Overview

Lupus (systemic lupus erythematosus) is a chronic autoimmune condition, where the immune system attacks normal cells by recognising them as foreign invaders. It involves all organs in the body, causing tissue damage and inflammation. It is characterized by red rashes, joint pain and fatigue. Lupus is difficult to diagnose due to the clinical presentation being similar to other diseases. Early diagnosis is important in preventing irreversible tissue damage. There is no cure for lupus. It is controlled through medication and management techniques. Healthcare providers may come up with a personalised treatment plan for the patient. With the appropriate therapy, patients can lead fulfilling lives.^1,2

Diagnosis

Diagnosing lupus may prove difficult as it presents symptoms similar to other disorders. The symptoms can also change over time, which makes it harder to diagnose. The diagnosis of lupus is determined through clinical presentation, laboratory testing and imaging studies.^3,4 

Clinical symptoms

The manifestation of lupus may vary in each patient. Common symptoms include red rashes, fatigue and joint pain.

Patients may also present with:

• Fever
• Headaches
• Weight loss
• Mouth ulcers
• Hair loss
• Swollen glands
• Anxiety and depression
• Nausea, vomiting, and abdominal pain
• Shortness of breath and chest pain
• Raynaud's phenomenon^1,5

Laboratory tests

Antinuclear antibody (ANA) test

The ANA test is commonly used in the diagnosis of lupus. It works by detecting antibodies that target the nucleus of your cells. Most patients with lupus test positive for ANA. However, patients have to undergo further testing as a positive ANA test may also involve other autoimmune diseases. 

Antinuclear antibody panel

This is a series of tests carried out after the patient tests ANA-positive. The test looks for antibodies, anti-double-stranded DNA (anti-dsDNA), and anti-Smith (anti-Sm).

Other blood and urine tests

• Full blood count: This test looks for unusual concentrations of the components of your blood. It looks at your haemoglobin concentration, red cell indices and morphology, white cell count and morphology and platelet count.
• Erythrocyte sedimentation rate(ESR): The ESR test may prove useful in indicating abnormal inflammatory activity in the body. This can be used to indicate conditions such as autoimmune disorders, infections or tumours.
• Kidney and liver function tests
• Urine tests to check for kidney damage^2,4,5

Imaging studies

Imaging studies look at whether there has been any organ damage, the extent of organ damage and also assess its function.

The imaging tests may include:

• Radiography: This may be used to assess joints.
• Renal ultrasound: This test examines the kidneys, it can be used to assess their size and whether their function is impaired.
• Chest X-rays.
• Electrocardiography: This test checks for any impairments in the heart function.

Renal biopsy

A renal biopsy is essential to determine a definitive diagnosis of lupus. This is where a small piece of the kidney is removed for examination. The biopsy may provide insight into the extent of kidney damage and may help healthcare providers when deciding what treatments to offer.^2,5

Classification criteria for Lupus

There are three different classification systems that may be used to diagnose lupus. These are the American College of Rheumatology (ACR) criteria, the Systemic Lupus International Collaborating Clinics (SLICC) Criteria and the European League Against Rheumatism (EULAR) criteria.

ACR criteria

Patients must meet criteria where they should have at least 4 of the 11 conditions to be diagnosed with lupus.

The conditions include:

1. Red rash on the cheeks.
2. Red and cracked patches on the skin.
3. Photosensitivity which causes rashes.
4. Mouth ulcers.
5. Serositis.
6. Arthritis.
7. Chronic Kidney Disease (CKD).
8. Neurological disorders.
9. Hematological (blood) disorders.
10. Presence of anti-dsDNA.
11. A positive antinuclear antibody (ANA) test- it is inconclusive on its own as it can be caused by conditions other than lupus.^3,4

SLICC criteria

The SLICC classification criteria is a newer classification compared to ACR. It is a more sensitive criterion and aims to help diagnose patients who may have been missed by previous classification systems. According to the SLICC criteria, patients must present with 1 clinical condition. 

These clinical conditions are similar to those in the ACR criteria, as well as:

• Acute cutaneous lupus
• Chronic cutaneous lupus

Alongside this, patients must have 1 immunologic criterion, these include:

• Positive ANA test
• Positive anti-dsDNA
• Positive anti-Smith
• Antiphospholipid antibodies
• Hypocomplementemia
• Direct Coombs test

The SLICC criteria are helpful in the early stages of diagnosis. However, care needs to be taken during diagnosis as there may be a risk of false positives.²

EULAR criteria

The EULAR criteria were developed to maintain the high specificity of the ACR criteria whilst also achieving a high sensitivity, similar to the SLICC criteria. Research suggests that it has reached this goal. The EULAR criteria require a positive ANA test of 1:80 or higher. They must also have at least 1 of the clinical criteria (similar to ACR criteria). Currently, this criterion is used for research and may be used in classifying clinical trial participants.^2,6

Treatment

The treatment of lupus involves achieving 4 main goals:

1. Controlling flare-ups caused by lupus and reducing symptoms. 
2. Controlling and limiting the activity of lupus. This involves medication such as immunomodulators and immunosuppressants.
3. Preventing organ damage.
4. Reducing and treating diseases secondary to lupus. Particularly accelerated atherosclerosis, which is a major cause of death.²

Medications

Immunomodulators

• Hydroxychloroquine is beneficial and a highly recommended treatment for patients with lupus. It increases survival in patients and is effective in alleviating symptoms. This includes preventing organ damage, reducing the risk of developing neuropsychiatric lupus, preventing seizures, and improving symptoms that present on the skin as well as arthritis. 
• Vitamin D has immunomodulatory and antifibrotic effects. Vitamin D supplementation is often given to patients with lupus as they tend to have a vitamin D deficiency. Research has shown correlations between vitamin D supplementation and a decrease in proteinuria, higher complement levels and improved disease activity. 
• Dehydroepiandrosterone DHEA in women showed a moderate improvement in disease activity, it also showed improvements in the regulation of cytokines and bone density. This medication should not be used in postmenopausal women as it may increase the chance of developing a malignancy.

Corticosteroids

Intramuscular triamcinolone is a type of corticosteroid that may prove effective in patients with mild to moderate flares. Studies have shown that it is fast-acting and due to its slow release, the effects of the medication last for roughly a month. Oral corticosteroids should be avoided as it is associated with an increase in cardiovascular disease and organ damage. Over time oral corticosteroids may cause cataracts, osteoporosis and coronary artery disease.

Cytotoxic immunosuppressants

• Methotrexate has anti-inflammatory effects. It works by stopping the cell cycle. It has proven effective in reducing disease activity and has been shown to improve joint and skin symptoms. 
• Mycophenolate mofetil is generally used in cases of lupus nephritis. In some cases, it has caused complete renal remission and is the most successful in preventing nephritis relapses. 
• Calcineurin inhibitors have also proven successful in treating lupus nephritis. It is also prescribed to patients who have had transplants to prevent rejection. They are also recommended by EULAR.

Biologic agents

• Rituximab may be used in cases where previous treatments have failed. Some studies have shown improvements in patients whereas others have not been so successful. Further research needs to be done to understand the true benefits of this treatment. Patients on this medication must be carefully monitored. 
• Belimumab is the first and only biologic agent to be approved by the EMA, FDA and NICE. It works by reducing B cell survival and antibody production. It has been effective in reducing disease activity and improving symptoms. It has also been successful in reducing flare-ups.²

Lifestyle changes

1. Use high-factor sun protection and wear a sun hat
2. Try to find a balance where you are not overexerting yourself
3. Try to keep active
4. Try to manage your stress through relaxation techniques
5. Inform your employer about your condition so that they can consider any changes to make it easier for you to manage your work.
6. Try to eat a balanced diet rich in vitamins and minerals
7. Smoking makes lupus worse, so try to avoid it
8. Avoid sitting in direct sunlight or spending long periods of time in a room with fluorescent lights¹

Long-term complications and management

Patients with lupus may also suffer from other disorders as a result. The main cause of death is cardiovascular-related disorders. Factors such as obesity, diabetes, smoking and lupus-related symptoms must be managed to decrease cardiovascular risk. Infections such as pneumonia are common in patients with lupus. Keeping up to date with immunisations is an important preventative measure. There is an increased risk of osteoporosis and fragility fractures in lupus. Adequate vitamin D and calcium, as well as quitting smoking and maintaining good health may help to improve bone health. Patients with lupus should undergo regular screening to detect any underlying disorders.²

Summary

Lupus is a chronic autoimmune disease characterised by joint pain, red rash and fatigue. Due to its similar presentation to other autoimmune conditions, patients must meet the criteria in order to be diagnosed with lupus. There are 3 classification systems described in detail above. The most sensitive and specific is the EULAR classification system. Early detection of lupus is key in preventing extensive organ damage. There are various treatment plans for lupus. The healthcare provider may tailor the treatment depending on the clinical presentation and extent of disease activity. Treatment for lupus is ongoing as there is no cure. There are also management techniques, which help to ease symptoms and reduce the risk of further complications. Further research into the way lupus works has paved the way for exciting new treatments. This may help in providing more effective and less toxic ways of treating lupus.