​Kembara Xtra - Medicine - Sytemic Lupus Erythematosus

​Kembara Xtra - Medicine - Systemic Lupus Erythematosus 
Multisystem autoimmune inflammatory disorder with variable presentation, disease course, and prognosis that can affect any organ system, but is most commonly seen in the immune, reproductive, renal, musculoskeletal, cardiovascular, pulmonary, and dermatological systems.

Epidemiology Incidence In the United States, the overall incidence ranges from 5 to 7 per 100,000 person-years.
 There is a considerable ethnic difference: White 3.3, Asian/Pacific Islander 4.6, Hispanic 5.6, American Indian/Alaska Native 7.4, and Black 16.0 per 100,000 people each year
 There is a strong gender disparity, with 9.8 against 0.8 per 100,000 person-years (about 12-fold greater) for females.
The peak incidence in females occurs between the third and seventh decades of life.
Male incidence peaked later in life, in the fifth to seventh decades.
Prevalence

The prevalence in the US as a whole varies from 70 to 100 cases per 100,000 people.
 Increasing as a result of improved recognition and elevated survival
Black women have the highest prevalence at 498 per 100,000.
Strong female predominance relative to male cases: 179 cases per 100,000 versus 21 cases (about nine times greater)


Pathophysiology and Etiology 
Pathogenesis is multifaceted and complex, involving genetic, environmental, immunoregulatory, hormonal, and epigenetic variables.
Genetics: Between 40% and 70% of phenotypic diversity is explained by genetics; more than 30 susceptibility loci for SLE have been identified in genome-wide association studies.
 Systemic lupus international collaborative clinics (SLICC) and the American College of Rheumatology (ACR) continue to apply their previous criteria in many therapeutic settings.


Risk factors include: family history of SLE or other autoimmune diseases; ethnicity (highest risk in black populations; intermediate risk in Asian, Hispanic, and American Indian/Alaska Native populations); hormonal factors (female sex, early menarche, endometriosis, surgical menopause, earlier age at menopause); environmental factors (smoking, exposure to crystalline silica, exogenous female hormones, specific medications (drug-induced lupus)

Antiphospholipid syndrome, depression, fibromyalgia, thyroid disease, and overlap syndromes of systemic sclerosis, polymyositis, dermatomyositis, and rheumatoid arthritis (RA) are all associated conditions.

Suspect in multisystem disease, with fever, tiredness, and indications of inflammation. New categorization criteria from the European League Against Rheumatism (EULAR) and American College of Rheumatology (ACR) in 2019: 96% sensitivity, 93% specificity Note: Don't simply base a patient's eligibility for therapy on classification criteria.


History Common presenting symptoms include weariness, joint pains, fever, mouth ulcers, hair loss, rash, and photosensitivity Symptoms are typically nonspecific, may affect any organ system, and may not occur at the same time.
Acute pericarditis, recurrent pregnancy loss, spontaneous venous thromboembolism, cerebrovascular accident in a young person, new-onset psychosis or seizures, unexplained cytopenias, or renal failure are a few more manifestations that could arouse suspicion.

clinical assessment 
Constitutional (common): fever, lymphadenopathy, and loss of weight
Skin (common) - Nonspecific: non-scarring baldness, painless ulcers in the mouth or on the nose, photosensitivity, vasculitis, Raynaud phenomenon - Lupus-specific
Acute cutaneous lupus erythematosus (ACLE) is characterized by the typical "butterfly" or malar rash, which spares the nasolabial folds.
Chronic cutaneous lupus erythematosus (CCLE) Includes discoid lupus Erythematous-violaceous lesions with secondary changes of atrophic scarring and dyspigmentation When found on the scalp, causes follicular hyperkeratosis and plugging, scarring alopecia
A skin biopsy reveals distinctive alterations in each person.
Musculoskeletal (common): Synovitis, particularly symmetric polyarthritis; Periarticular involvement (tendons, joint capsule), causing nonerosive joint abnormalities (Jaccoud arthropathy);
Other - Nonspecific signs may be present in any organ system, including cardiopulmonary manifestations of pneumonitis, pericarditis, pleural effusion, and venous thromboembolism.
Pallor, jaundice, and splenomegaly are signs of hematologic disease. Seizures, psychosis, delirium, mononeuritis multiplex, peripheral or cranial neuropathies, and cognitive impairment are signs of central nervous system disease. Edema or anasarca are signs of advanced renal disease.


Due to the disease's vast signs and changeable presentation, the differential diagnosis is extremely broad.
 Based on the presenting symptoms, take into account additional rheumatologic disorders, thyroid disease, fibromyalgia, or organ-specific diagnosis.
Take into account drug-induced lupus caused by regularly used medicines (hydralazine, procainamide, isoniazid, methyldopa, quinidine, and chlorpromazine).

Laboratory Results 

Initial examinations (lab, imaging)

Based on the appearance and level of suspicion, the initial test
Low suspicion: A complete blood count (CBC), complete metabolic panel (CMP), thyroid-stimulating hormone (TSH), and urine may be included in a limited initial laboratory evaluation.
 If you have a higher suspicion, run immunological tests.
- Particular to lupus
ANA: sensitivity 97.8%, specificity 74.7% (titer 1:80 via indirect immunofluorescence).
Anti-dsDNA: specificity 95%, sensitivity 70%.
Anti-Smith: specificity 98.6%, sensitivity 39.7%
Antiphospholipid antibodies (anti-cardiolipin, anti-2GP1, lupus anticoagulant), complement levels (low C3 and/or C4), imaging examinations based on specific signs and symptoms


Tests in the Future & Special Considerations

 To measure proteinuria, 24-hour urine collection or spot protein/creatinine ratioReticulocyte count, indirect bilirubin, haptoglobin, and a direct Coombs test to check for hemolysis are all tests for anemia. If it hasn't already been done, test for antiphospholipid syndrome during diagnosis.
Basic metabolic tests include a lipid panel, fasting blood sugar or hemoglobin A1c, vitamin D level, and TSH.
Other/Diagnostic Procedures
 Skin biopsy, if necessary, to validate clinical symptoms of cutaneous lupus; Renal biopsy for urine protein >500 mg/24 hr; Other diagnostic modalities, if indicated, based on specific manifestations
Interpretation of Tests
Skin biopsy: Immunocomplex deposition at the dermoepidermal junction may be present, as well as interface vacuolar dermatitis, which often consists of perivascular lymphohistiocytic infiltration and dermal mucus.
Renal biopsy: classified by the International Society of Nephrology/Renal Pathology Society

General therapy objectives include establishing remission or low disease activity, avoiding flare-ups and end-organ damage, boosting survival, and enhancing quality of life. Supportive treatments are also necessary. Preconception counseling and family planning - Sun protection - Smoking cessation - Adequate exercise - Managing cardiovascular risk factors (lipids, glucose, blood pressure, and weight) - Immunizations - 2019 EULAR recommendations for vaccination in autoimmune inflammatory rheumatic disease (see "Additional Reading")

First Line of Medicine
Unless contraindicated, hydroxychloroquine is advised for all SLE patients because it lessens flare-ups, enhances cutaneous and musculoskeletal symptoms, decreases thrombosis and bone mass loss, minimizes organ damage, and improves survival.- Safe for use during pregnancy- Dosage: 200 to 400 mg/day given as a single dose or in two evenly spaced doses; not to exceed 5 mg/kg/day (real body weight).
- Contraindications: known hydroxychloroquine hypersensitivity The most frequent and typically minor adverse events are gastrointestinal (nausea, vomiting, diarrhea, and abdominal discomfort) and cutaneous (rash).
- Safeguards
 Retinal damage
Risk factors include larger doses, renal insufficiency, concomitant macular disease, and concurrent tamoxifen use. They are less common at levels below 5 mg/kg/day.
 Baseline ophthalmologic screening (2)[C]
In the absence of additional risk factors, yearly screening may begin after 5 years (2)[C].
Cardiomyopathy: anomalies in conduction, such as a protracted QT interval; Proximal myopathy and neuropathy;
 Neuropsychiatric modifications
Low blood sugar
 Use with caution if you have kidney or liver illness (no specific dose reductions were specified)
- Communication
 Exercise caution while taking insulin and other antidiabetic drugs Exercise caution when taking drugs that influence cardiac conduction, particularly QT prolonging drugs
Glucocorticoids: Organ involvement and severity affect the dose and method of administration.
Topical steroids are used to treat cutaneous conditions.
 Oral steroids are frequently necessary for the first line of treatment, flare-ups, and/or maintenance therapy.
Pulsed intravenous (IV) methylprednisolone (250–1,000 mg/day for 1–3 days) is frequently needed for life-/organ-threatening flares. Chronic maintenance therapy dose should be reduced to 7.5 mg/day (the prednisone equivalent) at the earliest opportunity. Immunomodulatory medication that is started early on may reduce the requirement for glucocorticoids.
Next Line

The choice of agent is influenced by the disease's symptoms, the patient's characteristics (such as age and ability to have children), safety, and cost.
For patients who are not controlled on hydroxychloroquine, who are unable to taper glucocorticoids well, or who require initial treatment for a more severe illness, consider methotrexate, azathioprine, or mycophenolate.
If you experience frequent flare-ups or high levels of residual disease activity despite normal therapy, think about adding belimumab.
Consider cyclophosphamide or rituximab if your condition is severe and threatening your life or other vital organs.


Referral 

Mild illness without severe end-organ involvement may be suitable for primary care treatment.
 Typically necessitates the coordination of a multidisciplinary team with rheumatology
The best place to treat severe illness is a lupus center.

Surgical Techniques 
End-stage renal illness and kidney transplant

Supplements for alternative medicine that have shown some promise include vitamin D, omega-3 fatty acids, N-acetylcysteine, and turmeric.

Admission 

When SLE flares are life- or organ-threatening, IV pulse methylprednisolone (250 to 1,000 mg/day for 1 to 3 days) may be necessary to treat both conditions while a comprehensive evaluation is underway.


Patient Follow-Up Monitoring
The level of monitoring is based on the disease's severity, specific manifestations, treatment plan, and coexisting conditions.
Every six to twelve months, a stable, dormant condition without considerable organ involvement or comorbidities may be monitored.
The Systemic Lupus Erythematosus Disease Activity Index is one established measure of disease activity that should be included in every evaluation.
 Thorough surveillance (every 3 months) for kidney disease development in high-risk ethnicities, male sex, juvenile-onset, high serologic activity, and anti-C1q antibody positivity.Atherosclerotic cardiovascular disease (ASCVD) - Follow recognized criteria when monitoring and treating traditional risk factors.
– Take into account SLE-specific variables, such as high disease activity, high doses of glucocorticoids, lupus nephritis, and antiphospholipid antibodies, when using standard ASCVD risk calculators as they may underestimate risk in SLE.
All patients with osteoporosis: smoking cessation, weight-bearing activity, sufficient calcium and vitamin D intake, and moderate alcohol consumption
- 2017 ACR guideline for prevention and treatment of glucocorticoid-induced osteoporosis (see "Additional Reading") - Long-term treatment with glucocorticoids: clinical fracture risk assessment +/ bone mineral density measurement
 A glucocorticoid- and/or hydroxychloroquine-based ophthalmologic examination for cataracts and glaucoma (retinal damage)
Malignancy: Comply with recommendations for routine cancer screening for the general population.
Neuropsychiatric: Think about conducting a cognitive and mood problem screening.


Diet – Despite the likelihood that dietary components influence immune system function, there is not enough data to propose a specific dietary plan for SLE patients.
Complications or comorbidities (renal failure, diabetes, cardiovascular disease, osteoporosis, or high-dose glucocorticoids) may call for dietary change.


The likelihood of a long-lasting, treatment-free remission is low.
The standardized mortality ratio (SMR) with SLE is 2.6, which is higher than the SMR for the general population.
90% of 10-year survivors survive.

Obstetric complications, medication toxicity, malignancy (particularly hematologic, cervical, breast, and lung), renal failure, cardiovascular and thromboembolic events, infections, and mortality are among the complications.

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