Treatment of intestinal Whipple´s disease is performed on an empirical basis. There is no credible 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
outcome was explained by insufficient penetration of tetracylines through the blood-brain barrier.
In the 1980s, trimethoprim-sulfamethoxazole (cotrimoxazole) was recommanded, presuming that this drug
would 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 Tropheryma w.
( 5 )
Since the mid 1990s a more intensified treatment evolved. A regime of initial intravenous treatment with ceftriaxone (a cephalosporine), 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 clinical trial which was sponsered by Roche Pharmaceuticals (Germany). The "
Studie zur Initialtherapie bei Morbus Whipple " (SIMW) 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, more than 42 patients were enrolled. However, due to subsequent changes in the protocol and exemptions from randomization, the
trial lost it´s legitimate status as a prospective and randomized study. With these restrictions, it may be fair to say that either regimen proved to be efficient in intestinal WD.( 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antibiotic chloramphenicol) was successful.( 7 ) However, in two further patients, interferon-gamma was ineffective.(unpublished ) One of the latter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.
Of note, no effective treatment is established for the subset of patients with symptomatic cerebral WD. In some of them, an individual regimen was helpful.