Malnutrition and osteoporosis (vitamin D), peripheral neuropathy (vitamin

Malnutrition is a major complication of CD of
multifactorial origin, including reduced dietary intake, altered energy
metabolism, increased GI nutrient losses and increased nutrient requirements.
This phenomenon can cause the development of micronutrient deficiencies,
decreased osseous health, altered body composition and anaemia (Gerasimidis et
al., 2011). An analysis of the weekly diet of CD patients displayed that intake of
all main micronutrients, excluding Vitamin B12 but most notably calcium, folate
and vitamins C and E, were suboptimal despite adequate energy intake (Aghdassi
et al., 2007). The detrimental effects of these micronutrient deficiencies
include night blindness (vitamin A), stomatitis (vitamin B), anaemia (iron,
folate, vitamin B12), osteomalacia and osteoporosis (vitamin D), peripheral
neuropathy (vitamin E) and beriberi (thiamine) (Donnellan et al., 2013).

 

Abnormal bone mineral density (BMD)
measurements were found in 53.3% of CD patients which can lead to metabolic
bone disease, with osteoporosis being found in 11.7% of CD patients in a small
sample study (Lima et al., 2017). Certain treatments, including
corticosteroids, were believed to be the cause of the decreased BMD, but the
association of low BMD in untreated CD patients suggests that the inflammatory
process itself is the causative factor. Several PICs, including IL-1, IL-6 and
TNF-a, released as part of the inflammatory response in CD have been
identified as stimulators of osteoclastogenesis (Bernstein and Leslie, 2003).
Obtaining a CD diagnosis at >40 years of age has been associated with a higher
risk of low BMD (Lima et al., 2017). Management of BMD is important in young
people as peak bone mass reached during adolescence is the most important
factor in determining adult skeletal health (Gerasimidis et al., 2011).

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Chronic intestinal blood loss from the
inflamed mucosa and reduced dietary intake greatly increase the risk of iron
deficiency, the main cause of anaemia in CD patients. The second major cause of
anaemia in CD is anaemia of chronic disease which may be induced by thiopurines
and impaired absorption. A review has found that the weighted mean prevalence
of iron deficiency from the available literature is 45%, and prevalence rates
of anaemia range greatly from 6% to 74% dependant on the population studied and
the definition of anaemia, averaging a 17% prevalence (Gisbert and Gomollón,
2008). Anaemia is much more common in children with IBD compared to older
individuals, with a prevalence of 70% in children, 42% in adolescents and 40%
in adults (Goodhand et al., 2012).

 

Low BMI and difficulty in gaining weight is
greatly associated with CD and is believed to be multifactorial in origin.
Decreased caloric intake is the most likely primary factor, as an effect of
anorexia induced by PICs, premature satiety, and pain or nausea accompanied
with eating (Moeeni and Day, 2011). Children with active CD consumed a mean
energy intake that was 420kcal fewer in comparison with their healthy siblings (Thomas
et al., 1993). Malabsorption of these nutrients and calories due to the inflamed
mucosa is also a factor that could impact weight. In CD with a pre-pubertal
onset, there is a high risk of underdevelopment, with a significantly decreased
growth rate and reduced final height compared to the parental estimate
especially in boys. This can occur by the inhibition of chondrocyte activity in
growth plates by TNF-a, and the suppression of Insulin-like growth factor 1 (IGF-1), a key
mediator of the effects of growth hormone (Moeeni and Day, 2011). Delayed
puberty and menarche is also common, with a prolonged pubertal phase caused by
two mechanisms: reduced conversion of androgens into oestrogen resulting from
reduced fat mass observed in malnutrition, and the direct interactions between PICs
and the endocrine system resulting in an abnormal production of sex steroids in
the gonads (Gasparetto and Guariso, 2014).

 

Reports
have linked CD with the development of intestinal cancers, with mechanisms
including IL-6 counteraction of apoptosis, and promotion of cell survival
signalling as a result of TNF-a binding
to NF-?B. The cumulative probability of developing
colorectal cancer 10 years after a CD diagnosis is 2.9%, but evidence of the
risk at different durations of disease is lacking (Canavan et al., 2006). Small
bowel adenocarcinoma has been associated with CD, but possesses a low prevalence
of 1.6% and usually diagnosed at 45-55 years of age (Cahill et al., 2014). Myeloid
and lymphoid malignancies are being increasingly linked to CD indirectly with
the use of immunosuppressive and biological agents (Freeman, 2002).

 

Psychosocial issues

There is a current lack of evidence linking
CD and psychiatric conditions together, with most studies focusing on IBD as a
group. Several emotional factors can influence the mood of CD patients,
including concerns about the uncertainty of the future and living with an
incurable, chronic illness, fear of surgery and cancer risks, coping with the
pain and other symptoms of the disease, low body image and self-esteem, and
fear of sexual inadequacy (Sajadinejad et al., 2012). Depression and anxiety
are common psychiatric conditions prevalent in CD patients, with 25.3% exhibiting
depressive symptoms and 35.9% exhibiting anxiety symptoms. There is a clear
established link between disease activity and mood, with 40.7% of those with
active IBD experiencing depressive symptoms compared to 16.5% in remission, and
75.6% of IBD patients with active disease experiencing symptoms of anxiety
compared to 31.4% of those in remission (Neuendorf et al., 2016). Another
pooled study found that 21.2% of IBD patients had obtained a diagnosis of
anxiety and 25.8% diagnosed with depression, and that this value is typically
higher in younger individuals and females (Byrne et al., 2017). These
proportions are much higher compared to the percentages estimated by the World
Health Organisation (WHO), who predict that 4.4 and 3.6% of the global
worldwide population in 2015 suffered from depression or anxiety disorders
respectively (World Health Organisation, 2017). Various pharmacological
treatments, including corticosteroids, pose adverse effects of depression and
anxiety as a result of the drug’s action within the central nervous system, and
have also been linked to behavioural changes such as mood swings and psychosis
especially in adolescents (Stuart et al., 2005). There has been an increased
indication that both acute and chronic psychological stress can alter the
neuroendocrine system and the gut-brain axis to induce the release of substances,
such as PICs and cortisol, that can increase the recurrence of relapse and
symptom severity (Niess et al., 2002 and Mawdsley, 2005). Animal models have
shown that psychological stress can cause stress-induced barrier dysfunction,
resulting in an increased permeability to antigens, toxins and other
pro-inflammatory molecules from the gut lumen, increased leakiness of the
intestinal mucosa and increased stimulation of ion, water, mucus and IgA secretion
(Söderholm and Perdue, 2001). Other psychiatric conditions have been associated
with CD, with OCD found in 9.4% and panic disorders found in 1.6% of IBD
patients (Neuendorf et al., 2016). CD has also been linked to several
personality traits (neuroticism, alexithymia, perfectionism) which may be
possible risk factors for various psychiatric disorders and lowered quality of
life (Moreno-Jiménez
et al., 2007). New research has also emerged relating CD and mild cognitive
impairment, with cloudiness of thought, reduced concentration levels, and poor
sleep quality despite greater sleep duration (van Langenberg et al., 2016). A
small-scale, outdated study interviewing young adults identified that 56% of
those childhood-onset CD reported absences of at least 2 months during their
education, whilst impaired academic performance was common during CD relapses.
8% of these young adults testified that they had become involuntarily
unemployed as a consequence of their active CD (Ferguson et al., 1994). Further
studies directed to children with CD found that 80% believed they had
underachieved because of their CD and 67% were unable to participate fully in
sports, for reasons including fatigue and the presence of a stoma. Young
individuals with CD also often tend to withdraw themselves from social
activities, with examples including the refusal to attend events that require
long-distance travelling or lack toilet facilities, and the hesitation to stay
at a friend’s house (Rabbett et al., 1996 and Moody et al., 1999). Research with similar
aims but conducted on adults is lacking. The uncomfortable and disabling
physical and psychosomatic symptoms of CD, diminished body image and worries
that CD will reduce libido, and compromise intimacy, sexual performance and
relationship quality are factors that may affect relationships in those with
CD. (Jedel et al., 2015). 74.8% of women and 51.4% of men with IBD face body
image issues, and 57.6% of participants reported that IBD hindered the
frequency of their sexual activity (Muller et al., 2010)

 

Health-related
quality of life

Concept
of HRQOL

The WHO defines HRQOL as ‘an individual’s perception of their position in life in
the context of the culture and value systems in which they live and in relation
to their goals, expectations, standards and concerns” (Saxena and
Orley, 1997). The conventional approach by health care professionals was allopathic,
focusing on the suppression of pathologic processes and achieving clinical
outcomes. A more holistic approach has become more appropriate with the aim of
improving HRQOL and various instruments have been developed to assess the
effects the disease implicates on an individual’s life. HRQOL instruments are
constructed to measure various health domains: physical, mental and social well-being.
The effect that a condition has on these domains is identified by assessing the
extent of the condition has on friendships, relationships and difficulties in
daily functioning (Muragundi et al., 2012).

 

Application of HRQOL measures

The measures
acquired by HRQOL instruments can be utilised in numerous ways. HRQOL measures
are used to quantify the extent that condition impacts an individual’s life and
compare the consequences with other chronic conditions.

 

HRQOL instruments
There
are two types of instruments used to assess HRQOL: generic and
disease-specific. Generic HRQOL questionnaires broadly measure general health in
terms of physical and emotional functioning, and are developed to be applied
and compared amongst general populations, and also between different disease
populations. Disease-specific HRQOL instruments are vital when measuring HRQOL
in a population of patients with a particular condition as they incorporate the
impact of the disease on relevant, narrower, health dimensions (Jackowski and Guyatt, 2003
and Muragundi et al., 2012).

 

 

Generic HRQOL
Questionnaires

Short Form-36 Survey

The Short
Form-36 Survey (SF-36) is a commonly used 36-item generic health survey that
analyses eight health perceptions including physical items (general health
perceptions, bodily pain, energy levels, physical functioning, role limitations
due to physical health problems) and mental items (emotional well-being, social
functioning and role limitations due to personal/emotional health problems).
The algorithm generates eight scores based upon the selected answers and
presents the data on a 0-100 scale, where higher values denote a greater
perceived state of health (RAND, 2016). Several studies have identified that
this is a reliable and value questionnaire in both generic population use and in
patients with a specific condition. A limitation for using SF-36 in IBD
patients is its low responsiveness in sensing changes in health status as time
progresses (Jenkinson et al., 1994 and Bernklev et al., 2005).  

 

IBD-Specific HRQOL
Questionnaires

Impact III Form

The
Impact III form is a 35-item questionnaire used regularly to assess the HRQOL
children and adolescents with IBD. The instrument assesses five domains:
symptoms, body image, worry about stool, concerns and socialising. Each item contributes
to the calculated total score that ranges from 35-175, with a greater score
indicating a higher degree of HRQOL. Multiple studies have commended the ease
of understanding and completion by child respondents, and identified excellent
levels of instrument reliability and validity, with the latter achieved by
comparing scores between different severities of disease activity (intro?) (Otley et al.,
2006, Ogden et al., 2011, Werner et al., 2014). However, one study reported
that the test was only reliable upon the removal of two unidentified items
(Abdovic et al., 2013).

 

Short Health Scale

The
Short Health Scale (SFS) is a simple four point that utilises a visual analogue
scale with no intermediates designed to obtain the perceptions of IBD on an
individual’s HRQOL. The four questions of the instrument measure views on bowel
symptoms, daily functioning, worry and general well-being. The test has been
frequently validated, with HRQOL worsening with disease activity, and
reliability has been verified by repeating the study 2-4 weeks after the
initial completion date and observing strong test-retest correlations (intro?). Therefore, the
study is appropriate for use in both clinical practice and research (Stjernman et al., 2008 and McDermott et al., 2013). Both of these named IBD-specific
instruments have been authenticated as valid and reliable instruments of
measuring HRQOL in CD patients in the UK.