To the Editor: We read, with great interest, the studies by Kollman et al and Alajmi et al, which reported the efficacy of different dosages of low-dose naltrexone (LDN) in patients with Hailey-Hailey disease (HHD). Several studies have reported the efficacy of LDN in HHD over the past decade.1, 2, 3 There is no clear cutoff for LDN dosage, however. Interestingly, in Kollman et al, satisfactory 95% skin improvement was only achieved with 9-mg daily doses of naltrexone. Other studies have reported 2 patients successfully treated with 12.5 mg and 50 mg of naltrexone., We believe that the importance of dosage for naltrexone in HHD should be emphasized, and we have observed the efficacy of medium-dose naltrexone (MDN) in 2 patients.The first patient was a 112-kg woman in her 30s with a 10-year history of HHD poorly responsive to 0.05% topical clobetasol propionate, several courses of antibiotics during exacerbations, and a 2-month treatment with 20 mg methotrexate weekly. She consulted for disease exacerbation, with 15% body surface area (BSA) involvement associated with a Staphylococcus aureus superinfection. The methotrexate was stopped, and she was given a 5-day course of antibiotic treatment with clavulanic acid and amoxicillin and naltrexone at 12.5 mg per day (MDN), associated with 0.05% clobetasol propionate. After 2 weeks, her wounds began to heal. Three months later, she presented a complete response, which was sustained at 14 months (Fig 1), and she had no adverse reactions.
Fig 1
Patient 1—clinical response to 12.5 mg naltrexone daily. Clinical photographs show (A) intertriginous maceration of patient 1 at baseline and (B) sustained, complete response after 14 months of treatment.
Patient 1—clinical response to 12.5 mg naltrexone daily. Clinical photographs show (A) intertriginous maceration of patient 1 at baseline and (B) sustained, complete response after 14 months of treatment.The second patient was a woman in her 50s with a 20-year history of HHD. The state of her disease was persistent, with no interspersed remission periods in the previous 6 years despite topical corticosteroids and tacrolimus and several courses of systemic antibiotics. At admission, she weighed 52 kg and had 10% BSA involvement associated with a documented S aureus superinfection. Local skin treatment, 1 g pristinamycine 3 times daily, and 12.5 mg naltrexone daily were initiated. After 8 days of treatment, her wounds were almost healed, and she achieved complete remission 6 weeks after MDN initiation. At 10 months, she presented a sustained partial remission, with the exception of a discrete erythema in the inguinal and groin creases (Fig 2). Regarding safety, she only reported loose stools.
Fig 2
Patient 2—clinical response to 12.5 mg naltrexone daily. Clinical photographs show (A) extensive erosive plaques of patient 2 at baseline and (B) almost-complete resolution, except persistence of scabby red patches, after 5 months of treatment.
Patient 2—clinical response to 12.5 mg naltrexone daily. Clinical photographs show (A) extensive erosive plaques of patient 2 at baseline and (B) almost-complete resolution, except persistence of scabby red patches, after 5 months of treatment.The response to naltrexone seems to be heterogeneous according to different dosage regimens and wound severities. Given the effectiveness of MDN reported in the literature and the extended BSA involvement and weight-to-dosage ratio in our first obese patient, we chose a treatment of 12.5 mg MDN (0.1 mg/kg) rather than LDN. Her rapid, complete response prompted us to initiate the same dosage in our second patient, who also achieved a sustained and persistent response. Our hypothesis is that a higher dosage may be needed for greater BSA involvement in conjunction with severe inflammation. We also surmise that the dosage should be related to weight and suggest that MDN in patients with obesity could correspond to LDN in nonobese patients.
Fig 1
Fig 2