Cutaneous mucormycosis infection owing to Rhizomucor variabilis presenting as recurrent lower limb ulceration and cellulitis in a diabetic patient

Primary cutaneous mucormycosis is caused by environmental fungi and may complicate leg ulcers or traumatic wounds even in immunocompetent individuals. This case report highlights recurrent lower limb ulcers and cellulitis in a patient with type two diabetes mellitus, which was unresponsive to conventional antibiotic treatment. Histopathology revealed the diagnosis of cutaneous mucormycosis, and fungal cultures identified Rhizopus variabilis as the causative organism. Initial courses of oral azole antifungals yielded only partial response and he eventually required more aggressive treatment with i.v. amphotericin B and oral posaconazole. Good treatment outcomes for this condition require a high index of clinical suspicion, early histopathological and microbiological diagnosis, targeted systemic antifungal therapy, and surgical debridement if necessary

Overexpression of CDC42SE1 in A431 Cells Reduced Cell Proliferation by Inhibiting the Akt Pathway

Cell division cycle 42 (CDC42), a small Rho GTPase, plays a critical role in many cellular processes, including cell proliferation and survival. CDC42 interacts with the CRIB (Cdc42- and Rac-interactive binding) domain of CDC42SE1, a small effector protein of 9 kDa. We found that the expression of CDC42SE1 was reduced in human skin cancer samples relative to matched perilesional control. Exogenous expression of CDC42SE1 but not CDC42SE1H38A (mutation within CRIB domain) in A431 cells (A431SE1, A431SE1-H38A) reduced cell proliferation. Antibody microarray analysis of A431Ctrl and A431SE1 lysate suggested that reduced A431SE1 cells proliferation was due to inhibition of Akt pathway, which was confirmed by the reduced P-Akt and P-mTOR levels in A431SE1 cells compared to A431Ctrl cells. This suggests that CDC42SE1 modulates the CDC42-mediated Akt pathway by competing with other effector proteins to bind CDC42. A431SE1 cells formed smaller colonies in soft agar compared to A431Ctrl and A431SE1-H38A cells. These findings correlate with nude mice xenograft assays, where A431SE1 cells formed tumors with significantly-reduced volume compared to the tumors formed by A431Ctrl cells. Our results suggest that CDC42SE1 is downregulated in skin cancer to promote tumorigenesis, and thus CDC42SE1 might be an important marker of skin cancer progression

Two episodes of cutaneous non-tuberculous mycobacterial infection in a patient with psoriasis

Non-tuberculous mycobacteria (NTM) are a group of environmental pathogens, which cause a broad spectrum of disease. The incidence of NTM infection is increasing, especially in immunocompromized patients. The past three decades also saw a rapid increase in the incidence of NTM infection involving otherwise healthy subjects. We report a case of cutaneous NTM infection in a 79-year-old Chinese woman, who was receiving methotrexate for psoriasis. Mycobacterial culture grew <em>Mycobacterium abscessus</em>, and the lesions cleared with a combination of oral clarithromycin, ciprofloxacin and doxycycline. Interestingly, she then developed a second episode of cutaneous NTM infection with <em>Mycobacterium haemophilum</em> over the same body region, five years after stoppage of methotrexate. Both episodes were separated in time and involved different species, indicating that they were independent from each other. We further discuss the risk factors for cutaneous NTM infection, treatment, and highlight the need for diagnostic vigilance

Clinical and economic burden of herpes zoster and postherpetic neuralgia in patients from the National Skin Centre, Singapore

AbstractBackground/ObjectivesThere is a scarcity of recent data on the burden of herpes zoster (HZ) and postherpetic neuralgia (PHN) in Southeast Asia. We evaluated the prevalence, demographics, and disease burden of HZ and PHN in patients aged ≥ 50 years seen at a tertiary dermatological referral center, the National Skin Centre (NSC), Singapore.MethodsWe carried out a retrospective cohort analysis of NSC patient electronic medical records spanning >3 years from January 2010 to March 2013. Data on patient demographics, clinical characteristics, and medical management were collected.ResultsA total of 347 cases of HZ or PHN were included in this study. The mean age was 66.5 years with equal proportions of men and women. The majority of patients (85.6%) were of Chinese ethnicity. Patients presented to the NSC at various disease stages including acute HZ (83.0%), subacute HZ (10.7%), or PHN (6.3%). The most commonly affected anatomic site was thoracic dermatome (41.2%) and the most common prodromal symptom was pain (81.8%). In addition, pain was present in various stages of HZ, and it was the most unbearable symptom experienced during illness (85.5%). Patients in the older age group were more likely to suffer from pain for ≥6 months than patients in the younger age group. Most of the patients received antiviral treatment including acyclovir (70.9%) and valaciclovir (13.5%). Among all the patients, 85.0% received analgesia with the most common drugs being amitriptyline (25.4%) and gabapentin (21.9%). PHN led to significantly higher economic burden with a total cost of 414.69 Singapore dollars per patient versus 267.26 Singapore dollars for a non-PHN patient.ConclusionHZ and PHN cause a significant clinical and economic burden in Singapore

N-WASP attenuates cell proliferation and migration through ERK2-dependent enhanced expression of TXNIP

Neural Wiskott-Aldrich Syndrome Protein (N-WASP) regulates actin cytoskeleton remodeling. It has been known that reduced N-WASP expression in breast and colorectal cancers is associated with poor prognosis. Here, we found reduced N-WASP expression in squamous cell carcinoma (SCC) patient samples. The SCC cell line HSC-5 with reduced N-WASP expression was used to generate HSC-5CN (control) and HSC-5NW (N-WASP overexpression) cells. HSC-5NW cells had reduced cell proliferation and migration compared to HSC-5CN cells. HSC-5NW cells had increased phospho-ERK2 (extracellular signal-regulated kinase 2), phosphorylated Forkhead box protein class O1 (FOXO1) and reduced nuclear FOXO1 staining compared to HSC-5CN cells. Proteasome inhibition stabilized total FOXO1, however, not nuclear staining, suggesting that FOXO1 could be degraded in the cytoplasm. Inhibition of ERK2 enhanced nuclear FOXO1 levels and restored cell proliferation and migration of HSC-5NW to those of HSC-5CN cells, suggesting that ERK2 regulates FOXO1 activity. The expression of thioredoxin-interacting protein (TXNIP), a FOXO1 target that inhibits thioredoxin and glucose uptake, was higher in HSC-5NW cells than in HSC-5CN cells. Knockdown of TXNIP in HSC-5NW cells restored cell proliferation and migration to those of HSC-5CN cells. Thus, we propose that N-WASP regulates cell proliferation and migration via an N-WASP-ERK2-FOXO1-TXNIP pathway.Ministry of Education (MOE)Published versionThis work was supported by the Academic Research Fund Tier 2 (MOE 2013-T2-2-031) and Academic Research Fund Tier 1 (MOE) RG31/20 and RG154/17 grants from the Ministry of Education of Singapore