Efficacy of anifrolumab in long-term intractable alopecia due to discoid lupus erythematosus.

Alopecia associated with lupus erythematosus is broadly classified into reversible nonscarring alopecia seen in the acute phase, such as worsening of systemic lupus erythematosus (SLE) and cicatricial alopecia seen in chronic cutaneous lupus erythematosus represented by discoid lupus erythematosus (DLE). In DLE-induced alopecia, early therapeutic intervention before developing scarring alopecia is important, but the condition is often resistant to conventional treatment. Anifrolumab (ANI), a novel therapeutic agent for SLE that inhibits Type I interferon activity, has been shown to be effective against acute skin lesions, including alopecia, in patients with SLE. However, there are very few reports on the effect of ANI on alopecia due to DLE. We report on a 27-year-old Japanese woman with SLE whose alopecia due to chronic DLE was refractory to topical therapy and systemic therapy with oral glucocorticoid, multiple immunosuppressants, and belimumab for ∼8 years after onset and whose alopecia improved with ANI. ANI can be considered to be an effective treatment option in lupus patients presenting with alopecia due to DLE, even in the chronic refractory stage.

Correlations Between Serum Cytokine Levels and the Use of a Moisturizer in Elderly Women in Accordance with the Improvement of Objective and Subjective Skin Condition.

Purpose: In the skin of elderly people with dryness, the production of inflammatory cytokines tends to be induced under the influence of external stimuli. Therefore, there has been a hypothesis that the deterioration of skin conditions due to aging is linked to systemic inflammation. This study aimed to verify the possibility that the use of moisturizer improves skin condition and suppresses systemic inflammation. Methods: As an open study, the participants (n=75) were randomly assigned to either control group or moisturizer group. Participants in the moisturizer group used a moisturizer called Grafa Moisture Keep Milk MC at least twice a day for four weeks on the entire body below the neck. Objective skin conditions (overall dry skin score, water content of the stratum corneum, and transepidermal water loss) and serum cytokine levels (IL-1α, IL-1ß, IL-4, IL-5, IL-6, IL-8, and TNF-α) were evaluated before and after the study in both groups. Subjective skin condition (questionnaire evaluation) was also assessed in the moisturizer group after the study. Results: Serum IL-6 level was significantly reduced in the moisturizer group (n=16) compared with the control group (n=36). In addition, there was an inverse correlation between serum IL-5 and the subjective moisturizing effect in the questionnaire evaluation, suggesting that the moisturizer improved subjective symptoms of dryness by reducing IL-5 levels. Furthermore, there was a positive correlation between IL-5 and IL-6, indicating that they are regulated by common upstream factors. A significant positive correlation of transepidermal water loss with serum IL-4 levels was also detected. Conclusion: The application of the moisturizer to the entire body not only improved subjective and objective skin condition, it may also reduce the levels of circulating inflammatory cytokines. Umin Clinical Trials Registry: Registration number: UMIN 000052024.

GWAS for systemic sclerosis identifies six novel susceptibility loci including one in the Fcγ receptor region.

Here we report the largest Asian genome-wide association study (GWAS) for systemic sclerosis performed to date, based on data from Japanese subjects and comprising of 1428 cases and 112,599 controls. The lead SNP is in the FCGR/FCRL region, which shows a penetrating association in the Asian population, while a complete linkage disequilibrium SNP, rs10917688, is found in a cis-regulatory element for IRF8. IRF8 is also a significant locus in European GWAS for systemic sclerosis, but rs10917688 only shows an association in the presence of the risk allele of IRF8 in the Japanese population. Further analysis shows that rs10917688 is marked with H3K4me1 in primary B cells. A meta-analysis with a European GWAS detects 30 additional significant loci. Polygenic risk scores constructed with the effect sizes of the meta-analysis suggest the potential portability of genetic associations beyond populations. Prioritizing the top 5% of SNPs of IRF8 binding sites in B cells improves the fitting of the polygenic risk scores, underscoring the roles of B cells and IRF8 in the development of systemic sclerosis. The results also suggest that systemic sclerosis shares a common genetic architecture across populations.

Exome sequence analysis of Kaposiform hemangioendothelioma: identification of putative driver mutations

Abstract BACKGROUND: Kaposiform hemangioendothelioma is a rare, intermediate, malignant tumor. The tumor's etiology remains unknown and there are no specific treatments. OBJECTIVE: In this study, we performed exome sequencing using DNA from a Kaposiform hemangioendothelioma patient, and found putative candidates for the responsible mutations. METHOD: The genomic DNA for exome sequencing was obtained from the tumor tissue and matched normal tissue from the same individual. Exome sequencing was performed on HiSeq2000 sequencer platform. RESULTS: Among oncogenes, germline missense single nucleotide variants were observed in the TP53 and APC genes in both the tumor and normal tissue. As tumor-specific somatic mutations, we identified 81 candidate genes, including 4 nonsense changes, 68 missense changes and 9 insertions/deletions. The mutations in ITGB2, IL-32 and DIDO1 were included in them. CONCLUSION: This is a pilot study, and future analysis with more patients is needed to clarify: the detailed pathogenesis of this tumor, the novel diagnostic methods by detecting specific mutations, and the new therapeutic strategies targeting the mutation.