Christian Tigges

Lupus erythematosus tumidus: response to antimalarial treatment in 36 patients with emphasis on smoking.

OBJECTIVE To determine the efficacy of antimalarial drug use in patients with lupus erythematosus tumidus. DESIGN Retrospective single-center study. SETTING Dermatologic clinic at a university hospital. PATIENTS Thirty-six patients with multifocal lupus erythematosus tumidus. Intervention Treatment with either chloroquine phosphate or hydroxychloroquine sulfate. MAIN OUTCOME MEASURES Cutaneous Lupus Erythematosus Disease Area and Severity Index score. RESULTS Treatment with antimalarial drugs resulted in a significant reduction in the Cutaneous Lupus Erythematosus Disease Area and Severity Index score, from 4 (range, 2-8) at baseline to 1 (range, 0-6) after 3 months of therapy (P < .001). Twenty-two patients (61%) exhibited complete or almost complete clearance of skin lesions, consistent with a clinical score of 0 or 1. No difference in efficacy was noted between the chloroquine-treated group and the hydroxychloroquine-treated group (P = .40). Adverse effects (nausea, dizziness, and headache) occurred only in patients treated with chloroquine. Twenty-eight patients (78%) were smokers, and smokers had a significantly higher mean (SD) clinical score than nonsmokers (5.1 [1.8] vs 3.3 [1.6]; P = .03). Moreover, smokers had a significantly lower reduction in clinical score with antimalarial treatment compared with nonsmokers (r = 0.30; P = .03; 95% confidence interval, -0.05 to 0.57). Eighty-eight percent of nonsmokers (7 of 8 patients) but only 57% of smokers (16 of 28 patients) had a clinical score of 1 or 0 after 3 months of treatment with antimalarial drugs. CONCLUSIONS These retrospective study findings demonstrate that antimalarial treatment is highly effective in multifocal lupus erythematosus tumidus. Lower incidence of adverse effects and equal efficacy might favor the use of hydroxychloroquine. Patients who smoke should be encouraged to join smoking cessation programs because they will respond better to antimalarial treatment.

Local Tumor Treatment in Combination with Systemic Ipilimumab Immunotherapy Prolongs Overall Survival in Patients with Advanced Malignant Melanoma.

Too few patients benefit from immune checkpoint inhibition alone. However, patients with melanoma receiving systemic anti-CTLA-4 plus localized treatments had significantly prolonged overall survival. In a multivariate analysis, adding local treatment was an independent factor for improved survival. Immune checkpoint inhibition with ipilimumab has revolutionized cancer immunotherapy and significantly improved outcomes of patients with advanced malignant melanoma. Local peripheral treatments (LPT), such as radiotherapy or electrochemotherapy, have been shown to modulate systemic immune responses, and preliminary data have raised the hypothesis that the combination of LPT with systemic immune checkpoint blockade might be beneficial. Clinical data from 127 consecutively treated melanoma patients at four cancer centers in Germany and Switzerland were analyzed. Patients received either ipilimumab (n = 82) or ipilimumab and additional LPT (n = 45) if indicated for local tumor control. The addition of LPT to ipilimumab significantly prolonged overall survival (OS; median OS 93 vs. 42 weeks, unadjusted HR, 0.46; P = 0.0028). Adverse immune-related events were not increased by the combination treatment, and LPT-induced local toxicities were in most cases mild. In a multivariable Cox regression analysis, we show that the effect of added LPT on OS remained statistically significant after adjusting for BRAF status, tumor stage, tumor burden, and central nervous system metastases (adjusted HR, 0.56; 95% confidence interval, 0.31–1.01, P = 0.05). Our data suggest that the addition of LPT to ipilimumab is safe and effective in patients with metastatic melanoma irrespective of clinical disease characteristics and known risk factors. Induction of antitumor immune responses is most likely the underlying mechanism and warrants prospective validation. Cancer Immunol Res; 4(9); 744–54. ©2016 AACR.

Etanercept plus narrowband ultraviolet B phototherapy of psoriasis is more effective than etanercept monotherapy at 6 weeks

Background  A substantial portion of patients with psoriasis does not achieve a satisfactory response under antitumour necrosis factor (TNF)‐α biological therapies.

Upregulation of cathepsin S in psoriatic keratinocytes

Please cite this paper as: Upregulation of cathepsin S in psoriatic keratinocytes. Experimental Dermatology 2010; 19: e80–e88.

Impact of etanercept treatment on ultraviolet B‐induced inflammation, cell cycle regulation and DNA damage

Background  Current studies indicate that treatment with tumour necrosis factor (TNF)‐α blockers plus ultraviolet (UV) B phototherapy results in higher relative Psoriasis Area and Severity Index reduction as compared with TNF‐α monotherapy.

Significant upregulation of antimicrobial peptides and proteins in lichen sclerosus

Background  Lichen sclerosus (LS) is a chronic inflammatory T cell‐driven sclerotic skin condition in which skin barrier disruption frequently occurs. Inflamed and injured epithelia are a particularly rich source of antimicrobial peptides and proteins (AMPs).

Absolute count of T and B lymphocyte subsets is decreased in systemic sclerosis

BackgroundPrevious reports on lymphocyte subpopulations in systemic sclerosis (SSc) are conflicting. Therefore, we aimed to investigate the lymphocyte subsets in SSc patients who were not on immunosuppressive therapy.MethodsLymphocyte subsets were assessed in the peripheral blood of SSc patients (n = 29) and healthy controls (n = 29) using the four colour flow cytometry method. Correlation studies were also performed in order to assess the relationship between lymphocyte subsets and clinical parameters.ResultsThe absolute count of lymphocytes (P = 0.0042), CD3+ (P = 0.0014), CD4+ (P = 0.0070), CD8+ (P = 0.021), and CD19+ cells (P = 0.024) was significantly decreased in SSc patients when compared to healthy controls. CD4+/CD8+ ratio and the absolute count of CD56+ cells observed in SSc patients did not significantly differ from controls (P = 0.165; P = 0.632, respectively). There was no substantial relationship between the lymphocyte subset levels and clinical features (i.e., SSc subtype, autoantibody profiles, organ involvement), except for a significant inverse correlation of CD19+ cells and the modified Rodnan skin score (r = -0.43, P = 0.020).ConclusionOur data support previous reports indicating that subsets of T lymphocytes as well as B lymphocytes play a role in the pathogenesis of SSc.

Pulsed High-Dose Corticosteroids Combined With Low-Dose Methotrexate Treatment in Patients With Refractory Generalized Extragenital Lichen Sclerosus

BACKGROUND Lichen sclerosus (LS) is a rare, chronic inflammatory skin disease that predominantly affects the anogenital area. A few patients exhibit widespread extragenital disease that may lead to blister formation and superficial erosions. We evaluated the efficacy of pulsed high-dose corticosteroids combined with low-dose methotrexate treatment in patients with refractory generalized LS that had failed to respond to standard topical corticosteroid therapy. Observation Seven patients were included in this retrospective study, all of whom were treated with pulsed high-dose corticosteroids combined with low-dose methotrexate for at least 6 months. The outcome measure was an individual, nonvalidated clinical score. Overall, a significant decrease in the clinical score was observed, from a median score of 8 (range, 5 to 24) before treatment to 2 (range, 1 to 4) after treatment. Adverse effects observed during therapy were moderate and disappeared after the end of treatment. During the follow-up period of at least 3 months (mean, 4.7 [range, 3-8] months), none of the patients experienced a relapse of extragenital LS. CONCLUSIONS Patients with severe extragenital LS benefit from pulsed high-dose corticosteroids combined with low-dose methotrexate therapy. This combination therapy should be considered in generalized disease, especially disease that is refractory to conventional treatment.

Expression of antimicrobial peptides and proteins in etanercept-treated psoriasis patients

Recent papers highlight the role of dysregulated expression of antimicrobial peptides and proteins (AMPs) in the pathogenesis of psoriasis. Etanercept, a blocker of the pro-inflammatory cytokine tumour necrosis factor-α (TNF-α), is effective in the treatment of psoriasis. We aimed to evaluate the expression profiles of AMPs in psoriatic skin before and after a 6-week course of etanercept therapy. We included 12 psoriasis patients who underwent medium-dose etanercept treatment for 6weeks. At baseline and at the end of therapy immunohistochemistry from lesional skin was performed for psoriasin, LL-37, and human ß-defensin 2 (hBD-2). After 6-week treatment, the modified psoriasis area and severity index significantly decreased from 37.5±5.9 to 14±13.4. Lesional immunoreactivity scores of psoriasin, LL-37, and hBD-2 also significantly decreased after a 6-week course of etanercept. We have demonstrated that etanercept-induced improvement of psoriasic lesions is associated with a significant decline of AMP protein expression.

Glutathione-S-transferase T1 genotyping and phenotyping in psoriasis patients receiving treatment with oral fumaric acid esters.

Glutathione S‐transferases (GSTs) are involved in detoxification of xenobiotics such as fumaric acid esters (FAE).