RARE DISEASE
PANDAS
PANDAS
PANDAS
Synonyms: Pediatric autoimmune disorders associated with Streptococcus infections, Pediatric autoimmune neuropsychiatric disorders associated with Streptococcus infections
Synonyms: Pediatric autoimmune disorders associated with Streptococcus infections, Pediatric autoimmune neuropsychiatric disorders associated with Streptococcus infections
Synonyms: Pediatric autoimmune disorders associated with Streptococcus infections, Pediatric autoimmune neuropsychiatric disorders associated with Streptococcus infections
Drug discovery
1
drug
With orphan designation
Overview
PANDAS (Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal Infections) is a post-infectious autoimmune condition characterized by the abrupt onset of obsessive-compulsive disorder (OCD) or tics following Group A streptococcal infection. Key diagnostic criteria include prepubertal onset, episodic symptom course, and neurological abnormalities (e.g., motor hyperactivity). It is distinguished from idiopathic OCD by rapid symptom escalation and concurrent neuropsychiatric manifestations [1][6][16].
Burden
Associated with severe psychiatric comorbidities (e.g., anxiety, developmental regression) and academic decline [1][4].
Economic impact includes high hospitalization costs (e.g., $2,049/day average in Illinois) [19] and prolonged care needs.
Families report significant emotional and logistical strain, exacerbated by diagnostic delays and limited specialist access [4][19].
Therapies
Medical: Antibiotics (targeting infections), IVIG/plasmapheresis (modulating immunity), NSAIDs (reducing inflammation) [8][13][18].
Behavioral: Cognitive-behavioral therapy (CBT) and exposure-response prevention (ERP) for OCD/anxiety [3][13].
Integrative: Probiotics, vitamin D, and dietary adjustments as adjunctive options [8].
Categories: rare neurological diseases
Research Papers
151 drug discovery papers about PANDAS, with 2 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
151 drug discovery papers about PANDAS, with 2 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-07-03 | Therapeutic plasma exchange and immunomodulatory strategies in post-infectious syndromes: A review of immune dysregulation in PTLDS, long COVID, ME/CFS, and PANS/PANDAS.
Post-infectious syndromes including post-treatment Lyme disease syndrome (PTLDS), long COVID, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and pediatric acute-onset neuropsychiatric syndrome (PANS)/pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) share overlapping clinical phenotypes characterized by fatigue, cognitive dysfunction, sleep disturbance, and neuropsychiatric symptoms. Increasing evidence suggests that immune dysregulation-including persistent inflammation, autoantibody production, and cellular immune dysfunction-may underlie these conditions. This narrative review synthesizes peer-reviewed literature describing immune abnormalities across these syndromes and evaluates the rationale for immunomodulatory therapies, including intravenous immunoglobulin (IVIG), rituximab, and therapeutic plasma exchange (TPE). Evidence supporting immune-targeted treatment strategies is strongest in subsets of patients with identifiable immunologic abnormalities. Notably, the phase III RituxME trial in ME/CFS and a phase II trial of TPE in post-COVID condition both failed to demonstrate efficacy in unselected populations, reinforcing the importance of biomarker-guided patient stratification. TPE functions by removing circulating immune complexes, autoantibodies, and inflammatory mediators, and observational data suggest benefit in patients with demonstrable autoantibody burden. Further controlled studies incorporating immunologic phenotyping and early intervention are needed to define the therapeutic role of immune-directed interventions across these conditions.
2026-06-01 | Sudden-Onset Obsessive-Compulsive Disorder in a Pediatric Patient: A Case-Based Literature Review on PANDAS and Immunomodulatory Treatment Strategies
Introduction Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections (PANDAS) describe a subset of prepubertal children who develop an abrupt onset of obsessive-compulsive symptoms and/or tics following a Group A Streptococcus (GAS) infection. Although the diagnosis remains controversial, the proposed pathophysiological mechanism involves an autoimmune response in genetically susceptible individuals, where molecular mimicry leads to the production of antibodies that cross-react with antigens in the basal ganglia. Nevertheless, this hypothesis has not been conclusively confirmed in current literature. Treatment is typically symptomatic, however, there is potential for clinical improvement with immunomodulatory and antibiotic therapies in selected cases. Objectives To describe a pediatric case of sudden-onset OCD with suspected autoimmune etiology and favorable response to antibiotic treatment, and to review the current literature on therapeutic strategies for PANDAS, including antibiotics and immunomodulatory interventions. Methods A narrative literature review was conducted using PubMed with the following terms: (“PANDAS” OR “PANS”) AND (“Obsessive-Compulsive Disorder” OR “OCD”) AND (“Antibiotic treatment” OR “Immunomodulatory therapy”). Twelve research studies involving treatments such as penicillin, azithromycin, intravenous immunoglobulin (IVIG), plasma exchange, tonsillectomy, cognitive behavioral therapy (CBT), NSAIDs, and corticosteroids met inclusion criteria. Additionally, 65 case reports describing the use of antibiotics, immunomodulators, and/or psychotropics were identified. Results Twelve research studies met inclusion criteria, evaluating treatments such as penicillin, azithromycin, intravenous immunoglobulin (IVIG), plasma exchange, tonsillectomy, cognitive behavioral therapy (CBT), NSAIDs, and corticosteroids. Additionally, 65 case reports described the use of antibiotics, immunomodulatory therapies, and/or psychotropic medications. While antibiotics and IVIG showed potential benefit in selected cases, the overall quality of evidence was low, with high risk of bias and lack of randomized controlled trials. Corticosteroids and NSAIDs were used in acute phases with variable outcomes, and plasma exchange was reserved for severe, refractory presentations. CBT remained a consistent component of symptom management across studies. Conclusions This case supports the hypothesis of an autoimmune mechanism in a subset of pediatric OCD presentations. Although various immunomodulatory strategies have been explored, including antibiotics, IVIG, corticosteroids, NSAIDs, and plasma exchange, rigorously conducted research remains scarce. Further investigation is needed to establish standardized diagnostic criteria and evidence-based treatment protocols for PANDAS and related autoimmune neuropsychiatric syndromes. Disclosure of Interest None Declared
2026-05-27 | Functional Shifts in Gut Microbiota and Associated Metabolites Suggest Gut-Brain Axis Dysregulation in Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS).
Background: Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections (PANDAS) are characterized by neuropsychiatric symptoms linked to immune dysregulation. Emerging evidence highlights the role of host-microbiome interactions in modulating neuro-immune functions via gut-brain axis signaling; however, its contribution to PANDAS pathophysiology remains poorly understood. Methods: We conducted microbiome analysis from samples collected across multiple sites of PANDAS patients including nasal, throat and stool. We performed an integrated multi-omics analysis of stool samples from pediatric PANDAS cases and healthy controls, including discordant twin pairs. Microbial composition and function were assessed using 16S rRNA gene sequencing, shotgun metagenomics, while untargeted metabolomic profiling was performed using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS). Results: PANDAS cases exhibited reduced alpha diversity and significantly altered beta diversity compared to controls, indicating shifts in gut microbial composition. Shotgun metagenomic analysis revealed differential enrichment of functional pathways, including diminished quorum sensing, altered gamma-aminobutyric acid (GABA) biosynthesis, and microbial degradation processes. Multiple gut-brain modules (GBMs) and gut metabolic modules (GMMs) associated with neurotransmission, transport activities and metabolism were significantly perturbed in PANDAS. Metabolomic profiling showed reduced functional diversity and distinct clustering of metabolic profiles, with differential abundance of amino acids, bile acids, and neuroactive compounds. Integrative analysis further identified disrupted microbe-metabolite networks allied to gut-brain signaling. Conclusions: Our findings reveal significant functional shifts in gut microbiota composition, functional capacity and metabolite profile in PANDAS, suggesting dysregulation of the gut-brain axis signaling. This study provides a foundation for development of microbiome-based biomarkers and therapeutic strategies for pediatric neuropsychiatric disorders.
2026-05-25 | Antibody Profiles in Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections.
Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) is characterized by prepubertal abrupt onset of obsessive-compulsive disorder (OCD). The sine qua non is group A streptococcus (GAS) infection, which is hypothesized to elicit an IgG-class anti-GAS antibody response that cross-reacts with antigens in the basal ganglia. However, the association between GAS antibody (GAS-IgG) levels and PANDAS has been inconsistent, and qualitative differences in GAS-IgG profiles have not been carefully evaluated in well-phenotyped cohorts. Moreover, independent studies have yet to converge on anti-neural autoantibodies that are specific to PANDAS. Here, we used phage display immunoprecipitation sequencing (PhIP-Seq) to perform ultra-deep anti-pathogen antibody repertoire profiling of serum from definitive pediatric PANDAS patients (N = 34) collected as part of a prior double-blind, placebo-controlled clinical trial of intravenous immunoglobulin (IVIg). PANDAS cases were compared to pediatric controls without a history of neuropsychiatric illness (N = 31). To assess for objective evidence of neuroglial injury, serum neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) levels were compared to healthy pediatric controls. Within PANDAS, NfL and GFAP levels were compared between pre- and post-treatment sera. To evaluate for central autoantibodies, a subset of baseline cerebrospinal fluid (CSF) samples (N = 25) was profiled by full-length human protein microarray. Though GAS reactivity by PhIP-Seq was well correlated with clinical anti-DNaseB and anti-streptolysin O titers, there were no quantitative or qualitative differences in GAS-IgG profiles between PANDAS and controls. Furthermore, NfL and GFAP levels did not differ between cases and controls. Within PANDAS, changes in NfL or GFAP levels at six weeks did not differ between placebo and IVIg groups. However, CSF autoantibody profiling by protein microarray revealed infrequent but notable candidate autoantibodies. In one patient, we identified autoantibodies against Argonaute family proteins (AGO-IgG), a marker of autoimmune sensory neuropathy. Longitudinal measurement of AGO-IgG in sera revealed that titers were unchanged after placebo, but decreased after IVIg, coinciding with symptomatic improvement, including a decrease in that patient's CY-BOCS score. Overall, these results do not support an etiologic role for GAS-IgG in PANDAS. However, some individuals diagnosed with PANDAS may harbor anti-neural autoantibodies.
2026-04-06 | Immune dysregulation in pediatric tic disorders: mechanisms, biomarkers, and therapeutic frontiers.
Tic Disorders (TDs) are common neurodevelopmental disorders characterized by complex pathophysiological mechanisms. A growing body of evidence in recent years suggests that immune system dysregulation plays a critical role in the pathogenesis and clinical course of TDs in a subset of pediatric patients. This review aims to systematically summarize the current understanding of the core mechanisms of immune dysregulation in pediatric TDs, potential biomarkers, and related therapeutic frontiers. We detail three core pathophysiological pathways, Post infectious autoimmunity, represented by the Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) and Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) models. Its core mechanism involves the production of autoantibodies induced by molecular mimicry, which target basal ganglia neurons, such as cholinergic interneurons and dopamine receptors. Neuroinflammation is another critical pathway. This process involves T helper 17 (Th17) cell-mediated disruption of the blood-brain barrier and microglial activation. It is further characterized by elevated pro-inflammatory cytokines, such as Tumor Necrosis Factor-alpha (TNF-α) and Interleukin-12 (IL-12). Microbiota-gut-brain axis dysregulation, wherein gut dysbiosis and compromised intestinal barrier function influence central nervous system (CNS) function through the neuro immune endocrine network. Building upon this framework, we evaluate potential biomarkers across various dimensions, including the findings and limitations in serology (cytokines), cerebrospinal fluid analysis (oligoclonal bands, MCP-1), neuroimaging (volumetric changes in the basal ganglia and PET imaging of neuroinflammation), and genetics (variations in the IL-1RN gene). Finally, we discuss the evolution from conventional treatments to emerging immune-targeted therapies. This encompasses core immunomodulatory therapies (Intravenous Immunoglobulin (IVIG) and plasmapheresis) and promising future strategies, such as fecal microbiota transplantation (FMT), targeted B-cell therapies, and small-molecule anti-inflammatory drugs. In conclusion, a deeper understanding of the immunological basis of TDs is paving the way for the development of more precise diagnostic tools and novel, individualized immunomodulatory interventions.
2026-07-03 | Therapeutic plasma exchange and immunomodulatory strategies in post-infectious syndromes: A review of immune dysregulation in PTLDS, long COVID, ME/CFS, and PANS/PANDAS.
Post-infectious syndromes including post-treatment Lyme disease syndrome (PTLDS), long COVID, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and pediatric acute-onset neuropsychiatric syndrome (PANS)/pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) share overlapping clinical phenotypes characterized by fatigue, cognitive dysfunction, sleep disturbance, and neuropsychiatric symptoms. Increasing evidence suggests that immune dysregulation-including persistent inflammation, autoantibody production, and cellular immune dysfunction-may underlie these conditions. This narrative review synthesizes peer-reviewed literature describing immune abnormalities across these syndromes and evaluates the rationale for immunomodulatory therapies, including intravenous immunoglobulin (IVIG), rituximab, and therapeutic plasma exchange (TPE). Evidence supporting immune-targeted treatment strategies is strongest in subsets of patients with identifiable immunologic abnormalities. Notably, the phase III RituxME trial in ME/CFS and a phase II trial of TPE in post-COVID condition both failed to demonstrate efficacy in unselected populations, reinforcing the importance of biomarker-guided patient stratification. TPE functions by removing circulating immune complexes, autoantibodies, and inflammatory mediators, and observational data suggest benefit in patients with demonstrable autoantibody burden. Further controlled studies incorporating immunologic phenotyping and early intervention are needed to define the therapeutic role of immune-directed interventions across these conditions.
2026-06-01 | Sudden-Onset Obsessive-Compulsive Disorder in a Pediatric Patient: A Case-Based Literature Review on PANDAS and Immunomodulatory Treatment Strategies
Introduction Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections (PANDAS) describe a subset of prepubertal children who develop an abrupt onset of obsessive-compulsive symptoms and/or tics following a Group A Streptococcus (GAS) infection. Although the diagnosis remains controversial, the proposed pathophysiological mechanism involves an autoimmune response in genetically susceptible individuals, where molecular mimicry leads to the production of antibodies that cross-react with antigens in the basal ganglia. Nevertheless, this hypothesis has not been conclusively confirmed in current literature. Treatment is typically symptomatic, however, there is potential for clinical improvement with immunomodulatory and antibiotic therapies in selected cases. Objectives To describe a pediatric case of sudden-onset OCD with suspected autoimmune etiology and favorable response to antibiotic treatment, and to review the current literature on therapeutic strategies for PANDAS, including antibiotics and immunomodulatory interventions. Methods A narrative literature review was conducted using PubMed with the following terms: (“PANDAS” OR “PANS”) AND (“Obsessive-Compulsive Disorder” OR “OCD”) AND (“Antibiotic treatment” OR “Immunomodulatory therapy”). Twelve research studies involving treatments such as penicillin, azithromycin, intravenous immunoglobulin (IVIG), plasma exchange, tonsillectomy, cognitive behavioral therapy (CBT), NSAIDs, and corticosteroids met inclusion criteria. Additionally, 65 case reports describing the use of antibiotics, immunomodulators, and/or psychotropics were identified. Results Twelve research studies met inclusion criteria, evaluating treatments such as penicillin, azithromycin, intravenous immunoglobulin (IVIG), plasma exchange, tonsillectomy, cognitive behavioral therapy (CBT), NSAIDs, and corticosteroids. Additionally, 65 case reports described the use of antibiotics, immunomodulatory therapies, and/or psychotropic medications. While antibiotics and IVIG showed potential benefit in selected cases, the overall quality of evidence was low, with high risk of bias and lack of randomized controlled trials. Corticosteroids and NSAIDs were used in acute phases with variable outcomes, and plasma exchange was reserved for severe, refractory presentations. CBT remained a consistent component of symptom management across studies. Conclusions This case supports the hypothesis of an autoimmune mechanism in a subset of pediatric OCD presentations. Although various immunomodulatory strategies have been explored, including antibiotics, IVIG, corticosteroids, NSAIDs, and plasma exchange, rigorously conducted research remains scarce. Further investigation is needed to establish standardized diagnostic criteria and evidence-based treatment protocols for PANDAS and related autoimmune neuropsychiatric syndromes. Disclosure of Interest None Declared
2026-05-27 | Functional Shifts in Gut Microbiota and Associated Metabolites Suggest Gut-Brain Axis Dysregulation in Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS).
Background: Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections (PANDAS) are characterized by neuropsychiatric symptoms linked to immune dysregulation. Emerging evidence highlights the role of host-microbiome interactions in modulating neuro-immune functions via gut-brain axis signaling; however, its contribution to PANDAS pathophysiology remains poorly understood. Methods: We conducted microbiome analysis from samples collected across multiple sites of PANDAS patients including nasal, throat and stool. We performed an integrated multi-omics analysis of stool samples from pediatric PANDAS cases and healthy controls, including discordant twin pairs. Microbial composition and function were assessed using 16S rRNA gene sequencing, shotgun metagenomics, while untargeted metabolomic profiling was performed using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS). Results: PANDAS cases exhibited reduced alpha diversity and significantly altered beta diversity compared to controls, indicating shifts in gut microbial composition. Shotgun metagenomic analysis revealed differential enrichment of functional pathways, including diminished quorum sensing, altered gamma-aminobutyric acid (GABA) biosynthesis, and microbial degradation processes. Multiple gut-brain modules (GBMs) and gut metabolic modules (GMMs) associated with neurotransmission, transport activities and metabolism were significantly perturbed in PANDAS. Metabolomic profiling showed reduced functional diversity and distinct clustering of metabolic profiles, with differential abundance of amino acids, bile acids, and neuroactive compounds. Integrative analysis further identified disrupted microbe-metabolite networks allied to gut-brain signaling. Conclusions: Our findings reveal significant functional shifts in gut microbiota composition, functional capacity and metabolite profile in PANDAS, suggesting dysregulation of the gut-brain axis signaling. This study provides a foundation for development of microbiome-based biomarkers and therapeutic strategies for pediatric neuropsychiatric disorders.
2026-05-25 | Antibody Profiles in Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections.
Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) is characterized by prepubertal abrupt onset of obsessive-compulsive disorder (OCD). The sine qua non is group A streptococcus (GAS) infection, which is hypothesized to elicit an IgG-class anti-GAS antibody response that cross-reacts with antigens in the basal ganglia. However, the association between GAS antibody (GAS-IgG) levels and PANDAS has been inconsistent, and qualitative differences in GAS-IgG profiles have not been carefully evaluated in well-phenotyped cohorts. Moreover, independent studies have yet to converge on anti-neural autoantibodies that are specific to PANDAS. Here, we used phage display immunoprecipitation sequencing (PhIP-Seq) to perform ultra-deep anti-pathogen antibody repertoire profiling of serum from definitive pediatric PANDAS patients (N = 34) collected as part of a prior double-blind, placebo-controlled clinical trial of intravenous immunoglobulin (IVIg). PANDAS cases were compared to pediatric controls without a history of neuropsychiatric illness (N = 31). To assess for objective evidence of neuroglial injury, serum neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) levels were compared to healthy pediatric controls. Within PANDAS, NfL and GFAP levels were compared between pre- and post-treatment sera. To evaluate for central autoantibodies, a subset of baseline cerebrospinal fluid (CSF) samples (N = 25) was profiled by full-length human protein microarray. Though GAS reactivity by PhIP-Seq was well correlated with clinical anti-DNaseB and anti-streptolysin O titers, there were no quantitative or qualitative differences in GAS-IgG profiles between PANDAS and controls. Furthermore, NfL and GFAP levels did not differ between cases and controls. Within PANDAS, changes in NfL or GFAP levels at six weeks did not differ between placebo and IVIg groups. However, CSF autoantibody profiling by protein microarray revealed infrequent but notable candidate autoantibodies. In one patient, we identified autoantibodies against Argonaute family proteins (AGO-IgG), a marker of autoimmune sensory neuropathy. Longitudinal measurement of AGO-IgG in sera revealed that titers were unchanged after placebo, but decreased after IVIg, coinciding with symptomatic improvement, including a decrease in that patient's CY-BOCS score. Overall, these results do not support an etiologic role for GAS-IgG in PANDAS. However, some individuals diagnosed with PANDAS may harbor anti-neural autoantibodies.
2026-04-06 | Immune dysregulation in pediatric tic disorders: mechanisms, biomarkers, and therapeutic frontiers.
Tic Disorders (TDs) are common neurodevelopmental disorders characterized by complex pathophysiological mechanisms. A growing body of evidence in recent years suggests that immune system dysregulation plays a critical role in the pathogenesis and clinical course of TDs in a subset of pediatric patients. This review aims to systematically summarize the current understanding of the core mechanisms of immune dysregulation in pediatric TDs, potential biomarkers, and related therapeutic frontiers. We detail three core pathophysiological pathways, Post infectious autoimmunity, represented by the Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) and Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) models. Its core mechanism involves the production of autoantibodies induced by molecular mimicry, which target basal ganglia neurons, such as cholinergic interneurons and dopamine receptors. Neuroinflammation is another critical pathway. This process involves T helper 17 (Th17) cell-mediated disruption of the blood-brain barrier and microglial activation. It is further characterized by elevated pro-inflammatory cytokines, such as Tumor Necrosis Factor-alpha (TNF-α) and Interleukin-12 (IL-12). Microbiota-gut-brain axis dysregulation, wherein gut dysbiosis and compromised intestinal barrier function influence central nervous system (CNS) function through the neuro immune endocrine network. Building upon this framework, we evaluate potential biomarkers across various dimensions, including the findings and limitations in serology (cytokines), cerebrospinal fluid analysis (oligoclonal bands, MCP-1), neuroimaging (volumetric changes in the basal ganglia and PET imaging of neuroinflammation), and genetics (variations in the IL-1RN gene). Finally, we discuss the evolution from conventional treatments to emerging immune-targeted therapies. This encompasses core immunomodulatory therapies (Intravenous Immunoglobulin (IVIG) and plasmapheresis) and promising future strategies, such as fecal microbiota transplantation (FMT), targeted B-cell therapies, and small-molecule anti-inflammatory drugs. In conclusion, a deeper understanding of the immunological basis of TDs is paving the way for the development of more precise diagnostic tools and novel, individualized immunomodulatory interventions.
Access all drug discovery papers and probability of success in trials forecasts:
Access all drug discovery papers and probability of success in trials forecasts:
Drug Discovery Landscape
1 orphan drug designation for PANDAS.
1 orphan drug designation for PANDAS.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
sarcosine | small molecules | FDA | 2011-10-12 | — | Guochuan Emil Tsai, MD, PhD |
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