Dry syndrome, also known as autoimmune exocrine gland disease, is a systemic chronic inflammatory autoimmune disease. When this disease exists alone, it is called primary dry syndrome, and when it is secondary to other autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus, it is called secondary dry syndrome, and primary dry syndrome is more common than secondary dry syndrome. This article mainly introduces primary desiccation syndrome. Dry syndrome mainly invades the exocrine glands, lacrimal gland and salivary gland are most commonly involved, forming dry keratoconjunctivitis and oral dryness, and at the same time, it can also affect other organs to form various clinical manifestations.
Etiology and pathogenesis
The etiology of this disease is still unclear, and genetics is related to the development. Immunogenetic studies suggest that the development of dry syndrome is related to the frequency of certain HLA (human leukocyte antigen) genes, and the positive rate of HLA-B8, DR3 and DRw52 genes in patients with primary dry syndrome is significantly higher than that of the normal population. phenomenon. Estrogen can activate polyclonal B lymphocytes, and at the same time increase serum prolactin level, increase immune activity and accelerate the progress of autoimmune reaction, which is also the reason why dry syndrome is significantly higher in women than men.
Clinical manifestations]
Primary dry syndrome mainly occurs in women aged 40 to 60, the ratio of male to female is about 1:10, children and adolescents can also be affected. According to domestic reports, because the symptoms are not specific, the average time from onset to diagnosis is about 6 years. The symptoms of dry syndrome are partly exocrine gland involvement and partly systemic involvement. Damage to the exocrine glands causes destruction of the glands and reduction of secretion, resulting in dryness symptoms in the mouth and eyes.
(1) Dry mouth syndrome: frequent drinking of water for speech and solid food; smooth, dry, cracked or ulcerated tongue; rampant caries – blackened teeth, flaky loss, only remnants left; parotid and/or submandibular glands transient or chronic, recurrent enlargement (one side or both sides), may be accompanied by pain and pressure pain; nearly 50% of patients with primary dry syndrome have enlargement of salivary glands, while in In primary dry syndrome, nearly 50% of patients have enlargement of salivary glands, but in secondary dry syndrome, it is rare; periodontal disease and flat mossy lesions of oral mucosa caused by Candida infection or other microbial infections are easily seen in the mouth.
(2) Dry eye syndrome (dry conjunctivitis): dry eyes, foreign body sensation, few tears, photophobia, decreased vision and easy fatigue, etc.
(3) Dryness symptoms can appear in the respiratory tract, digestive tract, vagina, skin, nasal cavity and other parts.
Dry syndrome can also cause systemic symptoms: weakness is obvious, fever is mostly low fever, and individual patients are highlighted by repeated high fever.
Skin and mucous membrane lesions: purpura-like or erythema nodosum-like rash on both lower limbs, oral ulcers and Raynaud’s sign can be seen.
Bone, joint and muscle lesions: mild arthralgia, some may have swelling, joint destruction is rare; a few patients have myalgia and muscle weakness; severe osteoporosis may be combined.
Digestive system lesions: there may be hepatomegaly, splenomegaly, jaundice, increased transaminases, which may cause obstructive cholangitis and autoimmune cholangitis, acute and chronic pancreatitis and atrophic gastritis, which may cause swallowing difficulties. There may also be small intestine absorption and pancreatic exocrine function is low, gastric acid reduction, etc.
Renal lesions: mainly distal tubular lesions, but a few may also invade the glomerulus. It may lead to hypokalemic periodic paralysis, renal tubular acidosis, nephrogenic uropathy, nephrogenic chondromalacia and urinary stones.
Neurological lesions: There can be central and peripheral neuropathy, which originates from vasculitis. Peripheral neuropathy is more common, mainly involving the trigeminal nerve and other sensory nerve fibers, manifesting as sensory hypersensitivity and sensory loss, and motor impairment when involving motor nerves. Central neuropathy may include seizures, impaired consciousness, and psychiatric symptoms.
Respiratory and cardiac lesions: respiratory dryness, dry cough, interstitial lung fibrosis, pulmonary heart disease, pericardial effusion, and eventually respiratory and heart failure.
Lymphatic tissue hyperplasia: multiple lymph nodes are enlarged, pathology shows benign hyperplasia (pseudolymphoma), pseudolymphoma can also transform to malignant lymphoma.
Hematologic lesions: leukopenia and thrombocytopenia and anemia may be present.
Thyroid disease: It is not uncommon for the combination of chronic lymphocytic thyroiditis to lead to hypothyroidism.
Patients with primary dry syndrome often show signs and symptoms of arthritis or arthralgia, and often show high titer rheumatoid factor positivity, so sometimes they are misdiagnosed as rheumatoid arthritis. Primary dry syndrome is mainly polyarticular lesion, both large and small joints can be involved, often involving knee, ankle, metacarpophalangeal joint, shoulder joint and wrist joint, symmetrical or asymmetrical. Mostly manifested as arthralgia, often non-erosive arthritis, joint destruction is rare, rarely causes joint deformity, and X-ray examination rarely shows joint space narrowing or bone destruction.
Laboratory tests] In addition to various clinical manifestations, patients with dry syndrome may have many abnormal laboratory tests, such as positive ANA (anti-nuclear antibody), anti-SSA antibody and anti-SSB antibody, and rheumatoid factor is mostly positive in high titer in dry syndrome. The positive rates of anti-SSA antibody and anti-SSB antibody in dry syndrome are 70% and 40% respectively, which are both of great value for the diagnosis of dry syndrome. The positive rate of anti-SSB antibody is lower than that of anti-SSA antibody, but anti-SSB antibody has more specificity for diagnosis. Anti-SSA antibodies and anti-SSB antibodies are not related to disease activity and do not disappear with the remission of disease. In addition, antithyroglobulin antibodies can be measured in 50% of patients with primary dry syndrome, and anti-mitochondrial antibodies and anti-gastric lining cell antibodies can be measured in a few cases. Hyperglobulinemia is one of the characteristics of the disease. Patients may have an increase in globulin, a decrease in the proportion of albumin, and an increase in all immunoglobulins, mainly in IgG. The level of IgG is currently thought to correlate with disease activity.
Diagnosis】The diagnosis of this disease is not difficult, and the European diagnostic criteria and the international (classification) diagnostic criteria revised in 2002 are mostly used at present. European diagnostic criteria.
(1) Having dry eyes for more than 3 months, or sandy eyes, or needing artificial tears more than 3 times a day, with either 1 of the above is positive.
(2) A dry mouth for more than 3 months, or a need to send down with water when eating dry food, or recurrent or persistent enlargement of the parotid gland, with any one of the above items is considered positive.
(3) Filter paper test ≤5mm/5min or corneal staining index ≥4 is considered positive.
(4) Mononuclear cell infiltrate foci ≥1/4mm2 of lower lip mucosal biopsy were considered positive.
(5) Parotid gland imaging, salivary gland radionuclide scan, and positive salivary flow rate in any 1 of them.
(6) Positive serum anti-SSA and anti-SSB antibodies. Anyone who has at least 4 of the above 6 items can be diagnosed as primary dry syndrome. Those who have a certain definite connective tissue disease and have the above (1) or (2) at the same time, and have 2 positive items in (3), (4) and (5) are diagnosed as secondary dry syndrome.
International diagnostic (classification) criteria of dry syndrome revised in 2002.
I. Oral symptoms (1 or more of the 3 items)
1.Feeling dry mouth daily for more than 3 months.
2.Recurrent or persistent enlargement of the parotid gland in adults.
3.When swallowing dry food, water is needed to help.
II. Eye symptoms (1 or more of 3)
1.Feeling unbearable dry eyes daily for more than 3 months.
2.Feeling repeated sand in the eye or gritty sensation.
3.Need to use artificial tears 3 times or more daily.
III. Ocular signs (positive for any 1 or more of the following)
1.Schirmer’s test (+) (≤5mm/5min).
2, corneal staining (+) (≥4van Bijsterveld score method).
IV. Histological examination.
Small lacrimal gland lymphocytic foci ≥1 V, salivary gland damage (one or more positive).
1, salivary flow rate (+) (≤1.5 ml/15 min).
2, parotid angiography (+).
3, Salivary radionuclide examination (+).
VI. Autoantibodies.
Anti-SSA or anti-SSB (+) (double diffusion method). Specific determination criteria.
(1) Primary dry syndrome without any underlying disease, two of the following can be diagnosed.
(1) Four or more of the above six entries are met, but at least one positive entry is required for entries Ⅳ and Ⅵ.
② Positive for any three of the four entries III, IV, V and VI.
(2) Patients with secondary dry syndrome have underlying diseases (e.g., any connective tissue disease, meeting any 1 of entries Ⅰ and Ⅱ, while meeting any 2 of entries Ⅲ, Ⅳ and Ⅴ).
(3) Diagnosis 1 and 2 must exclude history of cervical cephalad facial radiation therapy, hepatitis C virus infection, AIDS, lymphoma, nodular disease, GVH disease, and application of anti-acetylcholine drugs (such as atropine, scopolamine, bromopamine tylenol, belladonna, etc.).
【Treatment】The disease is a chronic disease, which generally cannot be completely cured, but it is possible to stop the medication completely and achieve clinical remission. Mild cases require only symptomatic treatment, while severe cases require high-dose glucocorticoids or even chemotherapeutic drugs. The following treatment principles should be adopted.
(1) Patients with dry syndrome should develop treatment plans under the consultation of multidisciplinary physicians such as rheumatology, ophthalmology and stomatology; at present, it cannot be cured, but can only alleviate symptoms and delay or stop tissue damage.
(2) Symptomatic treatment should be given to those without multi-system damage. Those with dry mouth can drink more water to reduce the symptoms of dry mouth, or give symptomatic treatment with cyclopentethione tablets, or use pirocarbine and other drugs abroad. For dry eyes, artificial tears can be used to reduce the symptoms of dry eyes. Emollients are given for dry skin. In addition, symptomatic treatment can be given for non-specific symptoms, such as general weakness, sleep disorders, etc.
(3) Pay attention to oral hygiene, regular dental examination, use toothpaste without descaling agent to reduce the stimulation of the oral cavity, use toothpaste containing fluoride to reduce the loss of tooth enamel; use anti-fungal drugs topically when oral Candida infection and stomatitis occur; treat sinusitis promptly.
(4) Those with multi-systemic damage should undergo systemic systemic treatment along with symptomatic treatment.
(5) For combined joint and muscle lesions, oral treatment with non-steroidal anti-inflammatory drugs, etc.
(6) For kidney damage combined with hypokalemic periodic paralysis, intravenous potassium supplementation should be replaced by oral potassium supplementation for maintenance after the symptoms have stabilized. For longer duration of the disease, attention should be paid to calcium and active VitD supplementation.
(7) Combined with neurological lesions, renal damage, vasculitis, interstitial lung lesions, hematological lesions, etc., glucocorticoids (such as prednisone, methylprednisolone, etc.) can be applied for treatment.
Conclusion: Dry syndrome is a chronic disease with a relatively slow progression, and with standardized treatment, the prognosis is generally good, and the survival time of patients without visceral involvement is close to that of the general population. The main causes of death are: interstitial lung fibrosis combined with infection, pulmonary hypertension, renal failure, lymphoma, central neuropathy, etc.