OVERVIEW
An autoimmune disease characterized by damage to exocrine glands
Symptoms include dry eyes and dry mouth.
The cause of the disease is not clear, and is related to genetic, infectious and immunologic factors.
Treatment includes general treatment, medication, Chinese medicine, etc.
Definition
Dry syndrome is a diffuse connective tissue disease characterized by invasion of exocrine glands such as lacrimal and salivary glands, abnormal proliferation of B-lymphocytes, and infiltration of tissue lymphocytes.
Connective tissue mainly includes loose connective tissue, dense connective tissue, adipose tissue, and reticular tissue, etc. It is widely present throughout the body, especially in the walls of blood vessels, endocardium, kidneys, and synovium.
Once the connective tissue is diseased, it can produce symptoms in various systems and organs such as skin, bones and internal organs.
Classification
Primary Dry Syndrome
Mostly caused by disturbances in purine metabolism and/or decreased uric acid excretion.
Not suffering from another diagnosed connective tissue disease (e.g., systemic lupus erythematosus, rheumatoid arthritis, etc.).
Secondary Dry Syndrome
Secondary to another well-diagnosed connective tissue disorder or other disease.
Incidence
According to the literature, the prevalence of primary dry syndrome in our population is 0.33% to 0.77%.
The most common autoimmune connective tissue disease in middle-aged and elderly people.
It is most common in women aged 30-60 years, with a male-to-female prevalence ratio of 1: (9-10).
Incidence and prevalence are on the rise.
Causes
Causes
The etiology of the disease is not clear, and a large number of studies have shown that genetic, infectious, and immunologic factors are related to the development of the disease.
Genetic factors
Studies have shown that HLA-DRB1*0301, DQA1*0501, DQB1*0201 haplotypes have the strongest correlation with susceptibility to the development of primary desiccation syndrome.
Relatives in the family who also suffer from this disease are considered to have some relationship with genetics.
Infectious factors
Human herpesvirus, retrovirus and hepatitis C virus infections may induce dry syndrome.
Immunologic factors
Abnormal cellular and humoral immune responses produce a variety of mediators that cause tissue inflammation and destructive lesions.
Symptoms
Main Symptoms
Dry mouth
Dry, cracked, flushed tongue with tongue pain.
Smooth tongue with loss of concavity.
Frequent drinking of water.
Eating dry food requires water to help swallowing.
Need to get up at night to drink water.
Difficulty in eating may occur in severe cases.
Dry eyes
Dry eyes with foreign body sensation, frosting sensation and few tears.
Swelling of the eyelids may occur.
In severe cases, blindness may occur.
Swelling and pain in the parotid gland
Pain is intermittent.
It occurs unilaterally or bilaterally and may subside on its own.
Rampant dental caries
Rampant dental caries.
Teeth gradually turn black, followed by small pieces falling out, eventually leaving only the residual root.
Other symptoms
Skin rash
Characterized by a purpura-like rash that rises above the skin surface.
It is mostly found on the lower limbs.
The rash is a rice grain-sized, well-bordered papule that does not fade when pressed.
It appears in batches and may subside on its own.
After the rash subsides, brown pigmentation may remain.
Erythema nodosum is less common.
Raynaud’s phenomenon
Sudden onset of pallor and bruising of the skin at the ends of the fingers (toes) in response to stimuli such as cold or emotional stress.
It is relieved by warmth and lasts for varying periods of time.
Joint pain
Most commonly seen in the joints of the hands.
The pain is chronic, recurrent and not severe.
Joint swelling is rare.
Complications
As the disease progresses, other exocrine gland and systemic damage may occur, as described below.
Glomerulonephritis
Nasal hematuria, generalized edema (especially in the ankles, calves, and lower back), and oliguria or anuria may be present.
Distal renal tubular acidosis
Weakness, flaccid paralysis and polydipsia, polyuria and other manifestations are common.
Dry pharyngitis
Manifestations include pharyngeal discomfort, foreign body sensation and itching.
In mild cases, there are dry cough symptoms, and in severe cases, dyspnea may occur.
Interstitial lung disease
Manifested by shortness of breath after activity, dry cough, etc.
Pulmonary hypertension
Cough, dyspnea and hemoptysis are the most prominent symptoms.
Atrophic gastritis
Postprandial fullness, abdominal pain, heartburn, belching and abnormal bowel movements.
Primary biliary cholangitis
Weakness and itchy skin are the most common first symptoms.
It may also be characterized by rough skin, yellowing of the skin, emaciation, abdominal distension and bone pain.
Pancreatitis
Abdominal pain to the left of the center of the abdomen, and in severe cases, there are radiating pains on both sides of the lower back.
It may be accompanied by abdominal distension, nausea, vomiting and fever.
Peripheral nerve damage
Sensory and motor nerve abnormalities and hemiparesis may occur.
Lymphoma
Lymphoma is characterized by enlarged lymph nodes, fever, emaciation and bleeding tendency.
The risk of lymphoma is nearly 40 times higher than that of the general population.
Hyperthyroidism
Mostly manifested by eye protrusion, fatigue, excessive sweating, fear of heat, emaciation, irritability, strong appetite, and so on.
Hypothyroidism
Indifferent expression, facial edema, dry skin, loss of appetite, abdominal distension, constipation, memory loss, etc.
Consultation
Department of Medicine
Rheumatology and Immunology
If symptoms such as dry eyes and dry mouth, accompanied by skin rashes and joint pains occur, it is recommended to consult a doctor promptly.
Preparation
Preparing for your visit: registering, preparing your documents, and frequently asked questions.
Tips for your visit to the doctor
Record the progress of your condition for your doctor’s reference.
Preparation Checklist
Symptom list
Pay special attention to the time of onset of symptoms, special manifestations, etc.
What are the symptoms? How long have they been present?
Is there an increase in water intake?
Are the eyes dry? Is there any photophobia, foreign body sensation or burning sensation in the eyes?
Are there any symptoms of rash or joint pain?
Medical History Checklist
Has anyone in the family had dry syndrome?
Any history of viral infections, autoimmune or systemic diseases?
Checklist
Test results from the last six months, which can be brought to the doctor’s office
Laboratory tests: routine blood tests, autoantibody tests, erythrocyte sedimentation rate and C-reactive protein tests, liver and kidney function tests
Imaging tests: ultrasonography, magnetic resonance imaging, CT examination
Others: Saliva flow measurement, lip gland biopsy, tear flow rate test
Medication List
Medications used in the last 3 months, if available in boxes or packages, bring them to the doctor’s office
Analgesics: indomethacin, acetaminophen, diclofenac, ibuprofen
Other: hydroxychloroquine, methotrexate, prednisone
Diagnosis
Diagnosis is based on
Medical history
History of viral infection, autoimmune disease, or systemic illness.
Relatives who have had patients with the disease.
Clinical manifestations
Dry mouth, dry eyes, swollen parotid glands, rampant dental caries, skin rash, Raynaud’s phenomenon, joint pain.
The onset of the disease is usually insidious.
Laboratory Tests
Blood tests are helpful in determining the cause of the disease, as described below.
Routine blood tests
To find out the changes in blood cells (red blood cells, white blood cells, platelets) and hemoglobin.
Decreased white blood cell and platelet counts may be seen in patients with active disease.
Fasting is not necessary before the test.
Autoantibody Test
A variety of autoantibodies can be detected in the serum, which can be marker antibodies for the diagnosis of dry syndrome and indicators of disease activity.
Common autoantibodies are, in descending order, antinuclear antibody profile, rheumatoid factor, anticardiolipin antibodies, and antimelanotic antibodies.
Erythrocyte Sedimentation Rate and C-Reactive Protein
The erythrocyte sedimentation rate and C-reactive protein can be understood.
It is the main indicator to reflect the activity of the disease, and it is often seen that the erythrocyte sedimentation rate increases rapidly and C-reactive protein is elevated.
Serum immunoglobulin
The most commonly used method for checking humoral immune function helps to detect the levels of three types of serum immunoglobulins: IgG, IgM and IgA.
Generally, the most obvious result is an increase in IgG, and there may also be an increase in IgA and IgM.
Liver and kidney function
To understand the state of liver and kidney function, and to determine the damage of liver and kidney function.
Creatinine and urea nitrogen may be elevated in impaired renal function.
When liver function is impaired, aminotransferases are elevated, and bilirubin may also be elevated.
Fasting is required before the test, i.e., fasting for 6 hours and abstaining from drinking for 4 hours.
Imaging
Imaging tests such as CT, magnetic resonance imaging, and ultrasound are helpful in understanding lesions in various tissues and organs, such as the kidneys, lungs, and parotid glands.
Avoid wearing metal jewelry or clothing with metal button fittings when performing magnetic resonance imaging.
Specialty Examinations
Stomatologic Examinations
Salivary Flow Measurement: Measurement of the amount of saliva secreted over a certain period of time, which is one of the sensitive indicators for evaluating dry mouth.
Lip gland biopsy: resection of part of the glandular tissue, salivary gland pathology results help to diagnose dry mouth syndrome.
Parotid angiography: X-rays are taken after injecting contrast medium into the parotid ducts to observe the morphological changes of the ducts at all levels.
Salivary gland radionuclide examination: the specificity of parotid function for dry syndrome needs to be further determined.
Ophthalmologic examination
Tear flow rate: hang a strip of filter paper at the lower eyelid, close the eyes for a certain period of time, and measure the length of the filter paper soaked with tear fluid. This test reflects the ability of the lacrimal gland to secrete tears.
Tear film rupture time: to determine the time of tear film rupture without blinking. Usually a drop of sodium fluorescein is placed in the conjunctiva of the lower eyelid, and after the last blink of the eye, the eyes are opened wide, and the cobalt blue light of the slit lamp can be used to determine the time when the first black spot occurs on the surface of the tear film.
Corneal and conjunctival staining
Fluorescein sodium was dropped into each eye, and after a certain period of time, corneal staining was observed and scored using a slit lamp equipped with a cobalt blue filter. Ocular surface staining of a certain severity may suggest a diagnosis of dry syndrome.
Subjects must not have used eye drops prior to the test and must not have had corneal surgery or eyelid reconstructive surgery within 5 years.
Diagnostic Criteria
The International Classification Criteria for Desiccation Syndrome, as revised by the United States and Europe in 2002, are commonly used.
A history of radiotherapy to the head, neck and face, hepatitis C virus infection, AIDS, lymphoma, tuberculosis, graft-versus-host disease, use of anti-acetylcholine drugs (e.g., scopolamine, brompropyltargetine, belladonna, etc.), and IgG4-related disorders should be excluded.
Classification Criteria
Oral symptoms
1 or more of the following 3 items.
Daily dry mouth for more than 3 months.
Recurrent or persistent enlargement of the parotid gland in adulthood.
Swallowing dry food with the help of water.
Eye symptoms
1 or more of the following 3 items.
Have intolerable dryness of the eyes on a daily basis for more than 3 months.
Repeated sandy or gritty sensations in the eyes.
Need to use artificial tears daily.
Characteristics of the eyes
Positive for any 1 or more of the following tests.
Tear secretion test (+) (≤5 mm/5 min).
Corneal staining (+).
Histologic examination
Pathology of the lacrimal gland shows lymphocytic foci ≥1.
Salivary gland damage
Any 1 or more of the following tests are positive.
Salivary flowmetry (+) (≤1.5 mL/15 min).
Parotid gland imaging (+).
Radionuclide examination of the salivary glands (+).
Autoantibodies
Anti-SSA antibody/anti-SSB antibody (+).
Specific diagnostic criteria
Primary Dry Syndrome
In the absence of any underlying disease, the diagnosis is made according to the two entries below.
Fulfillment of 4 or more of the above entries, provided that at least one of the histologic tests and autoantibodies is positive.
Positive for any 3 of the 4 items, except for oral and ocular symptoms.
Secondary Dry Syndrome
The patient has an underlying disease (e.g., any connective tissue disease) that meets any 1 of the oral symptoms, ocular symptoms, and any 2 of the ocular features, histologic examination, and salivary gland damage.
Differential Diagnosis
Rheumatoid arthritis
Similarities: joint pain.
Differences: Rheumatoid arthritis is characterized by symmetrical polyarticular swelling and pain, morning stiffness, and joint deformity. Dry syndrome has milder joint symptoms with minimal joint destruction, deformity and functional limitation.
Systemic lupus erythematosus
Similarities: Both have joint pain and skin rash, and are more common in women.
Differences: Systemic lupus erythematosus usually does not present with obvious symptoms of dry mouth and eyes. It is often characterized by butterfly-shaped erythema on the face, mouth ulcers, hair loss, joint pain and swelling, and hematuria.
Hepatitis C virus infection
Similarities: both have dry mouth, dry eyes, purpura of lower limbs.
Differences: Hepatitis C serum is positive for anti-hepatitis C antibody and negative for anti-SSA/SSB antibody.
IgG4-related diseases
Similarities: both may present with enlarged lacrimal and parotid glands.
Differences: IgG4-related diseases are a group of diseases characterized by elevated serum IgG4 levels and the presence of IgG4-expressing plasma cells in tissues. Most of them do not have obvious systemic symptoms such as fever and malaise.
Treatment
Aims and principles of treatment
Treatment purpose: to prevent local damage due to prolonged drying of the mouth and eyes, and to prevent and control systemic damage of the disease.
Treatment principle: those without internal organ damage are mainly treated with alternative and symptomatic treatment, while those with internal organ damage need immunosuppressive treatment.
Treatment method
General treatment
Artificial saliva treatment is mostly unsatisfactory. Drink plenty of water and stop smoking and drinking alcohol.
Avoid taking drugs that cause dry mouth (e.g. scopolamine).
Keep the mouth clean, rinse the mouth diligently to prevent dental caries and secondary oral infections.
Pay attention to eye hygiene, can apply artificial tears (hyaluronate or carboxymethylcellulose) under the guidance of the doctor.
Medication
Non-steroidal anti-inflammatory drugs (NSAIDs)
With analgesic and anti-inflammatory effects, they can relieve joint pain symptoms.
Ibuprofen, indomethacin, loxoprofen, celecoxib, naproxen, meloxicam, and diclofenac are available.
Be aware of the risk of gastrointestinal ulcers, bleeding, and perforation.
Avoid taking two or more NSAIDs at the same time.
Relieves only the symptoms of pain, redness and swelling, does not control or stop the condition from worsening.
Antimalarials
Relieve systemic symptoms such as rash, joint pain, low-grade fever and malaise.
Hydroxychloroquine is commonly used clinically.
Long-term use of the drug to pay attention to psychoneurological symptoms (such as mood changes), retinopathy, visual changes and other adverse effects.
Glucocorticoid
It can control arthritis, interstitial pneumonia, liver function injury, renal tubular acidosis, glomerulonephritis, low blood cells, myositis, etc. and neurological injury.
Under the premise of effective control of the disease, short courses of treatment and low doses should be applied as far as possible.
Immunosuppressant
Mostly used in combination with glucocorticoid, can reduce the cumulative use of glucocorticoid and adverse effects.
Azathioprine, methotrexate, mycophenolate mofetil (mycophenolate mofetil), cyclophosphamide, leflunomide, cyclosporine, etc. can be used.
Biological agents
Suitable for those who do not get good results from conventional treatment.
Can be used to treat severe arthritis, severe hemopenia, and peripheral neuropathy.
B-cell-targeted biologics such as rituximab and belimumab may be considered to improve the condition.
Other drugs
Immunoglobulin: for those with lesions involving the nervous system or presenting with severe thrombocytopenia, intravenous administration of shock therapy.
Intravenous potassium supplementation or oral potassium tablets: to correct hypokalemia and prevent potentially life-threatening complications.
Cholinergic agonists: for those with impaired glandular function but with residual salivary gland function, available as cevimeline.
Ursodeoxycholic acid: for those with combined biliary cholangitis and cirrhosis.
Interleukin: interleukin has also been reported to reduce serum levels of relevant stimulating factors and relieve symptoms.
Special reminders
During the drug treatment, you should insist on following the doctor’s instruction strictly, and should not change the drug dosage without authorization or stop the drug suddenly to ensure that the treatment plan is implemented.
Traditional Chinese Medicine (TCM)
Doctors will choose targeted treatments (Diagnostic Therapy) according to the condition. Methods that may be used include Chinese herbal medicine and tonics.
Chinese medicines: Jin Gui Ren Qi Pills, Da Huang Hing Worm Pills, etc. may be used.
Soup medicine: may be used to add subtractions to the Blood Palace and Blood Stasis Tang, Sha Shen Mai Dong Tang, He Zhu Ye Gypsum Tang, and so on.
Chinese medicine treatment should be carried out in regular hospitals under the guidance of a doctor or by a doctor, do not believe in unidentified treatments such as local remedies, secret prescriptions, and biased prescriptions.
Prognosis
Cure
The disease cannot heal itself, nor can it be cured or eradicated.
The prognosis is good for those whose lesions are limited to exocrine glands such as salivary glands, lacrimal glands, and mucous membranes of the skin.
Those with internal organ damage can mostly be controlled with appropriate treatment.
The combination of progressive pulmonary fibrosis, central neuropathy, renal insufficiency, and malignant lymphoma may be life-threatening.
Hazards
Symptoms such as dry eyes, dry mouth, joint pain and fatigue often occur, which may affect normal work and life.
With the development of the disease, it will also lead to the damage of multiple organs such as lungs, brain and kidneys, which further affects the health and brings greater psychological and financial burden to oneself and family members.
Daily
Daily Management
Dietary management
For those without vital organs affected
Choose foods rich in protein and B vitamins, soft and easily digestible foods are preferred.
Avoid spicy and stimulating foods, such as alcohol, strong tea, coffee, raw garlic, ginger, chili peppers and curry.
Drink more water, 1500 to 2000 ml of water daily to prevent urinary tract infection and constipation. Available American ginseng, white chrysanthemum, honeysuckle and other tea to drink, but also moderate drinking plum soup, plum juice and other drinks (less sugar).
Promote stewing, boiling, blanching cooking methods, food should be soupy, easy to swallow and digest, such as porridge, soybean milk, egg custard.
If necessary, take iron, vitamin C and B vitamin supplements under doctor’s supervision.
People with mouth ulcers
It is recommended to eat small meals and prefer soft food.
Avoid pickled and smoked foods and spicy and other irritating foods to promote tissue healing.
Avoid high sugar foods or drinks to prevent dental caries.
People with combined renal insufficiency
Should choose a low-salt diet, daily salt intake of about the size of a fingernail cap, avoid seasonings such as dashi, soy sauce and pickled foods.
It is advisable to consume high-quality low-protein foods such as milk, beans, eggs, river fish, river shrimp and lean meat.
Follow your doctor’s advice to limit water intake.
Life Management
Appropriate exercise
Train in activities of daily living under doctor’s supervision to relieve fatigue, joint pain and other symptoms.
Exercise should be gradual and avoid strenuous exercise.
Pay attention to skin cleansing and moisturizing
Avoid frequent bathing and avoid using alkaline soap.
Apply a good moisturizing lotion after bathing.
Avoid applying cosmetics or skin care products to rashes or erythema.
Humidifiers can be used to increase indoor humidity appropriately.
Choose comfortable, breathable, loose-fitting underwear.
Keep your mouth clean
Brush or rinse your teeth in the morning and evening and after eating.
You can use fluoride mouthwash to rinse your mouth.
Have regular oral health checkups and care.
Improve eye habits
Avoid prolonged viewing of electronic products such as computers, cell phones and TV.
Reduce exposure to dry eye triggers such as air-conditioning and smoky environments.
Avoid rubbing your eyes with your hands.
Avoid cold stimuli
Observe weather changes and increase clothing appropriately in cold weather.
Minimize outdoor activities or work in cold weather.
Wear warm hats, masks, gloves and warm socks.
Wash your hands and feet with warm water.
Keep your joints warm when you sleep.
Avoid the sun
Wear a wide-brimmed hat when going outside.
Wear long-sleeved clothes and long pants.
Carry an umbrella.
Preventing Infection
Avoid crowded places.
Smoking cessation
Strictly abstain from smoking and avoid exposure to “second-hand smoke”.
Psychological support
Face the disease with a positive and optimistic attitude and build up confidence in overcoming the disease.
Talk to your family and friends about your feelings.
Family members should give sufficient care and comfort, and say more positive and encouraging words.
Strive to take care of your own life or participate in work that is within your ability to fulfill your life.
If severe anxiety, depression, insomnia, etc. occur, it is recommended to go to the hospital in time for formal psychological treatment.
Disease monitoring
If symptoms worsen, or new symptoms appear, prompt medical consultation is required.
Follow the doctor’s prescribed schedule for follow-up.
Prevention
If there is a relative suffering from dry syndrome, regular medical checkups should be conducted and timely consultation should be made if discomfort occurs.
Actively treat your own endocrine and immune system diseases.
Pay attention to personal hygiene, use medication cautiously and do not take medication indiscriminately, so as to avoid the disease being induced by infection or medication.
Take a balanced diet and diversify food types.
Adults should drink 1,500 to 2,000 milliliters of water daily.