Undifferentiated Connective Tissue Disease (UCTD)

Undifferentiated connective tissue disease (UCTD) and mixed connective tissue disease (MCTD) are conditions that have some similarities to other systemic autoimmune or connective tissue diseases, but there are distinctions which make them different.

Woman having knee examined.
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In a systemic autoimmune disease, the whole body is affected and the immune system, which normally protects the body by attacking foreign invaders, attacks the body's own tissues. In a connective tissue disease, as the name suggests, the connective tissue is attacked and affected. Connective tissue supports and connects various parts of the body and includes the skin, cartilage, and other tissues.

Mixed connective tissue disease is an autoimmune disease with overlapping characteristics of five other connective tissue diseases — systemic lupus erythematosus, scleroderma, polymyositis, rheumatoid arthritis (RA), and Sjogren’s syndrome . It is sometimes referred to as an overlap syndrome. On the contrary, undifferentiated connective tissue disease lacks enough of the features or criteria to be classified as any one of the autoimmune or connective tissue diseases. 

Features of Undifferentiated Connective Tissue Disease

Patients with undifferentiated connective tissue disease have symptoms (e.g., joint pain), lab test results (e.g., positive ANA), or other features of a systemic autoimmune disease, but they do not satisfy classification criteria for specific connective tissue diseases, such as lupus, rheumatoid arthritis, Sjogren's syndrome, scleroderma, or others. When there are insufficient characteristics to be classified as any one connective tissue disease, the condition is classified as "undifferentiated".

The terminology of undifferentiated connective tissue disease first came into play in the 1980s. Basically, it was applied to patients who were thought to be in the early stages of connective tissue disease. Latent lupus and incomplete lupus erythematosus were other names used to describe this group of patients.

It is thought that 30% or fewer patients with undifferentiated connective tissue disease progress to a definitive diagnosis of a connective tissue disease. Approximately one third go into remission, and the rest maintain a mild course of undifferentiated connective tissue disease.

Characteristic symptoms of undifferentiated connective tissue disease include arthritis, arthralgia, Raynaud's phenomenon, leukopenia (low white blood cell count), rashes, alopecia, oral ulcers, dry eyes, dry mouth, low-grade fever, and photosensitivity. Typically, there is no neurological or kidney involvement, nor the involvement of the liver, lungs, or brain. The majority of patients with undifferentiated connective tissue disease, perhaps 80%, have a simple autoantibody profile, often anti-Ro or anti-RNP autoantibodies. 

Diagnosing and Treating UCTD

As part of the diagnostic process for undifferentiated connective tissue disease, a complete medical history, physical examination, and laboratory testing is necessary to exclude the possibility of other rheumatic diseases. Regarding the treatment of undifferentiated connective tissue disease, there have been no formal scientific studies of specific treatments for undifferentiated connective tissue disease. The treatment selection is typically based on the symptoms presented and a doctor's previous success in prescribing a particular treatment for rheumatic diseases.

Usually, treatment for UCTD consists of some combination of analgesics and NSAIDs to treat pain, topical corticosteroids for skin and mucous tissue, and Plaquenil (hydroxychloroquine) as a disease-modifying anti-rheumatic drug (DMARD). If the response is insufficient, low dose oral prednisone may be added for a short time frame. High doses of corticosteroids, cytotoxic drugs (e.g., Cytoxan), or other DMARDS (such as Imuran) are generally not used. Methotrexate may be an option for hard-to-treat cases of undifferentiated connective tissue disease.

The Bottom Line 

The prognosis for undifferentiated connective tissue disease is surprisingly good. There is a low risk of progression to a well-defined connective tissue disease, especially among patients who experience unchanged undifferentiated connective tissue disease for 5 years or more.

Most cases remain mild and symptoms are treated without the need for heavy-duty immunosuppressants.

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