Combined Immunodeficiencies

So my friends in our last posts we talked about B and T cell deficiencies independently, but what will happen if we put them into a blender and mixed it: 

Well yes, we will have the combined (mixed) immunodeficiencies. And depending on the recipe, some people can put more B or T cells, we will end with: Severe combined immunodeficiency, Wiskott-Aldrich syndrome and ataxia telangiectasia.

1) SCID:  (a.k.a. alymphocyotosis)

In the first disorder, what if we used all our B and T cells in the mixture, well we will have a complete absence of the immune system right? so this will be SEVERE and COMBINED (B and T cells), being also the most SEVERE of the primary immunodeficiencies. Even inside this SCID we will find several types, being the X linked the most common, followed by Adenosine deaminase deficiency (ADA deficiency)

This patients present with highly increased risk of developing infections, and because of their susceptibility they are also called "bubble boys" 

Which infections can they have? Severe bacterial, viral, or fungal infections early in life and often present with interstitial lung disease, chronic diarrhea, and failure to thrive. Also they can present with ear infections, recurrent PCP, and oral candidiasis. 

What findings we can expect? a small or even absence of thymic tissue, and absence of lymphoid tissue. Remember no B or T cells. So this also correlates with the lab findings where we will have decrease lymphocytes, decrease or absent immunoglobulins and lack of antibodies production after receiving vaccines.

What's the treatment?  The most common treatment bone marrow transplantation (BMT), which has been successful using either a matched related or unrelated donor, or a half-matched donor, who would be either parent. This has to start early in life because patients without treatment usually die before 1 year old due to recurrent infections.

2) WAS: Wiskott-Aldrich Syndrome

In this mixture we won't use all our T cells so they will be low but not absent, and same with B cells, will be decreased but not absent. What is characteristic in this syndrome is:

T: thrombocytopenia

I: immune deficiency

E: eczema

So this patients will present early in life with petechiae and easy bruising due to thrombocytopenia, (which can also lead to bloody diarrhea), then during the first month they present eczema, and then by 3 months presents recurrent infections. 

 

What is characteristic in the lab findings? think about the name...Wiskott...this W looks like an M right? just inverted. That's the clue, in this disorder they will have decrease IgM (W), on the other hand the vowels (A and E) will be elevAtEd...you see elevAtEd: IgA and IgE: and IgG can be either elevated, normal or lower.

How can me treat it? First avoid anything that interferes with platelets function (aspirin and other non-steroidal anti-inflammatory drugs. If severe low platelet counts is present, they might require platelet transfusions or a splenectomy. If frequent infections are present, intravenous immunoglobulins (IVIG) can be given (monthly). As a current cure we have hematopoietic stem cell transplant, accomplished through a cord blood or bone marrow transplant.

3) Ataxia-telangiectasia (a.k.a. Louis–Bar syndrome)

In this case this mixture will be similar as WAS, low but not absent B and T cells. So then how can we recognized it? Read the name again: Ataxia: lack of voluntary coordination of muscle movements, and Telangiectasia: small dilated blood vessels. Also presenting the immune deficiency, and a increase risk of develop cancer due to impaired DNA repair.

The ataxia will be progressive, starting when the child is learning to walk, showing some clumsiness. Also because of the cerebellar involvement they can present with oculomotor apraxia (lack of coordination between head and eye movements). Also present with increased risk of developing lymphomas and leukemias. 

How can we diagnose it? we have some lab tests that can help. The immunoglobulins will be decrease, especially IgA, also elevated and slowly increasing AFP after 2 years of age, chromosomal instability, increased sensitivity of cells to x-ray exposure and in imaging we can find cerebellar atrophy (MRI)

How can we treat it? For the ataxia part, we can handle it (not reverse it) with physical therapy, being this just symptomatic and supportive. To treat the immune deficiency we can give IVIG (be careful if its a selective IgA deficiency!!!), and having as current cure the bone marrow transplant.

So in summary

1) SCID: is severe and combined (both B and T cells), remember types, X linked the most common and ADA deficiency in second place, remember lab: lymphopenia, no response after vaccines. Treatment: BMT

2) WAS: remember TIE (thrombocytopenia, immune deficiency and eczema), invert the W and you have the M which is the deficient Ig in this disorder, remember which ones are elevAtEd (Ig A and E). Treatment: IVIG and BMT.

3) A-T: remember the component: ataxia and telangiectasia. Increase risk of lymphoma. Low IgA, increase AFP, cerebellar atrophy on MRI. Treatment: IVIG (not if complete IgA deficiency) and BMT.

I hope you enjoy this post,

For the next post I'll be explaining ocular problems in children.

See you on the next post,

Carlos Albrecht

Phagocytic system disorders

Do you remember Pacman? the golden circle eating ghosts? well imagine if you can eat this ghosts but won't be able to digest them. 

Well in Chronic Granulomatous disease (a.k.a. Bridges–Good syndrome, Chronic granulomatous disorder, and Quie syndrome or CGD), our phagocytic system (neutrophils and monocytes) can EAT but CAN'T DIGEST (the catalase positive organisms). Was discovered first in 1950 in Minesota but described and named later in 1957

Why they can't digest? well due to a defect in forming reactive oxygen compounds (specially superoxide radical) needed to kill the catalase positive organisms. 

To remember this organisms, I found a nmemonic that might be useful: SPACE

Staph

Pseudomona aeroginosa

Aspergillus

Candida

Enterobacteriaceae (Klebsiella and Serratia)

Like the other immune disorders, patients will present with recurrent infections like: pneumonia, abscesses of the skin, tissues, osteomyelitis, bacteremia/fungemia and superficial skin infections such as cellulitis or impetigo. 

How to diagnosis? clasically is using the nitroblue-tetrazolium (NBT) test which is NEGATIVE in CGD (we are used to have positive test for diseases, but in this case negative test means disease...remember that), so if the nitroblue doesn't turn blue is negative, and the opposite if it's blue is positive meaning an adequate production of reactive oxygen products. Other test used is  the dihydrorhodamine (DHR) test where blood is mixed with DHR, incubated, and then is stimulated to produce superoxide radicals.

Do we have associations? well yes, if we go back to the name CGD = "granulomatous", we will find formation of granulomas, which can obstruct in different levels as pyloric, bladder, urethra and intestinal. 

And finally talking about the treatment, we might need to give antibiotics as prophylactics, also the use of interferon gamma 1b which will increase the immune system capacity to fight against infections, and as last treatment we have the hematopoietic stem cell transplat (which is the only known cure).

So, in summary, remember our system can eat but can't digest, remember the catalase positive organisms (SPACE), remember how to diagnosis it using either the NBT or DHR tests, the granulomas formation and finally remember the treatment (stem cell transplant)

Hope you enjoy this topic, the next one will be about combined immunodeficiencies which will be the last of this immune diseases.

See you on the next post,

Carlos Albrecht

T cells disorder

Hi everyone, today we are going to explain about the "soldiers", do u remember? the T cells. 

So, in this topic we will talk about the most well know T cell disorder: DiGeorge syndrome, also known as velo-cardio-facial syndrome, Shprintzen syndrome,conotruncal anomaly face syndrome, Strong syndrome, congenital thymic aplasia, and thymic hypoplasia (For the USMLE purpose DiGeorge is fine, Dr. DiGeorge described this syndrome in 1968).

This is a congenital disorder due to a deletion in chromosome 22 (22q11.2, this is the long arm of the chromosome). The patients will present hypoplasia or aplasia of thymus and parathyroids (remember that the problem here is in the 3th and 4th pharyngeal pouches)

In this case there is increase risk for opportunistic infections (remember we don't have our "soldiers"), so patients can present with fungi and viruses early in life.

To remember the features of the syndrome we have the nmenomic: CATCH - 22, where 22 is to remember the chromosome number, so here we go: C for cardiac abnormalities (Fallot), A stands for abnormal facies, T stands for thymic aplasia (hypoplasia), C stands for cleft palate and finally H stands for hypocalcemia and hypothyroidism, 

C: cardiac

A: abnormal facies 

T: thymic aplasia

C: cleft palate

H: hypocalcemia, hypothyroidism

Now in some cases the hypocalcemia might be helpful in the diagnosis, because sometimes the only presentation in a neonate are seizures (due to hypocalcemia). Other Lab findings include: decrease lymphocytes (with decrease CD3+ which is the marker for the T cells), and a normal level of immunoglobulins (remember that B cells are normal here)

Also a important thing to remember (and always asked) is the association of DiGeorge and the increase risk (up to 20 to 30 times) to develop schizophrenia. 

For the treatment we have to treat based on each case, if the patient have cardiac abnormalities, he might require cardiac surgery, if he is having infections he might need antibiotics or antifungals, for the hypocalcemia or hypothyroidism the patient may need vitamin D and calcium supplement, and in rares cases (of fully thymic aplasia) the patient may require thymic transplant.

So in summary, remember the chromosome number (22), the presentation (CATCH), the lab findings (hypocalcemia and hypothyroidism) and the association with schizophrenia.

The next topic will be about phagocytic system disorders, 

Hope you enjoy the reading,

See you on the next post

Carlos Albrecht  

   

B cells disorders

Remember about the factories? well now we will explain the B cells disorders. 

In general in this kind of deficiencies, we will have increase risk of recurrent infections with encapsulated bacterias, enteroviral, hepatitis viruses and sinopulmonary infections. They have in common in the physical exam that this will be normal (that means no increase in size of tonsils, nodes). And in the history we will have a patient who is healthy until he is around 6 to 9 months old, when he presents with recurrent infections as we said before.

Knowing this, here we go:

1. Bruton Agammaglobulinemia (also know as X-linked agammablobulinemia)

Ok, let's start from the name: A - gammaglobulinemia, "A" means lack, so in this case we will have a lack or absence of B cells and therefore we will have in the laboratory findings very low levels of Ig G,A,M,E (GAME) This means decrease CD19+ which is the marker for B cells, BUT having normal levels of T cells with their marker CD3+.

Treatment: regular use of what we lack: Ig, so we will give IVIG (intravenous immunoglobulin)

2. CVID (a.k.a. common variable immunodeficiency)

The main issue in this disorder is that even having a NORMAL number of B cells, they don't produce the amounts of Ig needed. So again in common with the B cell disorder our risk of having recurrent infections will increase. One specific characteristic of this disorder is the increase risk of autoimmune disorders like pernicious anemia and seronegatives diseases, and also the increase risk of lymphoma specially in females.

Treatment: again is using IVIG, but prior to this we will need to make screening for anti-IgA antibodies, if they are present is safer to use IVIG without IgA.

3. Selective IgA deficiency

Do we have to say more about this? Well yes. Obviously we will have a selective deficiency of IgA, this will increase the risk of respiratory and GI infections, like Giardia (remember where do we have IgA). But also this will have a increased risk of anaphylaxis in those who receive blood from a person with normal level of IgA and a increase risk of autoimmune disorders like in CVID.

Treatment: this one will have a different one, DON'T USE IVIG, why? because of the increase risk of anaphylaxis from anti-IgA antibodies, plus IVIG is almost 100% IgG. So just treat the infections as they appear.

So in summary:

Bruton: absence of B cells (low level of Ig), treated with IVIG

CVID: normal number of B cells with defective production of Ig (low level of Ig), lymphoma associated and treated with IVIG (screening for antiIgA needed prior to treatment)

Selective IgA Def: normal number of B cells with defective production of IgA, anaphylaxis with blood from normal patient, DON'T USE IVIG (again risk of anaphylaxis)

This is all for today, I hope you enjoy the lesson

See you on the next post: T cells disorders

Carlos Albrecht

Immune disease

This topic is very important but very confusing as well, I will try to explain in the next for four post, but first lets make an overview about it.

In the defense of our bodies we have "soldiers" that fight for us, we have several types, today we will review about four of them, B cells, T cells, phagocytic system and complement system.

B cells: think about this cells as factories, this cells will produces immunoglobulins (or antibodies) against antigens. They work in the humoral defense of the body.

T cells: this cells will be like the workers, the can be divided in different types like helper, cytotoxic and memory. They work in the cell-mediated defense of the body.

Phagocytic system: think about hungry dudes looking for food, basically are monocytes and macrophages.

And finally we have the complement system: as the name says, they complement the work of the other workers. They are part of the innate immune system, they attack following a cascade increasing their response creating what's known as MAC (membrane attack complex).

Keep this information in mind because we will need this basic knowledge for the next topics.

See you in the next post.

Carlos Albrecht

Abdominal Wall Defects

The first topic we are going to review today are the abdominal wall defects. 

So, we have first umbilical hernia, think of a weak portion in the belly and like a small mass protruding out of it. For this we have to think about number 4, what does it mean? If the hernia is less than 4 cm in size and doesn't have symptoms, we can just keep doing clinical follow up of the kid, but if even being less than 4 cm it present symptoms (like pain) this kid might need surgery. Again number 4, umbilical hernias, usually have to disappear by the age of...yes you did it right by the age of 4. But if we have a kid over 4 years old still with the hernia present, he also might need surgery because of the risk on increasing in size.

The next defect is called omphalocele, this word has Greek origin, where they called Omphalo to the Apollo Temple, being considered as the center Earth. In this type of abdominal defect we will have abdominal content like intestines or liver going outside the body, but in this case all this content is COVERED BY A SAC. Remember that in omphalocele further studies are needed in order to find out if its related with a genetic syndrome.

At last we have gastroschisis, again this word has Greek origin which means division, so again is a problem in the abdominal wall where abdominal content will be going out of the body, but in this case the main difference is the LACK OF SAC, so what does it mean? yes, all the content will be expose to amniotic fluid increasing the risk of adhesions, atresia and strictures with this increasing the need of resecting a section of the intestine (also leading to other problem: short bowel syndrome)

Treatment: for both omphalocele and gastroschisis will be surgery, but in this case the age of surgery will be determined by the size of the defect. If its a small defect can go straight to surgery, but in the other hand if its a big one, the option is create a silo over it, covering the lesion and returning it gradually to the abdominal cavity, why gradually? Imagine trying to put a melon inside an orange, hard right? well the same happens when you try to put a large lesion back to abdominal cavity, in this case will increase the risk of death of the patient because of respiratory failure (huge lesion make hard to breath!)

Next you can find a video for this lesson, I hope you enjoy it.

See you in the next topic,

Carlos Albrecht

Welcome to Pediatrics Review

Hi colleges, students and friends, welcome to Pediatrics Review the easy way.

This blog was created with the purpose of reviewing common topics of pediatrics trying to explain them in a easy way, using charts, draws and videos. This will be helpful for students, doctors and parents, to easily understand our kids.

Hope you enjoy the blog, and any comment or suggestion is welcome

Sincerely,

Carlos Albrecht