INTERNATIONAL JOURNAL OF CARDIOLOGY AND CARDIOVASCULAR MEDICINE (ISSN:2517-570X)

Patient suffering from undifferentiated connective tissue disease (UCTD) presents with a few features characteristic of known connective tissue diseases but laboratory test results of antinuclear antibodies do not support clinical picture to establish a definitive diagnosis. It could be due to genetic predisposition though precise mechanism of pathogenesis involved in UCTD remains unknown. It is thought to be due to faulty immune system that reacts and targets the tissues of one’s own body. We discuss a case of young individual with breathlessness and palpitation, who upon evaluation found to have massive hemorrhagic pericardial effusion (PE) secondary to early UCTD. Patient underwent emergency pericardiocentesis and recovered following steroid and csDMARD therapy. This case report shows that massive hemorrhagic PE could be the only presenting finding in a case of early UCTD and suggests that early, accurate diagnosis can lead to successful recovery without morbidity. 

Undifferentiated connective tissue disorder; Massive hemorrhagic pericardial effusion; Pericardiocentesis; Dr. Leroy

A varied presentation can be seen in a patient visiting to clinic with undifferentiated connective tissue disease (UCTD). Some of which are fatigue, Raynaud’s phenomenon, arthralgia/arthritis, sicca syndrome, peripheral neuropathy, malar rash, vasculitis, muscle weakness, oral/nasal lesions, photosensitivity, cytopenia and alopecia [1-3]. The previous studies also found evidence of major end organ damage (i.e kidneys, lungs and heart). The prevalence of cardiac involvement in UCTD ranges from 13 to 65%[1].A case of massive hemorrhagic pericardial effusion as initial manifestation in early UCTD has been seldom reported.

Case report

A 26 years old male presented to cardiac OPD with complaints of breathlessness, palpitations, generalized weakness, easy fatigability, abdominal discomfort, loss of appetite, dry cough, chest pain (on & off) and fever (on & off) of 8 days duration. No history of joint pain, Raynaud’s phenomenon, trauma to chest or bleeding diathesis noted. On admission, ECG revealed atrial tachycardia with Right bundle branch block (Figure 1). Patient’s Echocardiography revealed large ostium secundum atrial septal defect(OS ASD) measuring 32mm with left to right shunt, grossly dilated right atrium (RA)/ right ventricle (RV)/ pulmonary artery (PA), moderate pulmonary artery hypertension(PAH), ejection fraction 35% without RA/RV collapse and massive pericardial effusion & no evidence of cardiac tamponade. Patient’s blood report for hepatitis B, C and HIV were negative. Cardiac markers were negative. Total leukocyte count was 9300 cells/L. Chest X-ray on admission showed marked enlargement of cardiac outline (water bottle sign) (Figure 2).

Pericardiocentesis was done under echocardiographic guidance and a total of 800ml of hemorrhagic fluid aspirated. The fluid was sent for biochemical analysis, culture/sensitivity and fluid cytology. In view of hemorrhagic nature of fluid MDCT chest was performed to rule out mediastinal malignancy and tuberculosis. Post-pericardiocentesis MDCT chest showed moderate pericardial effusion with pulmonary hypertension, patchy consolidation & CT bronchogram in bilateral basal lung fields (L>R); few enlarged pre-paratracheal & prevascular lymph nodes (Figure 3). Biochemical analysis of pericardial fluid showed in (Table 1). Pericardial fluid cytology showed in (Table 2). Since fluid cytology showed lymphocyte predominance, fluid was also sent for Mycobacterium tuberculosis (M TB) culture and Gene Xpert MTB/RTF test. Results for fluid microscopy and AFB were negative. The fluid culture yielded no growth of bacteria or fungi after 48 hours of incubation. Gene Xpert MTB/RTF, a semi-nested real time PCR was negative for tuberculosis. M TB culture on LJ media yielded no growth after 8 weeks of incubation. Patient was managed with low dose diuretics and antibiotics during hospital stay. To rule out connective tissue diseases, anti-nuclear antibody (ANA) analysis were performed which was positive for antibodies against PCNA and Ribosomal-P-protein. Patient was diagnosed of early UCTD and started on conventional synthetic Disease Modifying Antirheumatic Drugs (csDMARD)

Patient underwent pericardial fluid aspiration subsequently on 4 occasions (150ml, 180ml, 230ml & 45ml respectively) during hospital stay on alternate days, showing decrease in effusion and fall in CRP after csDMARD therapy. Patient had trace pericardial effusion at the time of discharge (Figure 4).

Connective tissue disease (CTD) is complex in nature and relatively rare. Though, CTDs namely systemic lupus erythematosus (SLE), scleroderma, myositis, rheumatoid arthritis (RA), and Sjogren’s syndrome have criteria for classification, some cases do not meet these criteria & often diagnosed as UCTD [4]. It was Dr. Leroy, a rheumatologist at Department of Medicine, Medical University of South Carolina, who first proposed this concept in 1980. Based on his findings, UCTD cases may remain undifferentiated indefinitely or they may all eventually develop into a defined CTD or go into complete remission [5].

Today, UCTD has been accepted as distinct clinical entity. Mosca M, et al. [6] has proposed preliminary classification criteria for UCTD

I.Signs and symptoms suggestive of a connective tissue disease, but not fulfilling the criteria for any of the defined CTDs for at least three years.

II. Presence of antinuclear antibodies determined on two different occasions [6].

Recently, UCTD is further divided into ‘stable UCTD’ cases and ‘early UCTD’ cases which show recent onset of symptoms (< 3 years) and unclear clinical picture. The stable UCTD cases are clinically stable over time requiring only mild therapeutic intervention, whereas early UCTD cases are likely to develop into definite CTD over a period of time requiring disease monitoring and treatment decision making [7]. In our case, the patient had massive pericardial effusion of hemorrhagic nature, but had neither reduction of left ventricular internal dimension nor pulsus paradoxus to indicate cardiac tamponade. The development of cardiac tamponade was delayed due to equilibrium of flow across the ASD and patient was saved from the fatal consequences of cardiac tamponade.

Patient’s positive ANA analysis and raised CRP suggested an active autoimmune connective tissue disease. Since the patient did not meet the available classification criteria for any connective tissue disease, and also the disease duration was less than 3 years, patient was diagnosed as having early UCTD. Patient’s total leukocyte count was normal and culture yielded no growth of any bacteria or fungi which ruled out infective cause. No history of trauma to chest and bleeding tendencies indicated some other cause responsible for hemorrhagic nature of pericardial effusion. Tubercular etiology was excluded because of no growth on LJ media and negative Gene Xpert MTB/RTF (semi-nested real time PCR) report & for malignancy no evidence of atypical cells noted in pericardial fluid. MDCT chest ruled out malignancy as well as tuberculosis. After all common causes of hemorrhagic pericardial effusion were excluded, case was worked up for connective tissue disease, which revealed raised CRP and positive ANA analysis (positive for PCNA & ribosomal p protein antibodies). Patient was diagnosed of early UCTD and initiated on steroid+csDMARD therapy which reduced CRP value as well as made patient effusion free within a short duration of hospital stay. This case presents early UCTD as rare cause of massive hemorrhagic pericardial effusion and to the best of our knowledge, the case we described here is the first case report of massive hemorrhagic pericardial effusion as onset manifestation in a patient with early UCTD. Cardiac involvement is relatively common in established connective tissue diseases (CTDs) especially in scleroderma and systemic lupus erythematosus (SLE) patients but it is rare in early UCTD. Pericardial effusion of moderate to severe grade is usually caused by end stage renal disease, myocardial infarction, malignancy, iatrogenic or idiopathic; idiopathic cause being the most common cause [8]. The presentation in our case is peculiar as well as rare because patient had massive pericardial effusion of hemorrhagic nature without any features of CTD. Therefore, in differential diagnosis of any pericardial effusion UCTD should be considered as possible cause and should be evaluated to rule it out. These cases respond to steroids and DMARD therapy very well without recurrence of effusion.

All hemorrhagic pericardial effusion cases require exclusion of all causes carefully.

Early UCTD can present as causative etiology for massive hemorrhagic pericardial effusion.

Periodic follow up of patients with early UCTD is must, because they are at risk of developing known connective tissue diseases within 5 years of disease onset.

The authors declare that they have no known competing financial interest or personal relationship that could have appeared to influence the work reported in this paper. 

I would like to thank Dr Vivekanand Gajapati, Head of Cardiology Department, for his expert advice and encouragement. I would also like to thank Dr. Kirti L for her support.

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