Received: 25 April 2024 | Accepted: 5 March 2025

DOI: 10.1111/vde.13340

ORIGINAL ARTICLE

A blinded randomised split-­body clinical trial evaluating

the effect of fluorescent light energy on antimicrobial
management of canine interdigital furunculosis

A. Lange1 | U. Mayer1 | E. Bensignor2 | L. Cornegliani3 | D. Ferreira4 |

I. Matricoti5 | M. Mosca6 | L. Ordeix7 | D. Pin6 | F. Scarampella8 |
E. Videmont9 | A. Yu10 | O. Fantini11

1
Department of Dermatology, AniCura
Kleintierspezialisten Augsburg GmbH, Abstract
Augsburg, Germany Background: Canine interdigital furunculosis (CIF) is a complex, relapsing
2
Dermatology Referral Service, Clinique inflammatory condition, typically complicated by deep bacterial infections re-
Vétérinaire, Rennes-­Cesson, France
3
quiring prolonged systemic antibiotics.
Clinica Veterinaria S. Siro – Anicura,
Milan, Italy Hypothesis/Objectives: This split-­body study, where dogs acted as their
4
Dermatologia Veterinaria, Lisbon, own control, evaluated whether the adjunctive use of fluorescent light energy
Portugal (FLE) could shorten the time to clinical resolution of CIF and minimise sys-
5
Servizi Dermatologici Veterinari, Bologna, temic antimicrobial use.
Italy Animals: Thirty-­five client-­owned dogs with signs of interdigital furunculosis
6
VetAgro Sup, Interactions Cells in at least two paws.
Environment, Université de Lyon, Marcy
l'Etoile, France Materials and Methods: This prospective, single-­blinded, randomised, split-­
7
Fundació Hospital Clínic Veterinari and body multicentre clinical trial treated dogs with systemic antibiotics based on
Departament de Medicina i Cirurgia bacterial culture and sensitivity. One paw per dog was randomly selected
Animals, Facultat de Veterinària, using a coin-­toss method for weekly FLE application, while the other paw
Universitat Autònoma de Barcelona,
Bellaterra, Spain served as a control. Dogs were scored every 2 weeks over 56 days on two pa-
8
Studio Dermatologico Veterinario, Milan, rameters: a global lesion score (including haemorrhagic vesicles, fistulae with
Italy draining tracts, crusts and ulcers) and neutrophils engulfing bacteria score
9
Centre Hospitalier Vétérinaire, Saint-­ (NES, 0–4). Time to clinical resolution and lesion scores were assessed and
Martin Fillière, France compared between groups.
10
Guelph Veterinary Specialty Hospital, Results: At Day (D)28 and D56, the FLE group showed significantly more
Guelph, Ontario, Canada
11
healed paws (50% and 88%, p = 0.021) compared to the control (17% and
Vetoquinol SA, Paris, France
54%, p = 0.008). The median time to clinical resolution was shorter for the
Correspondence FLE group (35 days) compared to the control group (56 days, p = 0.017). No
A. Lange, Department of Dermatology, difference in NES score was observed between groups.
Anicura Kleintierspezialisten Augsburg
GmbH, Augsburg, Germany. Conclusions and Clinical Relevance: This blinded, randomised, split-­body
Email: [email protected] clinical trial demonstrated that FLE is an effective adjunctive therapy for CIF.
It reduces the time to clinical resolution and increases the resolution rate
Funding information while minimising the need for antibiotics.
Vetoquinol SA

KEYWORDS
dog, fluorescence photobiomodulation, interdigital cysts, interdigital furunculosis, low-­level
laser therapy, pododermatitis

INTRODUCTION to as pedal folliculitis and furunculosis, pododermatitis or

interdigital ‘cysts’ affected tissues may include interdigi-
Canine interdigital furunculosis (CIF) is a chronic inflam- tal spaces, footpads, nail folds or combinations thereof.4
matory skin condition affecting the pedal skin.1–4 The con- As the clinical appearance of the lesions on the paw
dition is a complex, multifaceted disease often referred can be identical regardless of the underlying condition,

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction
in any medium, provided the original work is properly cited and is not used for commercial purposes.
© 2025 The Author(s). Veterinary Dermatology published by John Wiley & Sons Ltd on behalf of ESVD and ACVD.

Veterinary Dermatology. 2025;00:1–11.  wileyonlinelibrary.com/journal/vde | 1

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2 |   
Veterinary Dermatology
LANGE et al.

veterinary surgeons find it frustrating to identify the pri- double-­investigator technique: the principal investigator
mary aetiology and institute appropriate therapy.4 CIF has was responsible for clinical (using the photographic
been associated with hypersensitivities (atopic dermati- documentation) and cytological assessment, and a
tis [AD], cutaneous adverse food reaction), demodicosis, co-­
investigator was responsible for randomisation,
endocrine diseases (hypothyroidism, hyperadrenocorti- dispensing the product and applying the FLE intervention
cism), foreign bodies and conformational problems with (Phovia; Vetoquinol SA). The co-­ investigator was not
secondary infections as a common sequela.5 Localised involved in the outcome assessment. The principal
areas of folliculitis can progress to furunculosis, leading investigator was unaware of the intervention assignment
to endogenous hair shaft keratin foreign body reactions and remained blinded until the last recheck was
and the formation of nodules and fistulae with draining performed on Day (D)56.
tracts.3,4,6 As a consequence of the persistent foreign
material within the skin, resolution of the secondary
bacterial infection often requires prolonged courses of Ethics
antibiotics, and relapse is common, even when the un-
derlying trigger is managed. In addition to recurrent an- This trial was conducted under good general conditions
tibiotic therapy, many clinicians use topical or systemic and per local legislation on the use of patients for clini-
anti-­
inflammatory drugs, including glucocorticoids and cal trials. Before treatments were started, informed con-
ciclosporin, to manage the inflammation caused by the sent was obtained by signing a form from all owners
foreign body reaction. Medical devices, including cold whose pets participated in this study; the study proto-
plasma therapy and photobiomodulation using low-­level col, owner responsibilities, all known risks and potential
light therapy, have been incorporated into wound and po- adverse events resulting from the FLE application were
dodermatitis therapeutic regimens.7–10 clearly explained. The study was conducted after ethical
Recent research on fluorescence photobiomodu- review and validation (no. 2024#08) at Vetoquinol and
lation has led to a novel approach for CIF through the complied with all animal welfare regulations.
activation of topical photoconverter substrates con-
taining specialised exogenous chromophores by expo-
sure to blue light (peak wavelength between 440 and Study population
460 nm), resulting in fluorescent light energy (FLE). FLE
modulates the inflammatory process in dermatological Inclusion criteria
disorders and has shown promising results in prelimi-
nary studies evaluating its use in superficial and deep Client-­owned dogs diagnosed with interdigital furun-
pyoderma and interdigital furunculosis.11–13 The aim of culosis by dermatological specialists at multiple cen-
this study is to evaluate the effect of FLE in the manage- tres in Europe, the United Kingdom and Canada were
ment of CIF, assessing whether the combination of sys- enrolled. Dogs with CIF on at least two paws were
temic antibiotics and FLE will accelerate time to healing recruited without age, breed, body weight or sex re-
versus the use of systemic antibiotics alone. strictions. CIF lesions included at least one or more of
the following lesions: haemorrhagic vesicles/bullae,
draining tracts, haemorrhagic crust/papules and ulcers/
MATERIALS AND METHODS erosions. Inclusion into the study required a disease se-
verity score of ≥2 and a global lesion score of ≥5 by add-
This was a prospective, multicentre, single-­ blinded, ing the scores from the different parameters (Table 1)
randomised split-­ body trial. At each of the 10 developed by Marchegiani et al.13 If dogs presented
facilities, blinding of the study was maintained by the with CIF in more than two paws, the most severe ones

TA B L E 1 Scoring chart for clinical signs of interdigital furunculosis.

Haemorrhagic vesicles/ Fistula with draining Haemorrhagic crust/

Lesion type bullae or nodules tracts papules Ulcers/erosions

Score Grade Lesion assessment for each paw

0 Healed Absent Absent Absent Absent
1 Mild Healing lesion Healing nondraining 1 small area Superficial erosions only
lesions only
2 Moderate 1–2 primary lesions Single active draining 2 small areas Single small area of ulceration,
lesion no other lesions
3 Severe 3–4 primary lesions 1–2 active draining 3–4 more extensive Single more extensive area
lesions with other areas combined with other lesions
lesions or two areas of extensive
ulceration without other lesions
4 Very severe ≥5 primary lesions ≥3 active draining ≥5 extensive areas ≥2 extensive areas combined
lesions with other with other lesions or ≥3
lesions extensive areas

Note: Small is defined as ≤1 cm in diameter, extensive lesions as >1 cm in diameter.

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FLUORESCENT ANTIMICROBIAL MANAGEMENT OF CANINE INTERDIGITAL FURUNCULOSIS    3
Veterinary Dermatology

were considered for the scope of the study. Dogs with engulfing bacteria score (NES; Table S1) and the
an underlying allergic skin disease were included pro- investigator's assessment of the FLE effect at clinical
vided that their pruritus was adequately controlled only resolution were recorded on D0, D14, D28, D42 and
with the use of heartworm, endo-­and ectoparasitic D56. Although the length of the study was 8 weeks,
preventatives, prescription diets, nonsteroidal anti-­ FLE application was stopped at clinical resolution.
inflammatory drugs, vitamin/mineral or essential fatty Treatment was continued for dogs not reaching clinical
acid supplements, routine vaccines, allergen-­specific resolution by D56 (Week 8). Further assessments were
immunotherapy (which had been initiated ≥8 months conducted during visits on D70 and D84 (Week 12).
before enrolment), monoclonal antibodies and topical Dogs that did not reach clinical resolution by Week 12
non-­antimicrobial shampoos (antiparasitic, conditioner continued treatment until they did. All dogs achieving
and hypoallergenic properties). Patients were allowed clinical resolution at any time up to a maximum of
to receive medication to control other underlying medi- 12 weeks of treatment were enrolled for a further 3-­
cal disorders, including thyroid supplementation (all month follow-­up period to assess for any recurrence
dogs on thyroid medication were shown to have a nor- of lesions, defined as the reappearance of one or a
mal thyroxine level before starting the trial), diuretics combination of lesions in the same previously affected
and cardiac drugs. site. Dogs not achieving clinical resolution after
12 weeks were not enrolled in the follow-­ up study.
During the follow-­up period, owners were contacted
Exclusion criteria monthly to determine if they had noticed any signs
of relapse. All owners were invited for a final clinical
Dogs were excluded on D0 if they were in poor examination 3 months after the follow-­ up period
general health based on a physical examination per- started. A FLE overall satisfaction score was completed
formed by a veterinarian, had lesions of the paw pads by the owners at clinical resolution as very satisfied,
or had evidence of Malassezia spp., fungal dermati- satisfied, neutral, dissatisfied or very dissatisfied.
tis or ectoparasites. Dogs also were excluded if they
were treated within the last 30 days with injectable or
oral short-­acting glucocorticoids; within 90 days with Intervention groups
repository glucocorticoids; or with oclacitinib, ciclo-
sporin or other anti-­inflammatory or immunosuppres- Every dog was treated with a systemic antibiotic. If only
sive medication. Dogs with an underlying disease that the front paws were affected, one paw received a topi-
might affect their ability to respond to antibiotics (e.g. cal application of FLE until clinical resolution (Group A),
hyperadrenocorticism, diabetes mellitus, leishmania- while the other remained without intervention (Group
sis), received concomitant treatment with photosen- B). If all paws were affected, the front and back paws of
sitising molecules (tetracycline antimicrobial family, the same side received a topical application of FLE until
clofazimine, dacarbazine, dapsone, griseofulvin, coal clinical resolution (Group A); the other ones were left
tar or topical retinoids) or had a known infection caused untreated (Group B). The paw(s) to receive FLE was/
by multidrug-­resistant (MDR) bacteria were excluded. were chosen randomly according to a biased coin ran-
Withdrawal from the analysis was required following: domisation. The randomisation was performed on the
poor compliance with the study protocol instructions day of inclusion: left side = heads; right side = tails. Each
regarding visits and medication; severe adverse ef- animal acted as its own control.
fects from any of the products used; the development
of any further comorbidities during the study that
would have impaired the ability to score study lesions Antibiotic intervention
or treatment outcomes; missing one FLE application
in the once-­a -­week regimen or two applications in the The systemic antibiotic options consisted of cephalexin
twice-­a -­week regimen; or worsening of pruritus in al- or amoxicillin and clavulanate at a dosage of 15 mg/kg
lergic dogs. twice daily and 12.5 mg/kg twice daily, respectively,
after verifying the efficacy of this molecule based on
antibiotic susceptibility testing; if the isolate was not
Study timeline susceptible to cephalexin or amoxicillin and clavulanate,
then another appropriate antibiotic was selected
This study was implemented over 8 weeks, with an based on the susceptibility results obtained. The
inclusion visit on D0 and recheck visits every 7 days. choice between cephalexin and amoxicillin/clavulanic
All visits had a margin of ±1–2 days for modification if acid was determined by several factors. Primarily,
needed. General examination, a detailed examination the treatment selection was at the discretion of the
of the skin and lesions, disease severity and scoring investigator, taking into account the clinical history of
assessment with the global lesion score (GLS) for each the patients. Additionally, the formulation that best
study paw, photographic documentation of lesions, matched the dogs' weight was considered to ensure
assessment and measurement of pruritus intensity adherence to the recommended dosage. Antibiotic
(via pruritus visual analogue scale [PVAS] score), a treatment was stopped upon clinical resolution of
cytological scoring of each body site, neutrophils
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4 |   
Veterinary Dermatology
LANGE et al.

lesions on the control paws and was not administered probability of treatment success between the groups
beyond Week 12. at different times was assessed using a binary general-
ised mixed model with a two-­factor analysis. A p-­value
<0.05 was considered statistically significant.
Blinding In our clinical study, we aimed to include 40 dogs,
each serving as their own control, to evaluate the effect
In order to account for differences between study of the treatment. This number is justified based on the
groups, blinding was maintained using a double-­ expected clinical resolution rates of 80% in the treatment
investigator technique. The principal investigator was group and 40% in the control group. To detect this 40%
responsible for clinical examinations and cytological difference with a significance level of 5% (alpha = 0.05)
analyses, which were performed every 2 weeks, while and a power of 80% (1–beta = 0.80), a sample size calcu-
the co-­investigator handled randomisation, product dis- lation indicated that approximately 34–40 dogs would be
pensing and the application of FLE. The co-­investigator required. This ensures that the study has adequate power
did not participate in outcome assessments. The prin- to detect a clinically meaningful difference in outcomes
cipal investigator remained blinded to the treatment between the treated and untreated paws.
assignments and was only unblinded after the final re-
check at Week 12.
RESULTS

FLE intervention Study population

Dogs were put in a comfortable position, with the le- A total of 38 dogs underwent an initial assessment for
sion accessible for the procedure and the animal's inclusion in the study. Three dogs were excluded at enrol-
head facing away from the light (or the eyes covered ment owing to MDR Staphylococcus spp. Consequently,
to protect them from the light, for example, with sup- 35 dogs were successfully enrolled, consisting of 19
plied safety goggles). If needed, hair that prevented full males (17 castrated) and 16 females (15 spayed). These
contact of the gel with the surface of the lesions was dogs belonged to a diverse range of breeds, with the
gently clipped. median age and weight of the cohort being 4 years and
Sedative and/or immobilising drugs could be employed 9 months (range 2.1–10 years) and 19.6 kg (range 12.2–
to manage anxiety, aggression, hyperactivity, discom- 43 kg), respectively. Predominant breed representation
fort and pain in patients during handling procedures. included French and English bulldogs (10 of 35), mixed-­
However, it is noteworthy that in this study, none of the breed dogs (12 of 35), Labrador retrievers and Golden re-
dogs required sedation or immobilisation. The exogenous trievers (5 of 35 each), West Highland white terriers (4 of
chromophore was transferred into the jar containing an 35), German shepherd dogs (3 of 35) and Staffordshire
urea peroxidase-­ containing gel, and the mixture was bull terriers (3 of 35). Detailed demographic information
stirred until the orange colour was uniform. The jar was is presented in Table S2.
covered until the time of application. Wearing gloves, the Among the 35 dogs, 16 were identified with canine
co-­investigator applied a layer of gel approximately 2 mm AD. These dogs were included in the study as their
thick to the surface of the whole lesion with a spatula. condition was adequately controlled with the admin-
Everyone in the room wore safety goggles when the istration of monoclonal antibodies, prescription diets,
lamp was turned on. The rim of the lamp window was essential fatty acids and topical shampoos without anti-
placed as close as possible to the lesion without touch- microbial therapy. No recurrence of pruritus or flare-­ups
ing the skin. Lesions were treated once a week with two was observed during the study. No other underlying
consecutive 2 min applications; that is, the gel mixture of diseases were identified during the study.
chromophore and carrier gel was applied, illuminated for
2 min, removed and a new mixture was re-­applied after a
1 min rest, illuminated for 2 min and removed again. Once
the procedure was completed, the gel was removed from
the lesion with saline-­soaked gauze.

Statistical analysis TA B L E 2 Bacteria isolated from canine interdigital lesions.

Bacteria isolated Number of paws

Statistical analysis was performed using SAS v9.1 (SAS
Institute Inc.). Clinical resolution rates were compared Staphylococcus pseudintermedius 35
in two nonindependent samples using the McNemar Staphylococcus schleiferi 6
test for dichotomous variables. Weekly GLS and NES Staphylococcus aureus 3
reduction were analysed via a two-­factor ANOVA with Streptococcus spp. 6
REML estimation, Kenward–Roger degrees of freedom Enterococcus faecalis 3
and specified variance structures. Median resolution
Bacillus spp. 5
times were estimated using the Kaplan–Meier meth-
Proteus spp. 8
odology and compared through log-­rank testing. The
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FLUORESCENT ANTIMICROBIAL MANAGEMENT OF CANINE INTERDIGITAL FURUNCULOSIS    5
Veterinary Dermatology

Culture and sensitivity Time to clinical resolution

Microbiological swabs of the lesions yielded In the primary end-­point analysis, the clinical resolution
Staphylococcus spp. (n = 35) as the predominant rate per visit (from day 0 to day 56) was assessed, with
pathogen, encompassing S. pseudintermedius Figure 1 depicting the results. Statistically significant dif-
and S. schleiferi as the isolated species. Several ferences in time to clinical resolution were observed on
other bacterial strains, including Streptococcus D28 (Figure 2) and D56, with the FLE group demonstrat-
spp., Escherichia coli and others, were infrequently ing a higher success rate. By D28, 50% of paws treated
detected (Table 2). Notably, five isolates exhibited with FLE achieved clinical resolution, compared to 17%
resistance to amoxicillin and clavulanic acid or in the control group (p = 0.021). By D56, 88% of paws
cephalexin, prompting the selection of appropriate treated with FLE achieved clinical resolution, compared
antibiotics based on susceptibility results (clindamycin, to 54% in the control group (p = 0.008). The median time
enrofloxacin, marbofloxacin and cefpodoxime). to clinical resolution was 35 days in the FLE group, com-
Eighteen dogs received amoxicillin and clavulanic acid pared to 56 days in the control group (p = 0.017).
with doses ranging from 12.5 to 18 mg/kg twice daily. The probability of achieving clinical resolution of le-
The median dose was 13.75 mg/kg with a standard devi- sions at each time point between the treatment groups
ation (SD) of approximately 0.88 and a mean duration of is illustrated in Table 3. Notably, on D28, the FLE group
52.2 days. Twelve dogs received cephalexin with doses exhibited a significantly higher probability of being
ranging from 15 to 21 mg/kg twice daily. The median cured compared to the control group. On D28, in the
dose was 18.0 mg/kg, with a SD of approximately 1.86 FLE group, the probability of treatment success was
and a mean duration of 56.4 days. One dog received 5.35-­fold higher compared to the control group, and this
clindamycin at 5.5 mg/kg twice daily for 59 days. One probability increased to 6.01-­fold by D56.
dog received enrofloxacin at 5.4 mg/kg once daily for
51 days; one dog received marbofloxacin at 2.14 mg/kg
once daily for 58 days and two dogs received cefpodox- Global lesion score and neutrophils
ime at 7 mg/kg once daily for 63 days. engulfing bacteria score

At D28 and D56, a statistically significant improve-

Clinical score ment in the mean GLS score was observed in the FLE
group compared to the control group, as illustrated in
All dogs that successfully completed the study presented Figure 3. Conversely, while NES scores improved in fa-
with various combinations of lesions, including haemor- vour of the FLE group at D14, D28 and D56, no statisti-
rhagic vesicles/bullae or nodules (n = 35), draining tracts cally significant difference was detected between the
(n = 8), haemorrhagic crust/papules (n = 31) and ulcers/ two groups (Figure S1).
erosions (n = 18). At enrolment, no statistically significant
difference was observed in global lesion scores between
the FLE and control groups (mean GLS 8.50 ± 1.91 for the Adverse effects
FLE group and 7.50 ± 1.43 for the control group).
Throughout the study duration, no adverse effects
were observed.

FIGURE 1 Percentage of paws healed by intervention at each time point. D, day; FLE, fluorescent light energy.
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6 |   
Veterinary Dermatology
LANGE et al.

F I G U R E 2 Impact of fluorescent light energy (FLE) versus control on canine interdigital furunculosis at different time points. (a,
b) FLE Day (D)0 and D28; (c, d) control D0 and D28.

TA B L E 3 Probability of cure between intervention groups at (p = 0.250). By D84, 96% of paws treated with FLE
each time point (Day [D]). achieved clinical resolution, compared to 86% in the
control group (p = 0.500). Thirty-­three dogs were en-
95%
Difference odds-­ratio
rolled in the follow-­up assessment period. Seven ex-
odds-­ratio confidence p-­value perienced a relapse during the 3-­month observation
Comparison Time estimate interval (significance) period. Among these seven dogs, five had lesions on
FLE versus D14 2.284 [0.316;16.514] 0.411 (NS) both the FLE-­treated and control paws, while two had
control D28 5.352 [1.221;23.465] 0.026 (S)
lesions only on the control paw. The GLS was two
D42 1.642 [0.446;6.039] 0.453 (NS)
for the FLE-­treated area and five for the control area
(p = 0.048). During the follow-­up period, the use of any
D56 6.013 [1.120;32.290] 0.037 (S)
drugs necessary to treat underlying conditions or any
Abbreviations: FLE, fluorescent light energy; NS, not significant; S, new conditions that arose was permitted.
significant.

DISCUSSION
Pet owner overall satisfaction score
Canine interdigital furunculosis is a challenging, multi-
All owners (35, 100%) completed the pet owner overall factorial condition that often leads to recurrent second-
satisfaction questionnaire, with 2 being very satisfied ary infections. In this study, Staphylococcus species
(7%), 20 being satisfied (57%), 12 being neutral (34%), were the primary pathogens, consistent with previ-
1 being dissatisfied (3%) and none being very dissatis- ous research on CIF and interdigital pyoderma.4,13,14
fied (0%). Notably, 3 of 38 dogs were withdrawn owing to MDR
organisms, highlighting the need for pre-­ treatment
culture and sensitivity testing to guide antibiotic selec-
Results obtained during the 3-­month tion, as recommended by prior studies on CIF manage-
follow-­up observation period ment.12 Fluoroquinolones are known to modulate the
immune system15 yet it is unlikely that these effects
By D70, 92% of paws treated with FLE achieved clini- had an impact on the outcome of the results, as only
cal resolution, compared to 75% in the control group two dogs were treated with fluoroquinolones for a
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FLUORESCENT ANTIMICROBIAL MANAGEMENT OF CANINE INTERDIGITAL FURUNCULOSIS    7
Veterinary Dermatology

FIGURE 3 Comparison of global lesional score between intervention groups at each time point. D, day; FLE, fluorescent light energy.

similar duration of antibiotic treatment compared to the studies16,17 no adverse events were observed during
other dogs in this study. the entire trial.
Our results demonstrated that FLE combined with The investigation herein is similar to the research by
systemic antibiotics significantly reduced the time to Marchegiani et al.13 in 2019 yet, the use of the split-­body
clinical resolution compared to antibiotics alone. By design in this study enhances the validity of the results
Week 4, 50% of paws in the FLE group achieved clin- and allows for a more direct comparison between FLE-­
ical resolution, compared to 17% in the control group treated and control paws within the same subject. The
and by Week 8, 88% of paws in the FLE group had split-­body design, where each dog serves as its own
healed, compared to 54% in the control group. This is control, provides a robust method to minimise interindi-
consistent with previous findings in CIF, where adjunc- vidual variability and reduce sample size while maintain-
tive therapies such as FLE showed similar efficacy in ing statistical power.19 However, limitations such as the
reducing lesion severity and accelerating recovery.11,13 exclusion of resistant infections and topical antimicrobial
Marchegiani et al.13 (2022) reported comparable resolu- agents should be addressed in future studies to assess
tion rates when FLE was used once or twice weekly, al- the full potential of FLE in real-­world clinical settings.
though their study involved a smaller sample size of 12
dogs. Our study, with a larger population, confirms and
strengthens the hypothesis that FLE can significantly CONCLUSIONS
enhance the treatment of CIF.
No significant differences were observed in NES be- In summary, our findings indicate that FLE, as an adjunct
tween the two groups, yet the GLS was consistently management option alongside systemic antibiotics, is
lower in the FLE group, with statistical significance at safe to use and has the potential to expedite clinical
D28 and D56. Similar results were observed in studies resolution in the treatment of CIF, thus decreasing the
on canine pyoderma and interdigital pyoderma, where reliance on prolonged antibiotic treatment regimens.
adjunctive FLE led to faster lesion resolution and im-
proved healing outcomes.13,14,16,17 The mechanism of AC K N OW L E D G E M E N T S
action is hypothesised to involve the upregulation of epi- This study was funded by Vetoquinol which made this
dermal growth factor and matrix metalloproteinase-­1, study possible. We are also grateful to the owners
which accelerate re-­epithelialisation and modulate in- and their patients who participated in this research
flammatory responses. This mechanistic pathway has and made this work possible.
been documented in other FLE studies, showing its po-
tential to promote wound healing and reduce inflamma- AU T H O R C O N T R I B U T I O N S
tory cytokines such as interleukin-­6.11,18 A. Lange: Investigation; writing – original draft;
Potential adverse effects associated with using the writing – review and editing. U. Mayer: Investigation;
FLE system include hair colour change, erythema that writing – review and editing. E. Bensignor:
regresses within 6–12 h, skin hyperpigmentation and Investigation; writing – original draft. L. Cornegliani:
transient pain at the wound site. As shown in previous Investigation; writing – original draft. D. Ferreira:
 13653164, 0, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/vde.13340 by Venezuela Regional Provision, Wiley Online Library on [26/04/2025]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
8 |   
Veterinary Dermatology
LANGE et al.

a murine model of full-­thickness skin wounds. Exp Dermatol.

Investigation; writing – original draft. I. Matricoti: 2017;26(2):156–62.
Investigation; writing – original draft. M. Mosca: 9. Hoisang S, Kampa N, Seesupa S, Jitpean S. Assessment of
Investigation; writing – original draft. L. Ordeix: wound area reduction on chronic wounds in dogs with pho-
Investigation; writing – original draft. D. Pin: Investigation; tobiomodulation therapy: a randomized controlled clinical trial.
Vet World. 2021;14(8):2251–9.
writing – original draft. F. Scarampella: Investigation;
10. Perego R, Mazzeo M, Spada E, Proverbio D. Critically appraised
writing – original draft. E. Vidémont: Investigation; topic on low-­level laser therapy (LLLT) in dogs: an advisable
writing – original draft. A. Yu: Investigation; writing – treatment for skin diseases? Vet Sci. 2022;9(9):505. https://​doi.​
original draft; writing – review and editing. O. Fantini: org/​10.​3 390/​vetsc​i9090505
Conceptualization; investigation; funding acquisition; 11. Marchegiani A. Klox fluorescence biomodulation system pro-
ceedings 61st BSAVA congress. 2018. p. 442.
writing – original draft; methodology; visualization;
12. Marchegiani A. Abstracts of the 29th annual congress of the
validation; writing – review and editing; formal analysis; ECVD-­ESVD, 7-­9 th September 2017, Lausanne, Switzerland.
project administration; supervision; data curation; Vet Dermatol. 2017;28(6):533–53.
resources. 13. Marchegiani A, Spaterna A, Cerquetella M, Tambella AM,
Fruganti A, Paterson S. Fluorescence biomodulation in the
management of canine interdigital pyoderma cases: a prospec-
F U N D I N G I N F O R M AT I O N
tive, single-­blinded, randomized and controlled clinical study.
The study was initiated and funded by Vetoquinol SA. Vet Dermatol. 2019;30(5):371 –e109.
14. Marchegiani A, Fruganti A, Gavazza A, Spaterna A, Cerquetella
C O N F L I C T O F I N T E R E S T S TAT E M E N T M. Fluorescence biomodulation for canine interdigital furun-
A.L. has not declared any conflicts of interest. All culosis: updates for once-­ weekly schedule. Front Vet Sci.
2022;9:880349.
other authors have received a lecture honorarium from
15. Assar S, Nosratabadi R, Khorramdel Azad H, Masoumi J,
Vetoquinol. O.F. is a Vetoquinol employee. Mohamadi M, Hassanshahi G. A review of immunomod-
ulatory effects of fluoroquinolones. Immunol Investig.
DATA AVA I L A B I L I T Y S TAT E M E N T 2021;50(8):1007–26.
The data that support the findings of this study 16. Marchegiani A, Fruganti A, Spaterna A, Cerquetella M, Tambella
AM, Paterson S. The effectiveness of fluorescent light energy
are available from the corresponding author upon
as adjunct therapy in canine deep pyoderma: a randomized clin-
reasonable request. ical trial. Vet Med Int. 2021;2021:6643416.
17. Marchegiani A, Fruganti A, Bazzano M, Cerquetella M, Dini F,
ORCID Spaterna A. Fluorescent light energy in the management of
A. Lange https://orcid.org/0009-0000-7785-9372 multi drug resistant canine pyoderma: a prospective explor-
atory study. Pathogens. 2022;11(10):1197. https://​doi.​org/​10.​
E. Bensignor https://orcid.org/0000-0002-0404-3185
3390/​patho​gens1​1101197
L. Cornegliani https://orcid. 18. Scapagnini G, Marchegiani A, Rossi G, Zago M, Jowarska J,
org/0000-0001-5291-4080 Wael M. Management of all three phases of wound healing
D. Ferreira https://orcid.org/0000-0003-2500-8298 through the induction of fluorescence biomodulation using flu-
M. Mosca https://orcid.org/0000-0002-7682-2452 orescence light energy. In: Proc. SPIE 10863, photonic diagno-
sis and treatment of infections and inflammatory diseases II,
F. Scarampella https://orcid.
108630W. 2019. https://doi.org/10.1117/12.2508066
org/0000-0002-4581-7263 19. Leducq S, Caille A, Le Cleach L, Samimi M, Tavernier E,
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mal keratinocytes by cold atmospheric-­pressure plasma. Clin
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FLUORESCENT ANTIMICROBIAL MANAGEMENT OF CANINE INTERDIGITAL FURUNCULOSIS    9
Veterinary Dermatology
Zusammenfassung
Hintergrund: Die interdigitale Furunkulose (CIF) des Hundes ist eine komplexe, wiederkehrende entzündliche
Erkrankung, die typischerweise durch tiefe bakterielle Infektionen verkompliziert wird und dadurch den verläng-
erten Einsatz von systemischen Antibiotika bedingt.
Hypothese/Ziele: Diese Split-­Body Studie, wo Hunde als ihre eigene Kontrolle dienten, evaluierte, ob der zusät-
zliche Einsatz von fluoreszierender Lichtenergie (FLE) die Zeitdauer bis zur klinischen Abheilung der CIF verkürzen
und den Einsatz systemischer Antibiotika minimieren könnte.
Tiere: Fünfunddreißig Hunde in Privatbesitz mit Zeichen von interdigitaler Furunkulose an mindestens zwei Pfoten.
Materialien und Methoden: Diese prospektive einfachblinde, randomisierte, Split-­Body Multicenter klinische
Studie behandelte Hunde basierend auf einer bakteriellen Kultur und Sensibilität mit systemischen Antibiotika. Eine
Pfote pro Hund wurde zufällig mittels Münzwurfmethode zur wöchentlichen FLE-­Anwendung ausgewählt, während
die andere Pfote als Kontrolle diente. Die Hunde wurden 56 Tage lang alle 2 Wochen in Bezug auf zwei Parameter
bewertet: ein globaler Läsionswert (inklusive hämorrhagische Bläschen, Fisteln mit Fistelgängen, Krusten und
Ulzera) und ein Wert, welcher das Ausmaß der Bakterien verschlingender Neutrophiler bestimmte (NES, 0-­4). Die
Zeit bis zur klinischen Heilung und die Läsionswerte wurden erfasst und zwischen den Gruppen verglichen.
Ergebnisse: Am Tag (D)28 und D56 zeigte die FLE-­Gruppe signifikant häufiger geheilte Pfoten (50% und 88%,
p = 0,021) im Vergleich zur Kontrolle (17% und 54%, p = 0,008). Der Medianwert der Zeit bis zur klinischen
Abheilung war in der FLE-­Gruppe kürzer (35 Tage) im Vergleich zur Kontrollgruppe (56 Tage, p = 0,017). Es wurde
kein Unterschied zwischen den Gruppen in Bezug auf den NES-­Wert festgestellt.
Schlussfolgerungen und klinische Bedeutung: Diese blinde, randomisierte, Split-­Body Studie zeigte, dass FLE
eine wirksame Zusatzbehandlung für CIF darstellt. Es reduziert die Zeit bis zur klinischen Heilung und erhöht die
Heilungsrate während es den Antibiotikaeinsatz minimiert.

摘要
背景: 犬趾间疖病 (CIF) 是一种复杂的复发性炎症疾病，通常因深部细菌感染而变得复杂，需要长期全身抗生素治疗。
假设/目标: 这项分体研究以犬作为自身对照，评估辅助使用荧光能量 (FLE) 是否可以缩短 CIF 的临床缓解时间并最大限
度地减少全身抗菌药物的使用。
动物: 三十五只客户拥有的犬，至少两只爪子有趾间疖病的迹象。
材料和方法: 这项前瞻性、单盲、随机、分体多中心临床试验根据细菌培养和敏感性对犬进行全身抗生素治疗。使用掷硬
币法随机选择每只犬的一只爪子进行每周 FLE 应用，而另一只爪子作为对照。在 56 天内，每 2 周对犬进行一次评分，评
分依据两个参数:整体病变评分(包括血疱、带引流道的瘘管、结痂和溃疡)和中性粒细胞吞噬细菌评分(NES，0-­4)。评估
并比较各组之间的临床缓解时间和病变评分。
结果: 在第 28 天和第 56 天，FLE 组的爪子愈合率明显高于对照组(分别为 17% 和 54%，p = 0.008)(分别为 50% 和 88%
，p = 0.021)。与对照组(56 天，p = 0.017)相比，FLE 组的临床缓解中位时间(35 天)较短。各组之间的 NES 评分无差异。
结论和临床意义: 这项盲法、随机、分体临床试验表明，FLE 是 CIF 的有效辅助疗法。它缩短了临床缓解时间并提高了缓
解率，同时最大限度地减少了对抗生素的需求。

Résumé
Contexte: La furonculose interdigitale canine (FID) est une affection inflammatoire complexe et récidivante,
généralement compliquée par des infections bactériennes profondes nécessitant une antibiothérapie systémique
prolongée.
Hypothèse/Objectifs: Cette étude à corps séparés, où les chiens ont agi comme leur propre contrôle, a évalué
si l'utilisation complémentaire de l'énergie lumineuse fluorescente (ELF) pouvait raccourcir le délai de résolution
clinique de la FIC et minimiser l'utilisation d'antimicrobiens systémiques.
Animaux: trente-­cinq chiens appartenant à des clients et présentant des signes de furonculose interdigitale sur au
moins deux pattes.
Matériels et méthodes: Cet essai clinique multicentrique prospectif, en simple aveugle, randomisé et à corps séparé
a traité les chiens avec des antibiotiques systémiques sur la base de la culture et de la sensibilité bactériennes. Une
patte par chien a été choisie au hasard à l'aide d'une méthode de pile ou face pour une application hebdomadaire de
FLE, tandis que l'autre patte a servi de contrôle. Les chiens ont été évalués toutes les 2 semaines pendant 56 jours sur
la base de deux paramètres : un score lésionnel global (comprenant des vésicules hémorragiques, des fistules avec des
voies de drainage, des croûtes et des ulcères) et un score d'engloutissement des bactéries par les neutrophiles (NES,
0-­4). Le délai de résolution clinique et les scores des lésions ont été évalués et comparés entre les groupes.
Résultats: Au jour (J)28 et J56, le groupe FLE présentait significativement plus de pattes guéries (50 % et 88 %,
p = 0,021) que le groupe témoin (17 % et 54 %, p = 0,008). Le délai médian de résolution clinique était plus court
dans le groupe FLE (35 jours) que dans le groupe témoin (56 jours, p = 0,017). Aucune différence de score NES n'a
été observée entre les groupes.
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10 |   
Veterinary Dermatology
LANGE et al.

Conclusions et pertinence clinique: Cet essai clinique en aveugle, randomisé et à corps séparés a démontré que
le FLE est un traitement d'appoint efficace pour la FIC. Il réduit le délai de résolution clinique et augmente le taux
de résolution tout en minimisant le besoin d'antibiotiques.

要約
背景: 犬の趾間癤腫症(CIF)は複雑な再発性の炎症性疾患であり、通常、抗生物質の長期投与を必要とする深在性細菌感
染を合併する。
仮説/目的: このスプリットボディ研究では、犬自身が対照群となり、蛍光灯エネルギー(FLE)の補助的使用がCIFの臨床
的治癒までの時間を短縮し、全身性抗菌薬の使用を最小限に抑えられるかどうかを評価した。
供試動物: 少なくとも2肢に趾間癤腫症の徴候がある35頭のオーナー所有犬。
材料と方法: この前向き、単盲検、無作為化、スプリットボディ多施設臨床試験では、細菌培養検査および薬剤感受性試
験に基づき、全身性抗菌薬による治療を行った。犬1頭につき片方の前足をコイントス法で無作為に選択し、毎週FLEを投
与し、もう片方の前足を対照とした。犬は2週間ごとに56日間にわたり、2つのパラメータについて採点された。すなわちグ
ローバル病変スコア(出血性小水疱、排膿路を伴う瘻孔、痂皮、潰瘍を含む)および好中球貪食細菌スコア(NES、0~4)で
ある。臨床的治癒までの期間および病変スコアを評価し、群間で比較した。
結果: Day(D)28およびD56において、FLE群はコントロール群(17%と54%、p = 0.008)と比較して、治癒した前足が有意
に多かった(50%と88%、p = 0.021)。臨床的治癒までの期間の中央値は、FLE群(35日)は対照群(56日、p = 0.017)に比べ
て短かった。NESスコアに群間差はみられなかった。
結論と臨床的意義: この盲検無作為化分割体臨床試験により、FLEはCIFに対する有効な補助療法であることが実証さ
れた。FLEは臨床的治癒までの期間を短縮し、抗生物質の必要性を最小限に抑えながら治癒率を高める。

Resumo
Contexto: A furunculose interdigital canina (FIC) é uma condição inflamatória complexa e recorrente, tipicamente
complicada por infecções bacterianas profundas que requerem antibióticos sistêmicos prolongados.
Hipótese/Objetivos: Este estudo de corpo dividido, onde os cães atuaram como seu próprio controle, avaliou
se o uso adjuvante de energia de luz fluorescente (FLE) poderia encurtar o tempo para resolução clínica da FIC e
minimizar o uso de antimicrobianos sistêmicos.
Animais: trinta e cinco cães de propriedade de clientes com sinais de furunculose interdigital em pelo menos duas
patas.
Materiais e métodos: Este ensaio clínico prospectivo, simples-­cego, randomizado e multicêntrico de corpo
dividido tratou cães com antibióticos sistêmicos com base na cultura bacteriana e sensibilidade. Uma pata por cão
foi selecionada aleatoriamente utilizando um método de cara ou coroa para aplicação semanal de FLE, enquanto
a outra pata serviu como controle. Os cães foram pontuados a cada 2 semanas ao longo de 56 dias em dois
parâmetros: uma escore global da lesão (incluindo vesículas hemorrágicas, fístulas com tratos drenantes, crostas e
úlceras) e escore de neutrófilos fagocitando bactérias (NES, 0–4). O tempo para resolução clínica e os escores das
lesões foram avaliados e comparados entre os grupos.
Resultados: No Dia (D)28 e D56, o grupo FLE apresentou significativamente mais patas curadas (50% e 88%,
p = 0,021) em comparação com o controle (17% e 54%, p = 0,008). O tempo médio para resolução clínica foi menor
para o grupo FLE (35 dias) em comparação com o grupo controle (56 dias, p = 0,017). Nenhuma diferença na
pontuação NES foi observada entre os grupos.
Conclusões e relevância clínica: Este ensaio clínico cego, randomizado e de corpo dividido demonstrou que o
FLE é uma terapia adjuvante eficaz para FIC. Reduz o tempo de resolução clínica e aumenta a taxa de resolução,
minimizando a necessidade de antibióticos.

RESUMEN
Introducción: la forúnculos interdigital canina (CIF, por sus siglas en inglés) es una afección inflamatoria compleja
y recurrente, típicamente complicada por infecciones bacterianas profundas que requieren antibióticos sistémicos
en uso prolongado.
Hipótesis/Objetivos: Este estudio de cuerpo dividido, en el que los perros actuaron como su propio control,
evaluó si el uso de energía de luz fluorescente (FLE) adjunta a otra terapia, podría acortar el tiempo de resolución
clínica de la CIF y minimizar el uso de antimicrobianos sistémicos.
Animales: Treinta y cinco perros de propietarios particulares con signos de furunculosis interdigital en al menos
dos patas.
Materiales y métodos: Este ensayo clínico multicéntrico, prospectivo, simple ciego, al azar y de cuerpo dividido
trató a perros con antibióticos sistémicos según el cultivo bacteriano y la sensibilidad. Se seleccionó aleatoriamente
una pata por perro mediante el método de lanzamiento de moneda para la aplicación semanal de FLE, mientras que
la otra pata sirvió como control. Se evaluó a los perros cada 2 semanas durante 56 días según dos parámetros: una
puntuación global de la lesión (incluyendo vesículas hemorrágicas, fístulas con tractos de drenaje, costras y úlceras)
y una puntuación de neutrófilos con bacterias fagocitadas (NES, 0-­4). Se evaluaron el tiempo hasta la resolución
clínica y las puntuaciones de la lesión, y se compararon entre los grupos.
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FLUORESCENT ANTIMICROBIAL MANAGEMENT OF CANINE INTERDIGITAL FURUNCULOSIS    11
Veterinary Dermatology
Resultados: En los días 28 y 56, el grupo FLE mostró significativamente más patas cicatrizadas (50 % y 88
%, p = 0,021) en comparación con el grupo control (17 % y 54 %, p = 0,008). La mediana del tiempo hasta la
resolución clínica fue menor en el grupo FLE (35 días) en comparación con el grupo control (56 días, p = 0,017). No
se observaron diferencias en la puntuación NES entre los grupos.
Conclusiones y relevancia clínica: Este ensayo clínico ciego, al azar y de cuerpo dividido demostró que la FLE
es una terapia adyuvante eficaz para la CIF. Reduce el tiempo de resolución clínica y aumenta la tasa de resolución
minimizando la necesidad de antibióticos.