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IN THIS ISSUE... (see article on p. 1121–1126)
Gram Negative Toe Web Infection – A Not So Rare
but Neglected Syndrome
In 1977 Leyden & Kligman (1) introduced the concept of
dermatophytosis complex and Gram negative toe web in-
fection. They stated that “ in our view, interdigital athlete’s
foot usually begins with invasion of the horny layer by
dermatophytes. Because of hot weather, sweating, exercise,
or tight shoes, enough moisture accumulates to stimulate an
overgrowth of bacteria. Large numbers of normally resident
aerobic diphtheroids cause the common wet, macerated type
of athlete’s foot, while an overgrowth of Gram negative orga-
nisms, such as Pseudomonas and Proteus, is responsible for the
more serious cases“. Gram negative infection of the foot was
therefore seen as a secondary consequence of dermatophyte
infection of the toe web spaces. The authors pointed out that
resolving the bacterial infection through treatment might lead
to return of the dermatophyte infection and the potential for
a cycle of infection. The clinical appearances described then,
and subsequently, were those of soggy and eroded interdigital
skin and there was frequently a greenish tinge to the border of
the cracked area indicating the presence of Pseudomonas in
the wound. Patients usually describe soreness or pain, which
can be severe and disabling, rather than itching in such lesions.
Subsequent work associated the emergence of Gram negative
toe web infection with wearing heavy footwear such as that
used in heavy industry and mining or in occupations, such as
the nuclear fuels industry, where protective footwear would
be used (2). A further study of British coal miners showed that
this Gram negative infection was also seen in miners working
under wet conditions – the so-called wet mines (3) where
pooling of water was an ever-present hazard at the coal face.
Gram negative foot infection is one of a number of different
syndromes involving cracking and erosion of the toe web spa-
ces that include other fungal infections, such as those caused
by Candida, Fusarium and Neoscytalidium along with those
caused by Gram positive bacteria e.g., coryneforms in eryth-
rasma of the toe web. Diagnosing the cause is an important
step in identifying the correct treatment.
Apart from the presence of a previous skin injury at the
site, including infection due to dermatophytosis, the other
constantly reported accompaniment of Gram negative foot
infection is excessive humidity which appears to be neces-
sary for the infection to develop. More recent studies using
molecular techniques to identify the skin microbiome have
shown that the toe webs of otherwise healthy subjects harbour
a specific and diverse, as well as variable, flora including, in
otherwise healthy individuals, Proteobacteria including Gram
negatives such as Pseudomonas (4). What triggers these to
change from a normal commensal to a pathogenic role is not
clear. It has been shown recently that some of the foot mi-
crobiota, particularly those affecting the toe web spaces (5),
may include coagulase negative Staphylococcal species that
are prolific produces of bacteriocins or bacteria biocides with
activity against other skin pathogens including bacteria and
doi: 10.2340/00015555-3335
Acta Derm Venereol 2019; 99: 1070
fungi. Changes in their population number and distribution
are likely to have profound effects on other microbes normally
resident in this area.
In this issue a team of French dermatologists has documen-
ted their experience of Gram negative foot infections across
a range of different hospitals (6). They recorded that half of
their 62 patients experienced more than one episode of Gram
negative toe-web infection. Pseudomonas aeruginosa was the
most prominent bacterium identified, but that many showed
mixed populations of microbes, including Staphylococcus
aureus. They recorded predisposing factors that included
eczema and psoriasis, suspected tinea pedis and exposure to
humidity or hyperhidrosis and vascular disorders. Five percent
of those studied were diabetic, an interesting observation
given the growing association between foot Gram negative
bacteria and diabetic foot ulceration or diabetic foot studied
using mixed techniques of culture plus 16S ribosomal RNA
(16SrRNA) genetic analysis (7). The French study included
patients with a severe spectrum of disease and over 75% had
more than one episode of Gram negative infection, often fol-
lowing failure of initial outpatient management.
The publication of this study is important as it re-empha­
sises the need for more information on the diagnosis and
management of this condition, Gram negative toe web infec-
tion, which is by no means uncommon. This echoes an early
systematic review of the condition published in 2018 (8)
which pointed out the relative paucity of reports and the need
for randomized controlled trials designed to provide evidence-
based therapies. The severity of some of the cases described
in this latest publication serves to underscore this need.
REFERENCES
1. Leyden JJ, Kligman AM. Interdigital athlete’s foot: new con-
cepts in pathogenesis. Postgrad Med 1977; 61: 113–116.
2. Noble WC, Hope YM, Midgley G, Moore MK, Patel S, Virani
Z, Lison E. Toewebs as a source of gram-negative bacilli. J
Hosp Infect 1986; 8: 248–256.
3. Hope YM, Clayton YM, Hay RJ, Noble WC, Elder-Smith JG.
Foot infection in coal miners: a reassessment. Br J Dermatol
1985; 112: 405–413.
4. Cundell AM. Microbial ecology of the human skin. Microb Ecol
2018; 76: 113–120.
5. O’Sullivan JN , Rea MC, O’Connor PM, Hill C, Ross RP. Hu-
man skin microbiota is a rich source of bacteriocin-producing
staphylococci that kill human pathogens, FEMS Microbiology
Ecology 2019; 95: fiy241.
6. Banerjee T, Das A, Singh A, Bansal R, Basu S. The microflora
of chronic diabetic foot ulcers based on culture and mole-
cular examination: a descriptive study. Wound Manag Prev
2019; 65: 16–23.
7. Goiset A, Milpied B, Marti A, Marie J, Leroy-Colavolpe V,
Pham-Ledard A, et al. Characteristics, associated diseases,
and management of Gram-negative toe-web infection: a
French experience. Acta Derm Venereol 2019; 99: 1121–
1126.
8. Weidner T, Tittelbach J, Illing T, Elsner P. Gram-negative
bacterial toe web infection – a systematic review. J Eur Acad
Dermatol Venereol 2018; 32: 39–47.
Roderick J. Hay
Section Editor
This is an open access article under the CC BY-NC license. www.medicaljournals.se/acta
Journal Compilation © 2019 Acta Dermato-Venereologica.