Introduction: There is a well-known gender-specific heterogeneity in clinical phenotypes of COPD. However, gender-specific differences in leukocyte subsets have not been fully defined yet in end-stage COPD patients. Aims: To investigate gender-specific differences in distinct leukocyte subpopulations of end-stage COPD patients. Methods: Consecutive end-stage COPD patients waiting for bilateral lung transplantation were included for a comprehensive polychromatic flow cytometry analysis. Fresh whole blood samples were acquired at the time of listing and immediately stained for phenotypic analysis by flow cytometry using validated lyophilized antibody panels. Results: 60 end-stage COPD patients were included in this analysis. 34 (56.6%) patients were male. Gender-specific significant differences were observed in naïve B cells (CD19+ IgD+ CD27- cells; p=0.003), marginal zone B cells (CD19+ IgD+ CD27+ cells; p=0.017), class unswitched memory B cells (CD19+ IgD+ IgM+ CD27+ CD38- cells; p=0.044), transitional B cells (CD19+ IgD+ IgM+ CD27- CD38dim CD38hi CD24+ cells; p=0.04), CD16+ myeloid DCs (HLA DR+ Lin- CD11c+ cells; p=0.033), monocytes (p=0.047) and CD16+ monocytes (p=0.04). Females showed more CD8+ T cells, marginal zone B cells, class unswitched memory B cells and CD16+ myeloid DCs, whereas male patients showed more monocytes, naive B cells and transitional B cells. Conclusion: To the best of our knowledge, this is the first comprehensive leukocyte characterization in end-stage COPD patients. Gender-specific differences were observed in several cell subsets suggesting distinct adaptive immune response in female COPD patients.

Zusammenfassung Vor über 30 Jahren wurde ein von der PUVA abgeleitetes Therapiekonzept zur Behandlung von therapierefraktären kutanen T‑Zell-Lymphomen (CTCL), insbesondere dem Sézary-Syndrom, entwickelt. R. Edelson hat Leukapherese mit Photochemotherapie verbunden, wodurch Zellen des peripheren Blutes extrakorporal nach Photosensibilisierung mittels Psoralen mit UVA-Licht bestrahlt und anschließend rückinfundiert werden. Im Jahr 1987 wurde dieses neue Behandlungskonzept mit dem Namen extrakorporale Photopherese (ECP) erstmals publiziert. Nach den ersten positiven Erfahrungen mit CTCL wurde diese Behandlung bei weiteren Indikationen erfolgreich angewendet, darunter Erkrankungen wie akute und chronische Graft-versus-Host-Reaktion (GvHD), Sklerodermie sowie atopische Dermatitis (AD). Eine zunehmende Anwendung hat die ECP in den letzten Jahren in der Behandlung von akuten und chronischen Abstoßungsreaktionen nach Organtransplantation, insbesondere Herz- und Lungentransplantation, erhalten. Im Jahr 2021 gibt es über 200 Zentren weltweit, welche die ECP erfolgreich einsetzen.

Introduction: The diagnosis and treatment of antibody-mediated rejection (AMR) after lung transplantation has recently gained recognition within the transplant community. Extracorporeal photopheresis (ECP), currently used to treat chronic lung allograft dysfunction, modulates various pathways of the immune system known to be involved in AMR. We hypothesize that adding ECP to established AMR treatments could prevent the rebound of donor-specific antibodies (DSA). Objectives: This study aimed to analyze the role of ECP as an add-on therapy to prevent the rebound of DSA. Methods: Lung transplant recipients who received ECP as an add-on therapy for pulmonary AMR between January 2010 and January 2019 were included in this single-center retrospective analysis. Baseline demographics of the patients, as well as their immunological characteristics and long-term transplant outcomes, were analyzed. Results: A total of 41 patients developed clinical AMR during the study period. Sixteen patients received ECP as an add-on therapy after first-line AMR treatment. Among the 16 patients, 2 (13%) had pretransplant DSA, both against human leukocyte antigen (HLA) class I (B38, B13, and C06). Fifteen patients (94%) developed de novo DSA (dnDSA), i.e., 10 (63%) against class I and 14 (88%) against class II. The median time to dnDSA after lung transplantation was 361 days (range 25–2,548). According to the most recent International Society of Heart and Lung Transplantation (ISHLT) consensus report, 2 (13%) patients had definite clinical AMR, 6 (38%) had probable AMR, and 7 (44%) had possible AMR. The median mean fluorescence intensity (MFI) of dnDSA at the time of clinical diagnosis was 4,220 (range 1,319–10,552) for anti-HLA class I and 10,953 (range 1,969–27,501) for anti-HLA class II antibodies. ECP was performed for a median of 14 cycles (range 1–64). MFI values of dnDSA against HLA classes I and II were significantly reduced over the treatment period (for anti-class I: 752; range 70–2,066; for anti-class II: 5,612; range 1,689–21,858). The 1-year survival rate was 55%. No adverse events related to ECP were reported in any of the patients. Conclusions: ECP is associated with a reduction of dnDSA in lung transplant recipients affected by AMR. Prospective studies are warranted to confirm the beneficial effects of ECP in the setting of AMR.

Preliminary data from this interim analysis of double lung transplanted patients receiving ECP as prophylactic treatment provide evidence that during ECP treatments the post-transplant decline in Treg frequency seen with standard immunosuppression is prevented.

Graft-versus-host disease (GvHD) is a commonly occurring immunological reaction and frequent complication following allogeneic hematopoietic stem cell transplantation. Its highly diverse manifestations including skin involvement as the most common appearance of GvHD, can dramatically influence patient's quality of life, in particular in the chronic stage, in addition to patient's decreased survival outcome. Hence, the role of the dermatologist has become very crucial in an interdisciplinary setting, particularly since appearances of GvHD in the skin can be multifaceted and challenging. Clinical manifestation of the acute GvHD (aGvHD) is limited to erythematous maculopapular rash and oral mucosal lesions while the chronic form manifests in a wider range in a localized area or disseminated including involvement of nail, scalp and genital area. This article aims to provide a comprehensive overview on the variable cutaneous presentations of acute and chronic GvHD for a proper and early diagnosis on the one hand, and to discuss updated therapeutic options for both acute and chronic GvHD on the other hand, to initiate an adequate treatment to obtain the most beneficial clinical outcome.

Purpose Extracorporeal photopheresis (ECP) is used at the Medical University of Vienna as an empiric treatment option for lung transplant recipients suffering from bronchiolitis obliterans syndrome (BOS). The objective of the present retrospective investigation was to evaluate hospital-related costs and the clinical value of ECP when applied as an adjunct to the local standard therapy of BOS compared to standard treatment alone. Methods The patient population consisted of 32 double-lung transplant recipients who had been diagnosed with BOS. Sixteen matched pairs, each pair comprising of one ECP-treated patient and one control patient was built (matched population). Preselect pair-match criteria were weighted. The primary matching criterion was the BOS grade at diagnosis. Secondary matching factors were the year of transplantation, age at transplantation, and gender. Results Study groups were identical in demographic characteristics and clinical parameters at baseline. Over the observation period of up to 15.5 years, survival probability was improved by approximately 30% in the ECP treated patients as compared to matched controls (see Figure A; p<0.05). The mean number of total re-admissions to the hospital was only 5 ± 3 (mean ± standard deviation) for the ECP group vs 27 ± 16 for the control group (p<0.05). Consequently, the total inpatient days of care were only 67 ± 58 days in ECP patients and 133 ± 94 days in control patients (p<0.05). Relevant parameters of lung function were not significantly affected. Conclusion Compared to standard BOS-directed therapies, ECP improves significantly survival probability in double-lung transplant patients diagnosed with BOS. ECP exerts a significant impact on the number of total re-admissions to the hospital, the total days of care, and the total patient days. Thus, ECP has proved highly effective and cost saving in the treatment of lung transplant patients presenting with BOS.

Background and objective : Pyogenic granuloma is a common benign vascular lesion of the skin and mucosa prone to ulceration and bleeding. Current therapeutic approaches include surgical excision, removal by means of electro caustic therapy, cryotherapy, and ablation with CO_2 or vascular lasers. The purpose of this study was to investigate the efficacy of a 532 nm potassium-titanyl-phosphate laser (KTP-laser) for the treatment of pyogenic granulomas in terms of efficacy, advantages in clinical outcome, technique and associated side effects. Methods : In this retrospective study we report on the response of 28 consecutive patients with pyogenic granulomas at multiple locations on the skin after having been treated with a 532 nm KTP laser (532 nm AuraTM Star Pulse laser, Laserscope, CA, USA). Treatment was performed with a 2 mm handpiece and energy fluences of 35–60 J cm^−2 and a laser pulse width of 50 ms or with a 1 mm handpiece and energy fluences of 200–240 J cm^−2 and a laser pulse width of 50 ms. All patients were treated on an outpatient basis at the department of dermatology, Medical University of Vienna, Austria. Results: In all of the 28 patients treated, we were able to demonstrate both symptomatic and clinical clearing of the lesions with excellent cosmetic results after the treatment. In 25 of the 28 patients a single treatment was sufficient to obtain optimal results. In three patients a second treatment session was required due to the recurrence of the lesion. The procedure required only local anesthesia, and postoperative care was limited to the application of a topical antibiotic ointment. No postoperative complications such as increased pain or wound infection and only minimal scarring were observed. Conclusions : This experience with excellent patient satisfaction suggests that treatment of pyogenic granulomas with the KTP laser is a safe, effective, and reasonable alternative to conventional therapy. As with many other limited interventions with this laser technology, the advantages include minimal postoperative pain, conservative site-specific minimally invasive surgeries and a very satisfactory cosmetic result with a high acceptance rate on the side of the patients.

Graft-versus-host disease (GvHD) is a complex multiorgan disease, which can occur as a complication following allogeneic stem cell transplantation. Involvement of the skin represents the most common appearance of GvHD. The role of the dermatologist is critical for diagnosis and initiation of treatment.The aim of this article is to provide a comprehensive review of the cutaneous types of GvHD and to present the most recent data on diverse therapy options for its acute and chronic form allowing the clinician to establish a definite diagnosis and to initiate proper therapy.Possible clinical appearances and recommended criteria to assist in making the right diagnosis are presented by means of expert recommendations.GvHD is still a complex entity whose diagnosis is often associated with challenges due to its variable presentation. Proper diagnosis and subsequent therapy is paramount for the optimal clinical outcome.

Zusammenfassung Das Grundprinzip der extrakorporalen Photopherese (ECP) besteht in der Isolierung von kernhaltigen Blutzellen durch Zentrifugalkraft (Leukapherese), Behandlung des Apheresates mit 8-Methoxypsoralen, Bestrahlung mit ultraviolettem Licht und Reinfusion. Diese Behandlung wurde vor 30 Jahren zunächst für die Therapie des kutanen T-Zell-Lymphoms entwickelt. Da die ECP eine Modulation der durch T-Zellen vermittelten Immunität bewirkt, wurde sie später auch in Indikationen, die auf einer Fehlregulation der zellulären Abwehr beruhen, etabliert. In der Dermatologie zählen hierzu v. a. die akute und chronische Graft-versus-Host-Krankheit, die systemische Sklerose, die therapierefraktäre atopische Dermatitis und bestimmte blasenbildende Autoimmundermatosen. Die ECP kann als wirksame und sichere Therapieoption für diese teils lebensbedrohenden, schmerzhaften und psychisch belastenden Hautkrankheiten angesehen werden. In den meisten Fällen erlaubt die ECP eine Dosisreduktion von Kortikosteroiden. In manchen Indikationen fehlen jedoch noch die für eine wissenschaftlich fundierte Bewertung notwendigen randomisierten Vergleichsstudien.

Introduction ECP is an established therapy for prevention of acute rejection perioperatively and for treatment of recurrent, therapy resistant rejections after heart transplantation (HTx). Data on cardiac allograft vasculopathy (CAV) prevention with ECP exist. There is no data on treatment with ECP immediately postoperative in HTx patients to achieve CNI delay and avoidance of induction therapy. Here we report our first experience on 3 patients that were successfully treated with ECP immediately postoperative to reduce the risk of sepsis or cancer recurrence. Case Report 3 patients underwent ECP with CNI delay after HTx due to high risk for cancer recurrence (n=2) or sepsis (n=1). All patients were female. Patient 1 (46 years at time of transplantation) was transplanted urgently with a progressive cardiac sarcoma (myxofibrosarcoma). Patient 2 (43y) had a history of osteosarcoma with pulmonary metastasis (20 years before HTx) and breast cancer (10 and 7 years before HTx). Patient 3 (33y) was transplanted in a high-urgent status after aortic dissection followed by complications and finally needed ECMO support and high dosage of catecholamines. All patients received postoperative ECP (10 treatments within first month, every 2 weeks in month 2+3, 1/month until month 6) with low maintenance immunosuppression with tacrolimus (target range 7-10ng/ml in month 1-3, 5-10ng/ml >3 months), mycophenolate mofetil for 2-3 weeks (2mg/day), everolimus after week 2-3 (target range: 3-8ng/ml) and steroids (0.2mg/kg starting on day 7, tapering to 0.03 mg/kg until end of first year). All patients are alive with excellent graft function 13, 8 and 5 months after HTx, respectively. Out of 13 biopsies (3, 6 and 4, respectively), 2 showed mild signs of cellular rejection (ISHLT 1A/1R): In patient 1, 13 days and in patient 3, 23 days after HTx. No signs of antibody-mediated rejection (ABMR) with C4d or C3d positivity were found. Moreover, non of the patients developed clinical infection during the first 6 months post transplantation. In both patients with history of cancer, no reoccurrence developed. Summary CNI delay with better survival in the ECP group was described in LTx patients but there is no evidence for HTx patients. In our experience, CNI delay and avoidance of induction therapy due to ECP is a safe and effective strategy for patients at risk for cancer recurrence or sepsis.

The term 'sclerosing diseases of the skin' comprises specific dermatological entities, which have fibrotic changes of the skin in common. These diseases mostly manifest in different clinical subtypes according to cutaneous and extracutaneous involvement and can sometimes be difficult to distinguish from each other. The present guideline focuses on characteristic clinical and histopathological features, diagnostic scores and the serum autoantibodies most useful for differential diagnosis. In addition, current strategies in the first-and advanced-line therapy of sclerosing skin diseases are addressed in detail. Part 1 of this guideline provides clinicians with an overview of the diagnosis and treatment of localized scleroderma (morphea), and systemic sclerosis including overlap syndromes of systemic sclerosis with diseases of the rheumatological spectrum.

The term 'sclerosing diseases of the skin' comprises specific dermatological entities which have fibrotic changes of the skin in common. These diseases mostly manifest in different clinical subtypes according to cutaneous and extracutaneous involvement and can sometimes be difficult to distinguish from each other. The present guideline focuses on characteristic clinical and histopathological features, diagnostic scores and the serum autoantibodies most useful for differential diagnosis. In addition, current strategies in the first- and advanced-line therapy of sclerosing skin diseases are addressed in detail. Part 2 of this guideline provides clinicians with an overview of the diagnosis and treatment of scleromyxedema, scleredema (of Buschke) and nephrogenic systemic sclerosis (nephrogenic fibrosing dermopathy).

BACKGROUND:Extracorporeal photopheresis (ECP) improves skin sclerosis in systemic sclerosis (SSc) patients. SSc is associated with an increased risk of lung cancer. As ECP is supposed to exert immunomodulatory effects, a possible impact of ECP on the incidence of lung cancer in SSc patients was evaluated.METHODS:Seventy-one SSc patients treated with ECP at the Photopheresis Unit of the Department of Dermatology at the Medical University of Vienna between 1991 and 2013 were analyzed retrospectively.RESULTS:We calculated a standardized incidence ratio (SIR) for lung cancer in ECP-treated SSc patients of 2.34 [95% confidence interval (CI) 1.63-2.49]. This is in accordance with recent meta-analyses demonstrating a significantly enhanced risk of lung carcinoma in SSc patients. Comparison of the lung cancer risks of these patients with our ECP-treated patients revealed that ECP has no influence. Each patient with lung carcinoma had previously been diagnosed with lung involvement of the non-specific interstitial pneumonitis (NSIP) type.CONCLUSION:We confirm that SSc patients are at significantly increased risk for lung cancer. However, ECP does not influence this risk. NSIP may be a risk factor for lung cancer in SSc patients.

BackgroundAfter the first investigational study on the use of extracorporeal photopheresis for the treatment of cutaneous T-cell lymphoma was published in 1983 with its subsequent recognition by the FDA for its refractory forms, the technology has shown significant promise in the treatment of other severe and refractory conditions in a multi-disciplinary setting. Among the major studied conditions are graft versus host disease after allogeneic bone marrow transplantation, systemic sclerosis, solid organ transplant rejection and inflammatory bowel disease.Materials and methodsIn order to provide recognized expert practical guidelines for the use of this technology for all indications the European Dermatology Forum (EDF) proceeded to address these questions in the hands of the recognized experts within and outside the field of dermatology. This was done using the recognized and approved guidelines of EDF for this task.Results and conclusionThese guidelines provide at present the most comprehensive available expert recommendations for the use of extracorporeal photopheresis based on the available published literature and expert consensus opinion.

Graft-versus-host disease (GvHD) is a serious complication of allogeneic hematopoietic cell transplantation causing significant morbidity and mortality. Corticosteroids are the established first-line treatment of GvHD. Patients not responding to corticosteroids have a dismal prognosis. Extracorporeal photopheresis (ECP) has objective activity in the treatment of both acute and chronic corticosteroid-refractory GvHD patients, has an excellent safety profile and is internationally well-established. ECP has been recommended by a significant number of renowned scientific organizations as an efficient treatment option for patients with GvHD. ECP has a proven corticosteroid-sparing effect and favourably impacts on survival and quality of life of responding patients.