Unilateral aquagenic keratoderma treated with botulinum toxin A

Abstract

Background

Aquagenic keratoderma is a rare transient disease that occurs after water immersion and disappears shortly after drying. Most cases involve the palms and fingers bilaterally but it can also affect the soles. Few cases have been associated with drugs but its pathogenesis remains unclear.

Main observation

We report a 60-year-old man with a 30-year-history of aquagenic keratoderma of the right palm without associated hyperhidrosis or history of drug intake. After unsuccessful treatment with 15% aluminium chloride hexahydrate gel, botulinum toxin A injections led to significant improvement within 2 weeks.

Conclusions

To our knowledge, this case is the first report of idiopathic unilateral aquagenic keratoderma in the medical literature. It is the third report of successful treatment with botulinum toxin A which is in favor of a role of sweat glands in the pathogenesis of aquagenic keratoderma.

Introduction

Aquagenic keratoderma (AK) is a rare condition characterized by acquired, recurrent and transient keratoderma after 2 to 10 minutes of water immersion, which disappears minutes to an hour after drying. It was first documented by English and McCollough[1] in 1996 and was termed "transient reactive papulotranslucent acrokeratoderma" at that time. Afterwards this relatively new entity was coined by "aquagenic palmoplantar keratoderma", "aquagenic syringeal keratoderma", "aquagenic keratoderma", "aquagenic wrinkling of the palms", and "aquagenic acrokeratoderma". AK is predominant in young females and usually occurs sporadically.[2] So far, 55 cases have been reported in the medical literature. We present a patient with unusual unilateral palmar AK who responded to treatment with botulinum toxin A.

Case Report

A 60-year-old man presented with a 30-year-history of episodes of wrinkling and desquamation of his right palm following hand immersion in water, especially when warm or hot. Physical examination showed hyperkeratosis of the right palm prior to water immersion, and whitish wrinkled thickening of the palm following the immersion [Fig. 1]. There was no associated hyperhidrosis, dysesthesia or history of drug intake. The history and clinical observation led to the diagnosis of AK.

Figure 1.

Confluent whitish papules on the right palm after 5 minutes of immersion of the hands in tap water.

Treatment with 15% aluminium chloride hexahydrate gel for 3 months was unsuccessful. Thus injections of 50 units of botulinum toxin A reconstituted in 5 mL of isotonic sodium chloride solution (concentration: 1 unit of botulinum toxin per 0.1 mL) were performed in the right palm, preceded by lidocaine injections (2% lidocaine) through a pressurized device (Med-Jet MBX).[3] Each lidocaine injection done with this device creates a whitish anesthetized wheal and should be separated by 1.5 cm from the other. Then one subdermal injection of 2 units of botulinum toxin using a 33-G needle is done inside each anesthetized wheal.

Botulinum toxin treatment led to significant improvement in our patient within 2 weeks [Fig. 2]. AK recurred after 6 months necessitating another treatment with botulinum toxin injections.

Figure 2.

Significant improvement of the right palm after immersion of the hands in tap water after 2 weeks of treatment with botulinum toxin injections.

Discussion

AK presents as translucent whitish and pebbly thickening of the palms and soles after immersion in water.[4] Most cases involve the palms and fingers bilaterally and few cases affect the soles.[2] To our knowledge, there was only one previous case of unilateral palmar AK in the medical literature.[5] That case was associated with aspirin intake while our case occurred without any history of drug intake. Warm water provokes the lesions of AK more rapidly than cold water, as in our patient.[2] The "hand-in-the bucket" sign, when patients submerge their hands in water to demonstrate the lesions, constitutes a clue to diagnosis.[3] Patients may report tightness, pruritus, mild pain, burning sensation and hyperhidrosis.[2,4,6] Histopathology is nonspecific and may show orthokeratotic hyperkeratosis and dilated eccrine ducts.[2,6]

The pathogenesis of AK remains unclear. MacCormack et al[7] suggested that the clinical manifestations of AK could be due to dilatation of eccrine ostia in order to release sweat to compensate for mild hyperkeratosis. Another theory proposed that AK is a disorder of the integrity of the stratum corneum, resulting in increased water absorption.[8] Our patient had a hyperkeratosis of the right palm developing progressively over the years which suggests that his hyperkeratosis is rather a secondary phenomenon induced by repeated exposure to water. Moreover he did not have associated hyperhidrosis. These findings do not support the hypothesis that AK is due to a defect in the palmar stratum corneum. A third theory, based on association of AK with cystic fibrosis[9] and intake of aspirin[5] or cyclo-oxygenase-2 inhibitors,[10] suggests that AK could be due to increased sweat salt concentration in the stratum corneum.[2,9]

Spontaneous resolution has been reported in 4 cases and some cases clear after a few years.[8,11,12] Table 1 shows a list of all the cases of AK reported in the medical literature and their response to treatment. Modalities of treatment usually used for hyperhidrosis, such as aluminium chloride hexahydrate and iontophoresis, have been efficacious in treating several patients with AK.[2,4,6] Moreover, there were 2 previous reports of successful treatment of AK with botulinum toxin.[6,11] The first case was associated with hyperhidrosis. The absence of hyperhidrosis in the second case as well as in our case is in favor of involvement of the sweat glands in the pathogenesis of AK. The first case treated with botulinum toxin recurred after 5 months of treatment while it was not mentioned whether there was a recurrence or not in the second case.[6,11] Our patient's AK recurred after 6 months of treatment. Thus, repeated injections of botulinum toxin might be necessary at intervals of 5 to 6 months in AK patients.

Table 1. Cases of aquagenic keratoderma reported in the medical literature, their treatment and response to treatment.

Cases of Aquagenic keratoderma	Treatment	Treatment result
Yan et al (3 cases)4 Bellotch et al (1 case)13 Katz et al (2 cases)14 Neri et al (1 case)15 Suchak et al (1 case)16 Kocatürk et al (1 case)17 Seitz et al (1 case)9 Katz et al (1 case)14 Baldwin et al (1 case)18   Flann et al (1 case)19 Kabashina et al (1 case)20 Diba et al (1 case)11 Bagazgoita et al (1 case)6 Our case The last 3 cases responded to botulinum toxin injections   Falcón et al (1 case)21 Pastor et al (3 cases)22 Pardo et al (1 case)23 Badazzi et al (1 case)12 Sais et al (1 case)24 Conde-Salazar (2 cases)25 Luo et al (2 cases)26	Aluminum-based Aluminum hydroxide                   Aluminum chloride hexahydrate               Aluminum chloride 20% Aluminumchloride hexahydrate 20% + urea cream20% Aluminum chloride + silicone-based protection cream Aluminum chloride Aluminum chlorohydrate 18%   3% potassium aluminum sulfate solution	Improvement Improvement Improvement Improvement Improvement Improvement Improvement No response No response   Improvement No response No response No response No response       No response Improvement Improvement Improvement No response Improvement Improvement
Saray et al (2 cases)27     Polat et al (2 cases)28 Yalcin et al (1 case)29 Adişen et al (1 case)30	Salicylic-acid based 20% salicylic based in vaseline 20% salicylic based in vaseline + 10% urea cream   5% salicylic acid in ointment	Complete resolution Complete resolution   Improvement but recurrence Improvement Improvement
Itin et al (1 case)8 Suchak et al (1 case: the same case improved with aluminium hydroxide)16 Luo et al (1 case: the same case improved with formalin 3%)26	Oral anntihistamines     Oral antihistamines combined with topical steroids	Improvement No response   No response
Luo et al (2 cases)26 Luo et al (1 case)2	Formalin 3% in alcohol	Improvement Improvement
Lowes et al (1 case)31	Iontophoresis (combined with aluminium hydroxide)	Improvement
Diba et al (1 case)11 Bagazgoitia et al (1 case)6 Our case	Botulinum toxin injections	Improvement Improvement Improvement
Drug-related: Carder et al (1 case: rofecoxib)10 Vildósola (1 case: celecoxib)32 Khuu et al (1 case: aspirin)5 Ludgate et al (1 case: tobramycin)33	Withdrawal	Complete resolution in all cases
Lim et al (1 case)34 MacCormack et al (2 cases)7 Itin et al (1 case)8	No treatment	Spontaneous resolution
English et al (2 cases)1 Schmults et al (1 case)35 Davis et al (1 case)36 Gild et al (1 case)37 Tan et al (1 case)38 Yoon et al (1 case)39 Xia et al (1 case)40 Garçon et al (1 case)41	Not mentioned or no treatment	Not mentioned or no treatment

Conclusions

This case is unusual by its unilateral idiopathic palmar involvement and by its long history. Moreover, it is the third reported case to respond favorably to botulinum toxin A. The successful treatment of AK with hyperhidrosis treatments points to the involvement of the sweat glands in the pathogenesis of this entity. AK is probably more prevalent than reported in the literature because of its transient nature; its recognition may provide a better understanding of the pathogenesis and appropriate modalities of treatment of this condition.