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The authors report a case of general and local poisoning after erroneous intravaginal administration of podophyllin for warts. The clinical course mainly showed a 10 day paralytic ileus, vaginal and urethral lesions and a severe peripheral neurological illness: paresthesia, dysesthesia and ataxia. The authors stress the potential toxicity of podophyllin and recommend great caution in using this product.
The effect of alcoholic solutions with 20% podophyllin from Podophyllum peltatum and Podophyllum emodi, 8% podophyllotoxin, and 8% colchicine, when applied to penile condylomata acuminata in 227 men, were statistically alike. Of the patients initially judged to be cured after 1-2 applications, 13% showed recurrence, thus bringing down the permanent cure frequency to only 43%. Local side effects were absent after only half the series of colchicine applications, whereas as much as about 3/4 of the treatment course with podophyllin and pure podophyllotoxin could be completed without provoking discomfort. Warts in the urinary meatus healed significantly less well than warts on the other genital mucous membranes. Eighty-nine per cent of patients who had previously been cured of concylomata became wart-free after 1-2 treatments, as opposed to only 40% of those who had never had this wart type previously. The use of the commercially available colchicine offers an opportunity to establish a standardized therapy; following application of an 8% solution, rinsing off should be performed after 6-8 hours.
A 22-year-old man developed a severe sensorimotor neuropathy following ingestion of podophyllin, which had been prescribed for genital condylomata. The initial toxic symptoms were vomiting and diarrhoea, followed by peripheral neuropathy. The neuropathy was still present 18 months later. Nerve conduction studies and sural nerve biopsy confirmed the presence of axonal degeneration.
Two patients developed podophyllin intoxication following ingestion of a broth of the Chinese herb guijiu. The neurological manifestations are described and the pathology of the peripheral neuropathy is fully documented with ultrastructural and quantitative studies.
HISTORY AND ADMISSION FINDINGS: A 57-year-old depressive and alcohol-dependent man was admitted because of frequent nausea and vomiting and abdominal complaints after he had ingested 40 ml of a tincture for treating warts. He was under the influence of alcohol, but normally oriented and without contributory findings other than his gastrointestinal complaints and tachypnea. INVESTIGATIONS: Transaminases were raised (GOT 1197 U/l, GPT 170 U/l, gammaGT 150 U/l, LDH 2047 U/l), as were creatine phosphokinase (426 U/l) and ferritin (12 200 ng/ml). Platelet count was 36000 mm3, Leucocytes count 11 700/mm (3). Gastroscopy showed marked mucosal necrosis along the entire esophagus and the pulled-up small intestine (state after gastrectomy). DIAGNOSIS, TREATMENT AND COURSE: The patient became comatose within 5 hours, acidotic, oliguric, required ventilation and went into severe shock. The symptoms and the fact that podophyllin (pod.) was the main agent in the wart preparation confirmed the suspicion of pod. poisoning. Symptomatic and intensive care measures stabilized his critically grave condition. He was extubated on the 7th day after ingestion and on the 10th day was discharged at his own request in a relatively good general state. When he was re-admitted after 4 weeks he was without psychiatric symptoms but deeply depressed, and he had signs of a polyneuropathy in all limbs, typical of pod. toxin poisoning. CONCLUSION: Pod. toxin, a spindle poison, is the toxic agent of pod., the resin from the roots and rhizomes of various Berberis plants. While the potential toxicity of the resin, taken either orally or applied externally, has been long known, the poorly definied raw product is still being added to anti-wart tinctures.
The effects of systemic Podophyllin toxicity on the bone marrow are a manifestation of this agent's potent antimitotic activity. Our patient experienced a transient aregenerative anemia with leukopenia and thrombocytopenia. The bone marrow was hypocellular with cytoplasmic vacuolation of myeloid precursors and increased numbers of mitotic figures. Megakaryocytes were normal in number and morphology. Hematologic resolution followed discontinuance of topical therapy.
We have described a 20-year-old man with recurrent intranasal papillomas that were successfully treated by twice-weekly applications of 25% podophyllin in tincture of benzoin.
One hundred and twenty-one children with plantar warts were treated with a topical preparation containing salicylic acid, 30%; podophyllin, 5%; and cantharidin, 1%. One hundred patients or their families were reached 6 months to 1 year later. This treatment was effective in 81 cases.
1 A 43-year-old man was admitted in a coma after oral ingestion of a suspected lethal dose of podophyllin solution in alcohol. 2 Hemoperfusion with a resin filter was started 7 h after ingestion. Hemoperfusion rapidly decreased plasma concentrations of podophyllotoxin with an extraction ratio of 0.76 over the filter. The relatively low plasma concentrations of podophyllotoxin and consequently small amount removed might be explained by the rapid metabolism of the drug to an unknown derivate. 3 This metabolite was completely cleared during passage over the filter, suggesting the removal of significant amounts of podophyllotoxin metabolites. 4 No neurological deficit was observed before or after hemoperfusion. At a two-month follow-up the patient remained healthy. Hemoperfusion may possibly prevent the development of coma and neurologic deficit with loss of deep tendon reflexes.
An extremely rare case of systemic podophyllin toxicity from local injection is presented with a review of the literature. There is only one other known similar case reported in the medical literature world wide. Clinical and pathologic findings will be discussed.
The toxicity of topically applied podophyllin in a 16-year-old girl is presented. Coma requiring respiratory support and major neurologic complications as well as hematologic and hepatic toxicity was observed. Therapy with a new modality, charcoal hemoperfusion, resulted in resolution of the acute toxicity, leaving a peripheral neuropathy which had not completely resolved after 4 months. The pharmacology and suggested treatment measures for the toxicity of this rarely reported agent are reviewed.
The application of an alcoholic solution of podophyllin resin at concentrations above 10 p. 100 on guinea-pig udders, produces in epidemic Langerhans cells the same cytological effects as those by colchicine and vinca alcaloid in culture cells. The Langerhans cells are a suitable experimental model in vivo because of its easy ultrastructural identification, its migratory character and its preferential localization in epidermis.
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