Progressive neurologic dysfunction in a psoriasis patient treated with dimethyl fumarate

Bartsch, Thorsten; Rempe, Torge; Wrede, Arne; Leypoldt, Frank; Brück, Wolfgang; Adams, Ortwin; Rohr, Axel; Jansen, Olav; Wüthrich, Christian; Deuschl, Günther; Koralnik, Igor J.

doi:10.1002/ana.24471

Cited by 45 publications

(53 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It is well known that individuals presenting with decreased T-cell immunity are at a higher risk of developing PML [29] . In all cases of DMF-associated PML cases in psoriasis and MS patients an association with lymphopenia was present, and where T-cell subsets were measured (4 out of 9), [21][22][23]26] CD4+ and CD8+ deficiencies were noted [26] .…”

Section: Discussionmentioning

confidence: 94%

Lymphopenia and CD4+/CD8+ Cell Reduction under Fumaric Acid Esters

Sondermann

Rompoti²,

Leister³

et al. 2017

Dermatology

View full text Add to dashboard Cite

Background: Fumaric acid esters (FAEs) are a broadly used therapy option for patients suffering from moderate-to-severe plaque psoriasis. Various studies in psoriasis have already shown peripheral blood lymphopenia during oral FAE therapy. Smaller studies also documented a reduction of CD4+ and CD8+ cell counts. Up to now, there are few case reports on opportunistic infections under FAE therapy - all of them associated with lymphopenia. Objective: To examine the influence of FAEs on white blood cells with special regard to leukocytes, lymphocytes, and CD4+ and CD8+ cells during psoriasis therapy. Patients and Methods: A cohort of 105 patients with diagnosed moderate-to-severe chronic plaque psoriasis was enrolled in this single-centre observational trial. For a cohort of 36 patients, T-cell subset analyses were performed. Results: Of the total, 65 patients were male (61.9%) and 40 (38.1%) female; the mean age was 43.3 years (range 16-73 years). The median lymphocyte count was significantly reduced by about 35.8% after the first 6 months of therapy. When assessing the lymphocyte count nadir over the whole period observed, 46.7% of the patients developed lymphopenia. Severe lymphopenia (<500/µL) was documented in 11.4% of the patients. The CD4+ and CD8+ cell counts were significantly reduced by about 30.2 and 45.3%, respectively. Conclusion: To the best of our knowledge this is the largest clinical investigation analysing prospectively CD4+ and CD8+ cell counts in psoriasis patients receiving FAEs. We suggest periodic monitoring of absolute lymphocyte counts as well as the establishment of the determination of T-cell subsets prior to and during therapy.

show abstract

Section: Discussionmentioning

confidence: 94%

Lymphopenia and CD4+/CD8+ Cell Reduction under Fumaric Acid Esters

Sondermann

Rompoti²,

Leister³

et al. 2017

Dermatology

View full text Add to dashboard Cite

show abstract

“…Dimethyl fumarate is now licensed to treat relapsing remitting multiple sclerosis (MS). Progressive multifocal leucoencephalopathy (PML) has been reported in 8 patients taking FAEs both for psoriasis ( n = 7) and MS ( n = 1) [3][4][5][6][7][8][9][10] . Recent recommendations from the European Medicines Agency (EMA) suggest full blood count monitoring every 4 weeks for the duration of therapy for psoriasis [11] .…”

Section: Introductionmentioning

confidence: 99%

The Implications of Recent Recommendations for Managing Patients with Psoriasis Treated with Fumaric Acid Esters

Foley

Molloy²,

Lally³

et al. 2017

Dermatology

View full text Add to dashboard Cite

Background/Aims: Fumaric acid esters (FAEs) are a well-established efficacious systemic treatment for psoriasis. Recent recommendations from the European Medicines Agency suggest monitoring of full blood count every 4 weeks for the duration of therapy for psoriasis. The aim of our study was to assess the incidence of lymphopenia in patients taking FAEs and the impact of recent recommendations for our practice. Methods: We reviewed 151 patients treated with FAEs for psoriasis between December 2013 and 2015. Results: Lymphopenia <700 × 10⁹/L was detected within the last 12 months in 36/151 (24%) and lymphopenia <500 × 10⁹/L in 10/151 (7%). Of 39 patients no longer on treatment, 7 (18%) stopped because of persistent lymphopenia. Conclusion: The implementation of these recommendations would have significant resource implications and also likely influence the acceptability of FAEs to patients. Cessation of FAEs necessitates the need for alternative therapy, commonly biologic therapy.

show abstract

“…In addition to patients with AIDS, hematologic malignancies, and transplant recipients, PML has been reported in a growing number of individuals with autoimmune diseases treated with immunomodulatory medications such as natalizumab (Clifford et al 2010; Dahlhaus et al 2013; Gheuens et al 2012b; Hoepner et al 2014; Marousi et al 2012; Tan et al 2011), dimethyl fumarate (Bartsch et al 2015; Dammeier et al 2015; Khatri et al 2015), or efalizumab (Carson et al 2009; Gadzia and Turner 2010; Korman et al 2009; Kothary et al 2011). Since seizures frequently occurred at or soon after PML onset, PML should be included in the differential diagnosis of new onset seizures in the aforementioned high-risk patients.…”

Section: Discussionmentioning

confidence: 99%

Predictors and characteristics of seizures in survivors of progressive multifocal leukoencephalopathy

et al. 2015

Self Cite

View full text Add to dashboard Cite

This study aims to determine the risk factors for epileptogenesis and characteristics of seizures in patients with progressive multifocal leukoencephalopathy (PML) who survive more than 1 year from onset of neurological symptoms (PML survivors). We reviewed clinical data including seizure history and MR imaging studies from PML survivors evaluated at our institution between 1997 and 2014. PML progressors who passed away within 1 year and patients with a history of seizures prior to PML diagnosis were excluded from the analysis. Of 64 PML survivors, 28 (44 %) developed seizures. The median time from the onset of PML symptoms to the first seizure was 5.4 months (range 0–159) and 64 % of patients with seizures had them within the first year. The presence of juxtacortical PML lesions was associated with a relative risk of seizures of 3.5 (p<0.02; 95 % confidence interval (CI) 1.3– 9.4) in multivariate analyses. Of all seizure types, 86 % were focal and 60 % most likely originated from the frontal lobes. Among seizure patients, 89 % required treatment, including one (54 %), two (25 %), or three (10.5 %) antiepileptic drugs. Seizures are a frequent complication in PML and can develop throughout the entire course of the disease. However, late onset seizures did not signify PML relapse. Seizures may require treatment with multiple antiepileptic medications and are a significant co-morbidity in PML.

show abstract

Progressive neurologic dysfunction in a psoriasis patient treated with dimethyl fumarate

Cited by 45 publications

References 57 publications

Lymphopenia and CD4+/CD8+ Cell Reduction under Fumaric Acid Esters

Lymphopenia and CD4+/CD8+ Cell Reduction under Fumaric Acid Esters

The Implications of Recent Recommendations for Managing Patients with Psoriasis Treated with Fumaric Acid Esters

Predictors and characteristics of seizures in survivors of progressive multifocal leukoencephalopathy

Contact Info

Product

Resources

About