Pathology Student

When people talk about immunodeficiency states, they’re usually talking about secondary immunodeficiencies, like AIDS. The primary immune deficiencies really don’t get much press. Which is unfortunate, because although they are much less common than secondary immune deficiencies, they still occur, and it’s important to understand them for that reason alone. Plus, they are very testable – either on board exams, or on class exams.

Time is short, though, and you need to know the basic points for each one without having to wade through a lot of chapters in a textbook. So, without further ado, here is a short, bullet-pointed list of the main disorders, with particular emphasis on the part of the immune system that is affected, and the clinical manifestations of the disease.

X-linked agammaglobulinemia

• Pre-B cells can’t differentiate into B cells
• Patients have no immunoglobulin (Ig)
• X-linked (so seen only in males)
• Presents at 6 months of age (when maternal Ig runs out)
• Patients get recurrent bacterial infections
• Treatment: intravenous pooled human Ig

Common variable immunodeficiency

• Group of disorders characterized by defective antibody production
• Affects males and females equally
• Presents in teens or twenties
• Basis of Ig deficiency is variable (hence the name) and often unknown
• Patients more susceptible to infections, but also to autoimmune disorders and lymphoma!

Isolated IgA deficiency

• Most common of all primary immune deficiencies
• Cause is unknown
• Most patients asymptomatic
• Some patients get recurrent sinus/lung infections or diarrhea (IgA is the major Ig in mucosal secretions)
• Possible anaphylaxis following blood transfusion (patients have anti-IgA antibodies, and there is IgA in transfused blood!)
• Increased incidence of autoimmune disease   (who knows why)

Hyper-IgM syndrome

• Patients make normal (or even increased) amounts of IgM
• But can’t make IgG, IgA, or IgE!
• X-linked in most cases
• Patients also have a defect in cell-mediated immunity
• Patients have recurrent bacterial infections and infections with intracellular pathogens (e.g., Pneumocystis jiroveci)

DiGeorge syndrome

• Developmental malformation affecting 3rd and 4th pharyngeal pouches
• Thymus doesn’t develop well
• Patients don’t have enough T cells
• Infections: viral, fungal, intracellular pathogens
• Patients may also have parathyroid hypoplasia
• Treatment: thymus transplant!

Severe combined immunodeficiency

• Group of syndromes with both humoral and cell-mediated immune defects
• Patients get all kinds of infections
• Lots of very different genetic defects
• Half of cases are X-linked
• Treatment: bone marrow transplantation

The best way to remember these might be to make a little chart, with the diseases in one column, and subsequent columns for transmission (X-linked or not),  immunologic defect (e.g., no immunoglobulin production), and clinical features (e.g., infant with recurrent bacterial infections).

Photo credit: Wikimedia (http://commons.wikimedia.org/wiki/File:Antibody_je2.png) via cc license.

The MHC (major histocompatibility) complex is a collection of genes on chromosome 6. It’s organized into three regions: the class I region, the class II region, and the class III region. Class I genes encode glycoproteins expressed on the surface of nearly every nucleated cell in the body. These glycoproteins, called MHC I receptors, present antigens (proteins made within that particular cell) to CD8+ T cells. Class II genes encode glycoproteins expressed only on the surface of antigen-presenting cells (macrophages and dendritic cells). These glycoproteins, called MHC II receptors, present antigens (which that antigen-presenting cell has eaten and processed) to CD4+ T cells. The MHC III region encodes a bunch of things, including complement proteins and cytokines.

So what?

Well, your T cells can’t recognize antigen unless it’s shown to them by an MHC receptor (the books say “presented in the context of an MHC receptor” but I like simpler words better). Helper (CD4 +) T cells recognize antigens only when they are presented by MHC II receptors; cytotoxic (CD8 +) T cells recongize antigens only when they are presented by MHC I receptors.

How are you supposed to remember which cells have MHC I receptors and which have MHC II receptors, and which T cell subset recognizes each one? I think of it like this. The MHC I receptor is kind of a low-class, ordinary, run-of-the-mill receptor (hence the common-sounding “I” designation). It’s present on virtually all nucleated cells in the body. The MHC II receptor is a high-class, specialized, advanced kind of receptor (hence the higher “II” designation). Only certain kinds of cells (antigen presenting cells) get to have this receptor. I’m sure that’s not why they named them that – but it helps me remember the numbers if I think of them in this way.

As to the cells that recognize each type of receptor – if you can remember the above, then you can figure out which type of T cell will recognize each receptor. Cytotoxic T cells recognize that type of MHC that is present on all cells in the body: the type I MHC receptor. It has to be this way, because any cell in the body can become infected, and cytotoxic T cells need to have a way to recognize and kill these cells. Helper T cells, on the other hand, recognize only that type of MHC that is present on antigen presenting cells: the MHC II receptor. Which makes sense, because helper T cells need the cytokines released by antigen presenting cells to help them do their job. So they lock onto the MHC II receptor on antigen presenting cells, and while they’re there, they get nice cytokine signals telling them to grow and differentiate.

Image credit: NIH.

Sometimes we (okay, I) get so caught up in describing pathologic mechanisms that real-life examples get the short end of the stick. Let’s look at some real diseases in which the underlying problem is a hypersensitivity reaction.

Type I (allergic) hypersensitivity
The big example (obviously) of this type of hypersensitivity is allergy. Pollen, cat dander, peanuts – they all have the same mechanism and this is it.

Type II  (antibody-mediated) hypersensitivity
There are a ton of diseases that have an underlying type II hypersensitivity reaction going on. Here’s a partial list:

1. Autoimmune hemolytic anemia: the patient makes antibodies to red cell antigens for some reason (not a good thing to do) which end up causing hemolysis.
2. Pemphigus vulgaris: the patient makes antibodies against the proteins connecting epithelial cells together, resulting in epithelial cell discohesion and bullae formation.
3. Goodpasture syndrome: the patient makes antibodies that react against proteins in both the glomeruli and the alveoli, leading to nephritis and lung hemorrhage.
4. Myasthenia gravis: the patient makes antibodies that bind to the acetylcholine receptor (on the muscle end plate), preventing acetylcholine from binding and doing its job; the end result is muscle weakness.
5. Graves disease: the patient makes antibodies that bind to the TSH (thyroid-stimulating hormone) receptor on thyroid epithelial cells, causing excessive stimulation of the receptor (just the opposite of what happens in myasthenia gravis!), leading to excessive production of thyroid hormone (hyperthyroidism).

Type III (immune-complex-mediated) hypersensitivity
There are a ton of diseases in this category too.

1. Lupus: the patient makes antibodies that bind to certain nuclear antigens; complexes lodge anywhere they please but especially in the kidneys, skin, and joints.
2. Post-streptococcal glomerulonephritis: in fighting a strep infection, the patient makes an antibody that reacts against the strep bug but also cross-reacts with some antigen in the glomerulus; antigen-antibody complexes lodge there and cause nephritis.
3. Serum sickness: after injection of foreign proteins into the patient (e.g., like they did in the old days when they used horse serum in vaccines!), the patient makes antibodies against the foreign proteins, and the resulting complexes lodge anywhere they want, but especially in the joints, kidneys, and vessels.
4. Arthus reaction: after injection of foreign protein into the skin, the patient (the original patient in Arthus’ 1903 experiments was a poor little bunny – but the same thing happens in humans) makes antibodies against this protein, and the resultant complexes stay in the skin, eliciting a nasty localized vasculitis and a big owie on the skin.

Type IV (T-cell-mediated) hypersensitivity
There are two kinds of this one (after all, there are two kinds of T cells!).

Delayed-type hypersensitivity
A good example of this is poison ivy exposure (patient gets exposed to poison ivy, helper T cells respond and some become memory cells; upon repeat exposure the memory T cells rush to the site, activating macrophages and causing inflammation). Another example is the Mantoux test; same principle.

T-cell-mediated cytotoxicity
Type I diabetes is a good example of this one. In this disease, cytotoxic T cells kill pancreatic islet cells. That’s not very nice. They are supposed to be killing infected cells, or tumor cells – not the patient’s own normal cells.

Photo credit: Joe Shlabotnik (http://www.flickr.com/photos/joeshlabotnik/506346418/in/photostream/).

Here’s a summary of those four pesky hypersensitivity reactions you will definitely be asked questions on at some point.

Sometimes, the best way to remember things is to boil them down to as few words as possible. I think you can summarize each hypersensitivity reaction in a one or two words:

Type I – allergy
Type II – antibodies
Type III – immune complex
Type IV – T cells

Here’s a little more information:

Type I hypersensitivity is the mechanism underlying the classic allergic response. It’s also called “immediate” hypersensitivity, which makes sense to any allergy sufferer (as soon as you start petting the cat, you start sneezing). It’s caused by an antigen (from an allergen, like cat dander) binding to IgE antibodies that are bound to the surface of mast cells. The antigen bridges the IgE antibodies, triggering release of nasty mediators (like histamine) from the mast cell. The end result: vessels dilate, smooth muscle contracts, and inflammation comes in and makes itself at home.

Type II hypersenstivity is also called “antibody-mediated” hypersensitivity. Which is kind of misleading, becase it’s not the only type of hypersensitivity reaction that involves antibodies. Oh well. In this type of hypersensitivity antibodies bind to antigens on a cell surface (any cell surface). Macrophages come in and eat up the cells (they think the Fc fragments of antibodies are yummy). Complement gets activated, inflammation comes in (harming tissue) and cells end up dying. Examples of this type of hypersensitivity include: autoimmune hemolytic anemia, pemphigus vulgaris, Goodpasture syndrome, myasthenia gravis, and Graves disease.

Type III hypersensitivity is also called “immune-complex-mediated” hypersensitivity. In this one, antibodies bind to antigens, forming complexes. These antigen-antibody complexes circulate (either throughout the whole body, or within one area of the body), get stuck in vessels, and stimulate inflammation, the end result being inflammation-mediated tissue damage and necrotizing vasculitis. Examples of this type of hypersensitivity include: systemic lupus erythematosus, post-streptococcal glomerulonephritis, polyarteritis nodosa, serum sickness, and the Arthus reaction.

Type IV hypersensitivity is also called “T-cell-mediated” hypersensitivity. This type of hypersensitivity has two subtypes. In one subtype, called delayed-type hypersensitivity, helper T cells secrete cytokines that activate macrophages (which eat the antigen) and induce inflammation (which damages tissue). A good example of delayed-type hypersensitivity is poison ivy. The other subtype, called T-cell-mediated cytotoxicity, involves cytotoxic T cells coming and killing target cells (like the cells of a transplanted organ, or the pancreatic islet cells in a patient with type I diabetes).

The nice kitty image is from anomalous 4 at: http://www.flickr.com/photos/31333486@N00/2066349843/

The second most common type of anemia (after iron-deficiency anemia) is anemia of chronic disease (ACD). This is a mild to moderate anemia accompanying infections, inflammatory disorders or malignant diseases that persist more than 1-2 months (examples include pulmonary infections endocarditis, rheumatoid arthritis, lupus, carcinoma, lymphoma, and myeloma). It’s characterized by low serum iron, despite lots of macrophage storage iron.

The pathogenesis of this anemia is multifactorial. Part of the problem is related to iron metabolism. For the most part, mucosal cells absorb iron okay, but they don’t release it into plasma (so the iron never makes it into red cell precursors!). Macrophages take up iron okay, but they release it very slowly. All of this is mediated, at least in part, by a substance called hepcidin, which is produced by the liver and released in response to inflammation (which, of course, you see in most chronic diseases).

In addition to the iron metabolism stuff, the red cells in this anemia have a shortened lifespan. The weird thing is that if you put cells from patients with ACD into normal patients, the red cells have a normal lifespan; but if you put cells from a normal patient into a patient with ACD, those red cells will die early! To top it all off, there is an impaired bone marrow response to anemia. There’s not enough iron available to make enough red blood cells; also, there’s not enough erythropoietin around, and bone marrow can’t respond to what little there is. Ugh. You’d think with all that stuff going on, the anemia would be severe – but it generally isn’t. Patients usually have no real symptoms related to the anemia; they have enough trouble with whatever chronic disease they suffer from.

The anemia is normochromic and normocytic, usually.  Some cases (about 25%) are microcytic (but MCV rarely gets below 72 fL). There is minimal anisocytosis and poikilocytosis. There’s really not a lot to look at under the microscope!

To make the diagnosis, you need to do iron studies. In ACD, you’ll see the following:
•    ↓ serum iron
•    ↓ TIBC (total iron binding capacity)
•    ↓ transferrin saturation
•    ↑ ferritin (remember: ferritin is an acute phase reactant! So it’s increased in these patients, because there is chronic inflammation present.)
•    ↑ bone marrow storage iron

This anemia usually is so mild that treatment is not necessary. The anemia develops during the first 2 months of the chronic disease, and it doesn’t progress thereafter. The important thing to remember is that you need to distinguish it from iron-deficiency anemia (use iron studies for this). You wouldn’t want to mix the two up, because anemia of chronic disease requires no further treatment, whereas a diagnosis of iron-defieciency anemia necessitates a search for possible sites of blood loss.

Photo credit: Ethan Hein (http://www.flickr.com/photos/ethanhein/2383172799/), under cc license.

We’ve talked about a whole bunch of different hemolytic anemias over the past few weeks. We’ve gone through the main hereditary hemolytic anemias: hereditary spherocytosis (and its less-common counterpart, hereditary elliptocytosis), glucose-6-phosphate dehydrogenase deficiency, the hemoglobinopathies (like sickle cell anemia) and the thalassemias. We’ve also talked about immune-related hemolytic anemia (warm and cold), which is an acquired hemolytic anemia.

The last main type of hemolytic anemia on our list is microangiopathic hemolytic anemia, or MAHA for short, which falls under the acquired group of hemolytic anemias. In this type of hemolytic anemia, the red cells are ripped apart by physical trauma. Often the trauma results from red cells getting snagged as they try to pass through vessels laden with fibrin strands (there are a ton of situations in which this occurs, as we’ll see). Sometimes the trauma is due to other types of trauma (like an artificial heart valve that busts a few red cells each time it closes).

Let’s take a look at the other-types-of-trauma group first because it’s a little easier to conceptualize. There are two main causes of MAHA in this group: artificial heart valves and coarctation of the aorta. They really should call this group “macroangiopathic hemolytic anemia” because the problem is in big (macro) not tiny (micro) vessels, but they didn’t ask me. In both of these causes, red cells are getting ripped up in large spaces – either by the smashing of cells within an artificial heart valve (the old ball-and-socket valves were the worst for this; the newer models are much kinder to red cells), or by the ripping apart of red cells in turbulent blood flow (as you would get in coarctation of the aorta).

The remaining cases of MAHA are due to red cells getting snagged as they try to traverse fibrin-laden vessels. There are tons of situations in which the patient starts forming fibrin at an increased rate. If you look at Robbins, or any hematology textbook, you’ll be quickly overwhelmed by the sheer number of disorders and conditions that are associated with a microangiopathic hemolytic anemia, such as:

1. Disseminated intravascular coagulation (DIC) – a nasty condition in which there is bleeding and clotting at the same time in the patient. Lots of things can cause DIC (like malignancy, obstetric complications, trauma, and sepsis) – and it’s complicated enough that we’ll get into it in a future post.
2. Thrombotic thrombocytopenic purpura (TTP) – a syndrome in which the patient gets little thrombi within the microvasculature anywhere in the body, but especially the CNS and kidneys. We’ve talked a little about TTP before.
3. Hemolytic-uremic syndrome (HUS) – a disorder often related to ingestion of food (especially raw hamburger, but also spinach, other vegetables, you name it) containing E. coli 0157:H7. The bug makes a toxin that damages endothelial cells, and for some reason, the kidneys are hit the hardest.

The blood smear is where the action is in MAHA. If you look carefully at a blood smear from a patient with MAHA, you’ll see fragmented red cells, or schistocytes. Schistocytes are smaller than normal red cells, and they have points on them. There are all kinds of permutations on this theme – some schistocytes have just one point, some look like they have little horns, some just look like little ragged red cell shards. If you look at the image above, you’ll see a whole bunch of schistocytes of varying shapes.

The most specific type of schistocyte is the “triangulocyte” (that’s really the name; would I make that up?), which is, as the name suggests, a triangular fragment of a red cell. These aren’t as common as the other types of schistocytes (there isn’t a triangulocyte in the above image). If you see one of those puppies, you better figure out what’s going on with the patient.

And that’s the main point I want to make about this type of hemolytic anemia. Given all the causes of this anemia – many of which carry a high mortality – you can’t just say the patient has MAHA, and move on to the next blood smear. You have to figure out what’s causing the hemolysis (or, rather, the clinician needs to figure it out); don’t miss this one. It could be a matter of life and death.

Photo credit: Ed Uthman at http://commons.wikimedia.org/ (DIC_With_Microangiopathic_Hemolytic_Anemia_(301920983).jpg)

We’ve been talking a lot about hemolytic anemias – we talked about how to figure out if your patient has a hemolytic anemia, and we talked about the DAT as a test that you would do to determine whether your patient’s hemolytic anemia falls into the immune category (warm or cold autoimmune hemolytic anemia) or the non-immune category.

Let’s look at the causes of hemolytic anemia, in general, and try to make sense out of a big list of disorders. We’ll go into depth on each disorder in separate posts.

One good way to think about the causes of hemolytic anemia is to break them down into inherited and acquired causes. The inherited causes of hemolytic anemia usually have some kind of defect in the red cell itself. Some involve  defects in the red cell membrane (like hereditary spherocytosis and hereditary elliptocytosis) such that the membrane becomes unstable; some involve enzyme deficiencies (like glucose 6 phosphate dehydrogenase deficiency, where the patient is missing an enzyme that detoxifies the red cell); and some involve defects in globin structure or synthesis (like the hemoglobinopathies, in which there are qualitative defects in hemoglobin, or the thalassemias, in which there are quantitative defects in hemoglobin).

Acquired causes of hemolytic anemia can be immune-related (we already talked about warm and cold autoimmune hemolytic anemia), infection-related (e.g., malaria or clostridium infection), drug related (tons of drugs can elicit hemolysis), or related to something outside the red cell that is ripping cells up (these are called microangiopathic hemolytic anemias, and there are tons of different “somethings” that can rip up red cells).

Usually, the inherited hemolytic anemias are chronic in nature. The patient often has a mild anemia (or no anemia) most of the time, because the bone marrow is working at its maximum to produce more red cells to replace the ones that are being destroyed. But sometimes, these patients undergo “crises,” in which something precipitates an increase in red cell destruction (parvovirus B19, for example, which loves to attack and destroy red cells) – and the already-maxed-out bone marrow can’t compensate, leaving the patient with way less red cells than normal. Acquired hemolytic anemias are usually acute in nature. Something happens to precipitate the anemia, and it’s a one-time, big hit to the red cells.

There are different ways to work up these anemias, but one thing that is done right away is the DAT. That will tell you whether your patient’s anemia falls into the immune category or not. If the DAT is positive, you have an immune process. If it’s negative, then you have a non-immune process – and we’ll talk about how to separate out all the non-immune causes of hemolysis when we discuss each disorder.

Note: the nice image of the red cell above was rendered by Andrew Mason, and can be found at: http://www.flickr.com/photos/a_mason/19191446/.

We talked recently about the direct antiglobulin test (DAT) which is a test used to find out whether a hemolytic anemia is immune-related or not. And we talked even more recently about the immune hemolytic anemias, starting off with warm autoimmune hemolytic anemia. As you now know, immune hemolytic amemias (also called autoimmune hemolytic anemias) come in two kinds: warm and cold. They are named that way because the antibodies in each type react best at different temperatures. That sounds like one of those useless, arcane facts likely to show up on a test somewhere. It may very well show up on a test somewhere (in which case, you’ll nail it), but it’s not arcane or useless, surprisingly; it has real relevance to what’s going on in the patient, as we’ll see in this post.

There are a couple things going on in cold autoimmune hemolytic anemia (AIHA): 1) the patient is making antibodies against his/her red cells, and 2) there is complement fixed to the patient’s red cells. As in warm AIHA, the patient is for some reason making antibodies to his or her red cells. The possible causes are numerous and include infections (like mycoplasma pneumoniae or infectious mononucleosis), lymphoproliferative disorders (like leukemia or lymphoma), and the good old “idiopathic” category (or, We Don’t Know What Is Causing It But We Don’t Want To Sound Silly). These antibodies are different than those in warm AIHA, though: they are IgM in nature (in warm AIHA they’re IgG), and they bind best at cold temperatures, like 4 degrees C or 39.2 degrees F (in warm AIHA, the antibodies bind best at warmer temperatures).

You may be thinking, yeah, so? Well, here’s the cool thing: because the antibodies bind best at cooler temperatures, they seem to bind to the red cells in distal parts of the body like the fingertips and earlobes (especially if the patient goes out in the cold), and they fall off in warmer, more central parts of the body. What’s more, because the antibodies are IgM in nature (remember, IgM is a pentamer), they are able to span several red cells, creating big agglutinates of red cells (you can see them in the image above). These agglutinates can plug up little vessels, creating ischemic conditions in these peripheral body parts. Which translates clinically into colorless (or blue), numb fingertips/earlobes/nose tips/whatever else is hanging out in the cold. Then, as the red cells circulate back into warmer, more central parts of the body, the IgM falls off, and the agglutination disappears.

So that’s the deal with the antibody. There’s also the matter of complement binding to the red cells. This is not good, because complement pokes holes in red cells! That’s where the hemolytic part comes in in cold AIHA – the red cells get busted open by complement, right in the circulation. It’s not like warm AIHA, where the hemolysis is happening mostly in the spleen; here it’s happening intravascularly. There is a little bit of macrophage action in the liver and spleen (macrophages see complement-coated red cells as yummy and eat them up) but mostly, the hemolysis is happening in the vessels.

Cold AIHA can hit any age, race, or sex. When it happens in elderly patients, it is usually related to some lymphoproliferative disorder; when it happens in kids, it’s usually related to an infection. The anemia is usually pretty mild, and the patient gets pallor (paleness) and/or cyanosis (blue discoloration due to lack of oxygen) in peripheral body parts, especially when exposed to the cold, because of those red cell agglutinates in tiny vessels.

When you look at a blood smear from a patient with cold AIHA, you’ll see big red cell agglutinates (but only if you have smart lab techs who cool the blood down first before making the smear, so you can see the agglutinates! Most lab techs are very smart.) You might see some spherocytes here and there too (because there is a little bit of macrophage nibbling going on) but they are way less numerous than they are in warm AIHA. To prove that your patient’s anemia is, in fact, an autoimmune hemolytic anemia, you need to do a DAT. The DAT will be positive in cold AIHA because the DAT looks for both IgG and complement bound to the patient’s red cells. Good thing they include the complement in the test (if they just included IgG, then cold AIHA cases would have a negative DAT).

The treatment for cold AIHA is what you’d expect: get rid of the underlying cause, if there is one (i.e., treat the infection), and keep the patient warm! The pallor/cyanosis in distal body parts is usually not severe enough to cause infarction – but it is annoying,  and patients should be kept warm so they don’t have to suffer from those symptoms, on top of everything else they are dealing with.

We talked recently about the direct antiglobulin test, which is a test used to find out whether a hemolytic anemia is immune-related or not. So let’s take a look at the immune hemolytic anemias!

The immune hemolytic anemias (also called autoimmune hemolytic anemias) come in two flavors: warm and cold, so named because the antibodies in each type react best at different temperatures. Which you would think is just a dumb laboratory observation, but as we’ll see, it actually has relevance to what’s going on in the patient.

Let’s start with warm autoimmune hemolytic anemia. The basic thing that’s happening in this anemia is that the patient, for some reason, is making IgG antibodies that stick to his/her red blood cells. These IgG antibodies work best at warm temperatures (37 degrees C, or 98.6 F – exactly at body temperature!). Most of the time there’s no known reason for the patient to be making the antibodies (instead of saying “we don’t know why,” though, say “idiopathic.” It sounds so much smarter.). Sometimes there is a known underlying cause – like lymphoma, leukemia, another autoimmune disease, an infection, or a drug (like penicillin) against which the patient is making antibodies (and those antibodies, unfortunately, also recognize epitopes on the patient’s red cells).

Whatever the cause, it’s not a good thing to have antibodies coating your red cells, because macrophages in the spleen see these antibody-coated red cells as yummy and gobble them up. Sometimes the macrophage eats the red cell whole, and sometimes it only gets a little nibble of it. In the latter instance, the red cell will lose a bit of membrane. When that happens, the red cell “rounds up” because it has less membrane to contain the same volume – and what you see is a spherocyte (as in the image above).

Warm autoimmune hemolytic anemia has no age, race, or sexual preference. It produces a variably severe anemia – sometimes mild, sometimes severe. The one thing that most patients have is a big spleen (because of all the eating going on in there).

And now, after reading the post on the DAT, you know how to diagnose an autoimmune hemolytic anemia! If the DAT is positive, you know it’s an autoimmune hemolytic anemia. The lab will be able to figure out whether it’s a warm or cold process; they’re smart that way.

Treatment involves eradicating the underlying cause, if possible (if it’s a drug, get rid of the drug). You can give the patient steroids, which inhibit immune reactions in general. If it’s really bad, and steroids aren’t helping, you can take out the spleen. Removing the spleen will remove the site of destruction, so the anemia should improve.

Next post: Cold autoimmune hemolytic anemia.

Ringworm is a superficial fungal infection of the skin, nails, or hair. The causative agent is not a worm, but a type of mold called a dermatophyte (“skin plant”). Dermatophytes love non-living and/or keratinized tissue, like the stratum corneum of the skin, the nails, and the hair. There are three genera, if you care: microsporum, trichophyton, and epidermophyton.

Most of the time, the dermatophytoses (a more official name than ringworm) are classified by their location. The word “tinea” (meaning, in this case, “dermatophytosis”) usually precedes the anatomic location. Here are some common dermatophytoses:

Tinea capitis (dermatophytosis involving the scalp)
Tinea barbae (dermatophytosis involving the beard area)
Tinea pedis (dermatophytosis involving the feet, commonly called “athlete’s foot”)
Tinea crurus (dermatophytosis involving the groin, commonly called “jock itch”)
Tinea corporis (dermatophytosis involving skin in any other anatomic location)
Tinea unguium (dermatophytosis involving the nails)

There are a couple unique kinds of dermatophytoses too, including tinea nigra (a tropical condition in which dark brown fungi cause brown/black macules on palms or soles) and piedra (a fungal infection of the hair shaft itself). 

Dermatophytoses affecting the skin have a characteristic ring-shaped lesion with a raised, red, sharply-demarcated border. This is probably where the worm idea came in – people thought the advancing borders of the lesion indicated the presence of a worm in the skin. These lesions are most common in warm, moist areas of the body, but they can occur anywhere, really. They are not dangerous – just bothersome.

Note: the nice picture of an athlete’s foot (perhaps with a ringworm infection between the first and second toes) was taken in the Capitolene Museum in Rome by Thrillho. It can be found at: http://www.flickr.com/photos/thrillho/916166760/.