Connective tissue disease is probably one of the most confusing clinical terms for patients. Doctors may diagnose “connective tissue disease”, “undifferentiated connective tissue disease”, “mixed connective tissue disease”; “systemic lupus erythematosus” with this doctor, but “connective tissue disease” with this doctor. systemic lupus erythematosus” at this doctor, but “connective tissue disease” at this doctor; “dry syndrome” at this doctor, but “connective tissue disease” at this doctor. What exactly is “connective tissue disease”? Is lupus a connective tissue disease? Is dry syndrome a connective tissue disease? Is scleroderma a connective tissue disease? What the heck are differentiation and undifferentiation? Today we will go into this mystery. What is connective tissue? First, let’s understand that the human body is composed of four major tissues: epithelial tissue, connective tissue, muscle tissue, and nerve tissue. Connective tissue, in a broad sense, includes blood, lymph, loose intrinsic connective tissue and stronger cartilage and bone. Connective tissue is widely distributed in the body and has various functions such as connection, support, nutrition and protection. Connective tissue constitutes almost every tissue, organ and system in the body and can be said to be ubiquitous. As mentioned above, the wide distribution of connective tissue determines the diversity of clinical manifestations of these diseases, which are often multi-organ and multi-systemic in nature, and therefore make treatment difficult. Diseases including systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis (scleroderma), polymyositis/dermatomyositis, systemic vasculitis, desiccation syndrome, adult Still’s disease, etc. are all connective tissue diseases, and although each of these diseases is different and has its own specificity, they have many commonalities, such as multisystem involvement (i.e., skin, joints, muscles, heart, kidney, hematopoietic system, central nervous system, etc.), Although each of these diseases has its own specificity, they have many common features, such as multi-system involvement (i.e. skin, joints, muscles, heart, kidney, hematopoietic system, central nervous system, etc. can be involved at the same time), long disease duration, complicated disease, irregular fever, arthralgia, vasculitis, visceral damage, increased blood sedimentation, increased immunoglobulin, positive autoantibodies, etc. Since SLE, dry syndrome and other diseases are all connective tissue diseases, what is the difference between them? Returning to the question at the beginning of the article, the diagnosis of “systemic lupus erythematosus” in this doctor’s office is “connective tissue disease” in this doctor’s office, and the diagnosis of “dry syndrome” in this doctor’s office is “Why is “connective tissue disease” diagnosed at this doctor? This has to start from the classification criteria of connective tissue disease. Many patients ask, “Doctor, am I diagnosed with lupus/dry syndrome (and a host of other connective tissue diseases)?” The answer to this question is actually quite difficult. This is because, unlike some diseases, there is a clear gold standard that is met to confirm the diagnosis. For example, in the diagnosis of hypertension, the standard is there if your blood pressure is high or not, and you will know it when you compare it with diabetes. For example, in the diagnosis of thyroid cancer, if you see a nodule on ultrasound, you will know whether it is cancerous or not, and the pathology report of the nodule by fine needle aspiration is there. However, as the song goes, “Who knows you better than me? It’s too much, too hard. We’re not the same!” What is different about connective tissue disease? As mentioned earlier, most connective tissue diseases are complex and of unknown etiology, involving multiple systems and resulting in dysfunction, and there is great heterogeneity in the course of the disease, clinical symptoms and disease outcome. What! No diagnostic criteria? Isn’t that nonsense? No, not really. Rheumatology has a different approach to diagnosis and treatment. In the clinic, for patients with different manifestations, we first rule out infectious and neoplastic diseases, on the basis of which we consider connective tissue diseases. On the basis of considering the diagnosis of connective tissue disease, we classify patients inductively, and a group of patients meeting certain characteristics we classify into one category: for example, the familiar classical SLE classification criteria of 11 selected 4, patients with connective tissue disease with common characteristics of this category we classify as SLE; for example, the familiar classical rheumatoid arthritis classification criteria of 7 selected 4, patients with Patients with this type of common features of connective tissue diseases, we classify as rheumatoid arthritis; and so on, including dry syndrome, systemic sclerosis (scleroderma), polymyositis/dermatomyositis, systemic vasculitis and other connective tissue diseases, are classified by the homogeneity of patients with connective tissue diseases. In other words, the various specific classification diagnoses simply classify patients with connective tissue diseases according to their clinical characteristics. Therefore, there are some patients with connective tissue diseases that achieve some of the characteristics of the disease typology that we have summarized so far, so we make the diagnosis of systemic lupus erythematosus, dry syndrome, rheumatoid arthritis, etc. in our clinic. There are some patients with connective tissue disease, although the diagnosis of connective tissue disease is considered clinically, but they are not classified and meet the classification criteria of these disease typologies that we have summarized, then we call them undifferentiated connective tissue disease. That is, undifferentiated connective tissue disease has some of the clinical manifestations of connective tissue disease, but does not meet the classification criteria for any particular disease. It may belong to the early stages of a specific type of connective tissue disease, and as the disease progresses, it may reach the classification criteria of specific connective tissue diseases such as systemic lupus erythematosus or desiccation syndrome, etc. Therefore, in clinical practice, it is common to see physicians prescribe “undifferentiated connective tissue disease: lupus tendency? and “undifferentiated connective tissue disease: tendency to dry syndrome?” In some patients, the diagnosis may be a separate disease that does not continue to differentiate into a particular type of connective tissue disease. Of course, human understanding of disease is advancing, and some patients with undifferentiated connective tissue disease may simply have a specific type that has not been summarily classified yet. For example, in recent years, a new type of specific connective tissue disease, IgG4-associated disease, has been summarized by the rheumatology community, and many patients with IgG4-associated disease were also diagnosed as undifferentiated connective tissue disease in the clinic before it was summarized and classified. Perhaps here again, some patients will say, “I know, mixed connective tissue disease is a condition in which two or more connective tissue diseases are present.” In fact, it is not. When two or more specific connective tissue disease classification criteria can be met at the same time, we call it “overlap syndrome”, also known as overlapping connective tissue disease. Common clinical conditions include: overlapping SLE and Scleroderma, overlapping SLE and polymyositis, overlapping SLE and rheumatoid arthritis (also known as Rhupus syndrome), overlapping SLE and polyarteritis nodosa, and overlapping Scleroderma and polymyositis/dermatomyositis. Mixed connective tissue diseases In contrast, mixed connective tissue diseases are a specific type of connective tissue disease. This group of connective tissue diseases is characterized by the presence of mixed manifestations of systemic lupus erythematosus, polymyositis, scleroderma, rheumatoid arthritis and other diseases with high titers of potent speckled antinuclear antibodies (ANA) and high titers of U1RNP antibodies in the blood. If you are still confused between overlap syndrome and mixed connective tissue disease, let’s summarize: mixed connective tissue disease is a single specific type of connective tissue disease that has features of multiple other connective tissue diseases; overlap syndrome is a condition in which the patient meets the classification criteria for two or more specific types of connective tissue diseases – that is, mixed connective tissue disease. -i.e., mixed connective tissue disease is one type of connective tissue disease, and overlap syndrome is when a patient has multiple connective tissue diseases at the same time. At this point, I’m sure half of our readers are already dizzy. No matter, Dr. Yu is going to introduce systemic vasculitis to confuse the remaining half of the readers as well. Systemic vasculitis is a group of connective tissue diseases manifested by inflammatory lesions of the blood vessels, and it is not a single disease, but includes many diseases. Among them, those characterized by large vasculitis are large arteritis, giant cell arteritis (temporal arteritis), etc.; those with predominantly medium vascular involvement include nodular polyarteritis, Kawasaki disease, etc.; those with predominantly small vasculitis include granulomatous vasculitis (Wegener’s granulomatosis), eosinophilic granulomatous vasculitis (Churg⁃Stauss syndrome), microscopic polyangiitis, allergic purpura, etc.; there are also vasculitis in which both small and large arteries and veins are involved, such as Behçet’s syndrome (that is, leukoaraiosis, Silk Road disease). The introduction of systemic vasculitis is not intended to be spread out or mastered, but simply to let patients with vasculitis know that they are also classified as a connective tissue disease will serve the purpose. It is the characteristics of connective tissue diseases, the wide range of organs and organs involved, which determines that rheumatology is different from other specialties in internal medicine. This also determines that the essence of rheumatology and immunology is the department of difficult diseases.