Interstitial Lung Disease in a Patient With Hydroxyurea-associated Dermatomyositis-like Eruption With Abnormal P53 Expression

Document Type

Conference Proceeding

Publication Date

5-21-2024

Publication Title

Am J Respir Crit Care Med

Abstract

Introduction: Although seldom reported, Hydroxyurea has been known to cause pulmonary toxicity and fibrotic Interstitial Lung Disease (ILD). Hydroxyurea is an antineoplastic medication used to treat leukemias, polycythemia vera, psoriasis and sickle cell anemia. It is a cell cycle specific agent that selectively inhibits DNA synthesis. Common side effects include bone marrow suppression and gastrointestinal and cutaneous manifestations. Cutaneous adverse effects of Hydroxyurea include Dermatomyositis-like eruption (DM-LE) and non-melanoma skin cancers (NMSC). We present a case of ILD in a patient with Hydroxyurea-associated DM-LE with abnormal p53 expression. Case Description: A 73-year-old Caucasian male, nonsmoker, with a history of polycythemia vera on hydroxyurea for 22 years, NMSC, and reflux presented for evaluation of dyspnea and cough for 4 months. On physical examination he had dystrophic nails, Gottron's papules, mechanic's hands, poikiloderma, telangiectasias, hyperkeratotic papules and tenderness in his PIP joints. Autoimmune workup revealed elevated Rheumatoid factor and aldolase levels. Computed tomography chest showed basilar predominant reticulation with traction bronchiectasis in a probable Usual Interstitial Pneumonia pattern. Pulmonary function testing showed a restrictive pattern with diffusion impairment. Skin biopsy showed interface dermatitis with vacuolar alteration and positive p53 staining, consistent with a diagnosis of DM-LE with abnormal p53 expression. Following evaluation in combined Rheumatology-ILD clinic and discussion at ILD multidisciplinary meeting, the differential diagnoses of Idiopathic pulmonary fibrosis (IPF), Hydroxyurea associated ILD, and ILD secondary to amyopathic DM were considered. Hydroxyurea was discontinued and the patient was started on Nintedanib for IPF/Progressive pulmonary fibrosis. He was started on Ruxolitinib, a JAK1 and JAK2 tyrosine kinase inhibitor, for the treatment of polycythemia vera and possible DM and he was referred to oncology for cancer screening for DM. Discussion: In patients on Hydroxyurea, druginduced pulmonary toxicity should be considered in the differential diagnosis of fibrotic ILD. Hydroxyurea can cause DM-LE due to a chronic phototoxic process involving aberrant keratinocyte p53 expression and UV radiation exposure. DM-LE, previously considered a benign entity, may represent a premalignant precursor of NMSC. DM-LE typically resolves after cessation of Hydroxyurea. However, persistence of lesions despite cessation of Hydroxyurea suggests unmasking of true amyopathic DM. JAK/STAT inhibitors such as Ruxolitinib have recently been suggested as a therapeutic option for ILD. This complex case highlights the multidisciplinary approach and diagnostic challenges of ILD with cutaneous manifestations suggestive of DM.

Volume

209

Issue

9

First Page

A7062

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