Interstitial Granulomatous Dermatitis Associated With the Use of Tumor Necrosis Factor α Inhibitors

Deng, April; Harvey, Valérie; Sina, Bahram; Strobel, David A.; Badros, Ashraf; Junkins‐Hopkins, Jacqueline M.; Samuels, Allen; Oghilikhan, Mana; Gaspari, Anthony A.

doi:10.1001/archderm.142.2.198

Cited by 152 publications

(112 citation statements)

References 20 publications

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“…In our patient, the disappearance of the skin manifestations after adalimumab discontinuation is consistent with other case reports of cutaneous granulomatous dermatitis involving TNFα inhibitors [11,16,17,22,[25][26][27][28][29]. Moreover, a causality assessment of the adverse drug reactions was demonstrated to be probable by using Naranjo adverse drug reaction probability scale, with a total score of 6 (meaning a probable adverse drug reaction) [30].…”

Section: Case Descriptionsupporting

confidence: 89%

“…The implicated drugs included calcium channel blockers, angiotensin converting enzyme inhibitors, beta-blockers, lipid-lowering agents, antihistamines, anticonvulsants and antidepressants. In 2006 Deng, et al described the first such reaction to the TNFα inhibitor adalimumab, and in 2010 Martorell-Calatayud, et al described another similar case [16,17]. Table 1 summarizes the recent case-reports in which RGD (IGD, PNGD, IGDR) were observed in patients with arthritis, receiving various TNF-α inhibitors (Table 1).…”

Section: Case Descriptionmentioning

confidence: 99%

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Reactive Granulomatous Dermatitis during Anti-TNF Therapy: A Case Report and Review of the Literature

Cassone¹

2017

Clin Med Rev Case Rep

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Tumor Necrosis Factor (TNF)-α blockers have been shown to be highly effective in the treatment of arthritis not responsive to traditional therapy. In parallel, there are an increasing number of reports about the development of cutaneous side effects after the administration of anti-TNF-α agents. Noninfectious cutaneous granulomatous reactions include granuloma annulare, non-caseating granuloma, sarcoid-like granulomatosis and also a wide spectrum of conditions recently unified under the term of reactive granulomatous dermatitis.The majority of the above reported granulomatous dermatitis is associated with an underlying inflammatory disorder, and almost all may be drug-induced. Moreover, a substantial overlap, both in clinical and histologic features, is present between these conditions. We describe a reactive granulomatous dermatitis in a patient with psoriatic arthritis treated with adalimumab, resolved after the TNF-α inhibitor discontinuation, and we summarize the recent case-reports in which reactive granulomatous dermatitis were observed in patients with arthritis receiving various TNF-α inhibitors. Reactive granulomatous dermatitis may be a possible long-term side effect of this class of drugs. Although TNF-α blockers are usually used in the treatment of granulomatous disorders, patients treated with these kinds of drugs should be carefully monitored as, in rare cases, TNF-α inhibitors may induce sufficient cytokine activation to support granuloma formation.

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Section: Case Descriptionsupporting

confidence: 89%

Section: Case Descriptionmentioning

confidence: 99%

Reactive Granulomatous Dermatitis during Anti-TNF Therapy: A Case Report and Review of the Literature

Cassone¹

2017

Clin Med Rev Case Rep

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“…Regression of lymphoid proliferations after cessation of therapy has been reported with several immunomodulator agents, including etanercept, 4,22 as well as infliximab and adalimumab. 23 It is uncertain if cessation of immunomodulator agent therapy can cause regression of associated lymphomas; one follicular lymphoma case in our series progressed in spite of cessation of infilximab therapy and a case of aggressive T-cell lymphoma after etanercept therapy failed to respond to cessation of therapy and progressed rapidly. 24 However, regression of a diffuse large B-cell lymphoma after cessation of in fliximab without the use of cytotoxic chemotherapy has been reported.…”

Section: Discussionmentioning

confidence: 80%

Immunomodulator agent-related lymphoproliferative disorders

Hasserjian

Chen²,

Perkins

et al. 2009

Modern Pathology

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The recent development of inhibitors of key immune response proteins has revolutionized the therapy of autoimmune diseases; these immunomodulator agents include monoclonal antibodies and receptor antagonists. However, as with all therapies, these new agents are not without side effects and complications. In particular, anti-tumor necrosis factor alpha (TNFa) agents have been reported to be associated with an increased incidence of lymphoproliferative disorders, infections, and vasculitis. We evaluated the clinicopathological features of 18 cases of immunomodulator agent-related lymphoproliferative disorders (IAR-LPD) from several institutions. These included 6 cases of B-cell lymphoma, 2 cases of T-cell lymphoma, 3 cases of classical Hodgkin lymphoma, and 7 atypical lymphoid proliferations that did not fulfill diagnostic criteria for lymphoma; two of the latter regressed after discontinuation of the immunomodulator agent therapy. All eight lymphoma patients with available information had also received prior chemotherapy (methotrexate or 6-mercaptopurine). EBV was strongly associated with the B-cell and classical Hodgkin lymphomas. This case series illustrates that a broad range of lymphoid proliferations can occur after immunomodulator agent therapy and that these immunomodulator agent-related lymphoproliferative disorders have considerable overlap with other well-defined lymphoproliferative diseases associated with iatrogenic immunosuppression. Further study is warranted to evaluate how these therapies interact with other immunosuppressive agents and the underlying abnormal immune system to enhance the development of lymphomas and atypical lymphoid proliferations.

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“…However, reduction in ECM production via inhibited TGF-␤1 or CTGF expression may be of equal importance (Peng et al, 2006;Gao et al, 2007) in defining the efficacy of these drugs. The new biological anti-inflammatory and immunomodulatory drugs, such as tumor necrosis factor inhibitors and the interleukin-1 inhibitor anakinra, may also cause adverse side-effects on the ECM, particularly in the skin (Deng et al, 2006;Regula et al, 2008). In clinical practice, glucocorticoids are probably the most well known drugs that cause marked side-effects via their influence on the ECM.…”

Section: Deleterious Effects Of Current Drugs On the Extracellularmentioning

confidence: 99%

Extracellular Matrix Molecules: Potential Targets in Pharmacotherapy

et al. 2009

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Interstitial Granulomatous Dermatitis Associated With the Use of Tumor Necrosis Factor α Inhibitors

Cited by 152 publications

References 20 publications

Reactive Granulomatous Dermatitis during Anti-TNF Therapy: A Case Report and Review of the Literature

Reactive Granulomatous Dermatitis during Anti-TNF Therapy: A Case Report and Review of the Literature

Immunomodulator agent-related lymphoproliferative disorders

Extracellular Matrix Molecules: Potential Targets in Pharmacotherapy

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