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Observation
September 2014

Development of Trichodysplasia SpinulosaCase Report of a Patient With Gorlin Syndrome Treated With Vismodegib

Author Affiliations
  • 1Department of Pathology, Indiana University School of Medicine, Indianapolis
  • 2Department of Dermatology, Indiana University School of Medicine, Indianapolis
  • 3Richard L. Roudebush Veteran’s Affairs Medical Center, Indianapolis, Indiana
JAMA Dermatol. 2014;150(9):1016-1018. doi:10.1001/jamadermatol.2013.9322

Vismodegib is approved by the US Food and Drug Administration for the treatment of unresectable basal cell carcinoma (BCC) as well as for Gorlin syndrome (basal cell nevus syndrome).1,2

Report of a Case

A man in his 40s with Gorlin syndrome had been treated with vismodegib (150 mg/d) for multiple, symptomatic, large BCCs. Within 3 months of starting this treatment, he developed multiple erythematous, exquisitely tender, pruritic perioral papules with white spicules (Figure, A). Topical clotrimazole and betamethasone were prescribed by an outside hospital, neither of which improved his condition.

Figure.
Clinical and Pathologic Images of a Patient With Gorlin Syndrome
Clinical and Pathologic Images of a Patient With Gorlin Syndrome

A, Tender perioral folliculocentric erythematous papules with firm white spicules; arrowheads mark white spicules, which represent early lesions. B, Trichodysplasia spinulosa, dilated and disorganized inner root sheath cells with cytoplasmic distensions showing both enlarged trichohyalin granules and central accumulations of parakeratotic debris.

Two weeks later he presented to the dermatology department, where he underwent a punch biopsy of a papule with a central hornlike projection. Histopathologic analysis revealed hair follicles with abnormally large trichohyalin granules within inner root sheath epithelium (Figure, B), consistent with virus-associated trichodysplasia spinulosa. Electron microscopy was attempted, but all lesional tissue was already exhausted. This rare entity is thought to be due to an associated polyomavirus and has only been reported in immunosuppressed patients. This patient’s medical history was negative for immunosuppression, including any potential medications. His complete blood cell count (with differential) and complete metabolic panel were both unremarkable. A human immunodeficiency screen was also nonreactive.

Topical clotrimazole and betamethasone treatments were discontinued. There was discussion of other treatment options: pausing the vismodegib therapy; beginning a course of valacyclovir, topical imiquimod or tretinoin; performing chemical peels or laser epilation. He was eventually given valacyclovir, which did not improve his condition over the few weeks he took it. Four months after developing the eruption, he agreed to try topical imiquimod, which only mildly improved his condition. The patient soon after decided to stop his vismodegib therapy, and approximately 1 month later, he began to see much improvement in his condition. On a return visit to the clinic, he had grown a beard without the formation of new spicules. He did not resume his vismodegib regimen for another 2 to 3 months, but within 2 weeks of restarting that therapy, the papules recurred. At last follow-up, pulse dosing was considered, as was imiquimod and cidofovir.

Discussion

Those with Gorlin (aka basal cell nevus) syndrome, an autosomal dominant familial syndrome, have a propensity of developing multiple BCCs early on. In 40% to 80% of cases, there is the induction of a constitutively active hedgehog pathway secondary to a heterozygous mutation in the tumor suppressor PTCH1.3 This leads to a deregulation of SMO, which allows for transactivation of downstream GLI1 responsive elements. Field treatment with photodynamic therapy or targeted systemic therapy, such as vismodegib, may be required when numerous lesions develop.

Trichodysplasia spinulosa, aka virus-associated trichodysplasia, was first recognized in a patient taking cyclosporine after visceral transplant, and few cases have since been reported.4 A human polyomavirus associated with trichodysplasia spinulosa (TSPyV) has been characterized.5

We describe herein, for the first time to our knowledge, a patient with Gorlin syndrome who developed perioral trichodysplasia spinulosa while undergoing treatment with vismodegib. Stopping the vismodegib therapy for 1 month led to resolution of this painful and disfiguring eruption. Rechallenge resulted in recurrence within 2 weeks. The link between vismodegib and trichodysplasia spinulosa is unclear at this time, since our patient does not appear to be immunosuppressed.

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Article Information

Corresponding Author: Justin D. Richey, MD, Department of Pathology, Indiana University School of Medicine, 350 W 11th St, Indianapolis, IN 46202 (jdrichey@iupui.edu).

Published Online: July 23, 2014. doi:10.1001/jamadermatol.2013.9322.

Conflict of Interest Disclosures: None reported.

Additional Information: Drs Richey and Graham contributed equally to this article.

References
1.
Axelson  M, Liu  K, Jiang  X,  et al.  U.S. Food and Drug Administration approval: vismodegib for recurrent, locally advanced, or metastatic basal cell carcinoma. Clin Cancer Res. 2013;19(9):2289-2293.
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Tang  JY, Mackay-Wiggan  JM, Aszterbaum  M,  et al.  Inhibiting the hedgehog pathway in patients with the basal-cell nevus syndrome. N Engl J Med. 2012;366(23):2180-2188.
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Soufir  N, Gerard  B, Portela  M,  et al.  PTCH mutations and deletions in patients with typical nevoid basal cell carcinoma syndrome and in patients with a suspected genetic predisposition to basal cell carcinoma: a French study. Br J Cancer. 2006;95(4):548-553.
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Haycox  CL, Kim  S, Fleckman  P,  et al.  Trichodysplasia spinulosa: a newly described folliculocentric viral infection in an immunocompromised host. J Investig Dermatol Symp Proc. 1999;4(3):268-271.
PubMedArticle
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Matthews  MR, Wang  RC, Reddick  RL, Saldivar  VA, Browning  JC.  Viral-associated trichodysplasia spinulosa: a case with electron microscopic and molecular detection of the trichodysplasia spinulosa-associated human polyomavirus. J Cutan Pathol. 2011;38(5):420-431.
PubMedArticle
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