When PANS and IBD Co-Occur: What This Case Series Suggests

When PANS and IBD Co-Occur: What This Case Series Suggests

Tang AW, Swedo SE, Pasternack M, Murphy T, et al. Eight cases of pediatric acute-onset neuropsychiatric syndrome: clinical characteristics. Developmental Neuroscience. 2025;47(4):287–302. doi:10.1159/000543969

PANS/PANDAS and inflammatory bowel disease (IBD) are usually seen as separate conditions. PANS/PANDAS involves sudden neuropsychiatric changes, while IBD is about ongoing gut inflammation. This article suggests that studying children and young adults with both conditions could help clinicians learn more about each and share treatment ideas between specialties.

Why the authors linked PANS and IBD in the first place

The paper describes PANS/PANDAS as immune-related illnesses marked by sudden changes in behavior, and IBD (ulcerative colitis and Crohn’s disease) as long-term gut inflammation. The authors explain that IBD likely results from an abnormal immune response to gut microbes in people with certain genes. IBD often causes inflammation outside the gut, too, especially in the joints, skin, and eyes. They also point out that symptoms like fatigue, depression, and anxiety are common in people with IBD.

The authors describe PANS as a childhood illness that often starts suddenly with OCD or restricted eating. It is usually accompanied by severe anxiety, regression, mood changes, sleep problems, urinary symptoms, and new movements. PANDAS was first defined as a strep-related condition in younger children, but the criteria for PANS were expanded because many patients do not fit the original definition and can have different triggers. In this article, ‘PANS’ is used to refer to both conditions.

Basal ganglia involvement is positioned as central

The authors highlight that problems with the basal ganglia seem to be a key part of PANS symptoms. They mention imaging studies showing differences in basal ganglia size and activity in people with PANS/PANDAS compared to others. They also note that many PANS patients have unusual movements or REM sleep without muscle relaxation, which is rare in children and is sometimes discussed in relation to predicting Parkinson’s disease risk in adults.

Immune dysregulation is presented as a plausible bridge

A main idea in the introduction is that problems with the immune system may be connected to changes in the basal ganglia in PANS. The authors discuss research showing that blood from children with PANS can affect certain brain cells in both mice and humans, and these effects improve when the children recover. They also mention a mouse study where repeated strep infections cause immune cells to enter the brain, disrupt the blood-brain barrier, activate brain immune cells, and lead to antibody deposits. About one-third of children who have a lumbar puncture for PANS show mild increases in certain proteins in their spinal fluid, which are considered possible signs of brain inflammation.

The “systemic inflammation” lens: comorbid immune disease isn’t rare

The introduction also summarizes evidence that PANS often appears alongside broader inflammatory and autoimmune patterns:

• Early clinic samples showed high rates of autoimmune or inflammatory disease in first-degree relatives of patients with PANS.

• Parent-reported survey data similarly found frequent autoimmune family history, including Hashimoto’s thyroiditis and psoriasis.

• Across additional cohorts, a subset of patients had preexisting autoimmune or inflammatory disease, and in one longitudinal Stanford cohort, many developed arthritis by adolescence, with thyroiditis and psoriasis among the most common autoimmune conditions.

They also describe a pattern of arthritis in PANS that is sometimes ‘dry’ and can show new imaging features, such as thickening of the joint capsule and tenderness in the finger joints. These features are also seen in adult psoriatic arthritis.

Why this matters clinically: psychiatric severity can mask somatic disease

The authors point out a real-world issue: sudden and severe psychiatric symptoms can make it hard to notice physical illness. However, taking a careful history in PANS patients often reveals signs of body-wide inflammation, such as fatigue, poor sleep, and digestive symptoms, which are common according to a Stanford clinic sample.

Two very different treatment landscapes

The paper contrasts how the fields typically treat these conditions:

IBD

• IBD care is presented as immunomodulatory at its core, with the field seeing expanding advanced therapies in recent years.
• In pediatrics, only infliximab and adalimumab are described as FDA-approved anti-TNFα options (as stated in the text you provided), with off-label biologics sometimes used in refractory disease.

PANS

• The authors outline three main steps for treating PANS: first, treat infections (especially strep); second, control inflammation with medications such as NSAIDs, corticosteroids, or IVIg in tough cases; and third, offer support and rehabilitation, such as cognitive-behavioral therapy and careful titration of medications.
• They note that some antibiotics have anti-inflammatory properties and cite azithromycin as potentially effective for reducing PANS-related OCD through that mechanism (as described in the text).

The case series: who was included

Across three specialty centers (Stanford, Cedars-Sinai, Dartmouth), the authors identified 12 patients who met criteria for both diagnoses, then excluded cases in which GI records could not confirm IBD or in which the IBD diagnosis was uncertain. The final series includes 8 individuals:

• 3 with ulcerative colitis
• 5 with Crohn’s disease

Key timing points in the series:

• Mean age at PANS onset: 3 years (range 3–16)
• Mean age at IBD diagnosis: 6 years (range 8–23)
• In 7 of 8 cases, PANS came first, on average by 4 years (range 1–14)
• In 1 case, IBD preceded PANS by 8 years
• Mean age at the time of report: 8 years (range 12–27)

Comorbid inflammatory features were common in these patients

The results section highlights frequent inflammatory and immune-related comorbidities in the cohort, including:

• eczema (n=6)
• asthma (n=5)
• arthralgia or inflammatory arthritis (n=5)
• low immunoglobulin levels (n=3)
• chronic rhinosinusitis (n=2)

Some patients had neurodevelopmental diagnoses before developing PANS (ADHD in two cases and ASD in one). Notably, the child diagnosed with ASD at age 8 (case CD-5) was no longer considered to have ASD after his neuropsychiatric symptoms improved with IBD treatment.

Family history signals: immune-mediated disease in first-degree relatives was striking

The paper reports that 7 of 8 patients (88%) had a first-degree relative with an immune-mediated disease. In particular, psoriasis or psoriatic arthritis was reported in 5 of 8 (71%). Other first-degree family history included idiopathic thrombocytopenia purpura, celiac disease, rheumatoid arthritis, and Hashimoto’s thyroiditis.

The discussion returns to this point and emphasizes that psoriasis/psoriatic arthritis in close relatives appears unusually frequent in this series and may signal a subgroup biology.

Did treating IBD affect PANS course?

Because PANS preceded IBD in most cases, the authors explored whether PANS improved once IBD was treated. They explain that in some cases it’s difficult to separate effects because treatments overlapped, and in one case, IBD remained active. For the remaining cases in which the course could be examined, they report that after IBD treatment started, PANS symptoms showed minor fluctuations but no major relapses.

They describe a clear example in case CD-5: PANS symptoms improved after each infliximab dose, which was given every 6 to 8 weeks. OCD and sleep returned to normal after treatment but got worse again 2 to 3 weeks before the next dose.

What the authors conclude, this might mean

In the discussion and conclusion, the authors frame the series as hypothesis-generating but highlight three recurring signals:

1. A very high rate of immune-mediated illness in first-degree relatives (especially psoriasis)
2. Frequent arthralgia/arthritis in the patients themselves
3. A tendency for PANS to appear years before IBD — and for PANS course to stabilize or improve once IBD is treated

They believe these findings support the idea that PANS has an immune-related cause. They suggest that the same cytokine pathways involved in IBD and arthritis (specifically IL-23, IL-17, and TNFα) might also play a role in neuropsychiatric symptoms for some patients.

They also propose a practical clinical implication drawn from their data: while not every child with PANS and GI symptoms can reasonably undergo endoscopy, those with arthritis plus a family history of psoriasis may warrant closer monitoring and a lower threshold for evaluation of GI inflammation (they explicitly reference markers like fecal calprotectin in the discussion).

Finally, they highlight that modern IBD care uses concepts such as risk stratification and treat-to-target, and contrast this with the current lack of risk stratification guidance in PANS, where care is often “step-up” due to limited markers and significant insurance barriers.