SLE CLINICAL DIAGNOSIS,

CLASSIFICATION CRITERIA AND

ASSESSMENT OF DISEASE ACTIVITY AND DAMAGE

Dr. Aliaa Omar El-HadyConsultant of

Rheumatology & Rehabilitation

Mataria Teaching Hospital

The assessment of SLE is marked by four components: 1. accurate diagnosis2. monitoring of disease activity3. recording of accumulated damage4. 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.

• 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.

Assessment of accurate diagnosis

ByHistory,Examination

& Investigations

DIAGNOSTIC CRITERIA FOR SLE

CONSTITUTIONAL

•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).

•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.

MUCOCUTANEOUS INVOLVEMENT

ACUTE RASHES

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.

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).

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

SUBACUTE RASHES

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).

• 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.

CHRONIC RASHES

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.

•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).

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.

OTHER RASHES

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.

Livedo reticularis

•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.

Raynaud's phenomenon

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

Photosensitivity:•either acute or chronic.

•unusual rash or symptom exacerbation after sun exposure, with expected duration of ~ 2 days in classic cases.

•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

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.

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

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

MUCOUS MEMBRANES

•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

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.

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

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

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.

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

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

MUSCULOSKELETAL INVOLVEMENT

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).

•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.

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.

•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.

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.

•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.

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.

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

•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.

•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.

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.

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

NERVOUS SYSTEM

INVOLVEMENT

•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.

 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

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?

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, catatoniaConsider cytotoxic therapy

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.

A variety of autoantibodies has been associated with the pathogenesis of different manifestations of NPSLE. Autoantibodies include:1. antineuronal antibodies2. antiganglioside antibodies3. anti-NR2 glutamate receptor antibodies4. anti-DNA antibodies5. antiribosomal (P) antibodies6. anti-β2-glycoprotein I antibodies7. antiprothrombin antibodies8. 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.

•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.

•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.

CARDIOVASCULAR INVOLVEMENT

•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.

•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.

•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.

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.

•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.

•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.

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

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.

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.

PLEURA AND LUNGS

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

•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.

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.

•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.

•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.

•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.

•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.

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.

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.

•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.

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

HEMATOLOGIC INVOLVEMENT

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 anemiaThe 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.

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.

•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.

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 destruction2. 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

•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.

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 drugsDiscontinue 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 myelodysplasiaTests for antiplatelet antibodies are not helpfulRule 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

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)

LIVER AND

GASTROINTESTINAL TRACT INVOLVEMENT

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.

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.

•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.

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. Peritonitis2. mesenteric vasculitis with intestinal

infarction3. Pancreatitis4. inflammatory bowel disease.

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.

•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.

•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.

•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.

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 failure2. 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.

OPHTHALMIC INVOLVEMENT

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.

•Corneal and conjunctival involvement is usually part of 2ry Sjögren's syndrome.

•uveitis and scleritis are extremely rare manifestations in SLE.

RENAL INVOLVEMENT

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.

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.

Types of Renal Involvement in Systemic Lupus Erythematosus

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.

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.

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.

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.

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.

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.

Renal BiopsyWhen 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).

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, Membranousnephropathy (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.

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.

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.

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.

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.

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.

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.[

Definite AssociationChlorpromazine MethyldopaHydralazine ProcainamideIsoniazid Quinidine

Possible AssociationBeta-blockers MethimazoleCaptopril NitrofurantoinCarbamazepine PenicillamineCimetidine PhenytoinEthosuximide PropylthiouracilHydrazines SulfasalazineLevodopa SulfonamidesLithium Trimethadione

Unlikely AssociationAllopurinol PenicillinChlorthalidone PhenylbutazoneGold salts ReserpineGriseofulvin StreptomycinMethysergide TetracyclinesOral contraceptives

Drugs Associated With Lupus Erythematosus

Diagnostic Studies

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 CRPComplement levelsLiver function testsCreatine kinase assaySpot protein/spot creatinine ratio

•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.

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.

•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.

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.

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

Test DescriptionANA 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% sensitivityAnti-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 RBCsAnti-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

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.

Chest imaging studies include:RadiographyCT scanning

These modalities used to monitor:•interstitial lung disease•Pneumonitis•pulmonary emboli•alveolar hemorrhage.

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).

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

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.

Joint EffusionArthrocentesis•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.

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.

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.

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.

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).

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.

monitoring of disease activity

&recording of accumulated

damage

History and review of systemsJoint pain and swelling, Raynaud's phenomenonPhotosensitivity, rash, hair lossShortness of breath, pleuritic chest painGeneral symptoms (depression, fatigue, fever, weight change)Physical examinationRashes (acute, subacute, chronic, nonspecific, others), alopecia, oral or nasal ulcersLymphadenopathy, splenomegaly, pericardial or pleural effusionsFunduscopic examination, edemaOther features as suggested by history and symptomsImaging and laboratory testsHematology[ ]∗

Chemistry[ ]∗

PT/PTT, antiphospholipid antibodiesUrinalysis[ ]∗

Serology (ANA, ENA including anti-dsDNA,[#] complement[#])Chest x-rayECGOther tests as suggested by history and symptomsDisease activity index (at each visit or at major changes in therapy)Side effects of therapyDamage index (SLICC) (every 1-2 yr)

 Recommended Initial Assessment and Monitoring of SLE

DIFFERENTIAL DIAGNOSIS

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

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.

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.

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.

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).

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

Differential DiagnosesAcute PericarditisAntiphospholipid SyndromeAutoimmune Hepatobilliary DiseaseFibromyalgiaHepatitis CInfectious MononucleosisInfective EndocarditisLyme DiseaseLymphoma, B-CellMixed Connective-Tissue DiseasePolymyositisRheumatoid ArthritisSclerodermaSjogren SyndromeUndifferentiated Connective-Tissue Disease