Unsachgemäße Systemtherapie bei schwerer atopischer Dermatitis – fatale Langzeitschäden

The therapeutic options for treatment of severe cases of atopic dermatitis have been limited until recently, but fundamentally improved with the approval of the first biological dupilumab at the end of 2017. With the biological tralokinumab and the Janus kinase inhibitors baricitinib and upadacitinib, further new systemic drugs have recently been approved. Nevertheless, there are cases in which modern treatment options are not taken into account, as shown by a 28-year-old patient with serious side effects from long-term treatment with systemic glucocorticoids. In addition to the extensive clarification of the consequential damage, guideline-based therapy with dupilumab was initiated as well as interdisciplinary cooperation with endocrinologists, ophthalmologists, osteologists and nutritionists

Mogamulizumab Combined with Extracorporeal Photopheresis as a Novel Therapy in Erythrodermic Cutaneous T-cell Lymphoma.

Primary cutaneous T-cell lymphomas (CTCLs) are rare lymphoproliferative malignancies characterized by significant morbidity and mortality in advanced disease stages. As curative approaches apart from allogeneic stem cell transplantation are lacking, establishing new treatment options, especially combination therapies, is crucial. This retrospective study included 11 patients with SS or MF receiving therapy with mogamulizumab in combination with ECP from four European expert centers. The response rates in the skin and blood as well as treatment use and adverse events (AE) were described. 8/11 patients (73%) showed an overall response (OR) in the skin. The mean mSWAT decreased from 98.2 ± 40.8 to 34.6 ± 23.8. The overall response rate (ORR) in the blood was 64% with two complete responses. During combination therapy, the mean number of Sézary cells decreased from 3365.3 × 10 <sup>6</sup> /L before treatment to 1268.6 × 10 <sup>6</sup> /L. The mean minimum known period without progress was 7.2 months in the skin and 7.6 months in the blood. The most common AEs were mogamulizumab-associated rash (MAR) (45.5%), anemia (27.3%), lymphocytopenia (27.8%), and infusion related reaction (16.7%). No AE led to treatment discontinuation. Our study presents the combination of mogamulizumab and ECP as an effective therapy in the blood and skin in CTCL with good tolerability, similar to mogamulizumab monotherapy

The optimal use of chlormethine gel for mycosis fungoides: An expert consensus from Germany, Austria and Switzerland (DACH region).

In Europe chlormethine gel is licensed for the management of patients with mycosis fungoides of all stages. However, the optimal regimen regarding frequency and dosing as well as combination and maintenance therapy is not well established. Ten experts experienced in research and management of cutaneous T-cell lymphomas from Germany, Austria, and Switzerland (DACH region) were asked in written form to report on indication for chlormethine gel, frequency of use, monitoring, concomitant therapies, adverse effects, combination therapies in later stages of the disease, maintenance therapy, and adherence to this therapy for mycosis fungoides. The structured answers were discussed in a consensus conference and recommendations were developed. Essential for therapy with chlormethine gel is an individualized and symptom-oriented management. Because of the lack of systemic resorption of topically administered chlormethine gel, systemic adverse events are unlikely. An allergic or irritative-toxic contact dermatitis is common but manageable with adaptation of the regimen, interruption of administration, and symptom-specific supportive measurements. A step-up initial approach with application of chlormethine gel every other day is associated with a better tolerability, especially if it is alternated with topical corticosteroids. The use of chlormethine gel in the management of mycosis fungoides is often limited by a concomitant contact dermatitis. An adequate therapeutic regimen and the management of adverse effects can preclude an unnecessary withdrawal of therapy so that more patients can benefit from this treatment option

Current and emerging systemic treatments targeting the neural system for chronic pruritus

Pruritus is a debilitating symptom that significantly affects the quality of life of patients who suffer from it. Many current and emerging systemic treatments targeting the neural system have been successful in treating itch of various underlying etiologies. A complete search of the PUBMED and Google Scholar databases was completed and literature pertinent to current and emerging systemic anti-pruritic drugs which target the neural system was compiled. The purpose of this review is to give the reader with an overview of the current and emerging systemic therapeutic options which target the neural system for chronic pruritus. The authors then provide the reader with their expert perspectives on the future of these therapies. Exciting new anti-pruritic therapies targeting the neural system which show promise include NK-1 inhibitors, opioid receptor modulators, and drugs targeting specific itch receptors such as Mrgpr, Na v 1.7, and PAR2, as well as selective GABA modulators. Future studies should be conducted in order to fully understand these exciting therapeutic options

Histopathological and immunophenotypical criteria for the diagnosis of Sézary syndrome in differentiation from other erythrodermic skin diseases: a European Organisation for Research and Treatment of Cancer (EORTC) Cutaneous Lymphoma Task Force Study of 97 cases

BACKGROUND: Patients with erythrodermic disease are a diagnostic challenge regarding the clinical and histological differential diagnosis. OBJECTIVES: To evaluate histopathological and immunohistochemical diagnostic markers for Sézary syndrome. METHODS: Ninety-seven erythrodermic cases [Sézary syndrome (SS), n = 57; erythrodermic inflammatory dermatoses (EIDs), n = 40] were collected by the EORTC Cutaneous Lymphoma Task Force histopathology group. Evaluation criteria were (i) epidermal and dermal changes; (ii) morphology of the infiltrate; (iii) immunohistochemical analysis of marker loss (CD2, CD3, CD4, CD5 and CD7); (iv) bystander infiltrate by staining for CD8, FOXP3 and CD25; and (v) expression of Ki-67, CD30, PD-1 and MUM-1. RESULTS: The workshop panel made a correct diagnosis of SS in 51% of cases (cutaneous T-cell lymphoma 81%) and of EID in 80% without clinical or laboratory data. Histology revealed a significantly increased degree of epidermotropism (P < 0.001) and more intraepidermal atypical lymphocytes (P = 0.0014) in SS biopsies compared with EID. Pautrier microabscesses were seen only in SS (23%) and not in EID (P = 0.0012). SS showed significantly more dermal cerebriform and blastic lymphocytes than EID. Immunohistochemistry revealed a significant loss of CD7 expression (< 50%) in 33 of 51 (65%) cases of SS compared with two of 35 (6%) EID (P < 0.001). The lymphocytic infiltrate in SS skin samples was found significantly to express PD-1 (P = 0.0053), MUM-1 (P = 0.0017) and Ki-67 (P < 0.001), and showed less infiltration of CD8(+) lymphocytes (P < 0.001). A multivariate analysis identified CD7 loss, increased numbers of small cerebriform lymphocytes, low numbers of CD8(+) lymphocytes and increased proliferation (Ki-67(+) lymphocytes) as the strongest indicators for the diagnosis of SS. CONCLUSIONS: A number of different histological and immunophenotypical criteria are required to differentiate between SS and EIDs