Infectious Granulomatous Disease: A Brief Review

Introduction

Granuloma is an inflammatory or hypersensitive reaction to a foreign body, resulting in an organized collection of epithelioid histiocytes. Granulomas predominantly consist of lymphocytes, macrophages, and other immune cells. The underlying cause for granulomatous disorders can be infectious or non-infectious. The infections causing granuloma formation are bacteria, fungi, and parasites. This article briefly discusses some of the infectious agents causing granulomatous disorder.

What Is Infectious Granulomatous Disease?

Infectious granulomatous disease is a rare genetic condition affecting the immune system. The disease develops when phagocytes (white blood cells) do not function appropriately. The phagocytes protect the human body by fighting against infections. When the phagocytes do not function properly, they cannot shield the body from fungal and bacterial infections.

Infectious granulomatous disease affects the lungs, skin, lymph nodes, liver, stomach, intestines, or other body regions. A cluster of white blood cells also forms in infected areas. The unique characteristic of infectious granulomatous disease is its chronicity, where the condition can persist for weeks or months before being diagnosed.

What Are the Infectious Agents Triggering Granulomatous Disease?

Few organisms cause the majority of infectious granulomatous diseases. Some of the infectious agents triggering granulomatous infection are:

1. Mycobacterial Infections: Mycobacterium is the predominant cause of granulomatous infection. All strains of mycobacterium can be associated with granulomas.

• Tuberculosis: Tuberculosis is the most common cause of granuloma formation and develops from Mycobacterium tuberculosis. A chronic inflammatory response develops when the immune system cannot eradicate the bacteria, which results in granuloma formation. The condition predominantly affects the lungs but can also involve other body parts. Most cases of tuberculosis produce caseating granuloma, while others can present with non-caseating granuloma.

• Mycobacterium Avium-Intracellulare Complex: The mycobacterium produces infections in individuals with weakened immunity. It commonly affects patients with HIV (Human Immunodeficiency Virus) or AIDS (Acquired Immunodeficiency Virus).

• Leprosy (Hansen’s Disease): Mycobacterium leprae produces chronic granulomatous disorder. The condition typically affects the skin and nerves. Skin biopsy of the affected individual presents with numerous acid-fast bacilli and well-defined giant cell granuloma.

• Buruli Ulcer: Mycobacterium ulcers cause chronic and painless cutaneous ulcers. The illness is prevalent in African and Australian countries.

• Swimming Pool (Fish Tank) Granuloma: The disease develops in individuals with minor skin abrasions who dip their hands in tropical fish tanks. At first, a solitary granuloma forms, which gradually ulcerates.

2. Fungal Infections: Fungal infections are a common cause of granuloma formation worldwide. Fungi associated with granuloma formation include Aspergillus, Cryptococcus, Candida, and Histoplasma. The granulomatous fungal infection presents as a localized infection or systemic illness.

• Histoplasmosis: The granuloma infection develops from Histoplasma capsulatum. The condition results from bird or bat droppings. It primarily affects the lungs but can develop in other organs. Histoplasmosis within the lungs of immunocompromised individuals appears as epithelioid-cell granuloma, which undergoes coagulative necrosis.

• Valley Fever (Coccidioidomycosis): Coccidioides immitis and Coccidioides posadasii are fungal organisms resulting in granulomatous infection. The infections develop in arid conditions and cause respiratory symptoms. The infection is endemic in the Southwestern United States. When spores of these fungal species are inhaled, a delayed hypersensitivity reaction forms, ultimately causing granulomatous lung lesions. The granulomatous lesions formed are clinically similar to histoplasmosis.

• Cryptococcosis: Cryptococcus neoformans cause fungal infections that affect the lungs and other organs in immunocompromised individuals.

3. Bacterial Infection: Fewer bacterial infections induce granuloma formation, which includes brucellosis, Q-fever, cat-scratch disease, Bartonella, melioidosis, Whipple’s disease, Nocardiosis, and actinomycosis.

• Cat Scratch Fever (Bartonellosis): Bartonella henselae is a bacteria transmitted through cat scratches or bites. Granulomas usually originate from inside lymph nodes.

• Brucellosis: The condition develops from Brucella bacteria. The disease affects multiple organs and results from contacting infected animals or consuming contaminated dairy products. Additionally, consuming raw camel or goat’s milk, raw sheep or goat’s liver, and reindeer bone marrow are associated with transmission of the disease and formation of chronic granulomatous disease.

• Melioidosis: A gram-negative bacteria is responsible for causing the condition. The presenting symptoms are septicemia, septic shock, and multiorgan involvement. Granulomatous osteomyelitis has also been noted.

4. Parasitic Infection: Parasitic infections inducing granuloma formation are Schistosomiasis, Leishmaniasis, and Dirofilariasis.

• Schistosomiasis: The condition results from parasitic worms of Schistosoma species. Contracting the infection results in granuloma formation in the liver, intestine, or other organs.

• Toxoplasmosis: Toxoplasma gondii is a protozoa causing infectious granulomatous disease. The granuloma forms in several tissues, especially in the central nervous system. Neonates can develop this infection from mothers who are infected while pregnant. The protozoa persist within nucleated cells in latency and reactivate with immunosuppression.

• Leishmaniasis: Leishmania is a protozoa transmitted by sandflies. The condition affects cutaneous, mucocutaneous, and visceral tissues.

5. Viral Infections: Rare viral causes for granuloma formation are cytomegalovirus, Epstein-Barr virus, and measles.

• Measles is an RNA (Ribonucleic acid) virus responsible for developing idiopathic granulomatous disease. The infectious spreads through respiratory droplets.

• Herpes: It is a sexually transmitted infection that spreads through close contact such as kissing or transfer of saliva.

What Are the Symptoms of Infectious Granulomatous Disease?

Symptoms can vary based on the affected organ's location. The common symptoms of infectious granulomatous disease include:

• Fever.

• Chest pain while inhaling or exhaling.

• Soreness and swelling in the lymph gland.

• Runny nose.

• Skin irritation, which includes rash, swelling, and redness.

• Redness and swelling in the mouth.

• Gastrointestinal symptoms such as vomiting, diarrhea, stomach pain, bloody stool, and painful pus pockets near anus.

How Is Infectious Granulomatous Disease Diagnosed?

Most cases of infectious granulomatous disease remain undiagnosed in childhood, but some cases are diagnosable during adulthood. Tuberculosis is identified as it forms caseating necrosis with granuloma. However, other infectious granulomas are hard to differentiate based on histological features. Recently, advancements in molecular diagnostic testing have helped identify organisms causing granulomatous disorders.

How Is Infectious Granulomatous Disease Treated?

Management of infectious granulomatous disease depends on the causative agent and the organ affected. Preventive and treatment approaches for infectious granulomatous disease are antibiotics, antifungals, and managing the inflammatory response. At times, immunosuppressive medications help control the immune system’s overactive response. Few patients may need bone marrow transplants to manage the disease. Treatment for infectious granulomatous disease must be continued for months to years before clinical symptoms resolve. Some patients will require surgery to remove granuloma or affected tissue.

Conclusion

Infectious granulomatous disorder is an illness that develops due to bacterial, fungal, viral, or parasitic infection. The infectious causes of granuloma are hard to diagnose and differentiate due to their similarity with other conditions. Treatment for infectious granulomatous disease is antimicrobials.