Cocaine and Tubulointerstitial Nephritis With Isolated ANA Positivity: Drug-Induced Autoimmunity or Lupus Mimicker?

Tubulointerstitial nephritis is a common cause of acute or chronic kidney injury, typically attributed to infectious, autoimmune, or toxic etiologies. Cocaine use, especially when adulterated with levamisole, has been linked to immunomodulatory agent known to trigger unusual autoimmune phenomena, even in the absence of classic lupus or ANCA-associated vasculitis criteria. Isolated antinuclear antibody positivity in this setting presents a diagnostic challenge. Its presence without other specific autoantibodies or immune complex-mediated glomerulopathy suggests a drug-induced autoimmune reaction or lupus mimicker.We present the case of a chronic drug user who developed TIN and isolated ANA positivity, and no other autoantibodies, raising the question: drug-induced autoimmunity or lupus mimicry?

A 51-year-old man with a history of chronic alcoholism and use of cocaine, methamphetamines clobenzorex, and energy drinks presented with subacute proximal muscle weakness, nausea, vomiting, generalized jaundice, nystagmus, and dark urine.Initial labs showed mild CK elevation, mixed hyperbilirubinemia with direct predominance, and a cholestatic pattern. Severe electrolyte disturbances were also found, including hyponatremia, hyperkalemia, hypochloremia, and mild metabolic acidosis. Abdominal ultrasound ruled out biliary obstruction, showing hepatic steatosis with perihepatic fluid (Figure 1). Hyponatremia was treated with cautious infusion of hypertonic saline under close monitoring.

Renal function tests revealed severe azotemia, urinalysis and urinary sediment  showed microscopic hyaline casts, abundant degenerating polymorphonuclear cells, isomorphic erythrocytes without acanthocytes and  no nephrotic-range proteinuria (Figure 2).

Immunologic workup revealed ANA titers of 1:640 with various patterns (homogeneous, centromere, nucleolar), but all specific autoantibodies and Serologies for HIV, HBV, and HCV were non-reactive and negative (Table 1). As an additional finding during metabolic evaluation, a diagnosis of type 2 diabetes mellitus was established based on an HbA1c of 9.5% and persistently elevated blood glucose levels. Given the autoimmune suspicion a kidney biopsy was performed.

Kidney histology showed active TIN with eosinophilic infiltrate, acute tubular injury, >50% interstitial fibrosis, class IIA diabetic mesangiosclerosis, and chronic arteriolosclerosis. Immunofluorescence was negative. The patient received three IV methylprednisolone pulses followed by a prednisone taper, without renal recovery. Hemodialysis was initiated. During hospitalization, he developed melena and acute anemia. Endoscopy revealed multiple Forrest III gastric ulcers. A direct Coombs test was positive without hemolysis, suggesting immune dysregulation.

This case highlights a rare but increasingly recognized entity of drug-induced eosinophilic TIN with isolated ANA positivity, mimicking lupus serologically but lacking diagnostic criteria. The absence of specific autoantibodies and immune deposits, combined with toxic exposure history, supports a drug-induced mechanism. Recognizing this diagnostic pattern is crucial to differentiate drug-induced injury from primary autoimmune disease and avoid misdiagnosis or overtreatment.