When I use a word . . . Medical anniversaries in 2025: digitalis and the treatment of dropsy

A pharmacological first

This year one of the medical anniversaries we are celebrating acknowledges the first use by a physician of a preparation of digitalis to treat dropsies.

I say “by a physician” because foxgloves, and other herbal remedies that contain similar compounds, such as squill, which contains proscillaridin, had been used medically before William Withering first used Digitalis purpurea 250 years ago, in 1775, to treat what he called “dropsy,” but he was the first medically qualified practitioner to do so. I also say “to treat dropsies,” because although other physicians had previously used foxgloves, they had used them for other reasons.1

Cardiac glycosides in plants

The active ingredients in foxgloves, effective in dropsies, are cardiac glycosides, of which many exist in other plants. Here is a short list—the plant first and then the main glycoside that it contains:

● climbing oleander (Strophanthus gratus)—ouabain and G-strophanthin;

● hellebore (Helleborus niger)—helleborin;

● lily of the valley (Convallaria majalis)—convallotoxin;

● oleander or rosebay (Nerium oleander)—neriantin;

● purple foxglove (Digitalis purpurea)—digitoxin;

● squill (Urginea maritima or Scilla maritima)—proscillaridin;

● woolly foxglove (Digitalis lanata)—digoxin and lanatoside C;

● yellow oleander (Thevetia peruviana)—thevetin.

There are hundreds more—one incomplete list runs to 26 pages.2

Squill, for example, was used by the ancient Egyptians and was also mentioned in the Syriac Book of Medicines for, among other things, shortness of breath. It was also used in the 18th century by physicians such as Gottfried van Swieten (1733–1803) for treating dropsies.3 Withering himself used it, as evidenced by the frequency with which he mentioned it in his monograph—in about 30 cases in all.

Foxgloves before Withering

Foxgloves are mentioned in the Bury St Edmunds herbal Herbarium Apuleius Platonicus, from the early 12th century. There the foxglove was called Apollinaris, from the legend that Apollo discovered it and gave it to Aesculapius, but what it was used for is not clear. The 13th century Welsh Physicians of Myddvai also mentioned the use of foxgloves several times in their pharmacopoeia, but they incorporated foxglove leaves in local plasters to treat a range of growths, such as boils, abscesses, and tumours. In one case they used them to treat paralysis. Here is a typical recipe, for an abscess: “Take mutton suet, oatmeal, foxglove, and maiden hair; boil them till they become a thick mass. Apply it to the part, and it will draw it.”4 The heat must have helped.

The idea that foxgloves were useful for local treatment persisted in 17th and 18th century herbals. Nicholas Culpeper, for example, wrote that it was “frequently and familiarly used by the Italians to heal any fresh or green wound, the leaves being but bruised and bound thereon.” 5

Withering’s discovery

In his 1875 monograph, titled An Account of the Foxglove and Some of its Medical Uses: with Practical Remarks on Dropsy and other Diseases, Withering described how, in 1775, he had been shown a “family receipt [i.e. a recipe] for the cure of the dropsy.” He was also told that “it had long been kept a secret by an old woman in Shropshire, who had sometimes made cures after the more regular practitioners had failed.” Withering then commented that the medicine “was composed of twenty or more different herbs; but it was not difficult for one conversant in these subjects, to perceive, that the active herb could be no other than the foxglove.”

This statement might be considered akin to a modern physician’s conclusion that if, say, a mixture of 20 different peptides was seen to be effective in relieving the symptoms of multiple sclerosis, it was obvious that one or other of the peptides was the substance that had produced the beneficial effects. How did Withering know? Assuming, of course, that he was correct and not just lucky in picking on digitalis, since we do not know all the other ingredients of the old woman’s recipe.

Many 18th century treatments were based on herbal remedies, and Withering had been told that the recipe caused vomiting and purging. Perhaps he knew that whatever the other ingredients were, none of them, apart from digitalis, had those effects.

The first patient

In his monograph Withering described 163 cases, including three patients whom he treated twice on separate occasions. Most of them were patients whom he had treated himself; a few were treated by apothecaries under his direction.

Case I in the series was the only one that he recorded as having treated in 1775, although his account suggests that he had already treated others before starting to make notes. The patient was a man of about 50 years of age with a history of asthma, who had a large belly with perceptible fluctuation, presumably due to ascites. Withering gave him a decoction of the leaves of Digitalis purpurea, which made him very sick for several days, “during which time he made a large quantity of water.” His breath improved, his belly subsided, and he recovered after about 10 days. The presence of asthma in this case suggests the wheezing that can accompany left ventricular failure, so-called “cardiac asthma.”

Withering continued to use digitalis in cases of dropsy, as follows:

● 1776—four patients;

● 1777—eight patients;

● 1778—six patients

● 1779—eight patients, in addition to several children with scarlatina, i.e. scarlet fever;

● 1780—30 patients;

● 1781—25 patients;

● 1782—25 patients;

● 1783—15 patients, fewer than before because Withering’s ill health forced him to slow down;

● 1784—34 patients.

In all 153 patients, three of whom were treated twice on separate occasions, as well as several patients whom Withering treated in 1785 but withheld details about, since their courses had not completely run. To these, Withering added a further seven who had been treated by apothecaries in Birmingham Hospital under his direction, giving a total of 163 episodes.

Meanwhile other physicians had started to use digitalis as well, and several of them contributed further cases, 50 or so, to Withering’s account.

Dropsy

What did Withering mean by “dropsy”?

The word comes from the Greek word ὕδρωψ, a derivative of ὕδωρ, meaning water. Directly transliterated into English this became hydrops or hydropsy, which was then shortened to dropsy. The Oxford English Dictionary (OED) defines it as “A morbid condition characterized by the accumulation of watery fluid in the serous cavities or the connective tissue of the body.”6

Withering used the term to refer to a collection of fluid anywhere in the body, including such conditions as those we would now call ascites or hydrocephalus (terms he also used), ovarian cysts, and pleural effusions, not just peripheral oedema, which is the condition that the term “dropsy” generally conjures up today.

In fact, most of the people whom Withering treated with digitalis had peripheral oedema with or without ascites, probably due to heart failure, either left ventricular failure, associated with what he called “asthma,” or congestive cardiac failure. In most of those cases digitalis produced a good diuresis and relief of oedema.

In a few cases of ovarian cyst, acute renal failure, and postpartum swelling of the legs, presumably due to venous thrombosis, digitalis was ineffective, as it was in patients with ascites associated with jaundice or a history of heavy drinking.

Digitalis after Withering

Although Withering carefully described the circumstances in which digitalis would be expected to be effective and those in which it would not, others failed to follow his advice and were unsuccessful. One notable case was that of John Coakley Lettsom (1744–1815), a distinguished physician and founder of the London Society of Medicine.7 Lettsom used digitalis in inappropriate cases and in the wrong doses. Of eight patients whom he treated, only three benefited and all suffered some degree of toxicity. Withering wrote scathingly to Lettsom: “I complain of the treatment this medicine has had in London ... I must suppose that he [sc. Lettsom] had forgotten what I had written .... [otherwise] he would hardly have thought it necessary to have published more instances of what I had stigmatized as bad practice.”

During the 19th century digitalis was used for many conditions for which it was not appropriate, on the basis of false logic. For example, it was used to treat any condition accompanied by a fever, because fevers caused an increased heart rate and digitalis slowed the heart rate.

It wasn’t until the late 19th and early 20th centuries that careful studies by investigators such as James Mackenzie (1853–1925), Arthur Cushny (1866–1926), and Karl Wenckebach (1864–1940) established the appropriate use of digitalis in cardiovascular medicine.1

A final thought

Withering’s understanding of the underlying physiology of the conditions in which he found digitalis to be effective was too rudimentary to allow him to develop a complete theory of how to use it. Nevertheless, little by little, over the 10 years between discovery and publication, he improved his practice by identifying the types of which it was most likely to be effective, how to formulate the medicine, and how to avoid or minimise the risk of toxicity by titrating the dosage to best effect. His insights paved the way for its modern use.

Few of the events whose medical anniversaries we are celebrating this year have had such a lasting impact as Withering’s discovery of the action of digitalis in treating dropsy.