The microbial flora of taxane therapy-associated nail disease in cancer patients

TO THE EDITOR

Taxanes are frequently associated with nail and periungual tissue afflictions such as paronychia, onychodystrophy, onycholysis, subungual hemorrhages, and pyogenic granulomas.¹ These therapy-associated nail abnormalities can cause physical symptoms and psychosocial distress, leading to impairments in patients’ quality of life (QoL). The changes in QoL may impact the number of therapy cycles that a patient can tolerate, and in some cases, they may lead to discontinuation of anti-cancer therapy.²

We conducted a retrospective chart review (8/2012–6/2015) of paclitaxel and docetaxel-treated patients referred to a dermatologist (M.E.L.). Of 114 patients, a majority were women with breast cancer, and had developed paclitaxel-associated acute paronychia (Table I). The clinical severity of the nail infections and changes was mostly grade 2, consistent with moderate severity adverse events (AEs) requiring local, noninvasive interventions (CTCAE v4.0³; Table I). We did not identify nail abnormalities with grade 3 or 4, suggesting that medically significant AEs may require prompt interruption of anticancer therapy and are therefore less likely to be seen in the outpatient setting.

Table I.

Characteristics of patients with taxane-associated nail infections and nail changes.

A. Descriptive summary of demographic characteristics of the study sample (n=114).
Feature	No.		(%)
Gender
Male	11		(9.6)
Female	103		(90.4)
Mean age	55.2
Cancer type or site
Breast	84		(73.7)
Lung	10		(8.8)
Gastrointestinal	10		(8.8)
Gynecologic	7		(6.1)
Other	3		(2.6)
Cancer treatment
Paclitaxel	95		(83.3)
Docetaxel	15		(13.2)
Paclitaxel and docetaxel	4		(3.5)
B. Clinical severity grading of taxane-associated nail infections and nail changes.
	Nail infection		Nail changes
	No.	(%)	No.	(%)
Grading noted
Grade 1	9	(11.7)	24	(26.1)
Grade 2	68	(88.3)	68	(73.9)
Grade 3	0	(0.0)	0	(0.0)
Grade 4	0	(0.0)	0	(0.0)
Grading not noted	4		5
C. Treatment instituted for taxane-associated nail infections and nail changes.
Feature	No.		(%)
Antimicrobial therapy (n=114)
Topical agents alone	37		(32.5)
Oral agents alone	0		(0.0)
Topical and oral combinations	77		(67.5)
Nail symptoms improved (n=82)
Yes	66		(80.5)
No	16		(19.5)
No dermatology follow-up	32

^*Topical agents included ciclopirox, bacitracin-polymyxin b, iodine, and others. Oral agents included cefadroxil, ciprofloxacin, and TMP-SMX, and others.

Microbiological cultures grew 21 distinct bacterial and fungal species (Figure 1). The most commonly isolated organism, Staphylococcus aureus, is a part of resident skin flora. In cancer patients however, it is associated with a high morbidity and mortality rate.⁴ Nearly half of the isolates in these patients were opportunistic and/or pathogenic (non-skin flora) organisms. This is reflective of the combined role of impaired resistance to colonization because of taxane therapy and exposure to healthcare environments where the acquisition of these organisms is more likely. In general, direct cytotoxic, antiangiogenic, or neurotropic effects of taxanes in the nail matrix appear to be the inciting factors, with a positive correlation to the number of treatment cycles (cumulative dose). In the setting of an impaired physical barrier due to the antimitotic effect of taxanes in the nail matrix, and suppression of the innate and adaptive immune responses related to systemic cytotoxic anticancer therapies, we hypothesize that these infectious agents may be responsible for nail abnormalities in some patients.

Figure 1.

Gram-positive bacteria (red bars), Gram-negative bacteria (gray bars), and fungi (blue bars) isolated from affected tissues in patients with taxane-associated nail infections and changes.

In 46 patients (40.4%), the culture sensitivity results necessitated treatment modifications. The most prescribed oral antibiotics were cefadroxil, ciprofloxacin, and sulfamethoxazole-trimethoprim. The most prescribed topical antimicrobials were ciclopirox, bacitracin-polymyxin b, and iodine. At follow-up, 80.5% of patients reported clinical improvement in their condition (Table I).

In the cancer patient population, we recommend routinely collecting bacterial and fungal culture swabs from affected periungual tissues. We propose empiric oral antibiotic treatment with fluoroquinolones or first- or second-generation cephalosporins in conjunction with topical antimicrobials. In the author’s (M.E.L.) experience, extended therapy (4–6 weeks) is often required, perhaps due to poor penetration of antibiotics into affected tissues and risk of treatment failure with shorter courses (≤ 2 weeks). Of note, nail infections and other nail changes are likely to recur if taxane therapy is ongoing. Instituting frozen gel sock and/or glove therapy for fifteen minutes before, sixty minutes during, and fifteen minutes after taxane infusion reduces the incidence of nail pathology.⁵ Patients will need routine supportive oncodermatology monitoring.

Abbreviations

QoL