Systemic lupus erythematosus (SLE)Systemic lupus erythematosus is a chronic inflammatory autoimmune disease characterized by vasculitis and immune complex deposition.
Systemic lupus erythematosus (SLE): Overview
Lupus erythematosus disseminatus, SLE, Erythemadodes visceralis
Systemic lupus erythematosus is classified as a collagenosis. It is an autoimmune disease and can theoretically affect any organ or organ system. The disease is characterized by the formation of autoantibodies against cell nuclear components. The course of the disease may be acute or subacute. Mostly, however, it is chronically recurrent.
The prevalence of the disease is about 30-50 cases/100.000 inhabitants in Europe. Systemic lupus erythematosus occurs worldwide. However, prevalence is highest among Africans, African Americans and Latin Americans. Systemic lupus erythematosus affects women four times more often than men (in Germany). The disease frequently manifests between the ages of 20. and 40. Year of life.
The etiology of the disease is unknown. A multifactorial genesis seems most likely to be present.
Genetic and hormonal factors are thought to be involved.B. Estrogens, play a role. In addition, a disturbed immune regulation (z.B. T-cell driven B-cell activation). Also, the involvement of environmental factors, for example, infections (z.B. Epstein-Barr virus) and UV light exposure, in the etiology of the disease are discussed. Nicotine abuse also favors the manifestation and activity of SLE.
In SLE patients, it has been shown that increased apoptosis and clearance defects of apoptotic material and immune complexes result in increased nuclear proteins. The immune complexes that are formed from the autoantibodies and the DNA or. ribonucleoproteins form with RNA, bind to Toll-like receptors on dendritic cells and monocytes, and lead to the formation of interferon-alpha. B-cell hyperactivity occurs, which increases the production of various autoantibodies.
In addition, the immune complexes can induce glomerulonephritis by binding to the basement membrane in the kidneys, where they u.a. lead to an activation of the complement system.
Systemic lupus erythematosus is accompanied by general symptoms such as fever, fatigue and weight loss. Initial symptoms, in particular, are nonspecific. In 95% of patients the musculoskeletal system is also affected by the disease. This manifests as arthralgias, myalgias and non-erosive arthritis. Chronic recurrent arthritides particularly affect the finger joints. This can lead to joint deformities. In addition, skin involvement is present in about 80% of cases. This leads to the appearance of photosensitivity. In 50% of cases to the characteristic butterfly erythema.
In addition, the nervous system may be affected. Patients then show, for example, cognitive changes, psychosis and also headaches. Pulmonary involvement can lead to pleurisy with recurrent pleural effusions. The heart can also be affected, which can manifest itself in pericarditis and coronary arteritis, for example. Early arteriosclerosis may occur in SLE patients. With associated complications, is one of the leading causes of death in SLE.
The kidney can also be affected by the disease in the context of lupus nephritis, a glomerulonephritis with proteinuria and erythrocyturia. About 50% of patients have renal involvement. Gastrointestinal involvement can lead to nausea, diarrhea, cheilitis, esophagitis, etc. lead. In addition, ocular involvement may be associated with, for example, sicca syndrome and conjunctivitis. At the beginning of the diagnostic process is the medical history. Physical examination of the patient. Diagnosis is based on characteristic clinical symptoms of skin, joints, etc. and on serological parameters. If SLE is suspected, a screening laboratory should be performed first. This includes ESR, CRP, differential blood count, renal parameters such as serum creatinine, urine status and sediment, and antinuclear antibodies (ANA). Almost all lupus patients have elevated ANA, but many healthy people do as well.
Therefore, additional criteria must be considered to establish the diagnosis of SLE. The so-called ACR (American College of Rheumatology)/EULAR (European League Against Rheumatism) criteria are available for this purpose. Four of the 11 criteria are required. In addition, the SLICC (Systemic Lupus International Collaborating Clinics) classification exists. To meet SLICC criteria, four criteria (at least one clinical. An immunologic) present or histologic diagnosis of lupus nephritis with positive ANA or positive dsDNA antibody evidence. The 17-SLICC criteria include clinical criteria and immunological criteria. Clinical criteria include oral ulcers, non-scarring alopecia, acute cutaneous lupus erythematosus including butterfly erythema, and synovitis of > 2 Joints. Immunological criteria include, for example, ANA titers above the laboratory reference value, the presence of anti-dsDNA antibodies, anti-Sm antibodies, and anti-phospholipid antibodies.
Inflammation of the kidney detected by biopsy is highly suggestive of SLE. In addition, it should be noted that the criteria may only be counted if no better explanation than SLE can be found for them.
Both classifications are currently used in parallel. Further diagnosis of SLE should be symptom-oriented. Involve interdisciplinary specialists of the corresponding discipline.
Various comorbidities can occur with SLE. These include, in particular, antiphosphoilipid syndrome, infectious diseases and cardiovascular diseases.
There is no causal therapy. The main goals of SLE therapy are to increase patient survival, prevent organ damage, and improve quality of life.
If possible, remission or at least low disease activity should be aimed for, which can usually be achieved by using the lowest possible glucocorticoid dose. According to the severity of each organ involvement, the appropriate ongoing therapies (glucocorticoids, immunomodulatory agents) should be adjusted by increasing the dose or changing the agents or adding new drugs.
General drug therapy
Different drugs are available in SLE therapy.
Unless contraindications exist, EULAR recommends the use of hydroxychloroquine (HCQ) in all SLE patients. Long-term use of HCQ may be associated with retinal toxicity. Therefore, ophthalmologic examinations should be performed before starting the therapy as well as after 5 years and annually thereafter. To minimize toxicity, a total daily dose of 5mg/kg body weight should not be exceeded.
Depending on the severity of the organ involvement, different dosages and forms of application should be chosen. A shock therapy using 250-1000 mg methylprednisolone i.v. promises an immediate therapeutic effect and allows to start with a low-dose oral glucocorticoid therapy. As maintenance therapy, EULAR recommends immunosuppressive therapy
Immunomodulatory therapy should be evaluated in patients who do not respond to HCQ therapy (alone or in combination with glucocorticoids) or patients in whom glucocorticoid therapy cannot be reduced to doses acceptable for maintenance therapy.
In SLE therapy, methotrexate, azathioprine or mycophenolate are available for this purpose. Cyclophosphamide can be used both in cases of impending severe organ damage or life-threatening courses of SLE and as salvage therapy in patients who do not respond to any other immunosuppressive drug.
In patients in whom both HCQ therapy and immunomodulatory therapy have failed to achieve sufficient therapeutic success, add-on therapy using belimumab may be considered.
In organ-threatening refractory patients or when intolerance/contraindications to the standard immunomodulatory agents are present, therapy with rituximab can be evaluated.
First-line therapy for skin involvement includes topical preparations (calcineurin inhibitors, antimalarials [HCQ, Quinacrine], and/or systemic glucocorticoids). In addition, methotrexate, retinoids, dapsone, or mycophenolate may be added to therapy if there is an inadequate response to therapy. EULAR recommends the use of glucocorticoids/immunosuppressants in neuropsychiatric involvement of SLE. Antiplatelet/anticoagulant therapy for atherothrombotic manifestations.
The acute therapy of SLE with hematologic involvement (z.B. Thrombocytopenia and autoimmune hemolytic anemia) includes high-dose glucocorticoid therapy and/or intravenous immunoglobulin G administration.
Immunosuppressive drugs such as myciophenolate, azathioprine, or cyclosporine may be used for maintenance therapy. Refractory cases can be treated with rituximab or cyclophosphamide.
For optimal therapeutic outcome, it is important to recognize early signs of renal involvement. Mycophenolate or low-dose intravenous cyclophosphamide is recommended by EULAR as initial therapy for renal involvement. In patients at high risk of renal failure, a similar therapeutic regimen should be used with the change that cyclophosphamide can be used in high doses intravenously. For maintenance therapy, mycophenolate or azathioprine can be used. In severe nephrotic syndrome or incomplete response to therapy, mycophenolate may be combined with low-dose calcineurin inhibitors.
SLE patients have an increased susceptibility to infections. Several factors contribute to this: On the one hand, immunosuppressive conditions result from drug therapy (e.g.B. with glucocorticoids) and secondly from high disease activity, severe leukocytopenia and the presence of renal involvement (±hypogammaglobulinemia in nephrotic syndrome).
SLE patients should be recommended to be vaccinated according to the EULAR recommendations. These include, for example, influenza vaccinations. Vaccinations against pneumococci. Vaccination protection in SLE should be regularly checked and updated. In addition, it is critical to diagnose sepsis promptly in SLE patients and initiate therapy.
SLE is a chronic autoimmune disease. Its course is variable from individual to individual, usually episodic, especially initially. As a rule, the intensity decreases over the years and the attacks become less frequent and less severe. In recent years, the life expectancy of patients has increased significantly and the 5-year survival rate is currently >90%. The most frequent complications of SLE are cardiac and vascular diseases. Kidney or CNS involvement in the disease is considered particularly unfavorable in terms of prognosis.
Sunlight can activate SLE. Therefore, consistent sun protection (UV protection) is recommended.