Rheumatoid Lysosomes

The pharmacology of these drugs, which are also used in the treatment of malaria, is presented on p. 351. The mechanism of their anti-inflammatory activity is uncertain. Besides inhibiting nucleic acid synthesis, they are known to stabilize lysosomal membranes and trap free radicals. In treating inflammatory disorders, they are reserved for rheumatoid arthritis that has been unresponsive to the NSAIDs or else they are used in conjunction with an NSAID, which allows a lower dose of chloroquine or hydroxychloroquine to be administered. These drugs have been shown to slow progression of erosive bone lesions and may induce remission. They do cause serious adverse effects (see p. 351). 

Correct answer - C. Gold salts may not provide clinical improvement until after several weeks of administration. They are thought to suppress phagocytosis and lysosomal enzyme activity in macrophages. Gold salts are used in rheumatoid arthritis that does not respond to NSAIDs. Auranofin can be taken by mouth. 

An 80-year-old Japanese woman presented with epigastric discomfort and nausea. She had a history of hypertension, rheumatoid arthritis, iron deficiency anemia, chronic renal insufficiency, and had taken oral ferrous sulfite for 19 months. Endoscopic examination of the duodenum showed marked pigmentation of the duodenal mucosa. Histological examination showed that the pigment had histochemical features compatible with hemosiderin and was located mainly within macrophage lysosomes in the lamina propria. Ferrous sulfite was withdrawn and the pigmentation disappeared within 7 months. 

Peltonen, L., Puranen, J., and Korhonen, S., Lysosomal hydrolases in different compartments of rheumatoid and osteoarthrotic joints. Scand. J. Rheumatol. 10, 97-106 (1981). 

---