Autoinflammation-PLCγ2-Associated Antibody Deficiency and Immune Dysregulation (APLAID)

Autoinflammation-PLCγ2-associated Antibody Deficiency and Immune Dysregulation (APLAID) is a very rare genetic immune disease. It happens when a change (mutation) in a gene called PLCG2 makes a white-blood-cell enzyme (phospholipase Cγ2) overactive. This faulty signaling causes ongoing inflammation in many organs and also weakens the body’s ability to make and use protective antibodies. People with APLAID often have early-life skin blisters or rashes, eye inflammation, joint pain, lung problems, and gut inflammation. They may get repeated bacterial infections because antibody responses are poor. The condition usually follows an autosomal-dominant pattern (one altered copy is enough). APLAID is closely related to, but different from, PLAID, which classically has cold-triggered hives; APLAID typically lacks cold urticaria and shows more systemic inflammation. NCBI+2Nature+2

APLAID is a rare, inherited autoinflammatory disease caused by single-letter changes (missense variants) in a gene called PLCG2. PLCG2 makes an enzyme (PLCγ2) that helps immune cells send signals. In APLAID, that enzyme becomes over-active (“gain-of-function”), which drives recurrent inflammation in the skin, lungs, joints, eyes, and gut. Many people also have antibody deficiency and get repeated sinus or lung infections because parts of the B-cell system don’t work normally. The disease usually runs in families in an autosomal dominant pattern, but new (“de novo”) variants can also occur. Frontiers+1

Another names

Doctors and databases may use any of these labels for the same condition:

• APLAID

• Autoinflammation, PLCG2-associated antibody deficiency and immune dysregulation

• Autoinflammation, antibody deficiency, and immune dysregulation (PLCG2-associated)

• Autoinflammation phospholipase C gamma 2–associated antibody deficiency and immune dysregulation

These synonyms appear in clinical genetics libraries such as MedGen and Orphanet. NCBI

APLAID is often confused with PLAID (PLCG2-associated antibody deficiency and immune dysregulation). They involve the same gene but are not the same disease.

• APLAID: usually due to missense PLCG2 variants that increase enzyme activity; patients have autoinflammation across several organs and antibody deficiency; cold-induced hives (cold urticaria) are typically absent.

• PLAID: commonly due to deletions that behave differently; patients classically have cold urticaria and immune problems.

Modern reviews and case series lay out these distinctions clearly. Frontiers+2Oncotarget+2

Types

Because APLAID is rare, doctors “type” it in practical ways that help with diagnosis and discussion:

1) By main organs involved.

• Cutaneous-predominant APLAID: recurrent vesiculo-pustular or blistering rashes; sometimes granulomatous or ulcerating lesions.

• Pulmonary-predominant APLAID: bronchiolitis or interstitial pneumonitis.

• Enteric/IBD-like APLAID: chronic enterocolitis or severe colitis.

• Ocular-inflammation APLAID: recurrent eye inflammation; cataracts or corneal problems may follow.
  People may fit more than one box over time. NCBI

2) By immunologic pattern.

• Antibody-deficiency-dominant: low IgG/IgA/IgM and reduced class-switched memory B cells with frequent sinus/lung infections.

• Inflammation-dominant: striking inflammatory flares with only mild antibody defects.
  These patterns are described across case reports and HPO annotations. Frontiers+1

3) By genetic variant.

• Classic p.Ser707Tyr (S707Y) variant in the cSH2 domain.

• Other reported missense or small in-frame changes (e.g., I169V, L845S, L848P, M1141K, etc.).
  Genotype–phenotype is evolving; not all variants behave exactly the same, but many show hypermorphic (over-active) PLCγ2 signaling. Frontiers+1

Causes

Strictly speaking, APLAID has one root cause: pathogenic PLCG2 variants. Below are 20 closely related reasons and drivers that together cause or amplify the disease process and its flares. I’ll separate firm facts from emerging ideas.

1) Missense variants in PLCG2 (root cause).
A single DNA letter change can make PLCγ2 over-active in immune cells. This is the core cause. Frontiers

2) Dominant inheritance.
One altered copy is enough to cause disease in a family. Penetrance (who shows symptoms) can vary. NCBI

3) De novo variants.
Sometimes the change arises for the first time in the affected person. Frontiers

4) Constitutive PLCγ2 signaling.
The enzyme sends “on” signals too easily, disturbing normal immune balance. Frontiers

5) Abnormal calcium flux in immune cells.
PLCγ2 over-activity boosts IP₃ and intracellular calcium, pushing inflammatory pathways. Frontiers

6) G-CSF–driven inflammation (new insight).
Recent work in an APLAID mouse model shows granulocyte colony-stimulating factor (G-CSF) is a key driver; blocking G-CSF reversed disease in mice. This points to a cytokine amplifier of human disease. Nature+1

7) B-cell abnormalities.
Reduced class-switched memory B cells and low immunoglobulins make infections more likely and can sustain inflammation. NCBI

8) NK-cell changes.
Some patients show reduced NK cells, which may weaken early defense against infections. Frontiers

9) Recurrent infections as flare triggers.
Because antibodies are low, sinus and lung infections recur; these infections can trigger inflammatory spikes. NCBI

10) Tissue-specific neutrophilic inflammation.
Skin and lung show neutrophil-heavy inflammation in reports and models, feeding local damage. Nature

11) Cutaneous barrier break and trauma.
Ulcers or biopsies can be slow to heal and may perpetuate local inflammation (reported in case literature). Frontiers

12) Gut immune dysregulation.
Enterocolitis reflects abnormal innate immune responses in the intestine. NCBI

13) Ocular immune dysregulation.
Eye tissues are vulnerable to sterile inflammation (uveitis/keratitis) leading to scarring or cataract. NCBI

14) Gene “hotspot” effects (cSH2 domain).
Some variants cluster in regulatory domains (like S707Y) that normally “brake” the enzyme; breaking the brake increases signaling. Oncotarget

15) Temperature-independent activation.
Unlike PLAID deletions, APLAID variants show no cold activation and tend to stay active at body temperature. That biochemical behavior helps explain clinical differences. Oncotarget

16) Cytokine loops beyond IL-1/IL-6/TNF.
Mouse data show that blocking single classic cytokines may be insufficient; the G-CSF axis looks more central. Nature

17) Variable penetrance and modifiers.
Some relatives with the variant have few symptoms, implying other genes or environment modify risk. Frontiers

18) Autoimmunity overlap without classic autoantibodies.
Immune dysregulation can look “autoimmune,” yet standard autoantibodies are often negative. NCBI

19) Lung microenvironment priming.
Cases describe interstitial pneumonitis/bronchiolitis; resident immune cells there may be primed by PLCγ2 signaling. NCBI

20) Developmental imprinting of B-cell pools.
Children can present early with small memory-B pools and low Ig levels, shaping the long-term course. NCBI

Common symptoms and signs

1) Recurrent fever.
Short-lived temperature spikes are common during flares of inflammation. Frontiers

2) Blistering or pustular skin rashes.
These can be widespread, painful or weepy, and may heal slowly; some patients develop ulcerating or granulomatous lesions. Frontiers

3) Skin infections or cellulitis.
Breaks in skin plus antibody deficiency increase the chance of local infections. NCBI

4) Arthritis or arthralgia (joint pain).
Flares can cause tender, swollen joints or just deep aches. Frontiers

5) Eye inflammation.
People can develop painful red eyes; untreated, scarring or cataract may follow. NCBI

6) Chronic cough or breathlessness.
Inflammation in small airways (bronchiolitis) or lung tissue (interstitial pneumonitis) can cause these symptoms. NCBI

7) Recurrent sinus and chest infections.
Because antibodies are low, sinusitis and pneumonia can come back again and again. NCBI

8) Abdominal pain and diarrhea.
An IBD-like enterocolitis can produce belly cramps, loose stools, and blood or mucus in severe cases. NCBI

9) Mouth or perineal ulcers, fistulas.
Some children show severe perineal disease or fistula formation during gut-inflammation phases. Frontiers

10) Enlarged lymph nodes or spleen.
Nodes and spleen may swell during active inflammation. Frontiers

11) Fatigue and malaise.
Whole-body inflammation often brings profound tiredness.

12) Elevated inflammatory markers.
CRP or white blood cells often rise during flares. Frontiers

13) Low immunoglobulins (antibodies).
IgG, IgA, and/or IgM may be reduced on testing. NCBI

14) Reduced memory B cells and sometimes low NK cells.
These immune-cell changes are common patterns on flow cytometry. NCBI

15) Skin ulcer that looks like pyoderma gangrenosum (rare).
A few cases report large, painful ulcers that resemble this condition. Frontiers

Diagnostic tests

A) Physical examination (what clinicians look for)

1) Full skin exam during a flare.
Doctors look for vesicles, pustules, plaques, ulcers, or granuloma-like lesions; photos over time help document patterns. Frontiers

2) Joint exam.
They check for warmth, swelling, range-of-motion limits, and tenderness in small and large joints. Frontiers

3) Lung exam.
Crackles or wheeze can suggest bronchiolitis or interstitial pneumonitis; oxygen saturation may be measured. NCBI

4) Eye (bedside) screening.
Light sensitivity, redness, and pain prompt urgent slit-lamp evaluation to prevent vision damage. NCBI

5) Abdominal and perineal exam.
Doctors assess tenderness, masses, perianal ulcers, or fistulas when bowel involvement is suspected. Frontiers

B) Manual or office-based procedures

6) Slit-lamp ophthalmology exam.
Direct visualization of cornea, anterior chamber, and lens to detect uveitis, keratitis, or early cataract. NCBI

7) Pulmonary function testing (spirometry).
Simple breathing tests can show small-airway obstruction seen in bronchiolitis. (Supportive alongside imaging.) NCBI

8) Stool calprotectin (point-of-care in some centers).
Helps detect intestinal inflammation in suspected enterocolitis; guides need for endoscopy.

9) Wound/skin care assessment.
Regular measurement and photography of ulcers to monitor healing and response to therapy. Frontiers

C) Lab and pathological tests

10) Complete blood count with differential and inflammatory markers.
Leukocytosis and high CRP are common during flares; eosinophils may be normal; platelets often normal. Frontiers

11) Serum immunoglobulins (IgG, IgA, IgM; sometimes IgE).
Many patients have low IgG/IgA/IgM; some cases report high IgE; these values may shift with disease activity. Frontiers

12) Lymphocyte subsets by flow cytometry.
Look for reduced class-switched memory B cells and sometimes low NK cells; T-cell numbers are often okay. NCBI

13) Specific antibody responses to vaccines.
Checks whether the immune system makes protective antibodies after routine vaccines; poor responses support antibody deficiency.

14) Autoantibody panel (ANA, ANCA, etc.).
Usually negative or nonspecific in APLAID, which helps separate it from classic autoimmune diseases. NCBI

15) Skin biopsy of active lesions.
Pathology often shows dense inflammatory (neutrophilic) infiltrates without infection; cultures can rule out bacteria. Frontiers

16) Cytokine panel (research/tertiary centers).
Some centers check cytokines; G-CSF has emerged as a potential driver in models, which may translate to human biology. Nature

17) Genetic testing (the pivotal test).
Targeted PLCG2 sequencing or exome/genome sequencing looks for heterozygous missense variants consistent with APLAID and helps distinguish from PLAID deletions. Variant interpretation uses clinical, laboratory, and family data. Frontiers+1

D) Electrodiagnostic tests

18) Electrodiagnostics are not routine for APLAID.
Nerve conduction studies or EEG are not standard unless specific symptoms suggest a separate problem (e.g., neuropathy or seizures). This category is included here only to emphasize its limited role in typical APLAID work-ups. (No dedicated source—this reflects absence in APLAID case series and reviews; standard practice follows organ-specific clues.)

E) Imaging and endoscopic tests

19) High-resolution chest CT (HRCT).
Shows bronchiolitis or interstitial pneumonitis patterns when lungs are involved. NCBI

20) Gastrointestinal endoscopy with biopsies (as indicated).
Colonoscopy/upper endoscopy can confirm enterocolitis and exclude infections; biopsies define inflammation type and guide care. NCBI

21) Ophthalmic imaging (OCT, corneal topography as needed).
Used by eye specialists to measure inflammation damage and lens changes. NCBI

22) MRI of symptomatic joints or areas of deep ulcers.
Assesses bone edema, erosions, and surrounding soft tissue when arthritis is severe or ulcers are deep. Frontiers

Non-pharmacological treatments

1. Personalized flare plan. A written plan (when to start anti-inflammatory meds, when to call the doctor, which labs to check) reduces delays and injury during flares. Purpose: faster control. Mechanism: early action limits cytokine cascades and tissue damage. NCBI

2. Infection prevention routine. Hand hygiene, dental care, prompt treatment of minor infections, and household vaccination protect people with weak antibody responses. Purpose: fewer infections. Mechanism: lowers exposure and bacterial load. Nature

3. Vaccination optimization with specialists. Inactivated vaccines are generally encouraged; timing and monitoring of titers are individualized in primary immunodeficiency. Purpose: maximize protection. Mechanism: boosts specific immunity where possible. Nature

4. Skin barrier care. Daily emollients, gentle cleansers, and careful wound care prevent secondary infection of blistering lesions. Purpose: protect skin. Mechanism: restores barrier and reduces bacterial entry. NCBI

5. Trigger management. Track infections, stress, sleep loss, and other personal triggers; adjust routines to reduce flares. Purpose: cut flare frequency. Mechanism: reduces innate immune activation peaks. PMC

6. Eye protection and urgent ophthalmology follow-up. Artificial tears, UV protection, and early steroid/biologic add-ons under specialist care preserve vision. Purpose: prevent sight loss. Mechanism: reduces local inflammatory injury. NCBI

7. Pulmonary hygiene. Airway clearance, chest physiotherapy when needed, and prompt antibiotics per culture. Purpose: protect lungs. Mechanism: clears secretions and limits infection/inflammation cycles. Nature

8. Nutrition for gut inflammation. Small, frequent meals; avoid ultra-processed foods that irritate the bowel; consider dietitian support. Purpose: maintain energy and gut healing. Mechanism: reduces mucosal stress. Frontiers

9. Physical therapy during remission. Gentle range-of-motion and strength work prevent joint stiffness from recurrent arthritis. Purpose: preserve function. Mechanism: improves synovial blood flow and mechanics. NCBI

10. Fever and pain self-care. Use antipyretics/analgesics safely as advised; hydration and rest help recovery. Purpose: symptom relief. Mechanism: lowers prostaglandin-mediated symptoms and supports immunity. PMC

11. Sleep hygiene. Consistent sleep strengthens immune regulation and reduces flare likelihood. Purpose: stabilize immune rhythms. Mechanism: normalizes neuro-immune signaling. PMC

12. Stress-reduction skills. Breathing practice, short mindfulness, or CBT-style coping help during chronic illness. Purpose: lower stress-triggered flares. Mechanism: dampens sympathetic cytokine priming. PMC

13. Sun/UV moderation for active skin disease. Protect inflamed skin; some rashes worsen with UV. Purpose: avoid flares and hyperpigmentation. Mechanism: reduces local damage. NCBI

14. Household sick-day rules. Masking and isolation when family is ill to protect the immunodeficient person. Purpose: fewer exposures. Mechanism: reduces pathogen dose. Nature

15. School/work accommodations. Flexible attendance during flares, permission for masks and frequent handwashing. Purpose: maintain life participation safely. Mechanism: exposure control. Nature

16. Heat/cold guidance. While cold urticaria is typical of PLAID, patients with APLAID should still avoid extremes that aggravate skin or joint pain. Purpose: comfort and stability. Mechanism: lowers neuro-immune triggers. MedlinePlus

17. Regular dental care. Prevents oral infections that can seed systemic flares. Purpose: infection control. Mechanism: lowers bacterial burden. Nature

18. Early travel planning. Vaccines, antibiotics on hand, and medical letters reduce risk during trips. Purpose: safe mobility. Mechanism: preparedness against exposures. Nature

19. Patient support and education. Learning about warning signs and treatment steps helps families act fast. Purpose: self-management. Mechanism: cuts delay to care. ScienceDirect

20. Multispecialty follow-up. Immunology, dermatology, ophthalmology, pulmonology, and gastroenterology teamwork improves outcomes. Purpose: organ protection. Mechanism: coordinated control of inflammation and infection. NCBI

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Drug treatments

Doses are typical adult ranges unless noted; individual plans must be made by the treating specialist.

1) Anakinra (IL-1 receptor antagonist; daily SC, e.g., 1–2 mg/kg in children or 100 mg/day adults). Purpose: calm flares and protect organs. Mechanism: blocks IL-1 signaling central to monogenic autoinflammation; many reports show benefit across IL-1-driven disorders and case reports in APLAID-like disease. Side effects: injection-site reactions, infection risk, neutropenia (rare). PMC+1

2) Canakinumab (anti-IL-1β monoclonal antibody; SC q4–8 weeks; weight-based). Purpose: longer-interval IL-1 blockade for flare prevention. Mechanism: neutralizes IL-1β; highly effective in monogenic autoinflammatory conditions and used off-label in APLAID case contexts. Side effects: infections, neutropenia (uncommon), injection reactions. PMC+1

3) Corticosteroids (e.g., prednisolone; variable short tapers). Purpose: quick crisis control of severe skin/eye/gut flares. Mechanism: broad cytokine suppression. Side effects: glucose rise, mood changes, osteoporosis, infection risk—keep lowest effective dose. PMC

4) Colchicine (0.6 mg once/twice daily). Purpose: reduce neutrophil-driven inflammation between flares. Mechanism: microtubule effects dampen neutrophil chemotaxis. Side effects: GI upset, cytopenias with interactions. PMC

5) Anti-TNF agents (e.g., adalimumab, infliximab; label dosing). Purpose: rescue for refractory gut/joint/skin inflammation. Mechanism: blocks TNF-α signaling. Side effects: TB reactivation risk, infections. PMC

6) Methotrexate (7.5–25 mg weekly + folate). Purpose: steroid-sparing for joints/skin. Mechanism: anti-metabolite with anti-inflammatory effects. Side effects: liver toxicity, cytopenias; monitor labs. PMC

7) Mycophenolate mofetil (1–3 g/day total). Purpose: ocular/gut inflammation control when IL-1 alone is insufficient. Mechanism: inhibits lymphocyte purine synthesis. Side effects: GI upset, leukopenia, infections. PMC

8) Azathioprine (1–2.5 mg/kg/day). Purpose: steroid-sparing maintenance. Mechanism: purine analog immunosuppression. Side effects: myelosuppression, hepatotoxicity; TPMT testing helpful. PMC

9) Cyclosporine (2–5 mg/kg/day). Purpose: refractory ocular/skin disease. Mechanism: calcineurin inhibition → lower T-cell activation. Side effects: nephrotoxicity, hypertension. PMC

10) Tacrolimus (topical or systemic; individualized). Purpose: skin/ocular surface control. Mechanism: calcineurin inhibition locally. Side effects: burning (topical), systemic toxicity if oral. PMC

11) IVIG (e.g., 0.4 g/kg monthly; individualized). Purpose: treat/reduce bacterial infections in antibody deficiency. Mechanism: provides pooled protective antibodies. Side effects: headache, aseptic meningitis (rare), hemolysis (rare). Nature

12) Prophylactic antibiotics (agent per local bugs). Purpose: prevent recurrent bacterial infections in those with poor specific antibodies. Mechanism: reduces bacterial load during risk windows. Side effects: resistance, GI effects; use judiciously. Nature

13) JAK inhibitors (e.g., tofacitinib/baricitinib; specialist use). Purpose: selected refractory cases with interferon-skewed signals. Mechanism: blocks JAK-STAT cytokine pathways. Side effects: infections, cytopenias, lipids—close monitoring. PMC

14) Ustekinumab (anti-IL-12/23) or vedolizumab (anti-integrin) for colitis (label dosing). Purpose: IBD-like gut inflammation not controlled by IL-1/TNF. Mechanism: targeted cytokine or gut-homing blockade. Side effects: infection risks vary by agent. Frontiers

15) Topical corticosteroids for skin/eyes (as prescribed). Purpose: local control with less systemic risk. Mechanism: local cytokine suppression. Side effects: skin atrophy, glaucoma/cataract with ocular overuse. NCBI

16) NSAIDs (e.g., naproxen, ibuprofen; as needed). Purpose: pain/fever relief. Mechanism: COX inhibition lowers prostaglandins. Side effects: GI upset, kidney strain—avoid during dehydration/infection. PMC

17) Rituximab (anti-CD20; infusion). Purpose: selected cases with B-cell–driven autoimmunity or refractory antibody abnormalities. Mechanism: depletes CD20+ B-cells. Side effects: infusion reactions, infections. PMC

18) Ocular biologic adjuncts per ophthalmology (e.g., adalimumab in uveitis). Purpose: vision preservation in severe eye disease. Mechanism: cytokine pathway control. Side effects: infection risk; TB screening. NCBI

19) Proton-pump inhibitor if chronic NSAID use. Purpose: GI protection. Mechanism: reduces gastric acid. Side effects: nutrient malabsorption with long use. PMC

20) Targeted avoidance of G-CSF unless essential. Purpose: recent data suggest G-CSF can drive autoinflammation in APLAID; use only if specialist judges clear benefit. Mechanism: G-CSF primes neutrophils and can worsen inflammation. Side effects: bone pain, potential flare. PMC+1

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Dietary molecular supplements

1. Vitamin D (e.g., 800–2000 IU/day; replete if low). Helps immune balance and bone health; low levels link with worse infections. Mechanism: modulates innate/adaptive immunity. PMC

2. Omega-3 fatty acids (EPA/DHA 1–2 g/day). May reduce inflammatory mediators from neutrophils and macrophages. Mechanism: pro-resolving lipid mediators. PMC

3. Zinc (10–20 mg/day short courses). Supports barrier repair and innate immunity; too much can harm copper status—use with guidance. Mechanism: enzyme cofactor for immune cells. PMC

4. Probiotics (strain-specific; clinician-guided). In colitis-prone patients, certain strains may help gut barrier and symptoms. Mechanism: microbiome modulation. Frontiers

5. Folate + B12 (dose per level). Supports cell turnover and reduces anemia risk when on methotrexate. Mechanism: nucleotide synthesis support. PMC

6. Calcium + vitamin D (per age/sex). Protects bone during steroids and chronic inflammation. Mechanism: improves bone mineral balance. PMC

7. Iron (only if iron-deficient). Corrects anemia from chronic inflammation or GI losses; monitor ferritin and CRP. Mechanism: restores hemoglobin and immunity. Frontiers

8. Oral rehydration salts during flares. Prevents dehydration with fever/diarrhea. Mechanism: sodium-glucose co-transport. Frontiers

9. Multinutrient shakes (dietitian-supervised) during severe colitis. Mechanism: maintains calories and micronutrients when intake is poor. Frontiers

10. Topical vitamin E/ceramide moisturizers for barrier repair. Mechanism: reduces transepidermal water loss and irritation. NCBI

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Immunity-booster / regenerative / stem-cell–oriented” drugs

1. IVIG (replacement immunoglobulin; individualized dosing). Function: supplies protective antibodies the body struggles to make, lowering severe infections. Mechanism: passive humoral immunity; Fc-mediated immunomodulation. Nature

2. Hematopoietic stem-cell transplantation (HSCT) – as a drug-like cellular therapy (specialist decision only). Function: replaces the immune system with donor cells that lack the PLCG2 defect. Mechanism: engraftment of healthy hematopoiesis; considered only for life-threatening, refractory disease. PMC

3. Long-acting IL-1 blockade (canakinumab) can act as “immune-normalizer” by resetting flare frequency and tissue damage. Function: prevents destructive inflammation that erodes immunity. Mechanism: sustained IL-1β neutralization. PMC

4. JAK inhibitors in selected interferon-skewed phenotypes. Function: dampen over-active cytokine networks, letting the immune system function more normally. Mechanism: JAK-STAT signal interruption. PMC

5. Rituximab in B-cell–driven complications. Function: removes aberrant B-cells, reducing autoimmune and inflammatory loops. Mechanism: anti-CD20 depletion. PMC

6. Future PLCG2-targeted therapies (research stage). Function: directly correct overactive PLCγ2 signaling. Mechanism: enzyme or pathway inhibition; concept supported by early PLAID mechanistic data. National Human Genome Research Institute

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Surgeries (why and when)

1. Urgent ophthalmic procedures (e.g., intraocular steroid delivery) when medical therapy cannot control uveitis—goal: prevent permanent vision loss. NCBI

2. Skin surgery/debridement only for severe, infected, or non-healing lesions—goal: remove necrotic tissue and allow healing. NCBI

3. Endoscopic procedures (diagnostic/therapeutic) for severe colitis—goal: confirm diagnosis, control bleeding/strictures. Frontiers

4. Pulmonary procedures (bronchoscopy) when recurrent infections require sampling—goal: targeted antibiotics and airway care. Nature

5. Central line placement (when frequent infusions like IVIG are required)—goal: reliable access, balanced against infection risk. Nature

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Preventions

1. Keep vaccinations up to date (inactivated types) with immunology guidance. Nature

2. Consider IVIG if antibody responses are poor and infections are frequent. Nature

3. Use prophylactic antibiotics only when clearly indicated by specialists. Nature

4. Follow skin care routines to protect the barrier. NCBI

5. Maintain eye follow-up to catch silent inflammation. NCBI

6. Practice respiratory hygiene and airway clearance during colds. Nature

7. Build a flare action plan and keep medicines on hand. ScienceDirect

8. Prioritize sleep and stress management to stabilize immune rhythms. PMC

9. Work with a dietitian for gut-friendly nutrition. Frontiers

10. Avoid unnecessary G-CSF exposure in APLAID unless benefits outweigh risks. PMC

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When to see a doctor

Seek urgent care for vision changes, severe eye pain, chest pain, trouble breathing, very high fever, dehydration, blood in stool, or confusion. These can mean sight-threatening uveitis, pneumonia, severe colitis, or sepsis in an immunodeficient host. Contact your specialist quickly for new blisters, spreading skin infection, persistent diarrhea, recurrent fevers, or more frequent chest infections, because treatment plans may need to change (e.g., move to IL-1 blockade or start IVIG). NCBI+2Nature+2

What to eat / what to avoid

Eat more:
• Lean proteins, fruits, vegetables, whole grains, and omega-3-rich fish—support healing and anti-inflammatory balance. PMC
• Probiotic-containing foods if tolerated (yogurt/kefir) during remission; discuss strains if you have active colitis. Frontiers
• Adequate fluids and oral rehydration during diarrhea or fever. Frontiers

Limit/avoid:
• Ultra-processed foods and high-sugar drinks that can worsen gut symptoms. Frontiers
• Excess alcohol which impairs immunity and interacts with drugs. PMC
• Food triggers you personally notice (keep a log; individual). Frontiers
• Raw/undercooked meats or unpasteurized products when infection risk is high. Nature
• High-dose herbal mixes without medical review—some suppress or overstimulate immunity. PMC
• Excess NSAIDs if you have active GI disease—ask about safer pain plans. PMC
• Grapefruit with calcineurin inhibitors (drug interactions). PMC

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FAQs

1) Is APLAID curable? Not yet. It is manageable with targeted anti-inflammatory drugs, infection prevention, and sometimes IVIG; HSCT is considered only for severe, refractory cases. Nature

2) How is it confirmed? By clinical features plus PLCG2 genetic testing and immune profiling. Frontiers

3) What is the usual age at onset? Often infancy or early childhood, but diagnosis may be delayed. Nature

4) Are cold hives required? No. That is typical for PLAID, not APLAID. MedlinePlus

5) Why do infections keep returning? The body struggles to make strong, specific antibodies; IVIG may help. Nature

6) Which medicines help most? IL-1 blockers (anakinra/canakinumab) are key options; others are added based on organs involved. PMC

7) Is G-CSF helpful for low counts? In APLAID, G-CSF can worsen autoinflammation; use only with expert guidance. PMC

8) Can I get vaccines? Yes—inactivated vaccines are generally encouraged with specialist planning; monitor responses. Nature

9) Will my child outgrow it? It is genetic; severity varies over time but ongoing care is needed. NCBI

10) Can stress or poor sleep trigger flares? They can worsen many autoinflammatory states; good sleep hygiene helps. PMC

11) Is diet a cure? No, but gut-friendly, anti-inflammatory eating supports recovery, especially with colitis. Frontiers

12) Are biologics safe with infections? They increase infection risk; careful screening and monitoring reduce danger. PMC

13) Could family members have it? Yes—autosomal dominant inheritance means first-degree relatives may carry the mutation. NCBI

14) What specialists should I see? Immunology plus organ-specific teams (derm, ophtho, pulm, GI). NCBI

15) What research is new? Recent studies identified novel PLCG2 variants and showed G-CSF can drive APLAID autoinflammation, guiding safer care. ACR Journals+1

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.

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