Systemic Lupus Erythematosus: Symptoms, Causes, Tests, Treatment

Systemic Lupus Erythematosus (SLE) is a chronic, multisystem autoimmune disease characterized by dysfunction of the immune system and the production of autoantibodies that target the body’s own tissues. The disease presents significant heterogeneity, both in terms of clinical manifestations and disease course, making diagnosis and monitoring particularly challenging.

Recent reviews highlight that the pathophysiology of lupus involves complex interactions between genetic, immunological, and environmental factors, while the production of antinuclear antibodies may precede clinical diagnosis by several years. At the same time, the need for an individualized approach through so-called precision medicine is emerging as a key objective of modern healthcare.

Within this context, laboratory investigation, including both conventional and functional medicine testing, plays a crucial role not only in diagnosis but also in understanding the underlying mechanisms of the disease.

Epidemiological Data

Systemic Lupus Erythematosus occurs worldwide, with significant variations depending on sex, age, and ethnic background.

The global incidence ranges from approximately 1 to 10 new cases per 100,000 individuals annually, while prevalence ranges between 20 and 150 cases per 100,000 individuals.
The disease occurs much more frequently in women, particularly during reproductive age, with a ratio of up to 9:1 compared to men.
Higher rates are observed in populations of African, Asian, and Hispanic origin.

In Greece, available data are limited; however, prevalence is estimated to be similar to other European countries, approximately 40 to 70 cases per 100,000 individuals. Additionally, Greek studies have shown an increased frequency of renal involvement in patients with delayed diagnosis. The disease is often diagnosed with delay due to its heterogeneous clinical presentation, which may lead to complications and worsening prognosis.

Symptoms and Signs

The clinical presentation of Systemic Lupus Erythematosus is highly heterogeneous, as it can affect almost any organ or system in the body. Symptoms often follow a relapsing and remitting course, making early recognition of the disease more difficult. In many cases, the initial manifestations are non-specific and may be misleading for both patients and clinicians. The most common manifestations include:

Cutaneous manifestations: The characteristic “butterfly” rash on the face is a classic finding, although it does not occur in all patients. Photosensitivity is frequently observed, meaning worsening of skin lesions after sun exposure. Other forms include discoid lesions and cutaneous vasculitis.
Musculoskeletal symptoms: Arthralgia and arthritis are among the most common early symptoms. They typically affect small joints and present with a symmetrical distribution, without the erosive changes seen in rheumatoid arthritis.
General symptoms: Fatigue, low-grade fever, weight loss, and malaise are common early features. Chronic inflammation and immune activation play a key role in their development.
Renal function disorders: So-called “lupus nephritis” is one of the most serious complications. It may present with proteinuria, hematuria, or even renal failure. Early detection is crucial for prognosis.
Hematological abnormalities: Anemia, leukopenia, and thrombocytopenia are frequently observed, resulting from autoimmune destruction of blood cells.
Neuropsychiatric manifestations: Lupus can affect the central nervous system, leading to headaches, cognitive dysfunction, depression, or even seizures.
Cardiopulmonary involvement: Pleuritis, pericarditis, and increased cardiovascular risk are common findings. Chronic inflammation contributes to accelerated atherosclerosis.

The diversity of symptoms highlights that lupus is not a “single-dimensional” disease. Instead, it requires a holistic evaluation of the patient, both clinically and through laboratory testing.

Underlying Causes

Systemic Lupus Erythematosus does not arise from a single cause, but rather from a complex interaction between genetic, immunological, environmental, and metabolic factors. Modern scientific approaches focus not only on identifying symptoms, but also on understanding the mechanisms that lead to immune system dysregulation. Investigating these underlying causes is a key principle of functional medicine.

Genetic predisposition: Genetic susceptibility plays an important role in the development of lupus. Multiple genes involved in immune regulation have been identified, particularly those related to the HLA system and type I interferon pathways. However, genetic predisposition alone is not sufficient for disease onset, indicating the need for additional triggering factors.
Immune system dysfunction: A central feature of lupus is the loss of immune tolerance. The immune system produces autoantibodies, such as antinuclear antibodies (ANA) and anti-dsDNA, which form immune complexes and trigger inflammation in various tissues. Overactivation of B lymphocytes and impaired function of regulatory T cells are key mechanisms involved.
Hormonal factors: The higher prevalence of lupus in women, especially during reproductive years, suggests a significant role of hormones, particularly estrogens. Estrogens appear to enhance immune responses and promote autoantibody production, contributing to both disease onset and exacerbation.
Environmental triggers: Various external factors have been associated with the onset or exacerbation of lupus. Ultraviolet radiation is one of the most important, as it can induce cell apoptosis and the release of autoantigens. Infections, particularly viral, as well as exposure to toxins or certain medications, have also been linked to disease activation.
Microbiome imbalance: In recent years, increasing attention has been given to the role of the gut microbiome. Dysbiosis, defined as an imbalance in gut microbial composition, appears to influence immune function and contribute to chronic inflammation. Studies show that patients with lupus exhibit distinct microbiome profiles compared to healthy individuals.
Chronic inflammation and oxidative stress: Increased production of free radicals combined with reduced antioxidant defenses leads to oxidative stress, which contributes to tissue damage and immune activation. Chronic inflammation acts both as a cause and a consequence of the disease, creating a vicious cycle that worsens its progression.

Laboratory Tests for Disease Investigation

The diagnosis and monitoring of Systemic Lupus Erythematosus rely on a combination of clinical evaluation and laboratory testing. Due to the complexity of the disease, no single test is sufficient. Instead, a multifactorial approach is required, including both conventional markers and more specialized functional medicine assessments.

(a) Conventional laboratory tests

Complete blood count: Reveals hematological abnormalities such as anemia, leukopenia, and thrombocytopenia, which are common in lupus.
Antinuclear antibodies (ANA): A fundamental screening test for autoimmune diseases. They are positive in the vast majority of lupus patients, although they are not disease-specific, as they may also be detected in other conditions or even in healthy individuals.
Anti-double stranded DNA antibodies (anti-dsDNA): A more specific marker for lupus. Their levels often correlate with disease activity, particularly with renal involvement.
Anti-Sm (Smith) antibodies: Highly specific for lupus, although less sensitive. Their presence supports the diagnosis.
Complement C3, Complement C4: Decreased complement levels indicate disease activity, as they are consumed during immune complex formation.
ESR and CRP: Inflammatory markers. ESR is often elevated, while CRP may remain normal unless infection is present.
Urinalysis: Useful for detecting proteinuria or hematuria, indicating renal involvement.
Urea and Creatinine: Assess kidney function, particularly important in cases of lupus nephritis.

(b) Functional Medicine Tests
Functional medicine testing aims to identify the underlying mechanisms that contribute to the onset and progression of lupus. These tests can reveal imbalances that conventional diagnostics miss.

ImmuneScan® - Th1 / Th2 / Th17 Balance Assessment: Evaluates the functional balance between key T-helper lymphocyte subsets (Th1, Th2, Th17), which regulate immune responses. Dysregulation of this balance is associated with autoimmune conditions such as systemic lupus erythematosus, where overactivation of specific pathways (particularly Th17) may occur. This test provides insight into immune dysregulation and supports the personalization of targeted interventions.
DetoxScan® – Oxidative Stress and Total Antioxidant Capacity: Evaluates oxidative damage and the body's ability to counteract it. Increased oxidative stress is characteristic in lupus and is associated with disease progression.
EnteroScan® – Gut microbiome analysis: Evaluates the composition and function of the gut microbiome. Dysbiosis has been associated with increased intestinal permeability and immune activation. This test helps identify pathogenic microorganisms and guides personalized interventions.
Zonulin and Lipopolysaccharides (LPS) – Intestinal permeability markers: These markers assess intestinal permeability (leaky gut). Increased permeability allows antigens to enter circulation, enhancing autoimmune responses. Their measurement provides important insights into systemic inflammatory burden.
OmegaScan® – Fatty acid profile: Analyzes the balance between omega-3 and omega-6 fatty acids. Imbalance is associated with a pro-inflammatory state. The test supports personalized nutritional interventions.
NutriScan® – Vitamin and micronutrient assessment: Deficiencies in essential micronutrients directly affect immune function. Vitamin D, in particular, has immunomodulatory properties and is often found at low levels in lupus patients.
HormoneScan® – Adrenal function via AdrenalScan®, thyroid hormones via Thyroid Extended Profile: Dysregulation of the hypothalamic–pituitary–adrenal axis can influence inflammatory responses. Additionally, autoimmune thyroid disorders frequently coexist with lupus.

(c) Additional specialized tests

Renal ultrasound: Imaging of kidney structure and potential abnormalities
Kidney biopsy: Determines the type of lupus nephritis and prognosis
Chest X-ray: Evaluation of pulmonary or pleural involvement
Echocardiography: Assessment of pericardial effusion and cardiac function
Brain MRI: Investigation of neurological manifestations

Therapeutic Approaches

The management of Systemic Lupus Erythematosus requires an individualized, multifactorial approach given the heterogeneity of the disease. The main goals of treatment are to control inflammation, prevent disease flares, and protect organs from permanent damage. According to current guidelines, treatment combines conventional pharmacological interventions with lifestyle modifications and supportive strategies.

(a) Conventional therapies
Treatment options depend on disease severity and the organs involved.

Antimalarial drugs, such as hydroxychloroquine: These are a cornerstone of therapy for most patients. They reduce disease activity and the risk of flares. Potential side effects include retinal toxicity, requiring regular ophthalmologic monitoring.
Corticosteroids: Used for rapid suppression of inflammation, particularly during disease flares. Although effective, they are associated with significant side effects, including osteoporosis, weight gain, hyperglycemia, and increased cardiovascular risk.
Immunosuppressive drugs, such as azathioprine, mycophenolate mofetil, and cyclophosphamide: These are used in more severe cases, especially when major organs such as the kidneys or central nervous system are involved. Close monitoring is required due to the risk of infections and drug toxicity.
Biologic agents, such as belimumab and voclosporin: These target specific pathways of the immune system. They represent newer therapeutic options and are used in selected cases, particularly when the disease is refractory to conventional treatments.

Proper use of medication can effectively control the disease; however, it does not always address the underlying mechanisms driving immune dysregulation.

(b) Natural approaches
A natural, supportive approach to lupus focuses on regulating inflammation, improving immune function, and supporting overall health. Increasing evidence suggests that nutrition and lifestyle interventions can improve quality of life and reduce disease activity.

Nutrition
Diet plays a key role in regulating inflammation and immune response. An anti-inflammatory dietary pattern, rich in whole and minimally processed foods, may significantly support disease management. Recommended strategies include:

Consumption of foods rich in omega-3 fatty acids, such as fatty fish, walnuts, and flaxseeds, which help reduce inflammation.
Increased intake of fruits and vegetables, providing antioxidants and phytonutrients.
Limiting processed foods, sugar, and trans fats, which promote inflammation.
Personalized dietary approaches, especially in cases of food sensitivities or gut-related disorders.

Diet should ideally be tailored to individual needs, based on laboratory findings.

Lifestyle
Lifestyle factors directly influence disease progression. Stress management is crucial, as chronic stress activates the hypothalamic–pituitary–adrenal axis and promotes inflammation. At the same time, key elements include:

Adequate and high-quality sleep, which supports immune regulation
Moderate physical activity, contributing to reduced inflammation and improved mental health
Avoidance of excessive sun exposure due to photosensitivity
Stress management techniques, such as meditation and breathing exercises

Adopting healthy lifestyle habits can reduce flare frequency and improve overall prognosis.

Supplements and herbal therapies
Certain supplements have been studied for their supportive role in lupus management, always under medical supervision. Indicatively:

Vitamin D: Exhibits immunomodulatory effects
Omega-3 fatty acids: Provide anti-inflammatory benefits
Curcumin: Has anti-inflammatory and antioxidant properties, with enhanced absorption when combined with piperine
Probiotics: Support gut microbiome balance, with strain selection ideally based on individual test results

Supplement use does not replace pharmacological treatment but may offer additional support, particularly when guided by personalized data.

Conclusion

Systemic lupus erythematosus is a complex autoimmune disease with multisystem involvement and significant heterogeneity, both in its symptoms and in its progression. Early recognition of indications and an accurate diagnostic approach are of critical importance for the prevention of complications and the improvement of patients’ quality of life.

Modern medicine is no longer limited solely to the management of symptoms, but is increasingly shifting toward the investigation of the underlying mechanisms that lead to disease. In this context, the combination of conventional testing with specialized functional medicine assessments provides a more comprehensive view of the body’s condition, enabling more targeted and personalized interventions. At the same time, the integration of interventions related to nutrition, lifestyle, and inflammation regulation may contribute substantially to disease management and to the reduction of disease flares.

Overall, the functional approach highlights the importance of prevention and personalization in modern healthcare and offers the opportunity and the appropriate tools for a deeper understanding of the causes associated with lupus, supporting both diagnosis and the long-term monitoring and management of the disease.

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