Transcript SULFASALAZYNA

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 druginduced 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

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·
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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.

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 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
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
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
and
bradyarrhythmias are less frequently encountered.
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.
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