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Various human papillomavirus of the genera α-, β-, γ-, μ- and η-papillomavirus induce type-specific extragenital warts. Plantar, common and plane warts are the most common types. The closely related Alpha-papillomaviruses HPV 2, 27 and 57 are responsible for the majority of therapy-resistant common warts. A wide armamentarium of surgical, physical, chemical or drug therapies is available but no modality cures all patients. In order to avoid overtreatment it is mandatory to differentiate between indolent warts which will spontaneously resolve, warts which cause acute discomfort and warts without any tendency to heal spontaneously. HPV type, wart type, localization, size, disease duration as well as age and immune status are parameters influencing self-healing and should be considered when choosing the appropriate wart therapy.

Human papillomaviruses infect the squamous epithelia of the skin and cause warts, and are occasionally found in squamous cell carcinomas. Since cell-mediated immunity plays a crucial role in the control of HPV-infections, organ transplant recipients, unable to mount an adequate T-helper 1 cell-mediated immune surveillance, frequently develop widespread and resistant induced warts. Skin tumors, especially squamous cell carcinomas, are the most common post-transplantation neoplasm. Warts, actinic keratoses and invasive squamous cell carcinomas are known to develop at the same time in the areas. The role of HPV in the development of invasive squamous cell carcinoma under immunosuppression, remains to be elucidated in respect to common risk factors and increased numbers of warts potentially identifying patients at increased risk for carcinoma. We prospectively studied 1690 organ transplant recipients in the dermatology clinic at the Charité University Hospital in Berlin, to evaluate risk factors being involved in the development of HPV-induced warts and to assess a potential association of with the development of non-melanoma skin cancers in this population. The cumulative incidence of warts steadily increased throughout the post-transplant years. The presence of more than 10 verrucae was associated with the development of actinic keratoses, invasive squamous cell carcinoma and basal cell carcinoma. This study shows clear evidence that certain risk factors of skin carcinogenesis in organ transplant recipient such as increased age at transplantation, a high dose of immunosuppression related to a specific type of graft and use of azathioprine or cyclosporine are strongly associated with an increased incidence of warts. Furthermore, HPV-induced verrucae vulgares could be used as a potential predictor for the development of coincidental non melanoma skin cancer in organ transplant recipients and therefore could serve as an early identification marker of skin cancer high-risk patients. The challenging management of warts in organ transplantation patients is reviewed.

Human papilloma viruses (HPV) lead to common warts in 5% of the population and genital warts in 1% of sexually-active individuals. Although about 50% of HPV infections regress spontaneously, the course is uncertain. Expectant waiting often leads to progression and dissemination. Plantar warts may cause pain on walking, while palmar and genital warts may impair social contacts. There are many treatments for warts, including a variety of laser systems. The CO(2) laser is the best ablative approach, producing cure rates of up to 75% for therapy-resistant common warts in cohort and case-control studies. Side effects such as bleeding, pain and reduced function over weeks must be weighed against the likelihood of success. Considering non-ablative approaches, pulsed dye lasers can be used for a selective, non-bloody destruction of extragenital and genital warts and may become the treatment of choice. In prospective randomized studies, they produced cure rates of up to 82% for therapy-resistant warts with few side effects.

While efficacy of topical photodynamic therapy (PDT) for the treatment of superficial non-melanoma skin cancer is already well-proven by several controlled clinical trials, there are only a few controlled studies showing efficacy of PDT for non-oncologic skin disorders. This report provides information on the use of PDT for inflammatory skin disorders, disorders of the pilosebaceous unit, infections of the skin, sclerotic skin diseases and cosmetic indications.

The term keratosis covers a variety of growths such as warts and pressure-induced callosities. Warts develop in the absence of pressure, and often clear up again after a certain period, usually without treatment. Clavi can develop as a result of wearing poorly fitting shoes, but also deformed toes or other anatomical deformities affecting the foot. The resulting non-anatomical stressing leads to the formation of pressure callosities and even to pressure sores.

Proliferative verrucous leukoplakia (PVL) is a seldom form of oral leukoplakia (OL) with high transformation tendency. It starts as a bold hyperkeratosis changing into an exophytic verrucous form spreading in the oral cavity. The clinical diagnosis therefore is a retrospective one.

A 6 year old girl presented with flat-topped, skin-colored, partly grouped papules with slightly roughened surface on the left side of the forehead and around the left orbit. In an off-label use imiquimod 5% cream was applied twice a week before bedtime and was rinsed off in the morning. After four weeks of treatment the lesions had vanished completely. We suggest imiquimod 5% cream as a treatment option for juvenile plane warts even in children and in the face.

According to guidelines of the German STD Association, appropriate treatment of extensive anogenital warts with comparable recurrence rates includes cryotherapy, surgical excision, electrosurgery, CO2- and Nd:YAG-laser vaporisation. All these procedures are associated with varying degrees of risk for bleeding, release of potentially infectious aerosol, deep thermal destruction, slow wound healing, and scarring.Using argon-plasma coagulation anogenital warts can be removed in layers in a controlled manner. High frequency current flows through the argon plasma to the tissue, allowing well-controlled, superficial tissue destruction.From January 2001 to March 2003, 54 patients with extensive genital, anal or anogenital warts were treated. After one treatment, 66% of the pa- tients remained disease-free in the following 4 months. Thirteen patients (24%) showed early recurrence after 4 weeks, five patients (9%) at a later date. In these patients, further treatment, in 9 cases combined with topical imiquimod cream, were necessary for complete remission.Compared to other therapeutic procedures, argon-plasma coagulation is a better controlled, quick and low-risk option for the treatment of anogenital warts. Depending on the type of involvement and individual risk factors, postoperative treatment with topical imiquimod cream may be useful.

A 42- year-old atopic patient had suffered from disseminated verrucae since he was 14 years old. He had been treated with various, often expensive immunomodulatory agents for a long time without appreciable success. Laboratory tests revealed a striking T-cell defect. Topical treatment with imiquimod (Aldara 5% Cream) led to the regression of all verrucae.

(1) Salicylic acid (SA) and 5-Fluorouracil (5-FU) are effective drugs in wart therapy. (2) In Germany, increasing data on the benefit and the economic efficiency of drugs at Level I of evidence-based medicine are needed.Evaluation of the effectiveness and benefits of a drug combination containing 0.5 % 5-FU and 10% SA in the therapy of (a) common and (b) plantar warts in form of a two-step procedure--(1) Systematic literature analysis, (2) Meta-analysis of the randomised-controlled studies (RCTs).(1) The efficacy of 5-FU/SA therapy was tested in a total of 625 patients (n=8 RCTs) with common warts and 101 patients (n=4 RCTs) with plantar warts. The therapeutic effect across all studies in common warts was 63.4% response (complete healing) for 5-FU/SA vs. 23.1% for the 5-FU-free controls, respectively. In plantar warts, the response was 63.0% vs. 11.0%. (2) A meta-analysis of n=7 RCTs on common warts (n=325 patients) showed a mean risk difference of 0.42 (CI 0.34-0.50, p0.05), thus a significant superiority of 5-FU/SA over SA. A comparable result was also found for plantar warts.The combination of 5-FU and SA is an effective and beneficial therapy for common and plantar warts.

This article gives and overview of the various types of verrucous skin changes (viral warts, seborrheic warts).

In the present field study the skin of the feet of 37 heavy draught horses of different breeds showing verrucous pastern dermatitis was examined clinically. Included were the degree of severity of the disease and the prevalence of anatomically normal structures associated with the skin: fetlock tufts of hair ("feathering"), ergots, chestnuts, bulges in the pastern region, cannon circumference. Each horse was examined for Chorioptes sp. skin mites. Information was also collected on the development of the skin alterations and housing conditions and feeding. These individual data were correlated with the clinical degree of severity of verrucous pastern dermatitis, which was evaluated using a numerical code (scoring system). In addition, punch biopsies were taken from the diseased skin of the feet and from healthy skin of the neck for comparative patho-histological examination (see Part III). Verrucous pastern dermatitis is a chronic disease which can be divided into four groups: scaling (group I), hyperkeratotic and hyperplastic plaque-like lesions (group II), tuberous skin masses (group III), and verrucous skin lesions with rugged surfaces (group IV). No correlation was found between the clinical degree of severity of the skin lesions and sex, breed, amount of work, use of stallions for breeding, grooming condition of the hair, white markings in the foot region, or Chorioptes sp. infestation. In regard to feeding it was found that the amount of maize and oats fed had some influence on the clinical degree of severity. Statistical analysis revealed a significant correlation between the clinical degree of severity and the age, the grooming condition of the hooves, and the mean cannon circumference. The prevalence of fetlock tufts of hair, chestnuts, ergots, and anatomically normal bulges in the pastern region also increased significantly with the clinical degree of severity. Furthermore the study revealed that the clinical degree of severity depended on the hygienic conditions of the stables and of the ground where the horses were kept outdoors.

Background: Common warts (verrucae vulgares) are human papilloma virus (HPV) infections with a high incidence and prevalence, most often affecting hands and feet, being able to impair quality of life. About 30 different therapeutic regimens described in literature reveal a lack of a single striking strategy. Recent publications showed positive results of photodynamic therapy (PDT) with 5-aminolevulinic acid (5-ALA) in the treatment of HPV-induced skin diseases, especially warts, using visible light (VIS) to stimulate an absorption band of endogenously formed protoporphyrin IX. Additional experiences adding waterfiltered infrared A (wIRA) during 5-ALA-PDT revealed positive effects. Aim of the study: First prospective randomised controlled blind study including PDT and wIRA in the treatment of recalcitrant common hand and foot warts. Comparison of "5-ALA cream (ALA) vs. placebo cream (PLC)" and "irradiation with visible light and wIRA (VIS+wIRA) vs. irradiation with visible light alone (VIS)". Methods: Pre-treatment with keratolysis (salicylic acid) and curettage. PDT treatment: topical application of 5-ALA (Medac) in "unguentum emulsificans aquosum" vs. placebo; irradiation: combination of VIS and a large amount of wIRA (Hydrosun® radiator type 501, 4 mm water cuvette, waterfiltered spectrum 590-1400 nm, contact-free, typically painless) vs. VIS alone. Post-treatment with retinoic acid ointment. One to three therapy cycles every 3 weeks. Main variable of interest: "Percent change of total wart area of each patient over the time" (18 weeks). Global judgement by patient and by physician and subjective rating of feeling/pain (visual analogue scales). 80 patients with therapy-resistant common hand and foot warts were assigned randomly into one of the four therapy groups with comparable numbers of warts at comparable sites in all groups. Results: The individual total wart area decreased during 18 weeks in group 1 (ALA+VIS+wIRA) and in group 2 (PLC+VIS+wIRA) significantly more than in both groups without wIRA (group 3 (ALA+VIS) and 4 (PLC+VIS)): medians and interquartile ranges: -94% (-100%/-84%) vs. -99% (-100%/-71%) vs. -47% (-75%/0%) vs. -73% (-92%/-27%). After 18 weeks the two groups with wIRA differed remarkably from the two groups without wIRA: 42% vs. 7% completely cured patients; 72% vs. 34% vanished warts. Global judgement by patient and by physician and subjective rating of feeling was much better in the two groups with wIRA than in the two groups without wIRA. Conclusions: The above described complete treatment scheme of hand and foot warts (keratolysis, curettage, PDT treatment, irradiation with VIS+wIRA, retinoic acid ointment; three therapy cycles every 3 weeks) proved to be effective. Within this treatment scheme wIRA as non-invasive and painless treatment modality revealed to be an important, effective factor, while photodynamic therapy with 5-ALA in the described form did not contribute recognisably - neither alone (without wIRA) nor in combination with wIRA - to a clinical improvement. For future treatment of warts an even improved scheme is proposed: one treatment cycle (keratolysis, curettage, wIRA, without PDT) once a week for six to nine weeks. Hintergrund: Vulgäre Warzen (Verrucae vulgares) sind humane Papillomvirus-Infektionen (HPV) mit einer hohen Inzidenz und Prävalenz, die am häufigsten Hände und Füße befallen und die in der Lage sind, die Lebensqualität zu beeinträchtigen. Etwa 30 in der Literatur beschriebene Therapieverfahren zeugen von einem Mangel an einer einzigen überzeugenden Strategie. Jüngste Veröffentlichungen zeigten positive Ergebnisse der Photodynamischen Therapie (PDT) mit 5-Aminolävulinsäure (5-ALA) in der Therapie von HPV-induzierten Hautkrankheiten, besonders Warzen, wobei sichtbares Licht (VIS) verwendet wird, um ein Absorptionsband des endogen aus 5-ALA gebildeten Protoporphyrin IX zu stimulieren. Weitere Erfahrungen, wassergefiltertes Infrarot A (wIRA) während der 5-ALA-PDT zusätzlich anzuwenden, offenbarten positive Wirkungen. Ziel der Untersuchung: Erste prospektive randomisierte kontrollierte Blind-Studie, die PDT und wIRA in die Behandlung von therapierefraktären vulgären Hand- und Fußwarzen einbezieht. Vergleich von "5-ALA-Salbe (ALA) vs. Placebo-Salbe (PLC)" und "Bestrahlung mit sichtbarem Licht und wIRA (VIS+wIRA) vs. Bestrahlung mit sichtbarem Licht allein (VIS)". Methoden: Vorbehandlung mit Keratolyse (Salizylsäure) und Kürettage. Photodynamische Therapie (PDT): topische Applikation von 5-ALA (Medac) in "Unguentum emulsificans aquosum" vs. Placebo; Bestrahlung: Kombination von sichtbarem Licht (VIS) und einem hohen Maß an wassergefiltertem Infrarot A (wIRA) (Hydrosun®-Strahler Typ 501, 4 mm Wasserküvette, wassergefiltertes Spektrum 590-1400 nm, kontaktfrei, typischerweise schmerzlos) vs. sichtbares Licht (VIS) allein. Nachbehandlung mit Vitamin-A-Säure-Salbe. Ein bis drei Therapiezyklen im Abstand von 3 Wochen. Hauptzielvariable: "Prozentuale Änderung der Gesamtwarzenfläche jedes Patienten über die Zeit" (18 Wochen). Globales Urteil von Patient und von Arzt sowie subjektive Einschätzung von Empfindung/Schmerz (visuelle Analogskalen). 80 Patienten mit therapierefraktären vulgären Hand- und Fußwarzen wurden randomisiert einer der vier Behandlungsgruppen (mit vergleichbarer Anzahl an Warzen in vergleichbaren Lokalisationen in allen Gruppen) zugeteilt. Ergebnisse: Die individuelle Gesamtwarzenfläche nahm während 18 Wochen in Gruppe 1 (ALA+VIS+wIRA) und in Gruppe 2 (PLC+VIS+wIRA) signifikant mehr als in den beiden Gruppen ohne wIRA (Gruppe 3 (ALA+VIS) und 4 (PLC+VIS)) ab: Mediane und Interquartil-Spannen: -94% (-100%/-84%) vs. -99% (-100%/-71%) vs. -47% (-75%/0%) vs. -73% (-92%/-27%). Nach 18 Wochen unterschieden sich die zwei Gruppen mit wIRA deutlich von den zwei Gruppen ohne wIRA: 42% vs. 7% komplett geheilte Patienten; 72% vs. 34% völlig verschwundene Warzen. Das globale Urteil von Patient und von Arzt und die subjektive Einschätzung des Empfindens waren in den zwei Gruppen mit wIRA viel besser als in den zwei Gruppen ohne wIRA. Folgerungen: Das oben beschriebene vollständige Therapieschema von Hand- und Fußwarzen (Keratolyse, Kürettage, Photodynamische Therapie, Bestrahlung mit VIS+wIRA, Vitamin-A-Säure-Salbe; drei Therapiezyklen im Abstand von 3 Wochen) erwies sich als effektiv. Innerhalb des Therapieschemas zeigte sich wIRA - als nicht-invasive und schmerzlose Therapiemodalität - als ein wichtiger, effektiver Faktor, während die Photodynamische Therapie mit 5-ALA in der beschriebenen Form nicht erkennbar - weder alleine (ohne wIRA) noch in Kombination mit wIRA - zu einer klinischen Verbesserung beitrug. Für die zukünftige Behandlung von Warzen wird ein weiter verbessertes Schema vorgeschlagen: ein Therapiezyklus (Keratolyse, Kürettage, wIRA, ohne PDT) einmal pro Woche für sechs bis neun Wochen.

Papillomaviruses are prevalent throughout the world. They can cause warts or papillomas. Some papillomaviruses are also involved in the pathogenesis of malignant tumors. Cutaneous and anogenital warts are the most frequent viral disease of the skin. The incidence of verrucae vulgaris and condylomata is estimated to be 7-10% in the European population and 1% in the American population. HPV infections can be verified by clinical examination, cytology and histology, detection of antibodies, molecular techniques and directly via viral structures. Antibodies against HPV are considered markers for prolonged infection and cumulatively high expression of viral particles since they persist with low titers years after a lesion has resolved. Sensitivity only reaches 50-60% even in HPV DNA-positive patients. Serodiagnosis does not appear to be appropriate for routine practice. No virustatic treatment exists. Depending on wart-specific factors, compliance of the patient, and experience of the attending therapist, all ablative, chemodestructive or novel immuno modulatory procedures are comparable. However, there are enormous differences in price and effort required for treatment, which should be considered when choosing the method.

Human papillomaviruses (HPV) infect exclusively the basal cells of the skin and of mucosal epithelia adjacent to the skin such as the mouth, the upper respiratory tract, the lower genital tract and the anal canal. HPV does not lead to a viremia. Basically there are three different types of HPV infection: Clinically visible lesions, subclinical HPV infections and latent HPV infections. Distinct HPV types induce morphologically and prognostically different clinical pictures. The most common HPV associated benign tumor of the skin is the common wart. Infections of the urogenitoanal tract with specific HPV-types are recognised as the most frequent sexually transmitted viral infections. So-called "high-risk" HPV-types (HPV16, 18 and others) are regarded by the world health organisation as important risk-factors for the development of genital cancer (mainly cervical cancer), anal cancer and upper respiratory tract cancer in both genders. Antiviral substances with a specific anti-HPV effect are so far unknown. Conventional therapies of benign skin warts and of mucosal warts are mainly nonspecific. They comprise tissue-destroying therapies such as electrocautery, cryotherapy and laser. In addition cytotoxic substances such as podophyllotoxin and systemic therapy with retinoids are in use. Systemically and topically administered immunotherapies represent a new approach for treatment. Both interferons and particularly the recently developed imiquimod, an interferon-alpha and cytokine-inductor lead to better results and are better tolerated then conventional therapies. HPV-specific vaccines have been developed in the last 5 years and will be used in future for prevention and treatment of benign and malignant HPV-associated tumors of the genitoanal tract in both sexes.

Immunomodulators include both immunostimulatory and immunosuppressive agents. Obligate contact sensitizers such as diphencyprone or dinitrochlorobenzene have been used against viral and autoimmune diseases. Newer agents such as the toll-like receptor agonists imiquimod and resiquimod have been clinically used to treat viral infections and skin cancers in immunocompetent and immunosuppressed patients. On the other hand, the topical immunosuppressive agents tacrolimus and pimecrolimus have been used with great success in the treatment of chronic inflammatory diseases in children and adults. The introduction of this new class of drugs (i.e. Calcineurin inhibitors) marked the beginning of the post-cortisone era in clinical dermatology. Toll-like receptor agonists and calcineurin antagonists will supplement corticosteroids to improve specific dermatological therapy. Topical immunotherapy with both immunostimulatory and immunosuppressive agents show potential for effective and patient-friendly treatment of inflammatory, infectious and neoplastic skin diseases. Long-term evaluation will define the tolerability and the safety profile.

Recalcitrants viral warts can pose a therapeutic challenge to the treating physician. In a clinical study, we documented the effect of imiquimod 5% cream (Aldara) on recalcitrants warts in 22 patients. A complete and partial clearing of the warts was achieved in 41% and 50%, respectively. In only 9% of patients no improvement could be observed. Beside the very often observed perilesional erythema, which correlated well with good treatment response, no relevant side effects were documented. Imiquimod 5% cream (Aldara) is an efficient, easy to perform ambulatory treatment modality for recalcitrants HPV induced warts with few side effects.

Verruciform xanthoma (VX), a rare, benign lesion of the skin and mucosa, is slow-growing, asymptomatic and characterized by a granular (verruciform) surface. It is yellowish-red or grey in color and up to 2 cm in diameter. Histologically, a papillary and/or verrucous proliferation of the squamous epithelium with hyperparakeratosis and numerous foam cells is present. These cells are predominantly located within the papillae of the lamina propria. For differential diagnosis, other papillomatous and verrucous lesions such as verrucous carcinomas or squamous cell carcinomas need to be ruled out.A 46-year-old patient with VX located on the alveolar process regio 26-28 is presented. Clinically, a 2 x 2 cm granular, oral mucosa surface lesion extending onto the palate occurred in regio 26-28. Biopsy was characterized light microscopically by the presence of swollen, elongated cells in the submucosa, an indication of VX alterations. Transmission electron microscopy demonstrated foam cells in the subepithelium containing numerous membrane-bound vesicles similar in diameter and showing a wide variation in electron density. Morphologically, these cells resembled macrophage-related cells. The lesion was excised in total with no evidence of recurrence after 9 months.The pathogenesis of VX is still unclear. The characteristic xanthoma cells may play a major role in VX. Microscopic analysis of the morphology of the foam cells indicated that they may represent a differentiated form of macrophages. Lipid vesicles inside these cells differed in their electron density indicating a heterogeneous biochemistry or different states of maturation.

Various approaches have been taken in the management of verrucae vulgares, but a treatment of choice has not been established.Over a period of 12 months, 99 Patients with recalcitrant or untreated verrucae vulgares on their hands or feet (2:1) were treated with a 585 nm flashlamp pumped pulsed dye laser (FPDL) every 2 to 4 weeks. Laser parameters were: energy density 8 J/cm2, spot size 7 mm, pulse duration 450 microseconds. No topical measures were employed during the course of laser treatment.93 patients finished the study, as 6 were lost to follow-up. Up to 8 laser treatments led to 63% total remission and 22% partial remission, 15% did not respond to this type of management. Relapses were not found in a follow-up period of 2 to 6 months.FPDL is efficient for the removal/reduction of verrucae vulgares and does not requires less patient compliance than other treatment options.