Intradermal tolerance

Intradermal tolerance of local anesthetics can be used as a screening selection criterion for finding an optimal local anesthetic. Luduena Hoppe (1952), Luduena et al. (1960) determined intradermal irritancy by the trypan blue method according to Hoppe et al. (1950). 

Subcutaneous Provocation Testing. When prick and intradermal tests are negative, subcutaneous provocation testing is started using 0.1 ml of the undiluted LA solution followed by 0.2, 0.5, 1.0 and 2.0 ml into the extensor side of the patients upper arm at 30-min intervals. For most of the patients it is possible to find a tolerable LA which is recommended for future applications [33] (table 3). In a long-term followup, Wasserfallen and Frei [32] found in 28 patients undergoing skin and subcutaneous provocative testing that over 3 years in 19 cases re-exposure to a tolerated LA was well tolerated without untoward reaction. 

Takabayashi K, Tibet L, Chisholm D, Zubeldia J, Horner AA Intranasal immunotherapy is more effective than intradermal immunotherapy for the induction of airway allergen tolerance in Th2-sensitized mice. J Immunol 2003 170 3898-3905. 

Epstein, J.E., E.J. Gorak, Y. Charoenvit, et al.. Safety, tolerability, and lack of antibody responses after administration of a PfCSP DNA malaria vaccine via needle or needle-free jet injection, and comparison of intramuscular and combination intramus-cular/intradermal routes. Hum Gene Ther, 2002.13(13) 1551-60. 

With regard to safety, pDNA has been found to be safe and well-tolerated in a variety of species. In mice, the repeated i.m. administration of pDNA has not been found to be associated with the induction of autoimmune disease in animals prone to developing autoimmune disease (Mor et al., 1997). In mice and rabbits, the repeated i.m. or combined i.m./intradermal (i.d.) administration of pDNA-based malaria... 

In all three trials, the candidate vaccines were well tolerated alone and in combination. Clinical signs were limited to reactions (soreness, redness, etc.) at the intradermal injection site, and no adverse events were considered to be related to vaccine treatment. 

Brogard JM, Bergoend H, Basset A (1969) Tolerance du traitement par la cephaloridine. Etude Clinique et application du test de Shelley aux recherches de sensibilisation croisee entre penicilline et cephaloridine. Nouv Presse Med 77 1539 Brooks AP (1974) Thrombocytopenia during treatment with ampicillin. Lancet 2 723 Brown BC, Price EV, Moore MB (1964) Penicilloyl-polylysine as an intradermal test of penicillin sensitivity. JAMA 189 599... 

A tolerance can be induced in guinea pigs already sensitized. It can be done in sensitized animals (according to the method of W. Frei, 1928), by injecting neo-arsphenamine intravenously and 6 hours later intradermally (Frey and coll., 1964). 

A 44-year-old woman, who had previously tolerated moxifloxacin, developed pmritus, urticaria, and angioedema 10 minutes after a dose of moxifloxacin [IV j. Skin tests were performed with various quinolones and only the intradermal test with moxifloxacin was positive. She tolerated an oral challenge with... 

With few exceptions, such as peptides and hormones, drugs and their precursors are typically low-molecular-weight compounds and, therefore, haptens. To build a complete antigen, they must bind to macromolecules e.g. human tissue or serum proteins. Some drugs are primarily reactive while, in others, reactive metabolites are only generated in vivo. Oral administration is usually better tolerated and may even induce tolerance. However, intermittent exposure by epi- or intradermal application or by inhalation, as it typically occurs in occupational settings, carries the highest risk of sensitization (Bircher 1996). 

Danaparoid is chemically distinct from heparin and generally shows little or no cross-reactivity in heparin-intolerant patients. It is a mixture of heparan sulfate, dermatan sulfate, and chondroi-tin sulfate and works by inhibiting factor Xa. Danaparoid should be included in tests on patients who cannot tolerate LMW heparins. Reported reactions to the drug include rash, pruritus, and reactions (some delayed) at the injection site. Prick tests are undertaken with undiluted commercial preparations and intradermal tests... 

Successful oral desensitization of a patient who experienced anaphylaxis to omeprazole was achieved after 5.6 h, starting with an initial dose of 1 pg of drag and ending with a full dose of 16 mg for a total cumulative dose of 32.6 mg. After the desensitization, the patient was able to tolerate the full dose uneventfully and the wheal size of the intradermal response to omeprazole was significantly reduced. 

Most work on saponins as immunological adjuvants has been done following parenteral inoculation. Saponins are more toxic by parenteral (i.p. or i.v.) administration than by the oral route, presumably because of a more complete uptake by the former. Toxicity associated with Quil A has limited its development to veterinary vaccines. The maximum well tolerated i.p. dose in mice was estimated to be 25 ig. Significantly lower toxicity was observed by subcutaneous, intradermal, and intramuscular routes of administration. The toxicity of individual saponins varies considerably. For example, the major peak saponin QS-18 (2) was found to be toxic in mice at low doses (80% mortality within three days after i.d. injection of 125 p,g) whereas QS-7 was non toxic (100% survival with 0.5 mg, the highest dose tested). A simple analogy between hemolytic activity and toxicity is not possible since QS-21 (3), which was shown to have a slightly higher hemolytic activity than QS-18 (2), was proven to be less toxic [9]. 

Immunologic Topical corticosteroids have been previously implicated in allergic contact dermatitis, but only rarely in systematic allergic reaction. Lips, nose, and eyelid angioedema and pruritic urticarial papules in face, chest, and arms of a 34 year old nonatopic woman were attributed to nasal budesonide, which was administered for common cold [32 ]. The adverse effects developed 8 h after the second administration of 256 gg of budesonide nasally (two puffs per nostril) and remitted gradually over 3-4 days and after treatment with hydroxyzine. Previously the patient had tolerated nasal budesonide without adverse effects. This case of systemic allergic reaction was confirmed by positive results in patch and intradermal test and without cross-reactivity with others corticosteroids. 

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