Methotrexate
(MTX) is one of the first-line treatments for moderate
to severe psoriasis, while the side effects caused by injection and
oral administration of MTX greatly restrict its clinical application.
Transdermal drug delivery offers a desirable alternative to the conventional
approaches, but the performances of the currently available skin penetration
enhancement techniques are not so satisfactory. To address these limitations,
we developed a dissolving microneedle (MN) patch made of hyaluronic
acid (HA) with excellent water solubility, biocompatibility, biodegradability,
and mechanical properties. The amount of MTX encapsulated in the needles
of the patch could be controlled during the fabrication process for
precise dosage. Interestingly, the MTX-loaded MNs successfully penetrated
imiquimod (IMQ)-induced thickened epidermis in mice and delivered
the drug intralesionally. Meanwhile, fast dissolution of HA endowed
the MNs with operability for patients. We found that the MTX-loaded
MNs not only showed well-maintained inhibitory effect in vitro but
also alleviated the psoriasis-like skin inflammation in mice. Moreover,
the MTX-loaded MNs were significantly more efficacious than taking
the same dose of drug orally. Consequently, a higher oral dose of
MTX was required for a comparable amelioration, which in turn increased
its systemic toxicity. Taken together, the proposed MTX-loaded dissolving
MN patch strategy provides a new opportunity for efficient and safe
treatment of psoriasis.
Summary
Background
Dermoscopy and reflectance confocal microscopy (RCM) are noninvasive techniques for the diagnosis of skin lesions. Their accuracy for amelanotic/hypomelanotic melanoma (AHM) has not been systematically studied.
Objectives
We aimed to investigate systematically the accuracy of dermoscopy and RCM and to compare the accuracy between them for diagnosing AHM.
Methods
We searched the PubMed, Web of Science, Embase and Cochrane Library databases for eligible studies about dermoscopy, RCM and AHM from inception to 31 June 2019. The quality of the studies was assessed with the Quality Assessment of Diagnostic Accuracy Studies tool. The pooled results were calculated using a random effects model in Stata 14, Meta‐DiSc, RevMan 5·3 and SAS 9·4. We also explored the sources of heterogeneity by sensitivity analysis.
Results
Seven studies with a total of 1111 lesions were included. The pooled sensitivity and specificity of dermoscopy for the diagnosis of AHM were 61% [95% confidence interval (CI) 0·37–0·81] and 90% (95% CI 0·74–0·97), respectively. The corresponding respective values of RCM for the diagnosis of AHM were 67% (95% CI 0·51–0·81) and 89% (95% CI 0·86–0·92). In three studies including the performance of both RCM and dermoscopy, the relative diagnostic odds ratio of RCM over dermoscopy was 4·69 (95% CI 0·81–27·3) (P = 0·068).
Conclusions
Our study demonstrates that both dermoscopy and RCM offer good diagnostic accuracy with high specificity and moderate sensitivity in the diagnosis of AHM. RCM is more accurate than dermoscopy in diagnosing AHM but the comparison needs to be confirmed.
What's already known about this topic?
Amelanotic/hypomelanotic melanoma (AHM) is the most lethal skin cancer. The diagnosis of AHM is a great challenge because of its nonspecific clinical manifestation. Early diagnosis can improve the prognosis. Dermoscopy and reflectance confocal microscopy (RCM) have high diagnostic accuracy for pigmented melanoma.
What does this study add?
Both dermoscopy and RCM offer good diagnostic accuracy with high specificity and moderate sensitivity for AHM. RCM might be more accurate than dermoscopy for diagnosis of AHM.
More research on the diagnostic accuracy of dermoscopy and RCM for AHM is required in support of these findings.
Linked Comment: Chi. Br J Dermatol 2020; 183:197.
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