1 lupus by dandanhuanghuang


									Emily Mathews                                                       Marker: Dr. Shane Clarke
January 2005                                                              Word count: 1,885

How to diagnose and manage SLE confidently and competently.

SLE (Systemic Lupus Erythematosus) is a chronic, multisystem inflammatory disease the
specific cause of which is unknown. It can affect any, or indeed every, system and organ of
the body. Its manifestations and course are highly variable between individuals, meaning that
its diagnosis is a complex and often confusing one. This essay will present the tools currently
available to the physician in the diagnosis of SLE and those useful for separating it from its
differential diagnoses. The various treatment options for this disease will also be discussed.

The Diagnosis

The correct diagnosis is important for several reasons, not least of which is to avoid the risks
of inappropriate treatment but also to avoid psychological harm from being incorrectly
informed of a diagnosis of a serious chronic disease and possibly economical disadvantage
too, in the form of not being able to obtain life insurance. Hence it is important for the
physician to be confident when informing the patient of a diagnosis of SLE that this is indeed
the correct diagnosis. Despite advances in serology, the time between onset of symptoms and
diagnosis in patients with SLE is still variable and often delayed (Maddison, 2002).

The diagnosis of SLE is made on a balance between clinical features and laboratory tests:

Clinical features

SLE is a multi-system disease and so its effects are wide ranging. Most features are due to
the consequences of vasculitis and they are summarised in the following table:

     System                                         Clinical features
General               Fever
Skin                  Malar (butterfly) rash
Respiratory           Serositis: Pleurisy (+/- effusion)
                      Restrictive lung defect (rare)
Musculoskeletal       Arthritis
                      Aseptic necrosis of hip (rare)
Nervous               Fits
                      Cranial nerve lesions
Cardiovascular        Serositis: Pericarditis
                      Aortic valve lesions
Gastrointestinal      Abdominal pain
                      Mouth ulcers
Renal                 Glomerulonephritis
Others                Raynaud’s phenomenon
The most common presenting feature in SLE is arthritis. Fatigue and general malaise, as well
as mouth ulcers are also common presenting symptoms. Although, obviously, not everyone
who presents with these symptoms has SLE, there are characteristics of the features which
can lead on to a suspicion of SLE. For example (Belilos & Carsons, 1995), the arthritis seen
in SLE is very similar to the pattern of rheumatoid arthritis: small joints of the hands and feet
as well as the ankles, knees and wrists are most often involved. Patients also usually
experience the stiffness and ‘gelling’ of rheumatoid arthritis. However, on examination,
joints usually display a less impressive synovitis and any deformity will usually be reducible
(Jaccoud’s arthropathy). Additionally, and again in contrast to rheumatoid, the arthritis seen
in SLE in typically non-erosive.

The malar or ‘butterfly’ rash is often the sign most associated with
SLE. In fact this is only present as a presenting feature in 30 % of
patients. Equally, Raynaud’s phenomenon is not at all specific for
SLE, being found in a whole host of other diseases as well as
standing alone in some cases (emedicine.com).

Differential diagnosis

In addition to the fact that SLE manifestations are so varied there are other reasons, which
make diagnosis complex. SLE is often seen as a disease of women of a childbearing age.
This is, in fact, the group amongst whom it is most commonly seen, but this knowledge can
also lead to a reduced index of suspicion in diagnosis in males, children and the elderly.
Mostly importantly, perhaps, there are a number of conditions that can mimic SLE. These are
shown in the following table along with distinguishing features of each one:

                                                                    Table taken from Maddison 2002.

Rheumatoid arthritis can often be confused as SLE and vice versa because the commonest
presentation in both is arthritis. A careful history, examination and serology should normally
distinguish one from the other but this is also confused by what are known as the ‘overlap
syndromes’ and also by undifferentiated connective tissue disease (UCTD).

A patient is said to have an overlap syndrome when they fulfil criteria for more than one
connective tissue disease, the most commonest overlap in SLE are with systemic sclerosis
and/or polymyositis or rheumatoid arthritis; ‘Rhupus’ patients (Maddison, 2002). In contrast
to the overlap syndromes, UCTD is said to occur in patients who have clinical and laboratory
features of a connective tissue disease but who do not fulfil the criteria of any one disease.
UCTD has no formal definition but it is important to consider as a diagnosis because although
many patients remain in the same state (often symptoms including arthritis, cutaneous
involvement and fatigue but rarely with major organ involvement), some people will go on to
develop full blown SLE.

Another differential diagnosis that should not be ignored, especially since it is entirely
treatable, is that of drug-induced lupus. The presenting features are very similar to SLE but
these patients tend to have less CNS or renal involvement. Drugs that can cause this
syndrome include procainamide, hydralazine, chlorpromazine, methyldopa and isoniazid
(Belilos & Carsons, 1995). The treatment is simply to discontinue these medications.


There are several laboratory tests available to be used as diagnostic aids in SLE. The
commonest performed is a test for the presence of ANA (anti-nuclear antibody). 98% of
people with active SLE are ANA positive (Maddison, 2002), however, because of its presence
in other diseases such as rheumatoid arthritis and in 15% of the normal population, the results
of an ANA investigation should only be considered when a full clinical picture has been

The most specific test for SLE is a test for anti-dsDNA antibodies (those that bind double-
stranded DNA) although only 50 % (Kumar & Clark, 2002) of patients with active SLE will
be anti-dsDNA positive.

A full blood count usually shows a lymphopenia, leucopenia, anaemia and/or
thrombocytopenia. The ESR will be raised in proportion to disease activity while CRP is
usually normal.

Other tests that will be positive in a certain proportion of patients include (Kumar & Clark,
2002; Maddison, 2002): Rheumatoid factor, anticardiolipin antibodies and antibodies to
various RNA-binding proteins such as La or Ro.

                                   A further test that has reduced in its popularity since the
                                   advent of readily available serology is the lupus-band test
                                   (Maddison, 2002).          In SLE, granular deposits of
                                   immunoglobulin and complement are laid down in a ‘band’
                                   between the dermis and epidermis in lesional and non-
                                   lesional skin. The lupus-band test is a histological test that
                                   looks for this lupus-specific sign. Only 50% of people with
                                   SLE will have this ‘banding’ and because serology is far
                                   easier to carry out, the use of this test has been reduced to
                                   only those patients who have atypical serology and/or
                                   clinical signs.

In 1997, the American College of Rheumatology (ACR) published its updated criteria for the
classification of SLE (Hochberg, 1997). These are as follows:

1. Malar rash
2. Discoid rash
3. Photosensitivity
4. Oral ulcers
5. Non-erosive arthritis
6. Serositis: pleurisy or pericarditis
7. Proteinuria >0.5g/24hrs or casts
8. Neurological: seizures or psychosis
9. Haematological: haemolysis/leucopenia/lymphopenia or thrombocytopenia
10. Immunological: anti-DNA or anti-Sm or antiphospholipid antibodies
11. Positive ANA

They claim that the presence of 4 or more of these criteria is 96% sensitive and 96% specific
for SLE. The criteria are designed as a means of standardising patient populations for the
purpose of research (Maddison, 2002) and there has been criticism of their use as a diagnostic
tool. Direct criticism of the content of the criteria has occurred. For example, it has been said
that the revised criteria lack a definition of the durations involved in serological testing
(Piette, 1998). Further evidence against the use of these criteria as diagnostic exists in the
form of a paper by Levin et al. which reports that 50% of their patients with lupus do not
conform to the criteria (Levin et al. 1982).

SLE is a highly variable disease, both in course and manifestations, making it’s diagnosis
very complex and one that is based on a detailed history, clinical exam and investigations.
These should all be tailored towards the individual patients and all results should be taken in
context with all other information available.

The Management

Patient education
One of the most important aspects in managing SLE, especially in newly diagnosed SLE, is
that of patient education. The patient should know all the possible outcomes of having SLE
and that often many cases of SLE are mild. They should know how to help themselves, such
as wearing sunscreen for most months of the year and, for women, avoiding oestrogen-
containing contraceptive pills.

Drug treatment in SLE
The aims of treatment in SLE are not only to control the disease itself but also to control co-
existent diseases such as diabetes or hypertension and to manage the results of the disease
such as end-stage renal failure, and the side effects of drugs. There are a number of drugs
available for use in the treatment of SLE. Again, treatment is individualised to the patient’s
‘own’ SLE.

Besides the use of anti-inflammatories (steroidal and non-steroidal) and painkillers for
treating symptoms such as those from the arthritis in SLE, the following drugs are used to
attempt to control the disease itself:

       Drug                            Manifestation of SLE best treated
Azathioprine       Treats a wide range of manifestations but most data on efficacy comes
                   from studies done on patients with lupus nephritis.
Cyclophosphamide   Considered standard treatment for SLE with major organ involvement.
                   Still debate on optimal administration protocol (Mosca et al. 2001).
Hydroxychloroquine Mainly used to control articular and cutaneous manifestations, but also
                   for fatigue and serositis. Recently shown to be beneficial on the lipid
                   profile of lupus patients (Mosca et al. 2001)
Methotrexate       Articular and cutaneous manifestations shown to respond best to
                   methotrexate (Ruiz-Irastorza et al. 2001), but methotrexate is only
                   indicated for these symptoms after non-responsiveness to steroids and
Thalidomide            Thalidomide has the potential to treat resistant cutaneous
                       manifestations of this disease but side effects can restrict its long-term
                       use (Ruiz-Irastorza et al. 2001).
Intravenous            Fever, arthritis and thrombocytopenia have been shown to respond
immunoglobulins        well to human intravenous immunoglobulins (Ruiz-Irastorza et al.

The use of drugs within the management of SLE is dependent upon the patients individual
needs and should be balanced with the side-effects of these drugs, especially considering that
many patients will be on these drugs for long periods of time. Another consideration when
choosing a drug or drugs is the need for monitoring. For example both azathioprine and
methotrexate require regular blood tests to confirm that there is no toxic effects.

New therapies such as immunoablative therapy, autologous marrow stem cell transplantation
are currently being developed. A phase I study combining these therapies showed promising
results (Traynor et al. 2000). Gene therapy for SLE has also been tried in mice (Xiaojing et
al. 2004).

Systemic lupus erythematosus is a multi-system inflammatory disease that affects most of the
different tissues and systems of the body. Its manifestations vary highly between individuals.
This means that the diagnosis of SLE is far from routine and the physician must use all of the
tools at his disposal in concert to correctly diagnose patients as near to the time of
presentation as possible. This essay cannot specifically answer the question of how to
diagnose SLE purely because each case is so different. This fact also applies to the
management of SLE patients – each is different and treatment is different for each.


Belilos E and Carsons SE, 1995. Systemic Lupus Erythematosus: Recognition and
        Management by the Primary Care Physician. Primary Care Update Ob/Gyns. 2, 80-
Hochberg MC, 1997. Updating the American College of Rheumatology revised criteria for
        the classification of Systemic Lupus Erythematosus. Arthritis and Rheumatism, 40,
Kumar P and Clark M, Editors, 2002. Clinical Medicine 5th ed. Saunders. P557-560
Levin DL, Roenigk HH, Caro WA & Lyons M, 1982. Histologic, immunofluorescent and
        antinuclear antibody findings in PUVA-treated patients. Journal of the American
        Academy of Dermatology, 6, 328-333
Maddison PJ, 2002. Is it SLE? Best Practice & Research Clinical Rheumatology. 16, 167-180
Mosca M, Ruiz-Irastorza G, Khamashta MA & Hughes GRV, 2001. Treatment of Systemic
        Lupus Erythematosus. International Immunopharmacology. 1, 1065-1075
Piette JC, 1998. Updating the American College of Rheumatology revised criteria for the
        classification of Systemic Lupus Erythematosus: comment on the letter by Hochberg.
        Arthritis and Rheumatism, 41, 751
Ruiz-Irastorza G, Khamashta MA, Castellino G & Hughes GRV, 2001. Systemic Lupus
        Erythematosus. Lancet, 357, 1027-1032
Traynor AE, Schroeder J, Rosa RM et al. 2000. Treatment of severe systemic lupus
        erythematosus with high-dose chemotherapy and haematopoietic stem-cell
        transplantation: a phase I study. Lancet. 356, 701-707
Xiaojing Y, Tong Z, Juan L & Xiao X, 2004. AAV-mediated gene therapy for systemic lupus
        erythematosus (SLE). Molecular Therapy 9, 16.

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