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Specific Detection of Trichodysplasia Spinulosa–Associated Polyomavirus DNA in Skin and Renal Allograft Tissues in a Patient With Trichodysplasia Spinulosa

Max K. Fischer, MD, MPH; Grace F. Kao, MD; Harrison P. Nguyen; Cinthia B. Drachenberg, MD; Peter L. Rady, MD, PhD; Stephen K. Tyring, MD, PhD, MBA; Anthony A. Gaspari, MD
Arch Dermatol. 2012;148(6):726-733. doi:10.1001/archdermatol.2011.3298.
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Background  Trichodysplasia spinulosa (TS) is a rare, disfiguring skin condition that affects immunosuppressed patients, universally involving the central face. New data point to the recently discovered TS-associated polyomavirus (TSPyV) as the causative agent.

Observations  We report a case of TS in a 48-year-old African American man after renal transplant; via polymerase chain reaction and sequencing, confirm the detection of TSPyV in lesional skin; and report the novel detection of TSPyV DNA in renal allograft tissue. Results of polymerase chain reaction analysis were negative for Merkel cell polyomavirus in lesional skin. Fifteen months later, urine cytologic findings showed morphologic evidence of a urinary tract polyomavirus infection. Results of SV40 immunohistochemical analysis were negative in lesional skin, renal allograft, and urine specimens.

Conclusions  To our knowledge, this is the first reported case in which TSPyV DNA has been detected in extracutaneous tissues and the third with combined ultrastructural and molecular confirmation of the presence of TSPyV in lesional skin. Lack of detection of other pathogenic human polyomaviruses in this patient's skin supports the specific role of this polyomavirus in the genesis of TS. Further basic science studies are needed to determine the exact pathomechanisms of this polyomavirus and to explore possible tumorigenic roles in other skin diseases.

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Figure 1. Folliculocentric trichodysplasia spinulosa lesions involving the central face accompanied by diffuse skin thickening. Some lesions, particularly those on the nose, exhibit spiny excrescences.

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Figure 2. Light and electron microscopic examination findings in the patient with trichodysplasia spinulosa. A, Dilated hair follicles without hair shafts demonstrate hyperplasia of the inner root-sheath cells (hematoxylin-eosin, original magnification ×40). B, A sparse lymphocytic interface dermatitis and focal perifolliculitis involve the infundibular portions of intervening vellus hair follicles, associated with incontinence of melanin pigment (hematoxylin-eosin, original magnification ×100). C, Inner root-sheath cells contain enlarged, deeply eosinophilic trichohyalin granules (hematoxylin-eosin, original magnification ×400). D, Transmission electron microscopy of an inner root-sheath keratinocyte demonstrates intranuclear viral inclusions composed of nonenveloped, icosahedral viral particles measuring 33 to 38 nm in diameter and enlarged cytoplasmic trichohyalin granules (uranyl acetate and lead citrate, original magnification ×15 000).

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Figure 3. Urine cytologic and immunohistochemical analysis findings in the patient with trichodysplasia spinulosa. A, Isolated polyomavirus (PyV)–infected cells with enlarged, round, hyperchromatic, smudgy nuclei (decoy cells) seen on urine cytologic examination more than 1 year after the patient's dermatologic presentation (Papanicolaou, original magnification ×400). B, An SV40 immunostain fails to reveal evidence of BKPyV or JCPyV infection; the positive control (inset) shows strong nuclear staining (SV40, original magnification ×400).

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Figure 4. Results of DNA analysis in the patient with trichodysplasia spinulosa (TS). A, Detection of TS-associated polyomavirus (TSPyV) DNA and absence of Merkel cell PyV (MCPyV) DNA by means of polymerase chain reaction (PCR) analysis in a TS lesion. For TSPyV detection, lane M contains fX174RF DNA marker (Promega Corporation); lane 1, TS lesion; lane 2, TSPyV negative control DNA extracted from peripheral blood mononuclear cells (PBMCs) (Promega Corporation); and lane 3, reagent control. In lane 1, an expected 597–base pair (bp) TSPyV-PCR product can be seen. For MCPyV detection, lane M contains fX174RF DNA marker (Promega Corporation); lane 1, TS lesion; lane 2, MCPyV positive control (plasmid with MCPyV DNA insert from small T antigen viral gene); lane 3, MCPyV negative control DNA extracted from PBMCs (Promega Corporation); and lane 4, reagent control. No MCPyV-PCR product was detected in lane 1 (TS lesion). In lane 2 (positive control), the expected 150-bp MCPyV-PCR fragment can be seen. B, Detection of TSPyV DNA by PCR in a renal allograft biopsy specimen from the TS patient. Lane M contains fX174RF DNA marker (Promega Corporation); lane 1, kidney biopsy specimen; lane 2, TSPyV negative control DNA extracted from PBMCs (Promega Corporation); lane 3, positive control, cloned DNA of TSPyV small T gene; and lane 4, reagent control. In lanes 1 and 3, the expected 597-bp TSPyV-PCR product can be seen.

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