Prevalence of the anti-CASPR2 autoantibody in patients with somatic symptom disorder accompanied by medically unexplained pain 2025 Shiwaku et al

[Andy]

Abstract​

Background​

Medically unexplained symptoms (MUS) with pain are classified as somatic symptom disorder (SSD) with pain in the field of psychiatry, although an undetected biological basis may underlie at least some of these cases. One such candidate etiology is autoantibodies. Autoantibody etiologies are suspected in MUS with pain, including fibromyalgia, which is highly related to SSD accompanied with pain. Furthermore, autoantibodies against contactin-associated protein-like 2 (CASPR2) are known to induce neuropathy and pain, yet no study has examined the prevalence or clinical significance of anti-CASPR2 autoantibodies in patients with SSD accompanied with pain. Thus, the current study aims to investigate the seroprevalence of the anti-CASPR2 autoantibody among patients with SSD accompanied with pain and their associations with disease characteristics.

Methods​

The serum samples obtained from 264 patients with SSD accompanied with pain and 260 healthy controls were screened for anti-CASPR2 autoantibodies using a cell-based assay. Among the 264 patients enrolled, 231 with oral dysesthesia (including oral cenesthopathy) were assessed for clinical symptom severity using the Visual Analog Scale (VAS), Pain Catastrophizing Scale (PCS), and Somatic Symptom Scale-8 (SSS-8).

Results​

Of the 264 patients, 18 (6.8 %) tested seropositive for anti-CASPR2 autoantibodies. Among the 231 patients with oral dysesthesia, 12 (5.4 %) were positive for anti-CASPR2 autoantibodies. These patients with oral dysesthesia who were positive for anti-CASPR2 autoantibody reported significantly higher SSS-8 scores than those who were negative for autoantibody.

Conclusion​

Among patients with SSD accompanied with medically unexplained pain, a small subgroup was seropositive for anti-CASPR2 autoantibodies.

Open access

 

[Andy]

1. Introduction​

The mechanism underlying medically unexplained pain remains unclear in medicine. Medically unexplained pain is a subset of medically unexplained symptoms (MUS). Patients with such pain were previously diagnosed with a somatoform “pain disorder” in accordance with the revised fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR). At present, these patients were diagnosed with a somatic symptom disorder (SSD) accompanied with pain in accordance with the DSM-5 criteria.

The prevalence of SSD is approximately 5 %–7 % in the general population (Kurlansik and Maffei, 2016). MUS is observed in 20 %–30 % of patients who are seeking primary care in internal medicine (Aggarwal et al., 2006; de Waal et al., 2004; Hatcher and Arroll, 2008; Peveler et al., 1997). Depending on clinical manifestations, MUS may be diagnosed as fibromyalgia, irritable bowel syndrome, or chronic fatigue syndrome. Many of these patients also exhibit psychological distress, including depression or anxiety (Henningsen et al., 2003). Consequently, when referred for psychiatric evaluation, they are often diagnosed with SSD. Thus, the high prevalence of SSD among individuals with fibromyalgia, irritable bowel syndrome, and chronic fatigue syndrome is consistent with these observations (Häuser et al., 2015).

 

[Hutan]

The mechanism underlying medically unexplained pain remains unclear in medicine.

That's a strange way for a paper that seems somewhat open to the idea of misdiagnoses to start.

The mechanism underlying 'medically unexplained pain' is that the doctor(s) that saw the patient was/were not able to find a cause to explain the pain and so labelled it 'medically unexplained pain'. And, because many doctors are uncomfortable with not having an answer, and many patients are too, a story has been made to supposedly explain the varied sorts of pain in that 'medically unexplained pain bucket'.

 

[Hutan]

So, potentially a subset of people with medically unexplained pain have anti-CASPR2 auto-antibodies. I guess you'd want to know how common these auto-antibodies are in people without pain.

There's this reference that might be relevant.

[24] Dawes JM, Weir GA, Middleton SJ, Patel R, Chisholm KI, Pettingill P, et al. Immune
or genetic-mediated disruption of CASPR2 causes pain hypersensitivity due to
enhanced primary afferent excitability. Neuron 2018;97:806–822 e10.

Oral dyesthesia? Burning mouth syndrome.

 

[Hutan]

I guess you'd want to know how common these auto-antibodies are in people without pain.

Anti-contactin-associated protein-like 2 antibody-associated encephalitis in children: A case report and literature review, 2022

Anti-CASPR2 antibodies can be identified in the serum of about 1% of healthy individuals and patients with various neuropsychiatric disorders (18). Therefore, clinical symptoms, imaging, additional laboratory tests, and elimination of other diseases are required in combination to diagnose this disease.

I haven't checked out that reference 18.
That 2022 paper is quite interesting - from Wuhan. Here's its abstract.

Background: Anti-Contactin-associated protein-like 2 (CASPR2) antibody-associated encephalitis is a rare group of autoimmune diseases that causes extensive damage to the central and/or peripheral nervous system.

Case presentation: Here, we reported a case of anti-CASPR2 antibody-associated encephalitis in a 12-year-old male patient with symptoms of headache, consciousness disturbance, mental abnormalities, urinary incontinence, fasciculations in the extremity muscles, and involuntary movements. The testing for autoimmune encephalitis-associated antibodies showed that CASPR2-associated antibodies were positive, and electroencephalography showed diffuse slow waves. No tumor was found after screening for malignancies. The child’s status signicantly improved after receiving immunotherapy with intravenous methylprednisolone and immunoglobulin.

Conclusions: Anti-CASPR2 antibody-associated encephalitis has been rarely reported in children. It has a complex clinical presentation and a low incidence of tumor. Most pediatric patients have a favorable prognosis and relapse is uncommon.

 

[rvallee]

Consequently, when referred for psychiatric evaluation, they are often diagnosed with SSD. Thus, the high prevalence of SSD among individuals with fibromyalgia, irritable bowel syndrome, and chronic fatigue syndrome is consistent with these observations

Hm, yes, quite. If you apply "QC passed" stickers on random objects, then evaluate whether they actually pass quality control, you can at least certify that they do, indeed, have a "QC passed" sticker. Good grief these people, what the hell is wrong with them? A child can easily see through this nonsense.

Sometimes I really wonder if they ever actually read what they write or hear what they say, because they are seriously in Tobias Funke from Arrested Development territory, a character whose main running gag is being a psychiatrist who says constantly weirdly explicit sexual things while being completely oblivious to it.