What is systemic lupus erythematosus and what are its causes?

Systemic lupus erythematosus (SLE) is one of the systemic connective tissue diseases (collagen diseases) caused by directing the immune system against the body (this process is called autoimmunity).

The word “systemic” comes from the fact that many tissues and organs are damaged. In systemic lupus erythematosus, the skin, joints and kidneys are most commonly affected, but the lesions can affect any organ or tissue. The disease has many different symptoms and a very varied course – from fairly mild forms, which constitute the majority of cases, to severe, even life-threatening.

Causes of systemic lupus erythematosus

The exact cause of systemic lupus erythematosus is unknown. Lupus is known to develop in people who are genetically susceptible to falling ill after an additional stimulus, such as:

• Exposure to sunlight – ultraviolet radiation causes damage to epidermal cells, fragments of which are removed by macrophages. In healthy people, this process runs smoothly, while in lupus, the removal of dead cells is disturbed, and the remaining fragments become a “target” for autoantibodies; In this way, the cascade of inflammation is triggered and characteristic skin lesions are formed, as well as the involvement of internal organs.
• infection-a number of microorganisms are suspected, including human retroviruses, Epstein-Barr virus, some bacteria
• Women suffer from disease much more often, which is related to the influence of sex hormones such asestrogensorprolactin; a greater risk of lupus development or an exacerbation of the disease is also suspected in women taking hormone replacement therapy and oral contraceptives.
• Medication: Some medications can induce so-calleddrug-induced lupus. Their list is long, including procainamide, chlorpromazine, methyldopa, hydralazine, isoniazid, TNF-alpha antagonists, and interferon. The disease is usually mild, does not involve internal organs, and resolves after drug discontinuation, but sometimes steroid treatment is necessary.
• Some chemicals, such as organic solvents, silicon compounds, and aromatic amines, as well as a high-fat diet and smoking, can stimulate the development of autoimmune diseases; unsaturated fatty acids and vitamin D have potential protective effects.

Autoantibodies formed in lupus (i.e. antibodies directed against one’s own cells and tissues) trigger the inflammatory process, leading to the destruction of the affected organ. They work in different ways, e.g. they are deposited in the kidneys, skin and blood vessels in the form of so-calledimmune complexesattack directly blood cells, change the activity of nerve cells or factors involved in blood clotting.

How common is systemic lupus erythematosus?

Systemic lupus erythematosus affects approximately 30-50 out of 100,000 people, most of whom are women of childbearing age. Women are sick about eight times more often than men. Lupus usually begins in the range of 16 to 55 years of age, but there are cases of lupus in younger people and also in the elderly.

How does systemic lupus erythematosus manifest itself?

The symptoms of lupus can be divided into “general” symptoms and those resulting from the involvement of individual organs. It should be noted that the disease is very different, depending on which organs are affected and to what extent. Most often, the periods of exacerbation of the disease alternate with the withdrawal of symptoms. Appropriate treatment can reduce the number of exacerbations and prevent many complications.

General symptoms

Fatigue, a feeling of distress, lack of appetite, weight loss, low-grade fever, and fever are non-specific, i.e., they may also occur in a number of other diseases. They are often the first symptom of the disease, and also indicate its exacerbation.

Symptoms of involvement of individual systems and organs

Joints– lupus affects joints in almost all patients, most often wrists, finger joints, knee joints and joints of the feet.Joint painoccurs , occasionallyswollenor exuding, and joint deformities rarely occur. Joint pain usually travels from one place to another. If it persists in one joint for a long time, it is an alarming symptom to exclude other overlapping causes, including aseptic osteonecrosis or joint infection.

Muscle– migrating, severity-changing muscle pain is a very common symptom of lupus; much less frequently, it may be the result of myositis or an undesirable effect of taking certain medications (glucocorticosteroids, anti-malariadrugs , statins); it can also be a symptom offibromyalgia, especially in a long-lasting disease. In addition to pain, there is also often muscle atrophy, which causes muscle weakness and weaker physical function.

Photo 1.Systemic lupus erythematosus – typical butterfly-shaped changes on the face

Fig. 2.Subacute cutaneous lupus – changes in the shape of rings with a brightening in the center

Fig. 3.Discoid erythema

Photo. 4.Reticular blueness
Fig. 1., 2., 4 .: Szczeklik A. (ed.): Internal diseases. Ed. 3. Krakow 2011; Photo 3. Dr. med. Jolanta Maciejewska

Skin and mucous membranes– characteristic butterfly-shaped erythema on the face → Fig. 1. appears after sun exposure in more than half of people during periods of high disease activity. It has the form of a flat or slightly raised reddening of the skin on the cheeks and the bridge of the nose, and can also appear on the forehead, around the eyes, on the neck and décolleté. As the disease activity decreases, this erythema disappears without a trace. Hypersensitivity to sunlight occurs in most cases; the sun can not only cause disseminated skin lesions, but also exacerbate the disease involving internal organs. In active disease, erosions of the oral cavity and nose mucosa, most often painless, also appear; be sure to show them to your doctor as this may or may not be one of the symptoms of lupus.

In the so-called in subacutecutaneous lupus erythematosus(SCLE), there are changes in the shape of the rings with a brightening in the middle → Fig. 2. or scaly papules; are mainly located on the torso, arms and thighs; they also disappear without leaving a trace. Approximately 1/4 of patients developdiscoid lupus erythematosus(DLE), which causes atrophy, scarring and discoloration of the skin → Fig. 3.

Other possible skin changes accompanying lupus areurticaria(usually lasting longer and withoutitching, thickening of the subcutaneous tissue,Raynaud’sphenomenon, erythema around the nails, erythema of the hand or reticulate blueness . hair.

Kidneys– nephritis occurs in 1/3 of patients and can lead to kidney failure. It usually manifests itself in the first two years of the disease and mainly affects young people, in addition, it is one of the most important causes of increased mortality in patients with systemic lupus erythematosus. Since there are no signs of kidney involvement at the onset of the disease, kidney function should be monitored by laboratory tests, such as urinalysis and bloodcreatininelevels. If kidney involvement is suspected, other tests, including a kidney biopsy, are required. As a late symptom of kidney disease, swelling and weight gain are associated with water retention in the body.

The heart– Libman-Sacks’ endocarditis, characteristic of lupus, is characterized by the presence of lumps (so-called vegetation) on the heart valves – in itself it is usually asymptomatic, while on the changed valves it is easier for various pathogens to settle. Therefore, in people with this problem, it is recommended to use an antibiotic before planned procedures to prevent infective endocarditis.

Lupus causes a significantly increased risk of coronary heart disease andheart attack, also in young people. Most often it is caused by the accelerated development ofatherosclerosis, less often (in the period of high activity of the disease) it may be the result of coronary vasculitis.

Blood vessels

• atherosclerosis– its accelerated development in lupus is caused by chronic inflammation, the use of steroids, as well as kidney disease often associated with lipid disorders andarterial hypertension. Complications of atherosclerosis (including heart attack,stroke, intestinal necrosis caused by obstruction of the arteries that supply them) are one of the leading causes of death in lupus patients. Therefore, it is very important to combat all risk factors for the development of these diseases – both “classic” (obesity, smoking, improper diet, diabetes, lipid disorders, hypertension) and those related to lupus itself – by inhibiting the activity of inflammation and using as much as possible the lowest doses of steroids;
  (look:What is atherosclerosis?,Hypertension,Myocardial infarction, Obesity ,Diabetes)
• vasculitis– this is when the walls of arteries or veins are inflamed; it is rare but may be associated with a highly active disease. Symptoms depend on which vessel is occupied and result from disturbed blood supply to the place it supplies. Vasculitis can cause, among other things skin ulcers, necrosis of the fingers, as well as a heart attack or bleeding into the lungs and brain.

Lungs– lupuspneumoniais rare, but can be severe, with high temperature,shortnessof breath ,coughand sometimeshaemoptysis; these symptoms require the exclusion of pneumonia caused by infection. Lupus can also cause pulmonary fibrosis, which should be considered if you experience dry cough and shortness of breath after exercise. Other rare complications of lupus arepulmonary hypertension(mainly whenantiphospholipid syndromeis present ) and “contracted” lung syndrome (a long-lasting disease causing significantweakness of therespiratory muscles).

Nervous system– lupus may develop a variety of neurological and psychological symptoms; then we are talking about the so-called a neuropsychiatric form of lupus. The most common are mild cognitive impairment (such as attention, memory, reasoning, planning), mood disorders (such as depression, apathy, or irritation), and anxiety disorders. However, there are also other manifestations, such as paresis, sensory disturbances, convulsions or psychosis.

Blood count disturbances, such as anemia, decreased number of white blood cells and platelets.

Digestive system– lupus can suffer from a variety of abdominal ailments, the most common beingheartburnand non-specific abdominal pain. The medications taken (mainly non-steroidal anti-inflammatory drugs) increase the risk of ulcer disease and gastrointestinal bleeding. Systemic lupus erythematosus can sometimes cause serious complications, such as intestinal infarction, pancreatitis orperitonitis. Alarm symptoms include severe stomach pain, tarry stools, vomiting,diarrheaor yellowing of the skin.
See:Heartburn,Peptic ulcer disease,Stool – altered appearance,Diarrhea

Serum membranes– inflammation of the lining of the lungs (pleura) and heart (pericardium) is quite common, usually mild, asymptomatic, sometimes there ispain in the chest, increasing when inhaling; Peritonitis may also develop, causing stomach pain,nausea and vomiting.

Eyes– the most common symptom is a feeling of dry eyes or a feeling of a foreign body under the eyelids, associated with the so-called dryness syndrome. Visual disturbances may occur after some medications, such as hydroxychloroquine or long-term use of glucocorticosteroids, therefore regular eye monitoring is recommended in people taking these drugs.

Osteoporosis– both systemic lupus and the glucocorticosteroids used in it significantly accelerate the development ofosteoporosis; it is important to start treatment early in order to reduce the risk of bonefractures.

Antiphospholipid syndrome– associated with the presence of antiphospholipid antibodies, which appear quite often in lupus; these antibodies increase the tendency to form clots that block blood flow in the vessels. The second feature of this syndrome are gynecological complications (eg recurrent miscarriages); to prevent them, drugs that reduce blood clotting are used.

Procreation– Today, women with lupus often become pregnant and have healthy children. However, in some situations, pregnancy can be harmful to the mother or the fetus – these include maternal kidney or heart disease, high lupus activity, the presence of an antiphospholipid syndrome or some type of antibody. Also, some medications used for lupus can harm the unborn child. Therefore, pregnancy should be properly planned so that fertilization occurs during the period of silencing the disease (optimally lasting at least six months).

Lupus of newborns

It is caused by the presence of anti-Ro (SSA) or anti-La (SSB) antibodies in the mother, which cross the placenta and may cause symptoms of lupus in the child (approx. 3% of pregnancies). Congenital heart block is a rare but serious complication (therefore it is necessary to frequently check the fetal heart rate from the 16th week of pregnancy). Other possible symptoms are skin lesions of the SCLE type,jaundice, and a decrease in the number of platelets, as a rule, they disappear by the age of 6 months, when the maternal antibodies are washed out from the baby’s blood.

What to do in the event of symptoms?

When symptoms of the disease appear, see a doctor. Patients with lupus should be under the specialist care of a rheumatologist or immunologist. Sometimes it is necessary to cooperate with other specialists, e.g. a nephrologist, dermatologist or neurologist. Rapid diagnosis and treatment of the disease improves the quality of life and reduces the risk of serious complications.

If you have lupus erythematosus, see your doctor urgently if:

• symptoms worsen or new symptoms appear – this may indicate an exacerbation of the disease, requiring more intensive treatment
• you have any symptoms of infection, such as fever, cough,sore throat, burning sensation when urinating, weakness, or a discomfort. Lupus and the drugs used in this case deteriorate the body’s ability to fight germs, so infections require prompt and effective treatment
• cough, shortness of breath, chest pain, reduced exercise tolerance – require urgent diagnosis for lung and heart diseases
• any neurological symptoms (e.g. abnormal sensation, weakness or weakness in limbs, severeheadache, visual disturbances) – these may be symptoms of a stroke or other neurological disease
• abdominal pain, dark-colored stool (or with an admixture of blood), vomiting, yellowing of the skin – require urgent diagnosis of abdominal diseases.

How does the doctor make a diagnosis?

Since systemic lupus erythematosus usually has an insidious onset, its diagnosis can be difficult. The initial diagnosis is often “undifferentiated connective tissue disease”, and only later, as symptoms develop, is lupus or another disease.

The following tests are used to diagnose the disease and assess its activity:

• antinuclearantibody_– ANA) are the basic test for systemic connective tissue diseases. At the beginning, the ANA 1 test is performed, i.e. a screening test to find out if antibodies are present and what type of light they have (e.g., homogeneous, granular, peripheral). If the ANA 1 result is positive, further tests (ANA 2 and ANA3) are performed to determine the exact type and titer of the antibodies. It should be noted that a “weak positive” ANA result can also occur in healthy people and is not a disease in itself. In systemic lupus erythematosus, antinuclear antibodies are present in over 90% of people, and some of them (anti-dsDNA and anti-Sm) are highly specific for this disease. A negative ANA result, especially if repeated after some time, is often sufficient to rule out this disease.
• antiphospholipid antibodies– these include anticardiolipin antibodies, anti-ß2 glycoprotein-1 and lupus anticoagulant; they occur in 30-40% of lupus patients; are associated with a higher risk of thromboembolic and obstetric complications (see question 3 – antiphospholipid syndrome). Their determination is especially important in women planning pregnancy, before the use of estrogens (e.g. in hormone replacement therapy or contraceptives), and also before surgery.
• Syphilis– Lupus is often positive despite the absence of syphilis
• inflammatory markers,e.g. ESR, CRP, proteinogram,complementlevels (C3c, C4)
• blood count
• coagulation indicators
• assessment of kidney function – creatinine,GFRindex , urinalysis – in the event of their abnormalities, further tests are performed, e.g. protein excretion in urine and kidney biopsy
• liver function assessment,e.g. AST, ALT
• lupus band test– it is an examination of a skin section under a microscope, especially helpful when the picture of the disease is unclear; characteristic glow indicates the presence of autoantibodies on the border of the epidermis and dermis (patches)
• capillaroscopy– performed in the presence of Raynaud’s phenomenon. It consists in examining the nail folds under a microscope – changes in the blood vessels present there may indicate the presence of a systemic connective tissue disease.

The doctor may also order other tests to rule out lupus-like diseases, including rheumatological and virological examinations, imaging examinations of the affected joints (X-ray, MRI, ultrasound).

What are the treatments?

The goal of treating systemic lupus erythematosus is to achieve lasting remission of the disease as soon as possible and to prevent organ damage. It must be tailored to each patient – a different procedure is required for a person whose main ailment is muscle and joint pain, and a different procedure for a patient with kidney or nervous system involvement.

General rules recommended for all patients

• protection from the sun – avoiding being in the sun when it is most active (especially in the summer between 11am and 3pm), wearing appropriate clothes, hats and sunglasses, using creams and lotions with a UV filter (SPF> 30), planning holidays in places without much sun exposure
• avoiding stress, relaxation
• engaging in regular, moderate physical activity
• prevention of atherosclerosis, incl. by eating healthy, maintaining a proper body weight, and stopping smoking
• prevention of osteoporosis
• preventing infections by observing the rules of hygiene and protective vaccinations (e.g. againstinfluenza, pneumococci). Vaccinations should be performed in the period of low disease activity. Vaccines containing live microorganisms are contraindicated, especially in people who are chronically treated with immunosuppressants (reducing the body’s resistance).
• pregnancy planning – women planning to have children should talk to their doctor about it in order to discontinue some medications that may harm the fetus early, and to perform pregnancy safety tests (such as assessment of kidney function and the presence of antiphospholipid antibodies). You should get pregnant during the disease remission period (preferably for at least six months). In addition to trying for a baby, contraception is recommended
• psychological support – diagnosis of lupus erythematosus is often associated with enormous stress and fear for the future. This is a natural reflex that most people with a chronic disease struggle with. That is why it is important to get help and support from loved ones and, if necessary, from specialist clinics. Some methods (e.g. biofeedback and behavioral therapy) are very effective in controlling symptoms of the disease and improving self-esteem. Don’t hesitate to discuss your concerns with your healthcare provider.

Further treatment will be tailored according to the patient’s symptoms:

• skin changes – in addition to avoiding exposure to sunlight, topical ointments or creams with glucocorticosteroid (the type of ointment is adapted to the body site) or tacrolimus are used. In some cases it is necessary to use systemic immunosuppressants (usually orally)
• pain in muscles and joints, general symptoms – taking non-steroidal anti-inflammatory drugs is often enough; with more severe symptoms, steroids, anti-malaria drugs or methotrexate are used
• involvement of internal organs (e.g. kidneys, nervous system, lungs) requires intensive immunosuppressive treatment and active control of other conditions that may accompany exacerbation of the disease (e.g. infections). In lupus nephritis, renal biopsy determines the management of the disease – it is crucial as it is important to distinguish active inflammation from irreversible lesions in which immunosuppressants are ineffective. In cases of threatening the development of renal failure, high doses of immunosuppressive drugs are used to quickly reduce the activity of the disease. A very important component of treatment is good blood pressure control, reduction of protein consumption to 0.8-1.0 g / kg body weight / day and cessation of smoking. Irreversible kidney damage and end-stage kidney failure require dialysis and considerationkidney transplants
• new therapies – intensive research is ongoing to find new effective drugs. The effectiveness of, among others, mycophenolate mofetil in the treatment of lupus nephritis and belimumab (which is also known as a biological agent), which may be beneficial especially in patients with moderately severe lupus. Several other substances are found in clinical trials
• prevention of cardiovascular diseases – keeping the disease activity low is essential; depending on the indications, it is used, inter alia, cholesterol-lowering drugs (statins), antihypertensive drugs, anti-diabetic drugs, aspirin, omega-3 acids (see:Prevention of coronary artery disease,Non-pharmacological management in arterial hypertension, i.e. a healthy lifestyle)
• in patients with antiphospholipid syndrome, drugs are used to reduce blood clotting
• prevention of osteoporosis – adequate supply of calcium and vitamin D, in patients treated with steroids it is necessary to use drugs against osteoporosis, which reduce the risk of bone fractures.

Is it possible to recover completely?

A complete cure of lupus erythematosus is currently not possible. There are cases of spontaneous resolution of symptoms, but they are very rare. The disease has very different course and impacts on quality of life. In mild and moderate stages, you can return to normal activity with some general recommendations in mind. Chronic medication is usually required to control the symptoms of the disease and prevent its worsening.

In cases of severe exacerbation of lupus, hospital treatment is necessary. The efficacy of the treatment of lupus has improved significantly in recent decades, e.g. 2/3 of patients with lupus nephritis achieve remission of the disease.

Currently, about 90% of patients survive 10 years, while in the 1950s, less than half of patients survived 5 years. Unfortunately, despite this, the mortality rate among patients with systemic lupus erythematosus is still three times higher than in healthy people. During the first two years, it is associated mainly with high disease activity, while later it results from complications of chronic inflammatory disease and immunosuppressive treatment – which is why early detection and treatment of infections, atherosclerosis andneoplasmsis so important .

What should I do after treatment is finished?

Systemic lupus erythematosus is a chronic disease that requires constant rheumatological control. At the beginning of the disease and during exacerbations, frequent visits to the doctor are necessary to determine the appropriate doses of drugs and achieve remission of the disease. In a stable period, visits may be less frequent (usually every 6-12 months). Various scales (eg SLEDAI, ECLAM, BILAG, SLICC) are used to assess the activity and progress of the disease. Laboratory tests are performed to assess the activity of inflammation and the functioning of internal organs. Some medications used require additional control (e.g. ophthalmological control with antimalarial drugs).

Regular gynecological checkups are also recommended. Periodically, other tests are performed, such as ultrasound of the abdominal cavity,chest X-ray, mammography. Due to the accelerated development of atherosclerosis, it is necessary to assess the cardiovascular risk, e.g. regular blood pressure monitoring, tests for diabetes and lipid disorders (at least once a year). You should also remember about the early treatment of osteoporosis to reduce the risk of bone fractures.

What to do to avoid getting sick?

We currently do not know how to prevent the development of systemic lupus erythematosus. Avoiding overexposure to the sun and adhering to the general principles of a healthy lifestyle seem to be beneficial. Drugs that can induce drug-induced lupus should be avoided if possible.