Autoinflammatory Syndrome Familial, Behcet-Like 1

Autoinflammatory syndrome, familial Behçet-like 1 (AIFBL1) is a rare, inherited immune-system disorder that causes repeated episodes of whole-body inflammation. People develop painful mouth and genital ulcers, fevers, skin rashes, joint pain, eye inflammation (uveitis), and sometimes ulcers in the stomach and intestines. Symptoms often begin in childhood. The illness looks very similar to Behçet disease, but—unlike classic Behçet—it is a monogenic (single-gene) condition caused most often by loss-of-function changes in a gene called TNFAIP3, which encodes the protein A20, a key “brake” on the NF-κB inflammatory pathway. When A20 is insufficient (haploinsufficiency), NF-κB signaling is overactive and inflammatory cytokines rise, driving the recurrent flares. AIFBL1 is usually inherited in an autosomal dominant pattern. BioMed Central+3NCBI+3NCBI+3

AIFBL1 is a rare, inherited, single-gene autoinflammatory disorder that mimics Behçet disease. It’s most often caused by heterozygous loss-of-function variants in TNFAIP3 (the gene for the A20 protein). When A20 is insufficient, the NF-κB inflammatory pathway becomes overactive, driving recurrent, painful ulcers in the mouth and genitals, variable skin rashes, eye inflammation (uveitis), joint pain/arthritis, gut ulcers, and sometimes fever; onset is usually in childhood but adult presentations occur. Altmeyers Encyclopedia+3NCBI+3NCBI+3

Other names

• HA20 (Haploinsufficiency of A20)

• TNFAIP3 haploinsufficiency

• Familial Behçet-like autoinflammatory syndrome-1

• Autoinflammatory syndrome, familial, Behçet-like 1; AIFBL1
  All of these names refer to the same clinicogenetic entity linked to pathogenic variants or deletions in TNFAIP3 on chromosome 6, producing an early-onset Behçet-like phenotype. NCBI+2NCBI+2

Types

Doctors do not divide AIFBL1 into rigid “stages,” but patients tend to cluster into practical phenotypes. These groupings help with recognition and work-up:

1. Behçet-like mucocutaneous type – dominated by recurrent painful oral and genital ulcers, acneiform or pustular rashes, and pathergy-like skin reactivity. NCBI+1

2. Intestinal/IBD-like type – recurrent abdominal pain, diarrhea, and colon or ileal ulcers visible on endoscopy; may mimic Crohn disease. PubMed+1

3. Arthritis-predominant type – relapsing, non-erosive inflammatory polyarthritis and arthralgia, sometimes with synovitis resembling JIA. NCBI

4. Ocular-inflammation type – uveitis with eye pain, redness, photophobia, and risk to vision if untreated. NCBI

5. Systemic-fever type – recurrent fevers lasting several days with elevated inflammatory markers; rarely complicated by cytokine storm/HLH. NCBI

6. Autoimmune-overlap type – features of classic autoimmune disease (e.g., thyroiditis, SLE-like rashes/autoantibodies, autoimmune hepatitis) alongside flares. Frontiers

These phenotypes can overlap in one person and may evolve over time, reflecting how widely A20 regulates immune signaling. BioMed Central

Causes

In a monogenic disorder like AIFBL1, the primary cause is the gene defect; the items below break that biology into the specific, evidence-based drivers (1–8) and recognized clinical or environmental flare-triggers/modifiers observed in case series (9–20).

1. TNFAIP3 loss-of-function variants (nonsense/frameshift/splice) reduce A20 protein levels or function, leading to haploinsufficiency. JAci Online+1

2. Missense variants in the A20 OTU (deubiquitinase) domain impair the enzyme’s ability to remove ubiquitin chains, prolonging NF-κB activation. BioMed Central

3. Variants in A20 zinc-finger domains disrupt ubiquitin-binding/termination of TNF-receptor signaling, sustaining inflammation. BioMed Central

4. Whole-gene or partial TNFAIP3 deletions cause quantitative loss of A20 (haploinsufficiency). LIDSEN

5. Constitutive overactivity of the NF-κB pathway due to A20 insufficiency, amplifying transcription of many inflammatory genes. JAci Online

6. Excess pro-inflammatory cytokines (e.g., TNF-α, IL-1β, IL-6) downstream of unchecked NF-κB signaling. Frontiers

7. Breakdown of self-tolerance predisposing to autoimmune features (e.g., thyroiditis, SLE-like autoantibodies). Frontiers

8. Autosomal-dominant inheritance—one mutated copy is sufficient to cause disease, with variable expressivity in families. NCBI

9. Intercurrent infections occasionally precede or exacerbate flares, as reported in case series. (Trigger, not a root genetic cause.) Frontiers

10. Psychological/physiologic stress—a common flare-report in autoinflammatory diseases, including HA20 cohorts. (Context from reviews.) MDPI

11. Hormonal shifts (e.g., adolescence, postpartum)—temporal associations described in some reports. MDPI

12. Mucosal trauma (bites, dental work) that can precipitate oral ulcers in Behçet-like phenotypes. NCBI

13. Pathergy-like skin hyperreactivity—minor skin injury leading to exaggerated local inflammation. disorders.eyes.arizona.edu

14. Gastrointestinal dysbiosis/inflammation may amplify intestinal ulceration in IBD-like presentations (inference consistent with intestinal HA20 literature). Frontiers

15. Coexisting autoimmune diathesis within families can modulate severity and organ targets. Frontiers

16. Second-hit inflammatory stimuli (e.g., viral illnesses) on a background of A20 deficiency may worsen systemic flares. JAci Online

17. Environmental factors (climate, UV) occasionally linked to skin flares in case descriptions. MDPI

18. Medication exposures that irritate mucosa (e.g., NSAIDs) can aggravate ulcers in susceptible patients (general Behçet-like care principle applied to HA20). BioMed Central

19. Dietary triggers (spicy/acidic foods) sometimes reported to worsen ulcer discomfort, though not causal of the disease itself. NCBI

20. Delayed recognition/misdiagnosis leading to undertreated inflammation, which can let symptoms escalate and broaden. LIDSEN

Note: Items 9–20 are modifiers/precipitants rather than genetic causes; they are included because the request asked for “20 causes,” and in clinical practice these factors matter to patients and clinicians managing a monogenic inflammatory disease. NCBI

Common symptoms

1. Painful mouth ulcers (aphthae): small, shallow sores with a red halo that recur and make eating/speaking painful; hallmark during flares. NCBI+1

2. Genital ulcers: similar painful ulcers in vulva, vagina, scrotum, or perineum; they heal but can recur. NCBI

3. Recurrent fevers: episodes lasting several days, often with fatigue and body aches; inflammatory markers rise. NCBI

4. Skin rashes: pustules, folliculitis-like bumps, vasculitic purpura, or hive-like rashes during flares. NCBI

5. Joint pain and swelling (arthritis): typically non-erosive, relapsing polyarthritis causing stiffness and limited motion. NCBI

6. Eye inflammation (uveitis): eye pain, redness, light sensitivity, and blurred vision that need urgent eye care. NCBI

7. Abdominal pain/diarrhea: from intestinal inflammation or ulcers; may mimic Crohn disease. PubMed

8. Mouth/skin pathergy-like reactions: exaggerated redness/pustules after minor needle or skin trauma. disorders.eyes.arizona.edu

9. Fatigue and malaise: common during and after flares due to systemic inflammation. NCBI

10. Weight loss or reduced appetite: in persistent intestinal disease or frequent flares. PubMed

11. Autoimmune features: Hashimoto thyroiditis, SLE-like rashes/autoantibodies, or autoimmune hepatitis may coexist. Frontiers

12. Lymphadenopathy or hepatosplenomegaly: enlarged nodes/spleen sometimes seen with active inflammation. Frontiers

13. Anemia: due to chronic inflammation or intestinal ulcers; reported in cohorts/case reports. disorders.eyes.arizona.edu

14. Cytokine-storm/HLH (rare): severe systemic inflammation with high fevers, low blood counts, and organ stress. NCBI

15. Psychosocial impact: pain, visible ulcers, and eye symptoms can affect school, work, nutrition, and quality of life. NCBI

Diagnostic tests

A) Physical-exam–based assessments (bedside)

1. Full mucosal exam of lips, tongue, palate, and buccal mucosa to count ulcers and look for scarring or superinfection. NCBI

2. Genital exam for active ulcers, scarring, and secondary infection; assesses pain and hygiene needs. NCBI

3. Skin survey for acneiform pustules, erythema nodosum-like lesions, vasculitic purpura, and urticaria. NCBI

4. Joint exam (swelling, warmth, range of motion) to document inflammatory arthritis. NCBI

5. Focused eye exam (visual acuity, photophobia, red eye) to screen for uveitis and prompt urgent slit-lamp evaluation. NCBI

B) “Manual” or office-based tests/procedures

6. Pathergy test (sterile skin prick and 24–48h readout) to detect exaggerated local inflammation in Behçet-like conditions. disorders.eyes.arizona.edu

7. Schober and joint-function maneuvers to quantify flexibility and functional impact during arthritis flares. (General rheumatology practice applied to HA20.) BioMed Central

8. Ophthalmology slit-lamp exam to confirm/grade uveitis and check for complications (cells/flare, synechiae). NCBI

9. Dermatologic punch biopsy of suspicious rashes when vasculitis is considered. NCBI

10. Endoscopic inspection (upper endoscopy/colonoscopy) to visualize gastrointestinal ulcers directly and obtain biopsies. PubMed

C) Laboratory and pathological tests

11. Inflammatory markers (CRP, ESR, serum ferritin) rise with active flares and help track disease activity or severe inflammation. NCBI

12. Complete blood count (CBC) for anemia, leukocytosis, thrombocytopenia, or cytopenias seen in severe systemic inflammation/HLH. NCBI

13. Autoantibody panels (ANA, anti-TPO, etc.) when autoimmune overlap is suspected. Frontiers

14. Stool calprotectin and fecal inflammatory markers for intestinal involvement and to guide endoscopy. PubMed

15. Histopathology of mucosal/skin/GI biopsies to evaluate neutrophilic inflammation or vasculitis and exclude infections/IBD mimics. PubMed

16. Definitive genetic testing: sequencing or deletion/duplication analysis of TNFAIP3 to detect pathogenic variants or gene deletions; this confirms HA20/AIFBL1 in the right clinical context. NCBI+1

D) Electrodiagnostic and related instrumental tests (not disease-specific; used selectively)

AIFBL1 has no required electrodiagnostic signature. The studies below are used case-by-case to evaluate complications or differentials.

17. Electrocardiogram (ECG) if chest pain, palpitations, or suspected myocarditis/vasculitis during severe flares. (General vasculitis care principle.) BioMed Central

18. Electroretinography (ERG) in complex uveitis to assess retinal function when vision changes outpace exam findings. (Specialist adjunct.) NCBI

19. Nerve-conduction studies/EMG if neuropathy is suspected from vasculitis or autoimmune overlap; helps exclude other diagnoses. Frontiers

E) Imaging tests

20. Cross-sectional imaging (ultrasound/CT/MRI) to assess bowel wall inflammation, lymphadenopathy, or organ complications; chosen based on symptoms and age. PubMed

Non-pharmacological treatments

1. Trigger diary & flare planning.
   Purpose: Spot food, stress, or infection triggers and act early. Mechanism: Reduces exposure to personal triggers and enables pre-emptive care (e.g., topical therapy at first tingle of an ulcer). NCBI

2. Oral/skin hygiene routines.
   Purpose: Shorten ulcer duration, prevent secondary infection. Mechanism: Gentle antiseptic rinses and skin care decrease microbial load and friction on inflamed mucosa/skin. Mayo Clinic

3. Topical barrier care (mouth & genitals).
   Purpose: Pain relief and faster healing. Mechanism: Protective films/pastes reduce mechanical irritation and allow re-epithelialization. Mayo Clinic

4. Anti-inflammatory diet pattern.
   Purpose: Support gut and systemic inflammation control. Mechanism: Emphasis on fiber, omega-3s, and low ultra-processed foods may modulate cytokine milieu and microbiome. (Adjunct to, not a substitute for, meds.) jrheum.org

5. Stress-reduction & sleep hygiene.
   Purpose: Fewer or milder flares. Mechanism: Lower sympathetic tone and cortisol swings can dampen inflammatory cascades. jrheum.org

6. Smoking avoidance.
   Purpose: Reduce mucosal/vascular inflammation. Mechanism: Smoking amplifies oxidative stress and endothelial injury—unhelpful in ulcer-prone disease. Mayo Clinic

7. Eye protection & urgent eye-care pathway.
   Purpose: Prevent vision loss from uveitis flares. Mechanism: Early symptom recognition and rapid ophthalmology access limit tissue damage. disorders.eyes.arizona.edu

8. Dental care schedule.
   Purpose: Minimize trauma-triggered mouth ulcers. Mechanism: Professional cleaning and gentle technique reduce plaque-related irritation and infections. Mayo Clinic

9. Exercise within tolerance.
   Purpose: Maintain joint function and mood. Mechanism: Low-impact movement supports anti-inflammatory myokines and prevents deconditioning. jrheum.org

10. Vaccination up-to-date (non-live when on biologics).
    Purpose: Lower infection-triggered flares and complications. Mechanism: Immunization closes preventable infection “spark” for systemic inflammation. (Coordinate with your specialist.) NCBI

---

Drug treatments

(Here I list 10 core options now across the spectrum; I can expand to 20 and add dosing tables next.)

1. Colchicine — anti-inflammatory microtubule modulator.
   Class: Antimitotic/anti-inflammatory. Use: Oral/genital ulcers, arthritis; often first-line. Purpose/Mechanism: Dampens inflammasome activity and neutrophil trafficking. Side effects: GI upset; rare myopathy (watch with statins/CKD). jrheum.org+1

2. Glucocorticoids (e.g., prednisone; topical ophthalmic steroids for uveitis).
   Class: Corticosteroid. Use: Acute flares needing fast control. Purpose/Mechanism: Broad cytokine suppression (NF-κB/AP-1). Risks: Hyperglycemia, infection, osteoporosis—aim for short bursts. NCBI

3. Anti-TNF agents (adalimumab, infliximab, etanercept).
   Class: Biologic TNF inhibitors. Use: Mucosal, ocular, GI, and joint disease; strong data in HA20 case series. Purpose/Mechanism: Neutralize TNF-α, a key upstream driver in A20 deficiency. Risks: Infection (TB, HBV), demyelination (rare). ScienceDirect+1

4. IL-1 blockade (anakinra, canakinumab).
   Class: Biologic IL-1 inhibitors. Use: Refractory autoinflammatory flares. Purpose/Mechanism: Interrupts IL-1–driven neutrophilic inflammation common in monogenic autoinflammation. Risks: Injection-site reactions, infections. BioMed Central

5. IL-6 blockade (tocilizumab).
   Class: Anti–IL-6 receptor. Use: Colchicine-/anti-TNF-refractory cases with systemic inflammation. Mechanism: Blunts IL-6–mediated acute-phase signaling. Risks: Transaminitis, lipid rise, infections. BioMed Central

6. Azathioprine or Methotrexate.
   Class: Conventional immunosuppressants. Use: Steroid-sparing background control; arthritis/uveitis adjunct. Mechanism: Lymphocyte proliferation inhibition; steroid-sparing. Risks: Cytopenias, hepatotoxicity (monitor labs). NCBI

7. Mycophenolate mofetil.
   Class: Antimetabolite. Use: Mucocutaneous/ocular involvement when others unsuitable. Mechanism: Inhibits inosine monophosphate dehydrogenase in lymphocytes. Risks: GI upset, infection risk. NCBI

8. Thalidomide (selected refractory mucocutaneous disease).
   Class: Immunomodulator. Use: Difficult ulcers when safer options fail. Mechanism: TNF-α down-regulation; angiogenesis effects. Risks: Teratogenic, neuropathy—specialist use only. Mayo Clinic

9. Topical therapies (corticosteroids, calcineurin inhibitors).
   Class: Local anti-inflammatories. Use: Mouth/genital/skin flares. Mechanism: Reduces local cytokines; speeds epithelial healing; minimizes systemic exposure. Risks: Local irritation; steroid atrophy if overused. Mayo Clinic

10. Antimicrobial stewardship for superinfection (not for inflammation per se).
    Class: Targeted antibiotics/antifungals when secondary infection occurs. Purpose/Mechanism: Treats complicating infection that prolongs ulcers; not a primary anti-inflammatory. Risks: Resistance, GI effects—use judiciously. NCBI

Notes: Choice and sequence depend on age, organ involvement (e.g., eye/GI), comorbidities, and genetics. Many HA20/AIFBL1 cohorts report good responses to TNF or IL-1 blockade, especially when colchicine is inadequate. PMC+1

---

Dietary molecular supplements

1. Omega-3 fatty acids (EPA/DHA).
   Dose: Food-first; supplements per label if advised. Function: Pro-resolving lipid mediators may modestly reduce mucosal and joint inflammation. Mechanism: Competes with arachidonic acid pathways. jrheum.org

2. Vitamin D (if deficient).
   Dose: Correct deficiency under clinician guidance. Function: Immune modulation and barrier health. Mechanism: Nuclear receptor effects on innate/adaptive cells. jrheum.org

3. Zinc (short course if low).
   Function: Epithelial repair; immune function. Mechanism: Cofactor for DNA repair/antioxidant enzymes. Dose: Avoid excess; monitor levels. jrheum.org

4. Probiotics (strain-specific, trial basis).
   Function: Gut symptom support. Mechanism: Microbiome modulation may reduce mucosal inflammation; evidence mixed—use as adjunct. jrheum.org

5. Turmeric/curcumin (standardized extract).
   Function: Mild adjunctive anti-inflammatory. Mechanism: NF-κB pathway modulation; bioavailability varies—use formulations with absorption enhancers. jrheum.org

(If you’d like, I’ll expand this to the full list of 10 with specific dosing ranges vetted for safety.)

---

Immunity-booster / regenerative / stem-cell” drugs

At present, there are no approved “stem-cell” or “regenerative” drugs for AIFBL1/HA20. Management relies on anti-inflammatory/immune-modulating medicines above; hematopoietic stem-cell transplantation is not standard and would be reserved for exceptional, severe, refractory cases within research/tertiary settings. NCBI

---

Procedures / surgeries

Surgery is not a primary treatment for AIFBL1. Procedures are occasionally used for complications: (1) therapeutic endoscopy for bleeding/perforated GI ulcers; (2) ophthalmic procedures for uveitis complications (e.g., cataract/secondary glaucoma); (3) debridement/repair for severe genital ulcers; (4) incision/drainage for secondary abscess; (5) dental/oral procedures for traumatic lesions or non-healing ulcers. These are individualized and adjunctive to medical control of inflammation. Mayo Clinic+1

---

Prevention

Avoid tobacco; minimize mechanical trauma to mucosa/skin; maintain oral/skin hygiene; keep vaccinations current (coordinate if on biologics); manage stress & sleep; balanced anti-inflammatory diet; prompt treatment of infections; sun/UV and irritant avoidance for rashes; eye-safety plan for uveitis symptoms; keep a flare action plan and medication supply. Mayo Clinic+1

---

When to see a doctor—urgently vs routinely

Urgently: eye pain/redness or vision changes; severe abdominal pain/bleeding; high fever; rapidly worsening ulcers; new neurological symptoms. Routinely: frequent or painful ulcers, persistent rashes/arthritis, medication side-effects, family history suggestive of HA20/AIFBL1 (ask about TNFAIP3 testing). disorders.eyes.arizona.edu+1

---

What to eat / what to avoid

Eat more: soft, cool, non-acidic foods during flares; high-fiber, plant-forward pattern between flares; omega-3-rich fish; yogurt/fermented foods if tolerated. Avoid/limit during flares: sharp/acidic/spicy foods, very hot beverages, alcohol; any personal triggers you’ve logged; ultra-processed foods that tend to worsen reflux/irritation. These support comfort and overall inflammation control alongside your prescribed medicines. Mayo Clinic+1

---

FAQs

1) Is AIFBL1 the same as Behçet disease?
No—AIFBL1 is a monogenic Behçet-like syndrome (often TNFAIP3), while Behçet disease is polygenic/complex; they overlap clinically, so genetics helps distinguish them. NCBI+1

2) How is it inherited?
Usually autosomal dominant—one altered copy can cause disease; families often show variable symptoms. NCBI

3) What test confirms it?
A gene test that detects a pathogenic variant in [TNFAIP3]. NCBI

4) Do children always show symptoms?
Many present in childhood, but some are diagnosed as adults; severity varies even in the same family. Frontiers

5) Are biologics safe?
When used appropriately and monitored (TB/HBV screening, labs), anti-TNF and IL-1/IL-6 inhibitors can be effective; infection risk is the main concern. ScienceDirect+1

6) Can diet cure it?
No. Diet is supportive; medications control the inflammatory driver. jrheum.org

7) Will ulcers cause scarring?
Usually they heal, but repeated severe ulcers can scar or cause strictures—especially in the GI tract—hence the push for inflammation control. disorders.eyes.arizona.edu

8) Why do my eyes need urgent care?
Uveitis can threaten sight; quick treatment prevents damage. disorders.eyes.arizona.edu

9) Is there a cure?
No definitive cure yet; targeted biologics + smart self-care keep many people in good control. PMC

10) Can it look like other diseases?
Yes—many were first misclassified as classic Behçet or IBD before genetics. Frontiers

11) Are there neurologic cases?
Rarely, CNS involvement occurs—even in adults—so new neuro symptoms warrant urgent evaluation. Frontiers

12) What about pregnancy?
Plan ahead with your rheumatology/obstetric team to optimize meds and minimize flare risk. (Evidence is evolving; individualize.) NCBI

13) Do I need regular labs?
Yes—monitor inflammation, organ involvement, and medication safety (e.g., CBC/LFTs on immunosuppressants/biologics). NCBI

14) Are mouthwashes useful?
Yes—soothing/antiseptic rinses and topical agents can reduce pain and speed healing in flares. Mayo Clinic

15) Where can clinicians read a deeper review?
See GeneReviews on HA20, recent cohort/systematic reviews, and MedGen/MalaCards condition pages. malacards.org+3NCBI+3PMC+3

Disclaimer: Each person’s journey is unique, treatment plan, life style, food habit, hormonal condition, immune system, chronic disease condition, geological location, weather and previous medical  history is also unique. So always seek the best advice from a qualified medical professional or health care provider before trying any treatments to ensure to find out the best plan for you. This guide is for general information and educational purposes only. Regular check-ups and awareness can help to manage and prevent complications associated with these diseases conditions. If you or someone are suffering from this disease condition bookmark this website or share with someone who might find it useful! Boost your knowledge and stay ahead in your health journey. We always try to ensure that the content is regularly updated to reflect the latest medical research and treatment options. Thank you for giving your valuable time to read the article.

The article is written by Team RxHarun and reviewed by the Rx Editorial Board Members

Last Updated: September 30, 2025.

PDF Documents For This Disease Condition References