Dermatology in a Week Premanshu Bhushan
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MODULE ONE

 
ANATOMY, HISTOLOGY, PHYSIOLOGY, AND BASICS
Skin is the largest organ in body with a surface area of 1.7m2 in adults.
LAYERS OF SKIN: There are three layers of skin namely, epidermis (top layer), dermis (middle layer) and subcutis (the deepest layer) (Fig. 1.1).
 
EPIDERMIS
  • It is a stratified squamous epithelium.
  • Thickness varies from 0.1 mm at the eyelids to nearly 1 mm on the palms and soles.
  • Keratinocyte is the principal cell.
Epidermis is composed of following layers:
  1. Basal Cell Layer (stratum basale): composed mostly of keratinocytes which are either dividing or non-dividing
  2. Prickle Cell Layer (stratum spinosum): Daughter basal cells migrate upwards and differentiate into polyhedral cells in this layer. Desmosomes interconnect these polyhedral cells and give rise to the “prickles/spines” seen at light microscope level. Keratin tonofibrils form the cytoplasmic supportive framework. Langerhans cells are mostly found in this layer. They are dendritic, immunologically active cells that play a role in antigen presentation [Basal and spinous layer together form Malpighian layer].
2
  1. Granular Cell Layer (stratum granulosum) cells become flattened and lose their nuclei. In the cytoplasm, there are keratohyalin granules as well as membrane-coating granules (Odland bodies) which expel their lipid contents into the intercellular spaces.
  2. Stratum Lucidum is probably artefactual seen on palms and soles.
  3. Horny Layer (stratum corneum): This layer is composed of layers of overlapping flattened cornified cells without nuclei called corneocytes. This layer is thickest on the palms and soles. The flattened corneoctyes develop a thickened cell envelope. Its cytoplasm is replaced by keratin tonofibrils in a matrix of keratohyalin granules. Whereas, the membrane-coating granules produce lipid glue that keeps the cells stuck together. This forms the hydrophobic barrier that protects the skin, and prevents water loss.
Epidermis contains following types of cells:
  • Keratinocytes (85% of cells in epidermis)
  • Langerhans cells (Derived from bone marrow)
  • Melanocytes (Derived from neural crest) wedged between basal keratinocyte in a ratio of 1 to 10; 1 melanocyte supplies pigments to approximately 36 keratinocyte.
    zoom view
    Fig. 1.1: Ultrastructure of skin
    3
  • Merkel Cells. (Neural Crest origin) associated with terminal filaments of cutaneous nerves. Merkel cells have a role in sensation. Neuropeptide granules, neurofilaments, and keratin can be seen in their cytoplasm.
 
DERMIS (Thickness of epidermis: dermis :: 1:20)
  • Thickest at the palms, soles and back (3 mm) and thinnest at the eyelids (0.3 mm) and penis.
  • Composed of upper papillary dermis (1/10th thickness of dermis) and deeper reticular dermis (9/10).
  • The ground substance consists of two glycosaminoglycans: hyaluronic acid and dermatan sulphate.
  • Other structures found in the dermis include: blood vessels, lymphatics, nerves, nerve endings and receptors, dartos muscles in scrotum, appendageal glands and their accessories e.g. arrector pili muscles.
  • Cell types: Fibroblast, mononuclear phagocytes, Lymphocyte, Langerhans cell, mast cell, dermal dendrocytes which are dendritic cells with immune function.
  • Collagen fibers make up 70 percent of the dermis and give structural toughness and strength. Type I collagen contributes 70 percent and type III nearly 15 percent.
  • Elastin fibers are loosely arranged in all directions and give elasticity to the skin.4
 
SUBCUTANEOUS TISSUE (SUBCUTIS)
  • It is made up of loose connective tissue and fat. It can be up to 3 cm thick on the abdomen.
  • Absent from the eyelids and the male genitalia.
  • It has abundant blood and lymphatic supplies.
 
Structure of Basement Membrane Zone (Fig. 1.2)
At the junction of the epidermis and dermis lies the basement membrane zone. Electron microscopy shows that it can further be divided into basal cell membrane, lamina lucida (20-40 nm), lamina densa (30-60 nm, Type IV collagen) and sublamina densa with anchoring fibrils (Type VII collagen), dermal microfibril bundles and Types I and III collagen fibers. The structures of the dermoepidermal junction provide mechanical support, adhesion and growth of the basal layer cells unless it gets diseased.
zoom view
Fig. 1.2: Ultrastructure of basement membrane zone
 
ADNEXAL STRUCTURE OF SKIN
 
Sweat Glands
  • Coiled tubular glands that reside in the dermis.
  • Produce a watery secretion.5
  • Two types: eccrine and apocrine.
    Eccrine:
    • Distributed all over our body except the vermilion border of the lips, the nail beds, the labia minora, the glans penis, and the inner aspect of the prepuce. They open directly (cf. apocrine glands) on skin.
    • Most dense on our axillae (arm pits), palms, soles, and forehead.
    • Under sympathetic cholinergic control.
    • Histologically, the intraepidermal duct has a spiral course and is lined by keratinized epidermal cells (3-4 layers); the intradermal duct is lined by 2 layers of small cuboidal, basophilic cells while the secretory portion has 1 layer of secretory cells (two types i.e. dark and clear cells) and outer layer of myoepithelial cells.
    Apocrine:
    • Open into hair follicles and are larger than eccrine glands
    • Densely populate the axillae, perineum, and areolae; (phylogenetic remnant of the mammalian sexual scent glands).
    • They discharge their contents by “decapitation” secretion.
    • Skin's bacteria produce odor in the otherwise odorless secretions.
    • They are innervated by (sympathetic Adrenergic nerve fibers)
    • Histologically, intraepidermal duct is straight while the intradermal duct has similar double layer of basophilic cells and the secretory portion which has larger coils than eccrine glands has single layer of secretory cells showing dome shaped apical caps.
 
Sebaceous Glands
  • Go hand in hand with hair follicles→ absent on non-hairy glabrous skin.
  • Especially prominent with the hair follicles of the face, scalp, chest, and back.
  • Produces an oily sebum by holocrine secretion.
  • Enlarge and become active around puberty due to their androgen sensitivity.
  • Histologically, it consists of several lobules lined by a peripheral layer of cuboidal cells and central 2-3 layers of large lipid containing foamy cells.
HAIR: The hair shaft is composed of an outer cuticle which encompasses a cortex of keratinocytes. In terminal hairs, the cortex contains an inner medulla. The hair bulb contains germinative cells which can be associated with melanocytes which produce pigment. Hair stands up forming “goose bumps” when the arrector pili muscle (rudimentary in humans) contracts due to cold, fear and emotion.6
 
KINETICS OF SKIN
Epidermis: Cell cycles time of keratinocytes: 311 hours (from G1, S, G2 to M phases); keratinocytes need 14 days to move from basal layer to horny layer and another 14 days to slough off from horny layer (i.e. from the basal layer to the environment requires 28 days); also known as epidermal turnover time.
 
Skin Appendages
  • Hair (scalp): growth rate: 0.37 mm/day, 90 percent in anagen at any one time; anagen phase: 3 years, catagen phase: 3 weeks, telogen phase: 3 months→ 8-9 percent of hairs.
  • Nail: fingernail growth rate: 1 cm/3 months (0.1 mm/day), toenail growth 1 cm/9 months
 
IMMUNOLOGICAL CELLS IN SKIN
  • Langerhans cell are part of macrophage-monocyte system and are dendritic, bone-marrow derived cells located in the epidermis which are involved in antigen presentation. They contain unique cytoplasmic organelles known as the Birbeck granules.
  • T Lymphocyte
  • B lymphocytes Not found in normal skin, but in some disease states
  • Mast cell: very similar to basophils—degranulation results in the release of histamine and other vasoactive mediators
  • Keratinocyte Produce IL-1 and express immune reactive molecules on their surface such as MHC class II antigens (HLA-DR) and intercellular adhesion molecules (ICAM-1).
Hypersensitivity reactions of the skin
Dermatological examples
Type 1 (Immediate, IgE mediated)
Urticaria, anaphylaxis, prick test
Type 2 (Antibody-Dependent Cytotoxicity)
Intraepidermal blisters, hemolytic anemia
Type 3 (Immune Complex Disease)
SLE, dermatomyositis, ENL (type 2 lepra reaction)
Type 4 (Cell-Mediated or Delayed)
Allergic contact dermatitis, tuberculin reaction, Lepromin testing, Patch test, Type 1 lepra reaction
FUNCTION OF SKIN and main component of skin responsible for these functions.
  • Protection from external environment, biological germs, ultraviolet light and chemicals: Epidermis
  • Shock absorber: Subcutaneous fat
  • Protection against mechanical shearing force: Dermis.7
  • Temperature regulation: Blood vessels and eccrine sweat glands
  • Sensation: Nerve endings
  • Lubrication: Sebaceous glands
  • Vitamin D synthesis: Epidermis with UVB radiation.
    (NB. Some details of hair nail and melanocyte biology is described under appropriate modules)
 
DERMATOLOGICAL TERMINOLOGY
 
 
Primary Lesions
Lesions that arise on normal skin early in the course of disease.
  • Macule — Change in normal skin color of any size, without change in skin texture.
  • Patch — A macule greater than 5 mm in diameter (unscientific, term should be avoided).
  • Papule — Discrete, elevated solid lesion less than 5 mm in diameter.
  • Plaque — Similar to a papule but greater that 5 mm in diameter. Often formed by the confluence or coalescence of papules.
  • Nodule — Discrete, solid, round or oval lesion of the skin that is better palpated than seen. Applies to processes involving any or all levels of the skin.
  • Vesicle — A circumscribed, clear fluid-filled elevated lesion less than 5 mm in diameter.
  • Bulla — Essentially a vesicle greater than 5 mm in diameter. May attain diameters of several cm and are described as tense, or flaccid.
  • Pustule — Essentially a vesicle with purulent content.
  • Wheal — an evanescent elevation of skin with a pale red color, arising from edema in the superficial dermis. Should be distinguished from angioedema, edema involving the deep dermis and subcutaneous tissues.
 
Secondary Lesions
Secondary lesions are changes seen superimposed on primary skin lesions.
  • Scar — A hard plaque of dense fibrotic tissue replacing normal tissue at the site of any physical or pathologic injury.
  • Atrophy — Atrophy usually refers to thinning of the epidermis leaving an easily wrinkled and/or shiny surface. Atrophy may also apply to dermal and/or subcutaneous tissue, with or without changes in the epidermis.
  • Erosion — A superficial denudation of the skin, usually implying the loss of the epidermis only.
  • Fissure — A deep, vertical splitting of the skin.
  • Crust — A dried up serum, blood, exudate or pus over lesion.8
  • Excoriation — A scratch mark, often with linear denudation of the skin and is a sign of itching.
  • Scale — A thin flake of condensed corneoctyes which is separated from the underlying intact skin. Scaling is produced as a result of abnormal cohesion of corneoctyes which causes interference with normal loss of corneoctyes from the surface of skin. In scaling many hundreds and thousands of stratum corneum cells separate from the underlying skin while they have not yet separated from each other thus producing visible flaking of skin.
  • Lichenification—A thickening and pigmentation of the skin surface with an increase of surface markings, usually seen with chronic eczemas.
 
Other Important Lesions
Lesions which are difficult to classify as primary or secondary.
  • Abscess: Localized pus collection usually in a cavity (more than 1 cm).
  • Petechiae: Pinhead size extravasation of blood into skin.
  • Ecchymosis: Larger extravasation of blood into skin.
  • Purpura: Blood in skin up to 2 mm in diameter, may be palpable.
  • Comedo (comedones): A keratinous plug of pilosebaceous glands seen in acne.
  • Burrow: A small linear or wavy tunnel in the skin with a minute papule/ vesicle at the end where scabies mite resides.
  • Telangiectasia: Visible dilatation of small cutaneous blood vessels.
  • Poikiloderma: Combination of Atrophy, Reticulate hyperpigmentation and Telangiectasia [ART].
  • Sclerosis: Induration or binding down of upper skin to the subcutaneous tissues.
  • Striae: Linear, atrophic, pink or white lesions due to rapid and enormous expansion causing repture of fibrous tissue.
 
Microscopic Terminology in Dermatology
  • Hyperkeratosis: Increased thickness of stratum corneum.
  • Orthokeratosis: Process of normal keratinization which leads to the production of a stratum corneum composed of anucleate corneoctyes.
  • Parakeratosis: Persistence of nuclei in stratum spinosum; abnormal in skin (usually a result of rapid epidermopoiesis), normal in mucous membranes.
  • Hypergranulosis: Increase in thickness of the granular layer
  • Acanthosis: Increase in thickness of spinous layer with thickening of the epidermis.
  • Papillomatosis: Increase in keratinocytes with projections from the surface of skin, i.e. papillae; typical example being a wart.
  • Psoriasiform epidermal hyperplasia: Increase in keratinocytes with elongation of rete ridges and elongation of dermal papillae; typical example is psoriasis.
  • Dyskeratosis: Cell death associated with premature keratinization. Corps Grains, Corps Ronds: Acantholytic, dyskeratotic, basophilic cells seen in Darier's and Grover's disease.
  • Spongiosis: Widening of the interspaces between keratinocytes due to edema fluid without detachment of cells from each other; seen in dermatitis.9
  • Acantholysis: Detachment of keratinocytes from each other due to loss of intercellular contacts (desmosomes).
  • Vacuolar change or liquefaction degeneration (vacuolization): The appearance of vacuoles within cells usually basal keratinocytes. It is seen in lupus erythematosus, dermatomyositis, and in early lichen planus.
  • Ballooning degeneration: Intracellular edema often secondary to viral injury.
  • Apoptosis: A general process of programmed cell death as individual cells. Civatte or Colloid Body: Eosinophilic, round homogeneous apoptotic bodies seen in the epidermis or upper dermis. They form by degeneration of epidermal cells and are most commonly seen in lichen planus.
  • Squamatization: Replacement of the columnar basal cells with flattened keratinocytes. This occurs mainly in lichenoid tissue reactions.
  • Pigment Incontinence: The deposition of melanin in the dermis, resulting from prior basement membrane damage.
  • Melanophage: Macrophage in dermis which has ingested melanin pigment.
  • Grenz Zone: A narrow area of uninvolved dermis between the epidermis and a dermal inflammatory or neoplastic infiltrate. “Grenz” is German for “border”.
  • Storiform: A Pattern of cellular arrangement where elongated cells intertwine mimicking the doormat weaves, typically seen in dermatofibrosarcoma protuberans.
  • MICROABSCESS: Small collection of inflammatory cells.
    • Munro microabscesses are composed of degenerated PMN's in the stratum corneum and are seen in psoriasis.
    • Spongiform pustules of Kogoj are pustules in the stratum spinosum seen in psoriasis.
    • Pautrier microabscesses are a collection of 3 or more atypical mononuclear cells within the epidermis in mycosis fungoides.
 
DIAGNOSTIC TECHNIQUES IN DERMATOLOGY
  1. Skin Biopsy: Specimen is sent for Histopathology, direct immunofluorescence study or culture and smear for AFB, fungus etc. IMP: biopsy is taken from perilesional area in bullous diseases for immunofluorescence because in the bulla the immunoreactants are diluted into fluid contents of bulla.
  2. Wood's Lamp Examination
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Uses
  • Infected hair in Tinea capitis caused by Microsporum (not Trichophyton) will fluoresce bright green.
  • Skin lesion of active pityriasis versicolor will fluoresce yellow.
  • Fresh urine in porphyria cutanea tarda fluoresces a reddish color.
  • Erythrasma will fluoresce coral red.
  • Pseudomonas infection of skin= Green fluorescence.
  • Vitiligo lesion appears whiter and ash leaf macule in Tuberous sclerosis is more apparent.
  • Red fluorescence of teeth in congenital erythropoietic porphyria.
  1. Patch Test
    • This tests the type IV hypersensitivity reaction and it is a confirmatory test for allergic contact dermatitis.
    • The test materials are applied to the back under aluminum discs with occlusion. The sites are inspected at 48 hours and test materials removed. The sites are re-inspected at 96 hours for delayed reaction.
  2. Mycology Examination (KOH scraping) for identification of suspected fungi
    The scales, nail or hair should be collected onto a slide and a drop of 10-20 percent KOH to dissolve the keratin. (Hastened by gently warming). The tissue can also be sent for mycology culture (Sabouraud's Dextrose Agar and Dermarophyte Test Medium) however, the culture result may not be available for 3 weeks.
  3. Mite Examination
    The purpose is to identify the burrow in common area e.g. finger webs. With the help of magnifying glass, the acarus may be seen as a tiny grey dot at the end of burrow. It can be removed by a sterile needle. If mites are not seen, burrow may be moistened with liquid paraffin or mineral oil and scraped with scalpel blade and material so obtained is transferred to slide for examination.
 
Other Tests
  • Prick testing is much less helpful in dermatology (Type 1 reaction). Multiple positive skin tests to commercially prepared diluted antigens may only imply the atopic tendency of the tested subject.
  • Dark-ground examination for suspected genital ulcer to look for Treponema pallidum is the investigation of choice. Animal inoculation (Rabbit intratesticular injection) is the gold standard.
  • Acetowhitening: Acetic acid test on genital or cervical papules facilitates detection of subclinical condylomata acuminata. Gauze saturated with 5 percent acetic acid is wrapped around area for 5 to 10 minutes and then using a colposcope or magnifying hand lens the lesional white papules are seen.
  • Cell cytology (Tzanck smear): It is useful for herpetic infections and acantholytic cells (pemphigus, SSS) as well as for evaluating superficial cutaneous malignancies.
  • Epiluminescence Microscopy: for early detection of Melanomas.
  • Gram stain of urethral discharge: intracellular Gram-Negative Diplococci (GNDC) → gonorrhea; only extracellular GNDC → chlamydial or non gonococcal urethritis.11
 
IMPORTANT CLINICAL SIGNS IN DERMATOLOGY
  • Diascopy (VITROPRESSION) consists of pressing a transparent slide over a skin lesion. It is of special value in distinguishing erythema which disappears and purpura which persists. It is useful to detect the glassy yellow-brown papules in sarcoidosis, tuberculosis (Apple Jelly Nodules) and other granuloma.
  • Darier's sign is positive when a brown macular or papular lesion of urticaria pigmentosa (cutaneous mastocytosis) becomes palpable wheal after being rubbed.
  • Grattage test and Auspitz's sign is positive when slight scratching or curetting of a scaly lesion reveals initially fine candle wax scales followed by red Berkley's membrane; which then gets removed to reveal punctate bleeding points(Auspitz's sign) within the lesion which suggests of psoriasis.
  • Nikolsky's sign is positive when a new blister is generated with ease by applying shearing force to skin or epidermis is dislodged (pemphigus, SSSS, TEN).
  • Asboe Hansen (Bulla spread) sign: Spread of bulla to normal skin by applying vertical pressure in Pemphigus (~ to Nikolsky's)
  • Carpet Tack Sign: or carpet en tack sign: removal of adherent scales in DLE reveals downward projection of scales which are in fact the follicular plugs.
  • Chandelier's sign: Pelvic Inflammatory Disease (PID) in women (intense pain on pelvic examination makes the patient leap towards the Chandelier).
  • Antenna sign: It is seen in Keratosis Pilaris.
  • Buttonholing sign: It is seen in NF 1 (with central vertical pressure the lesion disappears under the skin as if passing through a button-hole).
  • Dimpling sign: It is seen in dermatofibroma and dermatofibrosarcoma protuberans.
  • Koebner's phenomenon: Spread of lesions of same morphology (isomorphic phenomenon) at the site of trauma. Characteristically seen in lichen planus, psoriasis, vitiligo and by auto-inoculation in verruca, molluscum contagiosum etc.
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LEARNING QUESTIONS: MODULE 1
  1. Each of the following statements regarding the kinetics of skin is true EXCEPT:
    1. Mitoses are found mostly in the basal layer.
    2. The normal germinative cell has a DNA synthesis time of about 16 hours.
    3. In normal skin, the average time required for transit of a cell from the basal cell layer to surface is between 26 and 42 days.
    4. The passage of horny cells through the normal stratum corneum requires approximate 35 days.
  1. Regarding the keratin in skin each of the following statements is true EXCEPT:
    1. The epithelial keratins can be divided into basic and acidic groups.
    2. Simple epithelia are characterized by the keratins 6 and 16.
    3. The major keratins in the basal layer are keratins 5 and 14.
    4. Hyperproliferative conditions induce expression of keratins 6 and 16.
  1. Regarding the basement membrane zone, decide which of the following is FALSE:
    1. The lamina lucida separates the trilaminar plasma membrane from the lamina densa.
    2. The upper lamina lucida contains the sub-basal cell dense plate.
    3. Anchoring fibrils extend from the hemidesmosomes of the basal cell plasma membrane to the lamina lucida.
    4. The lamina lucida is 30 to 60 nm wide.
    5. Type 4 collagen is found within the lamina densa.
  1. All of the following are true about Odland bodies EXCEPT:
    1. They are discharged from the spinous cells into the intercellular space.
    2. They help establish a barrier to water loss.
    3. They mediate stratum corneum adhesion.
    4. They measure 300 to 500 nm in diameter.
  1. A 55-year-old lady presents with flaccid bullae and slow-healing erosions on head and trunk. She also has painful oral erosions. She gives history of similar episode in past which required treatment in hospital. The most likely structure damaged in the patient is:
    1. Desmoplakin
    2. Desmoglein 3 of Desmosomes
    3. Desmoglein 3 of Hemidesmosomes
    4. Desmoglein 1 of Desmosomes
    5. Desmoglein 1 of Hemidesmosomes
  1. Ramkumar a 22-year-old man complaints of appearance of very painful unilateral erythema on the right flank. A day later he developed multiple clear fluid filled blisters at the same site. His doctor scrapes the base of a fresh blister for microscopic examination. He is looking for:
    1. A modified keratinocyte
    2. Neutrophilic infiltrate to exclude bacterial super-infection
    3. Eosinophilic infiltrate to diagnose insect bite
    4. Acantholytic cells to diagnose autoimmune blistering disease.
  1. Melanocytes can NOT be identified with which of the following stains?
    1. Bloch dopa reaction.
    2. Silver stains.
    3. Fontana Masson stain.
    4. Congo red.
  1. Langerhans cells:
    1. Constitute 2 to 4 percent of the total epidermal cell population.
    2. Express immune response-associated antigens 1A and HLA DR.
    3. Express S100 protein.
    4. They play an important role in contact sensitization.
    5. All the above are true.
  1. Eccrine glands are present in the following sites EXCEPT:
    1. The labia minora
    2. The palms and soles.13
    3. The distal extremities.
    4. The axillae.
  1. All of the following are true of apocrine glands EXCEPT:
    1. Meibomian glands are apocrine in origin
    2. Mohl's glands are apocrine in origin
    3. Possess eosinophilic cytoplasm
    4. Are found in the axillae, eyelid, breast, and anogenital areas
    5. Secrete sialomucin
  1. Sebaceous glands produce the following lipids EXCEPT:
    1. Triglycerides.
    2. Phospholipids
    3. Esterified cholesterol.
    4. Free cholesterol.
    5. Waxes.
  1. Ground substance contains all of the following EXCEPT:
    1. Glycosaminoglycans
    2. Proteoglycans
    3. Hyaluronic acid
    4. Collagen
  1. For the following pairs of collagen and their locations, which is INCORRECT?
    1. Type 1 collagen—reticular dermis.
    2. Type 3 collagen—blood vessels and subepidermal regions.
    3. Type 4 collagen—basement membrane zone and perivascular regions.
    4. Type 2 collagen—cartilage.
    5. Type 7 collagen—anchoring filaments.
  1. Cells NOT involved in the immune response in the skin:
    1. Langerhans cells.
    2. Keratinocytes.
    3. Indeterminate dendritic cells.
    4. Melanocytes.
  1. Which of the following statements regarding skin biopsy is FALSE?
    1. Fresh vesicles should be biopsied for Immunofluorescence studies.
    2. Older lesions may show re-epithelialization making identification of level of clefting difficult and non-conclusive
    3. Culture from biopsy material in cases of infective dermatoses should be obtained.
    4. Biopsy material for immunofluorescence should be sent in Michel's medium.
  1. Heat can be lost through the skin surface by:
    1. Radiation
    2. Convection
    3. Conduction
    4. Evaporation
    5. All of the above
  1. All of the following can be considered primary lesions of the skin EXCPET:
    1. Nodule.
    2. Macule.
    3. Pustule.
    4. Excoriation.
    5. Wheal.
  1. Which of the following is FALSE about vitamin D synthesis in the skin?
    1. Vitamin D3 synthesis occurs mainly in stratum basale and stratum spinosum.
    2. It is synthesized from 7-dehydrocholesterol through the intermediate pre-vitamin D3.
    3. A plateau of vitamin D3 is reached when around 15 percent of 7-dehydrocholesterol has been converted.
    4. Vitamin D3 is synthesized in the skin mainly as a result of exposure to UVA.
  1. The mechanical properties of the skin depend primarily on the:
    1. Epidermis.
    2. Dermis.
    3. Subcutaneous tissue.
    4. Stratum corneum.
  1. Each of the following is true about hair EXCEPT:
    1. Anagen lasts around 3 years; telogen, 3 months; and catagen, 3 weeks.
    2. On the scalp, the average daily growth is approximately 0.4 mm.14
    3. A loss of around 100 scalp hairs daily is considered normal.
    4. Isthmus refers to the upper portion of the hair follicle extending from the entrance of the sebaceous duct to the surface of the skin.
  1. All of the following are true about parakeratosis EXCEPT:
    1. It refers to retention of nuclei by keratinocytes in the horny layer.
    2. It is usually associated with an increased granular cell layer.
    3. It is usually focal in psoriasis.
    4. It is a physiologic phenomenon in the oral mucosa.
  1. Which of the following giant cell types is matched with the correct histological description?
    1. Langhans giant cell/horseshoe nuclei pattern.
    2. Foreign body giant cell /random nuclei.
    3. Touton giant cell/wreathed nuclei along a foamy rim.
    4. Osteoclastic/giant cells with eosinophilic cytoplasm.
    5. All of the above.
  1. The main barriers to passage of water and electrolytes in the skin are the:
    1. Epidermis
    2. Stratum corneum
    3. Dermis
    4. All of the above
    5. A and B.
  1. Which of the following is INCORRECTLY matched:
    1. SLE: Type 4 Hypersensitivity reaction.
    2. Urticaria: Type 1 Hypersensitivity reaction.
    3. Lepromin reaction: Type 4 Hypersensitivity reaction.
    4. Pemphigus Vulgaris: Type 2 Hypersensitivity reaction.
  1. Which of the following is correctly matched:
    1. Grattage Test: Pityriasis Rubra Pilaris
    2. Buttonholing: Neurofibromatosis
    3. Carpet tack sign: Systemic lupus erythematosus
    4. Apple jelly nodules: Scrofuloderma
  1. Acetowhitening test is done for:
    1. Subclinical genital HPV infection.
    2. Clinically aggressive papilloma
    3. Excluding superinfections of genital warts
    4. Identifying precancerous warts caused by HPV 16, 18, 33 etc.
  1. A 7-year-old school child is diagnosed as Tinea capitis. Woods lamp examination demonstrates a bright green fluorescence. The most likely organism isolated on fungal culture is:
    1. Trichophyton tonsurans
    2. Trichophyton rubrum
    3. Microsporum canis
    4. Trichophyton schoenleinii
  1. Primary acantholysis is seen in all except:
    1. Pemphigus vulgaris
    2. Pemphigus foliaceous
    3. Darier's disease
    4. Toxic epidermal necrolysis.
  1. Contact dermatitis, if suspected, can be confirmed by patch testing. Ideally patients should not be on steroids or immunosuppressive, disease should be controlled and test site should not have active lesions. What is the best time schedule to read the results:
    1. 1-2 hour after patch application
    2. 48 and 96 hour after the patch application
    3. 72 hours after patch application as a single reading.
    4. Call the person in evening after morning application and in morning after evening application.
  1. Woods lamp filter is made of:
    1. Tin and chromium oxide.
    2. Nickel hydride and barium silicate.
    3. Nickel oxide and barium carbonate.
    4. Nickel oxide and barium silicate.15
 
SOLUTION OF LEARNING QUESTIONS: MODULE 1
    • D. Mitoses are mainly found in the basal layer of the epidermis. The normal epidermal stem cell, or germinative cell, has a DNA synthesis time of 16 hours and divides approximately every 19 days. The epidermal transit time is the time required for a cell to pass from the basal layer to the superficial layer. In normal skin, this is between 26 and 42 days divided into the passage through the Malpighian layer up to granular layer of 14 days and, the transit time through the stratum corneum of approximately 14 days. In conditions such as psoriasis, the epidermal transit time is much more rapid.
    • B. The epithelial keratins can be divided into two groups: the basic group (keratins 1-8) and the acidic group (keratins 9-19). The basic keratins are also known as type I keratins, and those in the acidic group are known as type II keratins. In epithelia, keratins are expressed in pairs with one member of each group (basic and acidic) required for keratin filament assembly. (Molls numbers) In simple epithelia, the keratin pair 8 and 18 is expressed. In the skin, keratins 5 and 14 are predominantly expressed in the basal layer. In the suprabasal layer, keratins 1 and 10 are expressed and are characteristic of epidermal differentiation. In hyperproliferative conditions such as psoriasis, the keratin pair 6 and 16 is expressed.
    • C. Anchoring filaments, rich in laminin 5, run through the lamina lucida and extend from the hemidesmosomes of the basal keratinocyte cell membrane to the lamina densa.
    • A. Odland bodies are also known as membrane-coating granules or lamellar granules. They are found within the granular layer of the epidermis (Mem Booster: GRAND OLD MAN: Granular layer Contains Odland bodies) and are rich in lipids, which include phospholipids, glycolipids, and free sterols. They discharge their contents into the intercellular spaces, helping to establish a barrier to water loss within the stratum corneum and mediate adhesion of the cells. Odland bodies measure 300 to 500 nm in diameter.
    • B. This patient has flaccid bullae as well as oral erosions which are seen in Pemphigus vulgaris. The pathogenesis of pemphigus vulgaris involves antibodies against Desmoglein 3 a component of desmosomes and not of hemidesmosomes. Hemidesmosomes are not involved in intra epidermal autoimmune blistering diseases.
    • A. This is a case of unilateral dermatomal vesicular eruption in an adult patient. The severe pain suggests neuralgia. The diagnosis is Herpes Zoster. Cytodiagnosis of herpetic infections includes Tzanck prep where one looks for Tzanck cells which are modified giant keratinocytes with Cowdry type 1 and 2 inclusions.
    • D. Melanocytes can be stained with the Bloch dopa reaction, the silver, and Fontana-Masson stains. The melanocytes stain black with this procedure. Melanin can be treated with silver nitrate solution and then reduced with hydroquinone to stain melanocytes black. Fontana-Masson with ammoniated silver nitrate also stains melanocytes. Congo red is used to stain amyloid tissue.
    • E. Langerhans cells are bone marrow-derived cells that are important in antigen processing and recognition. They constitute 2 to 4 percent of the total epidermal cell population and express la and HLA-DR antigen as well as S100 protein and actin-like and vimentin filaments. They can be identified with adenosine triphosphatase, aminopeptidase, OKT6, and gold chloride. Argentaffin stains melanocytes but not Langerhans cells. Because of their ability to present antigen to T cells, Langerhans cells are important in contact sensitization, skin graft rejection, and immune surveillance. Their numbers in the skin decrease after ultraviolet radiation.
    • A. Eccrine glands are present in all areas of the body except the vermilion border of the lips, the nail 16beds, the labia minora, the glans penis, and the inner aspect of the prepuce. Large numbers of eccrine glands are found in the palms, soles, and axillae.
    • A. Apocrine glands represent scent glands and differ from eccrine glands in location, size, and origin. They contain PAS-positive, diastase-resistant granules and originate from the hair germ. They are found in the axillae, eyelid, breast, and anogenital areas. They are tubular glands in which a sialomucin containing secretion occurs by “decapitation,” a process in which the cytoplasm of the secretary cell is pinched off. The secretary cells possess eosinophilic cytoplasm and have a larger lumen than that of eccrine glands. Ceruminous glands, Mammary glands and Mohl's gland in eyelids are modified apocrine glands. Fox Fordyce spots on lips, Meibomian glands in eyelids and Tyson's glands of penis are Sebaceous Glands.
    • D. Sebaceous glands are found throughout the skin with the exception of the palms and soles. They secrete a variety of lipids, including triglycerides (maximum), phospholipids, and esterified cholesterol, but no free cholesterol. Waxes are also present.
    • D. The dermis consists of protein fibers, principally collagen and elastin, embedded in a supporting matrix of ground substance. The composition of ground substance includes polysaccharides, also known as glycosaminoglycans (GAG). These are usually linked to proteins to form proteoglycans. This molecule has remarkable water-holding capacity and is the principal component of the connective tissue matrix. The principal GAG found in ground substance are hyaluronic acid, chondroitin, dermatan sulfate (chondroitin sulfate B), chondroitin sulfate A and C.
    • E. Type 1 collagen is mainly found in the reticular dermis. Type 2 collagen is found in cartilage. Type 3 collagen is found mainly in early fetal life, whereas in adult life it is limited to the subepidermal and periappendicular regions. Type 4 collagen is found in the basement membrane zone. Type 5 collagen is found in connective tissue, and Type 7 collagen is found in basement membranes, particularly in the anchoring fibrils.
    • D. The three types of cells that are known to be involved in the immune response in the skin are the Langerhans cell, the indeterminate dendritic cell, and the keratinocyte. Langerhans cells are important for antigen processing and presentation to lymphocytes. With electron microscopy, they are seen to contain characteristic racquet-shaped Birbeck granules. They occur in the dermis and the epidermis and can only be seen by electron microscopy. They demonstrate several of the molecules found on the surface of Langerhans cells but lack Birbeck granules. Keratinocytes participate in the immune response by producing thymus like hormones, α-interferon, prostaglandins, colony-stimulating factors, and a thymocyte-activating factor [Melanocytes have no immune function and a vitiligo patient has no decrease in cutaneous immune status].
    • A. Fresh vesicles give good histopathological picture, but due to blister fluid all immunoreactants are diluted. Therefore, Perilesional skin is best site to biopsy if immunofluorescence is contemplated.
    • E. Maintenance of a constant core temperature of the body is essential for human life. Skin plays a major role in thermoregulation. In a cold environment, heat is lost from the skin through convection, conduction, and radiation. Convection refers to the transfer of heat to moving air, which has a lower temperature than the body surface. It depends on blood flow to the skin and varies with the level of vasodilatation or constriction as well as with the vascular supply to different areas of the body. Conduction is the transfer of heat by direct contact. It is affected by the underlying tissue. Adipose tissue has a low conductivity and is thus a good heat insulator. At high environmental temperatures, sweat evaporation plays a crucial role in cooling down the skin.
    • D. Primary lesions are the basic lesions that first appear on the skin. They are important for description as well as diagnosis of different dermatologic diseases. Examples include macules, papules, patches, 17plaques, nodules, tumors, scars, wheals, and vesicles. Secondary lesions appear later on in the course of the disease and can be induced by rubbing, scratching, or infection. Examples are lichenification, erosions, ulcers, and excoriations.
    • D. Specific receptors for 1,25-dihydroxyvitamin D3, the active form of vitamin D, have been found in the skin. This hormone is synthesized mainly in the basal and spinous cell layers of the epidermis upon exposure to ultraviolet light B (UVB). 7-Dehydrocholesterol is converted to the intermediate predicament D3. When isolated skin is exposed to UVB radiation (Memory Booster: UVB BUILDS BONES), a plateau in previtamin D3 synthesis is reached when about 15 percent of the original dehydrocholesterol has been utilized. Further exposure leads to the conversion of previtamin D3 to two biologically-inactive isomers: lumisterol3 and lachysterol3.
    • B. The mechanical properties of the skin depend mainly on the dermis. This is achieved by the collagen and elastic fibers as well as the ground substance. Although the stratum corneum has a relatively high tensile strength, it offers little protection against mechanical forces. The subcutaneous tissue helps by providing a cushion against blunt trauma.
    • D. Hair grows at different rates in different regions of the body. On the human scalp, the daily growth rate is around 0.3 mm. In women, scalp and body hair grows faster and slower, respectively, than in men. The activity of hair follicles is intermittent. Anagen is the active period, which may last for 3 or more years. Telogen is the resting phase, usually lasting about 3 months. Catagen is the transition or regression phase, usually approximately 3 weeks in duration. In the human scalp, at any one point in time, approximately 84 percent of hair is in anagen, 14 percent in telogen, and 2 percent in catagen. Assuming that the scalp contains about 100,000 hairs, it can reasonably be expected that 100 hairs will be shed daily. Histologically, the hair follicle consists of three parts: the lower portion, which extends from the base of the follicle to the insertion of the arrector pili muscle; the isthmus, which extends from the insertion of the arrector pili muscle to the entrance of the sebaceous duct; and the infundibulum, which extends from the entrance of the sebaceous duct to the follicular orifice.
    • B. Parakeratosis refers to retention of nuclei by keratinocytes in the horny layer, usually associated with an underdeveloped or absent granular cell layer. It is physiologic in mucous membranes. The pattern of parakeratosis may be helpful diagnostically. In psoriasis for example, it is focal and scattered.
    • E. Langhans giant cells are multinucleated giant cells often found in allergic granulomas. In general, they are smaller than foreign body giant cells and often show a peripheral horseshoe, rather than irregular, arrangement of their nuclei. Touton giant cells, often found in juvenile xanthogranuloma (JXG), display a wreath of nuclei adjacent to a rim of foamy cytoplasm. Osteoclastic giant cells look similar to enlarged osteoclasts, with an eosinophilic cytoplasm and very high number of nuclei (at times > 50). They are typically found in giant cell tumor of tendon sheath. Floret giant cells are typically found in pleomorphic lipoma and have characteristic, overlapping peripherally placed nuclei, much like the petals of a flower.
    • E. A major function of the skin is to protect the body, be it against mechanical injury, radiation, fluid loss, or penetration of unwanted material. The barrier to inward or outward passage of water and electrolytes resides mainly in the epidermis and more specifically in the stratum corneum. This is achieved by the tight packaging of the cornified cells as well as by the lipid-rich intercellular material produced by the Odland bodies. The barrier properties of the skin vary, depending on the permeability constant of the substance involved (permeability constant equals the ratio of flux to the concentration applied), body site, age, and environmental conditions.18
    • A. SLE manifestations are immune complex mediated hypersensitivity. Other options are correctly matched. Other type 3 reactions can be dermatomyositis, ENL, and infective endocarditis.
    • B. Grattage test and Auspitz's sign is positive when slight scratching or curetting of a scaly lesion reveals initially fine candle wax scales followed by red Berkley's memb. This then gets removed to reveal punctate bleeding points(Auspitz's sign) within the lesion which suggests of psoriasis. Carpet Tack Sign: or carpet en tack sign: removal of adherent scales in DLE reveals downward projection of scales which are follicular plugs. Buttonholing sign: is seen in neurofibromatosis 1 lesions of skin where when pressed at the center of lesion the whole lesion disappears under the skin as if has passed through the buttonhole. Pityriasis rubra pilaris can have characteristic Nutmeg Grater on feeling the rough, hyperkeratotic, acuminate papules.
    • A. Sub-clinical genital HPV infection can be detected by applying glacial acetic acid to the suspected areas which turns them white visible areas. It does not detect aggressive, precancerous or infected warts.
    • C. Tinea capitis is caused by dermatophytes of Microsporum and Trichophyton genera. Most of Trichophyton species do not fluoresce under woods lamp while the Microsporum do. [Mem Booster: Trees do not move and Trichophyton do not fluoresce]. The green fluorescence of hair is caused due to pteridine residues. Rarely, some Trichophyton species give fluorescence, e.g. T. schoenleinii gives blue fluorescence.
    • D. Acantholysis is the process of detachment of epidermal cells from one another. It is primary if it is due to primary disorders of desmosomes, e.g. Pemphigus, Darier's disease, Hailey-hailey disease. However, if other diseases damage the desmosomes indirectly they can lead to clefting again a process called secondary acantholysis e.g. Burns, trauma, Herpetic infections, Toxic epidermal necrolysis etc.
    • B. Patch testing should be examined at 48 and 96 hours i.e. on 1st day apply → 3rd day remove disk and examine within an hour → examine again on 5th day for delayed sensitivities.
    • D. Woods' lamp is a lamp with a filter made of Nickel Oxide and Barium Silicate that emits radiations at a peak of 365 nm (Black light → MEM Booster:: Now Only Black Shines).