Leprosy (Hansen's Disease) Overview

Leprosy (Hansen's Disease)

• Caused by Mycobacterium leprae and Mycobacterium lepromatosis
• Worldwide distribution, endemic in the tropics
• Affects skin and peripheral nerves because the bacteria thrive in cooler areas of the body
• Mycobacterium leprae is an obligate intracellular, gram-positive, weakly acid-fast bacteria
• Incubation period: 3-5 years
• Two types:

  Tuberculoid Leprosy (Paucibacillary)

  • Occurs in individuals with strong cell-mediated immunity
  • Granulomatous response
  • Bacilli are rarely found

  Lepromatous Leprosy (Multibacillary)

  • Occurs in individuals with weak cell-mediated immunity
  • Lack of granulomatous response
  • Macrophages filled with bacteria (lepra cells) form aggregates
• Mycobacterium leprae does not produce exotoxins or endotoxins
• Lesions form due to:
  • Destructive granulomas (type IV hypersensitivity)
  • Interference with Schwann cell metabolism
• Morphology:
  • Tuberculoid leprosy:
    • Granulomatous lesions resemble tuberculosis
    • Epithelioid histiocytes surround small cutaneous nerves
    • Langhans giant cells may be present
    • Infiltrate can reach the epidermis
    • May destroy arrectores pilorum muscle
    • Bacilli are scarce
  • Lepromatous leprosy:
    • Macrophages (Virchow cells, lepra cells) form poorly circumscribed masses in the dermis
    • Few lymphocytes
    • Macrophages may contain large groups of leprosy bacilli (globi)
    • Bacteria are abundant in cutaneous nerves, endothelium, and media of vessels
    • May invade arrectores pilorum muscle
    • Subcutaneous nodules may form (erythema nodosum leprorum)

Syphilis

• Caused by Treponema pallidum, a gram-negative spirochete
• Chronic venereal disease
• Transmission:
  • Primarily sexually transmitted
  • Transplacental transmission (mother to fetus)
• World Health Organization (WHO) estimated 7.1 million new cases in 2020
• Increasing incidence in the United States
• Men who have sex with men and non-Hispanic individuals are disproportionately affected
• Often co-occurs with HIV
• Syphilis increases the risk of HIV and other sexually transmitted infections
• Stages:

  Primary Syphilis:

  • Chancre develops 3 weeks after infection
  • Solitary, painless nodule with superficial ulceration
  • Healing occurs in 3-6 weeks

  Secondary Syphilis:

  • Develops 1-3 months after infection
  • Lesions include:
    • Shallow oral ulcerations
    • Generalized skin rash
    • Generalized lymphadenopathy
  • Spontaneous or treatment-induced healing

  Tertiary Syphilis:

  • Untreated infection
  • Manifests years after primary infection (5-30 years)
  • Three main manifestations:
    • Cardiovascular syphilis
    • Neurosyphilis
    • Gummatous necrosis (formation of firm, nodular masses, particularly in the liver, bones, and testes)
• Histology:
  • Dense plasma cell inflammatory infiltrate
  • Proliferative endarteritis (endarteritis obliterans) affecting small vessels
  • In tertiary syphilis, gumma formation

Actinomycosis

• Caused by Actinomyces israellii, an anaerobic, gram-positive, filamentous bacteria
• Commensal in the mouth, gastrointestinal tract, and female genital tract
• Infection is rare, develops when the bacteria invade tissues
• Gross appearance:
  • Firm masses with numerous abscesses (honeycomb abscesses)
  • Yellowish granules (sulfur granules)
  • Sinuses and fistulae
• Microscopic appearance:
  • Slender, filamentous organisms aggregated into sulfur granules
  • Surrounded by neutrophils, plasma cells, eosinophils, and lymphocytes in a necrotic background
  • Multinucleated giant cells and noncaseating granulomas may be present
  • Reactive changes in local lymph nodes

### Leprosy

• Leprosy, also called Hansen's disease, is a chronic cutaneous infection caused by Mycobacterium leprae and Mycobacterium lepromatosis.
• It primarily affects the skin and peripheral nerves because these areas of the body have cooler temperatures, suitable for the bacteria's growth.
• The incubation period can be long, typically 3-5 years.
• Leprosy's pathology stems from the bacteria's lack of exotoxins or endotoxins.
• Tuberculoid leprosy occurs in individuals with a strong cell-mediated immune response, leading to the formation of granulomas.
• Lepromatous leprosy occurs in individuals with weak cell-mediated immunity, causing the formation of lepra cells, which are lipid-laden macrophages, often packed with masses of acid-fast bacilli.

Syphilis

• Syphilis is caused by the spirochete Treponema pallidum.
• The spirochete is a gram-negative, coiled, unicellular spiral-shaped organism.
• Transmission occurs primarily through sexual contact.
• It can also be transmitted transplacentally from mother to fetus.

Stages of Syphilis

• Primary syphilis: Characterized by a chancre, a painless nodule with superficial ulceration, appearing on the external genitalia.
• Secondary syphilis: Develops 1-3 months after infection with the initial lesion, manifesting as shallow oral ulcerations, generalized skin rash, and generalized lymphadenopathy.
• Tertiary syphilis: Occurs years later, manifesting as aortitis, neurosyphilis, and gummatous necrosis of skin, soft tissue, bone, and joints.

### Actinomycosis

• Caused by Actinomyces israellii, an anaerobic, gram-positive, long filamentous bacterium often found as a commensal organism in the mouth, gastrointestinal tract, and female genital tract.
• Infection manifests as firm masses containing numerous abscesses with yellowish granules, often called "sulfur granules," and can lead to sinus formation and fistulae.
• Microscopically, Actinomyces appear as slender filaments, usually aggregated into sulfur granules, intermixed with neutrophils, plasma cells, eosinophils, lymphocytes, and sometimes multinucleated giant cells and noncaseating granulomas.

Leprosy (Hansen's Disease)

• Leprosy, also known as Hansen's disease, is a chronic cutaneous infection caused by Mycobacterium leprae and Mycobacterium lepromatosis.
• It is a worldwide disease, especially prevalent in the tropics, due to travel and migration.
• The disease affects the skin and peripheral nerves because M. leprae and M. lepromatosis thrive in cooler areas of the body.
• Mycobacterium leprae is an obligate intracellular, gram-positive, weakly acid-fast organism.
• The incubation period can be lengthy, ranging from 3 to 5 years.
• Two main types of leprosy exist: Tuberculoid and Lepromatous.
• Tuberculoid leprosy occurs in individuals with robust cell-mediated immunity.
• Patients develop granulomatous responses with few bacilli.
• Lepromatous leprosy occurs in individuals with poor cell-mediated immunity. They fail to develop a granulomatous response, resulting in increased bacterial load.
• M. leprae does not produce exotoxins or endotoxins.
• Leprosy lesions are characterized by:
  • Destructive granulomas (type IV hypersensitivity)
  • Interference with Schwann cell metabolism.
• Tuberculoid leprosy (Paucibacillary), the less severe form, is characterized by:
  • Granulomatous lesions resembling those found in tuberculosis.
  • Strong host defense, leading to minimal bacilli, hence the name "Paucibacillary."
• Lepromatous leprosy (Multibacillary), the more severe form, is characterized by:
  • Large aggregates of lipid-laden macrophages (lepra cells) filled with acid-fast bacilli.
  • High bacterial load within lesions.
• Microscopic features of Tuberculoid leprosy:
  • Epithelioid histiocytes surrounding small cutaneous nerves.
  • Langhans giant cells may be present but without necrosis.
  • Infiltrates may reach the epidermis.
  • Possible destruction of arrectores pilorum muscle.
  • Bacilli are typically scarce.
• Microscopic features of Lepromatous leprosy:
  • Macrophages (Virchow cells, lepra cells) scattered in poorly circumscribed masses in the dermis.
  • Few lymphocytes.
  • Macrophages are often distended with groups of leprosy bacilli (globi).
  • Bacteria are numerous in cutaneous nerves, endothelium, and media of small and large vessels.
  • May invade arrectores pilorum muscle.
  • Subcutaneous nodules (erythema nodosum leprorum) may develop.

Syphilis

• Syphilis is caused by the spirochete Treponema pallidum, a gram-negative, coiled, unicellular spiral-shaped bacterium.
• It is a sexually transmitted chronic disease that can also be transmitted transplacentally.
• Epidemiology:
  • Estimated 7.1 million new adult cases worldwide in 2020.
  • Increasing incidence in the United States.
  • Men who have sex with men and non-Hispanic persons are disproportionately affected.
  • Dual diagnosis with HIV is common, and syphilis amplifies the risk of acquiring HIV and other sexually transmitted infections.
  • Transmission mainly occurs through vaginal, anogenital, and orogenital contact with infectious lesions.
  • Rarely transmitted through nonsexual contact, including skin-to-skin and blood transfusions.
  • Congenital syphilis is acquired through transplacental transmission or contact with an infectious lesion at birth.
• Stages of Syphilis:
  • Primary syphilis:
    • Lesion (chancre) develops within 3 weeks of infection on the external genitalia.
    • Chancre is a solitary, slowly enlarging, painless nodule with superficial ulceration.
    • Healing occurs spontaneously or after treatment.
  • Secondary syphilis:
    • Appears 1-3 months after infection.
    • Lesions include:
      • Shallow oral ulcerations.
      • Generalized skin rash.
      • Generalized lymphadenopathy.
    • Healing may occur spontaneously or after treatment.
  • Tertiary syphilis:
    • Develops several to many years (5-30) after primary infection in untreated individuals.
    • Characterized by:
      • Aortitis (typically in the thoracic portion).
      • Neurosyphilis.
      • Gummatous necrosis of skin, soft tissue, bone, and joint (Charcot joint).
    • Tertiary syphilis manifestations:
      • Cardiovascular: Aortitis.
      • Neurosyphilis: CNS involvement
      • Gumma: Firm to rubbery, multiple, nodular masses commonly found in the liver, bones, and testes. (Gumma is a granuloma with central coagulative necrosis).
• Histology of syphilis:
  • Dense plasma cell inflammatory infiltrate present in most cases.
  • Proliferative endarteritis (endarteritis obliterans) affecting small vessels.
  • Endothelial hypertrophy and proliferation leading to intimal fibrosis, with a surrounding plasma cell infiltration, are characteristic of all stages of syphilis.
  • In tertiary syphilis, gummas are present along with other histological findings.

Actinomycosis

• Caused by Actinomyces israellii, an anaerobic, gram-positive, long filamentous bacteria.
• It is a commensal organism found in the mouth, gastrointestinal tract, and female genital tract.
• Infection typically occurs when the organism invades tissues.
• Gross appearance:
  • Firm masses containing numerous abscesses (honeycomb abscesses).
  • Yellowish granules (sulfur granules) with sinuses and fistulae.
• Microscopic appearance:
  • Slender, filamentous, fungal-like organisms (Actinomyces) typically aggregated into sulfur granules.
  • Mural organisms intermixed with neutrophils, plasma cells, eosinophils, and lymphocytes in a necrotic background.
  • Multinucleated giant cells and noncaseating granulomas may also be present.
  • Reactive changes may occur in local lymph nodes.

Leprosy (Hansen’s Disease)

• Chronic cutaneous infection caused by Mycobacterium leprae and Mycobacterium lepromatosis
• Found worldwide but endemic in tropical regions.
• Affects skin and peripheral nerves because Mycobacteria grow in cool temperatures
• Mycobacterium leprae is an obligate intracellular Gram-positive and weakly acid-fast organism

Pathogenesis of Leprosy

• Incubation period typically 3-5 years
• Tuberculoid Leprosy: Occurs in individuals with good cell-mediated immunity, and patients develop a granulomatous response.
• Lepromatous Leprosy: Occurs in individuals with poor cell-mediated immunity, patients do not develop a granulomatous response.
• Mycobacterium leprae produces no exotoxin or endotoxin.
• The lesion is produced by:
  • Destructive granuloma (type IV hypersensitivity)
  • Interference with metabolism of Schwann cells

Morphology

• Tuberculoid Leprosy (Paucibacillary)
  • Granulomatous lesions similar to those found in tuberculosis.
  • Bacilli are rarely seen due to strong host defense.
• Lepromatous Leprosy (Multibacillary)
  • Lesions contain large aggregations of lipid-laden macrophages (lepra cells) often with masses ("globi") of acid-fast bacilli.

Tuberculoid Leprosy

• Characterized by epithelioid histiocytes surrounding small cutaneous nerves.
• Langhans giant cells may be seen but without necrosis.
• Infiltration may involve the papillary dermis up to the epidermis.
• May destroy the arrectores pilorum muscle.
• Bacilli are usually scarce.

Lepromatous Leprosy

• Macrophages (Virchow cells, lepra cells) are found in poorly circumscribed masses in the dermis, with few or no lymphocytes.
• Macrophages may be distended with large groups of leprosy bacilli (globi).
• Bacteria are present in large numbers in cutaneous nerves, endothelium, and media of small and large vessels.
• May invade arrectores pilorum muscle.
• May have subcutaneous nodules (erythema nodosum leprorum)

Syphilis

• Caused by Treponema pallidum, a spirochete.
• Chronic venereal disease.
• Transmitted through sexual contact.
• Can be transmitted transplacentally to the fetus.
• Treponema pallidum is gram-negative, coiled, unicellular, and spiral-shaped.

Epidemiology

• WHO estimated 7.1 million new cases of syphilis worldwide in 2020, with increasing incidence in the United States.
• Men who have sex with men and non-Hispanic persons are disproportionately affected.
• Dual diagnosis with HIV is common; syphilis increases the risk of acquiring HIV and other sexually transmitted infections.
• Most cases are transmitted through vaginal, anogenital, and orogenital contact with an infectious lesion during the primary or secondary stages of the disease.
• Rarely transmitted through nonsexual contact including skin-to-skin and blood transfusion.
• Congenital syphilis can be acquired at any stage via transplacental transmission or contact with an infectious lesion during birth.

Stages of Syphilis

• Primary Syphilis:
  • Lesion (chancre) develops a few days to 3 weeks after infection on the external genital.
  • Chancre is a solitary, slowly enlarging, painless nodule with superficial ulceration.
  • Healing occurs in 3-6 weeks either spontaneously or after treatment.
• Secondary Syphilis:
  • Usually develops 1-3 months after infection.
  • Lesions appear as:
    • Shallow oral ulcerations.
    • Generalized skin rash.
    • Generalized lymphadenopathy.
  • Healing may occur spontaneously or after treatment.
• Tertiary Syphilis:
  • Untreated syphilis can lead to tertiary syphilis years later.
  • Most common manifestations include aortitis, neurosyphilis, and gummatous necrosis of skin, soft tissue, bone, and joint (Charcot joint).
  • It appears several to many years after primary infection (5-30 years).
  • Tertiary Syphilis:
    • Cardiovascular Syphilis
    • CNS Neurosyphilis
    • Gumma: Formation of firm to rubbery, multiple, nodular masses most commonly found in the liver, bones, and testes. - Gumma is a granuloma with central coagulative necrosis

Histology

• Most cases demonstrate a dense plasma cell inflammatory infiltrate on histology.
• Proliferative endarteritis (endarteritis obliterans) affecting small vessels is characteristic of all stages of syphilis.
  • Endothelial hypertrophy and proliferation lead to intimal fibrosis.
• Gumma in Tertiary syphilis.

Actinomycosis

• Caused by Actinomyces israellii, an anaerobic, Gram-positive, long filamentous bacteria.
• A commensal organism in the mouth, GIT, and female genital tract.
• Occasionally invades tissues and produces infection.

Gross

• Infection produces firm masses containing numerous abscesses (honeycomb abscesses) bearing colonies as yellowish granules (sulfur granules) with sinuses and fistulae.

Microscopic (Histologic)

• Actinomyces visible as slender, filamentous, fungal-like organisms usually aggregated into sulfur granules.
• Mural organisms intermixed with neutrophils, plasma cells, eosinophils, and lymphocytes in a necrotic background.
• Multinucleated giant cells and noncaseating granulomas may also be present.
• Local lymph nodes may show reactive change.