**3. Systemic granulomatosis diseases**

## **3.1 Infectious disseminated granuloma**

Almost all infectious pathogens can induce granulomas (**Table 1**). Although the skin tends to be frequently affected, visceral involvement is usually coexisting, as is a systemic inflammatory process (fever, asthenia, etc.). There is no universal pattern of visceral or cutaneous involvement; the epidemiological and clinical context is essential, and physical history can provide data on the etiological agent.

Among infectious agents, mycobacteria are the most frequently involved. In tuberculosis and leprosy, there is either a true skin infection or tuberculids, which are regarded as a cutaneous hypersensitivity reaction to *Mycobacterium leprae* linked to the release of an antigen by an internal mycobacteria infectious focus. Skin tuberculid lesions are not contagious. The clinical manifestations of tuberculosis tuberculids are erythema nodosum, erythema induratum of Bazin, papulonecrotic tuberculids, lichen scrofulosorum, and lupus miliaris disseminatus faciei, whose differential diagnosis is granulomatous rosacea. Some agents have tropism due to specific viscera, such as bartonella due to the liver or the vascular affectation of syphilis. Some viruses are associated with specific vasculitic systemic processes, such as panarteritis nodosa in the case of hepatitis B or vasculitis cryoglobulinemia induced by the hepatitis C virus.

#### **3.2 Noninfectious disseminated granuloma**


**161**

**Table 2.**

*Granulomatous Diseases Mimicking Sarcoidosis DOI: http://dx.doi.org/10.5772/intechopen.92233*

Immune-mediated inflammatory diseases

• Bronchogenic granulomatosis • Inflammatory bowel disease • Autoimmune hepatitis • Primary biliary cirrhosis • Primary sclerosing cholangitis • Idiopathic eosinophilic gastroenteritis

• Chronic idiopathic inflammatory bowel disease

• Granulomatosis with polyangiitis (Wegener)

• Granulomatous reaction to metastases

• Eosinophilic granulomatosis with polyangiitis (Churg-Strauss)

◯ Cutaneous: mycosis fungoides T-cell lymphoma (granulomatous)

• Primary: lung, breast, uterus, prostate, hepatocellular carcinoma

I. Immunotherapy and growth factors: interferon α, G-CSF, anti-TNF-α, IFN-α

H. Drugs: antihypertensives (angiotensin-converting enzyme inhibitors, calcium channel blockers, beta blockers, diuretics, hydralazine), hypolipidemic agents, anticonvulsants (phenytoin, topiramate), quinidine, antihistaminics, allopurinol, antimicrobials (nitrofurantoin, isoniazid), and others (beryllium,

A. Organ specifies primarily • Sarcoidosis

B. Systemic

• Lupus erythematosus • Rheumatoid arthritis • Polyarteritis nodosa

Neoplasia/clonal diseases C. Hematological • Lymphoma

> ◯ Systemic: ◯ Hodgkin ◯ Non-Hodgkin • Myelodysplastic syndrome

D. Solid tumors

Metabolic

Toxic

E. Diabetes mellitus F. Dyslipidemia G. Thyroid disease

Immunodeficiency

Idiopathic

gold, copper toxicity, talc).

K. Wiskott-Aldrich syndrome L. Chronic granulomatous diseases

J. Common variable immunodeficiency

*Causes of noninfectious systemic granulomas.*

There are many etiologies of noninfectious disseminated granulomas (**Table 2**). Possibly sarcoidosis is the prototype of these diseases, although it will not be

#### **Table 1.**

*Common infectious diseases causing disseminated granulomatosis.*

Immune-mediated inflammatory diseases

	- Sarcoidosis

*Sarcoidosis and Granulomatosis - Diagnosis and Management*

Almost all infectious pathogens can induce granulomas (**Table 1**). Although the skin tends to be frequently affected, visceral involvement is usually coexisting, as is a systemic inflammatory process (fever, asthenia, etc.). There is no universal pattern of visceral or cutaneous involvement; the epidemiological and clinical context

There are many etiologies of noninfectious disseminated granulomas (**Table 2**).

*Candida* sp. *Aspergillus* sp. Cryptococcosis Histoplasmosis Blastomycosis Coccidioidomycosis Paracoccidioidomycosis Toxoplasmosis *Leishmania* sp. Bilharzia *Toxocara canis Capillaria hepatica*

*Ascaris Strongyloides Giardia lamblia Fasciola* Schistosomiasis *Enterobius vermicularis* (pinworms) *Echinococcus granulosus Echinococcus multilocularis*

*Penicillium Sporothrix schenckii Pneumocystis jiroveci*

Possibly sarcoidosis is the prototype of these diseases, although it will not be

**Bacteria Virus Fungi Parasites**

is essential, and physical history can provide data on the etiological agent. Among infectious agents, mycobacteria are the most frequently involved. In tuberculosis and leprosy, there is either a true skin infection or tuberculids, which are regarded as a cutaneous hypersensitivity reaction to *Mycobacterium leprae* linked to the release of an antigen by an internal mycobacteria infectious focus. Skin tuberculid lesions are not contagious. The clinical manifestations of tuberculosis tuberculids are erythema nodosum, erythema induratum of Bazin, papulonecrotic tuberculids, lichen scrofulosorum, and lupus miliaris disseminatus faciei, whose differential diagnosis is granulomatous rosacea. Some agents have tropism due to specific viscera, such as bartonella due to the liver or the vascular affectation of syphilis. Some viruses are associated with specific vasculitic systemic processes, such as panarteritis nodosa in the case of hepatitis B or vasculitis cryoglobulinemia induced by the hepatitis C virus.

**3. Systemic granulomatosis diseases**

**3.1 Infectious disseminated granuloma**

**3.2 Noninfectious disseminated granuloma**

Human

virus

immunodeficiency

Epstein-Barr virus Cytomegalovirus Hepatitis B virus Hepatitis C virus

*Common infectious diseases causing disseminated granulomatosis.*

*M. tuberculosis M. marinum M. chelonae M. avium* (MAI) *M. leprae T. pallidum* (syphilis) *Salmonella* sp. *Bartonella henselae Kleb. granulomatis* (donovanosis) Listeriosis *Brucella Pasteurella Yersinia Nocardia T. whipplei Rhodococcus equi* Tularemia Melioidosis *Coxiella burnetii Borrelia burgdorferi*

**160**

**Table 1.**


#### B. Systemic


Neoplasia/clonal diseases

	- Lymphoma
		- ◯ Cutaneous: mycosis fungoides T-cell lymphoma (granulomatous)
		- ◯ Systemic:
		- ◯ Hodgkin
		- ◯ Non-Hodgkin
	- Myelodysplastic syndrome
	- Primary: lung, breast, uterus, prostate, hepatocellular carcinoma
	- Granulomatous reaction to metastases

Metabolic


Toxic


Immunodeficiency


Idiopathic

#### **Table 2.**

*Causes of noninfectious systemic granulomas.*

addressed in this chapter. Not all immune-mediated systemic processes should be assimilated as diseases capable of producing granulomas. For example, in the disease related to IgG4, although cases of pulmonary lymphomatoid granulomatosis associated with it have been described, two findings are extraordinary and practically discard it, namely, the presence of granulomas and the presence of a neutrophilic infiltrate [4, 5]. In this same sense we must refer to the diseases included in the so-called xanthogranulomatous diseases (Langerhans cell histiocytosis, Erdheim-Chester disease, Rosai-Dorfman disease, hemophagocytic lymphohistiocytosis, and juvenile xanthogranuloma) where space-occupying lesions can be seen in imaging techniques and a histiocytic infiltrate in biopsies, but rarely granulomas [6].
