSAIDs, particularly inhibition of leukocyte influx in the carrageenan sponge, carrageenan pleurisy, and rat Arthus pleurisy models monocytes were affected more than neutrophils [408-411]. More recently, benoxaprofen was reported to inhibit the adhesion of monocytes to endothelium [412]. 

Type 3, immune complex vasculitis (serum sickness, Arthus reaction). Drug-antibody complexes precipitate on vascular walls, complement is activated, and an inflammatory reaction is triggered. Attracted neutrophils, in a futile attempt to phagocytose the complexes, liberate lysosomal enzymes that damage the vascular walls (inflammation, vasculitis). Symptoms may include fever, exanthema swelling of lymph nodes, arthritis, nephritis, and neuropathy. 

Arthus LJ. Measuring Programmer Productivity and Software Quality. New York Wiley, 1985. 

Arthus (reaction) Type III immediate hypersensitivity reaction. 

Type III Reactions These reactions involve the presence of antigen-antibody complexes, particularly those formed as a result of the production of autoantibodies. These complexes deposit in various tissues and involve inflammatory cells as well as complement, resulting in tissue damage due to the production of proteolytic enzymes by polymorphonuclear leukocytes and macrophages. A number of autoimmune diseases result from these reactions. Some clinical examples include systemic lupus erythematosus, rheumatoid arthritis, immune complex glomerulonephritis, Arthus reaction and serum sickness. 

A 45-year-old woman who had used insulin for 4 years had a biphasic hypersensitivity reaction to human insulin (or another component of the injection fluid) (135). Within 20 minutes after the injection a swelling developed and in a later phase papular lesions with lichenoid features and post-inflammatory hyperpigmentation emerged. Histologically, there was neutrophilic infiltration with erythrocyte extravasation and eosinophilic amorphous material, surrounded by neutrophilic infiltrate. Saline injection did not elicit an effect. IgE anti-insulin antibodies were not found. There was no Arthus reaction (type IV allergy). 

Other reactions are of the tuberculin granulomatous type or of the local vasculitis Arthus type. The local reactions can be accompanied, preceded, or followed by a generalized reaction, such as urticaria, nausea, vomiting, diarrhea, angioedema, wheezing, or anaphylactic shock. The last of these is rare, but sometimes fatal. 

Systemic lupus erythematosus (SLE or lupus), serum sickness, arthus reaction. Mediated by IgG and complement. 

General reactions (seen in some older children and adults) are usually limited to brief fever sustained fever and other systemic reactions are uncommon unless the person has been hyperimmunized. After the administration of DT vaccine, local reactions, generally erythema and induration, with or without tenderness, can occur. In hyperimmunized cases, Arthus-type hypersensitivity reactions can occur. These characteristically severe local reactions generally start 2-8 hours after an injection. People who have such reactions usually have very high serum antitoxin concentrations and one should be careful not to administer a booster more than once every 10 years. 

Arthus reactions and systemic reactions have commonly been reported after booster doses of polysaccharide vaccine and are thought to result from antigen-antibody reactions involving antibodies induced by the previous immunization (16). Data on revaccination of children are not yet sufficient to provide a basis for recommendation. 

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