SLE diagnosis and treatment: When early is early

doi:10.1016/j.autrev.2010.08.014

Autoimmunity Reviews

Volume 10, Issue 1, November 2010, Pages 55-60

https://doi.org/10.1016/j.autrev.2010.08.014 Get rights and content

Abstract

Around 1980 antinuclear antibody testing became widely used in routine laboratory practice leading to a tapering in the lag time between SLE onset and diagnosis. Since then nothing relevant has been introduced which could help us in making the diagnosis of SLE earlier than now.

Notably, there is increasing evidence that early diagnosis and treatment could increase SLE remission rate and improve patient prognosis. Although it has been shown that autoantibodies appear before clinical manifestations in SLE patients, currently we cannot predict which autoantibody positive subjects will eventually develop the disease. Thus, great effort should be made in order to identify new biomarkers able to improve our diagnostic potential. B lymphocyte stimulator (BLyS), anti-ribosomal P protein and anti-C1q antibodies are among the most promising.

In recent years, some therapeutic options have emerged as appropriate interventions for early SLE treatment, including antimalarials, vitamin D, statins and vaccination with self-derived peptides. All these immune modulators seem to be particularly useful when introduced in an early stage of the disease.

Section snippets

Diagnosis and classification of SLE

In clinical practice the diagnosis of SLE is usually made in a patient who has developed a combination of clinical and immunologic features specific to SLE. Of course diseases which can mimic SLE have to be concomitantly ruled out.

Criteria for the classification of SLE were elaborated by the American College of Rheumatology (ACR) firstly in 1971, then revised in 1982, and then again in 1997. Unfortunately, they are not diagnostic; in fact, they cannot be applied to every individual case, since

Timing of SLE diagnosis over years

The lag time between the onset and the diagnosis of SLE reported in major cohort studies was approximately 50 months before 1980 [1] and approximately 25–26 months after 1980 [2].

In our cohort of 487 SLE patients recruited between 1970 and 2008, the mean lag time between the onset and the diagnosis was 59 months in patients diagnosed before 1980, a figure similar to that reported by Wallace in 1981 [2], 28 months in those diagnosed between 1980 and 1989, 15 months in those diagnosed between 1990 and

When does SLE start?

Genetic susceptibility represents a relevant aspect in the pathogenesis of SLE. SLE is a multigenic disease; a combination of genome-wide scanning, family studies, and candidate gene approaches has led to the identification of a series of genes which determine the susceptibility to the disease. They are genes which on the one hand inhibit the clearance of apoptotic cells favouring autoantigen exposure and on the other hand predispose the immune system to an aberrant responsiveness.

In this

How can we identify patients with early SLE?

Of course, to perform tissue biopsies in asymptomatic patients in order to identify the preclinical stage is unethical. What we are currently able to identify in clinical practice are ANA, which are very useful in the diagnostic process; however, we know that only a small percentage of asymptomatic ANA-positive patients will eventually develop SLE, but, unfortunately, we cannot predict which of them.

When aspecific manifestations such as Raynaud's phenomenon or arthralgia occur in association

What is the importance of early diagnosis?

If we look at animal models, which represent suitable models from this point of view due to the possibility of manipulating them before disease occurrence, we can see that all successful interventions are most effective when they are introduced before the development of full-blown clinical lupus [22]. Only a few of them are also effective after the disease has established.

In humans, data on early interventions are very limited. It has been shown that a delay in renal biopsy higher than 24 months

How should we manage patients with early lupus?

The current treatment of early, mild lupus consists of the use of low-dose corticosteroids and antimalarial drugs. However, a number of other interventions have recently been proposed in the early stage of lupus.

Take-home messages

•
Early SLE diagnosis is crucial for an early therapeutic intervention which can increase the probability of disease remission and improve patient prognosis.
•
Biomarkers which help us to identify SLE patients in an early stage of the disease are urgently needed.
•
Antimalarials, vitamin D, statins and vaccination with self peptides are among the best candidates for early therapeutic intervention in SLE

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One in five patients with new-onset SLE manifest disease presentations required hospitalization. Although early diagnosis was achieved in the majority of cases, in approximately 20%, diagnosis was delayed. A lower SLERPI cut-off (≥5) in patients with fever or thrombosis could enhance early diagnosis.
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ReviewSLE diagnosis and treatment: When early is early

Abstract

Section snippets

Diagnosis and classification of SLE

Timing of SLE diagnosis over years

When does SLE start?

How can we identify patients with early SLE?

What is the importance of early diagnosis?

How should we manage patients with early lupus?

Take-home messages

Semin Arthritis Rheum

Autoimmun Rev

Autoimmun Rev

Autoimmun Rev

J Autoimmun

Best Pract Res Clin Rheumatol

J Autoimmun

J Autoimmun

Am J Kidney Dis

Am J Kidney Dis

J Autoimmun

Systemic lupus erythematosus-survival patterns. Experience with 609 patients

JAMA

Long-term prognosis and causes of death in systemic lupus erythematosus

Am J Med

Health-related quality of life in Italian patients with systemic lupus erythematosus. II. Role of clinical, immunological, and psychological determinants

Rheumatology

Lupus: improving long-term prognosis

Lupus

Further description of early clinically silent lupus nephritis

Lupus

Recurrent lupus nephritis after kidney transplantation: a surveillance biopsy study

Ann Rheum Dis

Defining unclassifiable connective tissue diseases: incomplete, undifferentiated or both?

J Rheumatol

Clinical and biological data integration for biomarker discovery

Drug Discov Today

Anti-ribosomal P protein antibodies and neuropsychiatric systemic lupus erythematosus: cross-sectional vs. prospective studies

Lupus

Review
SLE diagnosis and treatment: When early is early