Catatonia induced by antipsychotics in an adolescent male patient with systemic lupus erythematosus: A case report

Abstract

BACKGROUND

Systemic lupus erythematosus (SLE) can affect multiple organs or systems. The involvement of the central nervous system can result in the manifestation of epilepsy, an acute confusional state, and other rare neuropsychiatric presentations, such as catatonia.

CASE SUMMARY

We present a case of an adolescent male patient with first-onset SLE who presented with neuropsychiatric symptoms including epilepsy and delirium. The initial utilization of olanzapine to alleviate symptoms of agitation precipitated the emergence of catatonia, which was mitigated by discontinuing olanzapine and supplementing with lorazepam. In this case, whether the catatonia was secondary to the utilization of antipsychotics or to an organic disease is a question that warrants differential diagnosis.

CONCLUSION

Multidisciplinary collaborative management is the cornerstone for the successful management of severe cases of SLE.

Key Words: Catatonia; Systemic lupus erythematosus; Referral consultation; Antipsychotics; Benzodiazepines; Case report

Core Tip: Neuropsychiatric systemic lupus erythematosus (SLE) includes a variety of neurological and psychiatric features, whereas SLE is an underlying medical condition linked to catatonia, a potentially life-threatening neuropsychiatric condition. We present a case of an adolescent male patient with SLE who presented with neuropsychiatric symptoms including seizures and delirium, and who subsequently developed catatonia, independent of SLE, due to the use of antipsychotics. To our knowledge, this is the first documented case report of an adolescent patients with SLE who presented with catatonia secondary to the use of antipsychotics.

INTRODUCTION

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder that affects multiple organ systems[1]. Neuropsychiatric SLE (NPSLE) includes a variety of neurological and psychiatric features[2]. The American College of Rheumatology's (ACR) 1999 Nomenclature for NPSLE defined 19 syndromes indicating involvement of the central or peripheral nervous system, including seizures, delirium, and psychosis[3]. Catatonia is a potentially life-threatening neuropsychiatric condition that affects motor, speech and complex behaviors and is frequently accompanied by autonomic and affective disturbances[4]. In the International Classification of Diseases Eleventh Revision (ICD-11), catatonia is not only described as being associated with any mental disorder, induced by psychoactive substances (including medications), or secondary to medical conditions, but it is also recognized as an independent nosological entity in a new diagnostic grouping that has been added to the same hierarchical level as mood disorders, anxiety-related disorders, etc[5,6]. The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR) also acknowledges catatonia's association with diverse conditions[7]. SLE is an underlying medical condition linked to catatonia[4,5,7,8]. As a rare manifestation of SLE, catatonia has been documented in case reports[9]. We present a case of an adolescent male patient with SLE who presented with neuropsychiatric symptoms including seizures and delirium, and who subsequently developed catatonia, independent of SLE, due to the application of antipsychotics. To our knowledge, this is the first documented case report of an adolescent patients with SLE who presented with catatonia secondary to antipsychotics.

CASE PRESENTATION

Chief complaints

The case involved a 15-year-old male who initially presented with intermittent fever (37.4-38 ℃), sore throat, and fatigue one month prior to hospitalization. Antipyretics and cefuroxime failed to resolve this condition. Nausea, vomiting, diminished appetite, jaundice, and dark-colored urine appeared two weeks prior to hospitalization.

History of present illness

Upon meeting the 2019 European League Against Rheumatism/ACR Classification Criteria for SLE[10], a regimen of 100 mg hydrocortisone twice daily intravenously was initiated. Owing to the patient's intense vomiting, the attending physician opted for intravenous administration of hydrocortisone rather than administration via the oral route. This resulted in alleviation of fever, amelioration of fatigue, and improvement in appetite, although leukopenia, anemia, elevated liver enzymes, and hyperbilirubinemia improved only partially. The patient unexpectedly experienced a single episode of unconsciousness, coupled with bilateral palpebral retraction, mandibular clenching, unresponsiveness, bilateral upper limb convulsions, and bilateral lower limb rigidity. This phenomenon persisted for six minutes before spontaneously resolving, and consciousness returned after 10 minutes. The attending physician considered this manifestation to be an epileptic seizure, indicating potential central nervous system (CNS) involvement in SLE and necessitating hospital admission. Following the initiation of anti-epileptic medications (levetiracetam at 500 mg twice daily), the patient no longer exhibited seizures and there were no epileptiform discharges on the electroencephalogram.

History of past illness

The past medical and psychosocial histories of the patient were unremarkable, and he denied a history of substance use.

Personal and family history

He had no family history of severe physical diseases, autoimmune disorders, or mental disorders.

Physical examination

Upon admission, the patient exhibited intermittent nocturnal confusion characterized by disordered speech, disorientation, inattention, auditory and visual hallucinations, and a delusion of being manipulated. During the day, these manifestations were slightly attenuated, but the patient manifested conspicuous lethargy. The physician prescribed olanzapine 5 mg/day to alleviate the patient's psychotic symptoms and agitated behavior. Owing to symptoms of confusion; epilepsy; multiorgan involvement; and abnormal test findings including leukopenia, anemia, hypocomplementemia, and elevated anti-double-stranded DNA (anti-dsDNA) Abs binding, the SLE disease activity index-2000 score was 25, which suggested severe disease activity[11]. Within two days of initiating olanzapine therapy, the patient's hallucinatory symptoms and delusions had subsided, albeit accompanied by intermittent peculiar movements. Bedside observations revealed that the patient repeatedly elevated his buttocks while lying down and then maintained this unusual posture for several minutes for no specific reason. When the physician raised the patient's arms, the patient remained in this position until his arms were lowered. During the medical interview, the patient echoed the physician's questions rather than providing answers. There were also periods when the patient remained mute and immobile, marginally responsive to nociceptive and auditory stimulation, staring in one particular direction, and resisting physical examination.

Laboratory examinations

Prior to admission, preliminary laboratory tests revealed leukopenia, anemia, elevated liver enzymes, hyperbilirubinemia, elevated C-reactive protein levels, hypocomplementemia (both C3 and C4), positive antinuclear antibody (ANA), and increased binding of anti-dsDNA antibodies (Abs) at 311 IU/mL (ELISA method, normal range < 100 IU/mL). Urinalysis and stool examinations were unremarkable, whereas abdominal ultrasound revealed "mild splenomegaly". During hospitalization, the serum tests were repeated and revealed decreased and, eventually, negative anti-dsDNA Abs (154 IU/mL– 105 IU/mL - < 100 IU/mL), a gradual reduction in the ANA titer from 1:1280 to 1:160, and normal complement levels, which suggested a general improvement in the SLE disease activity. Excluding ANA and anti-dsDNA Abs, other autoantibodies, including antiphospholipid Abs and those associated with autoimmune encephalitis, such as anti-N-methyl-D-aspartate receptor Abs, anti-gamma-aminobutyric acid (GABA) Abs, and anti-voltage-gated potassium channel Abs, were negative. A cerebrospinal fluid examination was unremarkable.

Imaging examinations

A head magnetic resonance imaging (MRI) revealed slight widening of the sulci and fissures.

FINAL DIAGNOSIS

On the basis of these results, rheumatologists concluded that the patient's movement disorder was unlikely to be a manifestation of NPSLE. A psychiatric consultant identified catatonic symptoms, and the manifestations were rated 24 on the Bush-Francis Catatonia Rating Scale (BFCRS)[12].

TREATMENT

Discontinuation of olanzapine was recommended, and lorazepam was initiated at 3 mg daily in three divided doses. Subsequent evaluations revealed a significant reduction in the patient's catatonia, as illustrated in Table 1 by serial daily BFCRS scores of 24, 14, 8, 2, and 0. Once the catatonia had subsided, lorazepam was tapered off at a reduction rate of 0.5 mg per day.

Table 1 The patient’s Bush-Francis Catatonia Rating Scale score throughout hospitalization.

Items	Day 1	Day 2	Day 3	Day 4	Day 5
Total score	24	14	8	2	0
Excitement	1	1	1	0	0
Immobility/stupor	3	2	1	0	0
Mutism	2	2	1	0	0
Staring	2	2	1	0	0
Posturing/catalepsy	1	1	0	0	0
Grimacing	0	0	0	0	0
Echopraxia/echolalia	3	2	1	0	0
Stereotypy	1	1	0	0	0
Mannerisms	0	0	0	0	0
Verbigeration	0	0	0	0	0
Rigidity	0	0	0	0	0
Nagativism	2	1	1	1	0
Waxy flexibility	3	0	0	0	0
Withdrawal	0	0	0	0	0
Impulsivity	1	1	1	0	0
Automatic obedience	0	0	0	0	0
Mitgehen	0	0	0	0	0
Gegenhalten	0	0	0	0	0
Ambitendency	0	0	0	0	0
Grasp reflex	0	0	0	0	0
Perseveration	3	0	0	0	0
Combativeness	0	0	0	0	0
Autonomic abnormality	2	1	1	1	0

OUTCOME AND FOLLOW-UP

The patient's confusional state gradually improved and had resolved completely prior to discharge. Neuropsychological evaluation revealed cognitive deficits with a score of 21/30 according to the Montreal Cognitive Assessment (MoCA). No seizures or catatonia reoccurred.

Postdischarge follow-ups at 3 months, 1 year, 2 years, and 5 years revealed that the patient's condition remained stable, with no lupus flares or recurrence of epilepsy, altered consciousness, or catatonia. The memory deficit persisted at the 3-month follow-up (MoCA score 25/30) but had completely resolved by 1 year (MoCA score 30/30). Regular academic participation and interpersonal interaction were resumed. Corticosteroids were gradually discontinued, and hydroxychloroquine was started at 1-year postdischarge and maintained at 200 mg daily. The blood parameters were within normal limits: The ANA titer decreased to 1: 80, and other autoAbs, including anti-dsDNA Abs, remained negative. When interviewed regarding his experience with the disease, the patient reported limited recollection, possibly an outcome of the confused state. He recalled the fatigue and exhaustion necessitating rest. He was unable to recall the manifestations of catatonia, perceiving it to be humorous when the physicians mentioned signs such as waxy flexibility and negativism. The timeline of the patient's diagnostic and treatment course is depicted in Figure 1.

Figure 1 Timeline of the case. ANA: Antinuclear antibody; CRP: C-reaction protein; US: Ultrasound; EEG: Electroencephalogram; NPSLE: Neuropsychiatric systemic lupus erythematosus; SLEDAI-2K: SLE disease activity index-2000; BFCRS: Bush-Francis catatonia rating scale; MoCA: Montreal cognitive assessment.

DISCUSSION

We report the case of an adolescent male with SLE who presented with multiple neuropsychiatric symptoms during the disease process. SLE has the potential to involve multiple organs, with CNS involvement often indicative of severity[13]. The reported prevalence of mental disorders among patients with SLE ranges drastically from 14 to 95%, possibly due to inconsistent research settings and diagnostic instruments[14]. In our previous single-center retrospective study of hospitalized Chinese patients with SLE who received psychiatric consultations, the prevalence rates of delirium and psychosis were 54.4% and 11.9%, respectively[15]. It has been proposed that certain neuropsychiatric conditions may be related not to SLE but instead to organic influences[16]. Catatonia, once considered a unique manifestation of mental disorders, can in fact, be observed secondary to numerous medical conditions[4]. The pathophysiological mechanisms underlying catatonia remain unclear, although it has been postulated that it may be associated with GABAergic and dopaminergic neural pathways[17]. Although uncommon in clinical contexts, catatonia in patients with SLE has been documented in the literature since 1977[18]. In our case, the attribution of catatonia merits discussion.

Delirium with catatonia is also a condition that is observed during psychiatric consultations, such as in the case we previously reported[19]. In critically ill patients, catatonia may persist amid delirium because the psychomotor symptoms of catatonia are frequently overlooked in delirious patients with fluctuating levels of attention and cognition[4]. From a psychiatric diagnostic perspective, if catatonia manifests later and improves sooner than delirium does, catatonia should not be discerned independently, that is, not as a distinct diagnosis juxtaposed with delirium but as a manifestation of delirium[7]. In previous cases of secondary catatonia attributed to SLE, some patients demonstrated positivity for multiple autoAbs, including anti-ribonucleoprotein, anti-Smith, anti-ribosomal P and ACL Abs, all of which have frequently been correlated with NPSLE[9,20]. The patient in our case tested negative for all except ANA and anti-dsDNA Abs, and no notable abnormalities were observed on head magnetic resonance. Neuroimaging is insufficiently sensitive and specific for the diagnosis of NPSLE, with approximately 50% of patients exhibiting no neuroimaging abnormalities[14,21]. Alterations to the CNS on MRI in patients with NPSLE lack discernible correlations with clinical symptoms or neurological signs. However, research has indicated that 25% of patients with early SLE exhibit MRI imaging anomalies[21]. There were also other case reports with negative findings similar to our case[9,22]. It is possible that in these cases, neuropsychiatric manifestations, such as catatonia, are secondary syndromes with unidentified organic factors. In fact, of the patients reported to have catatonia in the context of SLE, a majority (60%) were treated with antipsychotics[23]. It is plausible that patients with NPSLE, who have altered brain function, experience increased vulnerability to antipsychotic-induced catatonia[23]. Currently, there is insufficient research to shed light on the prevalence of catatonia among patients utilizing antipsychotics, a subject worthy of deeper exploration. In our case, we postulate that catatonia was not secondary to SLE but rather, it occurred due to the use of olanzapine, as the chronologically manifestations of catatonia developed subsequent to the use of antipsychotics, which is a recognized predisposing factor for catatonia[4]. Following the discontinuation of olanzapine and the addition of lorazepam, the first-line treatment for catatonia, the patient's catatonic manifestations largely subsided. According to the Naranjo Adverse Drug Reaction Probability Scale, the score of catatonia caused by olanzapine in this case was 7, indicating probable causality[24]. In a separate case report of an adult female patient with SLE, haloperidol and loxapine induced a catatonic syndrome associated with extrapyramidal signs[25]. Notably, in this case and in our case, the antipsychotics were intended to ameliorate the psychotic symptoms associated with SLE, but they provoked the emergence of new psychiatric symptoms of catatonia.

CONCLUSION

In conclusion, precise identification and accurate differential diagnosis of neuropsychiatric syndromes is essential for guiding the appropriate management of patients with SLE. Simultaneously, monitoring for adverse effects involving the utilization of psychotropic agents in patients presenting with somatic illnesses is imperative. Clinicians should maintain vigilance for any change in behavior and cognition in patients with suspected neuropsychiatric involvement and should engage in interdisciplinary collaboration to promptly manage neuropsychiatric manifestations.

ACKNOWLEDGEMENTS

We would like to express our gratitude to the patient and his family, as well as to the entire medical staff who participated in the patient's treatment.