📚 Question Bank

Vesiculobullous lesions are not seen in secondary syphilis. They are a feature of early congenital syphilis.

The features of secondary syphilis include the following:

• Macular / roseolar rash is the earliest rash. It fades leaving hypopigmentation around the neck called leucoderma syphiliticum or necklace of Venus.
• Papular rash involves the palms and soles.
• In later stages, nummular lesions with scales are seen which resemble psoriasis. Due to the serous discharge of the lesions, the scales are easy to remove.
• Papules on oral mucosa form grey oval patches and coalesce to form the so-called snailtrack ulcers as seen below, although ulceration is rare.
• Condyloma lata refers to moist, well-demarcated papules and plaques which are seen on the genitalia. They are highly infectious.
• Syphilitic alopecia or motheaten alopecia as seen below is a form of non-scarring patchy hair loss.
• Generalized lymphadenopathy is also seen. Other systemic features of secondary syphilis include panuveitis, periostitis and joint effusions, glomerulonephritis, hepatitis, gastritis, and
• myocarditis.

The lesions of secondary syphilis resolve spontaneously in a variable time period and are followed by the stage of latent syphilis.

Ollendorff probe sign or Buschke-Ollendorff sign refers to the deep dermal tenderness elicited by pressing the papular lesions of secondary syphilis with a pinhead.

Option A: Buschke-Lowenstein tumor is another name for giant condyloma acuminatum or verrucous carcinoma. It is a malignant growth tumor associated with HPV infection. It is not a clinical sign.

Option B: Gorlin’s sign is the ability to touch the tip of the nose with the tip of the tongue as seen below. It is seen in patients with Ehler-Danlos syndrome.

Option C: Love’s sign refers to the exact localization of tenderness using a pinhead in a glomus tumor.

Development of skin includes activation of Wnt signaling. The lack of Wnt signaling promotes the neural fate of the neuroectoderm cells.

A single layer of neuroectoderm forms the nervous system or the skin epithelium depending on the molecular signals it receives. Activation of Wnt signaling blocks the response of ectoderm to fibroblast growth factors (FGFs) and the cells express bone morphogenetic proteins

(BMPs). This leads to the epidermal fate of the neuroectoderm.

Stratum corneum is underdeveloped in very low birth weight (VLBW) infants in the initial 7 days.

In preterm infants, the stratum corneum is permeable and becomes similar to the adult and full-term infant after 2-3 weeks of postnatal maturation.

The development of the layers of the epidermis starts from below upwards. Therefore, the stratum basale is the first to form and the stratum corneum is the last layer to form.

From superficial to deep, the layers of the epidermis are as marked in the image-

• Stratum corneum
• Stratum granulosum
• Stratum spinosum
• Stratum basale

The thick skin found in the palms and soles has an additional fifth layer, called the stratum lucidum, located between the stratum corneum and stratum granulosum.

The epidermis is made of superficial keratinized, stratified, squamous epithelium. The epidermis is a highly cellular layer but is avascular hence dependent on the underlying dermis for nutrition via diffusion through the dermoepidermal junction.

It is thinnest on the eyelid and thickest on the palms and soles.

The above image is suggestive of ichthyosis vulgaris which is due to the deficiency of filaggrin protein. They are found in the keratohyalin granules of stratum granulosum in the form of profilaggrin (made of filaggrin monomers).

Profilaggrin undergoes proteolytic processing to yield individual filaggrin monomers that bind and aggregate keratin bundles and intermediate filaments between the stratum granulosum and corneum to form the epidermal barrier of the skin.

The malpighian layer of the epidermis includes both stratum basale and stratum spinosum as a unit. It is named after Marcello Malpighi.

Skin, hair, nails, the subcutaneous tissue below the skin, and assorted glands constitute the integumentary system. The most important function of the integumentary system is the protection against external damage.

Granules of Eleidin are clear intracellular proteins present in the stratum lucidum of the thick skin of palms and soles.

The cytoplasm of this layer is packed with keratin filaments and Eleidin granules giving it a translucent appearance. It is also called the clear cell layer.

Stratum lucidum is the layer of the epidermis, which is present between the stratum corneum and stratum granulosum. It is present only in the thick skin of the palms and soles. It is also called the clear cell layer due to the presence of refractile granules of Eleidin.

The image below shows stratum lucidum sandwiched between stratum corneum above and stratum granulosum below.

The stratum corneum, also known as the horny layer, consists of cells without the nucleus and hence does not divide.

It prevents the entry of microbes from the environment into the body and prevents leakage of fluids from the body to the environment. This is called the barrier function.

As keratinocytes divide and move up to the stratum corneum from stratum basale, they undergo the following changes:

• Loss of nucleus and ability to divide
• Increase in size
• Change in shape and flattening
• Dehydration and loss of water
• Loss of metabolic activity

Note: In palmoplantar skin, there is an additional zone, also electronlucent, the stratum lucidum, which lies between the granulosum and corneum. These cells are still nucleated and may be referred to as transitional cells.

Odland bodies, lamellar bodies, or membrane-coating granules or keratinosomes are present in the stratum granulosum and upper stratum spinosum.

They discharge lipid components into the intercellular space that plays an important role in barrier function and intercellular cohesion.

The image below shows Odland bodies in stratum granulosum. Green arrows indicate lamellar granules in the cytoplasm. Red arrows indicate secreted lamellar granules.

Melanocytes are present in the stratum basale (marking D).

These cells produce melanin which is packed into organelles called melanosomes and transferred via finger-like processes called the dendrites to keratinocytes.

Melanocytes originate from neural crest cells.

Meissner's corpuscles are located in the skin just below the epidermis within the dermal papilla. They are concentrated predominantly over glabrous skin (non-hair bearing) like fingertips and lips.

Desmosomes connect keratinocytes in the epidermis of the skin.

Desmosome (macula adherens) is a cell structure specialized for cell-to-cell adhesion. They resist mechanical stress as they are strongly adhesive.

Desmosomes contain proteins like desmoglein (dsg), desmocollin (dsc), and desmoplakin (dp).

The loss of any one protein can lead to the separation of keratinocytes leading to acantholysis.

The given image shows the characteristic fish-net pattern of immunofluorescence seen in pemphigus vulgaris. It is an autoimmune disease caused by antibodies directed

against desmoglein present in desmosomes.

Loss of desmosomes results in loss of cohesion between keratinocytes (acantholysis) and blister formation. Desmosomes failure can result in diseases of both skin and the heart. Mutations within the desmosomes are the main cause of arrhythmogenic right ventricular cardiomyopathy (ARVC).

Hemidesmosomal plaque components include BPAg1/BP230 and plectin.

Hemidesmosome connects the basal cell layer to the dermo-epidermal junction or basement membrane zone.

The above scenario is suggestive of epidermolysis bullosa simplex. It is associated with mutations in the genes for K5/14 (keratin filaments). K5/14 keratin filaments are present in the stratum basale.

Keratin is an intermediate filament protein present in all keratinocytes. There are 2 types of keratin filaments:

Keratin filaments exist as heterodimers consisting of one acidic and one basic filament. Stratified squamous epithelia express various keratin pairs during epithelial differentiation:

Type 1

Acidic in nature

Type 2

Basic in nature

Type 1 Type 2

K˜-K10, K12-K28, K31- K40

K1 to K8, K71-K 8’

Keratin heterodim er

K5/14 K1/10

K2/K11

K3/K12 K4/K13 K’/K1’ K8/18

Site

Stratum basale

Stratum spinosu m

Stratum granulos um

Cornea

Buccal mucosa Nails

Simple epitheliu m

The lamina densa is an electron-dense layer present in the dermo-epidermal junction and it is composed mainly of type IV collagen.

Components of lamina densa:

• Collagen type IV
• Laminin 1/111
• BM-40
• SPARC
• Perlecan

Type VII collagen is the major component of anchoring fibrils of the dermo-epidermal junction.

The superficial vascular plexus of the skin is present below the papillary dermis.

The dermis is rich in vascular supply (unlike the epidermis, which is avascular). It can be divided into the papillary dermis (upper 1/10) and reticular dermis (lower 9/10).

The superficial vascular plexus is present between the papillary and reticular dermis (subpapillary plexus) and the deep vascular plexus is present below the reticular dermis.

The main functions are providing nutrients and oxygen. It also regulates body temperature by controlling blood flow through capillaries in the upper dermis such that the opening of blood vessels allows dissipation of excess heat while constriction conserves heat.

The image below shows the location of the papillary and reticular layers of the dermis.

Type-I collagen is the predominant type of collagen present in the dermis accounting for approximately 80 of the collagen in the dermis.

Dermis forms the major part of human skin and extends from lamina densa above to the subcutis below. It is highly vascular, largely acellular, and primarily consists of the extracellular matrix of connective tissue.

The four main classes of extracellular components present in the dermis are as follows:

• Collagen fibers to provide tensile strength (most abundant)
• Elastic structures to provide resilience like elastin
• Non-collagenous glycoproteins like fibrillins that facilitate cell-matrix interactions
• Proteoglycan molecules like hyaluronic acid, dermatan sulfate, and chondroitin sulfate

Stem cells are not known to occur at the base of apocrine sweat glands. The stem cells are present in:

• Bulge area of hair follicles
• Basal layer of the interfollicular epidermis
• Base of sebaceous glands.

Their function is to maintain skin homeostasis, regenerate skin appendages and repair itself after injury.

The image below shows the location of stem cells of the skin.

The ratio of type-I to type-III collagen in the adult human skin is 8:1.

Type-I collagen is the predominant collagen in the human dermis. Type-III collagen is known to predominate in the human skin during embryonic development, but during the early postnatal period, type-I collagen synthesis accelerates. This results in the ratio of type-I to type-III collagen in the adult human skin being approximately 8:1.

The area marked is the reticular dermis. It is made up of dense irregular connective tissue.

It is found in the regions that are under considerable mechanical stress and where protection is given to ensheathed organs. It is usually present in:

• Reticular dermis
• Superficial connective tissue sheaths of the muscle and nerves
• Adventitia of large vessels
• Capsules of various organs and glands (e.g., testis, sclera, periosteum, perichondrium)
• On the other hand, dense regular collagen fibers are found in tendons.