Introduction

Lupus is a chronic inflammatory autoimmune disease characterised by a wide range of clinical presentations. Based on its evolution and severity, it can affect multiple organ systems. There are four main types of lupus: neonatal, discoid, drug-induced, and systemic lupus erythematosus (SLE), the latter representing the most common form of disease.¹

The precise etiologic mechanism underlying this disorder is not known. However, various studies showed that the cause can be attributed to a combination of factors. Genetic, hormonal, and environmental factors, as well as immune abnormalities all play a role in developing lupus. 

There are four main types of lupus:¹ 

• Neonatal and paediatric lupus erythematosus (NLE)
• Discoid lupus erythematosus (DLE) 
• Drug-induced lupus (DIL)
• Systemic lupus erythematosus (SLE) 

Importance of discussing long-term complications 

Lupus is a serious autoimmune disorder that requires ongoing discussion to understand its long-term complications. This knowledge can shed light on the chronic burden of the disease and guide both patients and healthcare providers in developing comprehensive management strategies.² By understanding these complications, we can enable early detection and intervention, ultimately improving overall patient outcomes and quality of life.

Understanding lupus 

Explanation of autoimmune diseases 

An autoimmune disorder is a term used to describe a category of diseases in which, in simpler words, the immune system attacks healthy cells in the body. In these types of diseases, autoantibodies are created as a result of an over-activation of the immune system which is believed to be caused by an inadequate activation of two types of cells called T- and B cells.³ 

The presence of antigens from bacteria, viruses, toxins, and external blood and tissue can trigger an immune response wherein the body mistakenly attacks its healthy cells, aiming to rid itself of perceived threats. This can result in adverse events such as tissue damage, impairments in organ growth, and organ dysfunction.⁴

As of now, around 100 autoimmune diseases have been described with the two most prevalent types being type 1 diabetes mellitus (T1DM) and autoimmune thyroid disease (AITD).⁴ Autoimmune diseases are a leading cause of death among young and middle-aged women in the United States. 

Incidence rates vary, with estimates ranging from less than one case of systemic sclerosis to over 20 cases of adult-onset rheumatoid arthritis per 100,000 person-years. Prevalence rates range from fewer than 5 to over 500 per 100,000, with around 85% of patients being female in certain diseases (e.g.thyroiditis, systemic sclerosis, systemic lupus erythematosus, and Sjögren's disease).⁵ While most autoimmune diseases can occur at any age, some are more common in specific life stages or among certain ethnic and geographic groups.

How lupus affects the immune system 

Systemic lupus erythematosus (SLE) is a complex autoimmune disease in terms of underlying causes as well as clinical manifestations. In SLE occurs a breakdown of immune tolerance with autoantibodies being developed against nucleic self-antigens.⁶ 

SLE usually develops in a stepwise manner, in the course of many years. Early stages are characterised by the appearance of autoantibodies, when usually no symptoms are present, and later on, after a couple of years, symptoms start to appear.

Both the innate and adaptive immune systems play roles in the progression of SLE, triggering the activation of various cell types, inflammatory processes, intricate immunological networks, resulting in damage to end-organ tissues. Although strides have been made in identifying the fundamental immunological pathways contributing to SLE, our understanding of the disease remains incomplete.⁷

Common long-term complications of lupus 

Cardiovascular complications 

One of the complications that occurs in SLE is developing cardiovascular disease (CVD). There is a high incidence of CVD in SLE, some of which develop CVD at a young age. What is the reason for this high risk of CVD? It is believed to be due to a complex inflammatory process. In which many organic compounds such as multiple lipids, enzymes, and chemokines are involved along with multiple types of peripheral blood cells.⁸ 

Another factor that could play a role in the development of CV events is endothelial dysfunction- these are the cells lining our blood vessels. This represents an important factor in the pathogenesis of atherosclerosis in SLE patients, which ultimately leads to the development of CVD. 

Endothelial dysfunction is recognised by impaired vasodilation, increasing inflammation and thrombosis. These symptoms are usually present prior to the diagnosis of CV events and are associated with high levels of circulating apoptotic endothelial cells. 

In addition, arterial stiffness can be observed in SLE subjects. This can be correlated with the development of atherosclerotic plaque. Furthermore, atherosclerotic plaque is an indicator of higher CV risk.⁹ 

Apart from conventional cardiovascular risk factors, research has revealed a link between systemic lupus erythematosus (SLE) and other detrimental cardiac conditions like metabolic syndrome and high blood cholesterol.¹⁰ Certain medications that are often prescribed in SLE treatment have been found to somewhat affect normal heart functioning. 

Kidney complications 

Another complication of SLE is called lupus nephritis (LN). LN is a prevalent and severe organ complication that significantly contributes to morbidity and mortality among SLE patients. Around 20 to 50% of SLE patients are diagnosed with some sort of renal impairment. This significantly impacts their functional prognosis and survival. It is estimated that up to 20% of patients eventually develop end-stage renal disease (ESRD). 

The symptoms of LN are quite diverse. Some people can experience only symptomatic proteinuria while others show a spectrum of manifestations linked to nephritic and nephrotic syndromes, that lead in the end to ESRD.¹¹ 

A renal complication often found in SLE is called glomerulopathy and is a renal lesion that can cause mild symptoms like isolated proteinuria to nephrotic syndrome or rapidly progressive renal failure.¹² 

It has been found that prognosis can vary based on ethnicity in these types of complications but the primary prognostic factor remains the response to initial immunosuppressive therapy.

Neurological complications

Nervous system involvement in SLE is observed in 75% of patients, ranging from mild symptoms like headaches and mood disturbances to severe conditions such as acute confusion, stroke, and myelopathy.¹³ 

The diagnosis of neurological manifestations in SLE, collectively termed NPSLE, poses a significant challenge due to its wide range of presentations and differential diagnoses. The American College of Rheumatology (ACR) has outlined case definitions and classification criteria for 19 CNS and PNS syndromes observed in SLE.¹⁴ 

Approximately 40% of NPSLE manifestations develop before or at the time of SLE diagnosis, with 63% emerging within the first year.¹⁵ The cause of neurological manifestations in SLE is still unclear. It is believed that it might involve primary disease processes, and secondary complications but also unrelated coincidental findings. 

The NPSLE development comprises vascular abnormalities, autoantibodies, and inflammation. Some of the risk factors for NPSLE are high levels of antiphospholipid antibodies, anticardiolipin antibodies, cutaneous vasculitis, and arterial thrombosis.¹⁶ Early diagnosis and treatment are crucial for reducing morbidity and mortality in SLE patients with neurological involvement.

Bone complications 

Bone complications are prevalent in SLE and contribute significantly to morbidity and disability. Specifically, SLE patients exhibit higher rates of osteoporosis, avascular osteonecrosis, and osteomyelitis.¹⁷ SLE patients face the risk of reduced bone mineral density (BMD) for several reasons, including:¹⁸

• Inflammation associated with SLE
• Glucocorticoid usage 
• Vitamin D deficiency associated with SLE
• Premature ovarian failure, as commonly seen in those with SLE
• Conventional risk factors like age and gender

Impact on quality of life

Living with lupus presents numerous challenges that significantly affect an individual's quality of life. Physically, the disease can lead to debilitating symptoms such as joint pain, fatigue, and muscle weakness, limiting daily activities and mobility.¹⁹ 

The emotional and psychological toll is equally profound, with many patients experiencing anxiety, depression, and stress due to the unpredictable nature of the disease and its impact on their overall well-being.²⁰ Additionally, Lupus can also have a negative impact on social interactions. Several patients reported that they often felt misunderstood by others who were unaware of the complexities of their condition.²¹ 

Management and prevention

Currently, there is no cure for lupus. However, effective management strategies have been put into place which can help alleviate symptoms and overall improve patient outcomes. In terms of medications, patients usually get prescribed corticosteroids, immunosuppressants, and antimalarials. These can help in controlling inflammation and preventing organ damage.²² 

Besides medication, there are steps that can be taken to improve the quality of life. It has been observed that regular physical activity, balanced nutrition, and stress management techniques, can help reduce the risk of flare-ups and complications.²³ 

Moreover, it cannot be stressed enough for regular medical monitoring and check-ups. These can allow for early detection of any changes in disease activity and timely adjustment of treatment plans to optimise outcomes.²⁴

Research and future directions

There are various studies undergoing at the moment that aim to shed light on mechanisms underlying lupus. Moreover, various studies and clinical trials are doing significant work in identifying novel treatment approaches. The main focus is on getting a better understanding of the disease as well as analysing the role of genetics, environmental factors, and the microbiome in how lupus progressed and developed over time.²⁵ 

There are some very promising treatments that are being tested such as biologic agents and targeted therapies. These strategies have the potential to provide more effective and tailored management strategies for those affected.²⁶

Summary

In summary, lupus is an autoimmune disease that affects the entire body which often has a long-term impact on quality of life. It is important to get a better understanding of the physical, emotional and social issues associated with lupus. This will enable providing better support for patients in managing their condition and wellbeing. Continued awareness is also needed. This will not only help in continuing patient support but it can also support research efforts that could lead to the discovery of a cure.