Drug-induced lupus erythematosus pathophysiology

Jump to navigation Jump to search

Drug-induced lupus erythematosus Microchapters

Home

Patient Information

Overview

Historical Perspective

Pathophysiology

Causes

Differentiating Drug-induced lupus erythematosus from other Diseases

Epidemiology and Demographics

Risk Factors

Natural History, Complications and Prognosis

Diagnosis

History and Symptoms

Physical Examination

Laboratory Findings

Electrocardiogram

Chest X Ray

CT

MRI

Echocardiography or Ultrasound

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Surgery

Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Case Studies

Case #1

Drug-induced lupus erythematosus pathophysiology On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Drug-induced lupus erythematosus pathophysiology

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Drug-induced lupus erythematosus pathophysiology

CDC on Drug-induced lupus erythematosus pathophysiology

Drug-induced lupus erythematosus pathophysiology in the news

Blogs on Drug-induced lupus erythematosus pathophysiology

Directions to Hospitals Treating Drug-induced lupus erythematosus

Risk calculators and risk factors for Drug-induced lupus erythematosus pathophysiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

  • the exact pathophysiology of drug-induced lupus erythematosus is not fully understood.
  • some genetic risk factors include HLA-DR4, HLA-DR0301, and complement C4 null allele.

Pathophysiology

  • Three mechanisms are implicated in the causation of drug-induced lupus erythematosus:
  1. Slow acetylation with genetic deficiency of N-acetyltransferase. It is found that slow acetylators with genetic deficiency of N-acetyltransferase are at higher risk of DIL, especially from procainamide and hydralazine.
    1. Inhibition of DNA methylation of CD4+ T-cells. the demethylation of CD4+ T-cells makes them auto-reactive by over-expression of the LFA-1 adhesion molecule. These auto-reactive T-cells can then overstimulate autoantibody production by interaction with self class II MHC molecules on B-cells and induce apoptosis of macrophages by interacting with self class II MHC molecules on macrophages which release the highly antigenic apoptotic chromatin from the dying macrophages. This autoantibody production and release of antigenic macrophages chromatin is thought to contribute to the development of lupus-like autoimmunity.
      1. The metabolites of the offending drug are subjected to oxidative metabolism and serve as a substrate for myeloperoxidase; which is activated in polymorphonuclear neutrophils. This interaction results in the formation of reactive metabolites that directly affect lymphocyte function in the thymus making them auto-reactive. Virtually all lupus-inducing drugs undergo oxidative metabolism, whereas analogous non-lupus-inducing drugs do not. Also, both mouse and human studies implicate thymic activity in the pathophysiology of DILE.

Pathophysiology

References

Template:WikiDoc Sources