Table of Contents
What Is Podophyllin?
Podophyllin is a resinous cytotoxic mixture extracted from the dried rhizome and roots of the mayapple plant Podophyllum peltatum (North America) and Podophyllin hexandrum (from the Himalayan regions of India). One of the first use of this resin has been reported in the treatment of cancer. Podophyllin contains approximately 16 chemicals including podophyllotoxin, alpha and beta peltatin, desoxypodophyllotoxin, and quercetin. Out of these, the poisonous agent is reportedly podophyllotoxin (a lipid-soluble compound that easily crosses plasma cell membranes). This chemical along with its derivatives has a colchicine-like effect causing mitotic spindle arrest.
Neurotoxicity is also reported as one of its major toxic effects. Podophyllin has been used for treating anogenital warts and other skin diseases such as eczema, and molluscum contagiosum. It has also been used as a laxative and for snake bite treatment. However, podophyllin is no longer recommended as a treatment for genital warts due to the availability of safer alternative options. Podophyllin poisoning has been reported in adults and children following both oral consumption and topical application. It is a lethal poison.
What Is Podophyllin Poisoning?
Podophyllin poisoning has been reportedly seen in children as well as adults after both topical application and oral consumption. The fatal dose of podophyllin for humans has been calculated to be approximately 0.3 to 0.6 grams. It can be estimated to be a one-half teaspoon of 25 percent podophyllin chemical in benzoin tincture. Multiple adverse effects have been observed due to podophyllin toxicity. Neurotoxicity is the most serious effect of podophyllin toxicity. Multiorgan dysfunction and failure are usually reported after consuming podophyllin resin in excessive quantities.
What Is the Mechanism of Action of Podophyllin?
The main component of podophyllin is podophyllotoxin which is responsible for inhibiting the formation of microtubules. Podophyllotoxin-tubulin complexes are formed due to the reversible binding of podophyllotoxin to tubulin which prevents further formation of the microtubules at one end thereby disrupting the assembly and disassembly of microtubules and leading to microtubules degradation. Cells undergo necrosis after being treated with podophyllotoxin when they get arrested in the metaphase of mitosis. An antiviral effect of podophyllotoxin has also been reported. Several studies have shown that the core structure of deoxy podophyllotoxin is mainly responsible for cellular cytotoxicity.
The mechanism of action of podophyllin is comparable to that of colchicine, and vincristine. These compounds are called spindle poisons due to their mode of drug action. The cells are allowed to enter the mitosis phase, but the separation of doubled chromosomes does not take place due to the effect of these chemicals. The duplication of the cells is also stopped and the growth is ceased.
What Are the Effects of Podophyllin Poisoning?
The various effects of podophyllin toxicity can be summarized as:
Cutaneous Side Effects:
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Necrosis is a result of acute inflammatory reactions.
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Erythematous halo at the periphery, redness, swelling, and ulceration.
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Balanitis (inflammation and pain at the head of the penis) and phimosis (congenital narrowing of the foreskin opening) in men.
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Severe scarring with chemical burns.
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Fistula formation in the genital area.
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Allergic sensitivity to a frequently used base benzoin. It can also lead to dermatitis (skin inflammation).
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An acute inflammatory reaction resulting in hyperplastic epithelium due to the podophyllin application.
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Podophyllin cells that arebizarre, enlarged epidermal cells with pyknotic nuclei are usually seen on microscopic examination after podophyllin application to normal skin, warts of Verruca Vulgaris, and molluscum contagiosum. No atypical cellular features were seen.
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In unsuccessfully treated penile warts, squamous cell carcinoma–like changes are seen.
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When podophyllin is applied over warts around the eyes, corneal damage and anterior uveitis (inflammation of the middle layer of the eye) may be sometimes seen.
Systemic Side Effects:
The antimitotic (arrest the mitotic phase) effects of podophyllotoxin are partially responsible for causing systemic toxicity. This usually occurs when the drug is applied over a large area of the skin or the skin is in prolonged contact with the drug. Therefore, the tissues having a high rate of proliferation (bone marrow, lymphoid tissue, and intestinal mucosa) are most susceptible to podophyllin poisoning. Neurotoxicity is also reported as the most serious effect of systemic toxicity. It is attributed to its microtubular protein binding ability and inhibiting the axoplasmic flow.
The following systemic effects of podophyllin poisoning include:
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Severe headache along with nausea, vomiting, and diarrhea.
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Adynamic ileus (paralytic ileus when the food or drinks does not pass the bowel).
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High temperature.
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Tachypnea (rapid breathing).
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Tachycardia (rapid heart rate).
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On serum analysis, leukopenia, anemia, thrombocytopenia, and elevated liver enzymes are usually seen.
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Peripheral neuropathy (damage to the nerves outside the brain and spinal cord), confusion, laziness, coma, and finally death are the most serious effects of the toxicity. The central nervous system toxicity is usually reversible with recovery starting within nine to ten days after the exposure. Peripheral neuropathy usually takes several months to resolve, and sometimes leaves behind residual defects which can persist for years.
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Urticaria and high fever.
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Oliguria, Anuria (failure to produce urine by kidneys).
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Marked leukocytosis (increased neutrophil count).
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Podophyllin is toxic to the fetal embryo. Fetal abnormalities such as preauricular skin tags, malformations of the limb, heart defects of the septum, simian crease (single palmar crease), and polyneuritis (inflammation of several peripheral nerves simultaneously) have been found to be associated with pregnancy.
What Is the Management of Podophyllin Poisoning?
The management of podophyllin poisoning is mainly symptomatic. There is no specific antidote present for the toxicity. Activated charcoal is recommended for gastrointestinal decontamination after the recent ingestion of podophyllin. If topical toxicity occurs, the area should be washed with soap and water. Intensive care of the patient along with proper ventilation and circulation should be arranged. Proper monitoring for all the complications is required. Hemoperfusion (circulation of anticoagulated blood) is generally required for severe systemic poisoning since it has been found to be effective in minimizing the podophyllum toxin fraction from the plasma.
Conclusion
Both topical application and oral consumption can lead to podophyllin poisoning. Neurotoxicity is the most dangerous effect along with bone marrow depression, gastrointestinal irritation, and hepatic and renal failure. It is important to treat the condition immediately. Therapeutic management of podophyllin poisoning is mainly symptomatic. One should take the help of poison control centers to seek immediate help.
