What's already known about this topic?

• Antihistamines represent the first-line therapy for chronic spontaneous urticaria (CSU).
• In spite of their efficacy, CSU remains uncontrolled in a high percentage of patients receiving regular doses of antihistamines.
• Guidelines for the management of CSU recommend updosing antihistamines up to fourfold as a second-line therapy.

What does this study add?

• This is the first meta-analysis on updosing antihistamines for the treatment of CSU.
• In spite of the high recommendation, updosing antihistamines significantly improves control of pruritus but not weal number.
• There is a great need for large well-performed studies on this subject as the present studies that support updosing are relatively weak and have a high level of heterogeneity.

Linked Comment: Weller and Maurer. Br J Dermatol 2016; 175:1134–1135.

What's already known about this topic?

• Antiepidermal growth factor receptor drugs are used for cancer therapy.

• They are associated with prevention of skin rash and may be useful to decrease the severity of toxicity. Oral antibiotics are sometimes suggested as preventive measures.

What does this study add?

• We have reviewed all published trials about antibiotic prophylaxis.

• We confirm that tetracyclines are able to reduce the incidence of skin rash by 50%.

Linked Comment: van Doorn and van Zuuren. Br J Dermatol 2016; 175:1135–1136.

What's already known about this topic?

• Patients on chronic haemodialysis have a higher incidence of cancers, particularly those of the kidney, urinary tract and thyroid.

What does this study add?

• Patients on chronic haemodialysis carry a higher risk for nonmelanoma skin cancer (NMSC).
• Uraemic pruritus with long-term antihistamine treatment further increases the risk of NMSC.
• Ultraviolet B phototherapy might reduce the cutaneous inflammatory status of uraemic pruritus, thereby diminishing the risk of NMSC.

Linked Comment: Yanik. Br J Dermatol 2016; 175:1136–1137.

Plain language summary available online

What's already known about this topic?

• Studies in both Canada and Taiwan have recently reported a small but significantly increased risk of herpes zoster (HZ) in patients receiving statin treatment.
• As statins are one of the most widely prescribed drugs in the U.K., with around 45 million prescriptions every year, any adverse effects will have substantial public health implications.

What does this study add?

• In this large matched case–control study, statin exposure was associated with a modest increase in the risk of HZ.
• A dose–response relationship was observed, and there was an attenuation of the increased risk over time among people who stopped statin therapy, indicating that the increased risk is consistent with a causal effect.
• There may be extra motivation to maximize HZ vaccine uptake among eligible patients receiving a statin.

Linked Comment: Shalom and Cohen. Br J Dermatol 2016; 175:1137–1138.

What's already known about this topic?

• LL-37, an antimicrobial peptide, has been shown to be upregulated in systemic sclerosis dermal fibroblasts.
• LL-37 potentially contributes to dermal fibrosis through its antiapoptotic effect on those cells.

What does this study add?

• LL-37 potentially contributes to the development of skin sclerosis, interstitial lung disease and digital ulcers in systemic sclerosis.
• This further supports the critical role of antimicrobial peptides in the development of autoimmune and inflammatory diseases.

What is the translational message?

• LL-37 induction due to Fli1 deficiency in endothelial cells supports the notion that Fli1 deficiency is a key predisposing factor in the pathogenesis of systemic sclerosis.
• This has recently been demonstrated by the establishment of a new systemic sclerosis animal model, with mice double heterozygous for the Klf5 and Fli1 genes.

What's already known about this topic?

• Epidermodysplasia verruciformis (EV) is an unusual genodermatosis characterized by an increased susceptibility to β-human papillomavirus and is associated with a high risk of skin carcinoma.
• Inactivating mutations in EVER1/EVER2 account for most cases of EV.

What does this study add?

• Our study suggests an association between a novel splicing mutation in LCK and EV susceptibility.

What is the translational message?

• Patients with EV should be tested for T lymphocyte-specific protein tyrosine kinase deficiency and T-cell function, which will help guide treatment.

Linked Comment: Uitto and Vahidnezhad. Br J Dermatol 2016; 175:1138–1139.

What's already known about this topic?

• CXCR4 expression is associated with poor prognostic indicators including tumour ulceration, thickness and metastasis.
• Expression of CXCR4 is crucial in regulating melanoma chemotaxis to distant secondary sites of metastasis with high expression of the ligand, CXCL12.
• Previous studies suggest a lack of correlation between melanoma CXCL12 expression and disease progression or BRAF mutational status.
• CXCR7 is an atypical/decoy CXCL12 receptor that may act to shape CXCL12 gradients.

What does this study add?

• Elevated CXCR4 expression is a prognostic biomarker for AJCC stage II primary melanomas.
• Autocrine melanoma CXCR4–CXCL12 signalling promotes hyperactivation of prosurvival MAPK signalling.
• CXCL12 expression by stromal cells in the primary melanoma microenvironment protects from metastasis potentially by retaining tumour cells within the cutaneous microenvironment.
• Downregulation of melanoma CXCL12 is associated with an aggressive BRAF/NRAS mutant phenotype.
• CXCR7 expression by cutaneous vascular endothelium and not primary melanomas suggests a mechanism mediating tumour intravasation.

What is the translational message?

• CXCR4 expression defines a potential candidate biomarker for melanoma providing additional prognostic information to AJCC disease staging and a means of identifying high-risk patient subgroups.
• The reported role of CXCR4–CXCR7–CXCL12 chemokine signalling within the primary cutaneous melanoma microenvironment highlights the potential for targeting this chemokine axis to prevent the development of metastatic disease.

Linked Comment: Spender and Inman. Br J Dermatol 2016; 175:1140–1141.

Plain language summary available online

What's already known about this topic?

• BRAF targeting in BRAF-mutated melanomas fails to achieve a sustained therapeutic response.
• Previous work has shown this to be partially associated with its inability to downregulate c-Jun expression and activity.
• c-Jun N-terminal Kinase (JNK) signalling positively regulates c-Jun and its transcriptional target cyclin D1.

What does this study add?

• The current work demonstrates the requirement of JNK signalling in melanoma cell proliferation and survival.
• JNK blockade, while successfully suppressing c-Jun expression/activity, fails to mitigate cyclin D1 levels.
• MEK inhibition, although failing to suppress c-Jun expression/activity, successfully downregulated cyclin D1 levels.
• This forms a further mechanistic basis for evaluating dual JNK/MEK–ERK signalling inhibition in BRAF-mutated melanomas.

What is the translational message?

• MAPK (MEK–ERK) and JNK signalling pathway inhibition, paradoxically, fails to suppress c-Jun and cyclin D1, respectively.
• Suppression of c-Jun and cyclin D1 upon JNK and MEK–ERK pathway inhibition, respectively, seems intact in melanoma cells.
• Together these observations purport concomitant MEK–ERK and JNK signalling pathway blockade as a potential therapeutic strategy in human melanoma.

Linked Comment: Haass. Br J Dermatol 2016; 175:1139–1140.

What's already known about this topic?

• Oculocutaneous albinism (OCA) is a group of autosomal recessive disorders resulting from congenital hypopigmentation of ocular and cutaneous tissues.
• Defects in the tyrosinase gene (TYR) are a major cause of OCA in many countries. Incidentally, OCA is a major cause of childhood blindness in India.
• Limited experimental evidence suggests that retention of TYR in the endoplasmic reticulum (ER) is responsible for OCA1 pathogenesis.

What does this study add?

• This study reveals that ER retention of tyrosinase variant proteins is the principal cause of loss of enzyme activity.
• The study clearly demonstrates that a functional assay of suspect TYR variants is essential to correlate genotype to phenotype in patients with OCA.
• TYR single-nucleotide polymorphisms listed in dbSNP, specifically with low or no recorded frequency, could potentially be mutant alleles identified in phenotypically normal heterozygous individuals.

What is the translational message?

• Using OCA1 as a model disease, it is proposed that identification of rare or unique genetic variants in the causal gene of an inherited disease must be complemented with functional studies to implicate the suspect variants with the disease unequivocally.
• For genetic diseases, correct determination of causal mutations has far-reaching implications for genetic counselling and/or prenatal diagnosis, as appropriate.

What's already known about this topic?

• Severe hand eczema is a frequent skin disease and creates a significant socioeconomic burden.
• Alitretinoin has been shown to be effective in treating chronic hand eczema (CHE).
• Retinoids modulate the proliferation and differentiation of keratinocytes.

What does this study add?

• Systemic alitretinoin treatment results in normalization of a disrupted skin barrier gene and protein expression.
• The expression levels of several barrier genes correlate significantly with the clinical severity in hand eczema.
• Thymic stromal lymphopoietin expression is increased in CHE and correlates negatively with filaggrin expression.

What is the translational message?

• Systemic alitretinoin treatment normalizes barrier gene and protein expression in CHE.

Plain language summary available online

What's already known about this topic?

• Chemokines play important roles in the pathogenesis of Kaposi sarcoma (KS).
• Recent studies have independently implicated CXCL12, CXCR4 and CXCR7 in KS pathophysiology.

What does this study add?

• We observed a simultaneous CXCL12/CXCR4–CXCR7 upregulation in AIDS-associated KS and classic KS lesions that correlates with both the lesion severity and detection of latency-associated nuclear antigen, Ki67 and vascular endothelial growth factor.
• The detection of the CXCL12/CXCR4–CXCR7 trio could be used as a tissue biomarker for KS lesions.

What is the translational message?

• The CXCL12 axis has been shown to be involved in chronic skin inflammation and inflammatory angiogenesis; two components of KS pathogenesis.
• Histological detection of the CXCL12 axis could allow KS classification, patient stratification or KS progression prediction.
• Targeting the CXCL12 signalling axis might serve as a novel therapeutic strategy for KS.

Linked Comment: Spender and Inman. Br J Dermatol 2016; 175:1140–1141.

What's already known about this topic?

• Psoriasis is characterized by extensive new blood vessel formation.
• Early microvascular modifications in the psoriatic lesion have received limited attention in psoriasis pathogenesis.

What does this study add?

• Psoriasin expression is promoted by reactive oxygen species (ROS) and hypoxia in keratinocytes. It regulates the ROS-induced expression of several psoriasis-associated angiogenic factors, and acts on dermal endothelial cells to promote key features of the angiogenic process.

What is the translational message?

• Our data raise the possibility that psoriasin may be evaluated as a novel antiangiogenic target in psoriasis.

Linked Comment: Mishra et al. Br J Dermatol 2016; 175:1141–1142.

What's already known about this topic?

• Clinical patterns of nonimmediate cutaneous adverse drug reactions are well characterized, namely drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens–Johnson syndrome/toxic epidermal necrolysis, acute generalized exanthematous pustulosis and maculopapular exanthema (MPE).
• Occasional overlapping clinical patterns have been described.

What does this study add?

• We characterized an overlapping pattern between MPE and DRESS, with exanthema and less systemic involvement than DRESS.
• Culprit drugs and affected organs were similar but with a reduced latency period and duration of the reaction, suggesting a minor form of DRESS.

Linked Comment: Ortonne. Br J Dermatol 2016; 175:1142–1144.

What's already known about this topic?

• Optical coherence tomography (OCT) can be used for diagnosis and depth measurement of basal cell carcinoma (BCC).
• OCT features of subtypes of basal cell carcinoma have been described.

What does this study add?

• The clinical diagnostic accuracy of sBCC can be increased by the use of OCT.
• The depth of thin BCCs < 0·4 mm can be measured accurately using OCT.
• There is good interobserver agreement for sBCC diagnosis by OCT when performed by experienced operators.
• More research is necessary before it would be appropriate to recommend its use as a substitute for pathology in diagnosis and management.

Linked Comment: Ulrich. Br J Dermatol 2016; 175:1145–1146.

What's already known about this topic?

• Cancer Councils recommend that patients conduct regular skin self-examinations for the early detection of melanoma.
• Patient-initiated, self-performed mobile teledermoscopy may aid consumers in this process.

What does this study add?

• Older adults at high risk of melanoma are highly accepting of mobile teledermoscopy. However, complete trust in the telediagnosis was a concern among some participants.
• Most participants found mobile teledermoscopy easy to conduct.

Linked Comment: Rossi and Marghoob. Br J Dermatol 2016; 175:1146.

Plain language summary available online

What's already known about this topic?

• Repeated low-level exposures to simulated U.K. sunlight can produce vitamin D sufficiency in light-skinned people, but the concurrent impact on cutaneous DNA damage is unknown.

What does this study add?

• Low-level simulated sunlight exposures in people of skin phototype II conferred vitamin D sufficiency concurrently with DNA damage, which showed partial clearance at 24 h and no evidence of accumulated damage after 6 weeks of exposures.
• The same exposures produced minimal DNA damage but less vitamin D in brown-skinned people (phototype V).
• The findings are informative for sun-exposure guidance.

Plain language summary available online

What's already known about this topic?

• Dermoscopy is a well-established tool for the noninvasive diagnosis of skin diseases.
• The benefits of dermoscopy depend on correct use by trained physicians.
• Although considered to be widely used in Europe, reports on dermoscopy use by dermatologists have been carried out in only two European countries so far.

What does this study add?

• Our study is the first pan-European survey of dermatologists regarding the patterns of use, training and attitudes towards dermoscopy.
• We report on the demographic, practice- and training-related factors driving or hampering the use of dermoscopy in the daily practice of dermatologists in 32 European countries.

Linked Comment: Soura et al. Br J Dermatol 2016; 175:1150–1151.

Linked Comment: Roh. Br J Dermatol 2016; 175:1151–1152.