الفهرس 
Overview On Pathogenesis Of SLE& RAOnly 14 pages are availabe for public view
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Abstract
H
ydroxychloroquine (HCQ) is one of the antimalarial drugs that is extensively used in the long-term treatment of auto-immune diseases especially systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). It is also used in the management of photosensitive dermatoses, systemic inflammatory disorders with cutaneous manifestations, morphea and granuloma annulare (Yusuf, charbel, 2023).
HCQ is a 4-aminoquinoline which differs from chloroquine (CQ) in the addition of a hydroxyl group. The evidence suggesting that HCQ is less toxic than CQ has led to its increased use (Joyce et al., 2013). HCQ has an immunomodulatory capacity, including the ability to prevent disease flares, promote long-term survival in SLE and control autoimmune disease activity during pregnancies without evidence of fetotoxic or embryotoxic effects. Additionally, it can delay or prevent organ damage, including bone destruction (Akhavan et al., 2013).
Hydroxychloroquine gained popularity as a potential therapy for coronavirus disease-2019 (COVID-19) owing to its antiviral activities. However, recently no role of HCQ in COVID-19 treatment or prevention was suggested, and there are unanswered questions about its cardiac safety in patients with COVID-19 (Gagnon et al., 2022).
Although considered by clinicians to be relatively safe, serious side effects of HCQ have been documented. HCQ is known for its potential irreversible retinal toxicity and thus limited to a daily dose of 5 mg/kg and it is recommended to perform annual visual field screening and optical coherence tomography for retinal toxicity after the first 5 years of treatment by the American Academy of Ophthalmology guidelines (Marmor et al., 2016). Ototoxicity may occur as idiosyncratic phenomenon or mostly related to long term use and cumulative dose of antimalarials (Tharwat et al., 2022).
On the contrary, studies have highlighted the usefulness of HCQ in preventing the occurrence of cardiovascular disorders, particularly in inflammatory diseases such as SLE and RA (Ruiz-Irastorza et al., 2006) (Kaiser et al., 2009) (Fasano et al., 2017) (Jung at al., 2010).
HCQ through its effect on disease activity of SLE may reduce cholesterol, triglyceride, low density lipoprotein (LDL-C) and very LDL (VLDL) levels (Abdalla et al., 2017). Consequently it prevents the occurrence of thrombosis, limits atherosclerosis and reduces the risk of type 2 diabetes mellitus (Sharma et al., 2016).
Long-term treatment with CQ and HCQ may also induce cardiac toxicity through poorly understood mechanisms that may include provoking dysfunction of lysosomal enzymes leading to impairment of intracellular degradation processes and subsequent accumulation of metabolic products (Thomé at al., 2013).
Cardiomyopathy and conduction disorders are the main cardiac side effect described under CQ/HCQ therapy (Gagnon et al., 2022) and patients may present with an atrioventricular block or even complete heart block that may lead to cardiac arrest (Naqvi et al., 2005)( Costedoat-Chalumeau et al., 2007).
The diagnosis of drug toxicity is made more difficult because cardiac disorders may occur independently as a result of other causes. In many cases, heart failure arising from auto-immune diseases, hypertension, or valvular diseases could be misleading (Green et al., 2012).
By contrast with what is proposed for ophthalmologic assessment, there is no recommendation concerning electrocardiographic screening and survey of patients with prolonged treatment with HCQ (Costedoat et al., 2014).