Oral Magnesium: A Novel Approach in the Management of Hailey-Hailey and Darier Disease

To the Editor,

Darier disease (DD) and Hailey-Hailey disease (HHD) are autosomal dominant genodermatoses caused by mutations in genes encoding Ca²⁺ ATPase pumps: SERCA2 in the endoplasmic reticulum for DD and hSPCA1 in the Golgi apparatus for HHD. These alterations lead to abnormal intracellular calcium signaling, impairing the processing of junctional proteins. As a result, both diseases are characterized by acantholysis due to disrupted epidermal adhesion, while DD also presents dyskeratosis related to increased apoptosis. Clinically, HHD manifests with blistering and erosions in intertriginous areas, whereas DD presents keratotic papules in seborrheic and acral regions. Both conditions are often complicated by secondary infections, malodor, and vegetating plaques. Currently, no specific therapy targets acantholysis or dyskeratosis, and treatment mainly focuses on managing inflammation, infection, hyperkeratosis, and sweating (Supplemental Figure 1).

Recent reports have suggested a potential role for oral magnesium therapy in HHD, with possible benefits also hypothesized for DD.^{1 -3} We report 4 cases—2 with HHD and 2 with DD—treated with oral magnesium pidolate (4.5 g/day).

The first case involved a 67 year-old woman with longstanding erosive lesions in inframammary and axillary folds, confirmed as HHD by biopsy. Due to allergic contact dermatitis from topical corticosteroids, oral magnesium was initiated, resulting in marked improvement within 1 month. Treatment discontinuation led to relapse, while reintroduction restored disease control. No side effects or laboratory abnormalities were observed.

The second case was a 45 year-old woman with biopsy-proven HHD presenting with erosive and brownish papular lesions resembling an overlap between HHD and DD. After 3 months of magnesium therapy, erosive lesions healed, although papular lesions persisted. Treatment was well tolerated and continued with stable results over 1 year.

The third case involved a 28 year-old woman with DD, presenting with scattered brown papules and scaling. Despite multiple prior topical treatments, oral magnesium showed no clinical benefit after 3 months and was discontinued.

Similarly, the fourth case, a 23 year-old man with DD-resistant to topical therapies, did not experience significant improvement after 4 months of magnesium supplementation. No adverse effects were reported.

These observations support previous reports suggesting that oral magnesium therapy may be effective and safe in HHD but not in DD. The differential response may be explained by the distinct calcium pumps involved: hSPCA1 in HHD transports both Ca²⁺ and Mn²⁺ into the Golgi apparatus, and magnesium may enhance intracellular calcium availability, promoting desmosome assembly. In contrast, SERCA2 dysfunction in DD affects calcium transport into the endoplasmic reticulum, a mechanism not influenced by magnesium supplementation.^4,5

In conclusion, oral magnesium appears to be a well-tolerated and potentially effective therapeutic option for HHD, particularly during disease flares, while its role in DD remains unsupported. Larger clinical trials are needed to define optimal dosing and confirm efficacy in HHD patients.