2 LUPUS ERYTHEMATOSUSautoimmune disease expressed in both localized cutaneous and systemic multiorgan formscharacterized by humoral and cellular immunologic abnormalities that lead to tissue destruction through the deposition of immune complexes and autoantibodies
3 ETIOLOGY The exact etiology of LE remains unknown Factors contributing to the development of disease· exposure to ultraviolet· ancillary viral infections· psychological stress· Certain medications: procainamide, hydralazine (can lead to a drug-induced lupuslike syndrome)· women are much more likely to have lupus than men (in adults- ratio 10:1; in both prepubertal and postmenopausal - ratio 2:1 or 3:1.)· black, Asian, and Native American groups have a higher prevalence of lupus than do whites.· genetic markers that are associated with SLEthe class I major histocompatibility complex (MHC) molecule HLA-B8the class II MHC molecules HLA-DR2 and HLA-DR3deficiencies of complement components (class III MHC molecules), specially the absence of C2 or C4 or the presence of the C4A null allele
4 LUPUS ERYTHEMATOSUS INCIDENCE AND EPIDEMIOLOGY among white females two to three per 100,000and among black females seven to eight per 100,000.prevalencevary between one and ten per 10,000 in the general populationone per 100 among family members of patients
5 LUPUS ERYTHEMATOSUS CLINICAL FEATURES Systemic lupus is a multisystemic disease for which the diagnosis rests on the identification of a constellation of clinical findings with supportive laboratory tests.No single finding or test result confirms the diagnosis. However, some findings, such as a characteristic malar rash or discoid lesions or high titers of antibodies to double-stranded DNA or antibodies to the Sm antigen, in the context of a systemic illness are more suggestive than others.Criteria for the identification and classification of patients as having SLE suitable for clinical studies have been formulated by the American Rheumatism Association
7 LUPUS ERYTHEMATOSUS CONSTITUTIONAL FINDINGS · fever (fever due to infection must be differentiated from fever due to SLE. Acute severe LE may be accompanied by fever above 40 °C, but sustained fever above 39.5 °C is not common)· fatigue· anorexia,· nausea,· weight loss
8 LUPUS ERYTHEMATOSUS CUTANEOUS FINDINGS · Acute cutaneous lupus:facial (malar or butterfly) erythema involving the bridge of the nose and the cheeks, often with extension to the chin and ears. It heals without scarring, although telangiectasia may occur. More extensive erythema, either palpable or nonpalpable, may involve the arms and trunk, predominantly in sun-exposed areas (exacerbated by exposure to ultraviolet light) Widespread morbilliform or bullous eruption.· Subacute cutaneous lupus:superficial, nonscarring papulosquamous or annular lesions of the trunk with a widespread and symmetrical distribution (exacerbated by exposure to the sun) The involved skin may become hypopigmented and telangiectatic.· Chronic cutaneous lupus:discoid skin lesions, which are erythematous, raised, scaling patches most commonly found on the head and scalp. They are characterized by follicular plugging, atrophic central scarring, depigmentation, and telangiectasia
12 LUPUS ERYTHEMATOSUS MUSCULOSKELETAL FINDINGS arthralgia (arthritis presents classically as nonerosive, nondeforming polyarthritis with symmetrical involvement of the proximal interphalangeal joints, metacar-pophalangeal joints, wrists, and knees)myalgia. Muscle weakness may reflect general malaise, (sub)clinical myopathy, or overt inflammatory myositis. Electromyographic abnormalities are more common than elevations in the creatine kinase value; muscle biopsy may show myositis with fiber damage and inflammatory cells or a vacuolar myopathy. Muscle weakness may also reflect a corticosteroid-induced myopathy, a chloroquine-in duced myopathy, or a myasthenia gravis-like syndrome in addition to direct involvement of muscle by LE.
13 LUPUS ERYTHEMATOSUS CARDIOVASCULAR FINDINGS Pericarditis is the most common manifestation. Effusions demonstrable by echocardiography are present in more than half of patients, whereas symptomatic disease occurs in one fourth to one third of patients. Tam-ponade rarely occurs.Myocardial disease secondary to muscle inflammation or small vessel involvement can cause conduction defects and myocardial dysfunction leading to congestive heart failure.Verrucous endocarditis (Libman-Sacks syndrome) rarely leads to clinically important valvular lesions or embolic complications.Peripheral vascular manifestations include small vessel vasculitis, phlebothrombosis with or without thrombophlebitis, thrombosis without vasculitis, and, rarely, gangrene.Raynaud's phenomenon occurs in one fourth of patients.Accelerated atherosclerosis with early myocardial infarction and myocardiopathy is increasingly recognized as a cause of significant morbidity in LE patients, especially in those treated with glucocorticoids for long periods.
14 PULMONARY FINDINGS· Pleuritis is the most common pulmonary finding of LE. Pleural effusions occur in up to half the patients, whereas pleuritic pain is reported by at least two thirds.· Abnormal results of pulmonary functions tests with both restrictive and obstructive deficits occur more frequently than radiologi-cally overt interstitial fibrosis.Acute "lupus pneumonitis" may be extensive or more limited with only patchy infiltrates and platelike atelectasis on the chest film. Progression to acute pulmonary insufficiency with intrapulmonary hemorrhage is infrequent. Lupus pneumonitis is a diagnosis of exclusion; as with many other manifestations of LE, infection must be rigorously excluded.
15 RENAL FINDINGS· deposition of immunoglobulin in glomeruli is probably very common, but only about half of SLE patients have clinically evident nephritis with proteinuria, hematuria, and/or cylindruria.· In lupus nephritis the entire range of glomerular pathologic lesions (mesangial, membranous, proliferative, and membranoproliferative) as well as interstitial abnormalities have been reported.
16 NEUROLOGIC FINDINGS· seizures and psychiatric dysfunction, which may range to overt psychosis.· organic brain syndrome, both extrapyramidal and cerebellar dysfunction, optic neuritis, and aseptic meningitis as well as tissue infarcts and subarachnoid hemorrhage.· headaches, which may resemble migraine· peripheral nervous system involvement cranial nerve palsies, transverse myeitis with paraparesis or quadriparesis, and sensory or sensorimotor neuropathies.· depression and anxiety
17 HEMATOLOGIC FINDINGS· the lupus anticoagulant, leads to a mild prolongation of the prothrombin time and a more significant prolongation of the partial thromboplastin time. The lupus anticoagulant is also associated with a false-positive serologic test for syphilis (VDRL)· autoimmune hemolytic anemia occurs in about 10% of patients, although a much higher percentage may have a positive Coombs' test.· leukopenia is found is about half of patients and usually reflects a lympho-penia. Granulocytopenia may also occur. The leukopenia in SLE results from both antileukocyte antibodies and other mechanisms.· thrombocytopenia is usually mild, with platelet counts remaining above 80,000 to 100,000 cells per milliliter, but severe thrombocytopenia with bleeding or risk of bleeding may occur and require corticosteroid treatment
19 SYSTEMIC LUPUS ERYTHEMATOSUS DRUG TREATMENT · CORTICOSTEROIDS- oral mg/day- pulse i.v. methylprednisolone mg /day 2-3 days· CYCLOPHOSPHAMIDE- - pulse i.v. 500 mg-1 g /weekly for 3 weeks followed by monthly pulses for 3-12 months (+ MESNA to eliminate cystitis)- oral mg/day 10-days/20 day
20 ANTIPHOSPHOLIPID ANTIBODY (APL) SYNDROME the clinical constellation of:· venous and arterial thrombosis· recurrent fetal loss· thrombocytopeniaassociated with the occurrence of autoantibodies with an apparent specificity for anionic phospholipids
28 SCLERODERMASystemic sclerosis (SScI, scleroderma) is characterized by thickening and fibrosis of the skin (scleroderma) and by distinctive forms of internal organ involvement.
29 INCIDENCE AND EPIDEMIOLOGY SScI is believed to occur in four to 12 persons per million population per yearSScI is four times more common in women than in men and is found in all racial groups and geographic areasdisease onset is highest between ages 25 and 50.detailed study of HLA phenotypes has failed to reveal any consistent associations with SScI.
30 SCLERODERMA MUSCULOSKELETAL FEATURES The edema of the fingers and other locations is typically painless but may be accompanied by symptoms of morning stiffness, arthralgia, and carpal tunnel syndrome;. As skin thickening worsens, the underlying joints become tethered and restricted in motion.Arthritic complaints are common, and erosive arthropathy occurs in a minority. Restricted motion leads to disuse atrophy of muscles, and weakness may be worsened by accompanying skeletal muscle inflammationIschemic ulcerations of the fingertips occur in 10% to 20% of patients per year, and the fingers themselves may shorten and atrophy from both disuse and ischemic re-sorption of the phalanges.Skin tightening on the face may restrict the ability to open the mouth and impair adequate dental hygiene.
31 SCLERODERMA GASTROINTESTINAL INVOLVEMENT Weakness of the lower esophageal sphincter is associated with chronic reflux esophagitis.Hypomotility of the lower esophagus causes symptoms of dysphagia for solid foods, which may be significantly worsened by lower esophageal stricture secondary to chronic reflux.Small bowel involvement presents as intermittent abdominal cramping and diarrhea. Malabsorption may occur and weight lossColon involvement is typified by complaints of constipation. Gastrointestinal bleeding is most frequently due to erosive esophagitis, although bowel telangiectasia must also be considered.Hepatic involvement is uncommon, although patients with limited scleroderma may develop the complication of primary biliary cirrhosis.
32 SCLERODERMA CARDIAC INVOLVEMENT Patchy fibrosis of the myocardium occurs in as many as 80% of patients with SScI.Contraction band necrosis has been reported, suggesting intermittent myocardial ischemiaRaynaud-like reactivity of the coronary microvasculature is suspected.Symptoms of exertional dyspnea and palpitations are common, whereas chest pain and clinical congestive heart failure are not.Supraventricular and ventricular arrhythmias are seen in many patients, and the latter are strongly associated with mortality, including sudden death.Involvement of the conduction system and bradyarrhythmias are less frequently encountered.
33 SCLERODERMA PULMONARY INVOLVEMENT pulmonary involvement is a major cause of morbidity and mortality in SScl. Dyspnea on exertion is present in 50% to 60% of all patients. No organ illustrates the diversity of pathologic processes operative in SScl as well as the lung, where any combination of interstitial inflammation, fibrosis, and pulmonary vascular injury may be present.interstitial lung disease typified by basilar rales, abnormal chest radiographs, and loss of lung volume on pulmonary function testing.DIAGNOSTIC TESTSGallium scanning is relatively insensitive in recognizing pulmonary inflammation in SSclbronchoalveolar lavage reveals increased numbers of neutrophils, lymphocytes, and occasionally eosinophils in 40% to 60% of patients
34 SCLERODERMA RENAL INVOLVEMENT The sudden onset of accelerated to malignant hypertension and progressive renal insufficiency usually accompanied by microangiopathic hemolytic anemia constitutes the syndrome of scleroderma renal crisis.Obliterative vasculopathy with cortical infarction is present and marked hyperren-inemia the principal mechanism of hypertension. Peak onset occurs during cold weather months.A Raynaud-like mechanism overlying renal intimal fibrotic arteriosclerosis
35 SCLERODERMA ENDOCRINE AND EXOCRINE FEATURES Hypothyroidism occurs in as many as 50% of patients with SScl and is frequently occult.Vaginal dryness and dyspa-reunia are common.Impotence is recognized as a presenting feature in malesFertility is lowered in female patients
36 SCLERODERMA LABORATORY FINDINGS Nonspecific sero-logic abnormalitiesantinuclear antibodies in around 90%, most typically nucleolar in pattern; rheumatoid factor in 30%;polyclonal hypergammaglobulinemia and cryoglobulinemia in 20% to 40%.moderate elevations of ESR anemia of chronic disease,Anticentromere antibodyAnti-Scl 70 antibody is of low sensitivity, being present in only 30% to 40% of generalized scleroderma, but is highly specific for this diagnosis.
37 When a rash is also present, the term DERMATOMYOSITIS is used POLYMYOSITISchronic inflammatory disease of skeletal muscle characterised by symmetrical weakness of proximal limb girdle muscles as well as of the trunk, neck, and pharyngeal musculature.When a rash is also present, the term DERMATOMYOSITIS is used
38 POLYMYOSITIS ETIOLOGY AND PATHOGENESIS the cause - unknown.serum antibodies directed against certain nuclear and cytoplasmic proteins : anti-Jo 1, anti-PM-Scl, and anti-RNP,polymyositis has occurred in several patients with hypogammaglobulinemia,the relationship to malignancy should be consideredinfectious agents Influenza B1 virus infection echovirus, coxsackievirus B1 antigens Toxoplasma gondiithere is a 2:1 female predominance
39 POLYMYOSITIS CLINICAL FEATURES Proximal muscle - the onset of weakness is usually insidious, and it primarily affects the hip and/ or shoulder girdle and neck flexors. Inability to rise from a squatting or kneeling position or from a low chair, to climb stairs, and to raise arms above one's head are common early complaints that progress over a period of weeks or monthsPharyngeal muscles: dysphagia, difficulty swallowing liquids with nasal regurgi-tation, aspiration into the tracheobronchial tree, and dysphonia.Weakness in the distal extremities (forearm, hand, leg, foot) is less common (25%),Muscle pain, aching, or tenderness on palpation may be present in up to half of patients but is usually mild.Late findings include atrophy with wasting, joint contractures
40 When a rash is also present, the term DERMATOMYOSITIS is used POLYMYOSITISchronic inflammatory disease of skeletal muscle characterised by symmetrical weakness of proximal limb girdle muscles as well as of the trunk, neck, and pharyngeal musculature.When a rash is also present, the term DERMATOMYOSITIS is used
41 POLYMYOSITIS / DERMATOMYOSITIS ETIOLOGY AND PATHOGENESIS the cause - unknown.serum antibodies directed against certain nuclear and cytoplasmic proteins : anti-Jo 1, anti-PM-Scl, and anti-RNP,polymyositis has occurred in several patients with hypogammaglobulinemia,the relationship to malignancy should be consideredinfectious agents Influenza B1 virus infection echovirus, coxsackievirus B1 antigens Toxoplasma gondiithere is a 2:1 female predominance
42 POLYMYOSITIS / DERMATOMYOSITIS CLINICAL FEATURES Proximal muscle - the onset of weakness is usually insidious, and it primarily affects the hip and/ or shoulder girdle and neck flexors. Inability to rise from a squatting or kneeling position or from a low chair, to climb stairs, and to raise arms above one's head are common early complaints that progress over a period of weeks or monthsPharyngeal muscles: dysphagia, difficulty swallowing liquids with nasal regurgi-tation, aspiration into the tracheobronchial tree, and dysphonia.Weakness in the distal extremities (forearm, hand, leg, foot) is less common (25%),Muscle pain, aching, or tenderness on palpation may be present in up to half of patients but is usually mild.Late findings include atrophy with wasting, joint contractures
43 POLYMYOSITIS / DERMATOMYOSITIS CLINICAL FEATURES Cutaneous involvement may precede, accompany, or follow muscle weakness. classic facial rash (10%-15% of patients) - affects the upper eyelids and face with edema and has a lilac or heliotrope colorRed, scaly patches (Gottron's papules) are found over the extensor surfaces of the elbows, knees, and small joints of the hands and may be pruritic.Nailfolds show periungual erythema, thickening, and gross telangiectatic changes
47 POLYMYOSITIS / DERMATOMYOSITIS CLINICAL FEATURES Diffuse erythematous rash involving the forehead, neck, anterior chest, shoulders, and armsPulmonary interstitial disease (pneumonitis and/or fibrosis) occurs in 10% to 20% Dyspnea, a nonproductive cough, and bibasilar interstitial roentgenographic changes are found. Pulmonary function tests reveal restrictive disease, including a reduced diffusing capacity for carbon monoxide.Asymptomatic electrocardiographic abnormalities
48 POLYMYOSITIS / DERMATOMYOSITIS LABORATORY FINDINGS AnemiaESR -elevated in only one half of patients and does not appear to be a useful guide to disease activity.RF and antinuclear antibody are not usually present.serum autoantibodies - Jo-1 antibodyelevated serum levels of enzymes that diffuse from damaged muscle (95% patients)creatine kinase - most sensitive and specific of these enzymesaldolasetransaminaseslactate dehydrogenaseEMG - extremely sensitive but nonspecific tool;muscle biopsy - the most conclusive evidence of myositis