GOAP Dermatology Dermatological Diseases Treated with Therapeutic Apheresis Rolf Bambauer1 and Ralf Schiel2
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Review Article GOAP Dermatology Dermatological Diseases Treated with Therapeutic Apheresis Rolf Bambauer1 and Ralf Schiel2 1Formerly Institute for Blood Purification, 66424 Homburg, Germany 2Inselklinik Heringsdorf GmbH, 17424 Seeheilbad Heringsdorf, Germany *Correspondence: Rolf Bambauer, Frankenstrasse 4, 6424 Homburg, Germany, Tel: 0049/(0)6841/68500; Fax: 0049/(0)6841/68561; E-mail: [email protected] Abstract In dermatological diseases, TA is increasingly applied as support treatment for severe and/or refractory autoimmune bullous diseases. These diseases are autoantibody-mediated against structural proteins of the skin and/or mucous membranes. Autoimmune blistering diseases have a high morbidity and mortality. These diseases include among others pemphigus vulgaris, and bullous phemphigoid. Drug-induced pemphigus and other forms, such as dermatitis herpetiformis, herpes gestationis, scleroderma, pyoderma gangrenosum, epidermal necrolysis, Behcęt disease, psoriasis vulgaris, Henoch- Schönlein purpura, and porhyria cutanea tarda, are mentioned, too. Pathogenetical aspects are demonstrated in these diseases, in which they are clarified. TA has been shown to effectively remove the autoantibodies from blood and lead to rapid clinical improvement. Keywords: Therapeutic apheresis, Immunoadsorption, Extracorporeal photopheresis, Dermatologic diseases, Immunologic origin Introduction thrombocytes - that occurs when membrane hollow fiber are used is less than that occurring when centrifugation Therapeutic Apheresis (TA) has successfully used is used for cell separation [1]. in various antibody-mediated diseases. Since the pathogenetic relevance of autoantibodies could defined TA methods, such as therapeutic plasma exchange in various diseases, disease-specific adsorbers have been (TPE), and semi- or selective plasma exchange methods, developed for example, in dilated cardiomyopathy (β1- such as immunoadsorption (IA), were discussed by adrenergic receptors), in systemic lupus erythematosus Bambauer et al. [5]. Adsorptive cytapheresis mentioned (C1q), and in grouping ABO blood group antigens [1-4]. in previous studies is a therapeutic procedure in which Besides the selective removal of immunoglobulins from blood from the patient is passed through a medical a patient’s blood, the adsorbers also remove immune device that contains a column or filter that selectively complexes, etc. Some dermatologic immune-mediated adsorbs activated monocytes and granulocytes and the diseases respond to TA. In this review, the indications remaining part of the blood is returned to the patient of TA in autoimmune blistering diseases and atopic [6]. Extracorporeal photopheresis (ECP) is a procedure dermatitis are discussed. in which buffy coat, separated from patient’s blood, is Methods and Results treated extracorporeally with a photoactive compound (e.g. psoralens) and exposed to ultraviolet A light and The advantages of this method are a complete subsequently reinfused to the patient during the same separation of the corpuscular components from the treatment [6]. The guidelines on the use of TA provided plasma and higher efficacy due to increased blood by the Apheresis Applications Committee (AAC) of the flow rate. Furthermore, cell damage - especially to American Society for Apheresis (ASFA) has discussed in Goap Dermatol, 1(1): 35-45 (2019) 35 previous studies [6,7]. therapeutic options include dapsone, gold, and systemic antibodies. They are often used in combination with Dermatologic immune-mediated diseases represent other immunosuppressant agents, such as azathioprine, a heterogeneous group of disorders associated with methotrexate, and cyclophosphamide. Newer therapeutic circulating autoantibodies against distinct adhesion modalities, such as TPE, ECP, mycophenolate mofetil, molecules of the skin and/or mucosa. According to the chlorambucil, dexamethasone-cyclophosphamide, IVIG level of split formation, the disorders can classified as therapy, anti-CD20 monoclonal antibody (rituximab), intraepidermal blistering pemphigus, such as pemphigus have also been investigated [7]. vulgaris (PV), pemphigus foliaceus, and paraneoplastic pemphigus, and as subepidermal blistering pemphigoid The rationale for using TPE in the treatment of diseases, such as Bullous Pemphigoid (BP), pemphigoid PV based on the presence of circulating pathogenic gestations, and dermatitis herpetiformis [7]. autoantibodies. TPE was used in patients in all age groups (13-80 years old). The duration of disease prior The incidence of autoimmune blistering skin diseases to using TPE ranged between 1 month and 25 years. The for example in Germany has doubled during in the last 10 goal of TPE was to reduce the level of autoantibodies years, to about 25 new cases per million humans per year, with subsequent improvement in clinical symptoms. because of improved diagnostic techniques as well as the The decline in autoantibody titers, antikeratinocyte cell age of the population [8]. The incidence of pemphigus surface antibodies, and anti-desmoglein-3 correlated in Europe is one to two cases per million humans per with clinical response in a number of patients [7]. Many year, and 80% of pemphigus patients have PV [9]. BP is patients have treated successful clinical results of TPE, IA the most common type of subepidermal autoimmune and ECP in the treatment of PV [11-16]. blistering skin disease in Europe, with an incidence of about 13 cases per million humans per year. The other The antiepidermal antibodies, which usually belong common types are mucous membrane pemphigoid and to the IgG category, can be easily eliminated with TPE. pemphigoid gestationis [10]. The standard of diagnostic Many authors have reported successful clinical results testing for autoimmune blistering skin diseases is direct of TPE in the treatment of PV [17-21]. Standard therapy immunofluorescence (IF) microscopy to demonstrate the for PV based on a combined administration of high-dose presence of tissue-bound autoantibodies and/or of C3 in glucocorticoids and immunosuppressive drugs. Other patients’ skin or mucous membranes. therapy strategies include TPE, steroid pulse therapy, IVIG, various immunosuppressive agents (e.g. azathioprine, Pemphigus vulgaris (PV) is a severe, chronic disease of cyclophosphamide, cyclosporin, mycophenolate mofetil, the skin and mucous membranes, has poor prognosis and and mizoribine), and rituximab [18]. In the most intractable acantholytic blisters and erosion, and is characterized by cases, a combination of these adjuvant treatments may the presence of antibodies against epidermal intercellular be used [17]. substances. PV is a classic example of autoantibody- induced immune dermatosis, which can be recurrent or IA has successfully applied in patients with severe relapsing [1]. Both genders are equally affected with the atopic dermatitis and high total serum IgE levels [13]. mean age of onset in the sixth and seventh decade of During the last few years, various IA systems and life, and the patients present with skin lesions that occur immunosuppressive protocols have been used to reduce typically as flaccid blisters [7]. The blisters can be located the circulating autoantibodies [8]. IA must be combined on the entire body surface as well as on the mucous with immunosuppressant treatment. The complication membranes of the mouth. PV is characterized by the rates and side effects are low and comparable with those deposition of an autoantibody on the keratinocyte cell of the other extracorporeal circulations [20]. surface. The titers of IgG4 antikeratinocyte antibodies can be correlated with disease activity. The levels of autoantibody have been noted to rebound in the reported patient within 1-2 weeks PV was associated with a high morbidity and mortality. after discontinuation of treatment, which necessitates Introduction of corticosteroids reduced the mortality continuation of immunosuppression [7]. In the guidelines rate from 70% to 100% to a mean of 30% [7]. However, for the use of TA by the AAC of the ASFA, PV has category long-term administration of high doses of corticosteroids III for TPE, IA, and ECP with a recommendation of grade can be associated with severe side effects. Other (RG) 2B and 2C, respectively (Table 1) [7,8]. The rational Goap Dermatol, 1(1): 35-45 (2019) 36 approach should include monitoring of autoantibody rational discontinuation criteria should be similar as titers and clinical symptoms. For ECP, the treatments those for TPE [7]. were continued until clinical response was noted. The Table 1: TA in dermatological diseases with immunolgic origin (Category I: accepted for TA as first-line therapy; Category II accepted for TA as second-line therapy; Category III: not accepted for TA, decision should be individualized; Category IV: not accepted for TA IMB approval is desirable if TA is undertaken (6, 7). Dermatological Apheresis Application Committee of the ASFA [6,7] diseases treated with TA to date [1] TA Treated TA modality Category Recommenda- Treated Replacement Frequency modality with TA tion grade Volume Solution (TPV) Intraepidermal Human- Daily or blistering PV albumin every Other Pemphigus TPE, + TPE, IA, ECP III 2B, 2C 1-1.5 electrolyte day vulgaris IA + solution Subepidermal blistering BP Bullous TPE, + --- --- --- pemphigoid IA + D-penicil- TPE, + --- --- --- lin-amine-induced IA + pemphigus Cutaneous T cell TPE + Human- Daily or lymphoma (CTCL) albumin every Other -erythrodermic ECP, I 1B 1-1.5 electrolyte day -non-erythrodermic ECP III 2C