A Case of Hydroxyurea-Induced Interstitial Pneumonitis

Introduction: First synthesized in 1869, Hydroxyurea is known for its efficacy in treating myeloproliferative disorders, cervical cancer, and sickle cell disease. Usually well-tolerated, Hydroxyurea has numerous documented adverse effects, including bone marrow suppression, fevers, gastrointestinal upset, anorexia, and maculopapular rash. In addition, one rare side effect is interstitial pneumonitis, a potentially devastating complication if overlooked. We present one such case of Hydroxyurea-induced interstitial pneumonitis. Case Description: A 65-year-old man with a six-month diagnosis of Chronic Granulocytic Leukemia (CGL) on Hydroxyurea developed acute hypoxemic respiratory failure saturating 80% on room air with HR 102, RR 24, and increasing oxygen requirements (10 Lpm) after being admitted with complaints of worsening dyspnea, fatigue, and productive cough with yellow/green sputum. Physical examination was notable for cachexia, ill appearance, generalized weakness, hoarse voice, tachycardia, tachypnea, diffusely diminished breath sounds, and scattered rales on auscultation of lung fields. Initial imaging was notable for bilateral airspace disease and pulmonary opacities on chest radiography and bilateral pneumonia (concerning for COVID-19 pneumonia), mediastinal adenopathy, and splenomegaly on chest computed tomography. Initial laboratory results were notable for leukocytosis 62.5 th/uL, lactic acidosis 2.5 mmol/L, procalcitonin level 4.95 ng/mL, and negative COVID-19 PCR test. Prompt initiation of Vancomycin/Cefepime therapy ensued upon collection of blood cultures in light of possible sepsis. Flagyl, Valacyclovir, and Posaconazole were added to antimicrobial coverage, along with steroid therapy, due to minimal clinical improvement. Tachycardia with significant oxygen requirements alternating between BiPAP and heated high flow nasal cannula with FiO2 ranging from 70-85% persisted. Daily imaging also showed worsening airspace disease. Negative viral, bacterial, and fungal cultures led to subsequent discontinuation of Hydroxyurea therapy due to suspicion of medicationinduced pneumonitis. Three days after cessation of Hydroxyurea, the patient's oxygen requirements began to decrease and imaging revealed interval resolution of pneumonitic changes in the absence of antimicrobial therapy. The patient was later transitioned to Ruxolitinib for his underlying CGL prior to his discharge home without the need for home oxygen therapy. Discussion: Thought to be caused by hypersensitivity pneumonitis, pulmonary toxicity from Hydroxyurea can easily be misdiagnosed. Unfortunately, while much is known about the pancytopenic, gastrointestinal, and cutaneous side effects of Hydroxyurea, few cases in the literature highlight the potentially fatal interstitial pneumopathy caused by Hydroxyurea, first reported in 1999. Thus, this case serves as an additional contribution to the minutiae of literature detailing Hydroxyurea's adverse pulmonary side effect profile. (Figure Presented).