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Observation |

Disfiguring Generalized Verrucosis in an Indonesian Man With Idiopathic CD4 Lymphopenia FREE

Bachti Alisjahbana, MD; Rachmat Dinata, MD; Endang Sutedja, MD; Irene Suryahudaya, MD; Hardisiswo Soedjana, MD; Nucki N. Hidajat, MD; Rista D. Soetikno, MD; Ezra Oktaliansah, MD; April Deng, MD, PhD; Peter Rady, PhD; Stephen Tyring, MD, PhD; Anthony A. Gaspari, MD
[+] Author Affiliations

Author Affiliations: Departments of Internal Medicine (Dr Alisjahbana), Dermatovenereology (Drs Dinata and Sutedja), Anatomical Pathology (Dr Suryahudaya), Plastic Surgery (Dr Soedjana), Orthopaedics and Traumatology (Dr Hidajat), Radiology (Dr Soetikno), and Anesthesiology and Reanimation (Dr Oktaliansah), Medical Faculty, Padjadjaran University, Dr Hasan Sadikin Hospital, Bandung, Indonesia; Department of Pathology, University of Massachusetts, Worcester (Dr Deng); Departments of Dermatology (Drs Rady and Tyring), Microbiology/Molecular Genetics (Dr Tyring), and Internal Medicine (Dr Tyring), The University of Texas Health Science Center, Houston; and Departments of Dermatology and Microbiology/Immunology, School of Medicine, University of Maryland, Baltimore (Dr Gaspari).


Arch Dermatol. 2010;146(1):69-73. doi:10.1001/archdermatol.2009.330.
Text Size: A A A
Published online

Background  Human papillomavirus (HPV) infections cause a spectrum of clinical disease states, depending on the causative HPV and the characteristics of the infected host, especially the status of cell-mediated immunity. Generalized verrucosis is an unusual clinical presentation of a disseminated HPV infection associated with severe immunodeficiency status.

Observations  We present a case of extreme disfigurement associated with an HPV-2 (common wart virus) infection. Virologic studies, immune status of the patient, and treatment(s) are summarized.

Conclusions  The severe disfigurement of this patient was a result of an underlying severe immunodeficiency, permissive for a disseminated HPV-2 infection that was allowed to progress for many years before the initiation of therapy. Such a rare case illustrates the natural history of generalized verrucosis in the setting of severe immunodeficiency in the absence of sustained medical interventions. Medical and surgical treatments resulted in marked improvement in the general health of this patient, as well as improvement of the disfigurement that resulted from the generalized verrucosis.

Figures in this Article

Generalized verrucosis is a term used to describe widespread human papillomavirus (HPV) infections. A variety of disease states can result in such severe, potentially disfiguring infections. Generalized verrucosis is observed in patients with underlying immunodeficiency status that are either acquired (for example, AIDS or immunosuppression associated with organ transplantation)1,2 or rare congenital immunodeficiency syndromes (eg, epidermodysplasia verruciformis;3 warts, hypogammaglobulinemia, infections, and myelokathexis [WHIM] syndrome;4 combined immunodeficiencies;5 and cyclic neutropenia associated with chronic lymphopenia).6 We report a case of generalized verrucosis secondary to an HPV-2 infection that resulted in severe disfigurement. The underlying idiopathic CD4 lymphopenia resulted in susceptibility to the generalized verrucosis. The resulting skin disease was untreated for almost 10 years, which resulted in progressive, severe disfigurement, including massive cutaneous horns.

DNA EXTRACTION

From 3 wart biopsy specimens taken from the patient, DNA was extracted by means of a DNA extraction kit (Qiagen, Valencia, California). The quality of the DNA extracted for polymerase chain reaction (PCR) procedures was assessed by amplification of the reference control gene β-globin.7

HPV TYPING BY PCR AND SEQUENCING

The HPV PCR amplification was performed by means of 2 degenerate consensus primers, termed CP65 and CP70, with annealing sites located in the L1 open reading frame.8 Analysis isolation, cloning, and sequencing of putative HPV PCR products were performed as described previously.8 The obtained putative HPV sequences were aligned and compared with known HPV types available through the GenBank database by means of the Basic Local Alignment Search Tool (BLAST) program (National Center for Biotechnology Information, National Institutes of Health, Bethesda, Maryland).9

The patient is a 39-year-old Indonesian man who was in good health until the age of 15 years, when a warty lesion appeared on his knee. During the next 8 years, the skin lesions had spread over his entire skin surface and prevented him from working. At the age of 26 years (1994), he was evaluated and treated by a dermatologist in Bandung for almost 2 years, who diagnosed his condition as kutil batu (kutil meaning wart and bart meaning stone or rock). Because his skin condition continued to progress, he withdrew from further treatment and had been untreated since 1998. None of his family members, neighbors, or friends have any condition similar to his. Both his parents are alive, healthy, and nonconsanguineous. The patient also has a healthy brother and sister. He is divorced and the father of 2 healthy children. He is an unemployed construction worker. His medical history was unremarkable, and there were no risk factors for human immunodeficiency virus (HIV). He was not taking any medications. He had remained in his village since the onset of his disease until June 2007, when the Discovery Channel visited him to film a documentary about his condition.

On physical examination, widespread verrucous lesions were noted on his face, chest, and back (Figure 1A). His distal extremities contained confluent verrucous lesions, with no visible uninvolved skin. His hands were encased in a number of giant cutaneous horns ranging in size from 2 to 30 cm, many of which were curved and twisted (Figure 1B). A strong, foul odor was present. Numerous cutaneous horns were present on his lower extremities, but the soles of his feet were relatively spared.

Place holder to copy figure label and caption
Figure 1

Clinical appearance of the patient's warts in June 2007 before treatment. A, Chest; B, arm and hand; and C, lower extremities.

Graphic Jump Location

Assessment of cutaneous delayed-type hypersensitivity by intradermal skin testing with an extract of Candida albicans (1:100 dilution; Allerderm Laboratories, Petaluma, California) revealed cutaneous anergy (lack of induration and erythema at the skin test site at the 48-hour and 72-hour readings). A skin biopsy specimen taken from a lesion on his lower extremities revealed changes associated with a viral papilloma (Figure 2A and B). The computer analysis of the sequencing data obtained from the putative HPV PCR products revealed the presence of HPV-2 infections in all 3 wart samples (Figure 3). DNA sequencing of the E2 region of the HPV-2 genome was completed (Table 1) and compared with a reference strain, as well as another HPV-2 strain that was isolated from a patient with giant cutaneous horns.1012 The obtained sequencing data of the E2 region of HPV-2 from 3 clones of 3 warts were compared to the prototype HPV-2 sequences. Each of the 3 clones (CL1, CL2, and CL3) of the HPV-2 E2 viral region derived from 3 warts showed a similar base change from T to C at nucleotide position 3765 (the position based on prototype HPV-2a DNA; NCBI GenBank accession number X55964). This missense mutation resulted in an amino acid change at position 361 (Y to H) of the E2 viral protein. This amino acid change within the E2 region of HPV-2 was unique to our patient with generalized warts and was not present in E2 protein of HPV-2 viral isolates derived from other patients with huge verrucae vulgaris (Lei et al,10 2007). All 3 isolates revealed identical point mutations that rendered this isolate, as well as those isolates from another patient with giant cutaneous horns, distinct from the HPV-2 standard. The homogeneity of the DNA sequence in the E2 region in all 3 lesions suggested an infection with a single HPV that was genetically stable over time.

Place holder to copy figure label and caption
Figure 2

Skin biopsy specimens of warts. A, Skin biopsy specimen that reveals acanthosis and the presence of koilocytes (original magnification ×40). B, Skin biopsy specimen that reveals “church spire” hyperplastic changes (original magnification ×20).

Graphic Jump Location
Place holder to copy figure label and caption
Figure 3

Amplification of human papillomavirus (HPV) and β-globin sequences from 3 wart biopsy specimens of a patient with generalized warts. For HPV typing, polymerase chain reaction (PCR) products were visualized after electrophoresis in ethidium bromide–stained 2% agarose gel by UV illumination. Lanes: M, fX174 RF DNA molecular weight marker; W1 through W3, wart samples from the patient; PC, HPV-positive DNA control; NC, HPV-negative DNA control; and R, reagent control. A, Putative HPV PCR fragments can be seen in specimens from the patient (W1-W3) and in the HPV-25–positive DNA control (PC). The cloning and sequencing of the putative HPV PCR products from the wart samples revealed 452–base pair (bp) HPV-2 sequences. A faint extra–non-HPV–specific PCR band can be seen in the samples W1, W2, W3, and NC, which is described in the original methodologic article.8 B, β-Globin PCR fragments (268 bp) can be seen in wart specimens from the patient (W1-W3) and in the control DNA specimens (PC, NC).

Graphic Jump Location
Table Graphic Jump LocationTable 1 Missense Mutations Within the E2 Region of Human Papillomavirus 2 (HPV-2) Isolates

The local Indonesian Health Ministry hospitalized the patient in November 2007 and initiated evaluation and treatments. During this hospitalization, he was diagnosed as having a pulmonary infection with Mycobacterium tuberculosis (diagnosed on chest x-ray examination [not shown], Ziehl-Neelsen stain of sputum [strongly positive], and culture) for which he was successfully treated with combination antimicrobial therapy (rifampin, isoniazid, ethambutol hydrochloride, and ciprofloxacin). He also was diagnosed as having inactive hepatitis B infection. He also had an episode of herpes zoster that resolved without sequelae. His major laboratory findings are summarized in Table 2 and Table 3. Of note was a chronic CD4 lymphopenia (absolute CD4 cell count, 314/μL; reference range at reference laboratory, 410-1590/μL), which was found to be reproducible when these cell marker studies were performed on a number of separate occasions over time (not shown).

Table Graphic Jump LocationTable 2 Findings of Initial Laboratory Testing (June 2007)
Table Graphic Jump LocationTable 3 Findings of Cell Marker Studiesa

For the treatment of his cutaneous HPV infection, he underwent a series of surgical procedures. First, the cutaneous horns were debrided using a bone saw with the patient under general anesthesia. Since the debridement of the cutaneous horns from his hands, he has been using a compounded 40% salicylic acid lotion to retard the recurrence of the massive hyperkeratosis. Second, many of the verrucous lesions on the face and trunk were excised (elliptical excisions with layered closures and tangential plane excisions). He received a course of acitretin therapy, 25 to 50 mg/d, with little noticeable effect on growth or regression of his numerous warts. Intravenous cidofovir therapy (300 mg for each infusion in normal saline solution: a gift from Gilead Pharmaceuticals, Foster City, California) was attempted (along with hydration and oral probenecid therapy), but the renal function of the patient deteriorated, and this treatment was withdrawn after 2 intravenous infusions during a period of 1 month. He is currently being treated with ongoing surgical procedures to excise the remaining untreated or recurrent warts.

The patient described in this report has severe immunodeficiency syndrome characterized by a chronic CD4+ T lymphocytopenia. This patient meets the Centers for Disease Control and Prevention criteria for this syndrome because he lacked serologic or virologic evidence of HIV-1 or HIV-2 infection, had a CD4 cell count of approximately 300/μL on at least 2 occasions, had an abnormally low CD4/CD8 ratio, and exhibited disease indicative of impaired cellular immunity (generalized verrucosis caused by HPV-2).13,14 It is noteworthy that the CD4 lymphopenia of this patient persisted after he was successfully treated for pulmonary tuberculosis, which itself can be a cause of transient CD4 lymphopenias.15 A variety of opportunistic and atypical bacterial, viral, fungal, and protozoal infections can occur in patients with idiopathic CD4 lymphopenias, such as HPV, M tuberculosis, and varicella-zoster infections,14 all of which occurred in our patient. The spectrum of HPV infections that occurs in patients with idiopathic CD4 lymphopenias includes juvenile laryngeal papillomatosis,16 disseminated flat and common warts,17,18 recurrent vulvar intraepithelial neoplasia,19 and generalized verrucosis caused by HPV-2.6 There are also other immunodeficiency diseases associated with CD4 lymphopenias and susceptibility to HPV infections, such as WHIM syndrome.4 Such patients exhibit neutropenias, marked susceptibility to bacterial infections, hypogammaglobulinemia, and autosomal dominant inheritance. Other than peripheral CD4 lymphopenia, our patient lacked the features associated with WHIM syndrome (no history of recurrent pyogenic bacterial infections, no hypogammaglobulinemia, no myelokathexis on peripheral smear, and no apparent autosomal dominant inheritance because both his parents and all his siblings were healthy).

Another syndrome associated with marked susceptibility to disseminated HPV infection is epidermodysplasia verruciformis, which is an autosomal recessive disorder with disseminated flat warts (HPV-5, HPV-8, and others), an increased susceptibility to nonmelanoma skin cancer, and mutations in EVER1 and EVER2 (approximately 75% of patients with this disorder exhibit mutations of either 1 of these 2 genes).3 Our patient was infected exclusively with HPV-2 and did not develop any skin cancers despite having had the HPV infection for almost 25 years. This reflects the benign (nononcogenic) nature of the HPV-2 infection. However, this HPV-2 infection caused severe functional impairment and physical disfigurement.

Immunodeficiency syndromes that can result in generalized verrucosis rarely present with the severe deformity exhibited by our patient. A Chinese patient has been reported to exhibit giant cutaneous horns on his hands and feet as a result of an HPV-2 infection, similar to our patient.1012 There was no published information, to our knowledge, about the immune defect of this patient. In common with our patient, the Chinese patient lived in a rural area and was eventually treated successfully with radiation therapy to his hands and feet. We compared the open reading frame of the E2 region of the 3 isolates from our patient with that of the Chinese patient with massive cutaneous horns to a reference strain of HPV-2 and found that all 3 isolates from our patient exhibited distinct missense mutations compared with either the reference strain of HPV-2 or those isolates from the Chinese patient.12 This finding suggests that distinct missense mutations in the E2 region can result in aggressive infections, as noted in these 2 patients in whom the infecting HPV exhibited distinct open reading frame missense mutations. Functional studies of the effects of the enhancing effect of the E2 region from our patient's isolates on HPV promoter activity are ongoing. Our observation that all 3 HPV isolates from our patient exhibited identical E2 region mutations suggests a clonal origin of the infecting HPV-2, with genetic stability of the open reading frame of the E2 region in the many years of the progressive viral infection.

Our patient was treated with acitretin (unsuccessfully) and eventually cidofovir, the use of which was discontinued because of progressive nephrotoxicity after only 2 doses. Both acitretin (either alone or with interferon beta)20,21 and cidofovir2224 have been used with varying success in treatment of other patients with generalized verrucosis. Further characterization of his immunologic defect will be critical to designing successful immunotherapy for his generalized verrucosis. For example, there is a case report of a patient with generalized verrucosis with an underlying immunodeficiency characterized by chronic lymphopenia and a marked defect in TH1-lymphocyte cytokine production (ie, interferon gamma), who was successfully treated with granulocyte-macrophage colony-stimulating factor to stabilize her lymphocyte counts during a 9-month course of interferon gamma therapy.6 This regimen resulted in a marked regression of more than 95% of her generalized wart infection, with a sustained clearance of her HPV infection during a 5-year follow-up period.

In conclusion, this case represents a rare presentation of a severe, disfiguring HPV-2 infection as a result of an immunodeficiency associated with CD4 lymphocytopenia. Patients who present with massive cutaneous horns should be evaluated for HPV-2 infections and an underlying associated immunodeficiency.

Correspondence: Anthony A. Gaspari, MD, Departments of Dermatology and Microbiology/Immunology, University of Maryland School of Medicine, 419 W Redwood St, Ste 240, Baltimore, MD 21201 (agasp001@umaryland.edu).

Accepted for Publication: July 17, 2009.

Author Contributions: All authors had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Gaspari. Acquisition of data: Gaspari. Analysis and interpretation of data: Alisjahbana, Dinata, Sutedja, Suryahudaya, Soedjana, Hidajat, Soetikno, Oktaliansah, Deng, Rady, Tyring, and Gaspari. Drafting of the manuscript: Alisjahbana, Dinata, Sutedja, Suryahudaya, Soedjana, Hidajat, Soetikno, Oktaliansah, Deng, Rady, Tyring, and Gaspari. Critical revision of the manuscript for important intellectual content: Alisjahbana, Dinata, Sutedja, Suryahudaya, Soedjana, Hidajat, Soetikno, Oktaliansah, Deng, Rady, Tyring, and Gaspari. Administrative, technical, or material support: Alisjahbana, Dinata, Sutedja, Suryahudaya, Soedjana, Hidajat, Soetikno, Oktaliansah, Deng, Rady, Tyring, and Gaspari. Study supervision: Gaspari.

Financial Disclosure: None reported.

Funding/Support: This study was funded by National Institute of Arthritis and Musculoskeletal and Skin Diseases grant R0-1-AR46108-05 (Dr Gaspari).

Additional Contributions: The Indonesian minister of health, Siti Fadilah Supari, MD, and the director of Dr Hasan Sadikin Hospital, Cissy B. Sudjana Prawira, MD, provided stimulating suggestions, help, and support.

Memar  OMArany  ITyring  SK Skin-associated lymphoid tissue in human immunodeficiency virus-1, human papillomavirus, and herpes simplex virus infections. J Invest Dermatol 1995;105 (1) ((suppl)) 99S- 104S
PubMed
Tan  HHGoh  CL Viral infections affecting the skin in organ transplant recipients: epidemiology and current management strategies. Am J Clin Dermatol 2006;7 (1) 13- 29
PubMed
Gerwitzman  ABartlett  BTyring  S Epidermodysplasia verruciformis and HPV. Curr Opin Infect Ds 2008;21 (2) 141- 146
Kawai  TMalech  HL WHIM syndrome: congenital immune deficiency disease. Curr Opin Hematol 2009;16 (1) 20- 26
PubMed
Laffort  CLe Deist  FFavre  M  et al.  Severe cutaneous papillomavirus disease after haemopoietic stem-cell transplantation in patients with severe combined immune deficiency cause by common gamma cytokine receptor submit or JAK-3 deficiency. Lancet 2004;363 (9426) 2051- 2054
PubMed
Gaspari  AAZalka  APayne  D  et al.  Successful treatment of a generalized human papillomavirus infection with granulocyte-macrophage colony-stimulating factor and interferon gamma immunotherapy in a patient with a primary immunodeficiency and cyclic neutropenia. Arch Dermatol 1997;133 (4) 491- 496
PubMed
Resnick  RMCornelissen  MTWright  DK  et al.  Detection and typing of human papillomavirus in archival cervical cancer specimens by DNA amplification with consensus primers. J Natl Cancer Inst 1990;82 (18) 1477- 1484
PubMed
Berkhout  RJTieben  LMSmits  HLBavinck  JNVermeer  BJter Schegget  J Nested PCR approach for detection and typing of epidermodysplasia verruciformis-associated human papillomavirus types in cutaneous cancers from renal transplant recipients. J Clin Microbiol 1995;33 (3) 690- 695
PubMed
de Oliveira  WRPHe  QRady  PL  et al.  HPV typing in Brazilian patients with epidermodysplasia verruciformis: high prevalence of EV-HPV 25. J Cutan Med Surg 2004;8 (2) 110- 115
PubMed
Lei  Y-JWang  CGao  C  et al.  HPV-2 isolates from patients with huge verrucae vulgaris possess stronger promoter activities. Intervirology 2007;50 (5) 353- 360
PubMed
Wang  CWWLei  Y-JWang  J-Y  et al.  Multiple cutaneous horns overlying verrucae vulgaris induced by human papillomavirus type 2: a case report. Br J Dermatol 2007;156760- 762
PubMed
Wang  WWang  CXu  S  et al.  Detection of HPV-2 and identification of novel mutations by whole genome sequencing from biopsies of two patients with multiple cutaneous horns. J Clin Virol 2007;39 ((1)) 34- 42
PubMed
Laurence  J T-cell subsets in health, infectious disease and idiopathic CD4+T lymphopenia. Ann Intern Med 1993;119 (1) 55- 62
PubMed
Walker  UAWarnatz  K Idiopathic CD4 lymphopenia. Curr Opin Rheumatol 2006;18 (4) 389- 395
PubMed
Beck  JSPotts  RCKardjito  TGrange  JM T4 lymphopenia in patients with active pulmonary tuberculosis. Clin Exp Immunol 1985;60 (1) 49- 54
PubMed
Pasic  SMinic  PDzudovic  S  et al.  Idiopathic CD4+ lymphocytopenia and juvenile laryngeal papillomatosis. Pediatr Pulmon 2005;39 (3) 281- 283
Gubinelli  EPosteraro  PGirolomoni  G Idiopathic CD4+ T lymphocytopenia associated with disseminated flat warts and alopecia areata. J Dermatol 2002;29 (10) 653- 656
PubMed
Lopez  P MachadoRuiz de Morales  JMGRuiz González  IRodriguez Prieto  MA Cutaneous infections by papillomavirus, herpes zoster and Candida albicans as the only manifestation of idiopathic CD4+ T lymphocytopenia. Int J Dermatol 1999;38 (2) 119- 121
PubMed
Park  KMonk  BJWilczynski  SIto  JI  JrVasilev  SA Idiopathic CD4+ T-lymphocytopenia and recurrent vulvar intraepithelial neoplasia Obstet Gynecol 1994;84 (4 pt 2) 712- 714
PubMed
Iraji  FFaghihi  G Epidermodysplasia verruciformis: association with isolated IgM deficiency and response to treatment with acitretin. Clin Exp Dermatol 2000;25 (1) 41- 43
PubMed
Anadolu  ROskay  TErdem  CBoyvat  ATerzi  EGürgey  E Treatment of epidermodysplasia verruciformis with a combination of acitretin and interferon alfa-2a. J Am Acad Dermatol 2001;45 (2) 296- 299
PubMed
Preiser  WKapur  NSnoeck  RGroves  RWBrink  NS No apparent effect of cidofovir in epidermodysplasia verruciformis. J Clin Virol 2000;16 (1) 55- 57
PubMed
Cha  SJohnston  LNatkunam  YBrown  J Treatment of verruca vulgaris with topical cidofovir in an immunocompromised patient: a case report and review of the literature. Transpl Infect Dis 2005;7 (3-4) 158- 161
PubMed
Kottke  MDParker  SRS Intravenous cidofovir-induced resolution of disfiguring cutaneous human papilloma virus infection. J Am Acad Dermatol 2006;55 (3) 533- 536

Figures

Place holder to copy figure label and caption
Figure 1

Clinical appearance of the patient's warts in June 2007 before treatment. A, Chest; B, arm and hand; and C, lower extremities.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2

Skin biopsy specimens of warts. A, Skin biopsy specimen that reveals acanthosis and the presence of koilocytes (original magnification ×40). B, Skin biopsy specimen that reveals “church spire” hyperplastic changes (original magnification ×20).

Graphic Jump Location
Place holder to copy figure label and caption
Figure 3

Amplification of human papillomavirus (HPV) and β-globin sequences from 3 wart biopsy specimens of a patient with generalized warts. For HPV typing, polymerase chain reaction (PCR) products were visualized after electrophoresis in ethidium bromide–stained 2% agarose gel by UV illumination. Lanes: M, fX174 RF DNA molecular weight marker; W1 through W3, wart samples from the patient; PC, HPV-positive DNA control; NC, HPV-negative DNA control; and R, reagent control. A, Putative HPV PCR fragments can be seen in specimens from the patient (W1-W3) and in the HPV-25–positive DNA control (PC). The cloning and sequencing of the putative HPV PCR products from the wart samples revealed 452–base pair (bp) HPV-2 sequences. A faint extra–non-HPV–specific PCR band can be seen in the samples W1, W2, W3, and NC, which is described in the original methodologic article.8 B, β-Globin PCR fragments (268 bp) can be seen in wart specimens from the patient (W1-W3) and in the control DNA specimens (PC, NC).

Graphic Jump Location

Tables

Table Graphic Jump LocationTable 1 Missense Mutations Within the E2 Region of Human Papillomavirus 2 (HPV-2) Isolates
Table Graphic Jump LocationTable 2 Findings of Initial Laboratory Testing (June 2007)
Table Graphic Jump LocationTable 3 Findings of Cell Marker Studiesa

References

Memar  OMArany  ITyring  SK Skin-associated lymphoid tissue in human immunodeficiency virus-1, human papillomavirus, and herpes simplex virus infections. J Invest Dermatol 1995;105 (1) ((suppl)) 99S- 104S
PubMed
Tan  HHGoh  CL Viral infections affecting the skin in organ transplant recipients: epidemiology and current management strategies. Am J Clin Dermatol 2006;7 (1) 13- 29
PubMed
Gerwitzman  ABartlett  BTyring  S Epidermodysplasia verruciformis and HPV. Curr Opin Infect Ds 2008;21 (2) 141- 146
Kawai  TMalech  HL WHIM syndrome: congenital immune deficiency disease. Curr Opin Hematol 2009;16 (1) 20- 26
PubMed
Laffort  CLe Deist  FFavre  M  et al.  Severe cutaneous papillomavirus disease after haemopoietic stem-cell transplantation in patients with severe combined immune deficiency cause by common gamma cytokine receptor submit or JAK-3 deficiency. Lancet 2004;363 (9426) 2051- 2054
PubMed
Gaspari  AAZalka  APayne  D  et al.  Successful treatment of a generalized human papillomavirus infection with granulocyte-macrophage colony-stimulating factor and interferon gamma immunotherapy in a patient with a primary immunodeficiency and cyclic neutropenia. Arch Dermatol 1997;133 (4) 491- 496
PubMed
Resnick  RMCornelissen  MTWright  DK  et al.  Detection and typing of human papillomavirus in archival cervical cancer specimens by DNA amplification with consensus primers. J Natl Cancer Inst 1990;82 (18) 1477- 1484
PubMed
Berkhout  RJTieben  LMSmits  HLBavinck  JNVermeer  BJter Schegget  J Nested PCR approach for detection and typing of epidermodysplasia verruciformis-associated human papillomavirus types in cutaneous cancers from renal transplant recipients. J Clin Microbiol 1995;33 (3) 690- 695
PubMed
de Oliveira  WRPHe  QRady  PL  et al.  HPV typing in Brazilian patients with epidermodysplasia verruciformis: high prevalence of EV-HPV 25. J Cutan Med Surg 2004;8 (2) 110- 115
PubMed
Lei  Y-JWang  CGao  C  et al.  HPV-2 isolates from patients with huge verrucae vulgaris possess stronger promoter activities. Intervirology 2007;50 (5) 353- 360
PubMed
Wang  CWWLei  Y-JWang  J-Y  et al.  Multiple cutaneous horns overlying verrucae vulgaris induced by human papillomavirus type 2: a case report. Br J Dermatol 2007;156760- 762
PubMed
Wang  WWang  CXu  S  et al.  Detection of HPV-2 and identification of novel mutations by whole genome sequencing from biopsies of two patients with multiple cutaneous horns. J Clin Virol 2007;39 ((1)) 34- 42
PubMed
Laurence  J T-cell subsets in health, infectious disease and idiopathic CD4+T lymphopenia. Ann Intern Med 1993;119 (1) 55- 62
PubMed
Walker  UAWarnatz  K Idiopathic CD4 lymphopenia. Curr Opin Rheumatol 2006;18 (4) 389- 395
PubMed
Beck  JSPotts  RCKardjito  TGrange  JM T4 lymphopenia in patients with active pulmonary tuberculosis. Clin Exp Immunol 1985;60 (1) 49- 54
PubMed
Pasic  SMinic  PDzudovic  S  et al.  Idiopathic CD4+ lymphocytopenia and juvenile laryngeal papillomatosis. Pediatr Pulmon 2005;39 (3) 281- 283
Gubinelli  EPosteraro  PGirolomoni  G Idiopathic CD4+ T lymphocytopenia associated with disseminated flat warts and alopecia areata. J Dermatol 2002;29 (10) 653- 656
PubMed
Lopez  P MachadoRuiz de Morales  JMGRuiz González  IRodriguez Prieto  MA Cutaneous infections by papillomavirus, herpes zoster and Candida albicans as the only manifestation of idiopathic CD4+ T lymphocytopenia. Int J Dermatol 1999;38 (2) 119- 121
PubMed
Park  KMonk  BJWilczynski  SIto  JI  JrVasilev  SA Idiopathic CD4+ T-lymphocytopenia and recurrent vulvar intraepithelial neoplasia Obstet Gynecol 1994;84 (4 pt 2) 712- 714
PubMed
Iraji  FFaghihi  G Epidermodysplasia verruciformis: association with isolated IgM deficiency and response to treatment with acitretin. Clin Exp Dermatol 2000;25 (1) 41- 43
PubMed
Anadolu  ROskay  TErdem  CBoyvat  ATerzi  EGürgey  E Treatment of epidermodysplasia verruciformis with a combination of acitretin and interferon alfa-2a. J Am Acad Dermatol 2001;45 (2) 296- 299
PubMed
Preiser  WKapur  NSnoeck  RGroves  RWBrink  NS No apparent effect of cidofovir in epidermodysplasia verruciformis. J Clin Virol 2000;16 (1) 55- 57
PubMed
Cha  SJohnston  LNatkunam  YBrown  J Treatment of verruca vulgaris with topical cidofovir in an immunocompromised patient: a case report and review of the literature. Transpl Infect Dis 2005;7 (3-4) 158- 161
PubMed
Kottke  MDParker  SRS Intravenous cidofovir-induced resolution of disfiguring cutaneous human papilloma virus infection. J Am Acad Dermatol 2006;55 (3) 533- 536

Correspondence

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The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
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Indicate what change(s) you will implement in your practice, if any, based on this CME course.
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For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).
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