Day 2 Clinical Insights from the Inaugural RAPIDS Conference at the Hyatt Regency Grand Reserve in San Juan, Puerto Rico
Friday, April 11, 2025
Type 2 Inflammation (Douglas DiRuggiero, PA-C)
- IL-4 is involved in the immune response to parasitic infections and allergic diseases. IL-4 binds to Type 1 receptors on hematopoietic cells to convert Th0 cells into Th2 cells. Promotes B cells to switch class to IgE production. Enhances basophil cytokine production.
- IL-13 increases mucous secretions, increases muscle contraction in the gut, and promotes epithelial barrier repair (enhances IgE, which increases allergic responses. IL-13 also drives M2 macrophages (which help contain parasites and promote tissue repair), enhances eosinophil & mast cell response, AND inhibits Type 1 Immunity (to prevent excessive inflammation- suppresses Th1 and IFN-gamma responses.
- IL-31 induces itching (by activating sensory neurons), regulates inflammation in barrier tissues (by recruiting monocytes and T cells), and has a role in parasitic defense.
Atopic Triad - The Common Connection (Amanda Michaud, PA-C and Peter Lio, MD)
- Patients with Atopic dermatitis will have another atopic condition: ⅓ of patients develop asthma, ⅔ develop allergic rhinitis. Atopic march can occur at any age.
- Allergy can either be Immediate (IgE-mediated = Type I) or delayed (cell-mediated = Type IV). IgE-mediated reactions occur EVERY time the patient is exposed to the allergen, demonstrate IgE antibodies, occur at a predictable time after exposure (usually 10- 60 min), and require sensitization.
- Allergy testing is NOT diagnostic; it stratifies risk. Testing includes: Intradermal testing / Skin Prick (intradermal exposure with allergens, most useful for lower potency allergens, look at the sections of reactions like environmental or drug/food); Immunocap / RAST (Specific IgE testing, when “high or very high” consider referral for immunotherapy)
HS Medical and Surgical Management (Christopher Sayed, MD)
- Treatment of HS should be based on the Hurley Staging: Hurley stage I - Medical treatment, counseling on weight reduction, wound management, avoidance of triggers, tobacco cessation, etc. Hurley Stage II - Medical treatment with Biologics, NdYag laser, Deroofing/ surgical procedures, etc. Hurley Stage III - everything including wide local excision.
- Aggressive medical therapy reduces pain, drainage, and new lesions, BUT tunnels do NOT resolve with medical therapy alone. So use medical management as a bridge to surgery.
- If patients have localized disease, offer localized treatment with ILK and I&D without packing and deroofing. Providers may have to collaborate with Plastic surgeons, general surgeons, or reconstructive urologists for groin/genital lesions.
Beyond Antihistamines - Targeted Therapy in CSU (Amanda Michaud, PA-C)
- Chronic Spontaneous Urticaria= non-inducible, recurrent wheals that last <24 hrs +/- angioedema >/= to 6 weeks
- CSU pathophysiology includes Type 1 autoimmunity (autoallergy) driven by IgE antibodies and Type IIb autoimmunity (autoimmune) induced by IgG autoantibodies. This Type IIb autoimmunity leads to Type 2 inflammatory response, Mast cell and B-cell activation. Other endotypes include concomitant type I and type II b, and NON-type I/II b.
- Up to 30-60% of patients remain uncontrolled despite omalizumab. If they have elevated IgE, it is likely Type I (autoallergic) and will likely be responsive to omalizumab. If NO response to omalizumab within 6 months, cyclosporine 5mg/kg is recommended.
Inflammatory Cytokines in Acne and Rosacea (Hillary Baldwin, MD)
- Etiologies are not fully understood, but both involve innate and adaptive immunity. IL-1beta and TNF-mediated inflammation activate Th1/Th17 cells and the resultant release of cytokines and activation of mast cells.
- Rosacea triggers activate receptors (PAR2 and TLR-2 and channels on cells, which lead to the induction of the inflammasome and release of TNF-alpha, and IL-1.
- Early acne activated sebocytes, and keratinocytes upregulate IL-1b, IL-6(induce differentiation of Th17 cells), IL-12(drives Th1 differentiation), and TGFb. Overproduction of IL-17 and activation of Th17 cells have been shown to underlie the development of acne.
Itch Scratch Cycle - Neuro Immune Pathway (Peter Lio, MD)
- There are two totally separate subtypes of itch-sensitive neurons: Histaminergic neurons and non-histaminergic neurons.
- 4 categories of itch: Dermatologic (eczema, psoriasis), Neuropathic (brachioradial pruritis), Psychogenic (delusions of parasitosis), and Systemic (end-stage renal disease)
- The treatment of itch should be based on etiology. The treatment ladder should include: Topicals, then “safe” systemics, then more powerful systemics, then alternatives (including accupressure, hypnosis, mindfulness, and cryotherapy, to name a few.
Phenotypes in Prurigo Nodularis (Douglas DiRuggiero, PA-C)
- Prurigo Nodularis often has other related comorbidities, most commonly atopic dermatitis, due to the shared Th2 Cytokines: IL-4, IL-5, and IL-13.
- Prurigo Nodularis occurs in all age groups, but the median age =62, NO gender predilection, but in the US, it is ~3 times more common in African Americans.
- The lesions CAUSE itch; they are NOT just the result of picking. There has been an increased number of nerve fibers found in the papillary dermis of PN lesions, and nerve growth factor (NGF) is overexpressed.
Dermato-Allergy Panel - Cases from the Clinic (Marc Serota, MD, Peter Lio, MD, and Amanda Michaud, PA-C)
- For patients with combined Atopic Dermatitis and Asthma, consider Dupilumab first since it has both indications…if not enough clinical improvement it is unlikely that the IL-13s will help. Consider switching to IL-31 or JAK inhibitors for a different mechanism of action.
- There are now multiple ‘non-steroidal’ options for Mild to severe atopic dermatitis that can be used for flares or maintenance. Create an “Eczema Action Plan” with exact steps on when to apply what medications.
- For patients with severe pruritis and increased eosinophils, consider HES: Hypereosinophillic Syndrome. About 50% of cases are idiopathic, but important to exclude secondary cases. Patients need treatment if symptomatic or have signs of end-organ damage. Mepolizumab is an anti-IL-5 monoclonal antibody approved for patients with HES > 6 months for patients 12 and up.