<unk>  combines features of scleroderma, polymyositis, systemic lupus erythematosus, and rheumatoid arthritis (with some sources adding myositis, dermatomyositis, and inclusion body myositis) and is thus considered an overlap syndrome. The initial clinical manifestations of<unk>  usually are unspecific. They can consist of general malaise, arthralgias, myalgias, and fever. The specific signs to suspect this<unk>  is the presence of positive antinuclear antibodies (ANA), specifically anti-RNP, associated with Raynaud's phenomenon. Almost every organ can be affected by<unk> . Raynaud's phenomenon is the most common presenting symptom seen in patients, with arthralgia and swollen hands being the second and third most common respectively. With patients that meet full criteria for<unk> , arthritis is the most common symptom with Raynaud's, swollen hands, leukopenia/lymphopenia, and heartburn following in descending order. A 2016 epidemiological population based study found 3.6 years to be the average amount of time from the first manifestations of the<unk>  until all the criteria for diagnosis were met. Manifestations include: * Skin: Raynaud's phenomenon is universal and almost always is present at the beginning of the<unk>  course. The absence puts the diagnosis in question. The capillary alterations are similar to that of scleroderma. Other cutaneous alterations can be observed similar to the types observed in LES and scleroderma. * Arthritis: Swollen fingers and occasionally diffuse edema are distinctive signs. Arthritis usually is more frequent and severe than that observed in SLE. Approximately 60% present with an obvious arthritis, with deformities similar to those observed in rheumatoid arthritis. * Myositis: Myalgias – muscular aches and pains – are common, but in the majority of patients muscular debilitation, electromyographic alterations, and elevations in muscular enzymes, like in pure polymyositis are not observed. * Cardiac<unk> : Pericarditis is the most common cardiac manifestation, observed in 10–30% of patients. Myocardial involvement can also be observed, usually secondary to pulmonary hypertension, as well as conduction anomalies. * Pulmonary involvement: Is observed in 75% of patients. It can present as pleural effusion, pulmonary hypertension, interstitial lung<unk> , thromboembolic<unk> , and others. * Renal<unk> : The absence of severe renal<unk>  is a marker of<unk> . Membranous nephropathy can be observed in some cases. * Gastrointestinal<unk> : The most common change is the alteration of esophageal motility like that observed in scleroderma. * Central nervous system involvement (CNS): The original description of this<unk>  stressed the absence of changes to the CNS; however, there have been trigeminal neuropathies (cranial nerve V), sensorineural hearing loss, and headaches observed in patients with<unk> . * Hematologic anomalies: The presence of mild anemia and hypergammaglobulinemia are common, other hematologic anomalies such as those observed in SLE can also be observed. * Laboratory value changes: Rheumatoid factor is positive in 50–70% of patients, and anti–citrullinated protein antibody is detected in 50% of patients. The universal serological findings in patients with<unk>  is the presence of anti-nuclear antibody, with anti-nRNP specificity, especially antibodies against protein 68 kD.
Mixed connective tissue disease
Carnitine palmitoyltransferase II
Undifferentiated connective tissue disease
Scleroderma
Systemic scleroderma
Antisynthetase syndrome
CREST syndrome
Cryopyrin-associated periodic syndrome