Palladium causes bizarre skin hyperpigmentation in long-term dihydrocodeinone 'Braun' abusers.

BACKGROUND: 'Braun' is an illegal injectable dihydrocodeinone-enriched drug mixture of semi-synthetic opioids. It is prepared by palladium-catalysed hydrogenation from codeine-containing tablets. OBJECTIVE: We aimed to characterize the dermatologic consequences of long-term abuse of 'Braun'. METHODS: Skin biopsies of two long-term 'Braun' abusers were evaluated histopathologically, immunohistochemically and ultrastructurally. Palladium skin content was assessed by X-ray fluorescence (XRF) spectrometry. RESULTS: Both patients showed generalized diffuse dark blue-grey hyperpigmentation of the skin. In both, an abnormal population of cells containing intracytoplasmic brownish granular material was identified in the papillary dermis by light microscopy. Electron microscopy revealed a dense and minimally structured material that predominantly accumulated in macrophages, fibroblasts and vascular endothelial cells. XRF analysis confirmed elevated levels of palladium in the patient's skin in comparison to healthy controls. CONCLUSION: Long-term abuse of palladium-contaminated dihydrocodeinone ('Braun') results in excessive accumulation of granular material in various dermal cell types and causes generalized diffuse skin hyperpigmentation.

Biologics combined with conventional systemic agents or phototherapy for the treatment of psoriasis: real-life data from PSONET registries.

BACKGROUND: Biologics have greatly improved psoriasis management. However, primary and secondary non-response to treatment requires innovative strategies to optimize outcomes. OBJECTIVE: To describe the use of combined treatment of biologics with conventional systemic agents or phototherapy in daily clinical practice. METHODS: We collected data on frequency of use, demographics, treatment characteristics and drug survival of biologics combined with conventional systemic agents or phototherapy in five PSONET registries. RESULTS: Of 9922 biologic treatment cycles, 982 (9.9%) were identified as combination treatment. 72.9% of treatment cycles concerned concomitant use of methotrexate, 25.3% concerned concomitant UVB therapy, acitretin or cyclosporin and 1.8% concerned combined treatment with PUVA, fumaric acids or a second biologic. Substantial variation was detected in type and frequency of combination treatments prescribed across registries. Patients initiated on combined treatment had generally severe disease and were affected with psoriasis for many years. The extent to which patients had been priory treated with biologic monotherapy and the proportion of patients affected with psoriatic arthritis differed between registries. Survival rates for etanercept, adalimumab, infliximab and ustekinumab with methotrexate ranged between 43 and 92%, 28 and 83%, 65 and 87% and 53 and 77%, respectively, across registries after one year with no consistent superior survival for a particular biologic. Longest survival on a biologic combined with methotrexate, acitretin or cyclosporin was 103, 78 and 34 months, respectively. CONCLUSION: Methotrexate was the most commonly used concomitant treatment for patients on a biologic. Wide geographical variations in treatment selection and persistence of combination treatment exist. Data derived from ongoing studies may help to determine whether combined treatment is superior to biologic monotherapy.

Melanoma antigens are biomarkers for ipilimumab response.

BACKGROUND: Novel immunotherapy modalities significantly improve survival of patients with metastatic melanoma. However, CTLA-4-blocking monoclonal antibody ipilimumab is effective only in a small proportion of patients. Biomarkers for prediction of treatment response are indispensably needed. OBJECTIVE: To determine the utility of multimarker detection of circulating melanoma cells as prognostic and pharmacodynamic biomarker in patients with metastatic melanoma treated with ipilimumab. METHODS: Patients (n = 62) with metastatic melanoma in unresectable stage III or metastatic stage IV treated with ipilimumab were recruited prospectively. The values of four melanoma markers on circulating cells Melan-A, gp100, MAGE-3 and melanoma inhibitory antigen prior to the treatment and within the therapy were compared to the data collected at baseline - after the melanoma surgery. RESULTS: The immunotherapy pretreatment marker level was found to be prognostic of overall survival; lower levels were linked to longer survival time. Moreover, longitudinal follow-up of melanoma markers in patients treated with ipilimumab correlates with therapy response. A decline of marker levels by >30% at week 6 (in 83% of the responding subjects) to week 9 (in all responders) of ipilimumab administration was associated with response to therapy. Elevation of the tumour markers during the treatment precedes clinical progression and gives an early warning of treatment failure. CONCLUSION: Melanoma circulating cells hold potential as predictive and pharmacodynamic biomarker of immunotherapy.

[Pancreatic panniculitis with multiple osteolytic lesions]. / Pankreatische Pannikulitis mit multiplen osteolytischen Läsionen.

A 62-year-old man with a history of chronic alcohol abuse presented with severe pancreatic panniculitis associated with an acute exacerbation of chronic pancreatitis.

[Topical hemoglobin promotes wound healing of patients with venous leg ulcers]. / Einfluss von topischem Hämoglobin auf die Heilung von Patienten mit Ulcus cruris venosum.

BACKGROUND: Improvement of oxygenation is getting increasing attention as an important aspect in the modern wound care. The aim of such complementary wound care approaches is to improve and accelerate wound healing. PATIENTS AND METHODS: A solution comprising purified hemoglobin was added to the standard wound care procedure of patients with venous leg ulcers and compared to a second group without addition of the hemoglobin. In each group, 36 patients were included. The duration of treatment was 13 weeks. Primary end point was reduction of wound size or wound closing. RESULTS: In the group treated with the additional hemoglobin solution, an average of 53% of wound size reduction was obtained. No statistically significant reduction was observed in the second group. CONCLUSION: The addition of aemoglobin solution in the wound care procedure for venous leg ulcers showed a significant improvement of wound healing in comparison to a control group.

Current treatment goals are achieved by the majority of patients with atopic dermatitis treated with tralokinumab: results from a multicentric, multinational, retrospective, cohort study.

BACKGROUND: Tralokinumab is a human monoclonal antibody targeting interleukin-13 that is approved for the treatment of moderate-severe atopic dermatitis. Studies analyzing the efficacy and safety of tralokinumab in a real-world setting are scarce. RESEARCH DESIGN AND METHODS: A European, multicentric, real-world, retrospective cohort study was defined to assess the effectiveness and safeness profile of tralokinumab, investigating the achievement of pre-specified treatment goals; and to detect potential differences in terms of effectiveness and safeness across some selected patient subcohorts. RESULTS: A total of 194 adult patients were included in this study. A significant improvement in physician-assessed disease severity was detected at each follow-up visit as compared with baseline and similar trend was observed for patient-reported outcomes and quality of life. No meaningful difference in effectiveness was found when considering patient age (<65 versus ≥65 years), neither dissecting patient cohort in dupilumab-naive vs dupilumab-treated subjects. Among tralokinumab-treated patients, 88% achieved at least one currently identified real-world therapeutic goal at week 16. CONCLUSIONS: This retrospective multicenter study confirmed the effectiveness and safeness of tralokinumab throughout 32 weeks of observation, showing the achievement of therapeutic goals identified in both trial and real-world settings in a large proportion of tralokinumab-treated patients.

Multimarker real-time reverse transcription-PCR for quantitative detection of melanoma-associated antigens: a novel possible staging method.

BACKGROUND: Detection of melanoma cells in peripheral blood is a promising method for monitoring haematogenous spread of melanoma cells. It enables us to detect early metastasis and to better stratify candidates for adjuvant immunotherapy. Inconsistent data on the sensitivity and clinical relevance of this method have been reported. STUDY DESIGN: We developed a multimarker real-time reverse transcription-PCR (RT-PCR) for quantification of five melanoma markers: Melan-A, gp100, MAGE-3, MIA and tyrosinase. In this prospective study, 65 patients with resected cutaneous melanoma stage IIB-III were screened. Peripheral blood samples were collected every 3 months for the following 18 months, and circulating melanoma cells were examined and compared with clinical staging results. RESULTS: Eighteen patients relapsed during the trial and showed different types of melanoma progression. All these patients experienced statistically significant tumour marker elevation in the period from 0 to 9 months before the disease progression. MAGE-3 was the most sensitive progression marker. In patients with progression, we observed three concordant positive markers in 39% of cases, two concordant positive markers in 28%, and finally one marker in 33%. CONCLUSIONS: This report describes a multiple-marker real-time RT-PCR, which is able to provide quantitative data on melanoma markers in the peripheral blood of melanoma patients. Measurement of the studied molecular markers in our hands represents a prognostic factor and a useful method for early detection of metastasis and treatment response of melanoma patients.