Polyomavirus-associated Trichodysplasia spinulosa involves hyperproliferation, pRB phosphorylation and upregulation of p16 and p21.

Trichodysplasia spinulosa (TS) is a proliferative skin disease observed in severely immunocompromized patients. It is characterized by papule and trichohyalin-rich spicule formation, epidermal acanthosis and distention of dysmorphic hair follicles overpopulated by inner root sheath cells (IRS). TS probably results from active infection with the TS-associated polyomavirus (TSPyV), as indicated by high viral-load, virus protein expression and particle formation. The underlying pathogenic mechanism imposed by TSPyV infection has not been solved yet. By analogy with other polyomaviruses, such as the Merkel cell polyomavirus associated with Merkel cell carcinoma, we hypothesized that TSPyV T-antigen promotes proliferation of infected IRS cells. Therefore, we analyzed TS biopsy sections for markers of cell proliferation (Ki-67) and cell cycle regulation (p16ink4a, p21waf, pRB, phosphorylated pRB), and the putatively transforming TSPyV early large tumor (LT) antigen. Intense Ki-67 staining was detected especially in the margins of TS hair follicles, which colocalized with TSPyV LT-antigen detection. In this area, staining was also noted for pRB and particularly phosphorylated pRB, as well as p16ink4a and p21waf. Healthy control hair follicles did not or hardly stained for these markers. Trichohyalin was particularly detected in the center of TS follicles that stained negative for Ki-67 and TSPyV LT-antigen. In summary, we provide evidence for clustering of TSPyV LT-antigen-expressing and proliferating cells in the follicle margins that overproduce negative cell cycle regulatory proteins. These data are compatible with a scenario of TSPyV T-antigen-mediated cell cycle progression, potentially creating a pool of proliferating cells that enable viral DNA replication and drive papule and spicule formation.

Trichodysplasia spinulosa is characterized by active polyomavirus infection.

BACKGROUND: Recently a new polyomavirus was identified in a patient with trichodysplasia spinulosa (TS), a rare follicular skin disease of immunocompromised patients characterized by facial spines and overgrowth of inner root sheath cells. Seroepidemiological studies indicate that TSPyV is ubiquitous and latently infects 70% of the healthy individuals. OBJECTIVE: To corroborate the relationship between active TSPyV infection and TS disease by analyzing the presence, load, and precise localization of TSPyV infection in TS patients and in controls. STUDY DESIGN: TS lesional and non-lesional skin samples were retrieved from TS patients through a PubMed search. Samples were analyzed for the presence and load of TSPyV DNA with quantitative PCR, and for expression and localization of viral protein with immunofluorescence. Findings obtained in TS patients (n=11) were compared to those obtained in healthy controls (n=249). RESULTS: TSPyV DNA detection was significantly associated with disease (P<0.001), with 100% positivity of the lesional and 2% of the control samples. Quantification revealed high TSPyV DNA loads in the lesional samples (∼10(6)copies/cell), and low viral loads in the occasionally TSPyV-positive non-lesional and control samples (<10(2)copies/cell). TSPyV VP1 protein expression was detected only in lesional TS samples, restricted to the nuclei of inner root sheath cells over-expressing trichohyalin. CONCLUSIONS: The high prevalence and load of TSPyV DNA only in TS lesions, and the abundant expression of TSPyV protein in the affected hair follicle cells demonstrate a tight relation between TSPyV infection and TS disease, and indicate involvement of active TSPyV infection in TS pathogenesis.

Viral-associated trichodysplasia of immunosuppression: report of a pediatric patient with response to oral valganciclovir.

BACKGROUND: Viral-associated trichodysplasia of immunosuppression is an increasingly recognized entity characterized by follicular-based papules, primarily in the central part of the face, that produce variable degrees of alopecia and dysmorphic features. It has been primarily described in transplant recipients but has recently been recognized in patients receiving chemotherapy for leukemia and lymphoma. It is associated with distinctive histologic features such as dilated anagen hair follicles, absent hair papillae, and abrupt cornification of the inner root sheath. OBSERVATIONS: A 5-year-old boy presented with spiny follicular papules that caused thickening of the skin of the face 1 year after cardiac transplantation. He had been exposed to several immunosuppressive agents, including mycophenolate mofetil, tacrolimus, intravenous immunoglobulin, rituximab, cylcophosphamide, and prednisone. Despite the failure of multiple topical treatments, our patient's eruption improved with systemic valganciclovir therapy. CONCLUSIONS: We describe the youngest patient (to our knowledge) with viral-associated trichodysplasia of immunosuppression and discuss the characteristic clinicopathologic features. Our report supports the theory that immunosuppression is the predisposing factor to a folliculotropic papovavirus that alters follicular maturation.

Reasons prehospital personnel do not administer aspirin to all patients complaining of chest pain.

INTRODUCTION: Aspirin is administered to patients with acute coronary syndromes (ACSs), but prehospital providers do not administer aspirin to all patients with chest pain that could be secondary to an ACS. OBJECTIVE: To identify reasons prehospital providers fail to administer aspirin to all patients complaining of chest pain. METHODS: A convenience sample of prehospital providers was surveyed as they transported patients with a chief complaint of chest pain to the emergency department. The providers were asked if they had given aspirin, nitroglycerin, or oxygen, or if they utilized a monitor. If the medications had not been administered, the paramedic was asked about the reason. The patient's age and previous cardiac history also was recorded. RESULTS: A total of 52 patients with chest pain who were transported were identified over eight weeks, and all of the providers agreed to participate in the study. Only 13 of the patients (25%) received aspirin. Reasons given for not administering aspirin to the other 39 patients included: (1) chest pain was not felt to be cardiac in 13 patients (33%); (2) 10 patients already had taken aspirin that day (26%); (3) the medical provider was a basic-level emergency medical technician (EMT)-Basic and could not administer aspirin to six patients (15%); (4) pain subsided prior to arrival of emergency medical services (EMS) in these three patients; and (5) other reasons were provided for the remaining seven patients. CONCLUSIONS: The most common reason that paramedics did not administer aspirin was the paramedic's belief that the chest pain was not of a cardiac nature. Another common reason for not giving aspirin was the inability of EMT-Basic providers to administer aspirin.