Trichodysplasia spinulosa
Trichodysplasia spinulosa is a rare cutaneous condition that has been described almost exclusively in immunocompromised patients, usually organ transplant recipients, on regimens of immunosuppressive drugs. As of early 2016, a total of 32 cases had been reported in the medical literature. Despite its rarity, TS is believed to be underdiagnosed, and the growing population of patients on immunosuppressive drug regimens suggests its incidence may rise. TS has been described as an emerging infectious disease.
Symptoms and signs
The disease is characterized by flesh-colored to erythematous papules occurring in the central region of the face and sometimes elsewhere on the body, often accompanied by protrusive "spicules" or spines made of keratin and by alopecia of affected skin, typically the eyebrows and sometimes the eyelashes or scalp hairs. Pruritus has been described in about a third of reported cases. Facial papules are generally 1- to 3-mm in size. The condition is considered to be benign, but can be disfiguring; the spines are often prominent, and in later stages the affected facial skin thickens noticeably.Causes
TS has been reported almost exclusively in immunocompromised patients, primarily organ transplant recipients on regimens of immunosuppressive drugs, and also in patients with hematolymphoid malignancies. As of 2016 there were no case reports in the literature describing cases of TS in patients with HIV-AIDS.There is compelling evidence that trichodysplasia spinulosa is caused by a polyomavirus called trichodysplasia spinulosa polyomavirus or Human polyomavirus 8. There is evidence that exposure to the virus is common among healthy adults; estimates of seroprevalence in immunocompetent adults range from 70 to 80% in different sample populations. TSPyV infects the skin, but viral DNA is rarely detectable there in asymptomatic individuals even if they possess antibodies to the virus indicating exposure. It is not known whether TS represents new primary infection or opportunistic reactivation of a latent infection.
Mechanism
The hyperproliferation of keratinocyte inner root sheath cells in which large aggregates of viral particles can be found suggests that TSPyV actively replicates in these cells. This is thought to underlie the clinical manifestations of TS. However, the precise mechanism is not well characterized. There is limited evidence implicating the large tumor antigen as responsible for inducing cellular proliferation through pathways involving phosphorylated retinoblastoma protein.Diagnosis
TS can be diagnosed based on clinical observations, but is usually confirmed by histopathology of a lesional biopsy or a plucked spicule. Characteristic histological findings include enlarged and abnormally organized hair follicles and hyperproliferation of inner root sheath cells containing large eosinophilic trichohyalin granules. Antibodies against major capsid protein VP1, the major component of the viral capsid, can be used to confirm the presence of viral particles in cell nuclei. Electron microscopy can also be used to detect viral particles. Quantification of viral load can be performed using quantitative PCR, as affected skin demonstrates much higher viral loads compared to unaffected skin or to asymptomatic individuals who test positive for viral DNA.Differential diagnosis includes other visually similar conditions affecting the hair follicles, many of which appear as drug side effects. A proposed classification system lists TS as one of a group of cutaneous conditions with similar manifestations and distinct etiologies, collectively called the digitate keratoses. Although confirmed TS is rare, the condition is thought to be underdiagnosed.