Introduction

In the year 2000, the World Health Organisation (WHO) declared that leprosy had been eliminated as a public health concern (they defined the term ‘elimination’ when there are fewer than one case per 10,000 people). However, new cases continue to be reported in developing countries, particularly in Asia, Africa, and Latin America, where the disease has not been eradicated.¹ 

Leprosy is classified into various types. The two most commonly used classification systems are the Ridley-Jopling classification and the World Health Organisation (WHO) classification. The Ridley-Jopling classification system was introduced in 1966; it was used to classify leprosy based on clinical, histopathological, bacteriological, and immunological criteria.¹ 

On the contrary, the WHO classification, introduced in 1982, analyses leprosy according to two types, i.e., paucibacillary and multibacillary. It was developed to simplify leprosy diagnosis and treatment, especially in resource-limited or field settings where detailed laboratory and histopathological tests (required by the Ridley-Jopling system) were not always feasible.¹

Overview of leprosy

Leprosy, also known as Hansen’s disease, is caused by the bacteria Mycobacterium leprae and Mycobacterium lepromatosis. Males are more commonly affected, with a 3:2 male-to-female ratio. It has a long incubation period, ranging from a few weeks to 20 years, although the average is 2–7 years.^1,2 

Leprosy spreads mainly through respiratory droplets, although transmission can occur through broken skin as well. The various risk factors include living in crowded conditions, malnutrition, a weakened immune system due to HIV or other conditions, and close contact with infected individuals. In addition, environmental conditions, particularly humidity, favour bacterial survival and increase the risk of transmission, leading to an increased incidence of disease. Intriguingly, genetic factors also play a significant role in the development of leprosy, especially in monozygotic twins (identical twins) of affected individuals, who show a higher risk of developing the disease.^1,2 

Clinically, leprosy presents with hypopigmented or hyperpigmented skin lesions, which are often associated with sensory loss and loss of sweating. In the case of neuritis, nerves are clinically palpable and tender. This causes loss of sensation, pain, and temperature over skin lesions. Nerve damage leads to muscle weakness, neuropathy, or atrophy in some cases. Stocking and glove sensory loss pattern is seen in lepromatous cases. Commonly affected nerves include the ulnar, median, and tibial.^1,2

The patient will be diagnosed with leprosy by a clinician based on the presence of at least one of the following WHO criteria:^1,2

• Skin lesions that are either hypopigmented or reddish in colour are associated with loss of sensation
• Thickened peripheral nerves with associated loss of function
•  The detection of acid-fast bacilli (AFBs) in skin smears

A laboratory test is also used to help diagnose leprosy in patients. It involves skin biopsies, polymerase chain reaction (PCR), and serologic testing. Biopsies assess lesion severity and histological patterns, while PCR effectively detects M. leprae DNA, especially in lepromatous cases. Common lab findings include elevated C-reactive protein, elevated white blood cells, decreased haemoglobin, and liver abnormalities.^1,2

Treatment of leprosy includes the use of multidrug therapy, which has been recommended by the WHO since 1982. Multidrug therapy includes a combination of rifampin and dapsone for 12 months for tuberculoid leprosy and a combination of rifampin, dapsone and clofazimine for 24 months for lepromatous disease. This regimen is highly effective in curing the disease and reducing transmission. Multidrug therapy is typically free of charge in most endemic countries, which has significantly reduced the global prevalence of leprosy.^1,2

Ridley-Jopling classification

The Ridley-Jopling classification system is a widely used histopathological and immunological classification of leprosy. This system divides leprosy into five types based on clinical, histological, bacteriological, and immunological features. The five types include:^2,3

•  Tuberculoid Leprosy
•  Borderline Tuberculoid
•  Mid-borderline / Borderline
•  Borderline Lepromatous
•  Lepromatous Leprosy

Histopathological features

Histopathological features of different types of leprosy include:^2,3

 Tuberculoid leprosy

• It shows a granulomatous inflammatory response with characteristic perineural and periadnexal distribution in both the superficial and deep dermis
• The granulomas are noncaseating and composed of epithelioid cells, lymphocytes, and Langhans giant cells
• The epidermis is often eroded and thinned due to underlying granulomas
• Lymphocytes are commonly found surrounding the perineurium, and in some cases, nerves are embedded within granulomatous tissue
• Acid-fast bacilli (AFBs) are not detectable, but diagnosis is supported by a positive lepromin test and histological evidence of granulomas

Borderline tuberculoid leprosy

• It features similar granulomatous infiltration to the tuberculoid type, but epithelioid cells are less well-developed
• Lymphocytes are present within the granulomas
• The epidermis may not be as affected or thinned
• Nerves are moderately swollen, with granulomas present both within (intraneural) and around (perineural) nerves
• Lymphocytic infiltration is seen in the tissue sheath that surrounds a nerve fascicle (perineurium)

Borderline leprosy

• In this type, there are poorly formed granulomas with immature epithelioid cells
• Lymphocytes are spread diffusely throughout the tissue, but giant cells are typically absent
• Macrophages are present within the lesions
• The epidermis is atrophic, and there is no nerve swelling 

Borderline lepromatous leprosy

• It consists of lymphocytes and macrophages forming various patterns of infiltrates, such as patchy, diffuse, nodular, periadnexal, or perivascular
• These infiltrates are always separated from the epidermis by a clear zone known as the Grenz zone
• Macrophages exhibit a foamy cytoplasm
• Nerves show a thickened perineurium with an "onion-skin" appearance and are surrounded by lymphocytes
• Plasma cells are commonly observed

Lepromatous leprosy

• It is marked by the presence of diffusely distributed foamy macrophages throughout the dermis
• Scattered plasma cells and lymphocytes are visible, but epithelioid cells are absent
• A well-defined Grenz zone is present beneath an atrophic epidermis
• Macrophages cluster around nerves with onion-skin–like perineurial layers
• Numerous AFBs are seen that are arranged in parallel bundles, scattered clusters, or as globi (large bacterial aggregates)

Clinical features

Leprosy primarily affects the skin and peripheral nerves, with more widespread (systemic) involvement occurring in advanced (lepromatous) stages. Clinical signs mostly result from the immune system’s reaction to the bacteria rather than direct damage from the bacilli themselves. Clinical features of different types of leprosy include:^2,3

Tuberculoid leprosy

• It typically shows up as one or a few hypopigmented plaques with a stable reddish border in appearance
• Lesions are fewer than three, smaller than 10 cm, and have well-defined, sloping edges (classic plaque)
• Surfaces are dry, hairless, scaly, and numb, with absent sweating
• A nearby nerve is often thickened
• Skin smears are AFB-negative, and a strong immune response is confirmed by a positive lepromin test
• Prognosis is favourable

Borderline tuberculoid leprosy

• In this type, the lesions are similar to those found in tuberculoid leprosy, but they are larger, more numerous, and less defined
• Pseudopodia, or satellite lesions, are seen
• Lesions are dry, scaly plaques with diminished sensation
• Nerves show asymmetrical thickening

Borderline leprosy

• It is immunologically unstable and can shift toward either the tuberculoid or lepromatous end of the spectrum
• Lesions are mixed (dimorphic), showing features of both poles, such as papules, plaques, and nodules
• Common lesion type is an annular plaque (ring-shaped skin lesions) with a sloped outer edge and a sharp inner border, resembling Swiss cheese
• Nerve involvement is variable, symmetrical or asymmetrical, depending on disease progression
• AFB is present

Borderline lepromatous leprosy

• It presents with multiple, symmetrical lesions starting as hypopigmented macules with blurred edges, blending into normal skin
• Peripheral nerves are thickened, but the nerve damage is usually less severe than seen in the borderline type
• Patients can develop type 1, i.e., reversal reactions, or type 2, i.e., erythema nodosum leprosum reactions
• AFBs are strongly positive

Lepromatous leprosy

• In this type, the immune response is profoundly impaired, allowing widespread bacterial growth
• Skin smears show numerous AFBs
• There are numerous symmetrical lesions seen that affect the face, limbs, and trunk
• All lesion types may be seen simultaneously at different stages of development

Relevance of the Ridley-Jopling classification system in clinical practice

The Ridley-Jopling classification system plays an important role in the management of leprosy. It helps clinicians in the diagnosis, treatment and prognosis of disease. Various uses include:^2,3

• Histopathological evaluation: this system is helpful in cases when the clinical presentation is unclear or overlaps with other dermatological or neurological conditions
• Treatment guidance: the system helps in guiding the appropriate duration and regimen of multidrug therapy
• Research: the system serves as an important tool for research, particularly in advancing the understanding of the immunological and pathophysiological aspects of leprosy

Limitations of the Ridley-Jopling classification system

Histological interpretation in leprosy can be challenging due to several factors. Various factors include:^{2,3, 4}

• Overlap in histological features among borderline cases can lead to misclassification
• Tissue sampling can be a limitation, as biopsies can fail to capture the important diagnostic features of the disease
• The histological patterns can be altered by the occurrence of reactional states such as reversal reactions (Type 1) or erythema nodosum leprosum (Type 2)

Summary

Leprosy, also known as Hansen’s disease, is a chronic infectious disease which primarily affects the skin and peripheral nerves. If you suspect yourself to be suffering from leprosy, clinicians typically use either the Ridley-Jopling or the WHO classification. Ultimately, the Ridley-Jopling classification categorises leprosy into five types based on clinical, histopathological, bacteriological, and immunological features. This system of classification helps clinicians in accurate diagnosis, treatment, and prognosis. Future prospects include improved diagnostic tools, histopathology evaluation, vaccines, and digital tools, all of which aim to overcome current limitations, improve the quality of life for patients, and ultimately, disease eradication.