Therapeutic Apheresis and/or Monoclonal Antibodies in Dermatological Diseases

Abstract

Therapeutic Apheresis (TA) is increasingly applied as support treatment in dermatological diseases especially in severe and/or refractory autoimmune bullous diseases. Since the pathogenetic relevance of autoantibodies could defined in various diseases, disease-specific adsorbers have been developed.Especially, dermatologic immune-mediated diseases respond to TA.The different TA methods, such as Therapeutic Plasma Exchange (TPE), Immunoadsorption (IA),adsorptive cytapheresis, Extracorporeal Photopheresis (ECP) were discussed elsewhere [1,2]. Dermatologic immune-mediated diseases represent a heterogeneous group of disorders associated with circulating autoantibodies against distinct adhesion molecules of the skin and/or mucosa. The incidence of autoimmune blistering skin diseases for example in Germany has doubled during in the last 10 years, to about 25 new cases per million humans per year, because of improved diagnostic techniques as well as the age of the population [3]. The incidence of Pemphigus Vulgaris (PV) in Europe is one to two cases per million humans per year, and 80% of pemphigus patients have PV [4]. Bulbous Pemphigoid (BP) is the most common type of subepidermal autoimmune blistering skin disease in Europe, with an incidence of about 13 cases per million humans per year. Avens Publishing Group Inviting Innovations Citation: Bambauer R, Schiel R. Therapeutic Apheresis and/or Monoclonal Antibodies in Dermatological Diseases. J Clin Investigat Dermatol. 2021;9(1): 3 J Clin Investigat Dermatol 9(1): 3 (2021) Page 02 ISSN: 2373-1044 munosuppressive medication [14]. Rituximab, in usually dosages, is almost given as an adjuvant drug, i.e., in addition to another type of immunosuppressive treatment. Complications of rituximab in patients with autoimmune blistering skin diseases include infections, deep venous thrombosis of the lower limbs, pulmonary embolism, longterm hypogammaglobulinemia, and neutropenia with an overall mortality of 4%. Mycosis fungoides and its leukemic variant, Sézary syndrome (SS), are the most common types of Cutaneous T-Cell Lymphoma (CTCL) whose pathogenesis remains elusive [2]. CTCL is incurable. Therapy is aimed at alleviating symptoms, improving skin manifestations, controlling extra cutaneous complications, and minimizing immunosuppression [8]. Chemotherapy is recommended for aggressive SS, with alemtuzumab in usually dosages and stem cell transplantation being considered for refractory disease. In CTCL ECP is indicated. ECP involves the collection of circulating malignant CD4+ T cells, ex vivo treatment with 8-methoxypsoralen and UVA light and reinfusion of the cells. The therapeutic effect appears to be mediated by in vivo stimulation of antitumor immunity through the interactions of irradiated, apoptotic lymphoma cells with antigenpresenting dendritic cells [2]. ECP should be planned for a minimum of 6 months (2 to 3 treatments per week in the acute phase), or it can be reduced to once every 6-12 weeks. TPE is in combination with immunosuppression probably successful due to the pathogenesis of severe cases of dermatitis herpetiformis and herpes gestationis [15,16]. Herpes gestationis or pemphigoid gestationis is an autoimmune subepidermal blistering disease that occurs in women in the second or third trimesters of pregnancy or even puerperium. It is a rare skin disease, the incidence of which has been estimated of approximately one case in every 40,000–60,000 pregnancies [16]. Scleroderma or systemic sclerosis is a rare, generalized autoimmune disease. Scleroderma is characterized by vascular abnormalities, fibrosis, inflammatory changes, and late-stage atrophy/obliterative vasculopathy. Localized scleroderma forms show a longitudinal or circumscribed skin involvement [17]. The effectiveness of TPE in progressive scleroderma and dermatomyositis is still disputed. Pyoderma gangrenosum (PG) is a rare, polyetiological syndrome based on a pathological immune reaction. In over 40% of cases, this disease occurs together with colitis ulcerosa. In the vessel walls of vasculitic lesions, granular IgG, C3, complement, and IgM deposits have been observed [18]. PG is a non-infectious neutrophilic dermatosis that usually starts with sterile pustules that rapidly progress to painful ulcers of variable depth and size with undermined violaceous borders. In 17%-74% of cases, PG is associated with an underlying disease, most commonly inflammatory bowel disease, rheumatological or hematological disease, or malignancy. PG is characterized by painful, enlarging necrotic ulcers with bluish undermined borders surrounded by an advancing zone of erythema; its clinical variants include ulcerative or classic, pustular, bullous or typical, vegetative, peristomal, and drug-induced. It can be idiopathic or associated with cancer, infections, medications, and systemic diseases [19]. The treatment with corticosteroids and cyclosporin is documented as first-line therapy. In cases that do not respond to this treatment, alternative therapeutic procedures (e.g., systemic corticosteroids and mycophenolate mofetil; mycophenolate mofetil and cyclosporin; tacrolimus; infliximab in usually dosages, or TPE (8 to 10 treatments) are recommended [20]. Drug-induced Epidermal toxic necrolysis (TEN), also known as Lyell’s syndrome, is a life-threatening drug reaction characterized by extensive destruction of the epidermis and mucosal epithelia. The eyes are typically involved in TEN. The disease has a high mortality rate. TEN and the Stevens-Johnson Syndrome (SJS) are closely related, although their severity and outcome are different. The SJS and TEN are rare but present severe skin manifestation. They are estimated to occur in one to three people per million per year in Europe and the United States [21]. They are characterized by a low incidence but high mortality, and drugs are most commonly implicated in 80% of TEN cases. TEN is the most severe form of drug induced skin reaction and is defined as epidermal detachment of 30% of total body surface area [22]. In Lyell’s syndrome, the acute phase can be very successfully treated by TPE. The allergic or toxin-induced skin necrolysis is usually triggered by a drug acting like a hapten [23]. Lyell’s syndrome is fortunately very rare but has a high mortality rate, approximately 50%, and thus, early administration of TPE is justified, 6 to (8 to 10 treatments) every day or every other day. TPE is a safe intervention in severely ill TEN patients and may reduce the mortality in this severe disease [24]. Behcet disease a multisystem inflammatory disorder, presents with the involvement of muco-cutaneous, ocular, vascular, central nervous and gastrointestinal systems. It is an idiopathic, chronic, and recurrent disease characterized by exacerbation alternating with plasma of quiescence, episodic pan uveitis, and aggressive no granulomatous occlusive vasculitis of the arteries and veins of any size with explosive ocular inflammatory attacks that primarily affect the retinal and anterior segment vasculature of the eye [25]. Central nervous system involvement, most often due to necrotizing vasculitis, may be the most protean manifestation of the disease, leading to death. The frequency of ocular manifestations is 70%-85% in these patients. Although TPE has been has been successful in individual cases [26]. The frequency is 3 to 6 treatments daily or every other day, a chronic treatment of TPE with 1 treatment every two or four weeks for two or three months is possible, too. In recent years, there have been reports on the successful treatment with implementation of cyclosporin A, tacrolimus, or infliximab, etc. Psoriasis vulgaris is a common autoimmune chronic inflammatory skin disease that affects approximately 2% of the world’s population. Fundamental for its immunopathogenic mechanism is the secretion of type 1 (Th 1) cytokines by T cells and their activation [27]. TPE may be beneficial in patients with psoriatic arthropathy and not responding to conventional therapy [28]. However, blocking TNF-α by infliximab or etanercept has shown particular promise, especially in the management of psoriasis. Henoch-Schönlein purpura (HSP) is a systemic vasculitis that affects vessels of small size. The vascular purpura is usually confined to the lower limbs and is associated, at varying degrees, with joint, gastrointestinal, and renal involvement. It is a systemic disease Citation: Bambauer R, Schiel R. Therapeutic Apheresis and/or Monoclonal Antibodies in Dermatological Diseases. J Clin Investigat Dermatol. 2021;9(1): 3 J Clin Investigat Dermatol 9(1): 3 (2021) Page 03 ISSN: 2373-1044 where antigen-antibody (IgA) complexes activate the alternate complement pathway, resulting in inflammation and small-vessel vasculitis [29]. HSP is defined as the presence of two or more of the following criteria: age of disease onset (20 years or younger), palpable purpura, acute abdominal pain, and granulocytic infiltration in the walls of arterioles or venuoles. All patients develop palpable purpura. In the skin, these deposits lead to subepidermal hemorrhage and small-vessel necrotizing vasculitis producing the purpura (2). IgG autoantibodies directed at mesangial antigens may play a role in pathogenesis. In other organs, necrotizing vasculitis leads to organ dysfunction or hemorrhage. The recommendation for TPE are severe cases. Eight to 10 treatments daily or every other day until the antibodies disappeared. Porphyria cutanea tarda (PCT), a genetic enzyme defect, was also considered as being a treatable condition with possible indication for TPE (1). PCT is a metabolic disorder of the hem biosynthesis caused by decreased activity of uroporphyrinogen decarboxylase [30]. PCT is manifest by fragility, erosions, bullae, milia, and scars on sun-exposed skin. Excess porphyrins in the skin interact with light of approximately 400-nm-wave length radiant energy, forming reactive oxygen species. PCT is categorized