VIII. VITAMIN A DKFICIKNCV IX HUMAN BEINGS 159 



The latter epithelium is .stnitiHcd in type, but its more superficial cells are 

 constantly undergoing a fatty metamorphosis to produce, by the process of 

 holocrine secretion, the waxy sebum. Lack of vitamin A might merely in- 

 hibit the mechanism of secretory metamorphosis, but it seems more plau- 

 sible that failure of the altered duct epithelium to replace cells lost in the 

 secretory process is the pi'imary cause of sebaceous gland atrophy. Observers 

 have generally ignored the arrectores pilorum muscles of the pilosebaceous 

 apparatus, so that it is only presumed that they are normal. 



The sweat glands, which are also derivatives of the epidermis, possess 

 narrow, coiled excretory ducts contimious with excretory canals in the 

 epidermis which are merely intracellular clefts lined by epidermal cells. 

 Hyperkeratinization of the epidermis in avitaminosis A readily leads to 

 blockage of these excretory canals. The cuboidal epithelium of the duct 

 exhibits keratinizing metaplasia, especiallj^ in its terminal portion, contri- 

 buting also to blockage. Some dilation of acini occurs, probably as a result 

 of duct obstruction, but no metaplasia of glandular epithelium has been 

 observed. This is in accord with the promptness with which moistness of 

 the skin reappears after vitamin A therapy. 



F. MASSIVE VITAMIN A THERAPY IN CLINICAL MEDICINE 



Certain similarities between follicular hyperkeratosis and other skin dis- 

 orders involving pilosebaceous follicles and sweat glands, and postulations 

 that some of these lesions might represent a local, and possibly hereditary, 

 metabolic defect in utilization of vitamin A, have led dermatologists to 

 explore the therapeutic value of massive doses of \atamin A. The dosage 

 used has usually varied from 75,000 to 400,000 I.U. of vitamin A daily, in 

 the form of potent concentrates; this represents 15 to 80 times the recom- 

 mended daily allowance or 60 to 320 times the minimal daily requirement, 

 for adult man. This range of intake, extending over 3 to 6 months, produces 

 symptoms of hj'-pervitaminosis A in young children, as discussed below. 

 Although these studies are in an exploratory stage, reference to certain of 

 the observations reported seems pertinent, since they have particular bear- 

 ing upon the preceding discussion on cutaneous lesions and upon the ques- 

 tion of hypervitaminosis A to be dealt with later. 



Particular attention has been given to keratosis follicularis (Darier's 

 disease), a relatively rare condition, characterized by a benign dyskeratosis 

 associated with a moderate hyperkeratosis which leads to formation of 

 keratotic plugs not only in hair follicles but elsewhere on cutaneous sur- 

 faces.*^ The papular lesions are at first pale and discrete and later become 

 brown or reddi.sh as they tend to coalesce into papillomatous masses; the 

 palms and soles may become horny and thickened. 



" F. A. Ellis, Arch. Dermatol, and Syphilol. 50, 27 (1944). 



