G Model BONSOI-4099; No. of Pages 3
ARTICLE IN PRESS Joint Bone Spine xxx (2014) xxx–xxx
Available online at
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Case report
Immune reconstitution inflammatory syndrome during treatment of Whipple’s disease Marielle Vayssade a , Anne Tournadre a , Michel D’Incan b , Martin Soubrier a , Jean-Jacques Dubost a,∗ a Department of Rheumatology, Clermont-Ferrand 1 University, G. Montpied Hospital, 58, rue Montalembert, BP 69, 63003 Clermont-Ferrand cedex 1, France b Department of Dermatology, Estaing Hospital, Clermont-Ferrand 1 University, 1 place Lucie-et-Raymond-Aubrac, 63003 Clermont-Ferrand cedex 1 France
a r t i c l e
i n f o
Article history: Accepted 7 September 2014 Available online xxx Keywords: Whipple’s disease Immune reconstitution inflammatory syndrome IRIS
a b s t r a c t Immune reconstitution inflammatory syndrome is a rare complication of the treatment of Whipple’s disease. Here, we report the case of a 65-year-old man treated for Whipple’s disease affecting the joints, with positive Tropheryma whipplei PCR in CSF, who developed fever and nodular eruption on the trunk, arms and face in association with biological inflammatory syndrome 10 days after initiation of antimicrobial treatment. Skin manifestations and the patient’s general condition improved on corticosteroids (0.5 mg/kg prednisone), but as steroids were gradually tapered, new nodules appeared below a prednisone dose of 10–15 mg. One year after starting treatment, lumbar puncture showed asymptomatic meningitis with negative T. whipplei PCR results which had regressed spontaneously. Two years after the diagnosis, on prednisone 5 mg daily and antimicrobial treatment, the patient had only transient, episodic nodular rash without fever or inflammatory syndrome. © 2014 Société franc¸aise de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.
1. Introduction Immune reconstitution inflammatory syndrome (IRIS) was first described as a paradoxical inflammatory reaction to a preexisting infection (mainly tuberculosis) after initiation of antiretroviral therapy in AIDS patients [1]. In Whipple’s disease, IRIS is characterized by the reappearance of inflammatory symptoms, primarily fever and arthralgia, after a period of effective antibiotic treatment. It affects about 10% of treated patients [2,3]. We report the case of a patient who, after initiating antibiotic treatment, developed erythematous patches and nodules, fever, and steroid-responsive inflammatory syndrome followed by asymptomatic meningitis. 2. Case report Mr C., 65 years old, presented with intermittent episodes of arthritis and arthralgia affecting the knees, wrists and ankles since 1995 accompanied by persistent biological inflammatory syndrome since 2005. Flare-ups were controlled with salazopyrin and prednisolone 5 mg daily. In 2011, progressively worsening
∗ Corresponding author. Tel.: +04 73 75 14 88; fax: +04 73 75 14 89. E-mail address: [email protected] (J.-J. Dubost).
proteinuria (0.95 g/24 h) led to a diagnosis of IgA mesangial glomerulonephritis based on histological analysis of a renal biopsy. Because of persistent inflammatory syndrome and articular manifestations, esogastroduodenal endoscopy was performed. PAS-positive histiocytes were found in the biopsy specimens and PCR was positive for Tropheryma whipplei. PCR of blood and saliva was negative. Lumbar puncture did not show meningitis (0 leukocyte/mm3 , protein: 0.34 g/L). Based on these findings, Whipple’s disease was diagnosed and treatment with hydroxychloroquine 600 mg daily plus doxycycline 200 mg daily was introduced. Ten days after starting the antibiotics, the patient was hospitalized for febrile skin eruption characterized by nodules and erythematous patches without pruritus or pain, involving the trunk, arms and face (Fig. 1). The remainder of the examination was normal. Laboratory findings showed an inflammatory syndrome (CRP = 110 mg/L) and hyperleukocytosis (17,290 leukocytes/mm3 with neutrophil count of 15,600/mm3 ), without hypereosinophilia. Biopsy of one of the nodules showed an acute panniculitis containing an inflammatory infiltrate of altered polynuclear cells and PAS-positive foamy cells (Fig. 2). Tropheryma culture was sterile, but PCR on this same skin sample was positive. T. whipplei PCR of blood and saliva was still negative. Oral corticosteroid therapy (prednisone 0.5 mg/kg daily) improved all symptoms within
http://dx.doi.org/10.1016/j.jbspin.2014.09.002 1297-319X/© 2014 Société franc¸aise de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.
Please cite this article in press as: Vayssade M, et al. Immune reconstitution inflammatory syndrome during treatment of Whipple’s disease. Joint Bone Spine (2014), http://dx.doi.org/10.1016/j.jbspin.2014.09.002
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ARTICLE IN PRESS M. Vayssade et al. / Joint Bone Spine xxx (2014) xxx–xxx
the neurological examination was normal. CRP was < 2.9 mg/L. Biopsy by duodenal endoscopy no longer showed any foamy macrophages and T. whipplei PCR was negative. On the other hand, the lumbar puncture had high cellularity (120 leukocytes/mm3 : 90% neutrophils, 8% mononuclear elements, 2% lymphocytes), with elevated CSF protein (0.56 g/L), normal CSF glucose; standard bacteriologic and viral cultures were negative as well as T. whipplei PCR result. A second lumbar puncture a month later showed that CSF had normalized (3 leukocytes/mm3 , normal protein and glucose). Brain MRI was normal. One year later, on prednisone 5 mg daily associated with antibiotics and hydroxychloroquine, the patient had episodic eruptions of small nodules which resolved rapidly without fever, with CRP levels remaining in normal limits. In conclusion, this is a case of Whipple’s disease with articular manifestations, with initial positive PCR results in CSF but without meningitis, occurring in a patient with a 15-year history of inflammatory rheumatism. After initiation of antibiotic treatment, immune reconstitution inflammatory syndrome was diagnosed based on the development of skin nodules with fever and steroidresponsive inflammatory syndrome. This would also explain the appearance of asymptomatic meningitis with negative PCR results one year after treatment.
3. Discussion
Fig. 1. Erythematous nodules and patches on the limbs and trunk.
a few days. Two weeks later, PCR initially performed on CSF came back positive. Treatment with ceftriaxone IV was given for 15 days, relayed with sulfadiazine 3 g, doxycycline 200 mg and hydroxychloroquine 600 mg daily. The patient’s overall condition gradually improved, with weight gain, disappearance of arthralgia and regression of proteinuria. However, tapering of steroids to below 10–15 mg daily led to the reappearance of nodules, fever and inflammatory syndrome which responded well to an increase in steroid dose. One year after diagnosis, the patient was hospitalized for assessment of Whipple’s disease. He was treated with prednisone 11 mg daily, antibiotics and hydroxychloroquine. A few skin nodules were found on clinical examination. There was no arthritis and
Fig. 2. A. Skin biopsy showing septal panniculitis with inflammatory infiltrate (star) and foamy macrophages (arrows) (haematoxylin and eosin; original magnification × 10). B. The foamy macrophages contain granules that stain with periodic acid-Schiff (PAS) (arrows) (original magnification × 400).
Whipple’s disease was diagnosed in our patient based on the recurrent articular manifestations. This is the classic form of the disease and the presenting symptom in 75% of cases [4]. IgA nephropathy is not normally associated with Whipple’s disease although it has already been described [5]. What makes this case noteworthy is the appearance of an immune reconstitution inflammatory syndrome (IRIS) a few days after introduction of antibiotic treatment. IRIS constitutes a set of inflammatory reactions related to an excessive response of the immune system directed against T. whipplei antigens. A very recent study indicates that IRIS appears to result from reconstitution of CD4+ T-cells insufficiently counterbalanced by regulatory T-cells [3]. IRIS occurs in about 10% of patients treated for Whipple’s disease [2,3]. IRIS in Whipple’s disease usually presents as fever and arthralgia and may progress for several months. Skin nodules are uncommon but have already been described [2,6,7]. Our case is similar to that of Schaller et al. [6], who point out a parallel between the nodules seen in IRIS and the type 2 reactions observed during the treatment of leprosy (erythema nodosum leprosum), which correspond to hypersensitivity to bacterial antigens and most commonly occur in multibacillary forms [8]. As in our patient, erythema nodosum leprosum is characterized by cutaneous and subcutaneous erythematous nodules, which are often painful, affecting the face, trunk and the extensor surface of the extremities of prolonged course. Pathologically, an inflammatory infiltrate of neutrophils is observed, sometimes in association with panniculitis or vasculitis. According to published data, the risk of IRIS during treatment of Whipple’s disease is increased in case of prior immunosuppressive therapy [2,9]. Our patient did not receive immunosuppressive therapy, unlike the case of Schaller et al. However, it appears that some infections, particularly Whipple’s disease, can themselves have an immunosuppressive effect [2]. IRIS can also have other manifestations including inflammatory orbitopathy, intestinal perforation, pleurisy and uveitis [2]. Asymptomatic meningitis with neutrophil predominance and negative PCR after one year of antibiotic treatment in a patient with an initially positive PCR without meningitis is probably another manifestation of IRIS. Feurle et al. described another case which, unlike our patient, was symptomatic [2].
Please cite this article in press as: Vayssade M, et al. Immune reconstitution inflammatory syndrome during treatment of Whipple’s disease. Joint Bone Spine (2014), http://dx.doi.org/10.1016/j.jbspin.2014.09.002
G Model BONSOI-4099; No. of Pages 3
ARTICLE IN PRESS M. Vayssade et al. / Joint Bone Spine xxx (2014) xxx–xxx
The difficulty facing the clinician is to distinguish IRIS from refractory Whipple’s disease. IRIS is generally diagnosed from the chronology of inflammatory symptoms which appear several days to several weeks after introduction of effective antibiotic therapy. Feurle et al. proposed the following diagnostic criteria for IRIS [2]: • initial clinical response to antibiotic therapy; • reappearance of systemic or local inflammation, with or without fever, for at least seven days, after ruling out other potential causes; • successful treatment defined by negative histology and negative PCR for T. whipplei. In our patient, PCR of the nodule biopsy remained positive for 10 days after beginning antibiotic therapy. There are no published data on the exact interval in which PCR becomes negative during effective treatment, since positive PCR results can also be due to persistence of nonviable pathogen. Therefore, additional examinations, and PCR in particular, do not always differentiate between refractory Whipple’s disease and IRIS during the early phase of treatment. In our patient, PCR of all samples was negative one year after initiation of antibiotic therapy, thereby confirming the success of the treatment and ruling out refractory Whipple’s disease. Currently, there are no guidelines on the therapeutic management of immune reconstitution inflammatory syndrome outside the context of HIV infection. Oral corticosteroids (0.5–2 mg/kg daily) are generally used with success [5], although they should be reserved for severe or life-threatening disease because of their harmful side effects and so as not to compromise control of the infection. In case of corticosteroid resistance, thalidomide was found to produce a rapid response in two cases [7,10], as also observed in erythema nodosum leprosum. In our patient, treatment
3
with thalidomide was not indicated for the moment because the outcome was favorable. In conclusion, this case shows that IRIS can be a cause of meningitis in Whipple’s disease and that IRIS is a chronic condition whose course can be prolonged even if the long-term prognosis appears favorable. Disclosure of interest The authors declare that they have no conflicts of interest concerning this article. References [1] French MA. Immune reconstitution inflammatory syndrome: a reappraisal. Clin Infect Dis 2009;48:101–7. [2] Feurle GE, Moos V, Schinnerling K, et al. The immune reconstitution inflammatory syndrome in Whipple disease: a cohort study. Ann Intern 2010;153: 710–7. [3] Moos V, Feurle GE, Schinnerling K, et al. Immunopathology of immune reconstitution inflammatory syndrome in Whipple’s disease. J Immunol 2013;190:2354–6. [4] Puechal X. Whipple’s disease. Ann Rheum Dis 2013;72:797–803. [5] Stoll T, Keusch G, Jost R, et al. IgA nephropathy and hypercalcemia in Whipple’s disease. Nephron 1993;63:222–5. [6] Schaller J, Carlson JA. Erythema nodosum-like lesions in treated Whipple’s disease: signs of immune reconstitution inflammatory syndrome. J Am Acad Dermatol 2009;60:277–88. [7] Lagier J-C, Fenollar F, Lepidi H, et al. Successful treatment of immune reconstitution inflammatory syndrome in Whipple’s disease using thalidomide. J Infect 2010;60:79–82. [8] Britton WJ, Lockwood DNJ. Leprosy. Lancet 2004;363:1209–19. [9] Biagi F, Trotta L, Di Stefano M, et al. Previous immunosuppressive therapy is a risk factor for immune reconstitution inflammatory syndrome in Whipple’s disease. Dig Liver Dis 2012;44:880–2. [10] Le Blay P, Rakotonirainy H, Lagier JC, et al. A severe Whipple’s disease with an immune reconstitution inflammatory syndrome: an additional case of thalidomide efficiency. Joint Bone Spine 2013;81:260–2.
Please cite this article in press as: Vayssade M, et al. Immune reconstitution inflammatory syndrome during treatment of Whipple’s disease. Joint Bone Spine (2014), http://dx.doi.org/10.1016/j.jbspin.2014.09.002
ARTICLE IN PRESS Joint Bone Spine xxx (2014) xxx–xxx
Available online at
ScienceDirect www.sciencedirect.com
Case report
Immune reconstitution inflammatory syndrome during treatment of Whipple’s disease Marielle Vayssade a , Anne Tournadre a , Michel D’Incan b , Martin Soubrier a , Jean-Jacques Dubost a,∗ a Department of Rheumatology, Clermont-Ferrand 1 University, G. Montpied Hospital, 58, rue Montalembert, BP 69, 63003 Clermont-Ferrand cedex 1, France b Department of Dermatology, Estaing Hospital, Clermont-Ferrand 1 University, 1 place Lucie-et-Raymond-Aubrac, 63003 Clermont-Ferrand cedex 1 France
a r t i c l e
i n f o
Article history: Accepted 7 September 2014 Available online xxx Keywords: Whipple’s disease Immune reconstitution inflammatory syndrome IRIS
a b s t r a c t Immune reconstitution inflammatory syndrome is a rare complication of the treatment of Whipple’s disease. Here, we report the case of a 65-year-old man treated for Whipple’s disease affecting the joints, with positive Tropheryma whipplei PCR in CSF, who developed fever and nodular eruption on the trunk, arms and face in association with biological inflammatory syndrome 10 days after initiation of antimicrobial treatment. Skin manifestations and the patient’s general condition improved on corticosteroids (0.5 mg/kg prednisone), but as steroids were gradually tapered, new nodules appeared below a prednisone dose of 10–15 mg. One year after starting treatment, lumbar puncture showed asymptomatic meningitis with negative T. whipplei PCR results which had regressed spontaneously. Two years after the diagnosis, on prednisone 5 mg daily and antimicrobial treatment, the patient had only transient, episodic nodular rash without fever or inflammatory syndrome. © 2014 Société franc¸aise de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.
1. Introduction Immune reconstitution inflammatory syndrome (IRIS) was first described as a paradoxical inflammatory reaction to a preexisting infection (mainly tuberculosis) after initiation of antiretroviral therapy in AIDS patients [1]. In Whipple’s disease, IRIS is characterized by the reappearance of inflammatory symptoms, primarily fever and arthralgia, after a period of effective antibiotic treatment. It affects about 10% of treated patients [2,3]. We report the case of a patient who, after initiating antibiotic treatment, developed erythematous patches and nodules, fever, and steroid-responsive inflammatory syndrome followed by asymptomatic meningitis. 2. Case report Mr C., 65 years old, presented with intermittent episodes of arthritis and arthralgia affecting the knees, wrists and ankles since 1995 accompanied by persistent biological inflammatory syndrome since 2005. Flare-ups were controlled with salazopyrin and prednisolone 5 mg daily. In 2011, progressively worsening
∗ Corresponding author. Tel.: +04 73 75 14 88; fax: +04 73 75 14 89. E-mail address: [email protected] (J.-J. Dubost).
proteinuria (0.95 g/24 h) led to a diagnosis of IgA mesangial glomerulonephritis based on histological analysis of a renal biopsy. Because of persistent inflammatory syndrome and articular manifestations, esogastroduodenal endoscopy was performed. PAS-positive histiocytes were found in the biopsy specimens and PCR was positive for Tropheryma whipplei. PCR of blood and saliva was negative. Lumbar puncture did not show meningitis (0 leukocyte/mm3 , protein: 0.34 g/L). Based on these findings, Whipple’s disease was diagnosed and treatment with hydroxychloroquine 600 mg daily plus doxycycline 200 mg daily was introduced. Ten days after starting the antibiotics, the patient was hospitalized for febrile skin eruption characterized by nodules and erythematous patches without pruritus or pain, involving the trunk, arms and face (Fig. 1). The remainder of the examination was normal. Laboratory findings showed an inflammatory syndrome (CRP = 110 mg/L) and hyperleukocytosis (17,290 leukocytes/mm3 with neutrophil count of 15,600/mm3 ), without hypereosinophilia. Biopsy of one of the nodules showed an acute panniculitis containing an inflammatory infiltrate of altered polynuclear cells and PAS-positive foamy cells (Fig. 2). Tropheryma culture was sterile, but PCR on this same skin sample was positive. T. whipplei PCR of blood and saliva was still negative. Oral corticosteroid therapy (prednisone 0.5 mg/kg daily) improved all symptoms within
http://dx.doi.org/10.1016/j.jbspin.2014.09.002 1297-319X/© 2014 Société franc¸aise de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.
Please cite this article in press as: Vayssade M, et al. Immune reconstitution inflammatory syndrome during treatment of Whipple’s disease. Joint Bone Spine (2014), http://dx.doi.org/10.1016/j.jbspin.2014.09.002
G Model BONSOI-4099; No. of Pages 3 2
ARTICLE IN PRESS M. Vayssade et al. / Joint Bone Spine xxx (2014) xxx–xxx
the neurological examination was normal. CRP was < 2.9 mg/L. Biopsy by duodenal endoscopy no longer showed any foamy macrophages and T. whipplei PCR was negative. On the other hand, the lumbar puncture had high cellularity (120 leukocytes/mm3 : 90% neutrophils, 8% mononuclear elements, 2% lymphocytes), with elevated CSF protein (0.56 g/L), normal CSF glucose; standard bacteriologic and viral cultures were negative as well as T. whipplei PCR result. A second lumbar puncture a month later showed that CSF had normalized (3 leukocytes/mm3 , normal protein and glucose). Brain MRI was normal. One year later, on prednisone 5 mg daily associated with antibiotics and hydroxychloroquine, the patient had episodic eruptions of small nodules which resolved rapidly without fever, with CRP levels remaining in normal limits. In conclusion, this is a case of Whipple’s disease with articular manifestations, with initial positive PCR results in CSF but without meningitis, occurring in a patient with a 15-year history of inflammatory rheumatism. After initiation of antibiotic treatment, immune reconstitution inflammatory syndrome was diagnosed based on the development of skin nodules with fever and steroidresponsive inflammatory syndrome. This would also explain the appearance of asymptomatic meningitis with negative PCR results one year after treatment.
3. Discussion
Fig. 1. Erythematous nodules and patches on the limbs and trunk.
a few days. Two weeks later, PCR initially performed on CSF came back positive. Treatment with ceftriaxone IV was given for 15 days, relayed with sulfadiazine 3 g, doxycycline 200 mg and hydroxychloroquine 600 mg daily. The patient’s overall condition gradually improved, with weight gain, disappearance of arthralgia and regression of proteinuria. However, tapering of steroids to below 10–15 mg daily led to the reappearance of nodules, fever and inflammatory syndrome which responded well to an increase in steroid dose. One year after diagnosis, the patient was hospitalized for assessment of Whipple’s disease. He was treated with prednisone 11 mg daily, antibiotics and hydroxychloroquine. A few skin nodules were found on clinical examination. There was no arthritis and
Fig. 2. A. Skin biopsy showing septal panniculitis with inflammatory infiltrate (star) and foamy macrophages (arrows) (haematoxylin and eosin; original magnification × 10). B. The foamy macrophages contain granules that stain with periodic acid-Schiff (PAS) (arrows) (original magnification × 400).
Whipple’s disease was diagnosed in our patient based on the recurrent articular manifestations. This is the classic form of the disease and the presenting symptom in 75% of cases [4]. IgA nephropathy is not normally associated with Whipple’s disease although it has already been described [5]. What makes this case noteworthy is the appearance of an immune reconstitution inflammatory syndrome (IRIS) a few days after introduction of antibiotic treatment. IRIS constitutes a set of inflammatory reactions related to an excessive response of the immune system directed against T. whipplei antigens. A very recent study indicates that IRIS appears to result from reconstitution of CD4+ T-cells insufficiently counterbalanced by regulatory T-cells [3]. IRIS occurs in about 10% of patients treated for Whipple’s disease [2,3]. IRIS in Whipple’s disease usually presents as fever and arthralgia and may progress for several months. Skin nodules are uncommon but have already been described [2,6,7]. Our case is similar to that of Schaller et al. [6], who point out a parallel between the nodules seen in IRIS and the type 2 reactions observed during the treatment of leprosy (erythema nodosum leprosum), which correspond to hypersensitivity to bacterial antigens and most commonly occur in multibacillary forms [8]. As in our patient, erythema nodosum leprosum is characterized by cutaneous and subcutaneous erythematous nodules, which are often painful, affecting the face, trunk and the extensor surface of the extremities of prolonged course. Pathologically, an inflammatory infiltrate of neutrophils is observed, sometimes in association with panniculitis or vasculitis. According to published data, the risk of IRIS during treatment of Whipple’s disease is increased in case of prior immunosuppressive therapy [2,9]. Our patient did not receive immunosuppressive therapy, unlike the case of Schaller et al. However, it appears that some infections, particularly Whipple’s disease, can themselves have an immunosuppressive effect [2]. IRIS can also have other manifestations including inflammatory orbitopathy, intestinal perforation, pleurisy and uveitis [2]. Asymptomatic meningitis with neutrophil predominance and negative PCR after one year of antibiotic treatment in a patient with an initially positive PCR without meningitis is probably another manifestation of IRIS. Feurle et al. described another case which, unlike our patient, was symptomatic [2].
Please cite this article in press as: Vayssade M, et al. Immune reconstitution inflammatory syndrome during treatment of Whipple’s disease. Joint Bone Spine (2014), http://dx.doi.org/10.1016/j.jbspin.2014.09.002
G Model BONSOI-4099; No. of Pages 3
ARTICLE IN PRESS M. Vayssade et al. / Joint Bone Spine xxx (2014) xxx–xxx
The difficulty facing the clinician is to distinguish IRIS from refractory Whipple’s disease. IRIS is generally diagnosed from the chronology of inflammatory symptoms which appear several days to several weeks after introduction of effective antibiotic therapy. Feurle et al. proposed the following diagnostic criteria for IRIS [2]: • initial clinical response to antibiotic therapy; • reappearance of systemic or local inflammation, with or without fever, for at least seven days, after ruling out other potential causes; • successful treatment defined by negative histology and negative PCR for T. whipplei. In our patient, PCR of the nodule biopsy remained positive for 10 days after beginning antibiotic therapy. There are no published data on the exact interval in which PCR becomes negative during effective treatment, since positive PCR results can also be due to persistence of nonviable pathogen. Therefore, additional examinations, and PCR in particular, do not always differentiate between refractory Whipple’s disease and IRIS during the early phase of treatment. In our patient, PCR of all samples was negative one year after initiation of antibiotic therapy, thereby confirming the success of the treatment and ruling out refractory Whipple’s disease. Currently, there are no guidelines on the therapeutic management of immune reconstitution inflammatory syndrome outside the context of HIV infection. Oral corticosteroids (0.5–2 mg/kg daily) are generally used with success [5], although they should be reserved for severe or life-threatening disease because of their harmful side effects and so as not to compromise control of the infection. In case of corticosteroid resistance, thalidomide was found to produce a rapid response in two cases [7,10], as also observed in erythema nodosum leprosum. In our patient, treatment
3
with thalidomide was not indicated for the moment because the outcome was favorable. In conclusion, this case shows that IRIS can be a cause of meningitis in Whipple’s disease and that IRIS is a chronic condition whose course can be prolonged even if the long-term prognosis appears favorable. Disclosure of interest The authors declare that they have no conflicts of interest concerning this article. References [1] French MA. Immune reconstitution inflammatory syndrome: a reappraisal. Clin Infect Dis 2009;48:101–7. [2] Feurle GE, Moos V, Schinnerling K, et al. The immune reconstitution inflammatory syndrome in Whipple disease: a cohort study. Ann Intern 2010;153: 710–7. [3] Moos V, Feurle GE, Schinnerling K, et al. Immunopathology of immune reconstitution inflammatory syndrome in Whipple’s disease. J Immunol 2013;190:2354–6. [4] Puechal X. Whipple’s disease. Ann Rheum Dis 2013;72:797–803. [5] Stoll T, Keusch G, Jost R, et al. IgA nephropathy and hypercalcemia in Whipple’s disease. Nephron 1993;63:222–5. [6] Schaller J, Carlson JA. Erythema nodosum-like lesions in treated Whipple’s disease: signs of immune reconstitution inflammatory syndrome. J Am Acad Dermatol 2009;60:277–88. [7] Lagier J-C, Fenollar F, Lepidi H, et al. Successful treatment of immune reconstitution inflammatory syndrome in Whipple’s disease using thalidomide. J Infect 2010;60:79–82. [8] Britton WJ, Lockwood DNJ. Leprosy. Lancet 2004;363:1209–19. [9] Biagi F, Trotta L, Di Stefano M, et al. Previous immunosuppressive therapy is a risk factor for immune reconstitution inflammatory syndrome in Whipple’s disease. Dig Liver Dis 2012;44:880–2. [10] Le Blay P, Rakotonirainy H, Lagier JC, et al. A severe Whipple’s disease with an immune reconstitution inflammatory syndrome: an additional case of thalidomide efficiency. Joint Bone Spine 2013;81:260–2.
Please cite this article in press as: Vayssade M, et al. Immune reconstitution inflammatory syndrome during treatment of Whipple’s disease. Joint Bone Spine (2014), http://dx.doi.org/10.1016/j.jbspin.2014.09.002
