Control of Disease

The goal of CRS treatment is to achieve and maintain clinical control. Control is defined as a disease state in which the patient does not have symptoms or the symptoms are not bothersome, if possible combined with a healthy or almost healthy mucosa and the need for only local medication. Although the majority of patients with CRS can achieve control, some will not do so even with maximal medical therapy and surgery.

Patients who do not reach an acceptable level of control despite adequate surgery, intranasal corticosteroid treatment, and up to two short courses of antibiotics or systemic corticosteroids in the past year can be considered to have difficult-to-treat rhinosinusitis.

We do not know what percentage of patients with CRS actually can achieve control of disease, and further studies are necessary. In this chapter we propose an assessment of current clinical control of CRS. Further validation is necessary.

Severe Chronic Upper Airway Disease and Chronic Rhinosinusitis

Severe chronic upper airway disease (SCUAD) defines those patients with allergic rhinitis, nonallergic rhinitis, CRS with and without nasal polyps, and occupational rhinitis whose symptoms are inadequately controlled despite adequate (i.e., effective, safe, and acceptable) pharmacologic treatment based on guidelines.6 Intermittent and persistent inflammatory disorders of the upper airways are extremely common, with increasing public health and socioeconomic effect.7 Still, a noteworthy percentage of these are either inadequately treated or persistent despite adequate treatment. Thus, in relation to CRS, SCUAD should be regarded as a novel term influencing research toward unmet needs of difficult-to-treat CRS cases. More specifically, patients with CRS have an impaired quality of life, more bodily pain, and worse social functioning than patients with chronic obstructive pulmonary disease (COPD), congestive heart failure, or back pain. CRS represents a significant health problem, resulting in frequent surgical procedures, and a large financial burden on society.1

Aspirin-exacerbated Respiratory Disease

Aspirin-exacerbated respiratory disease, also known as acetylsalicylic acid (ASA)/aspirin triad disease (ASA triad) or Samter triad, is a disorder commencing around the 20th year of life and presenting with CRS with nasal polyps, asthma, and sensitivity to aspirin (and other nonsteroidal antiinflammatory drugs [NSAIDs]). The pathogenetic mechanism is not completely understood, even though it seems to include a defect in cyclooxygenase (COX-1, COX-2) activity, thus leading to an overproduction of proinflammatory cysteinyl leukotrienes and prostaglandin D₂ and a reduction in the production of antiinflammatory prostaglandin E₂, which leads to predominantly eosinophilic inflammation.8

Aspirin-sensitive patients have a particularly severe form of CRS with nasal polyps that is vulnerable to recurrence despite appropriate medical or surgical management. Medical management consists of avoidance of salicylates and NSAIDs, topical and systemic corticosteroids, and in some cases aspirin desensitization therapy.9 The prevalence of nasal polyps in the general population is ~4%, whereas in asthmatic patients, the prevalence appears to be 7 to 15%, and in NSAID-sensitive patients, the percentage rises to 36 to 60% ( Fig. 20.3 ).

Controversies in the Diagnosis of Chronic Rhinosinusitis

CRS with or without nasal polyps is defined as an inflammation of the mucosa of the nose and paranasal sinuses of at least 12 weeks’ duration, without complete resolution of symptoms. As in other respiratory inflammatory diseases like asthma, there is a discrepancy between symptoms and objective tests such as nasal endoscopy and computed tomography (CT) scan. There is a significant association of CRS signs seen on nasal endoscopy and doctor-diagnosed CRS with reasonable sensitivity and specificity.10 In a study comparing CT and endoscopy using a proprietary scoring system in patients with CRS, 65% of endoscopy-negative patients had radiographic evidence of disease, whereas in another study, this proportion was 36%. The definition of CRS as given by EPOS relies on symptoms and nasal endoscopy or CT scan. If nasal endoscopy is negative and there is a strong suspicion of CRS, it is wise to have a CT scan. Also, a CT scan can be very helpful to disprove CRS in patients with facial pain.

There are several disorders that can lead to or mimic CRS, and the main issue for physicians is to take a good history, then treat the disease etiologically. The first differential diagnosis is allergic and nonallergic rhinitis. From the point of view of epidemiological research this is an important issue in the daily treatment of difficult-to-treat CRS, it is seldom an issue. Although it is very difficult to separate allergic rhinitis from CRS, and thus very difficult to prove allergic rhinitis to be a causal factor in CRS, the symptom management for both groups is certainly overlapping.

Extra emphasis might be put on allergen avoidance; however, apart from occupational allergies, the effect is doubtful.

CRS shares a spectrum of symptoms with other pathologic entities. Headache and facial pain, olfactory dysfunction, and chronic cough—postnasal drip syndrome—are common complaints in patients suffering from a wide spectrum of diseases. A substantial differential diagnosis ( Table 20.3 ) is necessary in these cases to provide appropriate treatment. However, the boundaries between these entities are frequently blurred, leading to treatment failures.

Headache and Facial Pain

CRS is overdiagnosed as a cause of headache because of the belief that pain over the sinuses must be related to them. Facial pain that is not accompanied by rhinorrhea and/or nasal obstruction is very unlikely caused by CRS.11 Whether or not nasal obstruction can lead to chronic headache is controversial. A significant portion of the patients admitted to an otorhinolaryngologic department have headache or facial pain attributable to other causes, commonly migraine, tension-type or cluster headache, trigeminal neuralgia, temporal arteritis, temporomandibular joint syndrome, or neuropathic pain (for more details, see Chapter 10). Headache associated with paranasal sinus disease usually has a deeper, dull, aching quality, combined with heaviness and fullness, and is seldom if ever associated with nausea and vomiting, whereas sinuses themselves are relatively insensitive to pain. The pain associated with sinusitis comes from engorged and inflamed nasal structures: nasofrontal recess, turbinates, ostia, and superior nasal spaces. Sinusitis pain is not always the same. Maxillary sinusitis pain most typically is located in the cheek, the gums, and the teeth of the upper jaw. Ethmoid sinusitis pain is felt between the eyes, while the eyeball may be tender, and pain may be aggravated by eye movement. Frontal sinusitis pain is felt mainly in the forehead. Sphenoid sinusitis pain is felt in the vertex but has a more general localization.

An extra complicating factor is the many false-positive CT scans; abnormalities at the CT scan of the sinuses have been described as occurring in > 40% of the healthy population12 ( Fig. 20.4 ). The American Migraine Study II, a population-based survey that involved more than 20,000 U.S. households conducted in 1999, indicated that only 48% of patients who met International Headache Society (IHS) criteria for migraine reported a physician diagnosis of migraine. Follow-up data from the American Migraine Study II suggest that 42% of patients with migraine as defined by IHS criteria had received a diagnosis of sinus headache from a physician. Although some of these patients may have had coexisting sinus headache and migraine, misdiagnosis of migraine as sinus headache is probably common. In addition, sinus headache is often self-diagnosed incorrectly by patients. Furthermore, it seems that most individuals who believe, because of either self-diagnosis or physician diagnosis, that they have sinus headaches actually have headaches that fulfill criteria for migraine or probable migraine according to IHS criteria.

Olfactory Dysfunction

CRS is one of the most common causes of olfactory loss. Loss of olfactory function has an unpleasant impact on a patient′s quality of life, as it affects the patient′s appreciation of food and drink, has an impact on safety, and may also produce bodily insecurity: the patient′s own body odors are no longer self-perceived. In general, olfactory disorders have been attributed to several causes (for more details, see Chapter 11). Sinus CT scan is a valuable method not only for the assessment of the extent and severity of CRS, but also for the evaluation of the causes of olfactory dysfunction, while significant correlation is observed between the CT and the results of olfactory function tests.13 Olfaction scores are correlated with mucosal eosinophilia, with lower scores being found in eosinophilic CRS with nasal polyps, as compared with noneosinophilic CRS with nasal polyps.14 The loss of the sense of smell in patients with CRS with nasal polyps is caused not only by the obstruction but also by inflammation of the olfactory mucosa. For that reason the role of surgery in the treatment of hyposmia in CRS with nasal polyps is limited, and its effect is significantly less than that of systemic corticosteroids. Sometimes on the CT scan swelling is seen only in the olfactory cleft. In the differential diagnosis of CRS versus other causes of hyposmia/anosmia, the CT scan plays an important role in ruling out CRS as a cause of olfactory dysfunction.

Postnasal Drip and Chronic Cough

Chronic cough is a common problem often resulting in referral to secondary care. The diseases of nose and sinuses are reported to contribute to coughing in 20 to 40% of patients with chronic cough, with normal chest radiograph.15 Exclusion of conditions of the lower respiratory tract, including asthma and chronic bronchitis, as a cause of chronic cough is of utmost importance.

Postnasal drip, the drainage of secretions from the nose or paranasal sinuses into the pharynx, is considered to be a common cause of chronic cough. Clinically, the diagnosis of postnasal drip syndrome (PNDS) largely rests on the reporting by the patient of having something drip down into the throat, nasal discharge, or frequent throat clearing. The presence on examination of the nasopharynges or oropharynges of mucoid or mucopurulent secretions or cobblestoning of the mucosa also is suggestive. The problem encountered when trying to diagnose PNDS, however, is that there is no objective test for it and no way to quantify the amount of PND or to directly prove that it is causing the cough. Also, most patients with post-nasal drip do not complain of cough.16

According to the American College of Chest Physicians’ evidence-based clinical practice guidelines, the term upper airway cough syndrome (UACS) is more accurate and should be used instead of PNDS.17 Most patients with UACS cough will have symptoms or evidence of one or more of the following: drainage in the posterior pharynx, throat clearing, nasal discharge, cobblestone appearance of the oropharyngeal mucosa, and mucus in the oropharynx. The differential diagnosis includes allergic and nonallergic rhinitis, postinfectious rhinitis, rhinosinusitis, rhinitis due to physical or chemical irritants, occupational rhinitis, rhinitis medicamentosa, gastroesophageal reflux disease (GERD), and rhinitis of pregnancy.

The accurate relationship between CRS and chronic cough are not completely understood, and several mechanisms have been proposed, individually or in combination. It has been suggested that the cough-triggering nerves located in the hypopharynx or larynx are stimulated by secretions emanating from the nose and/or sinuses dripping down into these areas. However, there is no consensus about this hypothetical mechanism. First, postnasal drip is a common phenomenon, and only a small fraction of patients with it also complain about chronic cough.16 Conversely, a proportion (reportedly 20%) of patients with chronic cough attributed to CRS do not experience postnasal drip. It therefore seems unlikely that postnasal drip is the exclusive mechanism triggering chronic cough. Enhanced sensitivity to environmental factors has also been linked to chronic cough in CRS. The potential cough triggers may be unrelated to nasal disease.

Odontogenic Etiology

Especially in unilateral disease, but sometimes also in bilateral CRS without nasal polyps, odontogenic dentogenic foci may play a role.18 Often the common plain film imaging used in the dental field misses periapical tooth root disease that can contribute to sinusitis.19 Careful evaluation of a sinus CT, especially in coronal orientation, may show a halo-type lucency around a tooth root adjacent to the maxillary sinus floor, indicating a periapical abscess warranting dental treatment or extraction of the involved tooth ( Fig. 20.5 ).

Systemic Diseases, Immunodeficiency, and Chronic Rhinosinusitis

Several systemic diseases may mimic CRS or play a role in the pathogenesis of CRS by predisposing an individual to the development of CRS. They may alter the prognosis of CRS, leading to a more severe nasal disease or changing the applicable treatment paradigm. It is important for the physician dealing with a challenging case of CRS to be able to distinguish the prevalence of such a systemic disease to better guide his or her diagnostic, as well as therapeutic, approach.

Immunodeficiency

Several acquired and nonacquired immunodeficiencies influence and may even cause CRS without nasal polyps. Moreover, they can seriously alter the expected course or the sensitivity of the disease to usual medical and surgical treatment.

Sinusitis is one of the most common complications of nonacquired immunodeficiency. Local secretory or systemic humoral immunodeficiency, in particular, seems to predispose individuals to CRS. Other forms of immunodeficiency (lymphopenia and neutropenia) are mainly important in the pathogenesis of acute forms of rhinosinusitis, such as acute invasive fungal sinusitis. CRS symptom severity may not be affected by immunodeficiency, but CRS may be more refractory to common treatment approaches. Sinus abnormalities seem to be frequent in humoral immunodeficiency. CT findings of CRS are often detected in patients with agammaglobulinemia and common variable immunodeficiency, a heterogeneous group of disorders characterized by panhypogammaglobulinemia and recurrent infections ( Fig. 20.6 ). Patients with hypogammaglobulinemia may harbor bacteria or viruses in their sinuses and have unrecognized, subclinical CRS. Not uncommonly, humoral immunodeficiency is uncovered only after a patient has been treated over a period of years with multiple sinus surgeries. Correct diagnosis is important because the presence of immunodeficiency may alter the recommended course of treatment: antibiotic prophylaxis, early aggressive culture-directed antibiotic treatment, and the use of agents such as intravenous (IV) immunoglobulin. Early diagnosis and institution of IV immunoglobulin replacement therapy for agammaglobulinemia and common variable immunodeficiency reduce the prevalence of CRS, whereas delayed administration does not seem to reverse some of the chronic predisposing factors in CRS.20 Antitrypsin deficiency is another factor often associated with intractable CRS. Such patients often get severe lung infections and develop relatively early bronchiectasis.

The most common causes of acquired immunodeficiency in patients suffering from CRS are human immunodeficiency virus (HIV) seropositivity and bone marrow transplantation. CRS is one of the most common chronic problems in HIV and occurs in 20 to 68% of HIV-infected patients. Patients with HIV share a higher risk of developing CRS, especially at CD4-counts < 50 cells per mm.21 Diagnostic suspicion should rise in cases with poor response to common therapy, short remission periods between surgeries, and uncommon etiologic factors in cultures/biopsies. The primary therapeutic concern in this category of patients is the control of the underlying disorder. CRS treatment should be aggressive and pathogen specific. The most frequently found pathogens in HIV-positive patients with CRS are Staphylococcus aureus (coagulase negative), Pseudomonas aeruginosa, Streptococcus, and Aspergillus fumigates. Culture-specific antibiotics, along with symptomatic relief (nasal irrigation and local corticosteroids), are the preferred therapy; if this targeted medical treatment fails, functional endoscopic sinus surgery (ESS) is beneficial21 ( Fig. 20.7 ).

Bone marrow transplantation is also a frequent cause of an acquired immunodeficiency. Especially allogeneic bone marrow transplantation is notorious for causing impairment of cellular as well as humoral immunity, due to the necessity of intense immunosuppression. Approximately 30 to 40% of these patients develop CRS.22 Sinus microbiology reveals mainly gram-negative bacteria, including P. aeruginosa and Serratia marcescens, followed by gram-positive bacteria and various fungi. Again, treatment should primarily be directed against the causative pathogens. This suggests that a culture swab from the middle meatus or a biopsy should be performed. Limited surgical approaches with intensive postoperative care seems appropriate in a select group of bone marrow transplantation patients refractory to medical treatment for their CRS.

Both HIV and bone marrow transplantation patients may develop invasive fungal sinusitis, accompanied by a high mortality rate. If this condition is detected early, combined surgical and antifungal treatment may be beneficial23 ( Fig. 20.8 ).

Granulomatous/Connective Tissue Disorders

Granulomatous and connective tissue disorders are systematic conditions mostly affecting blood vessels and mucous membranes (see also Chapter 32). Nasal and sinus mucosa are most often involved presenting nonspecific symptoms such as persistent postnasal drip, obstruction, ulcer formation, and crusting. CRS is very common in these conditions, having a nearly normal physical presentation and course. Depending on the pathophysiology of each condition, the clinical manifestations as well as the diagnostic and therapeutic solutions may vary24,25 ( Fig. 20.9 ).

Caution

Several systemic diseases, such as Wegener granulomatosis and Churg-Strauss syndrome, may mimic CRS.

Wegener granulomatosis is a multisystemic disease of a complex genetic background. Its characteristic vasculitis, as well as the relevant granulomatous inflammation, may lead to damage in the nasal and paranasal mucosa evident as purulent rhinorrhea and sinusitis, sometimes with ulcerating abnormalities (see Fig. 20.9 ). Examination of the nose can reveal purulent infection with no clear abnormalities of the mucosa to a destructive/necrotizing granulomatous infection of the septal and lateral nasal wall mucosa. Destruction of the septum can result in the characteristic saddle nose deformity. Wegener granulomatosis can be diagnosed using laboratory testing. A positive cytoplasmic antineutrophil cytoplasmic autoantibody (cANCA) test and a raised erythrocyte sedimentation rate (ESR) are indicative of the disease. In case of a negative ANCA and clear mucosal changes, a biopsy should be taken from the affected mucosa while the patient is not using corticosteroids. There is no use in taking a biopsy from macroscopically normal-appearing mucosa. Untreated Wegener granulomatosis is usually fatal; therefore, patients should consult with a clinical immunologist. In generalized disease, the induction treatment is systemic and consists of cytostatics (e.g., cyclophosphamide) combined with steroids. Therapy for the maintenance of a remission usually consists of azathioprine. Localized nose involvement is treated as common CRS with a special role for cotrimoxazole.26 The outcome of ESS is frequently disappointing, and surgery should be avoided. Reconstruction of the saddle deformity can only be considered if the disease is in complete remission. Even then, nasal surgery could induce a disease exacerbation.26

Sarcoidosis is a chronic noncaseating granulomatous disease of unknown origin. It principally affects the lower airway. Sinonasal involvement is rare, with reported incidences of 0.7 to 6%. Most frequent complaints of nasal involvement are reduced airflow, rhinorrhea, anosmia, and crusting.27 In the nose, mucosal changes are noted, such as hypertrophy and a strawberry-like appearance, which should arouse suspicion, up to severe crusting, septal perforation, and even sometimes a saddle nose deformity. Diagnosis of sarcoidosis is made on the basis of clinical findings, a plain chest radiograph (showing bilateral hilar lymphadenopathy), raised angiotensin-converting enzyme (ACE) levels in serum, and a biopsy of the affected mucosa. Sarcoidosis patients with sinonasal involvement tend to have a smaller chance of remission and a higher need for long-term systemic treatment. Local steroid treatment of the nose is often not sufficient, and systemic treatment, in the form of oral steroids and immunosuppressants, such as methotrexate and azathioprine, is needed. Surgery for sinonasal sarcoidosis is controversial and generally should be avoided. Short-term results may help reduce symptoms, but surgery alone does not eradicate the disease or prevent recurrence; furthermore, it can result in very severe scarring27 ( Fig. 20.10 ).

Churg-Strauss syndrome is a rare necrotizing granulomatous vasculitis of unknown etiology. It affects small to medium-size blood vessels. The most frequently involved organs are the nose and sinuses, followed by the lungs and peripheral nervous system.28 Clinically, the disease can be divided into three phases. The prodromal phase consists of asthma possibly associated with CRS with nasal polyps. The second phase is characterized by peripheral blood eosinophilia and/or eosinophilic tissue infiltrates (i.e., eosinophilic pneumonia or gastroenteritis). The third phase is dominated by manifestations resulting from systemic vasculitis (i.e., polyneuropathy). Nasal involvement is seen in ~69 to 75% at the prodromal phase, which makes the ear, nose, and throat (ENT) evaluation highly important for the prognosis of the disease. Because the first phase of the disease is hardly distinguishable from any other patient with CRS and nasal polyps, ESS is usually performed. This does not negatively influence the disease outcome, but revision surgery is usually needed. Many of these patients need systemic steroids, and in severe cases, azathioprine or cyclophosphamide is administered for an extended period of time. Some patients may benefit from immunoglobulin or interferon-α (IFN-α) treatment.

Langerhans cell histiocytosis refers to a group of disorders associated with the accumulation of histiocytes in affected tissue. Three main groups of conditions are eosinophilic granuloma, Hand-Schüller-Christian disease, and Letterer-Siwe disease. Nasal involvement includes a nasal mass that can be evident through ostia blocking, epistaxis, and septal perforation. Diagnosis is possible only after biopsy showing the characteristic Birbeck granules and cytoplasmic inclusion bodies with “tennis racquet” appearance. Treatment typically includes surgical excision of the nasal-periorbital mass, local steroids, radiation, and for multiple sites or bone marrow involvement, chemotherapy.

Stay updated, free articles. Join our Telegram channel

Join