Emerging Terbinafine Resistance in Trichophyton: Clinical Characteristics, Squalene Epoxidase Gene Mutations, and a Reliable EUCAST Method for Detection.

In recent years, cases involving terbinafine-resistant Trichophyton isolates have been reported increasingly, particularly in India. We present 14 cases of terbinafine treatment failure in Trichophyton-infected Danish patients due to acquired resistance. Patients infected with Trichophyton rubrum (n = 12) or Trichophyton interdigitale (n = 2) with elevated terbinafine MICs during 2013-2018 were included. Antifungal susceptibility testing (AFST) was performed following a modified EUCAST E.Def 9.3.1 method (5 days of incubation) with or without cycloheximide and chloramphenicol (CC) supplementation of the growth medium. The squalene epoxidase (SE) target gene was sequenced, and 3-dimensional enzyme homology modeling was performed. Most patients (12/14 [86%]) were male. The mean age was 53.5 years (range, 11 to 77 years). The mean duration of infections was 4.8 years at the time of resistance detection. Prior systemic terbinafine treatment was documented for all patients, and topical therapy for 62% (information was missing in one case). Overall, nine isolates (64%) displayed high terbinafine resistance (MICs, 4 to >8 mg/liter), while two (14%) displayed moderate (MICs, 1 to 2 mg/liter) and three (21%) displayed low (MICs, 0.125 to 0.25 mg/liter) terbinafine resistance compared with control isolates. MICs generated with or without CC supplementation were similar, but CC prevented contamination. Known and novel SE amino acid substitutions (F397L, L393F, L393S, F415S, H440Y F484Y, and I121M V237I) were detected in resistant but not control isolates. Three-dimensional homology modeling suggested a role of the novel I121M and V237I alterations. Terbinafine resistance has been detected in Denmark using a modified EUCAST method, which facilitated susceptibility testing of dermatophytes. Action is needed for this emerging public health problem.

Affective and sensory dimensions of pruritus severity: associations with psychological symptoms and quality of life in psoriasis patients.

The subjective dimensions of pruritus and their associations with psychological symptoms and quality of life were explored in a sample of 40 psoriasis patients. The patients completed a scale with descriptors from the Structured Itch Questionnaire together with measures of depression, distress, sleep quality and pruritus-related quality of life. Psoriasis severity was assessed with the Psoriasis Area and Severity Index. Factor analysis of descriptors confirmed both an affective and a sensory pruritus severity dimension. Multivariate statistics, controlling for age, gender, disease duration and severity, showed affective, but not sensory, pruritus severity to be a significant predictor of depressive symptoms, global distress, impairment of sleep, and pruritus-related quality of life. Mediation analyses indicated that impaired sleep quality partly mediated the association between pruritus severity and psychological symptoms. The results confirm that pruritus is multidimensional and indicate that the affective dimension may be the most important predictor of pruritus-related psychological morbidity, and that the association may be mediated by its negative impact on sleep quality.

IL-8 as antibody therapeutic target in inflammatory diseases: reduction of clinical activity in palmoplantar pustulosis.

IL-8 is a chemokine that has been implicated in a number of inflammatory diseases involving neutrophil activation. HuMab 10F8 is a novel fully human mAb against IL-8, which binds a discontinuous epitope on IL-8 overlapping the receptor binding site, and which effectively neutralizes IL-8-dependent human neutrophil activation and migration. We investigated whether interference in the cytokine network by HuMab 10F8 might benefit patients suffering from palmoplantar pustulosis, a chronic inflammatory skin disease. Treatment of patients with HuMab 10F8 was well tolerated and significantly reduced clinical disease activity at all five endpoints, which included a >or=50% reduction in the formation of fresh pustules. IL-8 neutralization was monitored at the site of inflammation by assessing exudates of palmoplantar pustulosis lesions. HuMab 10F8 sequestered IL-8 in situ, as observed by rapid dose-dependent decreases of IL-8 concentrations immediately following Ab infusion. These data demonstrate a critical role for IL-8 in the pathophysiology of palmoplantar pustulosis. HuMab 10F8 is capable of interrupting IL-8 activity in vivo and represents a candidate for treatment of inflammatory diseases and other pathological conditions associated with IL-8 overproduction.

[Cosmetic soft-tissue augmentation treatment]. / Behandling med kosmetiske bløddelsfyldere.

An increasing number of patients undergo soft-tissue augmentation. The quality depends on the applied filler substance, the compliance of the patient and the physician. Long-term adverse reactions are referred to as nodules or granulomas. Nodules following degradable gels and polyacrylamide hydrogel are always caused by bacteria. Nodules following inert, hydrophobic silicone gel and combination gels may emerge years after the injection. They are often caused by a low-grade infection with ensuing enhanced fibrosis and treatment requires a specialist.