Treatment of intestinal Whipple´s disease is largely performed on a historical basis. Few retrospective studies have summarized the outcome of medium-sized series of patients at short- or long-term. There is no prospective study available  which would provide an evidence-base for therapy.

Historically, tetracyclines were widely used in the 1960s and 1970s.( 1, 2 )  Then in 1985 a retrospective evaluation of a cohort revealed that approximately one third of patients later developed symptoms which were interpreted as clinical relapses of Whipple´s disease, including cerebral manifestations.( 3 )  This poor outcome was explained by insufficient penetration of tetracylines through the blood-brain barrier.

In the 1980s, trimethoprim-sulfamethoxazole (cotrimoxazole) was recommanded, as this drug should efficiently penetrate the blood-brain barrier.( 3, 4 ) However, a decade later it became clear that cotrimoxazole does not reliably eradicate silent cerebral infection with T. whippelii.( 5 ) 

Since the mid 1990s a more intensified treatment evolved. A regime of initial intravenous treatment with a cephalosporine (ceftriaxone), 2 - 4g /day i.v. for 2 weeks, continued by oral medication with high-dose cotrimoxazole for 12 months, was observed to be effective in several of our patients.

This new concept was made subject to a prospective, randomized trial: the "Studie zur Initialtherapie bei Morbus Whipple". The SIMW trial compared the efficiency of an initial intravenous treatment with either ceftriaxone or meropeneme, followed by oral cotrimoxazole for 12 months. The SIMW trial started in Germany in September 1998. Until June 2003, 42 patients were enrolled. Unfortunatelaty, due to later changes in the protocol, the trial lost it´s legitimate status as a prospective and randomized study. With these restrictions, it is fair to say that either regimen proved to be efficient. ( 6 )

Rare patients with intestinal WD are refractory to antibiotic treatment. In one such patient, experimental immunotherapy with interferon-gamma (combined to the antibiotic chloramphenicol) was successful.( 7 )  However, in two further patients, interferon-gamma was ineffective.( unpublished )  One of the latter patients later died.

References

1. von Herbay A, Otto HF (1988). Whipple's disease: a report of 22 patients. Klin Wochenschr 66: 533-539
2. Fleming JL, Wiesner RH, Shorter RG (1988). Whipple´s disease: clinical, biochemical, and histopathologic features and assessment of treatment in 29 patients. Mayo Clin Proc 63: 539-551
3. Keinath RD, Merrel DE, Vlietstra R, Dobbins WO III (1985). Antibiotic treatment and relapse in Whipple's disease. Long-term follow-up of 88 patients. Gastroenterology 88: 1867-1873
4. Feurle GE, Marth T (1994). An evaluation of antimicrobial treatment for Whipple´s disease. Tetracycline versus Trimethoprim-Sulfamethoxazole. Dig Dis Sci 39: 1642-1648
5. von Herbay A, Ditton HJ, Schuhmacher F, Maiwald M (1997). Staging and monitoring in Whipple´s disease by cytology and polymerase chain reaction analysis of cerebrospinal fluid. Gastroenterology 113:  113: 434-441
6. Feurle GE, Maiwald M, Marth T, von Herbay A. (2007; unpublished)
7. Schneider T, Stallmach A, von Herbay A, Marth T, Strober W, Zeitz M (1998). Treatment of refractory Whipple´s disease with recombinant interferon-gamma. Ann Inter Med 129: 875-877

Recommendations for patient management  are outlined in more detail in this texbook,  chapter 54:

ADVANCED THERAPY IN GASTROENTEROLOGY AND LIVER DISEASE  5/e

T.M. Bayless, A.M.Diehl (eds.)
The Johns Hopkins University of Medicine

http://www.harcourt-internati onal.com/catalogue/title.cfm?I SBN=1550092480