UREMIC PERICARDITIS

Uremic pericarditis is a complication of chronic kidney disease (CKD), more frequent in the end stages of the disease, particularly in patients undergoing hemodialysis.
It is caused by the accumulation of uremic toxins, leading to a chronic inflammatory process with the formation of a fibrinous pericardial effusion. In dialysis patients, an altered immune response and an increased risk of infections may contribute to the development of a superimposed infectious pericarditis.

There are two main forms of uremic pericarditis:

• Pre-dialysis: occurs in patients with severe renal failure not yet undergoing replacement therapy, due to the accumulation of nitrogenous metabolites and pro-inflammatory cytokines.
• Post-dialysis: seen in patients already undergoing dialysis, often secondary to inadequate extracorporeal clearance, hypoalbuminemia, or chronic inflammatory state.

Pathophysiology

The pericardial damage in uremic pericarditis is related to the accumulation of nitrogenous metabolic waste and the action of pro-inflammatory cytokines (IL-6, TNF-α), which trigger a chronic inflammatory process, increasing capillary permeability and leading to progressive fluid accumulation in the pericardial space.
Additionally, uremic patients often exhibit platelet dysfunction and a coagulation cascade impairment, predisposing them to serosanguineous effusions.
In dialysis patients, the use of heparin as an anticoagulant may further increase the risk of intrapericardial bleeding.

Clinical Presentation

The clinical picture is similar to other forms of pericarditis, with pleuritic chest pain, dyspnea, and signs of cardiac tamponade in advanced cases. However, in uremic pericarditis:

• Chest pain may be less intense or absent in patients with severe uremia.
• Fever is generally absent unless there is a superimposed infectious pericarditis.
• The pericardial effusion can accumulate slowly, leading to a subtle clinical presentation until hemodynamic compromise occurs.

Diagnosis

In addition to standard diagnostic tests used for pericarditis (ECG, echocardiography, chest X-ray), in uremic pericarditis, the following are useful:

• Blood tests: elevated blood urea nitrogen (BUN), high creatinine levels, uremic anemia, electrolyte imbalances.
• Pericardial fluid analysis: essential in dialysis patients to rule out infectious pericarditis.

Treatment

The treatment of uremic pericarditis focuses on the removal of uremic toxins and inflammation control.

• Intensified dialysis: the first-line therapy, leading to progressive clinical improvement.
• Anti-inflammatory therapy: NSAIDs should be used with caution due to nephrotoxicity risk; corticosteroids may be considered in refractory cases.
• Pericardiocentesis: indicated for large effusions with signs of tamponade.
• Pericardiectomy: reserved for rare cases of refractory constrictive pericarditis.

Complications

The main complications of uremic pericarditis include:

• Cardiac tamponade: a medical emergency requiring immediate drainage.
• Constrictive pericarditis: rare but possible in cases of untreated chronic inflammation.
• Recurrences: frequent in patients with advanced renal failure who are not adequately dialyzed.

MYXEDEMA PERICARDITIS

Myxedema pericarditis is a complication of severe hypothyroidism, characterized by a slowly progressing pericardial effusion, which is usually asymptomatic but can become significant and, in severe cases, lead to cardiac tamponade.
Unlike inflammatory pericarditis, the pericardial fluid in myxedema pericarditis is typically non-inflammatory and contains a high concentration of mucopolysaccharides and proteins.

Pathophysiology

Hypothyroidism induces profound alterations in basal metabolism, affecting multiple systems, including the pericardium:

• Reduced pericardial fluid clearance: a slower metabolism results in fluid accumulation within the pericardial space.
• Increased capillary permeability: facilitates the extravasation of fluids into the pericardial cavity.
• Mucopolysaccharide accumulation: the pericardial fluid is dense and protein-rich, with a gelatinous consistency.

Since the progression is slow, the pericardium has time to adapt to the increasing effusion volume, reducing the immediate risk of tamponade compared to acute pericarditis. However, in cases of prolonged and severe hypothyroidism, the effusion can become massive, compromising cardiac function.

Clinical Presentation

Symptoms of myxedema pericarditis are often subtle and overlap with those of advanced hypothyroidism. They may include:

• Dyspnea: progressive, due to reduced pericardial compliance.
• Peripheral edema: a consequence of hypothyroidism and impaired fluid clearance.
• Bradycardia and hypotension: characteristic of thyroid dysfunction.
• Absence of fever and chest pain: the effusion develops gradually without a significant inflammatory response.
• Signs of cardiac tamponade: in severe cases, with jugular vein distension, hypotension, and pulsus paradoxus.

Diagnosis

In addition to standard diagnostic tests used for pericarditis (ECG, echocardiography, chest X-ray), myxedema pericarditis is confirmed by:

• Thyroid function tests: altered hormone levels consistent with hypothyroidism (elevated TSH, reduced FT3/FT4).
• Pericardial fluid analysis: serous fluid rich in mucopolysaccharides, with low cellularity and absence of inflammatory markers.

Treatment

The treatment of myxedema pericarditis focuses on correcting the hormonal deficit, leading to a gradual resolution of the effusion.

• Levothyroxine replacement therapy: results in spontaneous effusion resorption over weeks or months.
• Echocardiographic monitoring: to assess effusion progression and potential tamponade signs.
• Pericardiocentesis: rarely necessary, reserved for hemodynamically significant effusions.

Complications

The main complications of myxedema pericarditis include:

• Cardiac tamponade: if the effusion reaches critical volumes.
• Effusion recurrence: in patients with inadequately treated hypothyroidism.

PERICARDITIS ASSOCIATED WITH COLLAGEN DISEASES

Pericarditis associated with collagen diseases is a common manifestation of systemic autoimmune disorders, particularly connective tissue diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic sclerosis, and polymyositis/dermatomyositis.
It can present with pericardial effusion of varying severity, sometimes hemorrhagic or recurrent, and in chronic cases, it may evolve into constrictive pericarditis with fibrosis and calcifications.

Pathophysiology

Pericarditis in collagen diseases is caused by a direct autoimmune response against the pericardium, with the production of autoantibodies and immune complex deposition, triggering chronic inflammation.
This process leads to:

• Increased capillary permeability, resulting in pericardial fluid accumulation.
• Persistent inflammation that, in chronic cases, may progress to pericardial fibrosis.
• Potential hemorrhagic effusion, more common in SLE and RA.

Clinical Presentation

In addition to the typical symptoms of pericarditis (pleuritic chest pain, dyspnea, signs of cardiac tamponade in advanced cases), pericarditis in collagen diseases is distinguished by:

• Systemic involvement: fever, arthralgia, skin rash, Raynaud's phenomenon, mucosal dryness (depending on the underlying autoimmune disease).
• High tendency for chronicity: with potential recurrences.
• Risk of constrictive evolution: in patients with persistent pericardial inflammation.

Diagnosis

In addition to standard diagnostic tests for pericarditis (ECG, echocardiography, chest X-ray), the following are essential in pericarditis associated with collagen diseases:

• Autoimmune serology: detection of autoantibodies (ANA, anti-DNA, ENA, RF, anti-CCP, etc.) to confirm the underlying connective tissue disease.
• Pericardial fluid analysis: in SLE patients, it may show a serous or hemorrhagic effusion with high protein content.

Treatment

The treatment of pericarditis associated with collagen diseases focuses on controlling inflammation and the underlying disease.

• Corticosteroids: first-line treatment for severe autoimmune pericarditis.
• NSAIDs: for mild-to-moderate cases.
• Immunosuppressive drugs: methotrexate, azathioprine, or mycophenolate in refractory cases.
• Pericardiocentesis: indicated in the presence of cardiac tamponade.

Complications

The main complications of pericarditis associated with collagen diseases include:

• Recurrent pericarditis: particularly frequent in SLE.
• Constrictive pericarditis: in cases with chronic fibrotic evolution.

NEOPLASTIC PERICARDITIS

Neoplastic pericarditis is a form of pericarditis secondary to the infiltration of tumor cells into the pericardium.
It can result from the direct extension of primary pericardial tumors or, more commonly, from metastatic spread of extrapericardial malignancies, including:

• Lung cancer (the most common cause).
• Breast cancer.
• Lymphomas and leukemias.
• Melanoma (a malignancy with a high propensity for pericardial involvement).

The pericardial effusion in neoplastic pericarditis can be extensive, and in most cases, it has a characteristic hemorrhagic appearance. Its progression is often insidious, but in advanced cases, it can lead to cardiac tamponade, posing a potentially fatal condition.

Pathophysiology

Neoplastic pericarditis is caused by the dissemination of tumor cells into the pericardium, which can occur via:

• Direct extension: from primary cardiac or pericardial tumors.
• Lymphatic or hematogenous spread: common in lung, breast cancer, and hematologic malignancies.
• Paraneoplastic mechanisms: some tumors can induce pericardial inflammation without direct cellular infiltration.

The presence of malignant cells alters the vascular permeability of the pericardium, leading to an effusion that can be serous, serosanguineous, or frankly hemorrhagic.
In advanced cases, fibrotic reactions may occur, potentially evolving into constrictive pericarditis.

Clinical Presentation

The symptoms of neoplastic pericarditis can be nonspecific or completely absent until significant fluid accumulation occurs. The key clinical features include:

• Dyspnea: the most frequent symptom, due to progressive cardiac compression by the effusion.
• Dull, persistent chest pain: less intense compared to inflammatory pericarditis.
• Signs of cardiac tamponade: hypotension, jugular vein distension, and pulsus paradoxus in advanced cases.
• Peripheral edema and ascites: resulting from secondary cardiac dysfunction due to tamponade.

In oncologic patients, the onset of worsening dyspnea or signs of heart failure should raise suspicion for neoplastic pericardial effusion.

Diagnosis

In addition to standard diagnostic tests for pericarditis (ECG, echocardiography, chest X-ray), the following are critical in diagnosing neoplastic pericarditis:

• Echocardiography: detects the presence of a large effusion, often with tamponade signs. It may reveal pericardial masses.
• CT scan and cardiac MRI: useful for identifying the primary malignancy or tumor infiltration of the pericardium.
• Pericardial fluid analysis: obtained via pericardiocentesis, may reveal malignant cells or tumor markers.

Treatment

The management of neoplastic pericarditis aims to control the pericardial effusion and address the underlying malignancy.

• Pericardiocentesis: first-line treatment in cases of cardiac tamponade.
• Pericardiodesis: instillation of sclerosing agents (e.g., bleomycin, tetracycline) to prevent effusion recurrence.
• Oncologic treatment: chemotherapy, radiotherapy, or targeted therapy based on the primary tumor.
• Pericardiectomy: indicated in cases of refractory neoplastic constrictive pericarditis.

Complications

The major complications of neoplastic pericarditis include:

• Cardiac tamponade: a life-threatening condition requiring urgent drainage.
• Recurrent pericardial effusion: common in patients with advanced metastatic disease.
• Constrictive pericarditis: a possible chronic evolution with pericardial fibrosis.

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