chronic illness

Not Too Rare To Care

Vita

Yesterday was rare disease day 2023 * and I want to spread some awareness on one of my illnesses that is categorised as rare (which is: it affects less than 1 per 2000, CIPO is 9 in 1.000.000):

Chronic intestinal pseudo-obstruction (CIPO)

Like many other rare illnesses, CIPO is complex and its progressed form lacks treatment options. Despite its rarity and difficulty us patients want to be heard. We want to live and not only survive. Years (on average > 6) until it is diagnosed is only followed by lifelong suffering.

What is CIPO?

Chronic intestinal pseudo-obstruction (CIPO) is a severe motility disorder where parts of the intestine (oesophagus, stomach aka gastroparesis, small intestine, large intestine, rectum) and bladder don’t work properly. Depending on the affected organs and severity patients suffer from various symptoms that decrease quality of life, (co-)conditions that are life limiting or life threatening.

What are typical symptoms?

Depending on the affected organs there is a variety of symptoms such as:

from wikipedia, organ biology

Oesophagus:

  • Difficulty swallowing
  • Spasms, pain
  • Chest pain
  • Heartburn
  • Vomiting

Stomach/upper small intestine:

  • Abdominal distension
  • Vomiting
  • Nausea
  • Early satiety
  • Loss of appetite
  • Upper abdominal pain
  • Reflux

Large intestine/lower small intestine:

  • Constipation
  • Lower abdominal pain
  • (Pseudo)Diarrhea

Rectum:

  • Difficulty passing stool
  • Feeling of incomplete evacuation
  • Hard stools
  • Spasms
  • Tenesmuses

Where symptoms can be mixed, also between the organs. Pain, nausea and weight loss are often the earliest findings. Often, CIPO is defined as small intestine dysmotility, but in most patients other organs of the GI tract are affected as well. If only of the other organs is affected, the patient might suffer from other illnesses such as achalasia (swallowing disorder), gastroparesis (paralysed stomach), colonic inertia or severe slow transit constopation (paralysed colon) or pelvic floor dysfunction.

Bladder:

  • Inability to pass urine
  • Spasms
  • Frequent UTIs
  • Incontinence

Why ‘pseudo’ and how is it diagnosed?

Normal peristalsis isn’t possible such that the intestines cannot move its food/stool/fluids/gas forward. Symptoms suggest an intestinal obstruction (Ileus), but without a mechanical cause such as adhesions or an actual blockage; hence pseudo-obstruction. Severe CIPO is nothing but an ongoing paralytic (sub)Ileus. Diagnostics show no bowel sounds, dilated bowel loops, air-fluid levels, reverse or forward-backward peristalsis. Motility measurements at neurogastro centres (unfortunately not many exist) e.g. breath tests, imaging studies, manometries and also pathologies from full thickness resection are important in diagnostics.

More info about motility measurements etc can be found here, here and here, more details and personal experiences here, here and here .

What are the causes?

CIPO can be caused by damage of the nerves (neuropathy) e.g. loss (hypoganglionosis) or inflammation (ganglionitis) of ganglia in enteric nervous system (ENS), muscular damage e.g. atrophy of muscle cells (myopathy), metabolic issues (e.g. Diabetes often comes with gastroparesis), genetic forms (e.g. FLNA due to cytoskeleton damages, ACTG2 smooth muscle cell damages, MYH11), mitochondrial diseases, damages of the CNS (e.g. brain tumor) or ANS e.g. AAG. It can be primary or secondary due to other conditions such as connective tissue diseases, Parkinson and MNGIE as well as some infections e.g. Chagas or after chemotherapy. Doctors have to analyse the patient’s symptoms and history, fruther specific tests, blood results, biopsies, imaging, autonomic testings etc might be necessary.

Aside of the chronic form there also exists an acute form of a paralysed colon (ACPO), often after surgery or an infection.

Neuropathy leads to uncoordinated contractions, myopathy to too weak contractions. Often it is a mixture of both. Full thickness resection biopsies and manometry findings are needed to find the underlying issue.

What are the therapy options?

Depending on the location, cause and symptoms there are different therapy options from medication (anti-emetics against nausea, prokinetics for speeding up motility), pain management, food adaptions (frequent small meals, high/low fiber, low Fodmap, low fat, liquid, high calorie drinks etc), interventions e.g. nutritional support (tube feeding e.g. NJ tube to pass the stomach in isolated gastroparesis etc, parenteral nutrition via central venous catheters) and decompression (drainage tube, ostomies) and more (pacemakers, resections e.g. colectomy in isolated colonic inertia, transplant). Unfortunately, in severe cases there aren’t many treatment options that work efficiently and often patients are fully dependent on TPN which has its own complications. Intestinal or multi visceral transplant might be needed at some point, if possible. Depending on the cause additional therapy option like immunosuppressive drugs might be effective.

What are its risks?

CIPO comes along with weight loss due to lack of calories, malnutrition, malabsorption and/or lack of vitamins and minerals as well as dehydration. Weight loss itself leads to problems like osteoporosis. Often patients suffer from infections, inflammations or SIBO (small intestinal bacteria overgrowth) due to the lack of peristalsis. Bladder dysfunction leads to frequent UTIs and can reduce kidney function, beyond meds and self-catheterising more interventions might be needed.

Other organ issues follow from the complexity of their interdependence with the GI system.

Pain management is often very difficult. Especially, since severe pain at some point often is treated with opioids or other drugs that slow down motility which obviously increased the underlying problem. Patients are in a vicious cycle between severe pain without relief or pain treatment that increases the risk of obstructions.

Patients shouldn’t undergo surgery if it cannot be treated in another possible way. Any surgery is a major invasion in a system which is already under severe damage. However, often surgery cannot be avoided or patients undergo unnecessary surgery due to the lack of knowledge or late diagnosis.

If TPN is needed, liver damage or vascular issues e.g. thrombosis or loss of vascular access can occur, there is an increased infection risks, teh worst case is a life-threatening sepsis. Intestinal failure is a severe complication in CIPO. A small intestinal transplant or multi-visceral (if the liver has failed or the stomach is severly affected, too) might be the only therapy option left if such complications occur. If the patient cannot undergo the transplant, palliative care is the final way.

Obviously, these problems have to be dealt with as well, if possible.

Why spreading awareness?

Often CIPO is diagnosed after many years of diagnostics and, unfortunately, also (unnecessary) interventions. If surgery can be avoided patients shouldn’t undergo abdominal intervention since any further damage in the nervous system can amplify the illness.

Moreover, there are limited treatment options, especially for severe forms. Patients suffer daily from severest pain, nausea and more, have endless interventions and hospital stays, the day has to be planned according to the body’s needs. Multidisciplinary treatment is needed, but often not given. The condition along with its co-conditions and symptoms come with disability, uncertainty, unpredictability and poor prognosis.

Hence, there needs to be more awareness, education and communication. Generally, the field of neurogastroenterology needs improvement and spreading, patients need better access to diagnostics and treatment and there has to be more research in motility and motility diseases, the ENS etc.

From my own experience I can say that the diagnosis (or rather the official diagnosis as I was basically diagnosed with it) took so long that I underwent a major vascular compression surgery that obviously didn’t solve the main underlying issue of my symptoms (aside of the far too invasive approach that was chosen). Many patients with severe dysmotility such as CIPO undergo interventions due to desperation or lack of knowledge of their doctors or both. However, most interventions only damage motility even more via damage of the external nervous system (such as damages of the celiac ganglion, mesenteric ganglia), spinal damage or due to mechanical issues from adhesions etc. I can say for sure that if I hadn’t undergo the first surgery in 2017 (that led to the two emergency surgeries directly and the aneurym resection and autotransplant surgeries afterwards, complications, nerve damage, life-long issues that we aren’t even aware of now etc i.e. in total nerve damage plus lots of adhesions and with that further obstructions combined with the underlying CIPO that needed treatment) the dysmotility wouldn’t have progressed that much in the past years. I am fully TPN and fluid dependent, I am constantly in paralytic (sub)ileus states, I am constantly under severe pain and nausea, I suffer from severe vomiting episode, I suffer from so many co-conditions that are life-limiting/threatening that the list fills two pages, I have a very poor prognosis and a very poor quality of life. I survive.

Interested?

More information on dysmotility, CIPO, the enteric nervous system (ENS), the autonomic nervous system (ANS) etc as well as my own experience undergoing diagnostics or suffering from typical symptoms and complications have a look at my older posts such as here, here, here, here, here and here

to be continued.

Here ist a list of publications according to its topics.

Guidelines 

Intestinal dysmotility

  • Nightingale JMD, Paine P, McLaughlin J on behalf of the Small Bowel and Nutrition Committee and the Neurogastroenterology and Motility Committee of the British Society of Gastroenterology, et al, The management of adult patients with severe chronic small intestinal dysmotility, Gut 2020
  • Singh R et al., Current Treatment Options and Therapeutic Insights for Gastrointestinal Dysmotility and Functional Gastrointestinal Disorders, Sec. Gastrointestinal and Hepatic Pharmacology,Volume 13, 2022
  • Prichard DO et al., Dysmotility of the small intestine and colon, Yamada’s Textbook of Gastroenterology, Chapter 55, 2022
  • More about its treatment

Intestinal failure 

  • Grainger JT, Maeda Y, Donnelly SC, Vaizey CJ. Assessment and management of patients with intestinal failure: a multidisciplinary approach. Clin Exp Gastroenterol. 2018;11:233-241
  • Brockmann, J.G., Hüsing-Kabar, A., Bohlen, K. et al. Chronisches Darmversagen.  Chirurg 93, 205–214, 2022

Cipo

  • Zhu CZ, Zhao HW, Lin HW, Wang F, Li YX. Latest developments in chronic intestinal pseudo-obstruction. World J Clin Cases 2020; 8(23): 5852-5865 [PMID: 33344584 DOI: 10.12998/wjcc.v8.i23.5852]
  • Mann SD , Debinski HS , Kamm MA, Clinical characteristics of chronic idiopathic intestinal pseudo-obstruction in adults. Gut 1997;41:675–81.doi:10.1136/gut.41.5.675
  • Connor FL, Di Lorenzo C. Chronic intestinal pseudo-obstruction: assessment and management. Gastroenterology 2006; 130: S29-S36
  • Stanghellini V, Cogliandro RF, de Giorgio R. et al. Chronic intestinal pseudo-obstruction: manifestations, natural history and management. Neurogastroenterol Motil 2007; 19: 440-452
  • Seidl H, Pehl C, Schepp W. et al. Chronic intestinal pseudo-obstruction – review and update 2008. Z Gastroenterol 2008; 46: 704-711
  • Also: PMID: 18494042, PMID: 17564625, PMID: 35131150, PMID: 34007199 (Iatrogenic harm, diagnostics and treatment)
  • more: here
  • Genes associated to CIPO
  • enteric neuropathies PMID: 27426273, PMID: 22266104

Nutrition

Surgery

  • Abu-Elmagd KM, Armanyous SR, Fujiki M, Parekh NR, Osman M, Scalish M, Newhouse E, Fouda Y, Lennon E, Shatnawei A, Kirby D, Steiger E, Khanna A, Radhakrishnan K, Quintini C, Hashimoto K, Barnes J, Costa G. Management of Five Hundred Patients With Gut Failure at a Single Center: Surgical Innovation Versus Transplantation With a Novel Predictive Model. Ann Surg. 2019 Oct; 270(4):656-674. doi: 10.1097/SLA.0000000000003523. PMID: 31436550.
  • Masetti M et al., Intestinal Transplantation for Chronic Intestinal Pseudo-Obstruction in Adult Patients, American Journal of Transplantation, Volume 4, Issue 5, 2004
  • Richtlinien Warteliste Dünndarmtransplantation, siehe Bundesärztekammer (German)
  • A. Pascher et al , Present status and future perspectives of intestinal transplantation, 2007
  • DiLorenzo C, Surgery in Intestinal Pseudo-Obstruction: Pro, Journal of Pediatric Gastroenterology and Nutrition 41, 2005 doi:10.1097/01.scs.0000180311.55417.55
  • More: PMID: 24182815 (long term outcome), postoperative ileus, motility after digestive surgery, surgical treatment, PMID: 23026616 immunosuppression protocol after transplant
  • More information (German)

Medication

  • Effect of opioids: Rogers M , Cerda JJ, The narcotic bowel syndrome. J Clin Gastroenterol 1989; 11:132–5
  • Motility drugs: McQuaid KR (2018) Drugs used in the treatment of gastrointestinal diseases. In: Katzung BG (ed) Basic and clinical pharmacology, 14th edn. McGraw-Hill, New York, pp 1096–1098
  • Wu GY (2003) The pharmacology of prokinetic agents and their role in the treatment of gastro intestinal disorders. Int J Gastroenterol 1(4):6–13

Tests in dysmotility

More

ENS

  • Schemann M, Annahazi A, The enteric nervous system: “A little brain in the gut”,  De Gruyter, 2020
  • Furness JB. The enteric nervous system and neurogastroenterology. Nat Rev Gastroenterol Hepatol. 2012 Mar 6;9(5):286-94. doi: 10.1038/nrgastro.2012.32. PMID: 22392290. (Also CNS)
  • Knowles CH, De Giorgio R, Kapur RP, Bruder E, Farrugia G, Geboes K, Gershon MD, Hutson J, Lindberg G, Martin JE, Meier-Ruge WA, Milla PJ, Smith VV, Vandervinden JM, Veress B, Wedel T. Gastrointestinal neuromuscular pathology: guidelines for histological techniques and reporting on behalf of the Gastro 2009 International Working Group. Acta Neuropathol. 2009 Aug;118(2):271-301. doi: 10.1007/s00401-009-0527-y. Epub 2009 Apr 10. PMID: 19360428.
  • Fleming MA 2nd, Ehsan L, Moore SR, Levin DE. The Enteric Nervous System and Its Emerging Role as a Therapeutic Target. Gastroenterol Res Pract. 2020 Sep 8;2020:8024171. doi: 10.1155/2020/8024171. PMID: 32963521; PMCID: PMC7495222.
  • Kapur RP, Bellizzi AM, Bond S, Chen H, Han JS, LeGallo RD, Midgen C, Poulin AA, Szabo S, Uddin N, Warren M, Velázquez Vega JE, Zuppan CW. Congenital Myenteric Hypoganglionosis. Am J Surg Pathol. 2021 Aug 1;45(8):1047-1060. doi: 10.1097/PAS.0000000000001670. Erratum in: Am J Surg Pathol. 2021 Dec 1;45(12):1728. PMID: 33492848.
  • Gariepy, C. Intestinal Motility Disorders and Development of the Enteric Nervous System, Pediatr Res 49, 605–613 (2001).
  • Wood, J.D. Enteric Nervous System: Neuropathic Gastrointestinal Motility. Dig Dis Sci 61, 1803–1816 (2016)
  • Holland, A.M., Bon-Frauches, A.C., Keszthelyi, D. et al. The enteric nervous system in gastrointestinal disease etiology. Cell. Mol. Life Sci. 78, 4713–4733 (2021).
  • Chalazonitis A, Gershon MD, Greene LA. Cell death and the developing enteric nervous system. Neurochem Int. 2012 Nov;61(6):839-47. doi: 10.1016/j.neuint.2012.01.028. Epub 2012 Feb 8. PMID: 22342822; PMCID: PMC3398212.
  • Törnblom H , Lang B , Clover L , et al . Autoantibodies in patients with gut motility disorders and enteric neuropathy. Scand J Gastroenterol 2007;42:1289–93.doi:10.1080/00365520701396216
  • Inflammatories neuropathies: PMID: 15188182, PMID: 16624634, here
  • Virus infection PMID: 18593810, PMID: 34094993
  • Ganglionitis
  • More resources about the ENS https://www.mayo.edu/research/labs/cellular-molecular-physiology-gastrointestinal-disorders/overview , http://www.scholarpedia.org/article/Enteric_nervous_system , PubMed 36521049 , PMID: 10099684 (older, but explains the regulation of the GI system according to ENS functions)
  • Neuroimmunogastroenterology

ANS

  • Some general information: PMID: 26502768, PMID: 12352004, PMID: 31753129, PMID: 30969667
  • gAChR antibodies PMID: 10995864
  • More: https://thedysautonomiaproject.org/resources/
  • and GI:
    • Duan H et al., Regulation of the Autonomic Nervous System on Intestine, Front. Physiol., 14, Sec. Gastrointestinal Sciences, Volume 12, 2021
    • Bharucha AE , Low PA , Camilleri M , et al . Pilot study of pyridostigmine in constipated patients with autonomic neuropathy. Clin Auton Res, 2008
    • Kornum, D.S.; Terkelsen, A.J.; Bertoli, D.; Klinge, M.W.; Høyer, K.L.; Kufaishi, H.H.A.; Borghammer, P.; Drewes, A.M.; Brock, C.; Krogh, K. Assessment of Gastrointestinal Autonomic Dysfunction: Present and Future Perspectives. J. Clin. Med. 2021, 10, 1392
    • PMID: 36588909, PMID: 15088266
    • And autoimmune: Golden EP, Vernino S. Autoimmune autonomic neuropathies and ganglionopathies: epidemiology, pathophysiology, and therapeutic advances. Clin Auton Res. 2019 Jun;29(3):277-288. doi: 10.1007/s10286-019-00611-1. Epub 2019 May 15. PMID: 31093868.

SFN

  • Schofield protocol: How We Treat Autoimmune Small Fiber Polyneuropathy with Immunoglobulin Therapy DOI: 10.1159/000498858
  • Cascio MA, Mukhdomi T. Small Fiber Neuropathy, 2022
  • And GI dysmotility: PMID: 31998505 , case reports, PMID: 26711856

Chronic Pain

  • Butler D u. Moseley LG (2009): Schmerzen verstehen; Springer-Verlag, ISBN 978-3642016868
  • Louw A (2013). WHY DO I HURT? A  Patient book of the neuroscience of pain. International Spine and Pain Institute
  • Richter J (2021). Schmerzen verlernen – Anleitungen und Übungen zur Selbsthilfe, 4. Aufl. Springer
  • Kabat-Zinn J (2013). Schmerz: Meditationen zum Umgang mit chronischen Schmerzen, Arbor
  • Pain management in CIPO
  • Visceral hypersensitivity
  • see also here and here
  • Psychology and mindfulness in chronic illness/pain
    • Emmons, R. A., & McCullough, M. E. (2004). The psychology of gratitude (Series in affective science). New York, NY: Oxford University Press.
    • McCraty, R., & Childre, D. (2004). The grateful heart: The psychophysiology of appreciation. In R. A. Emmons & M. E. McCullough (Eds.), Series in affective science. The psychology of gratitude (pp. 230–255). New York, NY: Oxford University Press.
    • See also PMID: 21191529, PMID: 20451313

More

Videos

Further information on rare illnesses, the difficulty in diagnosis and treatment, the importance of support and research &the importance of awareness and education, to reduce ‘misdiagnosis, inequality and isolation’. Whether you are a patient with a rare illness, an undiagnosed condition, a caregiver or just interested:

**important guidelines in Europe and Leitlinien Deutschland (vor allem S3-Leitlinie Intestinale Motilitätsstörungen)

021-018l-s3i_intestinale-motilitaetsstierungen_2022-03_Download

**A rare disease is a condition that affects only a few people (less than 1 in 2000 patients in Europe). Many of those conditions are chronic (mostly congenital), progressing and either life-threatening or -limiting.

Often there are not many treatment options due to the lack of guidelines, stats and research. Additionally, possible treatment options are difficult to realise or only available on the other side of the Earth.

If you are lucky you get the diagnosis, if you are very lucky you find a team that is specialised in this particular rare disease and admits you and if you are exceptionally lucky this team will start treating you. 

There needs to be more awareness for the difficulties we undergo during the process of diagnostics and treatment (or lack of it). Sometimes the lack of knowledge and support can be more painful than the whole plethora of symptoms we have to face every single day, 

In times of lack of medical support and therapy options I am even more grateful for your emotional support.

I am not alone. You are not alone.

I will send some updates soon. There are many posts waiting to be published. Unfortunately, I haven’t been well enough to do so.

Published by Vita

Hey, I am Evita and 27 years old. Maths, physics and riddle enthusiast. Wonderer and wanderer. Explorer and mindfulness meditator. Nature and dog lover. Chronic illness warrior. Serendipity.

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