Mixed connective tissue disease

Page most recently updated 7 September 2026

This page focuses on the reported psychiatric associations, which may be the initial presenting manifestation, and on other clinical features that may assist the psychiatrist or primary care physician in identifying the underlying diagnosis, considered through the lenses of the diagnostic lenses framework.

Mixed connective tissue disease is an autoimmune connective tissue disease characterized by overlapping clinical features of systemic lupus erythematosus, systemic sclerosis, and polymyositis, with high-titre anti-U1 ribonucleoprotein (anti-U1 RNP) antibodies serving as a characteristic serological marker.

It can present with psychiatric features such as depression, anxiety, cognitive dysfunction, mood disturbance, confusion, and, less commonly, psychosis or behavioural change.

Other characteristic features include headache, seizures, peripheral neuropathy, trigeminal neuropathy, aseptic meningitis, and cognitive impairment in some patients. Distinctive features include overlapping clinical features of systemic lupus erythematosus, systemic sclerosis, and inflammatory myopathy, together with high-titre anti-U1-ribonucleoprotein (anti-U1-RNP) antibodies.

From a multisystemic lens perspective, clinical features in other body systems include (but are not limited to):

  • Cardiovascular: pulmonary arterial hypertension, pericarditis, and Raynaud phenomenon are common and clinically important manifestations.

  • Respiratory: interstitial lung disease and pleuritis may occur.

  • Musculoskeletal: inflammatory arthritis, myositis with proximal muscle weakness, arthralgia, and swollen ("puffy") hands are characteristic features.

  • Dermatologic: sclerodactyly, puffy fingers, photosensitive rashes, and other overlap connective tissue disease skin manifestations may occur.

Early diagnosis is important to enable timely immunomodulatory treatment, identify and manage organ-threatening complications (particularly pulmonary arterial hypertension and interstitial lung disease), reduce the risk of progressive neurological and systemic disability, and improve long-term prognosis and quality of life.

Selected references and further reading — Multisystemic lens

Cardinal RN, Bullmore ET. The diagnosis of psychosis. Cambridge: Cambridge University Press; 2011.

Sachdev PS, Keshavan MS, editors. Secondary schizophrenia. Cambridge: Cambridge University Press; 2010.

Levenson JL, editor. The American Psychiatric Association Publishing textbook of psychosomatic medicine and consultation-liaison psychiatry. 3rd ed. Washington (DC): American Psychiatric Association Publishing; 2019.

Stern TA, Beach SR, Smith FA, Freudenreich O, Vranceau AM, Fava M, editors. Massachusetts General Hospital handbook of general hospital psychiatry. 8th ed. Philadelphia: Elsevier; 2025.

Arciniegas DB, Yudofsky SC, Hales RE, editors. The American Psychiatric Association Publishing textbook of neuropsychiatry and clinical neurosciences. 6th ed. Washington (DC): American Psychiatric Association Publishing; 2018.

Agrawal N, Faruqui R, Bodani M, editors. Oxford textbook of neuropsychiatry. Oxford: Oxford University Press; 2020.

Boland R, Verduin M, editors. Kaplan and Sadock's comprehensive textbook of psychiatry. 11th ed. Philadelphia: Wolters Kluwer; 2024.

Loscalzo J, Fauci AS, Kasper DL, Hauser SL, Longo DL, Jameson JL, editors. Harrison's principles of internal medicine. 22nd ed. New York: McGraw Hill; 2025.