The human papillomavirus (HPV) causes the common wart or verruca vulgaris. This is the same virus that causes genital warts which leads to dysplasia and cervical cancer. Some estimates of the prevalence of HPV infection in the population range as high as 79%. Warts may arise on any skin surface, but occur most commonly at acral sites. Although treatment may remove the wart, the virus remains latent within the skin cells. However, treatment may diminish spread of HPV in the skin of the infected patient and possibly to uninfected contacts.
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EPIDEMIOLOGY CHARACTERIZATION SYNONYMS Warts
DISEASE ASSOCIATIONS CHARACTERIZATION RENAL TRANSPLANT
Interferon-gamma Treatment Induces Granulomatous Tissue Reaction in a Case of Localized Cutaneous Leishmaniasis.
Haas N, Hauptmann S, Paralikoudi D, Muche M, Kolde G.
Departments of Dermatology and Allergy (N.H., M.M., G.K.) and Pathology (S.H., D.P.), Charite, Humboldt-University Berlin, Berlin, Germany.
Am J Dermatopathol 2002 Aug;24(4):319-23 Abstract quote
Leishmania spp. suppress macrophage activity as part of their interaction with the immune system. Interferon-gamma (IFNgamma), a cytokine that participates in the activation of macrophages and the killing of intercellular parasites, induces healing of leishmaniasis.
We investigated a sequence of local and systemic inflammatory cell parameters after IFNgamma therapy in a patient with chronic, localized, cutaneous leishmaniasis caused by Leishmania donovani. Histology, immunohistochemistry, polymerase chain reaction (PCR) for L. donovani, and analysis of T-cell receptor gene fragments from skin lesions as well as peripheral blood phenotyping were performed before, during, and after IFNgamma therapy. During therapy, epithelioid cell granulomas developed with a high number of lesional human leukocyte antigen (HLA) DR+ macrophages, and HLA-DR expression on monocytes increased to high counts, indicating macrophage activation.
Simultaneously, T-cell receptor-beta gene-specific PCR showed a peak at 243 base pairs, indicating clonal expansion of Leishmania-reactive T lymphocytes. After therapy, PCR detected minimal residual leishmanial DNA in healing lesions, suggesting the destruction of the parasites. In conclusion, IFNgamma therapy compensates for the parasite-dependent major histocompatibility complex class II downregulation and induces healing of chronic cutaneous leishmaniasis.
PATHOGENESIS CHARACTERIZATION ANTIMICROBIAL PEPTIDE LL-37
The antimicrobial peptide LL-37 is expressed by keratinocytes in condyloma acuminatum and verruca vulgaris.
Conner K, Nern K, Rudisill J, O'Grady T, Gallo RL.
Division of Dermatology, University of California San Diego, and Veterans Affairs San Diego Healthcare System.
J Am Acad Dermatol 2002 Sep;47(3):347-50 Abstract quote
BACKGROUND: LL-37 is a peptide belonging to the cathelicidin family of antimicrobial peptides. Recent investigations have suggested that the expression of antimicrobial peptides is an important mechanism for resistance to microbial infection.
OBJECTIVE: The aim of this study was to determine whether LL-37 is expressed in papillomavirus-infected epidermis from patients with condyloma acuminatum or verruca vulgaris.
METHODS: Biopsy specimens from 3 patients with condyloma and 2 patients with verruca vulgaris and 6 normal skin samples were studied by immunostaining with an antibody specific to LL-37 and control rabbit serum. Western blots were performed on skin extracts from normal skin and verrucae.
RESULTS: A large increase in the expression of LL-37 was seen within keratinocytes of all involved samples and in the extracts of verrucae analyzed by Western blot.
CONCLUSION: This study shows the antimicrobial peptide LL-37 is induced within the epidermis during the development of verruca vulgaris. This expression represents a previously unknown immunologic response to papillomavirus infection and may represent an important step in the pathogenesis of this disorder.
APOPTOSIS BCL-2-related apoptosis markers in cutaneous human papillomavirus-associated lesions.
Erkek E, Bozdogan O, Atasoy P, Birol A, Kocak M.
Kirikkale University Faculty of Medicine, Ankara, Turkey.
Am J Dermatopathol. 2004 Apr;26(2):113-8. Abstract quote
BACKGROUND: Human papilloma virus (HPV) is an etiological agent in benign and malignant epithelial tumors. Resistance to apoptotic stimuli by viral strategies represents an immunologic escape mechanism during virus-induced tumor development and is critical for efficient replication of the virus.
OBJECTIVE: The aim of the present study was to investigate a role of bcl-family proteins in the anti-apoptotic pathways modulated by low-risk HPVs in the development of benign HPV-associated cutaneous tumors.
METHODS: Forty lesional biopsy specimens from HPV-associated cutaneous lesions and 11 non-lesional control skin biopsies were studied by immunohistochemical analysis for the differential expressions of HPV antigens, the pro-apoptotic bax protein, and the anti-apoptotic bcl-2 and bcl-x proteins.
RESULTS: Compared with the normal epidermis, bcl-2 and bcl-x expression were significantly reduced in the lesional epidermis. Bax was expressed in HPV-associated cutaneous lesions, although the expression did not reveal a significant deviation from that in normal skin.
CONCLUSION: These findings indicate a discordant expression of bcl-2/ bcl-x and bax proteins in HPV-associated skin lesions and suggest that low-risk HPVs mediate other pathways that bypass the action of anti-apoptotic bcl-2 and bcl-x proteins. The presence of bax expression with a prominent decrease in bcl-2/ bax ratio and the lack of massive apoptosis in HPV-associated benign epithelial lesions may imply that interference with the pro-apoptotic proteins of bcl-family may constitute one of the several mechanisms mediated by HPV oncoproteins for the suppression of apoptotic process.
HISTOPATHOLOGICAL VARIANTS CHARACTERIZATION ATYPICAL LYMPHOID INFILTRATE
Verruca Vulgaris With CD30-Positive Lymphoid Infiltrate: A Case Report
Anna M. Cesinaro, M.D.; Antonio Maiorana, M.D.
Am J Dermatopathol 2002; 24(3):260-263 Abstract quote
Expression of CD30 has been reported in reactive lymphoid cells that accompany some cutaneous viral infections. It is interpreted as a marker of lymphocyte activation in response to the infecting virus. We report on a case of viral wart presenting with an inflammatory infiltrate with numerous CD30+ atypical lymphoid cells. These cells comprised approximately 10% of the reactive cell population and showed a T-helper phenotype.
Infection by human papillomavirus should be included among the causes of cutaneous CD30+ reactive lymphoid infiltrates.
DIFFERENTIAL DIAGNOSIS CHARACTERIZATIOIN PERIANAL PSEUDOVERRUCOUS PAPULES AND NODULES OF INFANCY
J Pediatr. 1994 Dec;125(6 Pt 1):914-6. Abstract quote
We report two patients with Hirschsprung disease in whom severe diarrhea and a distinctive diaper dermatitis developed after delayed ileoanal anastomosis. The perianal papulonodular lesions cleared in months or years without specific treatment after resolution of the diarrhea.
These perianal pseudoverrucous papules and nodules represent a peculiar form of primary irritant diaper dermatitis, distinct from Jacquet erosive diaper dermatitis and granuloma gluteale infantum.
Arch Dermatol. 1992 Feb;128(2):240-2. Abstract quote
BACKGROUND--Pseudoverrucous papules and nodules were originally described as a reaction to irritation in association with urostomies. These changes have not been described as occurring on the perianal skin or around colostomies.
OBSERVATIONS--Five children had remarkably similar-appearing papules and nodules of the perianal and suprapubic skin. The rash consisted of more than a dozen 2- to 8-mm shiny, smooth, red, moist, flat-topped, round lesions. This peculiar and striking reaction appears to be the result of encopresis or urinary incontinence. Biopsy specimens reveal reactive acanthosis or psoriasiform spongiotic dermatitis. The lesions regress when the irritating factor is removed.
CONCLUSIONS--Recognition of this entity is important because pseudoverrucous papules and nodules may mimic more serious dermatoses and unnecessary workup may be initiated. Although this reaction involving perianal skin has not been reported previously, we believe it is not uncommon.
PROGNOSIS AND TREATMENT CHARACTERIZATION PROGNOSIS KERATIN SUBTYPES
Retinoids Strongly and Selectively Correlate With Keratin 13 and Not Keratin 19 Expression in Cutaneous Warts of Renal Transplant Recipients
Willeke A. M. Blokx, MD; Jurgen V. Smit, MD; Elke M .G. J. de Jong, MD, PhD; Monique M. G. M. Link; Peter C. M. van de Kerkhof, MD, PhD; Dirk J. Ruiter, MD, PhD
Arch Dermatol. 2002;138:61-65 Abstract quote
To compare the expression of keratin (K) 13 and K19 in cutaneous warts of renal transplant recipients (RTRs) and immunocompetent individuals (ICIs).
Retrospective, nonrandomized immunohistochemical study.
Patients and Methods
Specimens from cutaneous warts of RTRs and ICIs were retrieved from the archives of the Department of Pathology, University Medical Center St Radboud, Nijmegen, the Netherlands. Twenty-one warts from RTRs and 21 from ICIs were examined. Nine RTRs (10 specimens) received either systemic acitretin or topical all-trans retinoic acid, and their effect on both keratins was assessed.
Main Outcome Measures
Frequency and expression patterns of K13 and K19 in warts of RTRs vs ICIs and the effect of retinoids. Results A significantly higher percentage of warts of RTRs expressed K13 compared with warts of ICIs (86% vs 14%, 18 vs 3 cases, respectively; P<.001). In warts of RTRs, retinoid treatment correlated significantly with a particularly strong, segmental K13 expression pattern, which we termed zebroid. Without use of retinoids, K13 was mostly restricted to suprabasal single cells. Keratin 19 was absent in all warts of both patient groups.
Retinoids strongly correlate with K13 in a characteristic zebroid pattern in warts of RTRs, making K13 a sensitive marker for retinoid bioactivity in skin (lesions) of RTRs. In non–retinoid-treated RTRs, K13 is also frequently found in warts but without the dramatic zebroid pattern noted in retinoid-treated warts.
Dermatol Clin. 1997;15:331-340
Cryotherapy remains the first-line treatment
Keratolytics or cantharidin
VIRAL OR FUNGAL ANTIGENS
Intralesional Injection of Mumps or Candida Skin Test Antigens A Novel Immunotherapy for Warts
Sandra Marchese Johnson, etal.
Arch Dermatol. 2001;137:451-455 Abstract quote
Warts are common and induce physical and emotional discomfort. Numerous therapies exist, yet none is optimal. Despite theoretical advantages, immunotherapeutic modalities are often neglected as first-line wart therapies.
To compare treatment with intralesional skin test antigen injection of 1 wart vs cryotherapy of all warts.
University dermatology outpatient clinic.
A total of 115 consecutive patients with at least 1 nongenital wart. Interventions Patients with warts were tested for immunity to mumps and Candida using commercial antigens. Nonresponders received cryotherapy and immune individuals received cryotherapy or intralesional injection of 1 antiserum.
Thirty-four (30%) of the 115 patients did not respond to the test injections and 81 (70%) had detectable immunity. Of the immune group, 26 (32%) received cryotherapy, 45 (56%) received intralesional mumps antiserum, and 10 (12%) received intralesional Candida antiserum. Of the anergic patients, 28 (82%) were treated with cryotherapy; 6 (18%) refused cryotherapy. Of the 39 patients who were treated with immunotherapy and completed the protocol, 29 (74%) had complete clearing of the treated wart. Fourteen (78%) of 18 patients with complete resolution of their immunotherapy-treated wart also had resolution of untreated, distant warts.
Intralesional injection of mumps or Candida antigens into warts of immune individuals represents effective treatment. Observation of clearing of anatomically distinct and distant warts suggests acquisition of human papillomavirus–directed immunity in some patients. We conclude that this novel approach to immunotherapy may serve as first-line treatment in immune individuals with multiple or large warts and as second-line treatment in immune patients for whom cryotherapy fails.
CIMETIDINE AND LEVAMISOLE
Cimetidine and levamisole versus cimetidine alone for recalcitrant warts in children.
Parsad D, Pandhi R, Juneja A, Negi KS.
Department of Dermatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Pediatr Dermatol 2001 Jul-Aug;18(4):349-52 Abstract quote
Various immunomodulating agents have been used in the treatment of recalcitrant warts, but none is uniformly effective. Aggressive surgical therapy of warts in children is painful and may require general anesthesia. Drugs such as cimetidine and levamisole have been tried with varying success rates.
Given the different target of activities of immunomodulation by cimetidine and levamisole, we questioned whether the combination might be more effective and conducted a double-blind comparative trial of a combination of cimetidine and levamisole versus cimetidine alone.
Forty-four patients with multiple recalcitrant warts were assigned to one of two treatment groups (groups A and B) in double-blind fashion. Of the 44 patients, 19 in group A and 20 in group B could be evaluated. At the end of therapy, cure rates (complete clearance) obtained were 31.5% of those in group A and 65% of those in group B (combination treatment). A statistically significant improvement was seen in patients treated with the combination of levamisole and cimetidine (p=0.0150). The rate of regression was faster in group B (average regression period of 7.8 weeks compared with 11 weeks in group A).
The present study demonstrated that the combination of cimetidine with levamisole is more effective than cimetidine alone and is a highly effective therapy for the treatment of recalcitrant warts.
- Arch Dermatol. 2007 Mar;143(3):309-13. Abstract quote
OBJECTIVE: To evaluate the efficacy of duct tape occlusion therapy for the treatment of common warts in adults.
DESIGN: Double-blind controlled clinical intervention trial.
SETTING: Veterans Affairs medical center.
PARTICIPANTS: A total of 90 immunocompetent adult volunteers with at least 1 wart measuring 2 to 15 mm were enrolled between October 1, 2004, and July 31, 2005. Eighty patients completed the study.
INTERVENTION: Patients were randomized by a computer-generated code to receive pads consisting of either moleskin with transparent duct tape (treatment group) or moleskin alone (control group). Patients were instructed to wear the pads for 7 consecutive days and leave the pad off on the seventh evening. This process was repeated for 2 months or until the wart resolved, whichever occurred first. Follow-up visits occurred at 1 and 2 months.
MAIN OUTCOME MEASURE: Complete resolution of the target wart. Secondary outcomes included change in size of the target wart and recurrence rates at 6 months for warts with complete resolution.
RESULTS: There were no statistically significant differences in the proportions of patients with resolution of the target wart (8 [21%] of 39 patients in the treatment group vs 9 [22%] of 41 in the control group). Of patients with complete resolution, 6 (75%) in the treatment group and 3 (33%) in the control group had recurrence of the target wart by the sixth month.
CONCLUSION: We found no statistically significant difference between duct tape and moleskin for the treatment of warts in an adult population.
J Am Acad Dermatol. 1997;36:659-685.
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