Are You Confident of the Diagnosis?
Characteristic findings on physical examination
Most individuals will present with a complaint of malodorous feet. On inspection the soles will show small 1-3 mm pits within the epidermis (Figure 1). The condition is most often bilateral, with one foot almost always more severely affected. The weightbearing portion of the soles are most prominently involved (heel, toes, ball of foot). The vast majority of cases are asymptomatic. On occasion patients will complain of pain or a burning sensation with pressure bearing. Associated plantar and palmar hyperhidrosis is seen in approximately 2/3 of cases.
Expected results of diagnostic studies
Biopsies are not part of the workup and should not be routinely performed. In cases where biopsies have been performed, two histological variants have been described:
Minor type (superficial type): Bacteria is found on the surface of the skin.
Major type (classical type): Bacteria appear to be dimorphic in nature. Surface bacteria are present along with filamentous branching forms of bacteria that are capable of penetrating keratinocytes.
Electron microscopy has been described in one case. Crateriform pits were found along with filamentous bacteria.
No serological, laboratory, cultures or imaging tests are required for diagnosis. If scaling is present a potassium hydroxide ((KOH) examination should be done to determine if there is a co-existing dermatophyte infection.
Wood’s light examination may or may not show a coral red fluorescence. If the feet have been recently washed fluorescence is unlikely to be seen.
The differential diagnosis is narrow. It can include dermatophyte infections (annular scaling patches, nail involvement may be seen as can two feet one hand syndrome), keratolysis exfoliativa (superficial desquamation leaving collarettes of scale) and circumscribed palmoplantar hypokeratosis (a disorder of unknown etiology manifested by sharply demarcated depressions in the stratum corneum).
Who is at Risk for Developing this Disease?
Men outnumber women in some series by 7 to 1. Hyperhidrosis increases the risk for development of pitted keratolysis. A local environment that includes excessive moisture, humidity, and occlusive footwear increase one’s risk for development of pitted keratolysis. Occupations that require boots such as farmers, construction workers and military personal may be at higher risk.
The incidence is likely under-reported as the disease is easily diagnosed and treated.
What is the Cause of the Disease?
Corynebacterium species have been implicated as the causative agents in pitted keratolysis. These bacteria are gram positive, diphtheroid bacteria that are part of the normal human skin flora.
The specific bacterial species implicated include:
Kytococcus sedentarius (previously Micrococcus sedentarius)
Dermatophilus congolensis – aerobic gram positive
Other Corynebacterium are also felt to play a minor etiological role in the pathogenesis of pitted keratolysis; the role of Streptomyces species has yet to be fully defined.
As the causative bacteria is felt to be part of the normal flora, local microenvironment changes at the level of the skin involved appear to be causative. Hyperhidrosis is found in approximately 70% of cases. Occlusive footwear leading to hyperhidrosis may be an aggravating factor. It is not felt to be an infection that is contagious.
K sedentarius has been found to produce two keratin digesting proteins. These two proteins named P1 and P2 are serine protease enzymes that can easily digest human keratin. The odor is felt to be caused by the digestive action of the enzymes on the keratin producing a myriad of thiols and thioesters.
Systemic Implications and Complications
Pitted keratolysis can be seen in association with hyperhidrosis of the soles or palms. The pitted keratolysis is secondary to the hyperhidrosis.
Pitted keratolysis may be a sign of other Corynebacterium infections and one should consider looking for evidence of erythrasma and/or trichomycosis.
Treatment options are summarized in Table I.
|Medical – all topical therapy||Surgical||Physical|
|Erythromycin 2% topical lotion or gel||None||Dry affected regions thouroughly|
|Clindamycin||Change socks throughout the day|
|Benzoyl peroxide||Use of cedar shoe trees can decrease moisture in shoes|
|Micanazole or clotrimazole cream||Wear a different pair of shoes every other day|
|Mupirocin ointment||Cotton socks|
|Neomycin ointment||Wash feet daily and completely dry skin after bathing|
|Formalin ointment||Wash socks on high temperature to kill the bacteria|
|Agents to decrease sweating|
|Topical aluminum chloride|
|Botulinum toxin injection|
|Oral therapy – rarely if ever needed|
|Erythromycin or tetracycline|
Optimal Therapeutic Approach for this Disease
Patients need to be educated on proper foot care. Patients should wash their feet daily and completely dry the skin. This can be accomplished with a hair dryer on low heat. (Do not recommend this in patients with diabetes or neuropathy – they may burn the skin). They should try to use cotton socks, and change them at midday. Having two pairs of boots or shoes and alternating wearing them from one day to the next will decrease the accumulation of moisture in the boots/shoes (especially if a cedar shoe tree is used).
The physician should assess for hyperhidrosis. If hyperhidrosis is present, the patient will need to be treated with nightly aluminum chloride 20% application to the soles. This is used in combination with twice daily application of topical erythromycin gel or lotion for 4-6 weeks. This combination regimen is highly effective. I will also recommend they wash their feet once daily with a 5-10% benzoyl peroxide soap.
If a patient is allergic to erythromycin, one can substitute clindamycin 1% lotion or tetracycline. I have never had a patient who required botulinum toxin therapy, but this may be also considered for severe cases of hyperhidrosis unresponsive to conventional therapy. Oral therapy is almost never needed. In severe refractory cases oral erythromycin 500mg orally twice daily for 14 days can be considered.
Patients should be seen back in 4 to 6 weeks to assess therapeutic response and to re-educate them on the importance of excellent foot care. If the patients have cleared, therapy can be discontinued after 4 weeks. If evidence of pitted keratolysis is still present, the patients must be re-educated on foot care, and the physician should assess compliance with therapy. Hyperhidrosis should be treated, and consideration of changing to another topical agent should be considered. If any scaly patches are present, a KOH examination should be performed to determine if a co-existing dermatophyte infection is present.
Unusual Clinical Scenarios to Consider in Patient Management
Three to four percent of patients with pitted keratolysis may also have erythrasma and/or trichomycosis. (Corynebacterial triad) Less than 2% of cases are unilateral only.
A few cases of concurrent dermatophyte infection with pitted keratolysis have been described.
What is the Evidence?
Vlahovic, TC, Dunn, SP, Kemp, K. “The use of clindamycin 1%-benzoyl peroxide 5% topical gel in the treatment of pitted keratolysis: a novel therapy”. Adv Skin Wound Care. vol. 22. 2009. pp. 564-6. (Four males with pitted keratolysis were treated with a combination of clindamycin and benzoyl peroxide gel once a day. They also used aluminum chloride three times a week to decrease associated hyperhidrosis. After 2 months the pitted keratolysis was cleared in all four.)
Walling, HW. “Primary hyperhidrosis increases the risk of cutaneous infection: a case control study of 387 patients”. J Am Acad Dermatol. vol. 61. 2009. pp. 242-6. (Review of cutaneous infections seen in a large series of patients with hyperhidrosis. Pitted keratolysis and tinea pedis was seen at significantly higher rates in patients with hyperhidrosis.)
Blaise, G, Nikkels, AF, Hermanns-Le, T. “Corynebacterium-associated skin infections”. Int J Dermatol. vol. 47. 2008. pp. 884-90. (Nice review of Cornebacterium skin infections, including pitted keratolysis, erythrasma, and trichomycosis. Reviews risk factors, etiology, pathophysiology, and therapeutic options.)
Tamura, BM, Cuce, LC, Souza, RL. “Plantar hyperhidrosis and pitted keratolysis treated with botulinum toxin injection”. Dermatol Surg. vol. 30. 2004. pp. 1510-14. (Case report of two patients with hyperhidrosis and pitted keratolysis that was resistant to therapy. 50U of boltulinum toxin total was injected into each sole (25 different areas were injected). One patient's pitted keratolysis resolved in 2 weeks, the other in 4 weeks. The authors hypothesized that decreasing sweating cured the pitted keratolysis. The longest follow-up was 10 months in one of the patients.)
Longshaw, CM, Wright, JD, Farrell, AM. “Kytococcus sedentarius, the organism associated with pitted keratolysis, produces two keratin-degrading enzymes”. J Applied Microbiology. vol. 93. 2002. pp. 810-16. (In vitro studies purifying the P1 and P2 proteins. Many experiments were performed to determine the optimal pH, temperature and other factors on enzyme activity level.)
de Almeida, HL, de castro, LAS, Rocha, NEM. “Ultrastructure of pitted keratolysis”. Int J Dermatol. vol. 39. 2000. pp. 698-701. (Transmission and scanning electron microscopy were used to evaluate a biopsy specimen of pitted keratolysis. Tunnel-like spaces and pits were seen with associated bacteria.)
Schissel, DJ, Aydelotte, J, Keller, R. “Road rash with a rotton odor”. Military Medicine. vol. 164. 1999. pp. 65-7. (Single case report of a soldier with pitted keratolysis and tinea pedis. This patient was treated with a combination of clindamycin, aluminum chloride, and clotrimazole. He cleared totally in 8 weeks.)
Takama, H, Tamada, Y, Yano. “Pitted keratolysis: clinical manifestations in 53 cases”. Br J Dermatol. vol. 137. 1997. pp. 282-5. (Review of 53 patients with pitted keratolysis. Hyperhidrosis seenin 96% of cases, severe odor in 89%, and pain in 11%. Almost all lesions were seen on the pressure-bearing skin of the sole. 47 men, 6 women.)
Vazquez-Lopez, F, Perez-Oliva, N. “Mupirocin ointment for symptomatic pitted keratolysis”. Infection. vol. 24. 1996. pp. 55(Case series of four patients treated with mupirocin ointment. Each had a prompt response.)
Gurcharan, S, Chandra, N. “Pitted keratolysis”. Indian J Dermatol Venerol Leprol. vol. 71. 2005. pp. 213-5. (Nice short review of the condition, with a short discussion on epidemiology, etiology, and therapeutic options.)
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