Severe bullous pemphigoid associated with pembrolizumab therapy for metastatic melanoma with complete regression.

Bullous pemphigoid (BP) is considered to be a humorally mediated autoimmune disease, but autoreactive T-cells and T-regulatory cells (Tregs) have also been implicated in this disease. Tregs and the programmed death-1 (PD-1) : programmed death ligand (PD-L) pathway are both critical in terminating immune response, and elimination of either can result in breakdown of tolerance and development of autoimmunity. We report a patient with metastatic malignant melanoma (MM), who underwent pembrolizumab (anti-PD-1) therapy following unsuccessful treatment with ipilimumab [anti-cytotoxic T-lymphocyte-associated protein (CTLA)-4]. The patient developed BP with increasing serum titres of anti-BP180 IgG autoantibodies and increasing disease severity during pembrolizumab therapy. High doses of corticosteroids and methotrexate were needed to control the BP. Following the termination of pembrolizumab therapy, imaging showed complete regression of all metastatic sites. This result may indicate a crucial role for T-cell suppressive activity in controlling and preventing BP.

Flight-associated headaches-prevalence and characteristics.

Environmental factors in airplanes may precipitate headaches. We conducted a questionnaire-based study among consecutive travellers to determine the rate, severity and duration of flight-associated headaches (FAHA). Of the 906 eligible travellers (mean age 33.3 +/- 13.8 years), 22.3% reported headaches at least once per month. FAHA occurred in 52 travellers (5.7%), of whom 34 were women (P = 0.0023 vs. none FAHA). The duration of pain was 4.0 +/- 10.2 h after takeoff and continued for 5.7 +/- 14.2 h after landing. Migraine was diagnosed in 19.2% of those with FAHA. The magnitude of headache was 6 +/- 2 (on a scale of 1-10). Among those who suffer from FAHA, 45.4% reported that their pain was unilateral, in contrast to 72.7% among those with 'non-flight' headaches (P = 0.019). Nine travellers had headaches when descending to -400 m below sea level, and nine upon climbing to high altitude. This preliminary observation indicates that FAHA is not uncommon and should be further investigated.