Severe subcutaneous hematoma in a patient with psoriatic arthritis: Changes of platelet count in psoriatic patients with biologic agents.

The effectiveness of biologics has changed therapeutic strategies for psoriasis dramatically, but biologics are known to have various adverse effects. We report a 63-year-old woman with psoriatic arthritis who suddenly developed a subcutaneous hematoma after being successfully treated with adalimumab. As she had also suffered from alcoholic cirrhosis, we speculated that she had developed thrombocytopenia severe enough to cause a subcutaneous hematoma. Furthermore, we investigated the changes of platelet counts in 65 psoriatic patients treated with biologics at a single institute from 2010 to 2016. Platelet counts were found to have decreased by 17.4 ± 2.8% during adalimumab therapy (n = 16), 18.5 ± 3.8% during infliximab therapy (n = 17), 14.8 ± 2.1% during ustekinumab therapy (n = 20) and 18.5 ± 5.1% during secukinumab therapy (n = 12). Platelet counts decrease after the administration of biologics in accordance with disease activity, and there is the potential risk of subcutaneous hematoma and other adverse effects. When administrating biologics to psoriatic patients, especially to those with chronic liver disease, dermatologists should carefully monitor for thrombocytopenia.

Carboplatin plus Weekly Paclitaxel Combined with Bevacizumab as First-line Treatment for Non-small Cell Lung Cancer.

AIM: We aimed to evaluate the efficacy and safety of carboplatin plus weekly paclitaxel with bevacizumab in patients with advanced non-squamous non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with stage IIIB/IV or postoperative recurrent NSCLC (n=33) were treated with carboplatin (area under the curve of 6) on day 1; paclitaxel (80 mg/m2) on days 1, 8, and 15; and bevacizumab (15 mg/kg) on day 1 repeated every 4 weeks, for four to six cycles; followed by maintenance bevacizumab (15 mg/kg) every 3 weeks. RESULTS: The overall response rate was 76%. The median progression-free survival and overall survival were 8.4 months and 22.2 months, respectively. Grade 3-4 toxicities included neutropenia in 55% of patients, anemia in 18%, febrile neutropenia in 12%, and anorexia in 9%. No treatment-related deaths were observed. CONCLUSION: Carboplatin plus weekly paclitaxel with bevacizumab was effective and well tolerated by patients with advanced NSCLC.

[Clinicians' opinions on receiving the advance directives of terminal-stage patients vary according to the age of respondents].

AIM AND METHODS: We distributed 282 questionnaires to doctors to ascertain their opinions on obtaining the advance directives regarding the end-of-life treatment of patients at the terminal stage. We received 136 (48%) responses. RESULTS: A total of 62% of the respondents stated a desire for patients to indicate their advance directives "if at all possible". Only 36% stated that the need for advance directives "depended on the circumstances". A total of 80% of doctors aged under 40 wished patients to provide advanced directives "if at all possible", while 59% of doctors over 61 wanted advanced directives "depending on the circumstances" (p=0.008). A large number of doctors stated a desire for patients to indicate their preference in writing, particularly directives regarding the "use of a ventilator to prolong life" (76%) or the "use of artificial nourishment through a gastric fistula etc. as part of a proactive approach to sustaining life" (67%). Regarding the optimal timing of this declaration, 59% chose "at the first diagnosis of a terminal illness", and 47% chose "at the diagnosis of a chronic illness", regardless of whether it could become terminal. Of those respondents under 40, 32% believed that doctors should strictly follow the patients' advance directives, while only 11% of doctors over 61 years old believed the same. There was a statistically significant relationship between aging and dealing with advance directives of patients in the terminal stages of illness (p=0.002). CONCLUSION: These results suggest that doctors under 40 years of age should focus on how to correctly interpret the wishes of the patients expressed in the directives, while doctors over 61 should concentrate on the importance of the clinical application of advance directives, and how to balance the need to make qualified medical decisions on treatment in compliance with the wishes of end-stage terminal patients.

Acral peeling skin syndrome: a clinically and genetically heterogeneous disorder.

Acral peeling skin syndrome (APSS) is a rare, autosomal, recessive genodermatosis characterized by painless spontaneous exfoliation of the skin of the hands and feet at a subcorneal or intracorneal level. It usually presents at birth or appears later in childhood or early adulthood. Some cases result from mutations in the TGM5 gene that encodes transglutaminase 5, which has an important role in cross-linking cornified cell envelope proteins. We report a new APSS pedigree from Jordan that contains at least 10 affected family members, although sequencing of the TGM5 gene failed to disclose any pathogenic mutation(s). On the basis of probable consanguinity, we performed homozygosity mapping and identified areas of homozygosity on chromosomes 1, 6, 10, 13, and 16, although none of the intervals contained genes of clear relevance to cornification. APSS is a clinically and genetically heterogeneous disorder, and this Jordanian pedigree underscores the likelihood of still further heterogeneity.

A founder effect of c.1938delC in ITGB4 underlies junctional epidermolysis bullosa and its application for prenatal testing.

Junctional epidermolysis bullosa associated with pyloric atresia (JEB-PA) is one of the most severe inherited skin diseases, characterized by generalized blister formation and occlusion of the pylorus at birth. Most JEB-PA patients have mutations in the gene encoding ß4 integrin (ITGB4). No recurrent mutations in ITGB4 have been described as having founder effects. We collected three JEB-PA families with c.1938delC in ITGB4. Haplotype analysis using single nucleotide polymorphism markers throughout ITGB4 suggested one rare haplotype (2.8% of the Han Chinese and ethnic Japanese populations) in all alleles with c.1938delC. The parents of one of the three families sought prenatal diagnosis for a subsequent pregnancy. We succeeded in performing prenatal exclusion of JEB-PA using the foetal genomic DNA. Our study clearly demonstrated that recurrent c.1938delC in ITGB4 is a founder mutation in JEB-PA patients, and that genotyping of the mutation can be utilized for prenatal diagnosis of JEB-PA.