Photodynamische Therapie (PDT) und wassergefiltertes Infrarot A (wIRA) bei Patienten mit therapierefraktären vulgären Hand- und Fußwarzen

Background: Common warts (verrucae vulgares) are human papilloma virus (HPV) infections with a high incidence and prevalence, most often affecting hands and feet, being able to impair quality of life. About 30 different therapeutic regimens described in literature reveal a lack of a single striking strategy. Recent publications showed positive results of photodynamic therapy (PDT) with 5-aminolevulinic acid (5-ALA) in the treatment of HPV-induced skin diseases, especially warts, using visible light (VIS) to stimulate an absorption band of endogenously formed protoporphyrin IX. Additional experiences adding waterfiltered infrared A (wIRA) during 5-ALA-PDT revealed positive effects. Aim of the study: First prospective randomised controlled blind study including PDT and wIRA in the treatment of recalcitrant common hand and foot warts. Comparison of "5-ALA cream (ALA) vs. placebo cream (PLC)" and "irradiation with visible light and wIRA (VIS+wIRA) vs. irradiation with visible light alone (VIS)". Methods: Pre-treatment with keratolysis (salicylic acid) and curettage. PDT treatment: topical application of 5-ALA (Medac) in "unguentum emulsificans aquosum" vs. placebo; irradiation: combination of VIS and a large amount of wIRA (Hydrosun® radiator type 501, 4 mm water cuvette, waterfiltered spectrum 590-1400 nm, contact-free, typically painless) vs. VIS alone. Post-treatment with retinoic acid ointment. One to three therapy cycles every 3 weeks. Main variable of interest: "Percent change of total wart area of each patient over the time" (18 weeks). Global judgement by patient and by physician and subjective rating of feeling/pain (visual analogue scales). 80 patients with therapy-resistant common hand and foot warts were assigned randomly into one of the four therapy groups with comparable numbers of warts at comparable sites in all groups. Results: The individual total wart area decreased during 18 weeks in group 1 (ALA+VIS+wIRA) and in group 2 (PLC+VIS+wIRA) significantly more than in both groups without wIRA (group 3 (ALA+VIS) and 4 (PLC+VIS)): medians and interquartile ranges: -94% (-100%/-84%) vs. -99% (-100%/-71%) vs. -47% (-75%/0%) vs. -73% (-92%/-27%). After 18 weeks the two groups with wIRA differed remarkably from the two groups without wIRA: 42% vs. 7% completely cured patients; 72% vs. 34% vanished warts. Global judgement by patient and by physician and subjective rating of feeling was much better in the two groups with wIRA than in the two groups without wIRA. Conclusions: The above described complete treatment scheme of hand and foot warts (keratolysis, curettage, PDT treatment, irradiation with VIS+wIRA, retinoic acid ointment; three therapy cycles every 3 weeks) proved to be effective. Within this treatment scheme wIRA as non-invasive and painless treatment modality revealed to be an important, effective factor, while photodynamic therapy with 5-ALA in the described form did not contribute recognisably - neither alone (without wIRA) nor in combination with wIRA - to a clinical improvement. For future treatment of warts an even improved scheme is proposed: one treatment cycle (keratolysis, curettage, wIRA, without PDT) once a week for six to nine weeks. © 2004 Fuchs et al; licensee German Medical Science. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL : http://www.egms.de/en/gms/volume2.shtmlHintergrund: Vulgäre Warzen (Verrucae vulgares) sind humane Papillomvirus-Infektionen (HPV) mit einer hohen Inzidenz und Prävalenz, die am häufigsten Hände und Füße befallen und die in der Lage sind, die Lebensqualität zu beeinträchtigen. Etwa 30 in der Literatur beschriebene Therapieverfahren zeugen von einem Mangel an einer einzigen überzeugenden Strategie. Jüngste Veröffentlichungen zeigten positive Ergebnisse der Photodynamischen Therapie (PDT) mit 5-Aminolävulinsäure (5-ALA) in der Therapie von HPV-induzierten Hautkrankheiten, besonders Warzen, wobei sichtbares Licht (VIS) verwendet wird, um ein Absorptionsband des endogen aus 5-ALA gebildeten Protoporphyrin IX zu stimulieren. Weitere Erfahrungen, wassergefiltertes Infrarot A (wIRA) während der 5-ALA-PDT zusätzlich anzuwenden, offenbarten positive Wirkungen. Ziel der Untersuchung: Erste prospektive randomisierte kontrollierte Blind-Studie, die PDT und wIRA in die Behandlung von therapierefraktären vulgären Hand- und Fußwarzen einbezieht. Vergleich von "5-ALA-Salbe (ALA) vs. Placebo-Salbe (PLC)" und "Bestrahlung mit sichtbarem Licht und wIRA (VIS+wIRA) vs. Bestrahlung mit sichtbarem Licht allein (VIS)". Methoden: Vorbehandlung mit Keratolyse (Salizylsäure) und Kürettage. Photodynamische Therapie (PDT): topische Applikation von 5-ALA (Medac) in "Unguentum emulsificans aquosum" vs. Placebo; Bestrahlung: Kombination von sichtbarem Licht (VIS) und einem hohen Maß an wassergefiltertem Infrarot A (wIRA) (Hydrosun®-Strahler Typ 501, 4 mm Wasserküvette, wassergefiltertes Spektrum 590-1400 nm, kontaktfrei, typischerweise schmerzlos) vs. sichtbares Licht (VIS) allein. Nachbehandlung mit Vitamin-A-Säure-Salbe. Ein bis drei Therapiezyklen im Abstand von 3 Wochen. Hauptzielvariable: "Prozentuale Änderung der Gesamtwarzenfläche jedes Patienten über die Zeit" (18 Wochen). Globales Urteil von Patient und von Arzt sowie subjektive Einschätzung von Empfindung/Schmerz (visuelle Analogskalen). 80 Patienten mit therapierefraktären vulgären Hand- und Fußwarzen wurden randomisiert einer der vier Behandlungsgruppen (mit vergleichbarer Anzahl an Warzen in vergleichbaren Lokalisationen in allen Gruppen) zugeteilt. Ergebnisse: Die individuelle Gesamtwarzenfläche nahm während 18 Wochen in Gruppe 1 (ALA+VIS+wIRA) und in Gruppe 2 (PLC+VIS+wIRA) signifikant mehr als in den beiden Gruppen ohne wIRA (Gruppe 3 (ALA+VIS) und 4 (PLC+VIS)) ab: Mediane und Interquartil-Spannen: -94% (-100%/-84%) vs. -99% (-100%/-71%) vs. -47% (-75%/0%) vs. -73% (-92%/-27%). Nach 18 Wochen unterschieden sich die zwei Gruppen mit wIRA deutlich von den zwei Gruppen ohne wIRA: 42% vs. 7% komplett geheilte Patienten; 72% vs. 34% völlig verschwundene Warzen. Das globale Urteil von Patient und von Arzt und die subjektive Einschätzung des Empfindens waren in den zwei Gruppen mit wIRA viel besser als in den zwei Gruppen ohne wIRA. Folgerungen: Das oben beschriebene vollständige Therapieschema von Hand- und Fußwarzen (Keratolyse, Kürettage, Photodynamische Therapie, Bestrahlung mit VIS+wIRA, Vitamin-A-Säure-Salbe; drei Therapiezyklen im Abstand von 3 Wochen) erwies sich als effektiv. Innerhalb des Therapieschemas zeigte sich wIRA - als nicht-invasive und schmerzlose Therapiemodalität - als ein wichtiger, effektiver Faktor, während die Photodynamische Therapie mit 5-ALA in der beschriebenen Form nicht erkennbar - weder alleine (ohne wIRA) noch in Kombination mit wIRA - zu einer klinischen Verbesserung beitrug. Für die zukünftige Behandlung von Warzen wird ein weiter verbessertes Schema vorgeschlagen: ein Therapiezyklus (Keratolyse, Kürettage, wIRA, ohne PDT) einmal pro Woche für sechs bis neun Wochen

Mannan-Binding Lectin Levels and Activity Are Not Altered in Atopic Dermatitis Patients with a History of Eczema Herpeticum

Background. Eczema herpeticum (EH) is a potentially serious, systemic complication in subjects with atopic dermatitis (AD) caused by herpes simplex virus (HSV). The innate immune dysregulation that predisposes these subjects to cutaneous viral infections is not well understood. We tested the hypothesis that defects in mannan-binding lectin (MBL) may be associated with an increased risk of EH. Methods. We evaluated serum MBL levels and functional activity in 13 AD subjects with a history of EH (EH+) and 21 AD subjects with no history of EH (EH−). MBL levels were detected by enzyme immunoassay. MBL pathway functional activity was evaluated by determining MBL C4b deposition capacity. Results. We found no statistical difference in MBL serum levels or function between EH+ and EH− groups. Conclusion. Considering the limitations of this study (e.g., small samples size) our findings suggest that MBL defects do not play a role in EH

Clinical Study Mannan-Binding Lectin Levels and Activity Are Not Altered in Atopic Dermatitis Patients with a History of Eczema Herpeticum

Background. Eczema herpeticum (EH) is a potentially serious, systemic complication in subjects with atopic dermatitis (AD) caused by herpes simplex virus (HSV). The innate immune dysregulation that predisposes these subjects to cutaneous viral infections is not well understood. We tested the hypothesis that defects in mannan-binding lectin (MBL) may be associated with an increased risk of EH. Methods. We evaluated serum MBL levels and functional activity in 13 AD subjects with a history of EH (EH+) and 21 AD subjects with no history of EH (EH−). MBL levels were detected by enzyme immunoassay. MBL pathway functional activity was evaluated by determining MBL C4b deposition capacity. Results. We found no statistical difference in MBL serum levels or function between EH+ and EH− groups. Conclusion. Considering the limitations of this study (e.g., small samples size) our findings suggest that MBL defects do not play a role in EH

IL-5Rα marks nasal polyp IgG4- and IgE-expressing cells in aspirin-exacerbated respiratory disease

© 2020 American Academy of Allergy, Asthma & Immunology Background: The cause of severe nasal polyposis in aspirin-exacerbated respiratory disease (AERD) is unknown. Elevated antibody levels have been associated with disease severity in nasal polyps, but upstream drivers of local antibody production in nasal polyps are undetermined. Objective: We sought to identify upstream drivers and phenotypic properties of local antibody-expressing cells in nasal polyps from subjects with AERD. Methods: Sinus tissue was obtained from subjects with AERD, chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP), CRS without nasal polyps, and controls without CRS. Tissue antibody levels were quantified via ELISA and immunohistochemistry and were correlated with disease severity. Antibody-expressing cells were profiled with single-cell RNA sequencing, flow cytometry, and immunofluorescence, with IL-5Rα function determined through IL-5 stimulation and subsequent RNA sequencing and quantitative PCR. Results: Tissue IgE and IgG4 levels were elevated in AERD compared with in controls (P <.01 for IgE and P <.001 for IgG4 vs CRSwNP). Subjects with AERD whose nasal polyps recurred rapidly had higher IgE levels than did subjects with AERD, with slower regrowth (P =.005). Single-cell RNA sequencing revealed increased IL5RA, IGHG4, and IGHE in antibody-expressing cells from patients with AERD compared with antibody-expressing cells from patients with CRSwNP. There were more IL-5Rα+ plasma cells in the polyp tissue from those with AERD than in polyp tissue from those with CRSwNP (P =.026). IL-5 stimulation of plasma cells in vitro induced changes in a distinct set of transcripts. Conclusions: Our study identifies an increase in antibody-expressing cells in AERD defined by transcript enrichment of IL5RA and IGHG4 or IGHE, with confirmed surface expression of IL-5Rα and functional IL-5 signaling. Tissue IgE and IgG4 levels are elevated in AERD, and higher IgE levels are associated with faster nasal polyp regrowth. Our findings suggest a role for IL-5Rα+ antibody-expressing cells in facilitating local antibody production and severe nasal polyps in AERD