Complicated Whipple’s disease and endocarditis following tumor necrosis factor inhibitors

Table 2 Summary of cases treated with tumor necrosis factor alpha inhibitor and later diagnosis of Whipple’s disease

Patients (n)(sex, age, yr)	TNFI/time from treatment start of TNFI to diagnosis of WD	Other DMARDs	Clinical picture at the time of diagnosis of WD (after TNFI treatment)	Therapy for WD/outcome	Ref.
1 (F, 33)	Etarnecept; 6 mo	NSAID, MTX	Chronic inflammation, ankylosing spondylitis, arthritis, diarrhea, fever, weight loss	CFA + CTM; resolution	[12]
1 (M, 57)	Etarnecept; “mo“	Leflunomide, MTX	Endocarditis, aortic valve replacement	DCN, HCQ; resolution	[13]
1 (M)	Etanercept; not stated	Steroids, others not specified	Arthralgia, diarrhea, others not specified, IRIS after Abx	Long-term steroids, resolution	[14]
1 (M, 70)	Etarnecept; 19 mo	NSAID, sulfasalazine, MTX	Ankylosing sacroiliitis, endocarditis, dyspnea, fever, aortic valve replacement	DCN, CTM, HCQ; resolution	[15]
3 (M, 51-76)	Infliximab/2, etarnecept/2 “yr“	Steroids, MTX, gold, leflunomide, cyclophos-phamide, cyclosporine	IRIS after Abx, fever, 3 arthritis, pseudotumor orbitae	3 long-term steroids; 1 blindness; 1 jejunal perforation; 1 death after 3 yr	[16]
1 (M, 46)	Infliximab, adalimumab; 28 mo	MTX, steroids	Ankylosing sacroiliitis, fever, T. whipplei septicemia, diarrhea	CFA + CTM; resolution	[17]
1 (M, 35)	Etarnecept; 2 mo	None	Purpura, scurvy, diarrhea, pancolitis, granulomas, T. whipplei septicemia, arthritis	CTM; resolution	[18]
5 (4 M, 1 F, 38-67)	Etarnecept/4, infliximab/2, adalimu-mab/2; 2, 4, 9, 26, 85 mo	NSAID, MTX, abatacept, rituximab, chloroquine, steroids, leflunomide	Aortic endocarditis, 4 arthritis, 3 T. whipplei in blood or septicaemia, 3 weight loss, 2 diarrhea, 2 pericarditis, 2 meningitis, diarrhea, hemorrhagic colitis, lymphadenopathy	1 DCN 4 DCN + HCQ All with favorable outcome	[19]
1 (M, 34)	Infliximab; 0, 5 mo	NSAID, steroids, azathioprine, MTX	Erythema nodosum, diarrhea, weight loss, fever, sigmoido-vesical fistula, arthritis, lymphadenopathy	CTM; resolution	[20]
1 (M, 47)	Adalimumab; “mo“	MTX, steroids, leflunomide	Arthritis, recurrent fever, cough, weight loss	CFA + CTM; resolution	[21]
16	TNFI not specified; time not stated	Most had other immuno-suppressants	Immunosuppressants: 43% deterioration, 32% temporary relief, then deterioration, 25% ineffectiveness; TNFI: 2 patients with endocarditis	Not specified	[22]
1 (M, 62)	Etarnecept; “short“	NSAID, steroids, MTX	Polyarthritis, pericarditis, cutaneous lesions; T. whipplei septicaemia	Penicilllin G, CTM; persisting cutaneous lesions; DCN + HCQ; resolution	[27]
1 (F, 58)	Not specified; 24 mo	No data available	Arthritis	No data available	[28]
1 (M, 53)	Not specified; 12 mo	No data available	Pericarditis, polyarthritis, lower limb edema	No data available	[29]
1 (M, 67)	Etarnecept; “short“	MTX, steroids, sulfasalazine, leflunomide	Pericarditis, pulmonary hypertension, arthritis, candida esophagitis, segmental ulcerative intestinal lesions, episcleritis, fever	CFA + CTM; Stopped because of diarrhea; Cefixim, steroids, resolution	[23]
1	Etarnecept; not stated	No data available	No data available	No data available	[30]
2 (M, 42, 53)	Etarnecept/2, adalimu-mab/2; 13, 14 mo	NSAID	Deterioration of arthritis, spondylising arthritis, diarrhea, weight loss	1 DCN + HCQ, Sulfadiazin; 1 DCN + HCQ; 2 resolution	[24]
1 (M, 64)	Etarnecept; 6 mo	Steroids, MTX	Spondylising arthritis, multisegmental spondylitis, arthritis, weight loss, Giardia lamblia infection	CFA + CTM; Persistent inflamma-tion, then DCN +HCQ; resolution	[25]
1 (M, 52)	Etarnecept, adalimumab, infliximab; 24 mo	Steroids, MTX	Rash, hemiplegia, dysarthria, facial palsy, cognitive sequelae, headache, decrease of executive functions, arthritis, diarrhea, weight loss, lymphadenopathy	CFA + CTM, amelio-ration, but remaining cognitive sequelae, headache	[26]

CFA: Ceftriaxone; CTM: Cotrimoxazole; DCN: Doxycycline; F: Female; HCQ: Hydroxychloroquine; IRIS: Immune reconstitution inflammatory syndrome; M: Male; MTX: Methotrexate; NSAID: Non-steroidal anti-inflammatory drugs; steroids: Corticosteroids; TFNI: Tumor necrosis factor alpha inhibitor; WD: Whipple’s disease; DMARD: Disease modifying anti-rheumatic drug; T. whipplei: Tropheryma whipplei.