ME/CFS RESEARCH FORUM REPORT:
Adelaide Research Network 3 - 4 June 2005
UNIVERSITY OF ADELAIDE
Convenor: Alison Hunter Memorial Foundation
Dr Richard Schloeffel MBBS FRACGP
Sydney NSW Australia
Symptom profiles of 5 CFS cases with catastrophic GIT involvement
My experience in dealing with ME/CFS is spread over some 24 years with approximately 2500 patients being seen in that time, with variable symptom complex and degrees of severity. The following 5 case histories represent a severely affected subgroup of ME/CFS patients with catastrophic gastrointestinal involvement and potentially life threatening complications.heir difficulty in diagnosis and management will become apparent.
Case history 1
Patient H Female Age 53
H was first seen in April 2001 with a 5 year history of severe fatigue, being bedridden on and off over that period of time. She was experiencing significant sinus headaches and associated migraines. There was progressive weight loss, hypotension, dysphagia, reflux, markedly reduced gastric function with extreme multiple food and chemical sensitivity syndromes. H was also experiencing genital herpes with attacks occurring every 8-10 days, generalised myalgia, marked sleep dysfunction and overwhelming cognitive dysfunction with both memory and concentration impairment. Various treatments have been tried with major aggravation of her symptoms.
Over the past 4 years H's condition has deteriorated to a point where she is primarily bedridden and is only able to tolerate a diet of particular vegetables, gluten free bread and fish. No other foods can be tolerated without inducing severe migraines lasting for several days. Her migraines do have some response to Cafergot up to 2-3 taken per day but are totally unresponsive to analgesics and particularly to Imigran etc which seems to aggravate the severity of the headache and induce hyperemesis.
H is also experiencing total bowel inertia with absolute constipation requiring daily water enemas to remove any faecal material. Clinically, there is marked faecal loading throughout the whole colon and some degree of prolapsed rectum. Gastric emptying and colon transit studies have not been performed due to the severity of reaction to foods and additives. The bowel sounds are mostly absent and there is associated tenderness generally throughout the abdomen on palpation. Her weight is down to 42 Kg at present with an ideal body weight of 56 Kg.
Thorough investigation of H has been undertaken over the past few years with the following abnormal findings. A PCR test was performed on whole blood in 2001 with a positive Rickettsial australis. Rickettias antibodies were found subsequent to the PCR.
Two years of antibiotic therapy failed to have any benefit with regard to the Cricket illness, the original diagnosis given for her ME/CFS.
Herpes simplex virus swabs have been positive from vaginal lesions, and nasal swabs have shown Staphylococcus aureus. Faecal studies have shown dominance of Clostridia 37% in the gut with an unknown gram positive rod of 26% being isolated from her faecal material. H has a generalised IgG subset 3 deficiency with extremely low levels.
A urine test was performed to exclude mitochondrial disorders such as mitochondrial neurogastrointestinal encephalopathy MNGIE which was negative, but as yet no muscle biopsy has been done due to the severity of her illness.
The only medical treatment that has been effective is an injection of Gamma globulin 5 ml IMI very 2 weeks, which has generally controlled the genital herpes, and the only supplement that has been tolerated is Bio-zinc one a day.
H is currently in a very debilitated life threatening state. Prior to her first consultation with me she was seen by several physicians, gastroenterologists, neurologists and psychiatrists without any definite diagnosis or management protocol being effectively used to help her with her symptoms.
It is possible that H continues to have a number of very complex infections disturbing her immune system.
Case history 2
Patient V Female Age 33
V was first seen in July 2003 with a history of sever gastrointestinal infection 10 years previously, associated with severe vomiting and dehydration but no diarrhoea. At the time it was thought that she had viral gastritis. Since then V has developed worsening abdominal pain associated with any eating or drinking, progressive fatigue, muscle pain, generalised body weakness, constant nausea and extremely slow transit constipation.
V has a past history of cytomegalovirus and Epstein Barr virus. A PCR test on whole blood was positive for Chlamydia pneumoniae.
Over the past 12 months she has developed seizures "to foods, medications, smells, chemicals" associated with hypotension, muscle spasm and twitching of the body as well as loss of control of her limbs. Over the past 3 months she has developed anaphylactic reactions to foods and chemicals; for example, recently when her husband was cutting up capsicum in another room V developed an anaphylactic reaction requiring urgent admission to hospital and treatment with adrenalin and hydrocortisone.
The following investigations have been performed :gastric emptying study which showed a gastric emptying time of 49 minutes but the colon transit study had to be abandoned after 6 days, and it was predicted that it would be somewhere between 10 and 14 days before the isotope would be passed from the colon. Faeces analysis indicated an overgrowth of Clostridium species, low E. coli levels, infestation with Blastocystis hominus, and overgrowth of Candida albicans.
V also had an RNAse L test performed by Professor Kenny De Meirleir ,Belgium which was at a level of 500 indicating severe infection. Her 25 OH vitamin D level was extremely low, as was her vitamin B12 level and iron studies, including a very low ferritin. Nutritional analysis indicated marked deficiency in most amino acids, fats, free fatty acids and other lipids and all the nutritional minerals–consistent with a starvation profile.
A tilt table test was strongly positive and analysis of her body temperature indicates that she is primarily hypothermic most of the time, with a body temperature averaging 35.5 C. Urine analysis for MNGIE was negative. Due to the severity of V's illness a muscle biopsy has not yet been performed to exclude other forms of mitochondrial disorder.
Clinically, V is extremely thin, with a body weight of 40 Kg, BP 100/70 and a feeble pulse at 76 beats per minute. She exhibits extremely cold extremities and there are multiple trigger points throughout her body, with muscle spasms and pain.
V has a very restricted diet which includes soya products, rice bread, butter and a small amount of eggs. Other foods induce severe abdominal pain, seizures, generalised body weakness, as well as hypotension and incidents of anaphylactic shock. She is using water enemas twice daily to assist in the evacuation of her bowel due to the severe bowel inertia.
She has recently seen a gastroenterologist regarding options for treatment and parenteral nutrition. The greatest risk of these treatments is the extreme sensitivity V experiences to any form of treatment or dietary change.
V has catastrophic complications with all the manifestations of metabolic failure associated with an immune complex disorder and multiple infections, with the possibility of mitochondrial disorder.
Case study 3
Patient L Female Age 34
L was first seen by me in February 1999 with a history of post-Glandular Fever Chronic Fatigue Syndrome. Symptoms included severe insomnia, constipation, food and chemical sensitivity syndrome, weight loss, nausea, dysphonia, amenorrhoea and intractable fatigue. Over the past 6 years she has developed progressively worsening food sensitivity, bowel inertia requiring daily enemas and marked intolerance to not only foods but medication and most supplements. L also experiences constant oral Herpes simplex infections.
Investigations with positive results are gastric emptying and colon transit studies which were both grossly delayed with her gastric emptying taking up to 4 hours and predicted colon transit time of 10 days or so. A PCR test on whole blood indicated a Chlamydia pneumoniae infection, antigliadin antibodies IgA and IgG were both strongly positive, but tissue transglutamase and Endomyosial antibodies were negative. Faecal analysis indicated she had totally absent E coli in the gut, high Streptococcus and Staphylococcal growth, low Bacteroides but dominant Provetella and Clostridium species. A urine test for MNGIE was negative but there was some indication that L has a possible mitochondrial disorder which will need to be excluded by muscle biopsy when well enough to undertake the test.
Clinically L currently weighs 39 Kg, has a feeble pulse around 80/min with a BP of 90/60. She has dysphonia, looks frail, has grey hair and very thin skin.
Management includes the use of a mask and air filter to restrict the exposure to sensitising chemicals. Sleep is assisted with the use of Euhypnos (Temazepam) which has to be imported from the US due to severe chemical sensitivity to lactose which is present in all other forms of Temazepam in Australia. L is currently on pulsed Ampicillin therapy to reduce the bacterial overgrowth in her gut, on a markedly restricted diet and on a number of probiotics.
L also uses daily water enemas to address her almost total bowel inertia, and is taking Intal (sodium chromoglycate) orally to reduce the chemical and allergic reactions in her gut. Pancreatic enzymes appear to assist in her digestion and she has responded reasonably well to Nilstat oral capsules which have reduced some of her symptoms of food sensitivity. L has significant hypotensive reactions to glucose, gluten and lactose, and has had marked benefit from large doses of Co Enzyme Q10 indicating possible mitochondrial disorder.
This patient appears to be in life-threatened state. Numerous physicians, ENT specialists and gastroenterologists have failed to grasp the severity of her condition and are at a loss on how to manage her progressively worsening symptoms.
Case study 4
Patient A Female Age 45
A was first seen in October 2004 with a history of severe ME/CFS after being exposed to Aldrin in 1983. When she was initially exposed to this pesticide she experienced a miscarriage within 24 hours, and has never recovered from this time, with the development of severe chemical and food sensitivity syndrome associated with her ME/CFS.
Gastroparesis and bowel inertia have been confirmed, diagnosed and managed with ileostomy and PEG feeding some 3 years ago. Unfortunately she has continued to deteriorate over this time and currently weighs 29 Kg. A experiences grand mal fits when exposed to food, most medications and enemas that were being used to remove excessive bacterial overgrowth from the redundant large bowel.
Recently A has had an overwhelming urinary tract infection associated with a life threatening bacteraemia. A is currently being managed at home with palliative care nursing support as she experiences constant fitting when she is exposed to a hospital environment.
Clinically her weight varies between 29 and 34 Kg. She is skeletal, with a pulse of 100/min abd BP 90/60. The PEG has been removed as it appeared to be blocked and there was some degree of infection around it, but the ileostomy has some minimal function.
The following investigations have been performed - urine test for MNGIE was negative. with the raised uracil suggested the possibility of a mitochondrial disorder. A has been too unwell to undertake a muscle biopsy. A tilt table test was positive, bone density scan has shown marked osteoporosis, a full blood count indicated neutropenia, and she has raised liver function enzymes. Blood test results are consistent with marked dehydration.
Current diet includes rice, fish, egg whites, potato, honey, soy products and tomato soup. A can tolerate omega 3 oils, and is on Dilantin 300 mg daily and Rivotril 1 mg nocte to control her fits. The significant abdominal pain has been controlled with Kapanol (morphine) 10 mg 4 times a day, crushed to improve absorption.
A is in an extremely compromised state. Recently she has consulted a general surgeon who is considering a total colectomy. We believe the overgrowth of bacteria in her colon may be neuropathic and may be associated with her fitting, cognitive dysfunction and pain. Her prognosis remains grave. I believe any opportunistic infection may well threaten her life.
Case study 5
Patient B Female Age 27
B was first seen in August 1997 with history of post-glandular fever ME/CFS. At the time of diagnosis she developed blepharospasm of the left eyelid and extreme vomiting, up to 30 times a day. Following her original illness her weight loss was significant, down to 39 Kg .B had associated myalgia, amenorrhoea and total bowel inertia. I presented B's case history and poor prognosis at the 1999 Sydney International Conference for ME/CFS.
The investigations included a gastric emptying time and colon transit studies, which indicated extreme gastroparesis of 6 hours and a colon transit time predicted at 13 days. A whole blood PCR test demonstrated Mycoplasma fermentens. She was anaemic initially, had neutropaenia and iron deficiency. Urine analysis for MNGIE was negative.
The management of this patient has been long and protracted with numerous admissions to hospital, nasoduodenal feeding, parenteral nutrition, multiple vitamin infusions and injections and various medications to improve her bowel inertia.
In 2002 B had surgical implantation of a gastric pacemaker, with a reduction of vomiting and subsequent weight gain. B's bowel function responded well to Colgout (Colchicine) 500mg2 BD,intensive probiotics, magnesium oxide and digestive enzymes.
Her bowel has responded well to Colgout (Colchicine) 500mg 2 bd, intensive probiotic therapy, magnesium oxide and digestive enzymes.
B is now able to exercise, has a social life and has recently become engaged.
Unfortunately all is not well as the pacemaker has been infected for the past year with Staphylococcus aureus, Candida glabrata and more recently E coli bacteria have been isolated from a discharging sinus. She has been on rotational Rifampicin, Fucidin, Keflex and Diflucan. In the past few weeks she developed a right axillary and subclavian vein thrombosis and is currently on Warfarin. The cause of the thrombosis is unknown.
B's current diet includes mainly very soft or liquid food, and she continues to have Ensure daily. She also has a vitamin B complex injection every 2 weeks.
I believe B’s prognosis is much better than the others, possibly because of the absence of severe food and chemical sensitivity syndrome, and the positive outcome with gastric stimulation and bowel activation using medication.
A muscle biopsy is proposed to exclude mitochondrial disorder.
I have tried to present just a few of my severely affected patients with ME/CFS.
In my long years in general practice and in treating these patients I find it hard to imagine that many doctors do not believe there is an organic basis for these very complex and difficult syndromes. Psychiatric attributions such as somatoform disorder need to be abandoned as soon as possible to allow these patients access to proper medical management and to promote biomedical research into these complex disorders.
As part of the Adelaide meeting we discussed the need for a tissue bank to be established. Professor Kenny De Meirleir outlined a number of tests that would be useful in the diagnosis of ME/CFS and to assess the subtypes which would be consistent with the very variable symptom patterns of patients presentations.
Chronic infections such as Mycoplasma, Chlamydia, Lyme disease and other chronic viral, atypical bacterial, bacterial, fungal and parasitic infections need to be investigated in these patients. Immune status must be assessed to understand the variable immune responses to infections, foods and chemicals, and the obvious worsening of their symptoms when patients attempt to do anything outside their very restricted lives.
The collection of sample materials including blood, body fluids and tissues such as muscle biopsy, lymph node biopsy etc is very important to help in the understanding of the pathogenesis of these syndromes. There is currently no protocol for autopsy .
It is thought that there are approximately 140,000 Australians experiencing some form of ME/CFS. It is the duty and responsibility of all physicians to open their minds in a scientific endeavour to understand this illness and to offer compassionate and unwavering support to the numerous sufferers and their families.
The Canadian ME/CFS Consensus Document should be adopted as a matter of urgency. Funding is needed :
- to promote scientific research, diagnostic testing and management protocols to enable all medical and paramedical personnel to better assist their patients with ME/CFS
- to establish tissue banks for further study of ME/CFS
- to develop strict autopsy protocols to expand the knowledge of this devastating disorder.
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