Ochronosis

OCHRONOSIS (from Greek ochros-pale, light yellow), a term introduced by Virchow (Virchow) to denote a peculiar pathological condition characterized by abnormal pigmentation, ranging from light brown to ink-black, of cartilage and cartilaginous connective tissue (ligaments, periosteum, arterial intima). - Etiology. Albrecht was the first to establish that O. is a concomitant phenomenon, though not always, of alkaptonuria (see). Subsequently, Frank and Pope noted that O. occurs not only in alkaptonuria but also as a result of the introduction over a number of years (3-30 years) of small amounts of carbolic acid in the form of carbolic dressings made from 2-3% carbolic water or 5% carbolic oil, used in chronic leg ulcers. The homogentisic (alkaptonuric) acid found in the body in alkaptonuria apparently serves as the material for the formation of ochronotic pigment, the chemical structure of which has not been established. In carbolochronosis, homogentisic acid is formed from hydroquinone and benzocatechol (Pick). Thus, a distinction is made between endogenous (associated with alkaptonuria) and exogenous (with chronic introduction of carbolic acid) forms of ochronosis. Fischberg, up to 1924, had collected 42 cases of ochronosis in the literature: 26 cases in alkaptonuria, 8 cases of carbolochronosis, and 8 cases with unclear etiology. Pathological Anatomy. At autopsy, it is found that all cartilages (of ribs, joint surfaces, trachea, ear shells, nose, etc.), connective tissue, cartilaginous masses (ligaments, tendons, fasciae, cartilaginous layers of joints, periosteum, arterial intima, especially of the aorta) are peculiarly pigmented. This pigmentation is sometimes light gray, sometimes ink-black (see - separate table to the article Pemphigus, fig. 1). In severe cases, pigmentation may extend to smooth and striated muscle, as well as to the kidney parenchyma. Cysts found in the kidneys contain brown-black fluid. In the renal pelvis, there are coal-black, hard, ochronotic concretions, and on the surface of arterio- and arteriolosclerotic kidneys, separate brown or black points, which upon closer examination prove to be cysts. The heart valves are colored smoky-gray, sometimes with black stripes, dots, and spots. The inner surface of vessels is yellow-brown or light gray, sometimes with black stripes. Sclerotic plaques are surrounded by a black border. The base of atheromatous ulcers is mottled-black. The main disease - alkaptonuria - is often accompanied by erosive arthritis, although it is also observed in carbolochronosis. - Microscopic examination reveals a diffuse yellow coloration of the main cartilaginous or collagenous substance; this coloration only partially, in particularly intensely colored areas, also involves the cells. In the kidneys, ochronotic cylinders were rarely found. Ochronotic pigment appears mostly as diffuse, rarely granular. It is easily soluble in alkalis, difficult in acids, and insoluble in commonly used solvents, particularly in chloroform. With prolonged treatment with a 2% solution of H₂O₂ it is decolorized. It apparently does not contain iron. Like some melanins, it contains sulfur. It does not give absorption bands in the spectrum. The reaction with Sudan and osmic acid is negative (Pick). Virchow considered ochronotic pigment a derivative of hematine. Pick, Jantke, and others consider it closely related to melanins. In elucidating the genesis of ochronotic pigment, the experiments of Katsch are of great importance, who discovered that by varying degrees of oxidation with H₂O₂ from homogentisic acid, a series of dyes can be obtained - straw-yellow, pink, red, brown, and black. With prolonged action of H₂O₂, the decolorized solution is found to be free of homogentisic acid. Katsch believes that in the organism, physiologically, due to the oxidizing action of tyrosinase, a corresponding pigment is formed from tyrosine and homogentisic acid. Allard and Gross, by prolonged action of solutions of homogentisic acid on pieces of cartilage, obtained gray and black coloration of them, spreading from the surface into the depth of the tissue. Sterile pieces of various organs of rabbits, placed in a 1% solution of homogentisic acid in an incubator, quickly showed gray, brown, or black coloration of the surface. These experiments, in their opinion, indicate the enzymatic action of tissues. Ochronotic pigment is deposited first of all in cartilages. This is explained by the fact that in cartilage, as a tissue poor in blood vessels, the general metabolism and oxidative processes are slowed down, which creates favorable conditions for the accumulation of pigment. Similar conditions are also found in senile tissues. Ochronotic pigment is formed in all tissues, but with normally proceeding oxidative processes, the formation and breakdown of the pigment proceed uniformly (Fischberg). Symptomatology. In clinical examination, the most prominent symptom is external pigmentation, which accompanied all known cases of carbolochronosis and was sometimes absent in alkaptonuric O. The coloration of the skin is yellow-brown, earthy, or bronze. The cartilaginous parts of the ears, especially the auricles, are colored in all shades from gray-blue to dark blue. Spots of the same color are found on the sclera at the edge of the cornea. More or less pronounced bluish coloration of the palms and nails. On the mucous membrane of the lips, on the inner surface, dark spots are noted. During tracheoscopy, a grayish coloration of the tracheal rings was found. The excretion of black urine in carbolochronosis has been noted, or it darkened after standing (carbolic urine). - Clinical diagnosis is possible based on external pigmentation and examination of urine, in which homogentisic acid can be demonstrated. The differential diagnosis of both forms is based on the anamnesis. - Treatment. In carbolochronosis - cessation of phenol introduction. - In general, the prognosis of O. is unfavorable, especially in alkaptonuria, which represents a persistent anomaly of protein metabolism. In carbolochronosis, in rare cases, fading of external pigmentation was observed after cessation of phenol introduction. In animals, O. as such does not occur. The so-called osteohemochromatosis, incorrectly designated as O. of animals, actually has nothing in common with O. and rather can be compared with congenital hematoporphyria of man. The pigment observed in osteohemochromatosis (pigs, calves, cattle) contains iron, is identical with hematoporphyrin spectroscopically; unlike O., in it cartilages, ligaments, and tendons are not colored in a brown hue; only bones, partly bone marrow, spleen, kidneys, liver, lymph glands are colored. Osteohemochromatosis of animals is congenital, a morbid condition.