Apremilast

Abstract

Pseudotumor of the larynx, diarrhoea and abdominal pain: case report A 74-year-old woman developed pseudotumor of the larynx, diarrhoea and abdominal pain during treatment with apremilast for severe plaque psoriasis. The woman had a history of hypertension, atrial fibrillation and chronic obstructive pulmonary disease. She was a nonsmoker. She had been diagnosed with extensive plaque psoriasis 10 years ago. Her plaque psoriasis was initially treated with ultraviolet B phototherapy; however, there was a rapid relapse of the cutaneous plaques and severe pruritus. A subsequent treatment with methotrexate resulted in liver toxicity, despite the successful elimination of the plaques and the pruritus. She was continued on dense phototherapy sessions until October 2017 when exacerbated symptoms, mainly severe pruritus prompted a reassessment of the treatment strategy. Considering her age and cardiovascular comorbidities, treatment with biological agents (e.g., infliximab) was assessed by the dermatologist as inappropriate, thus a standard dose of apremilast 60mg twice a day was prescribed [route not stated]. Except for severe transient diarrhoea and a slight abdominal pain during the first 2 weeks, apremilast was well tolerated with a near-complete resolution of the psoriasis lesions. She was referred to the otolaryngology department in October 2018 with a 3-month history of dysphagia, unilateral odynophagia and dyspnoea. An oral contrast swallow examination had shown an expansive lesion in the right side of the hypopharynx. The clinical examination revealed a supraglottic submucosal mass without mucosal engagement, under the right aryepiglottic fold, extending posteriorly to hypopharynx, medially to false vocal cord and laterally to the lateral wall of the pharynx displacing epiglottis to the left side. The laryngeal vestibulum was partially occluded thus causing a mild inspiratory stridor. The laboratory investigations confirmed elevated levels of CRP and WBC count. Further investigation with a CT showed a 2.5-cm mass arising from the lateral wall of the pharynx, loading contrast irregularly, suggesting a possibly malignant tumour. Core needle biopsy from the lesion under general anesthesia showed fibrosis with chronic nonspecific inflammation and hyperplastic squamous epithelial fragments. A second suspension laryngoscopy was performed to obtain more representative specimens for pathology assessment. Despite the combination of CO2 laser dissection together with cold instruments, it was impossible to reveal a demarcated mass; however, deep cold forceps biopsies were obtained. Because of the progress of the expansive lesion within a few days and the risk for a compromised airway due to an unstable aryepiglottic fold with a tilting right arytenoid cartilage in the laryngeal vestibule, a tracheostomy was performed concurrently. Again, the biopsies were not conclusive, showing unspecific acute and chronic inflammation with fibrosis. Complementary pathological examination showed no signs of vasculitis, IgG4-related disease or amyloidosis. In a parallel immunological workup including ANA, ANCA, anti-CCP, a marginal increase in ANA was found not regarded though as diagnostic. Apremilast medication was discontinued in December 2018 following a suspicion that the pseudotumour could be a side effect of the treatment. In January 2019, she presented to the emergency department due to dislodgement of the tracheostomy tube. Laryngoscopy revealed a substantial reduction of the pseudo-tumour allowing for safe decannulation. Subsequent follow-up showed an almost complete remission of the pseudotumour, both clinically and radiologically. She recovered almost completely after 6 months having just a mild functional dysphonia. This previously unknown side effect (i.e. pseudotumor of the larynx) was reported to the Swedish Medical Products Agency [outcome of mild abdominal pain not stated].