1. Dipartimento di Reumatologia della Regione Basilicata
Direttore: Dott. Ignazio Olivieri
Le manifestazioni muscolo-scheletriche
della malattia di Whipple
Ignazio Olivieri

2. Whipple’s disease: definition
A rare, systemic infectious disease caused by the
bacterium Tropheryma whipplei.

3. Whipple’s disease: epidemiology
• No valid estimate of its actual prevalence.
• More than 1000 cases have been reported so far.
• Frequency <0.1% in postmortem studies.
• The typical patient is a middle-aged white man.

4. Whipple’s disease: history
Fenollar F, et al. N Engl J Med 2007;356:55-66.

5. Whipple’s disease: features
Fenollar F, et al. N Engl J Med 2007;356:55-66.

6. Whipple’s disease: two stages
The prodromal stage
protean symptoms, along with chronic nonspecific
symptoms, mainly arthralgia and arthritis.

7. Whipple’s disease: two stages
The steady-state stage
weight loss, diarrhea, or both, and occasionally
other manifestations.

8. Whipple’s disease: two stages
The average time between the prodromal and the
steady stages is 6 years.

9. Whipple’s disease: two stages
A more rapid progression may occur in patients
receiving corticosteroids, DMARDs or anti-TNFα
drugs.

10. Whipple’s disease: two stages
27 patients with Whipple’s disease (WP)
1. patients with immunosuppressive therapy before diagnosis
2. patients with NSAIDs before diagnosis
3. patients without such therapies
Arthritis occurred in the mean 8 years before diagnosis and was
the first symptoms in 63% of the patients.
In patients with immunosuppressives, diarrhoea occurred in the
median 4 months after the start of therapy and diagnosis of WP
was made after another 2 months.
Mahnel R, et al. Am J Gastroenterol 2005;100:1167-73.

11. Musculoskeletal manifestations
• Arthralgia and arthritis
• Spondyloarthritis
• Myalgia and cramps

12. Musculoskeletal manifestations
• Arthralgia and arthritis
• Spondyloarthritis
• Myalgia and cramps

13. Arthralgia and arthritis
• Intermittent and migratory
• Commonly involving ankles, knees, elbows
shoulders and finger joints
• Polyarthrtis is most common but oligoarthritis
may occur
• Chronic polyarthritis, which can be erosive and
resembling rheumatoid arthritis, is less frequent

14. Musculoskeletal manifestations
• Arthralgia and arthritis
• Spondyloarthritis
• Myalgia and cramps

15. Spondyloarthritis
The seronegative spondyloarthritides
1. Uncomplicated ankylosing spondylitis
2. Psoriatic arthritis
3. Reiter’s disease
4. Ulcerative colitis
5. Crohn’s disease
6. Behçet’s disease
7. Whipple’s disease
Moll JM, et al. Medicine (Baltimore) 1974;53:343-64.

17. Spondyloarthritis
18 patients with coexisting Whipple’s disease (WP)
and ankylosing spondylitis (AS).
Moll and Wright could agree with the diagnosis of
AS in only 4 of these 18 patients.
Kelly JJ, Weisinger BB. Arthritis Rheum 1963;6:615-32.

18. Spondyloarthritis
Subsequently, several cases of coexisting
Whipple’s disease and ankylosing spondylitis
have been reported.
Canoso JJ, et al.. J Rheumatol 1978;5:79-84.
Blaison D, et al. Ann Gastroentérol Hépatol 1991;27:51-5.

19. Spondyloarthritis
Studies examining patients with Whipple’s disease (WD)
for sacroiliitis and ankylosing spondylitis (AS):
• D’Eshougues R, et al. Rev Rhum 1976;43:565-73.
5 patients with sacroiliitis among 18 with WD
• Khan MA. J Rheumatol 1982;9:928-9.
1 patient with AS among 6 with WD

20. Spondyloarthritis
Studies on the frequency of HLA-B27 in patients with
Whipple’s disease (WD):
• Feurle GE, et al. Eur J Clin Invest1979;9:385-9.
4 of 9 patients with WD without sacroiliitis and AS were B27
positive
• Dobbins WO III. Arthritis Rheum 1987;30:102-5.
13 (28%) of 48 WD patients typed were positive for the B27
antigen.
12 of the 48 patients had sacroiliitis and only 2 of them were
B27 positive

21. Spondyloarthritis
Studies on the frequency of HLA-B27 in patients with
Whipple’s disease (WD):
• Bai JC, et al. Am J Gastroenterol 1991;86:992-4.
14 Argentinian WD patients typed
Frequency of the B27 antigen:
7% in patients with WD and 4% in blood donors

28. McCarty DJ, et al. Remitting seronegative
symmetrical synovitis with pitting edema.
RS3PE syndrome. JAMA 1985;254:2763-7.
• Esordio acuto
• Sinovite dei polsi, carpi, piccole articolazioni
delle mani e guaine dei flessori associata ad
edema improntabile sul dorso delle mani
• Negatività del fattore reumatoide
• Indici di flogosi elevati
• Risposta brillante alla terapia steroidea
• Risoluzione con la restitutio ad intengrum
• HLA B-7 nel 50% dei casi

29. Altre malattie infiammatorie
• Polimialgia reumatica/arterite di Horton
• Spondiloartriti
• Condrocalcinosi
• Artropatia amiloidosica
• LES
• Connettivite mista
• Sindrome di Sjögren
• Sclerosi sistemica
• Dermatomiosite
• Poliarterite nodosa
• Malattia di Whipple
• Sarcoidosi

30. Olivieri I, et al. J Rheumatol 2001;28:1294-7.
• No patient with a family history of spondyloarthritis.
• No patients with clinical manifestations of
spondyloarthritis such as peripheral enthesitis,
inflammatory spinal pain, chest wall pain or uveitis.
• No patient with sacroiliitis on pelvis x-rays
• No patient with the HLA-B27 antigen.

33. Practical Take Home Messages

34. Musculoskeletal manifestations
of Whipple’s disease
• Among the most common extra-intestinal symptoms
• May precede the gastrointestinal complaints by many
years
• Intermittent and migratory arthralgia and arthritis.
• Polyarthritis in most cases
• Tenosinovial involvement recently described
• Synovitis with pitting oedema over the hand and foot
dorsum may occur
• WD is not part of the spondyloarthritis complex