Diagnostic signs of cutaneous lymphomas.
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Biomarkers, Tumor↗
Biomedical subjects
G Burg
Publications and source records attributed to G Burg.
Reduction of tumor burden and stabilization of disease by systemic therapy with anti-CD20 antibody (rituximab) in patients with primary cutaneous B-cell lymphoma.
BACKGROUND: Primary cutaneous B-cell lymphoma (CBCL) is characterized by restriction to the skin, a high incidence of recurrence after various treatment modalities, and a variable but mostly favorable prognosis. METHODS: Ten patients with long standing primary CBCL (3 with follicular CBCL, 5 with cutaneous, large B-cell lymphoma, 1 with diffuse large cell lymphoma, and 1 with extranodal large cell lymphoma) were treated by intravenous application of a chimeric antibody against the CD20 transmembrane antigen that is present on malignant and normal B-cells. In 6 of 10 patients, several treatment attempts either had failed or could not be used due to severe side effects or underlying disease. RESULTS: The treatment regimen resulted in two complete regressions, five partial responses, and one mixed response, and two patients did not respond to the treatment. No severe side effects occurred, except for slight pain in the nodules after infusion and an urticarial reaction at the tumor sites. A prolonged, complete disappearance of B-cells from the peripheral blood was observed. The immunoglobulin serum levels and inflammatory markers were unchanged. Histologic examination of biopsies from two regressing tumor nodes showed necrotic tumor cells and infiltration with CD8 positive cells. CONCLUSIONS: Intravenous therapy with the anti-CD20 antibody rituximab is a nontoxic and effective treatment for patients with primary cutaneous B-cell lymphoma.
Adult↗
[Immunotherapy of melanoma].
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Cancer Vaccines↗
[Helicobacter pylori and skin diseases--a (still) intact myth?].
Helicobacter pylori plays a key role in the aetiology of peptic ulcer, gastric cancer and gastric MALT-lymphoma. Based on a number of reports, a possible relationship of Helicobacter pylori infection to a variety of different dermatoses has been suggested, including urticaria, rosacea, acne-rosacea, atopic dermatitis, alopecia areata, Sjögren's syndrome, Schönlein-Henoch purpura, and Sweet syndrome. Larger case-control studies, however, do not confirm this relationship. Therefore, Helicobacter pylori eradication therapy cannot be generally recommended in these dermatoses.
Helicobacter Infections↗
[Immuno-intervention in cutaneous lymphomas].
Cutaneous lymphomas are a heterogeneous group of lymphoproliferative disorders. Most of the cutaneous lymphomas present a rather good prognosis because they disseminate to internal organs late in the disease process, if at all. Since radiotherapy and intensive chemotherapy have limited efficacy, immunological interventions are regularly used in this disease group. These interventions include unspecific treatment modalities such as Interferon-alpha, Interleukin-2, but also rather specific interventions like photopheresis, fusion toxins and as a new development, antigen-loaded dendritic cells. A new humanized anti CD20-antibody can be used for patients with cutaneous B-cell lymphomas, expressing the B-cell antigen CD20 in most of the cases. We expect that new information on the immunobiology of these diseases will allow more specific immunological interventions, providing the basis for a better therapy with optimal tolerability for patients suffering from cutaneous lymphomas.
Humans↗
[Aging skin: physiological bases, preventive measures and therapeutic modalities].
The average lifespan has increased considerably in our society. Since the skin represents the most visible organ of ageing, there is increasing interest in the physiology and treatment of wrinkles, elastosis and senile xerosis. Cutaneous ageing is a complex phenomenon consisting of genetically determined intrinsic ageing and extrinsic ageing, the latter due to sun exposure, cigarette smoking and exposure to irritants. A number of biological changes can be found during the cutaneous ageing process, including decrease of epidermal, dermal and subcutaneous cellular components and changes in the immune system. Treatment modalities include the use of emollients in the treatment of senile xerosis, and topical retinoic and glycolic acid preparations, chemical peels, botulinum, collagen and hyaluronic acid injections, dermabrasion, CO2, and Nd:Yag laser resurfacing in the treatment of wrinkles.
Aged↗
[Toxin treatment of sweat pearls. A review of the treatment of hyperhidrosis with a special view of a new therapy option using botulinum toxin A].
Hyperhidrosis is defined as an excess of sweating beyond the amount needed to cool down elevated body temperature. We distinguish a primary and a secondary form, where an underlying endocrinological or neurological disease is found. The innervation of eccrine sweat glands is sympathetic but the transmitter is cholinergic (ACh). There are variable modalities in the treatment of focal hyperhidrosis, such as topical aluminium chloride application, tapwater iontophoresis, anticholinergic drugs or surgery (axillary sweat gland extraction, liposuction or thoracoscopic sympathectomy). Only recently botulinum toxin (BTX) has been introduced as a therapeutic tool for hyperhidrosis. As BTX inhibits the release of ACh at the cholinergic synapse, perspiration is arrested completely after intradermal injection. BTX is a very potent alternative to the surgical approach in the treatment of hyperhidrosis, though the treatment must be repeated regularly to maintain the effect.
Botulinum Toxins, Type A↗
[Type A botulinum toxin: a new methods in treating focal hyperhidrosis. A summary of various possibilities in hyperhidrosis therapy with special emphasis type A botulinum toxin injections].
Hyperhidrosis is defined as an excess of sweating over the amount necessary for thermoregulation. Essential focal hyperhidrosis is a overactivity of the sweat glands of the axilla, palms and soles probably due to a disorder of the sympathetic nervous system. The therapy is difficult, even though there are many therapeutic options. Beside the effort to treat the psychovegetative disorder (autogenic training or acupuncture), there are efforts to seal the lumen of terminal sweat ducts using aluminiumchlorhydroxide application or iontophoresis. Surgery has the aim to eliminate sweat glands either by excision or by denervation. It is also possible to use chemical denervation with systemic anticholinergics. Only recently the local chemodenervation with injections of botulinum toxin (BTX) was added to the therapeutic tools of focal hyperhidrosis. We present an overview of several therapeutic options in consideration of BTX.
Botulinum Toxins, Type A↗
Intralesional therapy with anti-CD20 monoclonal antibody rituximab in primary cutaneous B-cell lymphoma.
BACKGROUND: We report the use of a new treatment modality in 2 patients with primary cutaneous B-cell lymphoma. In a 58-year-old woman with progressive nodular lesions on the scalp and face, several treatment attempts either failed or could not be used because of severe adverse effects and underlying epilepsy. The patient declined radiotherapy. A 30-year-old man presented with recurrence of tumor nodules occipitally, thoracically, on the arm, and on the right thigh after several excisions. OBSERVATIONS: Intralesional injection of rituximab, a chimeric antibody directed against the CD20 transmembrane antigen present in malignant and normal B cells, resulted in partial regression of tumor nodules. No adverse effects occurred except pain during or shortly after injection and, in one patient, a slight rise in body temperature. Due to the treatment a prolonged complete disappearance of B cells from peripheral blood samples was observed. CONCLUSION: Intralesional rituximab therapy is a nontoxic and effective treatment for cutaneous B-cell lymphoma that deserves further investigation in larger clinical trials.
Adult↗
Accuracy, concordance, and reproducibility of histologic diagnosis in cutaneous T-cell lymphoma: an EORTC Cutaneous Lymphoma Project Group Study. European Organization for Research and Treatment of Cancer.
OBJECTIVE: To assess the level of observer variability in the histologic identification of cutaneous T-cell lymphoma (CTCL) and its discrimination from diseases with similar histologic features. DESIGN: Cutaneous T-cell lymphoma specimens and randomly mixed controls were evaluated twice by 3 examiners. SETTINGS: The European Organization for Research and Treatment of Cancer (EORTC) Cutaneous Lymphoma Project Group. PATIENTS: The study was conducted with histologic specimens from 32 patients with mycosis fungoides (MF). In addition, 13 specimens of spongiotic, lichenoid, or psoriasiform simulators of MF were blindly and randomly mixed with the CTCL specimens as controls. MAIN OUTCOME MEASURES: To evaluate the accuracy and concordance among and individual reproducibility of raters of histologic diagnoses. RESULTS: Overall, the concordance among raters was fair to moderate (range, 0.283-0.562; weighted overall kappa, 0.412). Individual reproducibility of examiners ranged from moderate to almost perfect (range, 0.473-0.896; weighted overall kappa, 0.709) and was not significantly different for the definite lymphoma (range, 0.551-0.921; overall kappa, 0.802) and nonlymphoma (range, 0.368-0.950; overall kappa, 0.793) categories. Accuracy was similarly variable among raters: sensitivity ranged from 49.3% to 78.1% (overall kappa, 0.654), and specificity (control series) ranged from 46.2% to 69.2% (overall kappa, 0.595). Adding the diagnoses of probable lymphoma to those of definite lymphoma, sensitivity ranged between 73.5% and 84.9%. Although for each examiner there was a trend toward a lower sensitivity in the detection of early lesions compared with later lesions, the difference in sensitivity between the 2 groups was not statistically significant. CONCLUSIONS: The levels of concordance and reproducibility found in this investigation were similar to those obtained with comparable studies in the most varied fields of pathology, confirming that the identification of CTCL for our observers did not cause particular problems. Our findings also revealed that pitfalls in CTCL identification are not only limited to early lymphomatous lesions, as commonly postulated.
Biopsy↗
Sporadic trichoepithelioma demonstrates deletions at 9q22.3.
BACKGROUND: Trichoepithelioma (TE) is a benign cutaneous tumor that originates from hair follicles and occurs either in multiple or solitary lesions. Multiple TE is transmitted as an autosomal dominant trait, and a region at 9p21 is thought to be involved in the tumorigenesis. Solitary TE occurs more commonly than multiple TE and is not inherited. Histologically, TE tumors contain horn cysts and abortive hair papillae. A basal cell carcinoma appearance in some or all regions of a TE tumor can happen. In sporadic basal cell carcinoma, frequent deletions at 9q22.3 (Drosophila patched gene) have occurred. The objective of this study is to test whether loss of heterozygosity (LOH) on either 9p21 or on chromosome 9q22.3 could be detected in archival sporadic TE. OBSERVATIONS: We studied 29 randomly selected cases of sporadic TE by microdissection and polymerase chain reaction using paraffin-embedded, formalin-fixed tissue specimens on glass slides. Analysis was performed with the polymorphic markers IFNA and D9S171 (9p21) as well as D9S15, D9S303, D9S287, and D9S252 (9q22.3). RESULTS: The LOH at 9q22.3 was identified in 14 (48%) of 29 cases with at least 1 marker, while LOH could not be demonstrated using the markers IFNA and D9S171 (9p21). CONCLUSIONS: The results show that the Drosophila patched gene LOH can be frequently identified in paraffin-embedded sporadic TE after routine processing and indicates a common gatekeeper mechanism for both TE and basal cell carcinoma.
Chromosomes, Human, Pair 9↗
A comparison of multilayer bandage systems during rest, exercise, and over 2 days of wear time.
OBJECTIVE: To study the interface pressure between the leg and 8 different multilayer bandage systems during postural changes, exercise (walking), and over 2 days of wear time. DESIGN: Comparison of 8 different compression bandages under standardized conditions. SETTING: Department of Dermatology, University Hospital of Zurich, Zurich, Switzerland. PARTICIPANTS: A series of 10 healthy volunteers, 5 females and 5 males, aged 26 to 65 years. INTERVENTION: An electropneumatic device was used to measure interface pressure at 12 points of the leg. MAIN OUTCOME MEASURES: (1) Pressure changes from the standing to the sitting and supine position at rest, (2) pressure amplitude during exercise (200-m treadmill walk at 3.2 m/s, 0 degrees incline), and (3) pressure decrease over 2 days of wear time. RESULTS: Results are given as median with the 10% to 90% confidence intervals. Multilayer bandages of short and medium stretch showed a larger pressure decrease when the patient was supine (eg, 3 short stretch bandages: 18.0 mm Hg [reference range, 15.5-19.5 mm Hg]) than systems of medium and long stretch bandages (eg, 4-layer bandage, 6.0 mm Hg [reference range, 4.5-7.0 mm Hg]) (P=.005). The amplitude of pressure waves during exercise was comparable among most multilayer bandage systems. The pressure loss over time was the smallest in elastic bandages (eg, 4-layer bandage, 6.0 mm Hg [reference range, 0.0-10.5 mm Hg]), compared with short stretch bandages (eg, 3 short stretch bandages, 18.0 mm Hg [reference range, 16.5-20.5 mm Hg]) (P=.005). CONCLUSIONS: Highly elastic multilayer bandage systems showed the smallest pressure loss over several days, but the small pressure decrease when the patient was supine makes them potentially hazardous to patients with arterial occlusive disease. Short stretch bandages and the Unna boot with an inelastic zinc plaster bandage generate large pressure waves while walking and showed a marked pressure decrease when the patient was supine, but they lose a lot of their pressure within the first hours of wear. Multilayer systems composed of short stretch and cohesive medium stretch bandages represent a good compromise between elastic and inelastic bandage systems (moderate pressure loss over time, large pressure decrease on lying down). The clinical effectiveness of the different types of compression still remains to be studied.
Adult↗
[Sporotrichoid infection with Mycobacterium marinum: successful therapy with oral tetracycline administration].
Atypical mycobacterial infections of the skin present a diagnostic and therapeutic challenge to dermatologists in many instances. We report on a patient who was diagnosed with atypical mycobacteriosis in its rarer, sporotrichoid form. Possible differential diagnoses are discussed. Efficient therapy using minocycline is demonstrated.
Administration, Oral↗
[Botulinum toxin: from poison to drug. A historical review].
Botulinumtoxin (BTX) is a neurotoxin produced from Clostridium botulinum under anaerobic conditions and is responsible for botulism, a notifiable, bacterial form of food poisoning. The first case of botulism is believed to have occurred in 1735. An epidemic in Southern Germany in 1793 claimed the death of over the half of those patients who had become ill through eating uncooked blood sausages. The term "pharmakon" is Greek and implicates that a drug originates from poison (potion, remedy). Theophrastus Bombast von Hohenheim known as Paracelsus (1493/94-1541) first described this duality with his dictum "alle ding sind gift und nichts on gift; alein die dosis macht das ein ding kein gift ist" (only the dose makes a remedy poisonous). In Baden-Württemberg in 1817, the poet and physician Dr. Justinus Christian Kerner described the symptoms of botulism, so that at this time botulism was also called Kerner disease. Until the turn of the century the reason for poisoning was not known. Van Ermengem succeeded in isolating the anaerobic bacterium causing botulism, but the specific mechanism of BTX was only established after the second World War. In the late seventies the ophthalmologist Dr. Alan Scott used BTX the first time in the treatment of strabismus. The drug was then used in the treatment of several muscle spasticities such as, for example, torticollis or hemifacial spasm. Only recently BTX has been successfully used for focal hyperhidrosis. We review the history of botulinum toxin from its discovery in the nineteenth century and the research into its effect in the middle of the 20th century up to its clinical use at the present time.
Botulinum Toxins↗
Pityriasis rosea--a virus-induced skin disease? An update.
Pityriasis rosea (PR) is an acute, inflammatory skin disease of unknown cause. Clinical and experimental findings indicate an infectious etiology of PR. Various infectious agents including viruses have been proposed as causative agents and their presence in PR samples has been extensively investigated. Recently, human herpesvirus 7 was linked to PR, but contradictory findings have been reported by various investigators. Here, we describe the features of PR that suggest an infectious cause and review the data from viral studies in PR reported in the literature. In addition, we present a pathogenetic model of PR which may be helpful in planning and evaluating studies for the search of a putative PR-associated virus. Based on the current state of knowledge, none of the known viruses could, so far, be conclusively associated with PR.
Acute Disease↗
Pathogenesis of cutaneous lymphomas.
Cutaneous lymphomas are a heterogeneous group of lymphoproliferative disorders derived from T cells, B cells and, in rare cases, natural killer cells. The precise mechanisms of the lymphomagenesis are still obscure. However, there are various factors involved. These factors include environmental, especially infectious factors, translocations, mutations and genetic instability. The special microenvironment in the skin is responsible for the peculiar behavior of these neoplasms by providing various key factors, such as adhesion molecules and cytokines. Newly identified molecular disturbances in cutaneous lymphomas might be targeted by specific molecular or immunologic interventions in the future.
Cell Transformation, Neoplastic↗
Allelic deletion at 9p21-22 in primary cutaneous CD30(+) large cell lymphoma.
The genetic alterations responsible for the development of cutaneous lymphoma are largely unknown. Chromosome region 9p21 contains a gene locus encoding an inhibitor of cyclin-dependent kinase 4, and heterozygous deletions of this tumor suppressor gene (p16) have been shown in a variety of malignant tumors. We studied 11 randomly selected cutaneous CD30-positive large cell lymphomas. Several areas containing 20-50 CD30-positive lymphocytes were microdissected in each case and subjected to single-step DNA extraction. Loss of heterozygosity analysis was performed using polymorphic markers at 9p21 (IFNA, D9S171, D9S169) and 17p13 (TP53). Samples from normal cells apart from CD30-positive lymphocytes, e.g., CD30-negative lymphohistiocytic infiltrates and normal epidermal layer, were also obtained in all cases from the same slide for comparison with the tumor samples. Expression of CD30 and T-lineage antigens (CD3, CD45Ro) was confirmed in all cases. Immunohistochemical staining for p16 and p53 was performed using the monoclonal antibodies sc-1661 and DO-7, respectively. Of the 11 informative cases, seven (64%) exhibited loss of heterozygosity at least for one marker at 9p21 (p16), whereas no allelic deletions were found for the polymorphic marker at 17p13 (p53). On immunohistochemistry loss of the p16 protein was detected in two of 11 cases. Nuclear staining for p53 protein was found in four of 11 cases. Here, we provide the first evidence of the involvement of the tumor suppressor gene p16 in primary cutaneous large cell lymphoma. Whether p16 deletion in these lymphomas is associated with disease progression and whether this method could serve as an early marker to detect lymphomas at an early stage needs to be addressed in future studies. J Invest Dermatol 115:1104-1107 2000
Adult↗
Biological activity and safety of adenoviral vector-expressed wild-type p53 after intratumoral injection in melanoma and breast cancer patients with p53-overexpressing tumors.
p53 mutations are common genetic alterations in human cancer. Gene transfer of a wild-type (wt) p53 gene reverses the loss of normal p53 function in vitro and in vivo. A phase I dose escalation study of single intratumoral (i.t.) injection of a replication-defective adenoviral expression vector containing wt p53 was carried out in patients with metastatic melanoma or breast cancer with increased p53 protein immunoreactivity in pretreatment tumor biopsies. The biological activity of the injected wt p53 was assayed by reverse transcriptase-polymerase chain reaction in tumor tissue. A total of six (five melanoma and one breast adenocarcinoma) patients were treated at dose levels dependent upon tumor size/dose escalation sequence. Five of six patients became positive for the transfer of wt p53 into tumor tissue 2 days after injection of the vector. Of the four patients assayed, all developed anti-adenoviral antibodies. Adverse reactions associated with i.t. injection were mild, with no obvious correlation between the incidence, severity, or relationship of the events and drug dose. p53 gene therapy by i.t. injection of a replication-defective adenoviral expression vector is safe, feasible, and biologically effective (with respect to transduction frequency) in patients with either metastatic melanoma or breast cancer.
Adenocarcinoma↗