Leprosy is a chronic infectious disease whose etiological agent is Mycobacterium leprae. Recently, Mycobacterium lepromatosis is also implicated as a causative agent and has been identified in different forms of the disease. Leprosy is a complex disease from a clinical, histopathological, and molecular point of view. The wide diversity of clinical presentation and histopathological characteristics observed throughout the disease spectrum and reactions render it a challenging disease in clinical and pathological practice. This chapter discusses the main aspects of the disease and its histopathological classification. An important approach to the bacilloscopic examination, which is fundamental for the histopathological classification of the disease, showing its quantitative and qualitative aspects, is discussed. The various photographic panels demonstrate the bacillus' ability to parasitize different types of tissues and cells of the skin and other organs of the human body. Multiple serial histological sections stained using different techniques allow the main points addressed in the text to be better understood through histopathological images. The entire content of this initial chapter (Chapter 1) will be the basis for understanding the other chapters. In the subsequent chapters, the clinical, histopathological, and bacilloscopic features of leprosy forms (Chapters 2, 3, and 4), the reactional phenomena (T1R - Chapter 5 and T2R - Chapter 6), the regressive changes observed in leprosy lesions during and after treatment or relapse (Chapter 7), and some variants with special clinical characteristics (Chapter 8) are discussed.

Leprosy in its indeterminate form (I) is a clinical presentation of the disease preceding the forms described in the Ridley and Jopling (R & J) classification and any other special forms of leprosy or the reactions. In this chapter, the histopathological and bacilloscopic characteristics of the I form of leprosy are described, and the main differential diagnoses are discussed. The histopathological criteria that distinguish the I form from the other forms of leprosy and the reaction processes that may occur during the disease course are also discussed. The identification of the histopathological characteristics of I leprosy is of great importance with respect to the selection of the treatment. I leprosy should not be confused with other forms of leprosy, especially the multibacillary forms, which require more prolonged treatment and which can develop reaction phenomena, causing permanent sequelae.

Leprosy is a spectral disease. Its two polar forms, tuberculoid (TT) and lepromatous (LL), are distinct presentations of the disease, both from a clinical and histopathological/bacilloscopic point of view. In this chapter, the histopathological characteristics that define the two polar forms (TT and LL) are presented, and their main differential diagnoses are discussed. These two forms also have significant differences in their treatment protocol. Histopathological recognition of both forms of the disease is important for choosing the correct treatment. Also, there are a large number of diseases that can have a clinical presentation similar to the TT and LL forms of leprosy. In this context, histopathological examination is essential for defining the diagnosis of leprosy.

Leprosy is a long-term spectrum disease and can present various clinical and histopathological aspects. Between the two poles of leprosy, there is a wide range of types, consisting of intermediate or borderline forms. In this chapter, the clinical, histopathological, and bacilloscopic characteristics of the intermediate forms (borderline-tuberculoid [BT], borderline-borderline [BB], and borderline lepromatous [BL]) are presented and discussed. The main clinical and pathological characteristics that allow the diagnosis and classification of leprosy among the different borderline forms are described and illustrated in panel form, as well as their most significant clinical and histopathological differential diagnoses are also discussed. The clinicalpathological classification of this disease has important implications in the choice of the correct treatment, the understanding of the pathophysiology, and the development of the reaction phenomena typical of leprosy.

A type 1 reaction (T1R) is also known as a reversal reaction. This phenomenon involves exacerbation of the immune system or delayed-type hypersensitivity in response to the antigens of Mycobacterium leprae present in parasitized tissues. It occurs in most patients of the tuberculoid and borderline forms of the Ridley & Jopling classification for leprosy. It is an important phenomenon that can occur before, during, or after leprosy treatment and can be destructive, causing tissue damage mainly in the nerves, as well as irreversible sequelae. The recognition of T1R in histological sections may be notified prior to clinical presentation. Histopathological recognition is vital in defining or confirming the presence of T1R, guiding the treatment of the reaction process, avoiding or reducing the possibility of serious sequelae, correcting possible mistakes in the classification of patients within the spectrum of leprosy, and ruling out other diseases that can clinically simulate a T1R. In this chapter, the histopathological characteristics that allow the recognition of T1R, various histopathological aspects of the common forms of leprosy, and histopathological differential diagnoses are discussed.

Type 2 reaction (T2R), also called erythema nodosum leprosum (ENL), is a reactional phenomenon that occurs in response to Mycobacterium leprae antigens in patients with borderline lepromatous or lepromatous forms of leprosy. T2R usually occurs after starting treatment and can affect any parasitic tissue in the body, causing neuritis, arthritis, painful lymphadenitis, buccopharyngeal lesions, laryngitis, hepatomegaly, splenomegaly, bone injuries, iridocyclitis, uveitis, orchitis, glomerulitis with proteinuria, and hematuria. Recognition of the histopathological characteristics of T2R is important for guiding early treatment of the reaction process, decreasing the likelihood of developing serious sequelae, especially when T2R affects the nerves, and to exclude different diseases that can simulate T2R over leprosy lesions during the course of the disease. In this chapter, the histopathological characteristics that allow T2R diagnosis are described, and some of its differential clinicopathological diagnoses and their possible pathophysiological mechanisms are discussed.

Immediately after leprosy treatment initiation, changes in leprosy lesions also commence. The histopathological and bacilloscopic characteristics of the regressing lesions undergo continuous changes over years or decades. It is important to recognize these changes as they allow for the assessment of whether a particular lesion is in regression or if there are signs of disease reactivation. Interpretation of the findings will depend on a close correlation among histopathological patterns, bacilloscopic characteristics, and clinical data. This chapter discusses the main factors that allow the recognition of the histopathological characteristics of regressive phenomena from initial phases to late or residual phases, the changes typical in regressive leprosy granulomas and their importance for assessing treatment effectiveness, the reaction phenomena triggered after treatment initiation on regressing lesions, and the evaluation of leprosy recurrence. Further, this chapter includes a discussion on the main differential diagnoses of leprosy regression and relapse.

In this chapter, some special forms of the clinical and histopathological presentation of leprosy are discussed: Lucio’s leprosy and Lucio’s phenomenon, histoid leprosy, nodular leprosy of childhood, and primary neural leprosy. The main clinical and histopathological characteristics of these forms and the condition under which they appear within the entire spectrum of leprosy and its reaction phenomena are presented. In addition, the main differential clinical and pathological diagnoses of each of these lesions are discussed. The use of fine-needle aspiration cytology for the diagnosis of leprosy, including its reaction phenomena, has also been addressed. The identification of the histopathological features of these special forms of leprosy is important to confirm the clinical diagnosis for guiding treatment and preventing the possible misinterpretation of clinical and histopathological findings.