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Background: Human papillomavirus (HPV) infec- Conclusions: The severe disfigurement of this patient
tions cause a spectrum of clinical disease states, depend- was a result of an underlying severe immunodeficiency,
ing on the causative HPV and the characteristics of the permissive for a disseminated HPV-2 infection that was
infected host, especially the status of cell-mediated im- allowed to progress for many years before the initiation
munity. Generalized verrucosis is an unusual clinical pre- of therapy. Such a rare case illustrates the natural his-
sentation of a disseminated HPV infection associated with tory of generalized verrucosis in the setting of severe im-
severe immunodeficiency status. munodeficiency in the absence of sustained medical in-
terventions. Medical and surgical treatments resulted in
marked improvement in the general health of this pa-
Observations: We present a case of extreme disfigure-
tient, as well as improvement of the disfigurement that
ment associated with an HPV-2 (common wart virus) in- resulted from the generalized verrucosis.
fection. Virologic studies, immune status of the patient,
and treatment(s) are summarized. Arch Dermatol. 2010;146(1):69-73
G
ENERALIZED VERRUCOSIS IS extraction kit (Qiagen, Valencia, California).
a term used to describe The quality of the DNA extracted for polymer-
widespread human ase chain reaction (PCR) procedures was as-
papillomavirus (HPV) in- sessed by amplification of the reference con-
trol gene -globin.7
fections. A variety of
disease states can result in such severe, po-
Author Affiliations: tentially disfiguring infections. General- HPV TYPING BY PCR
Departments of Internal ized verrucosis is observed in patients with AND SEQUENCING
Medicine (Dr Alisjahbana), underlying immunodeficiency status that are
Dermatovenereology either acquired (for example, AIDS or im- The HPV PCR amplification was performed by
(Drs Dinata and Sutedja), munosuppression associated with organ means of 2 degenerate consensus primers,
Anatomical Pathology transplantation) 1,2 or rare congenital termed CP65 and CP70, with annealing sites
(Dr Suryahudaya), Plastic located in the L1 open reading frame.8 Analy-
immunodeficiency syndromes (eg, epider-
Surgery (Dr Soedjana), sis isolation, cloning, and sequencing of puta-
Orthopaedics and Traumatology modysplasia verruciformis;3 warts, hypo-
gammaglobulinemia, infections, and myelo- tive HPV PCR products were performed as de-
(Dr Hidajat), Radiology scribed previously.8 The obtained putative HPV
(Dr Soetikno), and kathexis [WHIM] syndrome;4 combined
sequences were aligned and compared with
Anesthesiology and Reanimation immunodeficiencies;5 and cyclic neutrope- known HPV types available through the Gen-
(Dr Oktaliansah), Medical nia associated with chronic lymphopenia).6 Bank database by means of the Basic Local
Faculty, Padjadjaran University, We report a case of generalized verrucosis Alignment Search Tool (BLAST) program (Na-
Dr Hasan Sadikin Hospital, secondary to an HPV-2 infection that re- tional Center for Biotechnology Information,
Bandung, Indonesia; sulted in severe disfigurement. The under- National Institutes of Health, Bethesda,
Department of Pathology, lying idiopathic CD4 lymphopenia re- Maryland).9
University of Massachusetts,
sulted in susceptibility to the generalized
Worcester (Dr Deng);
Departments of Dermatology verrucosis. The resulting skin disease was REPORT OF A CASE
(Drs Rady and Tyring), untreated for almost 10 years, which re-
Microbiology/Molecular sulted in progressive, severe disfigure- The patient is a 39-year-old Indonesian
Genetics (Dr Tyring), and ment, including massive cutaneous horns. man who was in good health until the age
Internal Medicine (Dr Tyring), of 15 years, when a warty lesion ap-
The University of Texas Health METHODS peared on his knee. During the next 8
Science Center, Houston; and
Departments of Dermatology years, the skin lesions had spread over his
and Microbiology/Immunology, DNA EXTRACTION entire skin surface and prevented him from
School of Medicine, University working. At the age of 26 years (1994), he
of Maryland, Baltimore From 3 wart biopsy specimens taken from the was evaluated and treated by a dermatolo-
(Dr Gaspari). patient, DNA was extracted by means of a DNA gist in Bandung for almost 2 years, who
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603 bp
452 bp
310 bp
310 bp
268 bp
234 bp
treated with combination antimicrobial therapy (rif- The patient described in this report has severe immuno-
ampin, isoniazid, ethambutol hydrochloride, and cipro- deficiency syndrome characterized by a chronic CD4
floxacin). He also was diagnosed as having inactive hepa- T lymphocytopenia. This patient meets the Centers for
titis B infection. He also had an episode of herpes zoster Disease Control and Prevention criteria for this syn-
that resolved without sequelae. His major laboratory find- drome because he lacked serologic or virologic evi-
ings are summarized in Table 2 and Table 3. Of note dence of HIV-1 or HIV-2 infection, had a CD4 cell count
was a chronic CD4 lymphopenia (absolute CD4 cell count, of approximately 300/L on at least 2 occasions, had an
314/L; reference range at reference laboratory, 410- abnormally low CD4/CD8 ratio, and exhibited disease in-
1590/L), which was found to be reproducible when these dicative of impaired cellular immunity (generalized ver-
cell marker studies were performed on a number of sepa- rucosis caused by HPV-2).13,14 It is noteworthy that the
rate occasions over time (not shown). CD4 lymphopenia of this patient persisted after he was
For the treatment of his cutaneous HPV infection, he successfully treated for pulmonary tuberculosis, which
underwent a series of surgical procedures. First, the cu- itself can be a cause of transient CD4 lymphopenias.15 A
taneous horns were debrided using a bone saw with the variety of opportunistic and atypical bacterial, viral, fun-
patient under general anesthesia. Since the debride- gal, and protozoal infections can occur in patients with
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Position Prototype Isolate 1a Clones 1, 2, and 3b Position Prototype Isolate 1 a Clones 1, 2, and 3 b
3037 TTA TCA 118 L S
3387 TCA CCA 235 S P
3543 TAC CAC 287 Y H
3561 AGT CGT 293 S R
3765 TAC CAC 361 Y Ha
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