Undifferientiated Connective Tissue Disease (UCTD)

What is it?

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.”

A systemic autoimmune disorder means that it affects your whole body (systemic) and that your immune system, which normally protects you from outside invaders such as bacteria, turns on parts of your own body and attacks them as if they were invaders. Connective tissue is the “glue” that supports and connects various parts of the body; it includes skin, cartilage, and other tissue in the joints and surrounding the heart and lungs and within the kidney and other organs.]

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.)

In contrast, patients with UCTD will not have enough of the features of any one rheumatic disease to be firmly classified as such by the currently established diagnostic criteria. However, because they may have features from several known diseases, they are said to be “undifferentiated.”

The term undifferentiated connective tissue disease was first used in 1980s to identify people who were recognized as being in the early stages of a connective tissue disease (CTD) but who did not yet meet the standard criteria for a well-defined CTD. At that time, it was noted that a substantial proportion of these patients remained undifferentiated – or experienced a disease remission – and never evolved in to a more defined rheumatic disease. Other names used early on to describe some of these patients included “latent lupus” and “incomplete lupus erythematosus,” which meant that some features suggestive of lupus were present, but not enough to fulfill make the diagnosis. As many as a quarter of all patients seen by rheumatologists have UCTD.

Many researchers have been studying people with UCTD. They have been trying to identify serologic profiles (markers in the blood) that may predict who will eventually develop a well-defined connective tissue disease. They are also looking for markers to help predict whether the disease may go away, remain unchanged, or get worse. It is currently believed that less than 20% of patients with UCTD go on to develop a definite connective tissue disease.

What causes UTCD?

Pathogenesis refers to the origin and development of a disease. The actual cause of UCTD, like many rheumatic diseases, is not well understood. Indeed, there have been no rigorous attempts to define the basic science of UCTD. It is presumed that many of the same immunologic mechanisms that play a role in lupus and rheumatoid arthritis may be involved. Theories in those diseases include a genetic predisposition, which is subsequently triggered by some environmental factor, such as an infection, that is improperly handled by the immune system. This in turn causes the immune system to be “turned up high,” or activated, when it shouldn’t be and to target the tissues of one’s body instead of foreign invaders (such as bacteria). Which of – or whether – these elements might be involved in UCTD remains unknown. UCTD will be difficult to study because it includes a heterogeneous population – people with so many different symptoms and blood markers.

General profile of UCTD

In the studies of patients that have been done to date, the most common symptoms of UCTD are:

  • arthralgia (joint achiness);
  • arthritis (joints that are swollen and hot, often with redness of the overlying skin;
  • rashes, usually on the face, which can worsen due to sun exposure;
  • alopecia (hair loss);
  • Raynaud’s phenomenon (color changes in your hands and feet in response to cold);
  • oral ulcers (sores inside the mouth);
  • xerophthalmia (dryness of the eyes due to decreased tears);
  • xerostomia (dry mouth due to decreased saliva);
  • low-grade fever (usually under 100o f);
  • photosensitivity ( development of rashes or other symptoms after sun exposure).

Some people also develop:

  • leukopenia – decreased numbers of white cells (cells that help fight infection) in your blood;
  • anemia – decreased numbers of red blood cells (cells that carry oxygen to tissues in the body) in your blood;
  • thrombocytopenia – an abnormal decrease in the number of platelets (the parts related to blood clotting);
  • pleuritis or pericarditis – inflammation of the lining surrounding the lungs or heart, respectively, which may cause pain in the chest, especially with breathing;
  • neuropathy – abnormal nerve sensations, usually in the fingers or toes, ranging from numbness to tingling to pain.

Preliminary Classification Criteria for UCTD

  • Signs and symptoms suggestive of a CTD, but not fulfilling the criteria for any of the defined CTDs, for at least three years
  • Presence of ANA identified on two different occasions

(ANA refers to antinuclear antibodies found in the blood. These markers may indicate that your immune system is forming antibodies to parts of your body.)

At the present time, UCTD is diagnosed clinically by your doctor when the symptoms, labs and history fit the “pattern” which doctors are used to seeing with this disease. It is not based on meeting a checklist of required “criteria” alone. As doctors develop more specific criteria for UCTD, however, it will be easier to study the disease and learn about its causes and best treatments.

Treatment for UCTD

Most therapies are symptomatic and include:

  • 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;
  • 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.