N. J. Neumann

Afamelanotide for Erythropoietic Protoporphyria

BACKGROUND Erythropoietic protoporphyria is a severe photodermatosis that is associated with acute phototoxicity. Patients with this condition have excruciating pain and a markedly reduced quality of life. We evaluated the safety and efficacy of an α-melanocyte-stimulating hormone analogue, afamelanotide, to decrease pain and improve quality of life. METHODS We conducted two multicenter, randomized, double-blind, placebo-controlled trials of subcutaneous implants containing 16 mg of afamelanotide. Patients in the European Union (74 patients) and the United States (94 patients) were randomly assigned, in a 1:1 ratio, to receive a subcutaneous implant containing either afamelanotide or placebo every 60 days (a total of five implants in the European Union study and three in the U.S study). The type and duration of sun exposure, number and severity of phototoxic reactions, and adverse events were recorded over the respective 180-day and 270-day study periods. Quality of life was assessed with the use of validated questionnaires. A subgroup of U.S. patients underwent photoprovocation testing. The primary efficacy end point was the number of hours of direct exposure to sunlight without pain. RESULTS In the U.S. study, the duration of pain-free time after 6 months was longer in the afamelanotide group (median, 69.4 hours, vs. 40.8 hours in the placebo group; P=0.04). In the European Union study, the duration of pain-free time after 9 months was also longer in the afamelanotide group than in the placebo group (median, 6.0 hours vs. 0.8 hours; P=0.005), and the number of phototoxic reactions was lower in the the afamelanotide group (77 vs. 146, P=0.04). In both trials, quality of life improved with afamelanotide therapy. Adverse events were mostly mild; serious adverse events were not thought to be related to the study drug. CONCLUSIONS Afamelanotide had an acceptable side-effect and adverse-event profile and was associated with an increased duration of sun exposure without pain and improved quality of life in patients with erythropoietic protoporphyria. (Funded by Clinuvel Pharmaceuticals and others; ClinicalTrials.gov numbers, NCT01605136 and NCT00979745.).

Photopatch testing: recommendations for a European photopatch test baseline series.

In order to establish a consensus recommendation for performing photopatch testing, a photopatch test taskforce group was established under the joint umbrella of the European Society for Contact Dermatitis and the European Society for Photodermatology in 2000. After proposing the most adequate methodology in 2004 and completing a European multicentre photopatch test study in 2011, this taskforce is recommending a list of photoallergens that should form part of a baseline series for photopatch testing in Europe. It contains mainly ultraviolet filters and drugs, mostly non‐steroidal anti‐inflammatory drugs. The choice of chemicals was based on the results of a recent multicentre study, previous published cases of photoallergy, and use of the substances in the European market.

Treatment of Palmoplantar Psoriasis with Monochromatic Excimer Light (308-nm) Versus Cream PUVA

Palmoplantar psoriasis is a chronic disease, which is very resistant to treatment and often leads to severe disabilities. Photochemotherapy employing psoralens combined with UVA irradiation (PUVA) is a well-accepted therapy for palmoplantar psoriasis. Its topical application (bath PUVA; cream PUVA) avoids the typical side effects of orally applied psoralens. We compared the efficacy of cream PUVA therapy with monochromatic excimer light therapy, a treatment modality employing 308-nm UVB radiation generated by a new kind of light source. Ten patients with psoriasis of the palms and soles were randomly assigned to receive cream PUVA on one side and 308-nm UVB on the contralateral side. Based on the psoriasis area and severity index (PASI) score, clinical assessment was carried out before and 5 weeks after the beginning of the study. At the end of the treatment period both test groups showed a remarkable PASI score reduction (308-nm UVB, 63.57%; cream PUVA, 64.64%). No relevant adverse effects were observed, except for mild irritation in a few patients. After a 12-week follow-up, a relapse of the disease was only observed in one patient. Thus, mono-chromatic excimer light cleared palmoplantar psoriasis as rapidly as cream PUVA. In contrast to cream PUVA, monochromatic excimer light therapy is not associated with prior drug application. This might lead to a lower incidence of adverse reactions and better compliance. Therefore, monochromatic excimer light therapy seems to be a useful new therapeutic option for palmoplantar psoriasis.

Surgical Pearl: Nail splinting by flexible tube—A new noninvasive treatment for ingrown toenails☆☆☆★

From the Department of Dermatology, Heinrich-Heine-University. Reprint requests: Klaus W. Schulte, MD, Department of Dermatology, Heinrich-Heine-University Duesseldorf Moorenstr. 5, D-40225 Duesseldorf, Germany. J Am Acad Dermatol 1998;39:629-30. Copyright

Photodynamische Therapie bei kutaner Leishmaniose

ZusammenfassungWir berichten über einen 19-jährigen türkischen Patienten, der sich nach einem Urlaub in seinem Heimatland mit einer kutanen Leishmaniose infizierte. Die kutane Leishmaniose heilt häufig spontan mit einer lebenslangen Immunität ab, kann aber auch persistieren und zu ausgedehnter Narbenbildung führen. In der Literatur sind bis heute zwar viele therapeutische Optionen beschrieben, diese gehen aber teilweise mit erheblichen Nebenwirkungen einher. Bei unserem Patienten führte die photodynamische Therapie zu einer Abheilung der Läsion mit nur geringgradig ausgeprägter Hypopigmentierung.AbstractWe report about a 19-year-old Turkish patient who presented with cutaneous leishmaniasis after a holiday in Turkey. Cutaneous leishmaniasis often heals spontaneously leading to life-long immunity, but it can persist and lead to extensive scarring. In the literature, many therapeutic modalities have been reported; however, they can be accompanied by severe side effects. In our patient, photodynamic therapy resulted in healing of the lesion with only slight hypopigmentation.

Photodynamic therapy of cutaneous leishmaniasis. A promising new therapeutic modality

ZusammenfassungWir berichten über einen 19-jährigen türkischen Patienten, der sich nach einem Urlaub in seinem Heimatland mit einer kutanen Leishmaniose infizierte. Die kutane Leishmaniose heilt häufig spontan mit einer lebenslangen Immunität ab, kann aber auch persistieren und zu ausgedehnter Narbenbildung führen. In der Literatur sind bis heute zwar viele therapeutische Optionen beschrieben, diese gehen aber teilweise mit erheblichen Nebenwirkungen einher. Bei unserem Patienten führte die photodynamische Therapie zu einer Abheilung der Läsion mit nur geringgradig ausgeprägter Hypopigmentierung.AbstractWe report about a 19-year-old Turkish patient who presented with cutaneous leishmaniasis after a holiday in Turkey. Cutaneous leishmaniasis often heals spontaneously leading to life-long immunity, but it can persist and lead to extensive scarring. In the literature, many therapeutic modalities have been reported; however, they can be accompanied by severe side effects. In our patient, photodynamic therapy resulted in healing of the lesion with only slight hypopigmentation.

Phototoxic and photoallergic reactions

© Dt. Dermatologische Gesellschaft • Journal compilation

Type 2 Segmental Manifestation of Cutaneous Leiomyomatosis in Four Unrelated Women with Additional Uterine Leiomyomas (Reed’s Syndrome)

cholinergic agent, topical anesthetic, cryotherapy and CO 2 laser ablation [2] . Whereas the etiopathogenesis of solitary leiomyoma is unknown, multiple cutaneous and uterine leiomyoma syndrome (MIM No. 150800) – also known as Reed’s syndrome [3] – is a disorder inherited in an autosomal dominant pattern. In 2001, the gene for Reed’s syndrome was mapped to chromosome 1q42.3–43 [4] . One year later, the fumarate hydratase (FH) gene has been identifi ed as the responsible gene [5] . Fumarate hydratase is an enzyme involved in the tricarboxylic acid cycle. In Reed’s syndrome, the FH gene is thought to act as a tumor suppressor gene [4–7] . In some Reed’s syndrome families, the disease is associated with an additional predisposition to type 2 papillary renal cell carcinoma (hereditary leiomyomatosis with renal cell cancer, MIM No. 605939) [8] also caused by germline mutations in the FH gene [5, 9, 10, 18] . Multiple cutaneous leiomyomas can occur in different segmental patterns, sometimes reminiscent of the lines of Blaschko. Segmental cutaneous leiomyomatosis comprises two different types. Clinically, type 1 shows only lesions in a segmental area without any similar lesion on the integument [11] . In the more frequent type 2 segmental cutaneous leiomyomatosis, the segmental involvement is characterized by a more pronounced manifestation superimposed on the ordinary nonsegmental phenotype [12–15] . In this report, we present 4 unrelated women with type 2 segmental cutaneous leiomyomatosis. All 4 patients had previously developed additional uterine leiomyomas and had a positive family history of cutaneous or uterine leiomyomas. Thus, all 4 patients were – by defi nition – affected with Reed’s syndrome.

Photodiagnostische Testverfahren Teil 3: Fluoreszenzdiagnostik mit δ-Aminolävulinsäure-induzierten Porphyrinen (FDAP) in der Dermatologie

LernzieleVerständnis des Prinzips der FluoreszenzdetektionEntwicklung der Fluoreszenzdetektion von Tumoren der HautPrinzip der FDAPMöglichkeiten und Grenzen der FDAPSicherer und selektiver Einsatz der FDAPDie wichtigste Methode zur Diagnosesicherung von Hauttumoren und ihren Vorstufen ist die histopathologische Untersuchung. Präoperativ stehen bislang die Dermatoskopie und die Sonographie als nicht invasive Methoden zur Verfügung. Wir möchten die Fluoreszenzdiagnostik mit δ-Aminolävulinsäure-induzierten Porphyrinen (FDAP), ein neues diagnostisches, für die Dermatologie interessantes Verfahren vorstellen. Sie ermöglicht, neoplastisches oder entzündlich verändertes Gewebe von der umliegenden gesunden Haut durch Detektion der typischen, ziegelroten Porphyrinfluoreszenz abzugrenzen.

Time course of 8-methoxypsoralen-induced skin photosensitization in PUVA-bath photochemotherapy

In recent years PUVA‐bath photochemotherapy has been shown to be an effective treatment modality for several dermatoses. A limitation of PUVA‐bath photochemotherapy has been the lack of guidelines for optimal performance, including the time course of photosensitization of the skin exposed to the 8‐methoxypsoralen (8‐MOP) bath water solution. In the present study 12 healthy volunteers were exposed to a 20 min bath in 150 1 of an 8‐MOP water solution (0.5 mg/1, 37°C). Immediately, as well as 1, 2, 3 and 5 h after the 8‐MOP bath, irradiation was performed with increasing doses of UVA (0.5, 1, 2, 3, 5 J/cm2) on 2 cm2 test areas. The minimal phototoxic dose (MPD) was determined 72 h after the UVA exposure. In all volunteers, photosensitization was highest immediately after the bath, with a MPD significantly below 5 J/cm2 (0.5‐2 J/cm2). One hour after the bath, erythema could be induced by 2 to 5 J/cm2 UVA. Two hours after the bath, erythema could be induced using irradiation of 5 J/cm2 only in two volunteers. Three and five hours after the 8‐MOP bath, no erythema could be induced in any volunteer by UVA doses up to 5 J/cm2. Our results indicate that optimal bath‐PUVA requires UVA irradiation immediately after the 8‐MOP bath. Further, these results imply that no restrictions on further sun exposure are mandatory 3 h after the 8‐MOP bath, thus allowing the patient to pursue normal life activities.