Subcorneal pustular dermatosis (SPD), also known as Sneddon-Wilkinson disease, is a skin condition for which treatments are poorly codified. Anti-tumor necrosis factor alpha (TNFα) efficacy has been reported in multidrug-resistant SPD, as in our two cases. In the first case, an 83-year-old woman was monitored for SPD, associated with monoclonal IgA gammopathy. After multiple-line treatment failure, infliximab (5mg/kg) led to clinical improvement, noted few days following the first injection, and with complete remission at one month. At 12 months, the patient relapsed and concomitant serum anti-TNFα antibodies were found. A switch to adalimumab led to complete remission in three months with a follow-up of six months. In the second case, a 62-year-old woman was monitored for SPD associated with monoclonal IgA gammopathy recalcitrant to different lines of treatment. Treatment with adalimumab (40mg every two weeks) in combination with dapsone led to significant improvement after two injections. Five months later, she relapsed. It was then decided to reduce the interval between injections to once a week. Rapid improvement was achieved in one month allowing resumption of the original frequency of the injection without relapse after 20 months of follow-up. In conclusion, our cases confirm the previously reported efficacy of anti-TNFα in resistant SPD. They also highlight a risk of secondary loss of efficacy, reinforced by the literature data. Substitution of another TNFα blocker or shortening of interval between injections provided a renewal in response to treatment.