Trichodysplasia Spinulosa Research Articles

Seroepidemiology of the Newly Found Trichodysplasia Spinulosa–Associated Polyomavirus

Trichodysplasia spinulosa (TS)-associated polyomavirus (TSV) was recently (in 2010) discovered in TS lesions. To investigate the seroprevalence and primary exposure time of this virus, we set up a virus protein (VP1) viruslike particle (VLP)-based immunoglobulin G enzyme immunoassay. The seroprevalence of TSV was 5%, among children aged 1-4 years, rising to 48% at 6-10 years, and 70% among 149 adults. The TSV antibodies did not cross-react with corresponding Merkel cell polyomavirus VLPs, and their reactivity appeared conformational. TSV circulates widely in the human population and primary exposure is extensive in childhood, beginning at age 1-2 years.

Seroprevalence of Trichodysplasia Spinulosa–associated Polyomavirus

We identified a new polyomavirus in skin lesions from a patient with trichodysplasia spinulosa (TS). Apart from TS being an extremely rare disease, little is known of its epidemiology. On the basis of knowledge regarding other polyomaviruses, we anticipated that infections with trichodysplasia spinulosa–associated polyomavirus (TSV) occur frequently and become symptomatic only in immunocompromised patients. To investigate this hypothesis, we developed and used a Luminex-based TSV viral protein 1 immunoassay, excluded cross-reactivity with phylogenetically related Merkel cell polyomavirus, and measured TSV seroreactivity. Highest reactivity was found in a TS patient. In 528 healthy persons in the Netherlands, a wide range of seroreactivities was measured and resulted in an overall TSV seroprevalence of 70% (range 10% in small children to 80% in adults). In 80 renal transplant patients, seroprevalence was 89%. Infection with the new TSV polyomavirus is common and occurs primarily at a young age.

Cutaneous Squamous Cell Carcinoma: A Smoking Gun but Still No Suspects

A viral etiology for cutaneous squamous cell carcinoma (cuSCC) has long been suspected, primarily on the basis of its dramatically increased incidence in immunocompromised individuals. In this issue, Arron and colleagues report a comprehensive hunt for viral gene transcription in cuSCC. Their findings show that it is very unlikely that any currently known virus is commonly responsible for the maintenance of this cancer.

Viral-associated trichodysplasia spinulosa: a case with electron microscopic and molecular detection of the trichodysplasia spinulosa-associated human polyomavirus

Trichodysplasia spinulosa (TS) is a folliculocentric and clinically papular dermatological disorder occurring in the setting of immunosuppression typically in association with solid organ transplantation or hematolymphoid malignancies. We report the occurrence of TS in a 7-year-old girl with Down syndrome and pre-B-acute lymphoblastic leukemia who was completing chemotherapy at onset. The patient's affected follicles were dilated by an expansion of a dystrophic follicular inner root sheath cell population displaying enlarged trichohyaline cytoplasmic granules and progressing centrally to keratotic and parakeratotic debris, and superficially demonstrating some diminutive hair shaft-like material within the keratotic spicules. Electron microscopic studies of a follicular lesion showed extracellular viral particles suggestive of a polyomavirus within the central follicular keratotic debris. DNA polymerase chain reaction (PCR) and gene sequencing studies, performed on the tissue of the microscopic slide and paraffin block, for the recently identified TS-associated polyomavirus (TSPyV) resulted as positive for TSPyV. PCR for the Merkel cell polyomavirus was negative. To date, this case is unique in representing the first case of TS confirmed by electron microscopy in which a related viral pathogen has been molecularly identified. An additional 19 reported cases classifiable as TS are tabulated and reviewed.

Multiple minute digitate hyperkeratosis: A proposed algorithm for the digitate keratoses

Multiple minute digitate hyperkeratosis (MMDH) is a rare disorder of keratinization with many different names. We present a case of MMDH and review the literature. We propose and discuss the classification the digitate keratoses, which include MMDH, lichen spinulosus, phrynoderma, spiny keratoderma, arsenical keratosis, multiple filiform verrucae, postirradiation digitate keratosis, trichodysplasia spinulosa, and hyperkeratotic spicules. We present a table of suggested and synonymous terms and propose a diagnostic algorithm for these digitate keratoses. A literature search using PubMed and MEDLINE was performed. This included the search terms "MMDH," "familial disseminated filiform hyperkeratosis," "punctate porokeratotic keratoderma," "disseminated spiked keratosis," "minute aggregate keratosis," "digitate keratosis," "conical keratosis," "hyperkeratotic spicules," and "music box spine dermatosis." Acase of MMDH in an 89-year-old woman is described. The digitate keratoses are presented alongside their synonymous terms and are divided into those that are generalized or localized using an algorithm. Separate disease entities are likely to arise within the digitate keratoses with increased reporting of immunohistochemical keratin analysis and molecular genetic studies. We report a new case of MMDH and provide a clinical approach to diagnosis of the digitate keratoses.

Trichodysplasia Spinulosa-A Rare Complication in Immunosuppressed Patients

Immunosuppression is necessary in a large number of conditions to modify immune responses and control disease severity. It is a vital part of treatment regimes following organ and bone marrow transplants. However, the use of immunosuppressive drugs has been shown to cause infections with common and unusual pathogens. We present the case of a 5-year-old female heart transplant recipient. Nine months after the transplant, she developed a tender acneiform eruption on her face consisting of numerous small yellowish to pink papules and pustules. Many of the lesions had a central, firm, small spinulous excrescence or a central dell. Histopathology demonstrated abnormal maturation of the hair follicles, nucleated eosinophilic cells with trichohyalin granules. The clinical presentation and histological features were in keeping with trichodysplasia spinulosa, a rare complication in immunosuppressed subjects. Treatment trials included reduction of immunosuppression combined with topical and oral retinoids, topical acyclovir, and oral valganciclovir with limited success.

Discovery of a New Human Polyomavirus Associated with Trichodysplasia Spinulosa in an Immunocompromized Patient

The Polyomaviridae constitute a family of small DNA viruses infecting a variety of hosts. In humans, polyomaviruses can cause infections of the central nervous system, urinary tract, skin, and possibly the respiratory tract. Here we report the identification of a new human polyomavirus in plucked facial spines of a heart transplant patient with trichodysplasia spinulosa, a rare skin disease exclusively seen in immunocompromized patients. The trichodysplasia spinulosa-associated polyomavirus (TSV) genome was amplified through rolling-circle amplification and consists of a 5232-nucleotide circular DNA organized similarly to known polyomaviruses. Two putative “early” (small and large T antigen) and three putative “late” (VP1, VP2, VP3) genes were identified. The TSV large T antigen contains several domains (e.g. J-domain) and motifs (e.g. HPDKGG, pRb family-binding, zinc finger) described for other polyomaviruses and potentially involved in cellular transformation. Phylogenetic analysis revealed a close relationship of TSV with the Bornean orangutan polyomavirus and, more distantly, the Merkel cell polyomavirus that is found integrated in Merkel cell carcinomas of the skin. The presence of TSV in the affected patient's skin was confirmed by newly designed quantitative TSV-specific PCR, indicative of a viral load of 105 copies per cell. After topical cidofovir treatment, the lesions largely resolved coinciding with a reduction in TSV load. PCR screening demonstrated a 4% prevalence of TSV in an unrelated group of immunosuppressed transplant recipients without apparent disease. In conclusion, a new human polyomavirus was discovered and identified as the possible cause of trichodysplasia spinulosa in immunocompromized patients. The presence of TSV also in clinically unaffected individuals suggests frequent virus transmission causing subclinical, probably latent infections. Further studies have to reveal the impact of TSV infection in relation to other populations and diseases.

Progressive trichodysplasia spinulosa in a patient with chronic lymphocytic leukaemia in remission

A 70-year old Caucasian man with chronic lymphocytic leukaemia developed trichodysplasia spinulosa 2 months after ceasing chemotherapy. Histological features characteristic to this condition include dilated and enlarged hair follicles, hyperplastic hair bulbs, hyperplasia of inner root sheath cells with numerous large, eosinophilic, trichohyaline granules, and hypercornification. Although he was in remission for chronic lymphocytic leukaemia, lesions were slowly progressive 15 months after cessation of chemotherapy. We also describe a painless pull-test where spicules can be easily plucked and assessed microscopically for inner root sheath keratinization, or observed with surface microscopy in a clinic setting.

Trichodysplasia Spinulosa: More Evidence Supporting a Viral Etiology

Trichodysplasia spinulosa is a facial dermatosis associated with immunosuppression and characterized by follicular-based spiny papules. Merging of the

Trichodysplasia spinulosa associated with chemotherapy for acute lymphocytic leukaemia

We report two boys with trichodysplasia spinulosa associated with chemotherapy for acute lymphocytic leukaemia. Trichodysplasia spinulosa is a cutaneous viral infection of immunosuppressed patients that causes abnormal hair follicle maturation. Our patients presented with widespread papules, some extruding a central keratin spicule, which were most prominent on the face. Histopathology demonstrated hair follicles dilated by a proliferation of large eosinophilic cells containing numerous abnormal trichohyaline granules. Electron microscopy in case 1 revealed 30-nm viral particles in the stratum corneum consistent with a papovavirus. In case 1, the eruption persisted despite topical salicyclic acid 4%, ammonium lactate 17.5%, tretinoin 0.05% and oral acitretin. However, it resolved once the patient's immune function returned to normal (total duration of 2 years). In case 2, the eruption spontaneously resolved after 9 months. This case report discusses the characteristic clinicopathological features of trichodysplasia spinulosa and, for the first time, follows the condition's natural history.

Virus-Associated Trichodysplasia Spinulosa

Virus-associated trichodysplasia spinulosa (VATS) is a cutaneous eruption of spiny papules predominantly affecting the face that is associated with a distinctive histologic picture of abnormally maturing anagen follicles with excessive inner root sheath differentiation and hyperkeratotic infundibula. Ultrastructurally, intranuclear viral particles consistent with polyoma virus are found. Only 2 patients have thus far been reported. Both had developed the eruption after a kidney transplant. We report 2 additional cases of VATS. One is an 8-year-old boy who presented with facial papules after a kidney transplant. The other is a 19-year-old man with a history of acute lymphocytic leukemia who never had a transplant. He developed a papular facial eruption as well as alopecia. Light microscopic and ultrastructural examinations revealed a spectrum in the severity of the histologic alterations as well as the number of intranuclear viral particles. This report expands the range of pathologic alterations associated with VATS and documents for the first time that it can affect patients without a solid organ transplant. The similarity of the clinical and histologic features of VATS with those previously reported by others as cyclosporine-induced "follicular dystrophy" or "pilomatrix dysplasia" raises the possibility that the described phenomena may reflect the same entity. Increased awareness of the distinct histologic picture associated with VATS will likely lead to more frequent diagnosis of this underrecognized entity.

Virus‐Associated Trichodysplasia Spinulosa

Background: Virus‐associated trichodysplasia spinulosa (VATD) is a relatively new entity associated with a distinctive histologic picture of distended follicles with excessive production of inner root sheath material. Only two patients have thus far been reported. Both had developed the condition after a kidney transplant. Observation: We report two additional cases of VATD. One is a nineteen year‐old man with a history of acute lymphocytic leukemia, who developed a papular facial eruption as well as madarosis. The other is a nine year‐old boy, who presented with facial papules after a kidney transplant. Histologic examination of both cases reveals characteristic findings for trichodysplasia spinulosa, but also indicates a spectrum of histologic alterations. Ultrastructural studies confirm the presence of a variable number of intranuclear viral particles. Conclusions: Our cases illustrate the histologic spectrum seen in association with VATD. The severity of histologic alterations corresponds to the viral load seen by electron microscopy. This report documents for the first time that VATD can be found in patients without a solid organ transplant. Increased awareness of the distinct histologic picture associated with VATD will likely lead to more frequent diagnosis of this under‐recognized entity.