What Explains a Man’s Papular Eruption and Madarosis After Cardiac Transplant?

Ajay Amarnani, MD; Paul Wirth, BS; and Thomas Helm, MD

A 70-year-old man presented with a 1-month history of a progressing, pruritic, papular eruption on his ears, neck, glabella, eyebrows, and eyelids. His medical history was significant for undergoing cardiac transplant 15 months prior, secondary to cardiomyopathy. His antirejection medication regimen consisted of mycophenolate mofetil and tacrolimus.

follicular-based papular eruption

follicular-based papular eruption

Physical examination revealed a follicular-based papular eruption, most prominent on the man’s neck, ears, and central face, including the eyebrows, glabella, eyelids, nose, nasolabial folds, and cutaneous lips (Figures 1 and 2). A loss of eyebrows and eyelashes (madarosis) was noted. Papules on the neck and ears featured central hyperkeratosis. There was no evidence of vesicle or pustule formation.

Punch biopsies of papules on the ear were performed, the results of which are shown in Figures 3 and 4.

biopsies of papules

What is causing this man’s skin eruption and madarosis?

  1. Papular mucinosis
  2. Trichodysplasia spinulosa
  3. Cowden disease
  4. Spiny keratoderma

Answer on next page.

follicular-based papular eruption

Answer: Trichodysplasia Spinulosa

The patient was started on a prednisone taper at the time of his initial presentation, which decreased the pruritus. At follow-up, the prednisone was tapered, and the patient was prescribed topical cidofovir cream, 3%, for 6 cycles of daily application for 5 days, with 7 days off.


Trichodysplasia spinulosa (previously referred to as pilomatrix dysplasia of immunosuppression, cyclosporine-induced folliculodystrophy, spiny hyperkeratosis, and viral-associated trichodysplasia) occurs in the setting of immunosuppression in solid organ transplant or lymphocytic leukemia. Reports of the condition developing after treatment with cyclosporine, tacrolimus, azathioprine, prednisone, mycophenolate mofetil, rituximab, fludarabine, intravenous immunoglobulin A, and vincristine have been documented.1

Characteristic findings include follicular papules, often with white spinous processes, affecting the central face, ears, neck and, less commonly, the trunk and extremities. The eruption often is accompanied by madarosis.

In 2010, the trichodysplasia spinulosa-associated polyomavirus (TSPyV) was identified in lesional skin.2 Human polyomaviruses are ubiquitous, with an overall seroprevalence of approximately 70% in the general population and 89% in kidney transplant patients.3 Human polyomaviruses are implicated in BKPyV-associated nephropathy and hemorrhagic cystitis, progressive multifocal leukoencephalopathy, Merkel cell carcinoma, and trichodysplasia spinulosa.4 Recent investigation into pathogenesis has revealed that TSPyV increases cell proliferation via increased phosphorylated pRB, p16, and p21 proteins.5 The high seroprevalence of TSPyV in the general population suggests the role of immunosuppression in clinical manifestation of the virus.

Trichodysplasia spinulosa is characterized by enlarged anagen-phase follicles with prominent trichohyalin granules in cells of the inner root sheath.6 Absence of a hair papilla and abrupt cornification of the inner root sheath cells are additional associated features.6 Electron microscopy often reveals icosahedral viral particles in nuclei and cytoplasm of the affected inner root sheath cells and also may be found in follicular extracellular keratotic debris.7 In the setting of immunosuppression with characteristic clinical and histopathologic findings, identification of the virus is not a requisite for diagnosis.

A very similar clinical presentation can be seen in the follicular spicules of multiple myeloma, and this condition must be considered in the differential diagnosis. To date, TSPyV has not been identified in lesional skin; however, low levels of Merkel cell polyomavirus have been identified.8 Whether the presence of the virus is causative or coincidental has been debated, and the accumulation of immunoglobulin dysprotein is favored over a viral cause.9 Other conditions in the differential diagnosis include multiple minute digitate hyperkeratosis, lichen spinulosus, spiny keratoderma, and papular mucinosis. In solid organ recipients, graft-vs-host disease commands consideration; however, the clinical and histologic findings are distinct.

Consistent with a viral etiology, treatment with compounded topical cidofovir, 1% to 3%, or oral valganciclovir hydrochloride has shown success.1 No guidelines for therapy exist, but a double-blind study investigating cidofovir gel, 1%, for treatment of human papillomavirus demonstrated a good safety profile when applied once daily for 5 consecutive days, every other week, for a maximum of 6 cycles.10 Success with once daily or twice daily application also has been reported.1,2 The most frequently reported adverse effects were pain, pruritus, and rash at the application site.10 Reducing immunosuppression led to clinical improvement in one case; however, this often is not practical in organ recipients.4 Topical and oral retinoids, topical tacrolimus, topical and oral antibiotics, imiquimod cream, keratolytics, and benzoyl peroxide have proven ineffective.1

As solid organ transplantation continues to advance and increase in frequency, it is imperative that health care providers recognize the dermatoses associated with immunosuppression. Follicular spicules of the central face accompanied by madarosis in an immunosuppressed patient should raise concern for trichodysplasia spinulosa. A similar presentation in a patient not on immune suppression therapy should raise concern for underlying multiple myeloma.

The author discusses the case in this podcast:

Ajay Amarnani, MD, is in the Department of Dermatology at the Jacobs School of Medicine and Biomedical Sciences at the University at Buffalo, New York.

Paul Wirth, BS, is a student at the Jacobs School of Medicine and Biomedical Sciences at the University at Buffalo, New York.

Thomas Helm, MD, is in the Department of Dermatology at the Jacobs School of Medicine and Biomedical Sciences at the University at Buffalo, New York.


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