Case 20 Systemic Lupus Erythematosus

February 12, 2008 Group C10

History of Present Illness

Patient Data
• H.H., 19 y.o., Filipino female, single, Roman Catholic, a student from San Pedro, Laguna • • • • Source: patient and her mother Reliability: 80% Date of Admission: Jan 17, 2008 Date of Interview: Jan 25, 2008

Chief Complaint: Dyspnea
HPI: Two years prior to admission • Headache- more prominent on the right
– Self-medicated: mefenamic acid  offered relief

• Joint and muscle pains • Generalized weakness
– Persisted and progressed that patient needed help in order to ambulate

HPI: 51 weeks prior to admission

• Anorexia • Skin sores in the anterior thorax • Wounds on her breast around the areolar region • Recurrence of headache • Persistence of joint and muscle pains and generalized weakness • Prompted consultation at Medical City
– Tested for visual problems = (-) – Asked to consult psychiatrist =did not comply

HPI: 50 weeks prior to admission

• Continuous fever = 400C
– Persisted for a week

• Bluish discoloration of fingers • Prompted another consultation at Medical City • During consultation, suddenly experienced difficulty of breathing • Rushed to the ER then moved to the ICU because of

HPI: 48 weeks prior to admission

• Diagnosed with systemic lupus erythematosus (SLE) with class V lupus nephritis • Treated with hydrocortisone (unrecalled dosage) • Discharged with medications: prednisone • She was not compliant due to side-effects of treatment: weight gain and acne development

46 weeks prior to admission

HPI: 10 months prior to admission • Started to develop oral sores and ulcers over most of her buccal cavity • Prompted consultation and confined for five days at Medical City • Was given unrecalled medications and was discharged when sores were healed

HPI: 7 months prior to admission • Bilateral knee pain • Could not stand alone • Confined at Medical City for fifteen days • Treated with hydrocortisone and methyprednisolone (Solu-medrol) – unrecalled dosage • Soon experienced weakness and hair fall (alopecia) • Reduced dosage of the drugs improved her condition • Prescribed with prednisone, vitamins (for anemia), and calcium • Not compliant with

HPI: 1 month prior to admission • Abnormally enlarging abdomen • Self-medicated with previously prescribed steroids but to no avail • Consulted at USTH OPD • Prescribed with prednisone and hydroxychloroquine (Plaquenil)
– Abdominal flattened

8 days prior to admission

7 days prior to admission

• Returned to OPD for lab results • Diagnosed with UTI

HPI: 3 days prior to admission • Abdomen started to enlarge again • Accompanied by swelling of hands and feet • Progressed rapidly • Also experienced vomiting • Difficulty of breathing even at rest • Rushed to USTH emergency room and was admitted

2 hours prior to admission

Medical History

Obstetric and Gynecological History
• G0P0 • Menarche at 12 y.o. • Irregular menstrual flow (1-2 months with no period) • Menstrual periods last 5 days • Consumes 2-3 pads a day • LMP: December 2007 (unrecalled date)

Past Medical History
1988

• Bronchopneumonia: 3 months old • Dislocated left knee while dancing

2001

Past Medical History
2006

• SLE with lupus nephritis class V

Feb 2006

• Blood transfusion (1 bag packed RBC)

Past Medical History
• Has skin allergies with no identified trigger/agent – takes Celestamine • No history of surgery • Current medications: prednisone as treatment of SLE • Immunizations: given DPT, BCG, OPV; no hepatitis vaccines, MMR or influenza

Family History
• No family history of gout or arthritis, allergy, cancer or stroke • Mother: (+) anemia • Father: (+) hypertension, (+) heart disease • Grandmother, mother’s side: (+) DM

Personal and Social History
• Non-smoker, non-alcoholic, no illicit drug use • Fond of eating fried food, usually pork or chicken and rarely eats vegetables

Personal and Social History
• Household chores are the only form of exercise • Lives in Laguna with her parents and 2 younger sisters which are all healthy

Personal and Social History
• Piggeries around the house and a nearby river, but is not polluted • SLE has greatly affected her teenage lifestyle • Common concerns such as weight gain and acne development has made her non-compliant to steroid therapy

Review of Systems
• General: Has anorexia and weakness of the whole body. No significant weight changes. No fever, sweats, insomnia. • Skin: Has erythematous, flat rash over the malar eminences. No color change in the other parts of the body • HEENT: – Head: No history of head injury. – Eyes: No visual dysfunction or lacrimation. No itchiness, pain or recent changes in vision. – Ears: Hearing good. No tinnitus, vertigo, infections. – Nose, sinuses: No hay fever, sinus trouble. – Throat: No soreness or tonsilitis.

Review of Systems
• Neck: Has stiff neck. No lumps, goiter, pain. No swollen glands • Breasts: No lumps, pain, discharge • Respiratory: Has dyspnea. Cough productive of sputum that is difficult to expectorate. Has back pains. No orthopnea • Cardiovascular: Hypertensive with highest recorded BP 150/110. Has edema in the upper and lower extremities. No chest pain and palpitations. No PND, syncope

Review of Systems
• Gastrointestinal: Distended abdomen. No nausea, vomiting, indigestion. Has regular bowel movements. No abdominal pain. • Urinary: Has oliguria and flank pains. No other urinary problems • Genital: No straining, genital lesions or urethral discharge • Musculoskeletal: Has generalized edema and some limitations in movement of hands and feet. Has generalized weakness.

Review of Systems
• Endocrine: No neck surgery, irradiation, polydypsia or polyphagia. • Hematologic: Anemic. No bleeding problems. • Neurologic: No fainting, seizures, motor or sensory loss. Memory good. • Nails: No clubbing

ON ADMISSION

PHYSICAL EXAMINATION

ON ACTUAL EXAMINATION General Survey • Conscious, coherent, oriented as to time, place and person, not in cardio-respiratory distress • BP – 140/90 mmHg PR 96, regular, RR 24, regular pattern of breathing Temp 36.2 °C • Height- 5’6’’ Weight- 65 kg

General Survey • Conscious, coherent, ambulatory and in cardiorespiratory distress • BP -140/80 mmHg PR 140, regular RR 40 Temp 38.2°C

ON ADMISSION General Survey

PHYSICAL EXAMINATION

ON ACTUAL EXAMINATION General Survey • Skin is shiny, stretched due to edema • erythematous flat rash over malar eminences • non-erythematous macular lesions less than 1cm in the anterior thorax near the neck

• Warm, moist skin, no active dermatoses

Malar Rash

Source: http://www.emedicine.com/med/images/329097332244-5270.jpg

ON ADMISSION

PHYSICAL EXAMINATION

ON ACTUAL EXAMINATION HEENT • Pale palpebral conjuctiva, anicteric sclera • No ear and nasal dischage • Moist buccal mucosa, (+) oral ulcers • No palpable cervical lymphadenopathies, no neck masses

HEENT • Pale palpebral conjuctiva, anicteric sclera • No ear and nasal discharge • Moist buccal mucosa, (+) oral ulcers • No palpable cervical lymphadenopathies, no neck masses

ON ADMISSION Respiratory

PHYSICAL EXAMINATION

ON ACTUAL EXAMINATION Respiratory • Symmetrical chest expansion • no retractions • Resonant • decreased tactile and vocal fremiti in the left posterior lower lung region • fine rales heard

• Symmetrical chest expansion • no retractions • decreased tactile and vocal fremiti • decreased breath sounds on the left T6T7 down • (+) crackles on left lung field

ON ADMISSION

PHYSICAL EXAMINATION

ON ACTUAL EXAMINATION Cardiovascular • JVP 3.0cm above the sternal angle at 300 • CAP has rapid upstroke gradual downstroke • Adynamic precordium, apex beat at the 5th LICS, MCL. • Apex: Loud S1 followed by soft S2; base: Soft S1 followed by loud S2, splits at inspiration , no murmurs, no heaves, thrills, or lifts.

Cardiovascular • Adynamic precordium, apex beat 5th LICS MCL (apex: S1>S2; base: S2>S1), no murmurs

ON ADMISSION Abdominal • Flabby abdomen

PHYSICAL EXAMINATION

ON ACTUAL EXAMINATION Abdominal • Abdomen is distended and shiny with silvery white striae • normoactive bowel sounds, no bruits • (+) dullness over abdominal region • could not assess liver dullness

• normoactive bowel sounds

ON ADMISSION Abdominal

PHYSICAL EXAMINATION

ON ACTUAL EXAMINATION

Abdominal • no abnormal masses • soft, direct tenderness • no tenderness upon on LUQ palpation • no costovertebral angle tenderness • (+) bulging flanks, (+) • (+) shifting dullness, (+) fluid wave fluid wave

Extremities • Pulses full and equal, (+) edema, (-) cyanosis

Extremities • (+) edema

PHYSICAL EXAMINATION
Central and Peripheral Pulses
(0)=absent (+)=decreased (++)=normal (+++)=hyperactive (Br)=bruit

PULSE CAROTID BRACHIAL RADIAL FEMORAL POPLITEAL DOR PEDIS POST TIBIAL RIGHT LEFT ++ ++ ++ ++ ++ ++ ++ ++ ++ ++ ++ ++ ++ ++

PHYSICAL EXAMINATION ON ACTUAL EXAMINATION
Musculoskeletal • Temporomandibular joint: no skin changes, abnormal contours or deformities; no swelling or tenderness, good movement Upper extremities • Shoulder joint: no skin changes and deformities, symmetrical, no swelling and tenderness, no limitation in motion • Elbow joint: no skin changes and deformities, no tenderness and thickening, slight limitation in motion due to edema, right elbow has an IV so could not be moved

ON ACTUAL EXAMINATION Upper extremities • Forearm, wrist and hand: edematous, bulky hands; no redness, nodules, no metacarpophalangeal tenderness; no interphalangeal tenderness; right hand unable to make a fist and has limited extension and flexion; left hand has limited extension and slightly limited flexion. • Neck: Sternomastoid muscles are symmetrical, has no deformities nor abnormal postures; Trapezius muscles are tender; Cervical spinous processes and muscles between the scapulae are

PHYSICAL EXAMINATION

ON ACTUAL EXAMINATION Musculoskeletal • Back: no skin changes, abnormal contours and deformity; no swelling and tenderness of cervical, thoracic and lumbar spinous processes; no abnormal postures or lateral curvatures; no limitation in movement Lower Extremities • Hip joint: no skin changes, abnormal contours and deformity; no swelling and tenderness; no limitation in movement

PHYSICAL EXAMINATION

ON ACTUAL EXAMINATION Lower Extremities • Knee joint: no skin changes, abnormal contours and deformity; no muscle atrophies and thickening; slight swelling due to edema and no tenderness in the patellar region; no limitation in movement, no instabilities; (-) bulge sign, (-) balloon sign • Ankle and foot joints: edematous feet, (+) pitting edema = 3-4+, no abnormal contours and deformity; no muscle atrophies and thickening; no metatarsophalangeal tenderness; no interphalangeal joint swelling and tenderness;

PHYSICAL EXAMINATION

ON ADMISSION

PHYSICAL EXAMINATION

ON ACTUAL EXAMINATION
Neurologic • Conscious ,GCS 15 • Coherent, oriented to time, place and person; good registration, good attention, calculation and recall, good sense of language and constructional ability, good memory CN I – XII are all intact No muscle atrophy, good muscle bulk and tone, MMT 3/5 in the upper extremities while 4/5 in the lower extremities

Neurologic • Alert , awake. Can follow simple commands. • Pupils 2-3mm ERTL, EOMs full and equal. • V1V2V3 intact, can smile, clench teeth, raise eyebrows, tongue midline, can shrug shoulders • DTR: normoreflexive on knee and ankle jerk • MMT: All major muscle groups of bilateral UE/LE are 4/5

• •

ON ADMISSION

PHYSICAL EXAMINATION

ON ACTUAL EXAMINATION

Neurologic • ROM: No limitations on range of motion • (-) nuchal rigidity, (-) Kernig’s sign, (-) Brudzinski’s sign, (-) Babinski

Neurologic • Can do FTNT and alternating pronation and supination • Balance and equilibrium was not assessed • No sensory deficits • Reflexes was not assessed due to edema • (-) Babinski • Good neck mobility, (-) Brudzinski’s sign, (-) Kernig’s sign

SALIENT FEATURES Objective Findings
PERTINENT POSITIVES PERTINENT NEGATIVES

• Female, 19 years old (reproductive age) • Oral sores and ulcers • Skin sores on anterior thorax and breast • Erythematous flat rash over malar eminences • Anasarca

• No chest pain and palpitations • Normal JVP, CAP and adynamic precordium • No musculoskeletal deformities

SALIENT FEATURES Subjective Findings
PERTINENT POSITIVES PERTINENT NEGATIVES

• Headache • Fever • Joint and muscle pains • Generalized weakness
– Assisted ambulation

• Anorexia • Bluish discoloration of fingers • Difficulty of breathing • Bilateral knee pain • Skin allergies • Anemia

• No family history of gout or arthritis, allergy, cancer or stroke • No seizures • No memory loss

CLINICAL MANIFESTATION Hematologic Arthritis Skin Fever Fatigue Weight loss Renal CNS Pleuritis Myalgia Pericarditis Gastrointestinal Reynauds phenomenon Ocular Peripheral neuropathy

PREVALENCE IN PATIENTS, % 100 90 85 83 81 63 50 50 46 33 25 21 20 15 14

From Robbins and Cotran Pathologic Basis of Disease 7th ed.

1997 REVISED CRITERIA FOR CLASSIFICATION OF SYSTEMIC LUPUS ERYTHEMATOUS
CRITERION 1. Malar rash 2. Discoid rash 3. Photosensitivity 4. Oral ulcers 5. Arthritis 6. Serositis 7. Renal disorder 8. Neurologic disorder 9. Hematologic disorder 10. Immunologic disorder 11. Antinuclear antibody DEFINITION Fixed erythema eminence over the malar

Erythematous raised patches Skin rash as a result of exposure to UV light Oral or nasopharyngeal ulceration Nonerosive arthritis Pleuritis, Pericarditis Persistent proteinuria Seizures, Psychosis Hemolytic anemia, Leukopenia, Lymphopenia, Thrombocytopenia Anti-ds DNA, antiantiphospholipid An abnormal antibody titer of Sm, and/or

antinuclear

Data from Tan EM, et al. The Revised Criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 25:1271, 1982; and Hochberg, MC: Updating the American College of Rheumatology revised criteria for he classification of systemic lupus eryhtematosus. Arthritis Rheum 40: 1735, 1997

1997 REVISED CRITERIA FOR CLASSIFICATION OF SYSTEMIC LUPUS ERYTHEMATOUS
• • 11 criteria SLE – 4 or more are present – serially or simultaneuosly, during any interval of observation Patient – arthritis – oral ulcers – malar rash – renal disorder – hematologic disorder

Definition of Terms
• Rheumatology
– rheuma – that which flows as a river or stream – encompasses the autoimmune diseases, arthritis, and musculoskeletal conditions. While rheumatologists are generally thought to be specialists dedicated to rheumatoid arthritis, lupus and scleroderma, we also care for patients with a wide array of systemic, inflammatory, autoimmune diseases as well as very common musculoskeletal Source: http://en.wikipedia.org/wiki/Rheumatologyand disorders (e.g., osteoarthritis http://www.rheumatology.org/students/faq.asp (American osteoporosis) and sports-related injuries.
College of Rheumatology)

Definition of Terms
• Rheumatism
– non-specific term used to describe any painful disorder affecting the loco-motor system including joints, muscles, connective tissues, soft tissues around the joints and bones – A term used for acute and chronic conditions marked by inflammation, muscle soreness and stiffness, and pain in joints and associated structures Source: http://en.wikipedia.org/wiki/Rheumatology

Pathophysiology of SLE

Autoimmune Diseases
• autoantibodies react against self-antigens • autoantibodies are not always pathological • requirements to establish pathologic immunity
– presence of an autoimmune reaction – evidence that the reaction is not secondary to tissue damage – absence of another well-defined cause of the disease

TABLE 6-7 Autoimmune Diseases Organ-Specific Systemic
Hashimoto’s thyroiditis Autoimmune hemolytic anemia Autoimmune atrophic gastritis of pernicious anemia Multiple sclerosis Autoimmuse orchitis Goodpasture syndrome Autoimmune thrombocytopenia Insulin-depedndent diabetes mellitus Myasthenia gravis Graves disease Primary biliary cirrhosis Autoimmune (chronic active) hepatitis Ulcerative colitis Systemic lupus erythematosus Rheumat oid art hritis Sjögren syndrome Reiter syndrome Inflammatory myopathies Systemic sclerosis (scleroderma) Polyarteritis nodosa

From Robbins and Cotran Pathologic Basis of Disease 7th ed. p 223

Self-tolerance
• • • lack of responsiveness to an individual’s own antigens normal individuals: intact 2 postulated mechanisms
– Central Tolerance
• clonal deletions of self-reactive T and B cell clones occur during their maturation • some may still reach the periphery

– Peripheral Tolerance
• • • • anergy - permanent inactivation of lymphocytes deletion by apoptosis suppression by regulatory T cells antigen sequestration

From Robbins and Cotran Pathologic Basis of Disease 7th ed.

Mechanism of Autoimmune Disease
• susceptibility genes
– influence the preservation of self-tolerance

• environmental factors
– infection
• co-stimulators on APCs are indcued loss of anergy • molecular mimicry .

• progression and chronicity is sustained by the continued recruitment of autoreactive T cells that recognize previously cryptic self-antigens
From Robbins and Cotran Pathologic Basis of Disease 7th ed.

Systemic Lupus Erythematosus
• characterized by the presence ANA, anti-dsDNA, and anti-phospholipid Ab • acute or insidious onset • chronic, remitting, relapsing, and often febrile illness • injury to the skin, joints, kidney, serosal membranes • any other organ in the body may also be affected
From Robbins and Cotran Pathologic Basis of Disease 7th ed.

• tissue-binding autoantibodies and immune

Systemic Lupus Erythematosus
• affects 1 in 700 women of child-bearing age • 90% of patients are of child-bearing age • 9:1 female to male ratio • 2:1 female to male ratio for SLE occurring during childhood or after the age of 65 From Robbins and Cotran Pathologic Basis of Disease 7th ed. and Harrison’s Principles of
Internal Medicine 16th ed.

Systemic Lupus Erythematosus
• fundamental defect breakdown of mechanisms that maintain self-tolerance • Implicated factors
– – – – Genetic Environmental Hormonal Primary abnormality in the immune system

From Robbins and Cotran Pathologic Basis of Disease 7th ed. and Harrison’s Principles of Internal Medicine 16th ed.

Genetic Factors
• HLA-DQ genes in chromosome 6
– encode MHC class II molecules – dysfunction  production of anti-dsDNA, anti-Sm, and anti-phospholpid antibody – 1 susceptibility haplotype: 2x risk – 2 or more susceptibility haplotypes 4x-6x risk
From Robbins and Cotran Pathologic Basis of Disease 7th ed. and Harrison’s Principles of Internal Medicine 16th ed.

Genetic Factors
• Complement deficiency (C2, C4, C1q) – impaired removal of circulating immune complexes – C4 deficiency • loss of B-cell tolerance – C1q deficiency • failure of phagocytosis of apoptotic cells • nuclear components of such cells may induce an immune response • highest genetic risk
From Robbins and Cotran Pathologic Basis of Disease 7th ed. and Harrison’s Principles of Internal Medicine 16th ed.

Environmental Factors
• hydralazine, procainamide, and D-penicillamine  lupus-like response • UV exposure – exacerbations – stimulates keratinocytes to produce IL-1  apoptosis – apoptotic cells may become antigenic From Robbins and Cotran Pathologic Basis of Disease 7th ed. and Harrison’s Principles
of Internal Medicine 16th ed.

Hormonal Factors
• OC pills, HRT – 2x risk of developing SLE • Estradiol – bind to receptors on T cells and B cells – increased activation and survival  extended immune response

From Harrison’s Principles of Internal Medicine 16th ed.

Immunologic Factors
• hyperreactive and hypersensitive T cells and B cells • antigen-specific helper T cell-dependent B cell response  autoantibody production • impaired elimination of apoptotic cells and immune complexes • antigens, autoantibodies, immune complexes persist  tissue injury

From Robbins and Cotran Pathologic Basis of Disease 7th ed. and Harrison’s Principles of Internal Medicine 16th ed.

Autoantibodies
• ANAs can be grouped into:
– Antibodies to DNA – Antibodies to histones – Antibodies to nonhistone proteins bound to RNA – Antibodies to nucleolar antigens
From Harrison’s Principles of Internal Medicine 16th ed.

Autoantibodies
• Other autoantibodies are directed against:
– Red cells – Platelets – Lymphocytes – Proteins complexed to phospholipids
From Harrison’s Principles of Internal Medicine 16th ed.

*Figure 6-30. Taken from Robbins and Cotran Pathologic Basis of Disease 7th ed. p 229

Immune complex-mediated (Type III) Hypersensitivity
• causes majority of the visceral lesions in SLE • 3 phases • First phase: Immune complex formation
Taken from Robbins and Cotran Pathologic Basis of Disease 7th ed.

Immune complex-mediated (Type III) Hypersensitivity
• Second phase: Immune complex deposition
– Determinants if deposition will lead to a disease state
• size of complex: intermediate or small • Intact mononuclear phagocyte system

– Favored sites:
• • • • • • renal glomeruli joints skin heart serosal surfaces small blood vessels

Taken from Robbins and Cotran Pathologic Basis of Disease 7th ed.

Immune complex-mediated (Type III) Hypersensitivity
• Third phase: Inflammation
– from the activation of the complement cascade – neutrophil and macrophage activation – platelet aggregation and Hageman factor activation – microthrombi formation
• Vasculitis • Glomerulonephritis • Arthritis
Taken from Robbins and Cotran Pathologic Basis of Disease 7th ed.

Joints
• involvement is frequent • typical lesion: nonerosive synovitis with little deformity
– distinguishes this arthritis from that seen in rheumatoid disease

• acute phases of arthritis in SLE
– exudation of neutrophils and fibrin into the synovium – perivascular mononuclear cell infiltrate in the subsynovial tissue
From Robbins and Cotran Pathologic Basis of Disease 7th ed.

Disorders of Joints
• Localize the complaint
• ARTICULAR vs NONARTICULAR

• Determine pathologic process
• INFLAMMATORY vs NONINFLAMMATORY

• Determine extent of involvement
• MONOARTICULAR, POLYARTICULAR, FOCAL, WIDESPREAD

• Determine chronology
• ACUTE vs CHRONIC
From Harrison’s Principles of Internal Medicine 16th ed.

Articular vs Nonarticular
Synovium, synovial fluid, articular cartilage, intraarticular ligaments, joint capsule, juxtaarticular bone

Tendons, bursae, muscle, fascia, bone, nerve, skin Focal tenderness on areas distinct from articular structures Limited ROM only upon active movement

Deep or diffuse pain

Limited ROM on active and passive movement swelling

Crepitus, instability, deformity Seldom demonstrate crepitus, instability or deformity
From Harrison’s Principles of Internal Medicine 16th ed.

Inflammatory vs noninflammatory
• Infectious; crystal induced (gout); Immune related (RA or SLE); Reactive (rheumatic fever), or idiopathic • One or all four cardinal signs of inflammation (erythema, warmth, swelling, pain)
From Harrison’s Principles of Internal Medicine 16th ed.

• Related to trauma, ineffective repair (osteoarthritis), neoplasm, pain amplification • Pain without swelling/warmth • Absence of systemic features • Minimal/absent morning stiffness

• Onset – abrupt or indolent • Evolution
– Chronic, migratory, intermittent, additive

• Duration
– Acute, chronic (>6 weeks) *Chronic arthrides often include noninflammatory and immunologic disorders

• Involved articulations
– Mono-, oligo- or polyarticular
From Harrison’s Principles of Internal Medicine 16th ed.

• In SLE musculoskeletal complaints may be associated with systemic features such as fever, rash, or weakness

From Harrison’s Principles of Internal Medicine 16th ed.

From Harrison’s Principles of Internal Medicine 16th ed.

Dyspnea
• “abnormally uncomfortable awareness of breathing” • stimulation of receptors in the lungs, airways, respiratory muscles, or chest wall • excessive or abnormal activation of the respiratory centers in the From Harrison’s Principles of Internal Medicine 16 ed. brainstem
th

Pulmonary Manifestations in SLE
• most common pulmonary manifestations: pleuritis and pleural effusion – 50% of patients • alveolar injury – edema or hemorrhage
From Robbins and Cotran Pathologic Basis of Disease 7th ed. and Harrison’s Principles of Internal Medicine 16th ed.

• chronic interstitial lung disease

Pleural Effusion
• excess quantity of fluid in the pleural space • pleural fluid formation exceeds pleural fluid absorption

From Harrison’s Principles of Internal Medicine 16th ed.

Alveolar Hemorrhage
• abrupt onset with cough, fever, and dyspnea • hemoptysis – may be absent at the time of presentation in 1/3 of the cases • patient: no fever and no hemoptysis
From Harrison’s Principles of Internal Medicine 16th ed.

Interstitial Lung Disease
• involves lung parenchyma – alveoli, alveolar epithelium, capillary endothelium, perivascular and lymphatic tissue • inflammation and fibrosis (in SLE) or granuomatous reaction in intersititial or vascular areas
From Harrison’s Principles of Internal Medicine 16th ed.

Diagnostic Procedures

Laboratory Diagnosis
• Laboratory tests serve to:
– To establish or rule out the diagnosis – To follow the course of disease, particularly to suggest that a flare is occurring or organ damage is developing – To identify adverse effects of therapies

Harrison’s Principles of Internal Medicine 16th edition

Laboratory Diagnosis
• Tests for autoantibodies
– SLE is characterized by a heterogeneous and polyclonal antibody response, and the usual case of SLE has an average of three different circulating antibodies present simultaneously – Diagnostically, the most important autoantibodies to detect are ANA (antinuclear antibodies) since the test is positive in edition Harrison’s Principles of Internal Medicine 16>95% of patients, usually
th

Clinical Diagnosis and Management by Laboratory Methods 20th edition by John Bernard Henry

Laboratory Diagnosis
• ANA
– Diffuse staining pattern on indirect immunofluoresce nce
• The whole nucleus is evenly stained • Most strongly associated with SLE

Laboratory Diagnosis
• Tests for autoantibodies
– High-titer IgG antibodies to doublestranded DNA (dsDNA) (but not to single-stranded DNA) are specific for SLE
• Titer of anti-dsDNA correlates with disease activity, particularly of nephritis or vasculitis • ELISA, IF and Farr assay

Harrison’s Principles of Internal Medicine 16th edition

Laboratory Diagnosis
• Anti-dsDNA
– Immunofluorescent reaction of sera with the dsDNA in the flagellate Crithidia lucilliae

Laboratory Diagnosis
• Tests for autoantibodies
– Antibodies to Sm are also specific for SLE and assist in diagnosis
• Present only in about 30% of patients with SLE • Thus (+) test – SLE; (-) test does not rule out SLE • Do not usually correlate with disease activity and clinical manifestations

Harrison’s Principles of Internal Medicine 16th edition

Laboratory Diagnosis
• Tests for autoantibodies
– aPL (anti-phospholipid) antibodies are not specific for SLE but their presence fulfils one of the classification criterion and they identify patients at increased risk for venous or arterial clotting, thrombocytopenia and fetal loss
• ELISA, phospholipid-based prothrombin time (dilute Russell venom viper test)
Harrison’s Principles of Internal Medicine 16th edition

Laboratory Diagnosis

Harrison’s Principles of Internal Medicine 16th edition

Laboratory Diagnosis

Harrison’s Principles of Internal Medicine 16th edition

Laboratory Diagnosis
• Standard tests for diagnosis
– CBC
• Hemolytic anemia • Leukopenia (<4,000/μL) • Lymphopenia (<1500/μL)

– Platelet count
• Thrombocytopenia (<100,000/μL)

– Urinalysis
• Proteinuria (>0.5 g/d or ≥+3), or cellular casts
Harrison’s Principles of Internal Medicine 16th edition

Laboratory Diagnosis

Harrison’s Principles of Internal Medicine 16th edition

Laboratory Diagnosis
• Tests for following disease course - indicate the status of organ involvement known to be present during SLE flares
– Hemoglobin – Platelet count – Urinalysis – BUN, creatinine or albumin
Harrison’s Principles of Internal Medicine 16th edition

Radiology
• Pleural effusion
– Most common thoracic manifestation – Frequently bilateral – Blunting of costophrenic and cardio-phrenic angles – Lateral upward sloping of a meniscus-shaped Fraser and Pare’s Diagnosis of Diseases of the Chest 4 edition contour
th

Radiology
• Acute lupus pneumonitis
– Increased opacity and poorly defined markings in the mid and lower portions of the chest - (R) x-ray film

Fraser and Pare’s Diagnosis of Diseases of the Chest 4th edition

Radiology
• Pulmonary fibrosis
– Irregular linear opacities in the lower lung zones

Fraser and Pare’s Diagnosis of Diseases of the Chest 4th edition

Radiology
• Joint manifestations
– Metacarpophalangeal subluxations without erosions

Radiology of Bone Diseases 4th edition by Greenfield

Therapeutic Goals
• To control acute and severe flares • To suppress/ alleviate the symptoms • To prevent and treat complications

Treatment

Therapeutic Goals
• To control acute and severe flares • To suppress/ alleviate the symptoms • To prevent and treat complications

Treatment
Pharmacologic

GLUCOCORTICOIDS
• Indications:
• life-threatening manifestations of SLE, such as glomerulonephritis, CNS involvement, thrombocytopenia, and hemolytic anemia • debilitating manifestations of SLE (fatigue, rash) that are unresponsive to conservative therapy

Washington Manual of Therapeutics 31st Edition

GLUCOCORTICOIDS
• Prednisolone • Methylprednisolone MOA: inhibits COX-2 and phospholipase A2 which is responsible for the breakdown of cell membrane phospholipids into arachidonic acid
Goodman and Gillman Pharmacological Basis of Therapeutics 11th Edition

• Nonsteroidal Anti-inflammatory Drugs (NSAIDS)
– Used for its’ analgesic and antiinflammatory effects – compete in a reversible manner with arachidonic acid substrate at the active site of COX-1 and COX-2 decreasing prostaglandin synthesis – Indomethacin, Ibuprofen , Ketorolac , Mefenamic acid, Naproxen, Diclofenac
Goodman and Gillman Pharmacological Basis of Therapeutics 11th Edition

• Disease Modifying Antirheumatic Drugs (DMARDs)
– Drugs that modify the progression of common rheumatic diseases

DMARDS
• Antineoplastic agents
– Methotrexate
• For managing arthritis, serositis, cutaneous, and constitutional symptoms. • Blocks purine synthesis and AICAR, thus increasing anti-inflammatory adenosine concentration at sites of inflammation. Ameliorates symptoms of inflammation.

– Cyclophosphamide
• cross-links DNA, thereby preventing cell replication. • Standard for controlling life threatening active lupus nephritis

– Chlorambucil
• Alkylating agent, cross-links DNA, thereby preventing cell replication.
Basic and Clinical Pharmacology by Katzung 10th Edition

DMARDS
• Immunosuppressants
– Indications:
• such life-threatening manifestations of SLE as glomerulonephritis, CNS involvement, thrombocytopenia, and hemolytic anemia • the inability to reduce corticosteroid dosage or severe corticosteroid side effects

Washington Manual of Therapeutics 31st Edition

DMARDS
– Cyclosporine
MOA: inhibits IL-2 production by activated T cells

- Azathioprine
MOA: suppresses T and B cell functions

– Mycophenil mofetil
MOA: inhibits T cell proliferation and interferes leukocyte adhesion

– Corticosteroids
MOA: inhibits COX-2 and phospholipase A2

Basic and Clinical Pharmacology by Katzung 10th Edition

DMARDS
• Antimalarials
– Proposed mechanisms: T cell suppression, decreases WBC chemotaxis, stabilizes lysosomal enzymes, inhibits DNA and RNA synthesis, and free radical trapping – reduce dermatitis, arthritis, and fatigue – Chloroquine, Hydroxyhloroquine

Basic and Clinical Pharmacology by Katzung 10th Edition

Prevent Complications
• Sunscreen
– Photosensitivity – SPF >30

• Calcium and Vitamin D preparations

Harrison’s Principles Internal Medicine 16th Edition

Treat Complications
Complications Hypertension Generalized Edema UTI Pulmonary Infiltration Treatment Antihypertensive (B blockers) Corticosteroids Ciprofloxacin Corticosteroids

www.uic.edu/classes/pmpr/pmpr652/final/stevens/sle.html#SLE

• • • • • • • •

Adequate sleep and avoidance of fatigue Regular exercise Education about lupus and self-care Avoid smoking Eating a healthy balanced diet Salt restriction Developing a support system of family, friends, and health professionals For patients with photosensitive rashes use protective clothing, such as a hat and long sleeves, and avoidance of sun exposure are recommended to prevent flareups

Thank you!

Kidneys
• Nephritis
– Immune complex deposition in renal structures:
• Glomeruli • Tubular & peritubular capillary basement membranes

• Thrombosis
– Glomeruli – Extraglomerular vasculature
From Harrison’s Principles of Internal Medicine 16th ed.

Thrombosis
• Antiphospholipid antibody
– “lupus anticoagulant”

• Hypercoagulable state

From Harrison’s Principles of Internal Medicine 16th ed.

Laboratory Diagnosis
• Staging of lupus nephritis – light microscopy, IF and EM
– Class I - minimal mesangial lupus nephritis – Class II - mesangial proliferative lupus nephritis – Class III - focal lupus nephritis – Class IV - diffuse lupus nephritis – Class V - membranous lupus nephritis eMedicine.com: Nephritis, Lupus by Lawrence Brent MD, updated February 21, 2007

Laboratory Diagnosis
• Class V (membranous lupus nephritis)
– Light microscopy • Diffuse thickening of glomerular basement membrane without inflammatory infiltrate Lecture on Pathology of the Kidney by Normando Gonzaga MD Internet Pathology for Medical Education, Florida State University - http://library.med.utah.edu/WebPath/RENAHTML/RENALIDX.html • Spikes using

Laboratory Diagnosis
• Class V (membranous lupus nephritis)
– IF • Granular IgG and C3; diffuse • “Rosary beads” pattern

Lecture on Pathology of the Kidney by Normando Gonzaga MD Internet Pathology for Medical Education, Florida State University - http://library.med.utah.edu/WebPath/RENAHTML/RENALIDX.html

Laboratory Diagnosis
• Class V (membranous lupus nephritis)
– EM • Subepithelial deposits forming “humps and spikes”

Lecture on Pathology of the Kidney by Normando Gonzaga MD Internet Pathology for Medical Education, Florida State University - http://library.med.utah.edu/WebPath/RENAHTML/RENALIDX.html