Historia Clinica

476
Learning objectives:
• Use the epidemiology and natural history of
systemic lupus erythematosus (SLE) to inform
diagnostic and therapeutic decisions
• Describe and explain the key events in the
pathogenesis of SLE and critically analyse the
contribution of genetics, epigenetics, hormonal,
and environmental factors to the immune
aberrancies found in the disease
• Explain the keysymptoms and signs of the
diseases and the tissue damage associated
with SLE
• State the classification criteria of lupus and their
limitations when used for diagnostic purposes
• Describe and explain the clinical manifestations
of SLE in the musculoskeletal, dermatological,
renal, respiratory, cardiovascular, central
nervous, gastrointestinal, and haematological
systems
• Evaluate thechallenges in the diagnosis and
differential diagnosis of lupus and the pitfalls
in the tests used to diagnose and monitor
lupus activity
• Identify important aspects of the disease such
as women’s health issues (ie, contraception and
pregnancy) and critical illness
• Outline the patterns of SLE expression in
specific subsets of patients depending on age,
gender, ethnicity, and social class
•Classify and assess patients according to
the severity of system involvement and use
appropriate clinical criteria to stratify patients in
terms of the risk of morbidity and mortality
George Bertsias, Ricard Cervera, Dimitrios T Boumpas
A previous version was coauthored by Ricard Cervera, Gerard Espinosa and
David D’Cruz
Systemic Lupus
Erythematosus: Pathogenesis
and Clinical Features 201 Introduction
Systemic lupus erythematosus (SLE) is the prototypic
multisystem autoimmune disorder with a broad spectrum
of clinical presentations encompassing almost all organs
and tissues. Th e extreme heterogeneity of the disease has
led some investigators to propose that SLE represents a
syndrome rather than a single disease.
2 Major milestones in the history of
lupus
Th e term‘lupus’ (Latin for ‘wolf’) was fi rst used during the
Middle Ages to describe erosive skin lesions evocative of a
‘wolf’s bite’. In 1846 the Viennese physician Ferdinand von
Hebra (1816–1880) introduced the butterfl y metaphor to
describe the malar rash. He also used the term ‘lupus
erythematosus’ and published the fi rst illustrations in his
Atlas of Skin Diseases in 1856. Lupus was fi rstrecognised as a
systemic disease with visceral manifestations by Moriz Kaposi
(1837–1902). Th e systemic form was further established by
Osler in Baltimore and Jadassohn in Vienna. Other important
milestones include the description of the false positive test for
syphilis in SLE by Reinhart and Hauck from Germany (1909);
the description of the endocarditis lesions in SLE by Libman
and Sacks inNew York (1923); the description of the
glomerular changes by Baehr (1935), and the use of the term
20_Eular_Fpp.indd 476 4/21/2012 7:37:54 PM
Systemic Lupus Erythematosus: Pathogenesis and Clinical Features
477
disease starts with a preclinical phase characterised by
autoantibodies common to other systemic autoimmune
diseases and proceeds with a more disease-specifi c
clinically overtautoimmune phase (Bertsias et al 2010a).
During its course periods of fl ares intercept periods of
remission culminating in disease- and therapy-related
damage, such as alopecia, fi xed erythema, cognitive
dysfunction, valvular heart disease, avascular necrosis,
tendon rupture, Jaccoud’s arthropathy, and osteoporosis.
Early damage is mostly related to disease whereas late
damage—namelyinfections, atherosclerosis, and
malignancies—is usually related to complications of
longstanding disease and immunosuppressive therapy.
5 Aetiology and pathogenesis
Th e aetiology of SLE includes both genetic and
environmental components with female sex strongly
infl uencing pathogenesis. Th ese factors lead to an
irreversible break in immunological tolerance manifested by
immune responses...