Literature search
Pervasive refusal syndrome was first brought to our attention by a Dutch publication [25]. An extensive literature search (Cochrane, Embase, PsychInfo, PubMed), conducted in April 2008, yielded only 20 articles for the search term pervasive refusal syndrome. Three of the articles were irrelevant because they dealt with entirely different topics, and two described eating disorders [5, 10] with PRS mentioned only marginally. The remaining 15 articles [2–4, 7–9, 11, 13, 17–19, 23, 24, 26, 27], published between 1991 and 2006, described only 23 distinct cases of PRS. A supplementary article [12], brought to our attention by a colleague, mentioned 20 more cases of PRS. Owing to a lack of detail, however, these cases could not be incorporated into our study population (n = 24). Population characteristics of the 24 patients are presented in Table 1.
Table 1 Population characteristics PRS (n = 24)a, 1991–2006
The search on PsychInfo also yielded three textbooks on eating disorders [14, 16, 22] in which PRS is mentioned.
Remarkably, the two main textbooks on child and adolescent psychiatry [15, 20] contain no information at all about PRS. The DSM-IV [1] and ICD-10 [29] do not classify PRS.
Epidemiology
Pervasive refusal syndrome is most often seen in girls between the ages of 7 and 15. As illustrated in Table 1, 75% of the 24 patients were female and the mean age of the population was 10.5 years. Kate perfectly fits this profile. Occurrence of PRS in adults has not been reported. The incidence of the disorder is unknown [11].
Aetiology
In the first article published on PRS [13], there seemed to be an association between PRS and sexual abuse. Later articles denied such an association. Reviewing the literature, however, sexual abuse was reported in 21% of the 24 cases (see Table 2), which is not an insignificant percentage. Trauma, in general, seems to be an important aetiological factor, since PRS is also often seen in refugees and witnesses to violence (see Table 2).
Table 2 Aetiologic factors of PRS (n = 24)a, 1991–2006
Nunn and Thompson [18] introduced the concept of learned helplessness and hopelessness. They proposed that the symptoms seen in children with PRS emerge from the perceived uncontrollability of their future and the expectation that responses are futile. The helplessness and hopelessness can transfer from parents to children and from children to parents as they watch one another struggling with uncontrollable events [18].
Other theories concerning the aetiology of PRS have been postulated, such as the psychodynamic theory of lethal mothering [4] and a possible neurobiological contribution of the insula [24]. Viral infections are often seen as precipitating factors (see Table 2).
Von Folsach and Montgomery [27] proposed four important aetiologic factors: (1) a premorbid personality, (2) a history of child psychiatric problems, (3) parental psychiatric problems and (4) precipitating stressful events. Reviewing the literature, these four factors indeed seem to play an important role in the aetiology (see Table 2). Children with PRS are usually described as perfectionist, conscientious and high achievers. When such children are faced with stressful events that they feel they cannot control, they enter into a state of learned helplessness. Previous child psychiatric problems may indicate a vulnerability to develop PRS when faced with stressful events, and parental psychiatric problems may affect the parents’ ability to support and protect their children. Enmeshed mother–child relationships are often seen (63%), but it is unclear whether they are primary or secondary to the child becoming ill.
The aetiology of PRS in our case report remains unclear. Returning to Kate, the troubled relationship with the teacher can be considered a potential precipitating event, or a chronic stress factor, since he taught her for 2.5 consecutive years. Changing school only worsened the symptoms. This change, however, can be considered a supplementary stress factor. Physical or sexual abuse was explicitly denied. A precipitating viral infection could have been the trigger, since Kate’s complaints started with acute fatigue, a sore throat and a headache.
Kate also seems to fulfil criteria 1 and 2 of Von Folsach and Montgomery [27]. She was known as a perfectionist and high-achieving girl and had a history of an episode of behavioural disturbances. No parental psychiatric problems were present. During the period of admission to our hospital, we did notice an enmeshed mother–child relationship, as well as helplessness and hopelessness in both mother and child, but these seemed to be secondary effects.
Psychopathological consideration
Refusal, which is considered one of the core symptoms of PRS, is defined as a state in which one is unwilling to do something [28]. Withdrawal, another core symptom of PRS, can be defined as a retreat from external reality [6] or a state of ceasing to participate in an activity or to be a member of a team or organization [28]. In clinical psychiatry, a third and related psychopathological state exists: regression. This is defined as a return to a state of earlier development [6] or to earlier patterns of adaptation [21]. Refusal, withdrawal and regression have a resistance in common, a rejection of action [28], be it either active and/or passive. Clinically, an increasingly pervasive negative attitude towards all the activities of daily life can be seen, which can occur in a gradual spectral way from refusal, the one pole, via withdrawal to regression, the other pole. We propose calling this spectrum the RWR (refusal–withdrawal–regression) spectrum. The three manifestations (refusal–withdrawal–regression) can fluctuate in time due to the state of mind of the patient and the context. This state of mind is strongly influenced by the will and the patient’s faculty of judgement. Impaired judgement in children and adolescents is frequently linked to trauma, particularly chronic and severe trauma, but can also be due to a major psychiatric disorder. In adults, impaired judgement is most often due to a major psychiatric disorder, such as schizophrenia, an affective disorder or anorexia nervosa. This explains why these three clinically important manifestations of the RWR spectrum are frequently met in the full age range of clinical psychiatry. With PRS, which is diagnosed only in children, refusal and withdrawal are more prominent. In adults, regression is more common.
Diagnosis
In the diagnostic process, a two-track multidisciplinary diagnostic approach by a paediatrician and a child psychiatrist, as also seen in our case report, is essential from the very beginning, as in the case of a disabling psychiatric disorder, a somatic cause must always be excluded. Regarding Kate, no organic cause of her complaints could be traced.
Thompson and Nunn [24] were the first to introduce diagnostic criteria for PRS (see Table 3). We suggest an adaptation of these criteria (see Table 4). In the past, PRS was often seen as related to eating disorders [5, 10, 14, 16, 22] and therefore ‘clear food refusal and weight loss’ was seen as a separate criterion. However, both the literature search and our case report show that refusal can be seen in different domains, including eating. In which domain the refusal is most prominent depends on the individual expression of PRS. We therefore suggest attaching criterion 1, ‘clear food refusal and weight loss’, to criterion 3, ‘partial or complete refusal in two or more domains’. To underline the severity and disabling character of PRS, we would also like to add an extra criterion: ‘The endangered state of the patient requires hospitalization’.
Table 3 Current diagnostic criteria for PRS [24]
Table 4 Adapted diagnostic criteria for PRS
Differential diagnosis
Pervasive refusal syndrome has many forms of expression, resulting in symptom overlap with other psychiatric disorders [11]. Table 5 presents an overview of the most common differential diagnoses. None of these diagnoses, however, accounts for the whole variety of symptoms seen in PRS, as described in detail by Bryan Lask (vide infra) [11]. Moreover, the active resistance to any form of help is the distinguishing feature of PRS. Although many of the features of PRS are compatible with a diagnosis of depression, common features of a severe major depressive episode such as psychomotor slowing, a constantly depressed mood and sleep disturbance are uncommon in PRS [11]. Anxiety can be seen in children with PRS, but an anxiety disorder does not account for the whole range of symptoms seen in PRS. Both depression and anxiety can be seen as comorbid to PRS. Food refusal is often seen in PRS, but in general the refusal is neither particularly focused on nor exclusive to food [11]. It is motivated by a desperate need to refuse and not by a desire to lose weight. A diagnosis of eating disorder is therefore not applicable. Selective mutism and school refusal refer to a specific area of functioning, while the refusal seen in PRS is far more pervasive. Chronic fatigue is common in PRS, but by no means the most central feature. Children with chronic fatigue syndrome show very few of the other symptoms of PRS and are frustrated with their ill-health and have a strong wish to recover [11], in contrast to children with PRS.
Table 5 Main differential diagnoses of PRS (n = 24)a, 1991–2006
In our case report, the main differential diagnosis was factitious disorder, in contrast to most of the other published cases (see Table 5). A depressed mood was not found and Kate did not seem anxious at all. She showed situation-specific physical symptoms that had a strong intentional character, which ruled out a somatoform disorder. Her complaints seemed to fluctuate, particularly worsening when parents or medical/nursery staff were present, indicating either a factitious disorder or malingering. A diagnosis of malingering could be excluded because external incentives for her behaviour were not found and were explicitly denied by both Kate and her parents. Factititious disorder was considered but is typically characterised by help-seeking behaviour and not by an active resistance to help, as seen in our patient.
Regression has never been mentioned as a differential diagnosis of PRS in literature. We, however, consider regression as strongly correlated with PRS. In our opinion, and based on the above-mentioned definitions, refusal, withdrawal and regression can be considered different states of the same spectrum, with refusal being the less severe variant and regression the most severe (see “Psychopathological consideration”). A waxing and waning from one state into the other and back again is possible, as is a co-existence of the various states of the RWR spectrum. In PRS, for example, the refusal leads to an increasingly extended social withdrawal. However, as the patient becomes more withdrawn, the refusal remains present. Regression must be considered a more severe and mostly passive state of being with a massive loss of age-adequate psychological functioning. This is partially in contrast to PRS, where active resistance is much more dominant. As regression is mostly seen as a part of an axis-I disorder, PRS is considered an entity in its own right. However, the pervasive refusal and active resistance, which are so characteristic of PRS in children, can also be present in adult patients with an axis-I disorder (e.g. severely ill psychiatric patients with anorexia nervosa, a major depressive disorder or a schizophrenic psychosis who show a pervasive refusal and withdrawal from daily life, as well as an active resistance to treatment and who have been involuntary admitted under the mental health act). In line with the aforementioned, the presentations of the RWR spectrum can be seen as an end point in intensity of many untreated—and sometimes even treated—psychiatric disorders.
In contrast to PRS, which is only identified in children, regression is most often seen in adults with an axis-I disorder. It can, however, also affect children.
Treatment
Lask et al. [13] stated that ‘there is no one specific form of treatment for children as ill as these’. Nunn et al. [19], on the other hand, described a very detailed, specific management approach in the battle against the syndrome. However, no evidence-based treatment is known.
We believe that the treatment must involve a comprehensive multidisciplinary team approach and a structured yet flexible management plan with a clear rationale employed over months to years. Regular multidisciplinary feedback meetings are mandatory in order to minimize splitting.
Because PRS is such a severe condition, hospitalization, ideally in a child and adolescent psychiatric unit, is almost always required. Thompson and Nunn [24] described one treated outpatient. It can be argued that this outpatient treatment was successful. Although Thompson and Nunn described symptom-free periods, there were still periodic relapses of short-lived episodes of depressive symptoms or anorexia. In our opinion, inpatient treatment is therefore necessary (see Table 4).
Treatment must involve tender loving care. The carers must be very patient and sensitive. It takes a long time for the patients to recover, and pressuring them makes their condition worse. It typically takes a few months of treatment before it becomes possible to implement a very gradual rehabilitation programme. Therapeutic enthusiasm in the early stages is almost always counterproductive [11].
The role of the family in the treatment is important yet difficult, since withdrawal of the child from therapy is a major problem. It is important to involve the family in the treatment as it relieves family anxiety and distress. Nevertheless, it is vital to create some distance because over-involvement of the family may be counterproductive.
Medication appears to play a very limited role in the management of the syndrome, having value in the treatment of comorbid disorders only, for example antidepressants for comorbid depression.
Returning to Kate, treatment consisted of an inpatient multidisciplinary gradual rehabilitation programme, which was characterized by respectful tender loving care and activities just on demand. Parents were involved by means of regular meetings with the family therapist. The treatment goals of these sessions were encouragement, comfort and reduction of possible over-involvement.
Prognosis and outcome
Although the recovery process is painfully slow, most children with PRS fully recover with little residual pathology [11]. Complete recovery was achieved in 16 (67%) of the 24 cases, while partial recovery was seen in six cases (25%) (see Table 6). However, the condition of some of the partially recovered patients was still improving at the time of publication. In our case report, full recovery with little residual pathology (fatigue) was seen after a period of 4 months of inpatient treatment (1 month at our academic medical psychiatric unit and 3 months at the child psychiatric hospital). This seems a short period of time, because the average duration of therapy is 12.8 months (Table 6). Note, however, that the literature mentions cases of complete recovery after an inpatient treatment of only 2–8 weeks [24]. Concerning Kate, we still have no clue regarding the cause either of her PRS or of her miraculous, spontaneous recovery; but this is also not uncommon.
Table 6 Treatment characteristics of PRS (n = 24)a, 1991-2006