What is lupus?
Lupus is a common term to describe a group of autoimmune diseases more correctly known as lupus erythematosus. There are several distinct types of lupus which can be broadly divided into systemic, where the entire body is affected, or cutaneous, where it is restricted mostly to the skin. It may be further categorized by the causative factor or age group that is affected. The most common type of lupus is systemic lupus erythematosus (SLE) and therefore the general term ‘lupus’ is considered to be referring to SLE specifically.
Meaning of Lupus
Lupus is an autoimmune disease meaning that the immune system attacks the body’s own tissues. This applies to all types of lupus erythematosus. Since SLE is the most common type, it is worth noting the pathophysiology (disease mechanism) to gain a broad understanding of lupus erythematosus as a whole. There may, however, be slight differences in the pathophysiology particularly associated with the causative factors. The pathophysiology is not completely understood although there is sufficient evidence to support current theories. Lupus seems to be associated with genetic, environmental, hormonal and possibly even infectious factors.
The immune system normally produces antibodies as a means of tagging foreign invaders like viruses and bacteria. These antibodies are designed in accordance with individual proteins on the surface of the invaders which are known as antigens. Therefore specific antibodies are made for specific antigens. In this way the body can direct the appropriate immune response at the correct threat. The body’s cells are usually not affected because the proteins on the surface of these cells are recognized as not being foreign and therefore are not considered to be a threat.
In autoimmune disease like lupus, this self-protecting mechanism fails. It is believed that part of the problem arises when the body’s cells trigger cell death (apoptosis) but are not cleared out fast enough. The dead cells begin to breakdown and the components within the cell are then exposed. The immune system does not recognize these components as being part of the body since it is no longer bound within a cell membrane. Therefore antibodies are formed against the body’s own intracellular components – autoantibodies. In systemic lupus erythematosus, it mainly antinuclear antibodies (ANA) that are found which target the nuclear material normally shielded within the cell.
There are a host of other antibodies apart from those directed at the cell’s nuclear material. Some of these antibodies target the proteins in phospholipids and may have an affinity for certain types of blood components like red blood cells, platelets and lymphocytes. Certain types of lupus antiphospholipid antibodies, like lupus anticoagulants and anticardiolipin antibodies, have been implicated in serious and life-threateing cardiovascular complication of lupus. These antibodies, however, are not specific for SLE as several other diseases may also cause the development of some of these antibodies. For example, certain types of antinuclear antibodies (ANAs) may be seen with other autoimmune diseases like rheumatoid arthritis or anticardiolipin antibody may be detected in syphilis. Furthermore, not all of these different types are present in every patient with SLE although ANA is almost always present.
Causes of Lupus
The exact cause of lupus is not known but it appears to be associated with several factors. It is believed that it is not a single factor that is involved in lupus but rather a combination of factors, particularly genetic and environmental factors. It is important to note that these factors are not causes of lupus but simply risk factors meaning that a person with one or more of these factors have a greater chance of developing lupus. Some of these factors may be a trigger meaning that the potential to develop lupus was pre-existing and some factor just triggered the onset of the disease.
Family members of SLE patients have a greater risk of developing the disease thereby indicating an inherited predisposition. The risk is even greater among monozygotic twins when one twin has SLE. There is also a greater risk among certain ethnic groups – Asians, Africans, Native Americans, Hispanics and Pacific Islanders. Certain genes (MHC HLA-A1, B8, and DR3) and genetic deficiency of complement factors (C1q, C2, or C4) have been linked to SLE. Despite these findings, the exact genes responsible for SLE have never been identified further supporting the theory that it has a multifactorial etiology.
Ultraviolet light in sunlight has been implicated in the etiology of lupus. The exact reason is unknown but UV light may induce apoptosis (self-inflicted cell death) and alter the DNA in a way that makes it a target for antibodies. The exacerbation seen with sunlight exposure could also be associated with interleukin-1 (IL-1) produced by keratinocytes (epidermal skin cells), which then promotes inflammation. Ultraviolet light from long hours of exposure to fluorescent bulbs may also be responsible.
Other environmental factors which are also believed to play a role are mainly seen with long term and high exposure, as is the case in occupational settings. These factors include exposure to mercury, pesticides and silica. It has not been conclusively linked to SLE.
Certain medication have been linked to the development of SLE. Drugs like hydralazine, procainamide, and d-penicillamine may cause an SLE-like reaction referred to as drug-induced lupus erythematosus. It is now known that a number of other drugs may also play a role in triggering or exacerbating lupus including various sulfa drugs, sun-sensitizing drugs and a range of antibiotics.
The term stress with regards to lupus etiology is broad and includes the physical and psychological spheres. Factors that may serve as possible triggers includes severe physical trauma, major surgery, pregnancy, childbirth, and following a major debilitating illness particularly infections. Psychological stress may vary among people but situations such as divorce, grief due to death of a close family member, periods of mental illness and other stresses that may occur in life could serve as possible triggers of lupus.
The female hormone estrogen appears to play a role in the exacerbation of lupus and this may be associated with hormonal fluctuations in the menstrual cycle and pregnancy. It is also interesting to note that SLE is more likely to develop during the reproductive years when the hormones such as estrogen are present at higher levels within the body.
Lupus may develop after a chronic infectious illness although the exact reason for this trigger is not clearly understood. It has been noted that there is a greater risk associated with an Epstein-Barr virus (EBV) infection. The immune activity during the period of infection may play a role on autoimmunity and the subsequent ‘development of lupus. Other viruses may also be involved although none have been implicated to the extent of EBV. There may be flare ups of lupus with certain infections, like bacterial infections.
Types of Lupus
Lupus can be broadly divided into systemic and cutaneous forms and the common terms lupus and skin lupus are used respectively. However, systemic forms also have cutaneous (skin manifestations) and some mild non-cutaneous features may be seen with cutaneous forms.
- Systemic lupus erythematosus mainly occurs in females in early adulthood and can affect any part of the body but in particular the joints, skin, blood cells, kidneys, heart, lungs and brain. It is the most common type and the most serious form of lupus.
- Cutaneous lupus erythematosus is a broad category incorporating various types of lupus that predominantly affect the skin. The most notable of these is discoid lupus erythematosus (DLE). A small number of cases can progress to systemic lupus erythematosus (SLE).
- Drug-induced lupus erythematosus is similar to systemic lupus erythematosus but caused by the use of certain drugs. It is reversible once the drug is stopped unlike with SLE which is chronic.
- Neonatal lupus erythematosus is seen in newborn babies born to women with lupus or women with certain autoantibodies even though lupus has not developed as yet. It is a self-limiting disease that is isolated to the skin but in a minority of cases there may be serious heart defects in the newborn.
- Childhood lupus eythematosus is the same as systemic lupus erythematosus (SLE) in adults. The difference lies in that this form of SLE develops in childhood. It tends to affect young boys more often whereas SLE is more commonly seen in young female adults.