Hanna Przepiera-Będzak Klinika Reumatologii PAM, Szczecin

LUPUS 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

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 SLE the class I major histocompatibility complex (MHC) molecule HLA-B8 the class II MHC molecules HLA-DR2 and HLA-DR3 deficiencies of complement components (class III MHC molecules), specially the absence of C2 or C4 or the presence of the C4A null allele

LUPUS ERYTHEMATOSUS INCIDENCE 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 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 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 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 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 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.

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.

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 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 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.

t hrombocytopenia 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 LUPUS ERYTHEMATOSUS DRUG 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 pulses for 3-12 months (+ MESNA to eliminate cystitis) - oral 100-200 mg/day 10-days/20 day monthly

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

Clinical manifestation

Clinical manifestation

Clinical manifestation

Clinical manifestation

Clinical manifestation

ANTIPHOSPHOLIPID ANTIBODY (APL) SYNDROME LABORATORY

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.

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 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.

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 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.

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 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 bradyarrhythmias are less frequently encountered.

and

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 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

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

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

males

• Fertility is lowered in female patients

SCLERODERMA LABORATORY 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.

SJÖGREN’S SYNDROME chronic autoimmune rheumatic and lymphoproliferative disease characterized by a progressive lymphocytic and plasma cell infiltration of the salivary and lacrimal glands leading to xerostomia (dry mouth), salivary gland swelling and xerophtalmia (dry eyes) Primarily affects women 40-50 years (F:M ratio 9:1) PRIMARY SJÖGREN’S SYNDROME SECONDARY SJÖGREN’S SYNDROME: accompanying RA or other connective tissue disease

• o o

SJÖGREN’S SYNDROME Sicca syndrome Keratoconjunctivitis - Dry eyes with reduced tear production with gritty or sandy sensation under the lids; red eyes; photosensitivity Xerostomia sensation; Decreased difficulties with chewing, swallowing, and even speech; abnormality in taste and smell; dental caries; mucosal burning sensitivity to saliva spicy voice production and acidic leading foods to and beverages; increased risk for oral candidiasis; hoarseness of

• o o

Musculoskeletal symptoms Arthralgia, morning stiffness, nonerosive arthritis Myalgia, muscle weakness

• o o o

Cutaneous findings Raynaud phenomenon Nonthrombocytopenic purpura, especially of lower extremities Nasal, vaginal, and cutaneous dryness

SJÖGREN’S SYNDROME

•Gastrointestinal symptoms oDysphagia, nausea, epigastric pain oAchalasia (in children) oAchlorhydria, chronic atrophic gastritis oPrimary biliary cirrhosis •Pulmonary findings oDyspnea due to mild interstitial disease oDry cough •Renal findings

- Interstitial nephritis

•Other symptoms

- Fatigue, depression

SJÖGREN’S SYNDROME Physical examination

•Parotid gland enlargement •Corneal ulceration, vascularization •Vasculitic lesions - Purpura •Lymphadenopathy •Autoimmune thyroiditis •Neuromuscular manifestations oPeripheral sensorimotor neuropathy oCNS disorders, such as movement disorder, transverse

myelopathy, encephalopathy, aseptic meningitis, and dementia, have been described in some studies.

SJÖGREN’S SYNDROME Physical examination

•Arthritis oIntermittent synovitis oChronic nonerosive polyarthritis: Jaccoud arthropathy is

observed in adults.

•Oral cavity oMild erythema and thinning of the mucosa oErythema, fissuring, coating, and depapillation of the dorsal

tongue

oTraumatic erosions and ulcers, angular cheilitis, and chapped

lips

oFrothy, ropey, and thickened saliva

SJÖGREN’S SYNDROME LABORATORY

•CBC count with differential: Mild anemia and leukopenia are present. •Erythrocyte sedimentation rate (ESR): Elevated ESR is observed in

80-90% of patients; however, C-reactive protein (CRP) usually is within the reference range.

•Immunoglobulin levels: Hypergammaglobulinemia, up to several

grams of immunoglobulin G (IgG), is observed in 80% of patients.

•Autoantibodies oAntinuclear antibody (ANA) and rheumatoid factor (RF) - Usually

elevated

oAnti-Ro (SS-A), anti-La (SS-B) oOther autoantibodies to thyroglobulin, thyroid microsomal,

mitochondrial, smooth muscle, and salivary duct

•Rose Bengal staining: The dye stains the damaged corneal

epithelium and indicates keratoconjunctivitis.

SJÖGREN’S SYNDROME Imaging Studies

•Sialography

- A sensitive and specific radiographic technique to find evidence of sialectasis

•Technetium Tc 99 pertechnetate scintigraphy

- Delayed uptake in Sjögren syndrome, and correlates with pathological changes

•Magnetic resonance imaging (MRI)

determined.) - Visualization of the glandular parenchyma, in particular for the evaluation of cystic or solid masses (In addition, the volumetric estimate of the gland size can be

SJÖGREN’S SYNDROME Other Tests

• In the questionnaire for salivary hypofunction

, positive responses to all 4 of the following questions indicate major salivary gland hypofunction (adapted from Fox and others, 1998).

oDo you sip liquids to aid in swallowing dry foods? oDoes your mouth feel dry when eating a meal? oDo you have difficulties swallowing any foods? oDoes the amount of saliva in your mouth seem to be too

little?

•Schirmer tear test

: This test is used to evaluate tear production by lacrimal glands. A strip of filter paper is placed beneath the lower lid, and wetting of the paper is measured at 5 minutes. Less than 5 mm of wetting suggests decreased tear production.

SJÖGREN’S SYNDROME Other Tests

•Salivary gland biopsy oThe pathological findings are very useful in diagnosis. oBecause of the relative ease and lack of complications, labial

minor salivary gland biopsy is preferred over parotid gland biopsy, which can result in facial nerve damage.

oIn order to ensure that a representative sample has been obtained

for histopathologic examination, harvesting 5-10 lobules of minor salivary glands is important.

SJÖGREN’S SYNDROME Medical Care

•Xerostomia

saliva - Stimulation of salivary flow with sialagogues, such as pilocarpine or cevimeline; mechanical stimulation through the use of sugarless chewing gum or lozenges; topical tissue hydration or lubrication from drinking water or the use of artificial

•Oral hygiene •Keratoconjunctivitis

- Artificial tears

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 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 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

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

WEGENER'S GRANULOMATOSIS

• a systemic vasculitis of unknown cause associated with

sinopulmonary and renal system involvement and characterized by granulomatous arteritis of medium sized vessels

• incidence is unknown - much less common than giant

cell arteritis.

• no familial tendency • sinusitis - often relatively severe but may vary anywhere

from rhinorrhea to nasal perforation to bony dissolution

WEGENER'S GRANULOMATOSIS-CLINICAL FEATURES

• • • lung > 90% of patients

chest x-ray - multiple pulmonary infiltrates - often cavitary, pulmonary function tests - obstructive changes, restrictive disease atelectasis and small pleural effusions occur in less than 20% of patients.

joint involvement in half of the patients mild and nondeforming and strikes the large joints, polyarticular symmetrical eyes - in half the cases anterior chamber inflammatory changes; uveitis; optic neuropathies (III, IV, VI cranial nerves; proptosis

• •

cough

• renal disease

urine sediment abnormal, containing red blood cells, casts, and protein central nervous system 20% to 50% of patients .

WEGENER'S GRANULOMATOSIS LABORATORY FINDINGS

• ESR elevated • autoantibody to certain neutrophil cytoplasmic antigens (ANCA) • white blood count - increased • anemia of a normocytic normochromic type • platelets may be increased • complement levels in the serum are usually normal • mild eosinophilia • in patients with renal disease- urinalysis abnormal