A Puzzling Pericardial Effusion: Unraveling the Mystery of Isoniazid-Induced Lupus

Abstract Introduction: Drug-induced lupus (DIL) is a rare but clinically significant autoimmune disorder triggered by exposure to certain medications. With the increasing use of biologic agents and other novel drugs, over 100 medications have been linked to DIL, a list that continues to grow. Here, we report a case of a 70-year-old male who developed isoniazid-induced lupus after 4 months of treatment for pan-sensitive tuberculosis. Description of Case: A 70-year-old male with a history of pulmonary tuberculosis on rifampin and isoniazid, presented after a fall at home. Initial vital signs revealed a blood pressure of 72/58 mmHg with a mean arterial pressure of 58 mmHg requiring norepinephrine. Laboratory findings revealed an elevated serum creatinine of 14.96 mg/dl (baseline 0.6 mg/dl) with concomitant proteinuria, necessitating acute hemodialysis. Electrocardiography showed sinus bradycardia with low voltage QRS complexes, and subsequent transthoracic echocardiography identified a large pericardial effusion with concern for impending tamponade. He required a pericardiocentesis with fluid analysis testing negative for an infectious etiology. Autoimmune testing conducted to further elucidate the etiology of his pericardial effusion and acute renal failure revealed an elevated antinuclear antibody (ANA), anti-double-stranded DNA (anti-dsDNA), anti-chromatin, anti-histone and anti-cardiolipin antibodies, strongly suggesting DIL secondary to isoniazid. The patient was started on pulse-dose corticosteroids pending a renal biopsy. However, his clinical course was complicated by hypoxic respiratory failure, and he ultimately died before further diagnostic testing could be performed. Discussion: Isoniazid has been a cornerstone of tuberculosis therapy for decades but is also recognized as a potential trigger for drug-induced lupus, a syndrome that mimics systemic lupus erythematosus (SLE) in its clinical and serologic presentation. There are no universally accepted diagnostic criteria for DIL, however, the diagnosis is likely present when recent treatment with a known medication causes the development of clinical and laboratory evidence of SLE that resolves with discontinuation of the medication. The clinical features of DIL are often drug-specific, with serositis, particularly pericardial and pleural effusions, being characteristic diagnostic features. In this case, after excluding infectious causes for the pericardial effusion, the differential diagnosis expanded to include lupus nephritis, as the patient's renal failure and autoimmune serology were highly suggestive of DIL. Although pericardial effusion can arise from numerous etiologies, clinicians should consider DIL, especially in patients with a history of using medications known to be associated with this condition.