A Comprehensive Review of Major Skin Disorders: Etiology, Pathophysiology and Management

The skin is the body’s largest and one of its most functionally complex organ, covering an average surface area of approximately 2 square meters, with a thickness of about 1.2 mm and contributing nearly 16% of total body weight. Its structural organization enables it to perform multiple essential functions that preserve homeostasis and protect the body from environmental hazards. As a defensive barrier, the skin shields internal tissues from harmful physical, mechanical, and chemical insults while limiting the entry of microbes, allergens, and irritants. Beyond its protective role as a physical and chemical barrier, the skin also regulates transepidermal water loss, prevents dehydration, participates in thermoregulation through sweat production and vasomotor responses, synthesizes vitamin D upon ultraviolet (UV) exposure, and houses sensory receptors that facilitate tactile, thermal, and pain perception.

A remarkable characteristic of the skin is its innate ability to regenerate and repair itself due to the continuous proliferation of epidermal keratinocytes. However, despite its resilience, the skin remains highly vulnerable to a wide variety of disorders because of its constant exposure to environmental factors, infectious agents, allergens, toxins, and ultraviolet radiation. Internal factors such as genetic susceptibility, hormonal imbalances, immune system alterations, and metabolic dysfunction further contribute to the development of numerous dermatological diseases ^[1,2,3].

Skin is categorized into two distinct types:

• Glabrous (non-hairy) skin found on the palms and soles, which is structurally thicker and designed for enhanced mechanical resistance.
• Hair-bearing skin, which covers the majority of the body and contains hair follicles and sebaceous glands. Most dermatological conditions—including acne, folliculitis, and several inflammatory diseases—primarily involve hair-bearing skin due to its glandular and follicular components ^[4].

Infectious skin and soft-tissue diseases constitute one of the most commonly encountered conditions in clinical practice. These include bacterial infections such as cellulitis, erysipelas, impetigo, and deeper conditions such as necrotizing fasciitis; viral infections such as herpes simplex and herpes zoster; fungal infections like dermatophytosis and candidiasis; and parasitic infestations such as scabies. These conditions vary considerably in presentation, severity, and underlying pathology, with some infections associated with systemic symptoms such as fever. The incidence of several skin infections has significantly increased over recent decades, placing a substantial burden on healthcare systems ^[5-12].

The differential diagnosis of skin lesions is often complex because many infectious and non-infectious conditions can produce similar presentations, and a single disorder may manifest with multiple lesion types. Accurate identification of the underlying cause is therefore crucial for appropriate management ^{[13, 14, 15, 16, 17]}.

Dermatological therapy encompasses a wide spectrum of approaches, including topical treatments, systemic medications, physical and light-based therapies, and surgical interventions. As the skin serves as the initial barrier against ultraviolet radiation, pathogens, chemicals, and allergens, many conditions are linked to disruptions in epidermal function. The epidermis comprises keratinocytes, melanocytes, Langerhans cells, gamma delta T-lymphocytes, and Merkel cells, each contributing uniquely to structural integrity, pigmentation, immune defence, and sensation ^[11,12].

SKIN ANATOMY ^[16-19]

Skin anatomy forms the structural and functional foundation for understanding dermatological disorders. The architectural organization of the skin determines how it responds to external stimuli, withstands mechanical forces, and maintains internal physiological balance. A clear understanding of this structure is crucial to interpreting how abnormalities or dysfunctions in specific layers contribute to disease development. With this perspective, the following section provides a detailed explanation of the two primary layers central to most skin conditions: the epidermis and the dermis.

EPIDERMIS

The epidermis is the outermost protective layer of the skin. It forms the body's primary barrier against the external environment and is the first tissue encountered in most dermatological conditions. This layer is responsible not only for providing physical protection but also for determining visible skin characteristics, including complexion and pigmentation.

The epidermis is approximately 0.01 cm thick, though this thickness varies across body regions. Despite its relatively small thickness, the epidermis plays a critical role in maintaining skin integrity through a highly organized system of cell types and layers.

Figure 1: An anatomy of human skin layers

Cellular Composition of the Epidermis

The epidermis comprises a specialized arrangement of cells, each contributing to barrier function, pigmentation, immunity, and sensation. These include:

1. Keratinocytes

Keratinocytes make up 90–95% of the epidermal population. Their primary role is to synthesize keratin, a fibrous structural protein that provides strength and resilience. These cells originate in the basal layer and gradually migrate upward through the epidermal layers. During this journey, keratinocytes undergo morphological and biochemical changes, culminating in the formation of flattened, dead corneocytes in the stratum corneum.

2. Melanocytes

Melanocytes originate from the neural crest and reside predominantly in the basal layer. Their main function is to produce melanin, the pigment responsible for skin color. Melanin is synthesized within specialized organelles called melanosomes and transferred to surrounding keratinocytes. Two major forms of melanin—eumelanin (dark pigment) and pheomelanin (light pigment)—contribute to individual skin tone variation and UV protection.

3. Langerhans Cells

These dendritic immune cells function as antigen-presenting cells. They play a key defensive role by recognizing and internalizing foreign antigens encountered at the epidermal surface and initiating immune responses when pathogenic organisms or irritants penetrate the skin barrier.

4. Merkel Cells

Merkel cells are mechanoreceptors located within the basal layer. They interact with nerve endings to mediate tactile stimuli and are particularly important for fine-touch sensitivity.

Layered Organization of the Epidermis

The epidermis is composed of five distinct layers arranged from superficial to deep:

1. Stratum Corneum

The outermost layer consisting of dead, flattened corneocytes embedded in a lipid matrix. This layer serves as the main barrier against water loss and external chemical or microbial attack.

2. Stratum Lucidum

A thin, translucent layer found primarily in thick skin areas such as the palms and soles.

3. Stratum Granulosum

Characterized by keratinocytes containing keratohyalin granules, which are essential for keratin formation and barrier function.

4. Stratum Spinosum

Composed of polygonal keratinocytes connected by desmosomes, contributing to skin strength and flexibility.

5. Stratum Basale

The deepest layer containing proliferative keratinocytes, melanocytes, Merkel cells, and early-stage Langerhans cells. This is the regenerative zone responsible for replenishing the epidermal layers.

Keratinocytes continuously transition from the basal layer to the stratum corneum, undergoing differentiation processes that include lipid formation, protein synthesis, and eventually programmed cell death. This epidermal turnover cycle varies among individuals and can be influenced by age, disease, environmental exposure, and skincare practices.

DERMIS ^[20,21]

The dermis is the middle and structurally robust layer of the skin. It lies beneath the epidermis and above the hypodermis (subcutaneous tissue). The dermis provides the skin with strength, elasticity, and mechanical resistance due to its extensive network of collagen fibers, elastic fibers, and extracellular matrix.

Structural Components of the Dermis

1. Collagen Fibers

Collagen, particularly type I and III, is the main structural protein in the dermis. Its abundance provides tensile strength, preventing the skin from tearing under pressure or stretching forces.

2. Elastic Fibers

Elastic fibers contribute to the skin’s flexibility and allow it to return to its original shape after deformation. Although present in smaller quantities compared to collagen, elastin is essential for maintaining youthful skin properties.

3. Extrafibrillar Matrix

This matrix includes proteoglycans and glycosaminoglycans that attract and retain water, contributing to skin hydration and turgor.

4. Vascular and Neural Networks

The dermis contains an extensive system of blood vessels that supply nutrients to both the dermis and epidermis. It also houses nerve endings involved in sensations such as touch, pain, heat, and vibration.

5. Immune Cells

Fibroblasts, mast cells, macrophages, and other immune components reside in the dermis, contributing to wound healing, inflammatory responses, and defense mechanisms.

Dermal Subdivisions

The dermis is divided into two main layers:

1. Papillary Dermis

• Located directly beneath the epidermis, contains loose connective tissue, rich in capillaries and sensory receptors.

2. Reticular Dermis

• Thicker and denser, contains tightly packed collagen fibers, provides the bulk of the skin’s mechanical strength.

Biomechanical Properties

Research on dermal biomechanics demonstrates that the skin exhibits nonlinear elastic behaviour, meaning it stretches easily under low tension but becomes increasingly resistant under higher stress. Collagen fibers realign and straighten during stretching, accounting for this pattern. Studies have shown that the Young’s modulus of human dermis is significantly lower than that of materials such as rubber, highlighting its compliant nature.

INFECTIOUS SKIN DISEASES

Infectious skin diseases represent a major portion of dermatological conditions encountered in clinical practice. They are caused by a diverse range of microorganisms including bacteria, viruses, fungi, and parasites. These infections may remain superficial or spread deeper into the dermis and subcutaneous tissues, occasionally becoming systemic. Their clinical presentation varies widely—from localized lesions to generalized rashes accompanied by fever—making diagnosis and management both crucial and challenging.

In recent decades, the incidence of skin and soft tissue infections (SSTIs) has risen significantly, with some studies reporting an increase of up to 65%, partly due to changes in pathogen resistance patterns, lifestyle behaviors, and comorbid conditions such as diabetes and immunosuppression. SSTIs encompass a broad spectrum of conditions, including cellulitis, erysipelas, impetigo, abscesses, necrotizing fasciitis, and infections following trauma or bites.

A major diagnostic challenge is that infectious and non-infectious dermatological conditions often share similar visual features, making clinical differentiation difficult. Additionally, a single disorder may present with multiple types of lesions due to the limited range of morphological manifestations the skin can produce in response to stimuli.

Below, each category of infectious disease is discussed in detail.

A. BACTERIAL INFECTIONS

Bacterial infections of the skin vary in depth, severity, and etiological agents. Common bacterial pathogens include Staphylococcus aureus, including methicillin-resistant strains (MRSA), and Streptococcus pyogenes.

1. Impetigo

A highly contagious superficial infection characterized by honey-colored crusts, most commonly affecting children. It often arises following minor skin trauma or insect bites.

2. Cellulitis

A deeper infection involving the dermis and subcutaneous tissue, typically presenting with warmth, swelling, pain, and erythema. Fever is common, and rapid progression may occur. Cellulitis frequently results from breaches in the skin barrier, such as wounds or fissures.

3. Erysipelas

A form of cellulitis involving the upper dermis and superficial lymphatics, characterized by sharply demarcated erythematous plaques. It is commonly associated with Streptococcus species.

4. Folliculitis

Inflammation and infection of the hair follicles, presenting as small pustules. It may progress to deeper infections.

5. Furuncles and Carbuncles

• Furuncles (boils) are deeper follicular infections leading to abscess formation.
• Carbuncles are clusters of interconnected furuncles, often accompanied by systemic symptoms.

6. Abscesses

Localized collections of pus within the dermis or deeper tissue layers, typically requiring drainage.

7. Traumatic or Bite-Related Infections

Human or animal bites frequently introduce polymicrobial flora, leading to complicated infections involving both aerobic and anaerobic organisms.

8. Necrotizing Fasciitis & Fournier Gangrene

Severe, rapidly progressive infections involving the fascia, associated with high mortality. Early recognition and aggressive intervention are essential.

9. Leprosy (Hansen’s Disease)

A chronic granulomatous infection caused by Mycobacterium leprae. It affects skin, peripheral nerves, and mucosal surfaces. Manifestations range from hypopigmented patches with sensory loss to nodular and diffuse skin thickening. Disease type depends on host immune response.

B. VIRAL INFECTIONS

Viral pathogens commonly affect the skin and may cause localized or widespread manifestations.

1. Herpes Simplex Virus (HSV)

• HSV-1: Primarily associated with orolabial lesions (cold sores).
• HSV-2:Typically causes genital lesions.

Both viruses establish latency in sensory ganglia and may reactivate during stress, illness, or immunosuppression.

2. Herpes Zoster (Shingles)

Reactivation of varicella-zoster virus (VZV) produces painful vesicles distributed along a dermatome. Post-herpetic neuralgia is a common complication.

3. Warts

Caused by human papillomavirus (HPV), warts may appear on hands, feet, face, or genital areas. Over 100 HPV types exist, each associated with distinct lesion morphologies.

4. Molluscum Contagiosum

A poxvirus infection presenting as small dome-shaped papules with central umbilication. It spreads through direct contact and is common in children and immunocompromised individuals.

C. FUNGAL INFECTIONS

Fungal infections are classified as superficial, cutaneous, or systemic, depending on tissue depth.

1. Dermatophytosis (Ringworm)

Caused by fungi of the genera Trichophyton, Microsporum, or Epidermophyton.
Common types include:

• Tinea corporis (ringworm), tinea pedis (athlete’s foot), tinea cruris (jock itch), tinea capitis (scalp ringworm)

These infections thrive in warm, moist environments and frequently recur.

2. Yeast Infections (Candidiasis)

Candida species cause intertrigo, oral thrush, and genital infections. They particularly affect individuals with diabetes, obesity, or compromised immunity.

D. PARASITIC SKIN DISEASES

Parasitic organisms can invade or reside on the skin, causing intense inflammation, itching, and sometimes secondary infections.

1. Scabies

Caused by the mite Sarcoptes scabiei, which burrows into the skin to lay eggs. This results in severe itching, especially at night, and characteristic burrow lines.

2. Pediculosis (Lice Infestations)

Includes infestation of:

• Scalp (Pediculus humanus capitis)
• Body (Pediculus humanus corporis)
• Pubic region (Pthirus pubis)

Lice feed on human blood and cause itching, irritation, and excoriations.

3. Cutaneous Larva Migrans

A condition caused by hookworm larvae penetrating the skin. It presents with serpiginous, migrating tracks and intense itchiness.

E. DIAGNOSTIC COMPLEXITY IN INFECTIOUS DISEASES

Because many infectious and non-infectious disorders share overlapping clinical signs—such as rashes, papules, vesicles, or erythema—accurate diagnosis requires careful evaluation. Diagnostic difficulty arises from:

• Limited number of lesion morphologies, similar appearance of different etiologies, multifactorial presentations, systemic symptoms that mimic non-infectious conditions

Certain febrile illnesses, for instance, present with exanthems where rash + fever may indicate viral infections, drug reactions, or autoimmune flare-ups.

INFLAMMATORY AND AUTOIMMUNE SKIN DISEASES

Inflammatory and autoimmune skin diseases are among the most prevalent chronic dermatological conditions. They arise from complex interactions involving genetic predisposition, epidermal barrier defects, environmental triggers, microbial imbalance, and dysregulated immune responses. These disorders are often characterized by recurrent or persistent inflammation, altered keratinocyte activity, and immune cell infiltration, which together produce visible skin changes such as redness, scaling, thickening, itching, and pigmentary alterations.

A notable feature of inflammatory skin diseases is that the clinical manifestations often overlap, making differential diagnosis challenging. Many disorders exhibit combinations of erythema, papules, vesicles, plaques, scaling, or excoriations. Additionally, these diseases frequently worsen in response to triggers such as stress, allergens, infections, hormonal fluctuations, and climatic changes.

Below is a detailed discussion of major inflammatory and autoimmune conditions.

A. ECZEMA / ATOPIC DERMATITIS (AD) ^[22]

Atopic dermatitis is a chronic, relapsing inflammatory skin disorder characterized by intense pruritus, xerosis, and eczematous lesions. It is commonly associated with other atopic conditions such as allergic rhinitis and asthma.

Figure 2: Atopic dermatitis

Etiology

AD is multifactorial and involves:

1. Epidermal barrier dysfunction
   • Primarily due to filaggrin gene (FLG) mutations, which impair stratum corneum integrity, leads to increased transepidermal water loss, allows allergens, irritants, and microbes to penetrate more easily.
2. Immune dysregulation
   • Dominance of Th2-mediated immune responses, elevated levels of IL-4, IL-5, IL-13.

Clinical Features

• Xerosis (dry skin), erythematous patches, thickened, lichenified plaques in chronic stages, severe itching, often worsening at night, lesions vary by age group (flexural in adults, facial in infants).

B. ALOPACIA ^[23]

One of the more common dermatologic complaints seen by dermatologists and primary care physicians is alopecia or hair loss. The term pattern hair loss (PHL). Coverup techniques can be effective and there are many nonmedical treatments for PHL such as platelet-rich plasma injection, hair transplantation, or laser/light treatment.

Figure 3: Alopecia

C. PSORIASIS

Psoriasis is an immune-mediated disorder characterized by hyperproliferation of keratinocytes and chronic inflammation. It is driven primarily by Th1 and Th17 pathways, with TNF-α playing a major role.

Pathophysiology

• Excessive keratinocyte turnover (3–5 days instead of 28 days), accumulation of immature corneocytes, formation of erythematous plaques with silvery-white scales.
• Activation of dendritic cells and T lymphocytes, angiogenesis in the dermis contributes to redness and bleeding (Auspitz sign).

Types of Psoriasis

• Plaque psoriasis (most common)
• Guttate psoriasis
• Inverse psoriasis
• Pustular psoriasis
• Erythrodermic psoriasis

Triggers

• Infections (especially streptococcal), stress, medications (β-blockers, NSAIDs, lithium), trauma (Koebner phenomenon)

C. SEBORRHEIC DERMATITIS

A chronic inflammatory disease affecting sebaceous gland-rich areas (scalp, face, chest). It is associated with:

• Overgrowth of Malassezia yeast, altered immune response, excess sebum production

Features

• Greasy scales, itchy, erythematous patches, dandruff in mild cases

D. CONTACT DERMATITIS

Occurs when skin comes into contact with substances that cause irritation or allergy.

Types

1. Irritant contact dermatitis
   • Caused by chemicals, detergents, acids, solvents, non-immunologic.
2. Allergic contact dermatitis
   • Delayed hypersensitivity (Type IV reaction), common allergens: nickel, fragrances, dyes, rubber compounds, symptoms appear 24–72 hours after exposure.

E. AUTOIMMUNE SKIN DISEASES

These conditions occur when the immune system mistakenly targets skin components.

1. Lupus Erythematosus (Cutaneous Lupus)

Characterized by:

• Photosensitivity, discoid lesions, erythematous plaques with central atrophy, risk of systemic involvement, UV exposure often worsens the disease by inducing autoantigen formation.

2. Dermatomyositis

An inflammatory myopathy with distinctive cutaneous manifestations.

Cutaneous signs

• Heliotrope rash (purple discoloration around eyes)
• Gottron papules on knuckles, poikiloderma

Often associated with muscle weakness and systemic abnormalities.

3. Scleroderma

A connective tissue disorder involving excessive collagen deposition.

Cutaneous features

• Skin thickening, reduced elasticity, raynaud phenomenon, digital ulcers

4. Vitiligo (Autoimmune Melanocyte Destruction)

Vitiligo is a pigmentary autoimmune condition, but your text places it partly under inflammatory disorders so it is included here as well.

Pathogenesis

• Autoimmune destruction of melanocytes
• Dysfunction of T-cells and cytokines
• Oxidative stress contributing to melanocyte apoptosis

Clinical Presentation

• Well-demarcated depigmented macules, often symmetrical, frequently begins on face, hands, or joints

F. PERIORIFICIAL DERMATITIS

A chronic inflammatory facial condition affecting the perioral, perinasal, and periocular areas.

Etiology

Often triggered by:

• Prolonged topical steroid use, fluorinated toothpaste, heavy cosmetics, sunscreens, prolonged mask-wearing.

Clinical Features

• Clusters of erythematous papules, burning or tight sensation, sparing of the immediate vermilion border around lips.

Figure 4: Periorificial dermatitis

Management

“Zero therapy” — stopping all irritants, especially topical steroids — is a core part of treatment.

ACNE VULGARIS ^[24-29]

Acne vulgaris is one of the most common dermatological disorders, affecting adolescents, young adults, and in many cases, persisting into adulthood. Although traditionally viewed as a self-limited condition of puberty, acne is now recognized as a chronic inflammatory disorder of the pilosebaceous unit. Its development is influenced by a combination of hormonal, microbial, genetic, environmental, and immunological factors. Acne often involves the face, chest, shoulders, back, and upper arms—regions with high densities of sebaceous glands.

The condition has a significant impact on psychological well-being, social functioning, and self-esteem. Persistent or severe acne can lead to permanent scarring, making early recognition and intervention essential.

Figure 2: The process of acne formation on the skin

A. ETIOLOGY OF ACNE

Acne results from a coordinated sequence of events affecting the pilosebaceous unit:

1. Increased Sebum Production

One of the earliest changes in acne pathogenesis is androgen-driven sebum overproduction. During puberty, elevated levels of androgens stimulate the sebaceous glands to enlarge and produce excessive sebum.
Key points:

• Androgens such as testosterone and DHT (dihydrotestosterone) increase 5-α-reductase activity, sebum is rich in triglycerides, wax esters, squalene, and free fatty acids excessive sebum creates an ideal environment for microbial proliferation.

2. Follicular Hyperkeratinisation

The normal shedding of keratinocytes at the follicular opening becomes disrupted. Instead of exfoliating, keratinocytes accumulate and mix with sebum, forming a keratinous plug (microcomedone).

This process includes:

• Increased proliferation of keratinocytes, altered differentiation of follicular epithelium
• Reduced desquamation, excess keratin binding to sebum

3. Microbial Colonization by Cutibacterium acnes (C. acnes)

Formerly known as Propionibacterium acnes, this anaerobic bacterium flourishes in lipid-rich environments. Although part of normal skin flora, it becomes pathogenic when conditions inside the follicle change.

C. acnes contribute to acne through:

• Lipase production → breaking down triglycerides into pro-inflammatory free fatty acids, activation of toll-like receptors (TLR-2 and TLR-4), stimulation of cytokines such as IL-1β, IL-8, TNF-α, biofilm formation, which increases inflammation and comedone stability.

Different phylotypes of C. acnes may vary in inflammatory potential.

4. Inflammation

Inflammation is now understood to be present at every stage of acne, even before visible lesions appear. The inflammatory cascade is amplified by:

• Oxidative stress, lipid peroxidation of squalene, neutrophil recruitment, release of proinflammatory cytokines, rupture of follicular walls.

Inflammatory lesions include papules, pustules, nodules, and cysts. Severe inflammation often leads to post-inflammatory hyperpigmentation (PIH) and scarring.

B. TYPES OF ACNE LESIONS

Acne lesions are classified into non-inflammatory and inflammatory types.

1. Non-inflammatory Lesions

• Closed comedones (whiteheads): Follicles blocked completely by keratin and sebum.
• Open comedones (blackheads): Follicular plugs exposed to air where melanin oxidizes.

These lesions form the foundation of acne and indicate abnormal keratinization.

2. Inflammatory Lesions

Inflammatory lesions result from microbial proliferation, immune activation, and follicular rupture:

• • Papules: Red, tender bumps due to localized inflammation.
  • Pustules: Papules containing visible pus due to neutrophil accumulation.
  • Nodules: Large, painful, deep-seated lesions caused by extensive follicular damage and dermal inflammation.
  • Cysts: Deep, fluctuant, pus-filled sacs prone to scarring.

C. FACTORS THAT CONTRIBUTE TO ACNE DEVELOPMENT

1. Hormonal Influences: Puberty-associated androgens, polycystic ovarian syndrome (PCOS), menstrual cycle fluctuations, exogenous hormones or anabolic steroids.

2. Diet: Gradually, scientific evidence supports associations between acne and: High-glycaemic foods (sugary and processed foods), dairy products, whey protein, diets high in saturated fats.

These substances stimulate IGF-1 pathways, enhancing sebum production and keratinocyte proliferation.

3. Stress: Stress increases cortisol secretion, which can exacerbate inflammation and sebum production.

4. Genetics: A strong familial tendency exists. Multiple genes regulate sebum production, inflammatory pathways, and keratinization.

5. Cosmetic and Occupational Factors: Heavy, oily cosmetics (“comedogenic” products), Exposure to greasy environments (mechanics, cooks), occlusive clothing or helmets.

6. Medications: Certain drugs can trigger or worsen acne, including: Corticosteroids, lithium, isoniazid, phenytoin, vitamin B12 (high doses).

D. COMPLICATIONS OF ACNE

1. Scarring

Severe inflammatory acne leads to permanent scars:

• Ice-pick scars, rolling scars, boxcar scars , keloids and hypertrophic scars

2. Pigmentary Changes

• Pro inflammatory hyperpigmentation

3. Psychological Effects

Acne significantly impacts:

• Self-esteem, social confidence
• In some cases, severe acne is linked to depression and anxiety

PIGMENTATION DISORDERS ^[30-33]

Pigmentation disorders represent a group of conditions in which the production, distribution, or survival of melanocytes or melanin is disrupted. Melanin, synthesized by melanocytes in the basal epidermal layer, plays a vital role in determining skin, hair, and eye color and provides protection against ultraviolet (UV) radiation.

Figure 5: Types of pigmented skin

These disorders may arise from:

• Genetic factors, autoimmune reactions, hormonal imbalances
• Environmental triggers, inflammation, post-injury responses

Pigmentation disorders are broadly classified into hypopigmentation (loss or reduction of pigment) and hyperpigmentation (increased pigmentation).

Among the most common and clinically significant pigmentary conditions are Vitiligo, Melasma, and Post-Inflammatory Hyperpigmentation (PIH), each of which is discussed in detail below.

A. VITILIGO ^[34-36]

Vitiligo is a chronic pigmentary disorder characterized by the development of well-defined depigmented macules and patches. It results from the selective destruction or dysfunction of melanocytes, leading to complete absence of melanin in affected areas.

It affects individuals of all ages and ethnicities, with significant psychosocial impact due to changes in appearance.

Etiology and Pathogenesis

Vitiligo arises through a multifactorial process involving:

1. Autoimmune Mechanisms

• Considered the most widely accepted cause, cytotoxic CD8+ T-cells target melanocytes.
• Autoantibodies may also contribute to melanocyte destruction, increased levels of inflammatory cytokines (IL-2, IL-10, TNF-α) observed.

2. Genetic Predisposition

• Strong familial association, over 30 susceptibility genes identified, involving immune pathways and melanocyte function.

3. Oxidative Stress

• Elevated hydrogen peroxide and reactive oxygen species in the epidermis, oxidative stress triggers melanocyte apoptosis, disturbs melanocyte adhesion and melanin synthesis.

4. Neural Hypothesis

• Abnormal release of neurochemical mediators may damage melanocytes in segmental vitiligo.

5. Environmental and Triggering Factors

• Sunburn, chemical exposure, emotional stress, mechanical injury (Koebner phenomenon).

Clinical Features

• Sharply demarcated white patches, segmental form typically unilateral and localized.
• Common sites: face, hands, elbows, knees, feet, and around body orifices, hair in affected areas may turn white (leukotrichia).

Vitiligo often shows unpredictable progression, with periods of stability alternating with rapid spread.

B. MELASMA ^[37]

Melasma is a chronic acquired hyperpigmentation characterized by light-to-dark brown patches, typically occurring on sun-exposed areas such as the face (cheeks, forehead, upper lip). It is more common in women and individuals with darker skin types.

Figure 6: Irregular brown macules of melasma on common parts of the face: upper lip, forehead, cheeks and nose.

Etiology

Melasma results from increased melanin production and deposition. Key contributing factors include:

1. Ultraviolet Exposure

• UV-A and UV-B stimulate melanocyte activity, induces melanogenesis and oxidizes melanin, triggers inflammation and vascular changes.

2. Hormonal Influences

• Pregnancy (chloasma), oral contraceptives, hormone replacement therapy, elevated estrogenb and progesterone levels stimulate melanocyte activity.

3. Genetic Predisposition

• Familial tendency commonly noted, more prevalent among individuals with Fitzpatrick skin types III–V.

4. Phototoxic and Cosmetic Products

Some perfumes, oils, and skin-care products irritate the skin, worsening pigmentation.

5. Thyroid Disorder Associations

Hypothyroidism or autoimmune thyroid disease may influence melanocyte sensitivity.

Clinical Presentation

Melasma appears as:

• Symmetric, irregularly bordered brown macules
• Common patterns include:
  • Centrofacial (most common), malar, mandibular

The condition is chronic, often exacerbated by sunlight and heat, and has a tendency to relapse.

C. POST-INFLAMMATORY HYPERPIGMENTATION (PIH)

PIH is an acquired condition where inflammation or injury to the skin triggers excess melanin production, leading to dark discoloration.

Causes

PIH can follow:

• Acne lesions, eczema, psoriasis, burns, insect bites, trauma or cosmetic procedures allergic reactions, aggressive skin products.

In darker skin types (IV–VI), PIH is especially common and often more intense.

Pathogenesis

Inflammatory mediators—such as prostaglandins, leukotrienes, and cytokines—stimulate melanocytes to increase melanin production. Depending on the depth of melanin deposition:

• Epidermal PIH appears brown and tends to fade gradually
• Dermal PIH appears gray-brown and persists longer

The condition worsens with UV exposure because inflammation increases melanocyte sensitivity to sunlight.

Clinical Features

• Flat brown macules or patches, occur in areas where inflammation has resolved, more noticeable after acne flare-ups, may take months to years to fade if deep

WOUND HEALING AND IMPAIRED WOUND REPAIR ^[38,39]

Wound healing is a vital biological process that restores the structural and functional integrity of skin after injury. This complex sequence involves coordinated interactions among cells, extracellular matrix components, cytokines, chemokines, growth factors, and the vascular system. A normal wound-healing response progresses through four well-defined phases: haemostasis, inflammation, proliferation, and remodelling. Disruption in any of these stages can result in chronic non-healing wounds, abnormal scarring, or delayed tissue repair.

Wound healing can be influenced by systemic conditions (such as diabetes, age, nutritional status, vascular insufficiency, and immune disorders) as well as local factors (infection, repeated trauma, skin tension, and improper wound care).

A. PHASES OF NORMAL WOUND HEALING

Wound healing follows a highly regulated, overlapping sequence of events.

1. Haemostasis Phase

This phase begins immediately after injury.

• Vasoconstriction minimizes blood loss, platelet aggregation occurs at the injury site.
• Platelets release growth factors such as PDGF (platelet-derived growth factor) and TGF-β (transforming growth factor-beta), which launch the repair cascade.

The hemostatic plug also acts as a reservoir of cytokines that regulate later stages.

2. Inflammatory Phase

This phase clears pathogens and debris from the wound bed.

Key events:

• Vasodilation increases blood flow, mediated by histamine and nitric oxide.
• Neutrophils are first responders, eliminating microbes through phagocytosis.
• Macrophages follow and play a central role by:
  • Clearing debris, releasing cytokines (IL-1, TNF-α), guiding fibroblasts and endothelial cells toward the wound, transitioning the wound into the proliferative phase.

This phase typically lasts 2–3 days, but can extend longer in infected or chronic wounds.

3. Proliferative Phase

The proliferative phase restores tissue continuity and involves:

A. Fibroblast Activation

• Fibroblasts migrate into the wound bed and synthesize collagen (primarily type III), glycosaminoglycans, and proteoglycans.

B. Angiogenesis

• New blood vessels form through endothelial cell proliferation.
• Essential growth factors: VEGF, FGF, TGF-β.

C. Granulation Tissue Formation

• Pink, vascularized tissue composed of fibroblasts, new vessels, and extracellular matrix.
• Serves as a foundation for epithelial migration.

D. Re-epithelialization

• Keratinocytes proliferate at the wound edges and migrate across the wound surface.
• Re-establishes the epidermal barrier.

4. Remodelling (Maturation) Phase

This final phase may last months to years.

Major changes include:

Replacement of type III collagen with type I collagen, cross-linking and alignment of collagen fibers, increase in wound tensile strength (though healed wounds reach only ~80% of original strength), reduction in blood vessels and cellularity as scar matures, abnormalities during this phase can lead to hypertrophic scars or keloids.

B. IMPAIRED WOUND HEALING

When any component of the healing cascade is disrupted, wounds may heal slowly or incompletely, leading to chronic non-healing wounds.

Impaired wound healing may result from:

1. Systemic Factors

Diabetes Mellitus: High glucose levels impair neutrophil activity, reduced collagen synthesis, poor microcirculation, increased susceptibility to infection.

Advanced Age: Slower keratinocyte migration, reduced fibroblast activity, lower angiogenic response

Malnutrition: Deficiencies in proteins, vitamins (A, C, E), and minerals (zinc, iron) delay repair.

Immunosuppression: Due to medications, HIV, or systemic disease → decreases inflammatory response.

2. Local Factors

Repetitive Trauma or Pressure: Seen in pressure ulcers or wounds over bony prominences.

Hypoxia: Poor oxygenation impairs fibroblast function and collagen synthesis.

Excessive Wound Exudate: Breaks down the extracellular matrix and delays re-epithelialization.

C. ROLE OF PEPTIDES IN WOUND HEALING (FROM YOUR ORIGINAL TEXT)

Recent research highlights the promising role of therapeutic peptides in accelerating wound repair. These peptides may:

• Stimulate fibroblast proliferation, enhance collagen deposition, increase angiogenesis.
• Promote keratinocyte migration, reduce oxidative stress in the wound bed.

Examples include:

• Growth factor–mimicking peptides
• Antimicrobial peptides
• Matrix-modulating peptides

Their capabilities make them potential candidates for new wound care treatments.

Figure 7: Cyclic peptides as wound healing compounds

D. CLINICAL SIGNIFICANCE

Understanding wound healing is essential because:

Chronic wounds are major health burdens, diabetic ulcers, venous ulcers, and pressure sores lead to high morbidity, early identification of impaired healing improves outcomes, advanced therapies (peptides, growth factors, biomaterials) rely on a clear grasp of underlying mechanisms.

KUSHTHA (AYURVEDIC PERSPECTIVE ON SKIN DISORDERS)

In Ayurveda, skin diseases are collectively described under the umbrella term “Kushtha.” This term encompasses a wide spectrum of dermatological conditions, ranging from mild discolorations to chronic, deeply seated, and debilitating skin disorders. Classical Ayurvedic texts describe Kushtha as a pathological state arising from vitiation of the three fundamental doshas—Vata, Pitta, and Kapha—along with disturbances in essential body tissues (Dhatus) and waste products (Malas).

Ayurvedic literature identifies Mahakushta (major skin disorders) and Kshudra Kushtha (minor skin disorders), based on severity, chronicity, and involvement of tissues. Although the exact correlation between Ayurvedic descriptions and modern dermatological conditions varies, the fundamental principles emphasize internal imbalance, lifestyle factors, diet, and environmental exposures as key triggers for skin disease.

Figure 8: Kustha

A. ETIOLOGY OF KUSHTHA ^[40,41]

Ayurveda attributes the origin of Kushtha to a combination of dietary, behavioral, environmental, and constitutional factors. These causative elements disturb the normal functioning of doshas and dhatus, leading to pathological skin manifestations.

1. Dietary Causes (Ahara)

Certain foods and dietary habits are considered potent triggers for Kushtha:

• Excessive intake of incompatible foods (Viruddha Ahara)
• High consumption of oily, heavy, or unctuous foods

These dietary practices impair metabolism and digestion, leading to toxin accumulation (Ama) in the body.

2. Behavioral Causes (Vihara)

• Excessive sleep during the day
• Sedentary lifestyle

Such behaviors disrupt doshic balance and affect skin integrity.

3. Psychological Factors

Emotional disturbances, particularly chronic stress, fear, grief, and anger, are believed to aggravate doshas and weaken immune defenses, contributing to the onset and persistence of skin diseases.

4. Environmental Contributors

Exposure to extremes of climate, polluted surroundings, or contaminated water and soil are recognized as aggravating elements that disturb the skin’s natural protective functions.

B. PATHOGENESIS OF KUSHTHA (SAMPRAPTI)

The pathogenesis involves:

1. Vitiation of Tridoshas:
   • Vata → dryness, scaling, pitta → redness, burning, inflammation, kapha → thickening, oozing.
2. Impaired digestive fire (Agni) → formation of Ama (toxins)
3. Circulation of toxins throughout the body, settling in the skin and peripheral tissues
4. Obstruction of channels (Srotas)—especially   which carry plasma and blood.
5. Gradual impairment of Dhatus
   • Rasa (nutrient fluid), rakta (blood), mamsa (muscle), lasika (lymph).

A combination of these events results in chronic, recurrent skin conditions that are difficult to treat without addressing the root imbalance.

C. TYPES OF KUSHTHA

Ayurvedic classics categorize Kushtha into two broad divisions:

1. Mahakushta (Major Skin Disorders): These are severe, deeper, and chronic disorders involving multiple tissues and intense doshic imbalance.

2. Kshudra Kushtha (Minor Skin Disorders): These are milder and more superficial conditions with less systemic involvement.

Although the texts describe 18 types of Kushtha, specific classification varies among classical treatises.

D. CLINICAL FEATURES OF KUSHTHA

A wide variety of symptoms may appear depending on doshic dominance:

Vata-dominant Kushtha

• Dryness, rough patches, fissuring, scaling, painful lesions.

Pitta-dominant Kushtha

• Redness, burning sensation, inflammation, oozing, feverishness.

Kapha-dominant Kushtha

• Thickened skin, swelling, pale or whitish patches, heaviness, itching.

Most skin disorders in Kushtha manifest as combinations of these features, reflecting mixed dosha involvement.

E. MANAGEMENT OF KUSHTHA

Ayurvedic management emphasizes treating both the root cause and clinical manifestations through internal purification, external applications, and sustainable lifestyle modifications.

1. Nidan Parivarjana (Avoidance of Causative Factors):

Avoid incompatible foods, reduce oily, heavy meals, avoid day-time sleeping, correct sedentary habits, minimize exposure to irritants.

Eliminating such triggers supports restoration of normal doshic balance.

2. Shodhana (Purification Therapy)

These detoxification procedures remove toxins and deeply seated doshic imbalances:

• • Vamana (therapeutic emesis): Useful in Kapha-dominant skin disorders
  • Virechana (purgation therapy): Most effective in Pitta-related conditions such as inflammation and redness
  • Raktamokshana (bloodletting): Indicated when Rakta (blood) is vitiated

These therapies are performed under professional supervision.

3. Shamana (Palliative Therapy)

Aim to balance doshas without intense purification:

• Herbal formulations, decoctions (Kashayas).
• Grates (medicated ghee preparations), tailas (medicated oils), churnas (powders).

Popular formulations include:

• Mahatikta Ghrita — anti-inflammatory and detoxifying
• Mustadi Churna — purifies blood and promotes healing
• Kushthadi Taila — used for external application

4. External Therapies (Bahya Chikitsa)

Ayurvedic external therapies help reduce inflammation, itching, and scaling:

• Lepa (herbal pastes), abhyanga (medicated oil massage), pariseka (warm decoction pouring), udwartana (powder massage).

These treatments soothe the skin and improve circulation.

SKIN CANCERS ^[42-43]

Skin cancer refers to the abnormal, uncontrolled growth of skin cells, primarily triggered by DNA damage and mutations—most commonly caused by ultraviolet (UV) radiation from sunlight or artificial sources. It represents one of the most common malignancies worldwide. Skin cancer is broadly classified into melanoma and non-melanoma skin cancers (NMSCs), each with distinct biological behavior, risk factors, molecular pathways, and prognosis.

Melanoma is the most aggressive form, arising from melanocytes, whereas non-melanoma cancers—mainly basal cell carcinoma (BCC) and squamous cell carcinoma (SCC)—originate from keratinocytes. Each type involves different molecular mechanisms, with several signaling pathways implicated in tumor initiation, proliferation, angiogenesis, and metastasis.

Figure 9: Types of skin cancer