Hydroxychloroquine in systemic lupus erythematosus (SLE)

Expert Opinion on Drug Safety

Volumn 16, Issue 3, 2017, Pages 411-419

  Ponticelli, C ^a   Moroni, G ^b  

^a HUMANITAS CLINICAL AND RESEARCH CENTER   (Italy)

^b FONDAZIONE IRCCS CA GRANDA OSPEDALE MAGGIORE POLICLINICO   (Italy)

Author keywords

antimalarial agents; cutaneous lupus; hydroxychloroquine; lupus flares; lupus nephritis; retinopathy; Systemic lupus erythematosus

Indexed keywords

HYDROXYCHLOROQUINE; PHOSPHOLIPID ANTIBODY; STEROID; ANTIRHEUMATIC AGENT;

CARDIOVASCULAR DISEASE; DISEASE EXACERBATION; DRUG DOSE REDUCTION; DRUG EFFECT; DRUG EFFICACY; DRUG MECHANISM; DRUG SAFETY; EYE DISEASE; GASTROINTESTINAL DISEASE; HUMAN; LIVER DISEASE; MENTAL DISEASE; NEUROLOGIC DISEASE; RETINOPATHY; REVIEW; SKIN DISEASE; SYSTEMIC LUPUS ERYTHEMATOSUS; ANIMAL; CHEMICALLY INDUCED; FEMALE; LUPUS ERYTHEMATOSUS, SYSTEMIC; PATHOPHYSIOLOGY; PREGNANCY; RETINAL DISEASES;

ANIMALS; ANTIRHEUMATIC AGENTS; FEMALE; HUMANS; HYDROXYCHLOROQUINE; LUPUS ERYTHEMATOSUS, SYSTEMIC; PREGNANCY; RETINAL DISEASES;

EID: 85006142620     PISSN: 14740338     EISSN: 1744764X     Source Type: Journal    
DOI: 10.1080/14740338.2017.1269168     Document Type: Review

References (100)

1. Olsen NJ, Schleich MA, Karp DR., Multifaceted effects of hydroxychloroquine in human disease. Semin Arthritis Rheum. 2013;43(2):264–272.
2. Mindell JA. Lysosomal acidification mechanisms. Annu Rev Physiol. 2012;74:69–86.
3. Hurst NP, French JK, Gorjatschko L, et al. Chloroquine and hydroxychloroquine inhibits multiple sites in metabolic pathways leading to neutrophil superoxide release. J Rheumatol. 1988;15(1):23–27.
4. Kaufmann AM, Krise JP. Lysosomal sequestration of amine-containing drugs:analysis and therapeutic implications. J Pharm Sci. 2007;96(4):729–746.
5. Settembre C, Malta D, Polito VA, et al. TFEB links autophagy to lysosomal biogenesis. Science. 2011;332:1429–1433.•• The identification of a master gene, transcription factor EB that regulates lysosomal biogenesis and autophagy.
6. Ghodke-Puranik Y, Niewold TB. Immunogenetics of systemic lupus erythematosus:a comprehensive review. J Autoimmun. 2015;64:125–136.• An excellent review of genetic and epigenetic polymorphisms involved in SLE pathogenesis.
7. Bijl M, Kallenberg CG. Ultraviolet light and cutaneous lupus. Lupus. 2006;15:724–727.
8. Draborg AH, Duus K, Houen G. Epstein-barr virus and systemic lupus erythematosus. Clin Dev Immunol. 2012;2012:370516.
9. Simard JF, Costenbader KH, Liang MH, et al. Exposure to maternal smoking and incident SLE in a prospective cohort study. Lupus. 2009;18:431–435.
10. Fadeel B, Xue D, Kagan V. Programmed cell clearance:molecular regulation of the elimination of apoptotic cell corpses and its role in the resolution of inflammation. Biochem Biophys Res Commun. 2010;396(1):7–10.
11. Fenton K. The effect of cell death in the initiation of lupus nephritis. Clin Exp Immunol. 2015;179(1):11–16.
12. Niewold TB, Clark DN, Salloum R, et al. Interferon alpha in systemic lupus erythematosus. J Biomed Biotechnol. 2010;2010:948364.
13. Choi J, Kim ST, Craft J. The pathogenesis of systemic lupus erythematosus -an update. Curr Opin Immunol. 2012;24(6):651–657.
14. Moody KL, Uccellini MB, Avalos AM, et al. Toll-like receptor-dependent immune complex activation of B cells and dendritic cells. Methods Mol Biol. 2016;1390:249–272.
15. Niewold TB. Interferon alpha as a primary pathogenic factor in human lupus. J Interferon Cytokine Res. 2011;31:887–892.
16. Blanco P, Palucka AK, Gill M, et al. Induction of dendritic cell differentiation by IFN-alpha in systemic lupus erythematosus. Science. 2001;294:1540–1543.•• The capacity of SLE patients’ serum to induce dendritic cell differentiation depends on the actions of interferon-alpha.
17. Lamphier M, Zheng W, Latz E, et al. Novel small molecule inhibitors of TLR7 and TLR9:mechanism of action and efficacy in vivo. Mol Pharmacol. 2014;85(3):429–440.
18. Crispin JC, Kyttaris VC, Terhorst C, et al. T cells as therapeutic targets in SLE. Nat Rev Rheumatol. 2010;6:317–325.• Therapeutic approaches that limit the cognate interaction between T cells and B cells prevent inappropriate tissue homing and restore Treg cell function.
19. Jenks SA, Sanz I. Altered B cell receptor signaling in human systemic lupus erythematosus. Autoimmun Rev. 2009;8(3):209–213.
20. Liu Z, Davidson A. BAFF and selection of autoreactive B cells. Trends Immunol. 2011a;32(8):388–394.
21. Codogno P, Mehrpour M, Proikas-Cezanne T. Canonical and non-canonical autophagy:variations on a common theme of self-eating? Nat Rev Mol Cell Biol. 2011;13:7–12.
22. Levine B, Deretic V. Unveiling the roles of autophagy in innate and adaptive immunity. Nat Rev Immunol. 2007;7(10):767–777.• An important review showing the impact of autophagic processes on activation of innate and adaptive immunity.
23. Wang L, Law HK. The role of autophagy in lupus nephritis. Int J Mol Sci. 2015;16(10):25154–25167.
24. Gros F, Arnold J, Page N, et al. Macroautophagy is deregulated in murine and human lupus T lymphocytes. Autophagy. 2012;8(7):1113–1123.
25. Clarke AJ, Ellinghaus U, Cortini A, et al. Autophagy is activated in systemic lupus erythematosus and required for plasmablast development. Ann Rheum Dis. 2015;74(5):912–920.
26. Martinez J, Cunha LD, Park S, et al. Noncanonical autophagy inhibits the autoinflammatory, lupus-like response to dying cells. Nature. 2016;533(7601):115–119.• A demonstration that noncanonical autophagy can cause SLE-like phenomena, and may contribute to the pathogenesis of SLE.
27. Huang QQ, Pope RM. The role of toll-like receptors in rheumatoid arthritis. Curr Rheumatol Rep. 2009;11(5):357–364.
28. Kuznik A, Bencina M, Svajger U, et al. Mechanism of endosomal TLR inhibition by antimalarial drugs and imidazoquinolines. J Immunol. 2011;186(8):4794–4804.
29. Fox R. Anti-malarial drugs:possible mechanisms of action in autoimmune disease and prospects for drug development. Lupus. 1996;5(Suppl 1):S4–S10.
30. Kalish RS, Koujak S. Minocycline inhibits antigen processing for presentation to human T cells:additive inhibition with chloroquine at therapeutic concentrations. Clin Immunol. 2004;113(3):270–277.
31. Wozniacka A, Lesiak A, Boncela J, et al. The influence of antimalarial treatment on IL-1beta, IL-6 and TNF-alpha mRNA expression on UVB-irradiated skin in systemic lupus erythematosus. Br J Dermatol. 2008;159(5):1124–1130.
32. Goldman FD, Gilman AL, Hollenback C, et al. Hydroxychloroquine inhibits calcium signals in T cells:a new mechanism to explain its immunomodulatory properties. Blood. 2000;95(11):3460–3466.
33. Lotze MT, Maranchie J, Appleman L. Inhibiting autophagy:a novel approach for the treatment of renal cell carcinoma. Cancer J. 2013;19(4):341–347.
34. Rand JH, Wu XX, Quinn AS, et al. Hydroxychloroquine directly reduces the binding of antiphospholipid antibody-beta2-glycoprotein I complexes to phospholipid bilayers. Blood. 2008;112(5):1687–1695.• The demonstration that the antithrombotic effects of hydroxychloroquine are related to its binding to aPL-beta2 GPI complexes.
35. Rand JH, Wu XX, Quinn AS, et al. Hydroxychloroquine protects the annexin A5 anticoagulant shield from disruption by antiphospholipid antibodies:evidence for a novel effect for an old antimalarial drug. Blood. 2010;115(11):2292–2299.
36. Rainsford KD, Parke AL, Clifford-Rashotte M, et al. Therapy and pharmacological properties of hydroxychloroquine and chloroquine in treatment of systemic lupus erythematosus, rheumatoid arthritis and related diseases. Inflammopharmacology. 2015;23(5):231–269.
37. Furst DE. Pharmacokinetics of hydroxychloroquine and chloroquine during treatment of rheumatic diseases. Lupus. 1996;5(Suppl 1):S11–S15.
38. Wasko MC, McClure CK, Kelsey SF, et al. Antidiabetogenic effects of hydroxychloroquine on insulin sensitivity and beta cell function:a randomised trial. Diabetologia. 2015;58(10):2336–2343.
39. Tett SE, Cutler DJ, Beck C, et al. Concentration-effect relationship of hydroxychloroquine in patients with rheumatoid arthritis–a prospective, dose ranging study. J. Rheumatol. 2000;27:1656–1660.
40. Costedoat-Chalumeau N, Amoura Z, Hulot JS, et al. Low blood concentration of hydroxychloroquine is a marker for and predictor of disease exacerbations in patients with systemic lupus erythematosus. Arthritis Rheum. 2006;54:3284–3290.
41. Durcan L, Clarke WA, Magder LS, et al. Hydroxychloroquine blood levels in systemic lupus erythematosus:clarifying dosing controversies and improving adherence. J Rheumatol. 2015;42(11):2092–2097.• Useful guidelines for the use of HCQ in SLE.
42. Tye MJ, White H, Appel B, et al. Lupus erythematosus treated with a combination of quinacrine, hydroxychloroquine and chloroquine. N Engl J Med. 1959;260(2):63–66.
43. Jessop S, Whitelaw DA, Delamere FM. Drugs for discoid lupus erythematosus. Cochrane Database Syst Rev. 2009;4:CD002954.
44. Yokogawa N, Tanikawa A, Amagai M, et al. Response to hydroxychloroquine in Japanese patients with lupus-related skin disease using the cutaneous lupus erythematosus disease area and severity index (CLASI). Mod Rheumatol. 2013;23(2):318–322.
45. Francès C, Cosnes A, Duhaut P, et al. Low blood concentration of hydroxychloroquine in patients with refractory cutaneous lupus erythematosus:a French multicenter prospective study. Arch Dermatol. 2012;148(4):479–484.
46. Chasset F, Arnaud L, Costedoat-Chalumeau N, et al. The effect of increasing the dose of hydroxychloroquine (HCQ) in patients with refractory cutaneous lupus erythematosus (CLE):an open-label prospective pilot study. J Am Acad Dermatol. 2016;74(4):693–699.
47. Walling HW, Sontheimer RD. Cutaneous lupus erythematosus:issues in diagnosis and treatment. Am J Clin Dermatol. 2009;10(6):365–381.
48. Ben-Zvi I, Kivity S, Langevitz P, et al. Hydroxychloroquine:from malaria to autoimmunity. Clin Rev Allergy Immunol. 2012;42:145–153.
49. Petri M. Hydroxychloroquine use in the baltimore lupus cohort:effects on lipids, glucose and thrombosis. Lupus. 1996;5(Suppl 1):S16–22.
50. Wallace DJ, Linker-Israeli M, Metzger AL, et al. The relevance of antimalarial therapy with regard to thrombosis, hypercholesterolemia and cytokines in SLE. Lupus. 1993;2(Suppl 1):S13–S15.• One of the first papers showing benefits of HCQ on thrombosis, hyperlipidemia, and immune response.
51. Mok CC, Penn HJ, Chan KL, et al. Hydroxychloroquine serum concentrations and flares of systemic lupus erythematosus:a longitudinal cohort analysis. Arthritis Care Res (Hoboken). 2016;68(9):1295–1302.
52. Petri M. Use of hydroxychloroquine to prevent thrombosis in systemic lupus erythematosus and in antiphospholipid antibody-positive patients. Curr Rheumatol Rep. 2011;13(1):77–80.
53. Broder A, Putterman C. Hydroxychloroquine use is associated with lower odds of persistently positive antiphospholipid antibodies and/or lupus anticoagulant in systemic lupus erythematosus. J Rheumatol. 2013;40(1):30–33.
54. Belizna C. Hydroxychloroquine as an anti-thrombotic in antiphospholipid syndrome. Autoimmun Rev. 2015;14(4):358–362.
55. Gerosa M, Meroni PL, Erkan D. Recognition and management of antiphospholipid syndrome. Curr Opin Rheumatol. 2016;28(1):51–59.
56. Khamashta MA, Buchanan NM, Hughes GR. The use of hydroxychloroquine in lupus pregnancy:the British experience. Lupus. 1996;5(Suppl 1):S65–6.
57. Clowse ME, Magder L, Witter F, et al. Hydroxychloroquine in lupus pregnancy. Arthritis Rheum. 2006;54(11):3640–3647.
58. Diav-Citrin O, Blyakhman S, Shechtman S, et al. Pregnancy outcome following in utero exposure to hydroxychloroquine:a prospective comparative observational study. Reprod Toxicol. 2013;39:58–62.
59. Ponticelli C, Moroni G. Immunosuppression in pregnant women with systemic lupus erythematosus. Expert Rev Clin Immunol. 2015;11(5):549–552.
60. Moroni G, Ponticelli C. Pregnancy in women with systemic lupus erythematosus (SLE). Eur J Intern Med. 2016;32:7–12.
61. Mok CC, Mak A, Ma KM. Bone mineral density in postmenopausal Chinese patients with systemic lupus erythematosus. Lupus. 2005;14(2):106–112.
62. Stoyan G, Petri M. Atherosclerosis in systemic lupus erythematosus. J Cardiovasc Pharmacol. 2013;62(3):255–262.
63. Chen YM, Lin CH, Lan TH, et al. Hydroxychloroquine reduces risk of incident diabetes mellitus in lupus patients in a dose-dependent manner:a population-based cohort study. Rheumatology (Oxford). 2015;54(7):1244–1249.
64. Bourke L, McCormick J, Taylor V, et al. Hydroxychloroquine protects against cardiac ischaemia/reperfusion injury in vivo via enhancement of ERK1/2 Phosphorylation. Plos One. 2015;10(12):e0143771.
65. Virdis A, Tani C, Duranti E, et al. Early treatment with hydroxychloroquine prevents the development of endothelial dysfunction in a murine model of systemic lupus erythematosus. Arthritis Res Ther. 2015;17:277.
66. Gómez-Guzmán M, Jiménez R, Romero M, et al. Chronic hydroxychloroquine improves endothelial dysfunction and protects kidney in a mouse model of systemic lupus erythematosus. Hypertension. 2014;64(2):330–337.
67. Sun L, Liu M, Li R, et al. Hydroxychloroquine, a promising choice for coronary artery disease? Med Hypotheses. 2016;93:5–7.
68. Alarcón GS, McGwin G, Bertoli AM, et al. Effect of hydroxychloroquine on the survival of patients with systemic lupus erythematosus:data from LUMINA, a multiethnic US cohort (LUMINAL). Ann Rheum Dis. 2007;66(9):1168–1172.•• A large multiethnic study showing that the use of HCQ in lupus patients had a protective effect on survival.
69. Akhavan PS, Su J, Lou W, et al. The early protective effect of hydroxychloroquine on the risk of cumulative damage in patients with systemic lupus erythematosus. J Rheumatol. 2013;40(6):831–841.• A retrospective analysis showing that HCQ use was associated with less organ damage at 3 years after diagnosis of SLE.
70. Ruiz-Irastorza G, Ramos-Casals M, Brito-Zeron P, et al. Clinical efficacy and side effects of antimalarials in systemic lupus erythematosus:a systematic review. Ann Rheum Dis. 2010;69(1):20–28.
71. Wang JM, Li JY, Huang WC, et al. Confirmed false positive proteinuria in patients with systemic lupus erythematosus taking hydroxychloroquine:a spot sample measurement. Clin Lab. 2015;61(5–6):581–586.
72. Costedoat-Chalumeau N, Dunogué B, Morel N, et al. Hydroxychloroquine:a multifaceted treatment in lupus. Presse Med. 2014;43:e167–80.
73. Smith ER, Klein-Schwartz W. Are 1-2 dangerous? chloroquine and hydroxychloroquine exposure in toddlers. J Emerg Med. 2005;28(4):437–443.
74. Easterbrook M. Is corneal deposition of antimalarial any indication of retinal toxicity? Can J Ophthalmol. 1990;25(5):249–251.
75. Brandao LM, Palmowski-Wolfe AM. A possible early sign of hydroxychloroquine macular toxicity. Doc Ophthalmol. 2016;132(1):75–81.
76. Marmor MF, Kellner U, Lai TY, et al., American Academy of Ophthalmology. Recommendations on screening for chloroquine and hydroxychloroquine retinopathy (2016 revision). Ophthalmology. 2016;123(6):1386–1394.•• The updated recommendations of the American Academy of Ophthalmology on screening for hydroxychloroquine retinopathy.
77. Joyce E, Aurelie Fabre A, Mahon N. Hydroxychloroquine cardiotoxicity presenting as a rapidly evolving biventricular cardiomyopathy:key diagnostic features and literature review. Eur Heart J Acute Cardiovasc Care. 2013;2(1):77–83.
78. Baguet JP, Tremel F, Fabre M. Chloroquine cardiomyopathy with conduction disorders. Heart. 1999;81:221–223.
79. Nord JE, Shah PK, Rinaldi RZ, et al. Hydroxychloroquine cardiotoxicity in systemic lupus erythematosus:a report of 2 cases and review of the literature. Semin Arthritis Rheum. 2004;33:336–351.
80. Tönnesmann E, Kandolf R, Lewalter T. Chloroquine cardiomyopathy - a review of the literature. Immunopharmacol Immunotoxicol. 2013;35(3):434–442.
81. Roos JM, Aubry MC, Edwards WD. Chloroquine cardiotoxicity:clinicopathologic features in three patients and comparison with three patients with fabry disease. Cardiovasc Pathol. 2002;11(5):277–283.
82. Costedoat-Chalumeau N, Hulot JS, Amoura Z, et al. Cardiomyopathy related to antimalarial therapy with illustrative case report. Cardiology. 2007;107:73–80.
83. Soria A, Barbaud A, Assier H, et al. Cutaneous adverse drug reactions with antimalarials and allergological skin tests. Dermatology. 2015;231(4):353–359.
84. Callaly EL, FitzGerald O, Rogers S. Hydroxychloroquine-associated, photo-induced toxic epidermal necrolysis. Clin Exp Dermatol. 2008;33(5):572–574.
85. Murphy M, Carmichael AJ. Fatal toxic epidermal necrolysis associated with hydroxychloroquine. Clin Exp Dermatol. 2001;26(5):457–458.
86. Cameron MC, Word AP, Dominguez A. Hydroxychloroquine-induced fatal toxic epidermal necrolysis complicated by angioinvasive rhizopus. Dermatol Online J. 2014;20:11.
87. Jallouli M, Francès C, Piette JC, et al. Hydroxychloroquine-induced pigmentation in patients with systemic lupus erythematosus:a case-control study. JAMA Dermatol. 2013;149(8):935–940.
88. Malcangi G, Fraticelli P, Palmieri C, et al. Hydroxychloroquine-induced seizure in a patient with systemic lupus erythematosus. Rheumatol Int. 2000;20(1):31–33.
89. Stein M, Bell MJ, Ang LC. Hydroxychloroquine neuromyotoxicity. J Rheumatol. 2000;27(12):2927–2931.
90. Siddiqui AK, Huberfeld SI, Weidenheim KM, et al. Hydroxychloroquine-induced toxic myopathy causing respiratory failure. Chest. 2007;131(2):588–590.
91. Kwon JB, Kleiner A, Ishida K, et al. Hydroxychloroquine-induced myopathy. J Clin Rheumatol. 2010;16(1):28–31.
92. Good MI, Shader RI. Behavioral toxicity and equivocal suicide associated with chloroquine and its derivatives. Am J Psychiatry. 1977;134(7):798–601.
93. Makin AJ, Wendon J, Fitt S, et al. Fulminant hepatic failure secondary to hydroxychloroquine. Gut. 1994;35(4):569–570.
94. Giner Galvañ V, Oltra MR, Rueda D, et al. Severe acute hepatitis related to hydroxychloroquine in a woman with mixed connective tissue disease. Clin Rheumatol. 2007;26(6):971–972.
95. Abdel Galil SM. Hydroxychloroquine-induced toxic hepatitis in a patient with systemic lupus erythematosus:a case report. Lupus. 2015;24(6):638–640.
96. Angelakis E, Million M, Kankoe S, et al. Abnormal weight gain and gut microbiota modifications are side effects of long-term doxycycline and hydroxychloroquine treatment. Antimicrob Agents Chemother. 2014;58(6):3342–3347.
97. Kaul A, Gordon C, Crow MK, et al. Systemic lupus erythematosus. Nat Rev Dis Primers. 2016;2:16039.
98. Moroni G, Quaglini S, Gallelli B, et al. Progressive improvement of patient and renal survival and reduction of morbidity over time in patients with lupus nephritis (LN) followed for 20 years. Lupus. 2013;22(8):810–818.• The long-term outcome of patients with lupus nephritis improved over the time.
99. Harvey PR, Gordon C. B-cell targeted therapies in systemic lupus erythematosus:successes and challenges. BioDrugs. 2013;27(2):85–95.
100. Mok CC. Current role of rituximab in systemic lupus erythematosus. Int J Rheum Dis. 2015;18(2):154–163.