SYSTEMIC LUPUS ERYTHEMATOSUS

 an inflammatory, autoimmune connective tissue disorder that affects nearly every

organ in the body
 Incidence rate estimated to be 1.8-7.6 per 100,000 people, occurring 6 times
more frequently in women than men; 3 times more in African-American
populations than Caucasians.
 Other forms of adult lupus
o Discoid lupus erythematosus (which primarily affects the skin on the
face)
o Subacute cutaneous lupus erythematous (sun exposed areas affected
with sores)
o Drug-induced lupus (rarely includes brain or kidney effects and is usually
temporary).
 The course of SLE is mild for most, with periods of remission and
exacerbation
o Number and severity of flares tend to decline with time
o In some cases, it is a virulent disease with significant organ system
involvement
 People with active disease have an increase risk of infection (often
opportunistic and severe)
o Pneumonia and septicemia are the leading cause of death
o Followed by renal or CNS involvement

PATHOPHYSIOLOGY
 Begins with immune system’s inaccurate recognition of one or more
components of cell’s nucleus as foreign (as an antigen)
o Components such as nucleic acids, erythrocytes, coagulation proteins,
lymphocytes, and platelets
o causes development of a large variety of antibodies to the nuclear antigen
 The B cells (humoral response) in particular begin hyperactivity with
overproduction of antibodies
o with the help of multiple cytokines such as B-lymphocyte stimulator or
BLyS, overexpressed in antibodies
o this is due to disordered T-cell function (cellular immune resoponse)
o the most characteristic antibodies in SLE are produced in response to
nucleic acids (DNA, histones, ribonucleoproteins, etc.)
 Antigen-antibody complexes are formed with propensity to get trapped in the
capillaries of visceral structures, as the antibodies also attack host cells
o Inflammatory response leads to local tissue damage
o Kidneys are the frequent site of complex deposition and damage
  The immunoregulatory disturbance is hypothesized to be due to some
combination of four distinct factors: genetic, immunologic, hormonal, and
environmental
 Genetic origins of SLE has revealed likeliness of multiple genes being
implicated, as research suggests, supported by homozygous twins showing
higher incidence of SLE with their family members showing low prevalence
 The large majority of SLE are sporadic and unrelated to family history
 Female sex hormones (estrogen) is also a subject of interest, as it may
contribute to the body’s response of overreaction to own tissues
o Women with SLE have reduced levels of several active antibodies that
inhibit antibody responses
 Exogenous or environmental triggers are also hypothesized to be implicated
in the onset of the disease process, including:
o Cigarette smoke
o UV ray exposure
o Medications
o Infections
o Emotional stress
o Stress on the body
o Silica dust exposure
 A number of drugs can cause a syndrome that mimics lupus in people with no
other risk factors (drug-induced lupus)
o Procainamide (e.g. Procan-SR, Pronestyl) and hydralazine (e.g.
Hydralyn) are the most common drugs implicated, along with isoniazid
(INH)
o Renal and CNS manifestations rarely occur in drug-induced lupus, but
the other systemic symptoms are observed
CLINICAL MANIFESTATIONS
 Initially mimics rheumatoid arthritis manifestations
 In chronic states, symptoms are minimal or absent
 In acute flares, symptoms and lab results are elevated
 Systemic symptoms
o Fever
o Malaise
o Weight loss
o Anorexia
o Mucocutaneous, musculoskeletal, renal, nervous, cardiovascular, and
respiratory systems are most commonly involved
o Gastrointestinal tract, the liver and the ocular system less so.
 Cutaneous system manifestation in 80%-90% of cases
 o Acute cutaneous lesion
 Most familiar skin manifestation (occurring in less than 50% of
cases)
 Butterfly-shaped erythematous rash
 Smattered across bridge of nose and cheeks
o Subacute cutaneous lupus erythematosus
 Papulosquamous or annular polycyclic lesions
 Discoid rash (chronic rash with erythematous papules or plaques)
o In some cases, only discoid rash is seen.
o In some patients, the initial skin involvement is a precursor to systemic
involvement
o Lesions often worsen during exacerbations of systemic disease
o May possibly be provoked by sunlight or artificial UV light
o Oral ulcers
 May accompany skin lesions
 May involve buccal mucosa
 Occur in crops
 Associated with flares
o Other cutaneous manifestations
 Splinter hemorrhages
 Alopecia
 Reynaud’s phenomenon
 Joint symptoms
o Arthralgia, arthritis, or both occur in more than 90% of patients
o Earliest manifestation of disease process
o Joint swelling, tenderness, and pain on movement are common, with
accompanied morning stiffness
 Cardiac Issues
o Pericarditis is the most common cardiac manifestation
o Presentation of substernal chest pain aggravated by movement or
inspiration
o May be acute and severe or lasting several weeks
o Myocarditis, hypertension, cardiac dysrhythmias, and valuvular
incompetence may also be observed
o Women with SLE are at risk for early-onset atherosclerosis, increasing
likelihood of MI or stroke, possibly contributing to higher mortality rates in
women with SLE
o Inflammation as key factor in development and progression of
artherosclerosis
 Renal Problems
o Approximately 50% of cases experience renal manifestations, including
proteinuria, cellular casts, and nephrotic syndrome
 o Lupus nephritis occurs due to buildup of antibodies and immune
complexes, damaging the nephrons
o Serum creatinine levels and immune complexes used to screen renal
involvement
o Early detection to prevent renal damage
o Up to 10% develop renal failure as a result
 CNS involvement
o Widespread, encompassing entire range of neurologic disease
o Varied and frequent neuropsychiatric presentation are now widely
recognized, with inclusions of psychosis, cognitive impairment, seizures,
peripheral and cranial neuropathies, transverse myelitis, and strokes,
o Generally demonstrated with subtle behavioral or cognitive changes.

ASSESSMENT & DIAGNOSTIC FINDINGS

 Based on complete history, physical examination, and blood tests
 Special features as addition of assessment of patient with rheumatic
disease
o Skin inspection of erythematous rashes
 Cutaneous erythematous plaques with adherent scale
observed on scalp, face, or neck
 Areas of hyperpigmentation or depigmentation, depending on
phase and type
 Questioning of patient about skin changes
 Specifically sunlight or artificial UV light sensitivity
 Scalp inspection for alopecia
 Mouth and throat for ulcerations reflecting GI involvement
o Cardiovascular assessment
 Auscultation
 Pericardial friction rub (associated with myocarditis and
pleural effusions)
 Abnormal lung sounds (reflecting respiratory
insufficiency, pleural effusions, and infiltrations)
 Papular, erythematous, and purpuric lesions
 Fingertips
 Elbows
 Toes
 Extensor surfaces of forearms
 Lateral side of the hand
o Joint swelling, tenderness, warmth, pain on movement, stiffness and
edema on physical examination; often symmetric and similar to
Rheumatoid Arthritis
o Neurologic assessment
  For CNS changes
 Patient and family inquired about behavioral changes
(neurosis or psychosis)
 Signs of depression, seizures, chorea, or other CNS
manifestations are noted.
 The American College of Rheumatology has established a criteria for SLE
classification
o 11 distinct elements involved (four cutaneous, four systemic, and
three laboratory criteria)
o Diagnosis of SLE if 4 of the 11 criteria are present, either serially or
simultaneously
o Cutaneous Criteria
 Malar rash
 Discoid rash
 Photosensitivity
 Oral Ulcers
o Systemic Criteria
 Nonerosive arthritis
 Pleuritis or pericarditis
 Kidney disease
 Neurologic disease
o Laboratory Criteria
 Hematologic disorder
 Immunologic disorder
 Positive antinuclear antibody
 Other laboratory tests
o Anti-DNA (antibody developed against patient’s own DNA) more
specific as antibodies are rarely foind in other disorders
o Anti-ds DNA (antibody against DNA highly specific to SLE; helps in
differentiation from drug-induced lupus)
o Anti-Sm (antibody against Sm, a specific protein found in the nucleus)
o Blood work (CBC may reveal anemia, thrombocytopenia, leukocytosis,
or leukopenia)
o Serum complement levels usually decreased as complement is used
up or consumed by the antibody-antigen complexes
o Urinalysis shows mild proteinuria, hematuria, and blood cell casts
during disease exxacerbations
o Kidney biopsy to assess severity of renal lesions

MEDICAL MANAGEMENT
 SLE can be life-threatening, but advancements in its treatments led to improved
survival and reduced morbidity
 Acute interventions are directed at controlling increased disease activity or
exacerbations
 Disease activity is a composite of clinical and laboratory features reflecting active
inflammation secondary to SLE
 Chronic management involves periodic monitoring and recognition of
meaningful clinical changes prompting therapy adjustments
 Goals of treatment include
o Prevention of progressive organ function loss
o Reduction of likelihood of acute disease
o Minimizing disease-related disabilities
o Prevention of complications from therapy
 PHARMACOLOGIC THERAPY
o Based on pain management and nonspecific immunosuppression
o These medications have potentially serious side effects, including organ
damage
o Belimubab (Benlysta) is approved by FDA as SLE treatment
 monoclonal antibody specifically recognizes and binds to BLyS
(acts to stimulate B cells production of antibodies against own
nuclei)
 acts to render BLys inactive, preventing it from binding to B-cell
surfaces and stimulating B-cell activity
 this halts production of unnecessary antibodies, decreasing
disease activity
 research suggests reduction of disease activity and flares
 contraindication of live vaccines, and caution with use of all
concurrent medications
o Corticosteroids
 Topically for cutaneous manifestations
 Low oral doses for minor disease activity
 High oral doses for major disease activity
 IV administration as an alternative for traditional high oral doses
 Risk factors of osteoporosis and fractures; osteopenia reported in
25%-74% and osteoporosis in 1.4%-68% of cases
o Hydroxychloroquine, an antimalarial medication approved by the FDA
 Effective for managing cutaneous, musculoskeletal, and mild
systemic features
 NSAIDS used for minor clinical manifestations are used in
conjuction with corticosteroids to minimize corticosteroid
requirements
o Immunosuppresive agents (alkylating agents and purine analogues)
 Used for overall immune function effect
 Reserved for patients with serious forms of SLE that do not
respond to conservative therapies
 Cyclophosphamide, azathioprine, mycophenoli acid (Myfortic)
and methotrexate, are contraindicated in pregnancy and have
been used most frequently in SLE nephritis
 Certain cytotoxic or antineoplastic drugs are effective as
immunosuppressive agents
 Acts by decreasing cell proliferation within the immune
system