Primary Central Nervous System Immunomodulatory Therapy-Induced Lymphoproliferative Disorder in a Patient with Ulcerative Colitis: A Case Report and Review of the Literature

Alobaid, Abdullah; Torlakovic, Emina; Kongkham, Paul

doi:10.1016/j.wneu.2015.07.009

Cited by 6 publications

(4 citation statements)

References 32 publications

(31 reference statements)

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“…18 Alternatively, the lymphoma may be secondary to chronic immunosuppression resulting in iatrogenic immune dysfunction. 19 As observed in our second case, other patients treated with mycophenolate mofetil 20 or infliximab 19 for different conditions developed CNS B-cell lymphoma. 21 Finally, the chronic perivascular antigenic stimulation that occurs in the patients with CLIPPERS may lead to a malignant transformation of B cells targeting this antigen.…”

Section: Discussionsupporting

confidence: 60%

“…It is possible that CLIPPERS is a premalignant state, representing a host immune response preventing the clonal proliferation of malignant cells . Alternatively, the lymphoma may be secondary to chronic immunosuppression resulting in iatrogenic immune dysfunction . As observed in our second case, other patients treated with mycophenolate mofetil or infliximab for different conditions developed CNS B‐cell lymphoma .…”

Section: Discussionmentioning

confidence: 60%

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Is chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) in children the same condition as in adults?

Sá

Green

Abdel‐Mannan

et al. 2018

Develop Med Child Neuro

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Section: Discussionsupporting

confidence: 60%

Section: Discussionmentioning

confidence: 60%

Is chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) in children the same condition as in adults?

Sá

Green

Abdel‐Mannan

et al. 2018

Develop Med Child Neuro

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“…The increased risk for lymphoproliferative disorders in the post-transplant population [1,[41][42][43][44][45] and case reports with a clear relation in time between therapy initiation and the development of lymphoproliferative disorders [46,47] support the existence of a causative role between immunosuppressive/immunomodulatory therapy and lymphoproliferative disorders. This causative role of immunomodulatory/suppressive therapy in immunosuppressive/immunomodulatory agent-related lymphoproliferative disorders has been repeatedly suggested by case reports of lymphoproliferative disorders regression following discontinuation of methotrexate [48][49][50][51][52], anti-TNFα therapy [53][54][55][56] thiopurines [55], tacrolimus [57], and others [56]. A limitation in studying the effect of these drugs on lymphoproliferative disorder incidence is the still open question how long after cessation of therapy the immunosuppressive/immunomodulatory effects of these drugs linger.…”

Section: Discussionmentioning

confidence: 99%

Other immunomodulatory agent-related lymphoproliferative diseases: a single-center series of 72 biopsy-confirmed cases

et al. 2018

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Ongoing development of new drugs, as well as novel indications in the treatment of autoimmune diseases leads to the increasing use of immunomodulatory and immunosuppressive drugs. Immunomodulatory agent-related lymphoproliferative disorders are a known and potentially life threatening complication of chronic administration of these drugs, but are less well characterized compared with post-transplant lymphoproliferative disorders. The heterogeneous drug targets, various underlying disease indications, different drug combinations used and relatively low incidence render data collection and interpretation difficult. In this retrospective paper, we describe the clinicopathological characteristics of a larger single-center series of 72 immunomodulatory agent-related lymphoproliferative disorder cases. We divided the cases according to the therapy, administered in the year preceding diagnosis of a lymphoproliferative disorder, in an immunosuppressive drug, an immunomodulatory drug and a combination of immunosuppressive and immunomodulatory drugs group. We observed differences in "time to lymphoproliferative disorder development" with a shorter time for all the immunomodulatory drug-related cases combined (immunomodulatory and immunomodulatory + immunosuppressive = immunomodulatory-all) vs immunosuppressive-only (p = 0.0031). The proportion of malignant cases in patients receiving immunomodulatory therapy was, however, also significantly lower when compared with the immunosuppressive treated cases (43 vs 88%; p = 0.0184). The immunomodulatory/suppressive agent-related lymphoproliferative disorders were less often associated with the Epstein-Barr virus (EBV) (31 vs 66%; p = 1.829e-05) and the lymphoproliferative disorders incidence in the first year after immunomodulatory/immunosuppressive therapy initiation was lower (18 vs 41%; p = 0.04151)-compared with a published series of 140 post-transplant lymphoproliferative disorder cases from the same center. However, a similar histopathological spectrum from nondestructive, to polymorphic and monomorphic lesions as in post-transplant lymphoproliferative disorders is observed. With increasing use of immunosuppressive and especially immunomodulatory therapy, a higher incidence of immunomodulatory/suppressive agent-related lymphoproliferative disorders is to be expected. Life-long awareness for development of immunomodulatory/suppressive agent-related lymphoproliferative disorders with clinical follow-up and timely biopsies of suspicious lesions is required since these lymphoproliferative disorders arise both early after therapy initiation and many years later. Histopathological confirmation and correct classification is necessary to guide therapy and EBV ISH should be a part of routine pathological diagnostics.

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“…Ulcerative colitis is a condition that may result in toxic colonic dilatation, intestinal perforation, intestinal hemorrhage, polyps and colorectal carcinoma (24). The severity of inflammation increases the risk of ileo-anal anastomotic leak following a pouch procedure in patients with ulcerative colitis (25,26). In recent years, the efficacy of traditional Chinese medicines for the treatment of digestive tract diseases has attracted global interest (27,28).…”

Section: Discussionmentioning

confidence: 99%

Costus root granules improve ulcerative colitis through regulation of TGF-β mediation of the PI3K/AKT signaling pathway

Wang

Zhang

et al. 2018

Exp Ther Med

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Ulcerative colitis is a chronic nonspecific inflammatory disease that occurs in the colon and rectum. Costus root is a type of traditional Chinese medicine that exhibits antibacterial properties and serves an inhibitory role in the regeneration of gut bacteria. However, the molecular mechanisms underlying Costus root-mediated improvements in ulcerative colitis remain unclear. A complex formula of Costus root granules was created and investigated in the present study for its therapeutic effects in a rat model of ulcerative colitis. Ingredient dissolution into a traditional water decoction was used as a control. The potential mechanism mediated by Costus root granules was also analyzed in colonic epithelial cells isolated from the experimental rats. The results of the present study demonstrated that Costus root granule treatment inhibited inflammation in colonic tissue. Costus root granule treatment also suppressed the apoptosis of colonic epithelial cells isolated from the rat model of ulcerative colitis. Analyses of the underlying mechanisms of these effects indicated that the administration of Costus root granules increased transforming growth factor β expression, which activated the phosphoinositide 3-kinase/RAC-α serine/threonine-protein kinase signaling pathway in colonic epithelial cells. Notably, the administration of Costus root granules improved stomachache, diarrhea and hematochezia in and increased the body weight of, the ulcerative colitis rats. In conclusion, these results indicate that Costus root granules markedly ameliorate inflammation of the colonic epithelium, decrease the apoptosis of colonic epithelial cells and improve colonic function, which suggests that Costus root granules are an efficient agent for the treatment of ulcerative colitis.

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Primary Central Nervous System Immunomodulatory Therapy-Induced Lymphoproliferative Disorder in a Patient with Ulcerative Colitis: A Case Report and Review of the Literature

Cited by 6 publications

References 32 publications

Is chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) in children the same condition as in adults?

Is chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) in children the same condition as in adults?

Other immunomodulatory agent-related lymphoproliferative diseases: a single-center series of 72 biopsy-confirmed cases

Costus root granules improve ulcerative colitis through regulation of TGF-β mediation of the PI3K/AKT signaling pathway

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