Subacute lupus erythematosus (SCLE) (A-C) and discoid lupus erythematosus (DLE) (D). A-C, Patient with SCLE before and after 2 to 4 weeks of twice-daily treatment with ASF-1096 (Astion Pharma, Copenhagen, Denmark). D, Patient with DLE before and after 11 months of twice-daily treatment with ASF-1096.
Wulf HC, Ullman S. Discoid and Subacute Lupus Erythematosus Treated With 0.5% R-Salbutamol Cream. Arch Dermatol. 2007;143(12):1589-1603. doi:10.1001/archderm.143.12.1589
Treatment of discoid lupus erythematosus (DLE) and subacute lupus erythematosus (SCLE) includes topical or systemic glucocorticosteroid, chloroquine, methotrexate, retinoids, and even thalidomide.1 In severe cases, these treatments may be ineffective or not well tolerated leading to cessation of therapy or lack of compliance. Alternative treatments to modify the autoimmune response in the skin would therefore be useful.1,2
We investigated the effect of ASF-1096 (Astion Pharma, Copenhagen, Denmark) in an explorative study. The active substance is a sulfate salt of R-salbutamol in 0.5% concentration in an oil-in-water emulsion. R-Salbutamol has various anti-inflammatory effects and inhibits proliferation and secretion of IL-2 and interferon γ in human T cells stimulated with phytohemagglutinin.2 Furthermore, R-salbutamol inhibits superoxide generation and peroxidase release from stimulated human granulocytes.3,4 These effects might have therapeutic potential in cutaneous lupus.
Nine consecutive patients entered this prospective explorative investigation, 5 with treatment-resistant DLE and 4 with SCLE. Patients were asked to discontinue treatment with topical glucocorticosteroid and use R-salbutamol cream twice daily on affected skin areas or parts thereof. Photographic documentation was performed before and during treatment. The patients were seen every 2 to 3 weeks. The treatment efficacy was evaluated by the physician using assessment of symptoms and disease grade. The physician graded the effect of the treatment on a 4-point scale: 0, no effect; +, slight improvement; ++, some improvement; and +++, pronounced effect. The adverse effect of dermatitis was graded in the same way (Table).
Results and patient data are listed in the Table. Images of patients before and after treatment are presented in the Figure.
The 4 patients treated for SCLE all responded within a few days and had pronounced effect after 2 to 3 weeks. After “healing,” some patients reported that the skin reaction could change from day to day from totally cleared to slightly erythematous. After each application, some patients experienced diminished itch within minutes and complete relief from itch after a few days (Table).
After experiencing a primary beneficial effect, 2 of the patients developed an adverse event in the form of dermatitis in parts of the treated area, one in the face and the other on the back. This reaction started after 4 to 6 weeks of use and after the full effect had been obtained. The dermatitis ceased within 4 to 6 days of topical glucocorticosteroid application, leaving no flare in the lupus. Thereafter, treatment was resumed in 1 of the patients using a different cream vehicle, which was tolerated.
The 5 patients with DLE underwent treatment on hypertrophic lesions as well as relatively new and nonhypertrophic lesions. Some minor effect was seen on the hypertrophic elements beginning after 2 months of treatment (Figure, D). The relatively new and nonhypertrophic lesions responded well but to a lesser degree than the SCLE. Two patients reported excellent effect, while 2 others reported no effect. However, 1 of the latter had bad compliance.
The skin lesions fluctuated in severity over time, especially in SCLE. We can assume that these fluctuations were not related to the time of year because treatment was initiated at different times of the year. The fluctuations give a risk of bias; however, the effect of the treatment on new and nonhypertrophic lesions was very fast and was sustained during the treatment period, though without 100% clearance (Table). Old hypertrophic lesions are difficult to treat, and it was therefore positive to see a slow improvement over time even in these cases.
When salbutamol is used in a powder formulation for inhalation in patients with asthma, irritation of the mucosa is a known adverse effect, as are tremor and tachycardia.5 It was therefore interesting to notice that a dermatitis could be seen after dermal application as well, although different vehicle formulations were involved. Contact allergy could not be anticipated, since the dermatitis when present was not seen in all the treated areas, and the drug was reapplied without recurrence of the dermatitis in 1 of the patients. Even when treating areas up to 2000 cm2 twice daily, no signs of tremor or tachycardia were observed. No other adverse effects were reported.
An explorative investigation does not have the proper controls used in a controlled clinical trial. However, the results from this investigation seem very promising.
Correspondence: Dr Wulf, Department of Dermatology, Copenhagen University Hospital, Bispebjerg Bakke 23, 2400 Copenhagen NV, Denmark (email@example.com).
Financial Disclosure: Dr Wulf is member of the advisory board of Astion Pharma.