What tests are there for lupus erythematosus? American Rheumatology Association Criteria
Systemic lupus erythematosus (SLE) is a systemic disease affecting organs and systems. Its nature has not been sufficiently studied, but there is a hypothesis that the cause of the disease lies in changes in the immune system; the role of viruses in the development is not denied. The body begins to uncontrollably produce antibodies to its cells. With a disease such as lupus, diagnosis is complicated by the fact that many years may pass before the disease is identified.
How does lupus erythematosus manifest?
The disease can be sluggish or develop very acutely. Most often, lupus is characterized by the following symptoms:
- weight loss up to anerexia;
- growth retardation in children;
- changes in the blood;
- fever;
- skin changes in the form of rashes and plaques;
- nephritis;
- muscle pain;
- the lungs and heart are affected;
- symptoms of neuralgia appear.
There are two forms of the disease:
- discoid;
- systemic.
The first type of lupus primarily affects the skin:
- bridge of the nose, upper lip, cheeks, ear canals, scalp;
- upper chest and back;
- fingers.
The discoid form manifests itself mainly as red rashes, which grow and turn into plaques. Gradually, the entire surface of the plaques becomes covered with scales, the removal of which is very painful. It is very important to distinguish the discoid form from the systemic form based on its characteristics, since treatment methods and the prognosis for the patient’s life depend on this.
SLE is characterized by:
- atrophy of the epidermis is slightly expressed;
- there is no blockage of the follicle openings.
Lupus erythematosus cells (LE cells) are found in almost 100% of patients, while in the discoid form only in 5% on average, but this indicator also acts as a threat of the disease becoming systemic.
Signs of the disease
With a disease such as systemic lupus erythematosus, the diagnosis shows damage to the heart valve, skin, central nervous system, kidneys, lungs, circulatory system, joints. It is important that the intensity of the disease process does not decrease for many years.
SLE can have various manifestations:
- penetration and accumulation of fluid and other chemicals in the lungs;
- pulmonary hemorrhage;
- pathological changes in the vessels of the brain with circulatory disorders;
- spinal cord damage;
- formation of blood clots in the vessels of the lungs, intestines, limbs, and brain;
- inflammation of the lining of the heart;
- liver damage;
- decrease in platelets, accompanied by problems with stopping bleeding;
- joint pain;
- inflammation of the peritoneum, pleura and other serous membranes;
- inflammation of blood vessels of an immunopathological nature;
- various skin manifestations.
Indirect signs of the disease:
- destruction of red blood cells;
- decrease in leukocytes;
- protein in urine.
Diagnosis criteria
For diagnosis, the most significant are the emerging diseases of the central nervous system and lungs.
In SLE, half of the patients are affected both centrally and peripherally. nervous system. This is manifested by the following symptoms:
- dysmotility;
- circulatory disorders in cerebral vessels brain;
- loss of sensation;
- decreased muscle tone, loss of strength;
- the occurrence of frequent psychoses, headaches;
- the appearance of aggression, irritability, outbursts of anger.
Thus, involvement of the brain and spinal cord is the cause of a wide range of disorders from neuroses to serious mental disorders.
The following diseases can be manifestations of SLE in the lungs:
- pulmonitis - inflammation of the walls of the alveoli;
- vasculitis - inflammation of the blood vessels of the lungs;
- in 80% of cases, pleurisy is observed;
- thrombus formation in the pulmonary artery.
Modern medicine great importance in the diagnosis it is assigned to antiphospholipid syndrome, which is manifested by venous/arterial thrombosis and complications associated with pregnancy. Spectrum of clinical manifestations antiphospholipid syndrome very wide. Its most severe manifestation and even fatal is the defeat of the central nervous system and heart.
Among heart diseases that can serve as a symptom of systemic lupus erythematosus is pericarditis - inflammation of the outer lining of the heart. It is typical for one third of patients, and in the case of acute lupus erythematosus for half of the patients. In some patients, pericarditis is the first manifestation systemic disease. But the spectrum of cardiac damage is not limited to inflammation. The myocardium is affected coronary arteries, the rhythm is disrupted.
Most significant for diagnosis of SLE represents lupus glomerulonephritis - inflammation of the glomeruli of the kidneys. In all cases the disease is coming kidney pathology. It is observed in more than 90% of patients and is considered the most severe consequence of the disease and the cause fatal outcome. It is extremely rare that immunofluorescence and electron microscopy methods do not detect changes in the composition of urine, even in the absence of urinary syndrome. In almost 100% of cases, the dominant symptom is the presence of protein in quantities significantly higher than normal.
In addition to glomerulonephritis, the following diseases develop:
- renal failure;
- thrombosis of the arteries and veins of the kidneys;
- inflammation of kidney tissue and tubules.
However, it is not possible to diagnose systemic lupus erythematosus solely on the basis of kidney damage. But kidney damage is often the first manifestation of lupus and often occurs at the first stage of the disease or during its exacerbation. Often, a kidney biopsy can diagnose lupus.
From the outside gastrointestinal tract the lesion can be observed in any of its parts. They are typical for half of patients with autoimmune disease.
The musculoskeletal system is involved in 90% of cases. The most serious manifestation is bone necrosis, which leads to early disability in very young patients. The hip joints are most often affected, but any other joints are affected as well. Damage to the periarticular tissues, weakening and further rupture of the tendons are also possible.
Damage to the reproductive system, namely the onset of early menopause, is one of the signs of systemic lupus erythematosus in women.
Laboratory diagnostics
There is no single test that can diagnose SLE. But to establish the nature and extent of damage internal organs laboratory and instrumental studies are carried out:
- X-ray examination;
- blood and urine tests;
- syphilis test;
- Coombs test;
- CT scan;
- lupus stripe test;
- immunofluorescence reaction (RIF) to detect antibodies (with systemic lupus erythematosus, antibodies are found in both affected and healthy skin).
To make an accurate diagnosis, there are special criteria developed by Russian scientists and the criteria of the American rheumatological association. Systemic lupus erythematosus is diagnosed if 4 criteria from the list are present. It is mandatory to have a “butterfly” on the face and a large number of LE cells (more than 10 per 1000 leukocytes).
Systemic lupus erythematosus (SLE) affects several million people worldwide. These are people of all ages, from babies to the elderly. The reasons for the development of the disease are unclear, but many factors contributing to its occurrence have been well studied. There is no cure for lupus yet, but this diagnosis no longer sounds like a death sentence. Let's try to figure out whether Dr. House was right in suspecting this disease in many of his patients, whether there is a genetic predisposition to SLE and whether a certain lifestyle can protect against this disease.
We continue the series on autoimmune diseases - diseases in which the body begins to fight itself, producing autoantibodies and/or autoaggressive clones of lymphocytes. We talk about how the immune system works and why sometimes it starts to “shoot at its own people.” Separate publications will be devoted to some of the most common diseases. To maintain objectivity, we invited Doctor of Biological Sciences, corresponding member to become the curator of the special project. RAS, professor of the Department of Immunology of Moscow State University Dmitry Vladimirovich Kuprash. In addition, each article has its own reviewer, who delves into all the nuances in more detail.
The reviewer of this article was Olga Anatolyevna Georginova, Ph.D. medical sciences, rheumatologist, assistant at the Department of Internal Medicine, Faculty of Fundamental Medicine, Moscow State University named after M.V. Lomonosov.
Drawing by William Bagg from Wilson's atlas (1855)
Most often, a person comes to the doctor exhausted by febrile fever (temperature above 38.5 °C), and it is this symptom that serves as the reason for him to see a doctor. His joints swell and hurt, his whole body “aches”, The lymph nodes increase and cause discomfort. The patient complains of rapid fatigue and increasing weakness. Other symptoms reported at the appointment include mouth ulcers, alopecia and gastrointestinal dysfunction. Often the patient suffers from excruciating headaches, depression, and severe fatigue. His condition negatively affects his work performance and social life. Some patients may even experience mood disorders, cognitive impairment, psychosis, movement disorders and myasthenia gravis.
It is not surprising that Josef Smolen from the Vienna General Hospital (Wiener Allgemeine Krankenhaus, AKH) called systemic lupus erythematosus “the most complex disease in the world” at a 2015 congress on the disease.
In order to assess the activity of the disease and the success of treatment, about 10 different indices are used in clinical practice. They can be used to track changes in the severity of symptoms over a period of time. Each disorder is assigned a specific score, and the final score indicates the severity of the disease. The first such methods appeared in the 1980s, and now their reliability has long been confirmed by research and practice. The most popular of them are SLEDAI (Systemic Lupus Erythematosus Disease Activity Index), its modification used in the Safety of Estrogens in Lupus National Assessment (SELENA) study, BILAG (British Isles Lupus Assessment Group Scale), SLICC/ACR damage index (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index) and ECLAM (European Consensus Lupus Activity Measurement). In Russia, they also use the assessment of SLE activity according to V.A.’s classification. Nasonova.
Main targets of the disease
Some tissues are more affected by attacks from autoreactive antibodies than others. In SLE, the kidneys and cardiovascular system are especially often affected.
Autoimmune processes also disrupt the functioning of blood vessels and the heart. According to the most conservative estimates, every tenth death from SLE is caused by circulatory disorders that develop as a result of systemic inflammation. The risk of ischemic stroke in patients with this disease increases twofold, the risk of intracerebral hemorrhage increases threefold, and the risk of subarachnoid hemorrhage increases almost fourfold. Survival after stroke is also much worse than in the general population.
The totality of manifestations of systemic lupus erythematosus is immense. In some patients, the disease may only affect skin and joints. In other cases, patients are exhausted by excessive fatigue, increasing weakness throughout the body, prolonged febrile temperature and cognitive impairment. This may be accompanied by thrombosis and severe organ damage, such as end-stage kidney disease. Because of such different manifestations called SLE a disease with a thousand faces.
Family planning
One of the most important risks associated with SLE is the numerous complications during pregnancy. The vast majority of patients are young women of childbearing age, so family planning, pregnancy management and monitoring the condition of the fetus are now of great importance.
Before development modern methods diagnosis and therapy, the mother’s illness often negatively affected the course of pregnancy: conditions arose that threatened the woman’s life, pregnancy often ended in intrauterine fetal death, premature birth, preeclampsia. Because of this for a long time Doctors strongly discouraged women with SLE from having children. In the 1960s, women lost their fetuses 40% of the time. By the 2000s, the number of such cases had more than halved. Today, researchers estimate this figure at 10–25%.
Now doctors advise getting pregnant only during remission of the disease, since the survival of the mother, the success of pregnancy and childbirth depends on the activity of the disease several months before conception and at the very moment of fertilization of the egg. Because of this, doctors consider counseling the patient before and during pregnancy a necessary step.
In rare cases now, a woman finds out that she has SLE while she is already pregnant. Then, if the disease is not very active, pregnancy can proceed favorably with maintenance therapy with steroid or aminoquinoline drugs. If pregnancy, coupled with SLE, begins to threaten health and even life, doctors recommend an abortion or an emergency caesarean section.
About one in 20,000 children develops neonatal lupus- a passively acquired autoimmune disease, known for more than 60 years (case incidence is given for the USA). It is mediated by maternal antinuclear autoantibodies to the Ro/SSA, La/SSB antigens or to the U1-ribonucleoprotein. The presence of SLE in the mother is not at all necessary: only 4 out of 10 women who give birth to children with neonatal lupus have SLE at the time of birth. In all other cases, the above antibodies are simply present in the mothers’ bodies.
The exact mechanism of damage to the baby's tissues is still unknown, and most likely it is more complex than simply the penetration of maternal antibodies through the placental barrier. The prognosis for the newborn's health is usually good, and most symptoms resolve quickly. However, sometimes the consequences of the disease can be very severe.
In some children, skin lesions are noticeable at birth, while in others they develop over several weeks. The disease can affect many body systems: cardiovascular, hepatobiliary, central nervous, and lungs. In the worst case scenario, the child may develop life-threatening congenital block hearts
Economic and social aspects of the disease
A person with SLE suffers not only from the biological and medical manifestations of the disease. A significant portion of the disease burden is social, and this can create a vicious cycle of worsening symptoms.
Thus, regardless of gender and ethnicity, poverty, low levels of education, lack of health insurance, insufficient social support and treatment contribute to the deterioration of the patient’s condition. This, in turn, leads to disability, loss of working capacity and further decline social status. All this significantly worsens the prognosis of the disease.
One should not discount the fact that treatment for SLE is extremely expensive, and the costs directly depend on the severity of the disease. TO direct expenses include, for example, the costs of hospital treatment(time spent in hospitals and rehabilitation centers, and related procedures), ambulatory treatment(treatment with prescribed mandatory and additional medications, visits to doctors, laboratory tests and other studies, ambulance calls), surgical operations, transportation to medical institutions and additional medical services. According to 2015 estimates, in the United States, a patient spends an average of $33 thousand per year on all of the above items. If he developed lupus nephritis, then the amount more than doubles - to $71 thousand.
Indirect costs may even be higher than direct ones, since they include loss of working capacity and disability due to illness. Researchers estimate the amount of such losses at $20 thousand.
Russian situation: “for Russian rheumatology to exist and develop, we need state support”
In Russia, tens of thousands of people suffer from SLE - about 0.1% of the adult population. Traditionally, rheumatologists treat this disease. One of the largest institutions where patients can turn for help is the Research Institute of Rheumatology named after. V.A. Nasonova RAMS, founded in 1958. As the current director of the research institute, academician of the Russian Academy of Medical Sciences, Honored Scientist of the Russian Federation Evgeniy Lvovich Nasonov recalls, at first his mother, Valentina Aleksandrovna Nasonova, who worked in the rheumatology department, came home almost every day in tears, since four out of five patients died from in her hands. Fortunately, this tragic trend has been overcome.
Patients with SLE are also provided with assistance in the rheumatology department of the Clinic of Nephrology, Internal and Occupational Diseases named after E.M. Tareev, Moscow City Rheumatology Center, Children's City Clinical Hospital named after. BEHIND. Bashlyaeva DZM (Tushinskaya Children's city Hospital), the Scientific Center for Children's Health of the Russian Academy of Medical Sciences, the Russian Children's Clinical Hospital and the Central Children's Clinical Hospital of the FMBA.
However, even now it is very difficult to suffer from SLE in Russia: the availability of the latest biological drugs for the population leaves much to be desired. The cost of such therapy is about 500–700 thousand rubles per year, and the medication is taken for a long time, and is by no means limited to one year. At the same time, the list is vital necessary medications(VED) such treatment is not covered. The standard of care for patients with SLE in Russia is published on the website of the Ministry of Health of the Russian Federation.
Currently, therapy with biological drugs is used at the Research Institute of Rheumatology. First, the patient receives them for 2–3 weeks while he is in the hospital; compulsory medical insurance covers these costs. After discharge, he must submit an application at his place of residence for additional drug provision in regional office Ministry of Health, and the final decision is made by the local official. Often his answer is negative: in some regions, patients with SLE are not of interest to the local health department.
At least 95% of patients have autoantibodies, recognizing fragments of the body’s own cells as foreign (!) and therefore posing a danger. It is not surprising that the central figure in the pathogenesis of SLE is considered B cells producing autoantibodies. These cells are the most important part of adaptive immunity, having the ability to present antigens T cells and secreting signaling molecules - cytokines. It is assumed that the development of the disease is triggered by the hyperactivity of B cells and their loss of tolerance to the body's own cells. As a result, they generate a variety of autoantibodies that are directed at nuclear, cytoplasmic and membrane antigens contained in the blood plasma. As a result of the binding of autoantibodies and nuclear material, immune complexes, which are deposited in tissues and are not effectively removed. Many clinical manifestations of lupus are the result of this process and subsequent organ damage. The inflammatory response is exacerbated by the fact that B cells secrete about inflammatory cytokines and present T-lymphocytes not with foreign antigens, but with antigens of their own body.
The pathogenesis of the disease is also associated with two other simultaneous events: increased level apoptosis(programmed cell death) of lymphocytes and with the deterioration of the processing of waste material arising during autophagy. This “littering” of the body leads to an incitement of the immune response towards its own cells.
Autophagy- the process of recycling intracellular components and replenishing the supply of nutrients in the cell - is now on everyone’s lips. In 2016, for the discovery of the complex genetic regulation of autophagy, Yoshinori Ohsumi ( Yoshinori Ohsumi) was awarded the Nobel Prize. The role of self-food is to maintain cellular homeostasis, recycle damaged and old molecules and organelles, and maintain cell survival under stressful conditions. You can read more about this in the article on “biomolecule”.Recent research shows that autophagy is important for the normal functioning of many immune responses: for example, the maturation and function of immune cells, pathogen recognition, and antigen processing and presentation. There is now more and more evidence that autophagic processes are associated with the occurrence, course and severity of SLE.
It has been shown that in vitro macrophages from SLE patients ingest less cellular debris compared to macrophages from healthy controls. Thus, if disposal is unsuccessful, apoptotic waste “attracts the attention” of the immune system, and pathological activation of immune cells occurs (Fig. 3). It turned out that some types of drugs that are already used for the treatment of SLE or are at the stage of preclinical studies act specifically on autophagy.
In addition to the above features, patients with SLE are characterized by increased expression of type I interferon genes. The products of these genes are a very well-known group of cytokines that play antiviral and immunomodulatory roles in the body. It is possible that an increase in the amount of type I interferons affects the activity of immune cells, which leads to a malfunction of the immune system.
Figure 3. Modern representations about the pathogenesis of SLE. One of the main reasons clinical symptoms SLE - tissue deposition immune complexes formed by antibodies that bind fragments of cell nuclear material (DNA, RNA, histones). This process provokes a strong inflammatory response. In addition, with increased apoptosis, NETosis, and decreased efficiency of autophagy, unutilized cell fragments become targets of immune system cells. Immune complexes via receptors FcγRIIa enter plasmacytoid dendritic cells ( pDC), where the nucleic acids of the complexes activate Toll-like receptors ( TLR-7/9) , . Activated in this way, pDC begin the powerful production of type I interferons (including IFN-α). These cytokines, in turn, stimulate the maturation of monocytes ( Mø) to antigen-presenting dendritic cells ( DC) and the production of autoreactive antibodies by B cells, prevent apoptosis of activated T cells. Monocytes, neutrophils and dendritic cells under the influence of type I IFN increase the synthesis of the cytokines BAFF (a stimulator of B cells, promoting their maturation, survival and antibody production) and APRIL (an inducer of cell proliferation). All this leads to an increase in the number of immune complexes and even more powerful activation of pDC - the circle closes. The pathogenesis of SLE also involves abnormal oxygen metabolism, which increases inflammation, cell death and the influx of autoantigens. This is largely the fault of mitochondria: disruption of their work leads to increased formation active forms oxygen ( ROS) and nitrogen ( RNI), deterioration protective functions neutrophils and netosis ( NETosis)
Finally, oxidative stress, together with abnormal oxygen metabolism in the cell and disturbances in the functioning of mitochondria, can also contribute to the development of the disease. Due to the increased secretion of pro-inflammatory cytokines, tissue damage and other processes that characterize the course of SLE, an excessive amount of reactive oxygen species(ROS), which further damage surrounding tissues, promote a constant influx of autoantigens and specific suicide of neutrophils - netozu(NETosis). This process ends with the formation neutrophil extracellular traps(NETs) designed to trap pathogens. Unfortunately, in the case of SLE, they play against the host: these network-like structures are composed predominantly of major lupus autoantigens. Interaction with the latter antibodies makes it difficult to cleanse the body of these traps and enhances the production of autoantibodies. This creates a vicious circle: increasing tissue damage as the disease progresses entails an increase in the amount of ROS, which destroys tissue even more, enhances the formation of immune complexes, stimulates the synthesis of interferon... The pathogenetic mechanisms of SLE are presented in more detail in Figures 3 and 4.
Figure 4. The role of programmed neutrophil death - NETosis - in the pathogenesis of SLE. immune cells usually do not encounter most of the body's own antigens, since potential self-antigens are located inside cells and are not presented to lymphocytes. After autophagic death, residues dead cells quickly disposed of. However, in some cases, for example, with an excess of reactive oxygen and nitrogen species ( ROS And RNI), the immune system encounters autoantigens “nose to nose”, which provokes the development of SLE. For example, under the influence of ROS, polymorphonuclear neutrophils ( PMN) are subjected to netozu, and a “network” is formed from the remains of the cell. net), containing nucleic acids and proteins. This network becomes the source of autoantigens. As a result, plasmacytoid dendritic cells are activated ( pDC), releasing IFN-α and provoking an autoimmune attack. Other symbols: REDOX(reduction-oxidation reaction) - imbalance of redox reactions; ER- endoplasmic reticulum; DC- dendritic cells; B- B cells; T- T cells; Nox2- NADPH oxidase 2; mtDNA- mitochondrial DNA; black up and down arrows- amplification and suppression, respectively. To see the picture in full size, click on it.
Who is guilty?
Although the pathogenesis of systemic lupus erythematosus is more or less clear, scientists find it difficult to name its key cause and therefore consider the totality various factors that increase the risk of developing this disease.
In our century, scientists turn their attention primarily to hereditary predisposition to illness. SLE did not escape this either - which is not surprising, because the incidence varies greatly by gender and ethnicity. Women suffer from this disease approximately 6–10 times more often than men. Their incidence peaks at 15–40 years of age, that is, during childbearing age. Prevalence, course of disease and mortality are associated with ethnicity. For example, a butterfly rash is typical in white patients. In African Americans and Afro-Caribbeans, the disease is much more severe than in Caucasians, relapses of the disease and inflammatory disorders Kidney problems are more common in them. Discoid lupus is also more common in dark-skinned people.
These facts indicate that genetic predisposition may play a role important role in the etiology of SLE.
To clarify this, the researchers used a method genome-wide association search, or GWAS, which allows thousands of genetic variants to be correlated with phenotypes—in this case, disease manifestations. Thanks to this technology, it was possible to identify more than 60 susceptibility loci for systemic lupus erythematosus. They can be roughly divided into several groups. One such group of loci is associated with the innate immune response. These are, for example, the pathways of NF-kB signaling, DNA degradation, apoptosis, phagocytosis, and utilization of cellular debris. It also includes variants responsible for the function and signaling of neutrophils and monocytes. Another group includes genetic variants involved in the work of the adaptive part of the immune system, that is, associated with the function and signaling networks of B and T cells. In addition, there are loci that do not fall into these two groups. Interestingly, many risk loci are common to SLE and other autoimmune diseases (Fig. 5).
Genetic data could be used to determine the risk of developing SLE, its diagnosis or treatment. This would be extremely useful in practice, since due to the specifics of the disease, it is not always possible to identify it from the patient’s first complaints and clinical manifestations. Selecting treatment also takes some time, because patients respond to therapy differently, depending on the characteristics of their genome. For now, however, genetic tests not used in clinical practice. Ideal Model to assess susceptibility to disease would have to take into account not only specific gene variants, but also genetic interactions, levels of cytokines, serological markers and many other data. In addition, it should, if possible, take into account epigenetic features - after all, according to research, they make a huge contribution to the development of SLE.
Unlike the genome epi the genome is relatively easy to modify under the influence of external factors. Some believe that without them, SLE may not develop. The most obvious of these is ultraviolet radiation, since after exposure sunlight Patients often show redness and rashes on the skin.
The development of the disease, apparently, can provoke and viral infection. It is possible that in this case, autoimmune reactions occur due to molecular mimicry of viruses- the phenomenon of similarity of viral antigens with the body’s own molecules. If this hypothesis is correct, then the Epstein-Barr virus becomes the focus of research. However, in most cases, scientists find it difficult to name the specific culprits. It is believed that autoimmune reactions are provoked not by specific viruses, but by common mechanisms combat this type of pathogen. For example, the activation pathway of type I interferons is common in the response to viral invasion and in the pathogenesis of SLE.
Factors such as smoking and drinking alcohol, however, their influence is ambiguous. It is likely that smoking can increase the risk of developing the disease, exacerbating it and increasing organ damage. Alcohol, according to some data, reduces the risk of developing SLE, but the evidence is quite contradictory, and it is better not to use this method of protection against the disease.
There is not always a clear answer regarding the influence professional factors risk. If contact with silicon dioxide, according to a number of studies, provokes the development of SLE, then there is no exact answer about exposure to metals, industrial chemicals, solvents, pesticides and hair dyes. Finally, as mentioned above, lupus can be triggered by drug use: Common triggers include chlorpromazine, hydralazine, isoniazid, and procainamide.
Treatment: past, present and future
As already mentioned, cure “the most complex disease in the world" is not yet possible. The development of a drug is hampered by the multifaceted pathogenesis of the disease, which involves different parts of the immune system. However, with competent individual selection of maintenance therapy, deep remission can be achieved, and the patient will be able to live with lupus erythematosus simply as with a chronic disease.
Treatment for various changes in the patient’s condition can be adjusted by a doctor, or rather, by doctors. The fact is that in the treatment of lupus, the coordinated work of a multidisciplinary group of medical professionals is extremely important: a family doctor in the West, a rheumatologist, a clinical immunologist, a psychologist, and often a nephrologist, hematologist, dermatologist, neurologist. In Russia, a patient with SLE first of all goes to a rheumatologist, and depending on the damage to systems and organs, he may require additional consultation with a cardiologist, nephrologist, dermatologist, neurologist and psychiatrist.
The pathogenesis of the disease is very complex and confusing, so many targeted drugs are currently in development, while others have shown their failure at the trial stage. Therefore, in clinical practice, nonspecific drugs are still most widely used.
Standard treatment includes several types of medications. First of all, write out immunosuppressants- in order to suppress the excessive activity of the immune system. The most commonly used of these are cytotoxic drugs. methotrexate, azathioprine, mycophenolate mofetil And cyclophosphamide. In fact, these are the same drugs that are used for cancer chemotherapy and act primarily on actively dividing cells (in the case of the immune system, on clones of activated lymphocytes). It is clear that such therapy has many dangerous side effects.
IN acute phase patients accept diseases as standard corticosteroids- nonspecific anti-inflammatory drugs that help calm the most violent storms of autoimmune reactions. They have been used in the treatment of SLE since the 1950s. Then they switched the treatment for this autoimmune disease to a qualitatively new level, and still remain the basis of therapy for lack of an alternative, although their use is also associated with many side effects. Most often, doctors prescribe prednisolone And methylprednisolone.
For exacerbation of SLE, it has also been used since 1976. pulse therapy: the patient receives impulses in high doses methylprednisolone and cyclophosphamide. Of course, over 40 years of use, the regimen of such therapy has changed greatly, but is still considered the gold standard in the treatment of lupus. However, it has many severe side effects, which is why it is not recommended for some patient groups, such as people with poorly controlled hypertension and systemic infections. In particular, the patient may develop metabolic disorders and behavior change.
When remission is achieved, it is usually prescribed antimalarial drugs, which have been successfully used for a long time to treat patients with lesions of the musculoskeletal system and skin. Action hydroxychloroquine, one of the best known substances of this group, for example, is explained by the fact that it inhibits the production of IFN-α. Its use provides long-term reduction in disease activity, reduces damage to organs and tissues, and improves pregnancy outcomes. In addition, the medicine reduces the risk of thrombosis - and this is extremely important given the complications that arise in cardiovascular system. Thus, the use of antimalarial drugs is recommended for all patients with SLE. However, there is also a drop of tar in a barrel of honey. In rare cases, retinopathy develops in response to this therapy, and patients with severe renal or hepatic impairment are at risk for hydroxychloroquine-associated toxicity.
Used in the treatment of lupus and newer, targeted drugs(Fig. 5). The most advanced developments target B cells: the antibodies rituximab and belimumab.
Figure 5. Biological drugs in the treatment of SLE. Apoptotic and/or necrotic cell debris accumulate in the human body, for example, due to viral infection and exposure to ultraviolet radiation. This "garbage" can be taken up by dendritic cells ( DC), whose main function is the presentation of antigens to T and B cells. The latter acquire the ability to respond to autoantigens presented to them by DCs. This is how an autoimmune reaction begins, the synthesis of autoantibodies starts. Many people are now studying biological drugs- drugs that affect the regulation of the body's immune components. Targeting the innate immune system anifrolumab(antibody to IFN-α receptor), sifalimumab And rontalizumab(antibodies to IFN-α), infliximab And etanercept(antibodies to tumor necrosis factor, TNF-α), sirucumab(anti-IL-6) and tocilizumab(anti-IL-6 receptor). Abatacept (cm. text), belatacept, AMG-557 And IDEC-131 block costimulatory molecules of T cells. Fostamatinib And R333- splenic tyrosine kinase inhibitors ( SYK). Various B cell transmembrane proteins are targeted rituximab And ofatumumab(antibodies to CD20), epratuzumab(anti-CD22) and blinatumomab(anti-CD19), which also blocks plasma cell receptors ( PC). Belimumab (cm. text) blocks the soluble form BAFF, tabalumab and blisibimod are soluble and membrane-bound molecules BAFF, A
Another potential target of anti-lupus therapy is type I interferons, which were already discussed above. Some antibodies to IFN-α have already shown promising results in patients with SLE. Now the next, third, phase of their testing is being planned.
Also, among the drugs whose effectiveness in SLE is currently being studied, it should be mentioned abatacept. It blocks costimulatory interactions between T and B cells, thereby restoring immunological tolerance.
Finally, various anti-cytokine drugs are being developed and tested, e.g. etanercept And infliximab- specific antibodies to tumor necrosis factor, TNF-α.
Conclusion
Systemic lupus erythematosus remains a daunting challenge for the patient, a challenge for the physician, and an underexplored area for the scientist. However, we should not limit ourselves to the medical side of the issue. This disease provides a huge field for social innovation, since the patient needs not only medical care but also in various types of support, including psychological. Thus, improving the methods of providing information, specialized mobile applications, platforms with accessible information significantly improve the quality of life of people with SLE.
A lot of help in this matter and patient organizations- public associations of people suffering from some disease and their relatives. For example, the Lupus Foundation of America is very famous. The activities of this organization are aimed at improving the quality of life of people diagnosed with SLE through special programs, scientific research, education, support and assistance. Its primary objectives include reducing the time to diagnosis, providing patients with safe and effective treatment and expanding access to treatment and care. In addition, the organization emphasizes the importance of training medical personnel, communicating concerns to government officials and raising social awareness regarding systemic lupus erythematosus.
The global burden of SLE: prevalence, health disparities and socioeconomic impact. Nat Rev Rheumatol. 12 , 605-620;
Laboratory research
General analysis blood. An increase in ESR is often observed in SLE, but this sign does not correlate well with disease activity. An unexplained increase in ESR indicates the presence of an intercurrent infection.
. Leukopenia (usually lymphopenia) is associated with disease activity.
. Hypochromic anemia is associated with chronic inflammation, hidden stomach bleeding, taking certain drugs. Mild or moderate anemia is often detected. Severe Coombs-positive autoimmune hemolytic anemia is observed in less than 10% of patients.
Thrombocytopenia is usually detected in patients with APS. Very rarely, autoimmune thrombocytopenia develops associated with the synthesis of AT to platelets.
. An increase in CRP is unusual; noted in most cases in the presence of concomitant infection. Moderate increase in CRP concentration (<10 мг/мл) ассоциируется с атеросклеротическим поражением сосудов.
General urine analysis
Proteinuria, hematuria, leukocyturia are detected, the severity of which depends on the clinical and morphological variant of lupus nephritis.
Biochemical studies
Changes in biochemical parameters are nonspecific and depend on the predominant damage to internal organs during different periods of the disease. Immunological studies
. Antinuclear factor (ANF) is a heterogeneous population of autoantibodies that react with various components of the cell nucleus. ANF is detected in 95% of patients with SLE (usually in high titer); its absence in the vast majority of cases argues against the diagnosis of SLE.
Antinuclear AT. ATs to double-stranded (native) DNA (anti-DNA) are relatively specific for SLE; detected in 50-90% of patients ♦ AT to histones, more typical for drug-induced lupus. AT to 5m antigen (anti-Sm) are highly specific for SLE, but they are detected only in 10-30% of patients; AT to small nuclear ribonucleoproteins is more often detected in patients with manifestations of mixed connective tissue disease ♦ AT to Ro/SS-A antigen (anti-Ro/SSA) is associated with lymphopenia, thrombocytopenia, photodermatitis, pulmonary fibrosis, Sjögren's syndrome. AT to La/SS-B antigen (anti-La/SSB) is often found together with anti-Ro.
APL, false-positive Wasserman reaction, lupus anticoagulant and AT to cardiolipin are laboratory markers of APS.
Other laboratory abnormalities
In many patients, so-called lupus cells are detected - LE (ot lupus erythematosus) cells (leukocytes that have phagocytosed nuclear material), circulating immune complexes, RF, but the clinical significance of these laboratory abnormalities is small. In patients with lupus nephritis, a decrease in the total hemolytic activity of complement (CH50) and its individual components (C3 and C4), which correlates with the activity of nephritis (especially the C3 component), is observed.
Diagnostics
To diagnose SLE, the presence of one symptom of the disease or one identified laboratory change is not enough - the diagnosis is established on the basis of the clinical manifestations of the disease, data from laboratory and instrumental research methods and the classification criteria of the disease of the American Association of Rheumatology.American Rheumatology Association Criteria
1. Rash on the cheekbones: fixed erythema on the cheekbones, tending to spread to the nasolabial area.2. Discoid rash: erythematous raised plaques with adherent skin scales and follicular plugs; old lesions may have atrophic scars.
3. Photosensitivity: A skin rash that occurs as a result of an unusual reaction to sunlight.
4. Oral ulcers: ulceration of the oral cavity or nasopharynx; usually painless.
5. Arthritis: non-erosive arthritis affecting 2 or more peripheral joints, manifested by tenderness, swelling and effusion.
6. Serositis: pleurisy (pleural pain, or pleural friction rub, or the presence of pleural effusion) or pericarditis (confirmed by echocardiography or auscultation of a pericardial friction rub).
7. Kidney damage: persistent proteinuria >0.5 g/day or cylinder (erythrocyte, hemoglobin, granular or mixed).
8. Damage to the central nervous system: convulsions or psychosis (in the absence of taking drugs or metabolic disorders).
9. Hematological disorders: hemolytic anemia with reticulocytosis, or leukopenia<4,0х109/л (зарегистрированная 2 и более раза), или тромбоцитопения <100х109/л (в отсутствие приёма ЛС).
10. Immunological disorders ♦ anti-DNA or ♦ anti-Sm or ♦ aPL: -increased level of IgG or IgM (AT to cardiolipin); - positive test for lupus anticoagulant using standard methods; - false-positive Wasserman reaction for at least 6 months with a confirmed absence of syphilis using the Treponema pallidum immobilization test and the fluorescent adsorption test of treponemal AT.
11. ANF: increase in ANF titers (in the absence of taking drugs that cause lupus-like syndrome). The diagnosis of SLE is made when 4 or more of the 11 criteria listed above are found.
Diagnostic criteria for APS
I. Clinical criteria1. Thrombosis (one or more episodes of arterial, venous or small vessel thrombosis in any organ).
2. Pathology of pregnancy (one or more cases of intrauterine death of a morphologically normal fetus after the 10th week of gestation or one or more cases of premature birth of a morphologically normal fetus before the 34th week of gestation or three or more consecutive cases of spontaneous abortions before the 10th week of gestation ).
II. Laboratory criteria
1. AT to cardiolipin (IgG and/or IgM) in the blood in medium or high titers in 2 or more studies with an interval of at least 6 weeks.
2. Plasma lupus anticoagulant in 2 or more studies at least 6 weeks apart, determined as follows:
. prolongation of plasma clotting time in phospholipid-dependent coagulation tests;
. lack of correction for prolongation of clotting time of screening tests in tests of mixing with donor plasma;
. shortening or correction of prolongation of the clotting time of screening tests when adding phospholipids;
. exclusion of other coagulopathies. A specific APS is diagnosed based on the presence of one clinical and one laboratory criterion.
If SLE is suspected, the following studies should be performed:
. general blood test with determination of ESR and counting the content of leukocytes (with leukocyte formula) and platelets. immunological blood test with determination of ANF. general urine analysis. chest x-ray
. ECG, echocardiography.
Diagnosis of lupus erythematosus
General principles for diagnosing the disease
Diagnosis of systemic lupus erythematosus is set on the basis of special developed diagnostic criteria proposed by the American Association of Rheumatology or the domestic scientist Nasonova. Further, after making a diagnosis based on diagnostic criteria, additional examinations are performed - laboratory and instrumental, which confirm the correctness of the diagnosis and allow one to assess the degree of activity of the pathological process and identify the affected organs.Currently, the most commonly used diagnostic criteria are the American Rheumatology Association, not Nasonova. But we will present both schemes of diagnostic criteria, since in a number of cases domestic doctors use Nasonova’s criteria to diagnose lupus.
American Rheumatology Association Diagnostic Criteria the following:
- Rash in the area of the cheekbones on the face (there are red elements of the rash that are flat or slightly raised above the surface of the skin, spreading to the nasolabial folds);
- Discoid rashes (raised plaques above the surface of the skin with “black dots” in the pores, peeling and atrophic scars);
- Photosensitivity (the appearance of skin rashes after exposure to the sun);
- Ulcers on the oral mucosa (painless ulcerative defects localized on the mucous membrane of the mouth or nasopharynx);
- Arthritis (affecting two or more small joints, characterized by pain, swelling and swelling);
- Polyserositis (pleuritis, pericarditis or non-infectious peritonitis in the present or past);
- Kidney damage (the constant presence of protein in the urine in an amount of more than 0.5 g per day, as well as the constant presence of red blood cells and casts (erythrocyte, hemoglobin, granular, mixed) in the urine);
- Neurological disorders: seizures or psychosis (delusions, hallucinations) not caused by medications, uremia, ketoacidosis or electrolyte imbalance;
- Hematological disorders (hemolytic anemia, leukopenia with the number of leukocytes in the blood less than 1 * 10 9 , lymphopenia with the number of lymphocytes in the blood less than 1.5 * 10 9 , thrombocytopenia with the number of platelets less than 100 * 10 9 );
- Immunological disorders (antibodies to double-stranded DNA in an increased titer, the presence of antibodies to the Sm antigen, a positive LE test, a false-positive Wasserman reaction to syphilis for six months, the presence of an anti-lupus coagulant);
- Increased titer of ANA (antinuclear antibodies) in the blood.
Nasonova's criteria for lupus erythematosus include major and minor diagnostic criteria, which are listed in the table below:
| Large diagnostic criteria | Minor diagnostic criteria |
| "Butterfly on the Face" | Body temperature above 37.5 o C, lasting longer than 7 days |
| Arthritis | Unreasonable weight loss of 5 or more kg in a short period of time and disruption of tissue nutrition |
| Lupus pneumonitis | Capillaritis on the fingers |
| LE cells in the blood (less than 5 per 1000 leukocytes – single, 5 – 10 per 1000 leukocytes – moderate number, and more than 10 per 1000 leukocytes – large number) | Skin rashes such as hives or rashes |
| ANF in high credits | Polyserositis (pleurisy and carditis) |
| Werlhoff syndrome | Lymphadenopathy (enlarged lymph ducts and nodes) |
| Coombs-positive hemolytic anemia | Hepatosplenomegaly (enlarged liver and spleen) |
| Lupus jade | Myocarditis |
| Hematoxylin bodies in pieces of tissue from various organs taken during biopsy | CNS damage |
| A characteristic pathomorphological picture in the removed spleen (“bulbous sclerosis”), in skin samples (vasculitis, immunofluorescence of immunoglobulins on the basement membrane) and kidneys (glomerular capillary fibrinoid, hyaline thrombi, “wire loops”) | Polyneuritis |
| Polymyositis and polymyalgia (inflammation and muscle pain) | |
| Polyarthralgia (joint pain) | |
| Raynaud's syndrome | |
| Acceleration of ESR more than 200 mm/hour | |
| Decrease in the number of leukocytes in the blood to less than 4*10 9 /l | |
| Anemia (hemoglobin level below 100 mg/ml) | |
| Decrease in platelet count below 100*10 9 /l | |
| Increase in the amount of globulin proteins by more than 22% | |
| ANF in low credits | |
| Free LE bodies | |
| Positive Wasserman reaction in the confirmed absence of syphilis |
The diagnosis of lupus erythematosus is considered accurate and confirmed when any three large diagnostic criteria are combined, one of them must be either “butterfly” or LE cells in large numbers, and the other two must be any of the above. If a person has only minor diagnostic signs or they are combined with arthritis, then the diagnosis of lupus erythematosus is considered only probable. In this case, data from laboratory tests and additional instrumental examinations are required to confirm it.
The above criteria of Nasonova and the American Association of Rheumatology are the main ones in the diagnosis of lupus erythematosus. This means that the diagnosis of lupus erythematosus is made only on their basis. And any laboratory tests and instrumental examination methods are only additional, allowing one to assess the degree of activity of the process, the number of affected organs and the general condition of the human body. A diagnosis of lupus erythematosus is not made based only on laboratory tests and instrumental examination methods.
Currently, ECG, EchoCG, MRI, chest X-ray, ultrasound, etc. can be used as instrumental diagnostic methods for lupus erythematosus. All these methods make it possible to assess the degree and nature of damage in various organs.
Blood (test) for lupus erythematosus
Among the laboratory tests to assess the intensity of the process in lupus erythematosus, the following are used: - Antinuclear factors (ANF) – with lupus erythematosus are found in the blood in high titers no higher than 1: 1000;
- Antibodies to double-stranded DNA (anti-dsDNA-AT) – with lupus erythematosus are found in the blood of 90–98% of patients, but are normally absent;
- Antibodies to histone proteins - in lupus erythematosus are found in the blood, but are normally absent;
- Antibodies to the Sm antigen - with lupus erythematosus are found in the blood, but are normally absent;
- Antibodies to Ro/SS-A - in lupus erythematosus are detected in the blood if there is lymphopenia, thrombocytopenia, photosensitivity, pulmonary fibrosis or Sjögren's syndrome;
- Antibodies to La/SS-B – in lupus erythematosus are detected in the blood under the same conditions as antibodies to Ro/SS-A;
- Complement level – with lupus erythematosus, the level of complement proteins in the blood is reduced;
- The presence of LE cells - with lupus erythematosus they are found in the blood of 80 - 90% of patients, but are normally absent;
- Antibodies to phospholipids (lupus anticoagulant, antibodies to cardiolipin, positive Wasserman test in the confirmed absence of syphilis);
- Antibodies to coagulation factors VIII, IX and XII (normally absent);
- Increased ESR by more than 20 mm/hour;
- Leukopenia (decrease in the level of leukocytes in the blood less than 4 * 10 9 / l);
- Thrombocytopenia (decrease in the level of platelets in the blood less than 100 * 10 9 / l);
- Lymphopenia (decrease in the level of lymphocytes in the blood less than 1.5 * 10 9 / l);
- Increased blood concentrations of seromucoid, sialic acids, fibrin, haptoglobin, C-reactive protein of circulating immune complexes and immunoglobulins.
Diagnosis of lupus erythematosus, tests. How to distinguish lupus erythematosus from psoriasis, eczema, scleroderma, lichen and urticaria (recommendations from a dermatologist) - video
Treatment of systemic lupus erythematosus
General principles of therapy
Because the exact causes of lupus are unknown, there are no treatments that can completely cure the disease. As a result, only pathogenetic therapy is used, the goal of which is to suppress the inflammatory process, prevent relapses and achieve stable remission. In other words, the treatment of lupus erythematosus is to slow down the progression of the disease as much as possible, lengthen periods of remission and improve a person’s quality of life. The main drugs in the treatment of lupus erythematosus are glucocorticosteroid hormones(Prednisolone, Dexamethasone, etc.), which are used constantly, but depending on the activity of the pathological process and the severity of the person’s general condition, their dosage is changed. The main glucocorticoid in the treatment of lupus is Prednisolone. It is this drug that is the drug of choice, and it is for it that the exact dosages are calculated for various clinical variants and the activity of the pathological process of the disease. Dosages for all other glucocorticoids are calculated based on the dosages of Prednisolone. The list below shows dosages of other glucocorticoids equivalent to 5 mg Prednisolone:
- Betamethasone – 0.60 mg;
- Hydrocortisone – 20 mg;
- Dexamethasone – 0.75 mg;
- Deflazacort – 6 mg;
- Cortisone – 25 mg;
- Methylprednisolone – 4 mg;
- Paramethasone – 2 mg;
- Prednisone – 5 mg;
- Triamcinolone – 4 mg;
- Flurprednisolone – 1.5 mg.
So, at the first degree of activity pathological process Prednisolone is used in therapeutic dosages of 0.3 – 0.5 mg per 1 kg of body weight per day, at the second degree of activity– 0.7 – 1.0 mg per 1 kg of weight per day, and at the third degree– 1 – 1.5 mg per 1 kg of body weight per day. In the indicated doses, Prednisolone is used for 4 to 8 weeks, and then the dosage of the drug is reduced, but its use is never completely canceled. The dosage is first reduced by 5 mg per week, then by 2.5 mg per week, and after some time by 2.5 mg every 2 to 4 weeks. In total, the dosage is reduced so that 6–9 months after starting Prednisolone, its maintenance dose becomes 12.5–15 mg per day.
During a lupus crisis, involving several organs, glucocorticoids are administered intravenously for 3 to 5 days, after which they switch to taking drugs in tablets.
Since glucocorticoids are the main means of treating lupus, they are prescribed and used without fail, and all other medications are used additionally, selecting them depending on the severity of clinical symptoms and the affected organ.
Thus, with a high degree of activity of lupus erythematosus, with lupus crises, with severe lupus nephritis, with severe damage to the central nervous system, with frequent relapses and instability of remission, in addition to glucocorticoids, cytostatic immunosuppressants are used (Cyclophosphamide, Azathioprine, Cyclosporine, Methotrexate, etc.).
For severe and widespread skin lesions Azathioprine is used at a dosage of 2 mg per 1 kg of body weight per day for 2 months, after which the dose is reduced to a maintenance dose: 0.5 - 1 mg per 1 kg of body weight per day. Azathioprine is taken in a maintenance dosage for several years.
For severe lupus nephritis and pancytopenia(decrease in the total number of platelets, erythrocytes and leukocytes in the blood) use Cyclosporine at a dosage of 3 - 5 mg per 1 kg of body weight.
With proliferative and membranous lupus nephritis, with severe damage to the central nervous system Cyclophosphamide is used, which is administered intravenously at a dosage of 0.5 - 1 g per m2 of body surface once a month for six months. Then, for two years, the drug continues to be administered in the same dosage, but once every three months. Cyclophosphamide ensures the survival of patients suffering from lupus nephritis and helps control clinical symptoms that are not affected by glucocorticoids (CNS damage, pulmonary hemorrhage, pulmonary fibrosis, systemic vasculitis).
If lupus erythematosus does not respond to glucocorticoid therapy, then Methotrexate, Azathioprine or Cyclosporine are used instead.
With low activity of the pathological process with damage skin and joints Aminoquinoline drugs (Chloroquine, Hydroxychloroquine, Plaquenil, Delagil) are used in the treatment of lupus erythematosus. In the first 3 to 4 months, the drugs are used at 400 mg per day, and then at 200 mg per day.
With lupus nephritis and the presence of antiphospholipid bodies in the blood(antibodies to cardiolipin, lupus anticoagulant) drugs from the group of anticoagulants and antiplatelet agents (Aspirin, Curantil, etc.) are used. Acetylsalicylic acid is mainly used in small doses - 75 mg per day for a long time.
Medicines from the group of non-steroidal anti-inflammatory drugs (NSAIDs), such as Ibuprofen, Nimesulide, Diclofenac, etc., are used as drugs to relieve pain and relieve inflammation in arthritis, bursitis, myalgia, myositis, moderate serositis and fever.
In addition to medications, for the treatment of lupus erythematosus, methods of plasmapheresis, hemosorption and cryoplasmasorption are used, which make it possible to remove antibodies and inflammatory products from the blood, which significantly improves the condition of patients, reduces the degree of activity of the pathological process and reduces the rate of progression of the pathology. However, these methods are only auxiliary, and therefore can only be used in combination with taking medications, and not instead of them.
To treat skin manifestations of lupus, it is necessary to externally use sunscreens with UVA and UVB filters and ointments with topical steroids (Fluorcinolone, Betamethasone, Prednisolone, Mometasone, Clobetasol, etc.).
Currently, in addition to these methods, drugs from the group of tumor necrosis factor blockers (Infliximab, Adalimumab, Etanercept) are used in the treatment of lupus. However, these drugs are used exclusively as a trial, experimental treatment, since today they are not recommended by the Ministry of Health. But the results obtained allow us to consider tumor necrosis factor blockers as promising drugs, since the effectiveness of their use is higher than that of glucocorticoids and immunosuppressants.
In addition to the described drugs used directly for the treatment of lupus erythematosus, this disease requires the use of vitamins, potassium compounds, diuretics and antihypertensive drugs, tranquilizers, antiulcers and other drugs that reduce the severity of clinical symptoms in various organs, as well as restoring normal metabolism. For lupus erythematosus, you can and should additionally use any medications that improve a person’s overall well-being.
Drugs for lupus erythematosus
Currently, the following groups of drugs are used to treat lupus erythematosus: - Glucocorticosteroids (Prednisolone, Methylprednisolone, Betamethasone, Dexamethasone, Hydrocortisone, Cortisone, Deflazacort, Paramethasone, Triamcinolone, Flurprednisolone);
- Cytostatic immunosuppressants (Azathioprine, Methotrexate, Cyclophosphamide, Cyclosporine);
- Antimalarial drugs - aminoquinoline derivatives (Chloroquine, Hydroxychloroquine, Plaquenil, Delagil, etc.);
- TNF alpha blockers (Infliximab, Adalimumab, Etanercept);
- Non-steroidal anti-inflammatory drugs (Diclofenac, Nimesulide,
Professor Doctor of Medical Sciences Tatyana Magomedalievna Reshetnyak
Institute of Rheumatology RAMS, Moscow
This lecture is intended both for patients with systemic lupus erythematosus (SLE), and for their relatives, friends and generally for those who want to better understand this disease in order to help SLE patients cope with this disease. It provides information about SLE with explanations of some medical terms. The information provided provides an understanding of the disease and its symptoms, contains information about diagnosis and treatment, as well as current scientific advances in this problem. The lecture also discusses issues such as health care, pregnancy, and the quality of life of patients with SLE. If you have questions after reading this booklet, you can discuss them with your healthcare provider or email: [email protected].
Brief history of SLE
The name lupus erythematosus, in Latin as Lupus erythematosus, comes from the Latin word “lupus”, which translated into English “wolf” means wolf and “erythematosus” means red. This name was given to the disease due to the fact that the skin manifestations were similar to the damage caused by a bite from a hungry wolf. This disease has been known to doctors since 1828, after the French dermatologist Biett described skin signs. 45 years after the first description, another dermatologist, Kaposhi, noticed that some patients with skin signs of the disease also have symptoms of diseases of the internal organs. And in 1890 the famous English doctor Osler discovered that lupus erythematosus, also called systemic, can occur (although rarely) without skin manifestations. In 1948 the phenomenon of LE-(LE) cells was described, which was characterized by the detection of cell fragments in the blood. This discovery allowed doctors to identify many patients with SLE. Only in 1954 Certain proteins (or antibodies) were identified in the blood of SLE patients that acted against their own cells. The discovery of these proteins has been used to develop more sensitive tests for diagnosing SLE.
What is SLE
Systemic lupus erythematosus, also sometimes called lupus or SLE for short, is a type of immune system disorder known as an autoimmune disease. In autoimmune diseases, the body produces foreign proteins to its own cells and their components, causing damage to its healthy cells and tissues. An autoimmune disease is a condition in which the immune system begins to perceive “self” tissues as foreign and attacks them. This leads to inflammation and damage to various body tissues. Lupus is a chronic autoimmune disease that comes in several forms and can cause inflammation of the joints, muscles, and various other parts of the body. Based on the above definition of SLE, it is clear that this disease affects various organs of the body, including joints, skin, kidneys, heart, lungs, blood vessels and brain. Although people with this condition have many different symptoms, some of the most common include extreme fatigue, painful or swollen joints (arthritis), unexplained fever, skin rashes, and kidney problems. SLE belongs to the group of rheumatic diseases. Rheumatic diseases include those accompanied by inflammatory diseases of the connective tissue and characterized by pain in the joints, muscles, and bones.
Currently, SLE is considered an incurable disease. However, the symptoms of SLE can be controlled with appropriate treatment, and most people with the disease can lead active, healthy lives. In almost all patients with SLE, its activity changes throughout the course of the disease, alternating with moments called flares - exacerbations (in the English literature referred to as fire) and periods of well-being or remission. An exacerbation of the disease is characterized by the appearance or worsening of inflammation of various organs. According to the classification accepted in Russia, the activity of the disease is divided into three stages: I – minimal, II – moderate and III – severe. In addition, according to the onset of signs of the disease, our country distinguishes between the variants of the course of SLE: acute, subacute and primary chronic. This division is convenient for long-term observation of patients. Disease remission is a condition in which there are no signs or symptoms of SLE. Cases of complete or long-term remission of SLE, although rare, do occur. Understanding how to prevent flare-ups and how to treat them when they occur helps people with SLE maintain their health. In our country, at the Institute of Rheumatology of the Russian Academy of Medical Sciences, as well as in other world scientific centers, intensive research continues to achieve enormous strides in understanding the disease, which can lead to a cure.
There are two questions that researchers are studying: who gets SLE and why. We know that women suffer from SLE more often than men, and this ratio, according to various scientific centers, ranges from 1:9 to 1:11. According to American researchers, SLE is three times more likely to affect black women compared to white women, and is also more common in women of Hispanic, Asian and Native American descent. In addition, there are known familial cases of SLE, but the risk that a patient's child or sibling will also develop SLE is still quite low. There is no statistical information in Russia on the number of patients with SLE, since the symptoms of the disease vary widely from minimal to severe damage to vital organs and the onset of their appearance is often difficult to pinpoint accurately.
In fact, there are several types of SLE:
systemic lupus erythematosus, which is the form of the disease that most people mean when they say lupus or lupus. The word “systemic” means that the disease can affect many systems of the body. Symptoms of SLE can be mild or severe. Although SLE primarily affects people between the ages of 15 and 45, it can show up in both childhood and old age. This brochure focuses on SLE.
Discoid lupus erythematosus primarily affects the skin. A red, raised rash may appear on the face, scalp, or anywhere else. The raised areas may become thick and scaly. The rash may last for days or years, or may recur (go away and then return). A small percentage of people with discoid lupus erythematosus later develop SLE.
Drug-induced lupus erythematosus refers to a form of lupus that is caused by drugs. It causes some symptoms similar to those of SLE (arthritis, rash, fever and chest pain, but usually does not involve the kidneys), which disappear when the medication is stopped. Medicines that can cause drug-induced lupus include: hydralazine (Aresolin), procainamide (Procan, Pronestil), methyldopa (Aldomet), guinidine (Guinaglut), isoniazid, and some anticonvulsants such as phenytoin (Dilantin) or carbamazepine (Tegretol). ) and etc..
neonatal lupus. May affect some newborns, women with SLE, or certain other immune system disorders. Children with neonatal lupus may have severe heart damage, which is the most serious symptom. Some newborns may have a skin rash, liver abnormalities, or cytopenia (low blood cell count). Currently, doctors can identify most patients at risk of developing neonatal SLE, which allows them to quickly begin treatment for the child from birth. Neonatal lupus is very rare, and most children whose mothers have SLE are completely healthy. It should be noted that skin rashes with neonatal lupus usually do not require therapy and go away on their own.
What causes systemic lupus erythematosus?
Systemic lupus erythematosus is a complex disease whose cause is unknown. It is likely that there is not a single cause, but rather a combination of several factors, including genetic, environmental and possibly hormonal factors, which in combination can cause the disease. The exact cause of the disease may differ from person to person; the provoking factor may be stress, a cold, or hormonal changes in the body that occur during puberty, pregnancy, after an abortion, or during menopause. Scientists have made great progress in understanding some of the causes of some of the symptoms of SLE that are described in this leaflet. Researchers believe that genetics plays an important role in the development of the disease, however, the specific “lupus gene” has not yet been identified. Instead, it is believed that several genes may increase a person's susceptibility to the disease.
The fact that lupus can run in families shows that the development of the disease has a genetic basis. In addition, studies of identical twins have shown that lupus is more likely to affect both twins, who share the same set of genes, than two fraternal twins or other children of the same parents. Since the risk of getting the disease for identical twins is much less than 100 percent, scientists think that genes alone cannot explain the occurrence of lupus. Other factors must also play a role. Among them, which continue to be studied intensively, are solar radiation, stress, certain drugs and infectious agents such as viruses. At the same time, SLE is not an infectious or contagious disease and is not related to cancer or acquired immunodeficiency syndrome. Although the virus can cause disease in susceptible people, a person cannot “catch” lupus from someone else who has it.
In SLE, the body's immune system does not work as well as it should. A healthy immune system produces antibodies, which are specific proteins - proteins that help fight and destroy viruses, bacteria and other foreign substances that invade the body. In lupus, the immune system produces antibodies (proteins) against healthy cells and tissues in the body's own. These antibodies, called autoantibodies (“auto” means one's own), promote inflammation in various parts of the body, causing them to become swollen, red, warm, and painful. In addition, some autoantibodies combine with substances from the body's own cells and tissues to form molecules called immune complexes. The formation of these immune complexes in the body also contributes to inflammation and tissue damage in lupus patients. Scientists do not yet understand all the factors that cause inflammation and tissue damage in lupus and this is an active area of research.
Symptoms of SLE.
Despite the presence of certain signs of the disease, each case of SLE patient is different. Clinical manifestations of SLE can range from minimal to severe damage to vital organs and may come and go periodically. Common symptoms of lupus are listed in the table and include fatigue (chronic fatigue syndrome), painful and swollen joints, unexplained fever, and skin rashes. A characteristic skin rash may appear on the bridge of the nose and on the cheeks and, due to its butterfly-shaped appearance, is called a “butterfly” or erythematous (red) rash on the skin of the malar area. Red rashes can appear on any part of the skin of the body: on the face or ears, on the arms - shoulders and hands, on the skin of the chest.
Common symptoms of SLE
- Joint tenderness and swelling, muscle pain
- unexplained fever
- Chronic fatigue syndrome
- Red rashes on the face or changes in skin color
- Chest pain when breathing deeply
- Increased hair loss
- Whitening or blueness of the skin of the fingers or toes due to cold or stress (Raynaud's syndrome)
- Increased sensitivity to the sun
- Swelling (edema) of the legs and/or around the eyes
- Enlarged lymph nodes
Other symptoms of lupus include chest pain, hair loss, sensitivity to the sun, anemia (decreased red blood cells), and pale or purplish skin on the fingers or toes from cold and stress. Some people also experience headaches, dizziness, depression, or seizures. New symptoms may continue to appear years after diagnosis, and different signs of the disease may appear at different times.
In some SLE patients, only one body system is involved, such as the skin or joints, or the blood-forming organs. In other patients, manifestations of the disease can affect many organs and the disease is multiorgan in nature. The severity of damage to body systems varies among patients. More often, joints or muscles are affected, causing arthritis or muscle pain - myalgia. Skin rashes are quite similar between patients. With multiple organ manifestations of SLE, the following body systems may be involved in the pathological process:
Kidneys: Inflammation in the kidneys (lupus nephritis) can impair their ability to effectively eliminate waste products and toxins from the body. Because kidney function is so important to overall health, kidney damage caused by lupus usually requires intensive drug treatment to prevent permanent damage. It is usually difficult for the patient himself to assess the extent of kidney damage, so usually inflammation of the kidneys in SLE (lupus nephritis) is not accompanied by pain associated with the involvement of the kidneys, although some patients may notice that their ankles are swollen, swelling has appeared around the eyes. A common indicator of kidney damage from lupus is an abnormal urinalysis and decreased urine output.
Central nervous system: In some patients, lupus affects the brain or central nervous system. This may cause headaches, dizziness, memory problems, vision problems, paralysis or changes in behavior (psychosis), and seizures. Some of these symptoms, however, may be caused by certain medications, including those used to treat SLE, or by the emotional stress of learning about the disease.
Blood Vessels: Blood vessels can become inflamed (vasculitis), affecting the way blood circulates through the body. The inflammation may be mild and not require treatment.
blood: People with lupus may develop anemia or leukopenia (decreased number of white and/or red blood cells). Lupus can also cause thrombocytopenia, a decrease in the number of platelets in the blood that leads to an increased risk of bleeding. Some patients with lupus have an increased risk of developing blood clots in their blood vessels.
Heart: In some people with lupus, inflammation may be in the arteries that bring blood to the heart (coronary vasculitis), the heart itself (myocarditis or endocarditis), or the serosa that surrounds the heart (pericarditis), causing chest pain or other symptoms.
Lungs: Some SLE patients develop inflammation of the serous lining of the lungs (pleuritis), causing chest pain, shortness of breath and cough. Autoimmune pneumonia is called pneumonitis. Other serous membranes covering the liver and spleen may be involved in the inflammatory process, causing pain in the corresponding location of this organ.
Diagnosis of systemic lupus erythematosus.
Diagnosing lupus can be difficult. It can take months or even years for doctors to gather symptoms and accurately diagnose this complex disease. The patient may develop the signs mentioned in this part over a long period of illness or in a short period of time. Diagnosis of SLE is strictly individual and it is impossible to verify this disease by the presence of one symptom. Correct diagnosis of lupus requires knowledge and awareness on the part of the doctor and good communication on the part of the patient. Telling your doctor a complete, accurate medical history (such as what health problems you've had and for how long, what triggered the illness) is essential to the diagnosis process. This information, along with physical examination and laboratory test results, helps the doctor consider or actually confirm other conditions that may be similar to SLE. Making a diagnosis may take time, and the disease may not be verified immediately, but only when new symptoms appear.
There is no one test that can determine whether a person has SLE, but several laboratory tests can help a doctor make a diagnosis. Tests are used that detect specific autoantibodies that are often present in lupus patients. For example, antinuclear antibody testing is typically performed to detect autoantibodies that antagonize components of the nucleus, or “command center,” of a person's own cells. Many patients test positive for antinuclear antibodies; however, some medications, infections and other diseases can also cause a positive result. The antinuclear antibody test simply provides another clue for the doctor to make a diagnosis. There are also blood tests for individual types of autoantibodies that are more specific for people with lupus, although not all people with lupus test positive for them. These antibodies include anti-DNA, anti-Sm, RNP, Ro (SSA), La (SSB). A doctor may use these tests to confirm a lupus diagnosis.
According to the American College of Rheumatology diagnostic criteria, 1982 revision, there are 11 of the following:
Eleven diagnostic signs of SLE
- red rashes in the malar area (butterfly-shaped, on the skin of the chest in the décolleté area, on the back of the hands)
- discoid rash (scaly, disc-shaped ulcerations, most often on the face, scalp or chest)
- photosensitivity (sensitivity to sunlight in a short period of time (no more than 30 minutes)
- mouth ulcers (pain in the throat, mouth or nose)
- arthritis (pain, swelling, stiffness in the joints)
- serositis (inflammation of the serous membrane around the lungs, heart, peritoneum, causing pain when changing body position and often accompanied by difficulty breathing)_
- kidney involvement
- problems associated with damage to the central nervous system (psychosis and seizures not associated with medication)
- hematological problems (decreased number of blood cells)
- immunological disorders (which increase the risk of secondary infections)
- antinuclear antibodies (autoantibodies that act against the nuclei of the body's own cells when these cell parts are mistakenly perceived as foreign (antigen)
These diagnostic criteria are designed to allow the doctor to distinguish SLE from other connective tissue diseases, and 4 of the above signs are sufficient to make a diagnosis. At the same time, the presence of only one sign does not exclude the disease. In addition to the signs included in the diagnostic criteria, patients with SLE may have additional symptoms of the disease. These include trophic disorders (weight loss, increased hair loss before the appearance of patches of baldness or complete baldness), fever of an unmotivated nature. Sometimes the first sign of the disease may be an unusual change in skin color (blue, white) of the fingers or part of the finger, nose, ears due to cold or emotional stress. This change in skin color is called Raynaud's syndrome. Other common symptoms of the disease may include muscle weakness, low-grade fever, decreased or loss of appetite, and abdominal discomfort accompanied by nausea, vomiting, and sometimes diarrhea.
About 15% of SLE patients also have Sjogren's syndrome or the so-called “sicca syndrome”. This is a chronic condition that is accompanied by dry eyes and dry mouth. Women may also experience dryness of the mucous membranes of the genital organs (vagina).
Sometimes people with SLE experience depression or an inability to concentrate. Rapid mood swings or unusual behavior may occur for the following reasons:
These phenomena may be associated with autoimmune inflammation in the central nervous system
These manifestations may be a normal reaction to a change in your well-being.
The condition may be associated with unwanted drug effects, especially when a new drug is added or new worsening symptoms appear. We repeat that signs of SLE may appear over a long period. Although many SLE patients typically have multiple symptoms, most typically have multiple health problems that tend to get worse over time. However, most patients with SLE feel well during therapy, without any signs of organ damage.
Such central nervous system conditions may require the addition of drugs other than the primary medications to treat SLE affecting the central nervous system. That is why sometimes a rheumatologist needs help from doctors of other specialties, in particular a psychiatrist, neurologist, etc.
Some tests are used less frequently but may be useful if a patient's symptoms remain unclear. The doctor may order a biopsy of the skin or kidneys if they are affected. Usually, when making a diagnosis, a test for syphilis is prescribed - the Wassermann reaction, since some lupus antibodies in the blood can cause a false-positive reaction to syphilis. A positive test does not mean that the patient has syphilis. In addition, all these tests only help to give the doctor clues and information to make the correct diagnosis. The doctor must compare the complete picture: medical history, clinical symptoms and test data to accurately determine whether a person has lupus.
Other laboratory tests are used to monitor the progress of the disease from the time of diagnosis. A complete blood count, urinalysis, blood chemistry panel, and erythrocyte sedimentation rate (ESR) can provide valuable information. ESR is an indicator of inflammation in the body. She diagnoses how quickly red blood cells fall to the bottom of the tube containing non-coagulating blood. However, an increase in ESR is not an important indicator for SLE, but in combination with other indicators it can prevent some complications in SLE. This primarily concerns the addition of a secondary infection, which not only complicates the patient’s condition, but also creates problems in the treatment of SLE. Another test shows the level of a group of proteins in the blood called complement. People with lupus often have low complement levels, especially during an exacerbation of the disease.
Diagnostic rules for SLE
- Questioning about the appearance of signs of the disease (history of the disease), the presence of relatives with any diseases
- Full medical examination (from head to toe)
Laboratory examination:
- General clinical blood test with counting of all blood cells: leukocytes, erythrocytes, platelets
- General urine analysis
- Biochemical blood test
- Study of total complement and some complement components, which are often detected in low and high SLE activity
- Antinuclear antibody testing - positive titers in most patients, but positivity may be due to other reasons
- Test for other autoantibodies (anti-double-stranded DNA, anti-ribunucleoprotein (RNP), anti-Ro, anti-La) – one or more of these tests are positive in SLE
- The Wasserman reaction study is a blood test for syphilis, which in the case of SLE patients is a false positive, and not an indicator of syphilis disease
- Skin and/or kidney biopsy
Treatment of systemic lupus erythematosus
Treatment tactics for SLE are strictly individual and may change over the course of the disease. Diagnosis and treatment of lupus is often a joint effort between the patient and doctors and specialists in various specialties. The patient can see a family doctor or general practitioner, or can visit a rheumatologist. A rheumatologist is a doctor who specializes in arthritis and other diseases of the joints, bones and muscles. Clinical immunologists (doctors who specialize in immune system disorders) may also treat patients with lupus. Other professionals often help in the treatment process: these may include nurses, psychologists, social workers and also medical specialists such as nephrologists (doctors who treat kidney diseases), hematologists (who specialize in blood disorders), dermatologists (doctors who treat skin diseases ) and neurologists (doctors specializing in disorders of the nervous system).
Emerging new directions and effectiveness of lupus treatment give doctors more choice in their approach to treating the disease. It is very important for the patient to work closely with the doctor and take an active part in their treatment. Having diagnosed lupus once, the doctor plans treatment based on the patient’s gender, age, condition at the time of examination, onset of the disease, clinical symptoms and living conditions. SLE treatment tactics are strictly individual and may change periodically. Developing a treatment plan has several goals: to prevent flare-ups, treat them when they occur, and minimize complications. The doctor and patient should evaluate the treatment plan regularly to ensure that it is most effective.
Several types of medications are used to treat SLE. The doctor chooses treatment based on the symptoms and needs of each patient individually. For patients with pain and swelling of the joints, and increased joint temperature, medications are used that reduce inflammation and belong to non-steroidal anti-inflammatory drugs (NSAIDs), they are often used. NSAIDs may be used alone or in combination with other medications to control pain, swelling, or fever. When purchasing NSAIDs, it is important to follow your doctor's instructions, as the dosage for lupus patients may differ from the dosage recommended on the package. Common side effects of NSAIDs may include stomach upset, heartburn, diarrhea, and fluid retention. Some patients also report developing signs of liver or kidney damage while taking NSAIDs, so it is especially important for the patient to remain in close contact with the doctor while taking these drugs.
NON-STEROID ANTI-INFLAMMATORY DRUGS (NSAIDS)
Antimalarial drugs are also used to treat lupus. These drugs were originally used to treat the symptoms of malaria, but doctors have found that they also help with lupus, especially the skin form. It's not exactly known how antimalarial drugs "work" in lupus, but scientists think it does so by suppressing certain stages of the immune response. It has now been proven that these drugs, by affecting platelets, have an antithrombotic effect, and another positive effect of them is their hypolipidemic property. Specific antimalarials used to treat lupus include hydroxychloroquine (Plaquenil), chloroquine (Aralen), quinacrine (Atabrine). They can be used alone or in combination with other drugs and are mainly used to treat chronic fatigue syndrome, joint pain, skin rashes and lung damage. Scientists have proven that long-term treatment with antimalarial drugs can prevent the recurrence of the disease. Side effects of antimalarial drugs can include stomach upset and, quite rarely, damage to the retina, hearing, and dizziness. The appearance of photophobia, violation of color perception when taking these drugs requires an appeal to an ophthalmologist. SLE patients receiving antimalarial drugs should be examined by an ophthalmologist at least once every 6 months when treated with Plaquenil and once every 3 months when using Delagil.
The main treatment for SLE is corticosteroid hormones, which include prednisolone (Deltazone), hydrocortisone, methylprednisolone (Medrol) and dexamethasone (Decadron, Hexadrol). Sometimes in everyday life this group of drugs is called steroids, but this is not the same as anabolic steroids, used by some athletes to build muscle mass. These drugs are synthetic forms of hormones that are normally produced by the adrenal glands, endocrine glands located in the abdominal cavity above the kidneys. Corticosteroids refer to cortisol, which is a natural anti-inflammatory hormone that quickly suppresses inflammation. Cortisone and later hydrocortisone are one of the first drugs of this family, the use of which in life-threatening conditions in various diseases helped many thousands of patients survive. Corticosteroids may be given as tablets, skin cream, or injection. Since these are potent medications, the doctor will select the lowest dose with the greatest effect. Typically, the dose of hormones depends on the degree of disease activity, as well as the organs involved in the process. Damage to the kidneys or nervous system alone is already the basis for very high doses of corticosteroids. Short-term (rapidly resolving) side effects of corticosteroids include abnormal fat distribution (moon face, hump-like fat deposits on the back), increased appetite, weight gain, and emotional instability. These side effects generally disappear when the dose is reduced or the drugs are discontinued. But you cannot immediately stop taking corticosteroids, or quickly reduce their dose, so cooperation between the doctor and the patient is very important when changing the dose of corticosteroids. Sometimes doctors give a very large dose of corticosteroids by vein (“bolus” or “pulse” therapy). With this treatment, typical side effects are less severe and a gradual dose reduction is not necessary. It is important that the patient keep a medication diary, which should record the initial dose of corticosteroids, the beginning of their reduction and the rate of reduction. This will help the doctor evaluate the results of therapy. Unfortunately, in practice, in recent years we have often encountered drug withdrawal, even for a short period, due to the lack of the drug in the pharmacy chain. A patient with SLE should have a supply of corticosteroids, taking into account weekends or holidays. If prednisolone is not available in the pharmacy network, it can be replaced with any other drug from this group. In the table below we give the equivalent 5mg. (1 tablet) prednisolone doses of other corticosteroid analogues.
Table. Average equivalent anti-inflammatory potential of cortisone and analogues based on tablet size
Despite the abundance of derivatives of corticosteroids, prednisolone and methylprednisolone are desirable for long-term use, since the side effects of other drugs, especially fluorine-containing drugs, are more pronounced.
Long-term side effects of corticosteroids can include stretching scars - stretch marks on the skin, excessive hair growth, due to increased removal of calcium from the bones, the latter become fragile - secondary (drug-induced) osteoprosis develops. Undesirable effects during treatment with corticosteroids include increased blood pressure, damage to the arteries due to impaired cholesterol metabolism, increased blood sugar, infections are easily associated and, finally, the early development of cataracts. Typically, the higher the dose of corticosteroids, the more severe the side effects. Also, the longer they are taken, the greater the risk of side effects. Scientists are working to develop alternative pathways to limit or compensate for corticosteroid use. For example, corticosteroids may be used in combination with other, less potent medications, or the doctor may try to slowly reduce the dose after the condition has been stabilized for a long time. Lupus patients who take corticosteroids should take supplemental calcium and vitamin D to reduce the risk of developing osteoporosis (weak, brittle bones).
Another undesirable effect of synthetic corticosteroids is associated with the development of shrinkage (shrinkage) of the adrenal glands. This is due to the fact that the adrenal glands stop or reduce the production of natural corticosteroids and this fact is very important in understanding why you should not suddenly stop taking these drugs. First, taking synthetic hormones should not be interrupted suddenly, since it takes time (up to several months) for the adrenal glands to begin producing natural hormones again. Sudden cessation of corticosteroids is life-threatening and may result in acute vascular crises. This is why the reduction in the dose of corticosteroids should occur very slowly over weeks or even months, since during this period the adrenal glands can adapt to the production of natural hormone. The second thing to consider when taking corticosteroids is any physical stress or emotional stress, including surgery; tooth extraction requires additional corticosteroids.
For SLE patients who have vital organ involvement, such as the kidneys or central nervous system, or multiple organ involvement, medications called immunosuppressants may be used. Immunosuppressants, such as azathioprine (Imuran) and cyclophosphamide (Cytoxan), curb an overactive immune system by blocking the production of some immune cells and inhibiting the action of others. The group of these drugs also includes methotrexate (Folex, Mexat, Rheumatrex). These medications may be given as tablets or as an infusion (dropping the medication into a vein through a small tube). Side effects may include nausea, vomiting, hair loss, bladder problems, decreased fertility, and an increased risk of cancer or infection. The risk of side effects increases with the duration of treatment. As with other types of treatment for lupus, there is a risk of relapse of symptoms after discontinuation of immunosuppressive drugs, so treatment must be long-term and discontinuation and dose adjustment requires careful medical supervision. Patients receiving therapy with immunosuppressive drugs should also carefully record the dose of these drugs in their diary. Patients taking these drugs should regularly undergo a general blood and urine test 1-2 times a week, and it must be remembered that if a secondary infection occurs or the number of blood cells decreases (leukocytes below 3 thousand, platelets below 100 thousand), the drug is temporarily stopped. Resumption of treatment is possible after normalization of the condition.
Patients with SLE, who have multiple organ systems affected and are often accompanied by a secondary infection, can receive, in addition to corticosteroids, intravenous immunoglobulin, a blood protein that improves immunity and helps fight infection. Immuglobulin can also be used for acute bleeding in patients with SLE and thrombocytopenia or in the presence of infections (sepsis), or to prepare a patient with lupus for surgery. This makes it possible to reduce the dose of corticosteroids needed when megadoses are indicated in such conditions.
The patient's work in close contact with the doctor helps ensure that the treatment is chosen correctly. Because some medications can cause unwanted effects, it is important to report any new symptoms to your doctor right away. It is also important not to stop or change treatments without talking to your doctor first.
Because of the type and cost of medications used to treat lupus, their possible serious side effects, and the lack of a cure, many patients seek other ways to treat the disease. Some alternative attempts that have been suggested include special diets, nutritional supplements, fish oils, ointments and creams, chiropractic treatments and homeopathy. Although these methods may not be harmful in themselves, there is currently no research showing that they help. Some alternative or complementary approaches may help a patient cope with or reduce some of the stress associated with chronic illness. If the doctor feels that the attempt might help and would not be harmful, it may be included in the treatment plan. However, it is important not to neglect regular health care or treat serious symptoms with medications prescribed by your doctor.
Lupus and quality of life.
Despite the symptoms of lupus and the possible side effects of treatment, sufferers can generally maintain a high standard of living. To cope with lupus, you need to understand the disease and its effects on the body. By learning to recognize and prevent signs of SLE worsening, the patient can try to prevent its worsening or decrease in its intensity. Many people with lupus experience fatigue, pain, rash, fever, abdominal discomfort, headache, or dizziness just before a lupus flare-up. In some patients, prolonged exposure to the sun can provoke an exacerbation, so it is important to plan adequate rest and spend time outdoors during a shorter period of insolation (exposure to sunlight). It is also important for lupus patients to take regular care of their health, despite only seeking help when symptoms worsen. Constant medical monitoring and laboratory tests allow the doctor to notice any changes, which can help prevent exacerbation.
Signs of exacerbation of the disease
- Increased fatigue
- Pain in muscles, joints
- Fever
- Discomfort in the abdomen
- Headache
- Dizziness
- Preventing exacerbation
- Learn to recognize the initial signs of exacerbation, but not be intimidated by a chronic disease
- Reach an understanding with the doctor
- Define realistic goals and priorities
- Limit your time in the sun
- Achieve health with a balanced diet
- Try to limit stress
- Schedule adequate rest and sufficient time
- Moderate exercise whenever possible
The treatment plan is tailored to suit individual specific needs and circumstances. If new symptoms are detected early, treatment may be more successful. The doctor can advise on issues such as using sun protection, reducing stress and the importance of maintaining a routine, planning activities and rest, as well as birth control and family planning. Because people with lupus are more susceptible to infections, your doctor may recommend early cold vaccination for some patients.
Patients with lupus should undergo periodic examinations, such as gynecological and breast examinations. Regular oral hygiene will help avoid potentially dangerous infections. If the patient is taking corticosteroids or antimalarial drugs, an annual examination by an eye doctor should be performed to identify and treat eye problems.
Staying healthy requires extra effort and help, so it becomes especially important to develop a strategy for maintaining good health. Wellness includes increased attention to the body, mind and soul. One of the first wellness goals for people with lupus is to cope with the stress of acquiring a chronic disease. Effective stress management differs from person to person. Some attempts that may help include exercise, relaxation techniques such as meditation, and proper scheduling of work and free time.
- Find a doctor who will listen to you carefully
- Provide complete and accurate medical information
- Prepare a list of your questions and wishes
- Be honest and share your point of view on issues of concern with your doctor
- Ask to find out or explain your future if you are concerned about it
- Talk to other health professionals caring for you (nurse, therapist, neurologist)
- Feel free to discuss some intimate issues with your doctor (for example: fertility, contraception)
- Discuss any questions about changing treatment or using specific methods (herbal medicine, psychics, etc.)
Developing and strengthening a good support system is also very important. The support system may include family, friends, medical professionals, and in the United States these include community organizations and so-called support group organizations. Participation in support groups can provide emotional help, support for self-esteem and morale, and help develop or improve self-management skills. Learning more about your condition may also help. Research has shown that patients who are well-informed and proactive in taking care of themselves report less pain, visit the doctor less often, are more self-confident and remain more active.
Pregnancy and contraception for women with lupus.
Twenty years ago, women with lupus were discouraged from getting pregnant due to the high risk of worsening the disease and increasing the likelihood of miscarriage. Thanks to research and compassionate treatment, more women with SLE can have successful pregnancies. Although pregnancy is still high-risk, most women with lupus carry their baby safely to term until the end of the pregnancy. However, 20-25% of lupus pregnancies end in miscarriage, compared to 10-15% of pregnancies without the disease. It is important to discuss or plan for having a baby before you become pregnant. Ideally, a woman should not have signs or symptoms of lupus and not take medications in the 6 months before pregnancy.
Some women may experience mild to moderate flare-ups during or after pregnancy, others do not. Pregnant women with lupus, especially those taking corticosteroids, are more likely to develop high blood pressure, diabetes, hyperglycemia (high blood sugar) and kidney complications, so ongoing care and good nutrition during pregnancy are important. It is also advisable to have access to neonatal intensive care units during delivery in case the baby requires emergency medical attention. About 25% (1 in 4) of children of women with lupus are born prematurely, but do not suffer from birth defects, and subsequently do not lag behind in development, both physically and mentally, from their peers. Pregnant women with SLE should not stop taking prednisolone; only a rheumatologist can evaluate the dose of these drugs based on clinical and laboratory parameters.
It is important to consider treatment choices during pregnancy. The woman and her doctor must weigh the potential risks against the benefits for mother and baby. Some medications used to treat lupus should not be used during pregnancy because they may harm the baby or cause miscarriage. A woman with lupus who becomes pregnant needs to work closely with her obstetrician-gynecologist and rheumatologist. They can work together to assess her individual needs and circumstances.
The possibility of miscarriage is very real for many pregnant women with lupus. Researchers have now identified two closely related lupus autoantibodies: anticardiolipin antibodies and lupus anticoagulant (collectively called antiphospholipid antibodies), which are associated with the risk of miscarriage. More than half of all women with SLE have these antibodies, which can be detected by blood tests. Identifying these antibodies early during pregnancy can help doctors take steps to reduce the risk of miscarriage. Pregnant women who test positive for these antibodies and who have previously had miscarriages are generally treated with aspirin or heparin (preferably low molecular weight heparins) throughout pregnancy. In a small percentage of cases, children of women with specific antibodies, called anti-po and anti-la, have lupus symptoms, such as a rash or low blood cell counts. These symptoms are almost always temporary and do not require specific therapy. Most children with symptoms of neonatal lupus do not need treatment at all.
Even if, during an exacerbation of the SLE disease, fertility (the ability to become pregnant) decreases somewhat, there is a risk of pregnancy. An unplanned pregnancy during an exacerbation of SLE can negatively affect both the woman’s health, aggravating the symptoms of the disease, and create problems with pregnancy. The safest method of contraception for women with SLE is the use of various caps, diaphragms with contraceptive gels. At the same time, some women can use contraceptive medications for oral administration, but among them it is undesirable to take those with a predominant estrogen content. Intrauterine devices can also be used, but it must be remembered that the risk of developing a secondary infection in women with SLE is higher compared to a woman without this disease.
Exercise and SLE
It is important for SLE patients to continue their daily morning exercise. It is easier to continue when the disease is inactive or during an exacerbation you begin to feel better. Although, even during an exacerbation, some exercises are possible that do not require much physical exertion, which will help in some way to distract from the disease. Additionally, starting to incorporate exercise early will help you overcome muscle weakness. Physiotherapists should help you choose an individual set of exercises, which may include a complex for the respiratory and cardiovascular systems. Short walks with a gradual increase in time and distance, after the disappearance of fever and acute signs of the disease, will only benefit the patient not only in strengthening his own health, but also in overcoming chronic fatigue syndrome. It must be remembered that patients with SLE need balanced rest and physical activity. Don't try to do many things at once. Be realistic. Plan ahead, pace yourself, and schedule most difficult activities for a time when you feel better.
Diet
A balanced diet is one of the important parts of the treatment plan. If the disease is active and your appetite is poor, taking a multivitamin may be helpful, which may be recommended by your doctor. However, we remind you once again that excessive use of vitamins and exercise can complicate your illness.
Regarding alcohol, the main advice for SLE patients is abstinence. Alcohol has a potentially harmful effect on the liver, especially when taking medications such as methotrexate, cyclosphosphamide, and azathioprine.
Sun and artificial ultraviolet radiation
More than one third of SLE patients are too sensitive to sunlight (photosensitivity). Staying in the sun even for a short period of time (no more than 30 minutes) or procedures with ultraviolet radiation cause the appearance of various rashes on the skin in 60-80% of patients with SLE. Sun rays can generalize manifestations of cutaneous vasculitis, cause exacerbation of SLE, with manifestations of fever or involvement of other vital organs - kidneys, heart, central nervous system. The degree of photosensitivity may vary depending on the activity of SLE.
Current research.
Lupus is a topic of much research as scientists try to determine what causes lupus and how best to treat it. This disease is now considered a model of autoimmune diseases. Therefore, understanding the many disease mechanisms in SLE is key to understanding the immune abnormalities that occur in many human diseases. And this includes atherosclerosis, cancer, infectious diseases and many others. Some questions scientists are working on include: What exactly causes lupus and why? Why do women get sick more often than men? Why are there more cases of lupus in some racial and ethnic groups? What is disturbed in the immune system and why? How can we correct the functions of the immune system when it is disturbed? How to treat to reduce or cure the symptoms of lupus?
To help answer these questions, scientists are doing everything they can to better understand this disease. They conduct laboratory studies that compare various aspects of the immune system of lupus patients and healthy people without lupus. Special breeds of mice with disorders similar to those found in lupus are also being used to explain how the immune system functions in the disease and to identify the possibility of new treatments.
An active area of research is identifying genes that play a role in the development of lupus. For example, scientists suspect that lupus patients have a genetic defect in a cellular process called apoptosis, or “programmed cell death.” Apoptosis allows the body to safely get rid of cells that are damaged or potentially harmful to the body. If there is a problem with the apoptosis process, harmful cells can linger and damage the body's own tissues. For example, in a mutant breed of mice that develop a lupus-like disease, one of the genes that controls apoptosis, called the Fas gene, is defective. When it is replaced by the normal gene, the mice no longer develop signs of the disease. Researchers are trying to figure out what role genes involved in apoptosis may play in the development of human diseases.
Studying the genes that control complement, a series of blood proteins that are an important part of the immune system, is another active area of research in lupus. Complement helps antibodies destroy foreign substances that attack the body. If there is a decrease in complement, the body is less able to fight or break down foreign substances. If these substances do not leave the body, the immune system can become very active and begin to produce autoantibodies.
Research is also underway to identify genes that predispose some people to more serious complications of lupus, such as kidney disease. Scientists have identified a gene associated with an increased risk of kidney damage from lupus in African Americans. Changes in this gene affect the ability of the immune system to remove potentially harmful immune complexes from the body. Researchers have also made some progress in finding other genes that play a role in lupus.
Scientists are also studying other factors that affect a person's susceptibility to lupus. For example, lupus is more common in women than in men, so some researchers are looking into the role of hormones and other differences between men and women in causing the disease.
The current study, conducted by the National Institutes of Health in the United States, focuses on the safety and effectiveness of oral contraceptives (birth control pills) and hormone replacement therapy for lupus. Doctors worry about the common sense of prescribing oral contraceptives or estrogen replacement therapy for women with lupus, as it is widely believed that estrogens can make the disease worse. However, recent limited evidence suggests that these medications may be safe for some women with lupus. The scientists hope this study will provide a choice for safe, effective birth control methods for young women with lupus and the possibility of postmenopausal women with lupus using estrogen replacement therapy.
At the same time, work is underway to find a more successful treatment for lupus. A major goal of current research is the development of treatments that can effectively reduce the use of corticosteroids. Scientists are trying to identify a combination of drugs that would be more effective than trying to treat with a single drug. Researchers are also interested in using male hormones called androgens as a possible treatment for the disease. Another goal is to improve the treatment of lupus complications in the kidneys and central nervous system. For example, a 20-year study found that the combination of cyclophosphamide and prednisolone helped delay or prevent kidney failure, one of the severe complications of lupus.
Based on new information about the disease process, scientists are using new "biological agents" to selectively block parts of the immune system. The development and testing of these new drugs, which are based on a compound that occurs naturally in the body, is an exciting and promising new area of lupus research. It is hoped that these drugs will not only be effective, but will also have few side effects. The treatment of choice currently being developed is the reconstruction of the immune system through bone marrow transplantation. In the future, gene therapy will also play an important role in the treatment of lupus. However, the development of scientific research also requires large material costs.
