Pediatric Primer

[JaimeS]

activin enhances FSHbiosynthesis and secretion

I will say that I take Vitex, which encourages LH production and inhibits the release of FSH. If activin B is high in ME/CFS patients, then Vitex should counter some of the hormonal consequences.

 

[RogerBlack]

The full plain text paper is at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5474682/

 

[Dolphin]

ME/CFS is characterized by overwhelming fatigue with a substantial loss of physical and mental stamina. Cardinal features are malaise and a worsening of symptoms following minimal physical or mental exertion. These post-exertional symptoms can persist for hours, days, or weeks and are not relieved by rest or sleep.

I would have preferred if they had added "substantially" in front of relieved i.e. are not "substantially" relieved by rest or sleep.

This ["specifically"] is the language used in the Fukuda criteria.

Rest or sleep can alleviate to an extent.

I see this mentioned without substantially and I think it would sometimes be read to suggest resting or sleeping is bad.

 

[Dolphin]

It is generally accepted that young people with ME/CFS have a more favorable prognosis than adults. There have been few studies with sufficient numbers and duration of follow-up to be confident of the findings, but factors such as severity of symptoms or age at onset have not been shown to be reliable predictors of long-term outcomes. In a follow-up study of nearly 700 young people the average duration of illness of those who report having “recovered” was 4–5 years with a range from 1 to 15 years. By 5 years, 60% reported recovery, and by 12 years, 88% reported recovery. Of those who reported recovery, about one-third admitted to modifying their activities to remain feeling well (19). Several other studies found that although many patients improved, 20–48% showed no improvement or actually had worse fatigue and physical impairment at follow-up times ranging from 2 to 13 years (20–22). Even among those who report having completely recovered, many describe persistent symptoms that are not reported by healthy individuals (20).

I would have liked if they had also cited the 25-year follow-up of reference 20:

J Clin Psychol. 2012 Sep;68(9):1028-35. doi: 10.1002/jclp.21880. Epub 2012 Jun 29.
Understanding long-term outcomes of chronic fatigue syndrome.
Brown MM1, Bell DS, Jason LA, Christos C, Bell DE.
Author information

Abstract
OBJECTIVE:
This study sought to examine long-term health, symptom, and disability outcomes among patients with chronic fatiguesyndrome (CFS) by comparing those diagnosed with CFS 25 years ago with healthy controls.

METHOD:
Of the 25 participants diagnosed with CFS 25 years ago, 5 self-reported that they maintained a diagnosis of CFS, while 20 reported no longer having a diagnosis. These two groups were compared with healthy controls on outcomes related to functioning and symptom severity.

RESULTS:
Those who remitted from CFS showed significantly more impairment on 21 out of 23 outcomes compared with controls. On 17 outcomes, those who remitted had nonsignificant differences in impairment compared to those who maintained a CFS diagnosis.

CONCLUSIONS:
Findings from this study suggest that over time many individuals will not maintain a CFS diagnosis but will not return to their premorbid level of functioning.

PMID: 22753044
PMCID: PMC3940158

DOI: 10.1002/jclp.21880

http://onlinelibrary.wiley.com/doi/...ionid=61B21896F758EE0A7D70385453C9F1B5.f04t04

 

[Dolphin]

Feedback from young people indicated that an important determinant of their functioning as adults was the effort made to enable them to remain engaged in education. This might have followed relatively unconventional pathways but it enabled them to remain socially connected and to feel they were able to achieve their aspirations fully or in part. From this group, more than 95% were either studying or working part or fulltime (23).

I think this might be confusing correlation with causation. Probably the more mildly and moderately affected people could remain in education more easily than those more severely affected. So good to support people if they can undertake some form of education but don't be too forceful about the recommendation.

 

[Dolphin]

Establishing a diagnosis frequently provides the patient and parents much relief. Early diagnosis of ME/CFS can lessen the impact of the illness through timely support and intervention. The unequivocal advice for careful avoidance of overexertion can help to both avoid deterioration and facilitate improvement.

Good

Since there is no medication or intervention which will cure ME/CFS, clinical care focuses on managing symptoms and improving function.

Good

 

[Dolphin]

The health practitioner has an important role helping to ensure that the young patient receives the most appropriate schooling by educating the young person’s school personnel about the effect of the illness on scholastic performance, and providing appropriate documentation to education authorities.

Good

 

[Dolphin]

The underlying etiology of ME/CFS has not been established. Well-documented pathophysiological changes demonstrate that ME/CFS is a multisystem physical disease, not a psychological disorder.

Good

 

[Denise]

@Dolphin I am so glad you are going through the pediatric primer!
Thank you for sharing your thoughts and insight.


For what they are worth, I recently shared some of my thoughts about it on OccupyME

 

[Dolphin]

Perpetuating Factors

It is difficult to determine factors that perpetuate the illness, although it has been suggested that factors that aggravate the illness can also contribute to its persistence. Few studies have investigated this issue. Aggravating factors include: failure to diagnose the illness promptly, resulting in poor management in the early stages of the illness, overexertion resulting in “crashes,” stress, inadequate sleep, and co-morbid conditions, such as OI.

This is a lot better than what is usually said on the subject, usually by the biopsychosocial school.

 

[Dolphin]

Neuroendocrine Abnormalities

The similarity in symptoms between ME/CFS and adrenal insufficiency has prompted investigation into abnormal hypothalamicpituitary- adrenal axis function in both adults and adolescents. Several (albeit not all) pediatric ME/CFS studies have identified statistically lower cortisol levels and urine cortisol:creatinine values in ME/CFS patients compared to healthy controls (34, 44, 61–63). However, the cortisol values in those with ME/CFS are still within the normal range, raising questions regarding the clinical relevance of these findings. Treating ME/CFS with supplemental cortisol brings only modest clinical benefits, and in adult studies is associated with the development of potentially life-threatening adrenal insufficiency (64).

The last sentence seems potentially overly dramatic. I am not sure I have heard the results referred to in this way before.

JAMA.

1998 Sep 23-30;280(12):1061-6.
Low-dose hydrocortisone for treatment of chronic fatigue syndrome: a randomized controlled trial.
McKenzie R1, O'Fallon A, Dale J, Demitrack M, Sharma G, Deloria M, Garcia-Borreguero D, Blackwelder W, Straus SE.
Author information

Abstract
CONTEXT:
Chronic fatigue syndrome (CFS) is associated with a dysregulated hypothalamic-pituitary adrenal axis and hypocortisolemia.

OBJECTIVE:
To evaluate the efficacy and safety of low-dose oral hydrocortisone as a treatment for CFS.

DESIGN:
A randomized, placebo-controlled, double-blind therapeutic trial, conducted between 1992 and 1996.

SETTING:
A single-center study in a tertiary care research institution.

PATIENTS:
A total of 56 women and 14 men aged 18 to 55 years who met the 1988 Centers for Disease Control and Prevention case criteria for CFS and who withheld concomitant treatment with other medications.

INTERVENTION:
Oral hydrocortisone, 13 mg/m2 of body surface area every morning and 3 mg/m2 every afternoon, or placebo, for approximately 12 weeks.

MAIN OUTCOME MEASURES:
A global Wellness scale and other self-rating instruments were completed repeatedly before and during treatment. Resting and cosyntropin-stimulated cortisol levels were obtained before and at the end of treatment. Patients recorded adverse effects on a checklist.

RESULTS:
The number of patients showing improvement on the Wellness scale was 19 (54.3%) of 35 placebo recipients vs 20 (66.7%) of 30 hydrocortisone recipients (P =.31). Hydrocortisone recipients had a greater improvement in mean Wellness score (6.3 vs 1.7 points; P=.06), a greater percentage (53% vs 29%; P=.04) recording an improvement of 5 or more points in Wellness score, and a higher average improvement in Wellness score on more days than did placebo recipients (P<.001). Statistical evidence of improvement was not seen with other self-rating scales. Although adverse symptoms reported by patients taking hydrocortisone were mild, suppression of adrenal glucocorticoid responsiveness was documented in 12 patients who received it vs none in the placebo group (P<.001).

CONCLUSIONS:
Although hydrocortisone treatment was associated with some improvement in symptoms of CFS, the degree of adrenal suppression precludes its practical use for CFS.

They were instructed to take placebo or hydrocortisone pills, equivalent to about 16mg/m2 of body surface area per day, 20 to 30mg every morning at about 8 AM, and 5mg every day at about 2PM, for 12 weeks

The dosage seems quite high. When I was reading about it before it was suggested to take 20 mg or less, that that was a physiological dose to supplement what the body was already producing. Anything higher would suppress the body's own adrenal output.

Here is another CFS study that used a smaller dosage that didn't seem to have find any major problems:

Lancet. 1999 Feb 6;353(9151):455-8.
Low-dose hydrocortisone in chronic fatigue syndrome: a randomised crossover trial.
Cleare AJ1, Heap E, Malhi GS, Wessely S, O'Keane V, Miell J.
Author information

Abstract
BACKGROUND:
Reports of mild hypocortisolism in chronic fatigue syndrome led us to postulate that low-dose hydrocortisone therapy may be an effective treatment.

METHODS:
In a randomised crossover trial, we screened 218 patients with chronic fatigue. 32 patients met our strict criteria for chronic fatigue syndrome without co-morbid psychiatric disorder. The eligible patients received consecutive treatment with low-dose hydrocortisone (5 mg or 10 mg daily) for 1 month and placebo for 1 month; the order of treatment was randomly assigned. Analysis was by intention to treat.

FINDINGS:
None of the patients dropped out. Compared with the baseline self-reported fatigue scores (mean 25.1 points), the score fell by 7.2 points for patients on hydrocortisone and by 3.3 points for those on placebo (paired difference in mean scores 4.5 points [95% CI 1.2-7.7], p=0.009). In nine (28%) of the 32 patients on hydrocortisone, fatigue scores reached a predefined cut-off value similar to the normal population score, compared with three (9%) of the 32 on placebo (Fisher's exact test p=0.05). The degree of disability was reduced with hydrocortisone treatment, but not with placebo. Insulin stress tests showed that endogenous adrenal function was not suppressed by hydrocortisone. Minor side-effects were reported by three patients after hydrocortisone treatment and by one patient after placebo.

INTERPRETATION:
In some patients with chronic fatigue syndrome, low-dose hydrocortisone reduces fatigue levels in the short term. Treatment for a longer time and follow-up studies are needed to find out whether this effect could be clinically useful.

 

[Dolphin]

The diagnosis is often overlooked or delayed and is sometimes made retrospectively when the child is older.

Good

 

[Dolphin]

(d) gastrointestinal symptoms such as abdominal pain, nausea, and anorexia,

anorexia = lack or loss of appetite for food (as a medical condition).

I think they are probably not referring to anorexia nervosa which is sometimes abbreviated to anorexia. They probably should have said this explicitly.

 

[Dolphin]

The pattern of ME/CFS symptoms is distinctive and the diagnosis can easily be made in most cases, but there can be some diagnostic challenges. Younger children, especially those under 10 years of age, might not report symptoms accurately. They might not remember having experienced full health and might assume tiredness is normal. The first sign of the illness might be the child’s marked limitation of physical and/or mental activity, noticed by a parent or a teacher. Young patients with ME/CFS might not necessarily recognize that they have symptoms such as cognitive problems or malaise until their health has improved. Some patients might not consider themselves as having postexertional symptoms because they have learned to pace their activities. Symptoms of ME/CFS wax and wane over time. Some patients might report that one particular symptom was present previously, but has improved by the clinic visit. Symptoms that persist are more easily recalled.

This all seems reasonable.

 

[Dolphin]

Frequent monitoring of the patient once every 1–3 months, depending on the level of illness severity is important. Young patients who are ill appreciate continuing care.

This seems more regular than many services provide, a point I think Valentijn has made. She probably made some other points I am also repeating, I thought I would just go through my notes.

 

[Dolphin]

Functional improvement can be judged by determining how much activity generates post-exertional worsening of symptoms.

I think this is a good principle for people of all ages.

In patients who are improving, fatigue is often the last symptom to resolve, since young patients often prefer to increase their activities and tolerate the resulting fatigue.

Good

 

[Dolphin]

Physical Examination

A thorough physical examination, including a neurological exam is important to exclude other causes of fatigue. Physical signs in ME/CFS are subtle and none are diagnostic. Many patients do not look ill, but noticeable facial pallor is sometimes apparent and often precedes the onset of extreme tiredness in the patient. The pallor can be associated with sub-orbital dark shadows. The pharynx can show non-exudative pharyngitis and cervical and axillary lymph nodes might be palpable and tender. Muscle tenderness is a feature of co-morbid juvenile fibromyalgia. Fibromyalgia is less common in children with ME/CFS than in adults. The hands and feet can be unusually cold and dependent rubor of the legs is often present when standing or sitting. The physical exam should include an assessment for common co-morbid conditions such as OI [heart rate (HR) and blood pressure (BP) sitting and standing], joint hypermobility, and postural dysfunctions (see Comorbid Medical Conditions).

Rubor = 1. Redness, as one of the four signs of inflammation (r., calor, dolor, tumor)

I agree with the underlined points. My mother has often mentioned the pallor in me and others. She says as meetings go on she can notice people become pale.

I'm not sure the muscle tenderness should specifically be associated with fibromyalgia. I think it can be part of ME without fibromyalgia also.

Robor was a new term for me. I'm not sure what it would look like on legs. The soles of my feet are noticeably red.

 

[Dolphin]

At illness onset, pyrexia can be present and this can persist for some weeks. If fever is present several months into the illness, other causes of fever should be sought. In established cases, slightly subnormal temperature, 96.8–98.0°F (36.0–36.7°C), is common.

 

[Dolphin]

Laboratory Testing

Basic laboratory studies (Table 1) should be performed to identify other causes of fatigue and any organ system dysfunction. Most routine laboratory tests are within the normal range, and do not correlate with overall function, even in the presence of substantial debilitation. Measures of iron stores, vitamin B12 level, and screening for celiac disease are recommended because of their subtle or absent manifestations on physical examination.

It is probably useful that the underlined bit is explicitly said

 

[Dolphin]

The presence of post-exertional malaise and exacerbation of symptoms after increased cognitive or physical effort increases the likelihood that ME/CFS is the correct diagnosis

Good