SLE, Reactive Arthritis, Vasculitis Flashcards
1
Q
Systemtic Lupus Erythematosus
A
- A chronic inflammatory multi-system disease of unknown etiology
- Charactertized by:
- Production of autoantibodies
- Diverse clinical manifestations
2
Q
Etiology of SLE
A
The pathophysiology of SLE is multifactoral involving genetics, hormones, immunological factors, and environmental
- Genetics
- HLA-B8/DR3
- Defects in apoptotic clearance, resulting in fragements of nuclear particules being captured by antigens presenting cells and the development of anti-nuclear antibodies
- Cytokines involved = B-lymphocytes stimulator, IL-6, IL-17, IL-18, TNF-α
- Hormones
- Higher levels of estrogen are associated with SLE. I.e., increase incidence after puberty, decrease incidence after menopause, men with SLE have higher concentration of estrogen
- Immune abnormalities - there are numerous immune defects in SLE, primarily in immune regulation likely due to a loss of self-tolerance resulting in an autoimmune response.
- Immune complexes (Ag-Ab complexes) and autoantibodies form (these tend to be present for years before first disease symptoms appear). (Self-antigens tend to be found on cell surfaces, particularly those undergoing apoptosis).
- Phagocytosis and clearning of immune complexes is dysfunctional resulting in increase antigens and immune complexes.
- B-cells that make these autoantibodies are more persistently activated by B lymphocyte stimulator and by T-helper cells releasing B-supportive cytokines IL-6 and IL-10.
- Environmental factors - environment likely has a role via its effects on the immune system.
- Viruses - may stimulate antigen-specific cells in immune network
- UV light - may cause excess secretion of certain IL
- Cigarette smoking
- Allergies to medications, particularly antibiotics are reported more frequently in SLE patients.
3
Q
Renal Disease in SLE
A
- Renal disease in SLE is likely due to deposition of immune complexes in mesangium, subendothelial, or subepithelial space, with subsequent activation of complement.
- Immune complexes in renal SLE consist of nulcear antigens (i.e., DNA) and high-affinity, complement-fixing immunoglobulin G (IgG) antinuclear antibodies (ANA), and antibodies to DNA.
- Once deposited in mesangial or subendothelial part of GBM, immune complexes activate the complement system that generates chemotaxtic factors that attract infiltration of leukocytes and mononuclear cells. These cells then phagocytose the immune complexes and release inflammatory mediators, resulting in glomerular inflammation.
4
Q
Clinical Presentation SLE
A
SLE can affect almost every organ system and can vary dramtically between patients. The pattern of symptoms that predominate during the first few years of illness tend to persist throughout. SLE is characterized by periods of exacerbation and remission.
- Systemic - fever, malaise, weight loss, lymphadenopathy
- Arthritis and arthalgais - occurs in over 90% and is often a early manifestation
- Dermatologic - Lots of variability in type of skin involvement, but most common is the butterfly rash. Photosensitivity malar rash, discoid rash, oral ulcers, alopecia, purpura, panniculities, urticaria.
- Vascular - Raynaud’s phenomenon (vasospactic disorder characterisitically causing discolouration of fingers and toes), vasculitis, livedo recticularis (mottled discolouration of skin due to narrowing of blood vessles), thrombosis.
- Renal - HTN, peripheral edema, glomerulonephritis, renal failure
- Ophthalmic - keratoconjunctivitis sicca, episcleritis, scleritis, cytoid bodies (cotton woll exudates on fundoscopy)
- Cardiac - pericarditis, CAD, non-bacterial endocarditis, myocarditis, coronary vasculitis, malignant HTN, tamponde
- Respiratory - pleuritis, ILD, pulmonary HTN, PE, alveolar hemorrhage
- GI - Pancreatitis, SLE enteropathy, hepatitis, hepatomegaly, spenomegaly
- Neurologic/Psychiatric - headach, depression, psychosis, seizures, cerebritis, transverse myelitis, peripheral neuropathy, stroke
- Hematologic - hemolytic anemia, neutropenia, thrombocytopenia, TTP, thrombosis
5
Q
Investigations SLE
A
- Antinuclear antibody (ANA) - used to look for autoantibodies that attack components of cells’ nucleus (high sensitivity and poor specificity).
- anti-dsDNA and anti-Sm (high specificity)
- anti-dsDNA titre and serum complement (C3, C4_ are useful to monitor treatment response in patients who are clinically and serologically concordant
- Complement level C3 and C4 - lupus tends to have low levels of C3 and C4
- EST and CRP - indirect indication of inflammation. Generally high during active disease
6
Q
Assessment of disease activity SLE
A
Important to do lab work to assess disease acitivity and monitor organ specific complications
- CBC - leukopenia, anemia, and/or thrombocytopenia can reflect active disease. However, cytopenias may also be a sign of drug toxicities.
- Acute phase reactants (ESR and CRP) - usually elevated in SLE, but may still reflect incresae diseased activity
- Urinalysis and examination of urinary sediment - proteinuria, cellular casts, and/or hematuria may reflect renal involvement
- Creatinine and eGFR - may reflect lupus nephritis
- Anti-dsDNA - often fluctuates with disease activity, particularly in those with active glomerulonephritis
- Complement levels (C3 and C4) - low or elevated often indicate active lupus
- Depending on organ systems involved, may do additional tests - i.e., Echo, renal biopsy, etc.
7
Q
Nonpharmacologic and preventive interventions SLE
A
- Sun protection
- Diet and nutrition
- Exercise
- Smoking and cessation
8
Q
Pharmologic Therapies SLE
A
- In general all patients with SLE should be treated with hydroxychloroquine (plaquenil) or chloroquine unless contraindications - helps relieve symptoms and hydroxchloroquine may reduce flares
- If patients has arthritis - NSAIDs + Gastroprotective agents
- Patients with significant but non-organ threatening disease can also be put on short-term glucocorticoids, which should be tapered once hydroxychloroquine or chloroquine have taken effect. A steriod -sparing immunosuppressive agents (azathiprine or methortrexate) if often needed to control symptoms).
- Patients with severe of life threatening manifestations generally need initial period or intensive-immunosuppressive therapy (pulse glucocorticoids + other immunosupprossives)
- IV cyclophosphamide - for serious organ involvement
9
Q
Diagnositic Criteria of SLE
A
Need 4 or more out of 11 criteria
- S - Serositis (pleuritis or pericarditis)
- O - Oral/nasal ulcers (usually painless)
- A - Arthritis (symmetric, involvement ≥ 2 small or large peripheral joints, non-erosive)
- P - Photosensitivity
- B - Blood - all low
- R - Renal disorder (proteinuria, cellular casts)
- A - ANA
- I - Immunologic disorder (anti-dsDNA or anti-Sm)
- N - Neurologic disorder - seizures or psychosis
- M - malar rash (butterfly rash - spares nasolabial folds, no scarring)
- D - Discoid (may cause scarring due to invasion of basement membrane)
10
Q
Reactive Arthritis
A
- Arthritis that occurs following an infection
- Pathogens cannot be cultured from affected joint (seronegative).
- Considered a form of spondyloarthritis (SpA) - long-term chronic disease of the joints
- *A seronegative spondyloarthritis where patients have a peripheral arthritis (≥ 1month) accompanied by one or more extra-articular manifesations that appear shortly after certain infection of GI or GU tracts.
11
Q
Etiology Reactive Arthritis
A
- Reactive arthritis occurs following an infection of the GI or GU tract
- GI: Shigella Salmonella, Campylobacteria, Yersinia, C. Difficile Species
- GU: Chlamydia, Mycoplasma species
12
Q
Clinical Presentation Reactive Arthritis
A
Acute onset; 1-4 seeks post infection; lasts for weeks to years (usually resolves within 6 months and almost always within 1 year. If greater than 6 months it is considered chronic).
Signs and symptoms:
- Symptoms of preceding GI or GU infection that cause arthritis are diarrhea or urethritis (patients with arthritis induced by GI bacteria can develop aspectic urethritis). Many patients with these infections may be silent and are only detectable by lab testing
- Axial and/or peripheral MSK signs and and symptoms
- Peripheral arthritis - acute onset asymmetric oligoarthritis. Often affects lower extremities, especially the knee.
- Enthesitis - Enthesis is a site of insertionof ligments, tendons, joint capsule, or fascia to bone. Enthesitis is inflammation around this area. Swelling at the heels in characteristic
- Dactylitis - “sausage digits”
- Axial, especially low back pain - inflammatory low back pain is frequent as a accompanying symptoms. but is generally not the only presenting symptoms.
- Extraartricular signs and symptoms
- Occular symptoms - anterior uveitis, conjunctivitis
- GU tract symptoms - dysuria, pelvic pain, urethritis, cervicitis, prostatitis, salpingo-oophortisi, or cystis
- GI - diarrhea, oral ulcers
- Dermatologic - keratodermia blennorrhagica, erythmia nodosum
- Nail changes that resemble psoriasis
13
Q
Investigations Reactive Arthritis
A
- Antecendent or concomitant infection - may find pathogens in stoll culture or in urine and genital swabs. However, initial infection may be resolved by this point.
- Acute inflammatory changes - acute phase reactant like ESR and CRP may be elevated
- Genetic testing - prevalance of HLA-B26 is increased in paitents with spondyloarthritis
- Inflammatory synovitis - findings are non-specific and characteristic of inflammatory arthritis - elevated leukocytes
14
Q
Diagnosis Reactive Arthritis
A
- Clincial Diagnosis is based on findings and exclusion of other disease. Diagnosis is suspected if patients exhibits all 3 of the following:
- Characteristic MSK findings
- Evidene of preceding extraarticular infection - i.e., urethritis or diarrhea
- A lack of evidence for alternative diagnosis - i.e., septic arthritis, traumatic arthritis, crystal induced arthrits. RA, SLE, etc.
15
Q
Treatment Reactive Arthritis
A
- Antibitics for non-articular infections, particularly those with GU infections (generally not requried for uncomplicated GI infection).
- NASIDs - naproxen 500mg 2/3/day, diclofenac 50mg 3/day, or indomethancin 50mg 3-4/day
- If patient does not respond to NSAIDs, can try intraarticular glucocorticoids > systemic glucocotricoids (used if there are numerous joints or if patient does not respond to injection)
- If patient does not respond to NSAIDs or glucocorticoids can try DMARDs
- Chronic reactive arthritis (>6months) initiate DMARDs (sulfasalazine or methrotrexate). If they dont respond can try a TNF inhibitor.
