Excretion of hydroxyproline in patients with rheumatic and non-rheumatic diseases.

The amino acid hydroxyproline constitutes approximately 13 per cent of collagen (1, 2), and 1 to 2 per cent of elastin (2). It is present in no other protein of the body. For this reason, the determination of hydroxyproline has been utilized for the estimation of collagen in various animal tissues (3), and in the fibrinoid material of the subcutaneous nodule of rheumatoid arthritis (4). It is, at the present time, not clear whether in the diseases of the connective tissue, or "collagen diseases," significant alteration and degradation of the protein collagen occurs. The light microscope studies of Klinge (5) and of Bahrmann (6), who observed swelling of collagen in tissue sections of lesions from patients with rheumatic and other diseases, suggested that these changes do occur. Others (7-9) have shown in addition that swelling and focal degeneration of collagen fibers is a common and striking effect of anaphylactoid hypersensitivity reactions. Using the electron microscope, however, Gross (10) and Gale (11) did not find abnormal fibers in material from lesions of rheumatoid arthritis, rheumatic fever, disseminated lupus erythematosus, and scleroderma. Though Wolpers (12) did observe fibrils lacking cross striations in necrotic areas of old rheumatoid nodules, the fibers were normal in non-necrotic areas and in samples of collagen obtained from Arthus lesions. When cross sections of rheumatoid nodules were submitted to careful X-ray diffraction study by Kellgren, Ball, Astbury, Reed, and Beighton (13) normal collagen patterns were seen where collagen was present in the section, and the pattern of an amorphous material where fibrinoid was present.