DISCUSSION


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The pathophysiology of chemotherapy-associated paronychia is thought to originate with chemotherapy’s direct impact on nail apparatus changes, which includes the nail plate and the surrounding soft tissue structures. Nail plate changes from chemotherapy are believed to result from many factors, including defective nail plate production resulting from acute damage to the nail matrix, disruption of the nail plate secondary to chemotherapy’s toxic effects on cellular maturation, and direct toxicity to structures of and surrounding the nail apparatus.8 These structural disruptions, in combination with the inherent immunosuppression of the patient, allow for the nail apparatus to become secondarily infected. Numerous case reports and case series document secondary bacterial, fungal, and yeast infections of both the nail plate and periungual soft tissue structures.2,9–15

PVP-I is well recognized as a broad-spectrum, resistance-free biocidal agent that has a long track record of safety and tolerability given its long-term use as a presurgical antiseptic. Although immensely versatile in its ability to kill all known microorganisms including bacteria, viruses, yeasts, molds, fungi, and protozoa, PVP-I has been primarily only used in dermatology as a presurgical skin preparation. The mechanism of action likely involves impaired electron transport, inhibition of cellular respiration, destabilization of membranes, inhibition of protein synthesis, and denaturation of nucleic acids. PVP-I is a polymeric complex of long-chain polyvinylpyrrolidone units with associated iodine, trioiodide, and iodate species in a complicated equilibrium. Paradoxically, dilution of PVP-I increases its antimicrobial potency by releasing more free molecular iodine, the most active biocidal form of iodine present in PVP-I.16

Aside from its antimicrobial properties, PVP-I also has the ability to suppress the inflammatory component of paronychia. Anti-inflammatory properties of a liposomal hydrogel with PVP-I for wound healing were studied in vitro and found to be rapidly effective in its ability to scavenge superoxide anions, inhibit neutrophil production of reactive oxygen species, and stabilize mast cells.17 In this way, PVP-I can behave as both an oxidizing agent and a reducing agent, mainly by iodine’s free radical scavenging and reduction of superoxide.18 All of our patients noted that the pain associated with the paronychia substantially decreased within the first 48 hours after application, which could be explained by a generalized ant-inflammatory effect of PVP-I.

DMSO is an effective pharmaceutical vehicle known to enhance percutaneous penetration of small molecules when used in sufficiently high concentrations. It is a polar, aprotic solvent that has the ability to carry an enormous library of molecules through the stratum corneum and into the dermis. We have surprisingly found that DMSO can also deliver PVP-I through keratinized epithelial surfaces, despite the large size of the PVP-I complexes. PVP-I in combination with DMSO has the ability to penetrate the nail structure, quickly reduce inflammation and pain, and eradicate both fungal and bacterial organisms present in pretreatment cultures.

Nail changes occur with 34.9% and 17.2% of patients receiving taxanes and EGFR inhibitors, respectively.20,21 It has been reported that taxanes are associated most commonly with erythema, edema, exudate, suppuration, and onycholysis. Peripheral nerve fibers may play a role in the development of chemotherapy-induced onycholysis as the inflammatory process is maintained by postganglionic sympathetic terminals and nociceptive c-fiber afferents.22,23 Elevated protoporphyrin levels have also been suggested as causative, but a definitive mechanism has not been elucidated.24–26 EGFR inhibitors have the tendency to cause erythema, edema, exudate, and granulation tissue (both periungual and subungual) consistent with pyogenic granulomas. Increased VEGF has been postulated to be causative.27 This case review demonstrates considerable success with this novel, dilute PVP-I treatment. Our anecdotal results in this small number of severe cases are encouraging. Prospective evaluation in vehicle-controlled, double-blinded clinical trials may be warranted to further evaluate this promising new therapy.

Ethical statement

Sterling IRB was used. The waiver granted was an exemption from IRB Review Determination pursuant to the terms of the U.S. Department of Health and Human Service’s Policy for Protection of Human Research Subjects under 45 C.F.R. 46.101(b). Patient consent to review their medical records was not required by the IRB. Patient confidentiality was maintained according to established HIPPA guidelines.

Disclosure

Authors listed are equity holders in Veloce BioPharma, LLC. Drs. Capriotti are cofounders and paid consultants for Veloce BioPharma, LLC. The authors report no other conflicts of interest in this work.

Kara Capriotti,1,2 Joseph Capriotti,1,3 Jesse Pelletier,1,3 Kevin Stewart1,3

1Veloce BioPharma LLC, Fort Lauderdale, FL, 2Bryn Mawr Skin and Cancer Institute, Rosemont, PA, 3Plessen Ophthalmology Consultants, Christiansted, VI, USA

References

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