Antimalarials in cutaneous lupus erythematosus: mechanisms of therapeutic benefit

Woźniacka, Anna; Carter, A; McCauliffe, Daniel P.

doi:10.1191/0961203302lu147rr

Cited by 68 publications

(54 citation statements)

References 134 publications

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“…No similar trend was evident in the MTD or the IPD, indicating that they are possibly of lesser importance than the MED in defining photosensitivity. Two of eight subjects treated with antimalarials developed photoprovoked CLE, suggesting that these subjects may be to some extent protected by their treatment, as reported in previous studies (Wozniacka et al, 2002(Wozniacka et al, , 2007.…”

Section: Discussionsupporting

confidence: 78%

Photoprovocation in Cutaneous Lupus Erythematosus: A Multicenter Study Evaluating a Standardized Protocol

Kuhn

Woźniacka

Szepietowski

et al. 2011

Journal of Investigative Dermatology

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Photosensitivity is an important and distinguishing sign in various subtypes of cutaneous lupus erythematosus (CLE); however, it remains poorly defined. The purpose of this study was to evaluate whether standardized photoprovocation is a reproducible method to assess photosensitivity in subjects with CLE. A total of 47 subjects with CLE (subacute cutaneous lupus erythematosus (SCLE), n=14; discoid lupus erythematosus (DLE), n=20; lupus erythematosus tumidus (LET), n=13) and 13 healthy volunteers underwent photoprovocation at seven European sites. Of these, 22 (47%) subjects (57% SCLE, 35% DLE, and 54% LET) and none of the healthy volunteers developed photoprovoked lesions according to clinical analysis. Of these 22 subjects, 19 (86%) developed lesions that were histopathologically confirmed as specific for lupus erythematosus (LE). In CLE subjects who developed UV-induced lesions, 86% had Fitzpatrick's phototypes I or II, and the mean minimal erythema dose (MED) was significantly lower compared with subjects without UV-induced lesions (P=0.004). No significant differences in photoprovocation results were observed between study sites. Safety parameters showed no clinically meaningful differences between CLE subjects and healthy volunteers after photoprovocation. In conclusion, a standardized, safe, and reproducible protocol for photoprovocation using UVA and UVB radiation induced skin lesions in approximately half of all CLE subjects and showed comparable results across multiple sites. This method may therefore be used for future diagnostic testing and clinical trials.

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Section: Discussionsupporting

confidence: 78%

Photoprovocation in Cutaneous Lupus Erythematosus: A Multicenter Study Evaluating a Standardized Protocol

Kuhn

Woźniacka

Szepietowski

et al. 2011

Journal of Investigative Dermatology

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“…36 Interestingly, CQ and other antimalarial agents have long been used as therapeutic agents in the treatment of autoimmune conditions (e.g., rheumatoid arthritis and systemic lupus erythematosus 37,38 ), even though their precise mechanism(s) of action are still not known. 39 Our results indicate that CQ also has antihypertensive actions, possibly through regulation of TLR signaling, which may lower cardiovascular disease risk in autoimmune patients with hypertension. 40 Figure 4.…”

Section: Discussionmentioning

confidence: 66%

Chloroquine Suppresses the Development of Hypertension in Spontaneously Hypertensive Rats

McCarthy

Goulopoulou

Baban

et al. 2016

AJHYPE

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Inappropriate immune system activation has been proposed as a unifying mechanism linking the 3 major organ systems that are dysregulated in the development and maintenance of hypertension-the cardiovascular system, the kidneys, and the autonomic nervous system. 1,2 However, the exact mechanisms that initiate this deleterious response, thereby contributing to further increases in blood pressure, are not well understood. 1,2 Although the participation of the adaptive immune system, and specifically T cells, in the pathogenesis of hypertension is not in question, 3,4 there are still gaps surrounding how it is signaled for involvement in the first place.Immune system recognition and response to danger is becoming apparent in a wide range of disease states, including cardiovascular diseases. 5 In this paradigm, the immune system responds to stimuli that it perceives as indicative of danger. 6 As such, molecules released from cell injury and death, called damage-associated molecular patterns (DAMPs), as well as pathogen-associated molecular patterns, signals to the immune system that a response is required. Normally, endogenous molecules are shielded from the immune system via compartmentalization within plasma membranes. However, when a cell dies or undergoes undue stress, these molecules can be released and are able to activate pattern recognition receptors on immune and nonimmune cells. 5 Toll-like receptors (TLR) are a class of innate immune system pattern recognition receptors that recognize and respond to DAMPs. 2,7 We have recently observed that mitochondrial DNA (mtDNA), a DAMP that activates TLR9, is increased in the circulation of spontaneously hypertensive rats (SHR). 8 Specifically, TLR9 recognizes unmethylated cytosine-phosphate-guanine (CpG) dinucleotides and these are common in prokaryotic DNA and mtDNA, but not nuclear DNA. 9 Upon recognition of unmethylated CpG dinucleotides in BACKGROUNDInnate immune system responses to damage-associated molecular patterns (DAMPs) are involved in hypertension. However, the mechanisms of this contribution are not well understood. Circulating mitochondrial DNA is a DAMP that activates Toll-like receptor (TLR) 9 and is elevated in spontaneously hypertensive rats (SHR). Therefore, we hypothesized that lysosomotropic agent chloroquine (CQ) would impair TLR9 signaling, as well as prevent the development of hypertension and immune cell recruitment to the vasculature, in SHR.

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“…For example, HCQ is a weak base which can cross cell membranes and accumulates in acidic cytoplasmic vesicles as lysosomes or endosomes where it remains trapped in a protonated state.The pH in lysosomes increases as HCQ accumulates there, so, interfering in binding of antigenic peptides with class II molecules of the major histocompatibility complex, leading to inhibition of the production of cytokines which are responsible to the induction of inflammatory response [20,21].…”

Section: Discussionmentioning

confidence: 99%

“…Although the mechanism of cholesterol lowering effect of HCQ is not well indicated, it has beneficial properties as hypolipidemic drug in lupus patients [21]. It has been approved that HCQ acts as an inhibitor of cholesterol biosynthesis in the hepatocytes of the rats while in human fibroblasts, it has multiple effects on cholesterol metabolism by inhibition lysosomal hydrolysis of cholesterylesters through the increase in the pH within lysosomes and inactivates acid proteases.…”

Section: Discussionmentioning

confidence: 99%

The Effect of Hydroxychloroquine Treatment on Blood Sugar Level, Serum Lipid Profile and the Retina in Systemic Lupus Erythematosus Patients

Sarhan¹,

Shaban²,

Hamid³

et al. 2016

Med-Science

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Antimalarials in cutaneous lupus erythematosus: mechanisms of therapeutic benefit

Cited by 68 publications

References 134 publications

Photoprovocation in Cutaneous Lupus Erythematosus: A Multicenter Study Evaluating a Standardized Protocol

Photoprovocation in Cutaneous Lupus Erythematosus: A Multicenter Study Evaluating a Standardized Protocol

Chloroquine Suppresses the Development of Hypertension in Spontaneously Hypertensive Rats

The Effect of Hydroxychloroquine Treatment on Blood Sugar Level, Serum Lipid Profile and the Retina in Systemic Lupus Erythematosus Patients

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