What is a granulomatous disease?

Granulomatous Disease: Definition, Types, and Clinical Implications

A granulomatous disease is characterized by the formation of granulomas, which are focal compact collections of inflammatory cells, predominantly mononuclear cells, resulting from persistent non-degradable products and active cell-mediated hypersensitivity. 1

Pathophysiology of Granulomas

• Granulomas form through a complex interplay between invading organisms or prolonged antigenemia, macrophage activity, Th1 cell response, B cell activity, and various biological mediators 1
• Histologically, granulomas typically feature well-formed, concentrically arranged layers of immune cells with a central core of macrophage aggregates and multinucleated giant cells 2
• An outer layer of loosely organized lymphocytes (mostly T cells) often surrounds the central core, sometimes with isolated collections of B lymphocytes 2
• Granulomas can be classified based on their histological patterns as necrotizing, non-necrotizing, suppurative, diffuse, or foreign body giant cell reactions 3

Types of Granulomatous Diseases

Infectious Causes

• Mycobacterial infections (tuberculosis, leprosy) typically present with necrotizing granulomas 3
• Fungal infections, particularly dimorphic fungi, can cause granulomatous inflammation 4, 3
• Parasitic infections may lead to granuloma formation 1

Non-infectious Causes

• Sarcoidosis: Characterized by non-necrotizing granulomas affecting multiple organs, most commonly the lungs and intrathoracic lymph nodes 5
• Vasculitis: Granulomatosis with polyangiitis (GPA) and eosinophilic granulomatosis with polyangiitis (EGPA) feature granulomatous inflammation of blood vessels 2
• Chronic Granulomatous Disease (CGD): A primary immunodeficiency due to defective NADPH oxidase activity, leading to recurrent infections and granuloma formation 6, 7, 8
• Inflammatory Bowel Disease: Crohn's disease is characterized by granulomatous inflammation of the intestinal tract 2
• Drug-induced granulomatous reactions: Various medications can trigger granuloma formation 2
• Foreign body reactions: Non-degradable materials can induce granulomatous inflammation 3, 1

Organ-Specific Manifestations

Pulmonary Granulomatous Disease

• The lungs are among the most commonly affected sites for granulomatous inflammation 3
• Bilateral hilar adenopathy and perilymphatic nodules on chest CT are common findings in sarcoidosis 2, 5
• Pulmonary granulomas may present as multiple nodules, nodular infiltration, or occasionally solitary lesions 2

Cutaneous Granulomatous Disease

• Skin can be affected through direct inoculation, endogenous sources, or hematogenous spread 3
• Manifestations include lupus pernio, maculopapular lesions, erythema nodosum, and subcutaneous nodules 2, 5

Renal Granulomatous Disease

• Granulomatous interstitial nephritis (GIN) is more frequently due to drugs and sarcoidosis than infections 3
• Renal involvement in vasculitis can present as glomerulonephritis 2

Hepatic Granulomatous Disease

• Liver biopsy is essential for diagnosing granulomatous hepatitis 4
• Causes include sarcoidosis, tuberculosis, fungal infections, and drug reactions 4

Diagnostic Approach

• Histopathological examination is crucial for identifying granulomatous inflammation 2, 3
• Special stains should be performed to exclude infectious causes such as mycobacteria and fungi 4
• Imaging studies (CT, MRI, PET) can help identify organ involvement 2, 5
• Laboratory tests may include serum angiotensin-converting enzyme (SACE), calcium levels, and ANCA testing 2, 4

Treatment Considerations

• Treatment depends on the underlying cause and organ involvement 2, 5
• Infectious granulomatous diseases require appropriate antimicrobial therapy 8
• Non-infectious granulomatous diseases often require immunosuppressive therapy 5, 6
• Systemic corticosteroids are the mainstay of treatment for many granulomatous conditions 2, 5
• Steroid-sparing agents such as methotrexate, cyclophosphamide, and azathioprine may be used 2
• Biologic therapies, including TNF-alpha antagonists, have shown efficacy in refractory cases 2, 6

Prognosis and Monitoring

• Prognosis varies widely depending on the underlying cause and organs affected 5
• Regular monitoring of disease activity and treatment response is essential 2, 5
• Long-term follow-up is necessary to detect complications and comorbidities 2