Reclassifying MCS and MCAS: Toward Multi-Chemical and Environmental Hypersensitivity Disorders (MCEHD)

I live with both Multiple Chemical Sensitivity (MCS) and Mast Cell Activation Syndrome (MCAS). These conditions were never separate in my body. I flare when exposed to perfume, mold spores, tap water, or cleaning agents, and I stabilize when I gain control of air and environment, as patient communities have long reported (Ziem & McTamney, 1997; Gibson, 2014). To me, the distinction has always been artificial, created in journals and policy debates, not in lived experience (Ashford & Miller, 1998; Steinemann, 2018).

I arrived at this understanding through two traditions. One was inheritance, survival knowledge passed from generations of chemically sensitive patients, shared quietly in newsletters, patient networks, and websites like Seriously Sensitive to Pollution (2010) when mainstream medicine dismissed us (Caress & Steinemann, 2004; Gibson et al., 2016). The other was invention, frameworks I created out of necessity, turning survival hacks into structured, reproducible methods that could be tested, taught, and scaled (Adinig, 2025).

I inherited the Corsi–Rosenthal box design (Dal Porto & Corsi, 2022; Gasparrini & Rosenthal, 2022), the practice of off-gassing new items outdoors, the use of distilled or mineral-free water for cooking and cleaning, and the distinction between “fragrance-free” and “unscented” (Gibson, 2014). I learned to use rubbing alcohol to strip residues off my skin when tap water provoked reactions, a practice echoed in patient forums (Chemical Sensitivity Network, 1998). These patient-shared strategies taught me that environmental illness was manageable with careful experimentation (Sears, 2007).

I also invented. Out of crisis, I created the N95 Environmental Trigger Protocol™ (NET Protocol™), a 72-hour clean-air challenge to reveal environmental flare origins (Adinig, 2025). I developed the Carbon-Layer Method™, sandwiching an N95 with a carbon filter mask to block particulates and volatile organic compounds (VOCs) (Adinig, 2025). When HVAC filters were unavailable, I devised the VentSeal™ Hack, gluing N95s across vents for improvised filtration (Adinig, 2025). For clean air on the road, I created the HEPA-Onboard™ System, powering a full-size HEPA purifier in my car with a camping inverter, outperforming weak “car purifiers” (Adinig, 2025).

This white paper weaves inheritance and invention into one continuum. It argues that MCS and MCAS are vantage points on a shared hypersensitivity terrain, proposing a new classification, Multi-Chemical and Environmental Hypersensitivity Disorders (MCEHD), that unites them, honors patient ingenuity, and formalizes my frameworks. By drawing on voices across disciplines and regions, this view underscores universal threads, reminding us that healing begins with recognizing what patients endure (Steinemann, 2019; National Academies, 2024).

The goal is practical. Honor the lineage of patient ingenuity. Formalize the frameworks I built. Give clinicians, researchers, and policymakers one map to follow.

This Is Not New Biology. It Is New Clarity.

I am not introducing a new organ or a new cell type. I am drawing a clearer map. For seventy years patients and a handful of clinicians have described the same pattern from different angles. Environmental illness and chemical intolerance in one corner. Mediator storms and MCAS in another. Dysautonomia and post-viral collapse in another. Classic autoimmunity when mis-targeting sets in. The biology has been in plain sight. Mast cells guard the gates. Cytokines carry the messages. Barriers fail. Metabolism buckles. What is new here is the systematization. I am organizing the survival knowledge I inherited and the methods I invented into one terrain model, MCEHD within IACC, so medicine and policy can stop treating these as oddities and start treating them as a single, navigable domain.

Historical Context: How Politics Bent Classification

The story begins in the 1950s, when allergist Theron Randolph documented multisystem illness from low-level chemical and food exposures, naming it environmental illness (Randolph, 1956; Randolph, 1962). In Human Ecology and Susceptibility to the Chemical Environment (1962), he detailed fatigue, cognitive fog, and systemic flares, dismissed as psychosomatic (Ashford & Miller, 1991; Ziem & McTamney, 1997). By 1965, he founded the Society for Clinical Ecology, a haven for physicians validating patient experiences despite industry pushback (Randolph, 1965; Sears, 2007).

In 1987, Mark Cullen formalized Multiple Chemical Sensitivity (MCS) in the Journal of Occupational Medicine, tying it to workplace exposures and lending industrial legitimacy (Cullen, 1987; Kreutzer et al., 1999). Patient reports in the Environmental Illness Archives (1990) echoed Randolph’s findings, noting solvent-triggered flares mimicking later MCAS patterns (Gibson, 2014).

Recognition sparked resistance. Chemical manufacturers, fearing liability from links to solvents or

consumer products, lobbied against MCS’s biological framing (Ashford & Miller, 1998; Caress & Steinemann, 2004). Occupational health guilds joined the pushback (Donnay, 1999). In 1996, a World Health Organization workshop, led by Wolf, reframed MCS as “Idiopathic Environmental Intolerance,” erasing “chemical” to dodge industry threats (Wolf, 1996; IPCS/WHO, 1996; Genuis, 2010). Patient groups like the Chemical Sensitivity Network (1998) protested this political reclassification (Gibson et al., 2016).

In the 2000s and 2010s, mast cell biology advanced. Metcalfe et al. (1997) and Krishnaswamy et al. (2001) observed mediator flares—flushing, tachycardia, gut instability, neurological symptoms—in non-mastocytosis patients. Lawrence Afrin defined this as Mast Cell Activation Syndrome (MCAS), with criteria based on mediator levels, symptom clusters, and therapy response (Afrin, 2013; Molderings et al., 2011). Valent et al. (2012, 2020) standardized MCAS diagnostics, distinguishing clonal from non-clonal forms, while the Mastocytosis Society (2015) reported chemical sensitivities overlapping MCS (Cardet et al., 2013).

MCAS gained traction because mediators like histamine and tryptase were measurable, unlike MCS, which remained stigmatized (Pall, 2003; Dantoft et al., 2015). Patient advocates in Seriously Sensitive to Pollution (2010) documented shared triggers, perfumes, mold, chemicals—bridging MCS and MCAS (Gibson, 2014).

The COVID-19 pandemic shifted the landscape. Millions with Long COVID developed hypersensitivity, cytokine dysregulation, and delayed flares indistinguishable from MCS and MCAS (Low et al., 2023; Akrami et al., 2023; Seneviratne et al., 2023). The Solve ME/CFS Initiative (2023) and patient forums reported overlapping symptoms—chemical intolerance, fatigue, autonomic crashes—pushing mediator instability into focus (Steinemann, 2018). Theoharides et al. (2024) and Yong et al. (2024) highlighted SARS-CoV-2 exacerbating or mimicking MCAS, with immunological dysfunction mirroring chemical intolerance (Miller et al., 2024). The Bateman Horne Center (2025) amplified this, revealing shared inflammatory pathways and mast cell hyperactivity, urging unification (Komaroff et al., 2024).

The historical arc is clear: patients experienced one syndrome, split by liability, politics, and silos. Randolph’s insights (1956), patient networks (1990–2010), and post-COVID research (2023–2025) show MCS and MCAS as a shared terrain, backed by global consensus on mast cell disorders (Valent et al., 2020; National Academies, 2024).

The Biology That Unites MCS and MCAS

Mast cells, stationed at barrier surfaces, skin, airway, gut, vasculature, misfire in MCS and MCAS, unable to distinguish perfume, mold, or viral fragments (Metcalfe et al., 1997; Galli et al., 2016; Theoharides et al., 2024). The result is a mediator storm rippling across systems (Krishnaswamy et al., 2001; Frossi et al., 2017).

Histamine drives flushing, itching, tachycardia, and gastric instability (Maintz & Novak, 2007). Leukotrienes constrict airways, amplifying asthma-like symptoms (Ersoy et al., 2008). Prostaglandins provoke migraines and sensitize pain pathways (Kowalski et al., 2015). Cytokines like IL-6, IL-8, TNF-α, and IL-33 fuel systemic inflammation, causing fatigue, cognitive dysfunction, and poor healing (Nurieva & Chung, 2010; Brown et al., 2013). These mediators explain the multisystem flares of MCS and MCAS, as confirmed by the Mastocytosis Society (2015) and Chemical Sensitivity Network (2018) (Cardet et al., 2013; Steinemann, 2019).

The 36–72-hour flare delay, long noted by patients, is validated by studies showing mediator release kinetics (Theoharides et al., 2024; Low et al., 2023). Neuroimmune amplification via glial cells magnifies pain and fatigue, while mitochondrial dysfunction lowers trigger thresholds (Pall, 2003; Frossi et al., 2017). Mast cells link environmental triggers to inflammation through FcεRI receptors (Galli et al., 2016; Brown et al., 2013).

Genetic investigations reveal single-nucleotide polymorphisms (SNPs) tied to chemical intolerance, overlapping with MCAS dysregulation (Bock & Köhle, 2005; Miller et al., 2024). Environmental Health Perspectives (1997) and Toxicology (2005) report SNPs amplifying environmental responses, supporting MCS and MCAS as unified hypersensitivity syndromes (Ziem & McTamney, 1997; Genuis, 2010).

The IACC Terrain: Three Branches of Immune Dysfunction

Infection-Associated Chronic Conditions (IACC) are a terrain—a broken immune landscape with multiple end states. Patients often move between or live with multiple branches, differing not in root cause but in dominant dysfunction (Komaroff et al., 2024; National Academies, 2024; Bateman Horne Center, 2025).

1. The Autoimmune Branch: Mis-Targeting Autoimmune diseases involve autoantibodies and autoreactive T cells attacking thyroid, pancreas, joints, or connective tissue, causing irreversible damage. Lupus, Hashimoto’s, type 1 diabetes, rheumatoid arthritis, and Sjögren’s are examples. Infections like EBV, CMV, and SARS-CoV-2 trigger autoreactive clones (Proal & VanElzakker, 2021; Seneviratne et al., 2023).

2. The Mast-Cell Hypersensitivity Branch: Mis-FiringI n MCAS, MCS, and related syndromes, mast cells misinterpret perfumes, mold, food proteins, or sweat as threats, unleashing mediator storms—histamine, leukotrienes, prostaglandins, cytokines—without cumulative tissue damage (Afrin, 2013; Theoharides et al., 2024; Miller et al., 2024). Flares are systemic but reversible with trigger removal or stabilizers (Valent et al., 2020).

3. The Neuroimmune/Autonomic Branch: Mal-Adapting In ME/CFS, Long COVID, POTS, and dysautonomias, cytokine imbalance, mitochondrial stress, and autonomic instability drive crashes, post-exertional malaise, and metabolic shutdown. Unlike autoimmunity, damage is not structural; unlike hypersensitivity, it’s not just mediators. It’s systemic mis-calibration post-infection (Low et al., 2023; Yong et al., 2024).

A Shared Pathophysiology

All three branches emerge from the same fractured terrain:

• Cytokine instability priming overreaction (Nurieva & Chung, 2010; Low et al., 2023).

• Barrier dysfunction in gut, airway, and vasculature (Brown et al., 2013; Theoharides et al., 2024).

• Chronic inflammatory signaling that persists (Komaroff et al., 2024).

• Metabolic stress lowering reactivity thresholds (Frossi et al., 2017; Pall, 2003).

The differences are in end result, not origin:

• Autoimmune: mis-targeting and destruction.

• Mast-cell hypersensitivity: mis-firing and mediator storms.

• Neuroimmune/autonomic: mal-adaptation and shutdown.

Why This Matters for Classification

This model explains why patients cross categories. A lupus patient may flare to perfumes; a Long COVID patient may develop autoimmune markers and mast-cell reactivity (Seneviratne et al., 2023; Yong et al., 2024). Medicine’s silos are branches of one root system (National Academies, 2024).

Patients have named these overlaps for decades. Since the 1990s, MCS communities described flares mirroring MCAS, while ME/CFS and POTS patients linked post-viral crashes to hypersensitivity, especially among women and underserved groups facing dismissal (Chemical Sensitivity Network, 1998; Gibson et al., 2016; Yates et al., 2024).

Researchers like Miller (1997) and Theoharides et al. (2024) unified MCS and MCAS via toxicant-induced loss of tolerance (TILT) and mast cell hyperactivity, with 60% of MCAS patients reporting chemical intolerance (Miller et al., 2024).

Komaroff et al. (2024) and the National Academies (2024) defined IACC to include Long COVID, ME/CFS, POTS, and MCAS, rooted in cytokine instability and barrier dysfunction.

The CDC Foundation (2025) and Bateman Horne Center (2025) urge studying these overlaps, amplifying patient insights with science (Solve ME/CFS Initiative, 2023). MCEHD builds on this, merging the why (ending gaslighting) with the where (reclassified systems for equity).

By situating autoimmune disease within IACC alongside MCAS/MCS and dysautonomia, we validate patient knowledge as interdependent expressions of one terrain, paving the way for classifications that protect the vulnerable (Steinemann, 2019; Komaroff et al., 2024).

Inherited Survival Knowledge

When medicine abandoned chemically sensitive patients, we built archives. From Randolph’s disciples to newsletters and online communities like Seriously Sensitive to Pollution (2010), survival practices grew (Gibson, 2014; Sears, 2007). I inherited:

• Corsi–Rosenthal boxes, low-cost purifiers rivaling HEPA towers (Dal Porto & Corsi, 2022; Gasparrini & Rosenthal, 2022).

• Rubbing alcohol to strip skin residues when tap water provokes reactions (Chemical Sensitivity Network, 1998).

• Off-gassing new items outdoors (Gibson, 2014).

• Using distilled or mineral-free water for cooking and cleaning (Ziem & McTamney, 1997).

• Distinguishing “fragrance-free” from “unscented” labels (Gibson, 2014).

These were survival guides, honed by lived experience, not medical guidelines. Patient innovations also include avoiding scented products or pesticides, as noted in environmental health resources (Peden, 2019; Pizzorno, 2016). Functional medicine emphasizes trigger identification via elimination diets or environmental audits, reflecting community knowledge (Genuis et al., 2013).

Invented Survival Frameworks

I invented structured methods from necessity (Adinig, 2025):

• N95 Environmental Trigger Protocol™ (NET Protocol™): A 72-hour clean-air challenge using N95s to reveal environmental flare origins, scalable for patients, clinicians, and researchers.

• Carbon-Layer Method™: Sandwiching an N95 with a carbon mask to capture particulates and VOCs, bridging MCS and MCAS.

• VentSeal™ Hack: Gluing N95s across vents for emergency filtration when HVAC filters are unavailable.

• HEPA-Onboard™ System: Powering a full-size HEPA purifier in a car with a camping inverter, outperforming “car purifiers.”

These frameworks, born from lived experience, align with patient-driven adaptations like personalized detoxification or sensory management in naturopathic care (Genuis, 2010; Pizzorno, 2016).

The NET Protocol™ in Depth

The NET Protocol™ holds air dose steady to reveal delayed hypersensitivity (Adinig, 2025). Patients wear an N95 for 72 hours, journaling symptoms. Clinicians can pair it with vitals, peak flow, or mediator labs. Researchers can design crossover trials with sham conditions and delayed biomarker endpoints.

Why 72 hours? Mast-cell flares emerge 36–72 hours post-exposure (Theoharides et al., 2024; Low et al., 2023). Why N95s? They block 95% of particulates without hypoxia, even in asthma populations (Neupane et al., 2022).

Why carbon? VOCs pass particle filters but are adsorbed by carbon (Adinig, 2025). Why DIY? Corsi–Rosenthal boxes rival commercial HEPA systems (Dal Porto & Corsi, 2022). NET turns anecdote into structure, aligning with calls for evidence-based patient tools (Genuis et al., 2013).

Cultural and Global Lens

Culture shapes adoption. In East Asia, masks are normalized for pollen, pollution, and infection, making NET seamless (Bousquet et al., 2017). In the U.S., masks are politicized, coded as weakness (Yates et al., 2024). In Europe, occupational medicine offers a pathway for MCEHD (D’Amato et al., 2015). In low-resource countries, DIY methods like Corsi–Rosenthal boxes are frontline care (Gasparrini & Rosenthal, 2022). MCS affects diverse populations globally, with women comprising a majority, and evidence increasingly supports biological over psychogenic models (Steinemann, 2019; Miller et al., 2024).

Cost Comparison of Filtration Strategies

Filtration Method	Upfront/Replacement Cost	Monthly Running Cost	Notes & Use Case
Respro Allergy/Chemical-Particle Filters	~$12–15 per filter (twin pack)	Negligible (replace when saturated)	Portable VOC/fragrance control; pairs with N95 for dual-layer filtration (Bousquet et al., 2017).
Portable HEPA Air Purifier (Small/Medium)	~$100–200 per unit	Electricity: $3–10; Filters: $20–60/year	Single-room particulate control; limited VOC capture without carbon (Peden, 2019).
Large/Whole-House HEPA Systems	$300–2,000+	Electricity: $10–20; Filters: $50–200/year	Continuous large-space coverage; resource-intensive (Pizzorno, 2016).
Corsi–Rosenthal (CR) Box DIY	$60–120 in materials	Electricity: $1–3; Filters: ~$30–70/year	High-performance, low-cost particulate clearance; community-validated (Dal Porto & Corsi, 2022).

Key Insights: Respro filters offer low-cost protection; HEPA units excel for background filtration but incur high replacement costs; whole-house systems are inaccessible for many; CR boxes democratize access (Gasparrini & Rosenthal, 2022; Peden, 2019).

CYNAERA Position: Layered strategies (Respro + N95, CR Box, HEPA if affordable) balance cost and accessibility across MCEHD (Adinig, 2025).

Therapeutic Ladder and the Logic of Repurposing

MCEHD interventions interrupt the mast-cell mediator cascade (Theoharides et al., 2024):

• Antihistamines: H1 blockers (cetirizine, fexofenadine) calm dermal/neurologic symptoms; H2 blockers (famotidine) stabilize gastric reactivity (Kowalski et al., 2015).

• Stabilizers: Cromolyn sodium, used in asthma, works orally or nebulized for systemic symptoms; ketotifen blurs antihistamine/stabilizer roles (Wouters et al., 2010).

• Leukotriene/Prostaglandin Control: Montelukast reduces stress-induced mast-cell activation; zileuton blocks 5-LO but needs liver monitoring; low-dose aspirin calms prostaglandin D2 flares (Ersoy et al., 2008).

• Biologics: Omalizumab dampens IgE-mediated cascades (Berry et al., 2019).

• JAK Inhibitors: Tofacitinib reverses severe MCAS in case reports (Afrin, 2017).

• Neuroimmune Modulators: Low-dose naltrexone stabilizes glial activation, reduces pain, and raises thresholds (LDN Research Trust, 2023).

Repurposing targets the hypersensitivity cascade mechanistically, with global variations favoring mediator blockers or lifestyle adjustments based on access (Bousquet et al., 2017; D’Amato et al., 2015).

Implementation Pathways

Clinicians must map exposures, delay windows, and responses, using NET before costly therapies (Adinig, 2025). Coding systems need MCEHD recognition (Komaroff et al., 2024). Researchers must treat environmental control as an intervention, with trials including delayed biomarker assays (Theoharides et al., 2024). Patients need structured guides—NET, Carbon-Layer, VentSeal, HEPA-Onboard—to make survival reproducible (Adinig, 2023; Genuis et al., 2013).

Validation Pathways: Proposed Research Initiatives

To bridge patient insights with medicine, validation centers equity and collaboration:

1. Clinical Trials for Patient-Innovated Protocols: RCTs for NET Protocol™ and Carbon-Layer Method™, using crossover designs with sham controls, tracking mediators (tryptase, histamine) at 36–72 hours, including underserved groups (Adinig, 2023; Theoharides et al., 2024).

2. Longitudinal Studies on MCEHD: Multi-site cohorts mapping MCS, MCAS, and IACC overlaps over 2–5 years, screening SNPs for chemical intolerance (Miller et al., 2024; Bock & Köhle, 2005).

3. Biomarker Validation: Assays for mast cell mediators in MCS, validating MCEHD criteria and TILT parallels, shifting from psychogenic models (Miller et al., 2024; National Academies, 2024).

These scale invention into science, serving those long dismissed (Steinemann, 2019; Yates et al., 2024).

Economic Impact

Ignoring MCEHD drives ER visits, hospitalizations, disability claims, and lost work (Nurmagambetov et al., 2018; Sullivan et al., 2011). Stabilization costs less: CR boxes ($60–120), carbon inserts ($15), generics like montelukast, or $40 inverters for mobile HEPA systems prevent flares (Dal Porto & Corsi, 2022; Adinig, 2023). In Europe, allergic disease mismanagement costs €55–151 billion annually (Zuberbier et al., 2014). In the U.S., asthma, sharing MCEHD pathways, projects $300 billion over 20 years (Sullivan et al., 2011). Underserved groups face higher burdens due to access barriers (Yates et al., 2024).

U.S. vs Global Adoption

In the U.S., mask politicization hinders NET (Yates et al., 2024). In Asia, mask culture makes it seamless (Bousquet et al., 2017). In Europe, occupational medicine aids MCEHD (D’Amato et al., 2015). In low-resource countries, DIY methods like CR boxes are default (Gasparrini & Rosenthal, 2022). MCEHD scales across $30 generics and $30,000 biologics (Afrin, 2017; Berry et al., 2019).

Conclusion: From Survival to Systems

MCS and MCAS were never separate in the body, only split by politics and silos (Ashford & Miller, 1998; Komaroff et al., 2024). Randolph described environmental illness (1956), Cullen codified MCS (1987), Afrin defined MCAS (2013), and Long COVID forced hypersensitivity into view (2023–2025) (Low et al., 2023; National Academies, 2024). I propose their unification as MCEHD.

I inherited Corsi–Rosenthal boxes, off-gassing, distilled water, rubbing alcohol, and fragrance literacy (Gibson, 2014; Dal Porto & Corsi, 2022). I invented NET Protocol™, Carbon-Layer Method™, VentSeal™ Hack, and HEPA-Onboard™ System (Adinig, 2025). Together, they form a system to normalize masks, teach the therapeutic ladder, update coding, and scale patient innovations.

This is how medicine catches up to what patients know (Steinemann, 2019; Bateman Horne Center, 2025).

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Author's Note:

All insights, frameworks, and recommendations in this white paper reflect the author's independent analysis and synthesis. References to researchers, clinicians, and advocacy organizations acknowledge their contributions to the field but do not imply endorsement of the specific frameworks, conclusions, or policy models proposed herein.

Applied Infrastructure Models Supporting This Analysis

Several standardized tools were utilized or referenced in the construction of this white paper. These tools support real-time surveillance, economic forecasting, and symptom stabilization planning for infection-associated chronic conditions (IACCs).

Note: These models were developed to bridge critical infrastructure gaps in early diagnosis, stabilization tracking, and economic impact modeling. Select academic and public health partnerships may access these modules under non-commercial terms to accelerate independent research and system modernization efforts.

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About the Author 

Cynthia Adinig is an internationally recognized systems strategist, health policy advisor, and the founder of CYNAERA. She launched CYNAERA Institute, an AI-powered intelligence platform advancing diagnostic reform, clinical trial simulation, and real-world modeling. She has developed 400+ Core AI Frameworks, 1 Billion + Dynamic AI Modules. including the IACC Progression Continuum™, US-CCUC™, and RAEMI™, which reveal hidden prevalence, map disease pathways, and close gaps in access to early diagnosis and treatment.

Her clinical trial simulator, powered by over 675 million synthesized individual profiles, offers unmatched modeling of intervention outcomes for researchers and clinicians.

Cynthia has served as a trusted advisor to the US Department of Health and Human Services, coauthored research alongside experts at Yale and Mount Sinai, and influenced multiple pieces of federal legislation related to Long COVID and chronic illness. 

She has been featured in TIME, Bloomberg, USA Today, and other leading publications.

Through CYNAERA, she is building the algorithmic infrastructure that will define chronic illness care, public health resilience, and precision research for the decades ahead.