Lupus disease symptoms, what causes it and what are the treatment methods?

Lupus (SLE) is a chronic autoimmune disease in which the body’s immune system becomes overactive and attacks normal, healthy tissue, causing inflammation throughout your body.

Immune system; It is the mechanism that protects the body against diseases. A healthy diet is strengthened by adequate intake of minerals and vitamins. It works organized with lymph nodes in the body. If a disease-causing microbe enters the body, it stimulates the lymph nodes and produces warrior cells. These cells (antibodies) fight disease-causing microbes and try to protect the body.

In lupus, microbes take over the immune system. Accordingly, the immune system starts to damage the cells instead of protecting the body. In this disease, many organs such as the brain, blood cells, liver, lungs, kidneys, heart, joints, skin, and the surrounding cells are damaged by the immune system. In this respect, it is also called multifactorial inflammatory disease. Complaints occur in many different parts of the body of lupus patients. Therefore, the diagnosis of the disease is difficult.

It was first described as a chronic dermatological disorder by the French dermatologist Biett in 1833, and Cazanave used the name “Lupus erythematosus” in 1851. Osler drew attention to the systemic features of the disease in 1890. In 1948, Hargraves demonstrated the Lupus Erythematosus “LE” cell phenomenon, and in 1957 Frio demonstrated the presence of antinuclear antibodies (ANA) by indirect immunofluorescence method. Later, the detection of anti-DNA antibody proved the autoimmune feature of the disease and contributed to other developments. With the rapid increase in knowledge in the field of immunology and modern genetics, advances have been made in the pathogenesis and treatment of SLE, which is the prototype of systemic autoimmune diseases, in the last 10 years.

In the clinic, the disease varies from fever, swelling in the joints, erythematous rashes on the skin, to the involvement of organs and systems such as kidney, central nervous system and lung. Most of the patients may have nonspecific systemic symptoms such as fatigue, fever, muscle aches and weight loss, as well as specific organ and system symptoms. The disease may sometimes start with fever and imitate infection, or it may progress insidiously for months or years with symptoms of fever, fatigue, and malaise.

Quick Facts About Lupus Disease

Lupus is an autoimmune disease that causes problems in the body’s immune system. It can be mild or life-threatening.
Lupus is not contagious.
The type we just call “lupus” is known as systemic lupus erythematosus or SLE.
More than 90% of lupus patients are women.
This disease is more common between the ages of 15 and 45.
Most doctors believe that lupus is due to genetic and environmental stimuli.
Risk factors include extreme stress, exposure to sun (ultraviolet) light, smoking, certain medications and antibiotics, infections, Epstein-Barr virus (in children) and exposure to certain chemicals.
Although there is no definitive cure for lupus, lupus and its symptoms can be controlled with medications.
Lupus treatment options include corticosteroids, immunosuppressive medications, and lifestyle changes.

What does lupus cause?

It causes a red rash called ‘butterfly rash’ on the cheeks and bridge of the nose. There is also a coin-shaped, scaly and raised rash on the face, scalp, ears, chest and arms, which can leave scars as it heals.
Sensitivity to light, excessive skin reaction to sunlight are observed. It is generally not seen in the part covered by clothing.
Small, painless sores may appear in the mouth or nose. Those in the nose can cause nosebleeds.
Joint pain and swelling affect the vast majority of lupus patients. Pain can move from one joint to another and may appear symmetrically in the same joints on both sides of the body.
Inflammation of the lungs and the layers surrounding the heart can cause fluid to collect around the heart and lungs. It causes a type of chest pain that increases with breathing.
Almost all patients with SLE have kidney damage. Initially, it is usually asymptomatic and can only be detected by urinalysis and blood tests for kidney function. Those with significant kidney damage may experience protein and/or blood in the urine and swelling, particularly in the feet and legs.
It can also cause damage to the central nervous system; Neuro-psychiatric problems such as headache, seizures and difficulty concentrating and remembering, mood changes, depression and psychosis (a serious mental condition in which thinking and behavior are impaired) may be observed.
May cause blood cell disorders.

The Effect of Lupus Fatigue and Pain on Activities of Daily Living

According to a study conducted at Ege University between 30.09.2009 and 15.05.2010 on the effect of pain and fatigue on daily life activities in patients with Systemic Lupus Erythematosus;

Fatigue Severity Scale mean score was 6.0 (tired); Activities of Daily Living Index score average of 18.0 (independent); Instrumental Activities of Daily Living Index mean score was 24.0 (independent); According to the McGill Pain Scale, the mean pain score at the time of question was 1.56 (disturbing).

A low-level negative correlation was found between fatigue and Instrumental Activities of Daily Living Index scores. As the Fatigue Severity Scale score increases, the Instrumental Daily Living Activities Index score decreases.

It was found that there was a moderately positive and significant relationship between the Fatigue Severity Scale and the Pain Scale scores. As the Fatigue Severity Scale score increases, the pain severity score also increases.

This research has shown that pain and fatigue affect the daily living activities of patients with Systemic Lupus Erythematosus.

epidemiology

Although the frequency of SLE varies depending on the characteristics of the population studied (age, gender, ethnicity) and factors such as the duration of the study, it is thought to be 15-40/100.000. Since mild forms of the disease can be recognized earlier today, it is observed that the frequency of the disease is gradually increasing. It is 3-4 times more common in black race compared to white race. The female/male ratio is 9/1. The disease is common in women, especially during their childbearing years. The age of onset in 65% of the patients is between 16-55 years, 20% of the cases are diagnosed under the age of 16 and 15% are diagnosed above the age of 55. In childhood, girls are three times more likely to get sick than boys.

etiopathogenesis

The exact cause of the disease is unknown. Hormones play an important role in the pathogenesis of SLE, along with genetic and environmental factors. These factors contribute to the initiation of the immune response against endogenous antigens by causing the breakdown of immune tolerance.

A. Genetic Factors

There have been findings supporting the importance of genetic predisposition in some populations, families or twins. The probability of co-occurrence is 25% in identical twins and around 5% in fraternal twins. The incidence of the disease in more than one member of the same family was found to be between 5-12%. Other members of the asymptomatic family may have some similar blood tests positive. Studies have shown the importance of genes related to immune response and inflammation, and that all components of the disease immune system are mainly affected. It supports the effect of multiple genes in the development of SLE. However, genetic factors alone are not sufficient in the formation of the disease, the contribution of other factors is also important.

B. Environmental Factors

It is well known that environmental factors such as stress, medications, ultraviolet rays and infections trigger subtypes of the disease.

a. Infections: Infectious agents, especially viruses and some bacteria, have been seen as activating the disease. Some viruses and bacteria, toxins in the environment, and certain chemicals can lead to overactivity of the disease.

b. Sun Rays (UV): Sunlight is an environmental factor that triggers the development and exacerbation of the disease. Approximately 50% of patients describe light sensitivity, especially ultraviolet B is blamed.

c. Medications: Long-term use of some drugs, such as procaine amide, hydralazine, diphenilhydantoin, and isoniazid, causes ANA production and clinically lupus-like symptoms can be seen, this is known as “drug-induced lupus” or “lupus-like syndrome”. The common feature of these drugs and their metabolites is that they contain reactive aromatic amine and hydrazine groups, but their mechanism of action is not well known.

C. Hormones

Female gender is an important risk factor for the development of SLE. Estrogen, one of the sex hormones, increases the production of antibodies, while testosterone decreases it. Abnormalities in estrogen and androgen metabolism have been found in patients with SLE and mouse models of lupus. In male and female patients with SLE, increased estrogen hydroxylation and prolonged estrogenic stimulation can lead to B lymphocyte hyperactivity and various immune regulation abnormalities.

Symptoms of Lupus Disease

Since lupus can affect the whole body, it can present with very different signs and symptoms. Especially in the initial stages of the disease, joint pain and general disease symptoms are common. Some of the most common signs and symptoms of lupus are;

Tiredness
Weakness
Skin changes. A butterfly-shaped rash, especially on the nose and cheeks, is typical. However, a rash develops on any area of the skin that is exposed to the sun.
Findings related to inflammation in the veins. Small vessels of the skin are often affected and inflammation called vasculitis develops. There is a subcutaneous hemorrhage in the form of spots around the nails. It can also cause inflammation of the oral mucosa.
Hair-related findings. There may be regional shedding in the hair, and this hair loss usually does not replace the new ones.
Raynaud’s syndrome, in which there is a white and purple color change that occurs in the cold, is an important finding.
Joint findings. There is arthralgia, i.e. joint pain, in both large and small joints. The pain is more pronounced, especially in the morning. In some patients, swelling, redness and temperature increase due to arthritis, i.e. joint inflammation, are also seen.
Muscle involvement. Pain and inflammation develop in the muscles.
Kidney findings. Renal involvement is seen in 70% of patients. In these people, blood and protein are detected in the urine. Edema develops due to fluid retention in the tissues. In severe cases, kidney inflammation can be seen, which can progress to kidney failure.
There are symptoms and psychological problems related to the nervous system such as migraine, epilepsy, balance problems. Stroke may occur in some patients.
Digestive problems are common due to gastrointestinal involvement and pancreatitis.
There are signs of inflammation in the lining of the lungs or heart, such as chest pain. When there is fluid accumulation and inflammation between the lung membranes, a chest pain that increases with breathing occurs. Inflammation of the pericardium is called pericarditis and is common in lupus.
Pneumonia develops as a result of inflammation in the lung tissue.
There is enlargement of lymph nodes, spleen and liver.
Abdominal pain is seen because the peritoneum is inflamed.

Systemic Lupus Erythematosus Immunological and Pathological Features

Although the etiology is unknown, pathological findings related to cellular and humoral immunity disorders and immune regulation disorders are partially known.

Auto-antibodies have been found to be present years before the onset of lupus symptoms. The disease begins with the preclinical phase, in which auto antibodies are positive before the symptoms, and then more specific auto antibodies develop for the disease, but it has been reported that the presence of auto antibodies alone is not sufficient for the development of the disease, and genetic and environmental factors are also effective.

Pathology

The main pathological feature of SLE is inflammation and vascular pathology; It occurs with immune complex deposition and vasculitis/vasculopathy. Despite the presence of many pathological findings in SLE, their contribution to the diagnosis is not the same. A finding that strongly suggests a diagnosis of SLE is the presence of hematoxylin bodies.

A. Pathological Findings in Skin Lesions

Edema, vacuolization, fibrinoid necrosis, mononuclear cell infiltration around vessels and follicles may be found at the dermal-epidermal junction, hyperkeratosis, follicular plugs and atrophy of skin appendages may be found in chronic lesions. Deposits of immunoglobulin (IgG, IgM and IgA) and complement (C3) at the dermal-epidermal junction, which can be demonstrated by direct immunofluorescence method, indicate the presence of immune complexes in the tissue. This characteristic finding, which can also be seen in areas without skin lesions, is called “lupus band test”, it is helpful in diagnosis. , but can also be found in other connective tissue diseases such as rheumatoid arthritis and systemic sclerosis.

B. Pathological Findings in Vessels

Vasculitis of large vessels is rare, most patients have signs of vasculitis in small arteries and arterioles, more mononuclear cell infiltration and immune complex depositions in and around the vessel wall. Occlusive vasculopathy is common in the presence of antiphospholipid antibodies.

C. Pathological Findings in the Kidney

Most patients have changes in kidney biopsy. A classic finding for lupus on hematoxylin-eosin staining on light microscopy, the “wire loop” appearance shows eosinophilic thickening of the basement membrane of some glomerular capillary folds. In mild kidney pathology, mesangial cell increase with mesangial matrix thickening or segmental (focal) proliferation of glomerular capillary cells is observed. In diffuse proliferative glomerulonephritis, almost all glomeruli are involved in the disease, there is cell proliferation in and out of the capillaries, outward proliferation fills the Bowman capsule cavity, causing crescent (crescent) formation. Bowman’s capsule thickening leads to fibrous crescent formation. Immunofluorescence and electron microscopic examinations show immune deposits in the kidney. In lupus nephritis, interstitial inflammatory infiltrates, vasculitis and tubular lesions can be found outside the glomerulus.

D. Other Pathological Findings

Pericarditis is frequently seen in autopsy series, morphologically fibrinous exudate, edema on microscopic examination, cell infiltration around the vessel, fibrinoid necrosis and immune deposits are found. Clinically, severe myocardial disease is rare, with focal fibrinoid changes in small arteries and mild myocarditis with fibrinoid deposits close to the vessels, in the septa. Coronary artery disease and myocardial infarction may develop at an early age. The accelerating role of corticosteroids and hypertension in this clinical picture is known. Recurrent pleurisy and adhesions in the lung can lead to restrictive lung disease. Interstitial pneumonia may be seen. In the neuropathology of cerebral lupus, destructive and proliferative changes in small vessels are seen together with vasculitis, micro-infarcts and hemorrhages. Immunocomplexes can be found in the choroid plexus.

Clinical Findings

Systemic lupus erythematosus is a chronic disease with activation and remissions, and its onset and course differ from patient to patient. A progressive and rapid course is seen in a small number of patients. The typical disease picture is found in a minority of patients and facilitates the diagnosis. Diagnosis may be delayed in patients presenting with mild general symptoms. Clinically young age, alopecia, serositis, presence of discoid lupus are among the signs reminiscent of SLE.

1. General Symptoms

Non-specific general complaints such as malaise, fatigue, fever and weight loss are evident at the onset of the disease and during the activation periods, and the presence of skin, joint or other disease findings facilitates the diagnosis. Fever is present in approximately 80% of patients, usually a harbinger of disease activation and persists until appropriate treatment is given. Infectious causes must be ruled out before associating the fever symptom with SLE. Fatigue is found in 90% of patients, and anorexia and weight loss in 60% of patients. Chronic malaise and low-grade fever are two symptoms that often occur in a lupus exacerbation.

2. Musculoskeletal Findings

Joint manifestations are usually polyarticular, symmetrical, with occasional soft tissue swelling and arthralgia, and is the first symptom in approximately 90% of patients. Polyarthritis is less common, typically affecting the proximal interphalangeal and metacarpophalangeal joints, wrists, elbows, and ankles, often symmetrical. Short-term morning stiffness is found in 50% of patients. Due to joint features similar to rheumatoid arthritis, diagnosis may be difficult in the early stages of the disease. Inflammatory findings in the joint can sometimes be migratory or persistent, or become chronic.

Radiological findings are usually mild, there may be deformities around the joint or diffusely due to osteoporosis, soft tissue swelling and subluxations, but there is no erosion. Septic arthritis may rarely develop in patients receiving immunosuppressive therapy, which is confirmed by synovial fluid examination and culture results.

Depending on the disease or treatment, aseptic bone necrosis, which manifests itself with joint pain, mostly affects the hip, shoulder and knee joints in corticosteroid users.

Myalgia is present in 1/3 of patients at the onset of the disease and the muscles near the painful joint are affected. Some patients have muscle tenderness. Muscle weakness and muscle atrophy may also be present. Rarely, chronic myositis and fibrositis may develop. Myopathies due to corticosteroid or anti-malarial therapy are also seen.

3. Skin Lesions

After joint symptoms, skin findings (85%) are the most common. Histologically, there are lupus-specific and non-specific lesions. Specific ones; a. Acute, b. subacute and c. It is classified as chronic.

A. Specific Skin Lesions

a. Acute Skin Lesions:

The most characteristic acute skin lesion is malar rash, which is erythema localized on the face, back of the nose and cheeks, ranging from a slight pink to prominent redness. This appearance, which is similar to a butterfly according to the location, is also known as butterfly rash. It usually develops acutely, may be slightly edematous and itchy, nasolabial folds have normal skin color, are seen in approximately 50% of patients at the onset of the disease, persist for days or months, and usually increase with exposure to sunlight.

Erythema, telangiectasias and signs of inflammation around the nails (periungual) can be seen in various parts of the body, trunk, fingertips, sometimes palms or other parts of the skin exposed to mechanical trauma.

In the inactive stages of the disease, erythema tends to disappear without a trace. In some cases, when the erythema disappears, a brown pigmentation may remain. Bullous lesions are rare in SLE.

Sun sensitivity is detected in 50-60% of patients, besides an increase in skin lesions with sun rays, an increase in systemic findings can also be observed. Patients should be protected from the sun.

b. Subacute Cutaneous Lupus

Subacute cutaneous lupus is a superficial, non-scarring, sun-sensitive erythematous, characteristically annular lesions, usually located symmetrically on the shoulders, neck, and upper chest and back. Lesions progress with exacerbation and healing. Anti-Ro (SS-A) antibody is often positive. A relationship was found between subacute cutaneous lupus lesions and HLA-DR3 antigen.

B. Chronic Lesions

Discoid lesions may be present as a chronic skin finding in the clinical picture of SLE (10-15%), or may develop as a solitary skin lesion without SLE findings. The discoid lesion can be seen as a single or multiple lesion in the head and neck region, often on the face, on the zygomatic prominences, on the scalp, and on the outer ear, as well as commonly on the upper body and extremities. The lesion begins as well-demarcated, raised, purplish, erythematous macules or plaques, edematous in the acute stage. As the lesion develops, it is covered with squam adhered to the skin, usually heals by loss of pigment and leaving central atrophy, and lesions on the scalp and beard area cause permanent alopecia.

Diagnosis of Lupus

Lupus is diagnosed with the help of some blood tests along with clinical signs. Complete blood count, kidney tests, chest X-ray, LE cell, anti DNA and ANA are checked in the patients. If the physician deems it necessary and according to the suspected organ involvement, he may order many more tests. It is very difficult to diagnose in patients who initially do not show typical disease symptoms. SLE can be confused with many tissue diseases.

Clinical diagnosis is based on careful history, evaluation of clinical symptoms, and overall systemic examination. Routine blood and urine examination is required. SLE classification criteria, defined by the American Rheumatology Association (ARA) in 1982 and revised in 1997, are used to distinguish SLE from other similar conditions. If 4 out of 11 criteria were present in the patients, they were considered to be suitable for SLE criteria.

malar rash
discoid rash
sun sensitivity
Oral ulcers
non erosive arthritis
Serosite ( a) Pleuritis or b) pericarditis )
Kidney disorder (a) proteinuria> 0.5 g/day or 3+ or b) cell casts )
Neurological findings ( a) Seizures or b) psychosis )
Hematological disorders ( a) hemolytic anemia or b) leukopenia< 4000/mm3 (at least twice) or c) lymphopenia< 1500/mm3 (at least twice) or d) thrombocytopenia< 100 000/mm3 )
immunological disorders
1. Positive anti-ds-DNA antibody
2. Positive anti-Sm antibody
3. Presence of positive antiphospholipid antibodies;
4. Presence of IgG or IgM type anticardiolipin antibodies
5. Lupus anticoagulant test positivity with standard method
6. False-positive syphilis test positivity in the last 6 months
ANA positivity

Treatment of Lupus

There is no definite cure for lupus disease. Treatment is applied to stop the progression of the disease, prevent vital complications and relieve symptoms. Therefore, early diagnosis is of great importance. Because it is not possible to reverse the advanced disease.

Treatment is planned specifically for each patient according to the severity of the disease. It is essential to use anti-inflammatory drugs for inflammations occurring in many organs and tissues of the body. Steroid group drugs that suppress the immune system are also used. Anticoagulants such as aspirin are prescribed to patients with a tendency to blood clots.

As with most chronic autoimmune diseases, SLE is characterized by periods of low and high activity. It provides convenience in evaluating the activity of the disease at regular intervals, detecting activation periods early, initiating or changing the treatment. Treatment is planned according to the affected organs and is related to the type and severity of the findings. The complex picture of the disease requires the active participation of the patient as well as the physician in the continuation of the treatment. In general, patients who are not life-threatening and not associated with organ damage should be treated conservatively. Analgesics, NSAIDs and antimalarial drugs are given for this purpose. On the other hand, if the patient is at risk with irreversible loss of function of life-threatening major organs, aggressive treatment is required. This treatment includes immunosuppression. In some clinical manifestations of SLE, alternative treatment (such as anticoagulants, splenectomy, psychoactive drugs) other than immunosuppressive treatment and prophylactic treatment to prevent thrombosis may be required. Apart from these, ACE inhibitors or angiotensin II receptor blockers should be given to reduce proteinuria and protect renal functions, and statins should be given in case of hyperlipidemia. The main drugs used in the treatment of SLE are NSAIDs, anti-malarial drugs, glucocorticoids and immunosuppressive agents.

What the Patient Should Know About the Disease and Preventive Measures to be Taken

An emotional reaction and general uneasiness are observed in the newly diagnosed patient, therefore, the patient may need psychological support.

The patient should act carefully and consciously about sleep, rest, protection from sunlight, risk of infection, nutrition, exercise and birth control, and should consult a specialist when necessary.

In daily life, patients with SLE should rest more than normal. In case of active disease, importance should be given to rest.

Wide-brimmed hats and appropriate clothing should be worn to protect from ultraviolet light. It should not go out during the hours when the sun’s rays are strong. Ultraviolet B protective factor (> 15) creams should be used.

Some drugs (tetracycline) increase sensitivity to UV light.

In patients with lupus, conditions such as corticosteroid (cortisone) and immunosuppressive (immunosuppressive) therapy, heart valve abnormalities, ulcerated skin lesions, and chronic kidney failure increase the susceptibility to infection. It is important for patients with fever to apply to the physician in a short time, to examine whether there is an infection, and to start the necessary treatment early in appropriate doses.

Influenza (flu) vaccine should be given once a year.

Vaccines should be avoided during active periods of the disease. Immunization is less effective in patients on immunosuppressive therapy.

Surgery, infection, childbirth, miscarriage and psychological stress can exacerbate the disease.

Patients receiving chemotherapy and patients with active nephritis (kidney patients) should take contraceptive measures.

It is recommended that patients consult a doctor when they have symptoms such as unexplained weight loss, fatigue, fluid increase and fever.

With light or moderate exercises (including periods of rest and relaxation), joint movements are relieved, cardiovascular complications can be prevented.

In addition to the information that there is an increase in the risk of mild or moderate lupus exacerbation and thrombosis in ANA positive patients in the use of oral contraceptive drugs, the current approach can be considered for use in ANA negative, non-smoking young female patients with stable disease, and it is recommended to choose preparations containing low amounts of estrogen.

Note: Lupus is a serious immune chronic disease and may differ in each person, do not apply to alternative treatments and do not change your current treatment without consulting your specialist and living under the supervision of a doctor.