Grenz Ray Therapy for Darier Disease and Hailey‐Hailey Disease: A Case Series of Three Patients

Hailey-Hailey disease (HHD) and Darier disease (DD) are rare autosomal-dominant genodermatoses that share several clinical and pathological features. HHD is characterised by painful blisters, erosions and crusts, predominantly in intertriginous areas, and is caused by mutations in the ATP2C1 gene [1]. DD presents with greasy, hyperkeratotic papules that scale and scab in seborrhoeic areas and is caused by ATP2A2 gene mutations [2]. Treatment of these conditions is challenging, with limited effective treatment options for severe cases (Table 1) [1-3]. Topical corticosteroids Topical calcineurin inhibitors Topical synthetic vitamin D analogues Topical 5% 5-fluorouracil Topical antibiotics Topical iodine cadexomer Topical corticosteroids Topical calcineurin inhibitors Topical synthetic vitamin D analogues Topical 5% 5-fluorouracil Topical retinoids Topical non-steroidal anti-inflammatories Oral antibiotics (doxycycline, minocycline) Dapsone Oral corticosteroids Cyclosporine Methotrexate Thalidomide Azathioprine Anticholinergics Naltrexone Apremilast Magnesium Vitamin D Etanercept Dupilumab Oral antibiotics (doxycycline) Oral retinoids Vitamin A analogues Cyclosporine Magnesium Penicillamine Oral contraceptives Methylprednisolone Immunoglobulin Laser therapy Photodynamic therapy Dermabrasion Surgical excision Radiation (electron beam, Grenz rays) Botulinum toxin Laser therapy Photodynamic therapy Dermabrasion Surgical excision Radiation (electron beam, conventional X-rays, radiotherapy, photon radiation, Grenz rays) Radiation therapy, including Grenz ray therapy, has shown promise in treating these conditions [2, 3]. Grenz rays are a form of ultrasoft radiation that penetrates to a depth of approximately 2 mm into the skin [4, 5]. This treatment has proved useful in treating dermatoses including scalp and palmoplantar psoriasis, hyperkeratotic eczema, nail dystrophies, perianal pruritis, warts and disseminated superficial actinic porokeratosis [4, 5]. We present three cases of recalcitrant DD and HHD with an excellent clinical response to Grenz therapy. A 29-year-old female with severe DD, diagnosed at the age of 12, presented to the dermatology clinic with extensive disease affecting her abdomen, back shoulders, legs and face (Figure 1A). Previous treatments include bleach baths, oral and topical corticosteroids, valaciclovir, cephalexin, acitretin, isotretinoin, cyclosporin, photodynamic therapy, narrow-band UVB therapy, laser therapy and dermabrasion (Table 2). Treatment with Grenz rays, 2 Gy per session for six sessions per field, resulted in resolution of disease (Figure 1B). Her treatment was complicated by painful blisters in several treated areas lasting for 2 months after treatment. Polymerase chain reaction (PCR) testing was negative for viral DNA. Disease has not recurred in the areas treated with Grenz therapy after 58 months of follow-up. Bleach baths Topical corticosteroids Oral corticosteroids Valaciclovir Cephalexin Acitretin Isotretinoin Cyclosporin Photodynamic therapy Narrow band UVB therapy Laser therapy Dermabrasion Face Neck Shoulders Upper back Mid back Lower back Abdomen Thighs Calves Submammary areas Bleach baths Topical corticosteroids Oral corticosteroids Valaciclovir Clindamycin Cephalexin Acitretin Lower back Lower abdomen Buttocks Left hip Left thigh Topical tacrolimus Topical corticosteroids Oral corticosteroids Fluconazole Doxycycline Cephalexin Acitretin Naltrexone Botulinum toxin injections Bilateral groin Back Left breast Right thigh Right popliteal fossa A 62-year-old female with long-standing HHD was referred for Grenz therapy after failing to respond to treatments including bleach baths, oral and topical corticosteroids, valaciclovir, clindamycin, cephalexin and acitretin (Table 2). Her worst affected areas were the lower back, trunk and lower abdomen (Figure 1C). She underwent Grenz therapy, 2 Gy per session for six sessions per area, which resulted in near total clinical improvement without any complications (Figure 1D), with most areas remaining disease free at 24 months. A 57-year-old female with treatment-resistant HHD was referred for Grenz ray therapy. Previous treatments, including topical tacrolimus, oral and topical corticosteroids, fluconazole, doxycycline, cephalexin, acitretin, naltrexone and botulinum toxin injections, had been ineffective (Table 2). Her most affected areas included the back, groin, thighs and submammary region (Figure 1E). She was given 2Gy per session, six sessions per treated area and experienced significant clinical improvement in treated areas (Figure F), although the inguinal regions previously treated with botulinum toxin showed less response. She did not have any significant side effects to the treatment; however, she did experience relapse to the areas on her back and under her breasts approximately 6 months after treatment with Grenz was completed. These cases suggest Grenz therapy may be a valuable treatment option for recalcitrant HHD and DD. Particularly noteworthy is the long-term remission of the first patient, with no recurrence of disease in the treated sites after more than 6 years. Grenz therapy is proving increasingly difficult to access in Australia in recent years and has been discontinued in our centre this year. To our knowledge, there is only one centre, 'Just Skin' situated in Queensland, still providing the service nationally. While access to Grenz therapy may be limited, newer superficial radiation devices are becoming increasingly available and this treatment may become a viable option for treatment refractory HHD and DD patients. The authors have nothing to report. Consent was obtained from the patient for the publication of the case and clinical images. The authors declare no conflicts of interest. The data that support the findings of this study are available from the corresponding author upon reasonable request.