Chronic sinusitis in a patient with selective IgG4 subclass deficiency controlled with enriched immunoglobulins

Abstract

Key Clinical MessageA 71‐year‐old female patient with no major history of infection had presented with recurrent chronic purulent sinusitis over the past 3 years. These recurrent infections started in 2000 with otolaryngologists’ support before diagnosis of IgG4 deficiency be asked. The patient was treated with increasingly extensive courses of antibiotics and underwent several maxillary and sphenoidal sinus washouts. She continued to present with purulent nasal discharge containing Staphylococcus epidermidis. The blood and immune work‐ups were normal. Her antinuclear antibody count was 1/320, with no unusual types. The total immunoglobulin (Ig)E, serology, CD4 count, and lymphocyte B phenotype results were all normal. No humoral immune deficiency was detected. The analyses confirmed an underlying specific IgG4 deficiency with values of 3–4 mg/L over 4 months. The patient was treated in March 2011 with prophylactic antibiotic therapy, sinus drainage, and IV infusions of enriched immunoglobulins (IVIg 10%) administered at the outpatient clinic every 4 weeks for 3 months. The IgIV treatment was not interrupted. Her general condition improved within a few months, with her IgG4 levels rising to 44 mg/L. The IVIg infusions were well tolerated. The purulent nasal discharge was controlled, and the antibiotics were stopped. The follow‐up visits at 2 and 9 months after introduction of IVIg showed that her IgG4 level had improved, rising to 15 and 11 mg/L, respectively, although it had not yet returned to normal. The infusions were then given every 3 weeks. At her last visit, the patient's clinical condition had substantially improved. She was able to start using the subcutaneous Ig concentrate form (20% SCIg), 15 g every 2 weeks, leading to a clear improvement in her clinical condition, with stabilization of her otolaryngologists’ symptoms and signs. The complete blood count was normal, IgG4 were stable at 40 mg/L, and the other immunoglobulins and IgG subclasses were normal. It was then possible to reduce the SCIg dose to 10 g every 3 weeks, while continuing to monitor her clinical condition and laboratory test results. This is one of the rare cases of selective IgG4 subclass deficiency treated with immunoglobulins. Treatment resulted in a significant improvement in IgG4 levels versus pretreatment levels. The first improvement noted was the stabilization otolaryngologists’ infections particularly purulent nasal discharge.

Characterization of adult patients with IgG subclass deficiency and subnormal IgG2

“…Subnormal IgG1, subnormal IgG3, and subnormal IgG4 occurred in 50%, 100%, and 6% of the present 18 patients, respectively, although neither IgG1, IgG3, nor IgG4 levels were significantly associated with IgG2 levels, after adjustment for other variables. Selective subnormal IgG1 [25,31], selective subnormal IgG3 [23,26,38], and selective subnormal IgG4 [23,44] probably contribute to susceptibility to frequent or severe respiratory tract infection in adults with IgGSD. Subnormal IgG1 [34,45], subnormal IgG3 [34], and subnormal IgG4 [18,34] also occur in healthy adults without frequent or severe respiratory tract infection.…”

The Post-hunter-gatherer Era Microbes Hypothesis for Chronic Inflammatory Diseases

“…Chronically elevated IgG4 is thought to be a sign of chronic antigenic stimulation [263]. Selective IgG4 deficiency is associated with frequent respiratory infections [264,265], which might suggest IgG4's importance in protection against infections.…”