[Immunoglobulin treatment in dermatology].
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Adrenal Cortex Hormones↗
Biomedical subjects
B Volc-Platzer
Publications and source records attributed to B Volc-Platzer.
An HLA class-II allele frequent in Eskimos and Amerindians is found in the Tyrolean Ice Man.
DNA was extracted from specimens derived from the calcaneus of the Tyrolean Ice Man under sterile conditions in a laboratory, where no DNA extractions and PCR experiments had been performed before. Agarose gel electrophoresis and ethidium bromide staining did not reveal any evidence of genomic DNA in the preparation obtained, indicating a high degree of DNA degradation. Nevertheless, we performed PCR amplifications with this sample using primer pairs specific for HLA class II alleles. HLA-DRB and DQB1 alleles were amplified in a nested PCR approach. In one of the reactions, we observed a distinct amplification product, which we directly sequenced. By comparing the obtained nucleotide sequence with a database of HLA alleles we assigned the HLA-DRB1*1402 type to the amplified sample. None of the investigators involved possesses this allele, indicating that no contamination with modern DNA had occurred. The HLA-DRB1*1402 allele is extremely rare in Europe, but is common in Inuits and South American Indians and has previously only once been identified in the laboratory.
Alleles↗
Extracorporeal photochemotherapy in the treatment of severe steroid-refractory acute graft-versus-host disease: a pilot study.
Extracorporeal exposure of peripheral blood mononuclear cells to the photosensitizing agent 8-methoxypsoralen and UV-A radiation has been shown to be effective in the treatment of selected diseases mediated by T cells, rejection after solid organ transplantation, and chronic graft-versus-host disease (GVHD). We present 21 patients with a median age of 38 years who developed steroid-refractory acute GVHD grades II to IV after stem cell grafting from sibling or unrelated donors and were referred to extracorporeal photochemotherapy (ECP). Three months after initiation of ECP 60% of patients achieved a complete resolution of GVHD manifestations. Complete responses were obtained in 100% of patients with grade II, 67% of patients with grade III, and 12% of patients with grade IV acute GVHD. Three months after start of ECP complete responses were achieved in 60% of patients with cutaneous, 67% with liver, and none with gut involvement. Adverse events observed during ECP included a decrease in peripheral blood cell counts in the early phase after stem cell transplantation (SCT). Currently, 57% of patients are alive at a median observation time of 25 months after SCT. Probability of survival at 4 years after SCT is 91% in patients with complete response to ECP compared to 11% in patients not responding completely. Our findings suggest that ECP is an effective adjunct therapy for acute steroid-refractory GVHD with cutaneous and liver involvement. However, in patients with acute GVHD grade IV or gut involvement other therapeutic options are warranted.
Acute Disease↗
Regression of deeply infiltrating giant condyloma (Buschke-Löwenstein tumor) following long-term intralesional interferon alfa therapy.
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Adult↗
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.
Case-Control Studies↗
Criteria for assessing chronic GVHD.
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Chronic Disease↗
Primary mucinous carcinoma of the scalp.
Primary cutaneous mucinous carcinoma (MC) is a rare epithelial neoplasm derived from the sweat glands. Herein, we report a case of MC located on the head. A 66-year-old woman underwent excision of a nodular tumor with a reddish brown surface on the left parietal region. Histopathology revealed a neoplasm extending from the reticular dermis into the subcutaneous fat. The tumor cell aggregates showed cribriform and solid lobules and were embedded in lakes of mucin, separated by thin, fibrous septae. Focally single neoplastic cells were arranged in an Indian-file pattern. The tumor cells displayed an eosinophilic cytoplasm, large basophilic nuclei and some discrete nuclear atypia. Vascular spaces, filled by densely packed erythrocytes between the septae, were also observed. We compared the mucinous component with the tumor cell and the stromal component by light microscopy. Analyzing the tumor by an image analysis system in Alcian-blue-stained serial sections, we found the averaged total tumor area measuring 99.7 mm(2). The area of the mucinous component measured 92.4 mm(2), that of the tumor cells 3.7 mm(2) and that of the stromal component 3.6 mm(2). The extensive checkup of the patient disclosed no evidence for a further malignant neoplasm. After excision of the tumor an adjuvant radiotherapy was performed. The patient was free of recurrence and metastatic spread of the mucinous carcinoma during a 4-year follow-up.
Adenocarcinoma, Mucinous↗
Extracorporeal photochemotherapy in the treatment of severe graft-versus-host disease.
Advances in posttransplant 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 multicenter randomized study should help define the impact of ECP in the treatment of GVHD and overall survival of these patients.
Graft vs Host Disease↗
Desmoglein 3-ELISA: a pemphigus vulgaris-specific diagnostic tool.
BACKGROUND: Pemphigus vulgaris (PV) is an autoimmune-blistering disease of the skin and mucous membranes caused by autoantibodies against desmoglein 3 (Dsg3), an epidermal desmosomal adhesion protein of the cadherin family. Cloning of the Dsg3 gene and expression of the protein in a native conformation enabled the recent development of a specific and sensitive enzyme-linked immunosorbent assay (ELISA) for the detection of PV autoantibodies. OBJECTIVES: To evaluate serum samples from patients with PV and other dermatologic diseases for anti-Dsg3 antibodies. To compare ELISA values with autoantibody titers obtained by classic indirect immunofluorescence (IIF). DESIGN: Serum samples from patients with PV and various other bullous and nonbullous skin diseases were tested for anti-Dsg3 reactivity by ELISA. SETTING: Ambulatory and hospitalized patients from a university hospital. PATIENTS: Fifty-two serum samples from 11 patients with PV, and serum samples from 11 patients with bullous pemphigoid, 12 patients with other bullous diseases, 22 patients with various nonbullous skin disorders, and 10 healthy individuals were tested. RESULTS: Forty-seven (98%) of 48 serum samples from patients with PV that were positive by IIF on monkey esophagus were also reactive by Dsg3-ELISA, whereas 4 of 4 IIF-negative PV serum samples showed no reactivity by ELISA. In addition, negative ELISA results were obtained from 11 of 11 serum samples from patients with bullous pemphigoid, 10 of 12 serum samples from patients with other bullous skin disorders, 7 of 9 serum samples from patients with autoimmune-connective tissue diseases, and 13 of 13 serum samples from patients with other nonbullous skin diseases. Interestingly, 1 patient with paraneoplastic pemphigus had positive ELISA results. There was a positive correlation (r = 0.654) between ELISA values and IIF titers within the whole population with PV. In addition, when multiple serum samples from 1 patient with PV sampled over a 2-year period were tested, ELISA reactivity paralleled both the IIF titers and the clinical course. CONCLUSION: The Dsg3-ELISA is a sensitive, objective, and PV-specific test that should be considered as an adjunct test for the management of patients with PV.
Adult↗
Uptake of exogenous DNA via the skin.
Easy accessibility makes the skin extremely attractive for therapeutic gene transfer, but this feature may be equally responsible for inadvertent DNA uptake. Therefore we studied lacZ reporter gene expression after epicutaneous and intracutaneous administration of naked DNA, lipofection and transferrinfection to intact, tape-stripped, and wound-healing skin of hairless mice. Gold particles coated with 1 microg pCMVnlslacZ were inoculated with a gene gun as a positive control. Beta-galactosidase expression by skin cells, i.e., keratinocytes of the upper epithelial layers and single cells in the upper dermis, determined by X-Gal histochemistry was not observed except after ballistic gene transfer. By polymerase chain reaction we detected lacZ DNA after skin bombardment up to 4 weeks. After intracutaneous and epicutaneous application to normal and tape-stripped skin of the various delivery systems lacZ DNA was detectable up to 1 week. Epicutaneous application of the delivery systems to wounded skin resulted in lacZ DNA detectability up to 48 h only. Reverse-transcriptase polymerase chain reaction indicated transcription of the reporter gene after particle bombardment and intracutaneous injection, up to 48 h, but not after epicutaneous application of either delivery system. The possibility of inadvertent uptake of exogeneous DNA by intact and tape-stripped skin is evidenced by the detection of reporter gene DNA after epicutaneous application of naked DNA and DNA complexed to cationic lipids or transferrin-polylysine (transferrinfection). However, the effects of the presence and persistence of foreign genes in the target cells are not clear yet.
Administration, Cutaneous↗
Long-term follow-up of patients after related- and unrelated-donor bone marrow transplantation for chronic myelogenous leukemia.
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.
Acute Disease↗
Low transplant-related mortality in patients receiving unrelated donor marrow grafts for leukemia.
Transplantation with unrelated donor (UD) marrow has been shown to potentially cure patients with leukemia. Between January 1991 and April 1998, 54 patients with leukemia have received an UD BMT at our institution. Five patients received their UD BMT as a second transplant after a preceding autologous or syngeneic BMT and were excluded from further analysis. Forty-nine patients with leukemia (acute leukemia n = 26; CML n = 23) and a median age of 36 years (range 19-51) were analyzed. For conditioning, all patients received a combination of fractionated TBI and CY. GVHD prophylaxis consisted of MTX and CsA in all patients. As of 30 April 1998, 27 of 49 (55%) patients survive after a median observation time of 18 months. The probability of overall survival for standard risk and high risk patients is 54% and 31% (P = 0.05). Probability of transplant-related mortality (TRM) is 27%, 24% in standard risk and 31% in high risk patients (P = 0.44). Patients younger than 40 years (n = 33) had a similar TRM as patients 40 years and older (n = 16). The probability of relapse is 41% for the whole group, 29% for standard risk and 55% for high risk pts (P<0.05). Our data confirm that UD BMT is an effective treatment for patients with leukemia. TRM is almost similar to related sibling BMT, most probably due to improvements in HLA typing technology, conditioning regimen and supportive patient care.
Adult↗
Anaplastic squamous cell carcinoma (SCC) in a patient with chronic cutaneous graft-versus-host disease (GVHD).
We describe an allogeneic bone marrow (BM) recipient who developed aggressive, metastasizing squamous cell cancer (SCC) of the skin, and discuss possible risk factors in the development of this secondary solid tumor. The patient had been treated with cyclosporine (CsA), methyl-prednisolone and thalidomide for 3 years because of extensive de novo chronic cutaneous GVHD occurring 1 year after BMT. Ten years after BMT a locally invasive and metastasizing SCC occurred on the patient's neck, and diagnosis was confirmed by H&E histopathology and cytokeratin-immunohistochemistry. Analysis of genomic DNA did not reveal p53 mutations nor were HPV sequences detectable. Risk factors included conditioning for BMT with total body irradiation (TBI) and cyclophosphamide (Cy), immunosuppressive treatment for GVHD, and extensive exposure to UV radiation before and after BMT. Despite surgery and adjuvant chemotherapy with 5-fluorouracil (5-FU) the patient died 1 year after the diagnosis of SCC.
Adult↗
Pneumatosis [correction of Pneumocystis] cystoides intestinalis with pneumoperitoneum and pneumoretroperitoneum in a patient with extensive chronic graft-versus-host disease.
Pneumatosis cystoides intestinalis is a rare finding of intramural gasfilled cysts in the bowel wall and sometimes free air in the abdomen. A few conditions are reported to cause this disease, one of them being immunosuppression. We describe a 50-year-old Caucasian male with extensive chronic graft-versus-host disease (GVHD) of the gut and skin who developed PCI with pneumoperitoneum and pneumoretroperitoneum. To our knowledge, this is the first report of PCI occurring in a patient with active chronic GVHD which resolved spontaneously.
Bone Marrow Transplantation↗
Successful use of extracorporeal photochemotherapy in the treatment of severe acute and chronic graft-versus-host disease.
Extracorporeal exposure of peripheral blood mononuclear cells to the photosensitizing compound 8-methoxypsoralen and ultraviolet A radiation has been shown to be effective in the treatment of several T-cell-mediated diseases, including cutaneous T-cell lymphoma and rejection after organ transplantation. We present 21 patients (10 men and 11 women) with hematological malignancies with a median age of 36 years (range, 25 to 55 years) who had received marrow grafts from sibling (n = 12) or unrelated (n = 9) donors. Six patients had acute graft-versus-host disease (GVHD) grade II to III not responding to cyclosporine A (CSA) and prednisolone when referred to extracorporeal photochemotherapy (ECP). In 15 patients, 2 to 24 months after bone marrow transplantation (BMT), extensive chronic GVHD with involvement of skin (n = 15), liver (n = 10), oral mucosa (n = 11), ocular glands (n = 6), and thrombocytopenia (n = 3) developed and was unresponsive to conventional therapy, including steroids. All patients were treated with ECP on 2 consecutive days every 2 weeks for the first 3 months and thereafter every 4 weeks until resolution of GVHD. ECP was tolerated excellently without any significant side effects. After a median of 14 cycles of ECP, acute GVHD resolved completely in 4 of 6 patients (67%) and partially in another 2 patients. Cutaneous chronic GVHD completely resolved in 12 of 15 (80%) patients. Contractures of knees and elbows due to scleroderma resolved partially. Oral mucosal ulcerations resolved in all patients. Seven of 10 patients (70%) with liver involvement had complete responses after ECP. After discontinuation of ECP, no severe infections were observed. Our findings suggest that ECP is a safe and effective adjunct therapy for both acute and extensive chronic GVHD with skin and visceral involvement and resistance to conventional therapy.
Acute Disease↗
Immunoapheresis in paraneoplastic pemphigus.
BACKGROUND: Paraneoplastic pemphigus was first described in 1990 in 5 patients with extensive mucocutaneous erosions, a distinct set of autoantibodies, and underlying neoplasia. Since then, patients described have been middle-aged, have suffered from prognostically unfavorable malignant neoplasms, and have responded poorly to immunosuppressive agents. OBSERVATION: A 16-year-old boy was examined with extensive oral erosions, halitosis that interfered with his quality of life, and rapid weight loss. The suspected clinical diagnosis of paraneoplastic pemphigus was confirmed by histopathological, immunofluorescence, and biochemical (eg, immunoblotting and immunoprecipitation) findings as well as by the demonstration of an inflammatory myofibroblastic tumor of the left retroclavicular region. Despite administration of corticosteroids, followed by excision of the neoplasm, clinical symptoms improved only slightly, and autoantibody titers decreased only marginally. We therefore initiated an immunoapheresis regimen with the use of sheep anti-human-IgG bead-formed agarose gel (Sepharose; Pharmacia Biotech Comp, Vienna, Austria), which led to the disappearance of circulating autoantibodies and the patient's recovery. CONCLUSION: Immunoapheresis may represent a novel therapeutic option for patients with paraneoplastic pemphigus who show little improvement after curative treatment of their neoplasms.
Adolescent↗
[Cicatricial pemphigoid with autoantibodies to laminin 5 (epiligrin) in a patient with metastatic endometrial carcinoma].
A 71-year-old female patient presented with erosions of the oral, genital and ocular mucosa, but without skin lesions. One year prior to the onset of lesions, a metastatic adenocarcinoma of the endometrium had been diagnosed. In perilesional skin, direct immunofluorescence showed linear deposits of C3 and IgG along the basement membrane zone. Indirect immunofluorescence demonstrated anti-basement membrane zone antibodies which bound exclusively to the dermal side of 1M NaCl-split skin. In immunoprecipitation studies, the autoantibodies bound a set of proteins characteristic of epiligrin/laminin-5, and they specifically immunoblotted the alpha-subunit of this protein. These results confirmed our presumed diagnosis of anti-epiligrin cicatricial pemphigoid. Combined treatment with methylprednisolone and dapsone resulted in prompt remission, despite progression of her malignancy. So far, only eight patients with anti-epiligrin cicatricial pemphigoid have been reported worldwide. Our patient represents the first case from Austria and is clinically and immunopathologically similar to previously reported cases.
Adenocarcinoma↗