*3.2.2 Annular elastolytic giant cell granuloma*

It is usually a disease of middle-aged, Caucasian women [90]. Onset is sudden but progressive, and varying in duration from 1 month to 10 years [91]. Clinically, AEGCG presents as multiple, large, annular plaques with a raised, erythematous border and central atrophy. The lesions are mostly located on sun-exposed areas such as the face and neck, but they are also seen on nonexposed skin although rare reports of a papular variant of AEGCG exist [92, 93]. It is currently unclear whether they simply represent a variant of granuloma annulare occurring on sun-damaged skin or distinct disease. There are two patterns. One is a single, asymptomatic, atrophic-appearing, yellow thin plaque on forehead, and the other is multiple, upper extremity, and trunk lesions occurring mainly on sun-exposed areas predominantly in women (**Figure 19**). A papular and arciform variant is also described [90, 91]. The histopathologic features are best demonstrated by a biopsy of the elevated edge of the plaque [94]. The lesions may persist for months to years resolving with either mottled pigmentation or normal-appearing skin [95]. Association with temporal arteritis is reported [96]. There have been reported cases of AEGCG associated with diabetes, sarcoidosis, and hematological malignancies [97, 98]. Patient of AEGCG may associate with Barrett's esophagus. The patient had hepatic nodules that showed nonspecific granulomas with elastolysis, similar to the skin lesions [99].

**83**

*3.2.3 Necrobiosis lipoidica*

*Annular elastolytic giant cell granuloma.*

*3.2.4 Rheumatoid nodule*

long-term lesions have also been reported [105].

be affected.

**Figure 19.**

Necrobiosis lipoidica developed in the fourth decade of life and, in type 1 diabetes mellitus, in the third decade [100, 101]. Females are more affected than male (3:1). It is rare in childhood. NL is usually present on bilateral lower extremities, typically pretibial skin, but face, scalp, trunk, groin, and upper extremities can also

It forms as well-circumscribed papules and nodules with active erythematous borders that slowly coalesce into plaques. The plaques appear violaceous and contain a central area that initially appears red-brown but later progresses to a yellowbrown discoloration with atrophic, waxy appearance with prominent telangiectatic vessels [102]. But this classical presentation may not present in Indian patients where common presentation is erythematous plaque [103] (**Figure 20**). Lesions are 1–3 in number [102]. They are usually asymptomatic but may be painful or hypoesthetic or anesthetic [104]. NL lesions can also exhibit the Koebner phenomenon. Up to one-thirds of the patients with NL may develop ulcerations secondary to minor trauma [100]. Occasional reports of squamous cell carcinoma arising in areas of

Rheumatoid nodules are commonly found in patients with rheumatoid arthritis as later manifestation of active arthritic disease [106]. It occurs as subcutaneous nodules;

*Clinical Manifestations of Sarcoidosis and Granulomatous Disorders*

*DOI: http://dx.doi.org/10.5772/intechopen.92236*

*Clinical Manifestations of Sarcoidosis and Granulomatous Disorders DOI: http://dx.doi.org/10.5772/intechopen.92236*

**Figure 19.** *Annular elastolytic giant cell granuloma.*

### *3.2.3 Necrobiosis lipoidica*

Necrobiosis lipoidica developed in the fourth decade of life and, in type 1 diabetes mellitus, in the third decade [100, 101]. Females are more affected than male (3:1). It is rare in childhood. NL is usually present on bilateral lower extremities, typically pretibial skin, but face, scalp, trunk, groin, and upper extremities can also be affected.

It forms as well-circumscribed papules and nodules with active erythematous borders that slowly coalesce into plaques. The plaques appear violaceous and contain a central area that initially appears red-brown but later progresses to a yellowbrown discoloration with atrophic, waxy appearance with prominent telangiectatic vessels [102]. But this classical presentation may not present in Indian patients where common presentation is erythematous plaque [103] (**Figure 20**). Lesions are 1–3 in number [102]. They are usually asymptomatic but may be painful or hypoesthetic or anesthetic [104]. NL lesions can also exhibit the Koebner phenomenon. Up to one-thirds of the patients with NL may develop ulcerations secondary to minor trauma [100]. Occasional reports of squamous cell carcinoma arising in areas of long-term lesions have also been reported [105].

#### *3.2.4 Rheumatoid nodule*

Rheumatoid nodules are commonly found in patients with rheumatoid arthritis as later manifestation of active arthritic disease [106]. It occurs as subcutaneous nodules;

**Figure 20.** *Necrobiosis lipoidica.*

the most common extra-articular feature of RA [107, 108] is present in about 25–42% [107, 108] of RA patients, although similar nodules have been observed in nonrheumatoid conditions, such as granuloma annulare and necrobiosis lipoidica [109]. Nodules are skin colored, can be solitary or multiple, and range from <5 mm to many centimeters in diameter [106] (**Figure 21**). They lie deeply subcutaneously and can adhere to underlying periosteum, tendons, or bursae, although others may be epidermal and freely movable [110]. Most are firm and painless and often go unnoticed by the average patient, but those found on the plantar surfaces of the feet or palms may feel uncomfortable [110].

### *3.2.5 Reactive granulomatous disorders*

Reactive granulomatous disorders are reactive granulomatous processes, which present with a cutaneous granulomatous eruptions in response to medications, autoimmune disease, arthritides, and internal malignancies. There is a wide spectrum of clinical morphologic patterns and a broad array of histologic subtypes that may occur. The common RGDs are palisaded neutrophilic and granulomatous dermatitis (PNGD), interstitial granulomatous dermatitis (IGD), and interstitial granulomatous drug reaction (IGDR) [111].

The classic clinical presentation of PNGD is that of flesh-colored to erythematous papules, which may be umbilicated or crusted, appearing symmetrically on the extremities particularly around the elbows [112–114] (**Figure 22**). Palisaded neutrophilic and granulomatous dermatitis is seen in association with a number of systemic diseases. The diseases most commonly reported with PNGD include connective tissue diseases—particularly systemic lupus erythematosus—as well as inflammatory arthritis, hematologic disorders, and rarely infections or medications [111]. Patients

**85**

**Figure 21.** *Rheumatoid nodule.*

*Clinical Manifestations of Sarcoidosis and Granulomatous Disorders*

of all ages may develop PNGD, although reports in childhood are rare [114]. Women are affected more frequently (approximately 3:1 ratio), likely owing to the systemic

In interstitial granulomatous dermatitis (IGD), the initial description was linear subcutaneous cords or bands on the proximal trunk [115], and also erythematous to violaceous patches or plaques symmetrically on the upper trunk and proximal limbs are a frequent manifestation [116]. IGD is generally seen in the setting of an

There is contradiction whether interstitial granulomatous drug reaction (IGDR)

Xanthogranuloma (XG) is the most common non-Langerhans cell histiocytosis, which usually occurs in the early part of life [118]. It is rare in adults, usually occur-

is another entity or subtype of interstitial granulomatous dermatitis [111]. The classic description of IGDR is erythematous to violaceous plaques, often annular, concentrated on the inner arms, proximal medial thighs, proximal trunk, and

*DOI: http://dx.doi.org/10.5772/intechopen.92236*

diseases associated with PNGD [114].

**3.3 Xanthomatous granulomas**

*3.3.1 Adult-onset xanthogranuloma*

underlying systemic disease, similar to PNGD [111].

ring in the third and fourth decades of life [119].

intertriginous sites, with distinctive histologic features [117].

*Clinical Manifestations of Sarcoidosis and Granulomatous Disorders DOI: http://dx.doi.org/10.5772/intechopen.92236*

**Figure 21.** *Rheumatoid nodule.*

of all ages may develop PNGD, although reports in childhood are rare [114]. Women are affected more frequently (approximately 3:1 ratio), likely owing to the systemic diseases associated with PNGD [114].

In interstitial granulomatous dermatitis (IGD), the initial description was linear subcutaneous cords or bands on the proximal trunk [115], and also erythematous to violaceous patches or plaques symmetrically on the upper trunk and proximal limbs are a frequent manifestation [116]. IGD is generally seen in the setting of an underlying systemic disease, similar to PNGD [111].

There is contradiction whether interstitial granulomatous drug reaction (IGDR) is another entity or subtype of interstitial granulomatous dermatitis [111]. The classic description of IGDR is erythematous to violaceous plaques, often annular, concentrated on the inner arms, proximal medial thighs, proximal trunk, and intertriginous sites, with distinctive histologic features [117].

#### **3.3 Xanthomatous granulomas**

### *3.3.1 Adult-onset xanthogranuloma*

Xanthogranuloma (XG) is the most common non-Langerhans cell histiocytosis, which usually occurs in the early part of life [118]. It is rare in adults, usually occurring in the third and fourth decades of life [119].

**Figure 22.** *Palisaded neutrophilic and granulomatous dermatitis.*

Lesions of XG are usually orange or erythematous-brown papule nodule [120], varying the tonality with the age of the lesions [118]. XGA usually occurs as a single lesion in 2/3 of cases located on the face but may be seen in the trunk or limbs [119, 121].

There are three recognized main clinical forms of adult onset xanthogranuloma: a small nodular/papular (2–5 mm); large nodular (5–20 mm); and giant xanthogranuloma (more than 20 mm [122]). Multiple adult onset xanthogranuloma is defined when there are more than five XG lesions. It appears to be more common among men [121].

### *3.3.2 Adult onset asthma with periorbital xanthogranuloma (adult onset APXG)*

Adult onset asthma with periorbital granuloma (AAPOX) syndrome was first described in 1993 by Jakobiec et al. and is considered to be a periorbital disease with a specific granulomatous inflammation [123, 124].

Skin surrounding the orbit is yellow-orange in color, with swelling of mainly upper and also lower eyelid with compromised eyelid movement. There is associated allergic sinusitis and adult onset asthma [125].

### *3.3.3 Necrobiotic xanthogranuloma*

It is a chronic, progressive granulomatous disorder with cutaneous and extracutaneous involvement. The mean age is 61.6 years [126]. The mean (SD) age at presentation was 61.6 (14.2) years; females are more commonly affected (62.6%) than male. Most patients are white (87%) [126]. More than one site is usually involved [127].

**87**

*Clinical Manifestations of Sarcoidosis and Granulomatous Disorders*

It usually manifests as yellowish or yellow-orange, red or brown papules, plaques, and nodules [126]. The commonest site of involvement is the periorbital area [128]. Trunk [127] and also the extremities [126] are the second most

Dermatologic symptoms may present up to 60% of patients such as itching, burning, tenderness, and pain. Nearly half of patients may ulcerate, the most com-

It is a rare histiocytic proliferative disease in which joints, skin, mucous membranes, and internal organs are affected [129]. Onset is usually insidious; cutaneous

The peak occurrence is seen in middle age with the average age of 40–50 years at

The classic skin lesions are firm brown or yellow papule and plaque. Extensor surfaces are predominantly affected, particularly on the hands and forearm, and also the face, scalp, hands, and ears are often affected, but involvement of lower trunk and legs is rare. Coral bead-like lesions may occur around the nail folds which may lead to nail dystrophy. The size varies from a few millimeters to centimeters [134]. Lesions in proximity to joints may be largely nodular. Lesions may ulcerate. The vermicular erythematous lesions around the nostrils are thought to be a characteristic of MRH [135]. Mucosal lesions present from 30 to 50% patients [131, 133], oral and nasal mucosa are the frequently involved sites, but lesions may be distributed along the lips, buccal mucosa, tongue, and gingival and nasal septum. Usually

The hallmark of Rosai-Dorfman disease is massive cervical lymphadenopathy. Other lymph node groups like axillary, inguinal, and mediastinal nodes may also be affected. In about 10% of patients, the cutaneous manifestations present, which are asymptomatic xanthoma-like, yellowish, or reddish-brown papules, nodules, and plaques which may ulcerate [136]. Involvement of extra-nodal sites like the nasal cavity, paranasal sinuses, eyelids, orbit, skeletal system, salivary glands, and central nervous system has been reported [137, 138]. Fever, elevated ESR, neutrophilia, and

It occurs in children and adults and characterized by disseminated xanthomatous lesions. XD usually presents as erythematous, yellow brown papule and nodules, symmetrical in distribution. Lesions become confluent, sometimes form a

It usually starts before the age of 25 years in about 60% of patients. It is more common in males. It may occur anywhere on the body including the scalp, face,

XD typically involves the skin, particularly the flexor folds, face, and trunk. It

Mucous membrane involvement develops in 40–60% of patients, most com-

There are three clinical patterns of xanthoma disseminatum: (i) a common persistent form in which lesions may never resolve; (ii) a rare, self-healing form

monly affecting the oropharynx, larynx, or cornea and conjunctiva [142].

manifestations usually follow the articular signs and symptoms [130].

lesions are asymptomatic; around 25% patients complain of pruritus.

presentation, but MRH can present at any age [131–133].

polyclonal gammopathy are other common associations.

xanthomatous plaque, and may become verrucous [139].

may also manifest in the central nervous system [141].

*DOI: http://dx.doi.org/10.5772/intechopen.92236*

mon secondary feature [126, 127].

*3.3.4 Multicentric reticulohistiocytosis*

*3.3.5 Rosai-Dorfman syndrome*

*3.3.6 Xanthoma disseminatum*

trunk, and extremities [140].

common site.

#### *Clinical Manifestations of Sarcoidosis and Granulomatous Disorders DOI: http://dx.doi.org/10.5772/intechopen.92236*

It usually manifests as yellowish or yellow-orange, red or brown papules, plaques, and nodules [126]. The commonest site of involvement is the periorbital area [128]. Trunk [127] and also the extremities [126] are the second most common site.

Dermatologic symptoms may present up to 60% of patients such as itching, burning, tenderness, and pain. Nearly half of patients may ulcerate, the most common secondary feature [126, 127].
