Toe Web Infections, the Microbiome, and Toe Web Psoriasis: A Review

ABSTRACT

OBJECTIVE

To present the toe web space as an anatomically, physiologically, and pathologically unique part of the human body; characterize toe web infections and discuss why they occur; and highlight toe web psoriasis as an uncommon condition that providers should consider if toe web intertrigo does not respond to treatment.

DATA SOURCE

This review encompassed many years of clinical observation and photographs; medical textbooks; and a literature search of MEDLINE, PubMed, and Google Scholar.

STUDY SELECTION

Primary research keywords included intertrigo, toe web intertrigo, toe web infection, tinea pedis, microbiome, skin microbiome, toe web microbiome, ecology, psoriasis, psoriasis microbiome, intertriginous psoriasis, and Wood’s lamp. More than 190 journal articles met the search criteria.

DATA EXTRACTION

The authors sought data relating to what makes for a healthy toe web space and what makes for disease. They extracted and collated relevant information to compare and contrast among sources.

DATA SYNTHESIS

After understanding the normal toe web space and the microorganisms that normally reside there, the authors investigated why infections occur, how they should be treated, what complications may result, and what other diseases occur in the toe web area.

CONCLUSIONS

This review of toe web infection illustrates the effect of the microbiome and reports a rare form of psoriasis that is usually misdiagnosed as athlete’s foot. The toe web space is a unique part of the human body that can be affected by a variety of both common and unusual conditions.

INTRODUCTION

The toe web interspace is a small but important part of the human body. Within its confines reside a plethora of microorganisms that contribute to health or disease. The most common toe web abnormality is infection, which is usually caused by fungus. Toe web infections due to bacteria, or bacteria and fungus, are also frequent.

Noninfectious inflammatory diseases may also affect toe webs. Psoriasis is one such disease, usually manifesting as skin plaques and less commonly as the guttate, pustular, intertriginous, erythrodermic, or nail types. Interdigital psoriasis is a rare form of inverse psoriasis that mimics toe web infections. Psoriasis also induces systemic inflammation in various organs with serious comorbidities. Unsightly skin, pruritus, and embarrassment decrease quality of life in patients with psoriasis, but chronic joint pain, deformities, and disability impair their functional quality of life and independence. Failure to diagnose and treat psoriasis enables the unabated progression of inflammation with resultant sequelae.

The aims of this narrative review are to present the toe web space as a unique anatomic part, discuss toe web infections, and highlight toe web psoriasis as an uncommon condition that providers should consider if toe web intertrigo does not respond to treatment.

METHODS

Research for this review article began years before its writing with an interest in correctly diagnosing toe web intertrigo and attaining a successful resolution. This involved reviewing many photographs of challenging and routine patient encounters. The authors consulted recent and historic textbooks for relevant information and conducted a literature search for information related to intertrigo, toe web intertrigo, toe web infection, tinea pedis, microbiome, skin microbiome, toe web microbiome, ecology, psoriasis, psoriasis microbiome, intertriginous psoriasis, and Wood’s lamp in the databases PubMed, Google Scholar, and MEDLINE.

A highlight of this review is the presentation of a seemingly routine toe web problem that proved to be a unique medical condition: psoriasis affecting only the toe webs and no other body parts. All three authors could not remember such a unique patient in their combined clinical experiences. That patient is a retired nurse and gladly provided written permission to publish the details and photographs of her condition.

THE MICROBIOME

The human microbiome is the collective population of microorganisms and their byproducts that inhabit the human body. Colonization begins at birth and reaches an estimated 38 trillion bacteria in a 150-lb (70-kg) individual, constituting a total mass of approximately 0.44 lb (0.2 kg).¹ Each individual possesses a unique community of microbes.

The skin microbiome consists of trillions of bacteria, fungi, viruses, mites, protozoa, protists, and archaea (Figure 1).^2–5 It encompasses the entire skin surface, approximately 1.8 to 2 m² (or 25 m² including hair follicles and sweat ducts),^3,5 and is populated by beneficial and harmful microbiota. By punch biopsy, 1,000,000 bacteria inhabit 1 cm² of skin surface.⁶

Figure 1.

SCHEMATIC OF SKIN HISTOLOGY WITH MICROBIOME

Reprinted with permission from Kong and Segre.³ Copyright 2012 The Society for Investigative Dermatology.

Populations of microbes differ among individuals and among organ systems within the same person. They also differ among habitats (such as the toe web) and are influenced by dryness, oiliness, moisture, glands, follicles, oxygen, pH, and temperature.^6–8

TOE WEB INFECTIONS

The normal toe web space is a moist, polymicrobic area. It contains a mean of 14,130,000 aerobic bacteria,⁹ although this likely underestimates the actual count that could be identified by newer techniques. Gram-negative rods inhabit 10% of normal toe webs, so bacteria such as Acinetobacter, Klebsiella, Proteus, and Pseudomonas reside in normal interspaces as resident flora.¹⁰ Other notable residents of normal toe web interspaces include Corynebacterium minutissimum and Kytococcus sedentarius.

Dermatophytes are filamentous fungi that constitute part of the complex, invisible world of microorganisms. They exist in nature as growing, tubular filaments that are known as hyphae, which coalesce into multicellular masses, termed mycelia, or they bud into inactive spores, called conidia. Dermatophytes are acquired exogenously from humans, animals, or soil as they seek sustenance from keratin, a protein that is found in the epidermis, hair, and nails of humans and the beaks, claws, feathers, horns, hooves, and wool of animals. Dermatophytes are present in up to 23% of normal toe web spaces.^9–11

Historically, athlete’s foot has been synonymous with tinea pedis and attributed to dermatophytes.¹² Athlete’s foot manifests on a continuum from scaly, itchy toe webs to white, soggy, malodorous ones. Dermatophytes are reportedly found in 85% of scaly toe webs⁹ and 31% of macerated toe webs.¹⁰ Nondermatophyte fungi, such as Candida, Aspergillus, Fusarium, and Cladosporium also infect toe webs.^13,14

The prevalence of bacteria in macerated toe webs varies. For example, one study observed Staphylococcus aureus in 36% of macerated toe webs, compared with K sedentarius in 37%, Brevibacterium epidermidis in 54%, C minutissimum in 69%, and Pseudomonas species in 26%.¹⁰ Another study of 123 cases of Gram-negative toe web intertrigo found Pseudomonas aeruginosa alone or in association with other Gram-negative bacteria in 46.4% of patients and with Gram-positive bacteria in 17%.¹⁵ A different study noted P aeruginosa in 55% of macerated toe webs, Enterococcus faecalis in 41%, S aureus in 41%, coagulase-negative Staphylococcus in 29%, and mixed infection in 93%.¹⁶

PATHOGENESIS

An early hypothesis suggested that the primary event causing toe web infection was fungal invasion resulting from an altered habitat of hyperhidrosis and maceration. Later, it was proposed that the pathogenesis of athlete’s foot begins with invasion of the stratum corneum by dermatophytes.¹⁷ Bacterial involvement in toe web infections also garnered attention when both pathogenic fungi and staphylococci were demonstrated in abnormal, symptomatic toe web spaces.¹⁸ The role of bacteria in toe web infection was further advanced after a 1973 study found Gram-negative bacteria in 12 patients with macerated toe web infections.¹⁹ These contrasting views demonstrated the need for studies to determine the interplay between bacteria and fungi in toe web infections.

In a seminal study from 1978 by Leyden and Kligman,⁹ simple scaling between toe webs was termed dermatophytosis simplex to identify it as uncomplicated athlete’s foot due to fungus. Toe webs that were macerated were defined as dermatophytosis complex to emphasize the predominance of bacteria, with symptomatic inflammation and fissuring. The conclusion was that “interspaces free of fungi showed essentially no clinical changes” and that the dry, scaly toe web (dermatophytosis simplex) was “a pure fungal infection.” It was also proffered that after fungi damage the stratum corneum, in the presence of excess hydration, resident bacteria proliferate in the macerated skin (dermatophytosis complex).

Dermatophyte invasion with damage of the stratum corneum is now considered the primary event that precipitates interdigital toe web infections.^11,20–22 Ilkit and Durdu²³ created an informative diagram of the molecular pathogenesis of tinea pedis.

PATHOPHYSIOLOGY

Dermatophyte conidia extend fibrils for adherence to toe web stratum corneum.²⁴ They can reside as inactive spores that do not invade or can germinate into hyphae, seeking nutrition from keratin in the stratum corneum. Invasion is facilitated by a weakened skin barrier and an array of dermatophyte-secreted proteolytic enzymes.^25,26 Further, after dermatophyte damage to the stratum corneum, excess moisture can stimulate normally harmless bacteria that reside in toe web spaces to proliferate, transforming a purely fungal infection (scaly dermatophytosis simplex) into a mixed infection of bacteria and fungi (dermatophytosis complex).

The aforementioned seminal study by Leyden and Kligman determined large-colony diphtheroids to be the predominant overgrowing bacteria.⁹ Later, some of the proliferating bacteria were identified as K sedentarius, B epidermidis, C minutissimum, Corynebacterium jeikeium, S aureus, and Pseudomonas and Proteus species.^10,22 Bacteria, fungi, and occlusion are all necessary for the development of dermatophytosis complex.²¹ Interspaces that have not been damaged by dermatophytes resist bacterial damage, likely due to the thickness of the stratum corneum and its barrier properties.

The production of antibiotic-like substances by dermatophytes, recognized as early as 1932, is another notable factor in the pathophysiology of toe web infections.²⁷ These substances were later identified as penicillin-like and streptomycin-like compounds, having been isolated in vitro and in vivo. Such antibiotic-like substances influence the growth of pathogens and commensals.

The bacteria in toe web infections are also active, producing fungicidal sulfur compounds, promoting bacterial growth, and forcing dermatophytes into deeper, safer levels of the stratum corneum.^9,20–22 Bacteria also produce antibiotic peptides that inhibit the growth of other bacteria and activate Toll-like receptors on keratinocytes to generate antimicrobial peptides. Certain bacteria even synthesize proteolytic enzymes that digest keratin, weakening their structure and effecting further tissue damage. Kytococcus sedentarius is one such bacterium that may contribute to toe web erosions via keratinases, similar to what occurs in pitted keratolysis.¹⁰ If present, Pseudomonas can exacerbate tissue damage by producing proteolytic and keratinolytic enzymes.²⁸ The severity of toe web infections correlates with the overgrowth of resident bacteria and the virulence of pathogenic organisms.

Further, when dermatophytes injure keratinocytes, metabolic byproducts initiate nonspecific, delayed hypersensitivity inflammatory reactions,²⁹ inducing increased basal cell keratinocyte mitoses with epidermal proliferation, thickening, and scaling to clear the microbe. Excess exogenous moisture is then retained by the thickened epidermis, yielding whitish, macerated toe web skin.

In summary, ingravescent toe web infections result from the interactions among bacteria, fungi, and moisture. As moisture levels rise, dermatophytosis simplex shifts from a dry, fungus-dominated ecosystem to a wet, predominantly bacterial dermatophytosis complex, wherein dermatophyte-derived antibiotics influence bacterial selection.

Gram-Negative Toe Web Infections

Gram-negative toe web infections might be unique. Most reports postulate that dermatophytes first damage the stratum corneum, after which excess moisture, friction, and abrasions promote the growth of resident flora and opportunistic Gram-negative bacteria.^10,30 However, Gram-negative rods inhabit 10% of normal toe web spaces. And although Gram-negative bacteria have limited ability to damage normal toe web spaces, Pseudomonas thrives in superhydrated skin, leading some investigators to conclude that Gram-negative toe web infections may occur because of excessive hydration of the stratum corneum without initial injury by dermatophytes.

PREDISPOSING FACTORS

Factors that predispose individuals to toe web infections include a deficient skin barrier (eg, dermatitis), reduced sebum, dermatophyte presence, excess moisture, a warm environment, alkaline pH, previous toe web infections, topical medicaments (antifungals, antibiotics, and steroids), male sex, and immunosuppression. Interestingly, atopy,³¹ psoriasis,^32–34 vascular disease,^32,34 and diabetes^30,34–37 appear to be associated with a low risk of toe web infections.

DIAGNOSIS

The clinical manifestations of toe web infections are similar, with variations in scale or crust, erythema, moist white maceration, erosions, fissures, vesicles, purulence, and odor (Figure 2).

Figure 2.

TOE WEB INFECTIONS CAN BE CLINICALLY SIMILAR

A, Pseudomonas aeruginosa. B, Serratia marcescens, methicillin-resistant Staphylococcus aureus. C and D, Dermatophyte (tinea pedis), Morganella morganii, Citrobacter koseri, methicillin-resistant S aureus. E and F, Corynebacterium minutissimum (erythrasma). G and H, Dermatophyte (tinea pedis), scabies mite, Corynebacterium minutissimum (erythrasma).

Patients provided consent for their images to be published.

Distinguishing among a bacterial, fungal, or mixed toe web infection is difficult. A potassium hydroxide (KOH) examination for hyphae (dermatophyte) or pseudohyphae (candida, yeast) is often helpful for diagnosing fungus. Fungal cultures can be useful, although providers should initiate treatment before the results become available several weeks later. Maceration in the toe web space strongly suggests bacterial dominance, which can be identified by culture and sensitivity. If a greenish hue is present in lesional skin or socks, suspect Pseudomonas.

A separate test for diagnosing bacteria is the Wood’s lamp examination, in which UV radiation is emitted at 365 nm. When used in a darkened room, the appearance of greenish-yellow fluorescence identifies Pseudomonas, which produces pyoverdin pigment. In contrast, coral pink fluorescence indicates C minutissimum, which generates porphyrins and erythrasma. Dermatophytes that produce fluorescence very rarely affect the feet, but one example is Trichophyton schoenleinii, which fluoresces a dull blue.

Molecular diagnostics are also an important tool, generating rapid results and precisely identifying pathogens. They are somewhat limited, however, given their inability to distinguish between living and dead organisms.

Dermatophytes may not be recovered from toe web infection, especially macerated ones, and several explanations have been proposed. Based on skin biopsies, as maceration worsens, fungi move from a superficial location in the stratum corneum to a deeper area, reverting to the former upon drying of the toe web.⁹ Bacterial overgrowth and inflammation have also been implicated. In addition, bacteria in macerated toe webs can produce potent antifungal sulfur compounds that inhibit dermatophyte growth. Consequently, negative fungal studies do not exclude the presence of dermatophytes.

A biopsy for athlete’s foot is rarely necessary because noninvasive diagnostic tools usually suffice. A histologic examination with hematoxylin and eosin (H&E), periodic acid-Schiff (PAS), and direct immunofluorescence might be necessary if the toe web problem persists.

TREATMENT

Restoring the natural skin barrier to a healthy state is the most important factor in resolving toe web infections. It is a complex structure that promotes homeostasis with the external environment. Physical protection is provided by intact, keratinized, moist corneocytes, with regular 28-day sloughing of senescent cells to remove microbes and debris. Its antimicrobial functions are affected through its acid mantle (approximately pH 5.5), antimicrobial peptides, and lipids. Also, as a unique ecosystem of the microbiome, it harbors microbes that flourish locally and repel foreign invaders. Other barrier functions also exist.

Restoring the skin barrier to normal health involves several components. Dry, scaly toe webs are usually caused by dermatophytes and confirmed by KOH examination or culture. They usually respond to topical antifungal creams or powders that are applied 1 to 2 cm beyond the area of visible disease and continued for 1 week after apparent resolution (perhaps 2 to 3 weeks or 4 weeks if the skin is hyperkeratotic). Various topical antifungal treatments have proven effective for tinea pedis; a 2012 study of 104 randomized controlled trials showed that all topical antifungals were better than placebo with no significant differences between classes.³⁸

Refractory cases and those with extensive, inflammatory, or vesicular disease might require oral terbinafine, itraconazole, or fluconazole. A 2010 study of these three oral agents found terbinafine to be the most active in vitro in patients with or without non-insulin-dependent diabetes mellitus.³⁹

A certain level of skin moisturization is necessary for health, but excessive toe web moisture increases the growth of resident and pathogenic microorganisms, which can be mitigated by drying the web space. Dermatophytosis complex reverts to dermatophytosis simplex as bacterial levels diminish and dermatophytes that are deep within the stratum corneum approach the surface. A cool, slightly acidic skin with low moisture reduces overall microbial growth in most body regions. Accordingly, adequate circulation of air around the toes with wide, well-ventilated shoes lowers heat and friction. Moisture-wicking fabrics and physical drying with a towel or blow dryer also help.

It was recognized early that antifungal agents do not adequately treat macerated toe web infections. Aluminum chloride 30% was then found to be as successful as carbol-fuchsin (Castellani paint) in treating macerated toe web infections but without the unpleasant stain left by the dye (deemed necessary for its antimicrobial effect).¹⁷

Additional treatments may include foot soaks in 2% to 5% acetic acid or dilute silver nitrate (0.5%), gentian violet, Whitfield ointment, salicylic acid, zinc oxide, and other barrier creams. Mechanical debridement of unhealthy tissue might be necessary.^40,41 Negative-pressure wound therapy has been suggested,³⁰ and cryotherapy for recalcitrant candida has been reported.⁴²

Proper skin cleansing does not require the removal of all bacteria because resident bacteria are beneficial and rarely pathogenic. Excess washing may even be detrimental because it removes moisturizing lipids. The use of antimicrobial soaps can also prove harmful.^19,28 In addition, the acid mantle of the stratum corneum promotes the attachment of resident bacteria, versus alkaline soaps, which raise the pH and promote the dispersal of resident bacteria.⁴³ Therefore, providers should select cleansing products that maintain the stratum corneum. Skin care products can also alter the normally stable skin microbiome, with prolonged effects.⁴⁴ Sanitization products for contaminated footwear, socks, and textiles are commercially available but await improvements for better results.⁴⁵

Refractory toe web infection can result from inadequate treatment, antifungal or antibiotic resistance, nail involvement, and immune deficiency. Urea cream may be useful in preventing recurrent tinea pedis if thick, plantar skin is the reservoir, although thin toe web skin would necessitate a lower concentration. Prophylactic antifungals can reduce recurrence because dermatophytes migrate from the deeper stratum corneum to a more superficial area with reduced bacterial load.

COMPLICATIONS

Cellulitis, with complicating chronic lymphedema, is an important but avoidable morbidity that is related to tinea pedis.^34,46–48 Erysipelas of the legs is a more superficial variant of cellulitis and is also related to toe web intertrigo.^48,49 Although dermatophytes do not cause the cellulitis, they compromise the skin barrier, allowing the entry of colonized bacteria into the skin and soft tissue. In one study of 20 patients with cellulitis and interdigital athlete’s foot, β-hemolytic streptococci were cultured in 85% of interdigital spaces, compared with S aureus in 45% and Gram-negative rods in 35%.⁴⁶

Other avoidable complications include local recurrence or local spread of the infection, bacterial infection, vesiculobullous lesions, dermatophytid (id) reaction, tinea incognito, two feet-one hand syndrome, Majocchi granuloma, lymphadenopathy, lymphangitis, reduced mobility, osteomyelitis, endocarditis, and sepsis. Dermatophytes may also exacerbate asthma, allergies, chronic rhinitis, and atopic dermatitis.^47,50–52

DIFFERENTIAL DIAGNOSIS

Inflammatory vesiculobullous tinea pedis can be misdiagnosed as bacterial or herpetic cellulitis, especially in children.⁵³ Noninfectious causes include contact dermatitis (allergic or irritant), drug reactions, psoriasis (inverse), acrodermatitis continua of Hallopeau, erosive lichen planus, nutrition (phrynoderma), vesiculobullous disease (Hailey-Hailey, pemphigus, pompholyx), pityriasis rubra pilaris,⁵⁴ immunodeficiency, immersion foot, benign neoplasms (eg, nevus, soft corn), and malignancies such as verrucous carcinoma⁵⁵ or acral lentiginous melanoma.⁵⁶ Other toe web infections include scabies, secondary syphilis, and tungiasis.

CASE REPORT

A 75-year-old patient was treated unsuccessfully for a fungal infection of the toe webs at an outside clinic for 6 months. When the lead author first saw the patient in the office, the patient was distressed. She could only wear flip-flops and was planning to undergo a total knee replacement due to osteoarthritis. The patient stated that it was painful to walk, and no treatments had helped, thus reducing her quality of life. All eight toe webs exhibited varying degrees of redness, crusting, erosions, maceration, and fissuring (Figure 3). Wood’s lamp examination was negative, cultures were taken, and initial treatment was begun with oral cefdinir and Burow solution soaks. The bacterial culture was positive for heavy growth of Escherichia coli, Klebsiella oxytoca, and Proteus mirabilis. All three bacteria were sensitive to levofloxacin, prompting a change in antibiotic. A fungal culture revealed Candida parapsilosis.

Figure 3.

TOE WEBS OF PATIENT AT PRESENTATION

The bacterial culture was positive for Escherichia coli, Klebsiella oxytoca, and Proteus mirabilis.

Over the next 6 months, the toe web abnormalities would wax and wane but never clear. Hyperhidrosis and toe web occlusion were absent. Cultures were intermittently positive for E coli, P mirabilis, P aeruginosa, E faecalis, K oxytoca, Klebsiella pneumoniae, Streptococcus, Aspergillus species, or C parapsilosis. Wood’s lamp examination was positive several times for C minutissimum or Pseudomonas. Dermatophytes were never detected, and commercial patch tests were negative.

Treatments included saline cleanses, debridement with mineral oil and gauze, curettage, clindamycin solution, aluminum chloride, Burow solution soaks, clioquinol and hydrocortisone cream, gentian violet, Castellani paint, sodium hypochlorite wash, antiseptic soaks, cornstarch, lubricant jelly, various shampoos and soaps, manuka honey, econazole cream, ciclopirox cream, oral and topical terbinafine, cefdinir, and levofloxacin. Cephalexin was prescribed for an unrelated condition by the patient’s primary care physician but also failed. Triamcinolone cream 0.1% was then administered with some improvement.

Biopsies were taken from the dorsal toe web (Figure 4) for H&E and PAS staining and direct immunofluorescence to identify a potential inflammatory rather than infectious origin. Two biopsies were taken for H&E staining, and each revealed histopathologic evidence of psoriasis (Figure 5); the PAS stain and direct immunofluorescence were negative. There was no evidence of psoriasis on the skin, scalp, or nails, and there was no family history of psoriasis or of triggering infection or medication. Office samples of more potent topical steroids were then tried but without further improvement.

Figure 4.

toe webs of patient before biopsy

Figure 5.

HISTOPATHOLOGY OF TOE WEB BIOPSIES

Histopathology-epidermal diffuse parakeratosis, marked acanthosis, elongated rete ridges, hypogranulosis, multiple collections of neutrophils in stratum corneum, and dermal superficial perivascular and interface infiltrate of lymphocytes and numerous eosinophils. Periodic acid-Schiff stain negative. Direct immunofluorescent staining negative for immunoglobulins G, A, and M; complement 3; and fibrinogen.

Despite limited skin involvement, the location and reduced quality of life justified the use of systemic medication. Apremilast was initiated at 30 mg per day (limited by adverse gastrointestinal effects), and after 1 to 2 months, the toe webs were nearly clear, with occasional use of a topical steroid. The dose of apremilast was later increased to 30 mg twice daily, which resulted in total clearance. Four years after beginning apremilast, the patient remains totally clear and very pleased. No further evidence of psoriasis has appeared.

CASE DISCUSSION

This patient presented with an unusual case of toe web intertrigo. After she responded poorly to topical agents and antibiotics, diagnostic re-evaluation established the correct diagnosis with targeted therapy for successful resolution. Apremilast was initiated because of its favorable safety profile and previously successful use on the feet. Injectable biologic agents would have been offered if satisfactory results had not been achieved. Continued surveillance will be needed to monitor treatment efficacy and for complications of psoriasis.

Providers preferred psoriasis as the primary diagnosis rather than dermatophyte-induced damage of the stratum corneum with secondary bacterial infection and psoriatic koebnerization for several reasons. There was no history of prior fungal foot infection. Also, dermatophytes were never isolated by KOH examination, culture, or tissue PAS staining. Finally, remission occurred only after treatment for inflammation, not infection. If infection, moisture, and koebnerization had been the primary issue, the dermatophytes deeper in the stratum corneum would have migrated back to the surface and restarted the pathophysiologic process.

Skin psoriasis is usually readily recognizable, although variations can make it difficult. Toe web psoriasis may be the most problematic, given its mimicry of the much more common toe web infection. In the psoriatic toe web, the stratum corneum is thickened because of abnormal epidermal turnover, with white maceration from moisture retention and bacterial proliferation.

Toe web psoriasis may have been described in 1954 with four cases termed “pseudotinea interdigitalis pedum,”⁵⁷ although they were classified as a distinct entity rather than an atypical form of psoriasis.⁵⁸ It was not until 1961 that toe web psoriasis was first clearly defined as an atypical form of interdigital psoriasis (“white psoriasis”) with three distinct presentations: erythematous, keratodermic, and hyperkeratotic (white).⁵⁹ Afterward, interdigital psoriasis received little attention until its import was re-established with a 2004 report confirming its clinical appearance and histopathologic features, including the assertion that “interdigital psoriasis (or “psoriasis alba”) is mistaken for interdigital fungal infection in virtually every single case.”⁵⁸ Toe web psoriasis is now considered a rare form of inverse psoriasis and estimated to occur in 2.6% to 5% of psoriatic feet.^59,60 However, psoriasis that is limited to the toe web space is much more rare.

Establishing or restoring a favorable microbiome is an intriguing approach to managing psoriasis. It is possible that psoriasis may one day be treated with prebiotics, probiotics, postbiotics, novel antibiotics, or fecal transplantation. Recent studies have linked skin keratinocytes, skin microbes, the immune system, intestinal dysbiosis, and psoriasis.^61–65 Further, the epithelial tight junctions in the intestinal lumen of patients with plaque psoriasis exhibit excess permeability.^66,67 This was substantiated by the finding that bacterial DNA (especially E coli) from the intestinal flora could translocate into the bloodstream of patients with plaque psoriasis and was associated with significantly higher cytokine levels.⁶⁸ It has also been hypothesized that intestinal permeability induces systemic inflammation. In addition, a “psoriasis microbiome” was posited after studying the intestinal microbiomes of patients with psoriasis and finding them clearly different than those of controls.⁶⁹ Bacterial translocation to the bloodstream may even originate from the gut, skin, or oral cavity.⁶²

Despite these theories, establishing a “healthy” microbiome in the intestines or skin has eluded researchers, and the study of dysbiosis has yielded discordant results. Although high concordance exists between dysbiosis and psoriasis, countless variables complicate investigations, making causality difficult to prove and beneficial treatments elusive.⁷⁰

CONCLUSIONS

The toe web is a neglected area of the human body. Infections are a frequent cause of toe web concerns prompting visits to the medical office. They are so frequent that other causes of toe web problems are rarely considered, leading to incorrect diagnoses. This review has attempted to broaden clinical knowledge of the toe web space and associated diseases, as well as highlight psoriasis as a possible diagnosis. Future studies of the toe web should pursue the possible linkage of a disrupted microbiome to local disease.