Concomitant psoriasis and hidradenitis suppurativa responsive to adalimumab therapy: A case series.

Psoriasis and hidradenitis suppurativa are inflammatory dermatoses that have been associated with arthritis, metabolic syndrome, obesity, and smoking. They share common pathogenic mechanisms such as elevated levels of several proinflammatory cytokines including tumor necrosis factor (TNF), interleukin-17A, and impaired Notch pathway. Thus, treatments for both diseases are sometimes overlapping. Biological therapy such as adalimumab is effective for patients with hidradenitis suppurativa and psoriasis. Adalimumab is a monoclonal antibody that binds to TNF and inhibits the cytokine interaction with the TNF receptors, thus inhibiting the inflammatory cascade. Currently, data are lacking on the treatment for co-occurrence of psoriasis and hidradenitis suppurativa. This case series describes three patients with a diagnosis of concomitant psoriasis and hidradenitis suppurativa. In these cases, after 12 weeks of treatment with adalimumab 40 mg every other week, the average Psoriasis Area Severity Index score reduced from 21.4 to 2.9 for psoriasis, Hidradenitis Suppurativa-Physician's Global Assessment from 3.3 to 0.7, and pain Visual Analog Scale for hidradenitis suppurativa from 4.6 to 2. The results suggest that adalimumab is a treatment of choice for patients with concomitant hidradenitis suppurativa and psoriasis.

Using betaxolol for the prevention of paronychia induced by epidermal growth factor receptor inhibitors: a case-control cohort study.

BACKGROUND: High rates of posttreatment discomfort, infection, recurrence, and increased time to return to work have been noted after nail plate avulsion resulting from epidermal growth factor receptor tyrosine kinase inhibitor(EGFR-TKI)-induced paronychia, which may even interrupt the course of treatment for EGFR-TKI therapy. Thus, we conducted this study to determine how effectively a topical ß-blocker, betaxolol, prevents EGFR-TKI-induced paronychia. METHODS: This case-control cohort study included a total of 131 non-small-cell lung cancer patients. The prevention group comprised 40 patients treated with topical betaxolol 0.25% solution to prevent paronychia while they received EGFR-TKI therapy. The control group comprised 91 patients who did not preventively use topical betaxolol 0.25% solution while receiving EGFR-TKI therapy. The patients' age, gender, antineoplastic regimen, duration of antineoplastic treatment before the appearance of lesions, number of involved digits (fingernails or toenails) with lesions, grading of paronychia, and pain score were recorded. RESULTS: In terms of the cumulative incidence of paronychia, significant differences (P < 0.01) were noted at both the 2nd and 3rd months after starting EGFR-TKIs. Furthermore, the average visual analogue scale scores were 3.125 and 6.29 in the prevention group and control group, respectively (P < 0.01). The average grades of paronychia were 1.5 and 2.12 in the prevention group and control group, respectively (P < 0.01). The average numbers of involved digits were 2.25 (range: 1-5 digits) in the prevention group and 3.03 (range: 1-7) in the control group (P = 0.07). CONCLUSIONS: Preventively using topical betaxolol can significantly decrease the incidence, VAS score, and grading of EGFR-TKI-induced paronychia.

Treatment of epidermal growth factor receptor inhibitor-induced severe paronychia with pyogenic granuloma-like lesions with topical betaxolol: an open-label observation study.

BACKGROUND: Paronychia is a common adverse event caused by epidermal growth factor receptor (EGFR) inhibitors. However, high rates of post-treatment discomfort, infection, recurrence, and increased time to return to work have been noted after nail plate avulsion for EGFR inhibitor-induced paronychia. Furthermore, poor wound healing and malnutrition were common conditions found in cancer patients. The aim of this study is to find an effective, pain-relieving, and noninvasive treatment for patients with severe paronychia induced by EGFR inhibitors. METHODS: Data from a series of 35 non-small cell lung cancer cases suffering from EGFR inhibitor-induced paronychia with pyogenic granuloma-like lesions of digits treated with betaxolol 0.25% ophthalmic solution once daily were collected and analyzed. RESULTS: Of the 35 patients suffering from grade 2 or 3 paronychia with pyogenic granuloma-like lesions induced by EGFR inhibitors, 34 (97.1%) demonstrated complete resolution and only one (2.9%) had partial resolution after 12 weeks of topical betaxolol treatment. The grading of paronychia according to the Common Terminology Criteria for Adverse Events decreased from an average of 2.29 to 0.63 after 4 weeks of treatment (P = 5.55 × 10-16 ). All the patients had significant improvement (50% pain reduction), as their pain visual analogue scale scores decreased from an average of 7.06 to 2.26 after one week of treatment (P = 6.11 × 10-25 ). CONCLUSION: Betaxolol 0.25% ophthalmic solution is an effective, safe, and pain-relieving treatment for patients suffering from EGFR inhibitor-induced paronychia with pyogenic granuloma-like lesions and deep fissures.

Massively parallel sequencing and genome-wide copy number analysis revealed a clonal relationship in benign metastasizing leiomyoma.

Benign metastasizing leiomyoma (BML) is a rare disease entity typically presenting as multiple extrauterine leiomyomas associated with a uterine leiomyoma. It has been hypothesized that the extrauterine leiomyomata represent distant metastasis of the uterine leiomyoma. To date, the only molecular evidence supporting this hypothesis was derived from clonality analyses based on X-chromosome inactivation assays. Here, we sought to address this issue by examining paired specimens of synchronous pulmonary and uterine leiomyomata from three patients using targeted massively parallel sequencing and molecular inversion probe array analysis for detecting somatic mutations and copy number aberrations. We detected identical non-hot-spot somatic mutations and similar patterns of copy number aberrations (CNAs) in paired pulmonary and uterine leiomyomata from two patients, indicating the clonal relationship between pulmonary and uterine leiomyomata. In addition to loss of chromosome 22q found in the literature, we identified additional recurrent CNAs including losses of chromosome 3q and 11q. In conclusion, our findings of the clonal relationship between synchronous pulmonary and uterine leiomyomas support the hypothesis that BML represents a condition wherein a uterine leiomyoma disseminates to distant extrauterine locations.

Successful treatment of a newborn with congenital hyperinsulinism having a novel heterozygous mutation in the ABCC8 gene using subtotal pancreatectomy.

Congenital hyperinsulinism (CHI) is the most common cause of persistent hypoglycemia in newborns and infants. CHI is characterized by unregulated secretion of insulin from pancreatic ß: cells. Here, we reported the case of a large-for-gestational-age, full-term newborn that suffered from CHI and developed severe and persistent hypoglycemia at an early stage of life. The infant was nearly unresponsive to medical treatment, which included continuous intravenous glucagon infusion, oral diazoxide, and nifedipine. After medical treatment had failed, an 18-fluoro L-3,4-dihydroxyphenylalanine positron emission tomography scan of the patient showed a focal lesion at the neck of the pancreas. The patient received subtotal pancreatectomy, and shortly after the procedure, the patient's blood sugar returned to the normal range. The patient was confirmed to have a novel heterozygous mutation at position c.2475+1G>A of the ABCC8 gene. This is the first report of a focal form of CHI in a patient in Taiwan, which had preoperatively been confirmed using 18-fluoro L-3,4-dihydroxyphenylalanine positron emission tomography.

Design, synthesis, and anticancer activity of phosphonic acid diphosphate derivative of adenine-containing butenolide and its water-soluble derivatives of paclitaxel with high antitumor activity.

Synthesis of adenine derivative of triphosphono-gamma-(Z)-ethylidene-2,3-dimethoxybutenolide 4 was accomplished by treatment of phosphonate 3 with 5-phosphoribosyl 1-pyrophosphate in the presence of 5-phosphoribosyl 1-pyrophosphate synthetase. It was found that triphosphonate 4 functions as an irreversible stoichiometric inactivator of the Escherichia coli ribonucleoside diphosphate reductase (RDPR). Triphosphonate 4 exhibited potent inhibitory activity against murine leukemias (L1210 and P388), breast carcinoma (MCF7), and human T-lymphoblasts (Molt4/C8 and CEM/0) cell lines. Paclitaxel ester derivatives of adenine-containing triphosphono-gamma-(Z)-ethylidene-2,3-dimethoxybutenolide 8-10 were also synthesized. Like triphosphonate 4, compound 8 exhibited inhibitory property toward RDPR. It also induced microtubule assembly similar to paclitaxel (5). The structure of the chlorodiester linker in 8 was found to account for this dual property. After treatment of MCF7 cells with compounds 4, 5, and 8, fluorescence microscope examination demonstrated the presence of nucleus shrinkage or segmentation. Bifunctional prodrug 8 exhibited higher lipophilicity than 4 and higher water-solubility than 5. Pro-dual-drug 8 exhibited more pronounced anticancer activity relative to that of the triphosphonate 4 and paclitaxel (5). In contrast, compound 9, resulting from the linkage of triphosphonate 4 and paclitaxel (5) through a diester unit, was only found to function as a highly water-soluble prodrug for paclitaxel (5). It induced microtubule assembly in vitro, but did not show inhibitory property toward RDPR. On the other hand, compound 10, an aggregate of triphosphonate 4 and paclitaxel (5), neither functioned as an inhibitor of RDPR nor exhibited microtubule assembly stimulating activity in vitro.