Molecular mechanism of azoles resistant Candida albicans in a patient with chronic mucocutaneous candidiasis.

BACKGROUND: More and more azole-resistant strains emerged through the development of acquired resistance and an epidemiological shift towards inherently less susceptible species. The mechanisms of azoles resistance of Candida albicans is very complicated. In this study, we aim to investigate the mechanism of azole-resistant C. albicans isolated from the oral cavity of a patient with chronic mucocutaneous candidiasis (CMC). CASE PRESENTATION: CMC diagnosis was given based on clinical manifestations, laboratory test findings and gene sequencing technique. Minimum inhibitory concentration (MIC) of the fungal isolate, obtained from oral cavity termed as CA-R, was obtained by in vitro anti-fungal drugs susceptibility test. To further investigate the resistant mechanisms, we verified the mutations of drug target genes (i.e. ERG11 and ERG3) by Sanger sequencing, and verified the over-expression of ERG11 and drug efflux genes (i.e. CDR1 and CDR2) by RT-PCR. A heterozygous mutation of c.1162A > G resulting in p.K388E was detected in STAT1 of the patient. The expression of CDR1 and CDR2 in CA-R was 4.28-fold and 5.25-fold higher than that of type strain SC5314, respectively. CONCLUSIONS: Up-regulation of CDR1 and CDR2 was mainly responsible for the resistance of CA-R. For CMC or other immunodeficiency patients, drug resistance monitoring is necessary.

Aetiology of superficial fungal infections of the foot in urban outpatients in mainland China: A multicentre, prospective case study.

BACKGROUND: In China, the prevalence of superficial fungal infections of the foot is high and recurrence is common. However, a prospective, large-scale and multicentre study on the aetiology of superficial fungal infections of the foot is still lacking. OBJECTIVES: To study the epidemiology of aetiological agents of superficial fungal infections of the foot in urban outpatients in mainland China, as well as to understand the aetiology features of the pathogenic agent. METHODS: The study was designed as a multicentre, prospective epidemiological survey. A total of 1704 subjects were enrolled from seven geographical areas in mainland China. For each subject, one mycological sample and one bacterial sample were collected. KOH wet mount examination and culture were performed at local laboratories. The bacterial results were only reported in those with positive mycology. Further morphological identification and, if necessary, molecular biological identification were conducted in a central laboratory. RESULTS: Of 1704 enrolled subjects, 1327 (77.9%) subjects had positive fungal culture results. The incidence of dermatophytes, yeasts and moulds was 90.1%, 8.1% and 1.1%, respectively. The most frequently isolated aetiological agent (fungus) was Trichophyton rubrum. Moccasin form was the most commonly reported clinical diagnosis of superficial fungal infections. The most frequently isolated bacterial genus in patients was Staphylococcus. CONCLUSION: This study prospectively investigated the clinical and mycological features of human dermatophytosis in mainland China. T rubrum was the most frequently isolated fungus, and moccasin form was the most commonly reported clinical diagnosis of superficial fungal infections.

Whole transcriptome sequencing for revealing the pathogenesis of sporotrichosis caused by Sporothrix globosa.

This study aimed to investigate the molecular mechanism of sporotrichosis and identify possible novel therapeutic targets. Total RNA was extracted from skin lesion samples from sporotrichosis patients and used to construct a long-chain RNA transcriptome library and miRNA transcriptome library for whole transcriptome sequencing. The differentially expressed genes (DEGs) between the groups were identified, and then Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and Gene Set Enrichment Analysis enrichment analyses were performed based on the DEGs. An lncRNA-miRNA-mRNA ceRNA network was constructed. The expressions of JAK/STAT pathway-related proteins were detected in the patient and control tissues using RT-qPCR and Western blot analysis. Enrichment analysis showed that the DEGs were mainly enriched in various infectious diseases and immune response-related signaling pathways. Competing endogenous RNA network analysis was performed and identified the hub lncRNAs, miRNAs, and mRNAs. Compared with the control group, the mRNA expressions of SOCS3, IL-6, and JAK3 were significantly upregulated, while the expression of STAT3 did not change significantly. Also, the protein expressions of SOCS3, IL-6, JAK3, and STAT3, as well as phosphorylated JAK3 and STAT3, were significantly upregulated. We identified 671 lncRNA DEGs, 3281 mRNA DEGs, and 214 miRNA DEGs to be involved in Sporothrix globosa infection. The study findings suggest that the JAK/STAT pathway may be a therapeutic target for sporotrichosis.

Long-Term Efficacy and Safety of Stapokibart in Adults with Moderate-to-Severe Atopic Dermatitis: An Open-Label Extension, Nonrandomized Clinical Trial.

BACKGROUND: Stapokibart/CM310, a humanized monoclonal antibody targeting the interleukin-4 receptor α chain, has shown promising treatment benefits in patients with moderate-to-severe atopic dermatitis in previous phase II clinical trials. OBJECTIVE: We aimed to evaluate the long-term efficacy and safety of stapokibart in adults with moderate-to-severe atopic dermatitis. METHODS: Enrolled patients who previously completed parent trials of stapokibart received a subcutaneous stapokibart 600-mg loading dose, then 300 mg every 2 weeks up to 52 weeks. Efficacy outcomes included the proportions of patients with ≥ 50%/75%/90% improvements from baseline of parent trials in the Eczema Area and Severity Index, Investigator's Global Assessment, and weekly average of the daily Peak Pruritus Numerical Rating Scale. RESULTS: In total, 127 patients were enrolled, and 110 (86.6%) completed the study. At week 52, the Eczema Area and Severity Index-50/75/90 response rates were 96.3%, 87.9%, and 71.0%, respectively. An Investigator's Global Assessment 0/1 with a ≥ 2-point reduction was achieved in 39.3% of patients at week 16, increasing to 58.9% at week 52. The proportions of patients with ≥ 3-point and ≥ 4-point reductions in the weekly average of daily Peak Pruritus Numerical Rating Scale scores were 80.2% and 62.2%, respectively, at week 52. Improvement in patients' quality of life was sustained over a 52-week treatment period. Treatment-emergent adverse events occurred in 88.2% of patients, with an exposure-adjusted event rate of 299.2 events/100 patient-years. Coronavirus disease 2019, upper respiratory tract infection, and conjunctivitis were the most common treatment-emergent adverse events. CONCLUSIONS: Long-term treatment with stapokibart for 52 weeks showed high efficacy and good safety profiles, supporting its use as a continuous long-term treatment option for atopic dermatitis. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04893707 (15 May, 2021).

Microcystic adnexal carcinoma misdiagnosed as a "recurrent epidermal cyst": A case report.

BACKGROUND: Microcystic adnexal carcinoma (MAC) is a rare malignant cutaneous adnexal neoplasm, often presenting as a flesh-colored and slow-growing indurated plaque or cystic nodule in the mid-facial region. Its characteristic indolent presentation usually leads to initial misdiagnosis, resulting in tumor mismanagement and added morbidity due to increased propensity for local invasion. CASE SUMMARY: A 63-year-old Chinese male patient with a long-term history of excessive ultraviolet irradiation had received two surgeries for an "epidermal cyst" on his glabella and was presented to our hospital's Dermatology Department for further diagnosis and therapy of the lesion on his glabella. One month ago, his two 7 mm × 7 mm subcutaneous nodules were diagnosed as "recurrent epidermal cysts", and he underwent local excision surgery. Additionally, he has post medical history of surgery for right clear cell renal carcinoma. According to his biopsy, the patient was diagnosed as MAC in our hospital, and a tumor remnant was found on his wound. He then underwent wide local excision to achieve negative margins and reconstruction of full-thickness flap transplantation for tissue coverage. He remained tumor-free after six months of follow-up. CONCLUSION: This case highlights the importance of MAC's possible pathogenic factor of excessive ultraviolet exposure, its differential diagnosis to avoid misdiagnosis and mismanagement to adverse prognosis, the patient's particular medical history of clear cell renal carcinoma, the alert for any tumor recurrence in older patients, and his uncommon multiple nodules mess consisting of two 7 mm × 7 mm subcutaneous nodules, that will enrich the existing knowledge of MAC's clinical features.

Co-existence of cutaneous alternariosis and tinea corporis in a renal transplant recipient.

Alternariosis, caused by Alternaria spp., is a rare opportunistic infection often observed in immunocompromised patients. Alternaria is a ubiquitous saprophytic fungus that naturally is found on decaying plant materials. In this paper, a case of cutaneous alternariosis in association with tinea corporis is reported. The complicated infection was confirmed by histological examination and positive tissue culture. Although the cases of alternariosis in solid organ transplant recipients or Cushing's syndrome have been described elsewhere, this is the first report in a patient who had received two renal transplants who was co-infected with Alternaria spp. and Trichophyton rubrum.

Itraconazole therapy for infant hemangioma: Two case reports.

BACKGROUND: Infantile hemangiomas (IHs) are the most common childhood benign tumors, showing distinctive progression characteristics and outcomes. Due to the high demand for aesthetics among parents of IH babies, early intervention is critical in some cases. ß-Adrenergic blockers and corticosteroids are first-line medications for IHs, while itraconazole, an antifungal medicine, has shown positive results in recent years. CASE SUMMARY: In the present study, itraconazole was applied to treat two IH cases. The therapeutic course lasted 80-90 d, during which the visible lesion faded by more than 90%. Moreover, no obvious side effects were reported, and the compliance of the baby and parents was desirable. CONCLUSION: Although these outcomes further support itraconazole as an effective therapeutic choice for IHs, large-scale clinical and basic studies are still warranted to improve further treatment.

A double-blind, randomized, placebo- and positive-controlled phase III trial of 1% benvitimod cream in mild-to-moderate plaque psoriasis.

BACKGROUND: Benvitimod cream, a novel synthetic small molecule, was effective in treating mild-to-moderate plaque psoriasis. We conducted a phase III clinical trial to assess the efficacy and safety of benvitimod cream in patients with mild-to-moderate plaque psoriasis. METHODS: We randomly assigned 686 patients (2:1:1) to receive 1% benvitimod cream, 0.005% calcipotriol ointment or placebo twice a day for 12 weeks. The primary efficacy end points were the percentage of patients with a 75% or greater reduction from baseline in the psoriasis area and severity index (PASI 75) score and with a score of 0 or 1 in static physician's global assessment (sPGA) at week 12. RESULTS: The results showed that 50.4% of patients in the benvitimod group achieved PASI 75, which was significantly higher than that in the calcipotriol (38.5%, P < 0.05) and placebo (13.9%, P < 0.05) groups. The proportion of patients achieving an sPGA score 0 or 1 was 66.3% in the benvitimod group and 63.9% in the calcipotriol group, which were both significantly higher than that in the placebo group (34%, P < 0.05). In the long-term follow-up study, 50.8% of patients experienced recurrence. After retreatment with 1% benvitimod, 73.3% of patients achieved an sPGA score of 0 or 1 again at week 52. Adverse events included application site irritation, follicular papules, and contact dermatitis. No systemic adverse reactions were reported. CONCLUSION: During this 12-week study, benvitimod cream was demonstrated with high effectiveness and safety in patients with mild-to-moderate plaque psoriasis. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR), ChiCTR-TRC-13003259; http://www.chictr.org.cn/showprojen.aspx?proj=6300.

Sensitivities of periodic acid-Schiff staining, Grocott's silver staining and calcofluor white staining in the diagnosis of human sporotrichosis.

OBJECTIVE: This study aimed to investigate the sensitivity of periodic acid-Schiff (PAS) staining, Grocott's silver staining (GSS) and calcofluor white (CFW) staining in the diagnosis of sporotrichosis. METHODS: Paraffin embedded tissues (n = 100) which were diagnosed with sporotrichosis by fungal culture were subjected to PAS, GSS, and CFW staining, and the detection rate of sporotrichosis was determined. RESULTS: The sensitivity of PAS, GSS, and CFW staining was 31%, 40% and 74%, respectively, in the diagnosis of sporotrichosis. CONCLUSION: CFW staining has a high sensitivity in the diagnosis of sporotrichosis, and sections are easily observed and can be repeatedly stained after CFW staining. For patients suspected to have sporotrichosis, CFW staining may be employed for early diagnosis before a fungal culture.

Majocchi's Granuloma after Topical Corticosteroids Therapy.

Majocchi's granuloma (MG) is an unusual but not rare dermatophyte infection of dermal and subcutaneous tissues. Dermatophytes usually result in the infections of hair, epidermis, and nail, and are rarely involved in deep cutaneous and subcutaneous tissues. Now it is considered that MG includes two forms: one is a small perifollicular papular form and the other is a deep subcutaneous nodular form; the front one mainly occurs in healthy individuals and the latter one usually presents in immunocompromised hosts. The clinical manifestations of MG are many and varied, except the common presentations of erythema, papule and nodules, and Kaposi sarcoma-like and molluscum-like lesions have been reported in literatures (Kim et al. (2011), Bord et al. (2007), and Lillis et al. (2010)). This characteristic induces the difficulty of diagnosis, and thus it is so important and necessary to make direct microscopical and histological examinations. We describe a case of MG over the face in a patient who had been treated with topical corticosteroids over a long time.

Effect of FGF10 monoclonal antibody on psoriasis-like model in guinea pigs.

OBJECTIVE: To investigate the therapeutical effect of topical application of FGF10 monoclonal antibody on the guinea pig model with psoriasis. METHODS: Blank group, model group, hydrocortisone butyrate treatment group and high-dose (0.188 mg/ml), middle-dose (0.094 mg/ml) and low-dose (0.063 mg/ml) FGF10 antibody group were set, respectively. After two-week treatment, pathological changes of psoriasis-like models were observed by HE staining, and the difference in VEGF and PCNA expression levels among different groups was observed by immunohistochemical staining. RESULTS: All the test indicators of each treatment group were lower than those of the model group, and there was a significant difference (P<0.05). The inflammatory cell count of the high-dose FGF10 antibody group was not statistically different from those of the blank group (t=0.77, P=0.443), and the counts of the rest treatment groups were significantly higher than those of the blank group and the high-dose FGF10 antibody group (P<0.05). The epidermal thickness of each FGF10 antibody treatment group was significantly higher than that of hydrocortisone butyrate treatment group (P<0.05), while no statistical difference was found in the epidermal thickness among the FGF10 antibody treatment groups (P>0.05). FGF10 monoclonal antibodies can reduce the PCNA and VEGF expression in psoriasis-like model of guinea pig's ear. CONCLUSION: FGF10 monoclonal antibodies can affect keratinocyte proliferation and division and can also significantly inhibit the inflammatory response in the psoriasis model. Meanwhile, FGF10 monoclonal antibodies can produce a therapeutic effect on psoriatic lesions by inhibiting the abnormal epidermis cell proliferation and neovascularization of the dermis in the psoriasis model.

Combined treatment for cutaneous Rosai-Dorfman disease: a report of 2 cases.

We report 2 cases of cutaneous Rosai-Dorfman disease (CRDD). One was a 46-year-old Chinese woman who presented with a 10-year history of multiple papules and nodules on the left cheek. Another one was a 57-year-old Chinese woman who presented with a 7-month history of erythematous pruritic plaque on the Dorsum nasi. Their lesions consisted of proliferative large histiocytes occasionally showing emperipolesis. Immunohistochemistry showed these histiocytes were positive for CD68 and S-100, but negative for CD1a. A diagnosis of CRDD was made. Their lesions were improved after intralesional treatment with Compound Betamethasone, interferon and acitretin. To our knowledge, we for the first time reported the application of intralesional Compound Betamethasone and Lidocaine, intramuscular injection of interferon, and oral acitretin in the treatment of CRDD, and favorable outcome was achieved without recurrence over a 1-year follow-up period.

A case of cutaneous plasmacytosis.

The present study reports a case of cutaneous plasmacytosis in a 51-year-old patient suffering from infiltrated erythema of the right lower lateral femur for 4-5 years and perioral and abdominal erythema for 1 year. Histopathological examination showed that dense mature plasma cell-dominant inflammatory cell infiltration appeared in the deep dermis and between part of the subcutaneous tissues and that there were small numbers of lymphocytes and polykaryocytes. Immunopathogenetic analysis showed that the infiltrating plasma cells were positive for CD79a and CD138. The patient was diagnosed with cutaneous plasmacytosis.