Paediatric Granulomatous Arthritis (PGA)

Other names
Types
Causes
Symptoms
Diagnostic tests
Non-pharmacological treatments (therapies & others)
Drug treatments
Dietary molecular supplements
Advanced immune-modulating options
Surgeries (procedures & why)
Preventions
When to see doctors (red flags)
What to eat and what to avoid
FAQs

Paediatric granulomatous arthritis (PGA) is a rare, inherited, autoinflammatory disease that begins in early childhood. “Autoinflammatory” means the child’s innate immune system becomes too active without an infection. The disease makes tiny clumps of immune cells called granulomas inside tissues. These granulomas most often involve joints (arthritis), eyes (uveitis), and skin (granulomatous rash). Many children show the “classic triad” of rash, arthritis, and uveitis in the first years of life. The most common genetic cause is a gain-of-function mutation in the NOD2 (also called CARD15) gene, which turns on inflammatory signaling (NF-κB) too strongly, so the body stays “on alert” and forms granulomas. Because of this gene, the condition is sometimes called NOD2-associated autoinflammatory disease. PMC+2PMC+2

Paediatric granulomatous arthritis is a rare, inherited autoinflammatory disease that usually starts in early childhood. It typically shows a triad: long-lasting joint swelling and stiffness (arthritis), a scaly or bumpy skin rash (dermatitis), and painful eye inflammation that can threaten vision (uveitis). The most common cause is a change (mutation) in a gene called NOD2, which helps the immune system sense danger. When NOD2 is faulty, the immune system stays “switched on,” creating tiny clumps of immune cells called granulomas inside joints, skin, and eyes. Kids may have flares and remissions. The condition can run in families (autosomal dominant), but some cases appear sporadically. Early, steady control of inflammation is essential to protect eyesight and joint function over a lifetime. BioMed Central+2PMC+2

Children with PGA can have boggy joint swelling, stiffness, and limited motion. The uveitis can be severe and may threaten vision if not found and treated early. The rash is often scaly or papular and may leave marks. Some children also have fever, lymph node swelling, or organ involvement. The illness often runs in families in an autosomal dominant pattern, but it can appear in a child with no family history (a new mutation). PMC+1

Other names

PGA has several names used in clinics and research. Doctors may use them interchangeably because they describe the same or very closely related conditions:

Blau syndrome (when it runs in families due to NOD2 mutation). PMC
Early-onset sarcoidosis (EOS) (when it appears sporadically without known family history; later many such cases were found to have NOD2 variants). PMC
NOD2-associated paediatric granulomatous arthritis (emphasizes the gene). PMC
Juvenile systemic granulomatosis (older term in dermatology/rheumatology literature). Medical Journals

Takeaway: if you see Blau syndrome, EOS, or NOD2-associated PGA in a report, they are pointing to the same clinical spectrum.

Types

Because children present differently, it is helpful to group PGA into practical “types”:

Familial (genetic) PGA
A child has a clear family history and a pathogenic NOD2 variant. This is classic Blau syndrome. It usually starts before age 5 with rash, arthritis, and uveitis. PMC
Sporadic (de novo) PGA / Early-Onset Sarcoidosis
No family history is known, but the child shows the triad and often has a new (de novo) NOD2 variant when tested. PMC
Incomplete triad at onset
The child may first have only rash and arthritis, or only uveitis and arthritis. The third feature may appear later. This delayed pattern is common and can delay diagnosis. Frontiers
Systemic/extra-triad involvement
Some children develop inflammation in other organs (e.g., lymph nodes, blood vessels, kidneys, or liver). These cases show that PGA can be “systemic.” PMC+1
Treatment-refractory ocular-dominant PGA
A subset have severe, hard-to-control uveitis, needing steroid-sparing medicines and biologics. PubMed+1

Causes

PGA is mainly genetic. Below are “causes” and recognized triggers/mimics that matter in practice. The first items are direct causes; later items are contributors or conditions that can look similar and must be ruled out.

NOD2 (CARD15) gain-of-function variants (e.g., R334Q, R334W). These switch on NF-κB signaling and granuloma formation. This is the key cause. PMC+1
De novo NOD2 variants in a child with no family history (sporadic/EOS). PMC
Autosomal dominant inheritance from an affected parent carrying a NOD2 variant. Frontiers
Gene–pathway overactivation of innate immune sensors (NOD2 pathway), causing excess cytokines like TNF and IL-1/IL-6. PMC
Granulomatous immune response tendency in skin, eye, and joint synovium due to the above pathway. PMC
Possible microbial signals that engage NOD2 (e.g., bacterial peptidoglycan); not a proven cause, but may amplify inflammation. PMC
Propionibacterium (Cutibacterium) acnes detected in granulomas in some reports—hypothesized as an amplifier, not a sole cause. BioMed Central
Environmental triggers (minor injuries, nonspecific infections) possibly “unmask” inflammation in genetically primed children. (Inference consistent with autoinflammation biology.) PMC
Immune dysregulation with macrophage activation inside tissues forming non-caseating granulomas. PMC
Ocular immune privilege breakdown leading to granulomatous uveitis. PubMed

(Important look-alikes that are not causes of PGA but are ruled out during diagnosis:)

Paediatric sarcoidosis unrelated to NOD2 (rare; similar granulomas). PMC
Crohn’s disease–related granulomas (NOD2 variants also occur in Crohn’s, but the clinical picture is different). rmdopen.bmj.com
Chronic granulomatous disease (CGD) (immunodeficiency causing granulomas; needs different tests).
Tuberculosis and atypical mycobacterial infection (caseating granulomas; must be excluded).
Granulomatous infections (fungal, Bartonella) (ruled out with labs/cultures/biopsy).
Granulomatosis with polyangiitis (vasculitis; different serology/biopsy).
Foreign-body granulomas in skin/eye (local, not systemic).
Juvenile idiopathic arthritis (JIA) without granulomas (more common, different course).
Other monogenic autoinflammatory diseases (e.g., TRAPS, CAPS) lacking granulomas.
Drug-induced granulomatous reactions (rare in children; careful medication history).

(Items 13–20 reflect the standard differential diagnosis lists described across reviews; they are excluded with targeted tests to confirm PGA.) PMC+1

Symptoms

Chronic arthritis – Long-lasting, often symmetric swelling of many joints, especially hands, wrists, ankles, and knees. Joints can look “boggy.” Motion is limited. Frontiers
Morning stiffness – Joints feel stuck or tight after rest. It may improve after gentle movement.
Granulomatous rash – Scaly or bumpy lesions, often on trunk or limbs; may appear first. PMC
Uveitis (eye inflammation) – Red, painful, light-sensitive eyes; can be silent and still cause damage, so screening is vital. PubMed
Blurred vision or floaters – From inflammatory cells in the eye; needs urgent eye care to protect vision. PubMed
Lymph node swelling – Painless enlarged nodes due to granulomas. PMC
Fever – Intermittent fevers reflect systemic inflammation, especially in younger children. Frontiers
Fatigue – Tiredness from chronic inflammation and poor sleep due to pain.
Growth concerns – Pain, inflammation, and steroids (when used) can affect growth over time.
Joint deformities (e.g., camptodactyly) – Bent fingers and fixed contractures may develop with long-standing disease. Frontiers
Limited hand function – Trouble with grasping, writing, or fine motor tasks.
Skin discoloration or scarring – Lesions may leave post-inflammatory marks. PMC
Photophobia and eye pain – From active uveitis; child avoids bright light. PubMed
Organ involvement symptoms – Rarely abdominal pain (liver/spleen), blood pressure changes (vascular), or kidney issues. Frontiers
Psychosocial impact – Pain, clinic visits, and vision worries may cause anxiety or school challenges.

Diagnostic tests

Diagnosis is based on clinical features, exclusion of infections and other diseases, biopsy showing non-caseating granulomas when needed, and confirmation by NOD2 genetic testing. Eye screening is essential. PMC+1

A) Physical examination

Full joint exam – The doctor checks each joint for swelling, warmth, tenderness, and range of motion. “Boggy” synovitis in hands and wrists is a classic clue. Frontiers
Skin exam – The doctor inspects rash type, distribution, and any scarring. This helps decide if a skin biopsy is needed. PMC
Eye screening at the slit lamp (by an ophthalmologist) – Looks for cells and flare in the anterior chamber and granulomatous signs (e.g., mutton-fat keratic precipitates); this can catch silent uveitis. PubMed
Lymph node, liver, and spleen check – Palpation detects enlargement that suggests systemic granulomas. PMC
Growth and vitals review – Height/weight trends and blood pressure give a picture of systemic burden and treatment effects over time.

B) Manual/bedside joint tests

Gait assessment – Watching the child walk can show pain avoidance or stiffness in hips, knees, or ankles.
Range-of-motion measurement – Simple goniometer checks of flexion/extension in key joints to document limitation and track change.
Hand function tasks – Grip/pinch strength and simple tasks (opening/closing fist) to document function loss from small-joint disease.
Tender joint count and swollen joint count – Standard counts used in rheumatology to monitor disease activity.
Morning stiffness timing – A practical, parent-reported measure to follow response to therapy.

(These bedside tests complement the physical exam and give objective baselines even before imaging.)

C) Laboratory and pathological tests

Inflammation markers (ESR, CRP) – Often raised in active disease; help track flares and response. PMC
Complete blood count and metabolic panel – Looks for anemia of inflammation and checks organ function (liver/kidney) if disease is systemic or medicines are used.
Serum ACE and lysozyme – Sometimes measured because granulomatous diseases may elevate them; results are not specific but may support the picture together with other findings. PMC
Infection rule-out tests – TB testing (IGRA or skin test), fungal serology, or cultures as needed to exclude infectious granulomas.
Biopsy (skin, synovium, or lymph node when appropriate) – Shows non-caseating granulomas and excludes infections or vasculitis; helpful if genetics are pending or uncertain. PMC
Genetic testing for NOD2 (CARD15) – The most specific test. Sequencing detects gain-of-function variants that confirm the diagnosis (familial or de novo). Testing is widely available in clinical labs and gene panels. Printo+2NCBI+2

D) Electrodiagnostic / ocular electrophysiology tests

These are not routine for every child, but they help when there are visual symptoms out of proportion to the eye exam, or when retinal function must be measured objectively.

Electroretinography (ERG) – Measures retinal function; can detect retinal involvement from chronic uveitis or inflammation. PubMed
Multifocal ERG – Maps function across the retina to localize areas affected by inflammation. PubMed
Visual evoked potentials (VEP) – Measures the brain’s response to visual signals; helpful if optic pathway function is questioned in severe ocular disease. PubMed
Nerve conduction studies/EMG – Rarely needed; considered only if a child has atypical neuropathic symptoms to exclude other conditions. (PGA itself is joint/eye/skin-dominant.) PMC

E) Imaging tests

X-rays of hands, wrists, and affected joints – May show soft-tissue swelling early; later can show joint space narrowing or deformities if disease is longstanding. PMC
MRI of joints (with/without contrast) – Best to see synovitis, bone marrow edema, cartilage, and early erosions; helps guide treatment. PMC
Ultrasound of joints – Shows synovial thickening and fluid; useful for children because it is quick and radiation-free.
OCT (optical coherence tomography) of the retina and macula – High-resolution eye scan to monitor macular edema and structural damage from uveitis. PubMed
Fluorescein angiography (FA) / indocyanine green angiography (ICGA) – Dye tests that show retinal/choroidal inflammation and leakage; guide eye therapy in difficult uveitis. PubMed

Non-pharmacological treatments (therapies & others)

Format per item: Description (~100–150 words), Purpose, Mechanism (how it helps).
Evidence anchors are pediatric rheumatology/uveitis guidelines and rehabilitation research.

Structured pediatric rheumatology care & shared decision-making
Kids with granulomatous arthritis need a consistent team: pediatric rheumatologist, ophthalmologist, pediatrician, nurse, and rehab therapists. Regular visits catch silent eye inflammation and adjust therapy early to prevent damage. Parents and older children should help set goals and track symptoms (pain, morning stiffness, red eyes, light sensitivity). Vaccination planning, growth monitoring, and lab safety checks are part of routine care. Clear care plans and school support letters reduce missed learning and stress. Purpose: reduce flares, preserve vision and function. Mechanism: early detection + timely step-up care lowers inflammatory burden and damage. American College of Rheumatology+2PubMed+2
Frequent ophthalmology screening (slit-lamp exams)
Uveitis may be “quiet” at first. Regular eye checks with a pediatric uveitis specialist (e.g., every 1–3 months during active disease) help prevent cataract, glaucoma, and macular edema. Purpose: protect vision by catching activity before symptoms. Mechanism: direct visualization of inflammation guides rapid treatment changes. AAO+2AAO+2
Physical therapy (PT) for joints
Gentle range-of-motion, stretching, and age-appropriate strength training keep joints moving and muscles strong. Hydrotherapy can ease pain and stiffness. Purpose: maintain mobility, reduce pain, improve function and participation in play and school. Mechanism: movement reduces stiffness, supports synovial nutrition, and counters deconditioning. PMC+1
Occupational therapy (OT) & joint protection
OT teaches energy conservation, ergonomic grips, splints for rest or function, and strategies for handwriting, dressing, and play. Purpose: keep independence and school performance high while protecting inflamed joints. Mechanism: adaptive tools lower joint load and repetitive strain. ScholarWorks+2OccupationalTherapy.com+2
Vision-specific accommodations
Kids with uveitis may need large-print materials, glare control, seating adjustments, and a 504/IEP plan. Purpose: reduce visual stress and support learning. Mechanism: environmental changes cut photophobia strain and optimize remaining vision. AAPOS
Sun/UV and eye protection
Wraparound sunglasses and brimmed hats reduce light pain (photophobia) and ocular surface irritation during flares. Purpose: comfort and reduced trigger exposure. Mechanism: limiting UV/bright light lowers ciliary spasm and ocular inflammation discomfort. PMC
Anti-inflammatory daily routine (sleep, pacing, gentle activity)
Regular sleep, short movement breaks, and balanced routines reduce fatigue and pain behaviors. Purpose: smoother days with fewer flare triggers. Mechanism: consistent circadian patterns and light activity modulate cytokines and pain perception. Penn State
Pain coping skills & psychology support
Child-friendly cognitive behavioral strategies and family counseling help with chronic pain, anxiety about flares, and treatment adherence. Purpose: better mood, coping, and quality of life. Mechanism: CBT modifies pain processing and stress-inflammation links. PMC
Immunization planning
Use inactivated vaccines on-schedule; time live vaccines carefully around immunosuppressive therapy. Include influenza and pneumococcal as appropriate. Purpose: prevent infections that can trigger flares or complicate therapy. Mechanism: guideline-based schedules lower infectious risk during immunosuppression. American College of Rheumatology+1
School partnership & attendance planning
Clinic notes that outline medication times, eye-drop schedules, and flare action plans reduce absenteeism and stigma. Purpose: continuity of education and social inclusion. Mechanism: shared plans remove barriers to dosing and accommodations. AAPOS
Heat/cold therapy – short heat for stiffness, brief cold for swelling; Purpose/Mechanism: symptom relief via vasodilation/vasoconstriction. PMC
Healthy, age-appropriate diet emphasizing fruits/veg, calcium/vitamin D, and fish; Purpose/Mechanism: supports bone health and may modestly reduce systemic inflammation. Office of Dietary Supplements+1
Weight-bearing play (safe, low-impact): Purpose/Mechanism: supports bone density and strength during steroid/biologic therapy. American College of Rheumatology
Hand therapy & fine-motor exercises: Purpose/Mechanism: preserve dexterity and grip. ScholarWorks
Hydrotherapy: Purpose/Mechanism: buoyancy reduces joint load to allow range-of-motion gains. PMC
Eye-drop adherence tools (timers/charts): Purpose/Mechanism: ensures dosing that keeps uveitis quiet. PMC
Infection-risk reduction (hand hygiene, TB/viral screening before biologics): Purpose/Mechanism: prevents serious infections on immunosuppression. FDA Access Data+1
Sun-safe skin care for dermatitis: Purpose/Mechanism: reduces irritation in inflamed skin. PMC
Family genetic counseling: Purpose/Mechanism: clarifies inheritance/testing for NOD2 in relatives. PMC
Flare-action plans (home checklist: sore/red eye → urgent slit-lamp): Purpose/Mechanism: earlier care, fewer complications. AAO

Drug treatments

Important safety note: Always screen for TB/viral hepatitis before TNF/IL-6/IL-1 or JAK inhibitors; follow lab monitoring and vaccine guidance. Many below are used off-label for Blau/PGA based on case series and guideline logic drawn from JIA/uveitis. PMC+1

Adalimumab (Humira) – TNF-α inhibitor
Adalimumab is a monoclonal antibody that neutralizes TNF-α, a master cytokine driving granulomatous inflammation in joints, skin, and eyes. In pediatrics it is FDA-approved for polyarticular JIA and non-infectious uveitis (≥2 years); Blau patients with severe uveitis/arthritis often benefit similarly. Typical pediatric uveitis/JIA dosing uses weight-tiered subcutaneous regimens (for example, ≥40 kg: 40 mg every other week; label details multiple weight tiers). Purpose: control arthritis, quiet uveitis, prevent vision loss. Mechanism: blocks TNF signaling, decreasing granuloma-forming inflammation. Key side effects: infection risk, TB reactivation, injection reactions; rare demyelination or lupus-like syndromes; malignancy warnings. Follow vaccination and lab guidance. FDA Access Data+1
Infliximab (Remicade and biosimilars) – TNF-α inhibitor (IV)
Infliximab is an IV chimeric anti-TNF antibody often favored for severe, vision-threatening uveitis that needs rapid control or higher TNF blockade. Pediatric dosing is weight-based (e.g., 5 mg/kg at weeks 0, 2, 6, then every 4–8 weeks, per label for approved indications). Many Blau case series describe ocular and joint improvement with infliximab when methotrexate or etanercept fail. Purpose: fast, deep damping of TNF-driven granulomatous disease. Mechanism: neutralizes soluble and transmembrane TNF, reducing cell recruitment and granuloma maintenance. Key side effects: infusion reactions, TB/serious infections, rare hepatosplenic T-cell lymphoma; screen and monitor. FDA Access Data+1
Etanercept (Enbrel) – TNF receptor fusion protein (SC)
Etanercept is FDA-approved from age ≥2 years for polyarticular JIA. It reduces arthritis symptoms but is generally less effective for uveitis than monoclonal TNF antibodies; in Blau, etanercept may help joints/skin but often underperforms for eyes. Dose: weight-based SC per label for pJIA. Purpose: improve joint pain, swelling, stiffness. Mechanism: decoy receptor binds TNF. Side effects: infections; rare demyelination, cytopenias; monitor and vaccinate. FDA Access Data+1
Tocilizumab (Actemra, and biosimilars) – IL-6 receptor inhibitor
Tocilizumab is approved for systemic or polyarticular JIA (≥2 years) and may help Blau patients with systemic features or refractory uveitis in case reports. Dose: IV or SC weight-based per label. Purpose: control persistent inflammation when TNF blockade is inadequate or not tolerated. Mechanism: blocks IL-6 signaling, lowering acute-phase responses and granuloma supports. Side effects: infections, neutropenia, liver enzyme elevation, GI perforation in at-risk populations; lab monitoring is essential. FDA Access Data+1
Anakinra (Kineret) – IL-1 receptor antagonist
Anakinra targets IL-1, another pro-inflammatory driver. While approved for adult RA and certain autoinflammatory syndromes, pediatric off-label use is common in autoinflammation; some Blau patients improve, especially when fever/systemic features dominate. Dose: daily SC (weight-based; refer to label specifics). Purpose: reduce flares and systemic symptoms when IL-1 is prominent. Mechanism: blocks IL-1 receptor, dampening inflammasome-mediated pathways. Side effects: injection-site reactions, infections; monitor CBC and infection risk. FDA Access Data+1
Canakinumab (Ilaris) – IL-1β monoclonal antibody
Approved in children for several periodic fever syndromes and systemic JIA, canakinumab offers q8-week dosing that can be easier for families. Purpose: control persistent autoinflammation when IL-1 biology is strong. Mechanism: neutralizes IL-1β. Side effects: infections; injection reactions; routine monitoring advised. FDA Access Data+1
Methotrexate (low-dose weekly) – csDMARD
A backbone drug in pediatric arthritis that also supports biologic response and reduces anti-drug antibodies. Often used first-line with TNF inhibitors for joint and eye disease. Dose: weekly oral/SC (not daily); folate supplementation required. Purpose: disease control and steroid-sparing. Mechanism: anti-inflammatory via adenosine pathways and T-cell modulation at low doses. Side effects: nausea, liver enzyme elevation, cytopenias; teratogenic—strict precautions in teens. FDA Access Data+1
Azathioprine (Imuran) – purine antimetabolite
Used as a steroid-sparing agent for uveitis/arthritis when MTX is not tolerated. Dose: weight-based daily; TPMT/NUDT15 status can guide risk. Purpose: maintain control and reduce steroid need. Mechanism: inhibits purine synthesis, reducing lymphocyte proliferation. Side effects: leukopenia, hepatotoxicity, infection, rare malignancy risk; lab monitoring required. FDA Access Data+1
Mycophenolate mofetil (CellCept) – inosine monophosphate dehydrogenase inhibitor
Often used for uveitis control as a steroid-sparing agent. Dose: weight-based BID; formulations include oral suspension. Purpose: maintain ocular quiescence and protect vision. Mechanism: blocks guanine synthesis in activated lymphocytes. Side effects: GI upset, leukopenia, infection risk; teratogenic—counsel adolescents. FDA Access Data+1
Cyclosporine (Neoral/Sandimmune) – calcineurin inhibitor
Targets T-cell activation; helpful in some refractory uveitis cases, occasionally combined with MTX. Dose: weight-based; careful trough level and kidney/BP monitoring. Purpose: additional control when other DMARDs insufficient. Mechanism: blocks IL-2 transcription in T-cells. Side effects: nephrotoxicity, hypertension, tremor, gum hyperplasia—strict monitoring. FDA Access Data+1
Prednisone/Prednisolone (systemic) – corticosteroids
Short courses treat flares or bridge to DMARDs; long-term use risks growth delay, bone loss, and metabolic effects. Dose: individualized taper. Purpose: fast inflammation control. Mechanism: broad cytokine suppression. Side effects: weight gain, mood changes, hyperglycemia, infection risk—limit duration. FDA Access Data+1
Topical ophthalmic corticosteroids & cycloplegics
For anterior uveitis, prednisolone acetate eye drops and cycloplegics (e.g., atropine) reduce inflammation and pain; systemic immunosuppression is needed when disease is chronic or posterior. Purpose: relieve ocular inflammation and prevent synechiae. Mechanism: local cytokine suppression and ciliary muscle rest. Side effects: cataract, glaucoma—require specialist follow-up. EyeWiki+1
Tocilizumab biosimilars (e.g., tocilizumab-aazg) – IL-6R inhibitors
Provide similar labeling to originator for pJIA/sJIA; practical when access/coverage is an issue. Safety/monitoring mirrors tocilizumab. FDA Access Data
Tofacitinib (Xeljanz) – JAK inhibitor
Approved for polyarticular-course JIA (≥2 years); used off-label in refractory uveitis/Blau in select cases. Dose: weight-based oral solution or tablets; avoid combining with potent immunosuppressants like azathioprine/cyclosporine. Purpose: control arthritis when biologics fail/intolerant. Mechanism: blocks JAK-STAT cytokine signaling. Side effects: infections (incl. zoster), cytopenias, lipids—monitor labs/vaccinate. FDA Access Data
Canakinumab/Anakinra sequencing
Switching between IL-1 agents can help families balance dosing frequency and tolerance. Purpose: maintain low disease activity with acceptable burden. Mechanism/risks: as above (IL-1 blockade). FDA Access Data+1
Infliximab biosimilars (e.g., Avsola; SC infliximab-dyyb for maintenance)
Practical TNF options with similar efficacy/safety when access matters. Purpose: facilitate sustained TNF control. Mechanism/risks: as infliximab. FDA Access Data+1
Sulfasalazine (Azulfidine) – csDMARD
Sometimes useful for peripheral arthritis; less ocular benefit. Side effects: GI upset, rash; rare severe skin reactions—stop and seek care if severe rash. FDA Access Data+1
Leflunomide (Arava) – pyrimidine synthesis inhibitor
Alternative to MTX for arthritis control; counsel teens on strict pregnancy avoidance and use cholestyramine washout if needed. Side effects: hepatotoxicity; routine labs. FDA Access Data+1
NSAIDs (naproxen/ibuprofen) – symptom relief
Helpful for pain and stiffness but rarely enough alone for Blau/PGA. Risks: GI/CV warnings; use pediatric formulations and doses. FDA Access Data+1
Combination therapy (e.g., MTX + adalimumab; MTX + infliximab)
Common in uveitis-predominant disease to deepen response and reduce anti-drug antibodies; center case series in Blau favor potent TNF blockade (adalimumab weekly or infliximab). Risks: additive immunosuppression—monitor closely. ACR Meeting Abstracts

Dietary molecular supplements

Always clear supplements with your care team (interactions, lab monitoring). Evidence in pediatric arthritis/uveitis is modest or mixed.

Vitamin D – supports bone health on steroids and modulates immunity. Pediatric dosing is individualized to serum 25-OH-D; avoid excess. Mechanism: nuclear receptor signaling shapes innate/adaptive responses; helps calcium absorption. Office of Dietary Supplements
Omega-3 fatty acids (EPA/DHA) – adjunct anti-inflammatory nutrition via fish oil; typical pediatric doses are weight-based; watch GI/upset. Mechanism: membrane lipid mediators (resolvins) reduce cytokine signaling. Office of Dietary Supplements
Calcium (with vit D when needed) – protects bone during corticosteroid use and reduced activity. Mechanism: mineral supply to maintain bone mass. Office of Dietary Supplements
Probiotics (selected strains) – mixed data in JIA; generally safe but benefits are uncertain. Mechanism: microbiome-immune crosstalk. PubMed+1
Vitamin C – immune cofactor and antioxidant; avoid megadoses. Mechanism: supports phagocyte function and collagen turnover. PMC+1
Turmeric/curcumin – early evidence for anti-inflammatory effects; quality and dosing vary; avoid high doses that may affect liver or drug metabolism. Mechanism: NF-κB pathway modulation. NCCIH+1
Folate – standard with low-dose methotrexate to reduce mucosal and GI side effects; dose per clinician. Mechanism: repletes folate pools impacted by MTX. FDA Access Data
Zinc (if deficient) – supports growth and immune function; supplement only if low. Mechanism: enzymatic cofactor for immune cells. Office of Dietary Supplements
Lutein/zeaxanthin (eye health; optional) – general ocular antioxidant support; evidence for uveitis is limited. Mechanism: macular pigment/antioxidant effects. Office of Dietary Supplements
Magnesium (adequate intake) – supports muscle function and sleep; supplement if dietary intake is low. Mechanism: cofactor in energy and nerve conduction. Office of Dietary Supplements

Advanced immune-modulating options

These are specialist-directed, case-by-case—used when standard DMARDs/biologics fail.

Intravenous Immunoglobulin (IVIG) – pooled antibodies; sometimes tried as adjunct in refractory autoinflammatory/uveitis cases to modulate immunity. Dose: weight-based infusions. Function/Mechanism: Fc-mediated immune modulation; down-regulates pathogenic pathways. Note: Off-label in Blau. (General immunology practice references.)
Abatacept (CTLA-4-Ig) – blocks T-cell costimulation; approved in pJIA and sometimes considered after TNF/IL-1/IL-6 failure. Dose: IV/SC per JIA label. Function/Mechanism: reduces T-cell activation driving granulomatous inflammation. (See FDA abatacept label.)
Rituximab (anti-CD20) – depletes B cells; occasionally used for severe refractory uveitis. Dose: IV cycles. Function/Mechanism: reduces autoantibody-mediated and antigen-presentation pathways. (See FDA rituximab label.)
Janus kinase inhibitors (e.g., tofacitinib) – see above; oral small-molecule option in resistant arthritis/uveitis patterns. Function/Mechanism: multi-cytokine signal blockade via JAK-STAT. FDA Access Data
Hematopoietic stem cell transplantation (HSCT) – rare, last-resort for catastrophic, refractory autoinflammation; potential to “reset” immunity but with serious risks. Function/Mechanism: immune reconstitution. (Specialist literature; case-by-case ethics.)
Local steroid implants (e.g., intraocular) – surgical/office procedures delivering corticosteroid depot for chronic posterior uveitis when systemic therapy is limited. Function/Mechanism: sustained local anti-inflammatory effect; risk of cataract/glaucoma. EyeWiki

Surgeries (procedures & why)

Cataract extraction – treats steroid- or inflammation-related lens opacity to restore vision; timing depends on uveitis control and ocular pressure. EyeWiki
Glaucoma surgery (e.g., trabeculectomy/shunts) – for pressure damage unresponsive to drops due to chronic uveitis or steroid response. EyeWiki
Pars plana vitrectomy – clears persistent vitreous haze/membranes and helps manage complications like traction; also used to deliver therapy. EyeWiki
Synovectomy/tenosynovectomy – rarely, for localized, therapy-refractory synovitis impacting function. (Orthopedic practice references.)
Biopsy of skin/synovium – confirms granulomatous inflammation and excludes infection when diagnosis is uncertain. (Diagnostic pathology standards.)

Preventions

Keep regular eye exams; stick to follow-ups even when symptoms are quiet. AAO
Vaccines on schedule; plan live vaccines around immunosuppression. American College of Rheumatology
Infection screening (TB/hepatitis) before TNF/IL-6/IL-1/JAK therapy. FDA Access Data+1
Steroid-sparing strategy (use DMARDs/biologics) to protect growth/bones. PMC
Bone health: dietary calcium/vitamin D; weight-bearing play. Office of Dietary Supplements
Eye protection & UV control during flares. PMC
Medication adherence (drops, injections, lab checks) with reminders. PMC
School plans (504/IEP) to reduce stress and missed doses. AAPOS
Healthy sleep & daily movement to reduce fatigue and stiffness. PMC
Early flare-action: red/painful/photophobic eye → urgent slit-lamp today. AAO

When to see doctors (red flags)

See your pediatric rheumatologist or ophthalmologist urgently for: a suddenly red/painful eye, light sensitivity, blurry vision, new floaters, or eye pain; a hot or rapidly swelling joint; high fever, severe headache/neck stiffness; new cough, weight loss, or night sweats on biologics; severe abdominal pain, dark urine, yellow eyes/skin (possible drug toxicity); severe rash or peeling skin; persistent vomiting or dehydration with medicines; and any exposure to TB or chickenpox while immunosuppressed. Reason: these can signal active uveitis, severe flare, infection, or medicine side effects that need immediate treatment changes. PMC+1

What to eat and what to avoid

Eat: colorful fruits/vegetables daily—natural antioxidants that support general health. Avoid: ultra-processed snacks high in sugar/salt that worsen energy dips. Office of Dietary Supplements
Eat: fish 1–2×/week (or dietitian-guided omega-3). Avoid: excess fried foods. Office of Dietary Supplements
Eat: calcium + vitamin D sources for bones (dairy/fortified foods). Avoid: high-dose, unsupervised vitamin D supplements. Office of Dietary Supplements
Eat: whole grains and legumes for steady energy. Avoid: sugary drinks that spike then crash energy. Office of Dietary Supplements
Consider: modest turmeric in cooking (if tolerated). Avoid: high-dose curcumin capsules without clinician approval. NCCIH
Hydrate well, especially on MTX day, unless otherwise advised. Avoid: energy drinks/caffeine excess. FDA Access Data
Maintain: healthy weight for joint load. Avoid: restrictive fad diets in growing kids. American College of Rheumatology
If on steroids: prioritize protein, calcium, fiber. Avoid: excess sodium that worsens fluid retention. PMC
With mycophenolate: take consistently; discuss timing with meals if GI upset. Avoid: unvetted herbal mixes that may interact. FDA Access Data
With tofacitinib/biologics: keep vaccinations and food-safety hygiene sharp. Avoid: raw/high-risk foods if neutropenic. FDA Access Data

FAQs

Is Blau syndrome the same as pediatric granulomatous arthritis?
Yes—PGA often refers to NOD2-related Blau syndrome/early-onset sarcoidosis with arthritis, dermatitis, and uveitis. PMC
Is it contagious?
No. It’s an immune regulation problem, typically genetic, not an infection. PMC
Can children outgrow it?
Symptoms can wax and wane, but without treatment, arthritis and uveitis may cause lasting damage. Early control matters. BioMed Central
How is it diagnosed?
By clinical features, eye exam, biopsy showing granulomas when needed, and genetic testing for NOD2 variants. Other causes of granulomas and infection are excluded. PMC
What’s the main treatment goal?
Keep uveitis quiet and joints functional, using the lowest effective steroids plus DMARDs/biologics. PMC
Which drugs help the eyes most?
Monoclonal TNF inhibitors (adalimumab, infliximab) and systemic immunosuppression are commonly effective for non-infectious uveitis. FDA Access Data+1
Are these drug uses FDA-approved for Blau?
No. Approvals are for JIA/uveitis; Blau uses are off-label but evidence-informed. Labels guide dosing/monitoring. FDA Access Data
Are JAK inhibitors an option?
Yes, tofacitinib is FDA-approved for pcJIA and sometimes tried when biologics fail. Careful monitoring is required. FDA Access Data
Why combine methotrexate with biologics?
It can enhance response and reduce anti-drug antibodies, especially with TNF inhibitors. PMC
How often are eye checks?
During active disease, often every 1–3 months; schedule is individualized. AAO
Can diet cure it?
No. A healthy diet supports overall health, but immunosuppression is usually needed to prevent damage. PMC
Are vaccines safe?
Inactivated vaccines are recommended; time live vaccines around immunosuppression with your team. American College of Rheumatology
What are steroid risks?
Growth effects, weight gain, mood, bone loss, cataract/glaucoma in eyes—use the lowest dose for shortest time. FDA Access Data
What signs mean urgent eye care?
Red/painful eye, light sensitivity, decreased vision, new floaters—same day slit-lamp exam. AAO
What’s the long-term outlook?
With early diagnosis, tight eye surveillance, and modern DMARD/biologic therapy, many children keep good vision and joint function into adulthood. PMC

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