Sunday, October 13, 2013

IBD in the Age of Medicine

Historical Treatment of IBD:  Medical Treatment Overtakes Surgery

In 1859, Sir Samuel Wilks characterized Ulcerative Colitis as being differentiated from dysentery.  In 1932, Dr. Burrill Crohn, along with Dr. Leon Ginzburg and Dr. Gordon Oppenheimer, described a regional ileitis with granuloma formation, which would later be tagged “Crohn’s Disease”.(1)  The last article covered the treatments up through the turn of the century (1900) – this posting will cover the other historical treatments up through the present regimen. 

1950’s


The primary treatment for regional ileitis was surgical intervention, however there were other proposed treatments that were put forth.  On the moderate side, Cooke puts forth a regime that treats the symptoms (if not the underlying disease) and has many corollaries in today’s treatments, stating “It seems to me, therefore, that the basic background for treatment lies in an adequate period of rest, preferably with a sanatorium type of regime with supportive measures directed towards counteracting anaemia, protein deficiency or electrolyte depletion. This can best be done by a high protein low fat diet with due regard to any question of milk sensitivity, potassium supplements, Vitamin B.12 injections and folic acid.”  While vitamins are the subject of another posting, treating anemia and dehydration symptoms, coupled with rest (though not too much) is generally an adjunct treatment today.  Similarly, the high protein, low fat diet is still put forth as a good diet candidate (though the evidence for direct impact is wanting).(2)

In the same period, Machella put forth the use of cortisone to treat both Crohn’s Disease and Ulcerative Colitis.  A corticosteroid (which resulted in a Nobel prize), cortisone was not widely available as commercial production was limited through most of the early 1950’s.(3)  Corticosteroids are still used to treat inflammation, and prednisone would take over (being up to 4 times more effective than cortisone) within a few years as the treatment of choice.(4)

The other treatment being used in the first half of the century was x-ray therapy.  In addition to treating carcinomas of the colon, x-rays were used to treat areas of disease.  X-rays were found to cause mucosal damage, and the use of them in treating primary IBD were discontinued by the 1960’s.(5)

1960’s


The 60’s represented a decade of change in the treatment of Crohn’s Disease and Ulcerative Colitis.  What was a primarily invasive treatment regime (surgery was the still treatment of choice), or had potentially damaging outcomes (x-ray treatment) or resulted in dangerous side effects (corticosteroids) moved toward a more traditional medical approach that had a lot in common with today’s treatments.  A focus on anti-inflammatories and immunomodulators for many diseases resulted in new treatment options from IBD.  These had fewer side effects than corticosteroids and gradually took the place of early surgical intervention in most cases.

The use of sulfa drugs (antimicrobials that were used before modern antibiotics to treat infections), specifically Sulfasalazine, was popularized as a treatment for IBD.  In addition to being an antibiotic, it had an immunosuppressive and an anti-inflammatory capability and had shown some success in treating rheumatoid arthritis.  There were numerous side effects, including severe depression and infertility, which led to the use of one of its more innocuous metabolites, 5-aminosalicylic, in treating IBD by the mid 1960’s.  The 5-ASA drugs, including Asacol and Pentasa, had significantly fewer side effects with a similar efficacy profile.  The 5-ASAs are still used to treat mild Crohn’s and Ulcerative Colitis (though their efficacy has been called into question).(6)

Azathioprine (Imuran), an immunosuppressant used in organ transplants, was applied to Crohn’s and Ulcerative Colitis treatments during the 1960’s.  6-mercaptopurine, for which azathioprine is a prodrug, and azathioprine itself were used to treat both forms of IBD, however the clinical research at the time was light and mostly based on case-study anecdotal results.(7)  Both drugs had high side effects, including leukopenia and pancreatitis, but some individuals were able to better tolerate the 6-MP regimen.  Later clinical evidence confirmed the efficacy of the drugs in IBD treatment, including the closing of fistulae, and they remain a staple of treating active IBD today.(8)*

The 1950’s and 1960’s showed tremendous advances in the treatment of Crohn’s Disease and Ulcerative Colitis.  Several staples in the stable of drugs used to treat the conditions today were first applied, including immunosuppressants and anti-inflammatory treatments.  While many of the treatments were based on anecdotal evidence, the next decades showed an increase in clinical trials related to IBD.

Bottom Line


·         The 1950’s and 1960’s saw the development of many of the treatments for IBD still in use today. 
·         The major trend during the period was a move away from surgical intervention toward medical treatment.

* Many of the drugs were used in limited patients or for other purposes in prior decades – a trend that continues with new drugs.
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1.       Crohn, Burrill B., Leon Ginzburg, and Gordon D. Oppenheimer. "Regional ileitis." Journal of the American Medical Association 99, no. 16 (1932): 1323-1329.
2.       Cooke, W. T. "Nutritional and Metabolic Factors in the Aetiology and Treatment of Regional Ileitis: Hunterian Lecture delivered at the Royal College of Surgeons of England on 28th April 1955." Annals of The Royal College of Surgeons of England 17, no. 3 (1955): 137.
3.       Machella, Thomas E., and O. Roger Hollan. "The effect of cortisone on the clinical course of chronic regional enteritis and chronic idiopathic ulcerative colitis." Transactions of the American Clinical and Climatological Association62 (1950): 67.
5.       LEE, EC GRUEBEL, and B. Dowling. "Problems in the Surgical Manag, ement of Crohn's Disease of theColon." Afr. Med 50, no. 45 (1971): 914.
6.       Golde, DavidW. "Aetiology of regional enteritis." The Lancet 291, no. 7552 (1968): 1144-1145.
7.       Parks, A. G., B. C. Morson, and J. S. Pegum. "Crohn's disease with cutaneous involvement." Proceedings of the Royal Society of Medicine 58, no. 4 (1965): 241.
8.       Pearson, David C., Gary R. May, Gordon H. Fick, and Lloyd R. Sutherland. "Azathioprine and 6-mercaptopurine in Crohn diseaseA meta-analysis." Annals of internal medicine 123, no. 2 (1995): 132-142.

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