Young Ian Alston learns to ride a bicycle. When his father picks him up off the bike, he finds blood all over the back of boy's pants.
House, Wilson and Cuddy play poker at a Casino Night fundraiser for the hospital. A doctor alerts Cuddy that Ian is in the ER. The boy has bloody diarrhea, and although he is hemodynamically stable at the moment, he is developing coordination problems. Cuddy orders some fluids and says she'll check on him during her rounds. House asks about the heart rate and inquires if a head scan has been done. Cuddy just wants to focus on the cards, but House quits the game to go check on the boy. In the ER, I an has no problem following House's finger with his eyes. House then asks Ian to grab his cane, and Ian struggles to grasp it. House tells the Alstons that Ian's brain is losing control of his muscles. House goes back to the benefit to grab Chase. He wants the others to meet him upstairs.
House tells the team that there are two cases with identical symptoms, but one patient is six years old and the other is over seventy. He explains that many years ago he had a 73-year old female patient with this exact progression of symptoms, but she died before he could solve the case. Ian already has bloody diarrhea and ataxia. The previous patient, Esther, progressed from there to kidney failure in only 80 minutes. She died in less than a day.
The team is skeptical, figuring that Ian merely has food poisoning. House considers Erdheim-Chester, a disease that Chase mentions has only been recorded 200 times in history. House thinks he could have found case number 201 had Esther's family allowed an autopsy. He orders a colonoscopy for Ian. Cameron explains to the parents that Erdheim-Chester is an abnormal growth of some of the cells that fight infection. During the colonscopy, Foreman thinks they've found the purple papules that House was looking for. Chase is skeptical, figuring House is merely obsessed with a patient he lost long ago.
The papules are biopsied, but come up negative for Erdheim-Chester. House then requests a kidney biopsy. He examines the urine bag attached to the boy. The liquid is brown, which means Ian's kidneys are shutting down. Ian is reaching Esther's third symptom.
The team reconvenes to figure out the symptoms. Chase suggests E. Coli, but House points out he tried that last time. Cameron throws out lymphoma. House agrees that this is a possibility and asks for a blood smear and an MRI. They want to alert Cuddy that her original theory of gastroenteritis is not the cause, but House would rather not tell her anything in case she disagrees and interferes. House calls Wilson at the tables and asks him to keep Cuddy occupied.
The MRI shows that the base of Ian's brain has been infiltrated by a small mass, likely related to the pituitary. Pituitary failure was the fourth of Esther's symptoms. It also somewhat confirms lymphoma, although none of them actually saw it. The blood fact offers a contrary diagnosis. House walks out of the office.
The team finds him breaking into the commissary to get some coffee. He says that the next stop in the disease's progression is the liver. Growing frustrated, House orders the team to give Ian every drug they can think of that will protect the liver.
Chase informs House that the liver is holding, but Ian's platelets are dropping. Oddly, House is encouraged. This is a new symptom, different from anything Esther experienced. Ian begins gasping for breath as Foreman and Chase rush to help him.
House writes respiratory distress on the white board under Ian's symptoms. Respiratory failure was the last of Esther's symptoms before death. Feeling hopeless, House pushes the white board over. With Ian now on a ventilator, the team again tries to analyze the progression of symptoms. Ian is moving even faster than Esther did. Cameron tosses out that the interferon they put Ian on could possibly affect a type of leukemia. House calls Wilson for advice. Wilson comes upstairs to examine Ian's blood, but doesn't see anything askew.
Wilson suggests Kawasaki's disease, in which antibodies eat the inside of the arteries, slowly choking off blood to major organs. Intrigued by the possibility, House prepares to search Ian's coronary arteries for the disease, but the arteries are clear of aneurysms and the blood flow is normal. As he is about to shut down the scan, Chase notices a mass in Ian's right atrial valve. House immediately readies to perform a biopsy.
During the procedure, Ian goes into cardiac arrest. It takes repeated attempts, but House is able to shock the boy back to life. House goes back to the biopsy, which Chase thinks is reckless after eight minutes of arrest.
Back in the office, the team begins throwing other possible diseases against the wall. Cuddy, having been alerted to Ian's plight by the Alstons, barges into House's office and angrily accuses him of giving the young boy brain damage. She thinks he's still obsessed with Esther's case twelve years later. She orders him to stay away from Ian. When Cuddy leaves, House plows ahead anyway. He hands Cameron the piece of mass they extracted and asks how many tests they can complete. She thinks they can do three, even though there are seven potential diseases on their board. They elect to start with histiocytosis, figuring Cuddy will be smart enough to test for sarcoidosis on her own.
The test for histiocytosis is negative, so they turn back to the board. House opts to test for tubular sclerosis, mainly because the test for that is more reliable. Sclerosis also comes up negative. House is now stumped. He stands on his office balcony, lost in thought. Wilson comes out to report how he triumphed in the poker tournament by hiding his pocket aces. The story leads House to an epiphany about what else could have been hiding.
House realizes that when they tested for Erdheim-Chester earlier, it hadn't progressed far enough. He wants to use the last available piece of mass to test for it again. This time, the test confirms the ultra-rare disease. The team immediately starts the proper treatment.