JEADV
DOI: 10.1111/jdv.12875
REVIEW ARTICLE
Laser therapy for the treatment of Hailey–Hailey disease: a systematic review with focus on carbon dioxide laser resurfacing L.A. Falto-Aizpurua,* R.D. Griffith, M.A. Yazdani Abyaneh, K. Nouri Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL 33136, USA *Correspondence: L.A. Falto-Aizpurua. E-mail:
[email protected]
Abstract Benign familial chronic pemphigus, or Hailey–Hailey disease (HHD), is a recurrent bullous dermatitis that tends to have a chronic course with frequent relapses. Long-term treatment options include surgery with skin grafting or dermabrasion. Both are highly invasive and carry significant risks and complications. More recently, ‘laser-abrasion’ has been described as a less invasive option with a better side-effect profile. In this article, we systematically review the safety and efficacy of carbon dioxide laser therapy as a long-term treatment option for HHD, as well as provide a review of other lasers that have been reported with this goal. A total of 23 patients who had been treated with a carbon dioxide laser were identified. After treatment, 10 patients (43%) had had no recurrence, 10 (43%) had greater than 50% improvement, 2 (8%) had less than 50% improvement and 1 (4%) patient had no improvement at all (follow-up period ranged from 4 to 144 months). Laser parameter variability was wide and adverse effects were minimal, including dyspigmentation and scarring. Reviewed evidence indicates this therapy offers a safe, effective treatment alternative for HHD with minimal risk of sideeffects. Larger, well-designed studies are necessary to determine the optimal treatment parameters. Received: 19 July 2014; Accepted: 22 October 2014
Conflicts of interest None declared.
Funding sources None declared.
Introduction Benign familial chronic pemphigus, or Hailey–Hailey disease (HHD), is a genodermatosis that affects the adhesion of keratinocytes.1 It is caused by a loss-of-function mutation in the ATP2C1 gene, which is inherited in an autosomal dominant fashion or can be caused by new mutations. The disease usually presents as recurrent, symmetrical plaques with erosions and crusting in the intertriginous areas. It may be exacerbated by friction, sweat and superimposed infection. Histopathology shows full-thickness acantholysis resulting in suprabasal clefts and resembles a dilapidated brick wall. Mild dyskeratosis and a sparse perivascular lymphocytic infiltrate with scattered eosinophils in the papillary dermis may also be present. HHD has a chronic course and can be bothersome. Several treatment options have been described to control the disease, but frequent relapses are common.2 Topical and oral corticosteroids, antibiotics and anti-fungals are the usual treatment options.3 Recently, oral retinoids,4–6 methotrexate,7,8 tacrolimus,9–11 cyclosporine,12–14 botulinum toxin A15,16 and photody
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namic therapy17–19 have been reported with different success rates and eventual relapses.20 Long-term treatment options are excision with skin grafting21–23 and dermabrasion.24–27 Though these are successful treatments, they are highly invasive and carry a risk of significant complications such as infection, prolonged hospitalization and immobilization, contractures and infections of the skin graft.28 In contrast to dermabrasion and skin grafting, laser therapy is less invasive and has been reported to be a safe and effective treatment for HHD with less permanent adverse effects. Reports in the literature, however, are limited to case reports and case series. To our knowledge, a review of the available literature outlining the use of lasers for the treatment of HHD has never been performed. The ineffectiveness and adverse events associated with the most popular current therapies for HHD, coupled with the absence of a well-designed review on this topic, reflects the importance of this article to the dermatologic literature. In this article, we systematically review the literature for carbon dioxide (CO2) laser therapy as a long-term treatment option for HHD.
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In addition, the article will provide a review of other lasers that have been used for the treatment of HHD.
Methods A systematic literature review was performed on 2 April 2014 in order to identify articles relevant to the topic of laser treatment of HHD. The terms, ‘Hailey’ and ‘benign familial pemphigus’ were combined with ‘laser’ in separate searches of the National Library of Medicine’s Pubmed Database. Articles deemed irrelevant based on their title, abstract and overall content were excluded, as well as those not written in English. Furthermore, studies, case reports and case series in which laser therapy was not the primary treatment modality used for treating HHD were excluded. Twelve articles were selected for inclusion based on the relevance of the title and abstract. References of articles that met the criteria for inclusion were also considered. These articles comprised 29 patients with HHD that were treated with laser therapy. There were 23 cases where a CO2 laser was used, three cases treated with erbium-doped yttrium aluminium garnet (Er:YAG) laser, one case with a diode laser, one case with long-pulsed Alexandrite and one case with pulsed dye laser (PDL). Each article was reviewed and summarized in Tables 1–4.
Results Carbon dioxide laser
A total of 23 cases were identified where CO2 was used as the primary treatment modality of HHD. Of these, 13 were females (56%), the mean age was 49 (range 26–89), and the mean duration of disease prior to laser therapy was 13 years (range 5–30). Most of the patients had previously received several therapies without success. Lesions affected the axilla in 69.5% of the patients, groin 43%, genitalia 39% (scrotum, vulva, perivaginal area and perineum), thorax 30.4% (back, abdomen and chest), neck 21.7%, extremities 21.7% (arms, antebrachium, thighs and popliteal fossa) perianal region 13% and gluteal region 0.04% (Table 1). Technique for CO2 laser
In an effort to achieve maximal effectiveness while minimizing side-effects and patient discomfort, a number of different laser settings were used among the different studies.1,3,28–32 In the majority of cases, the CO2 laser was used in continuous, defocused mode with power settings ranging from 5 to 25 W and spot size from 1 to 9 mm. Others used pulsed lasers with lower power settings. These details are summarized in Table 2. Local anaesthesia was used in the majority of cases, while Pretel-Irazabal et al. used spinal or general anaesthesia, since they were treating various, large areas per session. The treatment endpoint for all studies was to observe normal/healthy dermis. All of the reports performed between one and five passes with most of
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them removing the char after each pass. Different techniques for wound care were described, and the healing period ranged from 1 to 4 weeks. Treatment efficacy was measured as the degree of improvement or recurrence of lesions at follow-up (range 4–144 months). Ten patients (43%) had healthy looking skin or had no recurrence, two patients (8%) had disease recurrence only at the periphery of the treated area, two (8%) had minimal local recurrence, six (26%) had greater than 50% improvement, two (8%) had less than 50% improvement and one patient (4%) had no improvement at all. Post-procedural adverse effects included pain, erythema and oedema. Long-term adverse effects included textural and pigment changes. Of the 23 cases, there was one report (4%) of minor scarring and two reports (8%) of hypertrophic scarring. There were three reports (13%) of post-inflammatory hyperpigmentation that improved over time and one case (4%) of permanent mild hypopigmentation. Technique for Er:YAG laser
Three patients, two males and one female (age range 42–62 years), were treated with the Er:YAG laser.2,20 Treated areas were the groin, axilla, lateral scrotum and sub-mammary region. A 2.94 lm Er:YAG laser was used with a spot size 1.6–5 mm (1000 mJ; frequency 5–10 Hz). Two of the three treatments were done in pulse mode (350 ls) while the last treatment was performed in partial overlapping mode. The procedure was performed under local anaesthesia (except for one case) until punctuate bleeding was observed. The debris was removed after each pass in two of the cases. Healing was completed in 7–12 days. At follow-up (8–12 months), no adverse effects were reported. Complete remission of HHD was achieved in two patients. The third patient had partial remission, with lesions recurring only at the edges of the treated area. Technique for diode laser
A 1450 nm diode laser was used to treat both axilla of a 35-yearold male patient.33 A fluence of 14 J/cm2, 6-mm spot size and a dynamic cooling device of 50 ms were used. A total of three treatment sessions were performed under topical anaesthetic. Despite the topical anaesthetic, the patient reported the procedure to be extremely painful. Otherwise, there were no adverse effects. There was no improvement of the disease except for reduction in sweating and malodour of the lesions. Technique for alexandrite laser
A 35-year-old male patient with disease localized to the groin was treated with long-pulsed alexandrite (5 ms) laser.34 A total of 13 treatments were performed, at 3–5 week intervals, where the fluence was gradually increased from 12 to 20 J/cm2 and spot sizes from 10 to 15 mm. Cooling coupling gel was applied prior to each session to augment cold air cooling. The patient experi
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Table 1 Carbon dioxide laser treatment for Hailey–Hailey disease Study
Age/Sex
Disease duration (years)
Previous treatments
Treated area
follow-up (months)
Results/observations
Don et al.28 (n = 1)
50/M
30
Topical antibiotics, anti-fungals, steroids; betadine soaks; aluminium acetate solution; dapsone; potassium permanganate dressings; oral antibiotics, prednisone
Groin
8
Excellent cosmetic results with no recurrences but continued disease in the periphery
Mc Elroy et al.29 (n = 2)
38/M
12
Topical steroids; oral erythromycin
Scrotum
12
No recurrence
56/F
16
IL & IM steroids; topical & oral antibiotics, steroids
Inguinal and perivaginal areas
4
Disease free
74/M
10
NR
Inguinal area and axilla
4–10
No improvement compared to control
37/F
10
NR
Neck
23
Healthy compared to control
59/F
18
NR
Axilla and neck
12–22
Healthy, no control available
33/M
6
NR
Axilla
27
Improvement compared to control
Kartamaa and Reitamo3 (n = 8)
54/F
12
NR
Lower abdomen, thorax
12
Healthy, no control available
55/M
20
NR
Axilla, antebrachium and gluteal region
18–27
Healthy compared to control
44/F
15
NR
Axilla and thighs
26
Healthy compared to control
39/F
17
NR
Neck
12
Healthy compared to control
Touma et al.30 (n = 1)
38/F
NR
Conventional therapy
Chest and axilla
18
Rare asymptomatic activity in 12
Recurrence in periphery
31/M
NR
NR
Axilla
6
No signs of disease
Pretel-Irazabal et al.1 (n = 8)
46/M
5
Topical & oral antibiotics; topical anti-fungal; pimecrolimus
Axilla, groin, scrotum and perianal region
12–144
47/F
11
Topical & oral antibiotics, steroids; dapsone
Groin and axilla
4 had >75% improvement; 2 had 50–75% improvement; 1 had 25–50% improvement; 1 had 2 passes
Christian and Moy31
396 ls dwell time; 25–28 J/cm2 2nd session: 90 ls pulse duration; 15 J/cm2
Anaesthesia: 1% xylocaine with 1:100 000 epinephrine L axilla: 2 passes 25 J/cm2 R axilla: 3 passes 28 J/cm2 2nd session: several foci treated with 2 passes
Did not clean char after last pass; petrolatum jelly to wounds until healing
None
Kruppa et al. 2000
Silk Touch Flashscanner CO2; 125-mm handpiece; 3-mm spot size; 6W scan time 0.2 s
Anaesthesia: prilocaine 1% 3 passes
Covered with polyvidon-iodine wound gauze
None
Pretel-Irazabal et al.1
Continuous-wave CO2 laser with computerized scanning; 200-mm handpiece; 20–25W; 450 ms pulse duration; 9-mm spot diameter
Anaesthesia: spinal or general 2–3 passes
Topical gentamicin application, covered with linitul or mepitel dressings covered with a gauze, daily for a week; all patients received prophylactic antibiotics and analgesic
Significant post-operative pain; intense erythema for months; 1 case of permanent mild hypopigmentation; PIH in 3 cases that improved with time. Small hypertrophic scar in 1 case
CO2, carbon dioxide; L, left; NR, not reported; R, right.
enced moderate discomfort and transient oedema and erythema during treatments. Over 95% clearance was achieved and maintenance sessions were done for a year at 3-month intervals. After 1 year, complete clearance remained with occasional minimal flares compromising less than 5% of baseline. The only reported adverse event was mild, persistent post-inflammatory hyperpigmentation. Technique for PDL
PDL treatment was started on a 35-year-old female for striaerubrae secondary to potent topical steroid use on the axilla and inframammary regions.35 Parameters were 595 nm, 10-mm spot size, 1.5 ms and 7.5 J/cm2. Treatments were performed at monthly intervals, for a total of 17 treatments. After the fourth laser treatment, the patient noticed improvement of her HHD as compared to her disease activity on the groin area that was not being treated with PDL. At the end of the treatment there were no lasting side-effects and appeared to induce full remission of the disease.
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Discussion The use of laser therapy, particularly fully and fractionated ablative lasers in substitution of many surgical treatments performed in dermatology has dramatically increased over the last years. Traditional ablative lasers, like the CO2 and Er:YAG lasers, vapourize tissue by targeting water. However, they carry a significant risk of scarring and other complications. Fractional ablative laser therapy greatly minimizes the side-effect profile observed with fully ablative laser therapy while obtaining positive results. Treatment of HHD with a continuous CO2 laser in defocused mode offers several advantages over the most widely used treatment modalities for HHD. The CO2 laser can selectively vapourize tissue at a superficial level (0.08–0.15 mm).1 Therefore, a large surface area can be treated in a short period of time. There is less intraoperative pain, and less post-operative bleeding and swelling than skin grafting or dermabrasion.3,28,30 Laser therapy offers better depth control and less scarring than dermabrasion and can be performed in an outpatient setting under local
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Table 3 Laser therapy for the treatment of Hailey–Hailey disease Previous treatments
Treated area
follow-up (months)
Result/observations
3
NR
Groins, lateral scrotum and axilla
8
Complete remission
42/M
3
NR
Groin and axillae
Er:YAG
62/F
15
NR
Submammary region
12
No relapse
Downs33 (n = 1)
1450 nm diode laser
35/M
20
Oral & topical antibiotic; topical steroids, antiseptics; hair removal with alexandrite laser
Axilla and groin
NR
No improvement, only reduction of sweating and elimination of malodour
Fisher and Rosenbach35 (n = 1)
PDL
35/F
6
Topical steroids
Axilla and inframammary region
NR
Disease clearance
Awadalla and Rosenbach34 (n = 1)
Long-pulsed (5 ms) alexandrite
35/M
12
Oral antibiotics & topical steroids
Groin
24
Complete clearance with occasional flares of
