Lupus is a complex disease, and its history, which spans centuries, is just as complex – an amazing story of discovery from 400 BC to the present.  Read on for a brief outline of the history of lupus.

• Introduction
• The History of Lupus
• The Classical Period
• The Neoclassical Period
• The Modern Period
• In Conclusion

Introduction

Lupus has been with us for a very long time, even though, in many ways, it seems like a relatively “new” disease.  That is because there is still so much about lupus that is not known.  Since lupus affects everyone differently, and it can mimic so many other conditions, it has taken medical science a very long time to fully recognize lupus as a definable condition and all the symptoms that it can cause … much less its own cause!   The following is a brief history of lupus – a story that reflects our changing understandings of health, illness and the immune system itself.  It is a process that continues to this day towards better treatments … and ultimately a cure!

The History of Lupus

The history of lupus is often divided into three time periods – each based upon how lupus as a disease was defined and treated at the time.

• The Classical Period spans thousands of years, from the first descriptions of lupus as a skin condition in ancient Greece and Egypt to the mid-19^th century –  when dermatology was the  field of medicine to research and treatment the disease.
• The Neoclassical Period begins in 1872 when lupus was finally identified as a systemic condition of the entire body, not just related to skin rashes and ulcerations.
• The Modern Period starts in 1948 with the discovery of the first lupus erythematosus cell (LE cell), which led to the understanding of lupus as an autoimmune condition and the subsequent revolution in treating the disease.

The following sections are an overview of each period with some interesting facts from each!

The Classical Period (400 BC – 1856 AD)

Lupus was first described as only a skin condition – since the most obvious external symptoms of the disease were the only ones noticed.  Because these skin ulcers resembled the wounds from the bite of a wolf, the condition was called “lupus,” which is Latin for “wolf.”   Of course, there have always been many causes for skin lesions, such as leprosy, tuberculosis, syphilis, and skin cancers. For much of this period, lupus was thought to be a form of tuberculosis.  That misunderstanding lasted until the discovery that bacteria caused tuberculosis, but not lupus.

As with other diseases before modern science, people living with lupus were often believed to have some moral failing and therefore blamed for their own suffering … adding insult to injury and making things worse.  Eventually, as medicine and specifically the field of dermatology developed in the mid-1800’s, lupus was better distinguished from other conditions and it was even seen that different forms of lupus could be identified.  This entire time period was quite long and advances came very slowly.

Some important people and dates during this time:

• In 400 B.C., the Greek physician Hippocrates described what is thought to be the first case of lupus as a skin ulcer. However, he used the term herpes esthiomenos, which means “gnawing skin disease.”
• The earliest known use of the term “lupus” appeared in a 10th-century account of Eraclius, the Bishop of Liege, who, the story goes, was healed when praying at the shrine of St. Martin.
• The 12^th century physician, Rogerius Frugard, an Italian surgeon, was the first to coin the term “lupus” in the medical sense.
• In 1230 AD, Rolando de Parma, a pupil of Rogerius Frugard, described two forms of lupus:  lupula (or “small she-wolf), referring to lesions on the lower limbs, and noli me tangere (meaning “don’t touch me”) for lesions on the face. It took another 300 years before the facial rashes alone were proven to be associated with lupus.
• In 1790, lupus is listed in Dr. Robert Willan’s book, On Cutaneous Diseases. This was the first atlas of skin diseases and contained the first illustration of a patient with lupus lesions of the face.
• In 1846, Ferdinand von Hebra, a Viennese physician, was the first to describe the distinctive facial rash of lupus as a “butterfly.” Hebra was also the first to describe lupus as a chronic condition that could remain dormant for years.
• In 1850, French dermatologist Pierre Cazenave was one of the first to describe lupus in a truly modern way. He coined the term lupus erythemateux (which later became erythematosus) and was the first to document both discoid lupus and that alopecia (hair loss) was a symptom.

The Neoclassical Period (1872 – 1948)

This period began in 1872 when Morizi Kaposi, a Vienna dermatologist and a student of Dr. Hebra, published a paper titled, “New Contributions to the Knowledge of Lupus Erythematosus.”  In it, he was the first to describe lupus as a systemic disease, that it was life threatening and that it often affected young women.  He also grouped lupus with inflammatory diseases like arthritis and pleurisy.  This began a whole new approach to diagnosing and treating lupus as much more serious than just the relatively benign skin conditions that were first seen.

In 1895, Sir William Osler was the first to identify how lupus could affect internal organs as well as the skin.  He added the word “systemic” to lupus erythematosus to distinguish it from discoid lupus erythematosus – creating the term that we use today – systemic lupus erythematosus (SLE)!  He was also one of the first to document “lupus flares” and describe how SLE could affect the nervous system.

 

Modern Period (1948 – present)

This period marks the use of modern scientific methods and technologies in identifying and treating all forms of systemic lupus erythematosus and as a condition specifically within the field of rheumatology.

The key discovery happened relatively recently, in 1948, when Malcolm McCallum Hargraves, a physician and histologist at the Mayo Clinic, found a strange cell in bone marrow that he would eventually call the LE cell (lupus erythematosus cell or Hargraves cell).  It was a type of white blood cell (WBC), which only occurred in SLE patients.  At that time, these LE cells became the most important markers for diagnosing lupus – but of course, it would require a bone marrow biopsy to make that diagnosis.  Also, since WBC’s are central to our immune system, this began the pivot to lupus as an autoimmune disease … and that meant entirely new directions for research and new kinds of treatment!

Important discoveries and milestones include:

• In 1951, the antimalarial drug, quinacrine, was first used to treat discoid lupus erythematosus.  This would lead to the use of hydroxychloroquine (Plaquenil), which would become one of the most important medications in the treatment of lupus – changing the lives of so many even today.
• In 1952, researchers Kendal and Hench discovered cortisone, which would lead to the corticosteroids that are so also commonly prescribed today.
• In 1954, Dr. Peter Miescher discovered antinuclear antibodies (ANAs), which would lead to the recognition that lupus is largely autoantibody driven. ANAs have since become an important and relatively easy diagnostic test for SLE – much easier than a bone marrow biopsy.
• In 1971, the American College of Rheumatology established the first clinical and immunological criteria to help identify lupus based on a better,  and wider group of symptoms.
• In the late 1990’s, Genentech’s CellCept (mycophenolate mofetil), an immunosuppressant developed for organ transplant patients, was introduced to treat severe SLE.
• In 2011, belumimab (Benlysta), a GSK’s biologic, was the first drug specifically approved by the FDA and EMA to treat systemic lupus erythematosus!  This opened the door to the promise of more targeted medications, with fewer systemic side effects.
• In 2021, Aurinia’s voclosporin (Lupkynis), an oral medication, was given FDA approval for treating lupus nephritis – the first to for that specific condition of SLE.
• Later that same year (2021), the FDA approved Saphnelo (anifrolumab-fnia), a biologic from AstraZeneca,  becaming only the third drug in history to be approved for treating some forms of SLE.
• The rate of discovery continues to accelerate!

In Conclusion

The history of lupus is not only a story about the disease, but a story about the lives and health of countless individuals, who have lived with lupus and who are living with it now.  From this long, historical perspective, it may seem like medical advances regarding lupus have been excruciatingly slow – and that is true.  Yet, think of all the centuries of careful observations by physicians and the research of dedicated entrepreneurs in labs throughout history.  These have not only brought us to the point where new medications and therapies, such as immunosuppressants and biologics have begun to improve the lives of so many people in our community, but they also bring the promise of much better treatments in the very near future.  There is not yet a cure for lupus, however medical research continues to accelerate and the future for lupus is very hopeful!

 

References

Benedek, T.G. (1993). History of Lupus. Kiple K. F. (Ed.), The Cambridge world history of human disease (1-14). Cambridge University Press.  Retrieved from  https://eu-ireland-custom-media-prod.s3-eu-west-1.amazonaws.com/UKMEAEU/eSample/9780323479271-sample-chapter.pdf

Felten, R. Lipsker, D, Sibilia, J. Chasset, F., & Arnaud, L. (2020). The history of lupus throughout the ages. Journal of the American Academy of Dermatology,  Retrieved from https://www.sciencedirect.com/science/article/abs/pii/S0190962220307726

Hepburn, A. L. (2001) The LE cell. Rheumatology, 40(7), 826-827. https://doi.org/10.1093/rheumatology/40.7.826

Hickman, R.J. (2018) A historical look at the characterization of lupus as a systemic disease. The Rheumatologist.Retrieved from https://www.the-rheumatologist.org/article/a-historical-look-at-the-characterization-of-lupus-as-a-systemic-disease/?singlepage=1

Norman, R. A. (2016) The history of lupus erythematosus and discoid lupus: From Hippocrates to the present. Lupus Open Access, 1(1), 1-10. Retrieved from https://www.longdom.org/open-access/the-history-of-lupus-erythematosus-and-discoid-lupus-fromhippocrates-to-the-present-Lupus-1000102.pdf

 

 

Author: Greg Dardis, MS

Professor Dardis was formerly the Chair of the Science Department at Marylhurst University and is currently an Assistant Professor at Portland State University.  His focus has been human biology and physiology with an interest in autoimmunity.

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