Pitted Keratolysis

Pitted keratolysis is a skin disorder characterized by crateriform pitting that primarily affects the pressure-bearing aspects of the plantar surface of the feet and, occasionally, the palms of the hand as collarettes of scale. The manifestations of pitted keratolysis are due to a superficial cutaneous bacterial infection.[1, 2]

Pitted keratolysis has gone through several name changes.[3, 4] Pitted keratolysis was described initially in the early 1900s as keratoma plantare sulcatum, a manifestation of yaws. Pitted keratolysis was identified in the 1930s as a unique separate clinical entity, and the name was changed to keratolysis plantare sulcatum. The current name, pitted keratolysis, describes the clinical presentation well and has remained the modern nomenclature to describe this entity.

Pitted keratolysis is caused by a cutaneous infection with Micrococcus sedentarius (now renamed to Kytococcus sedentarius); Dermatophilus congolensis; or species of Corynebacterium,Actinomyces, or Streptomyces.[5, 6, 7, 8] Under appropriate conditions (ie, prolonged occlusion, hyperhidrosis, increased skin surface pH), these bacteria proliferate and produce proteinases that destroy the stratum corneum, creating pits.[9] D congolensis liberates keratinases in appropriate substrate.[10, 11, 12] K sedentarius has been found to produce 2 keratin-degrading enzymes. They are protease P1 (30 kd) and P2 (50 kd).[8] The malodor associated with pitted keratolysis is presumed to be the production of sulfur-compound by-products, such as thiols, sulfides, and thioesters.[13]

In 2006, foot odor without pitted skin changes was discovered to be from overgrowth of Bacillus subtilis and specifically an isovaleric acid produced by Staphylococcus epidermidis overgrowth, a normal skin flora.[14]

It is a common problem among athletes, as heat, sweat, and humidity cause changes in the skin microbiome.[15, 16, 17]

Frequency

United States

Pitted keratolysis occurs worldwide. Pitted keratolysis can be seen in both tropical and temperate environments, and it can be related to occupation or sport activity.[18, 19] A study of 142 homeless men in the Boston, Mass area revealed that 20.4% of 142 examined patients had pitted keratolysis.[20]

International

International incidence rates of pitted keratolysis vary significantly based on the environment and occupation. Prevalence rates of pitted keratolysis have ranged from 1.5% of 4325 Korean industrial workers[21] to 2.25% (11 of 490 subjects randomly evaluated) in New Zealand.[6] In addition, 2.6% of 378 Turkish male adolescent and postadolescent boarding school students had pitted keratolysis,[22] and, in a 2-year study from Belgium, only 4.8 cases of pitted keratolysis occurred per 1000 dermatology visits.[23] In a study of 1012 patients with atopic dermatitis from Nigeria, only 19 (1.8%) had pitted keratolysis.[24] However, 66 (23.3%) of 283 Korean coal miners[21] and 341 (42.5%) paddy field workers in costal South India had pitted keratolysis due to persistent exposure to moist environments.[25]

In the tropical military setting, where heat, humidity, and boots combine to produce a microenvironment that predisposes to pitted keratolysis, prevalence rates are much higher. Of the 387 volunteer United States soldiers evaluated in South Vietnam, 53% had pitted keratolysis.[26] However, the incidence of pitted keratolysis in all military soldiers may not be so high because only 108 (12.8%) of 842 Korean soldiers were diagnosed with pitted keratolysis.[27] In 184 German athletes examined, 25 (13.5%) had pitted keratolysis.[15]

Race

No race predilection is reported for pitted keratolysis.

Sex

Theoretically, both males and females should be affected by pitted keratolysis; however, most written case reports or studies have involved male patients.

Age

Pitted keratolysis can affect patients of any age.

Pitted keratolysis is cured easily and has an excellent prognosis. No mortality is associated with pitted keratolysis. However, the excessive foot odor from this disorder may be socially unacceptable. Pitted keratolysis may be symptomatic; producing secondary painful feet, which can limit function.[28, 29] In 2005 in Turkey (East region), a study of dermatologic manifestations in 88 hepatitis B surface antigen carriers compared with 84 controls demonstrated a significantly higher prevalence of oral lichen planus and pitted keratolysis.[30] The mechanism is unknown and further studies are needed to confirm this association.

Educate patients with pitted keratolysis about the etiology of the disorder and regarding ways to prevent and treat pitted keratolysis. See Medical Care.

Patient with pitted keratolysis may report malodor, hyperhidrosis, sliminess, and, occasionally, soreness or itching associated with the pits[31] ; however, the pits normally are asymptomatic. Patients with primary hyperhidrosis have been shown to have a significant increase in pitted keratolysis compared with controls.[32]

The etiology of the tenderness in symptomatic cases of pitted keratolysis is unknown. In addition to pits, erythematous-to-violaceous macules to plaquelike lesions may be present.[29] In military personnel, whose long-term occlusive boot wearing exacerbates disease, lesions often become denuded, leading to foot pain and disability.[33] The palms of the hand also have been reported to be involved in some patients with pitted keratolysis of the feet.[34] Of the paddy field workers, 1.5% were diagnosed with palmar lesions in addition to foot lesions.[25] With hand involvement, a collarette forms around the keratolysis, rather than pits.

A triad of concurrent corynebacterial diseases (ie, erythrasma, trichomycosis axillaris, and pitted keratolysis) has been reported.[35] In a 2008 study, 108 of 842 South Korean male soldiers were diagnosed with pitted keratolysis, of which 13 (13%) of 108 had the triad.[27] Clinicians making a diagnosis of pitted keratolysis need to examine the patient for evidence of other corynebacterial infections.

The primary lesions of pitted keratolysis are pits in the stratum corneum ranging from 0.5-7 mm, with some development of confluence, irregular erosions, or sulci (see the images below).

A large plaque-like lesion of Pitted keratolysis on the large toe.

Pitted keratolysis with hyperkeratosis on the heel.

Classic pits of pitted keratolysis on the plantar aspect of the phalanges.

Pitted keratolysis forming sulci on the heel.

A variant of markedly enlarged lesions, called crateriform pitted keratolysis, also has been described.[36] This affects the entire width of the plantar surface of the foot underlying the metatarsophalangeal joints. The pits are rarely seen on non–pressure-bearing areas of the plantar surface, but this has been reported in the literature.[37]

Skin biopsies are not performed routinely because the diagnosis of pitted keratolysis can be made easily by means of visual examination and recognition of the characteristic odor. Wood lamp examination is of limited use because results are inconsistent.[38, 39]

If a cutaneous biopsy is performed, histological evaluation of hematoxylin and eosin (H&E)–stained plantar skin reveals a crater limited to the stratum corneum (see the image below).

Histopathology reveals a crater limited to the thick stratum corneum of the epidermis.

The microorganisms, cocci, and filamentous forms may be seen with H&E staining, but they are detected more easily with Gram stain, periodic acid-Schiff stain, or methenamine silver stain. In 2000, Wohlarb et al reported 2 histologic types.[15] The superficial minor type is coccoid bacteria found extracellularly on the surface of the stratum cornea. The classic or major type is coccoid and septated bacterium forms intracorneocytically in the horny layer. In patients with associated foot pain and with erythematous-to-violaceous macular lesions and pits, histological examination reveals only a mild dermal inflammatory reaction. In 2000, de Almeida et el studied pitted keratolysis with electron microscopy and noted transverse septated bacterium in tunnellike openings on the floor of the pits.[40]

Although no studies are published on hygiene, several protective measures for preventing pitted keratolysis have been recommended over time. Limit the use of occlusive footwear and reduce foot friction by wearing properly fitted footwear. Absorbent cotton socks must be changed frequently to prevent excessive foot moisture. Wool socks tend to whisk moisture away from the skin and may be helpful. In 2008, Blaise et al recommended that affected patients should wash their socks at a temperature of 60ºC to kill the Corynebacterium that may be transferred to the socks from skin scaling. In some cases, reducing any associated hyperhidrosis with the application of a roll-on antiperspirant, 20% aluminum chloride solution, may be helpful.[41]

The treatment of pitted keratolysis also lacks evidence-based studies; however, historically, dermatologists find that topical antibiotics are effective, even if the recommendations presented above are not followed. Topical antibiotics are certainly easy to use and are well accepted by patients. Twice-daily applications of erythromycin, clindamycin, or fusidic acid are effective.[29, 34, 42, 43] The combination topical gel of clindamycin 1%–benzoyl peroxide 5% has been found effective in 4 patients, but efficacy required the concurrent use of aluminum chloride hexahydrate solution.[38] Either solutions or gel formulations may be used. Topical mupirocin (Bactroban) also has been effective.[44, 45] A study of physicians treating Dutch army personnel concluded that preventive measures, topical antibiotic therapy, and adequate treatment of hyperhidrosis are the mainstay methods in the management of patients with pitted keratolysis.[46, 47]  Other data suggest benzoyl peroxide alone can be effective.[48]

For cases resistant to topical antibiotic treatments and/or associated with hyperhidrosis, the use of botulinum toxin injections has been effective.[49] The use of oral erythromycin was reported by Zaias in 1982 based on personal observation. Effective treatment of pitted keratolysis clears both the lesions and odor in 3-4 weeks.

Instruct patients with pitted keratolysis to return to the clinic if therapy is unsuccessful. Otherwise, care for pitted keratolysis proceeds on an as-needed basis.

The goals of pharmacotherapy for pitted keratolysis are to reduce morbidity and prevent complications.

Class Summary

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.

Clindamycin topical (Cleocin)

Clindamycin is a lincosamide for the treatment of serious skin and soft tissue staphylococcal infections. It is also effective against aerobic and anaerobic streptococci (except enterococci). It inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. Many clinicians find topical antibiotics to be effective, even without other measures. They are easy to use and well accepted by patients. Either solution or gel formulations may be used.

Erythromycin (E.E.S., E-Mycin, Ery-Tab)

Erythromycin inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. Erythromycin is used for the treatment of staphylococcal and streptococcal infections.

In children, age, weight, and severity of infection determine proper dosage. When twice-daily dosing is desired, half the total daily dose may be taken every 12 hours. For more severe infections, double the dose.

Mupirocin (Bactroban)

Mupirocin inhibits bacterial growth by inhibiting RNA and protein synthesis.