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Treatment of recalcitrant plantar warts with imiquimod.

Myrmecia are viral warts that result from the coalescence of plantar or palmar warts into large plaques. Treatment of these warts involves physical or chemical destruction of the verrucae, potent keratolytics or immunotherapy. Imiquimod 5% cream is a novel topical immunomodulator that has been used successfully in the treatment of genital and common warts. We report its successful use in a 35-year-old immunocompetent man who had had resistant plantar warts for 15 years.

Adult↗

Comparative study of aminolevulic acid photodynamic therapy plus pulsed dye laser versus pulsed dye laser alone in treatment of viral warts.

OBJECTIVE AND BACKGROUND: A number of scientific publications describe the removal of viral warts using photoselective laser destruction with pulsed dye laser (PDL) or photodynamic therapy (PDT). Although both methods represent an enormous improvement in therapy, the results are not sufficiently consistent to consider these methods as the "gold standard" for therapy. METHODS: With a view to further improvement we combined a photoselective dye laser (595 nm, 20 J.cm(-2)) with photodynamic therapy using aminolevulic acid. The results of this method were compared against traditional laser photodestruction (of identical physical parameters) and against traditional photodynamic therapy (of similar parameters). RESULTS: After combined therapy (PDT + PDL) of 86 warts in 24 patients, 100% were cured, with an average of 1.96 therapeutic sessions. Therapy with PDT alone failed in 3 of 76 warts even after 5 sessions (96%), with an average of 2.54 therapeutic sessions. Therapy with PDL alone failed in 21 of 112 warts even after 5 sessions, with an average of 3.34 therapeutic sessions. CONCLUSIONS: All three therapeutic methods are able to cure infectious warts with high probability (>80%). However, a combination of PDT and PDL is the most effective and the most favored therapy. If other investigators also confirm results near or equal to 100% success, this therapy could become a treatment of choice for this indication.

Aminolevulinic Acid↗

The management of warts of the oral cavity.

Heretofore most people affected by warts of the oral cavity were children, but during the past decade adults have become the most frequently seen patients with warts in the mouth. The popularity of fellatio among heterosexuals, teenagers, and adults has contributed to the spread of oral warts. Of epidemiologic interest is the observation that seldom are contacts of patients with oral warts found to have warts also. Seven cases are presented, and the methods of diagnosis and treatment are outlined.

Adult↗

Antigenic relationships between polypeptides derived from plantar and hand wart viruses.

Guinea pigs immunized with polypeptides derived from plantar and hand wart viruses developed both humoral and cell mediated immunity. The specificity of the antiserum was determined by indirect immunofluorescence (IF) tests and cellular immunity by intradermal tests. While whole plantar and hand wart virus particles (PV and HV) appeared to be immunologically analogous, they had different polypeptide patterns as shown by analysis on acrylamide slab gels. In particular, the P2 polypeptide (major virus protein) with different mol. wt. for PV (56750) and HV (54500) induced the production of high antibody titres in the animals and the immune sera specifically labelled wart substrates as shown in thie IF test, demonstrating that no cross humoral reaction occurs between these two polypeptides. Furthermore, a delayed hypersensitivity reaction was observed in P2 polypeptide-inoculated guinea pigs when whole particles were introduced in skin tests, but a total cross reactivity between PV and HV was noticed at the cellular level. However, the study of the virus isolated from the lesions of a patient (Ri) bearing extensive common hand warts has shown that the virus particles possessed all the biochemical and immunological characteristics of PV, in particular with regard to the P2 polypeptide. Such a case may represent plantar-like warts located on the hands.

Animals↗

An immunoelectron microscopic localization of wart associated antigens present in human papilloma virus (HPV) infected cells.

Wart associated antigens were observed by the indirect immunoperoxidase technique in light and electron microscopy. Positive reaction products could be found in the nuclei of wart cells, in which virus particles were labeled with a specific immune rabbit serum and with human sera from patients with warts. Tissue antigens, differing from the viral labeled inclusions, were detected within the cytoplasm of some infected cells, by means of IgM and IgG antibodies from patients with warts. In these particular cells the positive reaction occurred in irregular patterns giving microgranular precipitates, which suggests that the antigen was not uniform. No staining was observed on the cell surface. This study has shown direct immunomorphological evidence in vivo of a specific immune reaction in man directed against whole virus and wart specific cellular antigens.

Animals↗

Efficacy of silver nitrate pencils in the treatment of common warts.

Common warts are an important issue, especially in children and young adults. The methods proposed for common wart treatment are painful, destructive, and require special experience and devices. The chemical cauterization effect of silver nitrate on warts is noted in the classical pharmaceutical textbooks. In order to test this effect for this purpose, a placebo controlled clinical study was performed on 70 patients. On 35 randomly selected patients, a silver nitrate stick was used, and, on the other 35 patients, black ink was used. At the end of this study, of the patients treated with the silver nitrate stick, 15 (43%) were completely healed, 9 (26%) were partially healed, and 11 (31%) were not healed. Of the patients treated with black ink, 4 (11%) were completely healed, 5 (14%) were partially healed, and 26 (74%) patients were not affected. Thus the silver nitrate stick affected the warts of 24 (69%) patients. Therefore, this method appears to be an effective, economic, and easily applicable treatment for common warts.

Administration, Topical↗

In vitro assay of immunity to human wart antigen.

The cell-mediated and antibody responses to human wart antigen have been studied in patients with warts and in controls. Most patients show a positive cell-mediated response at or about the time of resolution of their warts but the detectable immunity is short-lived. The majority of patients with warts have antibodies and the percentage rises both with resolution of the warts and with increase in the duration of the infection. No correlation between the presence of antibodies and the development of cell-mediated immunity was found.

Adolescent↗

Genital warts: incidence of associated genital infections.

Two hundred and seventy-eight men and 200 women who presented to a Special Treatment Clinic with genital warts were screened for accompanying genital infections. One hundred and twenty-nine of 212 presentations (61%) in women compared to 98 of 303 presentations (32%) in men were accompanied by another genital infection P less than 0.001). Recurrent presentation with warts was commoner in men (P less than 0.001). In both sexes recurrences were less likely to be accompanied by another genital infection. (P less than 0.002). Yeasts (25%), C. vaginale (21%), N.gonorrhoea (12%) and T. vaginalis (12%) were the commonest pathogens in women. Non-specific genital infection (17%) and gonorrhoea (10%) were the commonest accompanying infections in men. The identification and treatment of these infections, especially in women, is important for the rapid eradication of warts, for, by increasing genital moisture they can create and maintain a favourable environment for wart proliferation. In addition to screening all patients with warts for other sexually transmitted diseases, women should be screened for yeasts and C. vaginale.

Candidiasis, Vulvovaginal↗

Surgical treatment of recalcitrant warts.

Cryosurgery is the first choice for surgical treatment of viral warts. It is applied in two ways: with blister induction in extraplantar common warts and without blister induction in genital, filiform, and mosaic warts. Plantar and periungual warts are enucleated with a spoon or scraped off with a curet after preparatory focal electrocoagulation with a ball probe. Genital warts may be treated with "extracutaneous" electrosection and electrocoagulation.

Cryosurgery↗

The treatment of palmar and plantar warts using natural alpha interferon and a needleless injector.

BACKGROUND: The treatment of palmar and plantar warts is difficult and often frustrating. The need for multiple destructive treatments and recurrences after apparent cure are common. OBJECTIVE: The purpose of this study was to determine if intralesional natural alpha interferon might offer an effective alternative therapy for common plantar and palmar warts. METHODS: A series of 22 private office patients with palmar and plantar warts were treated with intralesional natural alpha interferon using a needless injector. We treated twice weekly for a minimum of 8 weeks or until clear. RESULTS: Sixteen patients (73%) showed complete clearing of their warts in a mean of 11 weeks of twice weekly treatment. Upon follow-up, which averaged 9.5 months, 17 of 21 patients (81%) remained clear of their warts. CONCLUSION: Natural alpha interferon by needless injector appears to represent an effective alternative treatment for palmar and plantar human papillomavirus lesions. Further study of this modality is indicated.

Adolescent↗

Unusual HPV types in oral warts in association with HIV infection.

Human papillomaviruses (HPV) are associated with certain oral soft tissue lesions, such as papillomas, warts, condylomata, and focal epithelial hyperplasia (FEH). HPV types 2, 6, 11, 16, and 18 have been identified in some of these oral lesions, while HPV 13 and 32 are associated with FEH. Little is known about the HPV types in oral warts of persons infected with human immunodeficiency virus (HIV). In this study, oral warts in 17 HIV-seropositive individuals were biopsied. Southern blot analyses were performed and the HPV types found were HPV 7 (7/17), 13 (1/17), 32 (1/17), and 18 (1/17). The presence of HPV type 7 is unusual in that it normally is found only in butcher's warts. There was no correlation between HPV type, histopathology, and clinical appearance of the lesions examined, except that the flat (FEH type) warts contained HPV types 13, 18 and 32 (1 of each). HIV infection appears to predispose individuals to oral infection with unusual HPV types.

Adult↗

Characterization of a new type of human papillomavirus that causes skin warts.

A human papillomavirus (HPV) was isolated from the lesions of a patient (ML) bearing numerous hand common warts. This virus was compared with the well-characterized HPV found in typical plantar warts (plantar HPV). ML and plantar HPV DNAs have similar molecular weights (5.26 x 10(6) and 5.23 x 10(6), respectively) but were shown to be different by restriction enzyme analysis. When the cleavage products of both DNAs by endonuclease EcoRI, BamI, HpaI, or Hind were analyzed by electron microscopy, one, two, one, and four fragments were detected for ML HPV DNA instead of the two, one, two, and six fragments, respectively, detected for plantar HPV DNA. In contrast to plantar HPV DNA, a high proportion of ML HPV DNA molecules were resistant to these restriction enzymes. Most, if not all, of the molecules were either resistant to BamI and sensitive to EcoRI or sensitive to BamI and resistant to EcoRI. After denaturation and renaturation of the cleavage products of ML HPV DNA by a mixture of the two enzymes, the circular "heteroduplexes" formed showed one to three heterology loops corresponding to about 4 to 8% of the genome length. No sequence homology was detected between ML and plantar HPV DNAs by cRNA-DNA filter hybridization, by measuring the reassociation kinetics of an iodinated plantar HPV DNA in the presence of a 25-fold excess of ML HPV DNA, or by the heteroduplex technique. The two viruses had distinct electrophoretic polypeptide patterns and showed no antigenic cross-reaction by immunodiffusion or immunofluorescence techniques. Preliminary cRNA-DNA hybridization experiments, using viral DNAs from single or pooled plantar or hand warts, suggest that hand common warts are associated with viruses similar or related to ML HPV. The existence of at least two distinct types of HPVs that cause skin warts was demonstrated; they were provisionally called HPV type 1 and HPV type 2, with plantar HPV and ML HPV as prototypical viruses, respectively.

Antigens, Viral↗

Variation in the nucleotide sequence of cottontail rabbit papillomavirus a and b subtypes affects wart regression and malignant transformation and level of viral replication in domestic rabbits.

We previously reported the partial characterization of two cottontail rabbit papillomavirus (CRPV) subtypes with strikingly divergent E6 and E7 oncoproteins. We report now the complete nucleotide sequences of these subtypes, referred to as CRPVa4 (7,868 nucleotides) and CRPVb (7,867 nucleotides). The CRPVa4 and CRPVb genomes differed at 238 (3%) nucleotide positions, whereas CRPVa4 and the prototype CRPV differed by only 5 nucleotides. The most variable region (7% nucleotide divergence) included the long regulatory region (LRR) and the E6 and E7 genes. A mutation in the stop codon resulted in an 8-amino-acid-longer CRPVb E4 protein, and a nucleotide deletion reduced the coding capacity of the E5 gene from 101 to 25 amino acids. In domestic rabbits homozygous for a specific haplotype of the DRA and DQA genes of the major histocompatibility complex, warts induced by CRPVb DNA or a chimeric genome containing the CRPVb LRR/E6/E7 region showed an early regression, whereas warts induced by CRPVa4 or a chimeric genome containing the CRPVa4 LRR/E6/E7 region persisted and evolved into carcinomas. In contrast, most CRPVa, CRPVb, and chimeric CRPV DNA-induced warts showed no early regression in rabbits homozygous for another DRA-DQA haplotype. Little, if any, viral replication is usually observed in domestic rabbit warts. When warts induced by CRPVa and CRPVb virions and DNA were compared, the number of cells positive for viral DNA or capsid antigens was found to be greater by 1 order of magnitude for specimens induced by CRPVb. Thus, both sequence variation in the LRR/E6/E7 region and the genetic constitution of the host influence the expression of the oncogenic potential of CRPV. Furthermore, intratype variation may overcome to some extent the host restriction of CRPV replication in domestic rabbits.

Animals↗

Cryosurgery of genital warts in cases in which podophyllin treatment failed or was contraindicated.

A total of 56 cases with warts in which podophyllin treatment was either contraindicated or a failure, were treated with nitrous oxide using a Keymed 500 cryosurgical appliance. Forty-three patients who completed treatment were followed-up for three months. Thirty-seven of these had received applications of podophyllin twice weekly for an average period of three months before cryosurgery. The remaining cases in whom podophyllin was considered to be contraindicated included five with vulval warts (two were pregnant, two were bronchial asthmatics taking oral prednisolone, and one was taking oral clomiphene citrate), and a diabetic patients with penile warts. Thirty-two were cured and 11 relapsed. The latter were re-treated at the end of the follow-up period with two freezing cycles of 45 seconds at an interval of 30 minutes. Seven were cured and the remaining four men who failed to respond belonged to the podophyllin-resistant group and included three with metal warts and one homosexual with anogenital warts. Cryosurgery gave a cumulative success rate of 91%. A single freezing cycle was free from complications but a double freezing cycle was often followed by severe local reaction.

Cryosurgery↗

Topical anaesthesia with local anaesthetic (lidocaine and prilocaine, EMLA) cream for cautery of genital warts.

Removal of genital warts by thermocautery was performed in 108 patients (57 men and 51 women) under topical anaesthesia with a local anaesthetic cream, lidocaine and prilocaine (EMLA). Most men had warts in the preputial cavity, most women had warts situated on the mucous membranes of the vulva, and warts at multiple sites were common. About 1 ml of cream per lesion was applied to the warts for 20 to 105 minutes before the operation. Plastic film (Glad, Union Carbide) was applied over the cream when natural occlusion, such as under the prepuce or on the introitus, was not present. Local pallor was seen in 30% of the patients, redness in 53%, and oedema in 15%, but did not cause any discomfort and were clinically insignificant. Analgesia was sufficient in 96% of the men and in 40% of the women. Additional local infiltration was given to 60% of the women, but was not as painful as injections generally are in the genital area. The analgesic efficacy on women may be further improved by optimising the application time on the genital mucosa.

Adolescent↗

Oxidative stress in patients with nongenital warts.

Comparison of oxidative stress status between subjects with or without warts is absent in the literature. In this study, we evaluated 31 consecutive patients with warts (15 female, 16 male) and 36 control cases with no evidence of disease to determine the effects of oxidative stress in patients with warts. The patients were classified according to the wart type, duration, number, and location of lesions. We measured the indicators of oxidative stress such as catalase (CAT), glucose-6-phosphate dehydrogenase (G6PD), superoxide dismutase (SOD), and malondialdehyde (MDA) in the venous blood by spectrophotometry. There was a statistically significant increase in levels of CAT, G6PD, SOD activities and MDA in the patients with warts compared to the control group (P< .05). However, we could not define a statistically significant correlation between these increased enzyme activities and MDA levels and the type, the duration, the number, and the location of lesions. We determined possible suppression of T cells during oxidative stress that might have a negative effect on the prognosis of the disease. Therefore, we propose an argument for the appropriateness to give priority to immunomodulatory treatment alternatives instead of destructive methods in patients with demonstrated oxidative stress.

Adolescent↗

Topical 5% imiquimod long-term treatment of cutaneous warts resistant to standard therapy modalities.

BACKGROUND: Long-lasting cutaneous warts may represent an unbearable stigma to patients and therefore pose a singular challenge for the physician. Generally, these warts are induced by human papillomavirus (HPV) 2, HPV-27 or HPV-57. OBJECTIVES: The present study was conducted to evaluate the efficacy and safety of long-term treatment with imiquimod 5% cream applied to long-lasting (mean duration 6.3 years) common warts, which had been resistant to previous therapeutic interventions. PATIENTS AND METHODS: Imiquimod cream was self-applied by the patients twice daily. Assessment of response and occurrence of side-effects was performed every 4 weeks until clinical cure or up to a maximum of 24 weeks. A total of 37 patients were recruited. RESULTS: 31 out of 37 patients completed the treatment. 10 out of 37 patients experienced a total clearance of their warts (27%). The mean duration to clearance was 19.2 weeks. 18 patients (49%) showed a reduction of more than 50% and 5 patients (14%) a reduction of less than 50%. CONCLUSION: Our data demonstrate that the long-term topical application of imiquimod 5% cream is an effective treatment for otherwise therapy-resistant cutaneous warts without causing any meaningful side-effects.

Adjuvants, Immunologic↗

Analysis of risk factors for cutaneous warts in renal transplant recipients.

We have investigated some possible risk factors for cutaneous warts in a consecutive group of renal transplant recipients treated with three different immunosuppressive regimens: prednisolone + azathioprine (PA), prednisolone + azathioprine + cyclosporin (PAC), prednisolone + cyclosporin (PC). Kaplan and Meier analysis showed an earlier onset of warts in the PAC and PC groups than in the PA group (p < 0.0001), which might be related to the different immunosuppressive action of the pharmacological treatments including cyclosporin. Seven patients had skin cancer: 4 of them also had multiple warts on the cancer site. In 2 patients, histological examination demonstrated the neoplastic transformation of a wart. Maintenance posology of azathioprine, cyclosporin and prednisolone may be an important risk factor for cutaneous warts; on the other hand HLA-B mismatch and HLA-A11 seem to have no effect.

Adolescent↗