Version May 2024
INTRODUCTION — Pitted keratolysis (also known as keratolysis sulcata, keratolysis plantare sulcatum, and ringed keratolysis) is a superficial bacterial skin infection confined to the stratum corneum. Clinically, pitted keratolysis is characterized by malodor and multifocal, discrete, superficial crateriform pits and superficial erosions primarily affecting pressure-bearing areas of the plantar surface of the feet (picture 1A-D). Topical antibiotic therapy usually leads to resolution of the disease.
The clinical features, diagnosis, and management of pitted keratolysis will be reviewed here.
EPIDEMIOLOGY — Pitted keratolysis has a worldwide distribution but occurs most frequently in tropical and temperate regions with high humidity levels [1]. The disorder is not uncommon; in a mass examination of 4325 Korean industrial workers in 1981, 1.5 percent had pitted keratolysis [2]. In another study, 18 (2.6 percent) of 682 students (aged 14 to 25 years) from two Turkish boarding schools had pitted keratolysis [3]. There is no racial predilection [4-6].
Pitted keratolysis is most common in the age group of 21 to 30 years, with approximately 80 to 96 percent of affected patients between 10 and 40 years of age [7,8]. The male-to-female ratio is approximately 4:1 [8,9]. Presumably, the male predominance is due to more frequent use of occlusive footwear among males and females' better foot hygiene [8,10-12].
Occupations at risk include athletes, industrial workers, miners, farmers, marine workers, and military personnel [13-16]. Predisposing factors include hyperhidrosis, prolonged use of occlusive footwear such as vinyl shoes or rubber boots, thickened skin of soles and palms, increased skin surface pH, hot and humid weather, poor foot hygiene, obesity, diabetes mellitus, and immunodeficiency [11,17,18].
MICROBIOLOGY — Pitted keratolysis is most commonly caused by Corynebacterium species, Kytococcus sedentarius (formerly known as Micrococcus sedentarius), Dermatophilus congolensis, Streptomyces, and Actinomyces keratolytica [19-22]. Less commonly, the condition can be caused by Klebsiella, Pseudomonas, Acinetobacter, and Clostridium species [13].
PATHOGENESIS — Under optimal conditions of a moist and warm environment, the causative bacteria proliferate and produce extracellular proteases that enable them to digest keratin and dissolve the stratum corneum, resulting in the characteristic tunnel-like pits or craters [12,19,21,23]. The foul odor is due to sulfur compounds (eg, thiols, sulfides, and thioesters) produced by the bacteria [6,22,23].
CLINICAL MANIFESTATIONS — Pitted keratolysis usually presents with clusters of multiple, conspicuous, discrete, superficial, circular, "punched-out" pits (picture 1A-C) [17,24,25]. Some pits have a brownish color and may give the foot a dirty appearance [26].
The pits range from 0.5 to 7 mm in diameter and are 1 to 2 mm deep [17,19,27]. The pits may coalesce into bigger, irregular erosions, sulci, and crater-like lesions (picture 1D-E) [22,28]. The findings become more prominent when the foot is wet or soaked in water [14,26,29].
Sites of predilection include the pressure-bearing areas of the foot, such as the plantar aspect of the toe, the ball of the foot, and the heel [17,24,25]. The condition is usually bilateral but may be asymmetrical with one foot more affected than the other [8].
Additional characteristic features include a "rotten" odor and slimy texture of the skin on the feet [6,11]. Hyperhidrosis and maceration are frequently present [17,26,30]. Erythematous to violaceous macules may also be seen [4,5].
Pitted keratolysis is typically asymptomatic; however, pruritus, irritation, burning sensations, and pain during ambulation occasionally occur [9-11].
Clinical variants — In addition to the classic clinical presentation, there are several less common clinical variants:
●Involvement of nonweightbearing areas – Rarely, pitted keratolysis occurs on nonweightbearing acral skin (eg, instep and arch of the foot, dorsal aspect of the toe, or palms) with or without concomitant involvement of the typical sites on the feet [1,4,8,25]. Involvement of the palm is more common in certain professions (eg, paddy field workers) [13]. On the palms, pitted keratolysis tends to manifest as scaly collarettes or ringed keratolysis rather than pits [10,22,29,31].
●Painful plaque-like variant – A painful plaque-like variant characterized by tender erythematous to violaceous plaques with typical superficial pits and shallow erosions has been described in children and adults (picture 2) [32,33].
●Large crateriform depressions – Rarely, pitted keratolysis presents as large crateriform depressions [34]. Walking barefoot on wet earth may predispose to this variant.
●Corynebacterial triad – A corynebacterial triad of pitted keratolysis, erythrasma, and trichomycosis axillaris has been described [8,9,14,35].
HISTOPATHOLOGY — Histologic examination shows pits or erosions confined to the stratum corneum [24]. The pits and erosions have sharply inclined walls and a flat base consisting of a thin layer or localized absence of stratum corneum. Microorganisms with coccoid and filamentous forms can be detected in a scraping or thin-shaved specimen of the stratum corneum using a Gram stain, hematoxylin and eosin (H&E) stain, methenamine silver stain, or periodic acid-Schiff (PAS) stain [4,36].
Electron microscopy demonstrates tunnel openings of the crateriform pits where the causative bacteria reside [37]. Bacteria may be seen intercellularly on the surface of the stratum corneum and intracorneocytically in the horny layer [5,15,24,28].
DIAGNOSIS — The physical examination is usually sufficient for diagnosis, based upon the recognition of the distinctive clinical appearance of pitted keratolysis and the associated pungent odor. Physical findings that strongly support a diagnosis of pitted keratolysis include clusters of multiple conspicuous, discrete, white to yellow, superficial, 0.5 to 7 mm crateriform pits and superficial erosions on pressure-bearing areas of the soles (eg, ball and heel of the foot) (picture 1A-D) [17]. Less frequently, physical examination reveals bigger, irregular erosions, sulci, crater-like lesions, and plaques. Sliminess of the skin, hyperhidrosis, and maceration are common additional findings.
Dermoscopic examination can facilitate visualization of pits and pit walls [38]. Examination with a Wood's lamp may reveal coral red fluorescence as may be seen in erythrasma, but this finding is not consistently present [5,10].
Laboratory studies usually are not necessary. A potassium hydroxide preparation to detect fungus can be performed if there is scale or other findings suggestive of concomitant tinea pedis. A culture is rarely indicated but may show gram-positive bacilli or coccobacilli [19]. Culture requires special media such as brain heart infusion agar for aerobic culture and Robertson's meat medium for anaerobic culture [13,26].
A skin biopsy is seldom necessary for diagnosis. If performed, the biopsy will reveal the characteristic histopathologic features of pitted keratolysis. A superficial shave biopsy of the stratum corneum is sufficient [36]. (See 'Histopathology' above.)
ADDITIONAL EVALUATION — Examination of the intertriginous areas (axilla, groin) is prudent in patients with pitted keratolysis, as it may identify coexisting corynebacterial infections such as erythrasma and trichomycosis axillaris [26]. (See "Erythrasma".)
DIFFERENTIAL DIAGNOSIS — The differential diagnosis includes a variety of disorders that may present with punctate or hyperkeratotic lesions on the feet (table 1). Examples include [6,19,26]:
●Aquagenic palmoplantar keratoderma (picture 3)
●Arsenical keratosis (see "Arsenic exposure and chronic poisoning", section on 'Dermatologic')
●Darier disease (picture 4) (see "Darier disease", section on 'Skin lesions')
●Dyshidrotic eczema (picture 5) (see "Acute palmoplantar eczema (dyshidrotic eczema)", section on 'Clinical presentation')
●Exfoliative keratolysis (see "Peeling skin syndromes", section on 'Keratolysis exfoliativa')
●Focal acral hyperkeratosis
●Juvenile plantar dermatosis (picture 6) (see "Overview of dermatitis (eczematous dermatoses)", section on 'Juvenile plantar dermatosis')
●Nevoid basal cell carcinoma syndrome (picture 7) (see "Nevoid basal cell carcinoma syndrome (Gorlin syndrome)", section on 'Palmar-plantar pits')
●Plantar warts (picture 8) (see "Cutaneous warts (common, plantar, and flat warts)", section on 'Clinical features')
●Porokeratosis (see "Porokeratosis", section on 'Porokeratosis plantaris palmaris et disseminata' and "Porokeratosis", section on 'Punctate porokeratosis')
●Punctate palmoplantar keratoderma (picture 9) (see "Palmoplantar keratoderma", section on 'Punctate palmoplantar keratoderma')
●Tinea pedis (picture 10) (see "Dermatophyte (tinea) infections", section on 'Tinea pedis')
●Tungiasis (see "Skin lesions in the returning traveler", section on 'Tungiasis')
Often, the history and physical findings are sufficient to differentiate pitted keratolysis from these disorders. Key features of each disorder are reviewed in a table (table 1).
MANAGEMENT — Data on the management of pitted keratolysis are limited, contributing to uncertainty about the ideal approach to treatment [30]. Most patients can be effectively managed with topical antimicrobial therapy and adjunctive measures to improve foot hygiene. Oral antibiotic therapy is reserved for resistant disease.
First-line therapy — Topical antibiotics are the first-line treatments for pitted keratolysis. The topical antimicrobial benzoyl peroxide is an alternative first-line treatment.
Topical antibiotics — Topical antibiotics with activity against Corynebacterium and the other organisms responsible for pitted keratolysis (clindamycin, erythromycin, mupirocin, and fusidic acid) are our preferred first-line therapies based upon limited data from case reports and uncontrolled studies that suggest efficacy and the relative safety of these agents [10-12,19,28,39]. As an example, in an uncontrolled study of 97 patients treated with twice-daily application of erythromycin 3% gel, all patients had a complete remission of skin lesions within 10 days [12]. Fusidic acid is not available in the United States.
Topical clindamycin, erythromycin, mupirocin, or fusidic acid is applied twice daily until clinical resolution. Topical minocycline presumably would be effective as well. A complete response is expected within one to eight weeks, with patients usually responding within two to four weeks [6,11]. Skin irritation is an infrequent adverse effect of topical antibiotic use. Examples of rare side effects include contact dermatitis and Clostridioides difficile colitis.
Other antimicrobial agents — Benzoyl peroxide, an antimicrobial agent with keratolytic properties, is sometimes used as therapy for pitted keratolysis [14]. Benzoyl peroxide has been used alone or in combination with topical antibiotics, such as clindamycin [6,23].
Use of combination products containing clindamycin and benzoyl peroxide has been suggested based upon the idea that both compounds have antibacterial properties, and the keratolytic properties of benzoyl peroxide facilitate penetration of clindamycin into the skin [6]. In an uncontrolled study of four patients with pitted keratolysis, once-daily application of clindamycin 1%-benzoyl peroxide 5% gel for one to two months (with topical aluminium chloride hexahydrate solution added to the regimen after the first month) led to resolution of disease in all patients [6]. However, a study that compared outcomes of treatment with benzoyl peroxide alone, clindamycin alone, and combined application of benzoyl peroxide and clindamycin in 44 patients with pitted keratolysis did not find statistically significant differences in efficacy among the three regimens [40].
Benzoyl peroxide is applied once or twice daily until clinical resolution. As with topical antibiotics, significant improvement is expected within a few weeks. Skin irritation is a potential side effect.
A trial in 125 adults with pitted keratolysis randomly assigned subjects to either twice-daily application of erythromycin 4% gel or twice-daily cleansing with chlorhexidine 4% scrub for four weeks [41]. At the end of treatment, complete resolution occurred at similar rates in patients in the erythromycin and chlorhexidine groups (81 and 74 percent, respectively). Chlorhexidine was left on the skin for two minutes prior to rinsing.
Adjunctive measures — Although the efficacy of such interventions has not been studied, improvement of foot hygiene and treatment of concomitant hyperhidrosis are suggested as methods to promote resolution of pitted keratolysis and minimize risk for reinfection [5,12,27].
Foot hygiene — We encourage patients to engage in the following measures:
●Wear cotton or absorbent synthetic socks and change socks frequently
●Wash socks after wearing with soap and water at temperatures >60°C
●Wash feet with soap and water at least once daily
●Clean and thoroughly dry feet after exercise or bathing
●Avoid prolonged wearing of occlusive shoes; preferentially wear nonocclusive shoes or ventilating occupational shoes
●Wear properly fitted footwear to reduce friction on the feet
When necessary (eg, patients with frequent recurrences or recalcitrant disease), special ultraviolet C devices can be used to kill the bacteria in footwear.
Treatment of hyperhidrosis — Given that sweating and moisture may contribute to pitted keratolysis, patients with associated hyperhidrosis may benefit from treatment of this condition. Topical aluminum chloride hexahydrate solution (typically 20%, but lower concentrations are helpful as well) applied at night to completely dry soles or palms and washed off in the morning is typically used as first-line treatment for hyperhidrosis [30]. For severe and persistent hyperhidrosis that may render pitted keratolysis resistant to treatment, other interventions for hyperhidrosis, such as injections of botulinum toxin, oral anticholinergics, and iontophoresis, are options [1,19,42,43]. Topical glycopyrrolate, an anticholinergic agent used in the treatment of hyperhidrosis, may also be useful. In a case series, all three patients treated with glycopyrrolate 2% cream for pitted keratolysis had marked improvement [44]. (See "Primary focal hyperhidrosis", section on 'Palmar or plantar hyperhidrosis'.)
Refractory disease — Oral antibiotic therapy is typically reserved for pitted keratolysis that fails to respond to topical therapy. We typically use clindamycin or erythromycin according to the following regimens:
•Adults – 150 to 300 mg four times per day
•Children – 10 to 25 mg/kg per day in three to four divided doses (maximum 300 mg per dose)
•Base or stearate, adults – 250 to 500 mg four times per day
•Base or stearate, children – 30 to 50 mg/kg per day in four divided doses (maximum 2 g per day)
•Ethylsuccinate, adults – 400 to 800 mg four times per day
•Ethylsuccinate, children – 30 to 50 mg/kg per day in four divided doses (maximum 3 g per day)
The oral antibiotic should be prescribed for at least 10 days; the duration of treatment depends on disease severity and response to treatment [9,14,29]. (See 'Follow-up' below.)
Clindamycin is generally well tolerated. Possible adverse reactions include nausea, vomiting, abdominal pain, diarrhea, metallic taste, and rash. Less common adverse reactions include C. difficile colitis, polyarthritis, anaphylaxis, blood dyscrasias, hepatotoxicity, and renal dysfunction.
Possible adverse reactions to erythromycin include nausea, vomiting, abdominal pain, flatulence, diarrhea, headache, pruritus, and rash. Less common but more serious side effects may include allergic reactions, anaphylaxis, C. difficile colitis, liver dysfunction, tinnitus, reversible deafness, prolonged QT intervals including torsades de pointes, and interstitial nephritis. Exposure to erythromycin through breastfeeding may increase the risk of pyloric stenosis in the infant. (See "Infantile hypertrophic pyloric stenosis", section on 'Macrolide antibiotics'.)
Patients with contraindications to clindamycin and erythromycin or who fail to improve on these agents may be treated with oral tetracyclines. Adults may be treated with doxycycline (100 mg once or twice daily), minocycline (100 mg once or twice daily), or tetracycline (250 to 500 mg four times daily). Tetracyclines should not be given to children under nine years of age because of the risk for permanent tooth discoloration and reduced bone growth.
Adverse effects of oral tetracyclines include nausea, vomiting, diarrhea, candidal superinfection, and photosensitivity. Minocycline is the least photosensitizing of these agents, but it may cause vertigo and a lupus-like syndrome. If not swallowed with sufficient water, tetracyclines can cause esophagitis and esophageal erosions.
PREVENTION — Measures to improve foot hygiene may aid in the prevention of pitted keratolysis [12,27,30]. (See 'Adjunctive measures' above.)
PROGNOSIS — Untreated, pitted keratolysis may last for years with spontaneous remissions and exacerbations [8]. With proper treatment, the condition usually resolves in two to four weeks [6,19].
FOLLOW-UP — Periodic follow-up during treatment is helpful to assess therapeutic response and determine the ideal duration of treatment.
SUMMARY AND RECOMMENDATIONS
●Microbiology – Pitted keratolysis is a superficial bacterial skin infection confined to the stratum corneum that most often occurs on the soles of the feet. Corynebacterium species, Kytococcus sedentarius (formerly known as Micrococcus sedentarius), Dermatophilus congolensis, Streptomyces, and Actinomyces keratolytica are the most common causative organisms. (See 'Microbiology' above.)
●Epidemiology and risk factors – Pitted keratolysis primarily occurs in young adults and affects males more frequently than females. Risk factors include hyperhidrosis, prolonged use of occlusive footwear, thickened skin of soles and palms, increased skin surface pH, hot and humid weather, poor foot hygiene, obesity, diabetes mellitus, and immunodeficiency. (See 'Epidemiology' above.)
●Clinical manifestations – The most common clinical findings of pitted keratolysis are clusters of discrete, superficial, round, punched-out pits and erosions on weight-bearing areas of the soles of the feet (picture 1A-D). Patients often have an associated pungent odor from the feet and a slimy texture on the skin of the feet. (See 'Clinical manifestations' above.)
●Diagnosis – Pitted keratolysis usually can be diagnosed based solely on the physical examination. Culture and skin biopsy usually are not necessary. (See 'Diagnosis' above.)
●Management:
•Antimicrobial therapy – We suggest topical antibiotic therapy rather than oral antibiotic therapy for first-line treatment of pitted keratolysis (Grade 2C). Examples of effective topical antibiotics include clindamycin, erythromycin, mupirocin, and fusidic acid. Benzoyl peroxide may also be an effective topical antimicrobial therapy. Patients who cannot be successfully treated with topical agents may respond to oral antibiotic therapy. (See 'Management' above.)
•Adjunctive measures – Interventions to improve foot hygiene may aid in promoting resolution of pitted keratolysis and minimizing risk for reinfection. Because hyperhidrosis is a risk factor for pitted keratolysis, treatment of hyperhidrosis is also likely to be beneficial. (See 'Adjunctive measures' above.)
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