What is paediatric lupus?

Paediatric Lupus, also known as childhood-onset Systemic Lupus Erythematosus (SLE), or juvenile-onset Systemic Erythematous Lupus (SLE), is a chronic autoimmune disease that primarily affects children and adolescents.¹ It is characterised by the immune system attacking healthy tissues and organs, leading to inflammation and damage throughout the body. Paediatric lupus accounts for about 15-20% of SLE.² The main function of our body’s immune system is to protect from foreign invaders like viruses or bacteria, but in lupus, the body attacks itself. Despite being rare, paediatric lupus poses a significant challenge for affected children and their families.

What are the causes of paediatric lupus?

The causes of paediatric lupus, like systemic lupus erythematosus (SLE) in adults, are not entirely understood. However, a combination of genetic, environmental, and hormonal factors contributes to the development of the disease in children and adolescents.

Genetic factors

Genetics plays a significant role in the predisposition to lupus, with certain genetic variations increasing the risk of developing the disease. Studies have shown that relatives of individuals with lupus have a higher likelihood of developing lupus themselves, indicating a genetic component to the disease.³

Environmental triggers

Exposure to certain environmental factors may trigger the onset of lupus in genetically predisposed individuals. Environmental triggers implicated in lupus development include infections (such as Epstein-Barr virus), ultraviolet (UV) radiation from sunlight, certain medications (such as hydralazine and procainamide), and exposure to toxins or pollutants.

Hormonal factors

Hormonal factors, particularly the influence of oestrogen, may play a role in the development and worsening of lupus symptoms. Lupus predominantly affects females, with a female-to-male ratio of approximately 9:1, suggesting a hormonal influence on disease susceptibility.⁴

Immunological dysregulation

Paediatric lupus is characterised by dysregulation of the immune system, leading to the production of autoantibodies and inflammation. In lupus, the immune system mistakenly recognises self-antigens as foreign invaders and initiates an immune response against them, leading to tissue damage and inflammation. Abnormalities in immune cell function, cytokine production, and immune system regulation contribute to the development of lupus in children and adolescents.

Interaction of genetic and environmental factors

The development of paediatric lupus likely involves a complex interplay between genetic susceptibility and environmental triggers. Genetic predisposition sets the stage for the development of the disease, while environmental factors may trigger or worsen lupus symptoms in susceptible individuals.⁵

What are the symptoms associated with paediatric lupus?

Skin rash

Children with lupus may develop various types of skin rashes, including the classic butterfly-shaped rash across the cheeks and nose (malar rash), discoid lupus rash (raised, scaly patches), photosensitive rash (rash triggered by sunlight), and other nonspecific rashes.

Joint pain and swelling

Arthritis is a common symptom of paediatric lupus, characterised by pain, swelling, and stiffness in the joints. Children may experience arthritis in multiple joints, often affecting the hands, wrists, knees, and ankles.

Fatigue and malaise

Persistent fatigue, weakness, and a general feeling of malaise (feeling discomfort or unwell) are common symptoms of paediatric lupus, which can significantly impact a child's quality of life and daily activities.

Fever

Children with lupus may experience recurrent episodes of fever, which may be low-grade or moderate in intensity and may be accompanied by other symptoms such as fatigue, malaise, and joint pain.

Photosensitivity

Many children with lupus are sensitive to sunlight (photosensitive) and may develop skin rashes, worsening of lupus symptoms, or other adverse reactions upon sun exposure.

Oral ulcers

Ulcers or sores may develop inside the mouth (oral ulcers) or on the lips of children with lupus, causing discomfort and pain during eating, drinking, or speaking.

Renal involvement (Lupus Nephritis)

Lupus nephritis (inflammation of the kidneys), is a serious complication of paediatric lupus. Symptoms may include proteinuria (excess protein in the urine), haematuria (blood in the urine), hypertension (high blood pressure), oedema (swelling), and impaired kidney function.

Cardiovascular symptoms

Children with lupus may experience cardiovascular symptoms, such as chest pain (due to pericarditis or myocarditis), irregular heart rhythms, shortness of breath, and fatigue.

Neurological symptoms

Lupus can affect the nervous system, leading to various neurological symptoms, including headaches, cognitive impairment, mood disorders, seizures, and peripheral neuropathy.

Haematologic abnormalities

Children with lupus may develop abnormalities in blood cell counts, such as anaemia (low red blood cell count), leukopenia (low white blood cell count), and thrombocytopenia (low platelet count), which can cause fatigue, weakness, and an increased risk of infections or bleeding.

How is paediatric lupus diagnosed?

Diagnosing paediatric lupus requires a comprehensive evaluation by a healthcare provider, typically a paediatric rheumatologist, who is experienced in diagnosing and managing autoimmune diseases in children.

Medical history

The healthcare provider will obtain a detailed medical history, including information about the child's symptoms, their duration and severity, any factors that worsen or improve symptoms, and any family history of similar conditions.

Physical examination

A thorough physical examination will be conducted to assess for signs and symptoms suggestive of lupus, such as skin rash, joint swelling, oral ulcers, and other manifestations of the disease.

Laboratory tests

Laboratory tests play a crucial role in the diagnosis of paediatric lupus.

• Complete Blood Count (CBC): To assess for abnormalities in the blood cells
• Erythrocyte Sedimentation Rate (ESR) and C-reactive protein (CRP): Measures the level of inflammation that may be elevated in lupus
• Autoantibody Testing: Serologic tests for autoantibodies commonly associated with lupus, such as antinuclear antibodies (ANA), anti-double-stranded DNA (anti-dsDNA) antibodies, anti-Smith (anti-Sm) antibodies, and others
• Complement Levels: Measurement of complement proteins (C3 and C4) may help assess disease activity and severity
• Urinalysis: To detect abnormalities such as proteinuria, haematuria, and cellular casts, which may indicate kidney involvement (lupus nephritis)
• Other Tests: Depending on the clinical presentation, additional tests such as liver function tests, urine protein-to-creatinine ratio, and imaging studies (e.g., kidney ultrasound) may be ordered

Diagnostic criteria

Paediatric lupus is diagnosed based on established diagnostic criteria, such as those developed by the American College of Rheumatology (ACR) or the Systemic Lupus International Collaborating Clinics (SLICC).

American college of rheumatology (ACR) criteria

According to the ACR criteria, a diagnosis of lupus is considered if a patient meets at least four of the following criteria, either concurrently or serially:⁶

• Malar rash: Butterfly-shaped rash over the cheeks and nose
• Discoid rash: Raised, disk-shaped rashes
• Photosensitivity: Skin rash triggered by sunlight
• Oral ulcers: Ulcers or sores in the mouth or on the lips
• Arthritis: Nonerosive arthritis involving two or more joints
• Serositis: Inflammation of the lining of the lungs (pleuritis) or heart (pericarditis)
• Renal involvement: Persistent proteinuria or cellular casts in the urine
• Neurologic involvement: Seizures or psychosis without other known causes
• Haematologic abnormalities: anaemia (low red blood cell count), leukopenia (low white blood cell count), lymphopenia (low lymphocyte count), or thrombocytopenia (low platelet count)
• Immunologic abnormalities: Positive tests for antinuclear antibodies (ANA) or other lupus-specific autoantibodies, such as anti-double-stranded DNA (anti-dsDNA) antibodies, anti-Smith (anti-Sm) antibodies, or false-positive syphilis serology

Systemic lupus international collaborating clinics (SLICC) criteria

The SLICC criteria were developed to improve sensitivity and specificity for lupus diagnosis, particularly in patients who may not meet the ACR criteria. According to the SLICC criteria, a diagnosis of lupus is considered if a patient meets at least four criteria, including at least one clinical criterion and one immunologic criterion, or if there are biopsy-proven lupus nephritis with ANA or anti-dsDNA antibodies present.

Multidisciplinary evaluation

Given the multisystem involvement of lupus, children with suspected lupus may require evaluation by multiple specialists.

How is paediatric lupus treated?

The main treatment aim is to control symptoms, prevent flares, and minimise organ damage.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

Used to relieve pain and inflammation, particularly for arthritis and mild symptoms.

Corticosteroids

Prednisone or other corticosteroids may be prescribed to suppress inflammation and reduce disease activity during flares.

Disease-modifying antirheumatic drugs (DMARDs)

Medications like hydroxychloroquine are often used as first-line therapy to manage lupus symptoms and prevent flares.

Immunosuppressive medications

In severe cases or when organ involvement is present, drugs such as azathioprine, mycophenolate mofetil, or cyclophosphamide may be used to suppress the immune system and reduce inflammation.

Biologic therapies

In some cases, biologic agents like rituximab may be considered to target specific components of the immune system involved in lupus.

Lifestyle modifications

Sun protection (using sunscreen, wearing protective clothing), regular exercise, and a healthy diet are important for managing lupus symptoms and overall well-being.

Regular monitoring

Children with lupus require regular follow-up visits with healthcare providers to monitor disease activity, adjust treatment as needed, and address any complications or side effects of medications. Children with lupus often require ongoing care from a multidisciplinary team of healthcare providers to optimise outcomes and improve their quality of life.

Multidisciplinary care

A team-based approach involving paediatric rheumatologists, nephrologists, dermatologists, cardiologists, and other specialists is often necessary to provide comprehensive care for children with lupus.

Summary

Paediatric lupus is a complex autoimmune disease that requires a multidisciplinary approach to diagnosis and management. With early detection, appropriate treatment, and ongoing support, children and adolescents with lupus can lead fulfilling lives and achieve optimal health outcomes. Continued research into the underlying mechanisms of the disease and the development of targeted therapies are essential for improving outcomes and enhancing the quality of life for young patients with paediatric lupus.