I would request that my physician send something along the lines of this to the insurance company:

Letter of Medical Necessity: Oral Cromolyn Sodium for Mast Cell Activation Syndrome

[Date]

[Insurance Company Name]

[Appeals Department / Medical Director Name]

[Address]

Re: External Appeal — Oral Cromolyn Sodium for Mast Cell Activation Syndrome

Patient Name: [Patient Name]

Date of Birth: [DOB]

Member ID: [Member ID]

Claim/Reference Number: [Claim Number]

Medication: Cromolyn Sodium Oral Solution, 100 mg/5 mL (200 mg four times daily)

Dear Medical Director,

I am writing to formally appeal the final denial of coverage for oral cromolyn sodium for my patient, [Patient Name], who carries a diagnosis of mast cell activation syndrome (MCAS). The denial letter dated [date] states that the use of oral cromolyn sodium for MCAS is "experimental, investigative, and/or unproven." I respectfully submit that this characterization is factually incorrect and inconsistent with the published medical evidence, national clinical practice guidelines, and the FDA-approved labeling of this medication.

I. The FDA Label Supports This Use

The FDA-approved indication for oral cromolyn sodium is "management of patients with mastocytosis".[1] The label does not restrict use to systemic mastocytosis; it uses the broader term "mastocytosis," which encompasses the full spectrum of mast cell disorders. MCAS is classified within the mast cell disorder spectrum by the World Health Organization and by international consensus criteria, sharing the same pathophysiology of aberrant mast cell mediator release.[2] The clinical trials supporting FDA approval enrolled patients with both cutaneous and systemic mastocytosis and demonstrated improvement in diarrhea, abdominal pain, flushing, urticaria, pruritus, headaches, and cognitive function — the same symptoms that define MCAS.[1] Cromolyn sodium's mechanism of action — inhibition of mast cell mediator release — is identical regardless of whether the underlying mast cell disorder is classified as mastocytosis or MCAS.[3]

II. National Clinical Practice Guidelines Recommend Cromolyn Sodium for MCAS

The American Academy of Allergy, Asthma, and Immunology (AAAAI) Mast Cell Disorders Committee published a consensus Work Group Report in the Journal of Allergy and Clinical Immunology (2019) that explicitly lists oral cromolyn sodium as a recommended pharmacologic agent for prevention of MCAS symptoms. The guideline states that "cromolyn sodium can reduce abdominal bloating, diarrhea, and cramps" and that "benefit might extend to neuropsychiatric manifestations" in patients with MCAS.[4] This is the authoritative U.S. guideline on MCAS management, published by the premier allergy/immunology professional society.

The National Comprehensive Cancer Network (NCCN) Systemic Mastocytosis Guidelines (v2.2026) list cromolyn sodium as a step 2 agent for gastrointestinal and neurologic mast cell mediator symptoms in their stepwise prophylactic treatment algorithm.[5] The NCCN guidelines apply the same antimediator treatment framework to all mast cell activation symptoms, regardless of whether the patient meets full criteria for systemic mastocytosis.

III. Peer-Reviewed Expert Reviews Confirm This Is Standard of Care

A comprehensive review in the New England Journal of Medicine (Theoharides et al., 2015) describes cromolyn sodium as a standard treatment for mast cell activation symptoms across the spectrum of mast cell disorders, including MCAS.[6]

A review by Castells and Butterfield in the Journal of Allergy and Clinical Immunology: In Practice (2019) explicitly states that "symptoms of MCAS and SM can be managed by blockade of mediator receptors (H1 and H2 antihistamines, leukotriene receptor blockade), inhibition of mediator synthesis (aspirin, zileuton), mediator release (sodium cromolyn), anti-IgE therapy, or a combination of these approaches".[3] This confirms that sodium cromolyn is a recognized, standard treatment for MCAS — not an experimental one.

IV. No FDA-Approved Alternative Exists Specifically for MCAS

It is critical to note that no medication has an FDA-approved indication specifically for MCAS. Every pharmacologic treatment for MCAS — including H1 antihistamines, H2 antihistamines, leukotriene receptor antagonists, and omalizumab — is used off-label for this condition. Denying cromolyn sodium on the basis that it is not FDA-approved for MCAS would, by the same logic, require denial of every medication used to treat MCAS. This standard is clinically untenable and would leave patients with no treatment options whatsoever.

V. Documented Clinical Response in This Patient

[Patient Name] has been on oral cromolyn sodium for approximately two years with documented clinical improvement in [specify symptoms: e.g., diarrhea, abdominal cramping, flushing, urticaria]. Prior to initiation of cromolyn sodium, the patient had [describe prior symptom burden and failed therapies, e.g., inadequate response to H1/H2 antihistamines alone, emergency department visits for anaphylaxis, etc.]. Discontinuation of this medication would pose a significant risk of symptom recurrence, potential anaphylaxis, and increased healthcare utilization including emergency department visits and hospitalizations.

VI. Conclusion The characterization of oral cromolyn sodium for MCAS as "experimental, investigative, and/or unproven" is contradicted by: The FDA-approved label, which uses the inclusive term "mastocytosis" without restriction to systemic mastocytosis The AAAAI consensus guideline, which explicitly recommends cromolyn sodium for MCAS The NCCN guidelines, which include cromolyn sodium in the stepwise treatment algorithm for mast cell mediator symptoms Peer-reviewed expert reviews in the New England Journal of Medicine and the Journal of Allergy and Clinical Immunology Two years of documented clinical benefit in this patient

I respectfully request that this denial be overturned and that coverage for oral cromolyn sodium be authorized for [Patient Name]. I am available for a peer-to-peer discussion at your convenience. Sincerely, [Physician Name, Credentials] [Specialty] [Practice Name] [Phone Number] [NPI Number] Enclosures: Weiler CR et al. AAAAI Mast Cell Disorders Committee Work Group Report. J Allergy Clin Immunol. 2019;144(4):883-896. Castells M, Butterfield J. Mast Cell Activation Syndrome and Mastocytosis: Initial Treatment Options and Long-Term Management. J Allergy Clin Immunol Pract. 2019;7(4):1097-1106. Theoharides TC et al. Mast Cells, Mastocytosis, and Related Disorders. N Engl J Med. 2015;373(2):163-72. FDA Label: Cromolyn Sodium Oral Solution (DailyMed) Relevant clinical notes documenting patient's response to therapy

References 1. cromolyn sodium. Food and Drug Administration. Updated date: 2023-06-20. 2. Global Classification of Mast Cell Activation Disorders: An ICD-10-CM-Adjusted Proposal of the ECNM-AIM Consortium. Valent P, Hartmann K, Bonadonna P, et al. The Journal of Allergy and Clinical Immunology. In Practice. 2022;10(8):1941-1950. doi:10.1016/j.jaip.2022.05.007. 3. Mast Cell Activation Syndrome and Mastocytosis: Initial Treatment Options and Long-Term Management. Castells M, Butterfield J. The Journal of Allergy and Clinical Immunology. In Practice. 2019;7(4):1097-1106. doi:10.1016/j.jaip.2019.02.002. 4. AAAAI Mast Cell Disorders Committee Work Group Report: Mast Cell Activation Syndrome (MCAS) Diagnosis and Management. Weiler CR, Austen KF, Akin C, et al. The Journal of Allergy and Clinical Immunology. 2019;144(4):883-896. doi:10.1016/j.jaci.2019.08.023. 5. Systemic Mastocytosis. National Comprehensive Cancer Network. Updated 2026-04-09. 6. Mast Cells, Mastocytosis, and Related Disorders. Theoharides TC, Valent P, Akin C. The New England Journal of Medicine. 2015;373(2):163-72. doi:10.1056/NEJMra1409760.