Hydroxychloroquine (HCQ), which was initially used as an antimalarial drug, is now being used to treat other illnesses, especially rheumatic autoimmune disorders  such as systemic lupus erythematosus, primary Sjögren's syndrome, and rheumatoid arthritis, because it is safe, effective, and cost efficient. This drug has shown high efficacy and has become the first-line treatment for many of these diseases. Although HCQ has many therapeutic effects, it has unfortunately shown some complications, especially with its long-term use. One of these side effects is arrhythmia through prolongation of the QT interval. This narrative literature review focuses on the effects of HCQ on the QT interval in patients with rheumatologic diseases who have been prescribed this drug. In particular, we will focus on the increased risk of arrhythmia when HCQ is administered with other drugs, such as azithromycin and many others, along with drug-drug interactions. In addition, we investigated the safety of this drug in pregnant women.

Systemic lupus erythematosus (SLE) is a systemic autoimmune inflammatory disease that predominantly affects women of childbearing age and results in various adverse pregnancy outcomes (APOs). Pregnancy was formerly discouraged in patients with SLE because of unstable disease activity during the gestation period, increased thrombosis risk, severe organ damage, and inevitable side effects of immunosuppressive agents. Currently, most patients with SLE have successful pregnancies due to preconception counselling, strict monitoring, and improved therapy with minimised complications for both the mother and foetus. Hydroxychloroquine (HCQ) is extensively used and is beneficial for improving pregnancy outcomes. However, pregnant women with SLE have a high-risk of APOs, such as disease flare, preterm birth, intrauterine growth restriction (IUGR), preeclampsia, and pregnancy loss. Better understanding of the changes in maternal immunity and serum biomarkers, as well as their relationships with SLE-related APOs progression, would facilitate the investigation of molecular mechanisms for triggering and ameliorating APOs. Furthermore, it would enable us to explore and develop novel and effective therapeutic strategies to prevent disease activation. Therefore, this review briefly introduces the interaction between pregnancy outcomes and SLE, elucidates pathophysiological and immunological changes during SLE pregnancy. Furthermore, this review systematically expounds on the effective predictors of APOs and the molecular mechanisms underlying the SLE-related APOs to provide a solid foundation for the advanced management of lupus pregnancy.

Fetal congenital heart block (CHB) is the most commonly observed type of fetal bradycardia, and is potentially life-threatening. More than 50% of cases of bradycardia are associated with maternal autoimmunity, and these are collectively termed immune-associated bradycardia. Several methods have been used to achieve reliable prenatal diagnoses of CHB. Emerging data and opinions on pathogenesis, prenatal diagnosis, fetal intervention, and the prognosis of fetal immune-associated CHB provide clues for generating a practical protocol for clinical management. The prognosis of fetal immune-associated bradycardia is based on the severity of heart blocks. Morbidity and mortality can occur in severe cases, thus hieratical management is essential in such cases. In this review, we mainly focus on optimal strategies pertaining to autoimmune antibodies related to CHB, although the approaches for managing autoimmune-mediated CHB are still controversial, particularly with regard to whether fetuses benefit from transplacental medication administration. To date there is still no accessible clinical strategy for autoimmune-mediated CHB. This review first discusses integrated prenatal management strategies for the condition. It then provides some advice for clinicians involved in management of fetal cardiovascular disorder.

Macrophage activation syndrome (MAS) is a life-threatening hyperinflammatory syndrome and is caused by a severely dysregulated immune response. It has rarely been associated with neonatal lupus.

We present a female neonate with MAS born to a mother who had cutaneous lupus erythematosus with circulating anti-nuclear antibodies (ANA), anti-SSA, anti-SSB and anti-extractable nuclear antigen (anti-ENA) antibodies. Because of neonatal lupus (NLE) with a total atrioventricular block, epicardial pacemaker implantation was required on the sixth day of life. Following surgery she developed non-remitting fever and disseminated erythematous skin lesions. A diagnosis of MAS was made based on these symptoms, with hyperferritinemia, elevated transaminases, hypertriglyceridemia, and a skin biopsy that showed hemophagocytosis. Our patient was treated with steroids for 3 months with good effect. No relapse has occurred.

MAS is a rare complication of neonatal lupus that may be difficult to diagnose, but needs to be treated promptly. In this article, pathogenesis and overlap of MAS and hemophagocytic lymphohistiocytosis (HLH) has been described. Diagnosis of MAS can be difficult. Different diagnostic criteria are used in both diagnosing MAS and HLH. Validated criteria for diagnosis of MAS in other disease than systemic onset JIA have not been validated yet. In NLE, diagnosing MAS is even more difficult, since skin lesions are already common in NLE. We show the potential additional value of skin biopsy in diagnosing MAS.

Congenital heart block (CHB) is a rare but life-threatening disorder. More than half of CHB cases are associated with maternal autoimmune, which are termed as autoimmune-associated CHB. This review summarized the recent research findings in understanding autoimmune-associated CHB, discussed the current diagnostic approaches and management strategies, and summarized the problems and future directions for this disorder.

We retrieved the articles published in English from the PubMed database up to January 2017, using the keywords including "Autoimmune-associated", "Autoimmune-mediated", and "Congenital heart block".

Articles about autoimmune-associated CHB were obtained and reviewed.

Observational studies consistently reported that transplacental maternal antibodies might recognize fetal or neonatal antigens in various tissues and result in immunological damages, but the molecular mechanisms underlying CHB pathogenesis still need illuminated. Multiple factors were involved in the process of atrioventricular block development and progression. While several susceptibility genes had been successfully defined, how these genes and their protein interact and impact each other remains to be explored. With currently available diagnostic tools, fetal ultrasound cardiography, and fetal magnetocardiography, most of CHB could be successfully diagnosed and comprehensively evaluated prenatally. The efficacy of current approaches for preventing the progression and recurrence of CHB and other autoimmune-mediated damages was still controversial.

This review highlighted the relationships between autoimmune injuries and CHB and strengthened the importance of perinatal management and therapy for autoimmune-associated CHB.