*5.5. Severe*

As opposed to other primary immunodeficiencies, sIgAD rarely presents with severe manifestations. Therefore, differential diagnosis with other possible immunological disorders should be performed.

Patients with this phenotype suffer from recurrent and severe infections even in lower respiratory tracts [8]. One of the severe complications of severe respiratory infections is bronchiectasis. In such cases, it is crucial to eliminate other immunodeficiencies such as IgG2subclass, specific antibody deficiencies, and mannan-binding lectin deficiency [79].

Patients with this phenotype should be provided with extra care. In case of recurrent infections, prophylactic antibiotics should be considered, especially during autumn and winter [8]. The usage of IVIG replacement therapy in these patients is extremely controversial [116,154]. Usually, this treatment is recommended for individuals with both IgA deficiency and concomitant IgG2 subclass deficiency [155,156]. To determine if this treatment would be beneficial, the IgG antibody responses to protein and polysaccharide vaccines should be evaluated first [116].

#### **6. Complications**

In a prospective cohort study that examined mortality among patients with sIgAD turn out that they have an increased risk of death in the first 10 years after diagnosis [157]. Afterward, the mortality is similar to that of the general population. The most common causes of death include malignancy and cardiovascular diseases. There are a few lifethreatening complications of sIgAD. Even if their prevalence is not high, they should be known for physicians to provide proper help for their patients. Among those included in the literature, we differentiate progression to CVID, transfusion-related anaphylaxis, and malignancy.
