Immunological causes of recurrent implantation failure
Efstratios M. Kolibianakis, Christos A. Venetis in Recurrent Implantation Failure, 2019
Hydroxychloroquine, an antimalarial drug, is often used for various autoimmune diseases, particularly systemic lupus erythematosus. Its use in pregnant patients with antiphospholipid antibody syndrome (APS) was reported to improve pregnancy outcomes.59 It has anti-inflammatory, antithrombotic, and immunoregulatory properties and impairs complement-dependent antigen-antibody reactions.60 Besides, hydroxychloroquine was reported to restore trophoblast fusion and differentiation caused by aPL and diminished toll-like receptor 4 (TLR-4) expression.61 Those immunomodulatory effects led to its use in patients with RIF or RPL; however, there is a lack of robust clinical evidence to improve clinical outcome.49 One retrospective study has shown a 78% live birth rate in a few refractory APS patients after add-on treatment with hydroxychloroquine.59 Hydroxychloroquine reversed the aPL-inhibition of trophoblast IL-6 secretion and partially limited aPL inhibition of cell migration.62 Therefore, hydroxychloroquine may be beneficial to RIF patients, particularly with APS. Currently, the clinical data on the use of hydroxychloroquine in RIF are lacking, and prospective studies are necessary.
Systemic Lupus Erythematosus
Vincenzo Berghella in Maternal-Fetal Evidence Based Guidelines, 2022
Hydroxychloroquine sulfate was originally an antimalarial drug. 400 mg orally daily or divided bid. Maximum dose 5 mg/kg/day. Safe in pregnancy [18]. No increased risk of miscarriage, stillbirth, pregnancy loss, and congenital anomalies (including ocular abnormalities) in exposed pregnancies when compared to non-exposed group [19–21]. This is currently the safest and most effective therapy for SLE pregnant women who need therapy. Important not to stop drug periconception [11, 19, 22]. Hydroxychloroquine therapy is desirable in all pregnant SLE patients, for maternal and fetal benefit. If stable with no recent flares on hydroxychloroquine, it is recommended to continue it in pregnancy and postpartum. If not previously taking, consider initiating hydroxychloroquine therapy, unless contraindicated. Hydroxychloroquine >200 mg/d initiated prior to 10 weeks and continued through pregnancy decreases C-NLE recurrence by greater than 50% in women with prior affected offspring [23–25]. See CHB Prevention later in the chapter. Compatible with breastfeeding.
The Musculoskeletal System and Its Disorders
Walter F. Stanaszek, Mary J. Stanaszek, Robert J. Holt, Steven Strauss in Understanding Medical Terms, 2020
Systemic lupus erythematosus is diagnosed by presentation of a number of clinical symptoms, most commonly arthralgia (arth = joint, algia = pain) and arthritis. Laboratory tests show abnormal ANA titer, positive LE cell test. Several different drugs are utilized in the treatment of systemic lupus erythematosus. Aspirin and the NSAIDs are used to manage arthralgias or synovitis (inflammation of the synovium), pleurisy, headache, and low-grade fever. The antimalarial agent hydroxychloroquine is effective in treating arthralgias, arthritis, and skin disease. Corticosteroids are used to control the inflammatory response. Connective tissue disorders are treated by rest and exercise, physical and occupational therapy, heat, supportive or rehabilitative devices, education, nutrition, and orthopedic surgery.
Immune Responses to the Novel Coronavirus-2: Friend or Foe?
Published in Immunological Investigations, 2021
Ata Mahmoodpoor, Nader D. Nader
Controversy still exists in using immunomodulating agents to treat COVID-19 disease. Among these remedies, chloroquine and its hydroxy form have been used in China initially and were adopted elsewhere. Hydroxychloroquine is an antimalarial agent that is commonly used in patients with auto immune diseases such as rheumatoid arthritis. The original recommendation was based on anecdotal observations of less severity and fatality in patients who were taking these medications for other indications. Due to the rapid spread of the disease, and the lack of other treatment alternatives, several clinicians empirically used hydroxychloroquine alone or in combination with a macrolide antibacterial, azithromycin, to treat COVID-19 disease without available robust controlled trials. Recent studies failed to show any anticipated benefits with use of hydroxychloroquine, as it failed to alter the course of the disease in terms of decreasing the severity of the resultant respiratory distress and the mortality rate (Rosenberg et al. 2020). On its defense, in all studies that examined the efficacy of hydroxychloroquine, the drug was started well after an exuberant cytokine/inflammatory response had already started. Therefore, there may still be some theoretical benefit in its early initiation to prevent the immune response from activation. Additionally, due to non-randomized design of this study, hydroxychloroquine was more likely to be administered to patients who suffered from other systemic co-morbidities.
Acute and subacute oral toxicity of artemisinin-hydroxychloroquine sulfate tablets in beagle dogs
Published in Drug and Chemical Toxicology, 2023
Xiaobo Li, Jianjia Feng, Yueming Yuan, Shouya Zhang, Zhiyong Xu, Qin Xu, Jianping Song, Li Ru, Zheng Yuan, Wanting Wu
Hydroxychloroquine sulfate is a derivative of chloroquine, belonging to the 4-aminoquinolines, with similar effects to chloroquine, such as treating malaria, regulating immunity, antibacterial (Ben-Zvi et al. 2012). But chloroquine has serious drug resistance and side effects, leading to limited clinical application (Marques et al. 2014). Hydroxychloroquine, which is relatively less toxic than chloroquine, is currently one of the first-line drugs for the treatment of rheumatoid arthritis, but it is rarely used as an antimalarial in clinic (Hu et al. 2017, Jorge et al. 2018). Recently, we developed artemisinin-hydroxychloroquine sulfate tablets (AH) to treat malaria. Our previous studies have demonstrated that the combination of artemisinin and hydroxychloroquine sulfate has many benefits, including improving the therapeutic efficacy of malaria, decreasing the dose of both, reducing the toxic side effects of hydroxychloroquine, and postponing the progress of single drug resistance (unpublished data). In addition to being antimalarial, hydroxychloroquine and artemisinin are also antivirals with broad activity, such as anti-flavivirus and anti-coronavirus (Andreani et al. 2020, Cao et al. 2020, Liu et al. 2020, Wang et al. 2020). Recent reports showed they have been used in many clinical trials to treat COVID-19 (Nicol et al.2020, Lewis et al. 2021, Li et al.2021a). Hence, as a combination of hydroxychloroquine and artemisinin, AH has great potential in treating many diseases, particularly coronavirus infection.
Additive immunosuppressive effect of leflunomide and hydroxychloroquine supports rationale for combination therapy for Sjögren’s syndrome
Published in Expert Review of Clinical Immunology, 2019
Eefje HM van der Heijden, Sarita AY Hartgring, Aike A Kruize, Timothy RDJ Radstake, Joel AG van Roon
Hydroxychloroquine (HCQ), initially used as an anti-malarial drug, also exhibits immunomodulatory effects. HCQ mainly targets antigen-presenting cells such as dendritic cells and monocytes, illustrated by the fact that after exposure these cells have higher intracellular concentrations of the drug [25]. Antigen presentation is decreased by HCQ, as MHC class II molecules are moved to the endocytic compartments after synthesis. This mainly affects binding of low-affinity self-peptides instead of antigenic pathogen-derived peptides [25]. HCQ inhibits activity of pDCs, which are the strongest producers of type I IFN, and of B cells, by inhibiting Toll-Like receptor (TLR)-mediated responses [25,26]. This is due to the HCQ-mediated raise of endosomal pH leading to dysfunction of endosomal TLRs. By raising endosomal pH, HCQ interferes with the functional transformation of the TLRs needed for their activation [27]. Also, HCQ directly interferes with nucleic acid TLR ligands, resulting in structural alterations of the nucleic acid and prevention of its binding to TLRs [28]. In addition, HCQ inhibits autophagy, resulting in less cell proliferation [29].
Related Knowledge Centers
- Chloroquine
- Malaria
- Muscle Weakness
- Porphyria Cutanea Tarda
- Vomiting
- Allergy
- Headache
- Rheumatoid Arthritis
- Lupus Erythematosus
- Oral Administration