The etiology of UCTD is unknown and there are few studies but some investigators believe that some UCTD may be an early stage of systemic lupus erythematosus (SLE) or systemic sclerosis. (SSc) in its early stages. Therefore, its etiology should be the same as these two diseases. Studies suggest that the development of this disease may be the result of some environmental factors such as long-term exposure to chemical agents acting on susceptible individuals. Both environmental and genetic factors play an important role in its pathogenesis. In 1998, Lacey et al. studied 205 patients with UCTD and 2095 normal controls. It was found that 25% (52/205) of the 205 female UCTD patients had a clear history of chemical solvent exposure, whereas only 17% (364/2095) of the 2095 controls matched for ethnic composition, education, marital economic status, and alcohol and tobacco use had a clear history of chemical solvent exposure. A detailed study of the medical history revealed that chemicals, cosmetic products, drugs, rubber products, paints and pigments were significantly associated with the development of UCTD. Exposure to paints, cleaning agents and turpentine may also be associated with the development of UCTD. the study by Lacey et al. further suggested that medical implants such as catheters, metal fixation brackets for artificial joints and orthopedic surgery may also increase the risk of development. All of these studies suggest that environmental factors play an important role in the development of UCTD. Pathogenesis As with most connective tissue diseases, there is a genetic basis for the development of UCTD. In 1988, Ganczarczyk et al. compared the HLA subtypes of 22 patients with UCTD and 211 patients with SLE and found that the positive rates of HLA-B8 and HLA-DR3 subtypes were significantly higher in patients with UCTD than in normal subjects. In contrast, the HLA-DR1 subtype positivity rate in the 7 patients who eventually progressed to SLE was significantly lower than normal and similar to that in SLE patients. This suggests that the HLA-DR1 subtype may be an anti-UCTD gene. A study by Mosca et al. found an increased rate of recurrence in patients with UCTD during pregnancy. Six of the 22 study subjects (24%) had a relapse or exacerbation of the disease during pregnancy, while only 7% of the control group had a recurrence of the disease. Therefore, changes in sex hormone levels or imbalance in the ratio of estrogen to progesterone are likely to be associated with the development of the disease.