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Immunodeficiency can be classified as (1) primary or congenital and (2) secondary or acquired. Both types can be due to defects of the nonspecific or specific immune response. Table 6–1 lists some of the primary immunodeficiencies classified on the basis of the immune defect. The current names of the related syndromes are also reported.

Acquired immunodeficiency is gaining interest in the research community because there are many paraphysiological and pathological conditions that can cause it. It is difficult to find a classification similar to the one suggested for primary immunodeficiency because the etiologic factors (viral or bacterial infections, tumors, drugs, etc.) interact in different ways with the mechanism of the immune response that is differently influenced, either in its humoral or its cellular arm. Briefly, the main responsible factors for acquired immunodeficiency are premature birth, pregnancy, old age, viral infections, bacterial or helminthic infections, malnutrition, toxic factors (impaired renal or hepatic function, long treatment with corticosteroids or cytostatics, long antibiotic therapy), organ transplants, myelopathies, and lymphoid and nonlymphoid tumors.

The most common causes of immunodeficiency associated with chronic recurrent sinusitis are immunoglobulin deficiencies, including IgG subclass deficiencies. Human IgG consist of four subclasses based on antigenic differences in their heavy polypeptide chain. The IgG subclasses are found in normal serum in the following relative proportions: IgG1 (60–70%), IgG2 (14–20%), IgG3 (4–8%), and IgG4 (2–6%). IgG1 and IgG3 are thought to be the subclasses preferentially produced in response to protein antigen in adults, and IgG2 and IgG4 have been associated mostly with responses to carbohydrate antigens.

In particular, the IgG1 subclass is responsible for antibody response to bacterial protein antigens such as tetanus toxoid and diphtheria. If there is a deficiency of IgG1, a functional assessment of antibody titers should be performed before and after the administration of tetanus and diphtheria toxoid. IgG2 is responsible for antibodies directed against polysaccharide capsules such as Haemophilus influenzae and Streptococcus pneumoniae. The IgG3 subclass plays an important role in the primary response to Moraxella catarrhalis and the M component of Streptococcus pyogenes. The significance of IgG4 remains unclear.

Chronic or recurrent chest infections may be associated with IgG2 deficiency, with or without absent IgG4 and/or low IgA levels.¹ Scadding et al² demonstrated that in patients with chronic rhinosinusitis the subclass of IgG that was defective was IgG3.

The incidence of IgA deficiency is 1 case per 600 to 800 in the general population. This is the predominant subclass of immunoglobulin on mucosal surfaces. Selective deficit of IgA is the most frequent primary immunodeficiency, and it is often associated with infections of the upper airways. Patients with IgA deficiency often have a coexisting IgG subclass deficiency or an autoimmune disorder.

The ear, nose, and throat (ENT) manifestations of HIV infection are well known, and the findings in acquired immunodeficiency syndrome (AIDS) patients have been described.3 To understand why and how people suffering from AIDS are susceptible to ENT pathologies, in particular rhinosinusitis, it is useful to remember the characteristics of HIV virus and the means of defense of the nasal mucosa.

HIV is a retrovirus that attacks the immune system. The infection develops in four phases. In the initial stage, the virus colonizes helper T lymphocytes and macrophages and replicates unchecked.⁴ This phase is called primary acute infection; during this phase, from 30 to 70% of infected people develop a clinical syndrome marked by fever, pharyngitis, headache, and retro-orbital pain.⁵ Also during this phase the virus spreads and colonizes the lymphoid organs. The immune answer appears generally in 3 weeks and is associated with a decrease of viremia and the absence of symptoms.

The second phase, referred to as the asymptomatic stage, is variable in duration and is marked by the progressive depletion of T and B lymphocytes and the deterioration of the function of monocytes and macrophages. The third phase develops when the patient presents with persistent generalized lymphadenopathy. The fourth phase is the symptomatic, or AIDS, stage. Symptoms during this phase include persistent fever, diarrhea, a loss of weight (more than 10%), polyadenopathy, tumors, and opportunistic infections (Table 6–2).

Various studies have evaluated the manifestations of HIV in the head and neck. It appears that up to 84% of infected individuals have either symptoms or signs that may involve otolaryngologists.³ Initial infection may manifest itself as an acute seroconversion illness with an acute mononuclease-like syndrome. Thus, the symptoms that may be presented to the ENT specialist are odynophagia, retro-orbital pain, headache, and oral ulceration.

Numerous aspects of manifested AIDS also involve the otolaryngologist. For example, the most common neoplastic conditions associated with HIV are Kaposi’s sarcoma and lymphoma. Kaposi’s lesions are commonly found in the mucosa of the oral cavity, especially in the palatal and gingival areas.

The main nonspecific defense of the nose, paranasal sinuses, and upper airways is the integrity of physical and chemical barriers: anatomical integrity of skin and mucosa, efficiency of mucociliary clearance, normal microbial flora, and correct pH. Milgrim⁶ studied the correlation between HIV-positive status and alterations of mucociliary transport time. Through the saccharin clearance test a significant increase of MCTt was found in HIV-positive subjects. This alteration could contribute to the development of rhinosinusitis, even though it is not the main responsible factor.

Another important element involved in nasal immune response is the inflammatory response, which depends on many elements, among them neutrophils. When the level of neutrophils dips below 100/mm3, there is an increasing incidence of bacterial and fungal infections.7 The most important causes of neutrophilic loss are the alteration of their production in bone marrow and their destruction in the splenic site.

Neutrophilic loss is not a common aspect of AIDS. Instead, the loss of lymphocytes is the most relevant aspect of this disease. The decrease of lymphocytes is remarkable when these cells fall under 1000/mm3.

During HIV infection, there is a constant alteration in quantity and quality of T helper CD4. The virus links to this type of lymphocyte through a particular glycoprotein (p120) that is on its external membrane.

After that linkage, through fusion with the membrane of the T cell, the virus goes into the cytoplasm. Its RNA is then transcripted into DNA through inverse transcriptase so that the DNA of the virus becomes part of the cellular DNA. Because of the viral activation, new viral units are formed that leave the cell through a process called gemmation, destroying the cellular membrane. As the infection goes on, the number of lymphocytes decreases. When the level is below 200/mm3, the possibility of opportunistic infections is high.

Moss et al⁸ hypothesized that quantitative defects in immune cells of the nasal mucosa of HIV-positive subjects could mirror those in the peripheral blood and explain a predisposition to sinus disease in this population. To prove their idea, Moss et al analyzed nasal mucosa biopsies from AIDS patients, demonstrating a low level of CD3+ and CD4+ lymphocytes not only in the peripheral blood.

In conclusion, HIV infection creates the immunologic premise to develop nasal and paranasal diseases. Two predictors have been asssociated with a higher probability of rhinosinusitis: bilateral absence of maxillary infundibular patency and low total count (odds ratio 0.99; 95% CI = 0.99 − 1.00) and percentage of CD4+ (odds ratio 0.93; 95% CI = 0.88 − 1.00).⁹

HIV and Rhinosinusitus

Rhinosinusitis represents one of the expressions of manifested AIDS, set in group 4, subgroup C (Table 6–2), where we can find the secondary infectious diseases. Recurrent sinusitis has an incidence varying from 25 to 30% to 60% in HIV-infected patients.^10,11,12 Godofsky et al¹³ found that the incidence of rhinosinusitis shows a direct relationship with the decrease of CD4+ lymphocytes.

Two kinds of rhinosinusitis should be described in AIDS patients: allergic and infective.

Regarding allergic rhinosinusitis, HIV-positive subjects have a greater susceptibility than HIV-negative patients. Small et al¹⁴ showed that IgE-mediated nasal allergy is more common in patients infected with HIV who have higher levels of IgE and a smaller quantity of IgG. Garcia-Rodriguez et al⁹ reported that atopy was present in 18% of patients, according to the expected prevalence in their geographic area, and that most patients were severely immonosuppressed. They concluded that rhinosinusitis in HIV-infected individuals does not appear to be related to IgE-related immediate hypersensitivity. However, we have not found much literature on this topic; moreover, allergic rhinosinusitis in immunocompromised hosts does not seem to have any particular characteristics if compared with the aspects of this disease in normal subjects.

In contrast, infective rhinosinusitis is frequent and particular in AIDS patients. Among the differences between sinusitis in HIV- and non-HIV-infected patients, we must include pathogenesis, bacteriology, and management. The etiologic factors can be divided into two categories: (1) common and (2) opportunistic ones that are rare in normal subjects but frequent in immunocompromised patients. Among the common agents we can include Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Escherichia coli.

Regarding opportunistic infections, several agents have been reported: virus (Cytomegalovirus), bacteria (Staphylococcus epidermidis

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