Addressing Toe Web Space Infections In Patients With Diabetes

Toe web space infection can be associated with significant morbidity. Not infrequently, toe web space infections result in cellulitis. This may progress from initial tinea pedis and skin xerosis.1 One can appreciate the significance of preventing cellulitis, particularly in a patient with diabetes, by looking at a study predicting foot ulceration in VA patients.2 The study authors found that onychomycosis and tinea pedis are two of the top seven predictors of foot ulceration in this study population.2

Interdigital space infection may be secondary to erythrasma, tinea pedis, Candida infection, or it may be associated with dermatophytosis with secondary bacterial infection, both Gram-positive or Gram-negative. The differential diagnosis of these infections also includes interdigital psoriasis or interdigital eczema.

Interdigital tinea pedis is not at all uncommon and is typically bilateral particularly between the fourth and fifth toes. Fissuring, maceration, scaling and erythema of the interdigital spaces are characteristics of the condition. It is common in immunocompromised patients, particularly patients with diabetes.3,4

What You Should Know About Etiology

The etiology of toe web space infections is variable. It is important to consider taking cultures in patients who do not respond to seemingly appropriate therapy. Karaca and colleagues studied 184 patients with intertrigo and noted multiple agents to be responsible in 22 percent of cases.5 The most common single agents causing the infection included coagulase-negative staphylococci, Pseudomonas, dermatophytes and beta-hemolytic streptococci.

Others have reported variable incidence of organisms responsible for interspace infections. In a study of 509 outpatients with diabetes, toe web fungus was present in 24 percent with unilateral disease presenting more commonly than bilateral disease.6 Candida species and dermatophyte infection were commonly present in the study. In a study of 123 cases of intertrigo, Aste and coworkers found the most common organisms to be Pseudomonas aeruginosa, Escherichia coli, Proteus mirabilis, Morganella morganii and Gram-positive cocci.7 Elewski and colleagues found a high incidence of dermatophytes as well as yeast, Staphylococcus aureus, Pseudomonas aeruginosa, Corynebacterium minutissimum and Micrococcus sedentarius species.8

A Closer Look At The Clinical Significance Of Infection

Tinea pedis, including interdigital tinea pedis, is a significant problem in a patient with diabetes, in whom preexisting peripheral arterial disease (PAD), autonomic neuropathy associated sudomotor changes, and immunosuppression from diabetes may result in secondary significant bacterial infection and cellulitis, along with limb-threatening infection.

Physicians can frequently mistake tinea pedis in a patient with diabetes for dry skin or skin xerosis. Greater than 60 percent of patients with tinea pedis demonstrate sudomotor changes, suggesting a relationship between loss of sweat function from diabetic autonomic neuropathy and the presence of tinea pedis.9 Researchers have reported an extremely high incidence of tinea pedis in patients with diabetes, occurring from both dermatophytes such as Trichophyton rubrum and also Candida species.10

In patients with diabetes, studies have demonstrated interdigital tinea pedis as well as tinea pedis and onychomycosis to be associated with an increased incidence of severe infection as well as osteomyelitis.11 Given the relationship between pedal fungus infections and cellulitis in patients with diabetes, authors have called for improved surveillance and more aggressive treatment of tinea pedis and onychomycosis in patients with diabetes.12

Note that there is a relationship between onychomycosis and tinea pedis. In a patient with diabetes, aggressive management of both onychomycosis and tinea pedis is critical for the reduction of cellulitis, ulceration or significant limb-threatening infection. One should treat both the onychomycosis and tinea pedis concurrently. Patients with diabetes appear to be prone to interdigital tinea pedis infections at an earlier age than those without diabetes with common infecting organisms including Candida species as well as dermatophytes such as Trichophyton rubrum.13 Authors have suggested the concurrent treatment of onychomycosis together with tinea pedis as the most effective means to manage this problem.14

Treatment Considerations For Toe Web Space Infections

Over the years, I have participated in the care of numerous patients with diabetes who required hospitalization for fever, ascending cellulitis, inguinal lymphadenopathy and sepsis secondary to an initial interdigital toe web space infection. Checking for toe web space infection should be part of the assessment of every patient with diabetes. When this is present, one should aggressively treat interdigital tinea pedis. When onychomycosis is similarly present, treat it aggressively.

Given the high incidence of Pseudomonas species and Candida species as well as Gram-positive and other Gram-negative organisms responsible for such infections, one should culture recalcitrant or recurring infections to determine the presence of organisms such as methicillin resistant staphylococci, Pseudomonas or Candida species.

For initial treatment, clinicians frequently utilize either gentian violet or Castellani paint. When maceration is present, the use of toe separators and interdigital drying is helpful. We will frequently recommend the use of an antifungal powder.

Oral antibiotic therapy will frequently include the use of erythromycin, tetracyclines or ciprofloxacin (Cipro, Bayer). Direct antifungal therapy at coverage for dermatophytes such as Trichophyton mentagrophytes and also at interdigital Candida infections. Topical azole antifungals include agents such as naftifine (Naftin, Merz Pharmaceuticals) or more recently luliconazole (Luzu, Valeant Pharmaceuticals). Oral agents for the treatment of the underlying fungus include either terbinafine (Lamisil, Novartis) or fluconazole (Diflucan, Pfizer).

Concurrent treatment of onychomycosis is also frequently required. This may include oral antifungal therapy, removal of the infected toenails by surgical excision or the use of topically applied agents such as urea and salicylic acid for chemical ablation of the nails.

In my own practice, I will frequently utilize a topical compounded prescription that may include 40 to 50% urea, 10% salicylic acid, tea tree oil and either topical terbinafine, itraconazole or ketoconazole. Typically, the infected nail plates will lyse over 30 days. At this time, one can easily remove the majority of infected nail plate without the need for anesthesia. The addition of ibuprofen to a topical antifungal is frequently helpful as it provides a synergistic effect and increases the efficacy of topical azole antifungal therapy. Studies have demonstrated that combinations such as 40% urea plus a topical azole antifungal or the use of ibuprofen plus a topical azole antifungal, with the additional use of a tea tree oil, are safe and efficacious.15

Severe infections in my opinion require systemic therapy. Systemic terbinafine, itraconazole or fluconazole may be required as indicated by the particular infecting organisms.16 The use of oral antifungal therapy for the treatment of Trichophyton infections has been safe and effective in patients with diabetes.17 Authors have demonstrated that the mean minimum inhibitory concentration for the use of terbinafine, itraconazole or fluconazole is no different when comparing patients with and without diabetes.18

In Summary

Toe web space infections in patients with diabetes may be associated with significant secondary morbidity including increased incidence of cellulitis, ulceration and limb-threatening infection. The presence of toe web space infection is not at all uncommon in a patient with diabetes. It is important to recognize that a variety of organisms may be responsible for these infections. This may include common dermatophytes, Candida species and both Gram-positive and Gram-negative organisms. On occasion, these infections may be caused by Corynebacteria.

The treatment of these infections requires aggressive topical therapy and at times oral therapy, providing both antifungal and antibacterial therapy. It is particularly important to identify the causative organisms when such web space infections are recurrent and associated with recurring episodes of cellulitis in a patient with diabetes.

It is also important to remember that many patients have concurrent onychomycosis, which may serve as the reservoir for the infecting organisms. Therefore, in the presence of onychomycosis, it is important to consider aggressive treatment not only of the web space infection but also the coexisting onychomycosis.

References
1. Koutika R, Mylonakis E, Boyce J. Cellulitis: evaluation of possible predisposing factors in hospitalized patients. Diagn Microbiol Infect Dis. 1999;34(4):325-7.
2. Boyko EJ, Ahroni JH, Cohen V, et al. Prediction of diabetic foot ulcer occurrence using commonly available clinical information: the Seattle Diabetic Foot Study. Diabetes Care 2006;29(6):1202-7.
3. Hainer BL. Dermatophyte infections. Am Fam Physician. 2003; 67(1):101-8.
4. Bristow I. Non-ulcerative skin pathologies of the diabetic foot. Diabetes Metab Res Rev. 2008;24(Suppl1):S84-89.
5. Karaca S, Kulac M, Cetinkaya Z, Demirel R. Etiology of foot intertrigo in the District of Afyonkarahisar, Turkey: a bacteriologic and mycologic study. J Am Podiatr Med Assoc. 2008;98(1):42-44.
6. Mlnaric-Missoni E, Vukelic M, de Soy D, et al. Fungal infection in diabetic foot ulcers. Diabet Med. 2005;22(8):1124-5.
7. Aste M, Atzori L, Zucca M, et al. Gram-negative bacterial toe web infection: A survey of 123 cases from the district of Cagliari, Italy. J Am Acad Dermatol. 2001;45(4):537-41.
8. Elewski BE. Update on superficial fungal infections. An update. Postgrad Med. 1999; Spec 5.
9. Eckhard M, Lengler A, Liersch J, et al. Fungal foot infections in patients with diabetes mellitus – results of two independent investigations. Mycoses. 2007;50(Suppl2):14-19.
10. Garcia-Humbrial, Richard-Yegres N, Perez-Blanco M, et al. [Superficial mycoses: comparative study between type 2 diabetic patients and a non-diabetic control group]. Investigacion Clinica. 2005;46(1):65-74.
11. Vanhooteghem O, Szepetiuk G, Paurobally D, Heureux F. Chronic interdigital dermatophytic infection: a common lesion associated with potentially severe consequences. Diabetes Res Clin Pract. 2011; 91(1):23-25.
12. Bristow IR, Spruce MC. Fungal foot infection, cellulitis and diabetes: a review. Diabetic Medicine. 2009;26(5):548-51.
13. Legge BS, Grady JF, Lacey AM. The incidence of tinea pedis in diabetic versus nondiabetic patients with interdigital macerations: a prospective study. J Am Podiatr Med Assoc. 2008;98(5):353-6.
14. Daniel CR 3rd, Jellinek NJ. The pedal fungus reservoir. Arch Dermatol. 2006;142(10):1344-6.
15. Pina-Vaz C, Sansonetty F, Rodrigues AG, et al. Antifungal activity of ibuprofen alone and in combination with fluconazole against Candida species. J Med Microbiol. 2000;49(9):831-40.
16. Erbagci Z. Topical therapy for dermatophytoses: should corticosteroids be included? Am J Clin Dermatol. 2004;5(6):375-84.
17. Rich P. Onchomycosis and tinea pedis in patients with diabetes. J Am Acad Dermatol. 2000;43(5Suppl):S130-134.
18. Ozcan D, Seçkin D, Demirbilek M. In vitro antifungal susceptibility of dermatophyte strains causing tinea pedis and onychomycosis in patients with non-insulin-dependent diabetes mellitus: a case-control study. J Eur Acad Dermatol Venereol. 2010;24(12):1442-6.



Bruce Fridinger DPMsays: July 28, 2014 at 9:09 pm

Key is that once infection has resolved and skin is at optimal hydration balance, that regular monitoring of all interspaces be continued.

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