13.6.1 Lumbs And Bumps

Question 1

Warts
Def

Answer 1

Def
- Common dermatological condition caused by human papillomavirus (HPV) infection.
- Can occur anywhere on the body.
- Often a cosmetic concern, but can be painful or become cancerous.
- The pathogenesis of warts involves the interplay between the virus and the host immune response.

Question 2

HPV infections

Answer 2

• Comprise a large group of more than 150 genotypes that infect the epithelia of skin or mucosa.
• Most commonly cause benign papillomas or warts.
• Infections are transient, subclinical, and cleared by a cellular immune response.

Types - slide 6

Question 3

Types of cutaneous warts

Answer 3

• Common warts (verruca vulgaris)
• Plantar warts (myrmecial type) (verruca plantaris)
• Plantar warts (mosaic type)
• Plane warts (verruca plana)
• Filiform and digitate warts
• Butcher’s wart
• Epidermodysplasia verruciformis

Question 4

Type of wart & HPV type

Answer 4

• plantar - 1,2
• common - 1,2
• flat - 3,10
• butchers - 2,7
• condylomata accuminata - Low grade (6,11); High grade (16, 18)

Question 5

Warts: Viral infection and replication of HPV

Answer 5

• HPV infects basal keratinocytes in the epidermis.
• The viral DNA is released into the host cell’s nucleus, where it replicates using the host cellular machinery.
• The virus completes its life cycle within the keratinocytes, leading to the production of new viral particles.

Question 6

Warts: Transmission and Entry

Answer 6

• Warts are primarily transmitted through direct skin-to-skin contact or contact with contaminated surfaces, such as towels or gym equipment.
• HPV can enter the skin through microscopic breaks or abrasions in the epidermis, enabling viral access to the basal layer of the epidermis where active cell division occurs.

Question 7

Warts: Viral persistence and evasion

Answer 7

• HPV has developed various strategies to evade the host immune response and establish long-term persistence.
• Viral proteins interfere with antigen presentation, reducing the recognition of infected cells by immune cells.
• HPV modulates cytokine production, inhibiting the activation of immune cells.

Question 8

Warts: Epidermal Hyperplasia and wart formation

Answer 8

• HPV infection leads to abnormal proliferation and differentiation of infected keratinocytes.
• Infected cells in the basal layer exhibit increased mitotic activity, delayed maturation, and dyskeratosis.
• The epidermis thickens due to increased cell division and differentiation, resulting in the clinical appearance of a wart.

Dyskeratosis- abnormal keratinisatiion occurring prematurely within cells below the striatum granulosum

Question 9

Warts: Viral particle assembly and Release

Answer 9

• As infected keratinocytes mature and move toward the skin surface, viral particles are assembled.
• These particles accumulate within the cytoplasm and eventually become released into the environment.
• Released viral particles can potentially infect other individuals or spread to different areas of the patient’s own body.

Question 10

Warts: Factors influencing wart persistence

Answer 10

• Several factors can influence the persistence of warts, including the patient’s immune status, HPV type, viral load, and wart location.
• Immunocompromised individuals, such as organ transplant recipients or those with HIV, may experience more persistent or widespread warts.

Question 11

Define cysts

Answer 11

• Cysts are pathological structures characterized by an encapsulated sac or cavity containing fluid or semi-solid material.
• They can occur in various organs and tissues throughout the body.

Question 12

General characteristics of cutaneous cysts

Answer 12

• Consists of a cyst wall of basal cells, suprabasal cells, and cyst contents (e.g., keratin debris, sebaceous gland, sweat gland, or hair).
• Some skin cysts are surrounded by layers of dermal cells and a basement membrane between dermal cells and basal epidermal cells.

Question 13

Types of cysts

Answer 13

Slide 21

1. Retention Cysts:
- Retention cysts, also known as simple or non-neoplastic cysts, are the most common type.
- They develop when normal secretions or fluids become trapped within a closed cavity
or duct due to obstruction or impaired drainage.
- Examples include sebaceous cysts, mucous cysts, and renal cysts.

2. Developmental Cysts:
- Developmental cysts arise during embryonic development due to abnormal or incomplete formation of specific tissues or structures.
- Examples include dermoid cysts, branchial cysts, and arachnoid cysts.

3. Inflammatory Cysts:
- Inflammatory cysts occur as a result of chronic inflammation or infection.
- The inflammatory process leads to the formation of a cavity or encapsulated collection of inflammatory exudate.
- Examples include abscesses, pilonidal cysts, and cysticercosis.

Question 14

Define Molluscum Contagiosum

Answer 14

• Molluscum contagiosum is a common viral skin infection caused by a Pox virus: Molluscum contagiosum virus (MCV).
• It primarily affects children and immunocompromised individuals.

Question 15

MC: transmission and entry

Answer 15

• Molluscum contagiosum is transmitted through direct skin-to-skin contact or contact with contaminated objects.
• The virus gains entry into the skin through minor breaks in the epidermis, such as scratches or abrasions.

Question 16

MC: Viral replication and epidermal proliferation

Answer 16

• After entering the skin, MCV infects the basal layer of the epidermis.
• The virus replicates within the cytoplasm of infected keratinocytes, leading to the formation of characteristic molluscum bodies.
• Infected cells show hypertrophy and hyperplasia, resulting in the formation of raised papules.

Question 17

MC: Immune response and Immune evasion

Answer 17

• Pox virus possesses mechanisms to evade the host immune response.
• It encodes viral proteins that interfere with the host’s antiviral defenses, including evasion of complement-mediated lysis and inhibition of interferon signalling pathways.
  Interferon - chemical messengers secreted by immune cells that are able to interfere with viral replication
• This enables the virus to establish a chronic infection.

Question 18

MC: Autoinoculation and Dissemination

Answer 18

• Autoinoculation, where the virus spreads from one area to another on the same individual, is common in molluscum contagiosum.
• Scratching or manipulation of the lesions can lead to the transfer of viral particles to adjacent or distant sites on the skin.

Question 19

MC: Resolution and Spontaneous Clearance

Answer 19

• In immunocompetent individuals, molluscum contagiosum lesions typically resolve spontaneously over time.
• As the immune system recognizes the presence of the virus, an immune- mediated clearance process is initiated, leading to the regression of the lesions.

Question 20

MC: Complications and Secondary Infections

Answer 20

• Although molluscum contagiosum is generally a self-limited infection, complications can arise, particularly in individuals with impaired immune function.
• Secondary bacterial infections, such as impetigo, may occur due to scratching and breaks in the skin integrity caused by the lesions.
• These secondary infections can further contribute to the persistence and spread of the disease.

Question 21

Sporotrichosis

Answer 21

• Sporotrichosis is a chronic subcutaneous mycosis caused by the fungus Sporothrix schenckii.
• It is primarily transmitted through traumatic implantation of fungal conidia into the skin from plant materials.
• Sporothrix spp. are thermodimorphic fungi, presenting the filamentous form (saprophytic phase) in nature or in vitro at 25°C, and developing yeast-like cells (parasitic phase) in the mammal host or in vitro at 35- 37°C

Question 22

Sporotrichosis: Transmission

Answer 22

• The fungus is found in soil, decaying organic matter, and vegetation.
• Nursery workers, florists and gardeners acquire the disease from roses, sphagnum moss and other plants.
• Infection may be limited to site of infection (plaque sprorotrichosis) or extend along proximal lymphatic channels (lymphangitic sprorotrichosis)
• Contact with the skin leads to the entry of fungal conidia.

Question 23

Sporotrichosis: Factors contributing to Disease Progression

Answer 23

Factors influencing disease progression include:
- size of the fungal inoculum
- strain virulence
- host immune status
- anatomical site of infection.

• Immunocompromised individuals are more susceptible to severe forms of sporotrichosis.

Question 24

Erythema Nodosum General Pathogenesis and clinical findings

Answer 24

• Pathogenesis is Multifactorial

Pathogenesis:
- Genetic dysregulation
- Infections
- medications
- malignancies
- autoimmune conditions
- pregnancy

Slide 42

General

Question 25

Erythema Nodosum Pathogensis

Answer 25

• Delayed hypersensitivity response to a variety of antigenic stimuli including bacteria, viruses and chemical agents
• A complex series of intermediate steps is involved in the development of these lesions
• A variety of adhesion molecules and inflammatory mediators appear to be associated with erythema nodosum
  ➢ e.g. in erythema nodosum lesions, vascular cell adhesion molecule (VCAM-1; CD106), platelet endothelial cell adhesion molecule-1 (PECAM-1;CD31), HLA-DR and E-selectin are expressed on endothelial cells
  ➢ intercellular adhesion molecule-1 (ICAM-1;CD 54), very late antigen-4 (VLA-4), L-selectin and HLA-DR are expressed by inflammatory cells
• Neutrophils are often numerous in early lesions
  ➢ a higher % of circulating neutrophils in patients with erythema nodosum leads to the production of reactive oxygen intermediates
  ➢ these intermediates may inturn provoke inflammation and tissue damage
• Support for a pathogenic role for these cells and molecules is provided by studies on the effects of colchicine
  ➢ this inhibitor of neutrophil chemotaxis diminishes L-selectin expression of ICAM-1 on the endothelium
• Erythema nodosum especially in its chronic phase, is characterized by granuloma formation
  ➢ TNF is known to play a role in granuloma formation
  ➢ a link between deregulation of TNF alpha production and granuloma formation → there is a strong correlation of a polymorphism in the promoter region of the gene that encodes TNF alpha and the development of sarcoidosis associated erythema nodosum
• Wide range of precipitating factors – idiopathic = most common cause
  ➢ Infectious causes are common especially URTI (Streptococcal and non-streptococcal)
  ➢ Other common causes – Drugs, Sarcoidosis, Inflammatory Bowel Disease

Question 26

Erythema Nodosum Causes

Answer 26

• idiopathic and rarer causes
• streptococcal infections
• sarcoid
• medications
• TB
• Bechcet disease
• pregnancy
• Inflammatory bowel disease