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Prurigo pigmentosa (PP), a rare inflammatory disease of the skin, is mostly reported in the ethnic Japanese population. Its pathogenesis remains unclear. The chronic and recurrent nature of PP implies a possible role of viral infection in the pathogenesis. The anti-inflammatory mechanism of doxycycline, which is well documented as a good treatment for PP, is related to the suppression of interleukin expression. We identified and retrospectively analyzed 16 biopsy-proven and criteria-matched patients over a seven year period at a single medical center. DNA extracted from formalin-fixed, paraffin-embedded specimens was analyzed for herpes simplex virus-1 (HSV-1), HSV-2, and human herpes virus-6 (HHV-6) DNA by polymerase chain reaction. Immunohistochemistry was performed to determine the interleukin-6 (IL-6) and interleukin-8 (IL-8) expression in PP skin lesions. Clinicopathological findings in the ethnic Chinese population are similar to those reported in Japanese studies. All patients had a good response to doxycycline treatment, with a mean duration of use of 2.4 weeks. However, recurrence was noted in six patients. HSV-1, HSV-2, and HHV-6 DNA in PP skin lesions were negative. Immunohistochemistry showed IL-6 ( P = 0.035) to be more strongly expressed in PP skin lesions. There was no statistical significance of elevated IL-8 expression in PP ( P = 0.123). Prurigo pigmentosa is not uncommon in the ethnic Chinese population. There was no evidence of herpes virus DNA in PP skin lesions. Increased expression of IL-6 in PP skin lesions may explain the effects of doxycycline in terms of its anti-inflammatory properties. [ABSTRACT FROM AUTHOR]

Leukemic transformation often requires activation of protein kinase B (PKB/c-Akt) and is characterized by increased proliferation, decreased apoptosis, and a differentiation block. PKB phosphorylates and inactivates members of the FOXO subfamily of Forkhead transcription factors. It has been suggested that hyperactivation of PKB maintains the leukemic phenotype through actively repressing FOXO-mediated regulation of specific genes. We have found expression of the transcriptional repressor Id1 (inhibitor of DNA binding 1) to be abrogated by FOXO3a activation. Inhibition of PKB activation or growth factor deprivation also resulted in strong down-regulation of Id1 promoter activity, Id1 mRNA, and protein expression. Id1 is highly expressed in Bcr-Abl-transformed K562 cells, correlating with high PKB activation and FOXO3a phosphorylation. Inhibition of Bcr-Abl by the chemical inhibitor ST1571 resulted in activation of FOXO3a and down-regulation of Id1 expression. By performing chromatin immunoprecipitation assays and promoter-mutation analysis, we demonstrate that FOXO3a acts as a transcriptional repressor by directly binding to the Id1 promoter. ST1571 treatment, or expression of constitutively active FOXO3a, resulted in erythroid differentiation of K562 cells, which was inhibited by ectopic expression of Id1. Taken together our data strongly suggest that high expression of Id1, through PKB-mediated inhibition of FOXO3a, is critical for maintenance of the leukemic phenotype. [ABSTRACT FROM AUTHOR]

Background: Erythema multiforme major (EMM) is an immune-mediated mucocutaneous eruption mostly triggered by herpes simplex virus (HSV) infection. A vicious circle of recurrence may be developed due to HSV reactivation and prolonged use of systemic corticosteroids to control EMM. Levamisole is an immunomodulator and has been applied to prevent relapses of recurrent HSV infection., Objective: To evaluate the clinical efficacy and safety of levamisole in patients with recalcitrant recurrent EMM., Methods: We enrolled 23 patients with recurrent EMM treated with levamisole and 24 controls, and analyzed the demographics, treatments and outcomes., Results: Patients with recurrent EMM for years (mean 3.99 ± 2.71) showed significantly reduced recurrences after various durations of levamisole treatment (recurrences after and before treatment: 3.98 ± 1.04 vs 6.75 ± 1.45 times per year, p = 1.33x10 -8 ). The recurrences of EMM also significantly reduced after levamisole treatment comparing to that of patients without levamisole treatment (p = 3.77x10 -9 ). No patient was reported to have severe side effects during or after levamisole treatment., Conclusions: Levamisole was effective in reducing recurrences of recalcitrant recurrent EMM and can thus be considered an alternative or add-on therapy for this disorder., (Copyright © 2018 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.)