Systemic Lupus Erythematosus (SLE) Overview

Systemic Lupus Erythematosus (SLE) Overview

• SLE is a chronic autoimmune condition impacting various organs.
• Widespread microvascular inflammation characterizes SLE, alongside antinuclear and anti-double-stranded DNA antibodies.

Learning Objectives

• To investigate the prevalence of lupus
• To examine the origins of lupus
• SLE must be considered in the differential diagnosis.
• Identify lupus’s symptoms.
• Learn lupus diagnostic methods.
• Understand required lab tests for lupus evaluation.
• Discuss standard treatments for lupus
• To explore personalized medicine approaches for lupus.

Incidence of Lupus in America

• Around 1.5 million Americans have systemic lupus erythematosus (SLE) which is 1 in 200 people.
• SLE disproportionately impacts Blacks, Latinos, Asians, and Native Americans compared to whites.
• One in 250 Black women are affected by lupus.
• Women are ten times more likely to be affected than men.
• Almost 90% of SLE patients are female, aged 15-45.

Etiology

• Genetic factors account for about 10% of lupus cases.
• Potential Lupus causes include medications, environmental toxins, infections, stress, physical trauma, ultraviolet light, immunological factors, and hormonal factors.

Genetic Factors

• Over 50 genes or genomic loci have been linked to SLE, predominantly encoding proteins involved in immune system function.
• Associated genes activate both adaptive and innate immune systems.

Medications and Lupus

• Between 100 and 200 medications have the potential to induce lupus.
• 10% of lupus patients are believed to have developed the condition due to medication.
• Sulfa drugs are known to cause flares in patients with SLE.
• Common medications associated with Lupus are INH, Procainamide, Hydralazine, Calcium channel blockers, Angiotensin-converting enzyme inhibitors, Interferons, Thiazide diuretics, Terbinafine, Protein pump inhibitors, and Chemotherapy.

Enviromental Toxins

• Smoking is considered a risk factor, showing a dose-response relationship.
• Residential exposure to pesticides in urban populations of mainly African-American women correlates to a higher SLE risk.
• Agricultural pesticides can be associated with higher or lower risk of SLE/systemic sclerosis.
• Farming's overall risk is complex and is related to childhood exposure and other factors.
• Long-term exposure to ambient air pollutants highlights evaluating their effect in preventing SLE.
• Identifying individuals who smoke and have a genetic risk is crucial to minimizing the effects of air pollution.
• A threefold increased risk of developing lupus is found in women who frequently use dark hair dye.

Infections and Lupus

• Several viral infections may cause lupus through molecular mimicry.
• Children and adults with SLE have more antibodies against the Epstein-Barr virus (EBV).

Hormonal Factors

• Being female and hormonal influences are significant risk factors for SLE.
• Estrogen dominance and prolactin boost autoimmunity, increase B-cell activation factor production, and modulate lymphocyte and pDC activation.
• Estrogen-containing contraceptives can trigger flares and an increased SLE incidence.
• Elevated prolactin is linked to SLE.

Vitamin D Deficiency

• Vitamin D deficiency is typical among SLE patients.

Alfalfa Sprouts

• L-canavanine-containing alfalfa sprouts can trigger systemic lupus erythematosus (SLE) in monkeys.
• A human subject developed lupus hemolytic anemia after ingesting alfalfa seeds in a research study.

Silica Exposure

• Silica exposure may initiate systemic lupus erythematosus.

Systemic Lupus Erythematosus (SLE) Pathology

• Both adaptive and innate immunities are implicated in SLE pathogenesis.
• Innate immune activation is either Toll-like receptor dependent or independent.
• T and B lymphocytes are adaptive immune components that significantly contribute to SLE development.
• B and T cell interactions produce heightened autoimmunity.

Signs and Symptoms of Systemic Lupus Erythematosus (SLE)

• Common symptoms include prolonged fatigue (81%), arthralgias (95%), rashes (74%), and fever above 100°F (90%).
• Malar and other rashes associated with Lupus may burn, itch, and ooze if left untreated.
• Photosensitivity is present 30% of the time.
• Cardiac abnormalities occur in up to 55% of patients, and arthritis is present 90% of the time.
• Other common symptoms include cold extremities, Raynaud's syndrome (17-30%), premenstrual flares, dry eyes and mouth, easy bruising, edema, depression and neuropsychiatric issues.
• Further symptoms include anemia (71%), seizures (15%), pulmonary disease, migraine headaches (10-37%), weight loss, renal disease (50%), and hair loss (27%).
• Abnormal blood clotting, present in 40% of patients, involves antiphospholipid antibodies and causes premature blood clotting.
• Accelerated atherosclerosis is the most common cause of death in lupus patients.
• Lupus disease progression varies among individuals; some experience mild courses, while others deal with terminal issues.
• Additional symptoms common in SLE may include lupus pneumonitis (up to 10% of patients) and Lymphadenopathy (reveals follicular hyperplasia with giant cells, plasma cells infiltration of the interfollicular zones, and necrosis of the paracortical T-cell zones).
• Co-existing conditions include a 50% higher acute myocardial infarction (MI) risk.

Systemic Lupus Erythematosus (SLE) Diagnosis

• The diagnosis relies on the presence of four of the following symptoms/characteristics: malar rash, discoid rash (25% of lupus patients/can arise on the ears, scalp, arms, or upper back/can leave scarring if left untreated, photosensitivity (sensitivity to fluorescent and halogen lamps), arthritis (80-90% of SLE patients have musculoskeletal involvement with symptoms from mild arthralgia to deforming arthritis.)
• Musculoskeletal changes/serositis cause Avascular necrosis, found in 10% with SLE, is frequently bilateral and affects the hip joints.
• Inflammatory myopathy is similar to polymyositis but less severe, seen in 10% of SLE cases.
• Patients with SLE have high development risk of fibromyalgia, with 20% of patients experiencing this.
• Rheumatoid nodules have been observed in SLE patients.
• Further diagnostic features are oral ulcers (40%), and neurologic abnormalities (50%), CNS issues(intractable headaches), confusion, memory loss, seizures, and psychosis may occur.
• Immunologic abnormalities/Anti-DNA antibodies, LE cells, 90% of + patients can have other diseases, and Anti-Sm antibodies-diagnostic results in a false + syphilis test.
• Furthermore, a renal disorder may occur.
• 50% of kidney involvement will cause permanent damage.
• Additional symptoms include Hemolytic anemia, Thrombocytopenia, Leukopenia, and Lymphocytopenia
• Gastrointestinal symptoms that can occur are Esophageal dysmotility (upper one-third), and mesenteric vasculitis-lupus enteritis Peritonitis and ascites, protein-losing enteropathy, pancreatitis, and lupoid hepatitis
• Co-existing conditions include Patients with SLE, antiphospholipid antibody syndrome can develop Budd-Chiari syndrome, mesenteric vessel thrombosis, and hepatic veno-occlusive disease.

Differential diagnosis using Lab Studies of Lupus

• Antinuclear antibody (ANA) are 95% of lupus patients have a positive ANA test.
• A positive ANA test alone doesn't mean + result means you have lupus because 20% of the healthy female population or autoimmune relative can have positive ANA result.
• If titers are more than 1:320, it's uncommon.
• The test for + ANA can be seen in + pregnant or elderly patients and those with immune disorders.
• ANA has Speckled, homogenous, centromere, cytoplasmic, nucleolar, and dense fine speckled patterns The more tests that come, the less relevant the ANA is
• Dense fine speckled pattern (anti-DFS70), ANAs are less pathological, and pattern ANAs are not prone to autoimmune disorders.
• The speckled pattern means ANAs are directed against antigens SSA, SSB, Smith, RNP.
• Homogenous patterns means histones, chromatin, while centromere means Scleroderma

Rheumatological Disorders

• Having a positive ANA means you may develop drug-induced lupus, Systemic sclerosis, Polymyositis/dermatopolymyositis, Mixed connective tissue disease, Sjorgren's syndrome, Rheumatoid arthritis, Juvenile Idiopathic arthritis, Raynaud's, Cutaneous Lupus, and Fibromyalgia.
• • Several other AIDs with + ANA are Autoimmune hepatitis, Hashimoto;s thyroiditis, Multiple sclerosis, Thrombocytopenic Purpura.
• You should also test Antibodies to dna/ native and double-stranded

Double Stranded DNA

• Anti-ssDNA antibodies are commonly inaccurate and also seen in both laboratory errors/the healthy

• Anti-dsDNA is 95% but found within 60 to 70% of patients with + SLE

• Therefore, - anti did not mean you definitely done +

• Anti-SM means you search for Sm antibodies, which mean find antibodies against Sm with is lipoprotein in cells

• Anti-Sm antibodies are high Specific

• However, other autoimmune disease cannot use it and the prevalence 30 %

• Lupus Erythematous mean test LE can can for + RA for up to 20% the time

• To find test for a small number you need Sc

• Complement activation indicates is likely if C3 is low

Diagnosis of Lupus

• Markers of inflammation such as sed rate and C-reactive protein may be elevated.
• Complete blood counts, liver function tests and renal function tests including serum creatinine/Urinalysis and quantify is a must to see organs that are

Conventional Treatments

• Prevent organ damage to achieve remission. - Treatment is tailored is made systems with severity - Nsaids, GCs, Antimalarias: HCQ,CQ and Qunine

• Immunosuppressives means cytoxan Azrothropine and MTX

• Monocolal: Belmuimb and rituxiban

• Studies ongoing include: anifrolumab, ustekimumab - Barucltinib, Aacicept

Targeted classification method

• B-cell targeted blsiimo abacatacept t = Dab and Kinase Inhibitor - Controld and Silimomab

Personalized Medicine Therapies

• Holistic approaches are the main form - Treat the Gut - Detoxification and Diet Nutrients and glandular
• Address hormonal and immune response
• Herbal remedies

Environmental Factors

• Some medications causing SLE are like environmental compounds in agriculture Acetlalator: Amines used in Rockets/Petroleum used are dangerous and those affect by genetics 20% likely to get SLE

Diet for SLE

Gluten is bad for some with SLE and there needs to be allergy testing

• Avoid Alfalfa sprouts, corn, spinach, + sugars

• Low dat, High fat diet Try to take the TPE

Treatments

Vitamin D to Supplement and also increase in DHA and increase in O3 - 20 Grams Flax seed and vitamin to TCM herbs and also

Hormone for Testosterone

• Measure Levels. Can do salvia and also use

DHA decreases, this should have balance

PSK-PSK

• This comes from Termates versicolor (aka Coriolus versicolor) helps SLE Cordiceds which improves LI-2, steroidal saponin, kidney and DNA

Long-Term Outcomes

D to age/sex/ genetic and environmental risk, organ system and APE