16.3Head and Neck Manifestations

16.3.1 Ophthalmic

Dryness (xerophthalmia) is characteristic of SS and can lead to a variety of eye symptoms and signs. These will be described in detail in other chapters and will not be discussed here.

16.3.2 Oral

Xerostomia and oral pain are some of the most common presenting symptoms and key diagnostic features of SS [1, 2, 23]. However, there is

Table 16.2 Oral manifestations of SjšgrenÕs syndrome

Xerostomia

Dental caries

Periodontal disease

Early tooth loss

Mouth and throat pain

Denture problems

DifÞculty swallowing and chewing

Chronic erythematous candidiasis

Stomatopyrosis

Halitosis

Dysgeusia

Salivary gland enlargement

Angular cheilitis

Oral ulceration

Lymphoma

Fig. 16.1 Dental caries due to xerostomia

a plethora of signs and symptoms that may be found in the oral cavity of SjšgrenÕs syndrome patients (Table 16.2). Oral pain and dryness are debilitating and can markedly reduce quality of life by making speech and deglutition exceedingly difÞcult and uncomfortable [24]. Taste is reduced and atrophy of the lingual papillae may be seen. Hypersensitivity to spicy foods or strong tastes can occur, in some cases resulting in Òburning mouthÓ or stomatopyrosis [24]. Hyposalivation caused by salivary dysfunction also threatens dentition, with early dental loss contributing to poor mastication and food intake. Periodontal disease is commonplace and requires meticulous dental hygiene to prevent complications (Fig. 16.1). Up to three quarters of SS patients may show signs of chronic erythematous candidiasis often affecting the palate or buccal region [1, 2, 23Ð25]. Extension of candida to the laryngopharynx and esophagus is also frequently encountered (Figs. 16.2 and 16.3). Distal chip, high deÞnition video laryngoscopes, and ultrathin esophagoscopes have greatly increased our ability to diagnose subtle laryngeal and pharyngeal candidiasis often missed with traditional Þberoptic endoscopes. Regular dental examination is required and topical ßuoride treatment may be used to delay caries formation [23]. Patients may be aware of poor oral health but often require education in correct oral care techniques [24].

Saliva has a critical immune role, protecting oral tissue from bacterial adherence, carrying immune proteins such as lysozyme, lactoferrin, and secretory IgA that control oral ßora,

lubricate ingested material, and minimize traumatic damage [23Ð25]. Saliva ßow also mechanically ßushes the oral cavity and clears residue. It acts as a buffering solution stabilizing pH, is a solvent for ions critical to remineralization of teeth, and tastants that ßavor food [1, 23Ð25]. The composition and ßow rate of saliva are altered in SS [25]. The concentration of proteins is changed with a decrease in secretory IgA, which weakens the bodyÕs defense against plaque and caries [25]. Usually a total of 1.5 L of saliva is made per day. This can be reduced in SS to less than 30% of normal ßow. This may be compounded by medications such as anticholinergics and diuretics [25]. Pijpe et al. also

demonstrated a clear progressive loss of salivary function over time [26]. Patients frequently present with complaints of excessive throat clearing and the sensation of abundant throat mucus. The diminished viscosity of mucus often associated with SS can prolong hypopharyngeal transit of mucus through the pharynx and into the esophagus. Thus, although patients are making less saliva, what saliva they do produce adheres to the mucosa of the laryngopharynx and gives patients the sensation of excessive throat mucus. Patients often engage in habitual throat clearing in an illadvised attempt to clear the thick mucus. This can exacerbate laryngeal and pharyngeal inßammation and produce laryngeal edema, which

can aggravate the adherent mucus. Breaking people from this vicious cycle of habitual throat clearing is essential to optimize treatment outcomes.

Salivary gland enlargement is a frequent Þnding. Most often affecting the parotid gland, it may begin unilaterally but usually becomes bilateral. Gland size may ßuctuate initially then become Þrm, rubbery, and consistently enlarged. Pain and tenderness of the glands are rare. Massage and heat application can be symptomatically helpful for patients and prevent stasis of saliva within ectatic ducts [1, 2, 23]. B-cell and T-cell inÞltration of salivary tissue is found on histopathology, typically periductal in location. Although common thinking links acinar loss with T-cell and B- cell-mediated destruction (through cytokines and antibodies), neural loss or dysfunction may also be contributory, as antibodies against muscarinic receptors have been identiÞed [7, 11, 23, 25]. Cholinergic muscarinic stimulation results in serous secretion from acini. If muscarinic M3 receptors are disabled by autoantibodies then gland secretion would be poor despite functional acini being present. This is supported by evidence of large numbers of morphologically intact acini in defunct glands of patients with severe xerostomia [11, 23, 25].

A variety of autoantibodies against different cellular components are identiÞed in SS. Those against ribonucleoproteins known as antiRo (SSA) and anti-La (SSB) are seen commonly and are considered a diagnostic criteria [1, 6, 8, 9, 27, 28]. New studies have demonstrated the ability of anti-Ro and anti-La to penetrate cultured human salivary cells, induce DNA fragmentation and cleavage, and initiate caspase-driven apoptosis [28, 29]. This suggests a direct autoantibodymediated targeted destruction of the glandular tissue resulting in dysfunctional glands and xerostomia.

Persistent glandular enlargement may be due to the development of lymphoproliferative disease within either the substance of the gland or intraparotid lymph nodes [30]. Studies previously suggested a 44-fold increased risk of development of lymphoma in patients with pSS [2, 30, 31]. More recently Theander and colleagues have

reviewed over 500 patients with pSS and compared them to matched population controls. They found a 16-fold increased incidence of lymphoma and myeloma compared to the normal population [30]. The risk increased steadily with the longer duration of disease. Within the Þrst 5 years after the initial diagnosis, the risk was elevated 6.4-fold. Greater than 10 years after the initial diagnosis, the risk of malignancy was 20.8 times the general population. A 5% lifetime risk for development of lymphoma is estimated [2, 30Ð32]. The strongest predictor of lymphoma was an altered CD4+/CD8+ ratio, with patients with CD4+ lymphopenia showing signiÞcantly increased risk of death [30]. Other risk factors for malignancy development are hypergammaglobulinemia, purpura, and low C3 and C4 levels [1, 3, 8, 32Ð35]. Anti-B-cell therapy such as rituximab has shown some efÞcacy in treating SS patients including those with lymphomas [33].

16.3.3 Otologic

Approximately one-third of patients with primary or secondary SS have high frequency sensorineural hearing loss (SNHL) [2, 36Ð38]. Loss ranges from mild to severe and is not associated with an increased risk of retrocochlear pathology or correlated with the severity of disease or the level of autoantibodies [37Ð39]. Longer disease duration was associated with the level of hearing loss in one study [37]. A proposed mechanism is immune deposition within the stria vascularis, although no conÞrmatory evidence for this exists. In patients with other autoimmune disease, increased prevalence of high frequency SNHL has also been noted and, thus, may be a function of autoimmunity in general [11, 37, 38]. Possible autoantibodies to ciliar epitopes were identiÞed in mice but not in humans as yet [11]. There is no evidence that otitis media is more prevalent in patients with SS compared to the general population. The high prevalence of hearing loss in patients with SS is underappreciated by most clinicians. The prevalence of hearing loss is elevated enough to warrant a baseline audiogram in all patients with an established diagnosis.

16.3.4 Rhinologic

There are no pathognomonic signs or symptoms of SS that are found in the nose or sinuses. However, the mucosal lining of the nasal cavity and sinus cavities are also subject to the xerosis that affects other sites. This can lead to epistaxis, crusting, and a poor sense of smell. Approximately 50% of patients may have nasal mucosal atrophy [40]. Research suggests that there is dissociation between the gel and sol layers within the mucociliary transport system of the nose. This leads to poor transport of mucus and particulate matter in the nose [41]. This presents clinically as nasal bleeding and crusting. There is no clear evidence to suggest an increased prevalence of sinusitis or septal perforation as seen in WegenerÕs granulomatosis. Smell may be decreased due to the lack of solvent for dissolving odorants.

Careful nasal hygiene with saline rinsing, misted saline sprays, and avoidance of drying medications such as decongestant sprays and anti-histamines are recommended. Petroleumbased ointments can also provide longer moisture protection by limiting drying of the mucosa and can be applied several times daily. These do not need to contain antibioticÑit is the viscosity and desiccation-retardant properties of the ointments that are beneÞcial. We have found over-the- counter steamers to be beneÞcial and frequently recommend applying three drops of eucalyptus

oil to the water basin of the steamer as a form of Òvapor therapy.Ó Many herbal healers believe that eucalyptus oil can relieve the symptoms of colds and ßu, sore throat, cough, and rhinitis. Empiric treatment of SS patients with eucalyptus vapor therapy has been beneÞcial in our practice. Clinical evidence is lacking.

16.3.5 Laryngeal

Dysphonia is relatively frequent and can be the presenting symptom in some patients with SjšgrenÕs syndrome. We live in a communication age and voice problems can have devastating consequences on an individualÕs quality of life. Mucus is essential to normal mucosal vibration of the vocal folds. Mucus of high viscosity can adhere to the vocal folds and alter the normal frequency of a personÕs voice (Fig. 16.4). The voice can also become diplophonic, harsh, and raspy. Saliva, with its high concentration of bicarbonate, is essentially the bodyÕs endogenous antacid. All individuals reßux. Up to 50 reßux episodes from the stomach into the distal esophagus may be considered normal (physiologic reßux). Up to two reßux episodes (pH 4) into the laryngopharynx may also be considered normal. Patients with SS lack the innate buffering capacity of saliva. Even normal, physiologic amounts of reßux can cause extensive laryngeal damage and symptoms of laryngopharyngeal reßux (LPR) in patients