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We hope that making available the relevant information on Pachyonychia Congenita will be a means of furthering research to find effective therapies and a cure for PC. 2386 East Heritage Way, Suite B, Salt Lake City, Utah 84109 USA Phone +1-877-628-7300 • Email—[email protected] www.pachyonychia.org BJD THERAPEUTICS British Journal of Dermatology Botulinum toxin in the treatment of sweat-worsened foot problems in patients with epidermolysis bullosa simplex and pachyonychia congenita C. Swartling,* M. Karlqvist,*à K. Hymnelius,* J. Weis§ and A. Vahlquist* Departments of *Dermatology and §Radiology, and àCentre for Research and Development, County Council of Ga¨vleborg, Uppsala University, University Hospital, SE-751 85 Uppsala, Sweden Sophiahemmet AB, Hidrosis Clinic, Box 5605, SE-114 86 Stockholm, Sweden Summary Correspondence Background Painful foot blistering is a common problem in patients with epider- Carl Swartling. molysis bullosa simplex (EBS) and pachyonychia congenita (PC). Hyperhidrosis, E-mail: [email protected] a condition which can be effectively blocked by plantar injections of botulinum toxin (Btx), often exacerbates the blistering. Accepted for publication 22 June 2010 Objectives A retrospective evaluation of the effects of Btx injections in 14 patients with EBS and PC with foot blisters and painful callosities. Key words Methods After informed consent, patients with EBS (n = 6) and PC (n = 8), aged blisters, botulinum toxin, callus, epidermolytic 7–66 years, who had received Btx therapy at our centre since 2003, were disorders, hyperhidrosis, keratin mutation included. The treatment consisted of multiple plantar injections of Btx A or Btx B Conflicts of interest after prior regional or general anaesthesia. Patients were interviewed about the None declared. treatment effect and were asked to score the improvement from 0 to 5, where 5 is ‘excellent’. One patient with PC with painful callosities was studied by DOI 10.1111/j.1365-2133.2010.09927.x magnetic resonance (MR) spectroscopic microimaging before and after Btx injec- tions to disclose any underlying blisters. Results In total, 76 treatments were evaluated (one to 19 sessions per patient). Thirteen patients (93%) reported reduced plantar blistering and pain; the improvement score was ‡ 4 in four of six patients with EBS and six of eight patients with PC. The mean effect duration was 3 months. No adverse events, apart from mild anticholinergic side-effects in two patients, were noted. MR spectroscopic microimaging showed disappearance of intraepidermal blistering after Btx therapy. Conclusions Plantar injection of Btx is an efficient, long-lasting and safe treatment of painful blistering and callosities in EBS and PC that can be given repeatedly without loss of efficacy. Epidermolysis bullosa simplex (EBS) and pachyonychia con- [Dowling–Meara (DM); 1 : 200 000] with blistering all over genita (PC) belong to a group of congenital keratinopathies the body.4 PC (OMIM 167200 ⁄167210) has a prevalence of characterized by stress-induced epidermolysis and hyperkerato- about 1 : 100 000. It starts with thickening of the nails and is sis due to cytoskeletal fragility and clumping of intermediate later followed by foot blisters and painful callosities. Two filaments (IFs). There is no curative treatment for keratino- forms of PC exist: type 1 with mucosal involvement, and type pathies, but siRNA therapy has shown promising results in 2 with steatocystoma multiplex.5 PC.1 In patients with both EBS and PC, foot blisters and callosi- EBS and PC are caused by dominant negative keratin muta- ties deteriorate in a hot and humid environment, especially tions affecting the heterodimerization of IFs expressed in the when plantar hyperhidrosis is prominent. Alas, topical anti- basal and spinous layers of epidermis and encoded by sweating agents, such as glutaric aldehyde and aluminium KRT5 ⁄KRT14 and KRT6 ⁄KRT16 ⁄17, respectively.2,3 EBS (OMIM chloride, are insufficient to reduce the foot problems.6 How- 131800 ⁄131760) exists in two forms: the localized subtype ever, intracutaneous injection of botulinum toxin (Btx) is a previously called Weber–Cockayne; prevalence 1:25 000) with more efficacious treatment of focal hyperhidrosis.7,8 Btx inhib- predominantly foot blisters, and the generalized subtype its eccrine sweat glands by blocking the acetylcholine Ó 2010 The Authors 1072 BJD Ó 2010 British Association of Dermatologists 2010 163, pp1072–1076 Botulinum toxin for EBS and PC, C. Swartling et al. 1073 pathway. The anaerobic bacterium Clostridium botulinum produces PC were included in a previous report of the short-term different types of Btx named A to G. Type A and type B are effects of Btx therapy.11 commercially available. Btx A and Btx B differ in pharmaco- dynamics, covering proteins and additives in the vials. Differ- Anaesthesia ent Btx A preparations are not exchangable regarding the potency of 1 U.9,10 Foot analgesia was accomplished either by bilateral intrave- Several years ago, we began treating a few patients with PC nous regional anaesthesia (IVRA)13 with a low tourniquet and ) by plantar injections of Btx and noticed a spectacular reduc- 25 mL prilocaine (5 mg mL 1) given intravenously to each tion in pain from walking.11 We also reported preliminary foot (n = 39 sessions), or by general anaesthesia (n =37 good results in two patients with EBS with pedal blisters,11 sessions). The selection of method was dependent on the which was recently confirmed by others.12 We have now trea- patient’s age and attitudes to anaesthesia (see Table 1). ted a total of 14 patients with EBS and PC, and wish to report in a retrospective study our experience with Btx therapy for Botulinum toxin injections this indication. After reducing the callosities by curettage, all patients received plantar injections with Btx A (DysportÒ; Ipsen, Patients and methods ) Slough, U.K.) 100 U mL 1. The individual doses are shown in Table 1. Due to treatment resistance, three patients were Patients later switched to Btx B (NeuroblocÒ; Eisai, Stockholm, Swe- ) Six patients with EBS of localized type or DM (age den) 250 U mL 1. Our initial strategy was to distribute Btx 7–46 years) and eight patients with PC of type 1 or 2 (age evenly on the sole, injecting it intradermally every 15 mm 26–66 years) were included in the study after informed in a checked pattern. This regimen was later modified so that consent (Table 1). The patients were referred from all parts only weight-bearing areas of the feet were treated, distri- of Sweden and were followed for a maximum of 6 years. A buting the same total dose especially below blisters and diagnosis of EBS or PC was established using clinical criteria, callosities. inheritance pattern, and ⁄or KRT mutation analysis (kindly Similar procedures have been repeatedly approved by the performed by Dr Paul Bowden, Cardiff, U.K., and Dr Marie local ethical committee in Uppsala for other studies of Btx Virtanen, in Uppsala). All patients had a history of sweat- therapy performed over the years.13 All treatments were worsened blisters or painful hyperkeratoses that negatively performed at the Department of Neurology, Uppsala Univer- affected their activities of daily life. Three of the patients with sity Hospital. Table 1 Patient characteristics, global outcome and details of the therapy with botulinum toxin (Btx) Global Preferred Age Clinical Affected No. of Dose (U) of Btx A improvement Effect duration type of Patient (years) ⁄sex subtype Inheritance gene treatments or Btx B (score)a (months) anaesthesia EBS 1b 7 ⁄F Loc. AD NA 3 A: 170–250 5 4 General EBS 2b 46 ⁄M Loc. AD NA 1 A: 300 (one foot) 4 3 IVRA EBS 3 24 ⁄F Loc. AD NA 4 A: 580–700 5 3Æ5 IVRA EBS 4 46 ⁄F DM AD K5 3 A: 576–600 5 3 IVRA EBS 5 30 ⁄M Loc. AD K5 1 A: 300 (one foot) 0 0 IVRA EBS 6 33 ⁄M DM AD K5 1 A: 315 (one foot) 3 3 IVRA PC 1 32 ⁄F PC-2 AD NA 2 A: 600 4 2 General PC 2b 36 ⁄F PC-2 AD NA 6 A: 600–700 4 3 IVRA PC 3b 66 ⁄M PC-2 AD NA 1 A: 600 3 3 IVRA PC 4c 26 ⁄M PC-1 Spor.