Hailey-Hailey disease treatment with Botulinum toxin type A

Abstracts

Duas irmãs com doença de Hailey-Hailey, com lesões recorrentes - uma em axilas e outra em região inguinal -, e resposta limitada aos tratamentos clássicos. Elas foram tratadas com aplicação de toxina botulínica tipo A. Observamos que houve importante melhora na paciente tratada na região inguinal e remissão completa na paciente em cujas axilas sofreram tratamento. Além disso, foi possível poupar uso de antibióticos sistêmicos e corticoides tópicos. O alto custo é um fator restritivo para uso rotineiro e estudos maiores são necessários para definir eficácia e relação custo-benefício dessa intervenção.

Pênfigo familiar benigno; Terapia combinada; Toxina botulínica tipo A

CASE REPORT

Hailey-Hailey disease treatment with Botulinum toxin type A^*

Giancarlo Rezende Bessa^I; Thaís Corsetti Grazziotin^II; Ana Paula Manzoni^III; Magda Blessmann Weber^IV; Renan Rangel Bonamigo^V

^IDermatologist. On going master course in Pathology run by the Federal University of Medical Sciences of Porto Alegre - Porto Alegre (RS), Brazil

^IIDermatologist. On going master course in Pathology run by the Federal University of Medical Sciences of Porto Alegre - Porto Alegre (RS), Brazil

^IIIOn going doctorate course in Pediatrics of the Federal University of Rio Grande do Sul. Invited professor in the specialization course of Dermatology of the Federal University of Medical Sciences of Porto Alegre - Porto Alegre (RS), Brazil

^IVDoctorate degree in Medical Sciences - Pediatrics from the Federal University of Rio Grande do Sul. Associate professor of Dermatology of the Federal University of Medical Sciences of Porto Alegre - Porto Alegre (RS), Brazil

^VDoctorate degree in Medical Sciences from the Federal University of Rio Grande do Sul. Associate professor and head of the Dermatological Service of the Federal University of Medical Sciences of Porto Alegre - Porto Alegre (RS), Brazil

Mailing address

ABSTRACT

Two sisters with recurrent lesions, one on axillae and other on the groin, and with limited response to classical treatments were treated with injections botulinum toxin type A. We observed marked improvement in the patient treated in the groin and complete remission in the patient treated in the axillae. It was possible to spare the use of systemic antibiotics and topical corticosteroids. The high cost is a restrictive factor to routine use and large studies are necessary to access efficacy and cost benefit profile.

Keywords: Botulinum toxin type A; Combined modality therapy; Pemphigus, benign familial

INTRODUCTION

Hailey-Hailey disease (HHD) or familial chronic benign pemphigus, is a rare acantholytic disease, autosomal dominant clinically characterized by flaccid bullae and erosions on the intertriginous regions, mainly the axilary and inguinal. ¹ The rule is the occurence of symetrical bilateral eruption although there are reports of rare cases of mosaicism with unilateral lesions.² Mutations on the ATP2C1 gene that codifies a Ca2+ ATPase pump of the reticulum sarcoplasmatic leads to alterations in the intracelular signalling dependent on Ca2+, resulting in the loss of celular adhesion in the epidermis. To the loss of cohesion among the keratinocytes (acantholysis) it is added the effects of local factors such as frictio, humidity, heat, microbic colonization and secondary infections , which are decisive in the induction of the appearing of lesions on the intertriginous regions. ¹ Diagnosis is clinical and histopathologic and has as its main differential diagnosis Darier disease. Currently the two illnesses are considered distinct entities, although there are reports of the occurence of both disease (Darier and HHD) within the same family. ³

HHD is traditionally treated with corticosteroids and topic and systemic antibiotics. ⁴ The use of topic corticosteroids on the intertriginous areas , even for short periods , is associated to the risk of the occurence of atrophy, streaks, and telangiectasias. Oral antibiotics are efficient because the infections potentialize the acantholysis and have important role in the exacerbation and persistence of the disease. ¹ They might, however, lead to the appearing of bacterial resistance. ⁵ More recently there have been described surgical methods such as the excision of the affected area and healing of the site by second intention, excision with graft ⁶, dermoabrasion ⁷ and ablation with CO2 ⁸ or erbium:YAG⁹ laser^. However, these treatments need post operative care for variable periods and might not be feasible with patients with diffused disease.

Botulinum toxin type A (BTA) is a protein that produces chemodenervation when it blocks the liberation of acetylcholine in nerve terminations. Originally it was used in the treatment of neurologic, ophthalmologic and cosmetic diseases for its action in the motor plaque with production of muscularis weakness. Currently, new uses for BTA have been proposed for its blocking action to the cholinergic stimulus in the post ganglial symphathetic innervation and reduction of the production of sweat by the eccrine glands. As such it has also been used for the treatment of palmar and axillary hyperidrosis ^10,11 Heat and sweat are factors known to worsen the condition of patients suffering from HHD and frequently exacerbation occurs throughout the months of summer.

There are few reported cases about the use of BTA in the treatment of HHD in the international medical literature. It is generally used in association with other therapeutic modalities in patients with severe disease or resistant to conventional treatment.^12,13 It was reported, recently, an improvement in the disease with the isolated application of BTA comparable with its associated use of dermoabrasion and erbium:YAG laser. ¹⁴

In the present report it is shown the use of BTA as an adjuvant therapy in two sisters HHD carriers with limited response to classical treatment

CASE REPORTS

Patient 1: 48 year-old woman with HHD confirmed histhopathologically, undergoing topic and systemic treatment with corticoids and antibiotics for four years. Recurrent periods of exacerbation of the disease were reported especially throughout the summer. Clinical examination showed erythematous and pultaceous plaques, parallel rhagades, flaccid vesicles and bromhidrosis on the axillae, inframammary region and bilateral groin region (Picture 1). Throughout the first monitoring year, the patient presented temporary improvement with the systemic use of antibiotics such as trimethoprim/sulfamethoxazole and erythromycin and topic use of corticoids and clindamycin, as well as solutions and anti-septic soaps. The patient developed gastrointestinal intolerance to tetracycline and did not respond to limecycline (300mg/day for 60 days).

Patient 2: Woman, aged 65 years of age, described lesions in the intertriginous areas with pruritus and burning for more than 30 years. She had a histhopathological report done 4 years before diagnosing HHD.It was reported the frequent use of betamethasone and gentamicin cream, without regular medical checking. The clinical examination showed severe cutaneous atrophy in the inframammary region and bilateral axillary, erythematous and pultaceous plaques with rhagades on the groin regions (Picture 2). The patient was reccomended to stop the use of topic corticosteroids and it was started a treatment using oral trimethoprim/sulfamethoxazole, antiperspiring and topic anti-septic. After three months, it was attempted the suspension of the oral antibiotic but the patient presented recidivation of the lesions and gastrointestinal intolerance to the use of tetracycline. It was decided to reintroduce trimethoprim/sulfamethoxazole. Due to the absence of a satisfactory response to the treatments, it was decided to proceed with the application (Picture 3) of 125U of BTA ( bottle of 500U) in the right axilla of patient 1 and in the right groin region of patient 2 (50 marks of injection with distance of 1 cm, application of 2,5U in each mark). After two weeks, the left axilla of patient 1 was treated and also the left groin region of patient 2 with the same dose of BTA (Picture 4). In a medical consultation 30 days after the second application, we observed an important improvement in the patient who had treated the groin region and complete remission in the patient who had treated the axillae. All medication, either topic or systemic, was interrupted .One month later, patient 1 was examined and reported the occurence of lesions on the groin region, without occurence on the axillae (Picture 5) and patient 2 presented axillary lesions and discreet residual erythematous area minimally pultaceous on the groin regions (Picture 6). It was prescribed topic clindamycin and local measures.

Figure 1

Figure 2

Figure 3

Figure 4

DISCUSSION

HHD lesions usually occur immediately after puberty, affecting mainly the active years of life of patients¹⁵ The painful sensation or pruritus on the intertriginous regions of erosion and the fetid smell of the HHD lesions affect enormously the quality of life of the patients. For this reason, it is recommended an intensive treatment including those patients with few lesions. ¹⁶ Lapiere et al. reported the case of a patient who had had an applications of 50U of BTA in each axilla, having had complete remission of the lesions in these areas, ¹² similarly to patient 1 who, during the summer, developed lesions on the groin region, site not treated with BTA, while it remained asymptomatic on the axillae.

Figure 5

Figure 6

Kang et al. reported the use of BTA on the groin region of a 48-year-old woman with severe disease, that was being treated with high doses of oral corticosteroid. In this case, it was used the initial dose of 100U of BTA on the right side with posterior complementation on the left side. The corticosteroid dose was reduced althogh it was not possible to stop completely with the medication showing the adjuvant role of BTA in patients with severe disease.¹³ As for patient 2 of the present report it was used a smaller dose which might have contributed for the non complete remission of the lesions. However, the patient presented discreet lesions, in spite of the intense heat and humidity of our climate, at that time.

The postulate mechanism to explain the response to BTA in HHD is the reduction of sudoresis in response to the heat. The reduction of humidity probably acts in the reduction of the colonization by microorganisms (fungous and bacterial) involved in the exacerbations. It would also lead to less irritation stimulated by the natural rub in the areas of folds. ¹²

We presented here two cases in which the BTA proved to be a good adjuvant in patients with recurrent disease and limited response to classical treatment. Its use made it possible to save the use of systemic antibiotics and topic corticosteroids, which was particularly important for a patient that already presented advanced signs of cutaneous atrophy in the fold areas.

BTA is a therapy of easy application and good tolerance. The high cost is a limiting factor for its routinary use and broader studies are necessary to define the efficacy of the treatment and its cost-benefit.

ACKNOWLEDGEMENTS

We thank Galderma Laboratory for the donation of a bottle of Botulinum toxin used for treating the patients of this current study.

REFERENCES

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*

Trabalho realizado no Serviço de Dermatologia da Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA) - Porto Alegre (RS), Brasil.

Publication Dates

• Publication in this collection
  02 Dec 2010
• Date of issue
  Oct 2010

History

• Received
  01 June 2009
• Accepted
  31 July 2009