Lupus 101: What it is, Diagnosis & Treatments

By –  Hephzibah (M.Sc. in Molecular Biology)

Lupus is a long-term autoimmune disease, where the immune system becomes hyperactive and cannot differentiate between foreign bodies and the body’s own healthy tissues, and attacks the normal healthy tissues. [1]

Signs and symptoms of this disease last for more than six years and even for years.

Lupus is a systemic disease, implying that different body systems may be affected, including kidneys, lungs, central nervous system, lungs, heart, joints, and skin. [2] [3]

Types of Lupus

There are different types of lupus:

  • the systemic lupus erythematosus (SLE), which is the most common type of lupus, and affects many parts of the body;
  • discoid lupus, which is characterized by red, scaly patches on the skin;
  • subacute cutaneous lupus, wherein skin lesions form upon exposure to the sun;
  • drug-induced lupus, which is caused by certain medications for high blood pressure, heart diseases or even antibiotics, such as hydralazine, procainamide, and isoniazid;
  • neonatal lupus, which affects newborns of mothers with lupus. [4] [5]

Causes of Lupus

The exact cause of lupus is unknown.

However, it has been found that in lupus, accelerated cell death is prominent.

Additionally, deficiency in the clearance of old cells may result in the accumulation of nuclear antigens (substances capable of stimulating an immune response through antibody production) and production of autoantibodies (antibodies against the body’s own tissue). [6] [7] [8]

Risk Factors for the Development of Lupus

Although the cause of lupus is unknown, it develops in response to certain factors. These are genetics, hormones, and environment.

People with an inherited genetic predisposition for lupus develop the disease when they come in contact with an environmental trigger. [9] [10]

The risk factors in detail are as follows:

Genetics

SLE and other autoimmune disorders tend to run in certain families, who have a genetic variation that affects the risk of disease inheritance.

Normal variations in genes involved in immune system function can affect the risk of SLE inheritance. [11] [12]

In most cases, many genes are involved, and rare cases, variations occur in single genes. [13]

Ethnicity is another risk factor in the development of lupus. Certain ethnic groups having common genes are more prone to lupus than others are.

It is two to three times more common in African-Americans than in Caucasians. [14] [15]

It is also common among Hispanics, Asians, and Native Americans. [16]

Hormones

It is thought that hormones, particularly estrogen might play a role in the development of lupus. Both men and women synthesize estrogen, but women synthesize more.

Therefore, women are at greater risk of developing lupus than men, although anyone can develop lupus. [17] [18] [19]

Furthermore, it is most commonly observed in women between 15 and 45 years of age, which is the reproductive period, when hormones are at peak levels.[20]

Environment

In addition to genetic predisposition, environmental factors also play a role in the development of lupus. [21]

Some of the environmental factors include viral infections, such as those by Cytomegalovirus, Epstein-Barr, and Herpes zoster virus, diet, sunlight exposure, chemical exposure, and medications. [22] [23] [24]

Drug exposure has been pointed out in about 10% of SLE cases, and more than 80 drugs implicated in lupus have been identified.[25]

Some of the implicated drugs are those used for high blood pressure, heart diseases, and antibiotics, including hydralazine, procainamide, and isoniazid. [26]

Symptoms of Lupus

The symptoms of lupus differ from person to person. They may develop suddenly or slowly, be mild or severe, or be temporary or permanent.

The disease is characterized by flares (when symptoms become worse) and remissions (when symptoms become better). [27] [28] [29]

The symptoms of lupus that manifest in a patient depend on the affected body part. [30]

The most common lupus symptoms include:

  • prolonged or extreme fatigue and malaise
  • loss of appetite and weight
  • pain in the joints (arthralgia) and inflammation and swelling in the joints (arthritis) as well as muscle pain
  • swollen lymph nodes
  • skin rashes due to bleeding under the skin; the malar rash (butterfly-shaped rash covering the cheeks and nose) is a characteristic of lupus
  • mouth or nose sores/ulcers
  • extreme sensitivity to the sun (with skin lesions that appear or worsen with sun exposure
  • high fever
  • headaches and confusion
  • chest pain upon deep breathing (pleurisy) and shortness of breath
  • unusual hair loss
  • fingers and toes turning white or blue upon exposure to cold or during stressful periods (Raynaud’s phenomenon)
  • abdominal pain
  • dry eyes, eye inflammation, and eyelid rashes [31] [32] [33]

Lupus also has significant effects on other body systems, which are given below:

Kidneys: Inflammation of the kidneys (lupus nephritis), which is the most critical complication of lupus, the leading cause of deaths due to lupus

Lungs: Inflammation of the lining of the chest cavity (pleuritis) and possible pneumonia

Central Nervous System: Dizziness, depression, memory disturbances, vision problems, seizures, stroke, and changes in behavior, and numbness and weakness (due to damage to the spinal cord)

Blood vessels: Inflammation of the blood vessels (vasculitis)

Blood: Hemolytic anemia (with destruction of red blood cells), white blood cell count decrease (leukopenia), platelet count decrease thrombocytopenia), lymphocyte count decrease (lymphopenia; lymphocytes are a white blood cell type), increased risk of bleeding or clotting

Heart: Inflammation of the heart (myocarditis and endocarditis), inflammation of heart membrane (pericarditis), resulting in cardiovascular disease and heart attacks

Infections:  Increased susceptibility to infections such as urinary tract infections (UTIs), respiratory infections, yeast infections, salmonella infections, herpes, and shingles

Bone tissue death (avascular necrosis):   Bone breakage and collapse due to low blood supply to the bone, particularly of the hip joint

Pregnancy complications:  Miscarriage, pregnancy loss, preterm birth, and preeclampsia (pregnancy complication that includes high blood pressure) [34] [35] [36]

Diagnosis of Lupus

It is difficult to diagnose lupus, because the symptoms are not specific to lupus, and mimic those of other diseases.

Therefore, a single laboratory test is insufficient to correctly diagnose lupus. [37]

Some of the ways a health practitioner can use in combination to diagnose lupus are as follows:

Medical history: An account of symptoms experienced by patients as well as other problems can help the doctor gain an idea of the disease. [38]

Family history of lupus or other autoimmune diseases: Since lupus tends to run in families, doctors can corroborate their diagnosis with knowledge of the family history of lupus.

Complete physical examination: This is done to check for physically visible symptoms such as rashes, mouth or nose sores, joint swelling, and so on. [39]

Skin or kidney biopsy: A small sample of skin or kidney tissue is extracted from the patient, and observed under the microscope to identify symptoms of lupus. [40

Erythrocyte sedimentation rate (ESR; erythrocyte is the scientific term for red blood cell): It measures the speed at which red blood cells move towards the bottom of a test tube. [41] [42]

 In the presence of inflammation, blood proteins aggregate and fall to the bottom of the test tube.

The greater the speed of fall is, the higher the level of inflammation is. [43] [44]

Complete blood cell count (CBC): It measures the counts of different blood cell types since abnormal blood cell counts are usually observed in lupus.

Urine tests for lupus include

Tests for urine protein (microalbuminuria), which test for the presence of albumin protein in the urine

Tests measuring creatinine (a waste product synthesized when muscles use creatine, present naturally in muscles, to produce energy) clearance, indicating how effective the kidneys are at eliminating waste products

Urinalysis for the presence of protein, red blood cells, white blood cells, and cellular casts in the urine, which indicate kidney disease

Tests measuring the glomerular filtration rate (the rate at which the kidney filters and removes waste products from blood), which indicate the stage of kidney disease. [45]

Chemistry panel: It is a test used to assess kidney and liver function, and abnormalities could indicate lupus. [46]

Blood tests

As lupus is an autoimmune disease, it is characterized by the production of autoantibodies, which are as follows:

  • ANA (anti-nuclear antibody; against components of the cell’s nucleus; found in 95% of patients with lupus, but found in other autoimmune diseases also),
  • APL (antiphospholipid antibodies; against phospholipids, a kind of fatty acids; present in up to 60% of patients with lupus),
  • Anti-DNA (against DNA, the genetic material inside the cell’s nucleus; found in 70% of patients with lupus),
  • Anti-dsDNA (against double-stranded DNA; found in 75–90% of patients with lupus, indicates a high risk of lupus nephritis),
  • Anti-Sm (against Smith proteins, which are RNA-binding proteins found in the nucleus; found in up to 30% of patients with lupus),
  • Anti-U1RNP (against a specific ribonucleoprotein, which helps in packing DNA within the nucleus; found in 25% of patients with lupus),
  • Anti-Ro/SSA and Anti-La/SSB (commonly found together in 24–60% of patients with lupus),
  • Anti-histone (against histone proteins found in the nucleus)

Other blood tests include those for biomarkers of inflammation such as C-Reactive Protein (CRP) and serum complement test (complement proteins are involved in inflammation).

They are present at low levels in patients with active kidney disease.  [47]

Imaging tests

X-ray scans, MRI, and CT scans can help doctors see the affected organ and check for abnormalities. Chest X-rays can reveal lung inflammation. [48]

Echocardiogram (a diagnostic tool that uses sound waves to produce images of the heart) can reveal any problems with the heart. [49]

The classification criteria developed by the American College of Rheumatology are used to aid correct diagnosis. For a patient to be diagnosed with lupus, four of the following eleven criteria must be satisfied, either simultaneously or serially:

  • Malar rash – butterfly-shaped skin rash across cheeks and nose
  • Discoid rash – red, scaly patch on the skin
  • Photosensitivity – Skin rash due to an unusual reaction to sunlight
  • Oral or nasopharyngeal (along with the nose and throat) ulcers – usually painless ulcers in the mouth or nose
  • Nonerosive arthritis – characterized by swelling, fluid accumulation, or tenderness
  • Serositis (inflammation of the serous tissues, such as those lining the heart and lungs) – pleuritis or pericarditis
  • Renal (kidney) disorder – Proteinuria (presence of protein in urine) or presence of cellular casts in the urine
  • Neurologic disorder – seizures or psychosis
  • Hematologic disorder – Hemolytic anemia or lymphopenia or thrombocytopenia  or leukopenia
  • Immunologic disorder – Presence of Anti-Sm antibodies or positive finding of antiphospholipid antibodies or the presence of Anti-DNA antibodies
  • Antinuclear antibody – Abnormal antinuclear antibody level [50] [51]

Lupus Treatment Options

Although there is currently no cure for lupus, symptoms can be managed through lifestyle changes and medication.

Treatment depends on the signs and symptoms of lupus.

Treatment depends on several factors, such as overall health, age, organs affected, medical history, and lupus severity. [52] [53] [54]

The goals of lupus treatment are to:

  • prevent flares
  • treat symptoms when they appear
  • reduce organ damage and other complications [55]
  • Treatment includes medication for:
  • reducing swelling and pain
  • soothing the immune system to prevent it from attacking the body
  • reducing joint pain and damage
  • preventing or reducing organ damage [56]

Patients with lupus are required to consult different doctors, such as a primary care doctor, a rheumatologist (a physician who is concerned with diseases of joints, bones, and muscles), cardiologist (heart specialist), or other, depending on the affected body part. [57]

Some patients with the mild disease do not require treatment; however, those with serious complications require highly effective medication. Some of them are: .[58] [59] [60] [61] [62] [63] [64] [65] [66] [67] [68] [69] [70] [71]

Corticosteroids

This calms the immune system and helps counter the inflammation occurring in lupus by reducing swelling, tenderness, and pain.

Also called “steroids,” they come in the form of creams, which can be applied topically to rashes or tablets for mild/moderate lupus.

Higher doses are used when internal organs are affected.

Examples include prednisone and methylprednisone.

Nevertheless, these drugs cause side effects such as weight gain, diabetes, increased risk of infection, high blood pressure, thinning of bones, and easy bruising.

Therefore, the consumption of these drugs should be approved by a certified health practitioner.

Non-steroidal anti-inflammatory drugs (NSAIDs)

These drugs decrease joint pain and swelling, fever, and inflammation of the linings of the heart and lungs.

Examples are ibuprofen and naproxen.

Side effects are serious, like stomach bleeding or kidney damage.

It is advised to always consult a doctor before consuming these drugs.

Antimalarial drugs

Medicines used to prevent or treat malaria are used for joint pain, skin rashes, fatigue, and lung inflammation.

They help decrease the risk of lupus flares.

Examples are hydroxychloroquine and chloroquine phosphate.

Side effects include indigestion, diarrhea, stomach upset, and rarely, eye damage.

In addition to consultation with a certified healthcare provider, eye examinations are also recommended.

Immunosuppressants

These are drugs that suppress the immune system.

They are used in severe cases of lupus, where other medications seem ineffective.

Sometimes, they are used in combination with corticosteroids to effectively relieve symptoms.

Immunosuppressants such as methotrexate, mycophenolate mofetil, cyclophosphamide, and azathioprine are generally recommended.

Since these drugs suppress the immune system, they cause serious side effects such as the increased risk of infection, liver damage, decreased fertility, and increased risk of cancer.

These drugs should be consumed only with the prescription of a certified health practitioner.

Biologics/BLyS-specific inhibitors

These drugs help treat lupus by limiting the number of abnormal B-lymphocytes (cells of the immune system that produce antibodies).

These are monoclonal antibodies raised against specific proteins involved in the immune response.

They are used for patients who do not respond to other treatments.

The two biologics used for lupus are belimumab and rituximab.

Side effects include nausea, diarrhea, infections, and allergies to the infusion of the biologics.

As these drugs are not tested thoroughly for severe cases of lupus, consultation with a certified healthcare provider is mandatory.

Anticoagulants

These drugs help thin the blood to prevent clotting, which is a life-threatening symptom of lupus.

Examples include heparin, warfarin, and aspirin.

Other drugs

Other medicines used to treat complications associated with lupus, such as high blood pressure or osteoporosis (weak, fragile, and thin bones), may also be prescribed.

Combination treatment

Healthcare providers may combine different medications to control the symptoms of lupus.

Since each medicine has its own risks and side effects, upon the combination, doses could be reduced, and therefore, side effects could be reduced.

For example, immunosuppressants are prescribed in combination with corticosteroids for lupus.

Potential therapeutic molecules

Researchers are continuously developing new therapeutic substances for lupus. Some of them are as follows:

MRA

It is a monoclonal antibody synthesized in the laboratory against interleukin-6 (IL-6),

IL-6 is a protein that stimulates increased production of antibodies.

It plays a role in inflammation, which may underlie organ damage observed in SLE.

This molecule is currently under Phase I clinical trials.

Dihydroartemisinin (DHA)

It is a drug used to treat malaria.

Scientists are conducting Phase II clinical trial studies to study its efficacy in SLE.

Omega-3 fatty acids

Studies have reported that omega-3 fatty acids are anti-inflammatory lipids, which are involved in the synthesis of major mediators and regulators of inflammation.

A pilot clinical trial is conducted to analyze the effects on omega-3 fatty acids on levels of inflammatory markers in patients with SLE.

Anifrolumab

It is a human monoclonal antibody targeting the interferon α receptor.

The interferon α receptor is a cellular protein that binds interferons, which play important roles in host defense against viral infections and pathogenesis of several autoimmune diseases.

It is under a Phase III clinical trial for the treatment of moderate to severe, autoantibody-positive SLE

Precautions

Lupus requires extreme care. There are certain simple measures and precautions to take to prevent the occurrence of flares or to relieve them. They are outlined below:

It is important to have regular checkups and consultations with health practitioners instead of consulting them only when symptoms worsen, so as to prevent flare-ups. [73]

Additionally, it is necessary to form a good doctor-patient relationship, which can help patients cope with lupus.

Patients with lupus should follow medication instructions, as most medications for lupus have side effects and risks.[74]

It is advised that patients be involved in their healthcare, become well informed about lupus, medications prescribed, and progress expected. Being aware of the symptoms of lupus can help prevent or relieve flares. [75]

Getting the right amount of exercise is also important for patients with lupus. It helps with mental health and weight control. Exercise can help keep bones strong, reduce the risk of heart diseases, and promote general well-being. [76]

Patients with lupus must eat a healthy, well-balanced diet.  [77]

In the case of kidney damage, gastrointestinal problems, or high blood pressure, patients with lupus may have to follow dietary restrictions.[78] [79]

It is reported that smoking worsens the effects of lupus on the heart and blood vessels, as well as resulting in cancer and heart disease. Therefore, patients with lupus should not smoke or commit to quitting.  [80] [81]

It is recommended to avoid exposure to sunlight, as sunlight can trigger or aggravate flares. Patients are advised to wear protective clothing and use sunscreens with sun protection factors of at least 55. [82] [83]

It is important to make sure to get enough rest and sleep to ease fatigue, a common lupus symptom. [84] [85]

As stress is implicated in the development of lupus or its flares, it is necessary to avoid stress as much as possible or lower it. Practicing mindful and movement techniques, such as meditation or yoga, could help reduce stress. [86] [87]

Women with lupus should consult with their healthcare providers before planning a pregnancy. Pregnancies should be timed during remissions when lupus flares are minimal. [88] [89][90][91]

While pregnant, women with lupus should avoid certain medications, such as cyclophosphamide, cyclosporine, and mycophenolate mofetil, which can harm the fetus. Additionally, women with lupus should avoid warfarin.  [92] [93] [94]

Summary

Lupus is an autoimmune disease. The cause of lupus is unknown.

Symptoms are malar rash, fever, arthritis, sun sensitivity, chest pain, kidney damage, pericarditis, and pleuritis.

Antibody tests, imaging tests, tissue biopsies, and urine tests help diagnose lupus.

Corticosteroids, NSAIDs, immunosuppressants, antimalarials, and biologics are usually prescribed.