Clinical manifestations of mixed connective tissue disease

Clinical manifestations of mixed connective tissue disease

Clinical manifestations of mixed connective tissue disease

Mixed connective tissue disease (MCTD) is a systemic rheumatic disease that is characterized by the finding of high titre anti-U1 ribonucleoprotein (RNP) AB in constellation of clinical features that is commonly observed in SLE, scleroderma (SS), & polymyositis (PM). These finding commonly appear substantially over time, and usually takes several years before the full overlapping features have completed to be compatible with MCTD Dgx. The early clinical findings of MCTD are nons-pecific and that may include general malaise, arthralgias, myalgias, & low-grade fever. A +ve ANA + Raynaud phenomenon may point to 👉 MCTD Dgx. MCTD is much more commonly seen in females, and most ptns present in the 2^nd or 3^rd decade of life. Sun exposure is NOT a precipitating factor.  

 

Almost ALL body organs can be affected in MCTD. The clinical finding that point to a Dgx of MCTD may include:

1)    Early-onset Raynaud phenomenon,

2)    Swollen hands, puffy fingers &

3)    Insidious pulmonary hypertension (PH) development (no relation to lung fibrosis).

There’s characteristic absence of:

1)    severe kidney disease,

2)    CNS affection, &

3)    Destructive arthritis.

The progressive evolution of the clinical finding + high titre speckled ANA + fine specificity to anti-U1 RNP (particularly 68 kD protein) > is highly suggestive of an MCTD Dgx. Joint affection in MCTD is more common & frequently more severe as compared to the classic SLE, with an obvious arthritis in about 60 % of ptns. Hand deformity, with Jaccoud arthropathy-like changes, & small marginal erosions may occur, but severe destructive arthritis is infrequently seen.  

 

One of the 3 overlap finding may be required for MCTD Dgx is an inflammatory myopathy clinically & histologically simulating PM. Myalgia is a common Sm, but in most ptns there’re no observed weaknesses, EMG alterations, or raised muscle enzymes. Lungs are commonly involved in MCTD, (75 % of ptns). Interstitial lung disease (ILD) observed in 50-66 % of ptns. PH is a major cause of death, early detection of PH is crucial.

Echocardiography is 👉the most beneficial screening test for PH. Early Sms that should alert one to pulmonary affection: {dry cough, dyspnoea, & pleuritic chest pain}. Pericarditis is the most common clinical cardiac finding that’s observed in up to 40 % of ptns. Other cardiac findings: myocardial affection, often related to PH, as well as conduction abnormalities. Disordered motility in the upper GIT is the most common clinical overlap finding with SS, observed in 60-80 % of ptns.

 

 Renal disease: Lack of severe renal disease is a hallmark of MCTD. It’s possible that high titres of anti-U1 RNP AB that are characterising MCTD, may protect against the evolution of diffuse proliferative GN, independently of whether these AB presenting in MCTD or in classic SLE. However, some degree of renal affection can be observed in about 25 % of ptns. Membranous nephropathy is the most commonly seen finding, in addition, NRP (nephrotic range proteinuria) can be also observed. Hypertensive crises similar to SRC (scleroderma renal crisis) have also been reported.

 

Severe CNS affection is an uncommon finding; almost 25 % of ptns may show mild CNS involvement, e.g. trigeminal neuropathy, headache, or sensorineural deafness. Nonspecific hematologic/serologic alterations are prevalent in MCTD, e.g. anemia, leukopenia, & hypergammaglobulinemia. A high titter ANA that’s finely speckled staining pattern is related to AB against anti-U1 RNP antigens is the emblematic serologic finding in MCTD. RF & anti-citrullinated peptide AB are common in MCTD ptns with prominent joint affection. Antiphospholipid AB is less frequently seen than in SLE & is NOT complicated with thrombosis and/or spontaneous abortions. Raynaud phenomenon is a prototypical early feature of MCTD that’s seen with abnormal nailfold capillaroscopy simulating that seen in SS. A characteristic vascular lesion of MCTD is bland intimal proliferation + medial hypertrophy affecting medium/small-sized vessels. The impact of pregnancy on MCTD course & MCTD impact on the foetus is not certain.