Melanomas that have histopathologic features that overlap with those of Spitz nevus are referred to as spitzoid melanomas. However, the diagnostic concept is used inconsistently and genomic analyses ...suggest it is a heterogeneous category. Spitz tumors, the spectrum of melanocytic neoplasms extending from Spitz nevi to their malignant counterpart Spitz melanoma, are defined in the 2018 WHO classification of skin tumors by the presence of specific genetic alterations, such as kinase fusions or HRAS mutations. It is unclear what fraction of "spitzoid melanomas" defined solely by their histopathologic features belong to the category of Spitz melanoma or to other melanoma subtypes. We assembled a cohort of 25 spitzoid melanomas diagnosed at a single institution over an 8-year period and performed high-coverage DNA sequencing of 480 cancer related genes. Transcriptome wide RNA sequencing was performed for select cases. Only nine cases (36%) had genetic alterations characteristic of Spitz melanoma, including HRAS mutation or fusion involving BRAF, ALK, NTRK1, or MAP3K8. The remaining cases were divided into those with an MAPK activating mutation and those without an MAPK activating mutation. Both Spitz melanoma and spitzoid melanomas in which an MAPK-activating mutation could not be identified tended to occur in younger patients on skin with little solar elastosis, infrequently harbored TERT promoter mutations, and had a lower burden of pathogenic mutations than spitzoid melanomas with non-Spitz MAPK-activating mutations. The MAPK-activating mutations identified affected non-V600 residues of BRAF as well as NRAS, MAP2K1/2, NF1, and KIT, while BRAF V600 mutations, the most common mutations in melanomas of the WHO low-CSD category, were entirely absent. While the "spitzoid melanomas" comprising our cohort were enriched for bona fide Spitz melanomas, the majority of melanomas fell outside of the genetically defined category of Spitz melanomas, indicating that histomorphology is an unreliable predictor of Spitz lineage.
A subset of Spitz tumors harbor fusions of NTRK3 with ETV6, MYO5A, and MYH9. We evaluated a series of 22 melanocytic tumors in which an NTRK3 fusion was identified as part of the diagnostic workup. ...Tumors in which NTRK3 was fused to ETV6 occurred in younger patients were predominantly composed of epithelioid melanocytes and were classified by their histopathologic features as Spitz tumors. In contrast, those in which NTRK3 was fused to MYO5A were predominantly composed of spindled melanocytes arrayed in fascicles with neuroid features such as pseudo-Verocay bodies. To further investigate the effects of the fusion kinases ETV6-NTRK3 and MYO5A-NTRK3 in melanocytes, we expressed them in immortalized melanocytes and determined their subcellular localization by immunofluorescence. ETV6-NTRK3 was localized to the nucleus and diffusely within the cytoplasm and caused melanocytes to adopt an epithelioid cytomorphology. In contrast, MYO5A-NTRK3, appeared excluded from the nucleus of melanocytes, was localized to dendrites, and resulted in a highly dendritic cytomorphology. Our findings indicate that ETV6-NTRK3 and MYO5A-NTRK3 have distinct subcellular localizations and effects on cellular morphology.
It is well known that several psychiatric disorders may be related to childhood psychological trauma. Recent studies have associated childhood exposure to trauma to some skin diseases. Our study ...aimed at exploring whether psoriasis is related to the reported positive and negative traumatic life events in different age intervals beginning from early childhood to adulthood. Furthermore, we investigated differences between psoriatics with early and late onset according to traumatic experiences in different age intervals. Also, we investigated the possible correlation of traumatic experiences with the disease severity. One hundred patients with psoriasis and 101 controls (patients with skin conditions considered to be “non‐psychosomatic”) were enrolled in the study. All participants completed a specific questionnaire measuring traumatic life experiences (Traumatic Antecedents Questionnaire, TAQ). The TAQ assesses positive personal experiences (competence and safety) and negative personal experiences (neglect, separation, secrets, emotional, physical and sexual abuse, trauma witnessing, other traumas and exposure to alcohol/drugs) from early childhood to adulthood. The severity of psoriasis was estimated according to the Psoriasis Area and Severity Index (PASI), a standardized measuring instrument. The amount of positive experiences did not differ significantly among groups, except for safety scores that were higher in controls compared with both psoriatic groups (early and late onset). On the other side, negative traumatic experiences appeared more frequently in patients with psoriasis during all developmental periods. We found no correlation between severity of psoriasis and traumatic experiences. The present study demonstrates an increased history of childhood and adulthood negative traumatic experiences in patients with psoriasis compared to the control group. Our findings suggest a relationship between retrospectively reported negative traumatic experiences and psoriasis.
TNF-related apoptosis-inducing ligand (TRAIL) is recognized as an important regulator of immune responses during infections and various autoimmune-mediated pathologies. Its role in inflammatory ...dermatoses is largely unknown. We aimed to investigate the expression of TRAIL and its receptors DR4 and DR5 in psoriasis vulgaris. Immunohistochemistry for TRAIL, DR4 and DR5 was performed on samples of lesional (
n
= 10) and non-lesional (
n
= 10) skin of patients with plaque psoriasis and skin of healthy volunteers (
n
= 10). Expression of TRAIL and its receptors was further examined by means of double immunofluorescence staining and co-localization with CD4, CD8, CD11c, CD68, CD16 and CD56 markers. Immunohistochemical staining for TRAIL was significantly enhanced in psoriatic lesional as well as non-lesional epidermis compared to the epidermis of healthy skin. Lesional epidermis also showed increased immunoreactivity for DR5. In addition, expression of TRAIL and both of its receptors was significantly increased in the dermis of lesional skin. As evidenced by double immunofluorescence, TRAIL was readily expressed by most of the examined cells of the inflammatory infiltrate in psoriatic lesions. In contrast, the expression of DR4 was found mostly among CD4+ and CD8+ cells but was only nuclear, while DR5 showed cytoplasmic staining in rare CD16+, CD56+ and CD68+ cells. According to abundant in situ presence of TRAIL and its receptors in lesional psoriatic skin, it seems that this cytokine participates in the complex interplay between keratinocytes and cells of the dermal infiltrate and thus contributes to the inflammatory cycle in psoriasis vulgaris.
Background
Androgenetic alopecia (male pattern and female pattern hair loss) is characterized by thinning of the scalp hair. Intradermal injection of autologous platelet‐rich plasma (PRP) might have ...an effect on hair regrowth.
Aims
The aim was to evaluate efficacy and safety of platelet‐rich plasma compared to placebo or no treatment in people with pattern hair loss.
Patients/Methods
We searched the databases CENTRAL and MEDLINE on December 24, 2018 and included randomized controlled trials (RCTs). Primary outcomes were mean change of hair density from baseline and serious treatment‐related adverse events. Secondary outcome was mean change of hair thickness from baseline. Time point of outcome assessment was 6 months after start of treatment.
Results
We identified 13 relevant randomized controlled trials with 356 randomized (343 analyzed) people or half‐head areas who received PRP in a simple parallel or half‐head design. The pooled data of seven studies (171 analyzed people or half‐head areas) were favorable in the PRP group on hair density. We estimated a mean difference from baseline of 30.35 associated with a wide 95% confidence interval (1.77‐58.93), a considerable heterogeneity (I2 = 100%), and unclear risk of bias in most of the studies. Regarding hair thickness, data were also favorable in the PRP group, but these data were limited to a single study. We did not identify serious treatment‐related adverse events.
Conclusion
The results of seven RCTs indicated that autologous platelet‐rich plasma was associated with an increase of hair density when compared to placebo.
We present a 70‐year‐old female patient diagnosed with epidermal growth factor receptor‐mutated metastatic non‐small cell lung cancer (T4N2M1a), who developed afatinib‐induced toxic epidermal ...necrolysis (TEN). We have also performed a PubMed/Medline literature review to detect other possible cases of TEN/Stevens–Johnson syndrome associated with afatinib treatment and found only 5 other cases reported. To our best knowledge, this is the first case of afatinib‐induced TEN successfully treated with cyclosporine.
Background
Chronic plaque psoriasis is an immune‐mediated, chronic, inflammatory skin disease, which can impair quality of life and social interaction. Disease severity can be classified by the ...psoriasis area and severity index (PASI) score ranging from 0 to 72 points. Indoor artificial salt bath with or without artificial ultraviolet B (UVB) light is used to treat psoriasis, simulating sea bathing and sunlight exposure; however, the evidence base needs clear evaluation.
Objectives
To assess the effects of indoor (artificial) salt water baths followed by exposure to artificial UVB for treating chronic plaque psoriasis in adults.
Search methods
We searched the following databases up to June 2019: the Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We also searched five trial registers, and checked the reference lists of included studies, recent reviews, and relevant papers for further references to relevant trials.
Selection criteria
Randomised controlled trials (RCTs) of salt bath indoors followed by exposure to artificial UVB in adults who have been diagnosed with chronic plaque type psoriasis. We included studies reporting between‐participant data and within‐participant data. We evaluated two different comparisons: 1) salt bath + UVB versus other treatment without UVB; eligible comparators were exposure to psoralen bath, psoralen bath + artificial ultraviolet A UVA) light, topical treatment, systemic treatment, or placebo, and 2) salt bath + UVB versus other treatment + UVB or UVB only; eligible comparators were exposure to bath containing other compositions or concentrations + UVB or UVB only.
Data collection and analysis
We used standard methodological procedures expected by Cochrane. We used GRADE to assess the certainty of the evidence.
The primary efficacy outcome was PASI‐75, to detect people with a 75% or more reduction in PASI score from baseline. The primary adverse outcome was treatment‐related adverse events requiring withdrawal. For the dichotomous variables PASI‐75 and treatment‐related adverse events requiring withdrawal, we estimated the proportion of events among the assessed participants.
The secondary outcomes were health‐related quality of life using the Dermatology Life Quality Index, (DLQI) pruritus severity measured using a visual analogue scale, time to relapse, and secondary malignancies.
Main results
We included eight RCTs: six reported between‐participant data (2035 participants; 1908 analysed), and two reported within‐participant data (70 participants, 68 analysed; 140 limbs; 136 analysed). One study reported data for the comparison salt bath with UVB versus other treatment without UVB; and eight studies reported data for salt bath with UVB versus other treatment with UVB or UVB only. Of these eight studies, only five reported any of our pre‐specified outcomes and assessed the comparison of salt bath with UVB versus UVB only. The one included trial that assessed salt bath plus UVB versus other treatment without UVB (psoralen bath + UVA) did not report any of our primary outcomes. The mean age of the participants ranged from 41 to 50 years of age in 75% of the studies. None of the included studies reported on the predefined secondary outcomes of this review. We judged seven of the eight studies as at high risk of bias in at least one domain, most commonly performance bias. Total trial duration ranged between at least two months and up to 13 months.
In five studies, the median participant PASI score at baseline ranged from 15 to 18 and was balanced between treatment arms. Three studies did not report PASI score. Most studies were conducted in Germany; all were set in Europe. Half of the studies were multi‐centred (set in spa centres or outpatient clinics); half were set in a single centre in either an unspecified settings, a psoriasis daycare centre, or a spa centre. Commercial spa or salt companies sponsored three of eight studies, health insurance companies funded another, the association of dermatologists funded another, and three did not report on funding.
When comparing salt bath plus UVB versus UVB only, two between‐participant studies found that salt bath plus UVB may improve psoriasis when measured using PASI 75 (achieving a 75% or more reduction in PASI score from baseline) (risk ratio (RR) 1.71, 95% confidence interval (CI) 1.24 to 2.35; 278 participants; low‐certainty evidence). Assessment was conducted at the end of treatment, which was equivalent to six to eight weeks after start of treatment. The two trials which contributed data for the primary efficacy outcome were conducted by the same group, and did not blind outcome assessors. The German Spas Association funded one of the trials and the funding source was not stated for the other trial.
Two other between‐participant studies found salt bath plus UVB may make little to no difference to outcome treatment‐related adverse events requiring withdrawal compared with UVB only (RR 0.96, 95% CI 0.35 to 2.64; 404 participants; low‐certainty evidence). One of the studies reported adverse events, but did not specify the type of events; the other study reported skin irritation. One within‐participant study found similar results, with one participant reporting severe itch immediately after Dead Sea salt soak in the salt bath and UVB group and two instances of inadequate response to phototherapy and conversion to psoralen bath + UVA reported in the UVB only group (low‐certainty evidence).
Authors' conclusions
Salt bath with artificial ultraviolet B (UVB) light may improve psoriasis in people with chronic plaque psoriasis compared with UVB light treatment alone, and there may be no difference in the occurrence of treatment‐related adverse events requiring withdrawal. Both results are based on data from a limited number of studies, which provided low‐certainty evidence, so we cannot draw any clear conclusions.
The reporting of our pre‐specified outcomes was either non‐existent or limited, with a maximum of two studies reporting a given outcome.
The same group conducted the two trials which contributed data for the primary efficacy outcome, and the German Spas Association funded one of these trials. We recommend further RCTs that assess PASI‐75, with detailed reporting of the outcome and time point, as well as treatment‐related adverse events. Risk of bias was an issue; future studies should ensure blinding of outcome assessors and full reporting.
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