SLE Is One of Several Diseases Known As

SLE is one of several diseases known as "the great imitators"
because it often mimics or is mistaken for other illnesses. SLE is

a classical item in differential diagnosis, because SLE symptoms
vary widely and come and go unpredictably. Diagnosis can thus
be elusive, with some people suffering unexplained symptoms of
untreated SLE for years.
Common initial and chronic complaints
include fever, malaise, joint pains, myalgias, fatigue, and
temporary loss of cognitive abilities. Because they are so often
seen with other diseases, these signs and symptoms are not part
of the diagnostic criteria for SLE. When occurring in conjunction
with other signs and symptoms (see below), however, they are
considered suggestive.
Dermatological manifestations
As many as 30% of sufferers have some dermatological
symptoms (and 65% suffer such symptoms at some point), with
30% to 50% suffering from the classic malar rash (or butterfly
rash) associated with the disease. Some may exhibit thick, red
scaly patches on the skin (referred to as discoid lupus).Alopecia;
mouth, nasal, and vaginal ulcers; and lesions on the skin are also
possible manifestations.
Musculoskeletal
The most commonly sought medical attention is for joint pain, with
the small joints of the hand and wrist usually affected, although all
joints are at risk. The Lupus Foundation of America estimates that
more than 90 percent of those affected will experience joint and/or
muscle pain at some time during the course of their
illness. Unlike rheumatoid arthritis, lupus arthritis is less disabling
and usually does not cause severe destruction of the joints.
Fewer than ten percent of people with lupus arthritis will develop
deformities of the hands and feet. SLE patients are at particular
risk of developing osteo-articular tuberculosis.
It is suggested that there might be an association
between rheumatoid arthritis and SLE, and that SLE is associated
with an increased risk of bone fractures in relatively young
women.
Hematological
Anemia may develop in up to 50% of cases.
Low platelet and white blood cell counts may be due to the
disease or a side-effect of pharmacological treatment. People with
SLE may have an association with antiphospholipid antibody
syndrome[13] (a thrombotic disorder), wherein auto antibodies to
phospholipids are present in their serum. Abnormalities
associated with antiphospholipid antibody syndrome include a
paradoxical prolonged PTT Partial thromboplastin time (which
usually occurs in hemorrhagic disorders) and a positive test for
antiphospholipid antibodies; the combination of such findings
have earned the term lupus anticoagulant-positive. Another
autoantibody finding in SLE is the anticardiolipin antibody, which
can cause a false positive test for syphilis.
Cardiac
A person with SLE may have inflammation of various parts of
the heart, such as pericarditis, myocarditis, and endocarditis. The
endocarditis of SLE is characteristically noninfective (Libman-
Sacks endocarditis) and involves either the mitral valve or
the tricuspid valve. Atherosclerosis also tends to occur more often
and advances more rapidly than in the general population.[14][15][16]
Pulmonary
Lung and pleura inflammation can cause pleuritis, pleural
effusion, lupus pneumonitis, chronic diffuse interstitial lung
disease, pulmonary hypertension, pulmonary emboli, pulmonary
hemorrhage, and shrinking lung syndrome.
Renal
Painless hematuria or proteinuria may often be the only
presenting renal symptom. Acute or chronic renal impairment may
develop with lupus nephritis, leading to acute or end-stage renal
failure. Because of early recognition and management of SLE,
end-stage renal failure occurs in less than 5% of cases.
A histological hallmark of SLE is
membranous glomerulonephritis with "wire loop" abnormalities.
[17]
This finding is due to immune complex deposition along
the glomerular basement membrane, leading to a typical granular
appearance in immunofluorescence testing.
Neuropsychiatric
Neuropsychiatric syndromes can result when SLE affects
the central or peripheral nervous system. The American College
of Rheumatology defines 19 neuropsychiatric syndromes in
systemic lupus erythematosus. The diagnosis of neuropsychiatric
syndromes concurrent with SLE is one of the most difficult
challenges in medicine, because it can involve so many different
patterns of symptoms, some of which may be mistaken for signs
of infectious disease or stroke.
The most common neuropsychiatric disorder people with SLE
have is headache, although the existence of a specific lupus
headache and the optimal approach to headache in SLE cases
remains controversial. Other common neuropsychiatric
manifestation of SLE include cognitive dysfunction, mood
disorder, cerebrovascular disease,[20] seizures, polyneuropathy,
[20]
anxiety disorder, andpsychosis. It can rarely present
with intracranial hypertension syndrome, characterized by an
elevated intracranial pressure, papilledema, and headache with
occasional abducens nerve paresis, absence of a space-
occupying lesion or ventricular enlargement, and
normal cerebrospinal
fluid chemical and hematological constituents.[22]
More rare manifestations are acute confusional state, Guillain-
Barré syndrome, aseptic meningitis, autonomic
disorder, demyelinating syndrome, mononeuropathy (which might
manifest asmononeuritis multiplex), movement disorder (more
specifically, chorea), myasthenia
gravis, myelopathy, cranial neuropathy and plexopathy.
Neurological
Neural symptoms contribute to a significant percentage of
morbidity and mortality in patients with Lupus.[23] As a result, the
neural side of Lupus is being studied in hopes of reducing
morbidity and mortality rates[24]. The neural manifestation of lupus
is known as Neuro Psychiatric Systematic Lupus Erythematosus
(NPSLE). One aspect of this disease is severe damage to the
epithelial cells of the blood-brain barrier.
Lupus has a wide range of symptoms which span out throughout
the body. The neurological symptoms
include headaches[20], depression, seizures, cognitive
dysfunction, mood disorder,cerebrovascular
disease[20], polyneuropathy[20], anxiety disorder, psychosis, and in
some extreme cases, personality disorders.[25]
Systemic
Fatigue in SLE is probably multifactorial and has been related to
not only disease activity or complications such
as anemia or hypothyroidism but also pain; depression;
poor sleep quality; poorphysical fitness and perceived lack
of social support.[26][27]
[edit]Causes
There is no one specific cause of SLE. There are, however, a
number of environmental triggers and a number of genetic
susceptibilities.[28][29]
[edit]Genetics
The first mechanism may arise genetically. Research indicates
that SLE may have a genetic link. SLE does run in families, but no
single, causal, gene has been identified. Instead, multiple genes
appear to influence a person's chance of developing lupus when
triggered by environmental factors. The most important genes are
located in the HLA region on chromosome 6, where mutations
may occur randomly (de novo) or may be inherited. HLA class I,
class II, and class III are associated with SLE, but only class I and
class II contribute independently to increased risk of SLE.[30] Other
genes which contain risk variants for SLE
are IRF5, PTPN22, STAT4[31], CDKN1A,[32] ITGAM, BLK[31], TNFS
F4 and BANK1.[33] some of the susceptibility genes may be
population specific.[31]
[edit]Environmental triggers
The second mechanism may be due to environmental factors.
These factors may not only exacerbate existing SLE conditions
but also trigger the initial onset. They include certain medications
(such as some antidepressants and antibiotics), extreme stress,
exposure to sunlight, hormones, and infections. UV radiation has
been shown to trigger the photosensitive lupus rash and some
evidence suggests that UV light might be capable of altering the
structure of the DNA, leading to the creation of autoantibodies.
[citation needed]
Sex hormones such as estrogen play an important role
in the occurrence of SLE and it is observed that during
reproductive years, the frequency of SLE is 10 times greater in
females than in males.[citation needed]
Researchers have sought to find a connection between certain
infectious agents (viruses and bacteria), but no pathogen can be
consistently linked to the disease. Some researchers have found
that women with silicone gel-filled breast implants have produced
antibodies to their own collagen, but it is not known how often
these antibodies occur in the general population, and there is no
data that show that these antibodies cause connective tissue
diseases such as SLE. There is also a small but growing body of
evidence linking SLE to lipstick usage,[34][35] although lipstick
manufacturers do not appear to be concerned about it.[36]
[edit]Drug reactions
Drug-induced lupus erythematosus is a (generally) reversible
condition that usually occurs in people being treated for a long-
term illness. Drug-induced lupus mimics SLE. However,
symptoms of drug-induced lupus generally disappear once the
medication that triggered the episode is stopped. There are about
400 medications that can cause this condition, the most common
of which areprocainamide, hydralazine, quinidine, and phenytoin.
[3]
[edit]Non-SLE forms of lupus

Discoid (cutaneous) lupus is limited to skin symptoms and is
diagnosed by biopsy of rash on the face, neck, scalp or arms.
[edit]Pathophysiology
One manifestation of SLE is abnormalities in apoptosis, a type of
programmed cell death in which aging or damaged cells are
neatly disposed of as a part of normal growth or functioning.
[edit]Transmission
In SLE, the body's immune system produces antibodies against
itself, particularly against proteins in the cell nucleus. SLE is
triggered by environmental factors that are unknown.
"All the key components of the immune system are involved in the
underlying mechanisms [of SLE]" according to Rahman, and SLE
is the prototypical autoimmune disease. The immune system
must have a balance (homeostasis) between being sensitive
enough to protect against infection, and being too sensitive and
attacking the body's own proteins (autoimmunity). From an
evolutionary perspective, according to Crow, the population must
have enough genetic diversity to protect itself against a wide
range of possible infection; some genetic combinations result in
autoimmunity. The likely environmental triggers include ultraviolet
light, drugs, and viruses. These stimuli cause the destruction of
cells and expose their DNA, histones, and other proteins,
particularly parts of the cell nucleus. Because of genetic variations
in different components of the immune system, in some people
the immune system attacks these nuclear-related proteins and
produces antibodies against them. In the end, these antibody
complexes damage blood vessels in critical areas of the body,
such as the glomeruli of the kidney; these antibody attacks are
the cause of SLE. Researchers are now identifying the individual
genes, the proteins they produce, and their role in the immune
system. Each protein is a link on the autoimmune chain, and
researchers are trying to find drugs to break each of those links.[3]
[37][38]
SLE is a chronic inflammatory disease believed to be a type III

hypersensitivity response with potential type II involvement.
[39]
Reticulate and stellate acral pigmentation should be
considered a possible manifestation of SLE and high titers of
anticardiolipin antibodies, or a consequence of therapy.[40]
[edit]Abnormalities in apoptosis
 Apoptosis is increased in monocytes and keratinocytes

 Expression of Fas by B cells and T cells is increased
 There are correlations between the apoptotic rates of
lymphocytes and disease activity.
Tingible body macrophages (TBMs) – large phagocytic cells in
the germinal centers of secondary lymph nodes – express CD68
protein. These cells normally engulf B cells that have undergone
apoptosis after somatic hypermutation. In some people with SLE,
significantly fewer TBMs can be found, and these cells rarely
contain material from apoptotic B cells. Also, uningested apoptotic
nuclei can be found outside of TBMs. This material may present a
threat to the tolerization of B cells and T cells. Dendritic cells in
the germinal center may endocytose such antigenic material and
present it to T cells, activating them. Also, apoptotic chromatin
and nuclei may attach to the surfaces of follicular dendritic
cells and make this material available for activating other B cells
that may have randomly acquired self-specificity through somatic
hypermutation.[41]
[edit]Clearance deficiency
Clearance deficiency
The exact mechanisms for the development of SLE are still
unclear, since the pathogenesis is a multifactorial event. Beside
discussed causations, impaired clearance of dying cells is a
potential pathway for the development of this
systemic autoimmune disease. This includes deficient phagocytic
activity and scant serum components in addition to
increased apoptosis.
Monocytes isolated from whole blood of SLE sufferers show
reduced expression of CD44 surface molecules involved in the
uptake of apoptotic cells. Most of the monocytes and tingible body
macrophages (TBM), which are found in the germinal
centres of lymph nodes, even show a definitely different
morphology; they are smaller or scarce and die earlier. Serum
components like complement factors, CRP, and
some glycoproteins are, furthermore, decisively important for an
efficiently operating phagocytosis. With SLE, these components
are often missing, diminished, or inefficient.
Recent research has found an association between certain lupus
patients (especially those with lupus nephritis) and an impairment
in degrading Neutrophil extracellular traps (NETs). These were
due to DNAse1 inhibiting factors, or NET protecting factors in
patient serum, rather than abnormalities in the DNAse1 itself.
[42]
DNAse1 mutations in lupus have so far only been found in
some Japanese cohorts.[43]
The clearance of early apoptotic cells is an important function in
multicellular organisms. It leads to a progression of the apoptosis
process and finally to secondary necrosis of the cells if this ability
is disturbed. Necrotic cells release nuclear fragments as
potential autoantigens as well as internal danger signals, inducing
maturation of dendritic cells (DC), since they have lost their
membranes' integrity. Increased appearance of apoptotic cells
also simulates inefficient clearance. That leads to maturation of
DC and also to the presentation of intracellular antigens of late
apoptotic or secondary necrotic cells, via MHC
molecules. Autoimmunity possibly results by the extended
exposure to nuclear and intracellular autoantigens derived from
late apoptotic and secondary necrotic cells. B and T cell tolerance
for apoptotic cells is abrogated, and thelymphocytes get activated
by these autoantigens; inflammation and the production of
autoantibodies by plasma cells is initiated. A clearance deficiency
in the skin for apoptotic cells has also been observed in people
with cutaneous lupus erythematosus (CLE).[44]
Germinal centres
[edit]Accumulation in germinal centres (GC)
In healthy conditions, apoptotic lymphocytes are removed in
germinal centres by specialized phagocytes, the tingible body
macrophages (TBM), which is why no free apoptotic and potential
autoantigenic material can be seen. In some people with
SLE, accumulation of apoptotic debris can be observed in GC
because of an ineffective clearance of apoptotic cells. In close
proximity to TBM, follicular dendritic cells (FDC) are localised in
GC, which attach antigen material to their surface and, in contrast
to bone marrow-derived DC, neither take it up nor present it
via MHC molecules.
Autoreactive B cells can accidentally emerge during somatic
hypermutation and migrate into the GC light zone. Autoreactive B
cells, maturated coincidentally, normally do not receive survival
signals by antigen planted on follicular dendritic cells, and perish
by apoptosis. In the case of clearance deficiency, apoptotic
nuclear debris accumulates in the light zone of GC and gets
attached to FDC. This serves as a germinal centre survival signal
for autoreactive B-cells. After migration into the mantle zone,
autoreactive B cells require further survival signals from
autoreactive helper T cells, which promote the maturation of
autoantibody-producing plasma cells and B memory cells. In the
presence of autoreactive T cells, a chronic autoimmune
disease may be the consequence.
[edit]Anti-nRNP autoimmunity
Autoantibodies to nRNP A and nRNP C initially targeted
restricted, proline-rich motifs. Antibody binding subsequently
spread to other epitopes. The similarity and cross-
reactivity between the initial targets
of nRNP and Sm autoantibodies identifies a likely commonality in
cause and a focal point for intermolecular epitope spreading.[45]
[edit]Others
Elevated expression of HMGB1 was found in the sera of patients
and mice with systemic lupus erythematosus, High Mobility Group
Box 1 (HMGB1) is anuclear protein participating
in chromatin architecture and transcriptional regulation. Recently,
there is increasing evidence that HMGB1 contributes to the
pathogenesis of chronic inflammatory and autoimmune
diseases due to its pro-inflammatory
and immunostimulatory properties.[46]
[edit]Diagnosis
Microphotograph of a histological section of human skin prepared
for direct immunofluorescence using an anti-IgG antibody. The
skin is from a person with systemic lupus erythematosus and
shows IgG deposits at two different places: The first is a bandlike
deposit along the epidermalbasement membrane ("lupus band
test" is positive); the second is within the nuclei of
the epidermal cells (antinuclear antibodies are present).
Sodium pertechnate scan showing diffusely increased uptake in

lupus cerebritis
[edit]Laboratory tests
Antinuclear antibody (ANA) testing and anti-extractable nuclear
antigen (anti-ENA) form the mainstay of serologic testing for SLE.
Several techniques are used to detect ANAs. Clinically the most
widely used method is indirect immunofluorescence. The pattern
of fluorescence suggests the type of antibody present in the
patient's serum.
ANA screening yields positive results in many connective tissue
disorders and other autoimmune diseases, and may occur in
normal individuals. Subtypes of antinuclear antibodies
include anti-Smith and anti-double stranded DNA (dsDNA)
antibodies (which are linked to SLE) and anti-histone
antibodies (which are linked to drug-induced lupus). Anti-dsDNA
antibodies are highly specific for SLE; they are present in 70% of
cases, whereas they appear in only 0.5% of people without SLE.
[3]
The anti-dsDNA antibody titers also tend to reflect disease
activity, although not in all cases.[3] Other ANA that may occur in
SLE sufferers areanti-U1 RNP (which also appears in systemic
sclerosis), SS-A (or anti-Ro) and SS-B (or anti-La; both of which
are more common in Sjögren's syndrome). SS-A and SS-B confer
a specific risk for heart conduction block in neonatal lupus.[47]
Other tests routinely performed in suspected SLE
are complement system levels (low levels suggest consumption
by the immune system), electrolytes and renal function (disturbed
if the kidney is involved), liver enzymes, and complete blood
count.
Previously, the lupus erythematosus (LE) cell test was not
commonly used for diagnosis because those LE cells are only
found in 50–75% of SLE cases, and are also found in some
people with rheumatoid arthritis, scleroderma, and drug
sensitivities. Because of this, the LE cell test is now performed
only rarely and is mostly of historical significance.[48]
[edit]Diagnostic criteria
Some physicians make a diagnosis on the basis of the American
College of Rheumatology (ACR) classification criteria. The
criteria, however, were established mainly for use in scientific
research including use in randomized controlled trials which
require higher confidence levels, so some people with SLE may
not pass the full criteria.
[edit]Criteria
The American College of Rheumatology established eleven
criteria in 1982,[49] which were revised in 1997[50] as a
classificatory instrument to operationalise the definition of SLE in
clinical trials. They were not intended to be used to diagnose
individuals and do not do well in that capacity. For the purpose of
identifying patients for clinical studies, a person has SLE if any 4
out of 11 symptoms are present simultaneously or serially on two
separate occasions.
1. Serositis: Pleuritis (inflammation of the membrane around
the lungs) or pericarditis (inflammation of the membrane
around the heart); sensitivity = 56%;specificity = 86%
(pleural is more sensitive; cardiac is more specific).[51]
2. Oral ulcers (includes oral or nasopharyngeal ulcers).
3. Arthritis: nonerosive arthritis of two or more peripheral joints,
with tenderness, swelling, or effusion; sensitivity = 86%;
specificity = 37%.[51]
4. Photosensitivity (exposure to ultraviolet light causes rash, or
other symptoms of SLE flareups); sensitivity = 43%;
5. Blood—hematologic disorder—hemolytic anemia (low red
blood cell count) or leukopenia (white blood cell
count<4000/µl), lymphopenia (<1500/µl)
orthrombocytopenia (<100000/µl) in the absence of
offending drug; sensitivity = 59%; specificity = 89%.
[51]
Hypocomplementemia is also seen, due to either
consumption of C3 and C4 by immune complex-induced
inflammation or to congenitally complement deficiency,
which may predispose to SLE.
6. Renal disorder: More than 0.5 g per day protein in urine or
cellular casts seen in urine under a microscope; sensitivity =
51%; specificity = 94%.[51]
7. Antinuclear antibody test positive; sensitivity = 99%;
8. Immunologic disorder: Positive anti-Smith, anti-ds
DNA, antiphospholipid antibody, and/or false
positive serological test for syphilis; sensitivity = 85%;
specificity = 93%.[51] Presence of anti-ss DNA in 70% of
cases (though also positive with rheumatic disease and
healthy persons)[52]).
9. Neurologic disorder: Seizures or psychosis; sensitivity =
20%; specificity = 98%.[51]
10. Malar rash (rash on cheeks); sensitivity = 57%; specificity =
[51]
96%.
11. Discoid rash (red, scaly patches on skin that cause scarring);
sensitivity = 18%; specificity = 99%.[51]
The mnemonic to remember the 11 symptoms is 'SOAP BRAIN
MD'or 'DOPAMIN(E) RASH'.[53]
[edit]Criteria for individual diagnosis
Some people, especially those with antiphospholipid syndrome,
may have SLE without four of the above criteria, and also SLE
may present with features other than those listed in the criteria.[54]
[55][56]
Recursive partitioning has been used to identify more

parsimonious criteria.[51] This analysis presented two diagnostic
classification trees:
Simplest classification tree: SLE is diagnosed if a person has

1.
an immunologic disorder (anti-DNA antibody, anti-Smith
antibody, false positive syphilis test, or LE cells) or malar
rash. It has sensitivity = 92% and specificity = 92%.
2. Full classification tree: Uses 6 criteria. It has sensitivity =
97% and specificity = 95%.
Other alternative criteria have been suggested, eg. the St.
Thomas' Hospital "alternative" criteria in 1998.[57]
[edit]Prevention
SLE is not understood well enough to be prevented, but, when the

disease develops, quality of life can be improved through flare
prevention. The warning signs of an impending flare include
increased fatigue, pain, rash, fever, abdominal discomfort,
headache, and dizziness. Early recognition of warning signs and
good communication with a doctor can help individuals remain
active, experience less pain, and reduce medical visits.[58]
As longevity of people with SLE increases, the likelihood
of complications also increases in four areas: cardiovascular
disease, infections, osteoporosis, and cancer. Standard
preventive measures, screening for related diseases may be
necessary to deal with the increased risks due to the side effects
of medications. Extra vigilance is considered warranted in
particular for cancers affecting the immune system.[59]
[edit]Treatment
The treatment of SLE involves preventing flares and reducing

their severity and duration when they occur.
Treatment can include corticosteroids and anti-malarial drugs.
Certain types of lupus nephritis such as diffuse proliferative
glomerulonephritis require bouts of cytotoxic drugs. These drugs
includecyclophosphamide and mycophenolate.
Hydroxychloroquine (HCQ) was the last medication approved by
the FDA for lupus in 1955.[61] Some drugs approved for other
diseases are used for SLE 'off-label'. In November 2010, an FDA
advisory panel recommended approving Benlysta (belimumab) as
a treatment for the pain and flare-ups common in lupus.[62]
[edit]Medications
Due to the variety of symptoms and organ system involvement
with SLE, its severity in an individual must be assessed in order to
successfully treat SLE. Mild or remittant disease can sometimes
be safely left untreated. If required, nonsteroidal anti-inflammatory
drugs and antimalarials may be used. A number of potential
treatments are in clinical trials.[63]
[edit]Disease-modifying antirheumatic drugs
Disease-modifying antirheumatic drugs (DMARDs) are used
preventively to reduce the incidence of flares, the process of the
disease, and lower the need for steroid use; when flares occur,
they are treated with corticosteroids. DMARDs commonly in use
are antimalarials such
as plaquenil and immunosuppressants (e.g. methotrexate and az
athioprine). Hydroxychloroquine is an FDA-approved antimalarial
used for constitutional, cutaneous, and articular manifestations.
Hydroxychloroquine has relatively few side effects, and there is
evidence that it improves survival among people who have SLE.
[61]
Cyclophosphamide is used for severe glomerulonephritis or
other organ-damaging complications. Mycophenolic acid is also
used for treatment of lupus nephritis, but it is not FDA-approved
for this indication, and FDA is investigating reports that it may be
associated with birth defects when used by pregnant women.[64]
[edit]Immunosuppressive drugs
In more severe cases, medications that modulate the immune
system (primarily corticosteroids and immunosuppressants) are
used to control the disease and prevent recurrence of symptoms
(known as flares). Depending on the dosage, people who require
steroids may develop Cushing's syndrome, side-effects of which
may include obesity, puffy round face, diabetes mellitus, large
appetite, difficulty sleeping and osteoporosis. Those side-effects
can subside if and when the large initial dosage is reduced, but
long-term use of even low doses can cause elevated blood
pressure andcataracts.
Numerous new immunosuppressive drugs are being actively
tested for SLE. Rather than suppressing the immune system
nonspecifically, as corticosteroids do, they target the responses of
individual [types of] immune cells. Some of these drugs are
already FDA-approved for treatment of rheumatoid arthritis.
[61]
See also Belimumab and Atacicept. Lupuzor has given
encouraging results in a phase IIb trial[65]
[edit]Analgesia
Since a large percentage of people with SLE suffer from varying
amounts of chronic pain, stronger prescription analgesics (pain
killers) may be used if over-the-counter drugs
(mainly nonsteroidal anti-inflammatory drugs) do not provide
effective relief. Potent NSAIDs such as indomethacin and
diclofenac are relatively contraindicated for patients with SLE
because they increase the risk of kidney failure and heart failure.
[61]
Moderate pain is typically treated with mild prescription opiates

such as dextropropoxyphene and co-codamol. Moderate to
severe chronic pain is treated with stronger opioids, such
as hydrocodone or longer-acting continuous-release opioids, such
as oxycodone, MS Contin, or Methadone. The Fentanyl duragesic
transdermal patch is also a widely-used treatment option for the
chronic pain caused by complications because of its long-acting
timed release and ease of use. When opioids are used for
prolonged periods, drug tolerance, chemical dependency, and
addiction may occur. Opiate addiction is not typically a concern,
since the condition is not likely to ever completely disappear.
Thus, lifelong treatment with opioids is fairly common for chronic
pain symptoms, accompanied by periodic titration that is typical of
any long-term opioid regimen.
[edit]Intravenous Immunoglobulins (IVIGs)
Intravenous immunoglobulins may be used to control SLE with
organ involvement, or vasculitis. It is believed that they
reduce antibody production or promote the clearance of immune
complexes from the body, even though their mechanism of
action is not well-understood.
[66]
Unlike immunosuppressives and corticosteroids, IVIGs do not
suppress the immune system, so there is less risk of
seriousinfections with these drugs.[67]
[edit]Lifestyle changes
Avoiding sunlight is the primary change to the lifestyle of SLE
sufferers, as sunlight is known to exacerbate the disease. Drugs
unrelated to SLE should be prescribed only when known not to
exacerbate the disease. Occupational exposure
to silica, pesticides and mercury can also make the disease
worsen.[28]
[edit]Renal transplantation
Renal transplants are the treatment of choice for end-stage renal
disease, which is one of the complications of lupus nephritis, but
the recurrence of the full disease is common in up to 30% of
patients.[68]
[edit]Hughes syndrome
Hughes syndrome, also known as the antiphospholipid syndrome
or sticky blood syndrome, is also related to the onset of neural
lupus symptoms in the brain. In this form of the disease the cause
is very different from Lupus: blood clots or "sticky blood" form—
refers to the formation of thromboses (blood clots) in blood
vessels, which prove to be fatal if they move within the blood
stream[69]. If the thromboses migrate to the brain, they can
potentially cause a stroke by blocking the blood supply to the
brain. If this disorder is suspected in patients, brain scans are
usually required for early detection. These scans can show
localized areas of the brain where blood supply has not been
adequate. The treatment plan for these patients requires thinning
of the blood, either with aspirin or, in more severe cases, with
anticoagulants such as warfarin and/or leeches[70].
[edit]Prognosis
SLE is considered incurable, but highly treatable.

In the 1950s, most people diagnosed with SLE lived fewer than
five years. Advances in diagnosis and treatment have improved
survival to the point where over 90% now survive for more than
ten years, and many can live relatively asymptomatically.
Prognosis is normally worse for men and children than for
women; however, if symptoms are present after age 60, the
disease tends to run a more benign course. Early mortality, within
5 years, is due to organ failure or overwhelming infections, both of
which can be modified by early diagnosis and treatment. The
mortality risk is fivefold when compared to the normal population
in the late stages, which can be attributed to cardiovascular
diseases acquired from corticosteroid therapy, the leading cause
of death for people with SLE.[61]
To reduce potential for cardiovascular issues, high blood pressure
and high cholesterol should be prevented or treated aggressively.
Steroids should be used at the lowest dose for the shortest
possible period, and other drugs that can reduce symptoms
should be used whenever possible.[61] High serum creatinine,
hypertension, nephrotic syndrome, anemia and hypoalbuminemia
are poor prognostic factors.[71]
The ANA is the most sensitive screening test for evaluation,
whereas anti-Sm (anti-Smith) is the most specific. The dsDNA
(double-stranded DNA) antibody is also fairly specific and often
fluctuates with disease activity; as such, the dsDNA titer is
sometimes useful to monitor disease flares or response to
treatment.[72]
[edit]Epidemiology
The rate of SLE varies considerable between countries, ethnicity,

by gender, and has changed over time.[73] In the United States
the prevalence of SLE is estimated to be about 53 per 100,000,
translating to about 159,000 out of 300 million people in the US
being affected.[73][74] In Northern Europe the rate is about 40 per
100,000 people.[75] SLE occurs more frequently and with greater
severity among those of non-European descent.[74] That rate has
been found to be as high as 159 per 100,000 among those of
Afro-Caribbean descent.[73]
SLE, like many autoimmune diseases, affects females more
frequently than males, at a rate of almost 9 to 1.[73]
The incidence of SLE in the United States increased from 1.0 in
1955 to 7.6 in 1974. Whether the increase is due to better
diagnosis or to increasing frequency of the disease is unknown.[73]
[edit]History and culture
[edit]Etymology
There are several explanations ventured for the term lupus

erythematosus. Lupus is Latin for wolf [76], and "erythro" is
derived from ερυθρός, Greek for "red." All explanations originate
with the reddish, butterfly-shaped malar rash that the disease
classically exhibits across the nose and cheeks.
1. In various accounts, some doctors thought the rash

resembled the pattern of fur on a wolf's face.
2. In other accounts, doctors thought that the rash, which was
often more severe in earlier centuries, created lesions that
resembled wolf bites or scratches.
3. Another account claims that the term "lupus" did not come
from Latin directly, but from the term for a French style of
mask that women reportedly wore to conceal the rash on
their faces. The mask is called a "loup," French for "wolf."
4. Another common explanation for the term is that the disease
involves repeated attacks by wolves, leaving behind the red
blotches.[citation needed]
[edit]History
The history of SLE can be divided into three periods: classical,
neoclassical, and modern. The classical period began when the
disease was first recognized in the Middle Ages and saw the
description of the dermatological manifestation of the disorder.
The term lupus is attributed to 12th-century physician Rogerius,
who used it to describe the classic malar rash. The neoclassical
period was heralded by Móric Kaposi's recognition in 1872 of the
systemic manifestations of the disease. The modern period began
in 1948 with the discovery of the LE cell (the lupus
erythematosus cell—a misnomer, as it occurs with other diseases
as well) and is characterised by advances in our knowledge of the
pathophysiology and clinical-laboratory features of the disease, as
well as advances in treatment.[77]
Medical historians have theorized that people with porphyria (a
disease that shares many symptoms with SLE) generated folklore
stories of vampires and werewolves, due to the photosensitivity,
scarring, hair growth, and porphyrin brownish-red stained teeth in
severe recessive forms of porphyria (or combinations of the
disorder, known as dual, homozygous, or compound
heterozygous porphyrias).[77]
Useful medication for the disease was first found in 1894,
when quinine was first reported as an effective therapy. Four
years later, the use of salicylates in conjunction with quinine was
noted to be of still greater benefit. This was the best available
treatment until the middle of the twentieth century, when Hench
discovered the efficacy of corticosteroids in the treatment of SLE.
[77]
[edit]Notable cases
 Michael Jackson suffered from both SLE and vitiligo.

[78]
Diagnosed in 1986, and confirmed by his dermatologist, Dr.
Arnold Klein, who presented legal documents during court
depositions.
 Lady Gaga has been tested borderline positive for SLE,
however she claims not to be affected by the symptoms yet.
The revelations caused considerable dismay amongst her fans,
leading to Gaga herself addressing the matter in an interview
with Larry King,[79] saying she hopes to avoid symptoms by
maintaining a healthy lifestyle.[80]
 Louisa May Alcott, American author best known for her
novel Little Women, has been suggested to have had SLE.[81]
 Inday Ba (also known as N'Deaye Ba), a Swedish-born
actress who died from SLE complications at age 32.[82]
 Donald Byrne, American chess player who died from SLE
complications in 1976.[83]
 Portia de Rossi, Australian-American actress[84]
 Caroline Dorough-Cochran, sister of Howie D. of
the Backstreet Boys, died of SLE complications. He founded
the Dorough Lupus Foundation in her memory.
 J Dilla (also known as Jay Dee), a hip-hop producer and
beat maker who died of SLE complications in 2006.[85]
 Lauren Shuler Donner, American movie director.[86]
 Hugh Gaitskell, British politician who died of SLE
complications in 1963 aged 56.[87]
 Sophie Howard, British glamour model.[88]
 Teddi King, American singer, died of SLE complications in
1977.[89]
 Charles Kuralt, former anchor of CBS Sunday Morning, died
of SLE complications in 1997.[90]
 Ferdinand Marcos, former Philippine president, who died of
SLE complications in 1989.[91]
 Mary Elizabeth McDonough, American actress; blames her
SLE on leaky silicone breast implants.[92]
 Flannery O'Connor, American fiction writer who died of SLE
complications in 1964.[93]
 Elaine Paige, British actress and singer.[94]
 Tim Raines, former major league baseball player, primarily
with the Montreal Expos and Chicago White Sox who was
diagnosed with SLE in 1999 and spent the rest of the year
undergoing treatment and recovery.[95] Founder of the Tim
Raines Lupus Foundation.
 Mercedes Scelba-Shorte, America's Next Top Model Season
Two runner-up and model.[96]
 Ray Walston, character actor who died of SLE complications
in 2001 after a 6-year battle with the disease.[97]
 Michael Wayne, Hollywood director, and producer, part
owner of Batjac Productions, son of legendary actor John
Wayne, died of heart failure resulting from SLE complications
in 2003.[98]
[edit]Research
Since lupus is considered to be currently incurable, current

research is being geared towards finding a possible cause, a
cure, and more effective treatment plans to extend and increase
the quality of life for lupus patients.
Several papers discuss the importance of the presence of
antibodies in the brain that are only produced in patients with
lupus. One such paper highlights the inhibition of astrocyte
proliferation in brain tissue from lupus patient serum[99]. Astrocytes
are glial cells in the brain that participate in the support of cells
that form the blood brain barrier. They are extremely useful in that
they provide a nutritional balance between ions in the brain,
keeping it at a normal level[100]. In this study, researchers used
immunofluorescence to track the antibodies near the corpus
callosum to determine whether anticardiolipin antibodies have an
inhibitory effect on brain cells and whether they elicit thrombus
formation in brain vessels, which plays a part in neuropsychiatric
lupus.
However, the majority of the recent papers focus on the effect of
lupus on blood-brain barrier integrity. It was found that 20–70% of
lupus patients with neurological symptoms have some form of a
central nervous system involvement[101]. This can be determined
using various imaging methods as well as lumbar puncture (spinal
tap) to assess cerebrospinal fluid.
In a study conducted in London, researchers measured the
albumin content in the brain using imaging and spinal fluid. The
images were used to illustrate blood brain barrier damage while
the spinal tap was used to measure the protein content in the
brain. Albumin is a protein that can be carried into the brain
through the blood brain barrier by other transport proteins. If the
ratio of albumin outside the barrier to inside the barrier is high,
this means that either the barrier is damaged, or the transport
proteins are not functioning well. This blood brain barrier damage
can impact lupus patients by increasing their discomfort and
increasing the intensity of the disease[102].
A recent study called BLISS-76 tested the drug, Belimumab
(HGS1006, LymphoStat-B™ ), a fully human monoclonal anti-
BLyS antibody. BLyS stimulates and extends the life of B
lymphocytes, which produce antibodies against foreign and self
cells.[103] On November 16, 2010, Benlysta was given preliminary,
non-binding approval by a panel of FDA
advisers. GlaxoSmithKline, the producer of the drug, hopes to
have Benlysta on the market by early 2011. Notwithstanding the
approval, the FDA emphasized that the drug will not work in all, or
perhaps even most, cases, and that more research and advanced
therapies are called for.[62]
Introduction
Systemic lupus erythematosus (SLE) is the prototype
of systemic autoimmune diseases. The aetiology is not known
as yet and the pathogenesis is complex, involving immunological,
genetic, hormonal and environmental factors. Damage
to tissues and cells results from pathogenic autoantibodies
and immune complexes. It affects predominantly women
in their reproductive years. The median age of onset in Indian
SLE is 24.5 years and the sex ratio (F:M) is 11:11. Remissions
and relapses characterize the disease. The clinical manifestations
and their severity in individual patients may vary considerably
and, therefore, the treatment strategy needs to be
tailored accordingly.
Incidence and prevalence
SLE is rare in India. A prevalence study in India (carried
out in a rural population near Delhi) found a point prevalence
of 3 per 100,0002. This is a much lower figure than reported
from the west (varying from 12.5 per100,000 adults in
England3 to 39 per 100,000 in Finland4 and 124 per 100,000
in USA5). However, a fair number of cases of SLE are encountered
in any large hospital in India. Copcord Bhigwan
study ( an ongoing, prospective population study from Pune)
found a crude incidence rate of 1 per 25,000 person years i.e.
4 per 100,000 population per year (personal communication).
Despite its rarity, SLE has considerable impact on the patient,
her/his family and health services available.
General outlook of the disease
The prognosis of SLE is quite grim with more than
half of the patients developing irreversible organ damage over
time. Although the survival has improved in the west with
modern treatment to the tune of 80% at 10 years after diagnosis6,
the Indian figures are not so good (50%-60% survival at
10 years)7,8. Possible reasons for poor survival in Indian SLE

include delay in diagnosis, referral bias (only the most serious
cases are referred by practitioners), suboptimal health care
facilities and an inherently more severe disease (genetic factors?)
and endemic tuberculosis to which the lupus patients
are more susceptible. The major causes of death in the first
few years after diagnosis include disease activity and infections.
Late mortality i.e. 10 years after diagnosis, on the other
hand, is mainly attributed to atherosclerotic vascular disease9.
There is a fair amount of iatrogenic morbidity and mortality.
Indian guidelines on SLE: Why and for whom?
Since SLE is a rare disease, a general physician is
not likely to be familiar with the complexities of its presentation
and the therapeutic challenges and dilemmas it can pose.
It is a disease, which primary care physicians would find difficult
to manage without the help of a specialist. Firstly, they
should be able to recognize the possibility of this disease
among patients in their practice. An early referral to the specialist
is desirable for improving the outcome. Once the diagnosis
is established and appropriate treatment instituted by a
specialist, the patient can follow up with a primary care physician

provided the disease is mild and stable. All other patients
with SLE require periodic clinical reviews by a specialist.
A family physician can certainly collaborate with the specialist
in monitoring disease activity and treating patients with
moderate or severe disease. These guidelines have been formulated
to improve the quality of care for SLE patients. It is
hoped that the prognosis of Indian patients with SLE will improve
significantly with better awareness of diagnosis and treatment
of the disease among doctors.
Clinical features of SLE in India
Clinical features reported by workers from different
parts of India show some interesting regional variations10-15
and these are brought out in Tables 1-3. It is evident that oral
ulcers are seen in about one-half of patients at presentation in
those from eastern India as against about 10% from other parts.
Raynaud’s phenomenon is conspicuous by its absence in patients
from southern India where lymphadenopathy tends to
be a presenting feature more often. Low frequency of neuropsychiatric
manifestations at onset in northern India emerges
as another significant difference. When patients are followed

up for several years, significant differences can still be made
out. These include lower frequency of photosensitivity and
neuropsychiatric manifestations in western India, lower frequency
of nephritis in central India and the rarity of Raynaud’s
in southern India in comparison to other parts of the country.
INDIAN GUIDELINES ON THE MANAGEMENT OF SLE
A Kumar
J Indian Rheumatol Assoc 2002 : 10 : 80 - 96
81
Indian Guidelines on the Management of SLE
Table 1 Percentage frequency of presenting clinical features in

patients with SLE from different regions in India
Manifestations Northern Southern Western Eastern Central Mean
(n = 329)10 (n = 330)11 (n = 315)12, 13 (n =192)14 (n = 200)15
Arthritis 57 68.5 2nd* 75 50 63
Fever 44 52 1st* 60 50 50.6
Skin lesions 36 48 3rd* 50 50 45
Nephritis 8 7.4 NA 49 NA 17
Raynaud’s 6 0 NA NA 4 3.3
Oral ulcers 4 12.6 4th* 49 10 16

Neuropsychiatric 12 35 NA 30 NA 25
Gastrointestinal 1 2.2 NA NA NA 1.5
Lymphadenopathy NA 21 NA NA 8 16
Cardiac 1 5.2 NA NA NA 3
Thrombocyto-paenic purpura 4 1.5 NA NA NA 2.7
NA = not available, * = the 4 commonest presenting features (exact

figures NA)
Table 2 Cumulative percentage frequency of clinical manifestations in

patients with SLE from different regions in India
Manifestations Northern Southern Western Eastern Central Mean
(n = 329) (n = 330) (n = 315) (n =192) (n= 200)
Arthritis 92 90 71 88 NA 85
Fever NA 74 80 NA NA 77
Skin rash 85 74 81 90 NA 70
Photosensitivity 67 52 24 NA NA 48
Alopecia 82 75 53 70 NA 83
Nephritis 73 45 40 62 35 57
Raynaud’s 24 2 14 NA NA 13.3
Oral ulcers 64 51 41 52 NA 55
Neurological 63 42 27 34 37 51
Neuro-psychiatric 38 29 8 NA NA 25
Seizures 7 12.6 13 3 NA 11
Psychosis 15 7.5 8 NA NA 10
Focal neurological 13 9 9.5 2 NA 9
Others 12 6 4 NA NA 10
Hepatomegaly 44 23 6.3 NA NA 30
Splenomegaly 15 18 2 NA NA 15
Lymphadeno-pathy 47 39 23 NA NA 30
Cardiac 29 28 14 NA 15 22
Vascular 28 17 3.2 NA NA 20
Ocular 10 9 NA NA NA 9.5
Muscle 48 20 5.3 NA NA 30
S/C nodule 5 3 NA NA NA 4
Thrombocyto-paenia 11 17.5 9.5 NA NA 9
NA = not available
Diagnosis of SLE
The American College of Rheumatology has a
criteria for the classification of patients as having SLE16 (Table
4). If a patient has, at any time in his or her medical history, 4
of the 11 criteria documented, the diagnosis of SLE can be

made with about 95% specificity and 85% sensitivity. These
criteria are actually meant for epidemiological purposes (to
ensure that SLE patients reported in the literature do in fact
have the disease) and not for bedside diagnosis of an individual
patient. The diagnosis of SLE is based on clinical judgement.
SLE can be suspected whenever 2 or more organ systems
listed in Table 4 are involved. Thus, a lady with nephritis
and presence of ANA and anti-dSDNA meets only 3 criteria
but almost certainly has SLE.
Serology in SLE
Since SLE is associated with a number of auto antibodies,
it is important to understand their relevance in clinical
practice. Some of these are useful as diagnostic markers, others
help in quantifying disease activity and still others are primarily
of research interest, making no contribution to patient
care. A brief discussion follows:
1. Antinuclear antibody (ANA):
ANA is a good screening test for SLE because 95%
of cases show a high titre (1:80 or more) of this auto antibody.
A negative test result makes the diagnosis highly improbable.

ANA may be positive in other rheumatic disorders such as
systemic sclerosis, Sjogren’s syndrome, overlap syndrome,
antiphospholipid syndrome, polymyositis and rheumatoid ar-
Table 3 Frequency of laboratory abnormalities in Indian SLE
Abnormality Northern10 Southern 11 Mean
(n = 329) (n = 330)
Anaemia 38 52 45
Thrombocytopenia 10 7.5 9
Leucopenia 16 12.6 14
Lymphopenia 20 7.5 14
Haemolytic anaemia 7 1 4
Non-nephrotic 45 40 43
Nephrotic 8 5 6.5
Haematuria 23 20 22
Casturia 36 12.6 24
ANA 98 96 97
Anti-dSDNA 55 60.5 58
Anti-Sm 21 35 28
Anti-RNP 31 NA 31
Anti-Ro 34.5 40 37
Anti-La 18 14 16
Low C3 66 60 63
RF 21 6 13.5
STS (false positive) 5 12.5 9
ACL 28 41 34.5
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Table 4 Revised ACR classification criteria for SLE (1997 update)16
Item Definition
Malar rash Fixed erythema, flat or raised, over the malar eminences,
sparing nasolabial folds
Discoid rash Erythematous, raised patches with adherent keratotic

scaling and follicular plugging; atrophic scarring
may occur in older lesions
Photosensitivity Skin rash as a result of unusual reaction to sunlight by

history or on physical exam.
Oral ulcers Oral or nasopharyngeal ulceration, usually painless,

observed by physician
Non-erosive arthritis Involving 2 or more peripheral joints,
characterized by tenderness, swelling or effusion
Pleuritis/pericarditis a.Pleuritis- convincing h/o pleuritic pain or rub or

pleural effusion on physical examination OR
b.Pericarditis- documented by ECG, rub or e/o effusion
Renal disorder a. Persistent proteinuria > 0.5 gm/day or > +++, OR
b. Cellular casts- may be red cell, Hb, granular, tubular or mixed
Neurological disorder a. Seizures- in the absence of offending drugs, or

known metabolic derangement, e.g. uraemia,
ketoacidosis or electrolyte imbalance, OR
b. Psychosis- in the absence of offending drugs, or known metabolic

derangement, e.g. uraemia,
ketoacidosis or electrolyte imbalance
Haematological a. Haemolytic anaemia with reticulocytosis, OR
disorder b. Leukopaenia < 4000/cu mm on 2 or more occasions, OR
c. Lymphocytopenia < 1500 on 2 or more occasions, OR
d. Thrombocytopenia < 100,000/cu mm in the absence of offending

drugs
Immunological a. Anti-DNA: antibody to native DNA in abnormal titre,

OR
disorder b. Anti-Sm: presence of antibody to Sm nuclear antigen, OR

c. Positive finding of aPL antibodies based on: 1) ↑ serum level of IgG
or IgM aCL or 2) a positive
test result for lupus anticoagulant, using a standard method, or 3) a

false-positive test for syphilis for
at least 6 months and confirmed by TPI or FTA-abs test
Positive ANA An abnormal titre of ANA by immunofluorescence or an

equivalent assay at any point in time in the
absence of drug
thritis. Like the rheumatoid factor test, ANA may also be positive
in chronic infections, malignancies and in normal individuals.
Thus, the specificity of ANA for diagnosis of SLE is
quite low (app. 40% only).
Although many laboratories use ELISA technique for
the sake of convenience and economy, the gold standard
method for testing and reporting ANA is the indirect

immunofluorescence
method. The preferred substrate is a dividing
cell line such as ‘HEp-2’, with rat liver sections as the next
choice. Different types of staining patterns can be identified
by this method such as homogeneous (diffuse), speckled (fine,
coarse), rim (peripheral) and nucleolar. The staining patterns

have been associated with different sub-types of clinical manifestations
of lupus, though validated data are not published as
yet.
It is important to stress that the diagnosis of SLE must
be strongly suspected at the clinical evaluation before requesting
for ANA test. A positive result supports the diagnosis of
SLE. Also, performing serial titres of ANA in a diagnosed
case of SLE is of no clinical value because it does not correlate
well with disease activity. It can remain positive for long
periods in the absence of any disease activity. What we treat
is disease and not ANA.
ANAs are actually a family of autoantibodies, which
may be directed against any one of the following nuclear antigens:
1. Double stranded-DNA
2. Extractable nuclear antigens (ENA)
3. Histones
4. Nuclear RNA
Antibodies to the above subspecificities are also useful
in some situations and are discussed below:
Anti-double stranded DNA antibody (anti-dsDNA): This

test has high specificity for SLE. However, the technique must
ensure absence of any contamination with single stranded DNA
in the antigen used. Farr assay (radioimmunoassay) and
Crithidia lucilae method are very good in this regard but they
are cumbersome and hence not very popular with most laboratories.
Newer methods such as ELISA and haemagglutination
have become available and are reasonable alternatives. The
positivity of anti-dsDNA in SLE at the time of presentation is
in the range of 60% (although the cumulative positivity during
the course of disease may approach 90%). Hence, anti-ds
DNA can not be a good screening test for SLE. When positive,
the test establishes the diagnosis of SLE. The anti-dsDNA
titres most often correlate with disease activity.
Antibodies to extractable nuclear antigens (anti-ENA):
These include anti-Sm, anti-UIRNP, anti-Ro and anti-La antibodies.
Anti-ENA are found only in about 50% of sera which
are positive for ANA. High titres of anti-UIRNP are associated
with mixed connective tissue disease (MCTD) which is a
subset of SLE with prominent Raynaud’s phenomenon, sclerodactyly,
proximal myopathy and mild or no renal involvement.

Anti-Sm antibody is quite specific for SLE but it is found
only in 10-30% of patients. Anti-Ro is associated with ANA
negative SLE, Sjogren’s syndrome, congenital heart block,
neonatal SLE and subacute cutaneous lupus erythematosus.
Anti-La is associated with SLE and Sjogren’s syndrome. Antihistone
antibodies are associated with drug-induced SLE.
Anticardiolipin antibodies (aCL) and lupus anticoagulant:
This is discussed under ‘Antiphospholipid syndrome’ (please
see appendix)
Complement levels (C3 and C4): These two complement
components are useful in the diagnosis and follow up of SLE.
Their levels drop because of consumption. C3 and C4 levels
are negatively correlated with lupus activity.
Differential diagnosis of SLE: The following conditions need
to be considered in differential diagnosis of SLEUndifferentiated
connective tissue disease
Primary Sjogren’s syndrome
Primary antiphospholipid syndrome
Fibromyalgia with positive ANA
Idiopathic thrombocytopenic purpura

Drug-induced lupus
Early RA
Systemic vasculitis
Laboratory investigations to be requested:
Although investigation plan for a case of SLE will
depend on the clinical picture, the minimum laboratory workup
should include:
1. Haemoglobin, WBC, Differential count, ESR
2. Urine routine (preferably a fresh sample examined) and
microscopy, and 24 hour protein and creatinine
estimation if necessary
3. Serum chemistry (urea, creatinine, liver function tests,
lipid profile)
4. Chest x-ray
5. ANA, anti-dsDNA, C3, C4
Additional investigations can be obtained depending
on the clinical indications and these are mentioned at appropriate
places in this document.
Referral to Rheumatologist/Specialist:
Referral to a rheumatologist is indicated for the following

purposes:
1. Confirmation of diagnosis
2. Periodic evaluation of disease activity and severity
3. Management: general plan of treatment, patient
education, management of uncontrolled/serious, life
threatening disease, prevention and treatment of
drug-toxicities
4. Special situations such as pregnancy, antiphospholipid
syndrome, concomitant infection and surgery
Evaluation of disease activity and severity
A number of validated indices are available for quantifying
disease activity. The more popular indices include-
BILAG17, SLEDAI18, SLAM19 and LAI.20 These help in formulating
the overall treatment plan and assessment of prognosis.
Table 5 shows the details of scoring used in SLEDAI.
A valid measure of damage in patients with lupus is the SLICC/
ACR Damage Index (DI).21
84
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85
Table 5 SLE Disease Activity Index (SLEDAI)
Descriptor Definition Score
Seizure Recent onset, exclude metabolic, infectious or drug causes 8
Psychosis Altered ability to function in normal activity due to severe

disturbance in the perception
of reality. Include hallucinations, incoherence, markedly loose

associations, impoverished
thought content, markedly illogical thinking, bizarre, disorganised or

catatonic behaviour.
Exclude uraemia and drug causes
‘Organic brain Altered mental function with impaired orientation,

memory or other intellectual function, 8
syndrome’ or with rapid onset and fluctuating clinical features, inability

to sustain attention to
Acute confusional environment, plus at least 2 of the following:

perceptual disturbance, incoherent speech,
state insomnia or daytime drowsiness, or increased or decreased

psychomotor activity. Exclude
metabolic, drug or infectious causes
Visual disturbance Retinal changes of SLE. Include cytoid bodies, retinal

haemorrhages, serous exudates/ 8
haemorrhages in choroid or optic neuritis. Exclude hypertension,
infection or drug causes
Cranial nerve disorder New onset of sensory or motor neuropathy

involving cranial nerves 8
Lupus headache Severe persistent headache: may be migrainous, but

must be non-responsive to narcotic 8
analgesia.
CVA New onset of CVA. Exclude atherosclerosis. 8
Vasculitis Ulceration, gangrene, tender finger nodules, periungual

infarction, splinter 8
haemorrhages, or biopsy or angiogram evidence of vasculitis
Arthritis > 2 joints with pain and signs of inflammation (tenderness,

swelling or effusion) 4
Myositis Proximal muscle aching/weakness, associated with elevated

CPK/aldolase or EMG
changes or biopsy evidence of myositis 4
Urinary casts Haemoglobin, granular or RBC casts 4
Haematuria > 5 RBC/HPF. Exclude stone, infection or other causes 4
Proteinuria > 0.5 grams/24 hrs 4
Pyuria > 5 WBCs/HPF. Exclude infection 4
Rash Inflammatory type rash 2
Alopecia Abnormal, patchy or diffuse loss of hair 2

Mucosal ulcers Oral or nasal ulcerations 2
Pleurisy Pleuritic chest pain with pleural rub/effusion/pleural thickening

2
Pericarditis Pericardial pain with at least 1 of the following: rub,

effusion or ECG or Echo 2
confirmation
Low complement Decrease in CH50, C3 or C4 below the normal limit of

Lab 2
Increased DNA Increased DNA binding using Farr assay 2
binding
Fever > 38 Deg C. Exclude infection 1
Thrombocytopaenia < 100,000/cu mm, exclude drug causes 1
Leukopaenia < 3000/cu mm, exclude drug causes 1
Management
Patient Education
In order to obtain optimal results from drug therapy,
patient education plays a vital role and must be paid due attention.
This is discussed below:
86
A Kumar
General approach to the drug therapy of SLE:

Since there is a range of severity of disease manifestations,
proper categorization based on clinical and laboratory
features is the first therapeutic step. The following scheme
is recommended:
Category I (Mild SLE)
Characterised by arthritis, arthralgia, myalgia, fatigue,
mild mucocutaneous involvement, low-grade fever, mild serositis,
lupus headache
Musculoskeletal complaints are the commonest features
of SLE. For mild symptoms, NSAIDs and analgesics
may suffice. NSAIDs can occasionally cause adverse effects
which may resemble those produced by the disease itself such
as proteinuria, edema, renal failure and aseptic meningitis.
In some patients, the above symptoms may not be
alleviated with NSAIDs alone, and they should be prescribed
antimalarials (chloroquine, hydroxychloroquine). These drugs
are particularly useful for cutaneous manifestations of SLE.
These agents have multiple properties: immunosuppressive
anti-inflammatory and sun-blocking. They are also reported
to possess anti-platelet and cholesterol lowering effects. The

drug of choice is hydroxychloroquine (200 mg BD for 3
months and then 200 mg daily). The maintenance dose must
not exceed 6 mg/kg/day. Although the incidence of retinal toxicity
is very low, annual monitoring of vision with perimetery
using a red object is recommended (for chloroquine, 6-monthly
monitoring is desirable). The drug must be discontinued if a
central scotoma is detected at any stage. Other significant side
effects include nausea, pruritus, hyperpigmentation, myopathy
and rarely psychosis. Use of hydroxychloroquine during
pregnancy is controversial. When antimalarials are withdrawn
after prolonged administration, some patients may develop a
relapse of lupus activity. In refractory cases, quinacrine may
be combined with hydroxychloroquine. Alternatives include
dapsone and thalidomide. Quinacrine and thalidomide are,
however, not available in India.
Patients not responding to the above measures may
be treated with low-dose steroid therapy (Prednisolone 0.3-
0.5 mg/kg/day) for 4-6 weeks followed by slow tapering. For
lupus dermatitis, there is also a role of local steroids, including
topical creams and ointments and injections into unresponsive

skin lesions. However, the steroid cream application for
facial rash is not recommended. Adequate protection against
sun is essential (vide supra).
Category II (Moderate SLE)
Characterised by high-grade fever, toxaemia, severe
mucocutaneous manifestations, marked photosensitivity, moderate
to severe serositis, lupus pneumonitis, mild to moderate
myocarditis, mesangioproliferative or minimal change lupus
nephritis, haemolytic anaemia and thrombocytopenia
For moderate and severe manifestations, prednisolone
1 mg/kg orally per day is the drug of choice. Antimalarials
may be administered concomitantly. High dose of steroid must
be continued till disease activity is well controlled that usually
takes up to 6 weeks when it should be tapered off slowly
over 6 to12 months. In a toxic appearing patient, the administration
of intravenous pulse methylprednisolone (15 mg/kg,
max. 1 g) over an hour for 3 or 5 consecutive days may achieve
rapid control of lupus activity. Dexamethasone 100 mg is a
good, cheap and equally effective alternative steroid for pulse
therapy. Although rare, arrhythmias, accelerated hypertension,

psychosis, seizures and sudden death have been reported with
pulse therapy. The pulses should be followed by oral prednisolone.
Calcium supplements (1 gm/day) and vitamin D (800
units/day) prescribed along with steroids retard osteoporosis.
Alendronate 10 mg daily or 70 mg once a week is a good
antiresorptive drug for prevention of osteoporosis in patients
starting on long-term steroid therapy.
A maintenance dose of oral steroid (beyond 6 months)
is not necessary in the majority of these patients and most
often it is possible to maintain the remission with antimalarials
and intermittent use of NSAIDs. INH prophylaxis in Indian
patients has been a point of debate because of fear of promoting
INH resistance. However, this risk is very low because of
the small bacillary load present in this setting. One Indian study
on patients with SLE starting on steroids showed 82% protection
from tuberculosis with INH prophylaxis in one year.22 In
the Indian context, it may be better to use 2-drug prophylaxis
(Rifampicin + INH or INH + Ethambutol) for a period of one
year.
Category III (Severe SLE)

Characterised by organ/life-threatening features such
as focal/diffuse proliferative glomerulonephritis with or without
azotaemia/hypertension, lupus cerebritis with recurrent
seizures, acute confusional state, coma; systemic necrotizing
vasculitis such as one causing peripheral gangrene, GI bleeding
or mononeuritis multiplex.
A combination therapy consisting of high-dose daily
oral prednisolone (40-60 mg/day) and intravenous cyclophosphamide
pulses (0.75 gm/m2, maximum of 1 g, over 1 hour) is
recommended. The cyclophosphamide pulses are given once
a month for 6 months by which time usually remission is
achieved and then a maintenance pulse is administered every
3 months for a total of 2 years of cytotoxic therapy. Predniso-
87
lone is tapered off or reduced to a very low dose i.e. 5-7.5 mg
per day by 6 months. At least two-thirds of patients maintain
a long-term remission after this treatment regimen.
Haemorrhagic cystitis is rare if attention is paid to adequate
hydration after the pulse and prompt voiding of bladder and

co-administration of MESNA. The overall risk of irreversible
ovarian failure was noted to be 39% in one study. It was much
higher for women aged more than 30. Infertility is common in
men as well and sperm banking is recommended, if facilities
are available. Bone marrow suppression and secondary infections
(Herpes zoster, tuberculosis, pneumocystis carinii, staphylococcus,
pseudomonas etc.), sclerosing cystitis and bladder
carcinoma, are the other adverse outcomes.
Some authorities recommend the above regimen for
induction of remission (the first 6 months), which is then maintained
with azathioprine 2-2.5 mg/kg/day for about 2 years.
Alternatives include intravenous pulses of steroids on 3 consecutive
days each month, daily oral administration of cyclophosphamide
(2 mg/kg/day) or azathioprine from the beginning
or a combination of these two agents along with oral
prednisolone. The latter is believed to be the most potent (and
the most toxic) regimen. Cyclophosphamide based regimens
have been shown to be superior in achieving renal preservation..
Plasmapheresis, methotrexate, cyclosporine and
mycophenolate mofetil are other options.

Progressive organ damage may still occur over several
years despite achieving good short-term remissions in
these patients. Although the overall incidence of end stage
renal disease (ESRD) is reduced, there is no firm evidence
that patient survival is improved by double or triple drug regimens
compared with steroid alone. This is because the outlook
of ESRD is so much better now with the availability of
dialysis and renal transplantation services. However, in India
where more than 90% of eligible ESRD candidates do not
have access to maintenance dialysis or renal transplantation,
combination therapy offers definite survival advantage.
There are no definite protocols for lupus cerebritis
but cyclophosphamide pulses have been used in combination
with oral high-dose steroids, as in the case of lupus nephritis.
Category IV (SLE with miscellaneous features)
Characterised by antiphospholipid syndrome (recurrent
DVT, CVAs, recurrent foetal loss etc.), pure membranous
lupus nephritis, chronic sclerosing lupus nephritis, seizures
without other evidence of lupus activity, behavioural

disorders without other serious manifestations, resistant
thrombocytopenia
or haemolytic anaemia
Immunosuppressive therapy does not play any significant
role in these conditions. Treatment of antiphospholipid
syndrome is described in appendix.
If seizures or psychosis occur as isolated events with
no evidence of lupus activity elsewhere in the body, only symptomatic
treatment is recommended. Steroids are not indicated.
Pure membranous glomerulonephritis (WHO Class
V) may be treated initially with prednisolone 1 mg/kg/day. If
there is no response after 6 weeks (85-90% of cases), steroids
may be quickly tapered off because they are not likely to help.
There is no proven role of cytotoxic drugs in the treatment of
this condition in SLE. Renal failure occurs but is less frequent
as compared with proliferative glomerulonephritis. However,
transformation of pure membranous nephropathy to proliferative
nephropathy is well documented and can occur in about
one-third of patients in follow up.23 There must be awareness
of this fact and repeated urine examination should be done so

that the transformation, when it occurs, is picked up and treated
adequately.
Chronic sclerosing glomerulonephritis is best treated
with conservative therapy, dialysis and transplantation.

Immunosuppressive
therapy is not beneficial. At least, 3 months
of dialysis is recommended before considering renal transplant
as the outcome of the transplant is better in patients whose
lupus disease activity remains clinically stable on dialysis for
at least 3 months.
For refractory thrombocytopenia, danazol may be
useful. Colchicine and vincristine are sometimes useful to
improve the platelet count. Splenectomy may be indicated in
some cases where platelet count tends to be less than 50,000/
cu mm and maintenance requirement for steroids is high. Such
patients should receive pneumococcal vaccine.
Plasmapheresis may be employed in refractory cases
where steroid and cyclophosph-amide pulses do not produce
satisfactory results. Intravenous immunoglobulin has also been
used in similar situations. A few instances of successful remission

of refractory lupus following stem cell transplant are
reported.
88
A Kumar
NEUROPSYCHIATRIC LUPUS
Neuropsychiatric manifestations in SLE are an important
cause of morbidity and even mortality. These can be
the initial presenting symptoms or may come up subsequently
during the course of illness. The following entities have been
recognized as features of nervous system manifestations of
lupus:
I. Central nervous system II.Peripheral nervous system
a. Aseptic meningitis. a. Cranial neuropathy
b. Cerebrovascular diseases b. Polyneuropathy
c. Demyelinating syndrome c. Plexopathy
d. Headaches d. Mononeuropathy,
e. Movement disorders single/multiplex
(e.g. chorea) e. Guillaine Barre
f. Myelopathy syndrome (AIDP)
g. Seizure f. Autonomic disorder

h. Acute confusional state g. Myasthenia gravis
i. Cognitive dysfunction
j. Anxiety and mood disorder
k. Psychosis
a. Aseptic meningitis – Features of meningeal irritation are
present in up to 5% of patients. It is necessary to exclude pyogenic,
fungal and tuberculous infection. The CSF shows an
increased protein, lymphocytosis and a reduced glucose content.
All of these findings are encountered with fungal and
tuberculous meningitis and the differentiation is frequently
difficult.
b. Cerebrovascular disease – Stroke is seen in up to 15 % of
cases. The causes of stroke include large and small vessel
thrombosis, intracerebral haemorrhage and subarachnoid
haemorrhage. Ischemic stroke is partly attributable to the presence
of circulating antiphospholipid antibodies and premature
atherosclerosis. Large haemorrhage is less common and
is due to aneurysmal rupture and active vasculitis. The occurrence
of a cerebrovascular disease in patient with SLE adversely
affects survival.
c. Demyelinating syndrome – It refers to relapsing myelopathy
and optic neuropathy in patients with lupus. These were
earlier referred to as ‘lupoid sclerosis’ and reflect that multiple
sclerosis and SLE share several clinical features.
d. Headaches- The frequency of headache in lupus is not particularly
increased. However, intractable headache or headache
of recent origin could be due to stroke, encephalopathy,
subdural haematoma, cerebral sinus thrombosis and aseptic
meningitis. The earlier description of lupus headache as migrainous
has been refuted by recent studies.
e. Movement disorders – Chorea is characteristic and is
present in in up to 1% of patients. Hemiballismus and parkinsonian
like features are reported in fewer numbers.
f. Myelopathy- Transverse myelitis, is an acute illness with
symptoms of back pain, weakness or paralysis, bilateral sensory
deficits and loss of sphincter control which may progress
over hours to days. It occurs in approximately 1% of cases.
Diagnosis is made clinically and supported by CSF pleocytosis,
elevated protein or reduced glucose level, and magnetic
resonance studies showing focal cord edema. Antiphospholipid

antibodies have been associated with this entity. Up to 25% of
cases may have optic neuropathy.
g. Seizures are amongst the commonest neurological manifestations
(17-37%) and one of the features listed in ACR classification
criteria for SLE. Generalised, simple partial and partial
complex seizures have been reported. The aetiology is
multifactorial and secondary causes include metabolic derangement
due to uraemia, hypertensive crisis and
antiphospolipid antibodies. The presence of status epilepticus
is a grave prognostic sign.
h. Acute confusional state –The ACR nomenclature and case
definitions for neuropsychiatric lupus syndromes suggest using
the term ‘acute confusional state’ for the entire spectrum
of delirium to coma. Old term ‘organic brain syndrome’ has
been dropped. It is present in 2-40% of cases and has a serious
prognostic significance. The two most frequent causes of
coma in SLE are stroke and acute confusional state.
i. Cognitive dysfunction has been reported in 21-35% of
cases. This consists of difficulty in recall, calculation, concentration
and word finding. The use of instruments like Mini

Mental State and the Neurobehavioural Cognitive Status Examination
is required to bring out this abnormaility. It may
affect performance status at work.
j. Anxiety and mood disorder – This is commonly seen in
SLE but the cause is not clear. Reaction to the presence of a
chronic illness or SLE primarily could be responsible.
k. Psychosis - Occurs in up to 23% of cases. Presents as
parnoia and hallucinations (visual or auditory). Recovery is
complete but relapses are common. Distinction from corticosteroid
psychosis can be difficult.
Some of the above manifestations are known to be associated
with antiphospholipid antibodies, e.g. strokes, chorea, some
myelopathies and seizures. However, others such as cognitive
dysfunction, seizure, acute confusional state, psychosis, anxiety
and depression, myelopathy, peripheral neuropathies and
headache are non-thrombotic disorders and could be due to
antineuronal antibodies, antiribosomal P antibodies, immunecomplexes
and vasculitis. Other important considerations are
as follows:
89
SPECIFIC ISSUES IN THE MANAGEMENT OF SLE
1. Side effects of medications for the treatment of SLE –
Corticosteroid in particular can cause psychosis, euphoria and
altered moods. Antimalarials can induce hyperirritability and
seizures. NSAIDs are known to be associated with aseptic
meningitis.
2. CNS infections - Tuberculosis, bacterial endocarditis, herpes
simplex encephalitis, meningitis have been mistaken for
CNS lupus. A lumbar puncture for CSF fluid analysis is a
must to exclude infections.
3. Fluid and electrolyte imbalance: Hypokalemia, hyponatremia,
water intoxication and syndrome of inappropriate antidiuretic
hormone can induce psychosis.
Clinical and Laboratory evaluation:
a. Thorough history and detailed physical examination including
neurological and mental status evaluation.
b. Baseline haematology, chemistry and immunological studies.
The serology should include lupus anticoagulant,
anticardiolipin antibodies. If facilities are available anti ribosomal

P antibody levels and antineuronal antibodies may be
done.
c. CT and MRI are indicated in cases of stroke, stupor/coma
and psychosis. MRI is more sensitive than CT in picking up
haemorrhages, infarcts and oedema. CT is better for detecting
cortical atrophy.
d. CSF IgG index (CSF IgG / CSF albumin divided by serum
IgG / serum albumin) is often a useful test to differentiate
between cerebritis and vascular stroke as the cause of mental
disequilibrium or confusional state or loss of conciousness.
However, the normal index (usually around 0.5) must be established
for the laboratory and if it is higher than the normal,
then cerebritis or vasculitis is the more likely cause necessitating
aggressive immunosuppression whereas a lower index
value suggest vascular insufficiency and in absence of
haemorrhage proved by an imaging study, anticoagulation is
indicated.
Treatment
In diffuse disease, such as acute confusional state,
evidence of active inflammation in the brain, such as increased

cells and protein in the CSF, brain swelling on MRI or CT, or
psychosis is generally managed with prednisolone 1-2 mg/kg/
day administered orally. Those who are unresponsive to this
dose of prednisolone may be administered IV methylprednisolone
1000mg/day for 3 consecutive days. Pulse administration
of IV cyclophosphamide in a dose of 750 mg/m2 every
3-4 weeks may be tried in refractory cases. Focal disease
such as cerebral thrombosis, chorea and some cases of transverse
myelitis where anticardiolipin antibodies may be associated,
is treated on the lines of APS (vide infra). Steroids are
not useful in this condition.
Other specific entities
Transverse myelitis : Requires aggressive treatment with
prednisolone orally 1.5 mg/kg/day and IV cyclophsophamide
bolus. If there is no improvement, plasmapheresis should be
considered.
Seizures: For generalized seizure, phenytoin and barbiturates
are used and for focal, carbamazepine, valproate or gabapentin
is used.
Headaches: Most patients respond to NSAIDs. In intractable

cases steroid may be used.
Chorea: No specific therapy is required.
Cranial /autonomic and peripheral neuropathy: Oral Prednisolone
in a dose of 1mg/kg/day is useful.
Cognitive dysfunction: Consider reducing the dose of prednisolone.
If associated with APS, anticoagulate.
90
A Kumar
LUPUS NEPHRITIS
Lupus nephritis is currently defined as the presence
of more than +++ or 0.5 gram/24 hr proteinuria or presence
of cellular casts of any type (Table 4). Using this definition,
lupus nephritis occurs in about half of SLE patients (range:
35%-73%) in India (Table 2). It is rare for lupus nephritis to
present with progressive renal insufficiency with repeatedly
normal urinalysis. Also, nephrotic range proteinuria is uncommon
(app. 10%) in Indian lupus (Table 3). Thus, reliable urine
examination is the single most important investigation for early
diagnosis of lupus nephritis; clinical examination is generally
unhelpful. Renal tubular acidosis is known to occur more frequently

in SLE.
Renal histology can be studied by light microscopy,
immunofluorescence and electron microscopy. The WHO classification
scheme combines all 3 modalities (Table 6). Activity
and Chronicity indices can be derived by the pathologist
from the renal histology picture.
Table 6 : WHO Classification of lupus nephritis
Patterns Immunofluorecence Electron Microscopy
Mesangial Peripheral Mesangial Subendothelial Subepithelial
I. Normal 0 0 0 0 0
IIA. + 0 + 0 0
Mesangial
deposits
IIB.Mes. + 0 + 0 0
hyper
cellularity
III.Focalsegmental
++ + ++ + +
GN
IV.Diffuse ++ ++ ++ ++ +
GN
V.Memb + ++ + + ++
ranous
GN
Indications for kidney biopsy in SLE
1. A patient with glomerular disease in whom the diagnosis
of lupus is not certain
2. Mild proteinuria and haematuria
3. Nephrotic syndrome with a bland sediment
4. A repeat biopsy may be performed for late progression of
the disease to distinguish between active lupus (which may
require immunosuppressive therapy) and scarring of previous
inflammatory injury
In the first 3 situations, the histology may be focal or
diffuse proliferative disease, membranous lupus, or, less often,
thrombi associated with antiphospholipid antibodies. Each
of these disorders may require a different form of therapy.
Patients with acute renal insufficiency, active lupus serology,
and an active sediment (red cells and red and white cell casts)
almost always have diffuse proliferative disease; these patients

do not need histologic confirmation if there is clear clinical
and serologic evidence for SLE.
Principles of treatment of lupus nephritis
General measures: It is advisable to restrict salt if
hypertension is present, fat if hyperlipidemia or nephrotic syndrome
is present, protein should be restricted if azotaemia is
present and calcium should be supplemented with steroid
therapy. Meticulous control of hypertension is desirable. Pregnancy
should be avoided during active lupus nephritis with
suitable contraception (vide infra). NSAIDs should be avoided
in the presence of impaired renal function.
Immunosuppressive therapy: This is generally guided
by the WHO Class of lupus nephritis.
1. Class I: Immunosuppressive therapy is not indicated.
2. Class IIa: -do-
3. Class IIb: If proteinura is > 1 gram/24 hours, antidsDNA
is high and C3 is low, prednisolone
should be administered at a dose of
20 mg daily
for 6-12 weeks, followed by tapering over

next 3 months.
4. Class III & IV: Protocol for this group is already
described above (See Category III under
management).
5. Class V: Described under management above
(Category IV)
A high chronicity index correlates with poor renal
outcome with progression to end stage renal disease despite
treatment. High activity Index is also associated with poor
outcome if not treated aggressively with appropriate

immunosuppressive
therapy. Patients with high chronicity index and
serum creatinine more than 3 mg/dL should not be treated
aggressively unless activity index is also high. If serum creatinine
is chronically high and more than 5 mg/dL, aggressive
immunosuppressive therapy is harmful. Such patients will be
better managed with dialysis and transplantation in due course.
91
ANTIPHOSPHOLIPID SYNDROME
Antiphospholipid syndrome (APS) or Hughes syndrome
can present as a subset of SLE. More often, however, it
occurs as a primary condition.The hallmark of APS is thrombosis
(venous and/or arterial). The disease is characterised by
the presence of antiphospholipid antibodies (aPL) in the blood.
Cross-sectional studies reveal 30% frequency of thrombosis
in patients with aPL.
Clinical and laboratory features
Both arterial and venous thrombosis can occur in APS.
This contrasts with other prothrombotic conditions such as
protein C, S or antithrombin III deficiency where only venous
thrombosis is seen. The common clinical manifestations of
APS comprise recurrent pregnancy loss, recurrent deep venous
thrombosis and cerebrovascular accidents. Some patients develop
the catastrophic APS in which thrombosis affects the
blood vessels supplying vital organs simultaneously or in quick
succession leading to a picture, which may mimic TTP or DIC.
The prognosis of catastrophic APS is poor.
Antiphospholipid antibodies can be detected by 2
methods: an anticardiolipin ELISA and a haematological test

called lupus anticoagulant assay. Anticardiolipin antibody is
usually of IgG class and this may exist alone or in combination
with IgM aCL. However, as many as 12% of patients
may have only IgM aCL antibody. It is recommended that
both IgG and IgM aCL should be tested in a suspected case of
APS. Lupus anticoagulant is a less sensitive test but it is associated
with the clinical syndrome of thrombosis more often
than is aCL. A patient with APS may test positive for either or
both LAC and aCL. Both tests should be carried out when
investigating APS.
Diagnosis (Consensus Classification Criteria)
A. CLINICAL CRITERIA
1. Vascular thrombosis: One or more episodes of arterial,
venous or small-vessel thrombosis, occurring within any
tissue or organ
2. Complications of pregnancy: One or more unexplained
deaths of morphologically normal foetuses at > 10 weeks
of gestation, or One or more premature births of morphologically
normal neonates at < 34 weeks of gestation, or
Three or more unexplained consecutive spontaneous abortions

at < 10 weeks of gestation
B. LABORATORY CRITERIA
1. aCL: Anticardiolipin IgG or IgM antibodies present at
moderate or high titres on 2 or more occasions at least 6
weeks apart
2. LAC: Lupus anticoagulant antibodies detected on 2 or
more occasions at least 6 weeks apart
A diagnosis of definite APS requires the presence of
one clinical + one laboratory criterion
Treatment of APS
This can be considered under the following heads:
1. Deep venous thrombosis: The main purpose of treatment
here is to prevent pulmonary embolism. Standard measures
include bed-rest, elevation of the affected limb to allow the
oedema and tenderness to subside and anticoagulant therapy.
Heparin and warfarin should be started simultaneously so as
to allow an overlap of about 5 days. INR should be adjusted
between 3 and 4 on long-term warfarin therapy. The duration
of warfarin therapy is life-long in patients with recurrent venous
thrombosis. Thrombolytics such as streptokinase, urokinase

and tPA can be used but they are not more effective in preventing
pulmonary embolism. Thromboendarterectomy and
percutaneous insertion of IVC filter may be considered in special
circumstances.
2. Acute arterial thrombosis: In a patient with APS this usually
means a TIA or stroke, with MI and digital gangrene being
less common. In some patients with acute stroke (< 3 hours
duration), thrombolytics can be used but the standard of care
is usually heparin followed by warfarin. Low-dose aspirin is
strongly recommended in patients who continue having thrombotic
events despite full anticoagulation. APS patients with
acute MI can be treated with thrombolytics, angioplasty or
coronary stents. Peripheral arterial thrombosis can be treated
with thrombolytics or heparin or angioplasty.
3. Catastrophic APS: These patients develop thrombosis in
multiple organs and the features mimic DIC and TTP. Oral
contraceptives and other drugs, pregnancy, infection and surgical
procedures have been identified as predisposing factors.
Besides standard treatment, IVIG or plasmapheresis is recommended
in such patients. Still, prognosis remains poor.

4. Pregnancy (see next section)
5. Thrombocytopenia: This is usually mild and does not require
treatment. If the count tends to drop below 50,000/cu
mm, treatment on the lines of ITP may be started.
92
A Kumar
93
PREGNANCY IN SLE
SLE does not impair the woman’s fertility except during
periods of severe disease activity. However, there is increased
risk of abortions (2-3 times), intrauterine growth retardation
and stillbirth. Pregnancy increases the risk of disease
flare (40%-50% probability). The risk of flare is doubled
in women who have active disease at the time of conception.
About 10% patients develop severe flares and therefore, lupus
pregnancy is rightly labled ‘high-risk’ pregnancy. With
better understanding of lupus pregnancy, the outcome has
improved considerably in the last 2 decades. Published data
on lupus pregnancy from India are scant.24,25 Both studies reported

poor foetal outcome in lupus pregnancy (40% and 58%
respectively). Active disease at the time of conception correlated
with adverse foetal outcome. Laboratory monitoring
during pregnancy
1. Initial evaluation: Hb, WBC, DLC, platelets, urinalysis with
microscopy, 24-hour urinary estimation of protein and creatinine,
blood urea, glucose and serum creatinine, serum lipids
if patient is nephrotic or on steroids, Coombs’ test, aPL (IgG
and IgM aCL, LAC), VDRL, anti-dsDNA, C3. Anti-Ro and
anti-La should be done if there is a past history of giving birth
to a baby with neonatal lupus.
2.Monthly laboratory assessment includes: Hb, WBC, DLC,
platelets, urinalysis (with 24-hr analysis if nephritis), chemistry
panel as above, anti-dsDNA and C3. Elevated anti-dsDNA
and low C3 indicate active SLE or impending flare in over
80% of patients.
3.In case anaemia develops, peripheral smear should be reviewed
and Coombs’ test repeated.
General principles of treatment of lupus pregnancy
It is strongly recommended that the disease should

be in clinical remission for at least 6 months before the patient
plans pregnancy. At the onset of pregnancy, a complete
assessment of disease activity and severity should be made.
The spouse and other family members should be counselled.
If disease is in remission, patient should be seen once every
month in the first half of pregnancy and more frequently, later
on. Laboratory evaluation should be performed as mentioned
above. Blood pressure should be measured at every visit and
more frequently in patients with nephritis. The prime focus of
the entire exercise of follow up should be early detection and
prompt treatment of lupus flare during pregnancy and the postpartum
period. Presence of nephritis with or without hypertension
is an indication for low-dose daily aspirin from 10th
week till 36th week for prevention of pre-eclampsia. Patients
on long-term steroid therapy (> 2 years) are administered
‘stress doses’ of steroids during delivery. Indications for Caesarian
section include maternal reasons (avascular necrosis of
the hips with inadequate hip abduction) or foetal reasons (foetal
distress, abnormal nonstress test, cephalo-pelvic disproportion
and transverse presentation etc.).

Lupus flares should be treated with the appropriate
steroid dose. Cytotoxic drugs such as cyclophosphamide and
methotrexate should be avoided during first trimester except
in rare circumstances such as pulmonary alveolar haemorrhage
due to SLE. Azathioprine and cyclosporine can be used in
pregnancy with active SLE. More safety data are needed for
mycophenolate mofetil.
If antiphospholipid syndrome is present, there is
greatly increased risk of thrombosis and foetal loss. Warfarin
must be omitted as early as possible after conception (preferably
the next day her first menses are missed and pregnancy
confirmed) and daily subcutaneous injections of low molecular
weight heparin (either enoxaparin 40 mg/day or dalteparin
5000 units per day) or low dose of heparin sodium along wih
low dose aspirin must be continued until delivery. The heparin
is omitted 12 hours before delivery or cesarean section
whereas low dose aspirin may continued. After post partum
bleeding stops, usually within a week after delivery, warfarin
is restarted. Corticosteroids are not recommended for APS
alone because they increase maternal morbidity. In refractory

cases, IVIG can be tried.
Foetal health should be monitored with repeated ultrasound
examinations, foetal heart monitoring and nonstress
test. It is needless to emphasize that a neonatologist should be
available at the time of delivery. During the postpartum period,
the mother should be watched for infection and disease
exacerbation; both require aggressive treatment, when detected.
Breast-feeding is an important issue to be addressed
after successful pregnancy outcome. Majority of drugs are
excreted in human milk in variable amounts. From neonatal
perspective, maternal intake of prednisolone upto 30 mg/day,
warfarin, cyclosporine in standard doses and weekly chloroquine
for malaria prophylaxis are considered safe. If the dose
of prednisolone is greater than 30 mg/day, feeding should be
avoided for 4 hours after ingestion of the morning dose of
steroid. By this time the blood levels are quite low and very
limited amounts are secreted into the milk. However, breastfeeding
is contraindicated if mother is on cyclophosphamide,
azathioprine, hydroxychloroquine for SLE, salicylates, indomethacin
and sulindac.
DRUG-INDUCED LUPUS (DIL)
Drugs can sometimes induce lupus-like disease and
associated autoantibodies. The incidence of DIL is estimated
at about 10% of idiopathic SLE. Numerous drugs have been
incriminated or suspected. Those associated with moderate to
high risk include procainamide, hydrallazine and quinidine.
Others such as INH, minocycline, d-penicillamine, methyldopa,
captopril, chlorpromazine, carbamazepine and phenytoin
are associated with a low risk.
DIL typically develops several months to 3 years after
continuous intake of the drug. Patients present with
arthralgias, myalgias, malaise, fever, serositis and polyarthritis.
Rash and renal involvement are rare. Laboratory profile
consists of ANA (antihistone type, usually IgG anti-H2A and
H2B), leucopenia, thrombocytopenia, mild anaemia and raised
ESR. Serolgical markers which are conspicuous by their absence
include anti-DSDNA, anti-Sm, anti-RNP, anti-Ro/La and
hypocomplementaemia. Patients frequently do not satisfy
ACR criteria for classification of SLE. After withdrawal of
the suspected agent, clinical improvement follows within days

to weeks. However, autoantibodies may take several months
to disappear. Sometimes, NSAIDs and corticosteroids may
be required for a short period to obtain symptomatic relief
94
A Kumar
Salient features
Childhood SLE is an autoimmune multisystem connective
tissue disorder occurring in children below 16 years
of age. It is the second commonest paediatric rheumatic disorder
next to Juvenile Idiopathic Arthritis. Childhood SLE
usually occurs in the age group of 5-16 years (Mean age - 12
years) with female predominance (5:1). It is said that female
preponderance is lower in childhood but Indian experience
does not support this observation. The mean duration of illness
before diagnosis is about 1 year. Table 7 and 8 give the
clinical and laboratory features noted in 2 different series on
Indian children.26,27 Clinical features in children are generally
similar to those described in adults but the disease tends to be
more severe. Renal involvement is more common. Lymphadenopathy
is also seen more commonly in children.

Table 7 Clinical features of Indian children with SLE
Parameter Northern India Southern India
(n = 83)26 (n = 59)27
Female to male ratio 9.3 : 1 4.9 : 1
Age range 5 yrs-16 yrs 5 yrs-16 yrs
Fever 89% 80%
Rash 83% 69%
Photosensitivity 73% 20%
Arthralgia/arthritis 90% 87%
Lymphadenopathy 54% 61%
Hepatosplenomegaly 55% 40%
Renal involvement 79% 49%
Pulmonary involvement 29% 22%
CNS symptoms 21% 27%
Cardiac involvement 29% 10%
Raynaud’s 29% 0%
Children are extremely vulnerable to the psychological
impact of both lupus as chronic illness and the medications
that dramatically change their appearance. The peergroup
pressures may exert overwhelming effects on a child’s

mind. The complex interaction of these unique challenges with
the usual medical problems of SLE poses difficult dilemmas
before the treating physician. Patient and family education as
well as support play a crucial role. The basic principles of
treatment of childhood SLE, however, are similar to those
employed in adult SLE.
Neonatal lupus usually occurs in babies of mothers
with anti-Ro (SSA) and anti-La (SSB) antibodies (presence
of both is more specifically correlates with CHB). Mothers
may be asymptomatic. It may present as a transient syndrome
with cutaneous lesions like annular lesions, malar erythema
and discoid lesions either immediately after birth or within
the first few months of life. The cutaneous lesions may clear
with the disappearance of maternal antibodies. Treatment is
usually not required. Thrombocytopenia, haemolytic anaemia
and leucopenia also can occur. Complete heart block can also
occur which needs early delivery and pacing in 50% of cases.
Nephritis does not seem to occur.
The risk of a second baby with CHB being born to a
mother with neonatal lupus is only about 10%. It is not worthwhile

to treat the pregnant mother with plasmapheresis and
dexmathasone in an attempt to prevent the recurrence. When
foetal monitoring does reveal presence of CHB and hydrops
in foetus, dexamethasone and plasmapheresis may succeed in
controlling CHF but not CHB.
The revised ACR classification criteria (1997) for
SLE can be used for children, too.
Table 8 Laboratory features Indian children with SLE
Parameter Northern India Southern India
(n = 83)26 (n = 59)27
Anaemia NA 51%
Leucopenia 26% 18%
Thrombocytopenia 14% 12%
Haemolytic anaemia 13% 0%
Proteinuria 79% 49%
ANA 100% 100%
Anti-DSDNA 65% 92%
Low C3 80% 58%
References
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A Kumar

SLE Is One of Several Diseases Known As

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SLE is one of several diseases known as "the great imitators"

because it often mimics or is mistaken for other illnesses. SLE is

[edit]Non-SLE forms of lupus

SLE is a chronic inflammatory disease believed to be a type III

 Apoptosis is increased in monocytes and keratinocytes

Sodium pertechnate scan showing diffusely increased uptake in

Recursive partitioning has been used to identify more

Simplest classification tree: SLE is diagnosed if a person has

SLE is not understood well enough to be prevented, but, when the

The treatment of SLE involves preventing flares and reducing

Moderate pain is typically treated with mild prescription opiates

SLE is considered incurable, but highly treatable.

The rate of SLE varies considerable between countries, ethnicity,

There are several explanations ventured for the term lupus

1. In various accounts, some doctors thought the rash

 Michael Jackson suffered from both SLE and vitiligo.

Since lupus is considered to be currently incurable, current

Systemic lupus erythematosus (SLE) is the prototype

of systemic autoimmune diseases. The aetiology is not known

as yet and the pathogenesis is complex, involving immunological,

genetic, hormonal and environmental factors. Damage

to tissues and cells results from pathogenic autoantibodies

and immune complexes. It affects predominantly women

in their reproductive years. The median age of onset in Indian

and relapses characterize the disease. The clinical manifestations

and their severity in individual patients may vary considerably

and, therefore, the treatment strategy needs to be

SLE is rare in India. A prevalence study in India (carried

out in a rural population near Delhi) found a point prevalence

of 3 per 100,0002. This is a much lower figure than reported

from the west (varying from 12.5 per100,000 adults in

England3 to 39 per 100,000 in Finland4 and 124 per 100,000

in USA5). However, a fair number of cases of SLE are encountered

in any large hospital in India. Copcord Bhigwan

study ( an ongoing, prospective population study from Pune)

found a crude incidence rate of 1 per 25,000 person years i.e.

4 per 100,000 population per year (personal communication).

Despite its rarity, SLE has considerable impact on the patient,

her/his family and health services available.

General outlook of the disease

The prognosis of SLE is quite grim with more than

half of the patients developing irreversible organ damage over

time. Although the survival has improved in the west with

modern treatment to the tune of 80% at 10 years after diagnosis6,

the Indian figures are not so good (50%-60% survival at

10 years)7,8. Possible reasons for poor survival in Indian SLE

cases are referred by practitioners), suboptimal health care

facilities and an inherently more severe disease (genetic factors?)

and endemic tuberculosis to which the lupus patients

are more susceptible. The major causes of death in the first

few years after diagnosis include disease activity and infections.

Late mortality i.e. 10 years after diagnosis, on the other

hand, is mainly attributed to atherosclerotic vascular disease9.

There is a fair amount of iatrogenic morbidity and mortality.

Indian guidelines on SLE: Why and for whom?

Since SLE is a rare disease, a general physician is

not likely to be familiar with the complexities of its presentation

and the therapeutic challenges and dilemmas it can pose.

It is a disease, which primary care physicians would find difficult