Profound immunodeficiency with severe skin disease explained by concomitant novel CARMIL2 and PLEC1 loss-of-function mutations.

This study reports a patient with severe skin disease in the context of profound immunodeficiency explained by two concomitant genetic diseases caused by two novel homozygous loss-of-function mutations in PLEC1 and CARMIL2. The work provides additional information on the clinical and immunological manifestations of CARMIL2 deficiency and highlights the particular diagnostic and therapeutic challenge represented by the concomitant presence of two rare monogenic disorders.

Anti-Inflammatory Effects of Agrimoniin-Enriched Fractions of Potentilla erecta.

Potentilla erecta (PE) is a small herbaceous plant with four yellow petals belonging to the Rosaceae family. The rhizome of PE has traditionally been used as an antidiarrheal, hemostatic and antihemorrhoidal remedy. PE contains up to 20% tannins and 5% ellagitannins, mainly agrimoniin. Agrimoniin is a hydrolyzable tannin that is a potent radical scavenger. In this study we tested the anti-inflammatory effect of four PE fractions with increasing amounts of agrimoniin obtained by Sephadex column separation. First, we analyzed in HaCaT keratinocytes the expression of cyclooxygenase-2 (COX-2) induced by ultraviolet-B (UVB) irradiation. As COX-2 catalyzes the metabolism of arachidonic acid to prostanoids such as PGE2, we also measured the PGE2 concentration in cell culture supernatants. PE inhibited UVB-induced COX-2 expression in HaCaT cells and dose-dependently reduced PGE2. The PE fraction with the highest agrimoniin amount (PE4) was the most effective in this experiment, whereas fraction PE1 containing mainly sugars had no effect. PE4 also dose dependently inhibited the phosphorylation of the epidermal growth factor receptor (EGFR) which plays a crucial role in UVB-mediated COX-2 upregulation. A placebo-controlled UV-erythema study with increasing concentrations of PE4 demonstrated a dose dependent inhibition of UVB-induced inflammation in vivo. Similarly, PE4 significantly reduced UVB-induced PGE2 production in suction blister fluid in vivo. In summary, PE fractions with a high agrimoniin content display anti-inflammatory effects in vitro and in vivo in models of UVB-induced inflammation.

Gerbstoffe aus Potentilla officinalis wirken entzündungshemmend im UV-Erythem-Test und bei Anwendung auf atopischer Haut.

HINTERGRUND: Das Rhizom von Potentilla officinalis (PO) ist reich an Gerbstoffen und wird traditionell zur äußerlichen Behandlung von Entzündungen der Haut und der Schleimhäute verwendet. Ziel der vorliegenden Arbeit war die Bestätigung der antiinflammatorischen Eigenschaften von PO mittels eines UV-Erythem-Tests und einer klinischen Anwendungsstudie bei atopischer Haut. PROBANDEN UND METHODIK: Die antiinflammatorische Wirkung eines PO-Extrakts (standardisiert auf 2 % Trockensubstanz) wurde in einer prospektiven, randomisierten, placebokontrollierten Doppelblindstudie mit 40 gesunden Erwachsenen im UV-Erythem-Test im Vergleich zu 1 % Hydrocortisonacetat untersucht. Im Rahmen einer prospektiven nicht kontrollierten Studie wurde die Wirkung und Verträglichkeit der 2 % PO-Creme an zwölf Erwachsenen und zwölf Kindern mit atopischer Haut nach Anwendung über zwei Wochen in einem definierten Testareal anhand eines Teil-SCORAD untersucht. Zusätzlich wurde die Beeinflussung der Hautrötung im Testareal photometrisch gemessen. ERGEBNISSE: Im UV-Erythem-Test zeigte die PO-Creme eine signifikante Reduktion des Erythemindex im Vergleich zum Vehikel. Die antiinflammatorische Wirkung des Verums entsprach der der 1 % Hydrocortisonacetat-Creme. Die klinische Studie bei Atopikern zeigte eine signifikante Abnahme des Teil-SCORAD und des Erythems im Testareal. Es wurden keine Unverträglichkeitsreaktionen beobachtet. SCHLUSSFOLGERUNGEN: PO als 2%ige Zubereitung besitzt entzündungshemmende Eigenschaften und ist wirksam und gut verträglich auf atopischer Haut.

Tannins from Potentilla officinalis display antiinflammatory effects in the UV erythema test and on atopic skin.

BACKGROUND: Rich in tannins, the rhizome of Potentilla officinalis (PO) has traditionally been used in the topical treatment of inflammatory disorders of the skin and mucous membranes. The objective of the present study was to examine the antiinflammatory effects of PO in the UV erythema test as well as in patients with atopic skin. PATIENTS AND METHODS: Using the UV erythema test, the antiinflammatory effects of a PO extract (2 %) - compared to 1 % hydrocortisone acetate - were assessed in a randomized, prospective, placebo-controlled double-blind study of 40 healthy volunteers. In the context of a prospective non-controlled trial, the efficacy and tolerability of 2 % PO cream (applied to defined test areas twice daily for two weeks) was evaluated in twelve adults and twelve children with atopic skin using a partial SCORAD. In addition, the effects on the degree of erythema in the test areas was measured photometrically. RESULTS: In the UV erythema test, PO cream significantly reduced the erythema index compared to the vehicle. The antiinflammatory effects of PO cream were comparable to those of 1 % hydrocortisone acetate cream. The clinical study with atopic patients revealed a significant reduction in the partial SCORAD as well as erythema in the test areas. No adverse events were recorded. CONCLUSIONS: PO cream displays antiinflammatory effects in vivo. It is effective in and well tolerated by patients with atopic skin.

Case report: Minimal manifestations of mucous membrane pemphigoid in a young adult.

A male patient presented to our department at the age of 23 suffering from recurrent painful erosions in the urethral outlet area. In closer clinical examination gingival erosions, primarily around the teeth were identified as well. Indirect immunofluorescence on salt split skin with epidermal IgG deposition and positive anti-BP230 IgG ELISA diagnostics hinted toward the presence of mucous membrane pemphigoid (MMP). Direct immunofluorescence from oral mucosa confirmed the diagnosis. MMP in young adulthood is an underdiagnosed disease and latency of diagnosis was around 4 years in our case. Treatment with systemic glucocorticosteroids and dapsone led to clinical remission, prohibiting the development of MMP manifestations in further organs and complications associated with the disease, e.g., scar formation and miction problems.

Anti-inflammatory potential of a lipolotion containing coriander oil in the ultraviolet erythema test.

SUMMARY BACKGROUND: Coriander oil is used as an antimicrobial agent and as a natural fragrance. The present study investigated the anti-inflammatory potency of coriander oil in the ultraviolet (UV) erythema test in vivo. METHODS: 40 volunteers were enrolled in this monocentric,randomized,placebo-controlled double-blind study.Test areas on the back were irradiated with the 1.5 fold minimal erythema dose UV-B. Subsequently, the test areas were treated under occlusion for 47 hours with a lipolotion containing 0.5% or 1.0% essential coriander oil. Hydrocortisone (1.0%) and betamethasone valerate (0.1%) in the vehicle served as positive controls.The vehicle was used as place-bo.The effect of the test substances on the UV-induced erythema was measured photometrically after 48 hours.Additionally,the skin tolerance of the test preparations was assessed on non-irradiated skin. RESULTS: Compared to placebo, the lipolotion with 0.5% coriander oil significantly reduced the UV-induced erythema, but it was not as effective as hydrocortisone. The skin tolerance of both coriander oil concentrations was excellent. CONCLUSIONS: The lipolotion containing coriander oil displayed a mild antiinflammatory effect in this study. It could be useful in the concomitant treatment of inflammatory skin diseases.

In vivo photoprotective and anti-inflammatory effect of hyperforin is associated with high antioxidant activity in vitro and ex vivo.

Hyperforin, a major constituent of St. John's Wort (Hypericum perforatum, HP), provides anti-inflammatory, anti-tumor, and anti-bacterial properties. Previous studies have shown anti-oxidative properties of St. John's Wort extracts; however, its free radical scavenging activity in skin cells or skin has not been assessed in detail so far. Therefore, the free radical scavenging activity of hyperforin was tested in the H(2)DCFDA-assay in vitro in HaCaT keratinocytes irradiated with solar simulated radiation. Hyperforin (EC(50) 0.7 µM corresponding to 0.42 µg/ml) was much more effective compared to Trolox (EC(50) 12 µg/ml) and N-acetylcysteine (EC(50) 847 µg/ml) without showing phototoxicity. The radical protection factor of a cream containing 1.5%w/w of a hyperforin-rich HP extract was determined to be 200 × 10(14) radicals/mg, indicating a high radical scavenging activity. The cream was further applied ex vivo on porcine ear skin and significantly reduced radical formation after infrared irradiation. Finally, the UV-protective effect of the HP cream was tested on 20 volunteers in a randomized, double-blind, vehicle-controlled study. HP cream significantly reduced UVB-induced erythema as opposed to the vehicle. Occlusive application of HP cream on non-irradiated test sites did not cause any skin irritation. Taken together, these results demonstrate that hyperforin is a powerful free radical scavenger.