OCHRONOSIS 471 



however, suggested a relation of ochronosis to alkaptonuria, having 

 found honiogentisic acid in the urine of a case reported by him (see 

 "Alkaptonuria")- Osier's two patients were brothers with alkap- 

 tonuria, the evidence of ochronosis consisting of discoloration of 

 the cartilages of the ears. Langstein'"' has examined a specimen of 

 urine preserved from Hansemann's case, and found no evidence of 

 alkaptonuria.^*^ 



Pick" summarizes the results of his study of his case and of the 

 literature, as follows: Ochronosis is a definite form of melanotic pig- 

 mentation, the pigment of ochronosis being in most of the cases very 

 closely related to melanin. The pigment, or its chromogcn, circulating 

 freely in the blood, is imbibed not only by cartilage, but also by loose 

 connective tissue, voluntary and involuntary muscle-cells, and epi- 

 thelial cells, without any decrease in vitality of these cells being 

 observable; however, degenerated tissues show the greatest amount of 

 pigmentation. The diffuse pigment can become granular after a time; 

 it is iron-free, but under certain circumstances may contain fat. This 

 melanin arises from the aromatic nucleus of the protein molecule (tyrosine, 

 phenylalanine), and the related hydroxylized products, under the 

 influence of tyrosinase. In some cases the constant absorption of mi- 

 nute quantities of phenol from surgical dressings seems to have been the 

 cause of the condition. Besides this formation of pigment from such 

 "exogenous" aromatic substances, however, it is probable that in 

 alkaptonuria the "endogenous" aromatic substance (homogentisic 

 acid) present may be converted into pigment by the tyrosinase. 

 In many of the cases of ochronosis the pigment or a precursor may be 

 excreted in the urine, which then undergoes spontaneous darkening 

 when exposed to the air. The kidneys may also become pigmented 

 and granular masses of pigment may be present in the renal tubules. 



Poulsen^*^ states that of the 32 known cases of ochronosis (in 1911) 

 in 17 there was alkaptonuria, in 8 carbohc acid dressings had been 

 used for long periods, and in the remaining 7 cases the cause was not 

 determined. These facts are conclusive evidence of the origin of 

 ochronotic pigment from aromatic radicals, whether these radicals 

 are converted into true melanin or not. The localization of the pig- 

 ment is explained by the demonstration by Gross and Allard,^^ that 

 cartilage has a greater affinity than other tissues for homogentisic 

 acid. Ochronosis can be produced experimentally with homogentisic 

 acid, and often is associated with an arthritis. •*" There are, however, 

 numerous cases of alkaptonuria without ochronosis. The ochronosis 

 described in lower animals is not the same as human ochronosis, affect- 



35 Hofmeister's Beitr., 1903, (4)145. 



3« Also see Langstein, Berl. klin. Woch., 1906 (43), 597. 



" Berl. klin. Wochenschr., 1906 (43), 478. 



38 Mlinch. med. Woch., 1912 (59), 364. 



33 Arch. exp. Path. u. Pharm., 1908 (59), 384. 



" Gross, Deut. Arch. klin. Med., 1919 (128;, 249. 



