Le manifestazioni muscolo-scheletriche della malattia di Whipple

Dipartimento di Reumatologia della Regione BasilicataDirettore: Dott. Ignazio Olivieri

Ignazio Olivieri

Whipple’s disease: definition

A rare, systemic infectious disease caused by the bacterium Tropheryma whipplei.bacterium Tropheryma whipplei.

Whipple’s disease: epidemiology

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

Whipple’s disease: history

Fenollar F, et al. N Engl J Med 2007;356:55-66.

Whipple’s disease: features

Fenollar F, et al. N Engl J Med 2007;356:55-66.

Whipple’s disease: two stages

The prodromal stageprotean symptoms, along with chronic nonspecific protean symptoms, along with chronic nonspecific symptoms, mainly arthralgia and arthritis.

Whipple’s disease: two stages

The steady-state stageweight loss, diarrhea, or both, and occasionally weight loss, diarrhea, or both, and occasionally other manifestations.

Whipple’s disease: two stages

The average time between the prodromal and the steady stages is 6 years.steady stages is 6 years.

Whipple’s disease: two stages

A more rapid progression may occur in patients receiving corticosteroids, DMARDs or anti-TNFαreceiving corticosteroids, DMARDs or anti-TNFαdrugs.

Whipple’s disease: two stages

27 patients with Whipple’s disease (WP)1. patients with immunosuppressive therapy before diagnosis2. patients with NSAIDs before diagnosis3. patients without such therapies3. 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.

Musculoskeletal manifestations

• Arthralgia and arthritis

• Spondyloarthritis

• Myalgia and cramps

Musculoskeletal manifestations

• Arthralgia and arthritis

• Spondyloarthritis

• Myalgia and cramps

Arthralgia and arthritis

• Intermittent and migratory• Commonly involving ankles, knees, elbows • 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

Musculoskeletal manifestations

• Arthralgia and arthritis

• Spondyloarthritis

• Myalgia and cramps

Spondyloarthritis

The seronegative spondyloarthritides1. Uncomplicated ankylosing spondylitis2. Psoriatic arthritis2. Psoriatic arthritis3. Reiter’s disease4. Ulcerative colitis5. Crohn’s disease6. Behçet’s disease7. Whipple’s disease

Moll JM, et al. Medicine (Baltimore) 1974;53:343-64.

Spondyloarthritis

18 patients with coexisting Whipple’s disease (WP) and ankylosing spondylitis (AS).

Moll and Wright could agree with the diagnosis of 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.

Spondyloarthritis

Subsequently, several cases of coexisting Whipple’s disease and ankylosing spondylitishave been reported.

Canoso JJ, et al.. J Rheumatol 1978;5:79-84.Blaison D, et al. Ann Gastroentérol Hépatol 1991;27:51-5.

Spondyloarthritis

Studies examining patients with Whipple’s disease (WD) for sacroiliitis and ankylosing spondylitis (AS):

• D’EshouguesR, et al. Rev Rhum1976;43:565-73.• D’EshouguesR, et al. Rev Rhum1976;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

Spondyloarthritis

Studies on the frequency of HLA-B27 in patients with Whipple’s disease (WD):

• FeurleGE, et al. Eur J Clin Invest1979;9:385-9.• FeurleGE, 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

Spondyloarthritis

Studies on the frequency of HLA-B27 in patients with Whipple’s disease (WD):

• Bai JC, et al. Am J Gastroenterol1991;86:992-4.• Bai JC, et al. Am J Gastroenterol1991;86:992-4.14 Argentinian WD patients typedFrequency of the B27 antigen:7% in patients with WD and 4% in blood donors

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 maniedema 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

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

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.inflammatory spinal pain, chest wall pain or uveitis.

• No patient with sacroiliitis on pelvis x-rays

• No patient with the HLA-B27 antigen.

Practical Take Home Messages

Musculoskeletal manifestationsof Whipple’s disease

• Among the most common extra-intestinal symptoms• May precede the gastrointestinal complaints by many

years• Intermittent and migratory arthralgia and arthritis.• 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