**2.2 Foreign body granulomas**

Foreign body granulomas consist of an excessive cutaneous inflammatory response to any material in the dermis or subcutis (endogenous or exogenous). The clinical presentation and evolution depends on several factors: tissue response to the foreign body, anatomical site, penetration, composition, amount of material involved, quantity, and volume. They may appear as papules, nodules, or erythematous plaques which harden over time due to fibrosis. The time gap between entrance of the foreign body into the skin and appearance of granulomas is very variable, sometimes being as long as several years.

Among the endogenous substances, hair, calcifications, cholesterol crystals, or uric acid are common; while exogenous substances commonly include insects, silica (talc), beryllium, aluminum, or tattoo ink.

In recent years, the use of cosmetic materials and, in some cases, the implantation of medical material have been implicated in this regard. In recent years, a granulomatous and inflammatory systemic picture secondary to a foreign body reaction has been defined by diverse substances such as biomaterial injections and prostheses (mainly silicone, hyaluronic acid, acrylamides, and methacrylate compounds). The process is defined as autoimmune/inflammatory syndrome induced by adjuvants (ASIA) and is characterized by chronic fatigue, pyrexia, dry mouth, sleep disturbances, myalgia, myositis, muscle weakness, lymph nodes, arthralgia and/or arthritis, and foreign body-type granuloma, in the absence of any autoantibody, infection, or cancer. Symptoms may disappear after removal of the implant material [3].

### **2.3 Localized infectious granulomas**

Infectious granulomas are usually chronic and localized skin infections, the agent being mycobacteria (tuberculosis or atypical mycobacteria), parasites (leishmaniasis), or fungi (cryptococcosis) in an immunocompromised host. With the exception of cutaneous leishmaniasis, granulomatous infections have to be considered as skin manifestations of systemic infections. They thus require systemic treatment directed toward the cause.

## *2.3.1 Cutaneous tuberculosis (TB)*

Cutaneous tuberculosis (TB) accounts for less than 2% of all extrapulmonary tuberculosis manifestations and occurs in 10% of all patients with TB.

**159**

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

acupuncture, tattoos, etc.).

*2.3.2 Cutaneous lesihmaniasis*

crops, and the histopathology.

of Melkersson-Rosenthal syndrome.

syndrome [2].

Crohn's disease.

**2.4 Syndromic mucocutaneous granulomatous disorders**

Skin manifestations of TB represent a clinical polymorphism that can be explained by various factors such as the pathogenicity of the bacterial strain, the immune status of the host, previous treatment, or local factors (i.e., proximity to lymph nodes). Localized forms include lupus vulgaris, a violaceous yellowish cutaneous plaque with serpiginous centrifugal extension, desquamation, and central atrophy, scrofuloderma (an erythemato-violaceous painless nodule, with suppuration as sign of per contiguitatem extension of ganglionic, osteoarticular), or epididymal tuberculosis or verrucous cutaneous tuberculosis (a keratotic plaque with irregular edges and dystrophic scarring on the skin of the hands). Cutaneous atypical mycobacteria infections have heterogeneous clinical appearance, including nodules, papules, plaques, pustules, abscess, and ulcers. *Mycobacterium marinum* is the most commonly involved strain. It causes skin and soft tissue infections after exposure to aquatic environments or marine animals ("tank granuloma"). Patients typically show clusters of nodules, ulcers, or verrucous plaques that may spread from the arms or legs in a sporotrichoid pattern. Mycobacterium chelonae is a rapidly growing mycobacterium that causes dark red nodules and, occasionally, abscesses. The infection is related to skin wounds due to penetration procedures (injection, liposuction,

Cutaneous leishmaniasis involves exposed body parts, causing nodules, ulcers, and scarring. Acute cutaneous leishmaniasis or East button is the most common form. The lesion, initially papular, rounded or oval, and asymptomatic or mildly pruritic, may be single or multiple and commonly located on the face or areas of uncovered skin. Gradually it takes a darker reddish tone while it infiltrates and increases in size. The surface is occasionally covered with furfuraceous scales and, in 1–3 months, is transformed into a nodular lesion or a deep infiltrated plaque. Chronic cutaneous leishmaniasis includes cases that exceed the duration of 1–2 years. The lesions are usually more polymorphic (large indurated plaques with papular borders, eczematiform, warty, keloidal, etc.), and the clinical difficulty of the diagnosis is due to the lower sensitivity of microscopic smear examination, the

Cutaneous nonnecrotizing/necrobiotic granulomas may be part of syndromic

The constituent signs of Melkersson-Rosenthal syndrome include the association of recurrent facial and/or lip edema, recurrent facial paralysis, and fissured tongue. It has been associated with Crohn's disease. Miescher's cheilitis granulomatous consists of the appearance of recurrent labial edema in one or both lips, which can be persistent. It has traditionally been considered as a monosymptomatic form

Blau syndrome is an autosomal-dominant autoinflammatory condition that includes granulomatous inflammation in the skin, together with granulomatous iridocyclitis and granulomatous arthritis with camptodactyly. It is related to mutations in the CARD15/NOD2 gene complex and may also have a linkage to

complexes that include lesions in other organs and tissues as well. The two principal representatives of this group are the Melkersson-Rosenthal syndrome (orofacial mucocutaneous granulomatosis; cheilitis granulomatosa) and Blau

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

*Sarcoidosis and Granulomatosis - Diagnosis and Management*

*2.1.4 Lupus miliaris disseminatus faciei (acne agminata; necrotizing* 

in children and in the cephalic region [1, 2].

*granulomatous rosacea)*

**2.2 Foreign body granulomas**

scars [2].

of the nodule may be necessary if the diagnosis is uncertain. Over time, rheumatoid nodules often disappear or regress, evolving sometimes, independent of treatment. Rheumatoid nodules appearing without clinical or biological rheumatic symptoms are most often deep granuloma annulare or pseudorheumatoid nodules, particularly

Lupus miliaris disseminatus faciei is now believed to be a peculiar variant of rosacea. It presents with multiple reddish papules and nodules of the scalp and face, principally in young adults, and is centered on hair follicles, without pus formation. It usually persists for 2–3 years and then regresses, leaving residual

Foreign body granulomas consist of an excessive cutaneous inflammatory response to any material in the dermis or subcutis (endogenous or exogenous). The clinical presentation and evolution depends on several factors: tissue response

material involved, quantity, and volume. They may appear as papules, nodules, or erythematous plaques which harden over time due to fibrosis. The time gap between entrance of the foreign body into the skin and appearance of granulomas is very

Among the endogenous substances, hair, calcifications, cholesterol crystals, or uric acid are common; while exogenous substances commonly include insects, silica

Infectious granulomas are usually chronic and localized skin infections, the agent being mycobacteria (tuberculosis or atypical mycobacteria), parasites (leishmaniasis), or fungi (cryptococcosis) in an immunocompromised host. With the exception of cutaneous leishmaniasis, granulomatous infections have to be considered as skin manifestations of systemic infections. They thus require systemic

Cutaneous tuberculosis (TB) accounts for less than 2% of all extrapulmonary

tuberculosis manifestations and occurs in 10% of all patients with TB.

to the foreign body, anatomical site, penetration, composition, amount of

In recent years, the use of cosmetic materials and, in some cases, the implantation of medical material have been implicated in this regard. In recent years, a granulomatous and inflammatory systemic picture secondary to a foreign body reaction has been defined by diverse substances such as biomaterial injections and prostheses (mainly silicone, hyaluronic acid, acrylamides, and methacrylate compounds). The process is defined as autoimmune/inflammatory syndrome induced by adjuvants (ASIA) and is characterized by chronic fatigue, pyrexia, dry mouth, sleep disturbances, myalgia, myositis, muscle weakness, lymph nodes, arthralgia and/or arthritis, and foreign body-type granuloma, in the absence of any autoantibody, infection, or cancer. Symptoms may disappear after removal of the

variable, sometimes being as long as several years.

(talc), beryllium, aluminum, or tattoo ink.

implant material [3].

**2.3 Localized infectious granulomas**

treatment directed toward the cause.

*2.3.1 Cutaneous tuberculosis (TB)*

**158**

Skin manifestations of TB represent a clinical polymorphism that can be explained by various factors such as the pathogenicity of the bacterial strain, the immune status of the host, previous treatment, or local factors (i.e., proximity to lymph nodes). Localized forms include lupus vulgaris, a violaceous yellowish cutaneous plaque with serpiginous centrifugal extension, desquamation, and central atrophy, scrofuloderma (an erythemato-violaceous painless nodule, with suppuration as sign of per contiguitatem extension of ganglionic, osteoarticular), or epididymal tuberculosis or verrucous cutaneous tuberculosis (a keratotic plaque with irregular edges and dystrophic scarring on the skin of the hands). Cutaneous atypical mycobacteria infections have heterogeneous clinical appearance, including nodules, papules, plaques, pustules, abscess, and ulcers. *Mycobacterium marinum* is the most commonly involved strain. It causes skin and soft tissue infections after exposure to aquatic environments or marine animals ("tank granuloma"). Patients typically show clusters of nodules, ulcers, or verrucous plaques that may spread from the arms or legs in a sporotrichoid pattern. Mycobacterium chelonae is a rapidly growing mycobacterium that causes dark red nodules and, occasionally, abscesses. The infection is related to skin wounds due to penetration procedures (injection, liposuction, acupuncture, tattoos, etc.).

## *2.3.2 Cutaneous lesihmaniasis*

Cutaneous leishmaniasis involves exposed body parts, causing nodules, ulcers, and scarring. Acute cutaneous leishmaniasis or East button is the most common form. The lesion, initially papular, rounded or oval, and asymptomatic or mildly pruritic, may be single or multiple and commonly located on the face or areas of uncovered skin. Gradually it takes a darker reddish tone while it infiltrates and increases in size. The surface is occasionally covered with furfuraceous scales and, in 1–3 months, is transformed into a nodular lesion or a deep infiltrated plaque. Chronic cutaneous leishmaniasis includes cases that exceed the duration of 1–2 years. The lesions are usually more polymorphic (large indurated plaques with papular borders, eczematiform, warty, keloidal, etc.), and the clinical difficulty of the diagnosis is due to the lower sensitivity of microscopic smear examination, the crops, and the histopathology.

#### **2.4 Syndromic mucocutaneous granulomatous disorders**

Cutaneous nonnecrotizing/necrobiotic granulomas may be part of syndromic complexes that include lesions in other organs and tissues as well. The two principal representatives of this group are the Melkersson-Rosenthal syndrome (orofacial mucocutaneous granulomatosis; cheilitis granulomatosa) and Blau syndrome [2].

The constituent signs of Melkersson-Rosenthal syndrome include the association of recurrent facial and/or lip edema, recurrent facial paralysis, and fissured tongue. It has been associated with Crohn's disease. Miescher's cheilitis granulomatous consists of the appearance of recurrent labial edema in one or both lips, which can be persistent. It has traditionally been considered as a monosymptomatic form of Melkersson-Rosenthal syndrome.

Blau syndrome is an autosomal-dominant autoinflammatory condition that includes granulomatous inflammation in the skin, together with granulomatous iridocyclitis and granulomatous arthritis with camptodactyly. It is related to mutations in the CARD15/NOD2 gene complex and may also have a linkage to Crohn's disease.
