Undifferentiated Connective Tissue Disease (UCTD)

Undifferentiated connective tissue disorders are autoimmune connective tissue disorders with overlapping features of various other related disorders.

The term "undifferentiated connective tissue disorder" (UCTD) was coined in 1980 to describe disorders not fitting the criteria for specific connective tissue conditions such as lupus. A diagnosis of UCTD is used to describe arthritic conditions characterized by signs and symptoms that suggest a systemic autoimmune disease but that don’t fully satisfy the diagnostic criteria for specific connective tissue diseases, such as systemic lupus erythematosus (SLE), mixed connective tissue disease, and related disorders.

Incidence of UCTD

Undifferentiated connective tissue disease is seen worldwide and affects people of all races, although studies suggest that whites are more likely to be affected than individuals of other ethnicities. People of all ages may be affected, with the peak incidence occurring in middle age. Similar to most autoimmune disorders, women are affected about ten times as often as men, with nearly 80 percent of all cases seen in women.

Signs and Symptoms of UCTD

The most common signs and symptoms of undifferentiated connective tissue disease include arthritis, arthralgias, erosive arthritis, Raynaud’s phenomenon, eye dryness (sicca syndrome), pleuritis/pericarditis, peripheral neuropathy, vasculitis, fever, weight loss, fatigue, mucocutaneous manifestations, cutaneous (skin) involvement including malar rash, hives, skin tightening and alopecia, dilated or irregular nailfold capillaries, digital cracking or fissuring (mechanic's hands), oral or nasal ulcerations, Gottron’s sign and papules, respiratory symptoms, urethral discharge, muscle weakness, myositis, rash, seizures, psychosis, and leukopenia (low white blood cell count) in the absence of neurological symptoms or kidney involvement.

About 80 percent of patients with undifferentiated connective tissue disease have only one antinuclear autoantibody (ANA), usually anti-Ro or anti-RNP. In some cases, patients who are initially diagnosed with Raynaud’s phenomenon go on to develop UCTD.

Diagnosis of UCTD

UCTD is diagnosed in patients with symptoms of a connective tissue disease who fail to meet classic diagnostic criteria for a specific disorder. Although diagnostic criteria for UCTD haven’t been established, rheumatologists have proposed the following preliminary diagnostic criteria:

1. Signs and symptoms suggestive of a connective tissue disease that do not fulfill the diagnostic criteria for any of the defined connective tissue disorders for at least three years.
2. Positive ANA test results on two different occasions within three years.

Disease Course and Environmental Triggers

Similar to most autoimmune diseases, UCTD occurs in phases. The initial phase may occur many years prior to diagnosis, during which time the patient may be asymptomatic.

In the second phase, random low ANA titers may appear despite an absence of symptoms. The interval between autoantibody appearance and significant symptom onset is highly variable among individual patients and the specific autoantibodies.

In the third phase signs and symptoms of the autoimmune disease emerge, leading to a definitive diagnosis of UCTD or to the development of a specific connective tissue disorder. Environmental factors are thought to trigger the onset of this final stage. Suspected environmental triggers include low vitamin D levels, ultraviolet light and infection. Vitamin D insufficiency is associated with a more progressive disease course compared to individuals with adequate vitamin D.

In contrast to the defined connective tissue disorders, UCTD is characterized by a mild clinical picture. However, exceptions occur, and UCTD has been associated with severe, organ-involving, and life-threatening complications, including thrombotic thrombocytopenic purpura, myocarditis, nonspecific interstitial pneumonia, cardiovascular disease, vasculitis, cardiac tamponade, and hepatic injury. Survival rates associated with UCTD are similar to those associated with rheumatoid arthritis and SLE.

About 25 percent of patients with UCTD typically develop a specific autoimmune connective tissue disorder such as SLE within the first year or two from diagnosis. Most patients with UCTD who develop SLE do so about six years following their UCTD diagnosis. In one five-year study of patients newly diagnosed with SLE, most patients whose UCTD differentiated into a specific disorder developed Sjogren’s syndrome, followed by SLE, mixed connective tissue disease, systemic vasculitis, progressive systemic sclerosis, and poymyositis/dermatomyositis.

In addition, studies show that about 10 percent of newly diagnosed patients experience complete remission within one year. Within the first five years following diagnosis, about 65 percent of patients experience a reduction in symptoms, develop new symptoms, or continue to manifest the same signs and symptoms of UCTD indefinitely. A stable disease course is common in patients whose symptoms appear unchanged.

Treatment for UTCD

The treatment for UCTD depends on predominant symptoms and the severity of the disease course. Common treatments include nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, immunosuppressive agents, calcium channel blockers, and cyclooxygenase-2 inhibitors. ♦

© 20 NOV 2010 Copyrighted by Elaine Moore

Sources:

Bodolay E, Csiki Z, Szekanecz Z, Ben T, Kiss E, et al, Five-year follow-up of 665 Hungarian patients with undifferentiated connective tissue disease (UCTD), Clin Exp Rheumatol, 2003 May-Jun; 21(3): 313-320.

Hildebrand Bernard, Undifferentiated Connective-Tissue Disease, eMedicine from Web MD, Jul 24, 2009, assessed Nov 4, 2010.

Mosca M, Tani C, Neri C, Baldini C, Bomardieri S, Undifferentiated connective tissue diseases (UCTD), Autoimmune Rev, 2006 Nov; 6(1): 1-4.