PEDIATRIC DERMATOLOGY PHOTOQUIZ Editor: Antonio Torrelo, M.D.
LONG-STANDING SPICULES IN A PATIENT WITH ACUTE LYMPHOBLASTIC LEUKEMIA Lucia Seminario-Vidal, M.D., Ph.D., James D. Jensen, M.D., Katherine Fening, M.D., Kristopher McKay, M.D., Craig Elmets, M.D., and Amy Theos, M.D. Department of Dermatology, University of Alabama at Birmingham, Birmingham, Alabama
Case Report
What is the diagnosis?
A 6-year-old boy with a history of acute lymphoblastic leukemia (ALL) and a seizure disorder presented with a nonpruritic, nonpainful eruption on his face and body. The lesions had first appeared on his face approximately 4 years before evaluation and slowly spread to involve the rest of his body. He had completed a chemotherapeutic regimen consisting of vincristine, methotrexate, mercaptopurine, and cytarabine 4 months previously. At the time he was seen, his medications included levetiracetam and lacosamide. Although his family indicated that the eruption had seemed to improve slightly as his methotrexate dose had been decreased, they also reported no further improvement after chemotherapy was discontinued. They also noted that his skin lesions improved significantly when he was on a course of acyclovir for herpes labialis. On physical examination, there were multiple filiform, folliculocentric, skin-colored papules with keratin spines, predominantly on the face (Fig. 1) but also scattered over much of the rest of body. His eyebrows were sparse and he had a bulbous nose. No lymphadenopathy was found. Histologic findings from a biopsy specimen are shown in Fig. 2.
Figure 1. Scattered hyperkeratotic, folliculocentric, skin-colored papules with white spicules on the face.
© 2015 Wiley Periodicals, Inc.
Figure 2. Prominent dilated inner root sheath cells with homogeneous eosinophilic cytoplasmic inclusion bodies and basophilic intranuclear inclusions (hematoxylin and eosin, original magnification 2009).
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546 Pediatric Dermatology Vol. 32 No. 4 July/August 2015
Diagnosis: Trichodysplasia Spinulosa
Laboratory Findings and Clinical Course A punch biopsy of the left leg revealed a mild superficial perivascular lymphocytic infiltrate with prominent dilated follicular structures in the deep dermis. Within these follicles, the inner root sheath exhibited homogeneous eosinophilic cytoplasmic inclusion bodies and basophilic intranuclear inclusions. Laboratory tests including complete blood count and complete metabolic panel were within normal limits. The patient’s clinical picture, histopathology, and laboratory findings were consistent with a diagnosis of trichodysplasia spinulosa (TS). The patient received oral acyclovir, resulting in significant improvement after 1 month of treatment.
Discussion TS is a rare skin disease that Izakovic et al (1) first reported in 1995. A viral etiology was suggested in 1999, and the term trichodysplasia spinulosa was introduced when intracellular viral particles were identified in skin lesions using electron microscopy (2). Approximately 30 cases of TS have been reported using different names for the same condition (e.g., pilomatrix dysplasia, cyclosporine-induced folliculodystrophy, virus-associated trichodysplasia). It has been primarily described in immuno suppressed individuals, including transplant recipients (1–5), individuals receiving chemotherapy for leukemia and lymphoma (4,6–8), and in a patient treated with vismodigib for Gorlin syndrome (9). A TS-associated polyomavirus (TSPyV), which infects the nuclei of inner root sheath cells, causes TS (3,4). TSPyV seroprevalence is approximately 70% in the general population and is 100% in patients with TS (4). It has been suggested that exposure to the virus occurs at a very young age and that lymphoid tissue acts as a latency site (10). Clinically TS presents with folliculocentric papules with keratin spines known as spicules. It mainly affects the central face and in some cases can cause alopecia of hairbearing parts of the face and disfiguring lesions such as leonine facies. The lesions are typically asymptomatic, although symptoms of mild pruritus, burning, or tingling have been reported. Histopathologically, specimens demonstrate abnormal maturation of hair follicles with inner root sheath differentiation containing excessive amounts of trichohyalin and intraepithelial viral inclusions. The differential diagnosis includes follicular spicules in multiple
myeloma, which it has been suggested has a viral etiology that is not due to a polyomavirus (11). TS can be difficult to treat. Various antiviral treatments have been tried, along with reduction of immunosuppression. Effective reported therapies include topical cidofovir (6) and oral valganciclovir (5,8). Topical acyclovir, topical imiquimod, topical keratolytics, oral or topical retinoids, and oral valacyclovir have also been used with varying degrees of success (1–10). We aim to raise awareness of TS because TSPyV seroprevalence is frequent in healthy populations and dermatologists are seeing increasing numbers of immunocompromised patients.
References 1. Izakovic J, Buchner SA, Duggelin M et al. [Hair-like hyperkeratoses in patients with kidney transplants. A new cyclosporin sideeffect]. Hautarzt 1995;46:841–846. 2. 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;4:268–271. 3. Elaba Z, Hughey L, Isayeva T et al. Ultrastructural and molecular confirmation of the trichodysplasia spinulosa-associated polyomavirus in biopsies of patients with trichodysplasia spinulosa. J Cutan Pathol 2012;39:1004–1009. 4. Kazem S, van der Meijden E, Kooijman S et al. Trichodysplasia spinulosa is characterized by active polyomavirus infection. J Clin Virol 2012;53:225–230. 5. Holzer AM, Hughey LC. Trichodysplasia of immunosuppression treated with oral valganciclovir. J Am Acad Dermatol 2009;60:169–172. 6. Wanat KA, Holler PD, Dentchev T et al. Viral-associated trichodysplasia: characterization of a novel polyomavirus infection with therapeutic insights. Arch Dermatol 2012;148:219–223. ~oz C, Gonza lez-Vilas D, Sa nchez-Aguilar D et al. 7. Celeiro-Mun Viral-associated trichodysplasia secondary to antineoplastic treatment in a patient with lymphoblastic leukemia. Am J Dermatopathol 2014;36:e105–e107. 8. Benoit T, Bacelieri R, Morrell DS et al. Viral-associated trichodysplasia of immunosuppression: report of a pediatric patient with response to oral valganciclovir. Arch Dermatol 2010;146:871–874. 9. Richey JD, Graham TA, Katona T et al. Development of trichodysplasia spinulosa: case report of a patient with Gorlin syndrome treated with vismodegib. JAMA Dermatol 2014; 150:1016–1018. 10. Sadeghi M, Aaltonen LM, Hedman L et al. Detection of TS polyomavirus DNA in tonsillar tissues of children and adults: evidence for site of viral latency. J Clin Virol 2014;59:55–58. 11. van Boheemen S, Jones T, Muhlemann B et al. Cidofovir gel as treatment of follicular spicules in multiple myeloma. JAMA Dermatol 2015;151:82–84.
Address correspondence to Amy Theos, M.D., Children’s South Specialty Clinic, 1940 Elmer J. Bissell Road, Birmingham, AL 35243, or e-mail: [email protected].
LONG-STANDING SPICULES IN A PATIENT WITH ACUTE LYMPHOBLASTIC LEUKEMIA Lucia Seminario-Vidal, M.D., Ph.D., James D. Jensen, M.D., Katherine Fening, M.D., Kristopher McKay, M.D., Craig Elmets, M.D., and Amy Theos, M.D. Department of Dermatology, University of Alabama at Birmingham, Birmingham, Alabama
Case Report
What is the diagnosis?
A 6-year-old boy with a history of acute lymphoblastic leukemia (ALL) and a seizure disorder presented with a nonpruritic, nonpainful eruption on his face and body. The lesions had first appeared on his face approximately 4 years before evaluation and slowly spread to involve the rest of his body. He had completed a chemotherapeutic regimen consisting of vincristine, methotrexate, mercaptopurine, and cytarabine 4 months previously. At the time he was seen, his medications included levetiracetam and lacosamide. Although his family indicated that the eruption had seemed to improve slightly as his methotrexate dose had been decreased, they also reported no further improvement after chemotherapy was discontinued. They also noted that his skin lesions improved significantly when he was on a course of acyclovir for herpes labialis. On physical examination, there were multiple filiform, folliculocentric, skin-colored papules with keratin spines, predominantly on the face (Fig. 1) but also scattered over much of the rest of body. His eyebrows were sparse and he had a bulbous nose. No lymphadenopathy was found. Histologic findings from a biopsy specimen are shown in Fig. 2.
Figure 1. Scattered hyperkeratotic, folliculocentric, skin-colored papules with white spicules on the face.
© 2015 Wiley Periodicals, Inc.
Figure 2. Prominent dilated inner root sheath cells with homogeneous eosinophilic cytoplasmic inclusion bodies and basophilic intranuclear inclusions (hematoxylin and eosin, original magnification 2009).
545
546 Pediatric Dermatology Vol. 32 No. 4 July/August 2015
Diagnosis: Trichodysplasia Spinulosa
Laboratory Findings and Clinical Course A punch biopsy of the left leg revealed a mild superficial perivascular lymphocytic infiltrate with prominent dilated follicular structures in the deep dermis. Within these follicles, the inner root sheath exhibited homogeneous eosinophilic cytoplasmic inclusion bodies and basophilic intranuclear inclusions. Laboratory tests including complete blood count and complete metabolic panel were within normal limits. The patient’s clinical picture, histopathology, and laboratory findings were consistent with a diagnosis of trichodysplasia spinulosa (TS). The patient received oral acyclovir, resulting in significant improvement after 1 month of treatment.
Discussion TS is a rare skin disease that Izakovic et al (1) first reported in 1995. A viral etiology was suggested in 1999, and the term trichodysplasia spinulosa was introduced when intracellular viral particles were identified in skin lesions using electron microscopy (2). Approximately 30 cases of TS have been reported using different names for the same condition (e.g., pilomatrix dysplasia, cyclosporine-induced folliculodystrophy, virus-associated trichodysplasia). It has been primarily described in immuno suppressed individuals, including transplant recipients (1–5), individuals receiving chemotherapy for leukemia and lymphoma (4,6–8), and in a patient treated with vismodigib for Gorlin syndrome (9). A TS-associated polyomavirus (TSPyV), which infects the nuclei of inner root sheath cells, causes TS (3,4). TSPyV seroprevalence is approximately 70% in the general population and is 100% in patients with TS (4). It has been suggested that exposure to the virus occurs at a very young age and that lymphoid tissue acts as a latency site (10). Clinically TS presents with folliculocentric papules with keratin spines known as spicules. It mainly affects the central face and in some cases can cause alopecia of hairbearing parts of the face and disfiguring lesions such as leonine facies. The lesions are typically asymptomatic, although symptoms of mild pruritus, burning, or tingling have been reported. Histopathologically, specimens demonstrate abnormal maturation of hair follicles with inner root sheath differentiation containing excessive amounts of trichohyalin and intraepithelial viral inclusions. The differential diagnosis includes follicular spicules in multiple
myeloma, which it has been suggested has a viral etiology that is not due to a polyomavirus (11). TS can be difficult to treat. Various antiviral treatments have been tried, along with reduction of immunosuppression. Effective reported therapies include topical cidofovir (6) and oral valganciclovir (5,8). Topical acyclovir, topical imiquimod, topical keratolytics, oral or topical retinoids, and oral valacyclovir have also been used with varying degrees of success (1–10). We aim to raise awareness of TS because TSPyV seroprevalence is frequent in healthy populations and dermatologists are seeing increasing numbers of immunocompromised patients.
References 1. Izakovic J, Buchner SA, Duggelin M et al. [Hair-like hyperkeratoses in patients with kidney transplants. A new cyclosporin sideeffect]. Hautarzt 1995;46:841–846. 2. 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;4:268–271. 3. Elaba Z, Hughey L, Isayeva T et al. Ultrastructural and molecular confirmation of the trichodysplasia spinulosa-associated polyomavirus in biopsies of patients with trichodysplasia spinulosa. J Cutan Pathol 2012;39:1004–1009. 4. Kazem S, van der Meijden E, Kooijman S et al. Trichodysplasia spinulosa is characterized by active polyomavirus infection. J Clin Virol 2012;53:225–230. 5. Holzer AM, Hughey LC. Trichodysplasia of immunosuppression treated with oral valganciclovir. J Am Acad Dermatol 2009;60:169–172. 6. Wanat KA, Holler PD, Dentchev T et al. Viral-associated trichodysplasia: characterization of a novel polyomavirus infection with therapeutic insights. Arch Dermatol 2012;148:219–223. ~oz C, Gonza lez-Vilas D, Sa nchez-Aguilar D et al. 7. Celeiro-Mun Viral-associated trichodysplasia secondary to antineoplastic treatment in a patient with lymphoblastic leukemia. Am J Dermatopathol 2014;36:e105–e107. 8. Benoit T, Bacelieri R, Morrell DS et al. Viral-associated trichodysplasia of immunosuppression: report of a pediatric patient with response to oral valganciclovir. Arch Dermatol 2010;146:871–874. 9. Richey JD, Graham TA, Katona T et al. Development of trichodysplasia spinulosa: case report of a patient with Gorlin syndrome treated with vismodegib. JAMA Dermatol 2014; 150:1016–1018. 10. Sadeghi M, Aaltonen LM, Hedman L et al. Detection of TS polyomavirus DNA in tonsillar tissues of children and adults: evidence for site of viral latency. J Clin Virol 2014;59:55–58. 11. van Boheemen S, Jones T, Muhlemann B et al. Cidofovir gel as treatment of follicular spicules in multiple myeloma. JAMA Dermatol 2015;151:82–84.
Address correspondence to Amy Theos, M.D., Children’s South Specialty Clinic, 1940 Elmer J. Bissell Road, Birmingham, AL 35243, or e-mail: [email protected].
