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15.04.2020 Article

Understanding lupus, the disease treated by chloroquine and hydroxychloroquine

By Utibe Effiong & Akpabio Akpabio & Ekemini Hogan - The Conversation
A chemist displays hydroxychloroquine tablets in Kolkata,India 

 - Source: Photo by Debajyoti Chakraborty/NurPhoto via Getty Images
LISTEN APR 15, 2020
A chemist displays hydroxychloroquine tablets in Kolkata,India - Source: Photo by Debajyoti Chakraborty/NurPhoto via Getty Images

Chloroquine and hydroxychloroquine – until recently two fairly obscure drugs in the minds of the general public – have hit the headlines of late . This followed controversial statements by US president Donald Trump that they could be used to treat COVID-19. The US Food and Drug Administration has subsequently approved the drugs for “compassionate use” in the treatment of the new coronavirus infection.

But the jury is still very much out on the efficacy of the drugs. Trials still need to be conducted and these have been initiated by the World Health Organisation.

Chloroquine is a synthetic drug introduced in the 1940s. It is a member of an important series of chemically related agents known as quinoline derivatives. Hydroxychloroquine is a related compound that was introduced in 1955.

Both drugs are used in the treatment of tropical diseases such as malaria and amebiasis, a parasitic disease also known as amebic dysentery. They are also useful in the treatment of various skin conditions and diseases of the joints such as rheumatoid arthritis and lupus.

Lupus is an autoimmune disease that can affect almost any organ of the body. The two drugs are relatively cheap and are the “go to” treatments for different forms of lupus.

Myths and realities around lupus

Over the last few decades there's been increasing evidence of a steady rise in the frequency of autoimmune diseases. Global estimates indicate a prevalence of 7.6%–9.4%. Collectively, these diseases affect more than 24 million people in the US . The Lupus Foundation of America estimates that 1.5 million Americans, and at least five million people worldwide, have a form of lupus.

In the US lupus affects four times more people of African descent than caucasians. However in Africa, it remains grossly under-diagnosed . Several theories have been put forward over the years in an attempt to explain this.

For example, towards the end of the 20th century, there was a popular theory that the number of lupus cases progressively increased as one moved away from equatorial Africa. The prevalence gradient theory suggested that lupus was practically nonexistent in Africa. It was debunked at the turn of the century.

Another popular theory at one point in the 20th century was that environmental factors, such as vitamin D deficiency in the West, accounted for the disparity between the occurrence of lupus on the African continent compared to the US.

Other theories held that the immune response to endemic infections as well as the widespread use of chloroquine for malaria treatment protected against the development of the autoimmune disease.

But in the last decade improved knowledge about the diagnosis of lupus and other autoimmune conditions in sub-Saharan Africa has upturned these theories. Nevertheless, many cases still remain undiagnosed due to the dearth of rheumatologists in the region.

Similarly, very little attention is being given to lupus among African children. This is particularly true in Nigeria. Pediatric lupus represents 10% - 20% of all cases of lupus and is associated with higher disease severity, greater organ damage and increased overall mortality.

Last year a new set of criteria to improve diagnosis and early treatment was published. Unfortunately, it could lead to under-diagnosis in less developed settings where the baseline antibody screening test is unavailable or too expensive.

The dangers

Lupus affects people in different ways. It is a heterogeneous condition, which may involve almost all organs and tissues. Possible clinical manifestations include – but are not limited to – oral ulcers, skin rash, arthritis, anaemia, kidney disease and seizures.

Nonspecific symptoms such as fever, malaise, fatigue, muscle aches, headache, as well as loss of appetite and weight also occur frequently. If left untreated, lupus can damage the kidneys and other organs. Higher rates of morbidity and mortality are associated with kidney and nervous system involvement.

Overall, kidney failure is known to be more severe in people of African origin. Among children, lupus associated kidney disease affects 20%-80% of patients with juvenile-onset lupus and 10%-50% progress to end-stage renal disease requiring dialysis.

The double tragedy of lupus and kidney failure is not just about higher mortality rates, but includes increased morbidity and treatment costs. Treatment still remains out of reach for most patients.

Another tragedy of lupus is that it mainly affects women of reproductive age thus weakening the core of many families. Sick patients cannot cater for themselves or their loved ones.

Current concerns

There are concerns on a number of fronts.

The first concerns the two types of antimalarials most often prescribed for lupus – hydroxychloroquine and chloroquine. They are mostly given for mild forms of lupus involving the skin and joints. In moderate to severe lupus, steroids and immunosuppressive agents are usually added to retard disease progression.

The fact that the two drugs are being touted as a cure for COVID-19 has led to growing concern that chloroquine and hydroxychloroquine will soon become unavailable because they are being hoarded or diverted to treat patients in the developed world.

Secondly, lupus patients are at higher risk of COVID-19 because of their weakened immune system and this may lower their chances of recovery.

Improved awareness, early diagnosis and prompt commencement of lupus treatment remain the best way to prevent serious complications like kidney failure. Greater access to care and increased health research funding, especially in poorer countries, will reduce the burden of lupus at the population level.

Chloroquine and hydroxychloroquine remain key therapies for lupus patients. As the world battles to overcome COVID-19 there is need to ensure continued availability of antimalarials to patients whose lives literally depend on them.

The authors do not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and have disclosed no relevant affiliations beyond their academic appointment.

By Utibe Effiong, Board Certified Internal Medicine Physician and Public Health Scientist, MidMichigan Health, University of Michigan And

Akpabio Akpabio, Rheumatologist/Physician, The University of Uyo And

Ekemini Hogan, Paediatrician/Clinical Lecturer, The University of Uyo

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