Lupus

Systemic lupus erythematosus (SLE)

• Simply referred to as Lupus.
• “Systemic” refers to the connective tissues throughout the body that are affected.
• “Erythematosus” a clinical state where red, raised patches develop on the skin.

Discoid lupus erythematosus

• It’s distinct from SLE, as the symptoms are only skin related.
• It causes a red rash that develops on the face or scalp.
• Discoid Lupus patients often also have SLE, or develop it in the future.

Drug induced Lupus

• Some medications can cause Lupus, but generally goes away after stopping the triggering drug.
• Medications that may cause this include, oral birth-control, blood pressure-lowering drugs, antibiotics and antifungal medications.
• Drugs specifically linked with drug induced Lupus include:
• Procainamide – antiarrhythmic drug
• Hydralazine – Blood pressure lowering drug
• Quinidine – antiarrhythmic drug

Neonatal Lupus

• Develops in new born infants
• Quite rare, and is caused by autoantibodies that are transmitted from a mother with lupus to the baby
• More than half of these babies have problems with their skin, heart and gallbladder
• This does however resolve in the first few months of life, but may cause serious complications.
• Death is only in 10% of these neonatal lupus cases, and the causes being pneumonia or heart complications.

Signs

• Complex disease with many variations
• Some patients have many symptoms, others only a few
• Symptoms can be severe to others that remain mild
• Can be genetic or through environmental factors, which make it difficult for doctors to diagnose
• People have periods of feeling well - remission, and periods of worsening symptoms – flares
• Warning signs include – worsening fatigue, headache, fever, dizziness, rash or pain.
• Catching and treating flares early, may prevent symptoms from becoming severe.

Symptoms

• Intense fatigue
• Painful or swollen joints
• Muscle pain
• Red rash on face or response from sitting in the sun
• Pain in the chest after taking a deep breath
• Unexplained fever
• Swelling, often in legs and around the eyes
• Mouth sores
• Unexplained hair loss
• Raynaud’s phenomenon – cold fingers/toes, which are pale or purple in colour

Diagnosis

Malar Rash 

• Signs/Symptoms: A red rash on cheeks and bridge of nose, called “butterfly rash”.
• Test: Physical exam, medical history.

Discoid Rash

• Signs/Symptoms: Raised, hard patches of scaly skin.
• Test:Physical exam, medical history.

Photosensitivity 

• Signs/Symptoms: Red skin rash caused by sunlight exposure.
• Test: Physical exam, medical history.

Oral Ulcers

• Signs/Symptoms: Sores in mouth, usually painless.
• Test: Physical exam, medical history.

Non-erosive Arthritis

• Signs/Symptoms: Inflammation in joints, making them feel tender and swollen. Cartilage, which is protective tissue surrounding the bone, remains intact.
• Test: Physical exam, medical history, X-Ray.

Pleuritis and/or pericarditis

• Signs/Symptoms: Inflammation in the lining of the heart and lungs, may cause pain when breathing deeply, growing tired easily.
• Test: Lung function test, chest X-Ray to look for fluid in lungs, cardiac stress test, echocardiogram, uses sound waves to visualise the heart.

Neurologic disorder

• Signs/Symptoms: Reduced or abnormal brain function, headaches, seizures, memory loss, difficulty concentrating.
• Test: Physical exam, medical history, brain MRI, produces a high-resolution image of the brain.

Kidney disorder

• Signs/Symptoms: Usually no symptoms, signs are blood or high levels of protein in the urine.
• Test: Urinalysis.

Blood disorder

• Signs/Symptoms: Anaemia, with associated fatigue, dizziness, shortness of breath, increased susceptibility to infection, slow clotting, excessive bleeding.
• Test: Complete blood count, test for abnormal cell counts of platelets, red blood cells, lymphocytes, and leukocytes.

Immunologic disorder

• Signs/Symptoms: Possible increased susceptibility to infection, inflammation in various organ systems.
• Test: Assorted tests to detect antibodies from a blood sample.

Positive anti-nuclear antibodies

• Signs/Symptoms: Possible increased susceptibility to infection, inflammation in various organ systems.
• Test: Antinuclear antibody test, tests for the presences of antibodies that bind the cell nucleus, where the DNA that makes up genetic material is stored. 

• By calculating a SLEDAI score – systemic lupus erythematosus disease activity index
• This is based on the signs and symptoms shown over a period of 10 days, where a total score is calculated
  • E.g. protein present in urine = 1 point
• A point is assigned for each sign and symptom and depending on the total, it will either be mild or severe diagnosis.

Inflammation and tissue injury

• This is the inflammation caused by autoantibody complexes
• B-cells – immune cells which are found in bone marrow, and produce and secrete antibodies, which are proteins that bind to other molecules
• They target many molecules on the surface of microbes, like bacteria and viruses
• Antibodies bind to molecules on a microbe like a “key and lock” and gets removed by the body
• People with Lupus, the B-cells bind to healthy tissue instead of molecules or microbes.
• T-cells – made in the Thymus, called cytokines and help B-cells grow, and activate. They stimulate B-cells to produce antibodies.

• B cells become activated and produce autoantibodies which bind many self-molecules
• T cells are activated and produce proteins called cytokines and help activate more B cells
• Big complexes of antibodies stick to self-molecules are formed
• These complexes become lodged in many tissues in the body like kidneys and joints
• Complexes cause an increase of neutrophils, macrophages B cells and T cells into the tissue
• Pro-inflammatory cells secrete damaging reactive oxygen species and more proteins then cause tissue damage
• When inflammation is not treated over time, tissue may become permanently damaged.

Kidneys

• Kidney disease is common in people with Lupus up to 50%
• The damaging inflammation that causes the kidney disease is called Lupus Nephritis
• Circulatory system delivers blood to the glomeruli (small filtering units in kidneys) through small capillaries.
• They help to regulate the blood pressure and electrolytes by removing and reabsorbing fluids, and salt in amounts needed by the body.
• Kidney complications occur more or less 5 years after the onset of lupus symptoms.
• Kidney disease causes proteins to leak out of the kidney into the urine, high levels of protein in urine is indicative of kidney damage.

Heart and Cardiovascular

• Lupus patients have an increased risk of developing coronary artery disease
• Heart disease is the most common cause of death in patients with Lupus
• Factors that that is caused by people with Lupus;
  • Lupus-mediated inflammation directly damages the endothelium, the lining in the blood vessels, which lead to atherosclerosis
  • Type 2 Diabetes, high blood pressure, high cholesterol, are more present in Lupus patients, and have a higher risk for heart disease
  • People with Lupus are less active due to the symptoms of fatigue, joint pain and muscle stiffness, which has the result of weight gain, high blood pressure, and also a risk for heart disease

Nervous system

• Lupus can damage the nervous system
• Symptoms include confusion, excessive tiredness, seizures, difficulty concentrating and headaches
• Two factors:
  • Autoantibodies can target molecules on nerve cells, and cause inflammation and result in nerve damage
  • Inflammation in and around blood vessels which prevent the delivery of nutrients and Oxygen nerves need to stay healthy
• Other signs and symptoms are, stiff neck, high fever, psychosis, and seizures.
• Severe nerve damage may result in coma and even death

Muscles

• Lupus causes muscle pain, but the strength of the muscle is not affected
• This commonly affects the arms and legs

Bones

• Loss of bone density can lead to osteoporosis and leave patients at higher risk for bone fractures
• Exercise is difficult or painful, because of the muscle stiffness and joint pain
• Corticosteroids can accelerate bone loss

Blood disorders

• Very common in people with Lupus
• There are 4 different blood count abnormalities;
  • Anaemia – Too few red blood cells
  • Thrombocytopenia – Too few platelets in the blood, which may cause a delay in clotting of the blood or excessive bleeding
  • Leukopenia – Reduced level of leukocytes, white blood cells due to their lack of colour. This increases the risk for infections
  • Lymphopenia – Reduced level of subset white blood cells – Lymphocytes. Band T cells fall into this group. This will also increase the risk for infections.

Vitamin D is involved in the process of autoimmunity through the properties of B, and T cells towards 'tolerance' of self-tissues. This is done by many highly specialised cytokines and cell-signalling molecules. These become immune cells which either promote tissue destruction, or suppress tissue destruction. 

Patients who suffer from Lupus have high levels of effector cells, and low numbers of regulatory cells. Regulatory cells malfunction in people with Lupus. Vitamin D have many actions at cellular level, to balance effector and regulatory cells. 

• As woman are more likely to develop autoimmune diseases than men, prove that steroid hormones like oestrogen, progesterone, influence the immune system
• Oestrogen is pro-inflammatory, while progesterone, androgens and glucocorticoids are anti-inflammatory
• Low levels of progesterone in woman with Lupus, shows that an imbalance of oestrogen can contribute to immune reactivity in some female patients.
• Testosterone suppresses immune activity in cells from patients with Lupus
• Woman that have Lupus should have their sex hormone levels checked and ensure the progesterone and testosterone levels are sufficient
• If any of these levels are low, then it is recommended to use bio-identical hormone creams to restore levels to a normal range.

As Lupus targets many organ systems, treatment should be tailored for each individual. A healthy lifestyle should be obtained, which includes, conventional medicine, complementary medicine, exercise, good nutrition, not smoking, and avoiding excessive sunlight, to help reduce frequency and severity of flare ups.

Anti-inflammatory drugs

• Help to reduce inflammation
• Effective at reducing symptoms and prevent flare ups
• These medicines are linked to adverse long-term side effects.

Corticosteroids

• Type of steroid with powerful, anti-inflammatory effects
• Effectively reduce inflammation in people who suffer from Lupus
• Prednisone – commonly used to treat Lupus. Orally in pill form, injected for skin rashes, or intramuscularly for muscle inflammation
• Side effects – easy bruising, fat redistribution mainly around the abdomen, weight gain, insulin resistance, psychological changes – irritability, depression and euphoria
• Increase the risk of complications from diabetes, high blood pressure, glaucoma and higher levels of triglyceride and cholesterol
• Long term use can cause bone loss, an increase the risk of bone fractures
• Increased risk of atherosclerosis
• Lowest dose of corticosteroids are prescribed to help relieve symptoms. Injected only in severe diseases flares.

NSAIDs (Non-steroidal anti-inflammatory drugs)

• Suppress inflammation
• Less effective than corticosteroids in people who have severe Lupus
• But are both anti-inflammatory and analgesic, they provide relief of pain and reduce inflammation.
• Ibuprofen and Naproxen are examples of this medication
• These medicines are given by physicians who closely monitor their patients
• Side effects include – upset stomach, nausea, gastrointestinal bleeding, fluid retention, kidney damage, high blood pressure and risk of heart attack.

Aspirin

• Patients who have anti-phospholipid antibodies, can make the blood more prone to clotting.
• Aspirin has blood thinning, anti-inflammatory, analgesic effects
• Doctors recommend a low dose to reduce the risk of heart disease, and relieve aching joints

Anti-malarial drugs

• Used to treat malaria, as well as symptoms of Lupus.
• Helps to reduce inflammation in the lining of the lungs, heart, and improve joint and muscle pain, reduces fever and fatigue
• Side effects – nausea, vomiting, diarrhoea, stomach cramps, headache, dizziness, irritability, skin may become darker in colour and very dry

Immune system modulators

• Alter the number or function of immune cells
• Self-reactive immune cells are suppressed and the cells that fight against infections are also inhibited, and may lead to increased risk of infections
• Immune suppressive drugs:
  • Cyclophosphamide – effective in treating lupus related kidney disease. Side effects – nausea, vomiting, infertility, and hair loss. A low dose is also effective in treating lupus nephritis
  • Mycophenolate mofetil – Latest, more effective with less side effects. It’s the first line drug used to treat Lupus
  • Azathioprine – An immunosuppressive drug with fewer severe side effects

Monoclonal antibodies

• These antibodies are created through a process that involves culturing of specialized cells, that have disease specific antigens and purifying antibodies that are produced as a result.
• They are targeted at the surface of B cells that allow doctors to turn the immune system against itself, and destroy self-reactive B cells that are visible in Lupus patients.
• FDA approved-
  • Belimubab new drug specifically for Lupus
  • Rituximab Antibody drug that causes the immune system to destroy B cells. However not approved for treating Lupus, but often used off label by Doctors.

• Nonspecific cell type that has the potential to change into different types of specialised cells
• Cells can divide to produce another stem cell to replenish itself or grow into a specialised cell – nerve cell, brain cell, B cell
• Stem cells are taken from a person, then grown in a laboratory to specialised cells, and transplanted back into the person, and replaces diseased cells.
• Used to treat Lupus, by taking blood stem cells from a patient, growing them in a lab into healthy new B and T cells, that won’t attack self-tissues.
• These cells then replace the autoimmune B and T cells with the patient’s own new healthy cells
• This is known as autologous hematopoietic stem cell transplantation
• This treatment is only used on very severe disease cases who do not respond to conventional lupus treatments.

• Lifestyle – diet, physical activity, stress levels, all have an effects on chronic diseases, such as Lupus
• A healthy lifestyle, will help to prevent flares, and severity of diseases, as well as overall improvement of quality of life
• The level of stress in someone with Lupus can affect the disease by triggering flares and worsening the severity there of
• UV Light from the sun, may cause skin lesions, there for avoiding sun exposure is necessary to avoid these symptoms
• Avoiding sun exposure and applying sun screen is effective in preventing the damages caused by UV light exposure
• Exercise is good to prevent inflamed joints, becoming stiff and also keeps muscles, bones, and cartilage strong, can also improve feelings of depression and overall quality of life.

• Vitamin D – Important nutrient that is made in the skin after absorbing UV Light. It also includes fatty fish like salmon, mackerel, fortified foods, margarine, milk, breakfast cereals, and Vit. D supplements
  
  • Reduced levels of Vitamin D in people with Lupus are caused by:
    • Deficiency related to Lupus itself
    • Deficiency caused by avoiding sun exposure due to sun sensitivity
• Fish oil – Derived from fatty fish – mackerel, tuna, salmon, halibut, which are rich in omega-3 fatty acids, which promote health.The body needs these fatty acids, as the body can only produce a minimum itself. By taking fish oil it has been proven to relieve Lupus severity, as well as reduced serum lipids in people with Lupus. This is useful, as these patients are at greater risk for developing heart disease

Minerals and Vitamins

• Vitamin E – Helps to reduce different markers of inflammation. The antioxidant vitamins may help to delay or prevent diseases. Vitamin E helps stabilize membranes of immune cells that help to fight off intruders. It can also help prevent the onset of immune attacks by stabilising the membranes of lysosomes. It also reduces the level of autoantibodies in lupus patients.
• Vitamin A – Also referred to as retinol, is important for healthy skin, bones and soft tissue, and supports the healthy immune function too. People who have lupus run the risk of osteoporosis, as they have an abnormal immune system, thus making it important to have healthy levels of Vitamin A. By consuming beta-carotene – vitamin A precursor which is ideal to take in, but to take care not get vitamin A toxicity

Plants and Herbs

• Curcumin – It comes from the spice turmeric, and has antioxidant, anti-cancer, anti-inflammatory properties. It decreases the ability of autoantibodies to be produced in people with Lupus. It also helps to suppress inflammation before it begins, as well as helping with autoimmune diseases such as multiple sclerosis, rheumatoid arthritis
• Gingko – An herb used from dried leaves. Extracts contain a high concentration of flavonoids and terpanoids, which are antioxidants that help to improve blood flow.
• Pine bark extract – An extract from the bark of a pine tree, which helps to improve Lupus inflammation. The pine bark extract reduces oxidative stress and improves symptoms and signs of Lupus. 

DHEA

• It’s a hormone naturally produced in the adrenal gland and changed into sex hormones.
• It can also be derived from a Mexican Yam
• Low-levels of DHEA are prevalent in patients with Lupus and other inflammatory diseases
• DHEA has an influence over the immune system activity by regulating the production of multiple cytokines.
• DHEA improves bone mineral density in postmenopausal woman with lupus, as well as improving mental and emotional well-being.

Alfalfa

• May cause lupus like symptoms, such as autoimmune related anaemia. Alfalfa is rich in amino acid L-canavanine, which can trigger symptoms, thus people with lupus should avoid eating these seeds

Echinacea

• Used to promote a strong immune system and to prevent infections like flu and colds. People who have lupus should stay away from this as it is an immune system stimulant, and may cause to aggravate the severity of Lupus. Echinacea can make human immune cells secrete pro-inflammatory cytokines that play a role in Lupus disease.

Thunder God Vine

• It’s a Chinese herb that is associated with autoimmune diseases. Severe toxicity and even death is associated with using this herb, and the risks outweigh the benefit of using this plant. As the dose required for clinical use is close to the dose required to cause toxicity. This can also cause low bone density in woman when used.