**8. Differential diagnosis**

**Figure 2.** Characteristic facial appearance (lion face).

44 Hansen's Disease - The Forgotten and Neglected Disease

lead to stasis dermatitis and venous ulcers.

bone marrow) can be observed.

Corneal dryness, abrasion and ulceration are very common in patients with leprosy due to the secretory irregularity and corneal insensitivity. A careful eye examination should be performed in every leprosy patient to prevent serious complications that can result in blindness. Depending on the perforation and collapse of the nasal septum, saddle nose and rhinitis-like findings can be observed. Snoring due to nodule occurrence in vocal cords and larynx involvement, and gynecomastia, impotence and infertility as a result of decrease in blood testosterone

Venous insufficiency due to endothelial involvement of the valves of deep venous vessels may

In the advanced disease phase, multiorgan involvement (liver, spleen, peripheral lymph nodes,

level due to testicular involvement in male patients may be seen [61].

**6. Complications**

Although reduction and absence of sensory perception distinguish leprosy lesions from other diseases, this finding may not always be detectable. With the reason that a wide variety of cutaneous lesions are present, leprosy can be confused with many diseases. In suspected patients, the exact diagnosis is made by skin biopsy.

Hypopigmented lesions may mimic pityriasis alba, pityriasis versicolor, mycosis fungoides and sarcoidosis [66].

Figured erythematous plaques may be confused with fungal infections, annular psoriasis, sarcoidosis, mycosis fungoides, lichen planus, systemic lupus erythematosus [66].

Infiltrated plaques and nodules generate definitive diagnosis with cutaneous leiomyoma, sarcoidosis, syphilis, keloid, cutaneous lymphoma, granuloma annulare [66].

In addition, definitive diagnosis of type 1 reaction includes acute lupus erythematosus, drug reactions, cellulitis; the definitive diagnosis of the type 2 reaction should be considered to include other conditions that may cause vasculitis and panniculitis.

## **9. Diagnosis**

For diagnosis, leprosy must first come to mind. Although diagnosis is made substantially by clinic examination, diagnosis must be supported by laboratory for classification and treatment. Microbiological and pathological tests should be performed after history and clinical evaluation [67]. WHO recommends that individuals with one of the two cardinal findings in endemic regions are considered to be leprosy [68].

*9.2.2. Hystopathology*

and BL cases.

*9.2.3. Lepromin test*

prognostic purposes.

**9.3. Serology**

There is marked edema in the nerve tissue.

a feature of BL. The nerves have the onion skin perineurium.

structures are less prominent.

The main pathologic feature is a granulomatous reaction. Epithelioid cells, macrophages, lymphocytes, plasmocytes and rarely neutrophil and mast cells are observed. Different granulomatous reactions occur according to the immune response of the host. While epithelial cells are mostly observed in TT and BT cases, foamy macrophages are observed mostly in LL

An Update on the Epidemiology, Diagnosis and Treatment of Leprosy

http://dx.doi.org/10.5772/intechopen.80557

47

• *TL:* The reaction is mostly multifocal, periadnexal and perineural. Infiltrate is in dermis. The epidermis is usually atrophic. Giant langerhans cells are pathognomonic. Multinuclear giant cells can be seen while plasma cells are not expected to be observed. Perineurium is intact and is surrounded by lymphocytes. It can even infiltrate with granuloma structures.

• **BT:** Findings are similar to those for TT. Epithelioid cells are less maturated, giant cells are undifferentiated and small. Epithelioid granulomas are less organized and tubercular

• **BB:** Epithelioid cells are immature. Organized epithelial granuloma structures are absent. Lymphocyte spread is diffuse and macrophages are quite over. Nerve tissue is not edematous. It has been infiltrated and partially destroyed by epithelial cells and lymphocytes. • *BL:* Macrophage and lymphocyte predominant infiltration is present. Epithelioid cells are rare. Infiltration can be diffuse, nodular, perivascular and periadnexal. The epidermis and dermis are separated from each other by a narrow zone formed by the collagen. While macrophages contain more or less foamy cytoplasm, the formation of large vacuoles is not

• *LL:* The dermis is also characterized by diffuse macrophage invasion. There are no epithelioid cells. The epidermis is atrophic and has a very apparent grenz zone. Skin attachments are surrounded by macrophages and are atrophic. Macrophages contain gray cytoplasm with foamy changes. Large vacuolarizations can be seen. Perineural macrophage accumulation is present and perineum appears like onion skin. There is no sign of significant infiltration, and even the nerves can be quite normal. The nerves can be hyalinized or fibrotic [72].

About 0.1 ml of lepromin antigen is administrated intradermally on to the forearm. The test is interpreted twice, first 24–48 hours and then 21 days. The first reaction is indicative of susceptibility, but may cross-react with other mycobacteria. The second reaction is resistance indicator to bacillus. Nodule >5 mm is considered positive. The most important point for the lepromin test is that it is not a diagnostic test, it should be used for classification and

*M. leprae* is stimulating cell-mediated abnormal response. Although the Ig that are formed are not protective, the importance of detection of the IgM formed towards PGL-1 (phenolic


Hypoesthesia skin lesion is the most important diagnostic factor because it is not expected in another skin disease other than leprosy. After evaluation of skin lesions, peripheral nerves should be palpated for thickening, and nerve examination of lesions and distal extremities should be performed [69]. Conjunctiva and corneal examination should also be made.

#### **9.1. Sampling**

Skin smear, a rapid diagnostic method, requires experience. The skin compressed between the thumb and index finger is cut with lancet with a width of 5 mm and a depth of 3 mm. The collected dermal fluid is spread on the lame. Tissue fluid should not be bloody. The most preferred regions are the earlobe, elbow and knee extensor faces. It may require three to six repetitions. The result is generally negative in less bacillar and TT. Nasal sampling is not recommended, especially because of fragility in LL cases. A 4 mm punch biopsy is the ideal method for sampling. The biopsy should be taken from the most erythematous, contagious and expanding area. Nerve biopsy may be required to support diagnosis, especially in cases of pure nerve involvement [67].

#### **9.2. Microscopic examination**

In vitro *M. leprae* culture is not possible. Demonstration of acid-resistant bacilli in material taken by skin smear or biopsy is standard diagnostic technique. With Ziehl-Neelsen staining, acid-resistant basils are colored fuchsia in blue background [67]. Bacteriological index (BI) is determined by rating between 1+ (1 bacteria in every 100 area) and 6+ (min. 1000 bacillus in every area) with the amount of bacteria in each microscope area. Patients with BI scores lower than 2 are considered as PB, whereas BI scores above 2 are considered MB [69].

#### *9.2.1. Molecular methods*

One of the molecular diagnostic methods, PCR, is the detection of *M. leprae* DNA. Biopsy material, tissue fluid, blood, urine, nerve tissue, oral and nasal mucosa swab and ocular lesions can be used for PCR [70]. While the specifity can be 100%, the sensitivity ranges from 34% to 80% in cases with PB forms to greater than 90% in cases with MB forms of the disease. The support of diagnosis is an important diagnostic tool in treatment follow-up, transmission surveillance of the immediate surroundings of leprosy individuals and in cases characterized with particularly pure nerve involvement which is difficult to diagnose or atypical lesions [71].

#### *9.2.2. Hystopathology*

**9. Diagnosis**

• Positive skin smear.

of pure nerve involvement [67].

**9.2. Microscopic examination**

*9.2.1. Molecular methods*

**9.1. Sampling**

endemic regions are considered to be leprosy [68].

46 Hansen's Disease - The Forgotten and Neglected Disease

For diagnosis, leprosy must first come to mind. Although diagnosis is made substantially by clinic examination, diagnosis must be supported by laboratory for classification and treatment. Microbiological and pathological tests should be performed after history and clinical evaluation [67]. WHO recommends that individuals with one of the two cardinal findings in

• Lesions compatible with leprosy with sensory loss (with or without nerve thickening).

should be performed [69]. Conjunctiva and corneal examination should also be made.

Hypoesthesia skin lesion is the most important diagnostic factor because it is not expected in another skin disease other than leprosy. After evaluation of skin lesions, peripheral nerves should be palpated for thickening, and nerve examination of lesions and distal extremities

Skin smear, a rapid diagnostic method, requires experience. The skin compressed between the thumb and index finger is cut with lancet with a width of 5 mm and a depth of 3 mm. The collected dermal fluid is spread on the lame. Tissue fluid should not be bloody. The most preferred regions are the earlobe, elbow and knee extensor faces. It may require three to six repetitions. The result is generally negative in less bacillar and TT. Nasal sampling is not recommended, especially because of fragility in LL cases. A 4 mm punch biopsy is the ideal method for sampling. The biopsy should be taken from the most erythematous, contagious and expanding area. Nerve biopsy may be required to support diagnosis, especially in cases

In vitro *M. leprae* culture is not possible. Demonstration of acid-resistant bacilli in material taken by skin smear or biopsy is standard diagnostic technique. With Ziehl-Neelsen staining, acid-resistant basils are colored fuchsia in blue background [67]. Bacteriological index (BI) is determined by rating between 1+ (1 bacteria in every 100 area) and 6+ (min. 1000 bacillus in every area) with the amount of bacteria in each microscope area. Patients with BI scores lower

One of the molecular diagnostic methods, PCR, is the detection of *M. leprae* DNA. Biopsy material, tissue fluid, blood, urine, nerve tissue, oral and nasal mucosa swab and ocular lesions can be used for PCR [70]. While the specifity can be 100%, the sensitivity ranges from 34% to 80% in cases with PB forms to greater than 90% in cases with MB forms of the disease. The support of diagnosis is an important diagnostic tool in treatment follow-up, transmission surveillance of the immediate surroundings of leprosy individuals and in cases characterized with particularly pure nerve involvement which is difficult to diagnose or atypical lesions [71].

than 2 are considered as PB, whereas BI scores above 2 are considered MB [69].

The main pathologic feature is a granulomatous reaction. Epithelioid cells, macrophages, lymphocytes, plasmocytes and rarely neutrophil and mast cells are observed. Different granulomatous reactions occur according to the immune response of the host. While epithelial cells are mostly observed in TT and BT cases, foamy macrophages are observed mostly in LL and BL cases.


#### *9.2.3. Lepromin test*

About 0.1 ml of lepromin antigen is administrated intradermally on to the forearm. The test is interpreted twice, first 24–48 hours and then 21 days. The first reaction is indicative of susceptibility, but may cross-react with other mycobacteria. The second reaction is resistance indicator to bacillus. Nodule >5 mm is considered positive. The most important point for the lepromin test is that it is not a diagnostic test, it should be used for classification and prognostic purposes.

#### **9.3. Serology**

*M. leprae* is stimulating cell-mediated abnormal response. Although the Ig that are formed are not protective, the importance of detection of the IgM formed towards PGL-1 (phenolic glycolipid-1)-the only accessible test-is increasing day by day [67]. Search for effective diagnostic tests is accelerated by shifting the focus of the leprosy control strategy to early diagnostic and rapid treatment. Several studies have shown a correlation between serological titer and BI. The skin smear, the gold standard for classification, is thought to be a test that can be used as a support for clinical findings when histology is not possible [73, 74]. There was also a relationship between serology and reaction and relapse risk. Patients with a high PGL-1 Ig M level had a high risk of developing type 1 reactions [75]. In another study, posttreatment reactions were found to be more likely to develop in patients with positive serology after treatment [76]. In another important meta-analysis, seropositive healthy contacts were observed to develop three times more leprosy when compared to negatives [77]. In the light of these findings; additional studies are needed to determine serology, classification, early diagnosis, follow-up of disease, detection of individuals at risk, and determination of who should take prophylaxis among these individuals.
