Kerion Celsi due to Microsporum canis in an Adult Woman, Treated Successfully with Fosravuconazole.

A 64-year-old woman presented with a fist-sized, severely painful lesion with scales, crusts, pustules, erythema with subcutaneous abscess, and hair loss on the left temporal region. Direct microscopic examination revealed a large number of spores around the hair, which indicated ectothrix hair invasion, and some hyphae were also found. Histopathological examination showed significant inflammatory cell infiltration from the dermis to the subcutaneous tissues and into the hair follicles, destruction of the hair follicles with granulomatous reactions, and fungal masses along the hair within the hair follicles. Microsporum canis was identified based on morphological features via culture method and molecular biological analysis of the internal transcribed spacer region DNA sequence. The patient was diagnosed with kerion celsi caused by M. canis. For treatment of kerion celsi, we chose an oral antifungal agent, fosravuconazole (FRVCZ), which has been available since 2018 only in Japan. Clinical symptoms were cured in 12 weeks without scarring. No side effects were observed during oral administration of FRVCZ. The results of our case and several previous reports suggest that FRVCZ is effective in treating various types of dermatomycoses.

Severe hypoglycemia in propranolol treatment for infantile hemangiomas.

BACKGROUND: Infantile hemangioma (IH), formerly termed strawberry hemangioma, is a benign vascular tumor caused by capillary endothelial cell proliferation. The tumor regresses after 1 year of age, but sequelae occur in approximately half of the patients without systemic treatment. Propranolol (PPL) is currently the first-line therapeutic agent in Japan as well as in Western countries. It is not commonly known that PPL may induce severe hypoglycemia, in addition to cardiovascular and respiratory side effects. METHODS: We retrospectively analyzed patients with severe PPL-induced hypoglycemia in the 3 years since the launch of Hemangiol®, a PPL preparation specific for IH, in Japan in 2016. RESULTS: The incidence of severe hypoglycemia and of hypoglycemic convulsions following PPL treatment was estimated to be 0.54% and 0.35%, respectively. The incidence of hypoglycemic convulsions appeared to be higher in Japan than in Western countries. Severe hypoglycemia was common in infants aged >1 year, when PPL was used for ≥6 months. Severe hypoglycemia often develops from 05:00 a.m. to 09:00 a.m. and is frequently associated with prolonged periods of fasting, poor feeding, or poor physical conditions. CONCLUSION: To avoid the risk of hypoglycemia, the treatment should be initiated by 6 months of age during the proliferative phase at the latest, and should not be extended indiscriminately beyond 1 year of age. Guardians should be advised not to administer PPL on an empty stomach, in the presence of poor feeding, or who are in poor physical condition, not to prolong fasting after PPL administration, and to monitor the child's condition immediately after he or she wakes up.

Subcutaneous abscess in the shoulder caused by Prevotella bivia infection.

Prevotella bivia (P. bivia) is an anaerobic Gram-negative rod usually inhabiting in the urogenital system, and sometimes in the intra-oral space, whose infection to other parts of body is extremely rare. In this report, we describe a rare case of a recurrent infectious abscess due to P. bivia in the right shoulder of a middle-aged female.

Treatment Outcome with Fosravuconazole for Onychomycosis.

Fosravuconazole L-lysine ethanolate (F-RVCZ), a ravuconazole prodrug, is a newly available agent with high expectations for efficacy in the treatment of onychomycosis. However, clinical data regarding the efficacy of F-RVCZ are limited because the drug was launched only in Japan in 2018. Therefore, we analyzed the outcome of F-RVCZ therapy in the treatment of onychomycosis at outpatient dermatology clinics in Japan. We examined data for 109 patients (68 male, 41 female) with varying clinical type, including total dystrophic onychomycosis and dermatophytoma, and a wide range of age groups, including the elderly. The complete cure rate at 12 weeks was 6.4% (7/109) and 67.9% (74/109) at the last visit (mean time to last visit: 32 ± 14.2 weeks). Mean rate of improvement in the affected nail area was 49.1 ± 23.3% at 12 weeks and 86.8 ± 22.4% at the last visit. Efficacy at 12 weeks and the last visit, respectively, was as follows: none, 4 cases and 1 case; slight, 35 cases and 4 cases; moderate, 51 cases and 21 cases; significant, 12 cases and 9 cases; complete cure, 7 cases and 74 cases. There were no serious adverse events. This retrospective survey was the first large-scale analysis of actual clinical practice outcomes and had minimal exclusions. Compared to previous reports, our results demonstrated excellent efficacy of F-RVCZ therapy in a variety of patients. Considering our results and the ease of oral administration (1 capsule/day for 12 weeks) and few adverse events, F-RVCZ therapy appears to be a useful option for the treatment of onychomycosis.

A Case of Tinea faciei Due to Nannizzia gypsea: Inflammatory Eruption on the Medial Angle of the Eyelid.

Nannizzia gypsea is a geophilic dermatophyte, previously known as Microsporum gypseum before renaming under the new taxonomy. This organism is distributed all over the world and is considered to be involved in keratin degradation in the soil. Generally, human infection involves direct contact with fertile soil. Tinea caused by geophilic dermatophytes is much rarer than that caused by anthropophilic dermatophytes. According to the latest survey in Japan, dermatophytosis due to N. gypsea accounted for only 0.4% of cases. Clinical presentations vary and may mimic other inflammatory dermatitis, leading to incorrect diagnosis and delayed treatment. According to that past report, distal parts of the upper and lower extremities were more commonly affected, followed by the trunk, face and scalp, and rarely the nail plate. A 38-year-old woman presented with an approximately 3-week history of an itchy, solitary erythematous lesion on the left medial angle of the eyelid. Direct microscopic examination of scales revealed fungal elements, and the causative agents was identified as N. gypsea by morphological and molecular biological diagnoses. The eruption improved with systemic itraconazole treatment at 100 mg/day for 8 weeks. No recurrence has been seen for a year. However, she had no history of contact with any infectious source. Herein, we report a case of tinea faciei due to N. gypsea with an uncommon site and route of infection.

Retrospective Survey of Treatment Outcomes of Efinaconazole 10% Solution and Luliconazole 5% Solution for Onychomycosis in Our Facility.

Many clinicians prefer to treat onychomycosis systemically. However, systemic therapy may not be suitable for all onychomycosis patients due to drug interactions, side effects of oral medications, or comorbidities. Two topical agents (efinaconazole 10% in 2014 and luliconazole 5% in 2016) have recently been approved for treatment of onychomycosis in Japan. We investigated the efficacy of these topical agents at Teikyo University Mizonokuchi Hospital, Kanagawa, Japan. We conducted a retrospective survey among patients diagnosed with onychomycosis at our outpatient clinic and had been treated with either efinaconazole 10% solution or luliconazole 5% solution. Prior to commencement of treatment, the disease severity was evaluated using the Scoring Clinical Index for Onychomycosis (SCIO). Furthermore, the efficacies of these agents were evaluated using turbidity scoring at each visit to our outpatient clinic. Sixty-two patients (33 men, 29 women) applied efinaconazole 10% solution, and 72 patients (35 men, 37 women) applied luliconazole 5% solution. The mean SCIO scores were 18.1 and 17.4, respectively, and the mean 5-grade evaluation scores were 3.5 and 3.4, respectively. Complete cure rates were 40.3% (25/62) and 33.3% (24/72), respectively. The mean durations of treatment were 15.4 months and 11.9 months, respectively. There were no serious side effects in either treatment group. There were no significant differences between the two agents in improvement scores as assessed by the Tukey's test. Thus, efinaconazole 10% and luliconazole 5% topical solutions were effective for the treatment of onychomycosis. These topical agents may become important treatment options for this indication.

Prediction of therapeutic response before and during i.v. cyclophosphamide pulse therapy for interstitial lung disease in systemic sclerosis: A longitudinal observational study.

There have been no established parameters to predict responsiveness to i.v. cyclophosphamide (IVCY) pulse therapy in combination with corticosteroids in patients with interstitial lung disease (ILD) related to systemic sclerosis (SSc). This retrospective study was conducted to determine predictive factors for efficacy of IVCY at the time of before and during the treatment. Thirty-two Japanese SSc patients, ever treated for ILD with IVCY in combination with prednisolone, were analyzed retrospectively. We performed detailed time-course analyses of parameters derived from blood samples and pulmonary function tests. With the exclusion of eight unclassified patients, 24 patients were classified into 14 good responders (GR) or 10 poor responders (PR) on the basis of changes in percent predicted diffusing capacity for carbon monoxide (DLco). Pretreatment percent predicted DLco was significantly reduced in PR compared with GR. In addition, serum parameters such as Krebs von den Lungen-6 (KL-6), surfactant protein D (SP-D) and C-reactive protein were significantly higher in PR than in GR. Furthermore, our time-course analyses revealed a transient increase in serum KL-6 levels with a peak at 3 months after the first infusion of cyclophosphamide, which showed no relation to therapeutic efficacy. Moreover, continuously high serum KL-6 levels (>2000 U/mL) and rapid decrease in SP-D levels (<200 ng/mL) during IVCY were remarkably characteristic of PR and GR, respectively. ILD severity/activity before treatment and variability of serum KL-6 and SP-D levels during treatment may be useful to predict therapeutic effects of IVCY on SSc-ILD.

Efficacy and safety of oral propranolol for infantile hemangioma in Japan.

BACKGROUND: There have been few reports on the efficacy and safety of oral propranolol at 3 mg/kg/day for infantile hemangioma (IH) in Japanese patients. METHODS: A multicenter, open-label phase III study was conducted to evaluate the efficacy and safety of oral propranolol solution in Japanese infants aged 35-150 days with proliferating IH. Thirty-two patients were enrolled in the study, received propranolol solution for 24 weeks at 3 mg/kg/day, and completed the study. RESULTS: The success rate (complete or nearly complete resolution) at week 24 (primary endpoint) was 78% (95%CI: 60-91%). The improvement rate since the previous visit was 100% (32/32) after week 5. Overall, the IH surface area, maximum diameter, and color intensity all decreased over time. Consistency in assessment between the centralized and the investigator on-site assessments was observed in 26 patients. Of the 32 patients, 11 needed further treatment other than the study drug. The incidence of adverse events (AE) and drug-related AE was 97% and 31%, respectively. AE that occurred in ≥two patients were either typical of propranolol use (such as blood pressure decrease) or common events in infants. AE that resulted in dose reduction were observed in two patients, but no serious AE or AE that led to study drug discontinuation were observed. CONCLUSION: Oral propranolol solution at 3 mg/kg/day is effective and safe in Japanese IH patients.

A case of breakthrough Candida parapsilosis fungemia during micafungin therapy for a Candida glabrata bloodstream infection.

We describe a case of breakthrough Candida parapsilosis fungemia in an 80-year-old woman with pyoderma gangrenosum and rheumatoid arthritis. C. parapsilosis was detected in blood culture while the patient was treated with micafungin for a Candida glabrata bloodstream infection. The breakthrough infection was successfully treated with liposomal amphotericin B.

Gαi2 and Gαi3 Differentially Regulate Arrest from Flow and Chemotaxis in Mouse Neutrophils.

Leukocyte recruitment to inflammation sites progresses in a multistep cascade. Chemokines regulate multiple steps of the cascade, including arrest, transmigration, and chemotaxis. The most important chemokine receptor in mouse neutrophils is CXCR2, which couples through Gαi2- and Gαi3-containing heterotrimeric G proteins. Neutrophils arrest in response to CXCR2 stimulation. This is defective in Gαi2-deficient neutrophils. In this study, we show that Gαi3-deficient neutrophils showed reduced transmigration but normal arrest in mice. We also tested Gαi2- or Gαi3-deficient neutrophils in a CXCL1 gradient generated by a microfluidic device. Gαi3-, but not Gαi2-, deficient neutrophils showed significantly reduced migration and directionality. This was confirmed in a model of sterile inflammation in vivo. Gαi2-, but not Gαi3-, deficient neutrophils showed decreased Ca(2+) flux in response to CXCR2 stimulation. Conversely, Gαi3-, but not Gαi2-, deficient neutrophils exhibited reduced AKT phosphorylation upon CXCR2 stimulation. We conclude that Gαi2 controls arrest and Gαi3 controls transmigration and chemotaxis in response to chemokine stimulation of neutrophils.

Circulating galectin-1 concentrations in systemic sclerosis: potential contribution to digital vasculopathy.

AIM: To determine serum galectin-1 levels and their clinical associations in patients with systemic sclerosis (SSc). METHOD: Serum galectin-1 levels were examined by enzyme-linked immunosorbent assay in 66 patients with SSc and 24 healthy individuals. RESULTS: No significant differences were observed in serum galectin-1 levels between patients with SSc (9.4 ± 5.6 ng/mL), and healthy individuals (8.9 ± 1.3 ng/mL). Among patients with SSc, no significant differences were seen in serum galectin-1 levels between those with diffuse cutaneous SSc (8.8 ± 5.7 ng/mL; n = 31) and those with limited cutaneous SSc (10.0 ± 5.4 ng/mL; n = 35). Patients with SSc who had increased galectin-1 levels less often had pitting scars/digital ulcers than those with normal galectin-1 levels (17% vs. 49%; P < 0.01). Consistently, galectin-1 levels were significantly lower in SSc patients with pitting scars/digital ulcers than in those without pitting scars/digital ulcers (6.9 ± 4.8 vs. 10.9 ± 5.5 ng/mL; P < 0.01). CONCLUSION: These results suggest that galectin-1 is a protective factor against the development of digital vasculopathy in SSc. In addition, measurement of serum galectin-1 levels may be useful for risk stratification for the development of digital vasculopathy in the early phase of SSc.

Effect of ambrisentan on peripheral circulation in patients with systemic sclerosis.

Systemic sclerosis (SSc) is characterized by disturbed blood circulation. The effect of ambrisentan, an endothelin-A receptor-selective antagonist, on impaired peripheral circulation in SSc remains largely elusive. Here we show SSc patients, whose clinical symptoms such as cyanosis and Raynaud's phenomenon, were ameliorated by the treatment with ambrisentan. Additionally, objective evaluations with thermography showed improvement of hand coldness in steady-state and cold challenge tests. Ambrisentan might have a potential to improve peripheral circulation in SSc.

Association of anti-RNA polymerase III antibody and malignancy in Japanese patients with systemic sclerosis.

Patients with systemic sclerosis (SSc) have an increased risk of malignancy compared with the general population. Recently, SSc patients with anti-RNA polymerase III antibody have been reported to have an increased risk of malignancy as compared with those with other disease-specific autoantibodies in US, European and Australian populations. Therefore, we studied the relationship between disease-specific autoantibodies and malignancy in 261 Japanese SSc patients. The prevalence of malignancy was significantly higher in patients with anti-RNA polymerase III antibody (7/22, 31.8%) than in those with anti-topoisomerase I antibody (2/82, 2.4%) and in those with anticentromere antibody (8/137, 5.8%). Importantly, among seven patients with anti-RNA polymerase III antibody and malignancy, three patients (42.9%) developed malignancy from 6 months before to 12 months after SSc onset. Thus, malignancy complication in Japanese SSc patients with anti-RNA polymerase III antibody is as high as that in other races, suggesting that SSc patients with anti-RNA polymerase III antibody share the same pathological process among different ethnic groups.

Successful experience of rituximab therapy for systemic sclerosis-associated interstitial lung disease with concomitant systemic lupus erythematosus.

Previous studies have demonstrated that B cells play critical roles in autoimmune disorders including systemic sclerosis (SSc) and systemic lupus erythematosus (SLE). However, the effectiveness of rituximab (RTX), a chimeric anti-CD20 antibody, for SSc-associated interstitial lung disease (ILD) or SLE disease activity remains controversial. We herein report an SSc patient with severely progressed ILD and concomitant SLE treated by two cycles of RTX at baseline and half a year later. This treatment improved ILD and SLE activities, along with reduction of dermal sclerosis and serum anti-topoisomerase I antibody levels. In addition, our detailed time-course data indicate that half a year may be appropriate as an interval between each cycle of RTX therapy aimed at SSc-associated ILD or SLE. Overall, the current report could pave the way to establish RTX as a disease-modifying drug for patients with SSc and/or SLE showing resistance to other already approved medications.