Dedicated to the memory of Professor Simon Byl (1940-2018),

Belgian Hellenist at the Université Libre de Bruxelles.

On gout and joint diseases in the Corpus Hippocraticum

he knew and taught the most.

Introduction

“Gout (ποδάγρα/podagra): an illness which may appear in the upper limbs (cheiragra) or more commonly in the lower limbs (podagra) and is characterized by a red, hot swollen joint at the base of the big toe; it was thought to be caused mainly by an excess of yellow bile” [1].

The history of gout parallels that of the history of medicine. Gout is the oldest recorded inflammatory form of arthritis to affect humankind, with roots stretching back to 2640 BCE.  Kettridge and Downs by examining in 1957 an Egyptian mummy discovered a urinary stone dated 7000 years ago. Its nucleus was made of uric acid [2, 3].

Gout is a common, complex, systemic and well-studied form of chronic inflammatory arthritis in adults, for which many therapeutic options are now available. It is due to the deposition of sodium monourate crystals in peripheral joints and periarticular tissues driven by hyperuricemia (at or above 6.8 mg/dl). Hyperuricemias may result from: (i) renal overload (overproduction or extrarenal underexcretion due to dysfunctional variants of transporters in the gut and intestine); (ii) renal underexcretion; or (iii) a combination of both renal overload and renal underexcretion.

The kidney can be both a cause and a target of hyperuricemia (calculi, renal disease and its progression). At onset, gout affects one joint, frequently the metatarsophalangeal joint of the great toe that is self-limited, and heals in 2 weeks. Flares subsequently affect two or more joints. Gout becomes a chronic disease when tophi and joint erosions appear. Risk factors include conditions with high cell turnover, as well as a high intake of purine-rich foods (such as meat, crustaceans, alcohol, and fructose-containing syrup). Prevalence increases with age and women become hyperuricemic after menopause [4, 5].

Gout known as “the unwalkable disease” (Hippocrates), for which protection was granted by the Goddess Artemis Podagra (Clemens Alexandrinus), a disease with a heritable trait recognized by Galen, and by Aretheus. Soranus of Ephesus was the first who described tophi, later widely discussed by the Byzantine physician Alexander of Tralles (525-605 AD) who illustrated the virtues of hermodactyl. Its name derives from the Latin word gutta (meaning drop to indicate the drop of a humour in excess precipitating in the joint).

 

The goal of this study

This study aims to shed light on the contribution of Hippocrates to the knowledge of gout. It is a part of a program [6-9] on establishing the timeline of Podagra from the Corpus Hippocraticum to Renaissance, encompassing no less than 25 authors (Table 1).

Gout was present in Greece since 1700 BC [10]. Many mythological Greek heroes suffered with the gout: Priam of Troy, Achilles (as suggested by Lucian of Samosata), Bellerophon, Oedipus King of Tebe. Thus we are not surprised by its significant presence in the Corpus Hippocraticum.

Hippocrates (460–370 BCE)

Teophrastus (371-287 BCE)

Nicander (2nd century BCE)

Celsus (25 BCE–50 CE)

Aretaeus of Cappadocia (1st half, 1st century CE)

Scribonius Largus (1st century CE)

Dioscorides of Anazarbus (1st century CE)

Anonymus Parisinus (1st century CE)

Galen (c. 129–c. 216 CE)

Lucian of Samosata (c. 120–after 180 CE)

Oribasius (c. 320–400/403 CE)

Severus Iatrosophista (5th century CE)

Theodosius the Philosopher (5th century CE)

Jacobus Psychrestus (5th century CE)

Aëtius (mid-5th to mid-6th century CE)

Caelius Aurelianus (6th century CE)

Evagrius Scholasticus (6th century CE)

Paulus of Aegina (625–690 CE)

Rhazes (c. 854-925/935)

Avicenna (980–1037 CE)

Michael Psellus (1018–1078 CE)

Constantinus Africanus (floruit 1020–1087 CE)

Matthaeus Platearius (d. c. 1161 CE)

Demetrios Pepagomenos (13th century CE)

Nikolaus Myrepsos (floruit 1240–1280 CE)

John Actuarius (end of the 14th century CE)

Table 1. On the Timeline of Podagra from the Corpus Hippocraticum to the Renaissance.

 

Hippocrates’ short biography

Hippocrates (c.460-c.370), the father of medicine, was born in the age of Pericles, a bright period of prosperity, science and arts in Greece. He was born in Kos near the coast of Asia Minor. In the heart of the city, an Oriental Plane tree still stands, said to have provided shade for his public lectures.

“His contemporaries constituted perhaps the most remarkable galaxy of Genius ever known. They included Pericles, the statesman builder of Acropolis, the poets and playwrights Aeschylus, Sophocles, Euripides, Aristophanes, and Pindar, whose nephew was one of Hippocrates’ students, the philosopher Socrates with his disciples Plato and Xenophon, the venerable father of history (Herodotus) with his youthful rival Thucydides, the sculptor Phidias, and Chrysippus and Euryphon of Cnidos. Hippocrates’ writings are free of the prevailing superstitions which associated the cause of disease with divine wrath for sin, and much of contemporary therapy was magic” [11].

His grandfather (Hippocrates), and his father Heraclides – priest doctors – were descendant of Asclepius and passed down knowledge and skill to the family members, thus Hippocrates received medical training from them. Heleni Tsiompanou and Spyros Marketos [12] in a paper that appeared posthumous, after Marketos death, point out that Plato (Politics) calls him  ‘The great Hippocrates, the wise physician’,  whereas Aristotle calls ‘the famous physician of Kos’ (Protagoras).

Tsiompanou and Marketos also stress the fact that Hippocrates broke with the tradition of keeping the expertise in medicine within the family. He started the School of Kos where fellows received instruction for a fee [12]. We know very little about Hippocrates’ life. Probably he successfully diagnosed and treated, as court physician, King’s “love-sickness” in Macedonia, and cured Democritus’ madness in Abdera.

“Between 440 BC and 360 BC Hippocrates and his pupils wrote a number of medical  treatises,  only 60 treatises were saved from the fire that destroyed the Great Library at Alexandria. The surviving text were published under the title of Corpus Hippocraticum. Some of the texts may not be Hippocrates’own writings but all display his influence”. He died in Thessaly, in Larissa  [12].

He broke with the oral tradition and collected detailed reports of patients he cared for. He also introduced the need to review and analyze all pre-existing data. According to Hippocrates  ‘Full discovery will be made, if the inquirer be competent, conduct his research with knowledge of discoveries already made’ (Ancient Medicine).

 

Gout in the Corpus Hippocraticum

Simon Byl pointed out [13] that in the Corpus Hippocraticum joint diseases have been described as “arthritis, arthritika, arthron, ponoi, oidemata, and eparseis of the joints, kedmata and ischias”.

These conditions are attributed to an accumulation of phlegm linked to excessive food consumption. However, the text asserts “arthritis is not lethal” (On Diseases).

The Corpus Hippocraticum also differentiates gout from other joint diseases such as acute articular rheumatism and ankylosing spondylitis. Podagra (gout affecting the foot) was identified as the most severe form of joint disease, characterised as a chronic condition. It was noted to affect younger individuals more frequently than the elderly [13]. Gout is mentioned 20 times in the Corpus Hippocraticum, with specific references to podagra appearing 5 times. The terms podagrao and podagriao (indicating affliction with gout) are used 1 and 4 times, respectively, while podagrikos (relating to gout) appears 10 times. Additionally, Simon Byl observed that the corpus contains 314 references to the word arthron (joint). In the Corpus Hippocraticum, podagra associated with tophi is described as nearly incurable [13]. Even the most skilled physicians were unable to provide relief and cautioned against the use of drugs to relieve pain.

In Aphorisms, Hippocrates mentions gout 5 times [14].

1. “Eunuchs do not take gout, nor become bald” (VI, 28);
2. “A woman does not develop gout unless her menses be stopped” (VI, 29);
3. “A youth does not get gout before sexual intercourse”(VI, 30);
4. “In gouty affections inflammation subsides within 40 days” (VI, 49);
5. “Gouty affections become active in Spring and Autumn” (VI, 55).

However, the importance of the seasons was rejected by many authors of antiquity including Galen, Celsus and Seneca. “Hippocrates also learned by experience that an excess of wine could exacerbate or even cause gout, as did an excess of sexual activity and that the disease was more severe in the inherited form than in those who contract it by their unsafe lifestyles” [13].

In Affections of the parts, the chapter on Stranguria, sciatica and gout reads (VIII, 32) reads:

“Gout is a disease that induces burning pains in the joints; it comes to paroxysms, now in one limb, now in the other, where it causes ailments of variable severity. Cool compresses will be applied where there is pain, the intestines will be cleansed of the materials found there by giving enemas and administering a suppository; use for drink and liquid food what seems best suited. Once the pain has calmed down, purge him and then have the cooked whey and donkey’s milk taken. Gout is caused by phlegm and moving bile, which rush over the joints”.

“It can be short, acute and is not deadly. It is more frequent in youth than in old age.

Pain in the feet [podagra] is the most violent of all, most long and resistant. It is the effect of a defect in the blood altered in the small veins by the pituitary gland and bile; the disease is all the more fixed and difficult to heal if it establishes itself in small veins and if the violence exerted on many nerves and bone parts is serious. It is treated with the same means used or joint pain. It lasts for a long time, is very painful but is not deadly. Whenever the pain fixes in the fingers, the burning fire is placed above the joint using raw flax”.

In Prognostics (Book 1, Chapter 4, 19), age and conditions required to recover from gout are discussed as for gouty persons, Hippocrates says:

“It is my opinion that the old, those who have lumps in the joints, which leads to a painful life, who are habitually constipated, all these people, I say, cannot absolutely be cured, at least with no human means that I am aware of. They feel relief from the work of the viscera when it occurs, and in general, the downward colliquation of the humours benefits them. The gouty person who is young and free from knots in the limbs, active, vigorous, whose abdominal functions are regular, capable of subjecting himself to the method prescribed by the doctor, can hope for recovery”.

“These complaints are better removed by the occurrence of dysenteries or other evacuations downwards. His principal remedies are purgatives administered by the mouth or by injection, and local applications of cooling nature, and even pouring cold water on the foot. When the pain of the gout becomes fixed in a joint, it directs us to burn it with crude flax”.

In Prorrhetic II, where tophi are described as epiporomata, we are made aware of the difficulties of healing the elderly who have lumps in the joints:

“Elderly gouty sufferers who have tophi around the joints and adopt unhealthy lifestyles and whose bellies are dry are beyond the possibility of the human art… they can’t be healed, at least not by any human means I am aware of.  They benefit from evacuations when they occur.

The young gouty sufferer free of tophi in the joints, who adopts a healthy alimentation, is vigorous and practices exercise, has regular bowel movements, and is vigorous and active and accepts to follow the prescription of the doctor, he can hope to be healed”.

 

Treatments

Treatment was based on appropriate nutrition, abstention from wine, drastic purges, preferably black hellebore (Helleborus niger L.). An attack of dysentery represented the best natural remedy for gout. Burning the area above the joints with raw flax was also a possibility.

“Both cold and hot water poured abundantly over those who have no painful ulcerative tophi are very useful”.“Cold water moderates the pain, numbing the part, since mediocre numbness is a sedative. Hot water attenuates and softens; lotions and baths are used in the case of gout” (Treatise on Liquids).Salt, the ubiquitous simple, has a crucial role in treating podagra and its pains. “Apply salt on the swollen parts, the salt having been mixed with water in a paste. The paste is left in situ for three days, and after its removal, the parts shall be rubbed with red saltpeter mixed with honey for the subsequent three days” (Disease of Women I).

The paper can be concluded with a passage from Affections (first quarter of the fourth century BCE):

 “Podagra is the fiercest, longest and most tenacious of all joint diseases; it occurs when blood present in the vein has been contaminated by bile and phlegm, and since these are the thinnest and tightest vessels of the body (the same applies to the neighboring tendons and bones), pain is thus the most intense in this area. The same cure as used for arthritis is suitable in this case; the disease is long and painful, but not lethal. If the pain does not subside in the big toes, then one will cauterize the toe’s vessels above the condyle and this cauterization will be performed with raw flax” [13].

 

Acknowledgements

We thank Dr. Rosaria Di Martino, Head of Centro Servizio del Sistema Bibliotecario di Ateneo Università degli Studi della Campania Luigi Vanvitelli and Coordinator Biblioteche di Ateneo, for her expert assistance in literature searches. We are also indebted to Professor Joseph Sepe for editing the English version of the manuscript.

 

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