Background Treprostinil is a synthetic prostacyclin analog, commonly used in the treatment of pulmonary hypertension. It can be given intravenously, subcutaneously via continuous pump, orally, or by inhalation. Typical adverse effects of the oral version include headache, nausea, vomiting, diarrhea, flushing, and dizziness. Here, we present a case report of an 80-year-old male with pulmonary hypertension (PH) who developed diffuse erythematous maculopapular rash while transitioning from intravenous treprostinil via subcutaneous pump to oral treprostinil.

Case Presentation Patient is an 80-year-old male with severe pulmonary hypertension WHO group 1 and 3 who presented in clinic for evaluation of rash. He had previously been taking IV treprostinil 3.1 ng/kg/min via continuous subcutaneous pump for about eight months. He desired transition to oral treprostinil and began taking oral treprostinil 0.125 mg TID with plans to titrate up to 1 mg TID. On week two of the titration, while on 0.25 mg TID, the patient developed diffuse maculopapular erythematous rash, which was non-pruritic. He had no fever, mucosal involvement, or respiratory complications. Laboratory investigations revealed peripheral eosinophilia (0.84 K/uL, normal range <0.70 K/uL) but were otherwise normal. Serum IgE levels were within normal limits. Punch biopsy revealed orthokeratosis, mild spongiosis, and mild superficial perivascular and interstitial inflammatory infiltrate. These results indicated a dermal hypersensitivity reaction. Based on clinical picture, laboratory results, and histopathological findings, it was suspected that the patient’s rash was an idiosyncratic drug reaction associated with his upward titration of oral treprostinil. Patient was started on oral diphenhydramine 25 mg BID x10 days and oral prednisone 20 mg BID x7 days. The rash resolved within two weeks, therefore treprostinil titration was continued. The patient is now stable on oral treprostinil 1 mg TID without recurrence of rash.

Discussion Cutaneous adverse drug reactions (cADRs) pose a significant issue in the world of modern medicine, especially as medication regimens become more complex. Despite their frequency, information on incidence, symptomology, and long-term sequelae of cADRs is often underreported. Clinical trials of oral treprostinil have reported skin rash with little frequency. Furthermore, there do not appear to be any other case reports involving a maculopapular rash in response to oral treprostinil. Providers should be made aware of this rare reaction, espeically given the random, unpredictable nature of idiosyncratic drug reactions. Proper documentation of these cases is also crucial, as pharmacovigilance serves to advance scientific knowledge and improve patient care as a whole.