Undifferentiated, overlapping, and mixed connective tissue diseases

Undifferentiated connective tissue disease (UCTD) is a term used by many rheumatologists to define a group of diffuse connective tissue disorders that lack definitive characteristics of any particular well-defined disorder. Overlapping connective tissue disease is often used interchangeably with UCTD but they both refer to diseases that are in evolution before all the characteristic clinical and laboratory symptoms are manifested. However, the clinical features of some of the overlapping connective tissue diseases appear to be better defined. The classical one is mixed connective tissue disease, where features of systemic lupus erythematosus, progressive systemic sclerosis, and polymyositis may exist together with a positive anti-extractable nuclear antibody and high titers of anti-ribonuclear protein antibody. This review attempts to clarify the confusion between these terms. The problems in the clinical and laboratory diagnosis of common connective tissue diseases that coexist are addressed and treatment options discussed. The long-term implications of making a diagnosis of a definitive connective tissue disease before all the required criteria are met should be kept in mind because the patient may never develop the disease and yet be subjected to psychological, social, and economic hardships.