Lupus: What is it?
What is lupus?
There are different types of lupus. The most common type is systemic lupus erythematosus (SLE). Other types of lupus exist, such as discoid lupus erythematosus, drug-induced lupus and neonatal lupus.
Lupus is a chronic disease which can potentially affect several organs, mainly through skin, joint and kidney damage.
Lupus is also an autoimmune disease (AID), which means it is a disease in which the immune system goes beyond its role of defence against external agents to attack the body's own cells. Autoantibodies found in the blood of patients affected by lupus have the mark of this autoimmunity.
Finally, lupus develops from periods of flare-ups. The disease is therefore active with varied symptoms. They are interspersed by periods of remission which can last several months even years. The disease is therefore « quiescent » (meaning without visible symptoms).
Lupus is a rare disease
Lupus is a rare disease. In fact, a disease is known to be rare (within the European Union) when it affects less than 1 in every 2000 people.
The United Kingdom has an estimated prevalence (number of cases of the disease) of 28 per 100,000 in the adult population.
It is thought that currently up to 50,000 people in the UK have lupus.
Lupus mainly affects young women, who are less than 30 years old, but there are paediatric forms and early-onset damage to the elderly; 9 women to 1 man are affected.
Disease distribution is global. Even if it more often affects certain ethnic groups, such as African Americans or Asians.
There are also more cases of lupus in the Caribbean (prevalence of 94 per 100 000 habitants in Guadeloupe and 27 per 100 000 in Martinique).
Symptoms and complications of lupus
Clinical manifestations are numerous (the disease affects several organs) and vary from one individual to another.
They may be skin related:
- photosensitive facial erythema (meaning sensitive to sun exposure) “butterfly wings” (the word « lupus » which means « wolf » in Latin refers to this mask-shaped rash on the face, characterised by the disease)
- vascular lesions (inflammation of the blood vessels)
- ulcers in the mouth (aphthous ulcers) and nose
- purpura (purple spots that do not blanch on applying pressure)
- alopecia or loss of hair in patches, in some cases.
However, many other organs can be affected and there is damage:
- joints (very common): arthralgia (pain) and arthritis (inflammation of the joints, that become red, warm and swollen) transitory or persistent and migratory (moving from one joint to another), swelling (oedemas) and joint stiffness;
- kidneys: nephrotic syndrome (loss in the ability of the kidneys to filter the blood and abnormal passing of proteins in the urine or proteinuria), kidney failure;
- blood: anaemia (decrease in red blood cells or haemoglobin levels in the blood), leukophenia (reduction in the number of white blood cells), thrombocytopenia (reduction in the number of platelets, sometimes associated with bleeding);
- cardio-pulmonary: inflammation of the different layers of the heart (pericarditis, myocarditis, endocarditis) associated with thoracic pain; inflammation of the pleura (coating which surrounds the lungs) or pleurisy, or more rarely pneumonia, fibrosing alveolitis (inflammation and fibrosis of the pulmonary alveoli) associated with a cough and difficulty breathing;
- vascular: « Raynaud’s disease » (corresponding to a change in the colour of the fingers and toes, caused by the cold or stress, with an initial pallor that turns blue, possibly with pain), frequent high blood pressure and more significant risk of developing atherosclerosis (accumulation of fats in the walls of the large arteries), thrombosis or phlebitis (corresponding to the formation of blood clots in the veins):
- neurological: headaches (cephaleas), and more rarely psychiatric disorders, epilepsy, hemiplegia (paralysis of one side of the body) and other neuropathies, possibly depression.
- digestive, in rare cases: inflammation of the liver (hepatitis), of the pancreas (pancreatitis), of the peritoneum (membrane that surrounds the organs of the abdomen, peritonitis).
General signs such as a sudden fever, significant fatigue or unexplained weight loss may also appear.
Causes and risk factors of lupus
The root causes of immune dysregulation in lupus are not clearly defined, yet several risk factors of a different kind appear to be involved:
- Genetic: there is a certain degree of genetic predisposition, but if a person is affected, another person from the same family is also suffereing from it in less than 10% of cases.
- environmental: sun exposure (UV rays), exposure to some toxic substances (pesticides, mercury, silica), tobacco smoking, an Epstein-Barr virus infection (giving rise to infectious mononucleosis/glandular fever) or even stress may trigger lupus or encourage a flare-up. Hormones are also involved: given that women of childbearing age are most affected by lupus, a hypothesis has been issued of a link between female hormones and the disease. Estrogen intake and pregnancy may be the factors which trigger or worsen lupus.
Read our interview of “The risk factors, treatments and lupus-like flare-up symptoms”
In addition, there are drug-induced forms: procainamide, quinidine, hydralazine, isoniazid or even some betablockers or diuretics may be issued.
Maternal-fetal transmission (not genetic!) of anti-SSA and/or anti-SSB maternal antibodies, rarely anti-U1-RNP, can lead to neonatal lupus. There is a rare and transitory (around 1 case in every 10 000 births) which requires close monitoring during pregnancy.
The diagnosis of lupus is complex given the diverse symptoms and rarity of the disease. It s both clinical and biological.
Among the clinical signs characterised by systemic lupus erythematosus, we look for:
the presence of a rash in the form of butterfly wings on the face
- photosensitivity with an abnormal skin reaction following exposure to UV rays
- the presence of small lesions or ulcers in the mouth or nose
- Lasting polyarthritis with pain, inflammation and swelling of different joints (hand, fingers, neck...)
- kidney damage
- damage to the central nervous system (headaches, seizures...)
- pericarditis (inflammation of the pericardium) or pleurisy (inflammation of the pleura).
These signs are particularly suggestive if they appear in a young woman of reproductive age.
After observing these clinical signs, a biological examination is necessary.
A blood test is then carried out and a measure of the total antinuclear antibodies (ANA). Their title (blood count) is heightened in lupus but they are not specific to this disease. In fact, they are found in several other autoimmune diseases (AID) such as rheumatoid arthritis, Gougerot-Sjogren syndrome or autoimmune hepatitis as well and even some patients not suffering from any disease.
More specifically, anti-native DNA antibodies are specific markers of systemic lupus erythematosus. Their status is only partly correlated with the progression of the disease: the appearance or increase of status reports the clinical and biological monitoring that always involves a proteinuria review (rate of proteins in urine) to detect a kidney flare-up early. A negativation (no detection during the blood test) or a lowered status may be observed during a clinical remission (this is therefore markers for the diagnosis, prognosis and monitoring of the disease) yet certain patients in full remission remain under heightened status.
Furthermore, anti-histone antibodies are very common in lupus but are of little interest as a result of lesser diagnostic specificity (present in other auto-immune diseases, infections...). However, they show relevance towards a diagnosis of drug-induced lupus (in this case, anti-native DNA are usually absent).
At the same time, among antigen soluble nuclear antibodies (ENA), anti-SM antibodies have a diagnostic role in lupus due to a specificity of almost 100%.
Anti-SSa and anti-SSb antibodies meanwhile have a possible (though rare) pathogenic role in foetal cardiomyocytes. Therefore, if the mother carries these antibodies, there is a possibility of passive transfer to the baby through the placenta and a trigger for neonatal lupus. These antibodies are looked for within the context of a pregnancy because there is a risk of atrioventricular block (AV block) in the foetus, a very rare but potentially severe complication.
Complimentary system exploration, carried out using CH50, C3 and C4 dosing, is the exam for exploring lupus by primary intention. In fact, hypocomplementemia is observed through consumption at the time of flare-ups.
During exploration of the inflammatory system, an increase in the rate of sedimentation Rs (rate at which red blood cells fall in a tube of blood placed vertically) is also noticed at the time of flare-ups. This is called Rs/CRP dissociation because CRP (C-reactive protein), a marker which is usually increased in cases of inflammation, remains normal.
Therefore, the complement and Rs are follow-up markers of the disease.
In lupus patients, regular exploration of kidney function is required. Lupus nephropathy (kidney damage) is often asymptomatic but can be revealed in 30% of cases by nephrotic syndrome (loss in the ability of kidneys to filter the blood and presence of proteins in the urine). It is initial or is seen during the first year of the disease in 50% of cases. Its prevalence increases with signs of immunological activity and ¼ of cases progress to terminal kidney failure.
Urine strips are then used to evaluate proteinuria (protein levels in the urine), hematuria (presence of blood in the urine) and leukocyturia (presence of white blood cells in the urine). Plasma creatinine is measured and creatinine clearance (GFR or glomerular filtration rate) is calculated. A kidney biopsy puncture may potentially be performed in cases of significant proteinuria.
Antiphospholipid syndrome secondary to lupus (APS) should also be evaluated. It is characterised by the recurrent formation of blood clots in the vessels (arterial and/or venous thrombosis), repeated miscarriages in women and by the presence of particular antibodies in the blood, antiphospholipid antibodies (anti-cardiolipin antibodies and anti-β2GPI antibodies). The latter must be found positive on 2 occasions at 12 week intervals and are diagnostic markers of lupus.
Furthermore, other autoimmune diseases (AID) may be associated with lupus and are looked for as a result. It is particularly the case with Gougerot-Sjögren syndrome (which is associated with lupus in 30% of cases). This involves damage to the exocrine glands which most often manifests as a dry mouth and/or dry eyes.
Finally, a biopsy of skin lesions can sometimes reveal the presence of autoantibodies and thus help to make a diagnosis.
Among other tests, a joint x-ray can be performed to check for bone deformation and destruction (which may be the case in other autoimmune diseases). A chest x-ray (to observe the heart and lungs), an electrocardiogram (ECG) and a cardiac ultrasound (to evaluate the activity of the heart), an MRI or a brain scan (to observe the brain and its activity) are also to be considered.
The treatment of lupus does not cure the disease but avoids complications and reduces symptoms. Given the varying degrees of harm from one individual to another, treatment must be tailored to each individual.
The objectives of the treatment are to reduce inflammation, to obtain clinical remission of lupus and to prolong this period of calm symptoms.
Treatment of acute flare-ups
The treatment of outbreaks (active forms of the disease) is based on more or less high doses of corticosteroid treatment, depending on the severity of the damage or sometimes intravenously (methylprednisolone as a bolus injection).
Doses should then be gradually reduced to a minimum dose, or even stopping in case of remission. Prescription, as well as associated dietary recommendations (diet low in salt and especially sugar) should be strictly followed. In fact, corticosteroids may result in numerous side effects: gaining weight, high blood pressure, hormonal disturbances, cataracts, increased risk of infection, osteoporosis...
This is why this type of treatment is subject to particular monitoring.
A basic treatment is put in place to prevent the appearance of new lupus outbreaks, with the least side effects possible.
Therefore, synthetic antimalarials are used as a first line of treatment:
- Hydroxychloroquine (HCQ, Plaquenil®), as supplementary treatment or in prevention of systemic lupus relapses: on average 400mg/day if kidney function is normal in the prevention of relapses. It requires an initial ophthalmic exam with a look for retinopathy as well as heart monitoring in subjects at risk as it may be the cause of heart rhythm disorders.
- Chloroquine (CQ, Nivaquine®): in preventative treatment of systemic lupus flare-ups at 5mg/kg/day.
Corticosteroids are not indicated as an initial basic treatment. However, if corticosteroid treatment is introduced during a flare-up, low doses, such as 5 to 10mg/day of prednisone (Cortancyl®), are sometimes required long term (off-label or without marketing authorisation) and justifies considering the introduction of another immunomodulatory treatment than HCQ aimed to save cortisone.
Treatment of dermatological signs
Sun protection is required: high factor protective sun creams (> 50) and UV protective clothing should be used.
- In case of acute lupus (erythema "by wolf", more or less scaly, which is with the epidermal lamellae that detaches from the skin, localised at the level of the cheeks and nose), corticosteroids are sometimes prescribed in case of accompanying extracutaneous damage. Treatment with local cortisone is always favoured.
- For subacute lupus (annular or psoriasiform lesions which most often disappear without scarring) and discoid lupus (very limited patches that peel and leave permanent scars, especially on the face, ears and hairline) local treatments involving corticosteroids, such as hydrocortisone (Onctose®) or betamethasone (Diprosone®), and in case of resistance (Protopic® 0.1% excluding off-label), are used.
If local treatments fail, first line systemic treatment involves hydroxychloroquine and chloroquine where the effectiveness is evaluated after 3 months of treatment. There is no indication for general corticosteroids.
Second line systemic treatment is low-dose methotrexate (off-label).
Third line systemic treatment is thalidomide. The rules on prescription are strict: licensed doctor, exclusive hospital distribution and mandatory contraception.
Other unique treatments exist for resistant cutaneous lupus:
· Dapsone (licensed product for bullous lupus, rare complication of SLE): 100 to 150 mg/day. There is a risk of methemoglobinemia (inability for the red blood cells to store oxygen) and hemolysis (removal of red blood cells) dose dependent (a 5mg/day supplement of folic acid is therefore prescribed).
Treatment for osteoarticular manifestations
- NSAIDs (non steroidal anti-inflammatory drugs) and analgesics are used for low-intensity arthralgia and arthritis. However, some NSAIDS (especially ibuprofen and more rarely sulindac and diclofenac) may cause aseptic meningitis and are therefore contraindicated for patients with lupus.
- Antimalarials, usually hydroxychloroquine (Plaquenil®) to 400mg/day, are effective from 2 to 12 weeks on signs in the joints.
- Low-dose corticosteroids (lower than 0.25mg/kg) may be considered in case of resistance to previous treatments.
- Low-dose methotrexate (off-label) may be prescribed in case of chronic lupus polyarthritis resistant to antimalarials and corticosteroids. The usual dose is 15 to 20mg/week. Finally, intraarticular corticosteroid infiltrations may be performed.
Treatment for kidney damage
Depending on the type of lupus glomerulonephritis (inflammatory damage of the glomerulus, nephron component which is the functional unit of the kidney), treatments are different:
- The most serious damages are focal proliferative lupus glomerulonephritis (class III) and diffuse proliferative (IV): induction treatment is a high-dose intravenous corticosteroid (IV) then orally : prednisone (Cortancyl®) at 1mg/kg/day for 3 to 4 weeks, then gradual decrease, often maintained for several years (depending on the initial severity).
- Combination of an immunosuppressant with corticosteroid treatment is recommended (improves kidney prognosis). Among them, there is cyclophosphamide (Endoxan®) in IV, mycophenolate mofetil (CellCept®) used off label. They lower immune defences: therefore be alert to the increased risk of infections when taking them.
Finally, belimumab (Benlysta® is a human monoclonal antibody used in combination with standard treatment. It is administered in patients with non severe systemic lupus (no kidney or neurological damage) with the presence of autoantibodies and with both clinical and biological heightened activity of the disease (defined for example by the presence of anti-DNA antibodies and a small supplement) despite the use of other classic treatments (plaquenil + immunosuppressants). It blocks the delivery of the soluble protein BLyS (survival factor of B lymphocytes or Lyb) to its receptors on Lyb and also prevents the survival of Lyb, particularly the autoreactive Lyb, and decreases the differentiation of Lyb in plasmocytes (capable of producing antibodies).
The rate of BLyS is higher in patients suffering from systemic lupus and other autoimmune diseases. There is a link between the plasma levels of BLyS and systemic lupus activity. However the role BLyS in the physiopathology of systemic lupus is not entirely understood.
Living with lupus
When someone is affected with lupus, a regular follow-up about the illness is required in order to identify the activity and severity of the disease, prevent the appearance of flare-ups, evaluate the tolerance and effectiveness of treatments and detect the possibility of comorbidities (one or several associated diseases) and visceral damage.
Systemic lupus needs specialised management, in combination with the attending physician. Therefore, monitoring of this disease is carried out by a multidisciplinary team consisting of (according to the needs of each patient) a medical internist, a rhumatologist, a nephrologist, a dermatologist and a hematologist. A gynaecologist, a paediatrician, a kinesiotherapist, a dietician and a psychologist can also be involved.
The amount of consultations and tests must be adapted to the clinical state of the patient, the severity and progressive profile of the disease, to the type of visceral damage, to the treatments used (tolerance, side effects).
It is also possible to offer a clinical examination of the adult:
- every month at a minimum, in case of pregnancy or progressive lupus, particularly in case of serious visceral damage;
- every 3 months between stages;
- every 6 months during a period of quiescence (rest or recovery);
- even once a year after several years of quiescence or for mild lupus.
In children, a consultation every 3 months is recommended due to the high risk of lupus nephropathy.
The medical care and clinical follow-up exam are identified as those carried out during the inital diagnosis of the disease. However, it is necessary to be particularly vigilant to the patient’s understanding of their illness and to proper observation of treatment, to lifestyle (fight against tobacco smoking and prevention of infection), to the methods of contraception and to a possible desire for pregnancy.
In children, a regular follow-up of weight, growth and phychosocial development is very important.
Stopping tobacco smoking forms part of an integrative treatment of lupus. In reality, tobacco smoking promotes the development and complications of the disease, it increases cardiovascular issues and fragility of the lungs and lowers treatment efficiency, including that of the main substantive treatment.
It is important to avoid exposure to the sun’s rays worsening skin rashes from lupus. In order to protect yourself well in UV rays, it is recommended to wear protective clothing (long sleeves), a hat with a wide brim and sunglasses with an anti UVA/UVB filter. Sun cream with a high sun protection factor (> 50 and anti UVA/UVB) must be applied 30 minutes before exposure, then every 2 hours and after each swim. Direct or indirect exposure must be avoided as much as possible (rays, UVA passing through a window or a windshield of a car), places where the reflection is strong (seaside, high altitude) and going out at the hottest time of day (between 12pm and 4pm).
Diet must be balanced and varied to avoid becoming overweight (and to further avoid joint pain and improve overall wellbeing).
Treatment with corticosteroids requires a low salt diet and especially low in sugar and sometimes, taking a calcium and vitamin D supplement can prevent the risk of osteoporosis.
During periods of recovery (without symptoms), regular physical activity (eg. walking, swimming, cycling) is recommended.
It is important to ensure good hygiene (cleaning teeth and hands regularly...) to avoid the risk of infection, enhanced by taking high-dose immunosuppressants or corticosteroids.
Live attenuated vaccines (Chicken pox, rubella, measles, mumps, oral polio, yellow fever and BCG) are contraindicated for lupus in cases where cortisone or immunosuppressants are being taken. In contrast, inactivated vaccines (tetanus, injectable polio) are authorised. Likewise, certain vaccines (anti-influenza and anti-pneumococcal) are strongly advised as they protect against severe infection favoured by immunosuppression.
Finally, stress and fatigue should be avoided because they can aggravate symptoms or promote the appearance of an outbreak.
Contraception and pregnancy
Certain treatments for lupus (methotrexate, thalidomide, cyclophosphamide, mycophenolic acid...) can be toxic and lead to deformities of the foetus (teratogenic effect). Contrary to plaquenil which may be taken during pregnancy and breastfeeding.
Contraception is therefore essential in women with lupus of childbearing age.
The main forms of contraception are:
- a mechanical barrier type of contraception (condom, diaphragm);
- intra-uterine or sterile devices;
- oral progestins (progestin minipills):
- progestin implants.
If progestins are poorly tolerated, contraception, through combined contraceptions, is not strictly contraindicated except in case of antiphospholipid syndrome or a history of venous (phlebitis) or arterial thrombosis.
Emergency contraception (morning after pill), containing progestins, is available.
The plan to have a child when you have lupus is absolutely possible. However, any pregnancy should ideally be scheduled and should only begin after 6 to 8 months of recovery from lupus.
In fact, pregnancy may promote the occurrence of a new lupus outbreak, particularly with kidney damage. It also increases certain obstetric risks for the child (premature childbirth, intrauterine growth retardation) and for pregnant women (miscarriage, maternal high blood pressure, pre-eclampsia...)
Therefore, it is important to inform your specialist doctor about the desire to have children, to schedule a pre-conception consultation.
The course of pregnancy will be monitored by a multidisciplinary team.
Therefore, lupus is a chronic and complex autoimmune disease. But today there are several treatments to reduce symptoms and increase the probability of recovery. It particularly affects young women and the possibility of pregnancy is absolutely possible provided the necessary precautions are taken. Follow-up should be done regularly by the treating physician accompanied by a multidisciplinary team.
SLE evolves over time
Published 12 Jan 2020 • Updated 29 Sep 2021