Povidone-iodine in dermatology: A reappraisal

INTRODUCTION

In the present era of rapidly increasing antibiotic and antiseptic resistant strains of microbes worldwide, there is a need to explore and recollect more “traditional” methods of combating and preventing infections. This article recalls the importance of Povidone-iodine, an old antiseptic in retrospect as per the evidence and tries to shed some light on its future perspective in dermatology.

Medicinal iodine has evolved from the toxic, unstable, insoluble form first described over a 100 years ago into the well-known iodophor preparation of highly effective antimicrobial known as povidone-iodine (PVP-I) or “Betadine”. Iodophors are complexes of iodine and a solubilizing agent, which acts as a reservoir of the active “free” iodine. Iodine was detoxified by binding it to macromolecules to form PVP-I by Shelanski and Shelanski in 1956.^[1]

PHARMACOLOGY

PVP-I is a stable chemical complex of triiodide (I³) and the organic polymer polyvinylpyrrolidone, improving the chemical stability, solubility, and cutaneous tolerance of active free iodine. PVP-I allows to deliver higher effective concentrations of iodine safely to target tissues without local toxicity.

The polyvinylpyrrolidone component of PVP-I delivers iodine directly to the cell surface of microorganism; the free iodine penetrates the cell wall and targets nucleotides, proteins, and fatty acids, leading to the destruction of the cell.^[2,3] In contrast to various antibiotics that act only on the cell walls, PVP-I also effectively inhibits the release of pathogenic factors, such as exotoxins, endotoxins, and tissue-destroying enzymes.^[4]

The concentration of free iodine contributes to the bactericidal activity of PVP-I. The free iodine concentration increases with increasing dilutions of PVP-I: dilution weakens the iodine linkage to the carrier, increasing the availability of free iodine in the solution.^[3] This process might explain the paradoxical increase in the bactericidal action on increasing the dilution of PVP-I (0.1–1% solution has been proven to be more rapidly microbicidal than the 10% solution).^[3]

PVP-I has the broadest spectrum of antimicrobial activity of the available antiseptics, including bacteria (gram-positive and gram-negative), spores, viruses, fungi, and protozoans [Table 1]. It has no known acquired/cross-resistance and can penetrate biofilms.

PVP-I is used as various formulations in Dermatology [Table 2]. In the Asian region, the most widely used formulation is the 10% aqueous/alcoholic solution. PVP-I is also available as 10% ointment, 7.5% surgical scrub, and 2.5% dry powder spray. The commonly used 10% Betadine solution delivers about 1% of free molecular iodine. Recently, a preparation of liposomal PVP-I hydrogel has been developed with a unique mode of action, having the antiseptic and anti-inflammatory properties of PVP-I combined with the targeted drug delivery and moisturizing properties of liposomes.

USES IN DERMATOLOGY [TABLE 2]

ADVERSE EFFECTS

PVP-I has good skin tolerance with minimal side effects. However, there are few case reports of immediate or delayed allergic reactions to PVP-I, with povidone or nonoxynol as the most likely sensitizing agents [Figure 1].^[14,15] Hence, caution should be taken while using PVP-I in patients with a history of allergy to iodine products. Systemic toxicity is a rare occurrence with PVP-I. Systemic absorption due to the application of PVP-I over large surface area wounds may be a concern. PVP-I are both renally excreted; therefore toxicity has been reported commonly in a setting of renal impairment.^[16] Major systemic adverse effects include metabolic acidosis, cardiovascular instability (hypotension and bradycardia), renal failure, leukocytoclastic vasculitis, hyperthyroidism, and abnormal liver function. Other rare side effects include iodine acne, runny nose, conjunctivitis, gastroenteritis, bronchitis, parotid swelling.^[17] Iododerma due to systemic absorption from topical iodine use is extremely rare, with a few cases reported. It is essential to differentiate toxic reactions to the inappropriate use of PVP-I from actual allergic reactions. In case of toxic effects of PVP-I, it can still be used with a change in the concentration and method of application. On the contrary, if there is an actual allergic reaction to PVP-I or its additives, proven by prick tests if immediate or patch tests if delayed-type, the PVP-I or the offending additives must be avoided under all circumstances.

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Figure 1:

Irritant contact dermatitis secondary to povidone-iodine applied over chest for preoperative skin antisepsis.

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CONTRAINDICATIONS AND PRECAUTIONS

PVP-I is contraindicated in patients with a proven allergy to PVP-I or its additives and hyperthyroidism/thyroid cancer. It should be used with caution in pregnant, lactating women and infants. The use of PVP-I in children with a higher skin surface area per body weight and less developed skin barrier may lead to increased penetration and systemic absorption, so it should be done carefully.

CONCLUSION AND FUTURE PERSPECTIVES

PVP-I is a highly effective antimicrobial with a broad spectrum of activity and no known resistance. In addition, it is a cost-effective and readily available antiseptic and disinfectant. The side effects are minimal, however, cytotoxicity and local allergy should be taken into consideration. The liposomal formulation has been developed to optimize the use of PVP-I for particular areas and indications, with better efficacy and tolerance. With these advancements and emerging indications, PVP-I is poised to enter a renaissance in dermatology.