13.6.1 Lumbs And Bumps Flashcards
Warts
Def
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.
HPV infections
- 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
Types of cutaneous warts
- 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
Type of wart & HPV type
- plantar - 1,2
- common - 1,2
- flat - 3,10
- butchers - 2,7
- condylomata accuminata - Low grade (6,11); High grade (16, 18)
Warts: Viral infection and replication of HPV
- 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.
Warts: Transmission and Entry
- 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.
Warts: Viral persistence and evasion
- 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.
Warts: Epidermal Hyperplasia and wart formation
- 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
Warts: Viral particle assembly and Release
- 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.
Warts: Factors influencing wart persistence
- 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.
Define cysts
- 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.
General characteristics of cutaneous cysts
- 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.
Types of cysts
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.
Define Molluscum Contagiosum
- Molluscum contagiosum is a common viral skin infection caused by a Pox virus: Molluscum contagiosum virus (MCV).
- It primarily affects children and immunocompromised individuals.
MC: transmission and entry
- 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.
MC: Viral replication and epidermal proliferation
- 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.
MC: Immune response and Immune evasion
- 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.
MC: Autoinoculation and Dissemination
- 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.
MC: Resolution and Spontaneous Clearance
- 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.
MC: Complications and Secondary Infections
- 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.
Sporotrichosis
- 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
Sporotrichosis: Transmission
- 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.
Sporotrichosis: Factors contributing to Disease Progression
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.
Erythema Nodosum General Pathogenesis and clinical findings
- Pathogenesis is Multifactorial
Pathogenesis:
- Genetic dysregulation
- Infections
- medications
- malignancies
- autoimmune conditions
- pregnancy
Slide 42
General
Erythema Nodosum Pathogensis
- 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
Erythema Nodosum Causes
- idiopathic and rarer causes
- streptococcal infections
- sarcoid
- medications
- TB
- Bechcet disease
- pregnancy
- Inflammatory bowel disease
