Undifferentiated Connective Tissue Disease

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The term "Undifferentiated Connective Tissue Disease" (UCTD) is used to describe people who have symptoms and certain lab test results that look like a systemic autoimmune disorder or connective tissue disease. But they don't have enough of such characteristics to meet the diagnosis for a well-defined connective tissue disease, such as rheumatoid arthritis, lupus, or scleroderma. Thus, they seem to have another, similar disorder that doctors call undifferentiated connective tissue disease.

Although the word "undifferentiated" sounds vague, rheumatologists know this term describes a real problem. It does not mean that your doctor does not know what to call what you have.

This undifferentiated category is distinctly separate from another group of vague-sounding disorders called "overlap syndromes." People with these syndromes have enough features of more than one connective tissue disease to meet the diagnoses for several at the same time. Thus, they "overlap" two or more diseases. For example, mixed connective tissue disease [MCTD] is just such an "overlap" syndrome.

Because UCTD can affect so many different parts of the body, UCTD often has many symptoms.

Common symptoms of undifferentiated connective tissue disorder include:

  • Weight loss
  • Fatigue
  • Low-grade fevers
  • Rash
  • Joint pain
  • Joint swelling
  • Color changes of hands and feet with cold exposure, known as Raynaud’s
  • Dryness of the eyes
  • Dryness of the mouth
  • Lymph node swelling
  • Muscle weakness
  • Muscle pains
  • Difficulty swallowing
  • Heartburn
  • Cough
  • Shortness of breath
  • Chest pain

  • Causes:
    The cause of undifferentiated connective tissue disease is not known. As mentioned above, we do know that UCTD is an autoimmune disease. The abnormal immune response may lead to inflammation and damage of the various organs that are involved in a given individual.

    No formal study of various treatments in patients with UCTD has been conducted. Most therapies are borrowed from physicians' experiences of their effectiveness in other rheumatic diseases. However, it is unknown to what degree a particular therapy improves the symptoms of UCTD or decreases the rate of flare or the likelihood of evolution to a more defined connective tissue disease.

    Most therapies are symptomatic and include:

    1. Analgesics (pain killers such as acetaminophen) and non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen for musculoskeletal symptoms, such as joint and muscle aches or pains;
    2. Topical corticosteroids (creams, lotions or gels that have anti-inflammatory action) and anti-malarial pills such as hydroxychloroquine (Plaquenil) for skin and mucous tissue symptoms. Antimalarials have been found to modify immune system function.

    For symptoms that don't respond to these drugs, the physician may occasionally prescribe low dose corticosteroids in pill form (such as prednisone) for short periods of time. High doses of corticosteroids, cytotoxic agents (such as cyclophosphamide, brand named Cytoxan), and immunosuppressives (such as azathioprine, brand named Imuran) are almost never used.

    However, there is one interesting study of another immunosuppressive drug, methotrexate (brand named Rheumatrex,) that evaluated its use in lupus patients who did not have kidney disease and in 15 UCTD patients whose most common clinical findings were positive ANA, non-erosive polyarthritis, and Raynaud's phenomenon. Overall efficacy was noted in 53% of patients, including six out of 10 with arthritis; 60% had side effects, with 33% discontinuing the drug. It is possible that this drug may be useful for hard-to-treat joint and skin problems, although it is not commonly used at present.


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