Still’s disease and the mitochondrion: The other face of an old friend?
Introduction
When, in 1896, George Frederic Still first identified the disease that now bears his name, he based his description on consistent clinical findings: a specific aspect of joint manifestations (elastic, fusiform and symmetrical joint swelling), diffuse lymphadenopathy and splenomegaly [1]. By themselves, these manifestations permitted to distinguish this newly described disease from other forms of chronic rheumatic diseases of the child, and particularly from juvenile rheumatoid arthritis.
Subsequently, Still’s disease kept its peculiar place in the spectrum of juvenile idiopathic arthritides (JIA), due to an evolution marked by prolonged inflammatory attacks, sometimes ongoing beyond childhood, separated by free intervals, with intermittent fever, skin lesions, serous exsudates, and delayed osteo-articular destructive lesions, along with the possibility of severe complications (macrophage activation, AA amyloidosis) [2], [3].
Once its difference recognized, Still’s disease became at the same time a kind of orphan disease. Despite many common features with infectious diseases, all searches for a bacterial or viral origin remained so far negative, even though some infections can simulate Still’s disease, at the beginning [4].
Still’s disease most probably reflects a disorder of the innate immunity, without evidence of auto-immunity, and shares many similarities with auto-inflammatory diseases (AID) [5].
Section snippets
Hypothesis
In the absence of any familial aggregation, the integration of Still’s disease into the group of monogenic AIDs faces an important obstacle to overcome [6], [7], [8]. Taking this point into account, it seemed difficult to ignore the major progresses that have been made in the field of pro-inflammatory cellular pathways. In particular, it was really tempting to examine the possible implication of mitochondrial metabolism, since concordant works recently stressed the role played by mitochondria
Conclusion
The hypothesis of an ambiguous role played by mitochondria – an old friendly symbion reconverting itself as an aggressive enemy – could be the unexpected explanation of both start and autonomous increase of the inflammatory burst that is currently registered in Still’s disease. After a cellular – mitochondrial? – injury, whatever the cause, the systemic circulation of DAMPs could act as a potent stimulus on the innate immunity, whose persistent and abnormal activation should be explained by a
Conflict of interest statement
None declared.
Acknowledgments
The authors are indebted to Dr. Jamel Elbenna for his very helpful comments. They also thank Mrs. Hélène Grimot and Mr. Robert de Ferrer for her kind assistance in writing this manuscript.
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