Journal of Clinical Immunology | 2019
Successful Treatment of Sinusitis with Topical Human Milk in a Lymphoma Patient Using Rituximab
Abstract
To the Editor, Chronic respiratory infections are frequent manifestations in patients with both primary and secondary antibody deficiencies due to their poor production of serum and secretory immunoglobulins. Intravenous immunoglobulin (IVIg) replacement treatment usually reduces susceptibility to infections, although it is well-known that IVIg does not reach mucosae in significant amounts. Human milk, a major source of secretory IgA (SIgA), also contains several other anti-infectious factors, which interact among themselves and with infant digestive and upper respiratory tract mucosa, providing effective passive immunity [1]. Therapeutic uses of human milk have been anecdotal, and, as far as we could find in medical literature, this is the first report of humanmilk used as nasal adjuvant therapeutic proposal in a lymphoma patient with hypogammaglobulinemia due to rituximab treatment. After informed consent and discussion with ethics committee colleagues as a compassionate therapy, and especially considering its safety and lack of side effects, we decided to administer human milk serum intranasally to a 76-year-old woman with non-Hodgkin lymphoma, diagnosed in 2007 (see Fig. 1). After several rituximab cycles, she presented with persistent hypogammaglobulinemia (very low serum IgG levels, undetectable IgM and IgA, as well as salivary IgA) and extremely low peripheral B lymphocytes (0.01%). The patient also presented chronic pansinusitis, having been treated several times with antibiotics without significant and longlasting response. Regular IVIg administration in adequate doses (400 mg/kg), every 4 weeks, maintained IgG levels above 700 mg/dL (latest Ig levels as follows: IgG, 819 mg/ dL, IgM, 9 mg/dL, IgA, < 7 mg/dL, and IgE, < 2 kU/L). Despite this, she went on requiring frequent antibiotic treatments due to recurrent sinusitis without significant response. Due to the persistence of clinical manifestations and poor quality of life, particularly poor sleep quality and lack of appetite, we decided to introduce breast milk by the nasal cavity as an attempt to provide her with topical secretory IgA to improve upper respiratory symptoms. The milk was obtained from healthy donors from middleto high-income status at a nonprofit human milk bank located in a maternity hospital (Hospital e Maternidade Santa Joana, São Paulo). All donors had negative serology for HIV, hepatitis B and C, CMV, rubella, syphilis, and toxoplasmosis. The milk had been donated aiming to feed premature babies and we received leftover milk. Milk collection was performed at the hospital by a nurse under strict hygienic conditions, and all the samples were submitted to pasteurization. In our laboratory facilities, always working under sterile conditions, the received pooled milk samples were submitted to centrifugation at a low temperature to separate the fat and cellular layers, which were discarded, and the milk serum was then submitted to a second pasteurization (62.5 °C for 30 min). Total protein and IgA contents were determined by conventional techniques. The concentration of the solution was adjusted with sterile 0.9% NaCl to 14.4 mg/dL of the total IgA and to 5.95 mg/mL of the total protein content, and the final solution tested negative for bacterial and fungus growth. The solution was frozen (− 20 °C) in 2 mL individual doses until use. No preservative substances were added and the mildly cloudy solution was odorless and tasted similar to the saline vehicle. It was recommended to the patient to maintain the material at − 20 °C and to use 1 mL of the breast milk solution in each * Patricia Palmeira [email protected]