What are the Causes, Pathophysiology and Treatments of Lupus

 by Hamish Orr

Systemic lupus erythematosus (lupus) is an autoimmune disease whereby the body attacks many of the tissues around the body, mistakenly. The extremity of symptoms varies from person to person and can be both mild and severe. The common symptoms usually associated with lupus are joint pain and swellings, fevers, generalised pain and malaise as well as fatigue. A facial rash is also commonly associated. Given how general the symptoms are it can often be mistaken for other illnesses. It is for this reason when medical professionals are unsure of a diagnosis and lupus symptoms are present, it is normally considered as a differential diagnosis. (A possible diagnosis given the history and physical examination).

The exact cause of Lupus is unknown, as the body produces antibodies against the self protein antibody which is commonly found in the nucleus of cells. The antibodies attacking this protein found in cells throughout the body is a key cause of lupus, however, the reason the antibodies are produced against this self protein is less well understood. 

Another potential cause of lupus is a clearance deficiency. A clearance deficiency is the inability of phagocytic activities and lysosomal degradation of the cell components. If cells have not been cleared after apoptosis, they will be found by chemotaxis of macrophages and other antigen-presenting cells as during apoptosis ‘find me signals’ are released by the cell. The antigens from the cells are then presented and the antinuclear antibodies (such as anti-self-proteins) are released. 

Lupus can be diagnosed by testing for the presence of antinuclear antibodies (ANA). If ANA is negative Lupus can be ruled out however if it is positive then we cannot guarantee that it is caused by lupus as it can be caused by other diseases of connective tissues. Some antibodies are more commonly found in Lupus than other diseases such as the anti-double-stranded DNA antibodies (anti dsDNA). Which are found in approximately 70% of Lupus cases but only in 0.5% of people without lupus. In higher concentrations, anti dsDNA indicates that the disease may be in a’ flare up’. 

According to the American college of rheumatology, to make a diagnosis of Lupus, 4 of 11 symptoms would need to be present simultaneously or serially on two separate occasions. Examples include the rash on cheeks (malar rash), oral ulcers, Arthritis, photosensitivity, haemolytic anaemia, leukopenia, neurological disorders such as seizures and psychosis as well as protein found in the urine. 

The general treatment of lupus is in reducing the extremity of the flares of the disease with treatments such as corticosteroids, NSAIDs and disease-modifying anti-rheumatic drugs such as hydroxychloroquine and methotrexate. Hydroxychloroquine is an anti-malarial drug that reduces the chemotaxis of antigen-presenting cells and induces apoptosis of inflammatory cells, reducing the presence of proteins such as anti-self-proteins. In more severe cases of the disease immunosuppressive drugs can be offered as a means of controlling the disease. Kidney transplants might be needed as end-stage kidney disease is a common side effect of lupus. 

Although there is no cure for lupus, many with the disease can go on to live relatively symptom-free lives and reach a normal life expectancy, which is a huge improvement since in the past lupus was considered to be a death sentence with only 10% dying per year. This goes to show how far medicine has come.