IPP-Gelfand Syndrome (Alopecia–Antibody Deficiency)

IPP-Gelfand syndrome is a very rare immune system condition in which a person has severe hair loss (often total scalp hair loss, “alopecia totalis”) together with a defect in making antibodies. Antibodies are proteins that help us fight germs. Because antibody production is low or absent, people get repeated infections, especially of the ears, sinuses, lungs, and skin. Doctors first described this pattern in the 1970s, and since then it has been recorded as an alias for “alopecia antibody deficiency.” Rare Diseases Information Center+3ScienceDirect+3Monarch Initiative+3

IPP-Gelfand syndrome is a very rare condition first described in 1976 in which a person has both (1) alopecia areata—often severe, up to alopecia totalis (complete scalp hair loss)—and (2) antibody deficiency (a problem making protective antibodies), which leads to recurrent infections. In the first report, three patients had repeated infections plus alopecia; one had classic agammaglobulinemia and the others had milder antibody deficiency. The combination was proposed as a recognizable syndrome by the reporting authors (Ipp & Gelfand). PubMed+1

Subsequent rare-disease summaries classify this entity as a primary immunodeficiency characterized by alopecia areata totalis together with antibody deficiency. These entries emphasize how rare it is and that the literature has remained very limited since that 1976 paper. Orpha+2Rare Diseases Information Center+2

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Other names

• Alopecia–antibody deficiency (the most widely used label). Orpha

• IPP-Gelfand syndrome (eponym from the original authors). Monarch Initiative

• Antibody deficiency with alopecia / Alopecia areata totalis with immunoglobulin deficiency (descriptive phrasing seen in reviews citing the original paper). advancesinpediatrics.org

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Types

Because the published cases are so few, there isn’t an official, fixed “typing” system. Clinicians usually sort patients by how severe the hair loss is and what kind of antibody problem is present:

1. By alopecia pattern

• Patchy alopecia areata (discrete round/oval patches).

• Alopecia totalis (complete scalp hair loss).

• Alopecia universalis (loss of scalp and body hair).
  Alopecia areata across this spectrum is an autoimmune process in which immune cells attack the hair follicle. ScienceDirect+1

2. By antibody deficiency type

• Agammaglobulinemia (e.g., X-linked BTK defect) – very low/absent antibodies, low B cells; alopecia has been reported rarely in this disorder. Orpha

• Common variable immunodeficiency (CVID) – low antibodies and poor vaccine responses; alopecia areata/universalis can occur in CVID. Medscape

• Selective immunoglobulin deficiencies (e.g., IgA deficiency) – occasional cases link AA with IgA deficiency. PMC

• Specific gene-defined CVID-like states (e.g., NFKB2 variants) where B-cell/antibody defects co-exist with autoimmune hair loss. PubMed

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Causes

IPP-Gelfand is best viewed as a clinical label for “alopecia areata + antibody deficiency.” Because it is not a single known gene disorder, “causes” below list conditions and mechanisms that can produce this same combination. Each item briefly explains the link.

1. X-linked agammaglobulinemia (BTK mutations). Profound failure of B-cell maturation → very low antibodies; alopecia totalis has been reported in some patients. Orpha

2. Common variable immunodeficiency (CVID). Reduced Ig levels and poor vaccine responses; AA/AU are recognized autoimmune comorbidities in CVID. Medscape

3. Selective IgA deficiency. Most common primary antibody defect; occasional reports of AA with IgA deficiency. PMC

4. NFKB2-related immune deficiency. Autosomal-dominant defects in non-canonical NF-κB pathway can cause B-cell/antibody deficiency with alopecia. PubMed

5. TACI (TNFRSF13B) mutations. A well-known CVID gene affecting class-switching; can present with hypogammaglobulinemia and autoimmunity. (Mechanism summarized in CVID reviews.) Frontiers

6. BAFF-R (TNFRSF13C) defects. Impaired B-cell survival → low Ig levels; included among CVID-like causes. PMC

7. ICOS deficiency. Impaired T-cell help for B cells → defective antibody responses (CVID phenotype with autoimmunity). PMC

8. CD19 complex defects (CD19, CD81, CD21). B-cell signaling problems → hypogammaglobulinemia/CVID-like disease. PMC

9. AID/UNG (class-switch recombination) defects. Failure to switch antibodies → abnormal Ig pattern and infections. PMC

10. PI3K pathway defects (e.g., PIK3CD “APDS”). Dysregulated B-cell signaling → recurrent infections with antibody dysfunction, often with autoimmunity. PMC

11. PAX5 and other B-cell developmental gene defects. Disrupted B-cell maturation → antibody deficiency. PMC

12. CTLA4 haploinsufficiency / LRBA deficiency. Immune dysregulation syndromes with hypogammaglobulinemia and autoimmunity, which can include AA. PMC

13. Thymic/T-regulatory imbalances that secondarily impair B-cell responses. Some immune-dysregulation disorders produce both antibody failure and autoimmune hair loss. PMC

14. Chronic/recurrent infections in antibody deficiency triggering AA. AA is autoimmune; infections (including viral) can precipitate flares in susceptible people. Cureus

15. COVID-19 as a trigger for AA in someone with antibody problems. AA flares have been reported after infection; this may unmask the alopecia component. PMC+1

16. Family genetic susceptibility to AA plus independent primary antibody defect. AA has strong genetic/immune associations; co-occurrence can reflect two inherited risks. Karger

17. Environmental immune stressors (major illness, stress) acting on a background antibody defect. Such stressors are recognized AA triggers. ScienceDirect

18. Medication-related immune shifts revealing AA in a patient with underlying antibody problems (e.g., JAK/immune-pathway perturbations). Case literature links JAK/immune shifts with AA phenotypes. PubMed

19. Age-related maturation defects (in young children) that uncover a primary B-cell problem early together with AA. Many PIDs present in childhood; AA also often starts young. PMC

20. The original IPP-Gelfand cluster itself (idiopathic). The 1976 cases had recurrent infections plus AA and mild IgG reduction in some—highlighting that not every case maps neatly to a single modern gene label. PubMed

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Symptoms

Because IPP-Gelfand combines alopecia areata (AA) with antibody deficiency, symptoms come from both sides:

1. Round/oval patches of hair loss on the scalp (smooth skin, no scarring). ScienceDirect

2. Rapid spread to complete scalp loss (alopecia totalis) or even body hair loss (alopecia universalis) in severe cases. Karger

3. “Exclamation-mark” hairs and nail pitting/ridging, classic AA clues on exam. ScienceDirect

4. Eyebrow/eyelash thinning and beard involvement (in older children/adults). ScienceDirect

5. Psychosocial distress (anxiety, low mood) from visible hair loss—well documented in AA. JAMA Network

6. Frequent colds, sinus infections, or ear infections, often starting in childhood. Medscape

7. Recurrent bronchitis or pneumonia due to poor antibody defenses. Medscape

8. Chronic cough or wheeze, sometimes evolving to bronchiectasis if infections are repeated/untreated. PMC

9. Chronic or recurrent diarrhea, possible malabsorption (seen in some antibody deficiencies). Medscape

10. Skin infections/boils or impetigo, reflecting reduced antibody-mediated protection. PMC

11. Enlarged lymph nodes or absent tonsils (e.g., very small tonsils can be a clue in agammaglobulinemia). Orpha

12. Poor growth or “failure to thrive” when infections are frequent in childhood. PMC

13. Autoimmune companions (thyroid disease, vitiligo) that may travel with AA and with some CVID-like disorders. JAMA Network

14. Fatigue during/after infections and from the emotional load of AA. JAMA Network

15. Treatment-related symptoms (for example, after vaccines some patients with antibody defects don’t make protective titers and keep getting infections). AAAI

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Diagnostic tests

The goal is to confirm AA, prove an antibody problem, and look for complications of recurrent infection. These are the most commonly used, evidence-based tests and tools.

A) Physical examination

1. Full scalp and body hair exam. Looks for the pattern/severity of AA (patches, totalis, universalis) and signs like exclamation-mark hairs. ScienceDirect

2. Nail inspection. Nail pitting/ridging supports AA. ScienceDirect

3. ENT exam. Checks for ear fluid, sinus tenderness, tonsil size—clues to chronic/recurrent infections and possible agammaglobulinemia (small/absent tonsils). Orpha

4. Chest and respiratory exam. Listen for crackles/wheezes suggesting lower-airway infections or bronchiectasis. PMC

5. Growth chart and lymphoid organ check. Tracks growth, checks lymph nodes and spleen (some PIDs show splenomegaly or small nodes/tonsils). PMC

B) “Manual” bedside tests

6. Hair-pull test. Gentle traction at the margin of a patch; if many hairs come out, disease is active. (Standard AA bedside test.) ScienceDirect

7. Hair-tug test for fragility. Helps differentiate AA from hair-shaft fragility disorders. ScienceDirect

8. Combed-hair count at home. Low-tech way to monitor shedding between visits in active AA. ScienceDirect

C) Laboratory & pathological tests

9. Quantitative immunoglobulins (IgG, IgA, IgM ± IgE). Core screen for antibody deficiency; compare with age-matched ranges. PMC

10. Specific antibody titers to vaccines (e.g., tetanus protein and pneumococcal polysaccharide), pre- and post-booster, to test antibody function. annallergy.org+1

11. B-/T-/NK-cell immunophenotyping (flow cytometry). Measures CD19+ B cells and other lymphocyte subsets; very low B cells suggest agammaglobulinemia; normal counts with poor function suggest CVID. PMC

12. Complete blood count (CBC) with differential, ESR/CRP. Screens for infection/inflammation and cytopenias. PMC

13. Autoimmune panels as guided (e.g., thyroid-stimulating hormone and anti-TPO antibodies; sometimes ANA) because AA often coexists with autoimmune disease. JAMA Network

14. Microbiology as needed (sputum, sinus or ear cultures; stool studies if chronic diarrhea) to direct antibiotics. PMC

15. Genetic testing (targeted PID/CVID panels including BTK, NFKB2, TNFRSF13B/TACI, TNFRSF13C/BAFF-R, ICOS, CD19 complex, etc.) to define a molecular cause when possible. PMC+1

D) Electrodiagnostic/functional instrument tests

16. Spirometry (lung function). Recurrent chest infections can cause airflow obstruction; spirometry quantifies impact and tracks bronchiectasis-related changes. PMC

17. Pure-tone audiometry. Repeated ear infections may reduce hearing; audiometry documents deficits and guides ENT care. PMC

E) Imaging and device-assisted visualization

18. Dermoscopy/trichoscopy of the scalp. Noninvasive magnified look for AA features (yellow dots, black dots, broken hairs). ScienceDirect

19. Chest imaging (start with chest X-ray; escalate to high-resolution CT if recurrent pneumonia or suspected bronchiectasis). PMC

20. Sinus CT when chronic sinusitis is suspected (helps ENT plan treatment). PMC

Why these tests? Allergy/immunology guidelines emphasize starting with immunoglobulin levels, vaccine responses, and lymphocyte phenotyping, then adding targeted studies and genetics; dermatology tools (exam, hair-pull, trichoscopy) establish the AA component. annallergy.org+1

Non-pharmacological Treatments (therapies and others)

Goal: reduce infections, protect lungs and sinuses, support skin/hair, and improve quality of life.

1. Infection-prevention plan: hand hygiene, cough etiquette, masks in crowded settings, early culture-guided care.

2. Vaccination of household contacts: keeps germs from reaching the patient; avoid oral polio and other live vaccines in close contacts if advised by the specialist. Immunodeficiency UK

3. Food-safety routine: safe water, thoroughly cooked meat/eggs, pasteurized dairy; avoid buffets/raw sprouts.

4. Airway care bundle: saline nasal rinses, nasal steroid for rhinitis, chest physiotherapy as needed.

5. Dental and sinus hygiene: regular dental care; treat sinus disease promptly.

6. Allergen control: reduce dust, smoke, and pollutants at home.

7. Sleep optimization: 7–9 hours; regular schedule (supports immune function).

8. Stress-reduction program: mindfulness, CBT skills, or yoga to reduce alopecia flares.

9. Exercise plan: moderate aerobic activity most days; avoid over-training during infections.

10. Skin-barrier care: gentle cleansers, emollients; protect from irritants to reduce secondary infection.

11. Scalp camouflage options: fibers, micro-pigmentation, or wigs to reduce psychosocial distress.

12. Sun protection of scalp/face: hats, sunscreen on exposed areas.

13. Humidification and hydration: thin mucus; may reduce cough.

14. Action plan at first signs of infection: fever threshold, when to seek cultures/antibiotics.

15. Home infusion training (for SCIG users): safe technique, infusion logs. Immune Deficiency Foundation

16. Pulmonary rehabilitation if bronchiectasis develops.

17. Dermatology behavioral tips for alopecia areata: avoid tight hairstyles/harsh treatments; gentle detangling.

18. Peer/mental-health support: hair loss can be emotionally hard; counseling and support groups help.

19. Travel planning: vaccines for companions, antibiotics to carry, insurance info.

20. Smoking cessation and secondhand smoke avoidance.

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Drug Treatments

Doses below are typical references; individual dosing must be set by the treating clinician based on age, weight, kidney/liver function, drug interactions, and regional guidance.

Core immune therapy

1. Immunoglobulin replacement (IVIG) – 400–600 mg/kg every 3–4 weeks; reduces frequency and severity of infections. Mechanism: provides pooled IgG antibodies the patient lacks. Common effects: headache, infusion reactions (usually mild, slow the rate/pretreat if needed). AAAI+2PMC+2

2. Subcutaneous IG (SCIG) – typically 100–200 mg/kg weekly (or equivalent monthly dose split into weekly/biweekly infusions). Similar benefits with steadier IgG levels; local site reactions are common and usually mild. BioMed Central+1

Antimicrobials (used to treat or prevent infections; examples only)

3. Amoxicillin for acute bacterial sinusitis/otitis (dose per local guideline). Mechanism: cell-wall inhibition. Side effects: GI upset, rash.

4. Amoxicillin–clavulanate for β-lactamase producers in sinus/lung infections.

5. Azithromycin (e.g., 250–500 mg three times weekly) as prophylaxis in selected bronchiectasis patients; mechanism: antibacterial + anti-inflammatory macrolide effects; side effects: GI upset, QT prolongation risk.

6. Trimethoprim–sulfamethoxazole for skin/airway infections; watch for sulfa allergy, cytopenias.

7. Fluoroquinolones (e.g., levofloxacin) for severe pneumonia when needed; reserve due to tendinopathy/CNS effects.

8. Acyclovir/valacyclovir if HSV/VZV occurs; mechanism: viral DNA polymerase inhibition.

9. Fluconazole if Candida infections recur.

Hair-focused therapy (local and systemic)

10. Topical clobetasol 0.05% (scalp) in cycles – reduces autoimmune inflammation; side effects: skin thinning if overused.

11. Intralesional triamcinolone acetonide (2.5–10 mg/mL every 4–6 weeks) for active patches; side effects: local atrophy if too concentrated/superficial.

12. Topical minoxidil 5% twice daily – mechanism: lengthens anagen phase; side effects: irritation, unwanted facial hair.

13. Anthralin (dithranol) short-contact therapy – induces low-grade irritation to reset immune activity; side effects: staining, irritation.

14. Contact immunotherapy (DPCP or SADBE) by dermatology – controlled allergic reaction may prompt regrowth; side effects: dermatitis; requires expert supervision.

Systemic JAK inhibitors for severe alopecia areata

15. Baricitinib (Olumiant®) – 2 mg once daily; may increase to 4 mg if response inadequate. Mechanism: JAK1/2 inhibition; boxed warnings: serious infections, MACE, malignancy, thrombosis. FDA Access Data+1

16. Ritlecitinib (Litfulo®) – 50 mg once daily in adults/adolescents ≥12 y; mechanism: JAK3/TEC family inhibition; similar serious infection warnings. litfulo.pfizerpro.com+1

17. Deuruxolitinib (Leqselvi™) – 8 mg twice daily for adults with severe AA; same class warnings; monitor CBC/lipids/LFTs and infection risk. FDA Access Data+1

Important: In a patient who already has an immune-system deficit, systemic JAK inhibitors can further raise infection risk. Use only after specialist risk–benefit discussion and required screening (TB/hepatitis, CBC, lipids), with ongoing monitoring. Veterans Affairs

Other systemic agents sometimes used for alopecia areata

18. Short oral corticosteroid tapers for sudden, extensive shedding (bridge only; avoid long-term use due to immunosuppression).

19. Methotrexate (low-dose weekly) as a steroid-sparing option in selected cases; side effects: hepatotoxicity, cytopenias; folate supplementation needed.

20. Cyclosporine in refractory cases; side effects: hypertension, nephrotoxicity; generally avoided in frequent-infection phenotypes.

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Dietary “Molecular” Supplements

1. Vitamin D (correct deficiency; immunomodulatory) – typical repletion then 800–2000 IU/day maintenance per labs.

2. Zinc (short courses if deficient; supports epithelial and immune function).

3. Iron (if ferritin low) – hair growth and energy; avoid over-supplementing.

4. Biotin (only if true deficiency; otherwise routine use has little evidence).

5. Omega-3 fatty acids (anti-inflammatory; may help skin barrier).

6. Protein optimization (whey/pea protein if dietary intake is low).

7. Vitamin B12/folate (replete if low).

8. Selenium (thyroid/antioxidant; avoid high doses).

9. Probiotics: avoid without clinician approval in significant immunodeficiency due to rare bacteremia/fungemia risk.

10. Collagen peptides (hair/skin support; evidence limited; safe in moderation).

Always coordinate supplements with your clinician, especially if you use JAK inhibitors or other immunomodulators that have drug–nutrient interactions.

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Regenerative / stem-cell” therapies

1. Hematopoietic stem-cell transplantation (HSCT) – not routine for isolated antibody deficiency (e.g., XLA) because immunoglobulin replacement works well; considered only in exceptional, severe, refractory situations (e.g., life-threatening complications) at expert centers. Risks include transplant-related mortality and graft-versus-host disease. PMC+1

2. Gene therapy/editing for BTK-related disease – investigational; promising pre-clinical and early translational work shows B-cell development can be restored in models, but clinical availability is not here yet. Patients may be able to enroll in trials in the future. ScienceDirect+1

3. Facilitated high-volume SCIG (hybrid hyaluronidase-assisted) – not a “regenerative” drug but a modern way to deliver IgG less often with steady levels; improves quality of life for some. Immune Deficiency Foundation

4. G-CSF or GM-CSF – not standard for this syndrome (used for neutropenia, not antibody deficiency); may appear in edge cases if neutrophils are low for other reasons.

5. Biologic “immune boosters” sold online – avoid; no evidence and potential risks in PID.

6. Thymic or stem-cell “boosters” marketed direct-to-consumer – avoid outside trials; not proven and may be dangerous.

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 Surgeries/Procedures

1. Tympanostomy tubes for recurrent/persistent middle-ear effusions to protect hearing.

2. Functional endoscopic sinus surgery if maximal medical therapy fails for chronic rhinosinusitis.

3. Bronchiectasis procedures (rare): localized lobectomy only in severe, focal, refractory disease.

4. Venous access device (port) for IVIG if peripheral access is impossible (SCIG often avoids this).

5. Cosmetic scalp/eyebrow procedures (e.g., micro-pigmentation, microblading): appearance support; hair transplantation is usually not effective in active alopecia areata.

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Preventions

1. Keep IG therapy consistent (no missed cycles). AAAI

2. Early treatment of infections; don’t “watch and wait” if fever or chest symptoms start.

3. Vaccinate family/close contacts with inactivated vaccines; avoid live oral polio in close contacts per specialist advice. Immunodeficiency UK

4. Avoid live vaccines in the patient when there is significant antibody deficiency (specialist to decide). CDC+1

5. Food safety and safe drinking water.

6. No smoking exposure.

7. Regular dental and sinus care.

8. Annual flu and COVID-19 boosters as advised (inactivated platforms). CDC

9. Hand hygiene + masks during outbreaks/crowds.

10. Maintain fitness, sleep, and stress control (supports immune resilience).

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When to see doctors (red flags)

• Fever ≥38.3 °C (101 °F) or fever lasting more than 24 hours.

• Breathing trouble, chest pain, or new low oxygen.

• Persistent ear pain, sinus pain, or drainage despite treatment.

• Bloody sputum or weight loss.

• Severe headache, stiff neck, confusion (possible CNS infection in profound hypogammaglobulinemia).

• Rapid, widespread hair loss (consider prompt dermatology visit).

• Before starting ANY immunosuppressive drug (e.g., JAK inhibitor).

• If you are pregnant or planning pregnancy (live-vaccine and medication planning).

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What to eat and what to avoid

Eat more of: well-cooked lean proteins (fish, chicken, eggs), legumes, whole grains, colorful fruits/vegetables, nuts/seeds (if no allergy), yogurt only if clinician approves probiotics for you, and healthy oils. Aim for adequate protein and vitamin D, iron, and zinc through food and monitored supplements.

Limit/avoid: raw or undercooked meats/eggs/seafood; unpasteurized milk/cheese; deli meats unless reheated; buffets/salad bars with poor temperature control; high-sugar ultra-processed snacks; alcohol and tobacco; over-the-counter “immune boosters” that are unregulated; live-culture supplements (probiotics) unless your immunologist approves, because rare bloodstream infections can occur in immunodeficiency.

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Frequently Asked Questions

1) Is IPP-Gelfand syndrome a separate disease?
It’s best understood as a historical label for the combination of alopecia and antibody deficiency. Today, clinicians try to pinpoint the exact immune defect (for example, X-linked agammaglobulinemia) and then treat by modern guidelines. ScienceDirect+1

2) Is there a cure?
For most people with antibody deficiency, no permanent cure yet. IG replacement is the backbone of care. HSCT is not routine for isolated antibody deficiency; gene therapy is experimental but promising. AAAI+2PMC+2

3) Will hair grow back?
Sometimes yes. Alopecia areata can spontaneously remit, respond to local treatments, or, in severe cases, systemic JAK inhibitors may help. Results vary and must be balanced against infection risks in immunodeficiency. FDA Access Data+2FDA Access Data+2

4) Are JAK inhibitors safe if I already have a weak immune system?
They increase infection risk and carry boxed warnings. Use only with a specialist, after screening, and with close monitoring. Veterans Affairs

5) Do I need lifelong IG therapy?
If you have a fixed primary antibody deficiency, yes, IG is generally lifelong and individualized to keep you well. AAAI

6) Can I get vaccines?
Inactivated vaccines are usually recommended; live vaccines are generally avoided in significant antibody deficiency. Household contacts should be fully vaccinated with non-live options where relevant. Always follow your immunologist’s plan. CDC+1

7) What about diet and vitamins?
Correct deficiencies (vitamin D, iron, zinc). Avoid unpasteurized foods. Discuss any supplement with your clinician.

8) Can stress make hair loss worse?
Stress can trigger or worsen alopecia areata; stress-management can help.

9) Will I pass this to my children?
Some immune defects are inherited (e.g., BTK is X-linked). Genetics counseling helps define risks. Wikipedia

10) Can I exercise?
Yes—moderate, regular exercise supports lung health and mood; rest during active infections.

11) Should I avoid crowds?
During outbreaks or when you’re unwell, masks and spacing are sensible.

12) What if IVIG gives me headaches?
Infusion-rate adjustments, hydration, split dosing, or switching products often solve this. Your team can help.

13) Is SCIG better than IVIG?
Both work. SCIG gives steadier levels and home convenience; IVIG is less frequent. Choice depends on your lifestyle and medical factors. Immune Deficiency Foundation

14) Can antibiotics be used to prevent infections?
Sometimes, yes (e.g., macrolides in bronchiectasis), but plans are individualized to avoid resistance.

15) Who should coordinate my care?
An immunologist and a dermatologist, with support from ENT, pulmonology, and primary care.

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 13, 2025.

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