Summary
Background
Most data on chronic spontaneous urticaria (CSU) originate from highly selected patient populations treated at specialized centres. Little is known about CSU patient ...characteristics and the burden of CSU in routine clinical practice. AWARE (A World‐wide Antihistamine‐Refractory chronic urticaria patient Evaluation) is an ongoing global study designed to assess chronic urticaria in the real‐life setting.
Objective
To describe the baseline characteristics of the first 1539 German AWARE patients with H1‐antihistamine‐refractory CSU.
Methods
This prospective non‐interventional study included patients (18–75 years) with a diagnosis of H1‐antihistamine‐refractory CSU for > 2 months. Baseline demographic and disease characteristics, comorbidities, and pharmacological treatments were recorded. Quality of life (QoL) was assessed using the dermatology life quality index (DLQI), chronic urticaria QoL questionnaire (CU‐Q2oL), and angioedema QoL questionnaire (AE‐QoL, in cases of angioedema). Previous healthcare resource utilization and sick leave data were collected retrospectively.
Results
Between March and December 2014, 1539 patients were assessed in 256 sites across Germany. The percentage of females, mean age, and mean body mass index were 70%, 46.3 years, and 27 kg/m2, respectively. The mean urticaria control test score was 7.9, one in two patients had angioedema, and the most frequent comorbidities were chronic inducible urticaria (CIndU; 24%), allergic rhinitis (18.2%), hypertension (18.1%), asthma (12%), and depression (9.5%). Overall, 57.6% of patients were receiving at least one pharmacological treatment including second‐generation H1‐antihistamines (46.3%), first‐generation H1‐antihistamines (9.1%), and corticosteroids (15.8%). The mean DLQI, total CU‐Q2oL, and total AE‐QoL scores were 8.3, 36.2, and 46.8, respectively. CSU patients reported frequent use of healthcare resources, including emergency services (29.7%), general practitioners (71.9%), and additional allergists or dermatologists (50.7%).
Conclusions and Clinical Relevance
This study reveals that German H1‐antihistamine‐refractory CSU patients have high rates of uncontrolled disease, angioedema, and comorbid CIndU, are undertreated, have impaired QoL, and rely heavily on healthcare resources.
Recently, activating mutations in the TERT promoter were identified in cutaneous melanoma. We tested a cohort of ocular melanoma samples for similar mutations.
The TERT promoter region was analysed ...by Sanger sequencing in 47 uveal (ciliary body or choroidal) melanomas and 38 conjunctival melanomas.
Mutations of the TERT promoter were not identified in uveal melanomas, but were detected in 12 (32%) conjunctival melanomas. Mutations had a UV signature and were identical to those found in cutaneous melanoma.
Mutations of TERT promoter with UV signatures are frequent in conjunctival melanomas and favour a pathogenetic kinship with cutaneous melanomas. Absence of these mutations in uveal melanomas emphasises their genetic distinction from cutaneous and conjunctival melanomas.
Guidelines on the use of extracorporeal photopheresis Knobler, R.; Berlin, G.; Calzavara-Pinton, P. ...
Journal of the European Academy of Dermatology and Venereology,
January 2014, Letnik:
28, Številka:
s1
Journal Article
Recenzirano
Odprti dostop
Background
After the first investigational study on the use of extracorporeal photopheresis for the treatment of cutaneous T‐cell lymphoma was published in 1983 with its subsequent recognition by the ...FDA for its refractory forms, the technology has shown significant promise in the treatment of other severe and refractory conditions in a multi‐disciplinary setting. Among the major studied conditions are graft versus host disease after allogeneic bone marrow transplantation, systemic sclerosis, solid organ transplant rejection and inflammatory bowel disease.
Materials and methods
In order to provide recognized expert practical guidelines for the use of this technology for all indications the European Dermatology Forum (EDF) proceeded to address these questions in the hands of the recognized experts within and outside the field of dermatology. This was done using the recognized and approved guidelines of EDF for this task.
Results and conclusion
These guidelines provide at present the most comprehensive available expert recommendations for the use of extracorporeal photopheresis based on the available published literature and expert consensus opinion.
Background
Histopathological diagnosis including selection of lesions, the determination of the best point of time for biopsy and workup is not trivial in cutaneous graft‐versus‐host disease (GvHD).
...Objectives
To develop interdisciplinary recommendations on performing, the laboratory work up and reporting of the results of skin biopsies in patients with suspected cutaneous GvHD.
Methods
A working group consisting of dermatopathologists, dermatologists, transplant‐physicians and transplant‐pathologists prepared recommendations for performing skin biopsies, laboratory workup and evaluation of tissue samples, and reporting of the results in patients with cutaneous GvHD. After achieving a consensus within the working group, a survey that comprised the core issues of the recommendations was electronically sent out to 72 alloHSCT centres within Germany, Austria, and Switzerland and their Departments of Pathology. The answers were discussed in a Consensus Conference and final recommendations were established.
Results
Twenty‐five centres responded to the clinical and 17 centres to the histopathological survey. Questions addressed to the clinicians comprised the indication for skin biopsy in chronic GvHD (cGvHD) and acute GvHD (aGvHD) and the appropriate point of time for skin biopsy. Eighty‐eight per cent agreed that the skin biopsy is generally indicated in patients with suspected cGvHD lacking diagnostic features. In contrast, with suspected aGvHD, only 62% of respondents felt that skin biopsy was necessary even if GvHD had not been confirmed in another organ. Although restricted due to the fact that immunosuppression is often applied in an emergency setting most centres supported skin biopsies before initiation of topical or systemic immunosuppression. The majority of pathologists agreed that in non‐sclerotic GvHD a punch biopsy is adequate, whereas in sclerotic GvHD a scalpel biopsy is preferred.
Conclusion
While a consensus on the need for biopsies in cGvHD was reached the value of skin biopsies in aGvHD and subsequent biopsies during therapy requires further evaluation.
Since the majority of melanomas eventually become resistant and progress, combining selective BRAF inhibitors (BRAFi) with immunotherapies has been proposed to achieve more durable treatment ...responses. Here, we explored the impact of selective BRAFi on the hosts' immune system.
Clinical data, whole blood counts (WBC) and serum lactate dehydrogenase (LDH) of 277 vemurafenib- and 65 dabrafenib-treated melanoma patients were evaluated. The frequency and phenotype of lymphocyte subpopulations were determined by flow cytometry while T cell cytokine secretion was measured by multiplex assays.
Progression-free survival (PFS) as well as overall survival (OS) were similar in patients treated with either BRAFi. High pretreatment LDH was associated with shorter PFS and OS in both groups. During therapy, peripheral lymphocytes decreased by 24.3% (median, P < 0.0001) in vemurafenib-treated patients but remained unchanged in dabrafenib-treated patients (+1.2%, P = 0.717). Differentiation of peripheral lymphocytes of vemurafenib-treated patients showed a significant decrease in CD4+ T cells (P < 0.05). Within CD4+ T cells obtained during treatment, an increase in CCR7+CD45RA+ (naïve) and a decrease in CCR7+CD45RA- (central memory) populations were found (P < 0.01 for both). Furthermore, secretion of interferon-γ and interleukin-9 by CD4+ T cells was significantly lower in samples obtained during vemurafenib treatment compared with baseline samples.
While both compounds have comparable clinical efficacy, vemurafenib but not dabrafenib decreases patients peripheral lymphocyte counts and alters CD4+ T cell phenotype and function. Thus, selective BRAFi can significantly affect patients' peripheral lymphocyte populations. Fully understanding these effects could be critical for successfully implementing combinatorial therapies of BRAFi with immunomodulatory agents.
Summary
Epidermal naevi (EN) are considered mosaic disorders. Postzygotic mutations are thought to occur during early embryogenesis. They are usually arranged along Blaschko's lines and tend to be ...noted either at birth or shortly thereafter. Skin tumours arising on EN are occasionally reported, with ongoing discussion as to whether these are collision tumours or a malignant transformation of the EN. We describe a 76‐year‐old woman with segmentally arranged seborrhoeic keratoses that showed impending atypia and, in one lesion, even overt malignant transformation. In biopsies from various lesions we found FGFR3 and PIK3CA hotspot mutations but there was no consistent pattern of mutations explaining the premalignant or malignant growth. So far it is unclear whether the precancerous changes as noted in this elderly patient can be taken as an unusual manifestation of one of the established types of EN, or whether this may represent a separate disorder that could be called ‘SASKIA naevus’. The acronym would stand for segmentally arranged seborrhoeic keratoses with impending atypia.
What's already known about this topic?
Cases of multiple congenital seborrhoeic keratoses being arranged in a segmental pattern appear to be extremely rare.
What does this study add?
In a patient with unilateral congenital seborrhoeic keratoses, multiple precanceroses and one squamous cell carcinoma originating from these lesions were documented.
FGFR3 or PIK3CA mutations were found in several lesions, but a causal relationship with premalignant and malignant growth was unlikely.
The disorder may be taken as an unusual variant of the presently known keratinocytic naevi, or it may represent a new entity with the proposed name ‘SASKIA naevus’.
Zusammenfassung
Das Plattenepithelkarzinom (PEK) der Haut ist eine der häufigsten Krebsarten der kaukasischen Population und umfasst 20 % aller Hauttumoren. Seit 2019 liegt eine S3-Leitlinie des ...deutschen Leitlinienprogramms Onkologie vor. Die Diagnose basiert auf der klinischen Untersuchung. Eine Exzision und histologische Sicherung sind bei allen klinisch verdächtigen Läsionen erforderlich, um eine prognostische Einschätzung und korrekte Behandlung zu ermöglichen. Die Therapie der ersten Wahl ist die vollständige Exzision mit histologischer Schnittrandkontrolle. Bei kutanen PEK mit Risikofaktoren wie einer Tumordicke > 6 mm kann eine Sentinellymphknotenbiopsie („sentinel lymph node biopsy“, SLNB) diskutiert werden, derzeit gibt es aber noch keine klare Evidenz bezüglich der prognostischen und therapeutischen Bedeutung. Eine adjuvante Radiatio kann bei hohem Rezidivrisiko erwogen, eine Radiatio sollte bei inoperablen Tumoren geprüft werden. Bei inoperablen lokalen bzw. lokoregionären Rezidiven kann die Indikation zur Elektrochemotherapie geprüft werden. Bei inoperablen/metastasierten PEK ist der Immuncheckpointinhibitor Cemiplimab zugelassen und die Therapie der ersten Wahl. Bei Kontraindikationen können Chemotherapeutika, Inhibitoren des EGFR („epidermal growth factor receptor“) oder eine palliative Radiatio eingesetzt werden. Da die Evidenz hier gering ist, sollte eine Systemtherapie vorzugsweise in klinischen Studien erfolgen. Die Nachsorge sollte risikoadaptiert stattfinden und schließt eine dermatologische Kontrolle, ergänzt um Ultraschalluntersuchungen bei Hochrisikopatienten, ein.
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