"I confidently affirm that the greater part of those who are supposed to have died of gout, have died of the medicine rather than the disease - a statement in which I am supported by observation."[7]

"For humble individuals like myself, there is one poor comfort, which is this, viz. that gout, unlike any other disease, kills more rich men than poor, more wise men than simple. Great kings, emperors, generals, admirals, and philosophers have all died of gout. Hereby Nature shows her impartiality: since those whom she favors in one way she afflicts in another - a mixture of good and evil pre-eminently adapted to our frail mortality."[8]

Acute diseases, such as fevers and inflammations. he regarded as a wholesome conservative effort or reaction of the organism to meet the blow of some injurious influence operating from without; in this he followed the Hippocratic teaching closely as well as the Hippocratic practice of watching and aiding the natural crises. Chronic diseases, on the other hand, were a depraved state of the humours, mostly due to errors of diet and general manner of life, for which we ourselves were directly accountable. Hence his famous dictum: "acutos dico, qui ut plurimum Deum habent authorem, sicut chronici ipsos nos" ("I say what hurts, most over which God has authority, just like we ourselves over the chronic").

Sydenham’s most famous and enduring work was his 1683 treatise on gout , which took the art of clinical observation to a personal level.  Having suffered from frequent and debilitating attacks of gout from the age of thirty, he gave a descriptive first-person account of the affliction:

"The regular gout generally seizes in the following manner: it come on a sudden towards the close of January, or the beginning of February, giving scarce any sign of its approach, except that the patient has been afflicted, for some weeks before, with a bad digestion, crudities of the stomach, and much flatulency and heaviness, that gradually increase till the fit at length begins; which however is proceeded, for a few days, by a numbness of the thighs, and a sort of descent of flatulencies through the fleshy parts thereof, along with convulsive motions; in the day preceding the fit the appetite is sharp but preternatural.  The patient goes to bed, and sleeps quietly, till about two in the morning, when he is awakened by a pain, which usually seizes the great toe, but sometimes the heel, the calf of the leg, or the ankle.  The pain resembles that of a dislocated bone, and is attended with a sensation, as if water just warm were poured upon the membranes of the part affected; and these symptoms are immediately succeeded by a chillness, shivering, and a slight fever…."

He also described the physical and emotional comorbidities of gout, again incorporating his own experience:

"Moreover the patient is likewise afflicted with several other symptoms; as a pain in the hemorrhoidal veins, nauseous eructations, not unlike the taste of the ailment last taken in, corrupting in the stomach, happening always after eating any thing of difficult digestion, or no more than is proper for a healthy person, together with a loss of appetite, and a debility of the whole body, for want of spirits, which renders his life melancholy and uncomfortable."

"But what is a consolation to me, and may be so to other gouty persons of small fortunes and slender abilities, is, that kings, princes, generals, admirals, philosophers, and several other great men, have thus lived and died.  In short, it may, in a more especial manner, be affirmed of this disease, that it destroys more rich than poor persons, and more wise men than fools; which seems to demonstrate the justice and strict impartiality of Providence, who abundantly supplies those that want some of the conveniences of life, with other advances, and tempers its profusion to others with equal mixture of evil; so that it appears to be universally and absolutely decreed, that no man shall enjoy unmixed happiness or misery, but experience both: and this mixture of good and evil so adapted to our weakness and perishable condition, is perhaps admirably suited to the present state."

In modern medicine, gout has a known association with coronary artery disease, kidney stones, and sleep apnea. Sydenham is known to have had bouts of clinical hematuria and gout, and his death in 1689 is thought to have been related to both.  Given what is now known about the comorbidities of gout and its relationship to diet and sedentary lifestyle, it is very possible that he also suffered from metabolic disturbances that affected his heart, lung, and kidneys.