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Background The introduction of unclassified new psychoactive substances (NPS) on the recreational drugs market through open online sale ('legal highs' or 'Internet drugs') continues unabated and represents a growing health hazard. The use of NPS has resulted in numerous, severe, adverse events and fatalities, due to unintended overdose or unknown toxic side-effects. Objectives To try to find a possible common underlying cause for the skin-hair-eye symptoms complex observed in three men. Methods From late 2013 to mid-2014, three Swedish men aged 23-34 years with a history of recreational drug use independently presented with similar and very remarkable clinical signs, requiring extensive examination and prolonged treatment. Results Common clinical signs included hair depigmentation, hair loss, widespread folliculitis and dermatitis, painful intertriginous dermatitis, dry eyes, and elevated liver enzymes. Two of them also showed transverse white Mees' lines (leukonychia striata) on the fingernails and toenails, suggesting a temporary, drug-induced, disorganized keratinization. The clinical signs gradually disappeared over time. However, later on, two developed severe bilateral secondary cataracts requiring surgery. Because drug tests within the Swedish STRIDA project had demonstrated intake of the NPS opioid MT-45 in all patients, this was suspected to be the common causative agent. Conclusions These cases highlight the importance for physicians and health professionals to consider the increasing number of novel, untested recreational drugs, as a potential cause of unusual and otherwise unrecognized clinical signs and symptoms.

SummaryBackground Epidemiological data and the effect of sun exposure on atopic eczema (AE) suggest that vitamin D (vitD) may be involved in the pathogenesis. Objectives To investigate if vitD levels were associated with the presence or severity of AE in the first 2 years of life in children living in south-east Norway. Methods Infants, recruited to a clinical trial on acute bronchiolitis (n = 404) and from the general population (n = 240), were examined at 1–13 months (first visit) and at 2 years of age (second visit). Caregivers were interviewed using a structured questionnaire. AE was diagnosed clinically, based on well-established criteria. Disease severity was assessed using the SCORing Atopic Dermatitis index. Blood samples were taken for vitD measurements, using liquid chromatography–tandem mass spectrometry and for common filaggrin mutation analyses. Complete data on AE and vitD were available in 596 and 449 children at the first and second visit, respectively. Results Atopic eczema was diagnosed in 67 children (11%) at the first visit and in 103 children (23%) at the second. Mean vitD levels were 58·2 nmol L−1 at the first visit and 66·9 nmol L−1 at the second. Using vitD level tertiles in multivariate regression analysis, there was no association between vitD levels and AE at either visit, regardless of filaggrin mutation. In children without AE at the first visit, vitD levels did not predict AE at the second. Conclusions In this cohort of young children in Norway, we found no association between vitD levels and the presence or severity of AE.

Atopic dermatitis (AD), ichthyosis vulgaris (IV), and X-linked recessive ichthyosis (XLRI) are characterized by dry skin and impaired skin barrier. AD and IV are related to loss-of-function mutations in FLG (encoding filaggrin), whereas XLRI is caused by deletions or inactivating mutations in the steroid sulphatase gene (STS). Patients regularly use moisturizing creams, but little is known about the creams’ effects on the skin barrier.The present work combines objective scorings, non-invasive techniques, and molecular analyses of skin biopsies to characterize the skin in 57 patients with AD, IV, or XLRI, and in 14 healthy controls. Patients were classified according to their FLG and STS mutation status: AD with FLG+/+ (n = 14), AD with FLG+/– (n = 14), AD/IV with FLG–/– (n = 15), and XLRI with STS– (n = 14), as well as one man with a novel point mutation. Assessments were conducted at baseline and after four weeks of treatment with three different moisturizers applied to volar forearm skin.At baseline, dryness scoring and non-invasive assessments verified impaired skin barrier function in all patients. In patients with AD/IV, microarray analysis identified 300–3000 up- or downregulated mRNA transcripts involved in signalling pathways important for inflammation and barrier repair. The skin phenotype and number of altered transcripts were correlated with the FLG mutation status, with FLG–/– patients displaying the highest transepidermal water loss (TEWL) and the most altered transcript levels. In contrast, despite an equally dysfunctional skin barrier, only limited changes in mRNA transcripts occurred in XLRI patients. Treatment with moisturizers improved skin dryness similarly in all groups, but TEWL behaved differently: it decreased slightly in the AD/IV group and increased in the XLRI group, especially after urea treatment. Only minute effects on skin pH and mRNA expression were observed.In conclusion, FLG mutations elicit pro-inflammatory mechanisms probably aimed at restoring barrier competence. This does not occur in patients with XLRI, presumably because STS deficiency automatically increases the barrier thickness. Moisturizing treatment improves skin dryness in patients with AD, IV, or XLRI, but does not seem to normalize the altered epidermal gene expression profile in AD/IV patients.

In a commentary to our publication entitled “Acute skin and hair symptoms followed by severe, delayed eye complications in subjects using the synthetic opioid MT-45”,[1] Yip and Deng [2] argue that the lack of opioid symptoms would indicate involvement of another drug class, possibly arsenic or 2,4-dinitrophenol (DNP). In this respect, it should be emphasized that the patients did not seek hospital care for acute opioid overdose symptoms but for unexpected, late adverse side effects involving the skin, hair, and eyes. This article is protected by copyright. All rights reserved.