Access to Care in Pediatric Acute-Onset Neuropsychiatric Syndrome: A Survey of Families’ Journeys to and Experiences with Intravenous Immunoglobulin Treatment

Abstract

Background:

Pediatric acute-onset neuropsychiatric syndrome (PANS) is characterized by abrupt-onset neuropsychiatric symptoms, often infection-triggered. Intravenous immunoglobulin (IVIG) is recommended by expert guidelines in select cases, yet insurance denials and high out-of-pocket costs have been barriers to access.

Methods:

We surveyed 60 caregivers and adult PANS patients who pursued IVIG therapy, collecting data on insurance coverage, treatment protocols, financial strategies, and quality of life (QoL) before and after treatment.

Results:

Most patients (88%) eventually received IVIG, 10% were still in pursuit, and 2% discontinued trying. Insurance approval without appeal occurred for 24%, often for patients with comorbidities for which IVIG is typically covered. Only 5% of those receiving IVIG for PANS alone were treated within a month of the doctor’s order compared with 38% of those receiving IVIG for comorbidities plus PANS; 14% waited ≥9 months. Financial strain was routine: at least one-third of families without “substantial” insurance coverage (≥70% of expenses) reported extreme stress (10 on scale of 1 to 10), 58% borrowed money, and 21% sold major assets. Even families with substantial insurance coverage commonly depleted savings or took on additional work. Before IVIG, patient QoL ratings were poor (means 2.1–2.9 across domains), with over one-third selecting the lowest possible overall QoL rating. During the 6 months following IVIG initiation, mean ratings rose to 6.2–6.8, with over 60% reporting “good” to “exceedingly good” overall outcomes. Caregivers reported parallel gains, with family QoL ratings rising from 2.4–4.0 pretreatment to 5.7–6.6 posttreatment.

Conclusions:

Families pursuing IVIG for PANS reported prolonged delays, repeated denials, and financial strain, often resorting to loans, asset sales, and additional work. Despite these burdens, IVIG was correlated with marked improvements in perceived QoL for patients and caregivers.

Keywords

IVIG PANS quality of life caregiver burden

Introduction

Pediatric acute-onset neuropsychiatric syndrome (PANS) is a rare and frequently disabling disorder characterized by the sudden onset of obsessive-compulsive symptoms and/or severely restricted food intake, plus additional cognitive, behavioral, and somatic symptoms that may include anxiety, irritability, depression, sleep disturbance, urinary frequency, and significant academic and functional regression (Swedo, 2012). Although the diagnostic criteria for PANS require that onset be acute, they do not require a specific trigger—episodes may be triggered by infections, inflammatory events, or exposures, or triggers may be unknown. Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) has a similar clinical presentation but requires that acute onset closely follow a streptococcal infection (Swedo et al., 1998). Since children with PANDAS typically also have PANS, we use the term PANS to encompass PANS and PANDAS.

Mounting evidence supports the role of aberrant immune responses in PANS pathophysiology (Gagliano et al., 2023; Vreeland et al., 2023). A variety of inflammatory markers are present at elevated rates (Ma et al., 2024); and rates of immunological comorbidities are much higher than expected in both patients and relatives (Calaprice et al., 2017; Fernell et al., 2022; Frankovich et al., 2015). Imaging studies demonstrating localized abnormalities support a specific role for basal ganglia autoantibodies and/or inflammation in the disease mechanism (Giedd et al., 1996; Pittenger, 2023; Xu et al., 2024). Given the evidence for immune dysregulation, expert consensus guidelines recommend immunomodulatory treatment for PANS, often alongside psychiatric and behavioral interventions, in consultation with a multidisciplinary team and after the careful exclusion of other diagnoses (Frankovich et al., 2017).

Intravenous immunoglobulin (IVIG), an immune globulin product delivered by infusion, is the principal treatment for immunoglobulin deficiencies as well as a common treatment for neuroinflammatory conditions such as autoimmune encephalitis, Kawasaki’s disease, and polyneuropathy. Although many PANS patients respond to more conservative therapies, IVIG has emerged as a frequently prescribed, although off-label, option for those who do not. Current expert consensus guidelines recommend IVIG for moderate-to-severe cases, particularly those with evidence of immune dysfunction or failure to respond to first-line treatments (Frankovich et al., 2017), although the degree of consensus surrounding this recommendation is not uniform (AAP, 2025). IVIG is presumably helpful in such patients because of its compound actions in combating the infection(s) that may trigger flares, reducing neuroinflammation, and suppressing autoantibody production. Despite the published expert recommendations and its frequent use, however, rigorous data regarding the efficacy of IVIG in PANS remain limited. Although some clinical trials have been conducted, results have been mixed and their interpretation limited by factors common in rare disease research, including lack of a tailored outcome measure, restrictive eligibility criteria, and sample sizes too small to permit a full understanding of response heterogeneity (Cocuzza et al., 2022; Johnson et al., 2021).

Unlike the more commonly used, oral immunomodulatory agents, IVIG is extremely expensive, with costs typically ranging from 5000 to over 20,000 USD per infusion. The financial burden is often amplified by the need for repeated infusions to achieve satisfactory effect (Melamed et al., 2021). Insurance companies sometimes deny coverage for prescribed IVIG in PANS, citing its off-label status and the paucity of clinical trials (W. Bokhari of Claimable [claimable.com], personal communication, January 2026, citing compiled but unpublished data; California Department of Managed Healthcare, 2026). Families whose children have failed more conservative approaches must then decide between forgoing this treatment recommended by their physician, appealing coverage denials, or seeking alternative sources of funding. Success in appeals and/or fundraising is not assured, and even when it is ultimately achieved, these measures often take months or even years, leading to delays in treatment. Although additional research is necessary to better characterize the natural history of PANS, prolonged disease activity has been associated in early studies with more entrenched psychiatric symptoms, greater academic decline, and worsening family functioning (Calaprice-Whitty et al., 2023a, 2023b; Frankovich et al., 2015).

In response to these challenges, legislative initiatives in several U.S. states have sought to mandate insurance coverage for IVIG when prescribed for PANS, in keeping with expert guidelines. To date, however, no published data have addressed how families navigate obtaining IVIG for PANS, and whether the real-world outcomes are perceived to justify the costs. In this study, we surveyed families whose PANS children had been prescribed IVIG, some of whom received insurance approval and some of whom did not. Our aim was to report on influences that contributed to the decision to pursue IVIG treatment, types of ordering specialists, insurance review processes and outcomes, ultimate financial burdens and means of satisfying them, and functional and quality of life (QoL) outcomes for both PANS patients and their families.

Methods

Study design

This study utilized an online survey to assess the economic, functional, and QoL impacts of IVIG treatment among individuals who reported having been diagnosed by a healthcare practitioner with PANS. Using two nearly identical survey iterations, administered on the TrialKit and Qualtrics platforms, respectively (due to a technology transfer), quantitative and qualitative data were obtained regarding clinical history, influences on the decision to pursue IVIG, types of specialists from whom orders were obtained, insurance review processes and outcomes, treatment received, direct and indirect financial burdens and means of satisfying them, and perceived function and QoL before and after IVIG treatment for both the PANS patients and their families. To assess how these varied with IVIG treatment, many questions asked about experiences during three periods of time: the 3-month period before when IVIG was ordered by a medical professional; the “waiting period” between when IVIG was ordered and when administration began (of variable length); and the 6-month period beginning with the first IVIG administration. Data were collected between April 2024 and June 2025.

Recruitment and participants

Participants were recruited via targeted email outreach to multiple PANS/PANDAS-focused online communities. Advertisements were crafted to avoid bias with respect to outcomes and treatment perspectives, stating simply that the researchers sought to understand families’ experiences. Inclusion criteria required participants to be U.S. residents aged 7 or older, who had attempted to access IVIG treatment prescribed by a licensed clinician. Although the survey was open to subjects with either a formal diagnosis or strong clinical suspicion of PANS, only one respondent reported not having been formally diagnosed. Participants younger than 18 were required to be assisted by a parent or guardian in completion of the survey, and those older than 18 were instructed to consult their parents/caregivers about any questions relating to the time they were under their care. Upon participant request, Brain Inflammation Collaborative Clinical Research Associates (C.M. and M.H.) assisted participants in understanding survey questions but in no case suggested how questions should be answered.

The protocol, survey instruments, recruitment materials, and informed consent and assent language and process were approved by the WCG IRB (for the TrialKit iteration) and the Sterling IRB (for the Qualtrics iteration). Informed consent was obtained electronically via the survey technology for all adult participants, including both adult patients and caregivers. Assent was obtained electronically for minors. If eligibility criteria were not actively affirmed and consent and assent (as applicable) obtained, the participant was automatically exited from the technology system without having been able to view survey questions.

Data cleaning

Data review and cleaning were performed to remove any duplicate responses (based on a combination of email address and demographic traits) and any responses that were either too incomplete to be used (no information provided beyond demographics/baseline characteristics) or that appeared unreliable based on illogical content. For the TrialKit iteration, no responses required removal as part of this process; for the Qualtrics iteration, 40 responses were obtained and 30 remained after data cleaning. The TrialKit and Qualtrics datasets were merged, and the merged dataset contained a total of 60 responses. We processed the data using R statistical software (version 4.1.2), utilizing the following packages: dplyr for data manipulation; janitor for data cleaning; stringr for text processing; readxl and openxlsx for data import; purrr for functional programming; tibble for data structuring; tidygeocoder for converting IP addresses into broad geographic regions; and tidyverse.

Data analysis

Descriptive statistics, including means, medians, ranges, and proportions, were assembled using Microsoft Excel (Microsoft Office 365). No missing data were imputed. Ns vary across the tables and figures depending on the number of people who answered each question.

Subgroups were defined to facilitate description of key variables across participant characteristics. Regional subgrouping was determined based on participants’ self-reported locations. For participants who did not provide location information, general geographic locations were inferred from participant IP addresses captured by the survey. IP data were used solely to assign participants to regions and were not linked to personally identifying information. Insurance coverage was categorized as “none to minimal” if participants either reported receiving no coverage or indicated coverage of less than 10% of expenses. “Substantial coverage” was defined as reporting greater than 70% of treatment costs covered by insurance. No respondent fell between these two categories.

Results

Characteristics of participants and treatment

The PANS patients represented in this study were 50% male and 42% female at birth (8% not specified) and identified as 53% male, 40% female, and 3% transgender (5% not specified) (Table 1). Mean current age was 14.4 years and age at first IVIG treatment was 11.2 years. The majority of those completing surveys were parents, although 28% were patients. Respondents were distributed across the United States, with the largest portion in the Midwest (28%), followed by the West (25%), South (25%), and Northeast (20%). The majority of patients (79%) were insured under Preferred Provider Organization plans. Only a small number of subjects changed insurance providers during the process of obtaining and receiving IVIG treatment.

Table 1.

Characteristics of Patients and Respondents

Characteristic	Statistic
PANS diagnostic certainty	N = 54
Confirmed by a licensed medical professional	53 (98%)
Suspected	1 (2%)
Patient sex at birth	N = 60
Male, N (%)	30 (50%)
Female, N (%)	25 (42%)
Not specified, N (%)	5 (8%)
Patient current gender identity	N = 60
Male, N (%)	32 (53%)
Female, N (%)	24 (40%)
Transgender, N (%)	2 (3%)
Not specified, N (%)	3 (5%)
Patient age	N = 60
Mean	14.4
Median	14
Range	6–30
Patient age at first IVIG	N = 48
Mean	11.2
Median	10
Range	3–27
Respondent relationship to patient	N = 60
Mother, N (%)	23 (38%)
Father, N (%)	2 (3%)
Parent (undefined), N (%)	18 (30%)
Self, N (%)	17 (28%)
Geographic region	N = 60
Northeast, N (%)	12 (20%)
Midwest, N (%)	17 (28%)
South, N (%)	15 (25%)
West, N (%)	15 (25%)
Not specified and could not be determined, N (%)	1 (2%)
Type of insurance, before IVIG order	N = 48
Health maintenance organization (HMO), N (%)	4 (8%)
Preferred provider organization (PPO), N (%)	36 (75%)
State health plan (e.g., Medicaid), N (%)	4 (8%)
Uninsured, N (%)	2 (4%)
Type of insurance, after IVIG order	N = 48
Health maintenance organization (HMO), N (%)	7 (15%)
Preferred provider organization (PPO), N (%)	38 (79%)
State health plan (e.g., Medicaid), N (%)	4 (8%)
Uninsured, N (%)	1 (2%)

PANS, pediatric acute-onset neuropsychiatric syndrome; IVIG, intravenous immunoglobulin.

Eighty-eight percent of the patients surveyed eventually did receive IVIG treatment; 10% were still in pursuit; and one family had discontinued the quest (Table 2). Dominant influences on the decision to pursue IVIG included personal research (mean rating = 9.0/10; 86% of respondents endorsing ratings of 8, 9, or 10) and patient testimonials (mean = 8.9; 85% rating 8, 9, or 10). Recommendations from professionals (mean 8.7) and outcomes from previous treatments (mean = 8.0) also played key roles, while factors such as insurance/financial considerations, support group inputs, and side effect concerns were less influential.

Table 2.

Characteristics of Intravenous Immunoglobulin Treatment

Characteristic	Statistic
Received IVIG treatment, N (%)	N = 60
Yes	53 (88%)
Not yet, still pursuing	6 (10%)
No, and discontinued pursuing	1 (2%)

Significance of influences on decision to pursue IVIG treatment for PANS, on a scale of 1 (not influential at all) to 10 (highly influential)	Mean (N)	% providing rating of 8, 9, or 10
Personal research on IVIG effectiveness	9.0 (59)	86%
Expected outcomes and benefits of IVIG based on patient testimonials or case studies	8.9 (59)	85%
Recommendation from health care professionals	8.7 (59)	81%
Previous treatments tried and their outcomes	8.0 (58)	73%
Availability of IVIG treatment options	7.0 (59)	57%
Insurance coverage and financial considerations	6.9 (58)	58%
Advice or recommendations from support groups or communities	6.7 (58)	51%
Concerns about side effects and risks associated with other treatment	5.2 (59)	22%

Type of health care provider who ordered IVIG (original prescription), N (%)	N = 58
Pediatrician	19 (33%)
Neurologist	17 (29%)
Immunologist	9 (16%)
Integrative medicine provider	5 (9%)
Rheumatologist	2 (3%)
Infectious disease specialist	1 (2%)
Psychiatrist	1 (2%)
Other	4 (7%)
Diagnoses associated with IVIG order (not mutually exclusive), N (%)	N = 60
PANS/PANDAS	57 (95%)
Immune deficiency	7 (12%)
Infection	3 (5%)
Autoimmune disorder, other	2 (3%)
Cycles of IVIG in the 6-month period following first treatment, N (%)	N = 48
1	1 (2%)
2	4 (9%)
3	15 (33%)
4	5 (11%)
5	2 (5%)
6+	18 (40%)
IVIG dose, N (%)	N = 48
1.5 mg/kg or more	32 (67%)
0.6 mg/kg–1.4 mg/kg	8 (17%)
0.5 mg/kg or less	2 (4%)
I don’t know or I cannot recall	6 (12%)

IVIG, intravenous immunoglobulin. PANS/PANDAS, pediatric acute-onset neuropsychiatric syndrome/pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections.

For most patients (95%), IVIG was ordered specifically for PANS. For a few, however, IVIG was also, or alternatively, ordered for immune deficiency (12%) or other autoimmune or infectious conditions. Pediatricians (33%), neurologists (29%), and immunologists (16%) were the most frequent prescribers. Treatment regimens varied; the most common (40%) involved receipt of six or more IVIG cycles in the 6 months postinitiation. Most patients (67%) received doses ≥1.5 g/kg, and 89% received at least three treatment cycles.

Insurance coverage and appeals

In most cases, insurance coverage for IVIG was initially denied (Fig. 1; note that N = 17 because this question was only asked explicitly in the Qualtrics iteration of the survey). Only 24% of the families received approval without appeals, of whom half submitted claims for a non-PANS diagnosis. More than triple this number required at least two appeals before coverage was obtained and nearly this many were denied even after all possible appeals were exhausted. Actions described in the open-ended comments included filing for expedited review (N = 1), reaching out to employers (N = 2) or congressional representatives (1), threatening legal action (N = 1), participating in a research study (N = 1), or changing insurance (N = 1), before coverage was obtained.

FIG. 1.

Insurance coverage for IVIG treatment (N = 17). IVIG, intravenous immunoglobulin.

Those submitting IVIG claims for PANS alone were more likely than those submitting claims for comorbidities to wait at least a month before treatment could proceed (Fig. 2); only 5% of those receiving IVIG for PANS were treated within a month of the order, and in 14% of cases, the waiting period was 9 months or more. In contrast, those submitting claims for conditions other than or in addition to PANS most commonly (38%) received treatment in less than a month. As described in the open-ended comments, one patient qualified for IVIG for a comorbid condition but was then disqualified because the doctor’s note mentioned PANS/PANDAS and did not requalify for coverage until all mention of PANS/PANDAS was removed. The burdensomeness of the process was articulated by several respondents, with one describing it as “brutal” and another stating that they “can’t count the number of hours spent.” Delays in treatment access—sometimes stretching months or years—were linked in the comments to worsening psychiatric symptoms, academic decline, and family stress.

FIG. 2.

Waiting period between prescription and first IVIG treatment for PANS/PANDAS alone versus with immune deficiency and/or autoimmune diagnoses. IVIG, intravenous immunoglobulin; PANS/PANDAS, pediatric acute-onset neuropsychiatric syndrome/pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections.

Financial burden and coping strategies

Paying for PANS treatment was associated with substantial financial strain for many families regardless of whether insurance assistance was obtained, and before IVIG was ordered in addition to after (Fig. 3). According to the open-ended comments, some of this strain was associated with expenses not directly related to IVIG administration, primarily including the fees charged by out-of-network specialists. Once IVIG was prescribed, however, average levels of financial strain diverged for families with versus without “substantial” insurance coverage. For those without, financial strain often reached an extreme: during the 6-month period beginning with the first IVIG administration, 33% of these, versus 13% of those with substantial insurance coverage, reported strain levels at the extreme of the scale (10 on a scale of 1 to 10). For those with substantial insurance coverage, the fraction expressing extreme levels of financial strain went down by nearly a factor of two once IVIG administration began, whereas for those without, this fraction nearly doubled.

FIG. 3.

Level of financial strain experienced due to PANS treatment, by level of insurance coverage. PANS, pediatric acute-onset neuropsychiatric syndrome.

With or without substantial insurance coverage, families commonly accessed savings to pay for PANS treatment (74% of those with substantial insurance coverage, 84% of those without), borrowed money (30% of those with substantial coverage, 58% of those without), or took on additional work (33% of those with substantial insurance coverage, 57% of those without), and for those without substantial insurance coverage, it was not uncommon to sell major assets (21%) (Table 3). Those families who ultimately obtained substantial insurance coverage were three times as likely as those who did not to have negotiated with insurers both before and/or after IVIG treatment was obtained (48% of those with substantial coverage, 16% of those without).

Table 3.

Financial Strategies Used to Manage Costs of Pediatric Acute-Onset Neuropsychiatric Syndrome Treatment by Insurance Status and Time Period

Financial strategy	Substantial insurance coverage (N = 23)				Minimal/No insurance coverage (N = 19)
Financial strategy	3 months before IVIG	Waiting period	6 months after IVIG	Ever	3 months before IVIG	Waiting period	6 months after IVIG	Ever
Selling assets (car, etc.)	4% (1)	4% (1)	9% (2)	9% (2)	5% (1)	16% (3)	16% (3)	21% (4)
Borrowing money	17% (4)	17% (4)	26% (6)	30% (7)	32% (6)	53% (10)	32% (6)	58% (11)
Savings withdrawals	61% (14)	43% (10)	57% (13)	74% (17)	42% (8)	74% (14)	58% (11)	84% (16)
Applying for financial aid	17% (4)	22% (5)	26% (6)	30% (7)	5% (1)	21% (4)	16% (3)	26% (5)
Fundraising	9% (2)	4% (1)	9% (2)	13% (3)	5% (1)	5% (1)	0% (0)	5% (1)
Insurance negotiation	26% (6)	30% (7)	43% (10)	48% (11)	11% (2)	16% (3)	5% (1)	16% (3)
Additional work^a	22% (2/9)	11% (1/9)	22% (2/9)	33% (3)	19% (2/7)	43% (3/7)	57% (4/7)	57% (4)
Other	22% (5)	22% (5)	22% (5)	26% (6)	16% (3)	21% (4)	21% (4)	26% (5)

Only asked during second survey iteration, so lower N.

IVIG, intravenous immunoglobulin.

Quality of life

Across all measured domains, both patient and family/caretaker/cohabitant (hereafter “family”) QoL demonstrated marked improvement following IVIG treatment, in comparison with the months preceding the IVIG order and the waiting period between order and first treatment. In terms of overall QoL (Fig. 4), means for both patients and families were very low before the IVIG order (2.3 and 2.6, respectively, on a scale of 1 to 10, with 1 indicating “exceedingly poor” and 10 indicating “exceedingly good”), with the majority endorsing ratings of 1 or 2. These remained essentially unchanged during the waiting period. After IVIG treatment, mean overall QoL ratings more than doubled to 7.0 for patients and 5.7 for family. Only 4% of the patients and 15% of families remained at scores of 1 or 2, and nearly half of patients and a third of families endorsed scores of 8 or above. Posttreatment family ratings, but not patient ratings, were sensitive to the level of insurance coverage that had been obtained (Table 4).

FIG. 4.

Quality of life.

Table 4.

Patient and Family/Caretaker/Cohabitant Overall Quality of Life Before and After Intravenous Immunoglobulin Treatment, by Level of Insurance Coverage

Fraction of expenses covered by insurance	Patient (N = 44)			Family/Caretaker/Cohabitant (N = 42–43)
Fraction of expenses covered by insurance	3 months before IVIG order (mean)	Waiting period between order and dosing (mean)	6-month period after first IVIG (mean)	3 months before IVIG order (mean)	Waiting period between order and dosing (mean)	6-month period after first IVIG (mean)
None to minimal insurance coverage (≤10% of expenses covered)	2.1	2.7	7.0	2.3	2.6	4.9
Substantial insurance coverage (≥70% of expenses covered)	2.8	2.7	6.4	2.5	2.7	7.0

IVIG, intravenous immunoglobulin.

With respect to specific domains, patient physical and emotional well-being before IVIG intervention was on average poor (mean = 2.1, Table 5). Family physical and emotional well-being was similarly low (mean = 2.4) and both groups' scores remained low during the waiting period (patient mean = 2.5; family mean = 2.5). However, during the 6-month period post-IVIG, mean ratings more than doubled for both groups (patient mean = 6.8; family mean = 6.0). Scores for patients’ daily activities and interests were also low before the IVIG order (mean = 2.8) and persisted low through the waiting period, but posttreatment means again more than doubled to 6.8. Family ratings again tracked closely, increasing from 2.5 and 2.6 pretreatment to 6.1 after IVIG. Before IVIG treatment, impairment in academic and work performance was frequent among both patients (means 2.6 preorder and 2.9 during waiting period) and family (means 4.0 preorder, 3.9 waiting). During the 6-month posttreatment follow-up, however, mean ratings again more than doubled, to 6.8 for patients and 6.6 for caregivers. Social functioning and peer interactions followed a comparable trajectory.

Table 5.

Patient and Family/Caretaker/Cohabitant Quality of Life Before and After Intravenous Immunoglobulin Treatment: Specific Domains

Quality of life domain	Patient (N = 44)			Family/Caretaker/Cohabitant (N = 42–43)
Quality of life domain	3 months before IVIG order (mean)	Waiting period between order and dosing (mean)	6-month period after first IVIG (mean)	3 months before IVIG order (mean)	Waiting period between order and dosing (mean)	6-month period after first IVIG (mean)
Physical and emotional well-being	2.1	2.5	6.8	2.4	2.5	6.0
Social interactions	2.6	2.8	6.2	3.0	3.2	5.7
Educational/Work performance	2.6	2.9	6.8	4.0	3.9	6.6
Daily activities and interests	2.8	2.9	6.8	2.5	2.6	6.1

IVIG, intravenous immunoglobulin.

In the open-ended comment fields, respondents commonly reported severe lifestyle disruptions before treatment, with some caregivers forced to retire early (N = 1), quit jobs (N = 1), or risk unemployment due to missed work (N = 1). Comments relating to the posttreatment period largely revolved around the notable improvements in patients’ school attendance and functioning.

Discussion

Despite the very low prevalence of PANS and the small fraction of patients prescribed IVIG, there are now laws in at least 16 U.S. states mandating insurance coverage for IVIG and other therapies, with similar legislation under consideration in 15 more (PANS Legislative recap, 2026). Yet until now, no systematic study has examined how families come to pursue IVIG for PANS, what they experience in attempting to obtain it, or what effects this treatment has on QoL and functional outcomes for families. The current findings offer insights into the real-world costs, delays, stresses, and outcomes experienced by PANS families while awaiting IVIG treatment and in its wake.

With respect to the initial pursuit of IVIG, an interesting finding of this study was the extent to which families were influenced not only by medical professionals, but even more by their own personal research and the experiences of other families. Faced with a paucity of data regarding whether the impacts of IVIG could be expected to justify the risks and sacrifices, parents appear to put considerable faith in the experiences of peers. Previous studies have documented the challenges many PANS families endure in obtaining diagnosis and treatment (Calaprice et al., 2017; LaRusso et al., 2023; Tang et al., 2021), as well as levels of caregiver stress above the “burnout” level (O’Dor et al., 2022) and comparable to those experienced by caregivers of dementia patients (Frankovich et al., 2018) but with the added burden that few people can relate to their difficulties. The reliance of PANS caregivers on others who can relate closely to their own experiences may result from perceived weakness in the information and support available from other sources.

Also interesting was the range of specialists who ordered IVIG for the patients in our sample, reflecting the disorder’s lack of a specialty “home.” Although PANS presents primarily with psychiatric and neurological symptoms, its etiology and management are at least partly immunological, making it difficult to situate within one medical specialty. Not only does this fragmentation contribute to delays in diagnosis and effective treatment, but it may also lead to IVIG being ordered by practitioners who may not be expert in justifying its use to insurers or in identifying legitimate comorbid conditions for which obtaining coverage may be more straightforward. In our sample, IVIG had sometimes been prescribed for a comorbid immunological or neurological condition for which insurers generally provide coverage, and the insurance approval process was more expeditious in these cases. Patients with PANS alone, in contrast, frequently reported long waiting periods, often beyond 6 months, before either receiving approval or abandoning hope. Given our QoL findings, this appeared to prolong the period of poor QoL and function for both patient and family. Patients who experience prolonged delays before receiving effective treatment may also experience more negative outcomes over a period of years compared with those who are treated relatively promptly (Calaprice-Whitty et al., 2023a, 2023b).

Despite our survey respondents being relatively well-insured overall, many had resorted to exceptional measures to pay for IVIG treatment, and high levels of financial stress were reported by a large fraction. Many endorsed the extreme end of the Likert scale; even the families with “substantial” insurance coverage were more likely to endorse the extreme than were cancer patients in previous studies (e.g., Chino et al, 2014; Meeker et al, 2017), and mean financial stress ratings exceeded comparable figures associated with job loss during the COVID-19 pandemic (de Miquel et al, 2022). The fraction of families who resorted to measures such as loans, asset sales, and additional employment is consistent with the gravity of this result.

Despite the challenges and sacrifices associated with obtaining IVIG treatment, most respondents reported substantial improvements in function and QoL posttreatment for both the child and the family. Interestingly, posttreatment QoL metrics for most participants were not only higher than pretreatment levels but often above the neutral range, with gains reported in school and/or work attendance, well-being, enjoyment, and family and social life. Although this was an observational retrospective study and therefore unable to distinguish effects of IVIG from those of natural disease course (i.e., remission), placebo effects, or concurrent treatments, these results are generally consistent with those reported in published studies. Of the two randomized controlled trials of a single round of IVIG in PANDAS, one showed significant benefit (45% reduction in the OCD scale) (Perlmutter et al., 1999) and the other did not (Williams et al., 2016). In the latter, nonresponders during the first study phase were offered open-label IVIG thereafter, and a 49% decrease in OCD severity was seen in the 24 patients electing to receive it, raising the possibility that two rounds were needed to achieve impact in some patients. This possibility would be consistent with another study that found that 85% of serious-severe or extreme PANS symptoms improved or resolved with IVIG but ∼3/4 of patients required two courses (Pavone et al., 2020). In more recent trials examining multiple doses of IVIG (three to six courses every 3–4 weeks), significant improvements have been seen on OCD, tic, functional impairment, and PANS symptomatology scales (Hajjari et al., 2022; Melamed et al., 2024, 2021), and in one study, school absences after three courses dropped from 47% to 13% (Hajjari et al., 2022). In our study, most patients (98%) had received multiple courses of IVIG and improvements were substantial for both them and their parents; however, posttreatment QoL ratings improved more for the patients than for their families and more for the substantially insured families than for the underinsured, the discrepancy possibly reflecting lingering financial and logistical burdens.

This study had several limitations. Despite our efforts to recruit broadly and minimize selection bias, participants may have self-selected for strong opinions or extreme experiences. The retrospective nature of the data raises the possibility of recall bias, and our questions were not validated measures of stress or QoL. Diagnoses were self-reported and not verified as per the clinical record. Moreover, insurance coverage laws are evolving rapidly, and the experiences reported here may not reflect the current conditions in all U.S. states, let alone ex-United States. Ongoing investigation is needed to determine whether recent legislative mandates in the United States are resulting in meaningful improvements in access, as well as improved clinical and QoL outcomes. It must also be noted that IVIG is not without risks, including common side effects such as flu-like symptoms as well as rare but serious side effects such as aseptic meningitis and renal impairment (Guo et al., 2018). Additional clinical trials in PANS are needed, not only to better quantify the benefit–cost and benefit–risk ratio of IVIG, but also to better ascertain whether and in what patients more cost-effective treatments, for example, traditional disease-modifying antirheumatic drugs, antibiotics, and/or anti-inflammatory medications, may be sufficient to obtain the same level of clinical benefit.

Conclusions

In this study, families whose healthcare practitioners recommended IVIG treatment for PANS commonly experienced significant barriers to obtaining it, including prolonged delays and repeated insurance denials. Many experienced high levels of financial strain and were forced to adopt measures such as borrowing money, selling assets, or taking on additional work to access care. Despite these obstacles, IVIG treatment appeared to be associated with notable improvements in perceived quality of life for both patients and caregivers.

Clinical Significance

The present study may help to inform clinicians about the level of economic stress and consequences experienced by families pursuing IVIG treatment for PANS, the poor QoL of both patients and families before IVIG treatment and the often-meaningful improvements after, and the fact that information relating to the decision to pursue IVIG treatment is often gathered from nonmedical sources, suggesting that extra effort may be required to ensure that families fully understand the potential risks and benefits of IVIG for their child.

Authors’ Contributions

C.H., A.T., and D.C.—conception and design of the work. D.C. also drafted the article and interpreted the data. C.M., M.H., and M.F.—preparation of protocol/informed consent and ethics approval, recruitment of patients, and support of data acquisition and quality review. R.T., C.W., K.A., and J.H.—analysis, presentation, and interpretation of the data. R.T. also assisted in preparing the article for publication.

Footnotes

Acknowledgments

The authors thank the PANDAS Network for assistance with recruiting participants, the reviewers for their time and thoughtful suggestions, and Anvita Guda for assistance in preparation of the article.

Disclosures

The authors declare no conflicts of interest.

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