Vitiligo (Clinical)

Definition and Epidemiology

Definition

Vitiligo Vitiligo Vitiligo is the most common depigmenting disorder and is caused by the destruction of melanocytes. Patients present with hypo- or depigmented macules or patches which often occur on the face, hands, knees, and/or genitalia. Vitiligo is a progressive skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions condition in which there is destruction of melanocytes Melanocytes Mammalian pigment cells that produce melanins, pigments found mainly in the epidermis, but also in the eyes and the hair, by a process called melanogenesis. Coloration can be altered by the number of melanocytes or the amount of pigment produced and stored in the organelles called melanosomes. The large non-mammalian melanin-containing cells are called melanophores. Skin: Structure and Functions resulting in the loss of skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions pigmentation.

Epidemiology^[1]

• Most common cause of depigmentation Depigmentation Vitiligo
• Prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency: 0.1%–2% of the general population
• Occurs in children and adults
• Equal incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency in males and females
• No racial or ethnic predilection
• Age:
  • Onset generally occurs before 30 years of age.
  • Peak incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency: 10–30 years of age

Etiology and Pathophysiology

Etiology^[1,3,8]

The cause of vitiligo Vitiligo Vitiligo is the most common depigmenting disorder and is caused by the destruction of melanocytes. Patients present with hypo- or depigmented macules or patches which often occur on the face, hands, knees, and/or genitalia. Vitiligo is unknown but is postulated to be a result of multiple factors.

• Possible genetic component:
  • Up to 50% of affected individuals have a family history Family History Adult Health Maintenance of the condition
  • Approximately 36 susceptibility loci have been identified for nonsegmental vitiligo Vitiligo Vitiligo is the most common depigmenting disorder and is caused by the destruction of melanocytes. Patients present with hypo- or depigmented macules or patches which often occur on the face, hands, knees, and/or genitalia. Vitiligo.
• May be autoimmune-mediated:
  • Approximately 20% of affected individuals have an autoimmune condition.
  • Associated conditions:
    • Hashimoto’s thyroiditis Thyroiditis Thyroiditis is a catchall term used to describe a variety of conditions that have inflammation of the thyroid gland in common. It includes pathologies that cause an acute illness with severe thyroid pain (e.g., subacute thyroiditis and infectious thyroiditis) as well as conditions in which there is no clinically evident inflammation and the manifestations primarily reflect thyroid dysfunction or a goiter (e.g., painless thyroiditis and fibrous Riedel’s thyroiditis). Thyroiditis
    • Graves’ disease
    • Type 1 Type 1 Spinal Muscular Atrophy diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus mellitus
    • Addison disease
    • Pernicious anemia Pernicious anemia A megaloblastic anemia occurring in children but more commonly in later life, characterized by histamine-fast achlorhydria, in which the laboratory and clinical manifestations are based on malabsorption of vitamin B12 due to a failure of the gastric mucosa to secrete adequate and potent intrinsic factor. Megaloblastic Anemia
    • Alopecia areata Alopecia Areata Loss of scalp and body hair involving microscopically inflammatory patchy areas. Alopecia
    • Psoriasis Psoriasis Psoriasis is a common T-cell-mediated inflammatory skin condition. The etiology is unknown, but is thought to be due to genetic inheritance and environmental triggers. There are 4 major subtypes, with the most common form being chronic plaque psoriasis. Psoriasis
    • Inflammatory bowel disease
  • The presence of antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions to melanin Melanin Insoluble polymers of tyrosine derivatives found in and causing darkness in skin (skin pigmentation), hair, and feathers providing protection against sunburn induced by sunlight. Carotenes contribute yellow and red coloration. Seborrheic Keratosis has been noted.
• Oxidative stress Oxidative stress A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products. Cell Injury and Death: Melanocyte self-destruction may arise from toxic phenolic compounds formed during melanin Melanin Insoluble polymers of tyrosine derivatives found in and causing darkness in skin (skin pigmentation), hair, and feathers providing protection against sunburn induced by sunlight. Carotenes contribute yellow and red coloration. Seborrheic Keratosis synthesis Synthesis Polymerase Chain Reaction (PCR).
• Intrinsic defects of melanocytes Melanocytes Mammalian pigment cells that produce melanins, pigments found mainly in the epidermis, but also in the eyes and the hair, by a process called melanogenesis. Coloration can be altered by the number of melanocytes or the amount of pigment produced and stored in the organelles called melanosomes. The large non-mammalian melanin-containing cells are called melanophores. Skin: Structure and Functions
• Neural hypothesis Hypothesis A hypothesis is a preliminary answer to a research question (i.e., a “guess” about what the results will be). There are 2 types of hypotheses: the null hypothesis and the alternative hypothesis. Statistical Tests and Data Representation: Nerve endings near pigment cells may secrete a neurochemical mediator toxic to melanocytes Melanocytes Mammalian pigment cells that produce melanins, pigments found mainly in the epidermis, but also in the eyes and the hair, by a process called melanogenesis. Coloration can be altered by the number of melanocytes or the amount of pigment produced and stored in the organelles called melanosomes. The large non-mammalian melanin-containing cells are called melanophores. Skin: Structure and Functions.

Pathophysiology^[1,8]

• Destruction, or disappearance, of melanocytes Melanocytes Mammalian pigment cells that produce melanins, pigments found mainly in the epidermis, but also in the eyes and the hair, by a process called melanogenesis. Coloration can be altered by the number of melanocytes or the amount of pigment produced and stored in the organelles called melanosomes. The large non-mammalian melanin-containing cells are called melanophores. Skin: Structure and Functions → loss of pigmentation in the affected area of the skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions
• This process gives the appearance of white patches Patches Vitiligo on the skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions.

Clinical Presentation and Diagnosis

Clinical presentation

Vitiligo Vitiligo Vitiligo is the most common depigmenting disorder and is caused by the destruction of melanocytes. Patients present with hypo- or depigmented macules or patches which often occur on the face, hands, knees, and/or genitalia. Vitiligo results in hypopigmented or depigmented areas.

History^[8,9,11]

• Factors that preceded onset of skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions changes; recent cutaneous trauma ( Koebner phenomenon Koebner Phenomenon Lichen Planus)
• Rate of onset
• Associated symptoms
• Extent, duration, and spread of skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions lesions
• Current medications
• Concomitant diseases
• Occupational exposures
• Family history Family History Adult Health Maintenance of vitiligo Vitiligo Vitiligo is the most common depigmenting disorder and is caused by the destruction of melanocytes. Patients present with hypo- or depigmented macules or patches which often occur on the face, hands, knees, and/or genitalia. Vitiligo and autoimmune disease
• Document psychological impact on quality Quality Activities and programs intended to assure or improve the quality of care in either a defined medical setting or a program. The concept includes the assessment or evaluation of the quality of care; identification of problems or shortcomings in the delivery of care; designing activities to overcome these deficiencies; and follow-up monitoring to ensure effectiveness of corrective steps. Quality Measurement and Improvement of life

Physical Examination^[1,3,8]

• Distribution:
  • Widespread (generalized) with mucosal involvement
  • Segmental (entire body segments)
  • Localized 
• Lesions’ appearance:
  • Sharply demarcated
  • Macules or patches Patches Vitiligo
  • Milky or chalk-white color
• Most commonly affected areas:
  • Face
  • Periorificial areas:
    • Mouth
    • Anus
  • Genitalia
  • Elbows
  • Hands
  • Knees
• Hair in affected areas may also be depigmented ( poliosis Poliosis Blepharitis).

Classification

Vitiligo Vitiligo Vitiligo is the most common depigmenting disorder and is caused by the destruction of melanocytes. Patients present with hypo- or depigmented macules or patches which often occur on the face, hands, knees, and/or genitalia. Vitiligo can be classified based on affected sites and distribution:^[11]

• Nonsegmental vitiligo Vitiligo Vitiligo is the most common depigmenting disorder and is caused by the destruction of melanocytes. Patients present with hypo- or depigmented macules or patches which often occur on the face, hands, knees, and/or genitalia. Vitiligo (NSV; most common)
• Segmental vitiligo Vitiligo Vitiligo is the most common depigmenting disorder and is caused by the destruction of melanocytes. Patients present with hypo- or depigmented macules or patches which often occur on the face, hands, knees, and/or genitalia. Vitiligo (SV)
• Mixed
• Unclassified

Additionally, clinicians will want to assess disease stability:^[9]

• Stable:
  • No new depigmentation Depigmentation Vitiligo developed within the past 12 months, AND
  • Established areas of depigmentation Depigmentation Vitiligo did not progress within the past 12 months.
• Progressive:
  • New areas developed within the past 12 months, OR
  • Established areas progressed within the past 12 months.
• Rapidly progressive:
  • There is no international consensus definition.
  • May consider when there is:
    • Rapid development of new lesions
    • Rapid increase in size of established lesions
• Regressive: Spontaneous repigmentation occurs

Diagnosis^[1,3,8]

The diagnosis is usually clinical. However, the following examinations may be used if the diagnosis is unclear:

• Exam with a Wood lamp:
  • Handheld device that emits ultraviolet (UV) A light
  • Useful in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with pale skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions where vitiligo Vitiligo Vitiligo is the most common depigmenting disorder and is caused by the destruction of melanocytes. Patients present with hypo- or depigmented macules or patches which often occur on the face, hands, knees, and/or genitalia. Vitiligo lesions are more subtle
  • Accentuates hypo- or depigmented areas (appear white)
• Biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma:
  • Can be used to differentiate from other hypopigmented disorders
  • Findings:
    • Absence of melanocytes Melanocytes Mammalian pigment cells that produce melanins, pigments found mainly in the epidermis, but also in the eyes and the hair, by a process called melanogenesis. Coloration can be altered by the number of melanocytes or the amount of pigment produced and stored in the organelles called melanosomes. The large non-mammalian melanin-containing cells are called melanophores. Skin: Structure and Functions
    • Loss of epidermal pigmentation
    • Perifollicular lymphocytic infiltrate may be seen in some patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship.

Management and Prognosis

General management and considerations

No cure is currently available. Management generally aims to slow the progression of the disease and address cosmetic issues. The following is based on US, UK, and European guidelines.

Goals of treatment:

• Rapid stabilization of progressive and progressive disease
• Repigmentation of depigmented patches Patches Vitiligo

Basic measures:^[8,9]

• All patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship should practice sun avoidance and protection:
  • Sun protection factor (SPF) 50 sunscreen Sunscreen Chemical or physical agents that protect the skin from sunburn and erythema by absorbing or blocking ultraviolet radiation. Melanoma for UVA and UVB
  • Consider measuring vitamin D Vitamin D A vitamin that includes both cholecalciferols and ergocalciferols, which have the common effect of preventing or curing rickets in animals. It can also be viewed as a hormone since it can be formed in skin by action of ultraviolet rays upon the precursors, 7-dehydrocholesterol and ergosterol, and acts on vitamin D receptors to regulate calcium in opposition to parathyroid hormone. Fat-soluble Vitamins and their Deficiencies levels in individuals who avoid sun exposure.
• Avoid cutaneous trauma, when possible.
• Thyroid Thyroid The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland: Anatomy function testing should be performed due to the strong association with thyroid Thyroid The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland: Anatomy disease.
  • British Association of Dermatology guidelines recommend screening Screening Preoperative Care for thyroid Thyroid The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland: Anatomy antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions and thyroid Thyroid The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland: Anatomy function.^[9] 
  • US “Choosing Wisely” guidelines recommend against ordering laboratory tests for associated autoimmune diseases Autoimmune diseases Disorders that are characterized by the production of antibodies that react with host tissues or immune effector cells that are autoreactive to endogenous peptides. Selective IgA Deficiency in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with vitiligo Vitiligo Vitiligo is the most common depigmenting disorder and is caused by the destruction of melanocytes. Patients present with hypo- or depigmented macules or patches which often occur on the face, hands, knees, and/or genitalia. Vitiligo who do not have signs or symptoms of other autoimmune diseases Autoimmune diseases Disorders that are characterized by the production of antibodies that react with host tissues or immune effector cells that are autoreactive to endogenous peptides. Selective IgA Deficiency.^[10]  
• Counseling and other psychological intervention should be considered due to the effects of the disease on patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship‘ mental health and self-esteem.
• Cosmetic camouflage:
  • Includes:
    • Cosmetics (foundation-based)
    • Self-tanning products containing dihydroxyacetone
    • Dyes
    • Tattoos Tattoos The indelible marking of tissues, primarily skin, by pricking it with needles to imbed various coloring agents. Tattooing of the cornea is done to colorize leukoma spots. Cellular Accumulations (consider with caution owing to unpredictable nature of the disease)^[12]
  • May be an adequate treatment choice for some individuals

Choice of therapy depends on:^[8] 

• Type/subtype
• Severity
• Site location:
  • Face, trunk, mid-extremities → tend to respond better to therapy
  • Distal extremities, lips Lips The lips are the soft and movable most external parts of the oral cavity. The blood supply of the lips originates from the external carotid artery, and the innervation is through cranial nerves. Lips and Tongue: Anatomy → tend to be less responsive to therapy
• Percentage of body surface area (BSA) affected
• Whether lesions are stable or progressive
• Patient preference

When to refer to a specialist:^[9]

• Rapidly progressive disease
• Uncertainty in the diagnosis
• Disease causes significant distress to the patient.
• No response to topical therapies

Monitoring:^[8,9]

• Document the amount of BSA affected → take clinical photographs Photographs Ultrasound (Sonography) for monitoring
• Assess and monitor quality Quality Activities and programs intended to assure or improve the quality of care in either a defined medical setting or a program. The concept includes the assessment or evaluation of the quality of care; identification of problems or shortcomings in the delivery of care; designing activities to overcome these deficiencies; and follow-up monitoring to ensure effectiveness of corrective steps. Quality Measurement and Improvement of life and psychological distress → may use standard questionnaires for depression (Patient Health Questionnaire-9 (PHQ-9)), anxiety Anxiety Feelings or emotions of dread, apprehension, and impending disaster but not disabling as with anxiety disorders. Generalized Anxiety Disorder (Generalized Anxiety Anxiety Feelings or emotions of dread, apprehension, and impending disaster but not disabling as with anxiety disorders. Generalized Anxiety Disorder Disorder-7 (GAD7)), and others for quality Quality Activities and programs intended to assure or improve the quality of care in either a defined medical setting or a program. The concept includes the assessment or evaluation of the quality of care; identification of problems or shortcomings in the delivery of care; designing activities to overcome these deficiencies; and follow-up monitoring to ensure effectiveness of corrective steps. Quality Measurement and Improvement of life
• Keep in mind that 2–3 months of a chosen therapy may be needed before efficacy can be assessed.

Medical therapy^[8,9,12]

Topical corticosteroids Corticosteroids Chorioretinitis: 

• Useful in localized disease (< 10% of BSA involved)
• Options:
  • Associated with more limited systemic and local side effects:
    • Mometasone Mometasone Asthma Drugs 0.1% cream, lotion, or ointment 
    • Methylprednisolone Methylprednisolone A prednisolone derivative with similar anti-inflammatory action. Immunosuppressants aceponate
  • Superpotent corticosteroid: clobetasol Clobetasol A derivative of prednisolone with high glucocorticoid activity and low mineralocorticoid activity. Absorbed through the skin faster than fluocinonide, it is used topically in treatment of psoriasis but may cause marked adrenocortical suppression. Glucocorticoids 0.05% cream, gel, lotion, or ointment
• Dosing:
  • No guidelines on the optimal dosing or duration
  • Potential options:
    • Continuous dosing: daily application for no longer than 2–3 months
    • Discontinuous dosing: application for 15 days/month over 6 months
• Try to avoid on:
  • Face
  • Axillae
  • Groin Groin The external junctural region between the lower part of the abdomen and the thigh. Male Genitourinary Examination
• Best response is in:
  • Sun-exposed areas
  • Dark skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions
  • Recent lesions
• Monitor for:
  • Skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions atrophy Atrophy Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. Cellular Adaptation
  • Telangiectasias Telangiectasias Ataxia-telangiectasia
  • Hypertrichosis
  • Acneiform eruptions

Topical calcineurin inhibitors Calcineurin Inhibitors Compounds that inhibit or block the phosphatase activity of calcineurin. Immunosuppressants: 

• An alternative to topical steroids Steroids A group of polycyclic compounds closely related biochemically to terpenes. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (sterols), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus. Benign Liver Tumors
• Preferred in areas at high risk of skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions atrophy Atrophy Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. Cellular Adaptation (e.g., head/ neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess, genitals, intertriginous regions)
• Optimal for new or actively progressing lesions
• Options:
  • Topical tacrolimus Tacrolimus A macrolide isolated from the culture broth of a strain of streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro. Immunosuppressants 0.1% ointment 
  • Topical pimecrolimus Pimecrolimus Immunosuppressants 1% cream
• Dosing:
  • Data on optimal dosing and duration are limited.
  • Typically used twice daily
  • Start with an initial duration of 6 months.
  • If effective, can prolong duration of use
• Monitor for:
  • Burning sensation
  • Pruritus Pruritus An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. Atopic Dermatitis (Eczema)
  • Skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions hyperpigmentation Hyperpigmentation Excessive pigmentation of the skin, usually as a result of increased epidermal or dermal melanin pigmentation, hypermelanosis. Hyperpigmentation can be localized or generalized. The condition may arise from exposure to light, chemicals or other substances, or from a primary metabolic imbalance. Malassezia Fungi
• Black box warning: associated with increased risk of malignancy Malignancy Hemothorax

Topical ruxolitinib Ruxolitinib Targeted and Other Nontraditional Antineoplastic Therapy:^[8,13]

• Mechanism of action: Janus kinase (JAK) inhibitor
• Used for nonsegmental vitiligo Vitiligo Vitiligo is the most common depigmenting disorder and is caused by the destruction of melanocytes. Patients present with hypo- or depigmented macules or patches which often occur on the face, hands, knees, and/or genitalia. Vitiligo
• Dosing:
  • 1.5% cream applied in a thin layer twice daily 
  • Up to maximum of 60 g/week or 100 g/2 weeks
  • Treatment area should not exceed 10% BSA
• Safety concerns related to systemic absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption limit Limit A value (e.g., pressure or time) that should not be exceeded and which is specified by the operator to protect the lung Invasive Mechanical Ventilation the use of this drug.
  • Monitor for:
    • Erythema Erythema Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of disease processes. Chalazion
    • Pruritus Pruritus An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. Atopic Dermatitis (Eczema)
    • Acne
    • Inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation of the nasal passages and throat Throat The pharynx is a component of the digestive system that lies posterior to the nasal cavity, oral cavity, and larynx. The pharynx can be divided into the oropharynx, nasopharynx, and laryngopharynx. Pharyngeal muscles play an integral role in vital processes such as breathing, swallowing, and speaking. Pharynx: Anatomy
    • Headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess
    • UTI UTI Urinary tract infections (UTIs) represent a wide spectrum of diseases, from self-limiting simple cystitis to severe pyelonephritis that can result in sepsis and death. Urinary tract infections are most commonly caused by Escherichia coli, but may also be caused by other bacteria and fungi. Urinary Tract Infections (UTIs)
    • Fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever
  • Black box warning: associated with an increased risk of:
    • Serious infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease
    • Malignancy Malignancy Hemothorax
    • Cardiovascular events
    • Thrombosis Thrombosis Formation and development of a thrombus or blood clot in the blood vessel. Epidemic Typhus

Systemic glucocorticoids Systemic Glucocorticoids Glucocorticoids:^[8,9,12] 

• Oral or intramuscular
• 1st-line therapy for stabilization of rapidly progressive disease
• UK:
  • Oral betamethasone Betamethasone A glucocorticoid given orally, parenterally, by local injection, by inhalation, or applied topically in the management of various disorders in which corticosteroids are indicated. Its lack of mineralocorticoid properties makes betamethasone particularly suitable for treating cerebral edema and congenital adrenal hyperplasia. Glucocorticoids:
    • 0.1 mg/kg twice weekly for 3 months 
    • Dosing may need to be altered based on response.
  • Oral dexamethasone Dexamethasone An anti-inflammatory 9-fluoro-glucocorticoid. Antiemetics is a potential alternative.
• Rarely used as monotherapy
• Often combined with other therapies, such as narrow-band UVB

Systemic immunosuppressants Immunosuppressants Immunosuppressants are a class of drugs widely used in the management of autoimmune conditions and organ transplant rejection. The general effect is dampening of the immune response. Immunosuppressants:^[12] 

• Require specialty referral
• Options:
  • Methotrexate Methotrexate An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of tetrahydrofolate dehydrogenase and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA. Antimetabolite Chemotherapy
  • Mycophenolate Mycophenolate Immunosuppressants
  • Cyclosporin
  • Cyclophosphamide Cyclophosphamide Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the liver to form the active aldophosphamide. It has been used in the treatment of lymphoma and leukemia. Its side effect, alopecia, has been used for defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer. Immunosuppressants
• An alternative to systemic steroids Steroids A group of polycyclic compounds closely related biochemically to terpenes. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (sterols), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus. Benign Liver Tumors

Other therapies^[8,12,13]

Phototherapy Phototherapy Treatment of disease by exposure to light, especially by variously concentrated light rays or specific wavelengths. Hyperbilirubinemia of the Newborn:

• Often used in conjunction with medical therapy
• Used alone for stabilization of rapidly progressive disease if steroids Steroids A group of polycyclic compounds closely related biochemically to terpenes. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (sterols), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus. Benign Liver Tumors are contraindicated
• Narrow-band UVB:
  • 1st-line therapy for widespread vitiligo Vitiligo Vitiligo is the most common depigmenting disorder and is caused by the destruction of melanocytes. Patients present with hypo- or depigmented macules or patches which often occur on the face, hands, knees, and/or genitalia. Vitiligo
  • Treatments are 2‒3 times weekly for several months.
• For recalcitrant disease involving < 5%–10% BSA that does not respond to topical therapies:
  • Targeted phototherapy Phototherapy Treatment of disease by exposure to light, especially by variously concentrated light rays or specific wavelengths. Hyperbilirubinemia of the Newborn with excimer laser
  • Oral PUVA ( psoralen Psoralen Melanoma and UVA) photochemotherapy

Depigmentation therapy Depigmentation Therapy Vitiligo:

• For refractory and extensive disease involving > 40% of BSA
• Used on areas of unaffected skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions
• Goal is to match the diseased area for cosmetic satisfaction.

Surgical transplantation procedures:

• Techniques: skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions grafts, autologous melanocyte cultures
• May be used for stable, localized lesions

Prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas^[2,8]

• Vitiligo Vitiligo Vitiligo is the most common depigmenting disorder and is caused by the destruction of melanocytes. Patients present with hypo- or depigmented macules or patches which often occur on the face, hands, knees, and/or genitalia. Vitiligo is a chronic skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions condition.
• The clinical course is unpredictable.
  • Less favorable outcomes occur with long-standing or segmental disease.
  • 50% repigmentation may not be satisfactory to the patient
  • Often no response on hands, feet, and penis Penis The penis is the male organ of copulation and micturition. The organ is composed of a root, body, and glans. The root is attached to the pubic bone by the crura penis. The body consists of the 2 parallel corpora cavernosa and the corpus spongiosum. The glans is ensheathed by the prepuce or foreskin. Penis: Anatomy
• Partial repigmentation in sun-exposed patches Patches Vitiligo may predict response:
  • Most patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship have > 75% repigmentation with 1st-line therapies.
  • Expected goals:
    • 25% improvement after 3 months
    • 50% after 6 months
    • 75% after 9 months
• Lesions may stabilize or continue to progress and expand over the years, despite treatment.

Complications^[8,9,12]

• Psychological dysfunction and substantial interpersonal burdens
• Retinal and choroidal depigmentation Depigmentation Vitiligo (up to 40%)
• Treatment-induced permanent photosensitivity Photosensitivity Tetracyclines