Southwestern Internal Medicine Conference

Drug-Induced Lupus: Clinical Spectrum and Pathogenesis

Drug-induced lupus erythematosus (DILE) refers to a condition whose clinical, histological, and immunological features are similar to those seen in idiopathic lupus erythematosus but that occurs when certain drugs are taken and resolves after their withdrawal. Over 90 drugs have been linked to DILE to date and the list is growing. Like idiopathic lupus erythematosus, DILE has systemic, subacute cutaneous, and chronic cutaneous forms. A correct diagnosis is very important, as this condition usually resolves after withdrawal of the offending drug.

El término lupus eritematoso inducido por fármacos (LEIF) hace referencia a una entidad caracterizada por la aparición de manifestaciones clínicas, histopatológicas e inmunológicas similares a aquellas que aparecen en el lupus eritematoso idiopático, pero que cronológicamente coinciden con la toma de ciertos fármacos y que se resuelven tras la retirada de los mismos. Más de 90 fármacos se han asociado con la aparición de LEIF. Esta lista de fármacos implicados sigue aumentando. Al igual que el lupus eritematoso idiopático, el LEIF se puede subclasificar en lupus eritematoso sistémico inducido por fármacos, lupus eritematoso cutáneo subagudo inducido por fármacos y lupus eritematoso cutáneo crónico inducido por fármacos. Reconocer estas entidades es de gran interés, ya que este cuadro suele revertir tras la retirada del fármaco implicado.

Autoimmunity can follow exposure to drugs or other agents. There are increasing numbers of reports and case series of patients who develop autoantibodies and lupus-like syndromes following exposure to certain medications and environmental agents, resulting in the development of drug-related lupus (DRL). The most frequently reported clinical features include constitutional symptoms, arthralgias/arthritis, serositis, and the development of autoantibodies. Systemic lupus erythematosus (SLE) is an autoimmune disease for which the etiology remains undetermined despite intensive research. There is evidence to suggest that genetic factors play a major role in the pathogenesis of this disease. The term “drug-related lupus” refers to the development of a lupus-like syndrome following exposure to a certain drug. An important feature of DRL is a temporal association between the ingestion of an agent and development of lupus-like features with remission of the features and decrease in autoantibody titers following withdrawal of the offending agent. Typical features of DRL include constitutional symptoms, arthralgias/arthritis, myalgias, serositis, elevated ESR, and a positive ANA, which is generally accepted as a requirement for the diagnosis. Specific clinical features for the diagnosis of DRL have not as yet been defined. There are as yet no established criteria for the diagnosis of DR and the definitive treatment is withdrawal of the offending agent. Physicians need to be aware of possible associations between the development of autoimmune-like features and exposure to certain pharmacologic agents for both diagnostic and therapeutic reasons.

Systemic lupus erythematosus (SLE) is an autoimmune disease that affects many organ systems, is more prevalent in females, and has no known etiology. Moreover, the presentation of patients with the disease can be as diverse as the many systems in the body that it can affect. The systems commonly involved include muscle and joints, brain and peripheral nervous system, lungs, heart, kidneys, skin, serous membranes, and components of the blood. This disease is complex and often affects one organ system to the exclusion of others. Moreover, the clinical manifestations are protean, overlap with other illnesses, and are often subtle. The complex nature of lupus could explain the convergence of seemingly unrelated abnormalities and the varied nature of pathology observed from patient to patient in this illness. Although lupus is largely associated with specific immune response genes in the MHC class II or class III regions, there are new and exciting genetic associations that include other loci. Suspected pathogenetic factors, such as sex steroid hormones or gonadotrophins such as prolactin, may play a role in the severity of the disease and the different clinical presentations. Environmental factors such as drugs, diet, and toxins have also been implicated in the pathogenesis of SLE. Immunological tests, which are specific to most autoimmune diseases such as lupus, include the presence of specific cytotoxic lymphocytes and a variety of autoantibodies, including a persistently positive antinuclear antibody. Although there are a few nonimmunologic laboratory characteristics of SLE, these are not specific.

The relationship between age and the morbidity and mortality of systemic lupus erythematosus (SLE) is important and the incidence of disease varies in males and females depending on age. Gender and more specifically sex steroids play an important role in the maturation of organ systems that affect animals throughout life and are therefore important to the health of most vertebrates. The effects of sex steroids on the immune system are profound and long-lasting because they control the growth and maturation of various cell systems and may also influence susceptibility to disease through modulation of immune cell populations, alteration of cytokine levels, control of cell populations through processes such as apoptosis, and change of very basic molecular mechanisms. Lupus is one disease that is highly affected by hormones. Thus, sex steroids are potent modulators of immunity in all animal systems. They are very important in patients with SLE and may help explain the fluctuant activity in lupus disease. Their role in the maturation of the immune system and their effect on the development of organs such as the brain could explain some of the abnormalities found in these systems.

Systemic lupus erythematosus (SLE) is an autoimmune disease that affects many organ systems, is more prevalent in females, and has no known etiology. Moreover, the presentation of patients with the disease can be as diverse as the many systems in the body that it can affect. The systems commonly involved include muscle and joints, brain and peripheral nervous system, lungs, heart, kidneys, skin, serous membranes, and components of the blood. This disease is complex and often affects one organ system to the exclusion of others. Moreover, the clinical manifestations are protean, overlap with other illnesses, and are often subtle. The complex nature of lupus could explain the convergence of seemingly unrelated abnormalities and the varied nature of pathology observed from patient to patient in this illness. Although lupus is largely associated with specific immune response genes in the MHC class II or class III regions, there are new and exciting genetic associations that include other loci. Suspected pathogenetic factors, such as sex steroid hormones or gonadotrophins such as prolactin, may play a role in the severity of the disease and the different clinical presentations. Environmental factors such as drugs, diet, and toxins have also been implicated in the pathogenesis of SLE. Immunological tests, which are specific to most autoimmune diseases such as lupus, include the presence of specific cytotoxic lymphocytes and a variety of autoantibodies, including a persistently positive antinuclear antibody. Although there are a few nonimmunologic laboratory characteristics of SLE, these are not specific.

The relationship between age and the morbidity and mortality of systemic lupus erythematosus (SLE) is important and the incidence of disease varies in males and females depending on age. Gender and more specifically sex steroids play an important role in the maturation of organ systems that affect animals throughout life and are therefore important to the health of most vertebrates. The effects of sex steroids on the immune system are profound and long-lasting because they control the growth and maturation of various cell systems and may also influence susceptibility to disease through modulation of immune cell populations, alteration of cytokine levels, control of cell populations through processes such as apoptosis, and change of very basic molecular mechanisms. Lupus is one disease that is highly affected by hormones. Thus, sex steroids are potent modulators of immunity in all animal systems. They are very important in patients with SLE and may help explain the fluctuant activity in lupus disease. Their role in the maturation of the immune system and their effect on the development of organs such as the brain could explain some of the abnormalities found in these systems.