Medical education - Rheumatic diseases - SLE ppt by Dr. Aliaa Omar El-Hady - Consultant of Rheumatology & Rehab- Mataria teaching hospital

2. Dr. Aliaa Omar El-Hady
Consultant of Rheumatology & Rehabilitation
Mataria Teaching Hospital

3. The assessment of SLE is marked by four
components:
1. accurate diagnosis
2. monitoring of disease activity
3. recording of accumulated damage
4. integration of these with the patient’s own
perceptions of health status and quality of
life.
Multiple standardized measures have been
developed for each component, many of which
are effective in routine clinical practice.

4. • Detailed history, thorough physical
examination, and appropriate use of
laboratory and radiographic studies are
required at each clinic visit to fully assess SLE.
•Quarterly follow-up is recommended even for
the stable SLE patient.
•With the complex phenotype and variable
disease course of SLE, all four components are
equally important and essential in improving
the morbidity, mortality, and quality of life in
SLE.

9. •Fatigue, fever, arthralgia, and weight changes
are the most common symptoms in new cases
or recurrent active SLE flares.
•Fatigue, the most common constitutional
symptom associated with SLE, can be due to
active SLE, medications, lifestyle habits, or
concomitant fibromyalgia or affective
disorders.
•SLE-specific fatigue or fever generally occurs
in concert with other clinical markers.
•Fever may reflect active SLE, infection, and
reactions to medications (ie, drug fever).

10. •Always exclude an infectious etiology; patients with SLE are
considered immunocompromised and are therefore at
higher risk for developing infections and complications.
•Most infections are bacterial in origin, but clinicians should
always consider the possibility of atypical and opportunistic
infections, particularly when these individuals are receiving
immunomodulating or immunosuppressive therapy.
•Careful history taking may help differentiate between the
potential causes of fatigue or fever.
•Note that an acute infectious process may also trigger SLE
and that the two can occur concomitantly.
•Weight loss may occur in patients with active SLE.
•Weight gain may also be due to corticosteroid
treatment or active disease, such as nephrotic syndrome
(with anasarca) or myocarditis.

13. Malar Rash
•The classic lupus butterfly rash
•manifests acutely as an erythematous, elevated
lesion, pruritic or painful, in a malar distribution,
•commonly precipitated by exposure to sunlight.
•The rash may last days to weeks
•Is commonly accompanied by other inflammatory
manifestations of the disease.

14. The acute butterfly rash should be differentiated
from other causes of facial erythema:
•Rosacea
•Seborrheic
•Atopic
•contact dermatitis
•glucocorticoid-induced dermal atrophy
•flushing.
The sparing of the nasolabial folds and the absence
of discrete papules and pustules help to differentiate
this condition from acne rosacea (including
glucocorticoid-induced rosacea).

15. •Other acute cutaneous lesions include generalized
erythema and bullous lesions.
•The rash of acute cutaneous lupus erythematosus
can be transient and heal without scarring.

17. Subacute cutaneous lupus erythematosus (SCLE)
•is not uniformly associated with SLE.
•~ 50% of affected pts have SLE, and ~ 10% of pts with SLE
have this type of skin lesion.
•Patients with SCLE may present with annular or
psoriasiform skin lesions
•is strongly associat. with anti-Ro (SS-A) & anti-La (SS-B) abs
•have a high incidence of photosensitivity
•rarely can present with erythema multiforme–like lesions
(Rowell's syndrome).

18. • SCLE lesions begin as small, erythematous, slightly scaly
papules that evolve into either a psoriasiform
(papulosquamous) or annular form.
•The latter lesions often coalesce to form polycyclic or
figurative patterns.
•The lesions typically have erythematous, and sometimes
crusted margins.
•The most frequently affected areas in SCLE are the
shoulders, forearms, neck, and upper torso.
•The face is usually spared.

20. Discoid lupus erythematosus (DLE)
•lesions develop in 25% of patients with SLE
•may occur in the absence of any other clinical
features of SLE.
•Patients with DLE have ~ a 5% to 10% risk of
developing SLE, which tends to be mild.
•Patients with numerous and widespread lesions
seem to be more likely to develop SLE.

21. •Discoid lesions are characterized by discrete, erythematous,
slightly infiltrated plaques covered by a well-formed
adherent scale that extends into dilated hair follicles
(follicular plugging)
•Discoid lesions are most often seen on the face, neck, and
scalp, but also occur on the ears and infrequently on the
upper torso.
•They tend to expand slowly with active inflammation at the
periphery, and then to heal, leaving depressed central scars,
atrophy, telangiectasias, and dyspigmentation
(hyperpigmentation or hypopigmentation).

22. The differential diagnosis of discoid lesions includes:
•hypertrophic lichen planus
•Eczema
•actinic keratosis
•some early and scaly discoid lesions also must be
differentiated from psoriasis.

24. lupus profundus:
•presenting as a firm nodular lesion with or without an
overlying cutaneous lesion.
•The nodules are often painful
•consist of perivascular infiltrates of mononuclear cells plus
panniculitis
•manifested as hyaline fat necrosis with mononuclear cell
infiltration and lymphocytic vasculitis.
•The nodules usually appear on the scalp, face, arms, chest,
back, thighs, and buttocks
•ulcerations are uncommon
•they usually resolve leaving a depressed area.
•Some patients with lupus profundus exhibit no other
manifestations of SLE.

26. Livedo reticularis

27. •Dermatomyositis: Acute onset of
confluent macular erythema in a
periorbital and malar distribution
(involving the cheeks and extending over
the nasal bridge), with extension to the
chin in a female with juvenile DM.
•Note the perioral sparing.
•In some patients, there may be more
extensive involvement of the face,
including the perioral region, forehead,
lateral face, and ears.
•In contrast to SLE , in dermatomyositis
with malar erythema, the nasolabial
folds are not spared.

28. Raynaud's phenomenon

29. Tumid lupus
a rare variant, is characterized by
photodistributed lesions with chronic pink-to-
violaceous papules, nonscarring plaques, and
nodules.

30. Photosensitivity:
•either acute or chronic.
•unusual rash or symptom exacerbation after sun exposure,
with expected duration of ~ 2 days in classic cases.

31. •It refers to the development of a rash after
exposure to ultraviolet B (UVB) rad. in sunlight or
fluorescent lights.
•It occurs in 60% to 100% of patients with SLE.
•Some patients also are sensitive to UVA radiation
(emitted from photocopiers)
•rarely may be sensitive to the visible light spectrum.
•Not all photosensitive individuals have SLE.
•Acute, subacute, and DLE lesions and some bullous
and urticarial lesions are photosensitive.
•The severity of cutaneous reaction depends on the
intensity of the UV source and the duration of
exposure

32. Alopecia
•Hair loss occurs in most patients with lupus
•in some cases can precede other manifestations of SLE.
•Lupus alopecia may involve the scalp, eyebrows, eyelashes,
beard, and body hair.

33. Lupus hair is characterized by:
•thin hair that easily fractures
•usually occurs along the frontal hairline
•is associated with disease activity
•grows back normally as the disease subsides
SLE patients
with alopecia
before and
after therapy

34. Scarring alopecia is a complication of DLE that
typically affects the scalp.

36. •occurs in 25% to 45% of patients with SLE.
•The most common manifestations include:
• irregularly shaped, raised, white plaques
• areas of erythema
• silvery white scarred lesions
• ulcer with surrounding erythema on soft/hard
palate/buccal mucosa

37. The oral ulcers in SLE are:
•usually painless
•no apparent association between their
presence and systemic disease activity.
•may be the first signs of SLE.

38. These lesions should be distinguished clinically
from:
•lichen planus
•candidiasis
•aphthous stomatitis
•intraoral herpes
•Behçet syndrome (known as Adamantiades-
Behçet synd.)
•bite marks
•leukoplakia
•malignancy

39. Characteristic discoid lesions with
erythema, atrophy, & depigmentation
can occur on the lips.

40. Nasal ulcers have been noted in patients with SLE.
They usually are found in the lower nasal septum,
tend to be bilateral, and are associated with active
disease.
Nasal septum perforation has been reported in 4% of
SLE patients and is secondary to vasculitis.

41. N.B.
Involvement of the upper
airway mucosa also can
occur and cause
hoarseness.

42. The musculoskeletal system is the most commonly
involved system in SLE, affecting 53% to 95% of
patients.

43. Arthritis and Arthropathy
•Joint involvement in SLE is classically described as
nonerosive, nondeforming arthralgias and arthritis in a
distribution similar to that of rheumatoid arthritis, primarily
affecting the small joints of the hands, wrists
•It may be the presenting symptom of SLE or accompany
other manifestations during a flare of the disease.
•A study of hand arthritis in SLE found deforming arthritis in
only 17 of 176 patients.
•The authors described three patterns of deforming arthritis
in SLE: a deforming and typically nonerosive arthropathy
known as Jaccoud's arthritis (8 of 17), an erosive
arthropathy (3 of 17), and a mild deforming arthropathy (6
of 17).

44. •Patients' symptoms (pain and stiffness) are
usually out of proportion to the degree of
synovitis present on physical examination
•synovitis may be transient (resolving within a
few days in some patients), migratory, and
reversible.
•At the other extreme are a few patients with
an impressive synovitis indistinguishable from
rheumatoid arthritis, for whom the term
“rhupus” has been coined.

47. Radiologic features in lupus hand arthritis
include:
•scapholunate dissociation
•joint space narrowing
•cystic change
•palmar/ulnar subluxation in the wrist.
In the fingers:
•metacarpophalangeal hook erosions
•metacarpophalangeal subluxation
•cystic changes
•marginal erosions are rare.

51. •With the use of more
sensitive imaging techniques,
such as high-resolution
ultrasound combined with
power Doppler, wrist
synovial hypertrophy and
effusion were detected in
94% patients with SLE hand
arthritis.
•47% had erosions at the 2nd
and 3rd MCP jts.
•65% had evidence of
tenosynovitis, with power
Doppler signal in half of
them.

52. Tenosynovitis
•is an early manifestation of SLE
•tendon rupture syndromes have been reported in many
different sites in the body, including the patellar tendons,
the Achilles tendon, the long head of the biceps, the triceps,
and the extensor tendons of the hands.
Tendon rupture has been associated with:
•male gender
•Trauma
•oral and intra-articular steroid use
•long disease duration.
•Flexure tendon contractures of the elbow also have been
reported.

53. •Synovitis can induce the carpal tunnel syndrome, which
may be the initial manifestation of SLE or drug-induced
lupus (DIL).
•Although septic arthritis is uncommon in SLE, it should be
suspected when one joint is inflamed out of proportion to
all others.
•Aspiration and culture of the synovial fluid are essential to
rule out infection in this case.
•Subcutaneous nodules along the flexor tendons of the
hand can be found in SLE.
•The histologic appearance is similar to that of rheumatoid
nodules.
•Periarticular calcification has been reported in the small
joints of the hand, whereas soft tissue calcification is rarely
seen in SLE.

54. Myositis
•Generalized myalgia and muscle tenderness are
common, especially during disease exacerbations.
•Inflammatory myositis involving the proximal
muscles has been reported to occur in 5% to 11% of
patients and may develop at any time during the
course of the disease.
•The DD of proximal muscle weakness in SLE includes
drug-related myopathy 2ry to corticosteroid,
antimalarial, or statin medications use.
•Concurrent hypothyroidsm also can cause an
increase in CPK and proximal myopathy.

55. Muscle biopsy, EMG
studies, and elevation of
the serum CPK or aldolase
levels help to DD between
inflammatory and drug-
related myopathy.

56. •The histologic features of myositis in SLE may be
less striking than in idiopathic polymyositis.
•Histologic features include muscle atrophy,
microtubular inclusions, and a mononuclear cell
infiltrate.
•Fiber necrosis is an uncommon finding, but Ig
deposition is almost always present despite the
rarity of concurrent inflammation.
•A low serum CPK value can be found in patients
with connective tissue disease including SLE;
•a normal CPK value in the presence of symptoms
and signs of myositis should not dissuade the
physician from a diagnosis of myopathy.

57. •The skin lesions of dermatomyositis
also can appear in patients with SLE.
•Chest pain or discomfort 2ry to
costochondritis in SLE (must rule out
angina, Pericarditis, esophageal
spasm).
•Relapsing polychondritis also has
been described in patients with SLE
and in most cases responds to low-
dose corticosteroid treatment.

58. Avascular Bone Necrosis
•a major cause of morbidity and disability in patients with
SLE.
•Symptomatic avascular necrosis occurs in 5% to 12% of SLE
patients.
•Higher prevalences have been reported in series that used
MRI for its detection.
•Acute joint pain manifesting late in the course of SLE and
localized to a very few areas, especially shoulders, hips, and
knees, may indicate the development of avascular necrosis.
•The initial pathologic lesion that leads to osteonecrosis
begins by interruption of the blood supply to the bone
followed by reactive hyperemia of the adjacent bone
resulting in demineralization, trabecular thinning, and finally
collapse if stressed.

59. In SLE, factors that can induce ischemia leading
to bone necrosis include:
•Raynaud's phenomenon
•Vasculitis
•fat emboli
•Corticosteroids
•antiphospholipid antibody syndrome (APS).
Osteonecrosis often develops a short time
after the onset of corticosteroid therapy,
within 1 month in some patients who receive
high doses

64. •SLE affects the CNS and the peripheral nervous
system.
•Nervous system involvement in SLE is a major cause
of morbidity and mortality.
•The ACR described case definitions and
classification criteria for 19 CNS and peripheral
nervous system syndromes that have been observed
in patients with SLE, which collectively are referred
to as neuropsychiatric systemic lupus erythematosus
(NPSLE) syndromes
•Approximately 40% of the NPSLE manifestations
develop before the onset of SLE or at the time of
diagnosis, and 63% develop within the first year
after the diagnosis.

65. Neuropsychiatric Syndromes in Systemic Lupus
Erythematosus
Central Nervous System
• Aseptic meningitis
• Cerebrovascular disease
• Demyelinating syndrome
• Headache (including migraine
and benign intracranial
hypertension)
• Movement disorder (chorea)
• Myelopathy Seizure disorder
• Acute confusional state
• Anxiety disorder
• Cognitive dysfunction
• Mood disorder
• Psychosis
Peripheral Nervous System
• Acute inflammatory,
demyelinating,polyradiculo
- neuropathy (Guillain-
Barré syndrome)
• Autonomic disorder
• Mononeuropathy,
single/multiplex
• Myasthenia gravis
• Neuropathy, cranial
• Plexopathy
Polyneuropathy

66. Approach to the Management of Neuropsychiatric
Symptoms in SLE:
•Diffuse or focal process?
•Classify symptoms
•Primary or secondary?
•Evidence for generalized lupus activity?
•If yes, probably related to lupus
•Exclude nonlupus-related causes (e.g.,
infections, drugs, electrolyte abnormalities,
hypoxia)
•Recent evolving or old, inactive process?
•Thrombotic or inflammatory process?

67. Inflammatory:
Generalized lupus activity (clinical or serologic)
High-grade abnormalities in lumbar puncture (i.e., protein,
cells)
MRI findings suggestive of cerebritis or myelitis
Thrombotic:
Antiphospholipid antibodies or stigmata for APS
MRI findings suggestive of thrombosis
Severe inflammatory disease?
Myelitis, cerebritis, coma, status epilepticus, large (or
multiple) cerebrovascular accident, mononeuritis multiplex,
severe psychosis, catatonia
Consider cytotoxic therapy

70. prevalence ranging from 14% to 75%.
Neuropsychiatric events in SLE may be
caused by:
•primary manifestation of the disease
•secondary complications of the disease
•complications of therapy, such as
hypertension, infection, or drug-induced
aseptic meningitis, especially with NSAIDs
•a coincidental problem unrelated to SLE.

71. A variety of autoantibodies has been associated with the
pathogenesis of different manifestations of NPSLE.
Autoantibodies include:
1. antineuronal antibodies
2. antiganglioside antibodies
3. anti-NR2 glutamate receptor antibodies
4. anti-DNA antibodies
5. antiribosomal (P) antibodies
6. anti-β2-glycoprotein I antibodies
7. antiprothrombin antibodies
8. lupus anticoagulants.
Increased intracranial and intrathecal levels of cytokines,
such as IL-6, interferon-α, IL-10, IL-8, and TNF-α, have been
associated with seizures and psychosis.

72. •Cognitive dysfunction reported in 80% of SLE pts.
•Association bet. SLE & headache is controversial.
•Psychosis reported in 8% of SLE pts and is
characterized by the presence of either delusions or
auditory hallucinations.
•When psychosis is present, it must be distinguished
from other causes, as drug abuse, schizophrenia, and
depression.
•Generalized & focal seizures reported in 6% - 51% of
pts and may occur either in active generalized
multisystem SLE or as isolated neurologic events.
•Seizures frequently associated with the presence of
APL abs, which are associated with microangiopathy,
arterial thrombosis, & cerebral infarction.

73. •Demyelination, transverse myelopathy, and chorea
are rare manifestations of NPSLE and occur in 1% to
3% of patients.
•Clinical and neuroimaging evidence of
demyelination may be indistinguishable from MS.
•Transverse myelopathy and chorea manifest acutely
and often are associated with the presence of
antiphospholipid antibodies
•A peripheral sensorimotor neuropathy reported in
28% of SLE patients and may occur independently of
other disease characteristics.

75. •Pericarditis being the most common and found in
approximately ¼ of the patients.
•Pericardial effusions may be asymptomatic and are
usually mild to moderate.
•Tamponade is rare.
•Myocardial involvement is rare (<5% of patients)
and typically occurs in the presence of generalized
SLE activity.
•Clinical features of left ventricular dysfunction,
nonspecific ST/T wave changes, segmental wall
motion abnormalities, and decreased ejection
fraction are found in greater than 80% of patients.

76. •MRI has been used to detect clinical and
subclinical myocardial involvement in SLE.
•Patients may present with fever,
dyspnea, tachycardia, and congestive
heart failure.
•Patients with SLE have substantially
increased morbidity and mortality from
cardiovascular disease.
•Morbidity includes accelerated,
premature atherosclerosis and valvular
heart disease.

77. •Cardiovascular dis. and atherosclerosis
are a common cause of morbidity and
mortality in various SLE cohorts.
•An increased risk for myocardial
infarction or stroke compared with the
healthy population.
•Atherosclerosis—defined by coronary
artery calcification or carotid plaque
size—also is more common in SLE patients
than in healthy controls and it correlates
with disease activity and damage scores.

78. Valvular Heart Disease
•Is common in patients with SLE.
•The prevalence of valvular heart disease using
transesophageal ECHO was 61% in SLE patients.
•The most common abnormality was diffuse thickening of
the mitral and aortic valves followed by vegetations,
valvular regurgitation, and stenosis in decreasing order of
frequency.
•Valvular abnormalities frequently resolved, appeared for
the first time, or persisted.
•Mild or moderate valvular regurgitation did not progress to
become severe, and new stenoses did not develop.
•Neither the presence of valvular disease nor changes in the
echocardiographic findings were temporally related to the
duration, activity, or severity of SLE or to its treatment.

79. •The combined incidence of stroke, peripheral
embolism, heart failure, infective endocarditis,
and the need for valve replacement was 22%
in patients with valvular disease and 8% in
patients without valvular disease.
•Several pathologic studies of SLE patients
have shown active and healed valvulitis and
active Libman-Sacks vegetations with acute
thrombus, healed vegetations with or without
hyalinized thrombus, or active and healed
vegetations, in the same or different valves.

80. •Thrombotic vegetations 2ry to a
hypercoagulable state also have been
shown in patients with lupus.
•These vegetations cannot be clearly DD
from Libman-Sacks vegetations on ECHO.
•Valvular vegetations can embolize, which
may result in a change in their appearance
or resolution
•Acute and subacute bacterial
endocarditis may occur on previously
involved valves.

81. Lupus myocarditis. MRI shows enhancement of the myocardium,
which spares the endocardium

82. Echocardiography is used to assess for pericardial effusion,
pulmonary hypertension, or verrucous Libman-Sacks
endocarditis
This echocardiograph
image demonstrates
a large pericardial
effusion ("F")
compressing the
inducing tamponade
("H"), an uncommon
but potential fatal
complication of SLE.

83. Libman-Sacks endocarditis Diagnosis is best made via
echocardiography, which may reveal the characteristic valvular masses
(arrows). IVS = interventricular septum; LA = left atrium; LV = left
ventricle.

85. Pleuropulmonary Manifestation Common
•Pleuritic chest pain or pleurisy Common, with or without effusion or friction rub
•Pleural effusion Exudate; unilateral or bilateral
•Acute pneumonitis Not common; presentation includes fever,
nonproductive cough, infiltrates, hypoxia; high
mortality rates
•Interstitial lung disease Insidious onset of dyspnea on exertion,
nonproductive cough, pleuritic chest pain
•Bronchiolitis obliterans with organizing pneumonia Can be difficult to diagnose; requires biopsy;
responds to corticosteroids
•Pulmonary capillaritis or diffuse alveolar
hemorrhage
Rare, associated with antiphospholipid antibodies;
poor prognosis
•Shrinking-lung syndrome Occurs in patients with long-standing SLE;
diaphragmatic weakness possible cause
•Pulmonary embolism or infarction Common in patients with antiphospholipid antibodies
•Pulmonary hypertension Insidious onset of dyspnea on exertion, chronic
fatigue, weakness, palpitations, edema
•Lymphadenopathy Massive mediastinal lymphadenopathy uncommon in
patients with SLE alone; cervical and auxillary
lymphadenopathy common, correlates with disease
activity
•Infection Typical and atypical pathogens; caused by immune
dysfunction and immunosuppressive medications
Malignant tumor Lung cancer; lymphoma more common in SLE

86. •Pleuritic pain is present in 45% to 60% of patients and may
occur with or without a pleural effusion.
•Pleural effusions have been reported in 50% of patients
with SLE and may be found in 93% of cases at autopsy.
•Effusions are usually bilateral, but may be unilateral,
equally distributed between the left and the right
hemithoraces.
•Pleural effusions in SLE are invariably exudative, but with
higher glucose and lower lactate dehydrogenase levels than
those found in rheumatoid arthritis
•Pleural biopsy findings are nonspecific and include
lymphocytic and plasma cell infiltration, fibrosis, and
fibrinous pleuritis.
•Thoracoscopy has revealed nodules on the visceral pleura,
and immunofluorescence of biopsy samples of these
nodules revealed immunoglobulin deposits.

87. The chest x-ray from a patient with lupus demonstrates a right-sided pleural effusion
(yellow arrow) and atelectasis with scarring in the left lung base (blue arrow). In
severe complications, a fibrothorax may develop.

88. •Clinically significant interstitial lung disease
complicates SLE in 3% to 13% of patients, but is
rarely severe.
•Asymptomatic involvement is more common,
and abnormalities in pulmonary function tests
have been reported in 2/3 of patients with SLE
in some studies.
•Abnormalities in high-resolution CT have been
reported in 70% of patients with SLE.
•Symptomatic interstitial lung disease is rarely
an early or dominant feature of SLE, and
severe pulmonary fibrosis is extremely rare.

89. •Histologic features of interstitial lung disease
complicating SLE are nonspecific and include
varying degrees of chronic inflammatory cell
infiltrates, peribronchial lymphoid hyperplasia,
interstitial fibrosis, and hyperplasia of type II
pneumocytes.
•The presence of Raynaud's phenomenon,
swollen fingers, sclerodactyly, telangiectasia,
and nail-fold capillary abnormalities among
patients with SLE was associated with a higher
prevalence of restrictive defects and decreased
diffusing capacity.

90. •Acute lupus pneumonitis manifesting as
cough, dyspnea, pleuritic pain, hypoxemia, and
fever occurs in 1% to 4% of patients with SLE.
•Chest radiographs reveal infiltrates, which
may be unilateral or bilateral.
•Histologic features are nonspecific and
include alveolar wall damage and necrosis,
inflammatory cell infiltration, edema,
hemorrhage, and hyaline membranes.
•A microangiitis involving capillaries, with
fibrin thrombi and infiltration with necrotic
neutrophils, may be present.

91. •Pulmonary hemorrhage is a rare but potentially
catastrophic complication of SLE. Mortality :50% to 90%.
•Clinical features are nonspecific, but diffuse alveolar
infiltrates, hypoxemia, dyspnea, and anemia are ch.ch.
•Alveolar hemorrhage usually occurs in patients with a
known history of SLE, high titers of anti-DNA antibodies, and
active extrapulmonary disease.
•Fiberoptic bronchoscopy with bronchoalveolar lavage and
transbronchial lung biopsy is usually adequate to
substantiate the diagnosis in patients with suspected
alveolar hemorrhage.
•Lung biopsy specimens show extensive hemorrhage within
alveolar spaces and capillaritis.
•Deposits of IgG, C3, or immune complexes have been found
in 50% of patients with alveolar hemorrhage complicating
SLE.

92. The “shrinking lung syndrome” is
characterized by progressive dyspnea and
small lung volumes on chest radiographs
and is thought to be 2ry to diaphragmatic
dysfunction.
It can be difficult to differentiate from:
1. respiratory muscle weakness.
2. primary parenchymal disease.
3. pleural causes of low lung volumes
without the use of invasive studies.

93. LYMPH NODE AND SPLEEN INVOLVEMENT
•Lymphadenopathy occurs in approximately 40% of patients
usually at the onset of disease or during disease flares.
•The nodes are typically soft, nontender, and discrete, and
usually are detected in the cervical, axillary, and inguinal
area.
•Biopsy specimens reveal areas of follicular hyperplasia and
necrosis.
•The appearance of hematoxylin bodies is highly suggestive
of SLE, but is uncommon.
•Generally, patients with lymphadenopathy are more likely
to have nonspecific symptoms, such as fever and malaise.
•A lymph node biopsy may be warranted when the degree
of lymphadenopathy is out of proportion to the activity of
the lupus.

94. •Splenomegaly occurs in 10% to 45% of
patients, particularly during active disease,
and is not associated with cytopenias.
•Periarterial fibrosis, or “onionskin” lesions, in
the spleen has been considered
pathognomonic of SLE and is thought to
represent healed vasculitis.
•Splenic atrophy and functional hyposplenism
also have been reported in SLE and may
predispose to severe septic complications.

95. •Hematologic abnormalities are common and can be
the presenting symptom in SLE.
•Major clinical manifestations include anemia,
leukopenia, thrombocytopenia, and APS.

96. Anemia
common and affects most SLE patients at some time during the course
of their disease.
The mechanisms of anemia in SLE vary and include:
•anemia of chronic disease
•hemolysis (immune or microangiopathic)
•blood loss
•renal insufficiency
•Medications
•Infection
•Hypersplenism
•Myelodysplasia
•Myelofibrosis
•aplastic anemia
The mechanism is multifactorial and includes suppression of
hematopoiesis by inflammatory cytokines via apoptosis of progenitor
cells or other mechanisms and antibodies against red blood cell
growth factors or progenitor cells.

97. Leukopenia
•It can be the presenting symptom and usually is associated with
disease activity.
•A WBCs count of < 4500/μL reported in ~ 50% of patients, especially
patients with active disease.
•Severe leukopenia (neutrophil count <500/μL) is rare.
•Lymphocytopenia (lymphocyte count <1500/μL) occurs in ~ 20% of
pts.
•Cytotoxic lymphocyte antibodies have been detected in the serum of
SLE patients, and their titers have been correlated with the degree of
lymphocytopenia.
Neutropenia in SLE patients can result from:
•immune mechanisms
•Medications
•bone marrow suppression
•Hypersplenism.

98. •Decreased eosinophil and basophil
counts are usually secondary to
corticosteroid use in lupus.
•Leukocytosis in lupus can occur and
usually reflects an infection or the use
of high-dose corticosteroids.

99. Thrombocytopenia
•Mild thrombocytopenia (platelet counts 100,000 to
150,000/μL) reported in 25% to 50% of patient
•counts < 50,000/μL occur in only 10%.
The most common cause of thrombocytopenia in SLE is:
1. immune-mediated platelet destruction
2. increased platelet consumption as a result of
microangiopathic hemolytic anemia or
hypersplenism
3. Impaired platelet production as a result of bone
marrow suppression secondary to medications

100. •The major mechanism is immunoglobulin binding to
platelets followed by destruction in the spleen, as in
idiopathic thrombocytopenic purpura.
•Antibodies against thrombopoietin have been
reported in the serum of SLE patients and correlated
with thrombocytopenia.
•Idiopathic thrombocytopenic purpura may be the
first sign of SLE, followed by other symptoms even
many years later. In such cases, the presence of high-
titer ANAs or the presence of extractable nuclear
antigens raises the possibility of underlying SLE.
•A careful history and physical examination in many
of these cases may reveal additional features of SLE.

101. Lupus related?
Rule out drug effects. Ask about over-the-counter drugs such as quinine for leg
cramps, vitamins, supplements, or herbal medicines
Discontinue all but absolutely essential drugs
Discontinue agents that may interfere with platelet function (e.g., aspirin, NSAIDs)
Confirm autoimmune etiology by examining peripheral smear. Rule out platelet
clumping that can cause false thrombocytopenia and abnormalities of the white or
red blood cells
Consider bone marrow examination, especially in older patients, to rule out occult
myelodysplasia
Tests for antiplatelet antibodies are not helpful
Rule out thrombotic thrombocytopenic purpura or antiphospholipid-related
microangiopathic hemolytic anemia (anemia with pronounced reticulocytosis and
fragmented erythrocytes in the peripheral smear), antiphospholipid antibodies, or
antiphospholipid antibody syndrome
Look for evidence of lupus activity in other organs (especially major organs)
Management of Thrombocytopenia in SLE

102. Determine severity
Severe: platelets <20 × 103/μL
Moderate-to-severe: platelets 20-50 × 103/μL
Treat.
Goal is not a normal platelet count, but a safe
platelet count (30-50 × 103/μL)

104. Gastrointestinal manifestations
•25% to 40% of patients with
SLE
•reflect either lupus of the GIT
or the effects of medications.
•Esophageal involvement
reported < 5% of SLE patients.

105. Dysphagia caused by:
1. esophageal dysmotility and aperistalsis is the
most usual symptom, episodic, associated with
RP and the presence of antiRNP abs. The
esophageal dysmotility may be caused by an
inflammatory reaction in the esophageal muscles,
by ischemia, or by vasculitic changes in
Auerbach's plexus.
2. gastroesophageal reflux disease resulting in
esophagitis, esophageal spasm, and esophageal
strictures
3. esophageal candidiasis, esp in pts ttt with
corticosteroids or immunosuppressives or both
4. esophageal ulcers.

106. •Dyspepsia has been reported in 11% to
50% of patients with SLE.
•Peptic ulcers (usually gastric) reported
in 4% to 21%.
•These complications are more common
in patients treated with NSAIDs.
•It also has been suggested that SLE itself
predisposes to ulcer formation.
•Bleeding from peptic ulcer disease in SLE
is uncommon, and perforation is rare.

107. Abdominal pain accompanied by
nausea and vomiting occurs in 30% of
patients with SLE.
Special consideration should be given to
conditions associated with SLE, such as
1. Peritonitis
2. mesenteric vasculitis with intestinal
infarction
3. Pancreatitis
4. inflammatory bowel disease.

108. Mesenteric vasculitis with infarction is a serious and
potentially life-threatening manifestation.
Risk factors for the development of mesenteric
vasculitis include :
• peripheral vasculitis
• CNS lupus.
The clinical presentation is usually with insidious
symptoms that may be intermittent for months
before the development of an acute abdomen with
nausea, vomiting, diarrhea, gastrointestinal
bleeding, and fever. Patients with mesenteric
vasculitis occasionally have an acute presentation
with mesenteric thrombosis and infarction, often in
association with antiphospholipid antibodies.

109. •The diagnosis of mesenteric vasculitis may be
difficult to establish.
•Plain radiographic studies may reveal segmental
bowel dilation, air-fluid levels, “thumbprinting” or
narrowing of the lumen, and pseudo-obstruction.
•Abdominal CT scan findings compatible with
mesenteric vasculitis include prominence of
mesenteric vessels with a comblike appearance
supplying dilated bowel loops, small bowel
thickening, and ascites.
•Arteriography may reveal evidence of vasculitis or
ischemia of the small intestine or colon.
•Vasculitis generally involves small arteries, which
can lead to a negative arteriogram.

111. •Pancreatitis associated with SLE may result
from vasculitis or thrombosis and occurs in 2%
to 8% of patients.
•Elevated levels of serum amylase have been
described in patients with SLE without
pancreatitis and should be interpreted in light
of the overall clinical examination.
•The role of azathioprine and corticosteroids as
a cause of acute pancreatitis in patients with
SLE is controversial.

112. •Hepatic disease may be more common in SLE
than previously thought.
•Clinically significant hepatic disease is
generally unusual in SLE.
•The incidence of hepatomegaly is 12% to 55%.
Excessive fatty infiltration (steatosis) is a
common finding and may occur as part of the
disease process or may be secondary to
corticosteroid treatment.
•Liver function tests may be abnormal in
patients with active SLE or in patients receiving
NSAIDs.

113. Ascites is uncommon in SLE, and when detected,
infectious causes or perforation or both must be
excluded by paracentesis.
Other possible causes of ascites in patients with SLE:
1. Congestive heart failure
2. hypoalbuminemia 2ry to nephrotic syndrome or
protein-losing enteropathy
Protein-losing enteropathy has been described in
some patients with SLE and can be the first
manifestation of the disease.
It usually occurs in young women and is
characterized by the onset of profound edema and
hypoalbuminemia.

115. 8% of patients with SLE develop inflammation of the retinal
artery during the course of their disease.
An equal number of patients have infarction of the retinal
vasculature secondary to the presence of antiphospholipid
antibodies.
Both conditions can lead to the presence of cotton-wool
spots in the retina visible on ophthalmoscopy or fluorescein
angiography (where perivascular exudates and patches of
dye leakage along the vessels are seen).
Cotton-wool spots result from focal ischemia and are not
pathognomonic for SLE.
The presence of retinal vasculitis is usually associated with
generalized active systemic disease, and retinal vasculitis
occurs early in the disease process.

116. •Corneal and conjunctival
involvement is usually part of
2ry Sjögren's syndrome.
•uveitis and scleritis are
extremely rare manifestations
in SLE.

118. General Considerations
 Renal involvement is common in SLE and is a significant
cause of morbidity and mortality.
 It is estimated that up to 90% of SLE patients will have
pathologic evidence of renal involvement on biopsy, but
only 50% will develop clinically significant nephritis.
 The clinical presentation of lupus nephritis is highly
variable, ranging from asymptomatic hematuria and/or
proteinuria to frank nephrotic syndrome to rapidly
progressive glomerulonephritis with loss of renal
function.
 Lupus nephritis typically develops within the first 36
months of the disease, although there are
exceptions.Thus, periodic screening for the presence of
nephritis is a critical component of the ongoing
evaluation and management of SLE patients.

119.  Routine screening procedures include
inquiring about new-onset polyuria,
nocturia, or foamy urine and looking
for the presence of hypertension or
lower extremity edema.
 It is important to screen at regular
intervals for the presence of
proteinuria and/or hematuria and a
change in serum creatinine; in active
SLE patients, screening at 3-month
intervals is prudent.

120. Types of Renal Involvement in Systemic
Lupus Erythematosus

121.  Several forms of renal involvement have been noted in
SLE, including immune complex– mediated
glomerulonephritis (GN) (most common form),
tubulointerstitial disease, and vascular disease.
 GN is characterized by immune complex deposition and
inflammatory cell infiltration into the glomerulus.
 The pattern of glomerular injury is primarily related to
the site of immune complex deposition.
 Tubulointerstitial and vascular disease can occur with or
without immune complex–mediated glomerulonephritis.
 Tubulointerstitial disease has been observed in up to 66%
of SLE renal biopsy specimens and is characterized by
inflammatory cell infiltrates, tubular damage, and
interstitial fibrosis. The presence of tubulointerstitial
disease is a strong predictor of poor long-term renal
outcome.

122. Renal vascular lesions in SLE include “lupus vasculopathy,”
thrombotic microangiopathy (TMA), vasculitis, and
nonspecific vascular sclerosis.
 Lupus vasculopathy is defined as the presence of
immunoglobulin and complement containing hyaline thrombi
within the glomerular capillary or arteriolar lumina. Inflammatory
changes to the vascular wall are absent.
 TMA is characterized by the presence of fibrin thrombi within the
glomerular capillary or arteriolar lumina and may be associated
with the presence of antiphospholipid antibodies. The finding of
TMA should prompt consideration of antiphospholipid antibody
syndrome nephropathy (APSN).
 Although exceedingly rare, true vasculitis characterized by
leukocyte infiltration and fibrinoid necrosis of arterial walls can
occur.

123.  Nonspecific sclerotic vascular lesions characterized by
fibrous intimal thickening are commonly observed. The
presence of such vascular lesions is associated with
decreased renal survival.
 In addition to the lupus-related renal lesions described
previously, SLE patients may develop renal abnormalities
that are unrelated to their underlying SLE. Such
pathologic lesions include focal segmental
glomerulosclerosis (FSGS) , hypertensive nephrosclerosis,
and thin basement membrane disease.
 In an SLE patient in whom renal disease is suspected,
renal biopsy is critical in distinguishing between these
potential causes and in guiding appropriate management
decisions.

124. Urinalysis
 Performance of a urinalysis with microscopy is essential in the
screening and monitoring of lupus nephritis.
 Hematuria, pyuria, dysmorphic red blood cells, red blood cell casts,
and white blood cell casts may all be present.
 Red blood cell casts are very specific, but not sensitive, for the
diagnosis of glomerulonephritis.
 Early morning urine specimens, which tend to be concentrated and
acidic, are ideal for the detection of red blood cell casts.
 White blood cells, red blood cells, and white blood cell casts may
indicate the presence of tubulointerstitial involvement.
 Hematuria in the absence of proteinuria might be due to
urolithiasis, menstrual contamination, or bladder pathology,
particularly transitional cell carcinoma in a patient with previous
cyclophosphamide exposure.

125.  Accurate measurement of proteinuria is critical because proteinuria is a very
sensitive indicator of glomerular damage.
 In addition, studies of chronic kidney disease have shown that the magnitude of
proteinuria is a strong predictor of glomerular filtration rate decline.
 Normal daily protein excretion is less than 150 mg.
 Although the gold standard tool is an accurately collected 24-hour urine protein,
this test can be cumbersome for patients and is prone to errors in undercollection
and overcollection. Thus, many clinicians are currently using the random spot
urine protein-to-creatinine ratio out of convenience.
 Use of the spot ratio is controversial because data suggest that the spot ratio
often is not representative of the findings in a timed collection, especially in the
range of 0.5 to 3.0 (the range of most lupus nephritis flares). However, a spot
ratio can be a helpful screening test for the presence of proteinuria and is useful
in differentiating nephrotic from nonnephrotic range proteinuria.
 Urine dipstick should not be used for the quantification of proteinuria because it
reflects protein concentrations and varies depending on the volume of the
sample.
 Many experts currently recommend calculation of the protein: creatinine ratio
from a 12- or 24- hour urine collection as the gold standard of proteinuria
assessment.

126. Measurement of Renal Function
 Although easy to measure, serum creatinine is a fairly
insensitive indicator of early decline in glomerular
filtration rate (GFR).
 Creatinine is freely filtered across the glomerulus and is
also secreted by the proximal tubule.
 As GFR falls, the rise in serum creatinine is counteracted
by increased tubular creatinine secretion.
 In addition, hemodynamic changes such as those caused
by treatment with angiotensin-converting enzyme
inhibitors or nonsteroidal anti-inflammatory drugs are a
common cause of changes in serum creatinine levels in the
absence of progression of underlying renal disease.
 However, trending serum creatinine over time is a
reasonable method by which to follow a patient’s renal
function.

127. Renal Biopsy
When an SLE patient has clinical or laboratory features that
suggest the presence of nephritis, a renal biopsy should be
performed to confirm the diagnosis, evaluate the degree of
disease activity, and determine an appropriate course of
treatment.
Before renal biopsy, ultrasonography is recommended to
assess kidney size and structure and to rule out renal vein
thrombosis. Kidney size of less than 75% of normal is a
relative contraindication to biopsy.
SLE glomerulonephritis is classified by the International
Society of Nephrology/Renal Pathology Society (ISN/RPS)
into six categories based on light microscopic,
immunofluorescent, and electron micrographic findings
(Table and Figure).

129. A through D, World Health Organization types of
lupus. (See Table 80-4 for a detailed description of
histologic findings.) A, Normal glomerulus (type I).
B, Mesangial proliferative (type II). C, Proliferative
nephritis. Dramatic increase in mesangial and
endocapillary cellularity produces a lobular
appearance of the glomerular tufts and
compromises the patency of most capillary loops.
When less than 50% of glomeruli are involved,
nephritis is denoted as focal (type III). When more
than 50% of glomeruli are involved, nephritis is
denoted as diffuse (type IV). D, Membranous
nephropathy (type V). In membranous lupus
nephropathy, the capillary walls of the glomerular
tuft are prominent and widely patent, resembling
“stiff”structures with decreased compliance. E
through H, High-risk histologic features suggesting
severe nephritis. E, Fibrinoid necrosis with
karyorrhexis in a patient with focal proliferative
glomerulonephritis. F and G, Cellular crescents with
layers of proliferative endothelial cells and
monocytes lining Bowman’s capsule along with a
predominantly mononuclear interstitial infiltrate. H,
Severe interstitial fibrosis and tubular atrophy. Note
the thickening of the tubular basement membranes
and tubular epithelial degeneration with separation
of residual tubules caused by deposition of
collagenous connective tissue among tubules.

130. An individual biopsy might exhibit just one of the ISN/RPS
pathologic classes or a combination of classes.
Class I is characterized by normal appearing glomeruli on
light microscopy and mesangial immune deposits on
immunofluorescence.
Class II is characterized by mesangial proliferation on light
microscopy and mesangial deposits on
immunofluorescence.
Class III and IV lupus nephritis lesions are highly
inflammatory and are characterized by immune complex
deposition in the subendothelial space. They have
traditionally been described as “proliferative” because of
the presence of proliferating endocapillary cells within the
glomeruli. They are believed to be interrelated lesions that
differ in the distribution of endocapillary immune complex
deposition.

131. Class III denotes that less than 50% of
glomeruli are involved, and class IV denotes
that 50% or more of glomeruli are involved.
Class IV lesions are subcategorized according
to whether most glomeruli show focal (<50%
of the glomerular tuft) or global (≥50% of the
glomerular tuft) involvement. These lesions
are further described as active(A), chronic (C),
or a mixture of the two (A/C).
Thick subendothelial immune deposits form
classic “wire loop” lesions.

132. Class V lupus nephritis is characterized by immune complex
deposition in the subepithelial space, resulting in
widespread thickened capillary loops. These findings are
similar to those observed in idiopathic membranous
nephritis.
However, the presence of concomitant mesangial deposits
plus or minus tubuloreticular inclusion bodies would favor
the diagnosis of lupus. This lesion is commonly manifested
clinically as nephrotic range proteinuria.
Class V nephritis may occur in a pure histopathologic form or
in combination with features of class III or class IV nephritis.
Class VI nephritis is defined by the presence of more than
90% globally sclerotic glomeruli.

133.  Immunofluorescence studies are an important supplement to the
findings on light microscopy. Immunofluorescence reveals the type
and pattern of immune complex deposition.
 Lupus nephritis is characterized by a granular pattern of
immunofluorescence along the glomerular basement membrane,
mesangium, and/or tubular basement membranes.
 The characteristic findings of lupus nephritis are sometimes referred
to as the “full-house” pattern, because IgG, IgM, IgA, C3, and C1q
are all found in the deposits.
 Electron microscopy is useful in more precisely localizing the sites of
immune complex deposition.
 The finding of tubuloreticular inclusion bodies within endothelial
cells is strongly suggestive of the diagnosis of lupus nephritis.
 However, because tubuloreticular inclusion bodies are associated
with increased levels of interferon alpha, chronic viral infections
such as hepatitis B/C and the human immunodeficiency virus (HIV)
must be ruled out.

134.  Renal biopsy is especially important because urinary
parameters such as hematuria and the degree of
proteinuria imperfectly predict the underlying renal
pathology.
 Hematuria might be absent in patients with severe class
IV nephritis, and proteinuria can be modest in patients
with class V nephritis.
 A repeat renal biopsy may be indicated in certain clinical
settings (e.g., if a patient is not responding appropriately
to therapy, if a patient unexpectedly worsens after
having achieved a good response to therapy).
 Repeatrenal biopsy can be useful in detecting class
transformation that occurs in 15% to 50% of lupus
nephritis patients during the course of their disease.
Class transformation can occur spontaneously or as a
result of treatment.

135. Drug-induced lupus differs from SLE by the following
features:
• Sex ratios are nearly equal
• Antibodies to histones are usually found in 80-90%
• Nephritis and CNS features are not commonly present
• There are no antibodies to native DNA or hypocomplementemia
• Discontinuation of the drug leads to resolution of clinical
manifestations and reversion of abnormal lab. values to normal
• A syndrome of drug-induced SLE has been observed with
minocycline and propylthiouracil. Both drugs have a decreased
frequency of antihistone antibodies and anti–double-stranded DNA
antibodies, and results for antineutrophil cytoplasmic antibodies
are sometimes positive. Anti-TNF drugs are reported to cause
severe drug-induced lupus, including production of many SLE
autoantibodies and, rarely, even nephritis.[

136. Definite Association
Chlorpromazine Methyldopa
Hydralazine Procainamide
Isoniazid Quinidine
Possible Association
Beta-blockers Methimazole
Captopril Nitrofurantoin
Carbamazepine Penicillamine
Cimetidine Phenytoin
Ethosuximide Propylthiouracil
Hydrazines Sulfasalazine
Levodopa Sulfonamides
Lithium Trimethadione
Unlikely Association
Allopurinol Penicillin
Chlorthalidone Phenylbutazone
Gold salts Reserpine
Griseofulvin Streptomycin
Methysergide Tetracyclines
Oral contraceptives
Drugs Associated With Lupus Erythematosus

137. Diagnostic
Studies

138. The CBC count may help screen for leukopenia,
lymphopenia, anemia, and thrombocytopenia.
Urinalysis and creatinine studies may be useful
to screen for kidney disease.
Other laboratory tests that may be used in the
diagnosis of SLE are as follows:
ESR or CRP
Complement levels
Liver function tests
Creatine kinase assay
Spot protein/spot creatinine ratio

139. •Levels of inflammatory markers, including the
ESR and CRP, may be elevated in any
inflammatory condition, including SLE.
•However, the level of ESR elevation may show
a discrepancy relative to a normal CRP level in
SLE flares;
•if both markers are markedly elevated,
suspect the presence of an infectious process.
•CRP levels change more acutely, and the ESR
lags behind disease changes.

140. Measurement of complement may
be useful, because C3 and C4 levels
are often depressed in patients
with active SLE as a result of
consumption by immune complex–
induced inflammation.
In addition, some patients have
congenital complement deficiency
that predisposes them to SLE.

141. •Liver test results may be mildly
elevated in acute SLE or in
response to therapies such as
azathioprine or NSAIDS.
•CPK levels may be elevated in
myositis or overlap syndromes.
•The spot protein/spot creatinine
ratio may be used to quantify
proteinuria.

142. The 2012 ACR guidelines for lupus
nephritis indicate that a spot protein/spot
creatinine ratio > 0.5 g/day can substitute
for the 24-hour protein measurement and
that an active urinary sediment (defined
as >5 RBCs/high-power field [hpf]; >5
white blood cells [WBCs]/hpf in the
absence of infection; or cellular casts
limited to RBC or WBC casts) can
substitute for cellular casts.

143. Autoantibody tests
Table below, summarizes the
autoantibody tests that are
used in the diagnosis of SLE.

144. Test Description
ANA Screening test; sensitivity 95%; not diagnostic without clinical features
Anti-dsDNA High specificity; sensitivity only 70%; level is variable based on disease activity
Anti-Sm Most specific antibody for SLE; only 30-40% sensitivity
Anti-SSA (Ro) or Anti-SSB
(La)
Present in 15% of patients with SLE and other connective-tissue diseases such
as Sjögren syndrome; associated with neonatal lupus
Anti-ribosomal P Uncommon antibodies that may correlate with risk for CNS disease, including
increased hazards of psychosis in a large inception cohort, although the exact
role in clinical diagnosis is debated[93]
Anti-RNP Included with anti-Sm, SSA, and SSB in the ENA profile; may indicate mixed
connective-tissue disease with overlap SLE,scleroderma, and myositis
Anticardiolipin IgG/IgM variants measured with ELISA are among the antiphospholipid
antibodies used to screen for antiphospholipid antibody syndrome and
pertinent in SLE diagnosis
Lupus anticoagulant Multiple tests (eg, direct Russell viper venom test) to screen for inhibitors in
the clotting cascade in antiphospholipid antibody syndrome
Direct Coombs test Coombs test–positive anemia to denote antibodies on RBCs
Anti-histone Drug-induced lupus ANA antibodies are often of this type (eg, with
procainamide or hydralazine; p-ANCA–positive in minocycline-induced drug-
induced lupus)
ANA = antinuclear antibody; CNS = central nervous system; ds-DNA = double-stranded DNA; ELISA = enzyme-linked immunoassay; ENA =
extractable nuclear antigen; Ig = immunoglobulin; p-ANCA = perinuclear antineutrophil cytoplasmic antibody; RBCs = red blood cells; RNP =
ribonucleic protein; SLE = systemic lupus erythematosus; Sm = Smith; SSA = Sjögren syndrome A; SSB = Sjögren syndrome B.
Autoantibody Tests for SLE

145. Radiologic Studies
•Joint radiography often provides little
evidence of systemic lupus
erythematosus (SLE), even in the
presence of Jaccoud arthropathy with
deformity or subluxations.
•The most common radiographs in SLE
show periarticular osteopenia and soft-
tissue swelling without erosions.

146. Chest imaging studies include:
Radiography
CT scanning
These modalities used to monitor:
•interstitial lung disease
•Pneumonitis
•pulmonary emboli
•alveolar hemorrhage.

147. Vasculitis, antiphospholipid antibodies, and renal failure are commonly found in
patients with lupus; these conditions greatly increase the risk of developing
pulmonary emboli. The diagnosis in a patient with shortness of breath, hemoptysis,
and pleuritic chest pain is commonly made with ventilation-perfusion scans or
computed tomography (CT) angiography. The CT angiogram demonstrates a filling
defect in the left anterior segmental artery (arrow).

148. Brain MRI /magnetic resonance
angiography (MRA) is used to evaluate:
•CNS lupus white-matter changes
•Vasculitis
•Stroke
although findings are often nonspecific
and may be absent in as many as 42%
of cases with neuropsychiatric
symptoms.

149. This axial, T2-weighted
brain MRI demonstrates
an area of ischemia in the
right periventricular white
matter of a 41-year-old
woman with long-standing
SLE.
She presented with
headache and subtle
cognitive impairments but
no motor deficits.

150. Joint Effusion
Arthrocentesis
•Arthrocentesis may be performed in patients with
joint effusions, which can be inflammatory or
noninflammatory.
•The cell count may range from <25% PMNs in
noninflammatory effusions to >50% in inflammatory
effusions.
•Viscosity will be high in noninflammatory effusions
and low in inflammatory effusions.
•The gross appearance of these fluids will be straw-
colored or clear in noninflammatory cases and either
cloudy or yellow in inflammatory ones.

151. Lumbar puncture and CSF Studies
•Lumbar puncture may be
performed to exclude infection with
fever or neurologic symptoms.
•Nonspecific elevations in cell count
and protein level and decrease in
glucose level may be found in the
CSF of patients with CNSlupus.

152. Skin biopsies
•Skin biopsy can help in
diagnosing SLE or unusual
rashes in patients with this
condition.
•Many different rashes may
herald SLE, making review by a
dermatopathologist important.

153. Lupus skin rash often demonstrates
inflammatory infiltrates at dermoepidermal
junction and vacuolar change in the basal
columnar cells.
Discoid lesions demonstrate more-significant
skin inflammation, with hyperkeratosis,
follicular plugging, edema, and mononuclear
cell infiltration at the dermoepidermal
junction.

154. In many SLE rashes, immunofluorescent stains demonstrate
immunoglobulin and complement deposits at the dermoepidermal
basement
Lupus band test:
Microphotograph of a
histologic section of human
skin prepared for direct
immunofluorescence using
an anti-IgG antibody.
The skin is from SLE pt. and
shows IgG deposit at 2
different places: the first is a
band-like deposit along the
epidermal basement
membrane ("lupus band
test" is positive); the second
is within the nuclei of the
epidermal cells (ANA).

155. Microphotograph of a
fixed Hep-2 line cell
prepared for indirect
immunofluorescence.
The preparation was
exposed to a serum of
a patient with SLE and
labeled using a murine
anti-human IgG ab.
It shows IgG deposit in
nucleus & nonspecific
deposit in cytoplasm.

165. History and review of systems
Joint pain and swelling, Raynaud's phenomenon
Photosensitivity, rash, hair loss
Shortness of breath, pleuritic chest pain
General symptoms (depression, fatigue, fever, weight change)
Physical examination
Rashes (acute, subacute, chronic, nonspecific, others), alopecia, oral or nasal ulcers
Lymphadenopathy, splenomegaly, pericardial or pleural effusions
Funduscopic examination, edema
Other features as suggested by history and symptoms
Imaging and laboratory tests
Hematology[∗]
Chemistry[∗]
PT/PTT, antiphospholipid antibodies
Urinalysis[∗]
Serology (ANA, ENA including anti-dsDNA,[#] complement[#])
Chest x-ray
ECG
Other tests as suggested by history and symptoms
Disease activity index (at each visit or at major changes in therapy)
Side effects of therapy
Damage index (SLICC) (every 1-2 yr)
Recommended Initial Assessment and Monitoring of SLE

167. Because of the pleiotropic
manifestations of SLE, the
differential diagnosis is
large depending on the
specific manifestations in
each patient.

168. Differential diagnosis from other polyarticular
diseases affecting young women:
RA or Still dis, may not be easy in the initial stages.
Many other diseases also may be confused with
early SLE, including :
•undifferentiated CTD,
•primary Sjögren's syndrome
•primary APS
•fibromyalgia with positive ANA
•idiopathic thrombocytopenic purpura
•Drug induced lupus
•autoimmune thyroid disease.

169. The DD in patients presenting with fever or splenomegaly
and lymphadenopathy must include:
•infectious diseases
•lymphoma.
In febrile patients with known SLE, leukocytosis,
neutrophilia, shaking chills, and normal levels of anti-DNA
antibodies favor infection.
SLE may manifest with localized or generalized
lymphadenopathy or splenomegaly, but the size of lymph
nodes is rarely more than 2 cm, and splenomegaly is mild to
moderate. Patients with known or suspected SLE with
prominent lymphadenopathy, massive splenomegaly, or
expansion of a monoclonal CD19+/CD22+ B cell population
should raise the suspicion of non-Hodgkin's lymphoma.

170. In patients presenting with neurologic
symptoms, infections, cerebrovascular
accidents, or immune-mediated neurologic
diseases (e.g., multiple sclerosis, Guillain-Barré
disease) must be considered.
patients presenting with a pulmonary renal
syndrome, the disease must be DD from:
•Goodpasture syndrome
•antineutrophilic cytoplasmic antibody–
associated vasculitis.

171. In pts presenting with glomerulonephritis,
the DD includes:
• postinfectious GN (streptococcal,
staphylococcal, subacute bacterial endocarditis, or
hepatitis C virus),
• membranoproliferative GN
•renal vasculitis (antineutrophilic cytoplasmic
antibody or anti–glomerular basement membrane
associated).

172. Other problems to be considered in the differential
diagnosis of SLE include the following:
•Discoid skin lesions
•Erythematous macules
•Interstitial lung disease
•Leukemia
•Leukopenia
•Parvovirus or other viral infections
•Photodistributed rash
•Pleuritic chest pain
•Pneumonitis
•Polyarthritis/polyarthralgia
•Renal vasculitis
•Seizures
•Stroke
•Thrombocytopenia
•Vasculitis

173. Differential Diagnoses
Acute Pericarditis
Antiphospholipid Syndrome
Autoimmune Hepatobilliary Disease
Fibromyalgia
Hepatitis C
Infectious Mononucleosis
Infective Endocarditis
Lyme Disease
Lymphoma, B-Cell
Mixed Connective-Tissue Disease
Polymyositis
Rheumatoid Arthritis
Scleroderma
Sjogren Syndrome
Undifferentiated Connective-Tissue Disease