Treatment of Chronic-Relapsing Pitted Keratolysis with Glycopyrronium Bromide Cream: Case Report

Pitted keratolysis (PK), formerly named “keratolysis plantare sulcatum,” “keratolysis sulcata,” and “keratoma sulcatum” was first described by Conti Díaz [1] in 1910. It is a superficial bacterial infection located almost exclusively on the soles, in particular on the pressure-bearing areas. PK is more common in Tropical and Sub-Tropical countries, often in individuals who wear occlusive shoes for long periods, such as soldiers and sailors [2]. The most important predisposing factor is hyperhidrosis [2‒5]. PK is characterized clinically by small, isolated or confluent, crateriform, noninflammatory pits on the stratum corneum. Maceration and malodor are the two most important signs and symptoms [2‒4, 6]. Pruritus is rare [3, 4]. A hyperkeratotic variety of PK was described by Conti Díaz et al. [1, 2] in 1987. PK is sometimes associated with trichomycosis axillaris and erythrasma. Several bacteria were isolated and considered as etiological agents of PK, such as Dermatophilus congolensis [7], Microcossus sedentarius [8], Kytococcus sedentarius [9], and Bacillus thuringiensis [10]. Coccoid and diphtheroid bacteria and Corynebacterium sp. [1] were also isolated.

The therapy of PK is very often unsatisfactory. This is due to the challenge of achieving effective penetration with topical treatments, and the high likelihood of reinfection in moist environments. Furthermore, the lack of targeted treatment against specific bacteria makes it difficult to achieve long-term control. We report 2 patients with chronic-relapsing PK who were successfully treated with a cream containing 1% glycopyrronium bromide.

A 37-year-old Caucasian man was admitted with a clinical diagnosis of PK. The patient stated that he was in good general health and that he was not in therapy with systemic drugs. He worked as cleaner, for which he wore for 8 h/day occlusive shoes. He also stated that the dermatitis had appeared approximately 3 years before and that it was unsuccessfully treated with over the counter aluminum chloride antiperspirants (unknown concentrations), zinc oxide, clindamycin, erythromycin, fusidic acid, and oral amoxicillin/clavulanic acid. He declared to be deeply embarrassed because of the rank smell of his feet. Dermatological examination revealed a severe PK, with numerous isolated or confluent, crateriform, noninflammatory, macerated pits located on the pressure-bearing areas of the soles (Fig. 1, 2). Neither trichomycosis axillaris nor erythrasma were observed. General physical examination did not reveal anything pathological. Laboratory tests were within normal ranges. Bacteriological cultures were positive for S. aureus and S. epidermidis (to our knowledge, S. epidermidis was never isolated in PK). Mycological examinations were negative, excluding tinea pedis. Despite the presence of these two bacteria, we decided not to treat the patient with antibiotics: they were unsuccessfully used several times in the last 3 years. From May 2023, the patient was treated with 1% glycopyrronium bromide cream in order to reduce hyperhidrosis and maceration. The cream was applied once daily for 6 weeks, subsequently every other day for 6 weeks and, finally, twice/week for 6 weeks. From June to December 2023, no relapses of PK occurred and the patient was satisfied with elimination of unpleasant odor. No side effects were reported or observed.

A 27-year-old Filipino woman was admitted with a diagnosis of PK. The patient was in good general health and was not in therapy with systemic drugs. She worked as housekeeper, for which she wore for 8 h/day work shoes. She also stated that the dermatitis appeared in summer 2022 and that it was unsuccessfully treated with potassium permanganate, over the counter aluminum chloride antiperspirants (unknown concentrations also in this patient), zinc oxide, amikacin, and oral cefixime. She declared to be embarrassed because of the malodor of her feet. Dermatological examination revealed a typical PK, with isolated or confluent, crateriform, noninflammatory, macerated pits located on the pressure-bearing areas of the soles. Also in this patient, neither trichomycosis axillaris nor erythrasma were observed. General physical examination was normal. Laboratory tests were within normal limits. Bacteriological cultures were positive for Gram-positive, pleomorphic, aerobic bacteria. Mycological examinations were negative. Also in this patient, we decided not to use antibiotics. From May 2023, the patient was treated with 1% glycopyrronium bromide cream in order to reduce hyperhidrosis and maceration. As in patient #1, the cream was applied once daily for 6 weeks, subsequently every other day for 6 weeks and, finally, twice/week for 6 weeks. From June 2023 to January 2024, no relapses of PK occurred. A large lesion on the forefoot, characterized by scaling and crusts, was the final clinical result (Fig. 3). No side effects were reported or observed.

PK has been treated with zinc oxide [4], chlorhexidine [4], benzoyl peroxide [3], clindamycin [11], clindamycin/benzoyl peroxide [6], erythromycin [2, 11, 12], fusidic acid [11, 13] and mupirocin [11, 14]. Oral cephalexin [14], clindamycin [6], and erythromycin [5] were also used. Italian authors stated that, in PK, “hyperhidrosis is due to an eccrine sweat gland hyperfunction, probably secondary to bacterial infection” [12]. We respectfully have a different perspective since PK is caused by a bacterial proliferation due to chronic hyperhidrosis. The studies by Tamura et al. [5] and Kontochristopoulos et al. [15], who successfully used botulinum toxin injections [5] and topical 2% glycopyrrolate [15], respectively, confirm this hypothesis. On the other hand, in a study on 387 patients, it was demonstrated that primary hyperhidrosis increases the risks of bacterial infections of the skin [16]. Furthermore, in a study on 7 female patients with chronic-relapsing candidiasis of submammary folds, the use of 1% glycopyrronium bromide cream was effective to reduce hyperhidrosis and maceration and, consequently, to reduce the risks to develop candidiasis [17]. The results of our observations, although based on only 2 patients, would confirm that the reduction of hyperhidrosis by means of 1% glycopyrronium bromide cream is able to significantly reduce relapses of PK. The use of well-fitted shoes, avoiding keeping the shoes on for long periods of time and wearing cotton socks with frequent changes are also useful for prevention of PK relapses [13].

A study approval statement was not required for this study in accordance with local/national guidelines. Written informed consent was obtained from the patients for publication of the details of their medical case and any accompanying images. The CARE Checklist has been completed by the authors for this case report, attached as online supplementary material (for all online suppl. material, see https://doi.org/10.1159/000542484).

All authors declare that they have no conflicts of interest relevant to this manuscript.

No funding was received for conducting this study.

S.V. and R.S. examined, treated, and followed both patients; S.V. wrote the text of the article; I.F.A. and G.N. reviewed the literature.

The data that support the findings of this study are not publicly available due to their containing information that could compromise the privacy of research participants but are available from S.V. (corresponding author) upon reasonable request.