Introduction to Sjogren's Syndrome

Signs and Symptoms of Sjogren's Syndrome

The signs and symptoms of Sjogren's syndrome may be grouped as follows:

  • Oral manifestations
  • Ocular manifestations
  • Systemic manifestations

Oral Manifestations

The major oral manifestation of Sjogren's syndrome is dry mouth (xerostomia) resulting in a parched, dry sensation in the mouth and throat. It has been reported that approximately 94% of patients with Sjogren's syndrome experience dry mouth.

Swallowing flushes out the mouth by clearing the oral cavity of saliva, food debris and microorganisms. When this process is interrupted, as occurs in Sjogren's syndrome, there is an increase in many types of microorganisms in the mouth which lead to dental caries (cavities), periodontal disease, and infection.

The mouth may appear moist in the early stages of Sjogren's syndrome, but as the disease progresses, the dryness becomes more pronounced as saliva ceases to pool at the bottom of the mouth and extreme dryness sets in. This may cause the tongue to stick to the roof of the mouth and as a result affects speech clarity and/or may cause a clicking dimension to speech.

Other oral manifestations of the disorder may include:

  • Tongue

    • Dry, red, or painful tongue (glossodynia)
    • Ulcers on the tongue
    • Taste buds do not function properly
    • Tongue adheres to palate affecting speaking and eating

  • Eating function

    • Difficulty chewing and swallowing food, especially dry, crumbly foods such as crackers
    • Changes in the ability to taste food (dysgeusia)
    • Food adheres to dental surfaces

  • Oral mucosa

    • Fungal infections such as chronic erythematous candidiasis (causes red patches and thinning of mucosa on the palate and inner lining of the cheeks and lips) may affect up to 30% of patients
    • Cracked lips with fissures (cheilitis)
    • Angular cheilitis - a painful cracking and soreness that develops at the corners of the mouth
    • Fissures of the inner tissue lining the mouth and cheek

  • Oral cavity

    • Severe dryness
    • Burning or tingling sensation in the mouth or soreness
    • Unpleasant taste in the mouth
    • Halitosis (bad breath)
    • Tooth decay - first appears at the margins with the gums and then progresses further into the mouth. This affects about 70% of Sjogren's patients.
    • Cavities
    • Difficulty anchoring dentures in the gums
    • Gum sores due to dentures
    • Voice alterations such as hoarseness, coarse voice

  • Swelling of the salivary glands (particularly the parotid gland) - this occurs in approximately one third of patients with primary Sjogren's syndrome. It may begin on one side only and then develop into bilateral swelling. The enlargement may be chronic or episodic and leads to loss of function of the gland which results in a further decrease of salivary production and flow rates.

Ocular Manifestations

The most common ocular (eye) feature of Sjogren's syndrome is dry eye, also known as xerophthalmia and keratoconjunctivitis sicca. Approximately 65% of patients diagnosed with Sjogren's syndrome complain of dry eyes.

Other ocular manifestations of Sjogren's syndrome include:

  • Redness, soreness, burning, or itching
  • Foreign body sensation in eyes - sometimes described by patients as "grains of sand in eyes"
  • Difficulty tolerating contact lenses
  • Photophobia - avoidance of light
  • Eye fatigue - particularly when reading or watching television
  • Discharge or secretions from the eyes due to abnormal mucus production
  • Feeling a film or lack of acuity in the visual field
  • Corneal ulceration
  • Blurred vision

Some patients have reported that ocular symptoms associated with Sjogren's syndrome are often exacerbated by:

  • Low humidity
  • Dry climate
  • Exposure to cigarette smoke
  • Anticholinergic drugs

Systemic Manifestations

Sinus Symptoms

Nasal or sinus symptoms are attributable to Sjogren's syndrome partly because up to 50% of patients experience atrophy of the mucus lining of the nose. Symptoms include:

  • Nasal crusting
  • Epistaxis (nose bleeds)
  • Perforation of the septum
  • Hyposmia (diminished sensitivity to smell)
  • Hypogeusia (diminished sensitivity to taste)
Musculoskeletal Symptoms

Approximately 55% of patients with primary Sjogren's syndrome experience musculoskeletal symptoms including:

  • Arthralgia (non-inflammatory joint pain) or arthropathy (diseases of the joint) that occurs in up to 50% of patients
  • Arthritis (inflammatory joint pain) is thought to occur in at least 30% of patients with Sjogren's syndrome and tends to be relapsing and remitting. Some patients exhibit signs of arthritis 5-10 years before they are diagnosed with Sjogren's syndrome. Arthritis tends to occur symmetrically on the right and left sides.
  • Myositis - inflammation of muscle tissue
  • Myalgia - noninflammatory muscular pain - it is estimated that up to 20% of patients with Sjogren's syndrome suffer from fibromyalgia
  • Muscle weakness
Fatigue

One of the most debilitating systemic features of Sjogren's syndrome is fatigue which many individuals with Sjogren's syndrome describe as more distressing than any other symptom. Fatigue occurs in approximately 50-70% of patients with Sjogren's syndrome.

Sleep disorders are also common in patients with Sjogren's syndrome which may be a factor in fatigue. Patients report that they sleep but do not feel well rested when they wake up. Some clinicians are of the opinion that the excessive fatigue experienced by these patients may be related to subclinical hypothyroidism which is also associated with Sjogren's syndrome.

Cutaneous Symptoms

Estimates of the percentage of Sjogren's syndrome patients who experience skin problems range from 10-40%. Cutaneous vasculitis (inflammation of the blood vessels in the skin) is one of the most characteristic extraglandular manifestations of Sjogren's syndrome and is thought to be due to lymphocytic infiltration into the walls of the blood vessels. Typically, small blood vessels are affected more than large ones.

The most common forms of cutaneous vasculitis seen in Sjogren's syndrome patients (typically patients who have anti-Ro and anti-La antibodies) are:

  • Palpable or nonpalpable purpura (purple spots on the skin after blood "leaks" underneath; similar to a bruise) which can cause raised, red skin lesions
  • Urticarial lesions (hives)
  • Erythematosus micropapules - red spots

Patients with cutaneous vasculitis also may develop non-vasculitic lesions including:

  • Petechiae - pinpoint dots
  • Photosensitive cutaneous lesions - lesions which are sensitive to light (also seen in patients with systemic lupus erythematosus)
  • Livedo reticularis - marbled appearance of the skin
  • Lichen planus - small itchy pink or purple spots on arm and/or legs
  • Thrombocytopenic purpura - purple areas on the skin related to a decrease in blood platelets
  • Vitiligo - white patches on skin due to loss of pigmentation

Cutaneous vasculitis (as well as other forms of vasculitis - see below) is considered to be a significant prognostic indicator with the development of lymphoma and mortality. A large 2004 study of 558 Sjogren's syndrome patients diagnosed with cutaneous involvement reported that 58% of the patients had cutaneous vasculitis and showed a higher incidence of:

  • Peripheral neuropathy - damage to the nerves that supply the arms and legs characterized by burning, tingling, numbness and pain
  • Raynaud's phenomenon - a circulatory disorder caused by insufficient blood supply to the hands and feet
  • Renal (kidney) involvement
  • Presence of autoimmune markers such as antinuclear antibodies (ANA) and rheumatoid factor
  • B-cell lymphoma

Other skin problems that may be experienced by patients with Sjogren's syndrome include:

  • Dry skin - affects up to 55% of patients with Sjogren's syndrome (xerosis)
  • Itchy skin
  • Burning skin - may be experienced in up to 20% of patients with Sjogren's syndrome
  • Skin rashes - may be experienced in up to 10% of patients with Sjogren's syndrome
  • Raynaud's phenomenon - may appear before the development of symptoms of dry mouth and dry eyes by many years. It is estimated to occur in up to 30% of patients with Sjogren's syndrome and is usually of minor clinical significance.
Vasculitis

Vasculitis refers to inflammation of the blood vessels and is estimated to occur in up to 10% of patients with Sjogren's syndrome. It typically involves small and medium blood vessels and ranges from benign (most common) to life threatening (rare). Risk factors for development of vasculitis include:

  • Parotid scintigraphy - Grades III-IV (a diagnostic technique based on the detection of radiation emitted by radioactive substances injected into the body; also called radionuclide scanning). This is considered as an independent prognostic factor of development of vasculitis.
  • Low C3 and/or C4 levels in the blood (hypocomplementemia)
  • Cryoglobulinemia (low levels of immunoglobulins that congeal in cold temperature)
  • Anti Ro/La antibodies

Life-threatening vasculitis, however, is rare and appears to be related with the presence of cryoglobulinemia (elevated levels of cryoglobulins in the blood plasma).

Pulmonary Symptoms

The most common pulmonary (lung) symptom of Sjogren's syndrome is a dry cough due to xerotrachea (dry, scratchy trachea). Pulmonary involvement ranges from 9-75% of patients with Sjogren's syndrome depending upon the diagnostic techniques that are used but is rarely clinically significant. Evidence of pulmonary changes appears on up to 50% of lung scans by some estimates, but they usually remain subclinical. Progression is very slow and typically does not develop into clinically significant pulmonary disease. In one study examining the incidence of pulmonary involvement in patients with Sjogren's syndrome, approximately 87% of patients had some degree abnormal pulmonary function.

Recent studies show that pulmonary involvement is typically at the bronchial or bronchiolar level but interstitial disease (damage to lung tissue) can occur. Other pulmonary complications which may occur include:

  • Tracheobronchia sicca - dryness of the tracheal pathways leading to continual dry cough
  • Lymphocytic interstitial pneumonitis - a syndrome characterized by fever, cough, and shortness of breath with infiltrates of dense interstitial accumulations of lymphocytes and plasma cells
  • Pulmonary pseudolymphoma - a benign accumulation of inflammatory lymphoid cells in the lung
  • Alveolitis - inflammation of the air sacs (alveoli) in the lungs where the exchange of oxygen and carbon dioxide takes place
  • Various types of pneumonia, such as nonspecific interstitial pneumonia, organizing pneumonia (noninfectious inflammation of the bronchioles and surrounding lung tissue), usual interstitial pneumonia (changes in lung tissue that are indicative of fibrosis or scarring)
  • Primary lymphoma of the lung
  • Mucosa associated lymphoid tissue (MALT)
  • Lung hypersensitivity
  • Diffuse interstitial amyloidosis (deposit or accumulation of protein in lung tissue) - this is not a common development but is associated with progressive deterioration and a poor prognosis.

Tracheobronchial sicca and interstitial pneumonitis are the most common lung conditions associated with Sjogren's syndrome.

To read more about interstitial lung disease in primary Sjogren's syndrome, please click on the following link: http://www.medifocus.com/abstracts.php?gid=RH011&ID=17714766

Kidney/Bladder Symptoms

Kidney and other genitourinary symptoms are thought to occur in approximately 10% of patients with primary Sjogren's syndrome and are caused by the infiltration of lymphocytes into the kidneys. Clinically significant renal involvement is rare.

Renal conditions which may develop in patients with Sjogren's syndrome include:

  • Chronic interstitial cystitis - a chronic, inflammatory condition of the bladder wall that is a common condition among patients with Sjogren's syndrome. Recent studies have found that many people with Sjogren's syndrome also suffer from chronic interstitial cystitis in the absence of bacterial infection. The symptoms are similar to those of a urinary tract infection, however, urine cultures are negative. The diagnosis is confirmed by cystoscopy and biopsy.
  • Tubular disease such as tubulointerstitial nephritis - an inflammation of the tubules of the kidney and the spaces between the tubules and the glomeruli. Tubular involvement is usually found in younger patients and typically remains subclinical without developing into renal failure.
  • Renal tubular acidosis develops when the kidneys fail to excrete acids into the urine resulting in a build-up of acids in the bloodstream. Without proper treatment, this condition can lead to a variety of other complications including kidney stones and progressive kidney failure.
  • Glomerular diseases such as membranous glomerulonephritis - an inflammation of the glomeruli of the kidneys caused by the accumulation of protein in the bloodstream (proteinuria). Glomerular involvement is a severe manifestation of extraglandular disease involvement of Sjogren's syndrome. It typically appears later in the course of Sjogren's syndrome and is associated with morbidity and mortality. Early diagnosis and treatment is very important.
  • Renal calculi - kidney stones
  • Deterioration of renal function due to certain medications given to treat Sjogren's syndrome such as non-steroidal anti-inflammatory drugs
Gastrointestinal Symptoms

Saliva plays a major role in the initial phases of digestion and reduced amounts or absence of saliva can cause a disruption in the normal function of the gastrointestinal tract. Esophageal dryness is the most common gastrointestinal manifestation of Sjogren's syndrome and is the cause of dysphagia (difficulty swallowing) experienced by many people with Sjogren's syndrome. Other difficulties which patients may experience include:

  • Regurgitation of food
  • Reflux of gastric acid into the esophagus (neutralizing properties of saliva are lacking)
  • Nausea
  • Epigastric pain
  • Gastritis - irritation of the stomach lining that causes "heartburn"
  • Celiac spru - food sensitivity to gluten
  • Presence of Helicobacter pylori which is associated with MALT lymphoma
  • Gastrotracheal reflux - gastric acid refluxes not just to the esophagus but up to the trachea. Continual reflux can lead to abnormal changes in tracheal tissue.

Laboratory studies may show elevated levels of certain gastric enzymes (e.g., gastrin) and biopsy may show infiltration of lymphocytes into the gastric mucosa. Development of pancreatitis is rare in patients with Sjogren's syndrome.

Neurologic Symptoms

Approximately 10%-30% of Sjogren's patients (some estimates are as high as 60%) develop neurological symptoms including:

  • Sensory neuropathy- neuropathy involving sensory nerves (nerves involved in feeling) resulting in pain.
  • Peripheral neuropathy - affects the peripheral nerves of the hands and feet and can cause numbness, tingling, pain, and muscle weakness.
  • Cranial neuropathy - most often affects the trigeminal nerve and may cause a condition called trigeminal neuralgia (intense, sharp pain in the area of the face).
  • Transverse myelitis - an acute spinal cord disorder causing sudden low back pain, muscle weakness, and abnormal sensations in the lower extremities. This is one of several sclerosis-like syndromes that may occur in up to 1% of patients with Sjogren's syndrome.
  • Abnormal nerve conduction
  • Motor neuropathy
  • Demyelinating neuropathy
  • Myelopathy (conditions affecting the spinal cord)
  • Loss of small-diameter nerve fibers

It is sometimes difficult to differentiate between age-related and Sjogren's syndrome-related neurological symptoms since there is considerable overlap between them. Also, the most common age of onset of Sjogren's syndrome is at a time in life when common aging changes may occur naturally. Thus information is limited regarding specific neurologic symptoms in elderly patients with Sjogren's syndrome.

Gynecologic Symptoms

The most common gynecological manifestation of Sjogren's syndrome in women is vaginal dryness which leads to significant general discomfort. It has been estimated that up to 25% of women with Sjogren's syndrome complain of vaginal symptoms but fertility and childbirth do not appear to be affected by the presence of Sjogren's syndrome. Dyspareunia, painful intercourse, is thought to affect approximately 40% of premenopausal women and is secondary to insufficient lubrication of the vaginal region.

When vaginal dryness develops, it should be treated promptly because it can cause:

  • Uncomfortable vaginal itching
  • Difficulty in urination
  • Urinary tract infections
  • Yeast infections

It is thought that vaginal lubrication involves fluid from the bloodstream and from the cervical mucosa that flows through the vaginal wall, and is not related to fluid produced by local glands. When women develop Sjogren's syndrome, lymphocytic inflammatory cells infiltrate the vascular system supplying fluid to the vagina thereby causing a reduction in vaginal lubrication.

Hematologic Abnormalities

Hematologic abnormalities in Sjogren's syndrome are usually asymptomatic and include:

  • Elevated sedimentation rate - this is reported in up to 70% of patients with Sjogren's syndrome.
  • Anemia - the number of red blood cells in the bloodstream is lower than normal
  • Leukopenia - the number of white blood cells (leukocytes) in the bloodstream is lower than normal
  • Autoimmune cytopenia (reduced number of cells circulating in the blood) - this is usually a mild condition but can develop into a serious condition
  • Hyper/hypoglobulinemia (elevated/reduced levels of globulins in the blood)
Lymphoproliferative Disease

Lymphoma develops in approximately 5% of patients diagnosed with Sjogren's syndrome. It has been estimated that patients with primary and secondary Sjogren's syndrome have an approximately 44-fold increased risk for developing lymphoma as compared with healthy, age-matched controls. The most common form of lymphoma associated with Sjogren's syndrome is low or intermediate grade B-cell lymphoma that originates in mucosa-associated lymphoid tissue. Lymphoma occurs more frequently in patients with primary Sjogren's syndrome than secondary Sjogren's syndrome.

It is thought that the chronic stimulation and proliferation of monoclonal B cells in Sjogren's syndrome is related to the transition that takes place from an autoimmune status to the development of non-Hodgkin's lymphoma. Most lymphomas associated with Sjogren's syndrome are characterized as:

  • Low or intermediate-grade malignancy potential
  • Localized in extranodal spaces (spaces around the outside of the lymph nodes).

Clinical or laboratory evidence of an emerging lymphoma may include:

  • Persistent enlargement of parotid glands
  • Persistent enlargement of the spleen (splenomegaly)
  • Persistent enlargement of lymph nodes (lymphadenopathy)
  • Type II mixed monoclonal cryoglobulinemia
  • Low levels of complement factor C4 in the bloodstream
  • Vasculitis

Other lymph-related conditions that may develop with Sjogren's syndrome include:

  • Lymphopenia - a reduction in the number of circulating lymphocytes in the bloodstream
  • Waldenstrom's macroglobulinemia - this is a cancer of the B-lymphocytes (a type of white blood cell) which causes overproduction of monoclonal macroglobulins (IgM antibody)
  • Lymphadenopathy - an enlargement of the lymph glands
Cardiac Symptoms

Cardiac conditions which may be associated with Sjogren's syndrome include:

  • Pericarditis - inflammation of the sac surrounding the heart
  • Pulmonary hypertension - high blood pressure in the arteries that supply the lungs
  • Abnormal blood pressure related responses such as orthostatic hypotension (sudden drop in blood pressure when changing from sitting or lying to standing)
Hepatobiliary Symptoms

Some patients may also develop hepatitis C or a condition called primary biliary cirrhosis - a liver disease that slowly destroys the bile ducts and leads to the buildup of bile in the liver and eventual cirrhosis (hardening) of the liver. Typically, however, liver involvement in patients with Sjogren's syndrome is rare (up to 5% of Sjogren's syndrome patients) and when is does occur, is usually asymptomatic and subclinical.

Psychiatric Symptoms

The most common psychiatric conditions associated with Sjogren's syndrome are:

  • Depression
  • Anxiety

The high incidence of these conditions has led some researchers to believe that they may be part of Sjogren's syndrome rather than a reaction to the stress. Depression and anxiety also commonly precede the diagnosis of systemic lupus erythematosus as well as other autoimmune conditions. Other symptoms that may develop include subtle changes in cognitive function, memory, and concentration.

Thyroid Symptoms

Antibodies directed to the thyroid gland can be detected in approximately 50% of people diagnosed with Sjogren's syndrome while only half of these patients demonstrate abnormalities on thyroid function tests. Various thyroid abnormalities, including Hashimoto's thyroiditis (a type of autoimmune thyroid disease) and hypothyroidism have been associated with Sjogren's syndrome. It is estimated that approximately 10% of patients with autoimmune thyroid disease may have Sjogren's syndrome.

To read more about thyroid disease and Sjogren's syndrome, please click on the following link: http://www.medifocus.com/abstracts.php?gid=RH011&ID=17558463

Laryngeal Symptoms

Lesions of the vocal cords have been associated with Sjogren's syndrome and can cause hoarseness which in rare cases may be the first indication of Sjogren's syndrome. Conditions associated with these lesions include:

  • Bamboo node - this is an unusual white or yellow transverse lesion typically located in the middle third of the vocal cord. It is most frequently associated with autoimmune diseases.
  • Vocal cord nodules
Otologic Symptoms

Some patients with Sjogren's syndrome demonstrate a mild to moderate sensorineural hearing loss of high frequency sounds. The connection to Sjogren's syndrome pathology is not well understood.

For more information about extraglandular involvement in Sjogren's syndrome, please click on the following link: http://www.medifocus.com/abstracts.php?gid=RH011&ID=16039337