European dermatology forum: Updated guidelines on the use of extracorporeal photopheresis 2020 - Part 2.

BACKGROUND: Following the first investigational study on the use of extracorporeal photopheresis for the treatment of cutaneous T-cell lymphoma published in 1983, this technology has received continued use and further recognition for additional earlier as well as refractory forms. After the publication of the first guidelines for this technology in the JEADV in 2014, this technology has maintained additional promise in the treatment of other severe and refractory conditions in a multidisciplinary setting. It has confirmed recognition in well-known documented conditions such as graft-vs.-host disease after allogeneic bone marrow transplantation, systemic sclerosis, solid organ transplant rejection including lung, heart and liver and to a lesser extent inflammatory bowel disease. MATERIALS AND METHODS: In order to further provide recognized expert practical guidelines for the use of this technology for all indications, the European Dermatology Forum (EDF) again 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. All authors had the opportunity to review each contribution as it was added. RESULTS AND CONCLUSION: These updated 2020 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. The guidelines were divided into two parts: PART I covers Cutaneous T-cell lymphoma, chronic graft-vs.-host disease and acute graft-vs.-host disease, while PART II will cover scleroderma, solid organ transplantation, Crohn's disease, use of ECP in paediatric patients, atopic dermatitis, type 1 diabetes, pemphigus, epidermolysis bullosa acquisita and erosive oral lichen planus.

European dermatology forum - updated guidelines on the use of extracorporeal photopheresis 2020 - part 1.

BACKGROUND: Following the first investigational study on the use of extracorporeal photopheresis for the treatment of cutaneous T-cell lymphoma published in 1983, this technology has received continued use and further recognition for additional earlier as well as refractory forms. After the publication of the first guidelines for this technology in the JEADV in 2014, this technology has maintained additional promise in the treatment of other severe and refractory conditions in a multi-disciplinary setting. It has confirmed recognition in well-known documented conditions such as graft-versus-host disease after allogeneic bone marrow transplantation, systemic sclerosis, solid organ transplant rejection including lung, heart and liver and to a lesser extent inflammatory bowel disease. MATERIALS AND METHODS: In order to further provide recognized expert practical guidelines for the use of this technology for all indications, the European Dermatology Forum (EDF) again 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. All authors had the opportunity to review each contribution as it was added. RESULTS AND CONCLUSION: These updated 2020 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. The guidelines are divided in two parts: PART I covers cutaneous T-cell lymphoma, chronic graft-versus-host disease and acute graft-versus-host disease while PART II will cover scleroderma, solid organ transplantation, Crohn's disease, use of ECP in paediatrics practice, atopic dermatitis, type 1 diabetes, pemphigus, epidermolysis bullosa acquisita and erosive oral lichen planus.

Guidelines on the use of extracorporeal photopheresis.

BACKGROUND: After 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 METHODS: In 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 CONCLUSION: These 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.

Extracorporeal photochemoimmunotherapy in cutaneous T-cell lymphoma.

Extracorporeal photochemotherapy was originally conceived for the treatment of cutaneous T-cell lymphoma (CTCL) and as well as other T-cell mediated diseases. Evidence collected in the past 17 years has demonstrated that this treatment modality can have a very significant effect on the course of a subset of CTCL patients. The evidence available is positive but for a variety of reasons has been controversial within the medical community. A number of very well-designed multi-center trials which have been lacking since the first publication by Edelson et al. are being carried out so that hopefully a number of open questions will be resolved with greater clarity in the coming years. The fact remains that this innovative approach for the treatment of CTCL and T-cell mediated diseases has certainly opened new avenues of therapy and thought in photoimmunology and photomedicine. Clearly the very low side effect profile of this therapy has made it more attractive than the chemotherapeutic and immunosuppressive substances that are presently available or in experimental protocols. If and when the mechanisms of action are fully understood and appropriate studies investigating different treatment schedules and different combination therapies and modifications of its present form are performed the place of photopheresis in the therapeutics of CTCL as well as other T-cell mediated diseases and oncology will be better placed.

Modification of growth and tumorigenicity in epidermal cell lines by DNA-mediated gene transfer of M(r) 27,000 heat shock protein (hsp27).

In the present communication, the role of the M(r) 27,000 human small heat shock protein (hsp27) in tumorigenicity was examined. Stable transfectants of a melanoma cell line (A375) and an epidermal squamous carcinoma cell line (A431), isolated by cotransfection of a hsp27 expression vector (pSG-2711) and a neomycin-resistant plasmid, were obtained. Clones expressing high levels of hsp27 were analyzed using immunohistochemistry and immunoblotting. Cells transfected with only the plasmid for neomycin were used as control cells. Growth analysis of transfectants in A375 and A431 tumor cells showed in vitro a lower proliferation rate than control clones derived from both lines. To investigate the correlation of hsp27 expression and tumorigenicity, transfectants of each cell type and control cells were injected into nude mice. A delay in tumor development was detected in animals inoculated with cells overexpressing hsp27. However, after this initial delay, tumors appeared in some of these animals and no difference could be observed in their growth dynamics compared to control tumors. When tumors transfected with the hsp27 construct were analyzed using immunohistochemistry and PCR, no evidence for hsp27 expression was obtained which implicates instability of the transduced foreign DNA when maintained under nonselective conditions. The present study shows that genetic manipulation of tumor cells may provide valuable information on the role of hsp27 in tumor growth.

Expression of the small heat shock protein HSP 27 in developing human skin.

The 27 kDa heat shock protein (HSP 27) is expressed in keratinocytes of the upper epidermal layers, and recent evidence suggests that this protein is involved in the regulation of epidermal differentiation. The expression of HSP 27 was investigated in developing human skin by immunohistochemistry utilizing a specific monoclonal antibody. We used formalin-fixed, paraffin-embedded tissue of abdominal skin obtained from 34 human fetuses ranging between 13 and 30 weeks estimated gestational age (EGA). We found that HSP 27 is not expressed in keratinocytes until week 14 EGA. At this stage staining is observed in the periderm and the upper intermediate cells but not in hair germs. During further development, HSP 27 expression correlates with increasing epidermal differentiation, i.e. shedding of the periderm and beginning of keratinization. HSP 27 expression is confined to the upper cell layers and sparse basal cells. In hair follicles, HSP 27 can be detected in the innermost cell layer of the outer root sheath and in keratinocytes of the bulge identical to what is observed in adult skin. The hair papilla, matrix cells and sebaceous glands are negative for HSP 27 and remain so during further development. In eccrine sweat glands of the 24th week EGA, HSP 27 is confined to the superficial cell layer of the sweat ducts. In the present report we demonstrate differentiation-related expression of HSP 27 in developing human skin. Further in vitro studies will address the molecular function of HSP 27 in epidermal differentiation and development.