18th Century medicine: how a poisonous flower became a life-saver

Common foxglove (Digitalis purpurea)

As the 18th Century gave way to the 19th, the list of medications available to treat patients was very limited and many diseases were treated with non-pharmaceutical methods, such as bleeding and poultices.  Physicians generally practiced in cities where they could command a steady income, and apothecaries (pharmacists) treated those who did not have access to trained physicians.  In addition, there were often women who had learned traditional lore about herbs and their actions and would treat patients.  Not surprisingly, the trained physicians regarded these herbal healers (sometimes called witches) with disdain and discounted the ability of their possets and extracts to treat patients.  This is the story of what happened when a physician was open-minded enough to see what occurred  when an elderly herbalist treated one of his patients who was afflicted with congestive heart failure.

William Withering (1741-1799) was a traditional practitioner who had studied at the prestigious Edinburgh Medical School and was eventually named physician to Birmingham Hospital.  One of the frustrations of medical practice was the inability to treat dropsy, a now archaic term for edema, or swelling, and caused by heart failure, liver failure or kidney failure.  Cardiac dropsy, now called c0ngestive heart failure, was caused by the heart weakening and being unable to move the fluid load of the body as well as is necessary for health.  This failure would also limit how well the kidneys could excrete excess fluid as not enough blood was reaching them.  Patients would develop swelling in their ankles, which would become worse and worse until the heart failed completely or developed an irregular beat and the patient died.

When Withering’s patient was treated by the herbalist, he noticed that the patient improved.  He talked to the herbalist and found that she was using a concoction containing 20 different herbs for the dropsy.  He was an inquisitive physician, and tested the various ingredients alone until he deduced which one was actually active in cardiac dropsy:  an extract from the leaves of the common foxglove (digitalis pupurea).

Foxglove is a common and attractive garden flower, and was well-known to be highly poisonous if ingested; consuming just one of the upper leaves was enough to kill an adult human.  Withering carefully studied the dosage and action of the extract of foxglove leaves (called digitalin or digitalis) and found that it induced the heart to beat both more steadily and more strongly.  This improvement in the efficiency of the heart action helped reduce the swelling in patients and allowed them to return to a more normal life.  William Withering is thus credited with one of the major breakthroughs in medical therapeutics in 1785, but the road to medical history was not without a few bumps.  One of the patients that Withering had studied was referred by Withering’s friend Erasmus Darwin, and Darwin jumped in ahead of Withering in the publication of the results of the digitalis tests.  Fortunately, Withering had submitted his paper to the College of Physicians in London two months earlier, so he is given credit for the study.  Not surprisingly, his friendship with Erasmus Darwin did not survive.

As is well known in modern medicine, any medication can be toxic if taken in excess.  The dose that is high enough to be effective and low enough to not be toxic is called the therapeutic window.  Unfortunately, the therapeutic window for digitalis is very narrow so the dose must be very tightly controlled to produce the physiologic effect needed without harming the patient.  One of the difficulties with using digitalis that was extracted from foxglove in the 18th and 19th Centuries, was that the amount of the drug contained in the plant would vary with age of the plant and soil and weather conditions, so it had to be used very cautiously, and many herbalists avoided it.

Digitalis is still used to treat weak and irregular heart function and the activity of the medication is now standardized, but it must still be used with great caution.  Signs of overdose include nausea, vomiting, severe headache, diarrhea, hallucinations and other cerebral dysfunctions (included an unusual visual disturbance which causes everything to appear more yellow than normal).  The heart rate can be increased or decreased in an overdose, depending on how high the blood level is.  Newer medicines that have a more favorable therapeutic window are usually used today, but digitalis still has a place in the physician’s armamentarium.

Gout: From the 19th Century to the 21st Century

1799 caricature of gout by James Gillray

Gout is a metabolic problem that was very common throughout history and is mentioned in many historical novels (it is a great excuse for a grouchy personality if needed in a story).  The first known description was in Egypt in 2,600 BC, and it was well described by Hippocrates in ancient Greece, about 400 BC.  The uric acid crystals which are the cause of gout were first seen in 1679 by Dutch scientist Antonie van Leeuwenhoek.

This painful disease is caused by the buildup of uric acid crystals in  a joint, the base of the big toe (called podagra) being involved more than 50% of the time.  Other joints may also be affected, such as in the hands, elbows and knees, and other tissues can also be affected.  Uric acid crystals can deposit in the skin (gouty tophi), kidneys, tendons and other tissues.  High fever can also be associated with this problem.  The uric acid build up is caused by decrease in the breakdown of uric acid because of an enzyme deficiency, or increase in production because of dietary factors; in fact genetics and diet are both important factors for most people with clinical gout.  It has been known through history as “rich man’s disease” and “the king’s disease” because until the Twentieth Century only the wealthy ate enough of the foods that cause it.

Very simply, when uric acid crystallizes in joints, an immune response occurs and the subsequent inflammation makes for a hot, red joint.  Cold seems to be one of the precipitating factors, which might explain why it tends to involve the extremities such as toes and fingers and tends to begin at night.  The most common mimic of gout is septic arthritic (and infected joint), which a physician would suspect if the presumed gout does not respond to treatment.

In the Regency Era:

Physicians were aware that gout was caused by over-indulgence in elderly men and it was thought that red meat, rich food, and red wine, especially port wine, caused flares of gout.  Treatment of an acute gout attack included keeping the painful foot bandaged and elevated.  Bleeding or leeching would be used to decrease the inflammation and laudanum (tincture of opium) would be used for pain.  Various other treatments, such as soaking in mineral baths at spas such as those in Bath, England, as well as drinking the mineral water in the Pump Room were held to be helpful.  An acute attack of gout will resolve on its own in 5 to 7 days, so every physician has his own regimen that he felt worked, but none of these treatments, except dietary restriction, made a difference in the long term incidence of recurrent arthritis.

In the 21st century:

Modern medical science has learned that the precipitating factors for people predisposed to gout (which is most common in those with metabolic syndrome:  abdominal fat, type  diabetes, high blood lipids, and high blood pressure). The incidence of gout has doubled in the past twenty years, along with an increase in obesity and metabolic syndrome.  It is still more common in older men as well as post-menopausal women.

A patient who comes in with a red, hot joint will be evaluated with a blood test for blood uric acid levels.  If the patient clinically fits the diagnosis of gout, and the blood level of uric acid is high, then the diagnosis is made.  Unfortunately, half of patients with gout have normal uric acid levels, and other blood tests, such as the white blood cell count and sedimentation rate will be elevated for both gout and septic arthritis.  In these cases, a sample of synovial fluid (the fluid inside the joint space) is removed and examined microscopically for uric acid crystals (gout) or for bacteria (septic arthritis).

Treatment for the acute attack of gout is geared towards decreasing inflammation with non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen or naproxen, corticosteroids such as prednisone, or colchicine.  Pain relievers may be used to help get the patient through the acute attack.

Prevention is the crux of treatment for gout, because a patient who has had an episode has a high risk of having it recur, as well as having the risks of kidney and skin problems.  Patients should avoid drugs which can precipitate gout, such as aspirin, hydrochlorothiazide (a diuretic commonly used for hypertension), and long-term immunosuppressive drugs such as cyclosporine and tacrolimus (commonly used to prevent rejection after organ transplant).  Diet should avoid meat, fish, fructose, and alcohol.

Long-term drug treatment for those who have recurrent gout attacks include medications which inhibit the enzyme xanthine oxidase and thus decrease uric acid levels, or those which increase the amount of uric acid excreted by the kidneys. The choice of medications depends on how much uric acid the kidneys are removing, determined by a 24-your urine collection.  These drugs are generally not started until 2 weeks after the last acute attack because of a risk of worsening the attack.