What causes serosal thickening?

Causes of Serosal Thickening

Serosal thickening results from collagen deposition in response to inflammation, with the most common causes being neoplastic disease (approximately one-third of cases), infectious processes, autoimmune conditions, and idiopathic inflammation, though the etiology remains unknown in over one-third of patients. 1

Primary Etiologic Categories

Neoplastic Disease

• Malignancy represents the leading identifiable cause of serosal thickening, accounting for nearly one-third of cases in patients presenting with polyserositis 1
• In patients with previous cancer history, serosal involvement frequently represents disease recurrence (9 of 14 patients in one series) 1
• Asbestos exposure causes pleural thickening through collagen deposition in the subpleural space, which may subsequently calcify 2

Infectious Etiologies

• Bacterial and viral infections are significant causes, though proving an infectious etiology can be challenging 1
• Viral infections specifically are associated with intimal and serosal thickening through inflammatory mechanisms 3
• In appendiceal serosal inflammation, extra-appendiceal sources of intra-abdominal infection cause surface inflammatory reactions 4

Autoimmune and Inflammatory Conditions

• Autoimmune diseases constitute a major category, including systemic lupus erythematosus, rheumatoid disease, acute rheumatism, and endocrinopathies 5
• Positive antinuclear antibodies in serum are significantly associated with autoimmune causes of serosal inflammation 1
• Checkpoint inhibitor immunotherapy can cause sarcoidosis or sarcoid-like reactions with systemic manifestations 2
• Systemic sclerosis or scleroderma-like reactions present with skin thickening and may involve serosal surfaces 2

Metabolic Disorders

• Uremia causes metabolic serositis affecting peritoneal and other serosal membranes 5
• Cholesterolosis represents another metabolic cause of serosal inflammation 5

Other Specific Causes

• Genetic conditions: Recurrent hereditary polyserositis (familial Mediterranean fever) 5
• Allergic reactions: Eosinophilic serositis 5
• Granulomatous disease: Sarcoidosis, granulomatosis with polyangiitis 2
• Vasculitis: All vessel-sized vasculitis can manifest with serosal involvement 2

Anatomic Distribution Patterns

• Pleura and pericardium are the most commonly affected sites (83% of cases), followed by peritoneum 1
• In Crohn's disease, serosal fat wrapping and mesenteric thickening correlate with transmural inflammation, particularly lymphoid aggregates 6
• Asbestos-related pleural thickening may be diffuse or circumscribed, with duration from first exposure being the major determinant 2

Diagnostic Considerations

Laboratory Markers

• Elevated adenosine deaminase in pleural effusion significantly associates with autoimmune disease 1
• Increased lactate dehydrogenase levels in pleural fluid significantly associate with neoplastic causes 1
• Autoantibodies (ANA, ANCA, RF) are often absent even in inflammatory conditions 2

Pathophysiologic Mechanisms

• Serosal thickening results from collagen deposition and inflammatory cell infiltration 2
• In Crohn's disease, serosal connective tissue changes relate directly to underlying chronic inflammatory infiltrates 6
• Checkpoint inhibitor therapy may break immune tolerance, leading to cytotoxic T-cell activation and tissue damage 2

Critical Clinical Pitfalls

• Over one-third of serosal thickening cases remain idiopathic despite thorough investigation 1
• Cases of unknown etiology most frequently present as pleural and pericardial involvement, with the majority resolving spontaneously 1
• In maxillary sinus mucosa, thickening >2-5 mm may indicate altered physiology and increased risk of sinusitis, though some thickening occurs in asymptomatic individuals 2
• Serosal appendicitis represents inflammation from extra-appendiceal sources and may lead to unnecessary appendicectomy if not recognized 4