Distinguishing laboratory characteristics are a positive, speckled anti-nuclear antibody and an anti-U1-RNP antibody. After the original 1972 description of<unk>  by Sharp, there was some controversy over whether<unk>  was a distinct<unk><unk><unk> ; however, after four decades and more than 2000 publications, it seems that there is a consensus that<unk>  should be considered a distinctive clinical entity, and is thus considered as such by the majority of rheumatologists, though there is a subgroup of patients that could evolve in their<unk>  course towards another<unk><unk><unk> . Although almost any organ can be affected by<unk> , there are various clinical manifestations that make it more likely to suspect the<unk>  is<unk>  over other<unk><unk><unk> s: # Raynaud's phenomenon. # Edematous hands and swollen fingers. # Arthritis more severe than that of SLE. # Pulmonary hypertension (does not need to be pulmonary fibrosis) differentiates<unk>  from SLE and scleroderma. # Anti-RNP antibodies in elevated levels, especially antibodies against protein 68 kD. # Absence of severe renal or CNS<unk> . Several criteria have been described to standardize the diagnosis of the<unk> , some of the most used being those of Alarcón-Segovia, although there are no universally accepted criteria. Due to the wide range of signs and symptoms, there is no agreement on what the optimal criteria are for diagnosis. Even with a low anti-RNP antibody titer, a patient can show symptoms of MTD. The reverse is also possible: a patient with a high anti-RNP antibody titer can show no symptoms. In general the criteria require the presence of high titres of anti-RNP antibodies, the presence of some characteristic signs of the<unk>  – Raynaud or swollen hands/fingers – and the presence of some clinical manifestations of at least two other<unk><unk><unk> s – SLE, scleroderma, polymyositis.. A. Serologic criteria: Positive Anti-RNP at a titre> 1:1600 by hemagglutination B. Clinical Criteria 1. Edema of the hands 2. Synovitis 3. Myositis 4. Raynaud's phenomenon 5. Acrosclerosis<unk>  is present with: Criteria A together with 3 or more clinical criteria –one of which must be synovitis or myositis– It is often several years before sufficient signs and symptoms appear to make the diagnosis of<unk> , relative to the more sequential clinical manifestations of SLE, scleroderma, and polymyositis, so often, in the initial phases, the diagnosis most appropriate for patients is "undifferentiated<unk><unk><unk> ". If the patient has edematous hands and/or swollen fingers in conjunction with elevated titers of antinuclear antibodies, an elevated titre of anti-U1 RNP antibody is a good predictor of progressing to<unk> . The presence of this specific antibody is sine qua non for the diagnosis of<unk> , although its isolated presence does not guarantee that a patient has<unk>  or will develop it. If the dominant autoantibodies are antiDNAn, Sm, Scl70 or Ro, it is likely the patient will develop another<unk><unk>  distinct from<unk> . The clinical manifestations of<unk>  appear correlated more intensely to the antibodies against protein A’ and 68 kD of the U1 RNP complex. The typical phenotype of<unk>  also appears to be in part genetically determined, as patients with<unk>  are associated with HLA-DR4 or HLA-DR2, meanwhile those with SLE are associated with HLA-DR3 and those with scleroderma are associated with HLA-DR5. SLE, scleroderma, and in<unk>  have antibodies against anti-U1-snRNP at differing percentages. These antibodies are in most<unk>  patients but are seen in only 30–35% of SLE and 2–14% of scleroderma patients, therefore they can help differentiate<unk>  from other<unk><unk>  disorders. There are different haplotypes of SNRNP70 which due to their differences in patients with<unk>  versus those with SLE or scleroderma help substantiate the claim that<unk>  is a separate<unk> . The T-G-CT-G haplotype is more common in patients with<unk> , whereas the T-G-C-G haplotype is more commonly seen in scleroderma and SLE. Differential diagnosis includes CPT2.
Mixed connective tissue disease
Carnitine palmitoyltransferase II
Undifferentiated connective tissue disease
Scleroderma
Systemic scleroderma
Antisynthetase syndrome
CREST syndrome
Cryopyrin-associated periodic syndrome