Development of Cocaine-Induced Interstitial Lung Damage in Two CYP2C and VKORC1 Variant Allele Carriers
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CASE REPORT
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Development of Cocaine-Induced Interstitial Lung Damage in Two CYP2C and VKORC1 Variant Allele Carriers Petal A.H.M. Wijnen,1,2 Otto Bekers1,2 and Marjolein Drent2,3 1 Department of Clinical Chemistry, Maastricht University Medical Centre (MUMC), Maastricht, the Netherlands 2 interstitial lung disease (ild) care consultancy, Maastricht, the Netherlands 3 Department of Respiratory Medicine, MUMC, Maastricht, the Netherlands
Abstract
Background: Often, the connection between drug use and the development of related inflammatory damage or idiosyncratic toxicities is hard to recognize and objectify. The presence of cytochrome P450 (CYP) variant genotypes appears to be a substantial susceptibility risk factor in the development of drug-induced pulmonary adverse events. We hypothesized that the presence of variant alleles may be associated with serious complications of illicit drug use. Case Report: We report the cases of two cocaine users who developed a ‘flu-like’ syndrome with diffuse interstitial infiltrates after cocaine abuse. Genotyping for CYP (CYP2C9, CYP2C19) and vitamin K epoxide reductase complex 1 (VKORC1) allelic variants (-1639G/A and 1173C/T) was performed in these two patients. Both cases were heterozygous for VKORC1 variant alleles, and both possessed a CYP2C polymorphism (case 1: CYP2C19*1/*2; case 2: CYP2C9*1/*3). Conclusions: The described drug abuse cases suggest that an association between the presence of CYP2C and VKORC1 allelic variants and cocaine-induced interstitial lung damage is highly likely. It is assumed that these polymorphisms contribute to intra-individual variability in drug response and toxicity, including cocaine response and toxicity. Moreover, the importance of including pharmacogenomics in the work-up of patients with suspected drug-induced (lung) toxicity, such as alveolar hemorrhage, is highlighted by these cases.
1. Introduction Cocaine abuse represents one of the most serious medical and social problems of our time. Cocaine is the most commonly used illicit drug among patients seen in emergency departments and is the most frequent cause of drug-related deaths reported by medical examiners.[1] Cocaine and marijuana are very popular illicit drugs, acting as stimulants of the central nervous system. Besides heart rhythm disturbances, acute and chronic parenchymal lung injuries are not uncommon complications resulting from inhalation of these drugs in habitual drug users.[1] Different types of interstitial lung damage due to cocaine or marijuana inhalation – including acute pulmonary hemorrhage, diffuse alveolar infiltrates, and eosinophilic infiltrates – have been described.[2,3] Many inhaled chemicals are not hazardous as such but are biotransformed into reactive intermediates.[2] To date, the mechanism of the resulting lung injury is not fully
understood, but a direct toxic effect of the inhaled agent, occurring in a dose-dependent pattern, is most highly suspected.[1] To the best of our knowledge, no under
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