Beruflich Dokumente
Kultur Dokumente
E DITORIAL
ABSTRACT
Systemic lupus erythematosus (SLE) is a chronic, multifaceted autoimmune inflammatory disease
that can affect any part of the body. SLE is a disease of unknown aetiology with a variety of presenting
features and manifestations. Interest in the disease has been stimulated in recent years, and improved
methods of diagnosis have resulted in a significant increase in the number of cases recognized. It is ap-
parent that it can no longer be regarded as a rare disease. The majority of the pathology in SLE is related
to deposits of immune complexes in various organs, which triggers complement and other mediators of
inflammation. Symptoms vary from person to person, and may come and go, depend on what part of the
body is affected, can be mild, moderate, or severe. Diagnosis can be difficult because lupus mimics many
other diseases; it requires clinical and serologic criteria.
S
ystemic lupus erythematosus (SLE) is a complications such as anemia or hypothyroid-
disease that can affect persons of all ism (2). SLE is an autoimmune disorder charac-
ages and ethnic groups and both sex- terized by multisystem microvascular inflam-
es, but more than 90% of new patients mation with the generation of numerous
presenting with SLE are women in the autoantibodies, particularly antinuclear antibo-
childbearing years. SLE is a disease that affects dies (ANA). The disorder was recognized as
multiple systems (1). SLE symptoms vary wide- early as the Middle Ages, with the 12th century
ly. Fatigue in SLE is probably multifactorial and physician Rogerius being the first to apply the
has been related to not only disease activity or term lupus to the classic malar rash, and in
temporal regions or creates a patch like pattern in whom renal involvement is suspected. Renal
of hair loss. Other cutaneous manifestations re- biopsy need not be done routinely in patients
lated to but not specific to SLE include Rayn- with normal creatinine values and normal urine
aud phenomenon, livedo reticularis, panniculi- analysis (6).
tis (lupus profundus), bullous lesions, vasculitic
purpura, telangiectasias, and urticaria (2). Di- Neuropsychiatric manifestations
agnosis of lupus panniculitis was considered on Neurological manifestations of lupus are re-
clinical and histopathological grounds. Be- ported in 25 to 75% of patients and can involve
tween 70 and 80% of patients develop skin le- all parts of the nervous system (1). One study
sions during the course of disease. Approxi- showed that the incidence of elevated APL an-
mately 20% of them have skin lesions as an tibodies in patients with neurological symp-
initial presentation. The pathognomonic lupus toms is approximately two times higher than in
or butterfly rash across the nose occurs in only those without neurological symptoms. More-
30% of patients with SLE. The acute lupus rash over, APL antibodies antedated neurological
may be present elsewhere. Discoid or disc- symptoms in 81% of patients (2). SLE may be
shaped skin lesions, pathognomonic for discoid generalized or partial and may precipitate sta-
lupus, can manifest also in SLE. Photosensitivity tus epilepticus. Aseptic menigitis, myelopathy,
rash can appear even after mild sun exposure optic neuropathy, or other demyelinating disor-
(3). Livedo reticularis, a reddish purple rash, is ders may also require urgent evaluation. Trans-
usually present in patients with severe vasculitis verse myelitis with spastic paraparesis is a rare
or in individuals with elevated APL. Alopecia but serious complication of SLE (3). The CNS
with patchy or diffuse loss of hair with scalp Lupus nomenclature has been revised to cata-
scarring is another skin manifestation. Rayn- log many manifestations. Cognitive disorders
auds phenomenon can cause bluish discolor- may be variably apparent in patients with SLE
ation of digits and blanching of the skin (18). (19,20). Formal neuropsychiatric testing reveals
deficits in 21-67% of patients with SLE. Wheth-
Renal manifestations er this represents true encephalopathy, neuro-
Although almost in all cases deposits of im- logical damage, medication effects, depression,
munoglobulin are found in the glomeruli, only or some other process is unclear (21-23). Stroke
one half has clinical nephritis (2). Urine analysis and transient ischemic attack (TIA) may be re-
of asymptomatic patients often shows hematu- lated to antiphospholipid antibody syndrome
ria and proteinuria. Renal failure and sepsis are or vasculitis. Migraine headaches may also be
two main causes of death in patients with SLE. linked to antiphospholipid syndrome, although
The kidney is the most commonly involved vis- this is less clear (24). Headache and mood dis-
ceral organ in SLE. Although only approximate- orders may be the most commonly reported
ly 50% of patients with SLE develop clinically neurologic manifestation of SLE, but cause and
evident renal disease, biopsy studies demon- effect may be difficulty to distinguish. Neurop-
strate some degree of renal involvement in al- athies can be peripheral, autonomic, or cranial.
most all patients. Glomerular disease usually Transverse myelitis is coincident with a lupus
develops within the first few years of SLE onset flare and is a rheumatologic emergency (25-
and is usually asymptomatic. Acute or chronic 27).
renal failure may cause symptoms related to
uremia and fluid overload. Acute nephritic dis- Pulmonary manifestations
ease may manifest as hypertension and hema- Pulmonary manifestations of SLE may mani-
turia. Nephrotic syndrome may cause edema, fest acutely or indolently, representing many
weight gain, or hyperlipidemia (3). Lupus neph- complications (1). Serositis can affect both the
ritis is a common and potentially devastating cardiac and pulmonary systems, and cardiac
manifestation of SLE. In general, lupus nephritis and pulmonary serositis often coexist. Pleurisy
occurs in more than half of SLE patients. Lupus with pleuritic chest pain with or without pleural
nephritis is primarily caused by the deposition effusions is the most common feature of acute
of immune complexes. The classification of lu- pulmonary involvement in SLE. Shortness of
pus nephritis is based on renal biopsy. If possi- breath or dyspnea may be due to many causes.
ble, a biopsy should be obtained in any patient Serositis due to pericardial or pulmonary effu-
is keratoconjunctivitis sicca (KCS), occurring in are associated with risk of miscarriage. One-
approximately of 25% of patients. Conjunctivi- third to one-half of women with lupus has
tis, interstitial keratitis, episcleritis, and diffuse these autoantibodies, which can be detected
or nodular scleritis are less common. The sever- by blood tests. Pregnancy should be timed
ity of episcleritis and scleritis may closely mirror when disease is in remission (3). About 3% of
the activity of systemic disease. Necrotizing babies born to mothers with SLE will have neo-
scleritis is rare in patients with SLE. Retinal in- natal lupus, caused by maternal antibodies
volvement in SLE is the second most common crossing the placenta, and may be another con-
ocular manifestation after KCS. The classic sequence of SLE during pregnancy (4).
finding in lupus retinopathy is the cotton-wool
spot, which has been correlated with avascular Endocrine manifestations
zones on fluorescein angiography. The histo- Thyroid dysfunction is more frequent in SLE
pathological findings include infiltration of ves- patients than the general population and may
sel walls with fibrillar material causing vascular have a genetic basis, 3-24 % of patients with
constrictions and widespread hyaline thrombus lupus also have autoimmune thyroid disease.
formation. Typically, the vessel walls are free of Controversy whether SLE is an independent
inflammatory cells. Therefore, it is not consid- risk factor for thyroid disease or whether young
ered as a true vasculitis. Immunofluorescence to middle aged women who are most at risk for
staining reveals deposition of IgG with C1q and SLE are also at risk for autoimmune thyroid dis-
C3. It was shown that 88% of patients with lu- ease (32). Moreover, SLE patients with anti-
pus retinopathy have active systemic disease thyroid peroxidase (anti TPO) antibodies were
and a significantly decreased survival rate. more likely to have thyroid dysfunction than
Therefore, close monitoring and aggressive the control group, 14% of patients with SLE
treatment of these patients is critical. Uveitis, have anti-TPO and anti-thyroglobulin (anti-Tg)
though rare, may occur also in the absence of and 68 % of patients with SLE and thyroid dis-
retinal involvement. Choroidopathy is much ease vs. 5-6 % in general population (33,34).
less common in SLE than is retinopathy. Transu- Type 1 and Type 2 diabetes mellitus can be
dation of fluid through Bruchs membrane may seen but is not common in patients with lupus
result in multifocal retinal pigment epithelium (35). Fracture rates are higher in lupus than ex-
(RPE) and serous retinal detachments. Although pected (5 x higher than the general population)
more extensive pathological findings are seen (14). Vitamin D deficiency is common in SLE
in the choroid as compared to retina, they ap- partly due to avoidance of sun exposure. Pro-
pear to be subclinical. The neuroophthalmo- longed glucocorticoid use can suppress pitu-
logical manifestations of SLE are associated itary function, it is important to always taper
with damage to the optic nerve and brain, most steroids over time (36).
likely as a result of the ischemic process. How-
ever, a clinical picture similar to optic neuritis is Hematologic manifestations
reported as well. Therefore, all patients with
Patients with SLE have a complex array of
ocular lupus should be carefully evaluated for
abnormalities involving their immune system.
systemic involvement to detect potentially
A history of multiple cytopenias such as leuko-
treatable and preventable complications of the
penia, lymphopenia, anemia, or thrombocyto-
disease (30,31).
penia may suggest SLE, among other etiologies.
Leukopenia and, more specifically, lymphope-
Obstetric manifestations
nia are common in SLE, this and hypocomple-
Pregnancy outcome appears to be worse in mentemia may predispose persons with SLE to
SLE patients. SLE causes an increased rate of frequent infections. Anemia is occasionally
fetal death in utero. Pregnant women with SLE overlooked in young menstruating women.
are at higher risk of spontaneous abortions, Hemolytic anemia may occur. Thrombocytope-
stillbirths or fetal retardation. In patients with nia may be mild or part of a thrombotic throm-
APL, the risk of recurrent miscarriages is in- bocytopenic purpura (TTP)like syndrome or
creased. Researchers have now identified two antiphospholipid antibody syndrome (APS).
closely related lupus autoantibodies, anticar- ESR is elevated frequently during active dis-
diolipin antibody and lupus anticoagulant, that ease. Can be seen significantly elevated levels
of total cholesterol and triglycerides in patients patients with prior thrombotic events or fre-
with lupus compared to controls. C-reactive quent miscarriages (4,9,10,14,33,34).
protein levels are not necessarily elevated. His-
tory of recurrent early miscarriages or a single CONCLUSIONS
late pregnancy loss may be clues to lupus or
isolated APS. A family history of autoimmune
disease should also raise further suspicion of S ystemic lupus erythematosus is a chronic
autoimmune connective tissue disorder,
with a heterogeneous presentation. Systemic
SLE. Plasma homocysteine levels appear to be
another risk factor for stroke in SLE. Autoanti- lupus erythematosus is an immune-mediated
bodies in SLE are directed against a wide vari- systemic disease associated with diverse abnor-
ety of self antigens. Autoantibodies directed malities of the skin, kidney, and haematological
against nuclear self antigen are the most char- and musculoskeletal systems. The general
acteristic of SLE. Commonly found target nu- symptoms are not specific. Common manifes-
clear antigens in SLE include native DNA, de- tations may include arthralgias and arthritis,
naturated DNA, histone, Smith, U1-RNP, SSA, malar and other skin rashes, pleuritis or peri-
SSB, and ribosomal. Although patients with SLE carditis, renal or CNS involvement, and hema-
almost uniformly present with a positive ANA tologic cytopenias. SLE is protean in its mani-
test, other conditions exhibit positive ANA as festations and follows a relapsing and remitting
well. Therefore, it can be helpful, in diagnosing course. Disease severity is wide ranging, SLE
SLE, to look for these more-specific autoantio- can present major challenges because of ac-
bodies to help in establishing the diagnosis. It is crued organ damage, coagulation defects. SLE
also worth while to check for antiphospholipd is characterized by an autoantibody response
(APL) antibodies because SLE and APL com- to nuclear and cytoplasmic antigens. It is po-
monly coexist and are often found together in tentially fatal depending on organ involvement.
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