Table 1 Reports indicating alteration of the course of subacute Whipple’s disease during therapy with biological agents

[20]

Mahnel R. et al.

Am. J. Gastroenterol.

2005

27

Immunosuppressiva lead to earlier onset of diarrhea

[21]

Kneitz C. et al.

Scand. J. Rheumatol.

2005

1

Infliximab/MTX

Rapid weight loss Erythema nodosum diarrhea LN enlargement sigmoido-vesical fistula

Infliximab seems to increase the risk of exacerbation of WD

[22]

Razonable R.R. et al.

Transpl. Infect. Dis.

2008

1

Kidney Transplant and migratory poly arthritis, weight loss, GIT-symptoms for years

Azathioprim/Prednison

Chorioretinitis and Vitreitis

Tropheryma whipplei DNA in vitrous fluid and peripheral blood

[23]

Kremer AE. et al.

Z. Gastroenterolog.

2008

1

SNRA/4 yrs

Adalimumab/Leflunomid

Septic fever severe arthralgia weight loss

Immunmodulatory therapies, TNF blockers and Corticosteroids may lead to exercerbation of subacute, undiagnosed Whipples Disease

[24]

Spoerl D. et al.

Orphanet. J. Rare Dis.

2009

1

Multisegment spondylitis

TNF-a

Worsening back pain

TNF-a treatment worsened spondylodiscitis, leading to diagnosis of T. Whipplei from rebiopsy of vertebral specimen

[25]

Lagier J-C et al.

Medicine

2010

113

5 of 16 patients with endocarditis as initial symptoms had immunosuppressive treatment

Corticosteroids 50 (43 %) TNF-a antagonists 16 (14 %) Others 16 (14 %) Previous immuno suppressive Treatment 56 (50 %)

32 patients (28 %) experienced aggravation of various symptoms after immunosuppressive therapy

Patients with inflammatory rheumatoid disease who experience severe general involvment should be screened for T. Whippelii or the therapy is inneffective against polyarthritis

[26]

Hoppe E. et al.

Joint bone Spine

2010

5

RA(2), AS(2), SA(1)

TNF a antagonists

Failure to control the disease and other symptoms

Biological therapy probably worsened pre existing whipples disease

[27]

Vancsa A et al.

Joint Bone Spine

2010

1

Seronegative Oligoarthritis

Eternecept

Endocarditis

DMARDs resistant arthritis should prompt thourough search T.whippelii prior to initiation of TNF-a antagonists

[28]

Hmamouci I et al.

J. Rheumatol.

2010

1

Ankylosing spondylitis

Eternecept

Scurvy

Eternecept probably modified the cytokine environment and thus favoured exercerbation of whipples disease

[29]

Daien C.I. et al.

Rheumatology

2010

1

B-27- negative Ankylosing spondylitis

Eternecept

Endocarditis

Report of the first case of t. Whippeliis endocarditis, potentially induced by TNF-a antagonist therapy

[30]

Gaddy J.R.

Rheumatology

2012

1

Back pain; Arthritis

Various TNF a Inhibitors

Fever, migratory arthritis

Clinical deterioration despite TNF a antagonists lead to thorough search and T. Whipelli was found

[31]

Sparsa L et al.

La Revue de medecine interne

2013

2

Spondyloarthritis (both patients)

Eternecept/adalimumab (Both patients)

peristent elevated acute phase reactants

Whipples disease should be suspected in patients with treated with TNF a antagonists who do not improve during inflammatory rheumatism

[32]

Marth T.

World J. Cardiol.

2014

41vs 61vs1059

Arthritis

TNF-a/41 patients

12.2 % vs 1.6 % vs 0.16 % endocarditis rates

TNF-a triggered severe whipples disease complications particularly endocarditis

[33]

Marth T.

Aliment. Pharmacol. Ther.

2015

41

Arthritis, weight-loss, Diarrhea

Various TNF-a Inhibitors

Fever, septic temperatures (n, 16), Tropheryma whipplei septicemia (n, 6), Endocarditis (n, 5) etc.

In case of doubt, Whipples disease should be excluded before therapy with TNF-a