Why is breathing difficult & at times, painful in Ankylosing spondylitis?

June 26, 2016

The mechanical apparatus for breathing consists of the ribs, intercostals muscles, costochondral junctions & the diaphragm. Diaphragm is a muscle located at the base of the chest wall cavity. The ribs move at the joint formed by them with the vertebrae (costovetebral joint). The intercostals muscles are attached to the ribs & are responsible for the movements of the ribs during respiration.

costovetebral joint

During inspiration, the diaphragm moves downwards & expands the chest cavity. At the same time, the ribs move up & out to expand the thoracic cavity. This movement is akin to a bucket handle (moving up). The movement of the ribs is brought about by the contraction of the intercostal muscles.

 

 

In Ankylosing spondylitis, there is inflammation of the costovertebral joint. Later, as AS progresses, the joint may also get fused. This inflammation/ fusion then restricts the movement at the joint & consequently the chest expansion. Physically, this manifests as restricted chest expansion.

Ankylosing spondylitis also leads to inflammation at insertion of intercostal muscles to the ribs (enthesitis). This leads to pain in the rib cage area & also further difficulty in taking a deep breath.

Sneezing involves a rapid & high intensity contraction of the intercostal muscles. It is very painful due to the enthesitis & is almost felt like a ‘catch’

Tight control of AS with NSAIDs/ DMARDs/ biologics/ diet & deep breathing exercises are helpful in reducing this chest pain.

 


How does ankylosing spondylitis cause osteoarthritis of the hip? — the Pacman game

May 15, 2016

I’m sure all of you know that Ankylosing spondylitis (AS) is an autoimmune disease, which means that the body’s immune system considers its own joints as foreign & attacks them. We have not been able to pinpoint the exact reason for this.
If this immune attack is not controlled in time, it ends up destroying the joints; especially the hips. This is known as osteoarthritis of the hips. Ankylosing spondylitis is a unique disease as it causes destruction of the bones in the hip & at the same time it leads to excessive bone formation in the spine (syndesmophytes). So what starts as backache can well end up as deformities & disability.

But then, how does AS cause destruction of the hips?
Hip joint is lined by a thin membrane called the synovial membrane from the inside. The immune attack is targeted towards the synovial membrane. The synovial membrane swells up due to the attack. This inflamed synovium is like the pacman. Remember the pacman game?… pacman eats away all the dots. In a similar fashion, the pannus eats the cartilage & the bones around it. When it eats the bones, the same is known as erosion. Apart from the hips, these erosions are also seen in the sacroiliac joints. Destruction of the cartilage & the bone ultimately leads to osteoarthritis.

 

Rheumatoid_Arthritis_Knee_Joint

 

pacman

The Pacman game.. Pacman keeps eating the dots…just like the inflamed synovium keeps eating the cartilage & the bones. Note how the AS Pacman has destroyed the hip bones (above) & the sacroiliac joint (SI joint) (below).

 

Ankylosing_Spondylitis_CT_Scan

Can the hip osteoarthritis be prevented?
Yes, very much so. Seeing a Rheumatologist at the earliest & starting definitive treatment at the earliest can definitely tame this pacman & prevent osteoarthritis.


Low Starch Diet for Ankylosing Spondylitis: Part 2 – The Scientific Evidence

November 2, 2014

We have already seen (in the last blog) the theoretical possibility of a ‘Low starch diet’ being beneficial for Ankylosing Spondylitis. Let us now see whether it really works in real life & whether there is sound medical evidence to support it.

Today’s medicine works on the basis of evidence. If a new medicine/ intervention is thought to be useful, it is tested in clinical trials. A group of patients is given the standard treatment & placebo (an inert substance that has no effect on disease activity) while another comparable group is given the standard treatment & the experimental therapy/ intervention. A ‘double blinded study’ that ensures that neither the investigator nor the patient knows whether he is taking the experimental drug or placebo is ideal to avoid any bias; both on the investigator or the patient front. This is not possible for studies with dietary modifications as blinding is not possible & bias tends to creep in.

As against medicines, it is very difficult to keep an exact track of the diet of any patient for obvious reasons. It is extremely difficult to ensure that a patient sticks to a particular diet in the long run throughout the study period.

These two factors make studies based on dietary interventions difficult to conduct as well as interpret.

For the reasons mentioned, there are hardly any studies about ‘low starch diet’ in Ankylosing spondylitis. In 1996, Dr. Ebringer discussed the disease activity trend of one of his patients following the diet for a long period (1983- 1995). His ESR showed a continuously decreasing trend. In another study (mentioned widely on the internet with no reliable data available on any of the medical literature sites) 36 patients received Dr. Ebringer’s diet & showed considerable improvement in symptoms. These two studies would be highly inadequate for any definite conclusions.

So, as we have seen, the utility of ‘low starch diet’ in Ankylosing spondylitis is not yet proven scientifically.

One way of looking at things would be to give it a try & see whether it works. However it has to be weighed against the risks involved in pursuing such a diet.

In the next blogpost, let us look at what a ‘low starch diet’ includes/ excludes & the possible health hazards of such a diet.


“Low starch diet’ for ankylosing Spondylitis

October 25, 2014

Many patients keep asking me about the role of ‘Low starch diet’ to control Ankylosing Spondylitis. This has been a hot topic of discussion on most Ankylosing spondylitis groups on social media & many confirming the good results of a low starch diet.

The original idea of a ‘low starch diet for Ankylosing Spondylitis’ comes from Dr. Alan Ebringer, Prof of Immunology at King’s College London. He found high levels of a gut pathogen called Klebsiella Pneumoniae in stool samples of patients with Ankylosing spondylitis. He also found high levels of antibodies to klebsiella in the blood of patients with Ankylosing spondylitis. These findings indicated the presence of the bacteria in the gut of patients with Ankylosing spondylitis & the body’s immune reaction to it.

These findings evoked further research & Dr. Alan’s further research showed that K. pneumoniae was isolated more frequently during the active phase of Ankylosing Spondylitis & clinical relapse was preceded by appearance of the bacteria in fecal samples. This meant that Klebsiella Pnemoniae was somehow related to inflammation of Ankylosing Spondylitis.

Dr. Alan’s research continued & he went on to show that there are similarities in structure of the HLA-B27 molecule & enzyme Pullulanase produced by the Klebsiella bacteria. There is also similarity between the enzyme & type I, III & IV collagens found in joints & other organs. This gave rise to the ‘Molecular mimicry theory’. The human immunity recognizes Klebsiella as foreign & attacks it. However, since HLA-B27 & collagens have similar structure, they get attacked to. This may be responsible for the inflammation in joints & other structures like the eyes in Ankylosing spondylitis.

One can infer from the proposed ‘molecular mimicry theory’ that by reducing the klebsiella bacteria in the gut, one can reduce the inflammation associated with Ankylosing spondylitis.

Various studies have shown that the gut bacteria including klebsiella grow on undigested starch in the gut. Hence a reduction in starch in the diet may help reduce the klebsiella bacteria in the gut. Klebsiella bacteria is well adapted to the human gut & produces the Pullulanase enzyme that can break down the starch, derive nutrition & thrive in the gut.

The rationale of the ‘low starch diet’ is to cut down on the starch, make life difficult for the klebsiella bacteria. This may indirectly help control the Ankylosing spondylitis.

This is the exact basis of the ‘low starch diet’ for Ankylosing Spondylitis.

Now that we know the basis of the theory, we also need to look at the following points—
1. What is a ‘low starch diet’?
2. Are there any studies conducted in patients with Ankylosing spondylitis to prove the benefits of ‘low starch diet’?
3. If the concept looks so convincing, why do Rheumatologists not recommend it on a regular basis?

I would be answering these questions in the subsequent blog posts. These posts are coming soon & follow my blog so that you don’t miss out on any of those useful posts.

References: Erbinger A, Wilson C. J Med Microbiol 2000; 49: 305-311 http://jmm.sgmjournals.org/content/49/4/305.abstract


How does Ankylosing Spondylitis progress?

September 28, 2013

Whenever one speaks about Ankylosing spondylitis, I’m sure picture of a man with a hunchback & restricted mobility comes to your mind. This famous photograph from the ACR library clearly describes what a patient with Ankylosing spondylitis goes through in his life. Ever wondered what really happens behind the curtain?

Ankylosing spondylitis is a chronic inflammatory arthritis affecting the sacroiliac joints (joints beneath the buttocks), vertebral joints & the hips. The joints get inflamed & persistent inflammation in the long run leads to formation of new bone.

The inflammation is responsible for the pain & the bone formation leads to restriction in movements of the spine.

Let us have a look at a simple example to understand this. The spine is similar to multiple matchboxes hung by a set of flexible threads. The flexibility of the threads is responsible for the movements of the spine. However, if you put wax on the threads & let it set, the threads do not bend. This is exactly what happens with Ankylosing Spondylitis. The threads are akin to the ligaments of the vertebrae & the matchboxes to individual vertebrae. Once the threads become hardened by inflammation (wax) the mobility is lost.

final box

The hardened ligaments give the typical tram track or bamboo spine appearance on the X-Ray.

Ankylosing spondylitis progression xray 2

Ankylosing spondylitis progression xray final 1


Help me help this lady with Ankylosing spondylitis

April 11, 2013

It was a nice Wednesday afternoon. Saw this young lady with Ankylosing Spondylitis.

Reminded me of the typical Indian #rheum story.

She had been having symptoms since last 5 years. She had consulted an orthopedic surgeon for the same. She was diagnosed to have Ankylosing Spondylitis & was started on Sulphasalazine. She was 27 years old & the parents were eager to get her married. They found a groom in her hometown (Uttar Pradesh). It was a typical Indian village.

The parents did not reveal anything about the illness, medicines to the groom. The lady had a tough time after marriage. She had to manage household work with all the pain; more so since she was in a rural Indian setup where the newlywed is supposed to take care of all the work. Taking medicines daily was a big problem as the illness was never declared.

There was another major problem for her. The marriage plan was never discussed with any Doctor & they had never consulted a Rheumatologist. She was not even sure whether Sulphasalazine was safe in pregnancy. Contraception is never in the hands of rural women in India & she was no exception.

As days passed, the pain started becoming unbearable for her & started showing up in day-to-day life. The in laws & the husband soon realised that something was amiss. Due to the workload & stress, she was soon on the bed. The in laws felt cheated & sent her back to her parents.

And that is how they reached me, with anxiety & stress clearly showing in their face. This was some 3 months back. She saw me again this week. Ankylosing Spondylitis was now controlled, backache significantly reduced.

The next was the big question- what to do next? Should she go back to her in laws? If yes, what are they to be told…This caught me unprepared. Apart from the medical management, they also wanted me to help them reach a decision. ‘You must be seeing so many patients with such a problem- you help us take a decision’ they quipped.
Ankylosing Spondylitis being a chronic ailment, this decision is a tricky one.
• She is prone to have ups & downs, down the line. Would her family accept the future pain/ regular medicines?
• One thought was to call her husband/ in laws & counsel them about the disease. However, I was wondering whether they would really come all the way to discuss about her ailment.
• The other thought was to ask her to carry on with her life, concentrate on her health for the time being rather than the stress of going back to the in-laws, working hard in a hostile environment.
• At her in-laws’, she would be under pressure with regards to pregnancy & may find it tough to manage it with Ankylosing Spondylitis presently.
This patient has really caught me unprepared on the decision front. I thought I should be asking the #rheum community to help me out reach a solution for her & guide her.
• What is the best possible solution for her right now?
• What should the parents do prior to marriage as in this case.
Please post your opinion & help me help this lady!


Is HLA-B27 the only gene responsible for Ankylosing spondylitis?

November 27, 2011

We have already seen in the previous posts that HLA-B27 is the most common gene associated with Ankylosing spondylitis (AS). However, HLA-B27 does not seem to be the only gene associated with AS.

Strong indicators of this fact include-
1. AS can occur in individuals who do not carry HLA-B27 gene.
2. Amongst the HLA-B 27 individuals, only about 1-5% individuals develop AS.
3. HLA-B27 positive relatives of AS patients have a risk of developing AS that is 5.6 to 15 times that of HLA-B27 positive individuals in general population. This would mean that there are other non HLA-B27 familial genetic factors involved in causation of AS.

There has been some major work by the Wellcome trust case Control Consortium
& Australo-Anglo-American Spondyloarthritis Consortium to look into the genetics of AS. These (& other) studies have revealed that there are other genes & genetic loci responsible for Ankylosing spondylitis as well—
1. HLA-B60 seen in HLA-B27 positive as well as negative AS patients.
2. HLA-B 39 seen in HLA-B27 negative patients
3. ERAP-1— endoplasmic reticulum aminopeptidase-1
4. Interleukin-23 receptor gene—IL-23R
5. RUNX3
6. KIF21B
7. 2p15
8. IL12B
9. LTBR-TNFRSF1A
10. 21q22
11. ANTXR2
12. PTGER4
13. CARD9
14. TBKBP1

Out of these genes, ERAP-1 & IL-23 R have generated maximum interest. The researchers have found that some variants of ERAP1 protect against the development of Ankylosing spondylitis. For individuals who carry HLA-B27, their risk of developing Ankylosing spondylitis decreases by a factor of four if they carry two copies of the protective variant of ERAP1.

HLA-B27 presents the pathogen antigen to the immune cells. The ERAP-1 gene interacts with HLA-B27 to affect how these peptides are presented to the immune system. The researchers have found that some variants of ERAP1 protect against the development of Ankylosing spondylitis by reducing the amount of peptide available to HLA-B27 within cells. This could prove to be a target for treatment in the future.

Tests for these genetic markers are not available routinely as of now. But, then, if they are found to be clinically useful; tests should be available in the future.

References:
1. Investigating the genetic association between ERAP1 and ankylosing spondylitis. Harvey D & colleagues. Hum Mol Genet. 2009 Nov 1;18(21):4204-12.
2. Progress in the genetics of ankylosing spondylitis. Matthew A brown. Briefings in Functional Genomics (2011) 10 (5): 249-257.
3. Interaction between ERAP1 and HLA-B27 in ankylosing spondylitis implicates peptide handling in the mechanism for HLA-B27 in disease susceptibility. The Australo-Anglo-American Spondyloarthritis Consortium (TASC), the Wellcome Trust Case Control Consortium 2 (WTCCC2), Nature Genetics 43, 761–767 (2011)


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