**5.1 Differential diagnosis**

As mentioned above, because of the same clinical features of orofacial lesions in granulomatous diseases, differential diagnoses must be considered for such diseases and other conditions including [31]:


### **5.2 Diagnostic tests**

Due to the ambiguity and difficulty in the exact diagnosis of granulomatous diseases and OFG, appropriate clinical and laboratory tests as well as radiographic and endoscopic investigations and also staining techniques and biopsy can be helpful to differentiate between such diseases.

Useful evaluations for differentiating granulomatous diseases include, as follows [28]:


**OFG:** Blood tests, hemoglobin, C-1 esterase inhibitor, serum iron and transferrin, chest X-ray, and GI endoscopy/histopathology should be normal, and tuberculin skin test, PAS reaction and Ziehl-Neelsen stain, and polarized light microscopy for identification of foreign body materials should be negative. Also, noncaseating inflammation as well as elevated IgG and serum angiotensin-converting enzyme (ACE) levels are seen in this disease.

**Crohn's disease:** There are GI symptoms, decreased vitamin B12 and ferritin and increased CRP. Blood test, abdominal radiography, endoscopy, and colonoscopy should be considered.

**Sarcoidosis:** There are clinical symptoms, anemia, and also increased ESR, CPR, serum ACE, serum, and urinary calcium in sarcoidosis patients. Chest radiograph as well as negative microbial culture and negative staining are also helpful in diagnosis.

**Wegener's granulomatosis:** Clinical symptoms, vasculitis, and necrotizing granulomatosis are seen in this disease. Chest and sinus radiography as well as kidney function test anti-neutrophil cytoplasmic antibody (ANCA) and ESR should be done.

**5**

**Figure 1.**

*Introductory Chapter: Orofacial Sarcoidosis and Noncaseating Granulomatosis*

ing, chest X-ray, PPD, and PAS test are used for diagnosis.

accurate diagnosis, PAS and acid-fast staining are done.

**Tuberculosis:** Caseating granuloma is seen in the disease. Ziehl-Neelsen stain-

**Leprosy:** Granulomatous inflammation is present in this disease, and for more

**Foreign body granulomas:** Noncaseating granulomatosis and foreign bodies are

**Cheilitis granulomatosa (CG):** There is no evidence of GI involvement. Blood tests, chest radiography, and acid-fast staining should be done. Serum calcium and

Histopathologic evaluation is one of the useful methods in OFG diagnosis. Several studies have demonstrated that OFG and Crohn's disease are similar with regard to their orofacial features and histopathology or may be similar to other granulomatous diseases; so it can be said that OFG is a diagnosis of exclusion [22]. Therefore, other complementary techniques like special stains for fungal infections or Ziehl-Neelsen for bacterial infections, negative microbial culture for sarcoidosis,

Histopathological evidences indicate that in OFG lesions, noncaseating granulomas may not be present in all cases (from 43 to 82%) [11, 34–37] (**Figures 1** and **2**). Dilated lymphatics, edema of corium, slight fibrosis, with/without multiple noncaseating granulomas with Langerhans giant cells, and lymphocytes may be seen in OFG

The definite treatment of the disease in the lack of a causative factor remains to be elucidated. The first line in treatment is the use of local or systemic corticosteroids or both. Corticosteroids are effective in reducing facial swelling and preventing recurrence. Patients with mild swelling are treated locally [35]. Atrophy and hypopigmentation are the only side effects of local treatment, but side effects in the use of corticosteroids systemically are more important and must be avoided because of chronicity and recurrence of the disease and long-term nature of complications [38]. The use of triamcinolone 10 mg/ml is also often suggested in the treatment of

etc. should be done to exclude other causes of granulomatous conditions.

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

evident in this disease.

**5.3 Histopathology**

ACE and ESR are checked.

lesions [11] (**Figures 3** and **4**).

local swellings of the lips [39].

*Noncaseating granulomas of sarcoidosis in skin (H&E low power).*

**5.4 Treatment of OFG**

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

**Tuberculosis:** Caseating granuloma is seen in the disease. Ziehl-Neelsen staining, chest X-ray, PPD, and PAS test are used for diagnosis.

**Leprosy:** Granulomatous inflammation is present in this disease, and for more accurate diagnosis, PAS and acid-fast staining are done.

**Foreign body granulomas:** Noncaseating granulomatosis and foreign bodies are evident in this disease.

**Cheilitis granulomatosa (CG):** There is no evidence of GI involvement. Blood tests, chest radiography, and acid-fast staining should be done. Serum calcium and ACE and ESR are checked.

#### **5.3 Histopathology**

*Sarcoidosis and Granulomatosis - Diagnosis and Management*

the disease [28].

swelling [33].

differentiate between such diseases.

tous inflammation or not.

(ACE) levels are seen in this disease.

should be considered.

anemia and intestinal malabsorption.

• Biopsy: useful for the correct diagnosis.

**5.2 Diagnostic tests**

• **Wegener's disease**, an uncommon necrotizing granulomatosis condition with a set of clinical manifestations with a different immunopathogenesis [32].

• **Foreign body granulomas**, formation of noncaseating granulomas and also labial and mucosal swellings with foreign bodies as the main characteristics of

• **OFG**, a condition that is restricted to the orofacial region (some diseases such as Crohn's disease, sarcoidosis, cheilitis granulomatosa, Wegener's granulomatosis, granulomatous infections, etc. can mimic its features), specifically lip

Due to the ambiguity and difficulty in the exact diagnosis of granulomatous diseases and OFG, appropriate clinical and laboratory tests as well as radiographic and endoscopic investigations and also staining techniques and biopsy can be helpful to

Useful evaluations for differentiating granulomatous diseases include, as follows [28]:

• Microscopic investigations: for detection of granulomatous inflammation.

• Special stains: used to rule out deep fungal infections and bacterial infections.

• Polarized light microscopy: for identification of foreign bodies in the tissues.

• Chest radiography and assessment of serum levels of angiotensin-converting enzyme (ACE); complete blood count, erythrocyte sedimentation rate (ESR), and serum levels of folic acid, iron, and vitamin B12; and tuberculin skin test are done to assess whether a systemic disease is responsible for the granuloma-

• Gastrointestinal evaluation is essential, especially in the presence of signs of

**OFG:** Blood tests, hemoglobin, C-1 esterase inhibitor, serum iron and transferrin, chest X-ray, and GI endoscopy/histopathology should be normal, and tuberculin skin test, PAS reaction and Ziehl-Neelsen stain, and polarized light microscopy for identification of foreign body materials should be negative. Also, noncaseating inflammation as well as elevated IgG and serum angiotensin-converting enzyme

**Crohn's disease:** There are GI symptoms, decreased vitamin B12 and ferritin and increased CRP. Blood test, abdominal radiography, endoscopy, and colonoscopy

**Sarcoidosis:** There are clinical symptoms, anemia, and also increased ESR, CPR, serum ACE, serum, and urinary calcium in sarcoidosis patients. Chest radiograph as well as negative microbial culture and negative staining are also helpful in diagnosis. **Wegener's granulomatosis:** Clinical symptoms, vasculitis, and necrotizing granulomatosis are seen in this disease. Chest and sinus radiography as well as kidney function test anti-neutrophil cytoplasmic antibody (ANCA) and ESR should

**4**

be done.

Histopathologic evaluation is one of the useful methods in OFG diagnosis. Several studies have demonstrated that OFG and Crohn's disease are similar with regard to their orofacial features and histopathology or may be similar to other granulomatous diseases; so it can be said that OFG is a diagnosis of exclusion [22]. Therefore, other complementary techniques like special stains for fungal infections or Ziehl-Neelsen for bacterial infections, negative microbial culture for sarcoidosis, etc. should be done to exclude other causes of granulomatous conditions.

Histopathological evidences indicate that in OFG lesions, noncaseating granulomas may not be present in all cases (from 43 to 82%) [11, 34–37] (**Figures 1** and **2**). Dilated lymphatics, edema of corium, slight fibrosis, with/without multiple noncaseating granulomas with Langerhans giant cells, and lymphocytes may be seen in OFG lesions [11] (**Figures 3** and **4**).

#### **5.4 Treatment of OFG**

The definite treatment of the disease in the lack of a causative factor remains to be elucidated. The first line in treatment is the use of local or systemic corticosteroids or both. Corticosteroids are effective in reducing facial swelling and preventing recurrence. Patients with mild swelling are treated locally [35]. Atrophy and hypopigmentation are the only side effects of local treatment, but side effects in the use of corticosteroids systemically are more important and must be avoided because of chronicity and recurrence of the disease and long-term nature of complications [38]. The use of triamcinolone 10 mg/ml is also often suggested in the treatment of local swellings of the lips [39].

**Figure 1.** *Noncaseating granulomas of sarcoidosis in skin (H&E low power).*

**Figure 2.** *Confluent noncaseating granulomatosis of sarcoidosis.*

**Figure 3.** *Asteroid bodies and multinucleated giant cells in sarcoidosis.*

Other suggested treatments for OFG in the literature include hydroxychloroquine [35, 40], methotrexate, clofazimine [35], metronidazole, minocycline [41] alone or in combination with oral prednisone, thalidomide [42, 43], dapsone, and danazol. Surgery may be used in cases that do not respond to medical treatment. Altogether, a good prognosis is predicted for OFG.
