X. EFFECTS OF DEFICIENCY 389 



drome. '-^ It is now apparent (hat the cause of faihire in those studies in 

 wliich tlie t>T3i('al ])icture was not i)roduced was either the ])revity of the 

 experimental period'-^ or too high a level of riboflavin in the diet.'-*'"^" 

 Williams ct al.^-^ fed a diet containing between 0.8 and 0.9 mg. per day for 

 over 9 months, and Kej'^s et a/.'-^ gave 1.0 mg. for 5 months without pro- 

 ducing any clinical changes. Horwitt ct a/.'*" fed a diet containing between 

 0.8 and 0.9 mg. of riboflavin daily for over 2 years, and only one of twenty- 

 two subjects showed any signs (angular stomatitis) which might be attrib- 

 uted to a lack of riboflavin. However, when these workers'^' "'^* reduced the 

 riboflavin intake to 0.55 mg. per day, a level only slightly higher than that 

 used by Sebrell and Butler, incontrovertible signs of ariboflavinosis ap- 

 peared in less than 6 months. Subsequent studies'^'* have confirmed these 

 observations and have indicated that the course of the development and 

 healing of the lesions was not altered by low dietary levels of nicotinic acid 

 (6 mg.) and trj'ptophan (250 mg.). 



The oral lesions which are generally accepted to be part of the clinical 

 picture of riboflavinosis may be summarized as follows: angular stomatitis, 

 fissures in the angles of the mouth which resemble perleche, cheilosis, in- 

 volvement of the vermilion border of the lips including vertical fissuring, 

 and crusting and desquamation of the mucous membrane. Glossitis, includ- 

 ing the magenta tongue, may be seen, but "pure" riboflavin deficiencies 

 have been produced^^- without such defects. 



The characteristic facial lesions include seborrheic accumulations in the 

 folds of the skin, especially in the nasolabial folds. Mild infections of the 

 upper respiratory tract may initiate an inflammation of the nostrils and 

 spread as a weeping, crusty lesion over the skin of the septum. Fissures may 

 appear in the nasolabial folds. 



2. Lesions of Scrotum and Vulva 



Stannus^"-' '"^ was the first to record that scrotal involvement may be 

 the initial sign of deficienc}^ (nineteen of one hundred cases of ''pellagra"). 



'" M. Ellenberg and H. Pollack, ./. Aw. Med. Assoc. 119, 790 (1942). 



'" J. J. Boehrer, C. E. Stanford, and E. Ryan, Ajh. J. Med. Sci. 206, 544 (1943). 



128 R. D. Williams, H. L. Mason, P. L. Cusick, and R. M. Wilder, /. Nutrition 25, 

 361 (1943). 



•" A. Keys, A. F. Henschel, O. Mickelsen, J. II. Brozek, and J. H. Crawford, /. Nu- 

 trition 27, 165 (1944). 



"» M. K. Horwitt, E. Liebert, O. Kreisler, and P. Wittman, Bull. Nat. Research 

 Council (U.S.) 116 (1948). 



'^' E. A. Zeller, Advances in Enzymol. 2, 93 (1942). 



'" O. W. Hills, E. Liebert, D. L. Steinberg, and M. K. Ilorwitt, Arch. Internal Med. 

 87, 682 (1951). 



'" M. K. Ilorwitt, C. C. Harvey, (). W. Hills, and E. Liebert, J. Nutrition 41, 247 

 (1950). 



''^ M. K. Horwitt, Personal communication (1952). 



