شکیبی رضا محمد دکتر

LUPUS ERYTHEMATOSUSLUPUS ERYTHEMATOSUS

• autoimmune disease expressed in both localized cutaneous and systemic multiorgan forms

• characterized by humoral and cellular immunologic abnormalities that lead to tissue destruction through the deposition of immune complexes and autoantibodies

ETIOLOGYETIOLOGY

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 SLE

the class I major histocompatibility complex (MHC) molecule HLA-B8 the 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

LUPUS ERYTHEMATOSUSLUPUS ERYTHEMATOSUSINCIDENCE AND EPIDEMIOLOGYINCIDENCE AND EPIDEMIOLOGY

• incidence

among white females two to three per 100,000

and among black females seven to eight per 100,000. • prevalence

vary between one and ten per 10,000 in the general population

one per 100 among family members of patients

LUPUS ERYTHEMATOSUSLUPUS 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

LUPUS ERYTHEMATOSUSLUPUS 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

LUPUS ERYTHEMATOSUSLUPUS 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

LUPUS ERYTHEMATOSUSLUPUS 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.

LUPUS ERYTHEMATOSUSLUPUS ERYTHEMATOSUS CARDIOVASCULAR FINDINGSCARDIOVASCULAR 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.

PULMONARY FINDINGSPULMONARY 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.

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.

NEUROLOGIC FINDINGSNEUROLOGIC 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       

HEMATOLOGIC FINDINGSHEMATOLOGIC 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

SYSTEMIC LUPUSSYSTEMIC LUPUS ERYTHEMATOSUSERYTHEMATOSUSDRUG TREATMENTDRUG TREATMENT

CORTICOSTEROIDS

- oral 60-80 mg/day

- pulse i.v. methylprednisolone 500-1000 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 100-200 mg/day 10-days/20 day

ANTIPHOSPHOLIPID ANTIBODY (APL) SYNDROME

the clinical constellation of:

    venous and arterial thrombosis

    recurrent fetal loss

    thrombocytopenia

associated with the occurrence of autoantibodies with an apparent specificity for anionic phospholipids

Clinical manifestation

Venous thrombosis: Most common: deep or superficial veins of the legs

Less common: inferior vena cava, iliofemoral, axillary, renal, portal, hepatic, or retinal veins.

Clinical manifestation

Arterial thrombosis: Most common: Cerebral infarct, some strokes may be caused by cardiogenic emboli.

Less common: Coronary, retinal, and visceral artery

Clinical manifestation Other symptoms Cutaneous: livedo reticularis, splinter hemorrhages, leg ulcer, skin insarcts, blue toe syndrome

Neuro: multi-infarct dementia, chorea, transverse myelopathy, Pseudotumor cerebri, cerebral venous thrombosis

Cardiac: Coronary artery disease, valve vegetations, intracardiac thrombus

Hematologic: Thrmobocytopenia (40% of patients), hemolytic anemia

Obstetric: Late term pregnancy loss, intrauterine growth retardation.

Clinical manifestation Hypertension, coronary artery disease, hyperlipidemia, cigarette smoking, and a positive ANA are associated with an increased risk of stroke or TIA, whereas those on aspirin plus dipyridamole were at a decreased risk.

Stroke recurrence rate may be as high as 10% per year. Usually large or median branch artery infarcts and rarely causes lacunar infarcts.

Clinical manifestation

The best independent predictor of a thrombotic event is a history of thrombosis.

Cardiac valve thickening or vegetative lesions: may occur in > 30% of patients with primary Antiphospholipid antibody syndrome.

Recurrent spontaneous fetal loss: more common in the second or third trimester. Observed in 15% to 75% of Antiphospholipid antibody-positive women.

Clinical manifestation

Livedo reticularis, a lattice-like pattern of skin discoloration: most common cutaneous finding, seen in up to 80% of patients with Antiphospholipid antibodies.

Cutaneous ulcers, which may be refractory to treatment.

ANTIPHOSPHOLIPID ANTIBODY (APL) SYNDROMELABORATORY

anticardiolipin antibody: IgG, IgM

B2GP1

lupus anticoagulant

prolongation of aPTT

SCLERODERMA

Systemic sclerosis (SScI, scleroderma) is characterized by thickening and fibrosis of the skin (scleroderma) and by distinctive forms of internal organ involvement.

INCIDENCE AND EPIDEMIOLOGY

• SScI is believed to occur in four to 12 persons per million population per year

• SScI is four times more common in women than in men and is found in all racial groups and geographic areas

• disease onset is highest between ages 25 and 50. • detailed study of HLA phenotypes has failed to

reveal any consistent associations with SScI.

SCLERODERMAMUSCULOSKELETAL 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 inflammation

• Ischemic 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.

SCLERODERMAGASTROINTESTINAL 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 loss

• Colon 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.

SCLERODERMACARDIAC 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 ischemia

– Raynaud-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.

SCLERODERMAPULMONARY 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 TESTS• Gallium scanning is relatively insensitive in recognizing

pulmonary inflammation in SScl• bronchoalveolar lavage reveals increased numbers of

neutrophils, lymphocytes, and occasionally eosinophils in 40% to 60% of patients

SCLERODERMARENAL 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

SCLERODERMAENDOCRINE 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

males • Fertility is lowered in female patients

SCLERODERMALABORATORY FINDINGS

• Nonspecific sero-logic abnormalities • antinuclear 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 antibody • Anti-Scl 70 antibody is of low sensitivity, being present

in only 30% to 40% of generalized scleroderma, but is highly specific for this diagnosis.

POLYMYOSITIS

chronic 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

POLYMYOSITISETIOLOGY 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 considered •infectious agents Influenza B1 virus infection echovirus, coxsackievirus B1 antigens Toxoplasma gondii •there is a 2:1 female predominance

POLYMYOSITISCLINICAL 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 months

• Pharyngeal 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

POLYMYOSITIS

chronic 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

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 considered •infectious agents Influenza B1 virus infection echovirus, coxsackievirus B1 antigens Toxoplasma gondii •there is a 2:1 female predominance

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 months

• Pharyngeal 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

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 color

• Red, 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

POLYMYOSITIS / DERMATOMYOSITIS CLINICAL FEATURES

• Diffuse erythematous rash involving the forehead, neck, anterior chest, shoulders, and arms

• Pulmonary 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

POLYMYOSITIS / DERMATOMYOSITIS LABORATORY FINDINGS

• Anemia • ESR -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 antibody• elevated serum levels of enzymes that diffuse from damaged

muscle (95% patients) • creatine kinase - most sensitive and specific of these enzymes• aldolase• transaminases• lactate dehydrogenase • EMG - extremely sensitive but nonspecific tool; • muscle biopsy - the most conclusive evidence of myositis