Lupus Erythematodus

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Red wolf

While any subdivision of LE is arbitrary, a scheme based on the clinical presentation and disease course is practically useful despite the lack of a unifying etiology:
1) Systemic Lupus Erythematosus (SLE) (= Lupus erythematodes disseminatus (LED). The most serious
and recognized subset, where immune-complex mediated inflammation can affect any organ system.
Associated with increased mortality and antinuclear antibodies.
2) Discoid Lupus Erythematosus (DLE) (=chronic cutaneous LE(CCLE)).
Characterised by typical discoid (=”coin shaped”), scaling skin lesions,that may result in severe
scarring. Involves mostly the face, scalp and neck (typical V–shape), but can occur in areas not
usually exposed to sunlight. Erythematous and/or ulcerative mucosal lesions may be present.
Antinuclear antibodies found in a minority of patients. SLE developing in about 5 %.
3) Subacute Cutaneous Lupus Erythematosus (SCLE).
An LE subset with typical widespread annular skin lesions, easily provoked by
UV light exposition and associated with anti-SSA (Ro) antibodies. About half will have/develop SLE.
4) Neonatal Lupus Erythematosus (NLE). Passively transferred autoimmune disease, where maternal
antibodies against SSA(Ro) can induce reversible skin and hematological manifestations and frequently irreversible heart lesions (AV-block and cardiomyopathy) in the newborn.
5) Drug Induced Lupus Erythematosus (DILE). First described after hydralazine use, now associated with a long list of pharmaceutical drugs and environmental toxics; often presenting with joint and skin symptoms and associated with antibodies against the H2A-H2B subcomplex of the nucleosome. Rapid resolution after withdrawal of the offending drug is the rule.

SLE: 1:1000 adults among Caucasian females . Increased prevalence (and severity) in populations with non-Caucasian descent (1) . Female to male ratio about 10:1. Prevalence unknown for other subsets.

Genes and mutations
LE is a polygenic disorder (2). Strongest confirmed susceptibility genes for SLE are HLADR2 (DRB1*1501), HLADR3 (DRB1*0301), C1A*Q0, C2*Q0, C4A/B*Q0, FcγRIIA (H131R), FcγRIIA (F176V), PDCD1(PD1.3A)

LE is caused by an unexplained loss of tolerance to self-antigens leading to the activation of several immune cell types. This results in the production of characteristic autoantibodies, which may form immune-complexes with specific or closely related antigens throughout the body and have the potential to induce inflammation. T cell mediated activation of autoreactive B cells resulting in the production of nephritogenic anti-dsDNA antibodies trough antibody maturation has been elucidated as a pathogenic pathway in SLE patients. Still unknown remain the eliciting antigen(s) (nucleosomes, possibly altered during inappropriate apoptosis, are a possible culprit) and the specifics of the interaction between immune-complexes, intrinsic or planted antigens and immune cell receptors. The traditional lupus band test (immune complex deposition in both affected and unaffected skin) and experimental models serve as reminders that immune complex deposition alone is not the only requirement for the development of skin and glomerular lesions (3;4).

Diagnostic principles
Due to the lack of a specific test (S)LE remains a clinical diagnosis based on the recognition of a complex of symptoms in the context of autoimmunity (Table). While fulfilling four of the updated ACR–criteria for the classification of SLE is generally accepted as specific enough for defining patient cohorts for scientific purposes, their retrospective design makes them less suitable for diagnostic purposes in clinical practice(5). A widely applied strategy uses the presence of antinuclear antibodies (i.e. a positive ANA screening test by any assay) accompanied by three other ACR criteria as an alternative, but validated diagnostic approach (5). A negative ANA-screening test using the sensitive, but unspecific immunofluoresence assay with Hep2 cells as substrate, just about rules out SLE (with the standard exceptions). Ideally, positive ANA-screening findings should be accompanied by the presence of more specific markers for SLE (antibodies aginst dsDNA, Sm, ribosomal protein P or other ENA antibodies) to confirm the diagnosis, but this remains a matter of debate. Also, a considerable number of patients have other manifestations (e.g. Raynaud, hypocomplementemia, alopecia) and when not fulfilling the current ACR criteria, they are designated to have Lupus-like disease, incomplete LE or undifferentiated connective tissue disease (UCTD). Management is however similar to patients fulfilling ACR criteria.

Therapeutic principles
There is presently no cure for SLE. The remarkable clinical efficacy of corticosteroid therapy in SLE has resulted in a lack of solid data on Prednisone usage for SLE. Most randomized trials in SLE compared immunosuppressive drugs in proliferative lupus nephritis while disregarding the role of steroids. Observational studies have established the therapeutic efficacy of antimalarial drugs. Guidelines for SLE treatment in general are thus mostly eminence based; physicians need to take into account the severity of current clinical symptoms and the risk for subsequent end-organ failure (i.e. hot and unpredictable versus mild and consistent lupus) while balancing drug efficacy against side-effects. Pharmaceutical options to suppress disease manifestations range from NSAID, corticosteroids (topical, oral or iv push) and antimalarials to nonselective immunosuppressive drugs (cytotoxic drugs, cyclosporine/tacrolimus). Recently, more specific “biological” therapy with monoclonal antibodies resulting in B-cell depeleting (anti-CD20) or blockade of co stimulatory signals (CTLA4-Ig) has been introduced for refractory cases and drugs targeting other mediators of inflammation (CD40L,CRP,IL-6, Blys) are likely to follow. Given the increased life expectations, close attention should be paid to the prevention of comorbid conditions that occur with increased frequency in SLE patients. This includes reducing infections by an individually designed vaccination program and reducing the risk for accelerated atherosclerosis, thromboembolic disease and osteoporosis by addressing the relevant risk factors.
Original languageEnglish
Title of host publicationEncyclopedia of Molecular Mechanisms of Disease
PublisherSpringer NY
Number of pages3
Publication statusPublished - 2008


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