*3.3.4 Multicentric reticulohistiocytosis*

It is a rare histiocytic proliferative disease in which joints, skin, mucous membranes, and internal organs are affected [129]. Onset is usually insidious; cutaneous manifestations usually follow the articular signs and symptoms [130].

The peak occurrence is seen in middle age with the average age of 40–50 years at presentation, but MRH can present at any age [131–133].

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

#### *3.3.5 Rosai-Dorfman syndrome*

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 polyclonal gammopathy are other common associations.

#### *3.3.6 Xanthoma disseminatum*

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 xanthomatous plaque, and may become verrucous [139].

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, trunk, and extremities [140].

XD typically involves the skin, particularly the flexor folds, face, and trunk. It may also manifest in the central nervous system [141].

Mucous membrane involvement develops in 40–60% of patients, most commonly affecting the oropharynx, larynx, or cornea and conjunctiva [142].

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 with spontaneous resolution; and (iii) a very rare, progressive form with organ dysfunction and central nervous system involvement [143].

#### **3.4 Other granulomatous disorders**

#### *3.4.1 Granulomatous vasculitis*

Granulomatous vasculitis is a spectrum of diseases. Lung involvement is very much common in GV. Small vessel vasculitis with granulomatosis is seen in granulomatosis with polyangiitis (Wegener granulomatosis) and eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome), and large-vessel vasculitis with granulomatosis is seen in temporal arteritis: Takayasu arteritis.

In Wegener granulomatosis, the incidence of skin disease is 45% [144]. The lesions can take several forms including papules, vesicles, palpable purpura, ulcers, and subcutaneous nodules [145]. Palpable purpura may be the most frequent (47%) skin finding [146]. The skin disease rarely dominates the clinical picture and is usually a minor part of the multisystem involvement, generally responds promptly to therapy, and parallels disease activity in other organ systems [147]. Other organs include the lungs, kidney, heart, joint, eye, and nervous system involvement [148]. Cutaneous findings are variable and nonspecific and usually affect the lower extremities [146].

Eosinophilic granulomatosis with polyangiitis was previously named as Churg-Strauss syndrome. In one-third to two-thirds of patients, skin involvement is a dominant feature and presents in the form of nodules. Urticaria and ulceration are less common. Neurologic involvement is seen in 60–70% patients and is commonly in the form of multiple mononeuropathies or symmetric polyneuropathy [149].

#### *3.4.2 Lymphomatoid granulomatosis*

Lymphomatoid granulomatosis (LYG) is a progressive lymphoproliferative disease by Epstein-Barr virus (EBV), in which the abnormal cells directly accumulate within affected tissues, usually in the form of infiltrative nodular lesions and with T-cell invasion and destruction of blood vessels [150]. Its incidence is low, clinical features are overlapping, pulmonary disorders are more common, and all contribute to frequent delays in diagnosis [150]. The lung is virtually always involved in bilateral fashion [151]. The skin is the extrapulmonary organ most commonly involved in LYG, occurring in 40–50% of patients [151]. Skin manifestations of LYG are quite heterogeneous. They typically appear as scattered subcutaneous or dermal nodules that vary in size, seen predominantly on the extremities. Erythematous or purplish maculopapular eruptions are the most common skin lesions observed, but some patients will have indurated plaques. Varying degrees of ulceration accompany the skin lesions and may become necrotic when the disease is not well controlled (**Figure 23**). In up to 10% of patients, the skin lesions will antedate the lung lesions, and, in these cases, dermal biopsy may lead to the diagnosis [150]. Skin lesion may develop after lung involvement, but majority of skin lesions develop at the time of lung involvement [151].

#### *3.4.3 Foreign body reactions*

The foreign body granuloma is a response of biological tissue to any foreign material in the tissue [152]. Foreign body granulomas may be due to reactions of endogenous products like keratin, hair, fat, urate crystals, mineral, and/or oil products; plant and animal products; and synthetic agents [153]. Depending on the individual host response and type of foreign materials, clinical findings can be variable. Sites depend on the area involved by endo- or exogenous material. The lesions may be

**89**

**Figure 24.**

*Foreign body granuloma.*

**Figure 23.**

*Lymphomatoid granulomatosis.*

*Clinical Manifestations of Sarcoidosis and Granulomatous Disorders*

asymptomatic or tender, pink, red, red-brown or skin-colored, and firm papules, nodules, or plaques, which may or may not ulcerate or drain (**Figure 24**). Other presentations include sinus tracts and abscesses [153]. The foreign material may migrate, as in silicone, leading to granulomas at sites distant from the area of implantation [154].

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

asymptomatic or tender, pink, red, red-brown or skin-colored, and firm papules, nodules, or plaques, which may or may not ulcerate or drain (**Figure 24**). Other presentations include sinus tracts and abscesses [153]. The foreign material may migrate, as in silicone, leading to granulomas at sites distant from the area of implantation [154].

**Figure 23.** *Lymphomatoid granulomatosis.*

**Figure 24.** *Foreign body granuloma.*
