(67) Improving Cutaneous Manifestations of Autoimmune Progesterone Dermatitis with Janus Kinase-Inhibitors

Background: Autoimmune Progesterone Dermatitis (APD) is rare and usually diagnosed in women in their 20s and 30s. The hallmark presentation of APD is monthly cutaneous eruptions (urticaria, eczema, ulcerated oral lesions, targetoid rash, angioedema) occurring 2-10 days before the onset of menstruation; improvement is seen on days 2-3 of menses.

Case: A 14-year-old female presented with angioedema, oral ulcers, and targetoid skin papules of the hands. At first, she was diagnosed with presumed HSV gingivostomatitis and treated to no avail with acyclovir. Due to worsening symptoms and repeat hospitalizations, she underwent an extensive multi-disciplinary work-up (dermatologic, rheumatologic, gastroenterological, and infectious).
Early in her work-up, she had an oral biopsy consistent with viral-induced lichenoid mucositis that responded limitedly to a prednisone taper and empiric doxycycline for EBV mucositis. However, in the following months, she had bouts of generalized bodily urticaria and painful hand blisters, consistent with persistent erythema multiforme (PEM). She required multiple steroid courses and was also trialed on Colchicine and Etanercept.
Eventually, the eruptions were determined to have onset 2-3 days before menses, and she was subsequently referred to Pediatric Gynecology for suspicion of APD. Given the severity of her symptoms, instead of progesterone testing, she was trialed on a GnRH agonist (Lupron) for diagnostic and therapeutic purposes. While on Lupron, she became amenorrheic and continued to have mild oral flares but no other skin manifestations. She developed intolerable side effects with Lupron and was transitioned to a low-dose progesterone oral contraceptive pill (OCP). In addition, symptoms remitted with the initiation of Upadacitinib, a Janus kinase (JAK)-Inhibitor.

Comments: APD is difficult to diagnose due to complex manifestations, yet the prevalence of APD has increased by 43% from 2016 to 2021. Treatment usually consists of OCPs or GnRH agonist injections and can be definitively managed surgically with bilateral oophorectomy. Desensitization has had limited success in patients who don’t desire surgery or hormone therapy. Often, antihistamines and steroids alone are insufficient, but other drugs, tamoxifen, ulipristal acetate, and danazol, have shown some effectiveness in APD.
Marked symptom relief for patients with PEM has been observed with the inhibition of the JAK pathway by down-regulating IFN-γ and IL-15. Our patient’s striking progress after adding a JAK inhibitor is promising for future study of targeted immunologic therapy in patients unresponsive to hormonal management alone.