Autoimmunity Reviews 11 (2012) 219–225

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Autoimmunity Reviews
j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / a u t r ev

Review

Autoimmune diseases and rehabilitation

Peter Flachenecker ⁎
Neurological Rehabilitation Center “Quellenhof”, Kuranlagenallee 2, D-75323 Bad Wildbad, Germany

a r t i c l e i n f o a b s t r a c t

Available online 18 May 2011 This review gives an overview of the rehabilitation of autoimmune diseases. After general remarks on
rehabilitation, the effects of acute and chronic exercises on inflammatory markers are summarized. Most of
Keywords: the available literature deals with rheumatoid arthritis (RA) and multiple sclerosis (MS), and therefore,
Rehabilitation rehabilitation of these diseases is described in more detail. Exercise is the main component in the
Autoimmune diseases rehabilitation of patients with RA and aims at increasing physical capacity, muscle strength, aerobic
Rheumatoid arthritis
endurance, cardiovascular fitness and functional abilities, and helps to prevent secondary deconditioning due
Multiple sclerosis
to reduced activity levels. Since MS causes a wide range of symptoms, the rehabilitation of these patients
requires a multidisciplinary approach and encompasses physiotherapy, exercise therapy, hippotherapy,
cognitive rehabilitation, psychological therapy, strategies to improve fatigue and coping programs. The
ultimate goal of rehabilitation is to enable patients with chronic conditions to reach and maintain their
optimal physical, sensory, intellectual, psychological and social functional levels, and to attain independence
and self-determination as far as possible.
© 2011 Elsevier B.V. All rights reserved.

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 219
2. Effects of acute and chronic exercise on inflammatory markers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 220
3. Autoimmune diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 220
3.1. Rheumatic diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 220
3.2. Multiple sclerosis (MS) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 221
3.2.1. Neuronal plasticity and neurorehabilitation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 221
3.2.2. Physiotherapy and exercise therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 221
3.2.3. Cognitive dysfunction and affective disturbances . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 222
3.2.4. Fatigue . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 222
3.2.5. Coping and patient education . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 223
3.2.6. Multidisciplinary rehabilitation in MS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 223
Disclosure statement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 224
Take-home messages . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 224
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 224

1. Introduction This definition provided by the World Health Organization (www.

“Rehabilitation of people with disabilities is a process aimed at
enabling them to reach and maintain their optimal physical, sensory,
intellectual, psychological and social functional levels. Rehabilitation
provides disabled people with the tools they need to attain independence
and self-determination.”
⁎ Tel.: + 49 7081 173 202; fax: + 49 7081 173 215.
E-mail address: peter.flachenecker@quellenhof.de.
who.int) describes the aims of rehabilitation independent from the
underlying disease. With other words, rehabilitation is an active process
of education and enablement that is focused on the proper management
of disability and on the minimisation of handicap, with the goal of
achieving full recovery or, if a full recovery is not possible, the goals
become focused on achieving the optimal physical, mental and social
potentials of the patients so that they can remain or become integrated
into their most appropriate environment [1]. Rehabilitation may thus
improve independence and quality of life by maximizing ability
and participation. In accordance with this, German social laws have

1568-9972/$ – see front matter © 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.autrev.2011.05.016
220 P. Flachenecker / Autoimmunity Reviews 11 (2012) 219–225
strengthened the role of rehabilitation when stating in 2007 that
rehabilitation is a mandatory service rather than at the discretion of the
payer and has thus to be covered by the health insurances, with
participation in social life being the ultimate goal of all rehabilitation
efforts rather than functional improvement alone [2].
The essential components of successful rehabilitation include expert
multidisciplinary assessment, goal-oriented programs and evaluation of
impact on patient and goal achievement through the use of clinically
appropriate and scientifically sound outcome measures that incorporate
the patient's perspective [3]. While these principles seem intuitively
sound, the evidence-base underpinning multidisciplinary assessment
and goal-oriented programs is generally weak and mainly based on
expert opinions [3]. Similarly, the benefits of rehabilitation have not
been unequivocally demonstrated, although the clinical experience
point towards efficacy in the individual patient. Controlled studies are
rare due to difficulties in trial design since there is justifiable reluctance
on ethical grounds to withhold the best therapy from patients. Research
activities are further compromised as treatment blinding is never
possible apart from evaluator blinding, and by the large range of
outcome measures that are used. Moreover, the philosophy behind
rehabilitation and evidence-based medicine is often in conflict with
each other since the reductionism necessary for clinical trials is often
insensitive to the individually, tailored aims of rehabilitation medicine
[1]. In a comprehensive review of the exercise interventions literature
on persons with physical and cognitive disabilities, 80 different physical
activity/exercise interventions were identified involving aerobic (26%),
strength (25%), and combined aerobic and strength (23%) exercises.
Only 32 interventions were tested in randomized controlled trials.
Nearly half the studies targeted stroke (20%), multiple sclerosis (MS)
(15%), and intellectual disability (13%), with significantly fewer studies
dealing with other diseases [4]. With this broad scope of the literature,
generalizability is limited, and a new body of evidence is needed with
stronger research designs. Moreover, in comprehensive rehabilitation
programs, the demonstrated effects can only with difficulties be
attributed to a specific component of the program, and thus, the overall
performance of the programs, and not the individual components need
to be evaluated [5].
2. Effects of acute and chronic exercise on inflammatory markers
In healthy individuals, acute exercise has an effect on the immune
system [6]. Pro- and anti-inflammatory cytokines TNF-α, IL-1, IL-1ra,
IL-6 and IL-10 as well as leukocyte subsets such as neutrophils,
lymphocytes including T, B, NK cells and monocytes and plasma
concentrations of CRP can increase to various magnitudes, with the
most prominent changes seen after strenuous and eccentric exercise.
Extreme exercise such as marathon runs have been associated with a
depression of immune function which may increase the athlete's
susceptibility to infection; the risk of acute infection raised to 12.9% in
the week after the Los Angeles marathon compared to 2.2% of similar
experienced non-competitors [7]. In contrast to acute (normal)
exercise, participation in regular exercise such as endurance training
can reduce resting levels of many inflammatory markers [8]. Thus,
the effects of exercise on immune function in healthy individuals
are complex and dependent on the intensity, duration and type of
exercise, and inflammatory markers are differently affected in acute
vs. chronic exercise.
The attenuation of regular (chronic) exercise on basal levels of
inflammatory markers has been used to recommend exercise as an
anti-inflammatory therapy in chronic inflammatory diseases includ-
ing autoimmune disorders. In a comprehensive review on the effects
of acute and chronic exercises, 19 studies of chronic inflammatory
conditions including MS, diabetes mellitus and rheumatoid arthritis
were identified that evaluated inflammatory markers [9]. Although
the results indicated that both, acute and chronic exercises might
elicit different inflammatory responses compared to healthy controls,
i.e. exaggerated after acute exercise and attenuated after chronic
exercise, they also revealed a major gap of knowledge in basic
research. Differences in training programs, heterogeneity of the
population studied, and analytic methods in conjunction with the
paucity of studies all may contribute to the inconsistent results.
Moreover, training levels may also affect the responses of exercise on
inflammatory markers. Although serum levels of IFN-γ, IL-10 and
TNF-α raised similarly in MS patients and healthy controls after an
eight-week aerobic training program, cytokine levels were less
inducible in untrained MS patients compared to trained patients
and healthy individuals [10]. The impact of these findings on
rehabilitation of inflammatory diseases is not clear, and more research
is needed before exercise recommendations for patients with
autoimmune disease can be made in an attempt to ameliorate the
underlying inflammatory process.
3. Autoimmune diseases
A number of autoimmune diseases may cause chronic disabilities
and are thus suitable for rehabilitation. A MEDLINE search with
the keywords “rehabilitation”, “autoimmune diseases” and “review”
revealed the following conditions, ranked with increasing frequencies:
multiple sclerosis (MS), rheumatoid arthritis, diabetes mellitus,
Guillain–Barré syndrome, ankylosing spondylitis, systemic Lupus
erythematosus, Sjögren's syndrome, chronic inflammatory demyelin-
ating polyradiculoneuropathy, myositis, and myasthenia gravis. The
most relevant publications concerned rheumatoid arthritis and the
impact of neurorehabilitation; the most common autoimmune disease
undergoing neurorehabilitation is MS. Therefore, this review focuses –
after a brief summary of rehabilitation in rheumatic diseases – on MS
including recent findings from the literature and own experiences.
In addition, general principles as well as management of individual
symptoms are outlined exemplary for the rehabilitation of patients
with MS.
3.1. Rheumatic diseases
Multidisciplinary, comprehensive rehabilitation programs involv-
ing many healthcare professionals are widely available for patients
with rheumatic diseases. International guidelines on rheumatoid
arthritis and ankylosing spondylitis recommend non-pharmacological
interventions as adjunctive interventions to medications [11].
However, the evidence-base is sparse, particularly for ankylosing
spondylitis, systemic lupus erythematosus and Sjögren's syndrome,
with most of the published studies dealing with rheumatoid arthritis.
These support the use of exercise and educational interventions with
a cognitive behavioral component, while the evidence on other,
widely used components (electrophysical modalities, balneotherapy,
dietary interventions as well as alternative and complementary
interventions) is generally weak or inconclusive [11,12]. Assistive
technology has rarely been a subject for randomized controlled trials:
a Cochrane review identified only one study with 29 participants
addressing the effects of an eye drop device compared to a standard
bottle in patients with rheumatoid arthritis suffering from persistent
dry eyes [13]. Physical exercise of moderate to high intensity has also
been found to be effective in patients with both, lupus erythematosus
with mild to moderate disease and primary Sjögren's syndrome;
patients may benefit in terms of increasing their aerobic capacity and
physical function and ameliorating depression and fatigue, a domi-
nating and disabling symptom in rheumatic diseases [14].
Non-pharmacological treatment modalities are often used as an
adjunct to drug therapy in rheumatoid arthritis. Apart from educational
interventions, exercise is the main component in the rehabilitation of
these patients and aims at increasing physical capacity, muscle strength,
aerobic endurance, cardiovascular fitness and functional abilities,
and helps to prevent secondary deconditioning due to reduced activity
 P. Flachenecker / Autoimmunity Reviews 11 (2012) 219–225
levels. The effectiveness and safety of short-term (bthree months) and
long-term (Nthree months) exercise therapy programs (land- or water-
based) in patients with rheumatoid arthritis was assessed in an up-to-
date Cochrane review [15]. Randomized controlled trials were selected
if they fulfilled the following criteria: (1) frequency at least twice
weekly for N20 min, (2) duration N6 weeks, (3) aerobic exercise N55%
of the maximum heart rate and/or muscle strengthening exercises
starting at 30% to 50% of one repetition maximum, (4) performed under
supervision, and (5) including of one or more outcome measures for
functional ability, aerobic capacity, muscle strength, pain, disease
activity or radiological damage. Out of eight studies included in the
review, four fulfilled at least 8/10 methodological criteria, and four
different exercise programs were found: (1) short-term, land-based
aerobic capacity training, which was moderately effective on aerobic
capacity, (2) short-term, land-based aerobic capacity and muscle
strength training, which was moderately effective on aerobic capacity
and muscle strength, (3) short-term, water-based aerobic capacity
training which was limited effective on functional ability and aerobic
capacity, and (4) long-term, land-based aerobic capacity and muscle
strength training, which was moderately effective on aerobic capacity
and muscle strength. There were no safety concerns, with no deleterious
effects being found in any study. Based on these findings, the authors
concluded that aerobic capacity training combined with muscle
strength training should be recommended as routine practice in
patients with rheumatoid arthritis [15]. Moreover, the results clearly
underline the importance of goal-setting and the application of goal-
oriented, function-specific rehabilitation programs in order to improve
function in disabled people.
Although the evidence of exercise in patients with advanced disease
is conclusive, only a few randomized controlled trials address the
effectiveness of non-pharmacological treatment modalities in patients
with early rheumatoid arthritis. Multidisciplinary team-programs,
specialist nurse care, electrophysical modalities including passive
hydrotherapy, wrist orthoses and dietary interventions have not been
studied in these patients, but the effectiveness of dynamic exercise and
cognitive behavioral interventions, and to a lesser extent of joint
protection programs and foot orthoses is supported even in the early
stages of rheumatoid arthritis. [16]. Early identification, referral and
diagnosis are thus of utmost importance for the early initiation of proper
management including medications and non-pharmacological treat-
ment modalities in order to facilitate self-management, restore and
maintain functional abilities as long as possible and eventually improve
quality of life in patients with rheumatoid arthritis [17].
3.2. Multiple sclerosis (MS)
MS is a chronic inflammatory disease of the central nervous system
with presumed autoimmune etiology. The clinical presentation varies
and encompasses a wide range of symptoms such as visual
disturbances, weakness of lower limbs, coordination difficulties, and
sensory impairment. Moreover, “invisible” symptoms such as bladder
disturbances, fatigue, depression and cognitive impairment may
commonly be present even in the early stages of the disease [18].
These symptoms may cause significant disability and may have an
impact on participation in social life. Therefore, multidisciplinary,
goal- and deficit-oriented rehabilitation represents a key element in
the symptomatic management of MS [19]. A number of comprehen-
sive documents are available in an attempt to raise awareness of the
importance of management and neurorehabilitation in MS including
the consensus papers “Symptomatic Treatment of Multiple Sclerosis”,
produced by the Multiple Sclerosis Therapy Consensus Group and the
European MS Platform (EMSP) [19], “European-wide Recommenda-
tions on Rehabilitation for People affected by Multiple Sclerosis”,
produced by RIMS (Rehabilitation in Multiple Sclerosis) and EMSP
(www.emsp.org), “Principles to Promote the Quality of Life of People
with Multiple Sclerosis”, produced by the Multiple Sclerosis Interna-
221
tional Federation (MSIF) (www.emsp.org), and “Guidance for the
Management of MS” (Multiple Sclerosis: National Clinical Guideline
for Diagnosis and Management in Primary and Secondary Care),
produced by the UK National Institute of Clinical Excellence (NICE)
[20].
3.2.1. Neuronal plasticity and neurorehabilitation
There have been enormous advances in our understanding of the
basic mechanisms underlying improvement of neurological disabilities
in the last decades. Animal models and functional imaging studies
in humans show that even the mature brain can undergo plastic changes
[21]. Most of these studies investigated in a longitudinal way how
dynamic reorganization of the motor system relates to recovery of
function in stroke patients [22]. These compensatory changes are
present not only in learning or recovery of motor function after acute
injury such as stroke, but also in chronic conditions such as MS. During a
finger tapping paradigm, expanded brain activation has been reported
in MS patients with normal motor function compared to healthy
controls [23]. Similarly, brain activation was increased in MS patients
with memory deficits (according to the Wechsler Memory Scale)
compared to healthy controls during a sustained attention task.
Although both groups performed similarly on the Multiple Sclerosis
Functional Composite Score (MSFC) and the visual analog of the Paced
Auditory Serial Addition Task (PASAT), different patterns of cortical
activation were found, pointing to compensatory mechanisms as an
expression of neuronal plasticity even during the early stages of MS [24].
Recently, rapid-onset central motor plasticity was neither correlated to
motor impairment nor to measures of CNS injury and therefore, these
earliest steps of neuronal plasticity are unlikely to be responsible for
compensatory changes in MS patients which means that rehabilitation
efforts may need to focus on mechanisms supporting the later stages of
motor learning [25].
Long-term potentiation (LTP) represents one of these later stages
of plastic changes within the central nervous system. Since LTP may be
modulated by practice, and the philosophy behind neurorehabilitation
is the observation that patients improve with practice, these assump-
tions may bridge the gap between basic science and clinical expe-
rience. Several promising new rehabilitation techniques are based
upon the basic approach. These include impairment-oriented training,
constraint-induced movement therapy (CIMT), electromyogram-
triggered neuromuscular stimulation and robotic interactive therapies
[22]. It should be kept in mind, however, that the available evidence is
mainly derived from studies in patients with stroke or spinal cord
injuries, and that the evidence for the effectiveness of these therapies
in MS patients is rare. Recently, small studies with an open-label
design support the usefulness of CIMT [26], treadmill exercise [27], and
robot-assisted gait training [28] also in MS patients. These findings are
in line with the clinical experience in our rehabilitation center during
the last years.
3.2.2. Physiotherapy and exercise therapy
Physiotherapy remains the cornerstone in order to ameliorate
motor dysfunction and gait instability, enhance endurance and
walking capabilities, and improve fatigue and physical fitness in MS
patients. There are now about 50 randomized controlled trials dealing
with physiotherapy or related activities [29]. A large number of
techniques and methodologies are available including the neuro-
physiological concepts (for instance, Bobath, Vojta, Brunkow and
proprioceptive neuromuscular stimulation) as well as newer ap-
proaches such as constraint-induced movement therapy, treadmill
exercises, and equipment-supported training. Neither of these
techniques has shown superiority about another in MS patients and
thus, the appropriate method should be chosen depending not only on
the capabilities and disabilities of the individual patient, but also on
the knowledge and resources of the rehabilitation team. Besides the
classical treatment aimed at improving motor function and walking
222 P. Flachenecker / Autoimmunity Reviews 11 (2012) 219–225
disability, physiotherapy may help in treating breathing disturbances
and bladder problems when using task-specific, goal-oriented
training programs specifically directed towards respiratory muscle
and pelvic floor function, respectively [30].
Exercise therapy is considered to be an important part in
improving functional abilities and quality of life in patients with MS
[31]. In a systematic review of the Cochrane Collaboration, nine high-
methodological-quality randomized controlled trials with 260 partic-
ipants were identified that reported on exercise therapy for adults
with MS not presently experiencing an exacerbation, with outcomes
including measures of activity limitation or health-related quality of
life [32]. Best evidence synthesis based on six trials showed strong
evidence in favor of exercise therapy compared to no therapy in terms
of muscle power function, exercise tolerance functions and mobility-
related activities. Moderate evidence was found for improving mood,
but no evidence was observed for exercise therapy on fatigue and
perception of handicap. When comparing different interventions
(three trials), no evidence was found that any exercise program was
more successful in improving activities and participation than another
[32]. More recently, the subjective feeling of fatigue as well as
objective measures of fatigue could be ameliorated with an aerobic
training program [33,34]. With the increasing knowledge that
exercise benefits MS patients, low to moderate endurance training
as well as resistance training of moderate intensity have been
recommended to counteract both, the effects of the disease per se
and the reversible effects of an inactive lifestyle; both interventions
were well tolerated and did not cause any harm to the patients [35].
Hippotherapy utilizes the movement of a horse to provide sensory
feedback and has been used as a therapeutic intervention for different
neurological conditions. In a systematic review, only three case–
control studies or case-series could be identified; all studies reported
improvements in balance as measured by the Berg Balance Scale. Two
of these studies revealed that primary progressive MS patients
showed the largest amount of change compared to other subtypes
of MS [36]. Recently, we performed a prospective, randomized,
controlled, single-blinded trial comparing the effects of 20 min
hippotherapy per week in addition to the goal-oriented rehabilitation
program to 20 min additional conventional physiotherapy (control
group) over a three-week period [37]. In both groups, walking
capability and balance (six-minute walking test, Tinetti score, and
timed-up-and-go test) were significantly improved after three weeks,
whereas qualitative gait analysis and performance on the 10-m-
walking test showed only improvements in the hippotherapy group.
Moreover, immediate effects on all parameters were also only
observed in the hippotherapy group [37].
3.2.3. Cognitive dysfunction and affective disturbances
Between 40% and 65% of patients with MS have some degree of
cognitive deficit, which may occur early in the course of the disease
and thus have a long-term impact on employment, social activities
and daily living [1]. The most common abnormalities are prolonged
information processing speed, attention deficits, memory distur-
bances, visuo-constructive deficits, and executive dysfunction [38,39].
Symptoms of physical disability may arise independently which
means that cognitive dysfunction may be present also in patients with
less advanced EDSS grades. Little is known about the evolution of
cognitive deficits; the general belief is that they remain stable once
manifested, but improvement after a relapse may also occur. For the
proper initiation of effective rehabilitation strategies, it is essential
that cognitive impairments are recognized as early as possible by
referring patients to comprehensive neuropsychological testing.
Treatment strategies encompass neuropsychological training,
provision of aids, supportive psychotherapy, and pharmacological
measures. Evidence regarding the effectiveness of neuropsychological
therapy is limited, but promising results indicate that attentional
deficits could be improved by an intensive, specific computerized
training of attention [38]. The anti-cholinesterase agent donezepil
(10 mg per day) has been shown to improve verbal learning and
memory in the selective reminding test, but although the effects were
statistically significant, its clinical meaningfulness remains to be
determined [40].
The lifetime prevalence of affective disorders is approximately
50%, which is much higher than rates found in other chronic diseases
[41]. Depression in MS is likely to be an emotional reaction on disease-
related psychological stress, but it is also supposed to be caused by
specifically located brain lesions or immune dysregulation. Psycho-
logical problems may result not only in a decreased quality of life for
the person with MS, but may also have marked psycho-social
consequences such as sick leave, loss of job, and broken partnerships.
Careful assessment should be offered when a person experiences
psychological problems. The goals may be set in steps and revised
during treatment, with clarified frameworks that are advantageous
for the outcome.
The effectiveness of psychological interventions was evaluated in a
systematic review of 16 randomized controlled trials. Although
evidence is limited, the results suggest that psychotherapy may help
in MS patients with moderate to severe disability, and particularly
cognitive behavior therapy showed significant improvements in
depression [42]. In clinical practice, different kinds of psychological
intervention should be offered at different stages of the disease. All
members of the rehabilitation team should be able to offer at least
some kind of counseling, but psychological therapy should be carried
out by specialists (clinical psychologist, neuropsychologist, psychia-
trist), who have the sufficient professional background, a profound
knowledge about human interactions and defense mechanisms, and
about MS-related psychological and cognitive problems.
3.2.4. Fatigue
Fatigue is one of the most disabling symptoms of MS affecting 60–
90% of patients, even in the early stages of the disease, and may have
an enormous impact on daily life [18,43]. Assessment is mainly based
on questionnaires such as the Fatigue Severity Scale (FSS) or the
Modified Fatigue Impact Scale (MFIS) [43,44]. Recently, the WEIMuS
(Würzburg Fatigue Inventory for Multiple Sclerosis) and FSMC
(Fatigue Scale for Motor and Cognitive Functions) were validated in
large cohorts of MS patients and controls [45,46]. Both scales are able
to capture the subjective experience of fatigue from the patient's
perspective and could easily be administered in routine clinical
settings as well as in research projects. In a large study with 580 MS
patients and 162 healthy controls, the WEIMuS questionnaire has
been shown to differentiate between MS patients and healthy controls
on the one hand, and between MS patients with and without fatigue
on the other hand (Fig. 1) [45]. While the WEIMuS questionnaire
covers symptoms present during the last week and could therefore be
regarded as a measure of “state”, the FSMC scale deals more with the
long-lasting aspects of fatigue (“trait”). Attempts to objectively
measure the degree of fatigue have yielded encouraging results for
attentional testing. In two independent cohorts of MS patients, the
WEIMuS scale values were closely related to the mean reaction times
on measurements of tonic alertness [47,48]. Moreover, our results
could be recently replicated by another research group [49]. These
findings allow to monitor the improvement of fatigue during therapy
[47], and to diagnose fatigue as a symptom of MS relapse [50].
Despite its high incidence and impact, the majority of patients are
not treated [51]. As the consequences of fatigue involve many life
domains, the management should preferably be multidimensional
and is thus best suited within rehabilitation including exercise, body
cooling, energy conservation strategies, and psychological interven-
tions [52]. Exercise should administered as endurance training
with low impact aerobic exercise (e. g. bicycle or treadmill exercise,
or Nordic walking), relaxation techniques, and yoga [3,53]. Body
cooling can be reached either by cooling the environment, cold bath or
 P. Flachenecker / Autoimmunity Reviews 11 (2012) 219–225
Fig. 1. WEIMuS sum scores for the assessment of MS-related fatigue in healthy controls
(top), the whole MS population (middle), and the subgroup of MS patients complaining
of fatigue (bottom). For details, see text according to [45].
shower, or by using cooling garments such as cooling vests. Energy
conservation strategies include setting priorities, activity analysis and
modification, balancing rest and activity, ergonomic principles,
modification of the environment, proper body mechanics and living
a balanced lifestyle [54]. In addition, cognitive behavioral therapy
concentrates on changing cognitive attributions and behavior and
increasing self-efficacy [41].
3.2.5. Coping and patient education
The diagnosis of MS makes an on-going adjustment process
(“coping”) necessary in order to deal with the consequences of the
disease [55]. MS patients have to live with the unpredictability and
uncertainty of future disease progression and thereby advanced
disability — and so do the close relatives. As the early period after
getting the diagnosis is a very stressful time span for MS patients and
their partners, distress and anxiety are commonly encountered.
Despite the importance of adequate coping strategies, the theoretical
elaboration of stressful illness consequences as well as the develop-
ment of standardized intervention programs is still in their begin-
223
nings. Cognitive behavioral approaches are beneficial in helping
people adjust to and cope with having MS [42]. Written information
about normal psychological reactions, and different teaching courses,
for example about how to live with MS or more specific topics such as
sexuality, fatigue or cognitive problems and their management, may
also help to improve knowledge about MS and how to deal with its
consequences.
In an attempt to deliver information about the disease, help to
develop coping strategies, prevent psychological maladaptations and
somatic complications, and eventually increase quality of life in MS
patients, we have developed a coping program that was administered
during inpatient rehabilitation over three weeks in addition to the
individual, goal- and deficit-oriented rehabilitation program. It
included 11 h per week with single therapies, group treatments,
lectures and discussion rounds dealing with MS-relevant issues [56].
From 2005 to 2007, more than 400 patients were treated. Self-efficacy
(one's belief to have the ability to overcome challenges), fatigue and
depression were significantly improved after the three week
treatment period, but returned to baseline after 6 months. However,
long-lasting effects were observed for health-related quality of life
(SF-36), with minor improvement for the physical subscale, but major
changes for the mental subscale (Fig. 2).
3.2.6. Multidisciplinary rehabilitation in MS
The large range of symptoms associated with MS makes multi-
disciplinary rehabilitation highly contributive in this disease, with the
goals of increasing independence and improving functional capabili-
ties. A Cochrane review found eight randomized controlled trials that
compared multidisciplinary rehabilitation with routinely available
local services or lower levels of intervention; or trials comparing
interventions in different settings or at different levels of intensity
[57]. There was strong evidence that despite no change in the level of
impairment, inpatient rehabilitation can produce short-term gains at
the levels of activity (disability) and participation, whereas for
outpatient and home-based rehabilitation programs only limited
evidence was present for short-term improvements in symptoms and
disability with high intensity programs that translated into improve-
ment in participation and quality of life. Low-intensity programs
conducted over longer periods of time resulted in longer-term gains in
quality of life. Thus, although multidisciplinary rehabilitation does
not appear to change the level of impairment, it can improve the
experience of people with MS in terms of activity and participation
[58]. The available evidence suggests that rehabilitation services
should be provided on an inpatient base, with regular continuation on
a low-intensity level in order to maintain the achievements made
during inpatient rehabilitation. Since the effects of inpatient
Fig. 2. Health-related quality of life in MS patients before and after a three-week coping
program administered during in-patient rehabilitation, and at follow-up after
6 months. Left = physical subscale of the short-form 36 (SF-36), right = mental
(psychological) subscale of the SF-36. For details, see text according to [56].
224 P. Flachenecker / Autoimmunity Reviews 11 (2012) 219–225
rehabilitation diminish after 6–10 months [59], annual repetition of
multidisciplinary rehabilitation seems mandatory in MS patients
with functional incapacities in an attempt to reach and maintain their
optimal physical, sensory, intellectual, psychological and social
functional levels, and to attain independence and self-determination
as far as possible in this chronic, disabling disease.
Disclosure statement
The author discloses any actual or potential conflict of interest
including financial, personal or other relationships with other people
or organizations within the last 3 years that could inappropriately
influence his work.
Take-home messages
• Rehabilitation of patients with autoimmune diseases aims at
attaining independence and self-determination as far as possible.
• Acute and chronic exercises have an effect on inflammatory markers,
but the impact of these findings on rehabilitation of inflammatory
diseases is not clear.
• Exercise is the main component in the rehabilitation of patients
with rheumatoid arthritis (RA).
• Since multiple sclerosis (MS) causes a wide range of symptoms, the
rehabilitation of these patients requires a multidisciplinary approach.
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Lupus and QuantiFERON-TB

Interferon-gamma release assay (QuantiFERON-TB Gold) has been used for tuberculosis detection mainly for inividual at risk of latent
tuberculiosis. Recently, Fujii et al. (Lupus 2011;20:792-800) evaluated the performance of Quantiferon assay in comparison to tuberculin test
in 71 lupus patients, 279 patientsith other connective tissue diseases and 35 healthy controls. All patients, except for one, had no evidence of
active tuberculosis.The authors found 2.8% of positivity for QuantiFERON assay, 64.8% of negativity and 32.4% of indeterminate results. The
number of indeterminate tests were significantly higher in lupus than other connective tissue diseases (5.7%) or controls (0%). Multivariate
analysis revealed reduced lymphocyte counts,high SLEDAI and lupus itself as predictors of indeterminate results. In conclusion, this
study demonstrated that lupus patients have a high frerquency of indeterminate results for Quantiferon and it seems to be related to
disease activity.
Jozélio Freire de Carvalho MD, PhD