Palmoplantar keratoderma punctata type 1 (PPKP1, MIM 148600), also known as the Buschke-Fischer-Brauer type, is a hereditary disorder of keratinization, characterized by multiple hyperkeratotic papules with central indentation irregularly distributed on the palms and soles. The lesions gradually progress in size and number with age and can be painful during ambulation. Although it is considered as a rare entity, mild presentations are probably underdiagnosed and the real number of affected individuals is underestimated. This article is protected by copyright. All rights reserved.

Two female patients aged 45 and 51 years experienced curling of hair during treatment with alitretinoin (Toctino®). For one patient, the indication for use was severe chronic hand eczema, but for the second patient the indication was not reported. After 5 and 9 months, respectively, the patients developed hair texture changes and their straight hair began to curl. The dose of alitretinoin was reduced in both cases, but the patients' hair had not straightened at the time of reporting (9 months and 2 years after onset of the event). Based on the described reports received by the Netherlands Pharmacovigilance Centre Lareb, the case reports in the literature, and the possible mechanisms, we suggest a causal relationship between curling of the hair and the use of alitretinoin. Using the World Health Organization Uppsala Monitoring Centre (WHO-UMC) system for standardized case causality assessment, the association in our cases can be assessed as likely.

IgA pemphigus is an exceedingly rare autoimmune blistering disorder, caused by IgA autoantibodies against desmosomal proteins. No treatment option has been found to be universally effective. The disease is often recalcitrant to oral steroids and immunosuppressants. Here, we describe the use of systemic retinoids for the treatment of recalcitrant IgA pemphigus in 3 cases. Although the use of acitretin has been reported before, we present for the first time the positive effects of alitretinoin in treatment of 2 patients with IgA pemphigus. Besides hyperlipoproteinaemia requiring use of hypolipidemic agents in one case, alitretinoin was well-tolerated and has generally a more favorable side effect spectrum than immunosuppressants.

Chronic hand dermatitis is a debilitating inflammatory dermatosis that has a significant impact on the quality of life of those affected. Alitretinoin is an oral retinoid which has proven efficacy and safety in the treatment of chronic hand dermatitis through randomized controlled trials. Real-world evidence, information gathered in the clinic or community setting, as opposed to a research environment, can complement knowledge gained from clinical trials. Herein, real-world evidence supporting the safety and effectiveness of alitretinoin in the management of chronic hand dermatitis will be reviewed.

Systemic treatment with alitretinoin is registered for all clinical types of severe chronic hand eczema. However, it is especially effective in the hyperkeratotic subtype and less effective in non-hyperkeratotic forms. Cyclosporine A (cyclosporine) is prescribed for hand eczema in daily practice as well. It has shown to be particularly effective in patients with vesicular hand eczema. The primary objective of this study is to compare efficacy of alitretinoin and cyclosporine in the treatment of severe recurrent vesicular hand eczema.

Deciphering the molecular networks that discriminate organ-confined breast cancer from metastatic breast cancer may lead to the identification of critical biomarkers for breast cancer invasion and aggressiveness. Here metabolomics, a global study of metabolites, has been applied to explore the metabolic alterations that characterize breast cancer progression. We profiled a total of 693 metabolites across 87 serum samples related to breast cancer (46 clinically localized and 41 metastatic breast cancer) and 49 normal samples. These unbiased metabolomic profiles were able to distinguish normal individuals, clinically localized and metastatic breast cancer patients. 9-cis-Retinoic acid, an isomer of all-trans retinoic acid, was identified as a differential metabolite that significantly decreased during breast cancer progression to metastasis, and its levels were also reduced in urine samples from biopsy-positive breast cancer patients relative to biopsy-negative individuals and in invasive breast cancer cells relative to benign MCF-10A cells. The addition of exogenous 9-cis-retinoic acid to MDA-MB-231 cells and knockdown of aldehyde dehydrogenase 1 family member A1, a regulatory enzyme for 9-cis-retinoic acid, remarkably impaired cell invasion and migration, presumably through preventing the key regulator cofilin from activation and inhibiting MMP2 and MMP9 expression. Taken together, our study showed the potential inhibitory role for 9-cis-retinoic acid in breast cancer progression by attenuating cell invasion and migration.

Alitretinoin is a new oral retinoid authorized for use in grownups that have severe chronic hand eczema (CHE). A comprehensive search to solicit all studies of alitretinoin for the treatment of CHE. A comprehensive search to solicit all studies of alitretinoin for the treatment of CHE including randomized controlled trials (RCTs) or uncontrolled trials, re-treatment studies, open-label studies, or observational studies, along with case series of 10 or more participants. Physician global assessment (PGA), patient global assessment (PaGA) and modified total lesion symptom score (mTLSS) are the methods and outcomes criteria. Generated effect size and 95% confidence intervals were calculated for the outcomes. Heterogeneity and publication bias were also tested for all selected trials. When a noteworthy Q statistic (P< 0.1) demonstrates the heterogeneity crosswise over studies, an arbitrary impact model is used. On the other hand, a settled effect model is when heterogeneity is not shown. The initial search yielded 408 records of which 15 articles were selected. The 15 clinical trials included 3734 patients with CHE. Among alitretinoin-treated patients, the PGA effect size was directly proportional to the drug dosage, ranging from 40% to 69%, while the PaGA score ranged from 28.8% to 62.4%, and mTLSS ranged from 60.4% to 76.9%, much higher than placebo. A higher drug dose was about twice as effective as lower dose. The odds ratio for a better outcome with drug treatment taking duration into account was about 3-4 times that versus placebo. In conclusions, alitretinoin cleared lesions in about 50% of cases, particularly using a higher dose for a longer duration.