Appeal type: Medical necessity
Decision: Overturned

Diagnosis: Langerhans' cell histiocytosis
Treatment: Immunoglobulin injections
The insurer denied immunoglobulin injections.
The determination is overturned.

This is a female patient with a diagnosis of multisystem Langerhans Cell Histiocytosis. She presented with skin lesions and had quick progression to her gastrointestinal tract. She started therapy with vinblastine and prednisone, with slight improvement. However, 12 weeks into therapy she developed lesions in her spleen and her treatment changed to include hydroxyurea with the prednisone and vinblastine. After 2 cycles of this therapy, she continued to have disease and changed to single agent cytarabine. However, after 2 cycles of this treatment she developed skull involvement along with spleen, gastrointestinal (GI), and skin involvement. Since she had a BRAF (human gene that encodes a protein called B-Raf) mutation present in her disease biopsy samples, the provider recommended single agent dabrafenib, 15 milligrams (mg) by mouth, twice a day. She has been on this therapy since that time with stable disease. She has experienced recent infections with coronavirus disease (COVID), prolonged diarrhea, Serratia bacteremia, staphylococcus (staph) aureus bacteremia, thrush and fungal skin infections, staph epidermidis, bilateral otitis externa, and Klebsiella cellulitis. She has had persistently low immunoglobulin levels and due to concerns of her immunocompromised status, the provider has recommended intravenous immunoglobulin (IVIG) as treatment of her condition. The medical necessity of IVIG is under review.

The requested health service/treatment of immunoglobulin injections is medically necessary at this time.

This patient has a congenital multiorgan systemic Langerhans Cell Histiocytosis that has required chemotherapy and/or immunotherapy since 1 week after birth. More recently she has been having frequent infections and has low immunoglobulin levels. Due to her underlying treatment and disease process, she is unable to receive immunizations. The use of IVIG was recommended to help prevent further serious infections. The IVIG was denied as not medically necessary as it did not meet the policy criteria for this therapy. As per the policy language, for this child who essentially has congenital agammaglobulinemia given the issues since birth, the use of IVIG for this child requires there to be a history of an initial pre-treatment total serum IgG (immunoglobulin G) below the lower limit of age-adjusted laboratory reference range, and no evidence of renal and GI causes for the hypogammaglobulinemia. If this patient were considered more under the common variable immunodeficiency (CVID) setting, then there should be a history of recurrent sinopulmonary infections requiring antibiotic therapy, with lack of or inadequate response to immunization, and initial pre-treatment total serum IgG below the lower limits of the age adjusted lab reference range, and no evidence of the renal or GI causes for the hypogammaglobulinemia. This patient meets the criteria with the exception of the immunization response, as she is not able to safely receive immunizations at this time. This level of the criteria is not applicable to her situation.

There are associations between a familial Langerhans Cell Histiocytosis condition and immune deficiencies such as hypogammaglobulinemia, which appear to fit this patient's clinical situation. The standard treatment in this instance is IVIG therapy. While this patient has not had abnormal titers from vaccinations, since the patient cannot receive vaccines, this is not an appropriate way to monitor for appropriate need for therapy.

Given this patient's unique clinical situation, the current standards of care, and likely more serious nature of this specific condition, the request for IVIG therapy is clinically appropriate and medically necessary at this time.