One of the main themes is the blurry line between what is real and what is fiction. For example, the main character here, Dupris, is really Poe. And of course, the author, Avi, is pretending to be Poe pretending to be Dupris. Avi takes many actual incidents from Poe's own life to add texture and reality to his fictional tale of the author, further making "what is/isn't real" harder to discern. (A section at the back of the book about the actual incidents of Poe's life might help you determine where the "facts" are.)
Another theme is that of fraternal twins, two sides of the same person, as it were, for example, in "The Fall of the House of Usher" and here in the characters of Edmund and his sister. Both Avi and Poe seem to be saying that we have both a masculine and a feminine side of our personalities that have to be recognized and dealt with to avoid disaster.