STUDY CASE DIABETES MELLITUS, HYPERTENSION, AND INFECTION ADVERSE EFFECTS IN SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) PATIENT WITH METHYLPRENISOLON IMMUNE SUPPRESANT
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May 28, 2025
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Abstract
Systemic Lupus Erythematosus (SLE) merupakan penyakit autoimun kompleks yang menyerang berbagai sistem tubuh. Penyakit ini ditandai dengan pembentukan autoantibodi patogenik terhadap asam nukleat dan protein pengikatnya akibat adanya intoleransi terhadap komponen tubuh. Pasien SLE membutuhkan penekan imun untuk mengurangi inflamasi akibat autoantibodi tersebut serta digunakan berkepanjangan untuk mencegah perburukan kondisi dan mengurangi resiko kekambuhan. Salah satu obat penekan imun yang menjadi tatalaksana penyakit SLE ialah kortikosteroid seperti metilprednisolon (MP). Sayangnya, walaupun terdapat penggunaan regimen obat MP, namun penggunaan MP jangka panjang dapat meningkatkan resiko munculnya berbagai Efek Samping Obat (ESO). Efek samping MP yang dialami salah satu pasien di Rumah Sakit (RS) Fatmawati meliputi diabetes, hipertensi, dan infeksi. Dari hasil studi kasus tersebut, mekanisme ESO yang terjadi meliputi efek mineralokortikoid dan juga glukokortikoid dari kortikosteroid. Kerusakan organ dan perubahan fisiologi tubuh merupakan mekanisme utama dari efek tersebut. Upaya meminimalisasi ESO pada penggunaan MP jangka panjang meliputi penggunaan dosis minimal yang efektif, prinsip tappering off, dan penggunaan steroid-sparing-agent perlu diupayakan untuk meminimalisasi efek samping tersebut.
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References
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2. Griffiths B, Mosca M, Gordon C. Asessment of patients with systemic lupus Erythematosus and the use of lupus disease activity indices. Best Pract Res Clin Rheumatol. 2005;19(5 SPEC. ISS.):685-708.
3. RPRI (Rekomendasi Perhimpunan Reumatologi Indinesia. (2019). Diagnosis dan Pengelolaan Lupus Aritematosus Sistemik. Indonesia: Perhimpunan Reumatologi Indonesia.
4. Gordon C, Amissah-Arthur M-B, Gayed M, Brown S, Bruce IN, D’Cruz D, et al. The British Society for Rheumatology guideline for the management of systemic lupus Erythematosus in adults. Rheumatology. 2018;57:1-45.
5. Ammisah Arthur MB, Gordon C. Contemporary treatment of systemic lupus Erythematosus: an update for clinicians. Ther Adv Chronis Dis. 2010;1(4);163-75.
6. Sawah S Al, Zhang X, Zhu B, Magder LS, Foster SA, Likuni N, et al. Effect of corticosteroid use by dose on the risk of developing organ damage over time in systemic lupus erythematosus-the Hopkins Lupus Cohort. Lupus Sci Med. 2015;2[1]:e000066.
7. Kementrian Kesehatan RI. 2016. Pedoman Pengendalian Penyakit Lupus Eritematosus Sistemik (LES). Jakarta: Dirjen P2P.
8. Creswell, J. W. (2015). Penelitian kualitatif & desain riset. Yogyakarta: Pustaka Pelajar.
9. Herdiansyah, H. (2012). Metodologi penelitian kualitatif: untuk ilmu-ilmu sosial Jakarta: Salemba Humanika.
10. Liu XX, Zhu XM, Miao Q, Ye HY, Zhang ZY, Li YM. Hyperglycemia induced by glucocorticoids in nondiabetic patients: a meta-analysis. Annals of nutrition & metabolism. 2014;65:324-32.
11. Rice JB, White AG, Scarpati LM, et al. Long-term systemic corticosteroid exposure: a systematic literature review. Clin Ther 2017;39:2216-29.
12. Nurhasnah N, Ridha N, Diana L. Hubungan penggunaan kortikosteroid dengan kejadian infeksi pada pasien sindrom nefrotik di rumah sakit “x” jakarta. Media Farmasi, 15 (2). 2018. P. 122-131.
13. Chrousos GP. Adrenocorticosteroids and adrenocortical antagonist. Dalam: Katzung BG, Masters SB, Trevor AJ. Basic and clinical pharmacology. Edisi ke-12. New York: Mc-Graw-Hill Lange; 2012.h. 697-713.
14. Suherman SK, Ascobat P. Adrenokortikotropin, adrenokortikosteroid, analog sintetik dan antagonisnya. Dalam: Gunawan SG, Setiabudy R, Nafrialdi, Instiaty, penyunting. Farmakologi dan terapi. Edisi ke-6. Jakarta: Badan Penerbit FKUI; 2016. H 507-27.
15. Waterloo Wellington Diabetes. (2023). Managing Steroids & Hyperglicemua: A Guide for Health Care Professionals. Ontario: Waterloo Wellington Diabetes.
16. Gonzalez-Gonzalez, J.G., Mireles-Zavala, L.G., Rodriguez-Gutierrez, R. et al. Hyperglycemia related to high-dose glucocorticoid use in noncritically ill patients. Diabetol Metab Syndr 5, 18 (2013). https://doi.org/10.1186/1758-5996-5-18.
17. van Raalte DH, Nofrate V, Bunck MC, et al. Acute and 2-week exposure to prednisolone impair different aspects of beta-cell function in healthy men. Eur J Endocrinol. 2010; 162:729–735. PubMed: 20124412.
18. Yasuda K, Hines E 3rd, Kitabchi AE. Hypercortisolism and insulin resistance: comparative effects of prednisone, hydrocortisone, and dexamethasone on insulin binding of human erythrocytes. J Clin Endocrinol Metab. 1982; 55:910–915. PubMed: 6749880.
19. van Raalte DH, Ouwens DM, Diamant M. Novel insights into glucocorticoid-mediated diabetogenic effects: towards expansion of therapeutic options? Eur J Clin Invest. 2009; 39:81–93. PubMed: 19200161.
20. McKinnon CM, Docherty K. Pancreatic duodenal homeobox 1, PDX-1, a major regulator of beta cell identity and function. Diabetologia. 2001;44:1203-14.
21. van Raalte DH, Kwa KA, van Genugten RE, Tushuizen ME, Holst JJ, Deacon CF, et al. Islet cell dysfunction induced by glucocorticoid treatment: potential role for altered sympathovagal balance? Metabolism: clinical and experimental. 2013;62:568-77.
22. Linssen MM, van Raalte DH, Toonen EJ, Alkema W, van der Zon GC, Dokter WH, et al. Prednisolone-induced beta cell dysfunction is associated with impaired endoplasmic reticulum homeostasis in INS-1E cells. Cellular signalling. 2011;23:1708-15.
23. Ranta F, Avram D, Berchtold S, Dufer M, Drews G, Lang F, et al. Dexamethasone induces cell death in insulin-secreting cells, an effect reversed by exendin-4. Diabetes. 2006;55:1380-90.
24. Taskinen MR, Nikkila EA, Pelkonen R, Sane T. Plasma lipoproteins, lipolytic enzymes, and very low density lipoprotein triglyceride turnover in Cushing's syndrome. The Journal of clinical endocrinology and metabolism. 1983;57:619-26.
25. van Hooijdonk RT, Binnekade JM, Bos LD, Horn J, Juffermans NP, Abu-Hanna A, et al. Associations between bolus infusion of hydrocortisone, glycemic variability and insulin infusion rate variability in critically Ill patients under moderate glycemic control. Annals of intensive care. 2015;5:34.
26. Indah SW. Tinjauan Pustaka: Steroid Induced Mellitus. Unram. Jurnal Diabetes Kedokteran 2023;12(I):13721376. h.1373.
27. Mebrahtu TF, Morgan AW, West RM, Stewart PM, Pujades-Rodriguez M. Oral glucocorticoids and incidence of hypertension in people with chronic inflammatory diseases: a population-based cohort study. CMAJ. 2020 Mar 23;192(12):E295-E301. doi: 10.1503/cmaj.191012. PMID: 32392512; PMCID: PMC7101178.
28. Goodwin JE, Geller DS. Glucocorticoid-induced hypertension. Pediatr Nephrol. 2012 Jul;27(7):1059-66. doi: 10.1007/s00467-011-1928-4. Epub 2011 Jul 9. PMID: 21744056.
29. Provencher PH, Saltis J, Funder JW (1995) Glucocorticoids but not mineralocorticoids modulate endothelin-1 and angiotensin II binding in SHR vascular smooth muscle cells. J Steroid Biochem Mol Biol 52:219–225.
30. Kornel L, Nelson WA, Manisundaram B, Chigurupati R, Hayashi T (1993) Mechanism of the effects of glucocorticoids and mineralocorticoids on vascular smooth muscle contractility. Steroids 58:580–587.
31. Yang S, Zhang L (2004) Glucocorticoids and vascular reactivity. Curr Vasc Pharmacol 2:1–12.
32. Sato A, Suzuki H, Nakazato Y, Shibata H, Inagami T, Saruta T(1994) Increased expression of vascular angiotensin II type 1A receptorgene in glucocorticoid induced hypertension. Hypertens 12:511–516.
33. Kornel L, Prancan AV, Kanamarlapudi N, Hynes J, Kuzianik E (1995) Study on the mechanisms of glucocorticoid-induced hypertension: glucocorticoids increase transmembrane Ca2+ influx in vascular smooth muscle in vivo. Endocr Res 21:203–210.
34. Molnar GA, Lindschau C, Dubrovska G, Mertens PR, Kirsch T, Quinkler M, Gollasch M, Wresche S, Luft FC, Muller DN, Fiebeler A (2008) Glucocorticoid-related signaling effects in vascular smooth muscle cells. Hypertension 51:1372–1378.
35. Ong SL, Zhang Y, Sutton M, Whitworth JA (2009) Hemodynam ics of dexamethasone-induced hypertension in the rat. Hypertens Res 32:889–894.
36. Wallerath T, Godecke A, Molojavyi A, Li H, Schrader J, Forstermann U (2004) Dexamethasone lacks effect on blood pressure in mice with a disrupted endothelial NO synthase gene. Nitric Oxide 10:36–41.
37. Naray-Fejes-Toth A, Snyder PM, Fejes-Toth G (2004) The kidney specific WNK1 isoform is induced by aldosterone and stimulates epithelial sodium channel-mediated Na+ transport. Proc Natl Acad Sci USA 101:17434–17439.
38. Li C, Li Y, Liu H, Sun Z, Lu J, Zhao Y (2008) Glucocorticoid repression of human with-no-lysine (K) kinase-4 gene expression is mediated by the negative response elements in the promoter. J Mol Endocrinol 40:3–12.
39. Yang CL, Angell J, Mitchell R, Ellison DH (2003) WNK kinases regulate thiazide-sensitive Na-Cl cotransport. J Clin Invest 111:1039–1045.
40. Wilson FH, Disse-Nicodeme S, Choate KA, Ishikawa K, Nelson Williams C, Desitter I, Gunel M, Milford DV, Lipkin GW, Achard JM, Feely MP, Dussol B, Berland Y, Unwin RJ, Mayan H, Simon DB, Farfel Z, Jeunemaitre X, Lifton RP (2001) Human hyperten sion caused by mutations in WNK kinases. Science 293:1107 1112.
41. Kahle KT, Wilson FH, Leng Q, Lalioti MD, O'Connell AD, Dong K, Rapson AK, MacGregor GG, Giebisch G, Hebert SC, Lifton RP (2003) WNK4 regulates the balance between renal NaCl reabsorption and K+ secretion [see comment]. Nat Genet 35:372 376.
42. Rask E, Olsson T, Soderberg S, Andrew R, Livingstone DE, Johnson O, Walker BR (2001) Tissue-specific dysregulation of cortisol metabolism in human obesity. J Clin Endocrinol Metab 86:1418–1421.
43. Masuzaki H, Paterson J, Shinyama H, Morton NM, Mullins JJ, Seckl JR, Flier JS (2001) A transgenic model of visceral obesity and the metabolic syndrome. Science 294:2166–2170.
44. Paterson JM, Morton NM, Fievet C, Kenyon CJ, Holmes MC, Staels B, Seckl JR, Mullins JJ (2004) Metabolic syndrome without obesity: hepatic overexpression of 11beta-hydroxysteroid dehydrogenase type 1 in transgenic mice. Proc Natl Acad Sci USA 101:7088–7093.
45. Lv J, Zhang H, Wong MG, et al. Effect of Oral Methylprednisolone on Clinical Outcomes in Patients With IgA Nephropathy: The TESTING Randomized Clinical Trial. JAMA. 2017;318(5):432–442. doi:10.1001/jama.2017.9362
46. Remick DG. Pathophysiology of sepsis. Am J Pathol. 2007;170(5):1435–44. doi: 10.2353/ajpath.2007.060872.
47. Youssef J, Novosad SA, Winthrop KL. Infection Risk and Safety of Corticosteroid Use. Rheum Dis Clin North Am. 2016 Feb;42(1):157-76, ix-x. doi: 10.1016/j.rdc.2015.08.004. Epub 2015 Oct 24. PMID: 26611557; PMCID: PMC4751577.
48. Go CHU, Cunha BA Infections in patients on steroids. Infectious Disease Practice 2461, 2000.
49. Fauman AG. An overview of the adverse reaction to adrenal corticosteroids. Adverse Drug React Toxic 01 Rev 15203,1996.
50. Lefering R, Neugebauer EA: Steroids controversy in sepsis and septic shock A meta- analysis. Crit Care Med 231294, 1995.
51. Zoorob RJ, Cender D A different look at corticosteroids. Am Fam Physician 58443, 1998.
52. Liu D, Ahmet A, Ward L, Krishnamoorthy P, Mandelcorn ED, Leigh R, dkk. A pratical guide to the monitoring and management of the complications of systemic corticosteroid therapy. Allergy Asthma Clin Immunol. 2013;9:1-25. doi:10.1186/1710-1492-9-20.
53. Klein NC, Go CH, Cunha BA. Infections associated with steroid use. Infect Dis Clin North Am. 2001 Jun;15(2):423 32, viii. doi: 10.1016/s0891 5520(05)70154-9. PMID: 11447704.
54. Touma Z, Urowitz MB. Systemic Glucocorticoids. In: Tsokos GC, editor. Systemic Lupus Erythematosus Basic, Applied, and Clinical Aspects. Oxford: Elsevier; 2016. P. 521-31.
55. Kirou KA, Boumpas DT. Systemic glucocorticoid therapy. In: Wallace DJ, Hahn BH, editors. Dubois’ lupus erythematosus and related syndromes. 8th ed. Philadelphia: Elsevier Saunders; 2013. p. 591-600.
56. Frangou EA, Bertsias G. Boumpas DT. Cytotoxic-immunosupresive drug treatment. In: Tsokos GC, editor: Systemic lupus erythematosus: basic, applied and clinical aspects. Oxford: Elsevier, 2016. P. 553-41.
57. Aviña-Zibeita JA, Esdaile JM. Antimalarial medications. In: Wallace DJ, Hajn BH, editors. Dubois’ lupus erythematosus and related syndroms. 8th ed. Philadelphia: Elseview Saunders; 2013. P. 601-8.
58. Ruiz-Irastorza G, Ramos-Casals M, Brito-Zeron P, Khamashta CA. Clinical efficacy and side effects of antimalarial in systemic lupus erythematosus: A systemic review. Ann Rheum Dis. 2010;69(1):20-8.
59. Marmor MF. Kellner U, Lai TYY, MelSLE RB, Mieler WF, Lum F. Recommendations on screening for chloroquine and hydroxychloroquine retinopathy (2016 revision). Opthalmology. 2016;123(6);1386-94.
2. Griffiths B, Mosca M, Gordon C. Asessment of patients with systemic lupus Erythematosus and the use of lupus disease activity indices. Best Pract Res Clin Rheumatol. 2005;19(5 SPEC. ISS.):685-708.
3. RPRI (Rekomendasi Perhimpunan Reumatologi Indinesia. (2019). Diagnosis dan Pengelolaan Lupus Aritematosus Sistemik. Indonesia: Perhimpunan Reumatologi Indonesia.
4. Gordon C, Amissah-Arthur M-B, Gayed M, Brown S, Bruce IN, D’Cruz D, et al. The British Society for Rheumatology guideline for the management of systemic lupus Erythematosus in adults. Rheumatology. 2018;57:1-45.
5. Ammisah Arthur MB, Gordon C. Contemporary treatment of systemic lupus Erythematosus: an update for clinicians. Ther Adv Chronis Dis. 2010;1(4);163-75.
6. Sawah S Al, Zhang X, Zhu B, Magder LS, Foster SA, Likuni N, et al. Effect of corticosteroid use by dose on the risk of developing organ damage over time in systemic lupus erythematosus-the Hopkins Lupus Cohort. Lupus Sci Med. 2015;2[1]:e000066.
7. Kementrian Kesehatan RI. 2016. Pedoman Pengendalian Penyakit Lupus Eritematosus Sistemik (LES). Jakarta: Dirjen P2P.
8. Creswell, J. W. (2015). Penelitian kualitatif & desain riset. Yogyakarta: Pustaka Pelajar.
9. Herdiansyah, H. (2012). Metodologi penelitian kualitatif: untuk ilmu-ilmu sosial Jakarta: Salemba Humanika.
10. Liu XX, Zhu XM, Miao Q, Ye HY, Zhang ZY, Li YM. Hyperglycemia induced by glucocorticoids in nondiabetic patients: a meta-analysis. Annals of nutrition & metabolism. 2014;65:324-32.
11. Rice JB, White AG, Scarpati LM, et al. Long-term systemic corticosteroid exposure: a systematic literature review. Clin Ther 2017;39:2216-29.
12. Nurhasnah N, Ridha N, Diana L. Hubungan penggunaan kortikosteroid dengan kejadian infeksi pada pasien sindrom nefrotik di rumah sakit “x” jakarta. Media Farmasi, 15 (2). 2018. P. 122-131.
13. Chrousos GP. Adrenocorticosteroids and adrenocortical antagonist. Dalam: Katzung BG, Masters SB, Trevor AJ. Basic and clinical pharmacology. Edisi ke-12. New York: Mc-Graw-Hill Lange; 2012.h. 697-713.
14. Suherman SK, Ascobat P. Adrenokortikotropin, adrenokortikosteroid, analog sintetik dan antagonisnya. Dalam: Gunawan SG, Setiabudy R, Nafrialdi, Instiaty, penyunting. Farmakologi dan terapi. Edisi ke-6. Jakarta: Badan Penerbit FKUI; 2016. H 507-27.
15. Waterloo Wellington Diabetes. (2023). Managing Steroids & Hyperglicemua: A Guide for Health Care Professionals. Ontario: Waterloo Wellington Diabetes.
16. Gonzalez-Gonzalez, J.G., Mireles-Zavala, L.G., Rodriguez-Gutierrez, R. et al. Hyperglycemia related to high-dose glucocorticoid use in noncritically ill patients. Diabetol Metab Syndr 5, 18 (2013). https://doi.org/10.1186/1758-5996-5-18.
17. van Raalte DH, Nofrate V, Bunck MC, et al. Acute and 2-week exposure to prednisolone impair different aspects of beta-cell function in healthy men. Eur J Endocrinol. 2010; 162:729–735. PubMed: 20124412.
18. Yasuda K, Hines E 3rd, Kitabchi AE. Hypercortisolism and insulin resistance: comparative effects of prednisone, hydrocortisone, and dexamethasone on insulin binding of human erythrocytes. J Clin Endocrinol Metab. 1982; 55:910–915. PubMed: 6749880.
19. van Raalte DH, Ouwens DM, Diamant M. Novel insights into glucocorticoid-mediated diabetogenic effects: towards expansion of therapeutic options? Eur J Clin Invest. 2009; 39:81–93. PubMed: 19200161.
20. McKinnon CM, Docherty K. Pancreatic duodenal homeobox 1, PDX-1, a major regulator of beta cell identity and function. Diabetologia. 2001;44:1203-14.
21. van Raalte DH, Kwa KA, van Genugten RE, Tushuizen ME, Holst JJ, Deacon CF, et al. Islet cell dysfunction induced by glucocorticoid treatment: potential role for altered sympathovagal balance? Metabolism: clinical and experimental. 2013;62:568-77.
22. Linssen MM, van Raalte DH, Toonen EJ, Alkema W, van der Zon GC, Dokter WH, et al. Prednisolone-induced beta cell dysfunction is associated with impaired endoplasmic reticulum homeostasis in INS-1E cells. Cellular signalling. 2011;23:1708-15.
23. Ranta F, Avram D, Berchtold S, Dufer M, Drews G, Lang F, et al. Dexamethasone induces cell death in insulin-secreting cells, an effect reversed by exendin-4. Diabetes. 2006;55:1380-90.
24. Taskinen MR, Nikkila EA, Pelkonen R, Sane T. Plasma lipoproteins, lipolytic enzymes, and very low density lipoprotein triglyceride turnover in Cushing's syndrome. The Journal of clinical endocrinology and metabolism. 1983;57:619-26.
25. van Hooijdonk RT, Binnekade JM, Bos LD, Horn J, Juffermans NP, Abu-Hanna A, et al. Associations between bolus infusion of hydrocortisone, glycemic variability and insulin infusion rate variability in critically Ill patients under moderate glycemic control. Annals of intensive care. 2015;5:34.
26. Indah SW. Tinjauan Pustaka: Steroid Induced Mellitus. Unram. Jurnal Diabetes Kedokteran 2023;12(I):13721376. h.1373.
27. Mebrahtu TF, Morgan AW, West RM, Stewart PM, Pujades-Rodriguez M. Oral glucocorticoids and incidence of hypertension in people with chronic inflammatory diseases: a population-based cohort study. CMAJ. 2020 Mar 23;192(12):E295-E301. doi: 10.1503/cmaj.191012. PMID: 32392512; PMCID: PMC7101178.
28. Goodwin JE, Geller DS. Glucocorticoid-induced hypertension. Pediatr Nephrol. 2012 Jul;27(7):1059-66. doi: 10.1007/s00467-011-1928-4. Epub 2011 Jul 9. PMID: 21744056.
29. Provencher PH, Saltis J, Funder JW (1995) Glucocorticoids but not mineralocorticoids modulate endothelin-1 and angiotensin II binding in SHR vascular smooth muscle cells. J Steroid Biochem Mol Biol 52:219–225.
30. Kornel L, Nelson WA, Manisundaram B, Chigurupati R, Hayashi T (1993) Mechanism of the effects of glucocorticoids and mineralocorticoids on vascular smooth muscle contractility. Steroids 58:580–587.
31. Yang S, Zhang L (2004) Glucocorticoids and vascular reactivity. Curr Vasc Pharmacol 2:1–12.
32. Sato A, Suzuki H, Nakazato Y, Shibata H, Inagami T, Saruta T(1994) Increased expression of vascular angiotensin II type 1A receptorgene in glucocorticoid induced hypertension. Hypertens 12:511–516.
33. Kornel L, Prancan AV, Kanamarlapudi N, Hynes J, Kuzianik E (1995) Study on the mechanisms of glucocorticoid-induced hypertension: glucocorticoids increase transmembrane Ca2+ influx in vascular smooth muscle in vivo. Endocr Res 21:203–210.
34. Molnar GA, Lindschau C, Dubrovska G, Mertens PR, Kirsch T, Quinkler M, Gollasch M, Wresche S, Luft FC, Muller DN, Fiebeler A (2008) Glucocorticoid-related signaling effects in vascular smooth muscle cells. Hypertension 51:1372–1378.
35. Ong SL, Zhang Y, Sutton M, Whitworth JA (2009) Hemodynam ics of dexamethasone-induced hypertension in the rat. Hypertens Res 32:889–894.
36. Wallerath T, Godecke A, Molojavyi A, Li H, Schrader J, Forstermann U (2004) Dexamethasone lacks effect on blood pressure in mice with a disrupted endothelial NO synthase gene. Nitric Oxide 10:36–41.
37. Naray-Fejes-Toth A, Snyder PM, Fejes-Toth G (2004) The kidney specific WNK1 isoform is induced by aldosterone and stimulates epithelial sodium channel-mediated Na+ transport. Proc Natl Acad Sci USA 101:17434–17439.
38. Li C, Li Y, Liu H, Sun Z, Lu J, Zhao Y (2008) Glucocorticoid repression of human with-no-lysine (K) kinase-4 gene expression is mediated by the negative response elements in the promoter. J Mol Endocrinol 40:3–12.
39. Yang CL, Angell J, Mitchell R, Ellison DH (2003) WNK kinases regulate thiazide-sensitive Na-Cl cotransport. J Clin Invest 111:1039–1045.
40. Wilson FH, Disse-Nicodeme S, Choate KA, Ishikawa K, Nelson Williams C, Desitter I, Gunel M, Milford DV, Lipkin GW, Achard JM, Feely MP, Dussol B, Berland Y, Unwin RJ, Mayan H, Simon DB, Farfel Z, Jeunemaitre X, Lifton RP (2001) Human hyperten sion caused by mutations in WNK kinases. Science 293:1107 1112.
41. Kahle KT, Wilson FH, Leng Q, Lalioti MD, O'Connell AD, Dong K, Rapson AK, MacGregor GG, Giebisch G, Hebert SC, Lifton RP (2003) WNK4 regulates the balance between renal NaCl reabsorption and K+ secretion [see comment]. Nat Genet 35:372 376.
42. Rask E, Olsson T, Soderberg S, Andrew R, Livingstone DE, Johnson O, Walker BR (2001) Tissue-specific dysregulation of cortisol metabolism in human obesity. J Clin Endocrinol Metab 86:1418–1421.
43. Masuzaki H, Paterson J, Shinyama H, Morton NM, Mullins JJ, Seckl JR, Flier JS (2001) A transgenic model of visceral obesity and the metabolic syndrome. Science 294:2166–2170.
44. Paterson JM, Morton NM, Fievet C, Kenyon CJ, Holmes MC, Staels B, Seckl JR, Mullins JJ (2004) Metabolic syndrome without obesity: hepatic overexpression of 11beta-hydroxysteroid dehydrogenase type 1 in transgenic mice. Proc Natl Acad Sci USA 101:7088–7093.
45. Lv J, Zhang H, Wong MG, et al. Effect of Oral Methylprednisolone on Clinical Outcomes in Patients With IgA Nephropathy: The TESTING Randomized Clinical Trial. JAMA. 2017;318(5):432–442. doi:10.1001/jama.2017.9362
46. Remick DG. Pathophysiology of sepsis. Am J Pathol. 2007;170(5):1435–44. doi: 10.2353/ajpath.2007.060872.
47. Youssef J, Novosad SA, Winthrop KL. Infection Risk and Safety of Corticosteroid Use. Rheum Dis Clin North Am. 2016 Feb;42(1):157-76, ix-x. doi: 10.1016/j.rdc.2015.08.004. Epub 2015 Oct 24. PMID: 26611557; PMCID: PMC4751577.
48. Go CHU, Cunha BA Infections in patients on steroids. Infectious Disease Practice 2461, 2000.
49. Fauman AG. An overview of the adverse reaction to adrenal corticosteroids. Adverse Drug React Toxic 01 Rev 15203,1996.
50. Lefering R, Neugebauer EA: Steroids controversy in sepsis and septic shock A meta- analysis. Crit Care Med 231294, 1995.
51. Zoorob RJ, Cender D A different look at corticosteroids. Am Fam Physician 58443, 1998.
52. Liu D, Ahmet A, Ward L, Krishnamoorthy P, Mandelcorn ED, Leigh R, dkk. A pratical guide to the monitoring and management of the complications of systemic corticosteroid therapy. Allergy Asthma Clin Immunol. 2013;9:1-25. doi:10.1186/1710-1492-9-20.
53. Klein NC, Go CH, Cunha BA. Infections associated with steroid use. Infect Dis Clin North Am. 2001 Jun;15(2):423 32, viii. doi: 10.1016/s0891 5520(05)70154-9. PMID: 11447704.
54. Touma Z, Urowitz MB. Systemic Glucocorticoids. In: Tsokos GC, editor. Systemic Lupus Erythematosus Basic, Applied, and Clinical Aspects. Oxford: Elsevier; 2016. P. 521-31.
55. Kirou KA, Boumpas DT. Systemic glucocorticoid therapy. In: Wallace DJ, Hahn BH, editors. Dubois’ lupus erythematosus and related syndromes. 8th ed. Philadelphia: Elsevier Saunders; 2013. p. 591-600.
56. Frangou EA, Bertsias G. Boumpas DT. Cytotoxic-immunosupresive drug treatment. In: Tsokos GC, editor: Systemic lupus erythematosus: basic, applied and clinical aspects. Oxford: Elsevier, 2016. P. 553-41.
57. Aviña-Zibeita JA, Esdaile JM. Antimalarial medications. In: Wallace DJ, Hajn BH, editors. Dubois’ lupus erythematosus and related syndroms. 8th ed. Philadelphia: Elseview Saunders; 2013. P. 601-8.
58. Ruiz-Irastorza G, Ramos-Casals M, Brito-Zeron P, Khamashta CA. Clinical efficacy and side effects of antimalarial in systemic lupus erythematosus: A systemic review. Ann Rheum Dis. 2010;69(1):20-8.
59. Marmor MF. Kellner U, Lai TYY, MelSLE RB, Mieler WF, Lum F. Recommendations on screening for chloroquine and hydroxychloroquine retinopathy (2016 revision). Opthalmology. 2016;123(6);1386-94.