= (Leprosy) =
Artist/ Title/ Date
Unknown artist. Leper with a Clapper. Late 15th century. Illumination from Livre des propriétés des choses by Barthélemy l'Anglais. MS Français 9140, fol. 15v. Bibliothèque nationale de France, Département des Manuscrits, Paris.
Description of Disease & Etiology
Leprosy, also known as Hansen’s disease, is a chronic infectious disease caused by the bacterium Mycobacterium leprae. The disease primarily affects the skin, peripheral nerves, and mucosal surfaces. Characteristically a slowly progressive illness, individuals that go without treatment can exhibit mild skin lesions to severe deformities and nerve damage, depending on their immunologic response to this bacterium. The disease remains to this day one of the most common causes of non-traumatic peripheral neuropathy globally.1
The etiology of leprosy stems from the unique biology of M. leprae. This organism is an obligatory intracellular pathogen, meaning it requires host cells, particularly Schwann cells of the peripheral nervous system and macrophages, to replicate. The bacterium has a remarkably slow growth rate, with a doubling time of approximately 14 days, which contributes to the long incubation period of the disease, ranging from several weeks to decades. Transmission occurs primarily through prolonged, close contact with an infected person, often via respiratory droplets, though the disease has low infectivity.1
Signs/Signifiers of Illness
It is important to note that there are five clinical presentations to leprosy, and the clinical features of each are distinct.1 As a result, signs and signifiers of this section will refer to the more severe form, tuberculoid leprosy.
Key cutaneous signs include hypopigmented or erythematous macules, plaques, or nodules, often accompanied by sensory loss due to the bacterium's affinity for Schwann cells and peripheral nerves. Sensory deficits typically progress in a "glove and stocking" distribution, with involvement of cooler regions of the body such as the hands, feet, and face. Advanced cases may show skin thickening, leonine facies, or sight deficits.1-3
Neurological involvement is a hallmark of leprosy and can manifest as palpable thickening of peripheral nerves, such as the ulnar, median, peroneal, or posterior tibial nerves. Motor deficits include muscle weakness or atrophy, particularly of the intrinsic muscles of the hands and feet. Autonomic nerve involvement can result in anhidrosis and subsequent dryness of affected skin, predisposing it to fissures and secondary infections.7
Histopathological examination can reveal the presence of acid-fast bacilli bacteria, granulomatous inflammation, foamy macrophages, the presence of globi (accumulations of M. leprae within cells) within skin smears.1
Pathology
Leprosy manifests in a spectrum of clinical forms, depending on the host's immune response. Among symptomatic individuals the disease manifests itself along a horizontal spectrum based on clinical, bacilloscopic, and histopathological characteristics, containing two poles (tuberculoid and lepromatous) and three intermediate forms (borderline-tuberculoid, borderline-borderline, and borderline-lepromatous).1 The two extremes are characterized by differences in adaptive immunity responses between individuals. Tuberculoid leprosy is characterized by strong cell-mediated immune responses mediated by TH1 cells, leading to localized lesions and less bacterial load, while lepromatous leprosy is characterized by a humoral immune response mediated by TH2 cells, which results in widespread skin nodules, plaques, and a higher bacterial burden.4
Treatment
Depending on the age of the individual, the World Health Organization recommends different protocols involving three antibiotics: rifampicin, clofazimine, and dapsone. This multidrug therapy is effective at curing leprosy. Early diagnosis and treatment are critical to prevent irreversible complications such as nerve damage and deformities. Public health efforts aimed at reducing stigma and increasing awareness have also played a significant role in controlling the disease globally. However, the emergence of resistance to rifampicin by M. leprae promises to complicate future treatments.5
Author(s): Victoria Rhodes
Citations:
* 1) Bhat, Ramesh Marne, and Chaitra Prakash. “Leprosy: An Overview of Pathophysiology.” Interdisciplinary Perspectives on Infectious Diseases 2012, no. 1 (2012): 181089. https://doi.org/10.1155/2012/181089. * 2) Poondru, Sneha, Victoria Shi, and Anand Rajpara. “Leonine Facies of Lepromatous Leprosy.” JAMA Dermatology 159, no. 12 (December 1, 2023): 1385–86. https://doi.org/10.1001/jamadermatol.2023.3062. * 3) Pawar, Harpreet Singh, Harish Kumar Sagar, and Ankur Singh. “Lepromatous Leprosy with Vitiligo, a Clinical Diagnostic Challenge.” The American Journal of Tropical Medicine and Hygiene 107, no. 1 (July 2022): 8–9. https://doi.org/10.4269/ajtmh.22-0201. * 4) Froes Junior, Luis Alberto Ribeiro, Mirian Nacagami Sotto, and Maria Angela Bianconcini Trindade. “Leprosy: Clinical and Immunopathological Characteristics.” Anais Brasileiros de Dermatologia 97 (June 13, 2022): 338–47. https://doi.org/10.1016/j.abd.2021.08.006. * Li, Xiang, Yun Ma, Guoli Li, Guangjie Jin, Li Xu, Yunhui Li, Pingmin Wei, and Lianhua Zhang. “Leprosy: Treatment, Prevention, Immune Response and Gene Function.” Frontiers in Immunology 15 (February 19, 2024). https://doi.org/10.3389/fimmu.2024.1298749. * 1) Dharmawan, Yudhy, Ahmad Fuady, Ida Korfage, and Jan Hendrik Richardus. “Individual and Community Factors Determining Delayed Leprosy Case Detection: A Systematic Review.” PLOS Neglected Tropical Diseases 15, no. 8 (August 12, 2021): e0009651. https://doi.org/10.1371/journal.pntd.0009651. * 2) Calderone, A., Aloisi, M. C., Casella, C., Fiannacca, S., Cosenza, B., Quartarone, A., & Calabrò, R. S. (2024). The Neurological Impact of Leprosy: Manifestations and Treatment Approaches. Neurology International, 16(6), 1492–1508. https://doi.org/10.3390/neurolint16060111
Social Determinants of Illness
The social determinants of leprosy encompass a range of factors that influence its prevalence, transmission, diagnosis, and treatment outcomes. These determinants are rooted in socioeconomic, cultural, and environmental conditions that shape the responses of individuals to illness and their ability to seek medical care. The detection of leprosy, and its delay, has a pronounced effect on clinical outcomes for patients. Overall, factors that influence health-seeking behavior, and ultimately delay diagnosis, have the largest outcomes on individuals. Factors implicated in delayed health-seeking behavior include age, gender, and knowledge about leprosy signs. A compounding factor in the case of this disease is stigma.6