Systemic Lupus Erythematosus (SLE)
Last updated date: 28-Aug-2023
Originally Written in English
Systemic Lupus Erythematosus (SLE)
Systemic Lupus Erythematosus (SLE) is an autoimmune disease in which the immune system attacks its own tissues, resulting in extensive inflammation and tissue destruction in the organs involved. It has the potential to harm the joints, skin, brain, lungs, kidneys, and blood vessels. There is no cure for lupus, but medical treatments and lifestyle adjustments can help keep it under control.
The loss of immunological tolerance against self-antigens is influenced by genetic, immunological, endocrine, and environmental variables, resulting in the development of pathogenic autoantibodies that induce tissue damage via numerous pathways.
SLE diagnosis can be difficult, and while numerous categorization criteria have been proposed, their value in the clinical situation is still debatable. SLE management is controlled by organ system involvement, and despite various medicines that have been demonstrated to be effective in the treatment of SLE, the illness still poses a high morbidity and mortality risk in patients.
Systemic lupus erythematosus definition
Systemic lupus erythematosus (SLE) is an autoimmune disorder that affects many organ systems. There are numerous phenotypes of the illness, with clinical symptoms ranging from modest mucocutaneous signs to multiorgan and severe central nervous system involvement in individuals. Several immunopathogenic mechanisms contribute to the onset of SLE.
Hargraves identified the lupus erythematosus (LE cell) in 1948. Since then, several pathogenic autoantibodies have been found. Despite recent technological improvements and advances in knowledge of the pathological underpinnings and risk factors for SLE, the specific pathogenesis of SLE remains unknown.
SLE prevalence and incidence rates have been observed to vary, with discrepancies attributed mostly to demographic differences. The lupus registries in Georgia and Michigan revealed prevalence rates of 72.1 to 74.4 per 100,000 people and incidence rates of 5.6 per 100,000 person-years in largely Caucasian and African-American populations. African-Americans have the greatest rates, and Asian and Hispanic groups have greater rates than Caucasians. The illness strikes African-Americans at a younger age and is more severe.
SLE mostly affects women of reproductive age, with a 9 to 1 male to female ratio. However, the risk in women diminishes after menopause, although it remains twice as high as in males. According to studies, lupus in men, while rare, tends to be more severe.
SLE is affected by age, and while it is more frequent in women of reproductive age, it has been extensively documented in the juvenile and geriatric populations. SLE is more severe in youngsters, but in the elderly, it has a more gradual start, more pulmonary involvement, and more serositis, with less Raynaud's, malar rash, nephritis, and neuropsychiatric consequences.
SLE is a complex illness with an unclear etiology; nevertheless, various genetic, immunological, endocrine, and environmental variables all have a part in the disease's etiopathogenesis.
Although there is no evident pattern of inheritance, familial segregation and high concordance rates in identical twins imply a major genetic component to SLE. The proportion of identical twins who are concordant has been reported to be as high as 50%. More than 50 genes or chromosomal loci have been linked to SLE, with the majority encoding proteins involved in immune system function.
These genes are linked to immune system activation in response to external antigens, self-antigen production, and innate and adaptive immune system activation. Some uncommon gene variants are associated with an increased risk of SLE development. Women are 10 times more likely than males to have SLE, while the risk of SLE is 14 times higher in Klinefelter syndrome (47, XXY). This shows a link to X-chromosome genes, although, despite several investigations, the particular genes have yet to be found.
The use of estrogen-containing contraceptives and postmenopausal hormone replacement treatment can trigger flares in SLE patients and has been linked to an increased risk of SLE. Patients with SLE had elevated prolactin levels. Androgens, on the other hand, are thought to be protective.
Several environmental factors have been recognized as SLE triggers. Several medicines have been linked to the development of lupus-like symptoms by generating DNA demethylation and changes in self-antigens. While procainamide and hydralazine have the highest rates of producing drug-induced lupus, more than 100 medications have been linked to the disease. Furthermore, certain medicines, such as sulfa-drugs, are well recognized to provoke flares in SLE patients.
Sun exposure causes increased cell apoptosis, which is one of the well-known triggers for SLE. Several viral infections have been implicated, with molecular mimicry assumed to be the fundamental cause. Antibodies against the Epstein-Barr virus (EBV) are more common in children and adults with SLE than in the general population. Smoking is also considered to pose a danger, with a dose-response relationship. Various risk factors include silica exposure, other viral infections, a lack of vitamin D, alfalfa sprouts, and foods containing canavanine.
SLE pathogenesis is complicated, and our understanding of it is continually developing. When genetically sensitive people are exposed to environmental variables, a breach intolerance occurs, resulting in the activation of autoimmunity. Cell damage induced by viral and other environmental causes exposes the immune system to self-antigens, resulting in T and B cell activation, which becomes self-sustaining via a persistent self-directed immune response. The release of cytokines, activation of complement, and generation of autoantibodies all contribute to organ injury.
SLE is a multisystem illness with several phenotypes, and clinical symptoms can range from a relatively mild condition with only mucocutaneous involvement to a life-threatening disease with multiorgan involvement. SLE may affect any of the organ systems. An autoantibody profile can occasionally help predict disease progression and clinical characteristics.
Several investigations have found that serological problems emerge several years before clinical lupus. Pre-clinical lupus occurs when a patient has serological abnormalities associated with SLE and certain clinical symptoms but does not match the criteria for SLE.
There is evidence that a considerable proportion of these pre-clinical lupus patients, including those with incomplete lupus or undifferentiated connective tissue disease, may progress to clinical lupus and meet the SLE criteria later in life.
Constitutional symptoms are reported in more than 90% of SLE patients and are frequently the first presenting sign. It is usual to experience fatigue, malaise, fever, anorexia, and weight loss. While lupus flares may be the cause of fever in more than 40% of SLE patients, infections must always be cleared out first due to these patients' immunocompromised status. Furthermore, SLE is a relatively rare cause of unidentified fever.
More than 80% of SLE patients have mucocutaneous involvement, which is one of the most well-known and recognized clinical characteristics. Skin lesions in SLE may be lupus-specific, but there are also various non-specific lesions. Lupus-related lesions include
- Acute cutaneous lupus erythematosus (ACLE), which includes localized, malar, and generalized
- Subacute cutaneous lupus erythematosus (SCLE), which includes annular and papulosquamous, and
- Chronic cutaneous lupus erythematosus (CCLE), which includes classic discoid lupus erythematosus (DLE),
Acute cutaneous lupus erythematosus (ACLE) can be localized or systemic in nature. The malar rash, also known as the butterfly rash, is an erythematous raised pruritic rash that affects the cheekbones and nasal bridge. The rash might be macular or papular, and it does not affect the nasolabial folds (photoprotected). It generally has a sudden start, although it can linger for several weeks and produce induration and scaling. The malar rash may also change in response to lupus disease activity.
Rosacea, erysipelas, seborrheic dermatitis, and perioral dermatitis are all rashes in this area that must be distinguished from ACLE malar rash. ACLE manifests as a broad maculopapular or macular rash with a photosensitive pattern. ACLE lesions normally cure without leaving scars.
The rash of subacute cutaneous lupus erythematosus (SCLE) is photosensitive, broad, nonscarring, and nonindurated. SCLE can be papulosquamous (like psoriasis) or annular/polycystic (with center clearing and periphery scaling). SCLE lesions can continue for several months, however they normally heal without leaving scars.
The most frequent type of chronic cutaneous lupus erythematosus is discoid lupus erythematosus (DLE) (CCLE). DLE can develop with or without SLE and can be localized (just affecting the head and neck) or universal (above and below the neck). Disk-shaped erythematous papules or plaques with adherent scaling and center clearing characterize the lesions. DLE heals with scarring and, if present on the scalp, is linked to permanent baldness.
Mucosal DLE lesions in the oral cavity are painful erythematous spherical lesions with white radiating hyperkeratotic striae. Histologically, hypertrophic DLE may resemble squamous cell cancer. Lupus panniculitis is more likely to develop above the waist and is less likely to be related to SLE. The lesions cause depressed regions and are characterized as lupus profundus when they are coupled with DLE lesions covering them.
Lupus chilblains is characterized by erythematous painful plaques on the fingers and toes. The lesions of Lupus tumidus are erythematous edematous smooth plaques with little epidermal involvement.
Oral and nasal ulcers are frequent in SLE and, in the early stages, are generally painless. They might manifest as progressive onset erythema, macules, petechiae, erosions, or ulcers involving any area of the oral cavity, with the hard palate, buccal mucosa, and vermilion border being the most prevalent places. Photosensitivity is present in more than 90% of SLE patients and is defined by an aberrant skin reaction to ultraviolet A/B and visible light exposure, which can persist for weeks to months.
Sun exposure also causes these individuals' systemic symptoms to worsen. Alopecia in SLE can be caused by DLE (scarring) or by brittle, easily broken lupus hair in the temporal/parietal area (non-scarring).
SLE is associated with a number of additional cutaneous symptoms that are not unique to the disease. These include cutaneous vasculitis (leukocytoclastic or urticarial), vasculopathy (livedo reticularis, superficial thrombophlebitis, Raynaud's syndrome, erythromelalgia, and periungual telangiectasia), sclerodactyly, rheumatoid nodules, calcinosis cutis, bullous lesions, urticaria,
Approximately 80% to 90% of SLE patients experience musculoskeletal involvement at some time throughout their illness course, which can vary from moderate arthralgias to deforming arthritis. Lupus arthritis is a non-erosive, symmetrical inflammatory polyarthritis that primarily affects the tiny joints of the hands, knees, and wrists, however any joint can be affected.
Jaccoud arthropathy is caused by a joint capsule and ligament laxity, resulting in non-erosive abnormalities of the hands such as ulnar deviation and metacarpophalangeal joint subluxation, which can mimic rheumatoid arthritis. These malformations are usually reducible, although they can become permanent in exceptional cases. Avascular necrosis (with or without steroid usage) can develop in up to 10% of SLE patients, is frequently bilateral, and affects the hip joints.
In fewer than 10% of SLE patients, inflammatory myopathy with histological characteristics similar to but less dramatic than polymyositis has been seen. Patients with SLE are at a greater risk of developing fibromyalgia, with occurrences as high as 20% recorded. Rheumatoid nodules have been identified in SLE patients.
Hematologic and reticuloendothelial manifestations
Anemia is found in more than half of SLE patients, with chronic illness anemia being the most frequent. Iron deficiency anemia, coomb's positive autoimmune hemolytic anemia, red blood cell aplasia, and microangiopathic hemolytic anemia, which may be related to antiphospholipid antibody syndrome, are all possible causes of anemia in SLE. Leukopenia caused by neutropenia or lymphopenia is also common and can be severe.
Thrombocytopenia can be mild or severe, and it is sometimes linked with an antiphospholipid antibody syndrome and autoantibodies against platelets, glycoprotein IIb/IIIa, or the thrombopoietin receptor. Pancytopenia is not uncommon and is sometimes related to myelofibrosis. Although rare occurrences of histiocytic necrotizing lymphadenitis have been recorded, soft non-tender lymphadenopathy is typical in SLE . Splenomegaly is prevalent in SLE, and splenic atrophy and asplenism have been documented as well.
Although the diagnosis of SLE can be complex, both the central (CNS) and peripheral (PNS) nervous systems may be implicated, in addition to various mental symptoms. Intractable headaches are the most prevalent CNS symptom, occurring in more than half of all patients.
Seizures, whether focal or widespread, may occur and are related to disease activity, despite the fact that they have a positive prognosis. Aseptic meningitis, demyelinating disease (including optic neuritis and myelitis), movement abnormalities such as chorea, and cognitive impairment are some of the other CNS symptoms. Patients with SLE are also at a higher risk of having an ischemic stroke.
The peripheral nervous system symptoms include cranial and peripheral (sensorimotor, axonal) neuropathies, mononeuritis multiplex, autonomic neuropathies, and syndromes resembling Guillain-Barré syndrome Myasthenia gravis.
Psychiatric symptoms, which can vary from sadness and anxiety to outright psychosis, are particularly challenging to identify and manage.
Lupus nephritis is a well-known and widespread SLE consequence. The severity of the involvement might range from moderate subnephrotic proteinuria to diffuse progressive glomerulonephritis with chronic kidney damage. Lupus nephritis is typically diagnosed early in the course of SLE. New-onset hypertension, hematuria, proteinuria, lower extremity edema, and creatinine increase should raise the possibility of lupus nephritis.
A biopsy is essential for diagnosing lupus nephritis and ruling out alternative causes. The histology portion of this article discusses the six types of lupus nephritis. The management of lupus nephritis is determined by the biopsy findings, and the prognosis varies by class, with classes I and II having a great prognosis and classes III and IV having poor outcomes.
Except for the complications of nephritis syndrome, such as thromboembolism, which are prevalent in this class, Class V has a generally fair prognosis. Thrombotic microangiopathy, interstitial nephritis, lupus vasculopathy, vasculitis, and arteriolosclerosis are some of the other renal symptoms.
The most frequent pulmonary symptom is pleuritis, which is not usually coupled with pleural effusion. Exudative pleural effusions, acute lupus pneumonitis with bilateral pulmonary infiltrates, interstitial lung disease (NSIP or UIP), diffuse alveolar hemorrhage associated with capillaritis, pulmonary arterial hypertension, pulmonary embolism (with or without antiphospholipid antibody syndrome), and shrinking lung syndrome are other pulmonary manifestations.
SLE may affect any of the heart's layers, including the pericardium, myocardium, endocardium, and even the coronary arteries. The most frequent cardiac symptom is pericarditis with exudative pericardial effusions. Cardiac tamponade is uncommon. Myocarditis is uncommon and is linked to anti-Ro (SSA) antibodies. Hydroxychloroquine-associated cardiomyopathy must be checked out, which may necessitate an endomyocardial biopsy on occasion.
Valvular abnormalities, such as Libman-Sacks endocarditis of the mitral valve, are prevalent and may be linked to antiphospholipid antibody syndrome. Patients with SLE are more vulnerable to coronary artery disease, either as a result of coronary vasculitis or, more commonly, as a result of widespread atherosclerosis.
SLE can affect any portion of the gastrointestinal system, and symptoms include esophageal dysmotility (particularly in the upper one-third of the esophagus), mesenteric vasculitis, lupus enteritis, peritonitis and ascites, protein-losing enteropathy, pancreatitis, and lupoid hepatitis. Budd-Chiari syndrome, mesenteric vascular thrombosis, and hepatic veno-occlusive disease can also occur in people with SLE and antiphospholipid antibody syndrome.
Patients with SLE who have positive antiphospholipid antibodies are more likely to have spontaneous miscarriages and fetal loss, as well as preeclampsia and maternal thrombosis. Anti-Ro (SSA) and anti-La (SSB) antibodies can enter the placenta and cause fetal heart block as well as newborn lupus with a photosensitive rash, cytopenias, and transaminitis. The risk is 2% in the first pregnancy, but it rises to 20% if there is a history of neonatal lupus in previous pregnancies.
SLE typically worsens during pregnancy, especially if the disease was uncontrolled in the six months previous the pregnancy. Lupus nephritis can be difficult to distinguish from pre-eclampsia, however various clinical and laboratory markers (low complements, positive Anti-Ds-DNA antibody, normal blood uric acid level, and active urine sediment) may aid in the diagnosis. Patients with more severe SLE signs, such as pulmonary hypertension, serious cardiovascular illness, or cerebrovascular accident, are at exceptionally significant risk of pregnant mortality.
Eye involvement is prevalent, and keratoconjunctivitis sicca is common in SLE, whether secondary Sjogren syndrome is present or not. Other visual signs include retinal vasculitis, optic neuritis, uveitis, scleritis, peripheral ulcerative keratitis, and episcleritis.
SLE patients are also more vulnerable to drug-induced ocular damage, such as steroid-induced glaucoma or cataract and hydroxychloroquine-induced maculopathy. The involvement of the ear may result in acute sensorineural hearing loss. Patients with SLE and antiphospholipid antibody syndrome may experience an adrenal infarction due to adrenal artery thrombosis.
SLE diagnosis can be difficult, and no one clinical symptom or test abnormalities will confirm an SLE diagnosis. SLE is diagnosed based on a combination of signs and symptoms, as well as an adequate laboratory workup. Imaging and histology may also be important.
Several autoantibodies with varying degrees of sensitivity and specificity have been reported in SLE. While certain autoantibodies may be linked to a specific clinical subtype of SLE, others may operate as a marker of disease activity.
Antinuclear antibodies (ANA) are the disease's hallmark and should be the first test conducted. The immunofluorescence assay is regarded as the gold standard test for ANA, and while alternative techniques of detection, such as ELISAs and multiplex tests, are widely available, they are insensitive. A positive ANA is found in more than 97 percent of SLE patients, but it can also be found in various other illnesses, as well as a considerable proportion of the healthy population, with a specificity of just 20 percent.
As a result, while a positive ANA does not establish the diagnosis of SLE, a negative ANA renders it exceedingly unlikely. ANA negative SLE has been documented seldom, albeit it is thought to be due to systematic mistake, and those individuals had either a positive ANA on immunofluorescence or a positive Anti-Ro (SSA) antibody. ANAs have been documented in a variety of patterns, including speckled, homogeneous, centromere, cytoplasmic, nucleolar, and dense fine speckled patterns.
With the emergence of highly precise ANAs targeting specific antigens, the staining patterns of ANAs are no longer considered relevant. ANAs with a dense fine speckled pattern (Anti-DFS70) is thought to be the least pathological, and patients with this pattern are less likely to develop systemic autoimmune disorders.
When ANAs are directed against antigens such as SSA, SSB, Smith, and Ribonucleoprotein, a speckled pattern is observed. The homogeneous pattern is related to ANAs that target Histones, Chromatin, and Ds-DNA, whereas the centromere pattern is associated with Anti-centromere antibodies found in restricted systemic sclerosis.
ANAs can be observed in a variety of illnesses other than SLE, as previously mentioned. More than 20% of the healthy normal population, particularly females and relatives of autoimmune disease patients, can have a positive ANA, albeit titers greater than 1:320 are unusual. Drug-induced lupus, systemic sclerosis, polymyositis/dermatomyositis, mixed connective tissue disease, Sjogren syndrome, rheumatoid arthritis, juvenile idiopathic arthritis, Raynaud's disease, cutaneous lupus, and fibromyalgia are some rheumatological illnesses linked with a positive ANA.
A positive ANA is related to a number of different autoimmune illnesses, including autoimmune hepatitis, multiple sclerosis, Hashimoto thyroiditis, and idiopathic thrombocytopenic purpura. A positive ANA has also been linked to a number of illnesses and cancers.
A positive ANA should be followed by testing for more specific autoantibodies to identify the antigen that caused the positive ANA. It should be highlighted that a positive ANA is usually not related with any of the known more specific autoantibodies.
There are various potential targets for ANAs, with each peptide generated inside the cell's nucleus acting as a potential antigen; however, only a handful have been recognized as having therapeutic significance thus far. A positive ANA with negative autoantibody testing is less likely to be linked with systemic autoimmune illness.
Anti-Ds-DNA antibodies show a greater than 95% specificity for SLE but are found in only around 60% to 70% of SLE patients. As a result, a negative Anti-Ds-DNA test does not rule out the possibility of SLE. Notably, Anti-Ss-DNA antibodies are regarded as non-specific and may be observed as a laboratory mistake or in the general population. Although it is not widely used, the Farr radioimmunoassay test is regarded the gold standard for detecting Anti-Ds-DNA antibodies. There are ELISA tests available, however they have a significant chance of producing false-positive results.
The Crithidia Luciliae immunofluorescence test can be used to validate the existence of Anti-Ds-DNA antibodies. Anti-Ds-DNA antibodies can also be observed in drug-induced lupus, particularly when anti-TNF and interferon-alpha are used. Low titers of Anti-Ds-DNA antibodies have been identified in rheumatoid arthritis and Sjogren syndrome on rare occasions. Anti-Ds-DNA antibodies in SLE can be associated with disease activity and the development of lupus nephritis.
Anti-Ro (SSA) and anti-La (SSB) antibodies are antibodies that target ribonucleoprotein particles. Anti-Ro and anti-La antibodies are found in up to 90% of patients of Sjogren syndrome, although they can also be seen in SLE (Anti-Ro in up to 50 percent and Anti-La in up to 20 percent ). They may be linked to secondary Sjogren syndrome and keratoconjunctivitis sicca in SLE, as well as photosensitivity, congenital heart block, and newborn lupus.
Anri-Smith antibodies are found in fewer than 30% of SLE patients yet have a 95% specificity for SLE. They are more common among African-American SLE patients. Anti-Smith antibodies are almost often coupled with Anti-U1-RNP antibodies, which are seen in up to 30% of SLE patients.
Anti-centromere and anti-topoisomerase-I (SCL70) antibodies are seen in systemic sclerosis, but not in SLE (less than 5 percent ). Myositis is characterized by anti-Histidyl-tRNA-synthetase antibodies. Patients with SLE may also have antiphospholipid antibodies (lupus anticoagulants, anti-cardiolipin, and anti-beta-2-glycoprotein I antibodies), which are linked to an increased risk of thrombosis and bad pregnancy outcomes.
The objective of SLE therapy is to avoid organ damage and establish remission. Therapy is determined on the organ system(s) affected and the level of involvement and ranges from basic (NSAIDs, antimalarials) to rigorous treatment (cytotoxic drugs, corticosteroids).
Patient education, physical and lifestyle changes, and emotional support are all important components of SLE management. Patients with SLE should be adequately informed on the disease pathophysiology, probable organ involvement (including brochures), the significance of treatment, and the importance of monitoring compliance. Stress management measures, excellent sleep hygiene, exercise, and the usage of emotional support will be promoted.
Smoking can exacerbate SLE symptoms, and patients should be informed on the significance of quitting smoking. Dietary suggestions will include avoiding alfalfa sprouts and echinacea, as well as include a vitamin-D-rich diet. Photoprotection is essential, and all SLE patients should avoid direct sun exposure by timing their activities appropriately, wearing light-weight loose-fitting dark clothing that covers the majority of the body, and using broad-spectrum (UV-A and UV-B) sunscreens with a sun protection factor (SPF) of 30 or higher.
- Cutaneous manifestations:
Mild cutaneous symptoms are frequently treated with topical corticosteroids or calcineurin inhibitors like tacrolimus. Hydroxychloroquine is the treatment of choice for the majority of cutaneous symptoms and is quite effective. Quinacrine can be administered if hydroxychloroquine causes intolerance or undesirable effects.
Methotrexate can be used if hydroxychloroquine does not work. Systemic corticosteroids, mycophenolate mofetil, and belimumab may be recommended for severe or resistant illnesses. Thalidomide, cyclophosphamide, IVIG, and rituximab are among more options.
- Musculoskeletal manifestations:
Hydroxychloroquine is the first-line treatment for lupus arthritis. If there is no response, methotrexate or leflunomide may be used. In refractory situations, belimumab and rituximab may be tried.
- Hematological manifestations:
Drug-induced cytopenias must be avoided. Mild cytopenias normally do not require therapy. Corticosteroids are the backbone of treatment for moderate to severe cytopenias, while azathioprine or cyclosporine-A can be administered as a steroid-sparing drug. Severe refractory cytopenias may necessitate intravenous pulse steroid therapy, mycophenolate mofetil, rituximab, cyclophosphamide, plasmapheresis, or splenectomy.
- Cardiopulmonary manifestations:
Serositis is often treated with NSAIDs or moderate to high doses of oral corticosteroids. Steroid-sparing medicines include hydroxychloroquine and methotrexate. Acute lupus pneumonitis necessitates high-dose IV pulse corticosteroids, whereas plasmaphereses and/or cyclophosphamide may be required if there is diffuse alveolar bleeding.
Low to moderate doses of corticosteroids combined with immunosuppressive drugs such as azathioprine or mycophenolate mofetil can be used to treat interstitial lung disease. Vasodilator treatment is required for pulmonary arterial hypertension, whereas anticoagulation is required for thrombotic consequences such as pulmonary embolism. Corticosteroids at high doses are necessary for the treatment of myocarditis and coronary arteritis.
- CNS manifestations:
Before beginning therapy for neuropsychiatric aspects of SLE, it is crucial to get an accurate diagnosis and rule out other possible causes. Inflammation-related neuropsychiatric symptoms such as optic neuritis, aseptic meningitis, demyelinating illness, and others are treated with high dosage corticosteroids combined with immunosuppressive drugs such as cyclophosphamide, azathioprine, or rituximab.
In situations of thromboembolic CNS events linked with antiphospholipid antibody syndrome, warfarin should be taken for the rest of one's life. Although there is no convincing research on this, high dosage corticosteroids can be utilized in cognitive impairment.
- Renal manifestations:
Lupus nephritis (LN) must be verified by a biopsy, which not only confirms the diagnosis but also rules out alternative causes and aids in disease classification. Renin-angiotensin-aldosterone system blockage is recommended for Class I and II LN. Immunosuppression with high-dose corticosteroids followed by azathioprine is recommended only if proteinuria exceeds 1 gram per day.
The Renin-angiotensin-aldosterone system must also be blocked in patients with Membranous LN (Class V). If proteinuria exceeds 1 gram/day (common in Class V LN), induction therapy with high-dose corticosteroids and azathioprine (mild disease) or tacrolimus/cyclosporine-A/mycophenolate mofetil/IV cyclophosphamide (moderate to severe disease) followed by maintenance therapy with azathioprine, mycophenolate mofetil, or cyclosporine
During maintenance therapy, corticosteroids should be progressively decreased. Proliferative LN (Class III/IV) necessitates more severe treatment. Induction treatment consists of IV pulse dose methylprednisolone, followed by high dose oral steroids combined with mycophenolate mofetil, IV cyclophosphamide, or azathioprine (only in mild disease in whites). Mycophenolate mofetil or azathioprine maintenance treatment must be continued for at least three years.
For severe illness, 1 year of IV pulse cyclophosphamide might be considered maintenance treatment. Patients with lupus nephritis require frequent monitoring of their renal function and proteinuria, as well as other SLE disease activity indicators. Flares and partial remission are common. Some people may require renal replacement treatment or a transplant.
- Pregnancy manifestations:
Pregnancy must be considered only if the condition was dormant at the time of and 6 months before the pregnancy, due to an elevated risk of flares otherwise. If contraception is required until then, it must be progesterone-only. Hydroxychloroquine is regarded safe during pregnancy, has been linked to a considerable reduction in flares and disease activity, and should be used throughout the pregnancy.
Mild symptoms can be treated with azathioprine and low-dose corticosteroids. Other immunosuppressive drugs, such as methotrexate, leflunomide, mycophenolate mofetil, and cyclophosphamide, are teratogenic and should be avoided during pregnancy. During pregnancy, rituximab and belimumab should also be avoided. Before pregnancy, patients with antiphospholipid antibody syndrome should be switched from warfarin to low-molecular-weight heparin and aspirin.
Females with positive Anti-Ro or Anti-La antibodies and a history of neonatal lupus in a prior pregnancy should have weekly or alternate-weekly fetal echocardiogram during the second trimester. First or second-degree heart block should be treated as soon as possible with dexamethasone, while prevention with dexamethasone is not advised. A full heart block is irreversible and necessitates the use of a pacemaker in the newborn. Hydroxychloroquine reduces the likelihood of fetal heart block.
- Other management considerations:
Hydroxychloroquine should be administered in all SLE patients since it has advantages more than merely managing current symptoms, such as anti-thrombotic effects and avoiding flares. Patients using hydroxychloroquine will need to have regular ophthalmology exams to check for the uncommon but irreversible maculopathy linked with this medication.
Corticosteroids are often used in SLE, and many patients are unable to discontinue them entirely. Long-term side effects of corticosteroids, including as osteoporosis, glaucoma, cataract, and avascular necrosis, must be evaluated and monitored. Patients taking large doses of corticosteroids will also require antibiotic prophylaxis to avoid infection.
Most immunosuppressive medications used to treat SLE have a number of possible side effects, ranging from cytopenias and hepatotoxicity to an increased risk of urinary bladder cancer with cyclophosphamide. These individuals will be thoroughly followed for any harmful effects of these drugs.
Systemic Lupus Erythematosus is a chronic inflammatory illness for which there is no treatment. Without proper care, it can impair several organs and lead to very poor quality of life. Premature death is prevalent due to a variety of factors. An interprofessional team should educate and manage SLE patients to decrease morbidity and death.
The patient should be educated by the primary care provider and nurse practitioner about avoiding triggers that induce flare-ups. Furthermore, the patient should be advised to avoid UV rays and limit sun exposure. When going out, wear proper clothing, sunglasses, and a wide-brimmed hat. The dietician should educate the patient on the significance of following a low-fat diet in order to prevent hyperlipidemia.
Furthermore, because lupus patients are advised to avoid the sun, vitamin D tablets are advised. The physical therapist should teach the patient the value of exercise. The pharmacist should inform the patient about the necessity of medication adherence and quitting smoking. The patient should be counseled on family planning and contraception by the nurse practitioner.
Many medicines used to treat are teratogenic, hence contraception is strongly advised. In administering and monitoring SLE, multispecialty cooperation is frequently required. While a rheumatologist is essential, additional specialists such as dermatology, cardiology, neurology, pulmonology, ophthalmology, nephrology, gastrointestinal, and gynecologist may be required.
Close communication between doctors and patients and families, as well as consideration of patient preferences while deciding on therapy, is strongly advised.