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Abstract
Verrucae vulgares zeigen häufig äusserste Therapieresistenz gegenüber verschiedenen konventionellen Behandlungsmethoden, wie
beispielsweise der Kryo- oder Lasertherapie, Lokaltherapie mit Salizylsäure oder mechanischer Abtragung. Die intraläsionale
Applikation von Bleomycin wird seit 1970 bei therapieresistenten Warzen eingesetzt. Über die Jahre entwickelten sich unterschiedliche
Applikationsformen des Chemotherapeutikums bei der Behandlung von Warzen. Wir behandelten eine 27-jährige Patientin mit Sharp-Syndrom,
die aufgrund der systemischen Immunsuppression über 9 Jahre an therapieresistenten palmaren und plantaren Warzen litt. Bei
der Patientin wurde die Bleomycinprickmethode gewählt, bei der Bleomycin (1 mg/ml 0,9% NaCl) mit Hilfe einer Pricklanzette
in die Warze appliziert wird. Nach durchschnittlich 16 Behandlungen an Händen und Füßen kam es zur fast kompletten Remission
der Warzen.
Common warts can be highly resistant to conventional treatments such as cryotherapy, laser surgery, salicylic acid and mechanical
removal. Intralesional bleomycin has been described as an effective treatment for common warts since 1970. We treated a 27-year-old
woman with Sharp's syndrome who was on immunosuppressive drugs and had suffered for nine years from therapy-resistant warts
on palms and soles. A bleomycinprick technique using a bifurcated needle to introduce bleomycin sulfate (1 mg/ml sterile saline
solution) into the warts resulted in almost complete remission after 16 treatment sessions.
Background
Plantar warts are common and often painful. Treatment of plantar warts is difficult and requires multiple treatments. Several clinical trials have proven the efficacy of bleomycin, but relatively high concentrations have been required and considerable side effects have been experienced.
Objective
To evaluate the efficacy and safety of low-concentration (0.1 U/mL) bleomycin using a translesional injection technique for the treatment of plantar warts.
Methods
The study included 23 patients with single or multiple plantar warts. Very low-concentration bleomycin was injected into a single wart or the largest plantar wart in the case of multiple lesions. Injections were performed at 4-week intervals until resolution of the warts or development of side effects. The translesional multipuncture technique was used.
Results
Thirteen patients were male (56.5%), and the mean age was 27.7 years. The results revealed complete clearance of warts in 17 of 23 (74%) patients, partial response in 1 (4.3%) patient, and no response in 3 (13%) patients. Recurrence was observed in 2 patients at 3 months of follow-up. Among those two, one patient showed complete clearance after the second injection at 6 months of follow-up. All patients were followed for 6 months after the initial treatment. No significant long-term adverse effects were noted. Only three patients (13%) had localized moderate pain for 2 to 3 days after the injection.
Conclusion
Translesional injection by very low-concentration (0.1 U/mL) bleomycin appears to be a simple, effective, and safe treatment modality for plantar warts.
Im Allgemeinen kann sich ein bösartiger Tumor ausbreiten durch:
Infiltration in das umgebende Gewebe (per contiguitatem ),
entlang anatomischer Strukturen (per continuitatem ) wie z. B. Ducti oder Gewebeschichten (Strecksehnen; Beugesehnenscheide etc.) und
über die Lymph- und Blutgefäße.
Background: Warts are often a difficult treatment problem for dermatologists. Cimetidine is a H2 histamine receptor antagonist that has been used mainly to treat peptic ulcer disease. The successful use of cimetidine in the treatment of viral warts has been reported previously using doses of 40 mg/kg/day and has the advantage of being painless and easy to administer. Objective: In this study we evaluated the effect of cimetidine as an immunomodulating agent on multiple warts. Methods: We have now treated 24 patients, including 7 children, with multiple viral warts on the hands, feet or faces with high dose cimetidine for 3 or 4 months (14 female, 10 male, age range 6 - 46 years). Results: Of the 24 patients who completed the study, 19 patients (79.2%) had either complete resolution or partial resolution of their warts within 3 months of cimetidine therapy without any adverse effects. Conclusion: This study confirms that high-dose cimetidine therapy is beneficial and safe in the treatment of recalcitrant and multiple warts.
Background: It is often a difficult problem for dermatologists to treat verruca plana. Cimetidine is a H2 histamine receptor antagonist that has been used mainly to treat peptic ulcer disease. The successful use of cimetidine in the treatment of viral warts has been reported previously using doses of 40 mg/kg/day and has the advantage of being painless and easy to administer. Objective: The purpose of this study was to evaluate the clinical effects of high dose cimetidine therapy for verruca plana. Methods: Thirty-six patients with verruca plana were treated with high dose cimetidine therapy (22 females, 14 males; age range 7-56 years). Results: Of the 36 patients who completed the study, 15 patients (41.7%) showed complete remission. 8 patients (22.2%) showed partial remission. There was no significant differences among the complete remission, the partial remission and the no response groups. There were a few adverse effects including transient liver enzyme elevation and gynecomastia which were normalized after the cimetidine was discontinued. Conclusion: High dose cimetidine therapy is an effective treatment modality for verruca plana without severe adverse effects.
Background: Warts are benign tumors of the skin and mucosa and are caused by human papilloma virus (HPV). They are one of the most common skin diseases found mainly in children and adolescents. Although most of the warts disappear spontaneously or respond to the usual therapeutic measures, resistant forms of the warts impose a problem in dermatology. Intralesional injection of bleomycin has been tried in the treatment of resistant warts with variable results in different studies.
Ein 31-jähriger Mann wurde wegen mehrjähriger Rhinokonjunktivitis und Niesattacken während der Monate März bis Mai vorstellig. Darüber hinaus berichtete der Patient über rezidivierende urtikarielle Reaktionen nach Hautkontakt mit einem Chamäleon (Chamaeleo calyptratus). Innerhalb weniger Minuten kam es speziell an den Berührungspunkten mit den Tierkrallen zu transienter Quaddelbildung mit Erythem und Juckreiz. Bei anderen Personen traten vergleichbare Reaktionen nicht auf. Die Allergietestung ergab eine Sensibilisierung gegen die Frühblüher Hasel, Erle, Birke und Esche, gegen Hausstaubmilbe und Katze sowie Ficus benjamina. Ein kausaler Zusammenhang zwischen den Lokalreaktionen und der Ficus-Sensibilisierung ergab sich aus dem Umstand, dass sich das Reptil regelmäßig auf einem zimmerhohen Ficus benjamina aufhielt und dabei offensichtlich seine Krallenspitzen mit dem allergenen Milchsaft der Pflanze kontaminierte. Bei genauer Inspektion der Blätter konnten unzählige Einstiche der spitzen Krallen gefunden werden. Inhalative Beschwerden durch Ficus benjamina sowie eine Unverträglichkeit von Ficus-assoziierten Nahrungsmitteln bestanden bei unserem Patienten nicht.
The treatment of periungual warts is a therapeutic challenge. Various treatment modalities can be ineffective and may cause scarring and permanent nail changes.
A prospective pilot study to investigate the efficacy and safety of a low concentration (0.1 U/mL) of bleomycin in the treatment of periungual warts.
Periungual warts were injected with bleomycin (0.1 U/mL) every 4 weeks until elimination of the lesions or until the injections were discontinued because of adverse effects. Bleomycin was administered using the translesional multipuncture technique.
We recruited 15 patients with periungual warts from March 2007 to March 2008. Thirteen patients were male (86.6%); median age was 30. Seven patients (46.6%) demonstrated complete clearance 1 month after the first injection; two required two treatment sessions. Thirteen (86.6%) patients had complete clearance of the treated wart at the 6-month follow-up with only one injection. Wart recurrence was observed in two patients. All patients were followed for 6 months after the initial treatment. No significant long-term adverse effects were noted. Only one patient demonstrated mild postinflammatory hyperpigmentation, which resolved after 1 month, and nine (60%) had localized moderate pain for 2 to 3 days after the injection.
Translesional multipuncture treatment with a low concentration (0.1 U/mL) of bleomycin is an effective modality for periungual warts that results in minimal side effects. Larger controlled studies are needed.
The benzene extract of the leaves of Ficus benjamina (variety comosa) afforded a new triterpene, named serrat-3-one (Fc-2), along with the known phytoconstituents pentacontanyl decanoate (Fc-1), friedelin and beta-sitosterol. Their structures were established on the basis of chemical and physical evidence (IR, (1)H NMR, (13)C NMR and MS). The aqueous and alcoholic extracts of leaves of F. bejamina showed significant antinociceptive activity in an analgesiometer test.
• A multiple puncture technique using a bifurcated vaccination needle to introduce bleomycin sulfate (1 U/mL sterile saline solution) into warts resulted in elimination of 92% of a random series of 258 warts after a single treatment. Recurrence was not observed during a 6-month follow-up period. Six of the 66 patients required two to seven treatments for wart eradication, and four patients requested alternative therapy after initial failure with a single bleomycin treatment.(Arch Dermatol. 1991;127:234-236)
The cytotoxic effect of the antitumor antibiotic bleomycin toward cultured mouse FM3A cells was greatly enhanced by exposure of the cells to local anesthetics either before or together with treatment with bleomycin. Such local anesthetics include dibucaine, tetracaine, butacaine, lidocaine and procaine. Dibucaine-induced cell sensitization to bleomycin cytotoxicity produced a decrease in cell survival that became dependent on dose and time of bleomycin treatment. This effect of local anesthetics seems to be selective to bleomycin, since dibucaine and lidocaine do not enhance the cytotoxic effect of other antitumor agents including adriamycin, mitomycin C and -diamminedichloroplatinum(II).
Intralesional injection of bleomycin sulphate is a safe and almost completely effective treatment for warts. One thousand and fifty-two warts were injected with bleomycin sulphate, resulting in a cure rate of 99.23% after 12 weeks. No systemic manifestations of bleomycin toxicity were observed during the trial. After failure of injection of saline, it would appear that it is the cytotoxic effect of bleomycin and not the physical interference with the wart that effects the cure.
To the Editor.— The currently employed manipulations for the treatment of common and plantar warts depend mainly on physical and chemical destruction of the warts. 1,2 One of the disadvantages in these maneuvers is associated pain at the treated site. Herein, we report the usefulness of pressure-sensitive adhesive tape containing bleomycin sulfate for common and plantar warts. Acrylic adhesive was casted on a nonwoven fabric laminated polyurethane film as a backing. The adhesive surface of the tape was coated evenly with a solution containing bleomycin sulfate (5.3 mg/mL in ethanol and water [9:1]) and dried at room temperature. The final content of bleomycin sulfate was 60 μg/sq cm of the tape, as assessed by high-performance liquid chromatography. Placebo tape did not contain bleomycin sulfate. Seven patients with common warts and two with plantar warts were selected to participate in our study. They had not been treated previously for warts. Bleomycin
The development of Raynaud's phenomenon in a 34-year-old female after intralesional bleomycin treatment of finger warts is presented. Other complications of this therapy are briefly discussed.
The effectiveness of intralesional bleomycin (1 U/ml) in the treatment of warts refractory to conventional methods of treatment has been shown in well-controlled studies. We have now evaluated more dilute concentrations of bleomycin in the treatment of recalcitrant warts. Warts were assigned for therapy with intralesional bleomycin at a concentration of 0.25 U/ml, 0.5 U/ml, or 1 U/ml at 3-week intervals. If warts persisted after three injections or had recurred by 3 months' follow-up, treatment was considered a failure. Twenty-six patients whose warts had persisted after conventional treatment entered the study. Three patients had spontaneous regression of untreated warts during therapy and were not included in the results. Of seventy-nine warts treated with intralesional bleomycin, sixty-two (78%) were cured after one to three injections. Responding warts showed a hemorrhagic eschar even with the lower bleomycin concentrations and healed without complication. Almost all treated warts responded, although not all were cured. Treatment with bleomycin at 0.5 U/ml was as effective as treatment with 1 U/ml. Bleomycin at 0.25 U/ml is effective therapy but not enough warts were treated to permit a conclusion when compared with higher concentrations.
A 1 U/ml solution of bleomycin sulfate in physiologic saline solution was injected intralesionally in 38 patients, and was compared with physiologic saline solution injection into paired warts in the same patient. No patient received more than 2 ml of bleomycin. Ninety-seven of 143 warts (67.8%) showed complete resolution after one or two bleomycin injections, while 25 warts (17.5%) showed incomplete resolution. Bleomycin local injection failed to elicit any therapeutic response in 21 warts (14.7%). The cure rate was 77% for warts on the extremities, 71.4% for periungual warts, and 47.6% for the plantar warts. The responsive warts showed hemorrhagic eschars that healed without scarring. It is concluded that this form of treatment for resistant warts, up to the dose used, is safe, reliable, and accepted by the patient.
Bleomycin is gaining increasing popularity in the treatment of warts, but its efficacy has not been examined in well-controlled studies. We evaluated bleomycin in a double-blind placebo-controlled crossover study in recalcitrant warts treated unsuccessfully by conventional methods. Patients were assigned alternately to placebo or bleomycin groups and treated by intralesional injections of bleomycin, 1 U/ml, or saline, at 2-week intervals. If warts persisted, patients were changed after two injections to the alternate group and retreated with up to two further injections. Forty patients entered the study. Of 151 warts treated with intralesional bleomycin, 123 were cured after one or two injections (81%). The cure rate for plantar warts (60%) was lower than that for periungual warts (94%) and warts elsewhere on the extremities (95%). Fifty-five warts were injected with normal saline; none was cured. Responding warts showed a hemorrhagic eschar and healed without scarring, atrophy, or pigmentary change. Pain was usually mild and patient acceptance superior to that with liquid nitrogen. There was no evidence of systemic toxicity. Bleomycin is highly efficacious in the treatment of recalcitrant warts, is convenient, and has high patient acceptance. Long-term safety requires further study.
The plasma concentration of bleomycin after injection of bleomycin into warts is unknown, as is the long-term stability of bleomycin solution.
Our purpose was to measure plasma bleomycin concentration after injection of bleomycin into warts, to relate histologic and immunocytochemical changes in warts to possible mechanisms of action of bleomycin, and to asses the long-term stability of stored frozen bleomycin solution.
One milligram of bleomycin was injected into warts on the hands of seven men. Blood samples were taken 15 to 120 minutes after injection, and plasma bleomycin was measured by radioimmunoassay. Warts were removed 2 hours and 48 hours after treatment and studied histologically by light microscopy and for the presence of bleomycin by immunocytochemistry. The bleomycin concentration in 8 aliquots of solution stored at -20 degrees C for varying periods was measured by radioimmunoassay.
Peak levels of bleomycin of 7 to 113 ng/ml were reached by 45 minutes after injection. Plasma bleomycin exposure ranged from 515 to 5137 ng/ml/min between 15 and 120 minutes after injection. The most pronounced histologic changes at 48 hours were individual keratinocyte apoptosis throughout the epidermis merging into areas of complete epidermal necrosis, diffuse neutrophil accumulation, and microabscess formation at the granular layer. Immunocytochemistry demonstrated tissue-fixed bleomycin in all levels of the epidermis except the basal layer and most prominently in the granular layer. Bleomycin in solution stored for up to 27 months at -20 degrees C in glass showed no significant loss of immunoreactivity.
The use of bleomycin for the treatment of warts results in significant systemic drug exposure; thus it would be prudent to exclude pregnancy before treating women of child-bearing age. Bleomycin probably has a direct toxic effect on keratinocytes. Dilute bleomycin solution stored at -20 degrees C in glass is stable.