Beatrix Volc-Platzer

Aerobic capacity in adult dermatomyositis/polymyositis patients and healthy controls

OBJECTIVE Assessment of myositis patients has relied on symptoms, strength testing, and serum muscle enzyme activity. Recently, functional assessments and evaluation of strength by dynamometry and of disease activity by magnetic resonance imaging have also been added. Aerobic testing in selected patients has been considered useful. DESIGN Case-control study. SETTING University Hospital, Vienna, Austria. PATIENTS Twenty-two subjects (8 outpatients with chronic dermatomyositis and 3 outpatients with chronic polymyositis, and 11 healthy controls) participated, allowing the identification of 11 case-control pairs matched by age (+/-3 years) and gender (mean age, 48+/-14 yrs; ratio of women to men, 18/4). MAIN OUTCOME MEASURES Target parameters were peak oxygen uptake (peak VO2) to estimate aerobic exercise capacity and peak isometric torque for muscle strength. Creatine phosphokinase (CPK) was measured to assess elevation of muscle enzymes. RESULTS The mean peak VO2 in patients with dermatomyositis/polymyositis was 15.3 mL/min/kg (SD = 5.8) and in the healthy controls 28.7 mL/min/kg (SD = 7.8). Cardiorespiratory capacity expressed as peak VO2 was thus significantly reduced at 53% (p = .0001) of the control value. Muscle strength expressed as peak isometric torque was significantly lower (p = .01) in patients (mean 148+/-73 Nm) when compared to the control group (mean 261+/-99 Nm). In myositis patients peak VO2 and peak isometric torque correlate well with each other (r = .7631; p = .0001), but not at all with serum CPK levels (r = .056; p = .869). CONCLUSION Peak VO2 is significantly diminished in patients with dermatomyositis/polymyositis, compared with age- and sex-matched controls. Serum CPK did not significantly correlate with VO2. Aerobic exercise testing may be a useful assessment parameter in selected patients with dermatomyositis/ polymyositis.

Extracorporeal Photochemotherapy in the Treatment of Severe Graft-Versus-Host Disease

Advances in posttransplanl immunosuppression have to the present not been able to prevent the development of graft-versus-host disease (GVHD) in patients given related or unrelated stem cell grafts for cure of hematologic diseases. Patients with GVHD not responding to first line therapy with corticosteroids remain at high risk of death due to severe infections or organ failure. Extracorporeal exposure of peripheral blood mononuclear cells to the photosensitizing agent 8-methoxypsoralen and ultraviolet A radiation has been shown to be effective in treatment of selected T-cell mediated diseases, including cutaneous T-cell lymphoma and rejection after organ transplantation. Extracorporeal photochemotherapy (ECP) is also a safe and efficacious adjunct therapy for both acute and chronic extensive GVHD with skin and visceral involvement and resistance to conventional immunosuppressive therapy. A multi-center randomized study should help define the impact of ECP in the treatment of GVHD and overall survival of these patients.

Long-term follow-up of patients after related- and unrelated-donor bone marrow transplantation for chronic myelogenous leukemia

Abstract Between January 1983 and December 1997, 88 patients (36 female, 52 male, median age 37 years, range 19–57) with chronic myelogenous leukemia (CML) underwent allogeneic bone marrow transplantation (BMT) at the University Hospital of Vienna. Sixty patients were in chronic phase, 18 in accelerated phase, and ten in blast crisis. Marrow donors were HLA-identical siblings for 64 patients (BM 58, PBSC 6), 2-antigen-mismatched related donors (RD) for two, HLA-identical unrelated donors (URD) for 17, and 1-antigen-mismatched URD for five. The median time from diagnosis to BMT was 22 months (range 2–91), and 63 patients had received prior interferon (IFN)-alpha therapy, 46 (73%) for more than 6 months. Conditioning therapy consisted of cyclophosphamide (CY) and total body irradiation (TBI) in 71 patients and CY and busulfan (BU) in 16. One patient received etoposide and TBI. For graft-versus-host disease (GVHD) prophylaxis methotrexate (MTX) was given to 12 patients, MTX and cyclosporin A (CSA) to 67, CSA alone to four, and CSA and methylprednisolone to five. Durable engraftment was documented in 80 of 82 patients (98%). As of December 31, 1997, 52 patients (59%) were alive, 38 (58%) after sibling transplantation with a median observation time of 73 months and 14 (64%) after URD transplantation with a median observation time of 12 months. Probability of overall survival is 59%, for patients undergoing transplantation in chronic phase and 44% for patients undergoing transplantation in advanced stage CML. Probability of disease-free survival (DFS) after sibling and URD BMT is 55% and 59%, respectively. Ten patients (12%) experienced relapse of CML. Transplant-related mortality was 32% both after RD and after URD transplantation. Acute GVHD occurred in 53 of 80 evaluable patients (66%), consisting of grade III or IV in 14 patients (18%). Chronic GVHD developed in 40 of 63 eligible patients (63%), including extensive disease in 26 patients (41%). Thus, sibling and URD BMT offer high cure rates with acceptable toxicity to patients with CML.

Prospective, Randomized, Multicenter, Double-Blind Placebo-Controlled Trial Comparing Adjuvant Interferon Alfa and Isotretinoin With Interferon Alfa Alone in Stage IIA and IIB Melanoma: European Cooperative Adjuvant Melanoma Treatment Study Group

PURPOSE The combination of interferon alfa (IFNalpha) and isotretinoin has shown a direct antiproliferative effect on human melanoma cell lines, but it remained unclear whether this combination is more effective than IFNalpha alone in patients with metastatic melanoma. We evaluated safety and efficacy of IFNalpha and isotretinoin compared with IFNalpha alone as adjuvant treatment in patients with primary malignant melanoma stage IIA and IIB. PATIENTS AND METHODS In a prospective, randomized, double-blind, placebo-controlled trial, 407 melanoma patients in stage IIA (301 patients) and IIB (106 patients) were randomly assigned to either IFNalpha and isotretinoin (isotretinoin group; 206 patients) or IFNalpha and placebo (placebo group; 201 patients) after excision of the primary tumor. IFNalpha was administered three times a week at a dose of 3 million units subcutaneously for 24 months. Isotretinoin at a dose of 20 mg for patients < or = 73 kg, 30 mg for patients greater than 73 kg, or placebo daily for 24 months. RESULTS A scheduled interim analysis revealed no significant differences in survival rates, with the isotretinoin group and the placebo group showing 5-year disease-free survival rates of 55% (95% CI, 46% to 65%) and 67% (95% CI, 59% to 75%), respectively, and overall 5-year survival rates of 76% (95% CI, 67% to 84%) and 81% (95% CI, 74% to 88%), respectively. The trial was stopped for futility. CONCLUSION The addition of isotretinoin to an adjuvant treatment of low-dose IFNalpha in patients with stage IIA and IIB melanoma had no significant effect on disease-free or overall survival and is therefore not recommended.

Perforating folliculitis, angioedema, hand-foot syndrome--multiple cutaneous side effects in a patient treated with sorafenib.

A patient with clear cell renal cell carcinoma was treated with sorafenib, a multikinase inhibitor, which induced a variety of cutaneous side effects. In addition to xerosis, he developed angioedema (AE), hand‐foot syndrome (HFS) and perforating folliculitis (PF). The latter three occurred in a dose‐dependent manner. AE was observed at the recommended daily dose of 800 mg. Dose reduction to 400 mg prevented its recurrence. At this dose level, the patient exhibited HFS, which cleared upon further reduction of the dose. While receiving 200 mg, the patient developed PF. To the best of our knowledge, this is the first description of a case of PF during treatment with sorafenib.

Sacroileitis im Rahmen eines SAPHO Syndroms – promptes Ansprechen auf Etanercept

SummaryPainful, aseptic osteitis remains the major problem in the treatment of patients with SAPHO syndrome. We present a child suffering of both sacroiliitis and acne conglobata in the context of SAPHO syndrome. While acne lesions responded well to systemic isotretinoin, sacroiliitis associated pain could be controlled neither by NSAR nor by intralesional or systemic steroid injection. Worse pain limited substantially patients mobility. This changed immediately after starting etanercept. Within a few days, pain resolved and the patient regained his mobility. This favourable response lasted for 8 months when we tried to stop etanercept under protection with the DMARD sulfazalazin. Unfortunately, within a few days, pain and immobility re-occurred requiring reinstitution of etanercept. This case demonstrates that, similar to other reports, TNF blockade is able to induce prompt and long-lasting response of SAPHO syndrome associated osteoarthritis to TNF blockade.ZusammenfassungBeim SAPHO-Syndrom stellen die aseptischen, schmerzhaften Osteitiden oft ein großes therapeutisches Problem dar. Wir stellen einen Patienten vor, der sowohl an einer Sakroileitis als auch an einer Akne conglobata im Rahmen eines SAPHO-Syndroms litt. Während die Akneläsionen sehr gut auf eine Therapie mit Isotretinoin ansprachen, waren die durch die Sacroileitis verursachten Schmerzen mittels NSAR und Steroidapplikationen (lokal und systemisch) nicht anhaltend zu beeinflussen. Sie führten zu einer massiven Beeinträchtigung seiner Mobilität. Dieser Zustand änderte sich prompt nach Einleitung einer Therapie mit Etanercept. Innerhalb weniger Tage sistierten die Schmerzen, die Beweglichkeit kehrte zurück. Der Patient war bis zu einem Etanercept-Auslassversuch, der 8 Monate nach Therapiebeginn unter DMARD-Schutz erfolgte, beschwerdefrei. Innerhalb weniger Tage rezidivierten die Beschwerden derart, dass Etanercept wieder begonnen werden musste. Unser Fall zeigt, ähnlich wie bisher in der Literatur in Einzelfallberichten beschrieben, dass die Gabe von TNF-Blockern zu einer schnellen und anhaltenden Besserung der osteoartikulären Beschwerden beim SAPHO-Syndrom führt.Painful, aseptic osteitis remains the major problem in the treatment of patients with SAPHO syndrome. We present a child suffering of both sacroiliitis and acne conglobata in the context of SAPHO syndrome. While acne lesions responded well to systemic isotretinoin, sacroiliitis associated pain could be controlled neither by NSAR nor by intralesional or systemic steroid injection. Worse pain limited substantially patients mobility. This changed immediately after starting etanercept. Within a few days, pain resolved and the patient regained his mobility. This favourable response lasted for 8 months when we tried to stop etanercept under protection with the DMARD sulfazalazin. Unfortunately, within a few days, pain and immobility re-occurred requiring reinstitution of etanercept. This case demonstrates that, similar to other reports, TNF blockade is able to induce prompt and long-lasting response of SAPHO syndrome associated osteoarthritis to TNF blockade.

Successful therapy of sacroiliitis in SAPHO syndrome by etanercept

SummaryPainful, aseptic osteitis remains the major problem in the treatment of patients with SAPHO syndrome. We present a child suffering of both sacroiliitis and acne conglobata in the context of SAPHO syndrome. While acne lesions responded well to systemic isotretinoin, sacroiliitis associated pain could be controlled neither by NSAR nor by intralesional or systemic steroid injection. Worse pain limited substantially patients mobility. This changed immediately after starting etanercept. Within a few days, pain resolved and the patient regained his mobility. This favourable response lasted for 8 months when we tried to stop etanercept under protection with the DMARD sulfazalazin. Unfortunately, within a few days, pain and immobility re-occurred requiring reinstitution of etanercept. This case demonstrates that, similar to other reports, TNF blockade is able to induce prompt and long-lasting response of SAPHO syndrome associated osteoarthritis to TNF blockade.ZusammenfassungBeim SAPHO-Syndrom stellen die aseptischen, schmerzhaften Osteitiden oft ein großes therapeutisches Problem dar. Wir stellen einen Patienten vor, der sowohl an einer Sakroileitis als auch an einer Akne conglobata im Rahmen eines SAPHO-Syndroms litt. Während die Akneläsionen sehr gut auf eine Therapie mit Isotretinoin ansprachen, waren die durch die Sacroileitis verursachten Schmerzen mittels NSAR und Steroidapplikationen (lokal und systemisch) nicht anhaltend zu beeinflussen. Sie führten zu einer massiven Beeinträchtigung seiner Mobilität. Dieser Zustand änderte sich prompt nach Einleitung einer Therapie mit Etanercept. Innerhalb weniger Tage sistierten die Schmerzen, die Beweglichkeit kehrte zurück. Der Patient war bis zu einem Etanercept-Auslassversuch, der 8 Monate nach Therapiebeginn unter DMARD-Schutz erfolgte, beschwerdefrei. Innerhalb weniger Tage rezidivierten die Beschwerden derart, dass Etanercept wieder begonnen werden musste. Unser Fall zeigt, ähnlich wie bisher in der Literatur in Einzelfallberichten beschrieben, dass die Gabe von TNF-Blockern zu einer schnellen und anhaltenden Besserung der osteoartikulären Beschwerden beim SAPHO-Syndrom führt.Painful, aseptic osteitis remains the major problem in the treatment of patients with SAPHO syndrome. We present a child suffering of both sacroiliitis and acne conglobata in the context of SAPHO syndrome. While acne lesions responded well to systemic isotretinoin, sacroiliitis associated pain could be controlled neither by NSAR nor by intralesional or systemic steroid injection. Worse pain limited substantially patients mobility. This changed immediately after starting etanercept. Within a few days, pain resolved and the patient regained his mobility. This favourable response lasted for 8 months when we tried to stop etanercept under protection with the DMARD sulfazalazin. Unfortunately, within a few days, pain and immobility re-occurred requiring reinstitution of etanercept. This case demonstrates that, similar to other reports, TNF blockade is able to induce prompt and long-lasting response of SAPHO syndrome associated osteoarthritis to TNF blockade.

Expression of the monoclonal antibody HECA-452 defined E-selectin ligands in Langerhans cell histiocytosis.

The cutaneous lymphocyte associated antigen (CLA) recognized by the monoclonal antibody (moAb) HECA-452 plays a major role in the homing of lymphocyte subpopulations to the skin by binding to E-selectin on dermal microvessels. The factors responsible for the immigration of Langerhans cells (LC) and their precursors into the skin are still unknown, but because normal resting LC are also capable of expressing CLA, the antigen was proposed as a candidate LC-homing structure. To gain insight into these mechanisms, the expression of HECA-452 on neoplastic LC within and outside the skin was investigated in paraffin-embedded sections from 44 patients with localized and disseminated forms of Langerhans cell histiocytosis (LCH) presenting with proliferating cells positive for CD45, CD1a, S100 and HLADR. Irrespective of the clinical presentation or the type of organ involved, HECA-452-positive LC were detected in all biopsies tested (range 5->90%). The most prominent HECA-452 reactivity was observed in skin lesions and in areas with accumulations of eosinophilic granulocytes. Our data provide evidence for a heterogeneous expression of sLex/sLea structures in various stages of activated and/or differentiated LCH cells. Remarkably, CLA-antigen expression on LCH-cells was not restricted to cutaneous sites. In view of recent findings on the expression of HECA-452 on resting epidermal LC, our data are compatible with the view that local cytokine production by keratinocytes or cells from the surrounding infiltrate induce and/or modulate CLA expression on LC in both cutaneous and extra-cutaneous sites.

Europäische Leitlinien (S1) für die Anwendung von hochdosierten intravenösen Immunglobulinen in der Dermatologie: Europäische Leitlinien (S1) für die Anwendung von hochdosierten IVIg

Die Behandlung schwerer dermatologischer Autoimmunerkrankungen und der toxischen epidermalen Nekrolyse (TEN) mit hochdosierten intravenösen Immunglobulinen (IVIg) ist ein bewährtes therapeutisches Verfahren in der Dermatologie. Da eine IVIg‐Therapie in der Regel nur bei seltenen Erkrankungen oder bei schweren Fällen in Betracht gezogen wird, stützt sich die Anwendung von Immunglobulinen zumeist nicht auf Daten aus randomisierten kontrollierten Studien, wie sie in der evidenzbasierten Medizin erforderlich sind. Da Indikationen für die Anwendung von IVIg selten sind, ist es unwahrscheinlich, dass solche Studien in absehbarer Zeit durchgeführt werden. Wegen der hohen Kosten für IVIg im First‐Line‐Einsatz wurden die ersten klinischen Leitlinien für die Anwendung von IVIg bei dermatologischen Erkrankungen im Jahr 2008 herausgegeben und im Jahr 2011 überarbeitet.

Gemella morbillorum Bacteremia after Anti-Tumor Necrosis Factor Alpha as Acne Inversa Therapy

ABSTRACT We present a case of fever, brain abscesses, and Gemella morbillorum bacteremia after anti-tumor necrosis factor alpha (TNF-α) therapy in a 21-year-old acne inversa patient currently taking long-term dapsone. To the best of our knowledge, this is the first report describing such a case. During antimicrobial therapy, the patient developed systemic varicella infection with severe thrombocytopenia.