A Case of the Itchy Feet
The Patient: Jack is an 18-year-old boy who presents to the hospital after experiencing a heart attack and massive vomiting. During the work-up, he tests positive for a number of bacteria.
The Diagnosis: Chronic granulomatous disease (CGD)
Working Backwards: In this case, the diagnosis wasn't impossible to make. Fairly early in the episode, House and his underlings run into an interesting finding: positive tests for Hepatitis A, syphilis, Eikenella, and botulism.
"So, we knocked down one infection and three more pop up? I think this game is rigged." - HouseWell actually, any disease that targets the immune system can make you prone to recurrent infections. A relatively common disease that is often tested for in patients with unusual or widespread infections is Human Immunodeficiency Virus (HIV). But since when do House's patients come in with relatively common conditions? Seeing as how 2 of the last 3 House diagnoses (Episodes 305 and 307) have been genetic diseases, it's not a huge leap of the imagination that the writers of House would pick another hereditary condition for this episode. In all fairness, medical students acquire a knee-jerk reaction to thinking about hereditary immune deficiencies when the words "recurrent infections" show up in questions, so the final diagnosis was in some ways not entirely unexpected. However, chronic granulomatous disease isn't the only disease that fits into the category of genetic immune deficiencies, and here's where the medicine becomes interesting.
The Medicine: In order to understand how House arrived at the diagnosis of chronic granulomatous disease (CGD), you need to know a little bit about how the normal immune system works. The immune system is made up white blood cells, which are often fancily referred to as leukocytes or WBCs. There are five major types of white blood cells that make up the immune system: lymphocytes, monocytes (aka macrophages), basophils, neutrophils, and eosinophils.
Lymphocytes come in three flavors, B-cells, T-cells, and Natural Killer (NK) cells. B-cells can become plasma cells and produce antibodies. T-cells exist in 2 forms, helper T-cells and killer T-cells. Helper T-cells are a bit like antibodies and help tag bacteria for destruction. Killer T-cells and NK cells do exactly what it sounds like they do -- they kill bacteria. Monocytes are big and slow Pacman-like cells that eat other cells whole. It can take 3-5 days for these bad boys to arrive on the scene, and so the immune system has neutrophils, which are smaller and stealthier. Basophils are basically wimps. Eosinophils fight crime in the form of parasitic infections.So where does CGD fit into all this? Well, CGD affects the ability of neutrophils to eat bacteria. Just before healthy neutrophils eat a cell, they like to spray it with it with detergent (Picture bleach being splattered onto a bacterium and the bacterium writhing in pain). Why the need for detergent? Well, as sad as it is, neutrophils lack teeth and so they need a way to chew up the bacteria so that they can swallow it (apparently, neutrophils have throats and stomachs). They take electrons from a compound known as NADPH (nicotinamide adenine dinucleotide phosphate-oxidase) and transfer it onto oxygen to make superoxide, which is toxic to cells. In CGD, the enzyme that makes superoxide is broken, so the neutrophils suck at their jobs. Infections run rampant.
Not all infections run rampant though. This is the basis for the kooky "test" that House runs by injecting Jack with all those different bacteria. Interestingly, bacteria are neutrophil-wannabes in one way. Bacteria also have an enzyme that makes superoxide. Instead of using superoxide to kill bacterial cells, bacteria release superoxide to kill human cells. Sometimes, with all the superoxide flying around, bacteria can get caught in the crossfire and die off. Certain bacteria have an enzyme (called catalase) that can disarm superoxide, which prevents them from being killed by the crossfire. Bacteria (and fungi) that have catalase include Staphylococcus, Aspergillus, and Gram-negative rods (which includes Serratia and sometimes Eikenella). This is why when House injected all those different organisms into Jack, Serratia won out. Syphilis (caused by the bacterium Treponema pallidum) and botulism (caused by Clostridium botulinum) generally do not have catalase, although this doesn't exlude their ability to infect Jack, given that he has other catalase-containing bacteria to help out.
One final point: CGD is usually passed from one generation of a family to the next on patients' X-chromosomes, which means that males are predisposed to manifesting the condition. Since neither of Jack's parents were seemingly affected, his mom was the likely carrier (since her other normal X-chromosome made up the losses of the mutated one).
What's the deal with the itchy feet? For some reason, House was really caught up on Jack's itchy feet. Apparently, according to Harrison's (a big thick textbook), CGD can be associated with seborrheic dermatitis, which could in theory cause itching. I actually got thrown off by this whole itching symptom because one of the immune deficiencies that is classically associated with itching (in the form of eczema) is Wiskott-Aldrich syndrome. Lastly, the itching could have been due to a fungal infection, seeing as how Jack's immune system isn't so great. Most likely, Cameron was right when she said that he got it from wearing sweaty socks while running around at work. That's how my feet feel when I'm post-call.
posted by k-deep at 7:37 PM
1 Comments:
Wow, a programme referencing CGD! I am the CGD clinical nurse specialist for the UK and I thought I would add a few comments.
CGD is not only X-linked, and in fact many women who are X-linked carriers suffer with Lupus like symptoms. In the case featured the inheritance may have been autosomal recessive (a non-dominant gene), which will only result in CGD if both parents pass on this gene to their child. The carrier parents would be symptomless and around 40% of CGD is inherited in this way, and therefore affects women as well as men.
House’s ‘kooky test’ may have told us something interesting about CGD and the nature of the fight between the body’s defences and invaders. However, a simple NBT (nitroblue tetrazolium) test would also have confirmed his diagnosis. This involves adding substances to a sample of the patients blood, making the neutrophils change colour as they are stimulated to produce superoxide (or not in the case of the CGD patient. I do appreciate that this method does not make such good TV!
Why not find out more about CGD and the amazing genetics research being done by visiting the website of the CGD Research Trust at: www.cgd.org.uk
Rhian Lant
Clinical Nurse Specialist for CGD.
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