**6.1 Organ involvement**

Sarcoidosis is a multisystem disorder that may affect any organ system such as the lungs, lymph nodes, skin, eyes, liver, heart, and nervous, musculoskeletal, renal, and endocrine systems [52]. The lungs are the site of involvement and

granuloma formation [52]; 90% of patients have clinical manifestation of sarcoidosis in the lungs [53]. Oral involvement has been considered as the first feature of the disease although intraoral presentations of sarcoidosis and also tongue sarcoidosis are particularly rare and uncommon [54]. Sarcoidosis signs and symptoms vary depending on which organs are affected and also the stage of the disease [4].

#### **6.2 Disease course**

Disease course of sarcoidosis is usually favorable. Patients with asymptomatic organ involvement have a high rate of spontaneous resolution that often happens within 6 months of onset [3, 55]. Every 3 months in the first year after diagnosis, follow-up visits need to be carried out and after that once a year for 3–5 years in patients without problems [3, 56, 57]. In patients having a disease course that is progressive, immunosuppressive treatment is recommended. Long-term corticosteroids in patients must be limited because of major problems such as obesity and development of complicated metabolic syndrome [56, 58]. Mortality in sarcoidosis is low [59].

#### **6.3 Diagnosis of exclusion**

Without definitive diagnostic criteria, diagnosis of sarcoidosis requires exclusion of other granulomatous diseases such as tuberculosis, Crohn's disease, etc. [3]; therefore systemic disease evidence as well as compatible clinical and radiological abnormality, histological confirmation of noncaseating granulomas, and exclusion of other granulomatous diseases (that are able to present similar histological and clinical features) can be useful in the diagnosis [60].

#### **6.4 Laboratory markers**

Serum angiotensin-converting enzyme (ACE) is the first widely used marker that has been used as diagnostic and prognostic marker of sarcoidosis but has low specificity as a marker because of its poor predictive value [61–63]. In sarcoidosis, ACE is released by pulmonary endothelial cells into blood vessels to perform its functions. ACE is elevated in affected patients [64]. Serum ACE levels are currently considered as a marker of granuloma formation with limited sensitivity and specificity, and because of its limitation, it must be investigated with other markers in sarcoidosis. As mentioned before, ACE can be used for diagnosis and follow-up, but it must be correlated with clinical phenotypes and radiological findings [65]. In addition, several markers of inflammation that can be involved in the pathogenesis of the sarcoidosis have also been reported, which include lysozyme, cytokines, chemokines, and various molecules produced by activated macrophages or lymphocytes [66–68].

#### **6.5 Pattern of onset**

Sarcoidosis have been known as a time-limited disease with disease course of 1–3 years in half of the patients, less than 5 years in most remaining cases, and rarely for decades [69].

Abrupt onset is the characteristics of acute sarcoidosis, while chronic sarcoidosis has a progressive onset. According to the annual organ screening tests, most types of organ involvement in sarcoidosis occur within 2 years of the onset of disease [70]. For treatment and prognosis of sarcoidosis, mode of onset is one of the most valid factors [71].

**9**

*Introductory Chapter: Orofacial Sarcoidosis and Noncaseating Granulomatosis*

Appropriate decision for treatment in sarcoidosis is difficult especially in the absence of a causative agent. Sarcoidosis treatment is proposed on the basis of prevalence of asymptomatic organ involvement, rate of spontaneous resolution, and complications of long-term corticosteroids therapy [3, 56]. There is a general rule that if only organ function is threatened, organ involvement should be treated [56, 57, 69]. Laboratory testing, biopsy, imaging studies, physical examination, and any other diagnostic tests are required before any treatment. For example, pulmonary function tests and stress testing are required before any treatment for pulmonary sarcoidosis [56]. Corticosteroid therapy is considered the first line in treatment for acute and chronic sarcoidosis and may be used alone or with other medications [57, 72]. Treatment of sarcoidosis is variable between asymptomatic cases and severe cases with systemic corticosteroid therapy [4]. For patients with neurological or ocular involvement or progressive respiratory disease, systemic therapy is prescribed [4]. Immunosuppressive combination therapy is the second line in treatment of sarcoidosis in order to limit the corticosteroid dose [55]. Accumulating evidence suggests that systemic corticosteroids should be used for at least 6 months and then should be reduced

OFG is an uncommon immunologically mediated disorder with unknown etiology that affects the soft tissues of the oral and maxillofacial region. Although the precise cause of OFG is still unknown, allergy, infection, and genetic predisposition as well as immunological reaction have been suggested as probable causes that can be effective in pathogenesis of OFG. Clinical features of OFG are nonspecific, and various presentations in disease make it difficult to diagnose, so a comprehensive clinical, laboratory, and microscopic evaluation is required for exact diagnosis and treatment [28]. A number of granulomatous disorders, such as deep fungal infections, tuberculosis, angioedema, leprosy, Wegener's granuloma, Crohn's disease, and sarcoidosis, are similar to OFG in clinical features specifically persistent lip swelling, so differential tests are needed for diagnosis of OFG [33]. Because of similarity between OFG and some of the granulomatous diseases, this point arises that whether or not OFG is a distinct clinical disorder [12]. In this context, further studies are needed to differentiate OFG from this

*DOI: http://dx.doi.org/10.5772/intechopen.83364*

**6.6 Treatment outcome**

gradually [57].

**7. Conclusion**

group of disorders.

*Introductory Chapter: Orofacial Sarcoidosis and Noncaseating Granulomatosis DOI: http://dx.doi.org/10.5772/intechopen.83364*

### **6.6 Treatment outcome**

*Sarcoidosis and Granulomatosis - Diagnosis and Management*

clinical features) can be useful in the diagnosis [60].

**6.2 Disease course**

is low [59].

**6.3 Diagnosis of exclusion**

**6.4 Laboratory markers**

cytes [66–68].

**6.5 Pattern of onset**

rarely for decades [69].

valid factors [71].

granuloma formation [52]; 90% of patients have clinical manifestation of sarcoidosis in the lungs [53]. Oral involvement has been considered as the first feature of the disease although intraoral presentations of sarcoidosis and also tongue sarcoidosis are particularly rare and uncommon [54]. Sarcoidosis signs and symptoms vary depending on which organs are affected and also the stage of the disease [4].

Disease course of sarcoidosis is usually favorable. Patients with asymptomatic organ involvement have a high rate of spontaneous resolution that often happens within 6 months of onset [3, 55]. Every 3 months in the first year after diagnosis, follow-up visits need to be carried out and after that once a year for 3–5 years in patients without problems [3, 56, 57]. In patients having a disease course that is progressive, immunosuppressive treatment is recommended. Long-term corticosteroids in patients must be limited because of major problems such as obesity and development of complicated metabolic syndrome [56, 58]. Mortality in sarcoidosis

Without definitive diagnostic criteria, diagnosis of sarcoidosis requires exclusion of other granulomatous diseases such as tuberculosis, Crohn's disease, etc. [3]; therefore systemic disease evidence as well as compatible clinical and radiological abnormality, histological confirmation of noncaseating granulomas, and exclusion of other granulomatous diseases (that are able to present similar histological and

Serum angiotensin-converting enzyme (ACE) is the first widely used marker that has been used as diagnostic and prognostic marker of sarcoidosis but has low specificity as a marker because of its poor predictive value [61–63]. In sarcoidosis, ACE is released by pulmonary endothelial cells into blood vessels to perform its functions. ACE is elevated in affected patients [64]. Serum ACE levels are currently considered as a marker of granuloma formation with limited sensitivity and specificity, and because of its limitation, it must be investigated with other markers in sarcoidosis. As mentioned before, ACE can be used for diagnosis and follow-up, but it must be correlated with clinical phenotypes and radiological findings [65]. In addition, several markers of inflammation that can be involved in the pathogenesis of the sarcoidosis have also been reported, which include lysozyme, cytokines, chemokines, and various molecules produced by activated macrophages or lympho-

Sarcoidosis have been known as a time-limited disease with disease course of 1–3 years in half of the patients, less than 5 years in most remaining cases, and

Abrupt onset is the characteristics of acute sarcoidosis, while chronic sarcoidosis has a progressive onset. According to the annual organ screening tests, most types of organ involvement in sarcoidosis occur within 2 years of the onset of disease [70]. For treatment and prognosis of sarcoidosis, mode of onset is one of the most

**8**

Appropriate decision for treatment in sarcoidosis is difficult especially in the absence of a causative agent. Sarcoidosis treatment is proposed on the basis of prevalence of asymptomatic organ involvement, rate of spontaneous resolution, and complications of long-term corticosteroids therapy [3, 56]. There is a general rule that if only organ function is threatened, organ involvement should be treated [56, 57, 69]. Laboratory testing, biopsy, imaging studies, physical examination, and any other diagnostic tests are required before any treatment. For example, pulmonary function tests and stress testing are required before any treatment for pulmonary sarcoidosis [56]. Corticosteroid therapy is considered the first line in treatment for acute and chronic sarcoidosis and may be used alone or with other medications [57, 72]. Treatment of sarcoidosis is variable between asymptomatic cases and severe cases with systemic corticosteroid therapy [4]. For patients with neurological or ocular involvement or progressive respiratory disease, systemic therapy is prescribed [4]. Immunosuppressive combination therapy is the second line in treatment of sarcoidosis in order to limit the corticosteroid dose [55]. Accumulating evidence suggests that systemic corticosteroids should be used for at least 6 months and then should be reduced gradually [57].
