Inflammation: an engine in the Journey of UCTD

So what is happening in my body on this Journey of UCTD? As I have said in the earlier blogs and in the ones about allergies, the body has the ability to recognise something as foreign and attempts to get rid of it. The allergen gets attacked by the white blood cells and produces an inflammatory response. This process is called inflammation.  Thus the inflammatory response takes place when there is injury to the cells from micro-organisms, any physical or chemical agents as well as those perceived as foreign in the body.

Physiology of inflammation

Inflammatory response is the body’s natural defence mechanism. It protects by neutralising and destroying any toxic substances. It helps to limit the spread of these toxins to other parts of the body and restore homeostasis. There are 4 main characteristics of inflammation – redness, swelling, heat and pain. If inflammation occurs over a part that is involved in mobility then it also will cause restriction or loss of mobility of that part.  

When injury occurs, and in case of UCTD the injury is caused by the damage to connective tissue which is not recognised as self, a number of changes take place to form the inflammatory response. The site will release substances like histamine and bradykinin. Histamine is released from any injured cells that contains it as well as by in response to the chemicals produced by neutrophils (a type of white blood cell). Bradykinin is help to attract neutrophils to the site of injury. There is also an increase in the production of chemicals called prostaglandins. These prostaglandins are potent vasodilators and they enhance the effect of histamine and bradykinin.

These chemicals increase dilation of the blood vessels causing more blood to flow into the area. This gives redness to the area. It also increases the permeability of the blood capillaries allowing fluid and defensive substances to ooze out into the extra cellular space of the surrounding tissues. This causes the swelling seen in the inflammatory response. The defensive products are white blood cells and clot forming chemicals. The white blood cells will destroy any micro-organisms, damaged tissue and foreign substances. The increased blood supply also helps to remove the toxins and dead cells from the site. A clot forms around the site to prevent the micro-organisms and its toxins from spreading.

Another response by the body is to increase metabolism and heart rate so that blood can reach the injured site quickly. The warmth at the site of inflammation is due to the warm blood gathering in the area as well as increased metabolism. The other symptom, pain, occurs due to the irritation of nerve endings by the toxic chemicals and due to pressure caused by the swelling. Prostaglandin also intensifies and prolongs the pain caused during inflammation. The bradykinin also causes the intense pain by affecting the nerve endings. I will discuss pain in more detail in another blog.

Lastly the loss of function or mobility can take place if this inflammation is over or near a joint, its tendons and ligaments.

What does this mean in UCTD?

Once we understand what normally happens in the body as a defence then we can understand what happens in UCTD. Within this autoimmune disease which has not differentiated into any specific kind, the entire body’s connective tissue is open to having an antigen – antibody response. This means there can be injury due to this antigen-antibody response and inflammation will result. So from the realms of general body defence we move to understand the specific body defence.

What is Immune response?

When the resistance is specific to a disease or organism then it is called immunity. When a particular antigen (organism or protein) enters the body and it is recognised as foreign, the body will produce an antibody specific to that antigen. Mostly antigens are proteins of some kind, nucleoproteins, lipoproteins, glycoproteins and some large polysaccharides. With regards to bacteria the flagella, the wall and even the toxins can be the antigen, but non microbial kind varies widely, from pollen, egg white, nuts, oils, perfumes, incompatible blood cells to transplanted organs.

Antibodies are formed against specific sites on the surface of the antigen. Generally antigens are substances that are not usually part of the body. The body has the capacity to recognise itself and so only substances that are ‘non self’ will stimulate antibody production. Need I point out that this is where things go haywire in UCTD? The body cannot differentiate between self and non self, and thinks the connective tissue is an antigen!

The antibody produced is also a protein that is able to combine with a specific antigen. The collective name for antibodies is immunoglobulins as the antibodies are made of proteins called globulins. There are 5 types of immunoglobulins – IgG (increases phagocytosis, neutralizes toxins and protects foetus and new born), IgA (provides protection on the mucosal surface), IgM (effective against microorganisms), IgD (stimulated the antibody production) and IgE (participate in an allergic reaction). These also can be not recognised by the body and can produce antibodies of its own.

When the antibody attaches itself to the antigen, it forms the antigen-antibody complex that the body will destroy and remove. When the antigen happens to be ‘self’ then it will produce an inflammatory response to this perceived injury to its tissue. 

So where is this connective tissue in the body?

Connective tissue is formed by cells and large amount of intercellular matrix and extracellular elements. It forms the framework, connecting, supporting and packing tissue in the body. There are 6 types of connective tissues:

Tissue with cells floating in a fluid matrix – Blood.

Tissue with cells in a semi-solid matrix – mesenchyme, found in embryo and subsequently gives rise to all other connective tissue. 

Tissue with cells in semi-solid matrix with a fine network of reticular fibres in the extracellular space. The tissue forms a 3 dimensional framework for organs such as spleen, bones and lymph nodes. The cells within are capable of ingesting particles, that is they are phagocytes.

Tissue with cells in semi-solid matrix with thicker collagenous and elastic fibres. These are 5 types –

·        Loose Fibrous tissue which form the packing between organs, sheaths of muscles, nerves and blood vessels.

·        Dense Fibrous tissue which is strong and inelastic but pliable and is found in ligaments, capsules of joints and heart valves.

·        Elastic tissue is strong, flexible and extensible and found in blood vessels and air passages.

·        Adipose tissue contains fat and forms a protective cushion around the organs as well as function as an insulating layer in the skin.

·        Tendon is tough and formed by inelastic cords of dense fibrous tissue that allows muscles to be attached to bones.

Tissue with cells in solid elastic matrix with fibres – cartilage which is also of 3 different kinds-

·        Hyaline cartilage which is firm yet resilient and us seen in air passages and ends of bones at joints.

·        White fibro-cartilage is tough but resistant to stretching and found between vertebrae where it acts as shock absorber.

·        Elastic or Yellow fibro-cartilage is more flexible but resilient and found in larynx and the ear.
 
T   Tissue with cells in a solid rigid matrix which is impregnated with calcium and magnesium salts – bone, which forms the rigid framework of the body.

Making sense of UCTD

Now you can connect all three sections – connective tissue, immune response and the process of inflammation and it will give you a fair understanding of what is happening to the body in an autoimmune disease. When specific connective tissue involvement is there, it gives a particular pattern of symptoms and changes to blood constituents and so categorised to a particular autoimmune disease. However, luckily or unluckily, within Undifferentiated Connective Tissue Disease there is no specific pattern or blood changes and so does not allow a specific diagnosis. It is almost as if the body has not decided on which parts are not self. The symptoms fluctuate randomly between various symptoms and so we say that the disease has not differentiated itself. 

One must not assume that the title reflects the inability of the medical profession to make a diagnosis. It is actually a disease in its own right and pretty difficult to pin down as there is no pattern of either the symptoms or of blood and body changes. However, the inflammatory response is seem pretty strongly and can comprise of the whole body. You can look back at the symptoms I have described in the previous blogs to make sense of the pathophysiology of this disease. The medical profession do take a long time to make a diagnosis not only because the investigation results fluctuate but also it takes time for the disease to develop and most would rather wait and see than label the disease immediately. About a quarter of the patients are likely to achieve remission and be disease free. About a quarter will develop and differentiate into one or 2 specific diseases over 5 years. The rest will remain in the undifferentiated category.  

Height of Meanness or Stinginess?

I do some work online of proofreading, editing as well as resume writing for people on a couple of sites. I find the work interesting and certainly stimulating as the kind of work is very diverse.

I have proof read and edited cook books and learnt some interesting recipes. The budding authors have sent me chapters and even whole books to edit and polish, from poetries, stories to self-help books. Then, there were papers being readied for publication or presentation of academic nature or business plans. The diversity of the writing is what makes it all interesting. I have formatted a compilation of short files made for various categories of quotes. The level of writing skills differ considerably as those who are skilled will just ask for proof reading services with some formatting while novice writers will want considerable editing done. I do not charge a lot and prefer to help people but also get a small remuneration.

Often people want proof and samples of my work to see if my services would be acceptable. Now it makes me wonder how they can judge this with their own lack of writing skills. I can provide snapshots of a few odd paragraphs which include track changes but nothing more than that. Then, you have people who wish to get work done, a very small piece to be edited, but ask me to take a test! Neither the work is substantial nor the price asked for doing it bank breaking and you want a test? Then I get a WinZip file with God knows what all in it. I guess the test was to find their test file! I do not think I want to give tests and await results as that actually consumes more time than it would take to do the actual work. Some buyers do not appear to be kind of people who would require specialist service but I guess they do not have time for trivial things like well written and presented writing and that gives me the work.

As for resume writing, that also has brought in interesting variety. I have done resumes for people from all over the world. They can be established professionals or starting out new, post formal education. There have been people who were either running their own business or been in the same employment for a while. These are the resumes that require a lot of effort as I need to weed out the right phrases to describe the role and the achievements in the execution of those responsibilities. The formatting has changed considerably and has to be succinct and concise with regards to the actual specialist skills, soft skills and achievements. There is an emphasis on professional qualification to display the attitude of continuing professional development. Generally the jobs within the last 10 years need to be detailed, while those prior are just listed. Many do not like the idea, but it is important to include interests / hobbies at the end. This helps the reader to see that you are a well-rounded person. I have had a few people curtly tell me that they keep their private life separate from professional one.

I have had people get annoyed that the wording in their ‘job descriptions’ was just copied and pasted with a few words changed. But is it realistic to have a completely rewritten job description? After all it is what your company has deemed to be your work. I can polish it and contract it so that it is not very lengthy. The skills of developing the resume, in such cases, are mainly with bringing out the achievements and skills. I have had people get upset and cancel as they expected me to rewrite the resume for different jobs, as they were pleased with what I had done. I did warn them that the difference from the original would be in the nuances, as embellishing is different from outright lies. I cannot in all honesty write in skills when they are not a part of the job description of any of the jobs in the resume. Even if I did it, surely the employer would be astute to see the lies. In fact, it would be more detrimental to the chance of being interviewed should this lie be noticed. I know, often we can think that yes I could do that or learn it quickly and so I will apply for the job but fabricating your resume is not the way to go. Build up on the transferable skills and work your appropriateness for the job in the personal statement and cover letter.

I think people do not realise that most human resource department and the job agencies tend to do work searches on the resumes and cover letter as a first line of eliminating inappropriate ones.  Therefore, the importance lies in ensuring the right words being used and not falsifying the data. Some people are good and will respond to the request for more information promptly. It is so much easier if one can get the right dates, addresses / cities where the individual was employed. Having a list of courses, workshops and where and when they were achieved is important and most do not have that information in detail in their old resumes.

I can work with all the eccentricities and always provide work on time.  In case of people who have failed to respond, I tend to write in red what needs to be inserted at specific places. Some resumes come in with about 9 pages and have to be whittled down to 3 – 4 pages while some are barely make it into page 2. The cover letters can be generic or specific to a particular job application. There is a skill of writing these 2 different versions and yet keep the individual at the centre of it. People realise they need help in doing their resumes but they have an opinion and get upset if corrected. Again, if you know what should be done and can do it, why are you buying the service? You are coming to me because I am a professional and selling you a service at a miniscule cost. I can give examples of resumes, as I have anonymised a few to use them as such. One or two have tended to get aggressive and taken up a bullying tone and then are shocked to see a feedback highlighting that as the issue with the buyer.

Oh the best thing is seeing how many people want me to believe that they really did not see the appropriate tabs to click in relation to the price of each item they were buying. Often, if the person who I can see is desperately looking for a job and asks for a specific cover letter for just basic price, I do it. But that does not mean people can expect freebies. Some people have bought the order and when told that they have underpaid can feign such innocent ignorance. I had someone send in one order which I did and then they said they had more editing to be done. After checking that I was free to do I was sent the work. I took it on faith that they had paid the correct amount. It was only when I got half way through the work (since it was individual short files) that I realised they had sent me lot more then paid for. When I pointed it out, there was such innocence stating that they misunderstood and that the amount paid was for that basic plus the additional words. They actually had to pay for the basic plus the additional which included the word limit and so I ended up being underpaid. This buyer has promised more work and actually stopped with just one more order as they had to pay the proper price. Again, the price for my expertise is pittance but people wish to take advantage of that as well.

Indeed, I have had orders cancelled after I have started work when I have pointed out that the word limit they have paid for is not even half of the actual word count. I also pointed out that they paid less that the price of the declared word count, came as a shock horror to the buyer. Do people genuinely think I will not notice? Or are these people so inept that they cannot read basic instructions regarding payment. In either case it is a sad vision of humanity for they are either ignorant or cheats. I have decided to be upfront and quote proper price when someone asks if I can do a particular job and not leave it to them to read and click on the right tab. As for people who want to test my skills before they give me work, I have no time for it, if the job is very small. Indeed, if someone is giving me a substantial document, I would be happy to do a page for them as a sample of my work after all that large work will incur a substantial payment.

I have been doing this work for the past 7 months and certainly have learnt a lot about diversity of writing, professions, experiences and skills. It keeps me occupied and polishes my own skills while providing me with some pocket money.

The Gut also comes on the Journey of UCTD

A while back I wrote about allergies and their impact on the gastrointestinal tract. It links in right here as the gut does not get left behind but demands its own compartment in this Journey of UCTD. All the things that happen due to food allergies can happen here as well. If you intend to feel upset about the graphics descriptions of the effects may be this blog is best left unread.

Well the gut can get inflamed as a result of the autoimmune disease. The gastrointestinal tract is made of involuntary muscles. From my earlier blogs you must have sussed that my muscles have been affected by this disease and so is it surprising that I am having GI symptoms too?  Now the first time I ready ever thought about the impact was when I had difficulty in swallowing. I found that it took a bit too long for that well chewed morsel of food to actually pass down the throat. In fact, I could actually feel it slide slowly and often painfully down the oesophagus. This was particularly noticeable when the drink was very cold or hot. Sometimes it felt as if the bolus had stopped in transit and I was thumping my chest to get it moving. As if the blocked pipes get unblocked with a thump? But when your eyes are watering due to the pain and your breath stops, you try even the silliest thing. This was making me feel reluctant to eat and drink. This does not bode well for the body that is being pumped with ibuprofen and bouts of steroids. 

The other thing that happened during this time was a tendency to get constipated. Was this due to lack of adequate fluids and fibre?  Well, I told my rheumatologist and GP about this and next thing I know I am being trotted off to the gastroenterologist. He is not ready to discuss differential diagnosis at this point but suggests that we can go for a gastroscopy and see what is happening. It would help to visualise the state of the mucosa, biopsy the walls and check for coeliac disease. He opined that all my problems could be just part of coeliac disease. So I agreed to undergo this investigation. 

When you get a date with the scope there is some preparation for it. Not as extensive as scoping the other end but still, a nil by mouth overnight. I could take my pills with very little water at 6 am as I was due to be on the table at 10 am. I had an option to be sedated or not for the procedure. Having chatted about this with a friend, I was told it was better not to be sedated as you can help by voluntarily swallowing when the scope was being introduced. Well hindsight is always 20 / 20 and I will never advice anyone to refuse sedation. In fact I would have been very happy if I had been anaesthetised for it. 

I do not think I was totally relaxed as when that mouth guard is inserted you suddenly realise it is hard to swallow with your mouth open. You are lying on your side facing away from the TV screen. I am even denied that small entertainment. Then the gastroenterologist (one who I had never met before) says I am going to spray some local anaesthetic to help numb the mucus membranes. No one tell you that it stings like hell before the numbing can take place. Also that numbing does not mean total loss of sensation. I have been at the other end of this scoping business and remember telling the patient its ok, it is a small scope and fairly thin. But on the receiving end it seems to be more like a drainpipe! Needless to say that this was one procedure that had me sobbing and I wished I was asleep through it. I wanted to yell – I am trying and what do you think I am doing? When the nurse / doctor kept saying swallow, a bit more…. 

I think it only lasted about 30 mins and that’s how long eternity was, for me. I was asked to get dressed and wait outside while the nurse rang my husband and asked him to collect me. If I was hoping for some sympathy, it was in short supply as he was working nights and had to come get me in the middle of his sleep. My throat was sore for a few days. The initial report was that the gut looked good especially considering the hefty doses of ibuprofen being pumped in daily. A couple of weeks later the gastroenterologist told me that coeliac disease has been ruled out after all.

During this waiting period I had developed anaemia and also diarrhoea which can be attributed to the ibuprofen, reduced vitamin B 12 and also the new medication of hydroxychloroquin (Plaquneil). 

  The alternative reason of diarrhoea also related to the food allergies, particularly since some days my husband worked 12 hour shifts, we relied on frozen meals. I was given Vitamin B12 injections and you may have already read my saga about taking iron. I wish one could just lick some rust off the nails. The issue of this being a side effect of plaquenil was very real and dealt with by antihistamine. Actually I needed the antihistamine for the rash that I got after starting plaquenil, and noticed that it helped to control the diarrhoea too. 

So when I saw the gastroenterologist for the results of my gastroscopy, he was concerned about the low Hb and diarrhoea. Since he did not find anything in the upper GI tract, he wanted to do a colonoscopy. His explanation was we just might find the reason for your illness; maybe you have a bleed somewhere which is causing your anaemia, may be you are not absorbing the nutrients as you should. But naturally I will not be absorbing nutrients if I am having the runs. I do not see any blood fresh or otherwise to indicate any bleeds. I think I shocked the young registrar by refusing to get a colonoscopy done on a whim or a vague idea that this might just provide us with a diagnosis. I said I would prefer to wait and see how I respond to the Vitamin B12 injections, iron and antihistamines before I decide to opt for colonoscopy. 

Part of the decision was based on the fact that I had a poor experience of gastroscopy and did not relish the idea of being awake through yet another invasive investigative procedure which might turn out to be just a fishing expedition for the lads. Since then I have had iron injections too and my ferritin levels are back to normal. I am careful in what I eat to ensure I keep allergic reactions to a minimum and having cetirizine / zyrtec daily keeps the side effects dampened down.

Since I have got stabilised, well sort of, I have noticed that just as with other organ systems I tend to have cycles for the GI tract too. I get periods of normal, then slowing of the gut movement when I can have swallowing difficulty, feeling full and slow stomach emptying to being constipated. Then the pendulum swings back and everything speeds up. I do feel a bit hungrier as the stomach empties quicker. I also tend to have a bit of diarrhoea on the days I have to take methotrexate but it is all mostly manageable. So result – no one has asked me to go for a colonoscopy!