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Overlap Syndrome/MCTD


MCTD 
PRaSSH
  • Polymyositis
  • Raynauds 
  • Systemic Sclerosis 
  • SLE
  • High titer of anti-U1-ribonucleoprotein (RNP) antibodies
    • SLE patients can have anti-U1 RNP ab. This does not mean it is a MCTD by default
    • In contrast to SSc, MCTD often responds to glucocorticoids, and the long-term prognosis is better than that of SSc. Whether MCTD is truly a distinct entity or is a subset of SLE or SSc, remains controversial.
Clinical Features
  • Similar to each component of Diseases
    • Based on PRaSSH - criteria included in SHARP, KASUKAWA or ALARCON-SEGOVIA et al include 
    • SHARP 
      • Major Critehria for SHARP
        • 1. Myositis for P
        • 2. Raynaud's for SSc 
        • 3. Synovitis and Edema of hands for SSc   
        • 4. ILD for P or RA or S or S
        • 5. High Titer anti-U1 RNP 
      • Minor criteria resemble SLE 11 clinical criteria on most part 
    • KASUKAWA 
      • Common clinical: Raynaud's and Swollen hand and fingers , and then they have MIXED symptoms 
    • ALARCON-SEVOGVIA - Cliinical criteria include the 5 major of SHARP ; Sensitivity and specificity of 63 % and 86% 
    • In addition, there is a KHAN criteria. Last two are supposed to be the best (Ref: Uptodate)
  • Arthritis is usually non-erosive however, RA like erosive arthritis can occur

Ref: UPtodate
5 major diffuse connective tissue exists - SLE, RA, DM, PM, SSc, Sixth is Sjogren syndrome often mixed with these or can be primary 

Prominent early symptoms are puffy fingers, easy fatigability, poorly defined myalgias, arthralgias, and Raynaud phenomenon. The common diagnostic considerations at this juncture are usually rheumatoid arthritis (RA), SLE, SSc or UCTD. 

If the patient has swollen hands and/or puffy fingers in association with a high titer speckled antinuclear antibody (ANA), they should be carefully followed for the evolution of overlap features. A high titer of anti-RNP antibodies in such a patient is a powerful predictor of a later evolution to MCTD. 

Other, less common, early features include severe inflammatory myopathy, acute arthritis, aseptic meningitis, transverse myelitis, digital gangrene, high fever, acute abdomen and trigeminal neuropathy, and sensorineural hearing loss.

The major reason for considering MCTD a distinct clinical entity is the frequent observation that high titers of anti-U1 RNP antibodies are associated with several distinctive clinical characteristics. 

Patients with U1 RNP antibodies seldom i.e RARELY develop diffuse proliferative glomerulonephritis, psychosis, or seizures; these abnormalities are a major source of morbidity and mortality in SLE.

Patients with U1 RNP antibodies nearly always have an early development of the Raynaud phenomenon and a nailfold capillary pattern that is the same as in SSc but that is different from classical SLE. The Raynaud phenomenon only occurs in about 25 percent of patients with classical SLE.

Patients with U1 RNP antibodies are more likely to develop pulmonary hypertension than patients with classical SLE or SSc. Pulmonary hypertension is the major cause of death in MCTD.

Patients with U1 RNP antibodies are more likely than SLE patients to test positively for rheumatoid factor or antibodies to cyclic citrullinated peptide (anti-CCP)  and they are also more likely to develop an erosive arthritis.

Patients with a preponderance of immunoglobulin M (IgM) anti-U1 small nuclear ribonucleoprotein (snRNP) antibodies are more likely to have SLE. One study has reported that a combined IgM reactivity for fragments of U1C and U1A of U1 RNP is capable of classifying SLE and MCTD patients with an accuracy of 71.3 percent


There are several hierarchies of antibody response in patients who eventually develop MCTD, with each higher level being associated with an increased expression of the MCTD clinical profile:

Level 1 – Positive ANA

Level 2 – High titer, speckled ANA pattern

Level 3 – Anti-U1 RNP antibodies

Level 4 – Anti-68 kD and A' antibodies

U1 RNP consists of ribonucleic acid (RNA) plus three proteins (A', C, and a 68-70 kD protein). The clinical picture of MCTD most closely correlates with the presence of IgG antibodies to the 68 to 70 kD and A' proteins


Ref for above: UPtodate




RAESE is the most common clinical features 
Raynauds 
Arthritis / Arthralgai 
Edema of Hands 
Sclerodactyly
Esophagus dysmotility
Pulmonary involvement


Instead of above pneumonic, alternatively use the clinical features from the SHART or ALARCON-SEGOVIA et al. as that is more clinically more meaningful 


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