XI. PHARMACOLOGY 471 



have occunctl alik(> with picparalioiis Iroin (lilTorent manufacturers and 

 al.so with a(iucous sohitions of i-rystaliine thiamine hydrochloride. 



Since the «ym|)tomatolt)ji;y of these reactions is consonant with most, if 

 not all, aspects of anaphylactic shock, the most likely explanation for the 

 mechanism of tlu> reactions seems to be an anaphylactic one. In many of 

 the cases the ol)servers have obtained immediate whealing on intradermal 

 injection of thiamine, and, in some, positive transference of the sensitivity 

 has been accomplished. Since the manifestations of the thiamine reactions 

 are those known to occur with certain immunologic alterations and since 

 these patients have been shown to have such immunologic alterations, it 

 would appear reasonable to associate the tw^o. It is conceivable that a 

 combination of thiamine with protein develops which is antigenic to the 

 host. The eA'idence is, at present, not conclusive, and the anaphylactogenic 

 properties of thiamine require further investigation. If thiamine is an ob- 

 ligatory whealing agent,'*^ positive intradermal tests may not be valid proof 

 of individual sensitivity. Attempts to sensitize rabbits by massive and 

 repeated injections of thiamine have failed.'*^ 



Positive patch tests obtained in individuals with these reactions do not 

 present immunologic evidence for the immediate anaphylactic type of 

 reaction. They rather indicate the existence of the delayed eczematous 

 type of hypersensitivity which would be the immunologic substrate for the 

 contact dermatitis type of reaction. In persons handling pharmaceutical 

 preparations of thiamine, occurrence of contact dermatitis on the hands 

 and forearms has been observed.*^ 



Recently, on the basis of the similarity of hypotensive effects of thiamine, 

 acetylcholine, and histamine on intravenous injection in dogs, the sugges- 

 tion has been made^' *^ that overdoses of thiamine may cause an accumu- 

 lation of acetylcholine in excessive quantities in tissues which in turn may 

 be responsible for the occurrence of the untoward reactions observed in 

 man. Such an explanation lacks experimental evidence: the sudden onset 

 of these reactions, lack of correlation to dose administered, limitation to 

 parenteral injection, the manifestations comprising the entire spectrum of 

 anaphylactic signs and symptoms, and other facts militate against such an 

 assumption. 



*^ F. Kalz, J. Invest. Dermatol. 5, 135 (1942). 



"T. J. Haley and A. M. Flesher, Science 104, 567 (1946). 



*'' F. C. Combes and J. Groopman, Arch. Dermatol, and Sijphilol. 61, 858 (1950). 



« S. H. Jaros, Ann. Allergy 9, 133 (1951). 



