Totally endoscopic concomitant aortic and mitral valve surgery in junctional epidermolysis bullosa: a case report.

BACKGROUND: Junctional epidermolysis bullosa is a rare skin and mucosal disorder characterized by blister formation in response to minor trauma and extracutaneous manifestations. There have been no reports of cardiac surgery and prognostication in patients with epidermolysis bullosa due to skin and mucosal fragility. CASE PRESENTATION: A 55-year-old man presented with congenital junctional epidermolysis bullosa, hypertension, and vasospastic angina. He complained of dyspnea on exertion, and transthoracic echocardiography revealed severe aortic valve regurgitation, moderate aortic valve stenosis (tricuspid valve), and severe mitral valve regurgitation. Considering that the skin condition in the right chest wall was relatively healthy, the right thoracotomy approach was preferred and totally endoscopic concomitant mitral valve repair and aortic valve replacement were performed using a sutureless bioprosthetic valve (Perceval™ (Corcym, Group, Milan, Italy)). Polyurethane and silicon dressing foams were used to protect the skin at the site of contact with the bag valve mask, arterial pressure catheter, intravenous catheter, and the tracheal intubation tube. Vertical mattress sutures were used for the skin sutures. The postoperative course was uneventful, and the patient was discharged nine days after the operation. There was no indication for reoperation until three years follow-up period. CONCLUSIONS: The totally endoscopic concomitant aortic and mitral valve surgery using Perceval™ prosthesis can be performed safely in patients with junctional epidermolysis bullosa by adequate protection of the skin and mucosa.

Recent treatment and prognosis in 643 patients with extramammary Paget's disease.

Information about extramammary Paget's (EMPD) treatment is limited because of the rarity of the disease. The prognosis differs between in situ EMPD and invasive EMPD; therefore, therapy should be planned according to the disease stage. We collected data on 643 EMPD cases treated between 2015 and 2019 in Japan and assessed recent trends in EMPD treatment and prognosis based on the EMPD-oriented TNM staging. Among the 643 patients, 317 had stage 0 (49.3%), 185 had stage I (28.8%), 51 had stage II (7.9%), 18 had stage IIIA (2.8%), 48 had stage IIIB (7.5%) and 24 had stage IV (3.7%) disease. Each stage showed a distinct survival curve, with the exception of stages II and IIIA. Curative surgery was most common in patients with stage 0-III disease. Chemotherapy was the first-line therapy, mainly in patients with stage IIIB and IV disease, most commonly with docetaxel (DTX), followed by DTX + tegafur gimeracil oteracil potassium (TS-1) and TS-1. Patients with local disease exhibited a 4.4% recurrence rate. Univariate analysis revealed no prognostic differences according to age, sex or primary tumour site. SLNB was not related to disease-specific survival. In multivariate analysis, female sex significantly predicted local relapse in stage 0-I (HR 3.09; 95% CI, 1.13-8.43), and initial treatment with curative surgery was significantly protective in terms of disease-specific survival in stage II-IIIA (HR, 0.17; 95% CI, 0.04-0.71) and stage IIIB-IV (HR 0.16; 95% CI, 0.05-0.51). Further clinical studies are needed to improve the prognosis of patients with stage II-IV EMPD.

Perianal Bowen's disease treated with radiotherapy preserving anal function with a unique skin reaction considered as 'tumoritis'.

Bowen's disease (BD) is a form of intraepidermal squamous cell carcinoma (SCC), and it occasionally occurs on the perianal site. BD is often treated with surgical excision; however, sometimes surgical excision for perianal BD cannot preserve anal function. We report the case of a 72-year-old man presenting with perianal pain and BD. He was treated with Radiotherapy (RT) and preserved his normal anal sphincter function without any recurrence or late adverse event. Moreover, we observed the unique skin reaction called 'tumoritis', which is characterized by mucosal inflammation. Tumoritis indicates the true extent of the tumor and evaluating the tumor or lesion size based on the extent of tumoritis when performing RT is important.

Summary of the current status of clinically diagnosed cases of Schnitzler syndrome in Japan.

BACKGROUND: Schnitzler syndrome is a rare disorder with chronic urticaria, and there is no report summarizing the current status in Japan. METHODS: A nationwide survey of major dermatology departments in Japan was conducted in 2019. We further performed a systematic search of PubMed and Ichushi-Web, using the keywords "Schnitzler syndrome" and "Japan" then contacted the corresponding authors or physicians for further information. RESULTS: Excluding duplicates, a total of 36 clinically diagnosed cases were identified from 1994 through the spring of 2022, with a male to female ratio of 1:1. The median age of onset was 56.5 years. It took 3.3 years from the first symptom, mostly urticaria, to reach the final diagnosis. The current status of 30 cases was ascertained; two patients developed B-cell lymphoma. SchS treatment was generally effective with high doses of corticosteroids, but symptoms sometimes recurred after tapering. Colchicine was administered in 17 cases and was effective in 8, but showed no effect in the others. Tocilizumab, used in six cases, improved laboratory abnormalities and symptoms, but lost its efficacy after several years. Rituximab, used in five cases, was effective in reducing serum IgM levels or lymphoma mass, but not in inflammatory symptoms. Four cases were treated with IL-1 targeting therapy, either anakinra or canakinumab, and achieved complete remission, except one case with diffuse large B-cell lymphoma. CONCLUSIONS: Since Schnitzler syndrome is a rare disease, the continuous collection and long-term follow-up of clinical information is essential for its appropriate treatment and further understanding of its pathophysiology.

Segmental cutaneous leukocytoclastic vasculitis associated with herpes zoster: a case report and literature review.

Varicella zoster virus (VZV) infection may cause large or medium vessel vasculitis, including granulomatous arteritis of the nervous system and central nervous system vasculitis. However, small vessel vasculitis, such as cutaneous leukocytoclastic vasculitis (LCV) associated with localized cutaneous VZV infection, herpes zoster, is uncommon. Herein, we present the case of a 75- year-old man with segmental leukocytoclastic vasculitis associated with herpes zoster on the leg. To the best of our knowledge, there are four cases of segmental leukocytoclastic vasculitis in herpes zoster reported in the English literature; we compared our case with these previous reports. Our review of five patients suggests that most patients were immunosuppressed. We also found that the leg is susceptible to LCV associated with herpes zoster. Anti-viral treatment was effective for LCV as well as herpes zoster. Prior reports have proposed etiologies inducing LCV; for example, immune complexes are mediated by vessel wall damage. In support of this, histopathology in our case showed a C3-positive reaction with the small vessel walls in the dermis in direct immunofluorescence. Although the mechanism of LCV associated with herpes zoster remains unclear, we should consider LCV while diagnosing and treating patients with herpes zoster, especially immunosuppressed patients.

Case Report: Acute Generalized Exanthematous Pustulosis Caused by Praziquantel.

Praziquantel is widely used for treating parasitic infections globally, especially in countries with endemic schistosomiasis. However, severe hypersensitivity to praziquantel has rarely been reported. We report the case of a 30-year-old Japanese man who developed acute generalized exanthematous pustulosis (AGEP), which is a rare and severe cutaneous reaction usually triggered by drugs, after taking praziquantel. During medical examination, eggs of Diphyllobothrium nihonkaiense were found in his stool. He took praziquantel 600 mg for 1 day and developed skin rashes and fever the next day. Pruritic generalized maculopapular erythematous eruptions were observed over the entire body. He had elevated white blood cell count, liver enzymes, and C-reactive protein level. We prescribed acetaminophen, fexofenadine hydrochloride, loxoprofen sodium, and topical ointments including difluprednate and hydrocortisone. Over the next 3 days, he developed pinhead-sized, non-follicular pustules on his diffusely erythematous skin. Histological findings of the pustular lesion showed spongiform subcorneal pustules with perivascular inflammatory cells. Approximately 8 days after taking praziquantel, the pustules resolved with desquamation. He became afebrile on day 9 and his laboratory parameters returned to normal levels on day 16. He was diagnosed with AGEP caused by praziquantel. Physicians need to be aware that praziquantel could cause AGEP, although it is generally considered a safe drug.

Aprepitant for refractory nivolumab-induced pruritus.

Although substantial progress has been made in the treatment of non-small-cell lung cancer (NSCLC) patients with immune checkpoint inhibitors (ICIs), severe immune-related adverse events (irAEs) sometimes occur. Here, we report a case of severe refractory pruritus after Stevens-Johnson syndrome (SJS) in a patient with NSCLC treated with nivolumab. The patient was a 76-year-old Japanese woman with advanced NSCLC treated with nivolumab. After the second dose, she experienced severe rash with mucous involvement. We diagnosed SJS and started 50mg of oral prednisolone (1mg/kg). The rash completely resolved after prednisolone was started, but we could not manage the severe pruritus with emollients, antihistamines, and steroids. Finally, we administered aprepitant, an oral neurokinin-1 receptor antagonist, for her refractory pruritus. Her symptoms improved within 5days. Severe refractory pruritus can arise from ICIs, and aprepitant may be a useful treatment.

Pneumatosis cystoides intestinalis associated with toxic epidermal necrolysis: A case report.

Toxic epidermal necrolysis (TEN) is a severe adverse drug reaction, which is characterized by erythema, blisters, and/or erosions of the mucous membranes and skin, but intestinal involvement is rare. In contrast, pneumatosis cystoides intestinalis (PCI) is a rare condition associated with a wide variety of underlying diseases, but to date no patient has presented with PCI associated with TEN. A 55-year-old man was admitted to intensive care unit for treatment of TEN caused by phenobarbital. On day 8 after admission, he presented with progressive abdominal distention and hypotension. Computed tomography (CT) showed gas in the superior mesenteric vein and air filled cysts in the walls of the small intestine. He was suspected of having septic shock due to PCI. As there were no indications of bowel ischemia or necrosis, the patient was managed conservatively with antibiotics and oxygen therapy. On day 10 after admission, he was weaned off catecholamines, with CT on day 11 showing complete resolution of gas in the superior mesenteric vein and air filled cysts. To our knowledge, this article describes the first patient presenting with PCI associated with TEN.

Phase II clinical trial of CD34+ cell therapy to explore endpoint selection and timing in patients with critical limb ischemia.

BACKGROUND: A prior phase I/IIa clinical trial provided evidence for safety, feasibility and potential efficacy of i.m. injection of granulocyte colony-stimulating factor (G-CSF)-mobilized CD34+ cells in patients with critical limb ischemia (CLI). METHODS AND RESULTS: A phase II trial of CD34+ cell therapy was conducted in patients with CLI to explore endpoint selection and timing. No-option CLI patients (n=11) underwent i.m. transplantation of G-CSF-mobilized CD34+ cells isolated by magnetic sorting. Ischemic rest pain scales improved from week 2 vs. baseline (P<0.05). Skin perfusion pressure (P=0.0175), transcutaneous partial oxygen pressure (P=0.0446) and pain-free walking distance (P=0.0056) improved from week 2, total walking distance from week 8 (P=0.0182) and toe brachial pressure index from week 12 (P=0.0174) vs. baseline. These parameters peaked at week 36 or 52. Rutherford's category improved from week 24 vs. baseline (P=0.0065). CLI-free ratio serially increased and peaked (85.7%) at week 36. Serial change in Rutherford's category correlated with that in Rest Pain Scale (P=0.0374), but not with that in any physiological parameters. CONCLUSIONS: Ischemic rest pain scales and physiological parameters improved relatively early after cell therapy, then plateaued later accompanied by recovery from the CLI state. Rutherford's category and CLI-free ratio at week 36 or later may be suitable endpoints in cell therapy clinical trials for CLI. Functional parameters should be evaluated independently of such clinical endpoints for ischemia severity. ( CLINICAL TRIAL REGISTRATION: URL: https://dbcentre3.jmacct.med.or.jp/jmactr/Default.aspx. Unique identifier: JMA-IIA00022)

Long-term clinical outcome after intramuscular transplantation of granulocyte colony stimulating factor-mobilized CD34 positive cells in patients with critical limb ischemia.

BACKGROUND: Our phase I/IIa clinical trial revealed that intramuscular transplantation of autologous, GCSF-mobilized CD34+ cells was safe, feasible and potentially effective at week 4 and 12 post cellular therapy in 17 patients with chronic critical limb ischemia (CLI) (5 patients with atherosclerotic peripheral arterial disease (PAD) and 12 with Buerger's disease). However, long-term outcome of the cell therapy has yet to be reported. METHODS AND RESULTS: Incidence of major clinical events and physiological parameters of limb ischemia were evaluated at week 52, 104, 156 and 208 post CD34+ cell therapy. No patients died by week 104, whereas 3 patients with PAD died by week 156 and 1 patient with Buerger's disease died by week 208 due to cardiac complications. No patients underwent major amputation, whereas 1 patient with Buerger's disease underwent unplanned minor amputation by week 104. CLI-free ratio was 88.2% at week 52 and 104, 92.3% at week 156 and 84.6% at week 208 in all patients. Significant improvement of toe brachial pressure index versus baseline was sustained up to week 208 and that of transcutaneous partial oxygen pressure was kept up to week 156. The Wong-Baker FACES pain rating scale, ulcer size and exercise tolerance significantly improved at week 52, the final evaluation time point, compared with baseline. Subgroup analysis revealed the similar outcome in patients with Buerger's disease. CONCLUSIONS: Favorable clinical outcomes as well as physiological evidences strongly indicate the long-term benefit of GCSF-mobilized CD34+ cell transplantation for retrieval from CLI, especially in patients with Buerger's disease.

XRCC1 Arg194Trp polymorphism, risk of nonmelanoma skin cancer and extramammary Paget's disease in a Japanese population.

The X-ray repair cross-complementing groups 1 gene plays an important role in base excision repair. At least three common single nucleotide polymorphisms frequently occur in this gene (Arg399Gln, Arg194Trp and Arg280His). Recent studies reported that these polymorphisms were associated with not only risk of visceral malignancy but also that of skin cancer such as basal cell carcinoma and squamous cell carcinoma, whereas the results of previous study vary among races. In this case-control study, we investigated whether these single nucleotide polymorphisms were associated with the risk of skin cancer in a Japanese population. The study population was composed of 197 patients with skin cancer (27 actinic keratoses, 47 basal cell carcinomas, 27 squamous cell carcinomas, 29 Bowen's diseases, 46 malignant melanomas and 21 extramammary Paget's diseases) and 93 control subjects. We genotyped two single nucleotide polymorphisms (Arg194Trp and Arg399Gln) using polymerase chain reaction-restriction fragments length polymorphism analysis. We found a significantly increased risk for basal cell carcinoma, squamous cell carcinoma and extramammary Paget's disease associated with Arg194Trp [adjusted odds ratio (AOR) = 2.347, 3.587, 3.741, 95 % confidence interval (CI) 1.02-5.39, 1.19-10.8, 1.15-12.2, respectively]. We also found a significantly decreased risk for basal cell carcinoma associated with Gln399Gln (AOR = 0.259, 95 % CI 0.07-0.96). Our data suggest that the Arg194Trp polymorphism could be associated with nonmelanoma skin cancer and extramammary Paget's disease risk in a Japanese population.

Polymorphisms of glutathione S-transferase in skin cancers in a Japanese population.

Variations in the Glutathione S-transferase (GST) supergene family have been reported to influence cancer susceptibility in Caucasian. However the genetic backgrounds and skin types are quite different between Caucasian and non-Caucasian. We therefore investigated the distribution of GST gene polymorphism in non-Caucasian population to ascertain the role of this polymorphism in skin carcinogenesis. One-hundred and fifteen patients with skin cancers and 92 controls who visited Kobe University Hospital between April 2004 and November 2010 were enrolled in this study. Genotype of GST gene was determined by using polymerase chain reaction-restriction fragments length polymorphism analysis. The frequencies of GSTM1 positive genotype were significantly higher in squamous cell carcinomas than those in controls (adjusted odds ratio = 3.09, 95% confidence interval 1.04 - 9.21). The polymorphism of GSTM1 locus could be an important factor in susceptibility to squamous cell carcinoma among Japanese population.

Axillary accessory breast associated with galactorrhea in an adolescent girl.

We present herein a case of right axillary accessory breast associated with galactorrhea in an adolescent girl. A 14-year-old Japanese girl presented with an 11-month history of a tender, subcutaneous lesion in the right axillary fossa. Seven months later, she experienced menarche. Subsequently, the patient noticed pressure-induced galactorrhea from both nipples. Physical examination revealed an elastic, firm and well-demarcated subcutaneous tumor 3 × 2 cm in size. A biopsy specimen showed proliferation of mammary gland tissue in the stroma located below the subcutaneous fat tissue. On the basis of these findings the patient was diagnosed with an accessory breast. Interestingly, the galactorrhea ceased after surgical removal of the accessory breast.