LAUSR

Dear Editor, Rosacea is a common skin condition with multiple pathophysiologic pathways and triggers involved (alcohol, heat, neurovascular dysregulation, aberrant innate immunity, skin barrier dysfunction, and Demodex folliculorum infestation). This manuscript reports what we believe to be the first case of rosacea triggered by selexipag, a recently approved oral selective nonprostanoid prostacyclin receptor (IP receptor) agonist. The only indication of this drug is the treatment of advanced pulmonary arterial hypertension (PAH). A 22-year-old woman presented to our Dermatology Department with a history of facial asymptomatic erythema, papules, and pustules that had started to appear 2 weeks after initiating oral selexipag. She had a history of idiopathic PAH that had been diagnosed 3 years prior to the initiation of selexipag, the main symptoms of it being dyspnoea and syncopes. She had previously received sildenafil and macitentan, but they were discontinued due to the lack of symptom control and worsening of right ventricular function. Selexipag was started at a dose of 200 mg twice a day. During the initial weeks of the new treatment, only mild malar erythema developed. With the weekly increases of the dosing and the reach of the maintenance dose of 1 mg twice a day, a papular component started to appear. Apart from PAH, the patient had no other comorbidities. Dermatological examination 16 weeks after initiation of selexipag showed erythematous papules and pustules over a background of persistent facial erythema, distributed mainly on the forehead, malar area, and chin (Figure 1). There were no other skin regions affected. The patient was only taking oral selexipag, and she was not applying any topical treatments nor any other cosmetic creams. As this case presented to our department prior to the COVID-19 pandemic, the patient was not using a facial mask that could have worsened the clinical presentation. She was treated with oral doxycycline (100 mg daily) for 3 months. After that period, the papulopustular component cleared, but a mild background of erythema still persisted (Figure 2). The patient did not want further treatment for the erythema. Possible treatments would have been topical brimonidine (0.33% gel) or pulsed dye laser. Selexipag acts as a selective agonist of the IP receptor, which is a G protein-coupled receptor. Upon activation, it increases intracellular levels of cyclic adenosine monophosphate (cAMP), thus leading to vasodilation. The IP receptor is mainly expressed on platelets and smooth muscle cells. Agonists of the prostacyclin pathway have been used through recent medical history as a treatment for Raynaud disease and PAH due to its vasodilating effects. It is known that prostacyclin and other prostaglandins are an exogenous cause of facial flushing. Thus, we could hypothesize that a continuous agonist effect on the IP receptor induced by selexipag could lead to a persistent state of vasodilation of the facial skin vessels. In this way, predisposed individuals could be more prone to developing rosacea. Papules and pustules have been linked to an increase in Th17, Th1 cells, and neutrophil-recruiting chemokines. With the knowledge we have today, we still lack a convincing explanation for the inflammatory component.