This, we think, was first articulated by John Decker, MD, a distinguished and authoritative rheumatologist who was the director of the National Institute of Arthritis and Metabolic Diseases, National Institutes of Health, and president of the American Rheumatology Association (now the ACR). Lack of 11 beta-hydroxysteroid dehydrogenase 1 (11β-HSD1) enzyme activity leads to impaired conversion and poor availability of the active steroid molecule. In such instances, treatment with prednisolone or methylprednisolone, already in an active form, may be effective. Several studies have documented impaired conversion of prednisone to prednisolone in patients with liver disease and suggested that prednisolone be used preferentially in these conditions. Also, there are patients who have deficiency of the 11β-HSD1 enzyme, needed to convert prednisone to prednisolone. This condition, termed acquired cortisone reductase deficiency (ACRD), was recognized as a partial deficiency of 11β-HSD1, which may modulate the levels of both endogenous and exogenous steroids at the tissue level, and it is ubiquitously present in the skin, central nervous system, adipose tissues, and other organs, including synovium, synovial fluid, and bone, that are responsive to endogenous cortisol.6
Recently, polymorphisms within the 11β-HSD1 gene and the gene coding for hexose 6 phosphate dehydrogenase (a coenzyme which supplies reducing equivalents to 11β-HSD1) have been identified with a population prevalence of 3% and 4% respectively.7 This may have implications both for disease susceptibility and therapy.
Physicians, perhaps especially of the younger generation(s), should be aware of this possible explanation for unexpected prednisone unresponsiveness. I think it is real, has a scientific basis, is not widely appreciated, and is important in optimally caring for our patients with chronic inflammatory diseases.
Dr. Panush is professor of medicine, division of rheumatology, department of medicine, Keck School of Medicine, University of Southern California in Los Angeles.
References
- Killingsworth MA, Gilbert DT. A wandering mind is an unhappy mind. Science. 2010;330:932.
- Olson DP, Windish DM. Communication discrepancies between physicians and hospitalized patients. Arch Intern Med. 2010;170:1302-1307.
- Thirumalaiselvan G, Sapru S, Panush RS. An analysis of resident applications for fellowships from a community hospital, 2001–2006: What predicts success? New Jersey Chapter Scientific Meeting, American College of Physicians, Woodbridge, New Jersey, Feb. 2008.
- Norcini JJ, Boulet JR, Dauphinee WD, Drantz ID, Anderson ST. Evaluating the quality of care provided by graduates of international medical schools. Health Affairs. 2010;29:1461-1468.
- Sen D, Rajbhandary R, Carlino A, Anderson R, Schur PH, Panush RS. Are there patients with inflammatory disease who do not respond to prednisone? J Rheumatol. 2010;37:1559-1561.
- Raza K, Hardy R, Cooper MS. The 11β-hydroxysteroid dehydrogenase enzymes—arbiters of the effects of glucocorticoids in synovium and bone. Rheumatology. 2010;49:2016-2023.
- Van Oosten M, Dolhain RJEM, Koper JW, et al. Polymorphisms in the glucocorticoid receptor gene that modulate glucocorticoid sensitivity are associated with rheumatoid arthritis. Arthritis Res Ther. 2010;12:R159
