Long-acting paliperidone in Ekbom’s syndrome in Lewy body dementia: A case report

1 Introduction

Ekbom syndrome (ES), also known as delusional parasitosis, is a term that defines a group of neuropsychiatric disorders characterised by the unwavering, fixed, delusional belief that one’s body or immediate environment is infested by parasites, insects, other vermin, or even unanimated materials [1], which is usually accompanied by abnormal cutaneous sensations such as itching, tingling, formication, or pain [2]. These tactile hallucinations are explained with subjective certainty through the aforementioned infestations and often lead to self-mutilation through erosions, excoriations, obsessive cleaning, or even burns and cuts, which represent the subject’s attempt to remove the fictitious parasites [3]. Patients dedicate a lot of time and effort attempting to demonstrate the existence of the pathogens, which drives them to seek help from many physicians, particularly dermatologists and infectivologists, as well as clinical laboratories [3]. Because they are unable to criticise the delusion despite the lack of clinical evidence to support their claims, there is a significant delay in first contact with a psychiatrist and initiating psychopharmacological therapy [1].

ES is a relatively rare condition, with an estimated incidence of 1.9 in 100,000 person-years [4], though more recent studies suggest a prevalence of 27.3 per 100,000 person-years. It seems to occur more frequently in middle-aged and older women [5]. In 14.4% of cases, it might present as a Folie a deux, a condition in which the delusion of one individual affects another close to them, usually a family member, to the point where both share the same delusional ideation [6]. ES might occur as a primary delusional disorder, but it may as well be related to substance use or present as a secondary condition to other disorders, namely psychiatric, somatic, and iatrogenic [7]. It can most often result from schizophrenia, dementia, depression, diabetes, neuropathies, and cardiovascular disorders [7].

Overall, the literature suggests that ES should be managed by treating the core symptomatology with antipsychotics (APs) and, when applicable, addressing the underlying illness with adequate therapy in the case of secondary ES [1]. Due to the aforementioned features of rarity and elusiveness of the condition, the literature lacks controlled trials, and thus response rates for AP treatment are yet to be established, as evidence is currently restricted mostly to systematic reviews and heterogeneous case reports [8]. Even though studies have shown no clinically relevant differences in the effectiveness between treatment with first-generation APs and second-generation APs (SGA), current medical practice and the most recent studies suggest using SGA due to their safety and tolerability profile [9]. Despite the intrinsic lack of illness awareness and subsequent poor compliance to therapy, patients with ES have a good prognosis and remission of all florid psychotic symptoms when treated with continuity, with success rates ranging from 70 to 75% [9,10]. Therefore, APs in long-acting injectable (LAI) formulations could represent a preferred treatment option in ES due to their lower occurrence of adverse effects compared to oral counterparts as well as the guarantee of better treatment adherence [1].

In this case, we describe a patient who presented with ES, lately diagnosed with dementia with Lewy bodies (DLB). DLB is the second most common cause of degenerative dementia, but it is still underdiagnosed [11]. It may present itself as a variety of clinical pictures with symptoms involving sleep pattern, motor functions, cognitive impairment, cholinergic deficiency, and neuropsychiatric symptoms [11,12] – the latter typically consist of visual hallucinations (identified as one of the core symptoms for DLB diagnosis [13]) and delusions, as well as changes in mood and affect, more frequently with depressed mood, anxiety, and apathy. Hallucinations are reported by 50% of the patients suffering from LBD. They usually appear in the early stages as visual hallucinations that manifest as recurring, well-formed complex images, in contrast to schizophrenia spectrum disorders, where early-stage hallucinations are predominantly non-visual [14]. It is not uncommon that patients with undiagnosed DLB may present with late-onset psychiatric symptoms, with these symptoms potentially preceding the DLB diagnosis by many years, as described in prodromal DLB, posing a challenging differential diagnosis for clinicians [15]. Identification of the underlying cause is especially crucial in these presentations, as DLB – and, in general, dementia patients – typically shows neuroleptic sensitivity, which poses a high risk of developing important adverse reactions if psychiatric symptoms are treated as usual [16]. In these cases, the presence of other core symptoms, such as rapid eye movement (REM) sleep disorder or parkinsonism, may offer a useful hint, whereas cognitive impairment may prove difficult to evaluate as acute psychotic symptoms could act as a confounding factor [15].

ES is a rare but possible presentation of DLB [17], yet very few cases have been reported [18,19] and different therapeutic approaches have been further investigated. In particular, in one case [18], a patient was initially treated for depression, and then developed an olothymic ES. This event, associated with parkinsonism and cognitive deterioration, led to a DLB diagnosis. She was treated with an association of mirtazapine and low-dose aripiprazole, and when the psychotic symptoms relapsed with therapy suspension, she was treated with a synergic association of donepezil and low-dose aripiprazole, which resulted in ES remission. Aripiprazole was chosen in light of its D₂ partial agonist action, which is connected to a reduced risk of extrapyramidal symptoms, despite the literature showing no specific benefit. In another case [19], a patient with depression and ES was treated with citalopram and rivastigmine, with the improvement of positive symptoms. In both these cases, DLB was diagnosed before treatment choice, allowing them to avoid treatment that could potentially heighten the risk of neuroleptic sensitivity.

2 Patient information

We describe the case of a 70-year-old Caucasian woman who presented to the Emergency Department (ED) with new-onset delusions of infestation associated with pervasive visual and tactile hallucinations that significantly impaired her behaviour. This symptomatology had emerged about 9 months prior to the hospitalisation with an exaggerated preoccupation regarding the possibility that her home could be infested by insects. Therefore, she promptly called several disinfestation services to solve the problem. These behaviours were initially not so evident to her friends as she progressively withdrew socially, also due to the COVID-19 lockdown. Progressively, she started to experience a plethora of symptoms that became extremely pervasive, particularly during the month before her hospitalisation, with the emergence of delusions and hallucinations associated with progressive social withdrawal and the emergence of potentially risky behaviours for her health due to the various disinfestations. In fact, she was so absorbed by overcleaning, disinfecting, and numerous attempts of disinfestation of her home, clothes, and vehicle that she had a car accident – albeit with no repercussions on her or anyone else’s health – as she was trying to clear the windscreen from these hallucinatory insects whilst driving. The patient had no previous history of psychiatric or substance use disorder, but she had been experiencing recently (less than 1 month) occurring sporadic episodes of amnesic aphasia. At the time of her hospitalisation, she had only a previous medical history of systemic hypertension that had been adequately treated with atenolol. Prior to the previous 9 months, she had reportedly shown no sign of social or psychological impairment. She had been a teacher for 35 years and married for 17 years, until her husband died 9 years before.

A full description of a clinical case of ES has been provided here, in accordance with the CARE (CAse REport) Statement, Checklist and Guidelines [20]. The patient described herein gave written consent for the publication of the presented findings. She was monitored through consecutive clinical examinations, clinical and neurocognitive assessment tests, and neuroimaging examinations, as well as routine blood tests, in accordance with a precise diagnostic flowchart previously proposed by our research team [1] (Table 1). The patient was observed for an overall period of 8 months. She was first evaluated at the moment of admission (T ₀), then again after 2 weeks at the time of discharge from the hospital (T ₁); furthermore, she was monitored through a follow-up starting 1 month after discharge (T ₂), consisting of monthly appointments (T ₂–T ₈, with an exception where T ₇ occurred 2 months after T ₆).

Moreover, following the neurologist’s consultation, further neuroimaging studies were performed during the 6-month follow-up period, including a brain magnetic resonance imaging (MRI) (Figure 1) and a dopamine transporter scan (DaT Scan) (Figure 2).

Figure 1

Brain MRI of the patient. The imaging was obtained at T ₆ and shows global alterations suggesting a primary neurodegenerative condition. Relative preservation of medial temporal lobe volume can be observed.

Figure 2

DaT Scan of the patient. The imaging was obtained between T ₇ and T ₈.

1. Ethical approval: The research related to human use has complied with all relevant national regulations, institutional policies, and the tenets of the Helsinki Declaration and has been approved by the authors’ institutional review board or equivalent committee.

2. Informed consent: Informed consent has been obtained from all individuals included in this study.

3 Timeline

4 Discussion

The present case report described a new-onset ES in a woman without a previous psychiatric history, which was effectively and rapidly managed with risperidone oral treatment. Given the poor treatment adherence and the high chance of full remission if adequately treated with APs, it was chosen to switch to an LAI formulation, as recommended by the literature [1]. PP-LAI was preferred, due to the positive clinical response achieved with oral risperidone and its good tolerability profile. In this case, PP-LAI assured continuity in pharmacotherapy, which led to a stable remission of delusions and hallucinations, as confirmed by all clinical assessments and examinations over the follow-up observation. Regardless of PP-LAI discontinuation due to the onset of adverse effects, the patient did not manifest a relapse of positive symptoms over the entire 8-months of clinical observation.

There are few studies investigating the pharmacologic approach to ES [6,7,9,55,56,57,58], with most studies suggesting treatment with SGA, mainly due to their acceptable safety and tolerability profile [1,59]. In general, the choice of the type of SGA should mainly be derived from their tolerability profile and the risk of concomitant pharmacological interactions. The choice to prescribe an LAI AP should yet be fully confirmed in ES. In fact, only a few case reports have been published so far [60,61]. Therefore, the use of LAI AP therapy in patients with ES is still under investigation, although it may represent a promising therapeutic approach, particularly in those subjects with poor treatment adherence and compliance. That is specifically valuable for ES patients who often tend to avoid contact with psychiatric services, despite the fact that AP may often be successful and able to provide the patient with a good prognosis with a full clinical remission [1]. The psychiatric symptomatology remission and persistent stability allowed clinicians to periodically monitor and perform a complete neurological, neurocognitive, and neuroimaging assessment, which finally confirmed the underlying organic condition to ES, otherwise fully/partially masked by psychotic symptomatology. These specialistic evaluations led to a diagnosis of ES secondary to DLB, which became more clinically evident through a dramatic decline in cognitive functions and loss of autonomy in everyday life.

However, this treatment option with LAI APs is not advisable when symptoms of ES appear in elderly patients with no history of previous psychotic symptoms and/or disorder, where an underlying neurological cause should always be suspected and carefully investigated before treatment choice. In this case, the late diagnosis of DLB resulted in the patient being treated with AP drugs despite her neuroleptic sensitivity, ultimately leading to extrapyramidal symptoms. This risk is especially prominent with LAI formulations, which should have been avoided entirely if the final diagnosis had been known, because they expose the patients not only to the occurrence of mild neuroleptic sensitivity, as experienced by this patient, but also to severe idiosyncratic forms that can result in a neuroleptic malignant syndrome [16]. DLB should have been promptly investigated as the patient presented with a pattern compatible with psychiatric onset DLB [15], characterised by late-onset psychosis with hallucinations in visual and other modalities and systematised delusions (ES), in the presence of anxiety and depression, severe enough to require hospitalisation. Furthermore, the patient presented cognitive impairment, despite arduous to explore given the psychotic symptoms, and she presented parkinsonism after a period of treatment with neuroleptics in LAI formulation, all features that contributed to corroborate the hypothesis of an underlying DLB. Unlike previously reported cases of ES in a DLB [18,19], the diagnosis was delayed, as it mostly relied upon proper identification of neurocognitive symptoms in a patient with poor explorability of her mental state due to psychiatric-onset DLB. It could have been obtained sooner and with more precision in the observation period through the use of indicative biomarkers (earlier DaT imaging, myocardial scintigraphy, and polysomnography) [13,15,18,19].

Finally, a patient-tailored, multidisciplinary approach associated with continuity of care in specialistic settings and close periodic follow-up visits may ensure a definitive diagnosis and allow the patient to prompt treatment for DLB.