Psoriasis (Clinical)

Overview

Epidemiology^[11,12]

• Relatively common in children and adults
  • 0.5%–11% of people worldwide
  • 1%–3% of people in the United States
• Can be seen at any age, but 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 peaks at the ages of 20–30 and 50–60 (median age is 28 years)
• ⅓ of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship have a first-degree relative with the disease.
• Seasonal variation: worse in winter Winter Pityriasis Rosea than summer
• Slightly more prevalent in women
• Men are more likely to have ocular disease.
• More common in Caucasians

Etiology^[11,12]

• Genetic predisposition:
  • Major histocompatibility complex Major histocompatibility complex The genetic region which contains the loci of genes which determine the structure of the serologically defined (sd) and lymphocyte-defined (ld) transplantation antigens, genes which control the structure of the immune response-associated antigens, human; the immune response genes which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement. Innate Immunity: Phagocytes and Antigen Presentation (MHC) genes Genes A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. DNA Types and Structure → psoriasis-susceptibility locus Psoriasis-Susceptibility Locus Psoriasis ( PSORS1 PSORS1 Psoriasis)
  • HLA-Cw6 → allele Allele Variant forms of the same gene, occupying the same locus on homologous chromosomes, and governing the variants in production of the same gene product. Basic Terms of Genetics most strongly associated with early-onset 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
  • HLA-B27 → psoriatic arthritis Psoriatic Arthritis A type of inflammatory arthritis associated with psoriasis, often involving the axial joints and the peripheral terminal interphalangeal joints. It is characterized by the presence of hla-b27-associated spondyloarthropathy, and the absence of rheumatoid factor. Psoriasis
• Environmental triggers:
  • 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 → erythrodermic and plaque Plaque Primary Skin Lesions 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:
    • Streptococcus Streptococcus Streptococcus is one of the two medically important genera of gram-positive cocci, the other being Staphylococcus. Streptococci are identified as different species on blood agar on the basis of their hemolytic pattern and sensitivity to optochin and bacitracin. There are many pathogenic species of streptococci, including S. pyogenes, S. agalactiae, S. pneumoniae, and the viridans streptococci. Streptococcus → guttate psoriasis Guttate Psoriasis Psoriasis
    • Human immunodeficiency Immunodeficiency Chédiak-Higashi Syndrome virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology ( HIV HIV Anti-HIV Drugs) → erythrodermic psoriasis Erythrodermic Psoriasis Psoriasis
  • Cold weather
  • Trauma 
  • Medications:
    • Lithium Lithium An element in the alkali metals family. It has the atomic symbol li, atomic number 3, and atomic weight [6. 938; 6. 997]. Salts of lithium are used in treating bipolar disorder. Ebstein’s Anomaly, beta-blockers Beta-blockers Drugs that bind to but do not activate beta-adrenergic receptors thereby blocking the actions of beta-adrenergic agonists. Adrenergic beta-antagonists are used for treatment of hypertension, cardiac arrhythmias, angina pectoris, glaucoma, migraine headaches, and anxiety. Class 2 Antiarrhythmic Drugs (Beta Blockers), and antimalarials are the most common. 
    • Interferon-alpha Interferon-alpha One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells. In addition to antiviral activity, it activates natural killer cells and B-lymphocytes, and down-regulates vascular endothelial growth factor expression through pi-3 kinase and mapk kinases signaling pathways. Interferons, tumor Tumor Inflammation necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage factor ( TNF TNF Tumor necrosis factor (TNF) is a major cytokine, released primarily by macrophages in response to stimuli. The presence of microbial products and dead cells and injury are among the stimulating factors. This protein belongs to the TNF superfamily, a group of ligands and receptors performing functions in inflammatory response, morphogenesis, and cell proliferation. Tumor Necrosis Factor (TNF))-alpha inhibitors, and nonsteroidal anti-inflammatory drugs ( NSAIDs NSAIDS Primary vs Secondary Headaches) may also contribute.
    • Corticosteroid use → pustular and erythrodermic psoriasis Erythrodermic Psoriasis Psoriasis
  • Alcohol and tobacco use
  • Obesity Obesity Obesity is a condition associated with excess body weight, specifically with the deposition of excessive adipose tissue. Obesity is considered a global epidemic. Major influences come from the western diet and sedentary lifestyles, but the exact mechanisms likely include a mixture of genetic and environmental factors. Obesity
  • Smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases
  • Pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care
  • Stress

Pathophysiology^[11‒13]

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 is a complex disease marked by a deregulated T-cell–mediated inflammatory process, resulting in keratinocyte Keratinocyte Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell. Erythema Multiforme proliferation and dysfunctional differentiation.

• Not completely understood
• Initiation phase: keratinocytes Keratinocytes Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell. Skin: Structure and Functions respond to an environmental trigger Trigger The type of signal that initiates the inspiratory phase by the ventilator Invasive Mechanical Ventilation → stimulate dendritic cells Dendritic cells Specialized cells of the hematopoietic system that have branch-like extensions. They are found throughout the lymphatic system, and in non-lymphoid tissues such as skin and the epithelia of the intestinal, respiratory, and reproductive tracts. They trap and process antigens, and present them to T-cells, thereby stimulating cell-mediated immunity. They are different from the non-hematopoietic follicular dendritic cells, which have a similar morphology and immune system function, but with respect to humoral immunity (antibody production). Skin: Structure and Functions → cytokine production (inflammatory response) → T-helper cell differentiation 
• Maintenance phase: T-helper cells release cytokines Cytokines Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. Adaptive Immune Response → activate keratinocyte Keratinocyte Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell. Erythema Multiforme proliferation → activate more inflammatory cells, resulting in a self-amplifying inflammatory response
• Leads to:
  • Epidermal hyperplasia Epidermal Hyperplasia Leukoplakia (acanthosis)
  • Accelerated cell turnover → cell retention of nuclei in the stratum corneum Stratum corneum Skin: Structure and Functions ( parakeratosis Parakeratosis Persistence of the nuclei of the keratinocytes into the stratum corneum of the skin. This is a normal state only in the epithelium of true mucous membranes in the mouth and vagina. Actinic Keratosis)
  • Keratinocytes Keratinocytes Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell. Skin: Structure and Functions fail to release lipids Lipids Lipids are a diverse group of hydrophobic organic molecules, which include fats, oils, sterols, and waxes. Fatty Acids and Lipids needed for cell adhesions → leads to flaking, scaly plaques
  • Microabscesses
  • Vascular engorgement Engorgement Mastitis from superficial blood vessel dilation

Clinical Presentation

Major subtypes

• Chronic plaque Plaque Primary Skin Lesions 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:^[1,11,12,17]
  • Most common form (approximately 80% of cases)
  • Symmetric, well-defined, salmon-colored plaques 
  • Thick, silvery scales Scales Dry or greasy masses of keratin that represent thickened stratum corneum. Secondary Skin Lesions 
  • Pruritus Pruritus An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. Atopic Dermatitis (Eczema)
  • Most common locations:
    • Elbows (extensor side) 
    • Knees (extensor side) 
    • Scalp 
    • Umbilicus 
    • Gluteal cleft
  • Classification based on body surface area:
    • Mild-to-moderate disease → < 5% 
    • Moderate-to-severe disease → > 5% 
  • Nail involvement is common
  • Auspitz sign Auspitz Sign Psoriasis: pinpoint bleeding with the removal of scales Scales Dry or greasy masses of keratin that represent thickened stratum corneum. Secondary Skin Lesions
  • Koebner phenomenon Koebner Phenomenon Lichen Planus: lesions induced by trauma, such as scratching
• Guttate (“drop-like”) 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:^[16]
  • Acute eruption of multiple small, salmon-colored papules
    • 1–10 mm MM Multiple myeloma (MM) is a malignant condition of plasma cells (activated B lymphocytes) primarily seen in the elderly. Monoclonal proliferation of plasma cells results in cytokine-driven osteoclastic activity and excessive secretion of IgG antibodies. Multiple Myeloma in size
    • Appear as “dew drops” with fine overlying scales Scales Dry or greasy masses of keratin that represent thickened stratum corneum. Secondary Skin Lesions
  • Found on the trunk and proximal extremities
  • Strong association with streptococcal 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
• Pustular psoriasis Pustular Psoriasis Psoriasis:^[8,13] 
  • Painful patches Patches Vitiligo or plaques 
  • Localized: primarily involves the palms and soles
  • Generalized annular Annular Dermatologic Examination:
    • Recurring, subacute eruption of annular Annular Dermatologic Examination erythematous plaques
    • Peripheral pustules and scale Scale Dermatologic Examination
  • Von Zumbusch variant:
    • Widespread, painful erythematous patches Patches Vitiligo with pinhead-sized pustules
    • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship may have 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, malaise Malaise Tick-borne Encephalitis Virus, leukocytosis Leukocytosis A transient increase in the number of leukocytes in a body fluid. West Nile Virus, and hypocalcemia Hypocalcemia Hypocalcemia, a serum calcium < 8.5 mg/dL, can result from various conditions. The causes may include hypoparathyroidism, drugs, disorders leading to vitamin D deficiency, and more. Calcium levels are regulated and affected by different elements such as dietary intake, parathyroid hormone (PTH), vitamin D, pH, and albumin. Presentation can range from an asymptomatic (mild deficiency) to a life-threatening condition (acute, significant deficiency). Hypocalcemia.
    • Can have mucosal involvement
  • Life-threatening complications:
    • Sepsis Sepsis Systemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by hypotension despite adequate fluid infusion, it is called septic shock. Sepsis and Septic Shock
    • Neutrophilic cholangitis
    • Pneumonitis Pneumonitis Human Herpesvirus 6 and 7
    • Acute respiratory distress syndrome Acute Respiratory Distress Syndrome Acute respiratory distress syndrome is characterized by the sudden onset of hypoxemia and bilateral pulmonary edema without cardiac failure. Sepsis is the most common cause of ARDS. The underlying mechanism and histologic correlate is diffuse alveolar damage (DAD). Acute Respiratory Distress Syndrome (ARDS)
  • In pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care, the condition is known as impetigo Impetigo Impetigo is a highly contagious superficial bacterial infection typically caused by Staphylococcus aureus (most common) and Streptococcus pyogenes. Impetigo most commonly presents in children aged 2 to 5 years with lesions that evolve from papules to vesicles to pustules, which eventually break down to form characteristic “honey-colored” crusts. Impetigo herpetiformis.
• Erythrodermic psoriasis Erythrodermic Psoriasis Psoriasis:^[15] 
  • Uncommon
  • Can be acute or chronic
  • Generalized erythema Erythema Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of disease processes. Chalazion with varying scaling
  • Affects the entire body surface → ↑ risk of complications due to 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 barrier
    • Sepsis Sepsis Systemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by hypotension despite adequate fluid infusion, it is called septic shock. Sepsis and Septic Shock → 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 and chills Chills The sudden sensation of being cold. It may be accompanied by shivering. Fever
    • Fluid loss → dehydration Dehydration The condition that results from excessive loss of water from a living organism. Volume Depletion and Dehydration and electrolyte imbalance

Special sites^[11,12]

• Inverse (intertriginous) 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: 
  • Found on intertriginous areas Intertriginous areas Malassezia Fungi:
    • Inguinal
    • Perineal and genital 
    • Intergluteal 
    • Axillary 
    • Inframammary
  • Symmetric, smooth, shiny, erythematous plaques
  • Does not usually have a scale Scale Dermatologic Examination due to the moistness of the area
• Nail psoriasis Nail Psoriasis Psoriasis:
  • Tiny pits across the nail are characteristic.
  • Other findings:
    • Leukonychia Leukonychia Psoriasis (white lines or dots appearing on the nail)
    • Lunula red spots Lunula Red Spots Psoriasis 
    • Onycholysis Onycholysis Separation of nail plate from the underlying nail bed. It can be a sign of skin disease, infection (such as onychomycosis) or tissue injury. Psoriasis (painless detachment from the nail bed Nail bed Skin: Structure and Functions)
  • Especially common in individuals with psoriatic arthritis Psoriatic Arthritis A type of inflammatory arthritis associated with psoriasis, often involving the axial joints and the peripheral terminal interphalangeal joints. It is characterized by the presence of hla-b27-associated spondyloarthropathy, and the absence of rheumatoid factor. Psoriasis
• Palmoplantar psoriasis Palmoplantar Psoriasis Psoriasis:
  • Involves the palms or soles
  • Erythematous, hyperkeratotic plaques
  • Can have painful fissures

Associated disorders^{[3,11,12,22,23]}

• Psoriatic arthritis Psoriatic Arthritis A type of inflammatory arthritis associated with psoriasis, often involving the axial joints and the peripheral terminal interphalangeal joints. It is characterized by the presence of hla-b27-associated spondyloarthropathy, and the absence of rheumatoid factor. Psoriasis:
  • Seen in up to 30% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with 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
  • Often asymmetric distribution
  • Can be disabling
  • Symptoms: 
    • Joint pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways
    • Back pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways
    • Morning joint stiffness
  • Exam findings:
    • Distal arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis, particularly of the distal interphalangeal (DIP) joints
    • Enthesitis Enthesitis Ankylosing Spondylitis ( 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 at site of tendon insertion) 
    • Tenosynovitis ( 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 fluid-filled sheath surrounding a tendon)
    • Dactylitis Dactylitis Ankylosing Spondylitis (“ sausage digits Sausage Digits Reactive Arthritis”)
    • Arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis mutilans (resorption of bones leading to soft tissue Soft Tissue Soft Tissue Abscess collapse)
    • Spondyloarthropathy Spondyloarthropathy Ankylosing Spondylitis
• Ocular disorders:
  • Blepharitis Blepharitis Blepharitis is an ocular condition characterized by eyelid inflammation. Anterior blepharitis involves the eyelid skin and eyelashes, while the posterior type affects the meibomian glands. Often, these conditions overlap. Blepharitis ( 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 eyelid)
  • Conjunctivitis Conjunctivitis Conjunctivitis is a common inflammation of the bulbar and/or palpebral conjunctiva. It can be classified into infectious (mostly viral) and noninfectious conjunctivitis, which includes allergic causes. Patients commonly present with red eyes, increased tearing, burning, foreign body sensation, and photophobia. Conjunctivitis
  • Xerosis Xerosis Sjögren’s Syndrome (dryness)
  • Corneal lesions 
  • Uveitis Uveitis Uveitis is the inflammation of the uvea, the pigmented middle layer of the eye, which comprises the iris, ciliary body, and choroid. The condition is categorized based on the site of disease; anterior uveitis is the most common. Diseases of the Uvea
  • Associated symptoms:
    • Ocular discomfort 
    • Red eyes 
    • Swollen eyelids Eyelids Each of the upper and lower folds of skin which cover the eye when closed. Blepharitis 
    • Flaking or crusting in eyelashes 
    • Visual changes 
    • Psoriatic lesions on lids
• Comorbidities Comorbidities The presence of co-existing or additional diseases with reference to an initial diagnosis or with reference to the index condition that is the subject of study. Comorbidity may affect the ability of affected individuals to function and also their survival; it may be used as a prognostic indicator for length of hospital stay, cost factors, and outcome or survival. St. Louis Encephalitis Virus (likely due to inflammatory processes and/or maladaptive immune responses): 
  • Cardiovascular disease (and risk factors):^[3]
    • Obesity Obesity Obesity is a condition associated with excess body weight, specifically with the deposition of excessive adipose tissue. Obesity is considered a global epidemic. Major influences come from the western diet and sedentary lifestyles, but the exact mechanisms likely include a mixture of genetic and environmental factors. Obesity 
    • Metabolic syndrome Metabolic syndrome Metabolic syndrome is a cluster of conditions that significantly increases the risk for several secondary diseases, notably cardiovascular disease, type 2 diabetes, and nonalcoholic fatty liver. In general, it is agreed that hypertension, insulin resistance/hyperglycemia, and hyperlipidemia, along with central obesity, are components of the metabolic syndrome. Metabolic Syndrome 
    • Hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension 
    • 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 
    • Atherosclerotic disease
  • Inflammatory bowel disease 
  • Malignancy Malignancy Hemothorax 
  • 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 
  • Autoimmune disorders

Diagnosis

Diagnosis is established by the clinical history and physical examination findings. A skin biopsy Skin Biopsy Secondary Skin Lesions can be performed if the diagnosis is unclear, though it is typically not needed.

Skin biopsy Skin Biopsy Secondary Skin Lesions^[11,12]

• May be used for confirmation, but is rarely necessary 
• Findings:
  • Acanthosis with elongated rete ridges Rete Ridges Lentigo Maligna
  • Parakeratosis Parakeratosis Persistence of the nuclei of the keratinocytes into the stratum corneum of the skin. This is a normal state only in the epithelium of true mucous membranes in the mouth and vagina. Actinic Keratosis 
  • Neutrophilic microabscesses Neutrophilic Microabscesses Psoriasis ( Munro’s microabscess Munro’S Microabscess Psoriasis)
  • Thinned, or absent, granular cell layer 
  • Dilated dermal papillary capillaries Capillaries Capillaries are the primary structures in the circulatory system that allow the exchange of gas, nutrients, and other materials between the blood and the extracellular fluid (ECF). Capillaries are the smallest of the blood vessels. Because a capillary diameter is so small, only 1 RBC may pass through at a time. Capillaries: Histology
• Periodic acid–Schiff with diastase (PAS-D) → rule out superficial fungal infection

Screening Screening Preoperative Care and diagnosis of psoriatic arthritis Psoriatic Arthritis A type of inflammatory arthritis associated with psoriasis, often involving the axial joints and the peripheral terminal interphalangeal joints. It is characterized by the presence of hla-b27-associated spondyloarthropathy, and the absence of rheumatoid factor. Psoriasis^[22]

• Physical exam findings
• Negative rheumatoid factor Rheumatoid factor Antibodies found in adult rheumatoid arthritis patients that are directed against gamma-chain immunoglobulins. Autoimmune Hepatitis
• ↑ Erythrocyte sedimentation rate Erythrocyte Sedimentation Rate Soft Tissue Abscess ( ESR ESR Soft Tissue Abscess) and C-reactive protein (CRP)
• HLA-B27 testing (helpful if 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 are absent)
• Radiographs of affected joints and spine Spine The human spine, or vertebral column, is the most important anatomical and functional axis of the human body. It consists of 7 cervical vertebrae, 12 thoracic vertebrae, and 5 lumbar vertebrae and is limited cranially by the skull and caudally by the sacrum. Vertebral Column: Anatomy:
  • Periarticular erosions Erosions Corneal Abrasions, Erosion, and Ulcers and bone resorption Bone resorption Bone loss due to osteoclastic activity. Bones: Remodeling and Healing → “pencil-in-cup” appearance
  • Bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types proliferation → “fuzzy” appearance to the bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types around the joint
  • Osteolysis Osteolysis Dissolution of bone that particularly involves the removal or loss of calcium. Paget’s Disease of Bone and articular collapse → arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis mutilans
  • Sacroiliitis Sacroiliitis Inflammation of the sacroiliac joint. It is characterized by lower back pain, especially upon walking, fever, uveitis; psoriasis; and decreased range of motion. Many factors are associated with and cause sacroiliitis including infection; injury to spine, lower back, and pelvis; degenerative arthritis; and pregnancy. Ankylosing Spondylitis

Assessing disease severity

Validated tools can be used to follow disease severity and progression over time. The 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 Area and Severity Index (PASI) is the most widely used tool for assessing clinical severity.

The PASI:^[1,6,18,19]

• Calculator
• Not validated for children or young people
• Assesses the following items for different body regions:
  • Erythema Erythema Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of disease processes. Chalazion (E)
  • Induration Induration Dermatologic Examination/thickness (I)
  • Scaling/ desquamation Desquamation Staphylococcal Scalded Skin Syndrome (SSSS) (S)
  • Percentage of the region affected (A)
• Scoring for the first 3 items (E, I, S):
  • None = 0 points
  • Slight = 1 point
  • Moderate = 2 points
  • Severe = 3 points
  • Very severe = 4 points
• Scoring “percentage of body area affected” (A):
  • 0% = 0 points
  • 1%‒9% = 1 point
  • 10%‒29% = 2 points
  • 30%‒49% = 3 points
  • 50%‒69% = 4 points
  • 70%‒89% = 5 points
  • 90%‒100% = 6 points
• Interpretation:
  • Mild disease: < 7
  • Moderate disease: 7‒12
  • Severe disease: > 12

Other validated scoring systems:^[6,19]

• Physician Global Assessment (PGA):
  • More subjective than the PASI → does not quantify body surface area involvement
  • Assesses erythema Erythema Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of disease processes. Chalazion (E), induration Induration Dermatologic Examination (I), and scaling (S)
  • E, I, and S are all scored on a scale Scale Dermatologic Examination of 0 (clear) to 4 (severe), and the result is averaged.
• Dermatology Life 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 Index (DLQI): dermatology-specific 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 tool

Clinical classification based on percentage of the body surface area affected:^[1]

• Assume that 1% of body surface area is approximately the entire palmar surface (including fingers) of one hand Hand The hand constitutes the distal part of the upper limb and provides the fine, precise movements needed in activities of daily living. It consists of 5 metacarpal bones and 14 phalanges, as well as numerous muscles innervated by the median and ulnar nerves. Hand: Anatomy
• Mild disease: < 3% of total body surface area
• Moderate disease: 3%‒10% of total body surface area
• Severe disease: > 10% of total body surface area

Management

Treatment is based on severity, lesion distribution, type, comorbidities Comorbidities The presence of co-existing or additional diseases with reference to an initial diagnosis or with reference to the index condition that is the subject of study. Comorbidity may affect the ability of affected individuals to function and also their survival; it may be used as a prognostic indicator for length of hospital stay, cost factors, and outcome or survival. St. Louis Encephalitis Virus, patient preference, and response. The following information is based on US, European, and UK guidelines.

For all patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship^[6]

• Provide information and education on:
  • Their diagnosis
  • Lifestyle risk factors
  • Available treatments and how to use them effectively
  • When to seek care
• Regularly monitor:
  • Disease severity
  • For signs of psoriatic arthritis Psoriatic Arthritis A type of inflammatory arthritis associated with psoriasis, often involving the axial joints and the peripheral terminal interphalangeal joints. It is characterized by the presence of hla-b27-associated spondyloarthropathy, and the absence of rheumatoid factor. Psoriasis
• Reassess management if/when:
  • Disease severity changes
  • Additional comorbidities Comorbidities The presence of co-existing or additional diseases with reference to an initial diagnosis or with reference to the index condition that is the subject of study. Comorbidity may affect the ability of affected individuals to function and also their survival; it may be used as a prognostic indicator for length of hospital stay, cost factors, and outcome or survival. St. Louis Encephalitis Virus arise
  • Lifestyle or social situation changes
  • New treatments become available
• Keep in mind:
  • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship may have refractory disease or suffer multiple relapses. 
  • Goal of treatment is an approximately 75% reduction of 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 or a reduction to < 3% of body surface area.

Overview of management options based on severity^[1,2,4,19]

• Mild-to-moderate disease:
  • Topical corticosteroids Corticosteroids Chorioretinitis ( hydrocortisone Hydrocortisone The main glucocorticoid secreted by the adrenal cortex. Its synthetic counterpart is used, either as an injection or topically, in the treatment of inflammation, allergy, collagen diseases, asthma, adrenocortical deficiency, shock, and some neoplastic conditions. Immunosuppressants, triamcinolone Triamcinolone A glucocorticoid given, as the free alcohol or in esterified form, orally, intramuscularly, by local injection, by inhalation, or applied topically in the management of various disorders in which corticosteroids are indicated. Glucocorticoids, fluocinonide Fluocinonide Glucocorticoids)
  • 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 analogs ( calcitriol Calcitriol The physiologically active form of vitamin d. It is formed primarily in the kidney by enzymatic hydroxylation of 25-hydroxycholecalciferol (calcifediol). Its production is stimulated by low blood calcium levels and parathyroid hormone. Calcitriol increases intestinal absorption of calcium and phosphorus, and in concert with parathyroid hormone increases bone resorption. Parathyroid Glands: Anatomy, calcipotriene) 
  • Topical retinoids Retinoids Retinol and derivatives of retinol that play an essential role in metabolic functioning of the retina, the growth of and differentiation of epithelial tissue, the growth of bone, reproduction, and the immune response. Dietary vitamin A is derived from a variety of carotenoids found in plants. It is enriched in the liver, egg yolks, and the fat component of dairy products. Fat-soluble Vitamins and their Deficiencies (tazarotene)
  • Coal tar Coal Tar A by-product of the destructive distillation of coal used as a topical antieczematic. It is an antipruritic and keratoplastic agent used also in the treatment of psoriasis and other skin conditions. Occupational exposure to soots, tars, and certain mineral oils is known to be carcinogenic according to the fourth annual report on carcinogens. Psoriasis 
  • Phototherapy Phototherapy Treatment of disease by exposure to light, especially by variously concentrated light rays or specific wavelengths. Hyperbilirubinemia of the Newborn 
  • Calcineurin inhibitors Calcineurin Inhibitors Compounds that inhibit or block the phosphatase activity of calcineurin. Immunosuppressants ( 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, pimecrolimus Pimecrolimus Immunosuppressants)
• Moderate-to-severe disease:
  • Retinoids Retinoids Retinol and derivatives of retinol that play an essential role in metabolic functioning of the retina, the growth of and differentiation of epithelial tissue, the growth of bone, reproduction, and the immune response. Dietary vitamin A is derived from a variety of carotenoids found in plants. It is enriched in the liver, egg yolks, and the fat component of dairy products. Fat-soluble Vitamins and their Deficiencies 
  • 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
  • Cyclosporine Cyclosporine A cyclic undecapeptide from an extract of soil fungi. It is a powerful immunosupressant with a specific action on T-lymphocytes. It is used for the prophylaxis of graft rejection in organ and tissue transplantation. Immunosuppressants
  • Apremilast Apremilast Phosphodiesterase Inhibitors (phosphodiesterase inhibitor)
  • Biologic agents Biologic Agents Immunosuppressants (note: TNF-alpha inhibitors can also exacerbate 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)
  • Phototherapy Phototherapy Treatment of disease by exposure to light, especially by variously concentrated light rays or specific wavelengths. Hyperbilirubinemia of the Newborn

• Adjuvant Adjuvant Substances that augment, stimulate, activate, potentiate, or modulate the immune response at either the cellular or humoral level. The classical agents (freund’s adjuvant, bcg, corynebacterium parvum, et al.) contain bacterial antigens. Some are endogenous (e.g., histamine, interferon, transfer factor, tuftsin, interleukin-1). Their mode of action is either non-specific, resulting in increased immune responsiveness to a wide variety of antigens, or antigen-specific, i.e., affecting a restricted type of immune response to a narrow group of antigens. The therapeutic efficacy of many biological response modifiers is related to their antigen-specific immunoadjuvanticity. Vaccination therapy:
  • Moisturizers
  • Emollients Emollients Oleaginous substances used topically to soothe, soften or protect skin or mucous membranes. They are used also as vehicles for other dermatologic agents. Pityriasis Rosea
  • Lifestyle modifications to reduce risks of associated comorbidities Comorbidities The presence of co-existing or additional diseases with reference to an initial diagnosis or with reference to the index condition that is the subject of study. Comorbidity may affect the ability of affected individuals to function and also their survival; it may be used as a prognostic indicator for length of hospital stay, cost factors, and outcome or survival. St. Louis Encephalitis Virus (e.g., cardiovascular disease)
    • Weight loss Weight loss Decrease in existing body weight. Bariatric Surgery 
    • Stress reduction
    • Smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases cessation
• Additional considerations:
  • Inverse psoriasis Inverse Psoriasis Psoriasis:
    • Low-potency corticosteroids Corticosteroids Chorioretinitis 
    • Affected areas have an increased risk for corticosteroid-induced cutaneous 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.
  • Guttate psoriasis Guttate Psoriasis Psoriasis may resolve spontaneously without intervention.
  • Pustular and erythrodermic psoriasis Erythrodermic Psoriasis Psoriasis: hospitalization Hospitalization The confinement of a patient in a hospital. Delirium for severe disease and complications

Indications for referral to dermatologist, rheumatologist, or other 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 specialist^[6]

• Diagnostic uncertainty
• Disease is uncontrolled with topical therapy alone
• Severe disease
• Psoriatic arthritis Psoriatic Arthritis A type of inflammatory arthritis associated with psoriasis, often involving the axial joints and the peripheral terminal interphalangeal joints. It is characterized by the presence of hla-b27-associated spondyloarthropathy, and the absence of rheumatoid factor. Psoriasis
• Guttate psoriasis Guttate Psoriasis Psoriasis (need for phototherapy Phototherapy Treatment of disease by exposure to light, especially by variously concentrated light rays or specific wavelengths. Hyperbilirubinemia of the Newborn)
• Generalized pustular psoriasis Pustular Psoriasis Psoriasis
• Erythrodermic psoriasis Erythrodermic Psoriasis Psoriasis
• Children and young people

Topical therapies^[2,6]

Topical therapies are typically considered 1st-line treatment. They are often used in combination with systemic agents in moderate-to-severe disease.

Emollients Emollients Oleaginous substances used topically to soothe, soften or protect skin or mucous membranes. They are used also as vehicles for other dermatologic agents. Pityriasis Rosea and other moisturizers:

• An important adjunctive treatment to reduce itching, desquamation Desquamation Staphylococcal Scalded Skin Syndrome (SSSS), and affected body surface area
• Should be applied after a bath/shower

Topical corticosteroids Corticosteroids Chorioretinitis:

• Beneficial properties (for 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 treatment):
  • Antiinflammatory
  • Immunosuppressive
  • Antiproliferative effects
  • Vasoconstrictive effects
• Choice of potency and preparation:
  • Should be based on severity, location, and age
  • The preparation (ointment, cream, gel, etc ETC The electron transport chain (ETC) sends electrons through a series of proteins, which generate an electrochemical proton gradient that produces energy in the form of adenosine triphosphate (ATP). Electron Transport Chain (ETC).) affects potency (e.g., mometasone Mometasone Asthma Drugs furoate 0.1% is class II as an ointment, but is class IV as a cream or lotion).
  • Moderate- (class V) through high- (class II) potency 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 typically recommended as initial therapy in adults. 
  • Lower-potency (classes VI and VII) 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 recommended for use on the face, in intertriginous areas Intertriginous areas Malassezia Fungi, and in other areas susceptible to steroid 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. 
  • Ultrahigh-potency (class I) may be recommended for areas with thick, chronic plaques.
• Frequency of dosing depends on the steroid and preparation selected.
• Duration of treatment:
  • Typically 2‒4 weeks (no more than 12) → then transition to alternative agents for maintenance
  • Specialists may consider use for > 12 weeks under careful supervision.
• All can be used in combination with any of the biologic agents Biologic Agents Immunosuppressants for moderate-to-severe disease
• Risks:
  • 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, striae, telangiectasia Telangiectasia Permanent dilation of preexisting blood vessels creating small focal red lesions, most commonly in the skin or mucous membranes. It is characterized by the prominence of skin blood vessels, such as vascular spiders. Chronic Venous Insufficiency, purpura, folliculitis
  • Exacerbation of acne, rosacea Rosacea Rosacea is a chronic inflammatory disease of the skin that is associated with capillary hyperreactivity. This condition is predominantly seen in middle-aged women, and is more common in fair-skinned patients. Rosacea, or perioral dermatitis Dermatitis Any inflammation of the skin. Atopic Dermatitis (Eczema)
  • Hypothalamic-pituitary-adrenal (HPA) axis suppression Suppression Defense Mechanisms (considered relatively low risk with topical use)

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 analogs:

• Inhibit proliferation of keratinocytes Keratinocytes Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell. Skin: Structure and Functions and stimulate their differentiation (exact mechanisms unclear)
• Options:
  • Calcipotriene (also called calcipotriol) 0.005% (cream, ointment, foam, solution)
  • Calcitriol Calcitriol The physiologically active form of vitamin d. It is formed primarily in the kidney by enzymatic hydroxylation of 25-hydroxycholecalciferol (calcifediol). Its production is stimulated by low blood calcium levels and parathyroid hormone. Calcitriol increases intestinal absorption of calcium and phosphorus, and in concert with parathyroid hormone increases bone resorption. Parathyroid Glands: Anatomy 3 µg/g (ointment)
  • Tacalcitol (not available in the US)
  • Maxacalcitol (not available in the US)
• Application (all agents): once or twice daily to the affected areas
• Duration of treatment: may be used long term (up to 52 weeks)
• May be used alone (as an alternative to) or in combination with a topical corticosteroid
• Some maintenance regimens recommended by the American Academy of Dermatology (AAD)^[2] include:
  • 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 analogs + potent (class II or III) 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 used up to 52 weeks
  • 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 analog twice daily on weekdays + high-potency topical corticosteroids Corticosteroids Chorioretinitis twice daily on weekends
  • High-potency topical corticosteroid in the morning + topical 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 analogs in the evening

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

• Inhibit T-cell activation and the synthesis Synthesis Polymerase Chain Reaction (PCR) of several key inflammatory cytokines Cytokines Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. Adaptive Immune Response
• Used as steroid-sparing agents
• Especially helpful on thinner 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:
  • Face
  • Intertriginous areas Intertriginous areas Malassezia Fungi
• Options:
  • 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
  • Pimecrolimus Pimecrolimus Immunosuppressants 1% cream
• Application (both agents): apply to the affected areas twice daily
• Duration of treatment: 4‒8 weeks
• Risks:
  • Both agents have a black-box warning about the 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 malignancies and lymphoma Lymphoma A general term for various neoplastic diseases of the lymphoid tissue. Imaging of the Mediastinum; however, there is no evidence of increased risk with topical use
  • Flushing with alcohol use

Topical retinoid (tazarotene 0.05%‒0.1%):

• Affects keratinocyte Keratinocyte Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell. Erythema Multiforme differentiation and proliferation plus has some antiinflammatory effects
• ↑ Efficacy when combined with a topical corticosteroid (a combination product with halobetasol propionate exists)
• AAD notes that it is especially helpful for:
  • Mild-to-moderate 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
  • Palmar–plantar 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
  • Nail psoriasis Nail Psoriasis Psoriasis
• Risks:
  • 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 irritation (less when used with topical corticosteroids Corticosteroids Chorioretinitis)
  • Teratogenicity

Other agents:

• Anthralin (dithranol):
  • A polycyclic aromatic hydrocarbon derivative thought to prevent T-cell activation and promote keratinocyte Keratinocyte Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell. Erythema Multiforme differentiation
  • Used for mild-to-moderate 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
  • Start at 0.1% concentration, which can be titrated up as tolerated.
  • Duration of use: typically, 8‒12 weeks
  • Evidence-based regimens:
    • Applied once daily for up to 2 hours 
    • Applied twice daily for 1 minute
  • Risks: 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 irritation (avoid application to the face)
• Coal tar Coal Tar A by-product of the destructive distillation of coal used as a topical antieczematic. It is an antipruritic and keratoplastic agent used also in the treatment of psoriasis and other skin conditions. Occupational exposure to soots, tars, and certain mineral oils is known to be carcinogenic according to the fourth annual report on carcinogens. Psoriasis:
  • Effective, older agent
  • Available over the counter as creams, lotions, ointments, and shampoos
  • Used once daily
  • Many preparations are considered “messy” by patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship.
• Salicylic acid:
  • A topical keratolytic agent
  • Duration of use: 8‒16 weeks
  • Can be combined with topical corticosteroids Corticosteroids Chorioretinitis for moderate-to-severe 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 if affected body surface area is ≤ 20%
• Newest agents (approved in 2022):
  • Tapinarof 1% cream
  • Roflumilast Roflumilast Phosphodiesterase Inhibitors 0.3% cream

Phototherapy Phototherapy Treatment of disease by exposure to light, especially by variously concentrated light rays or specific wavelengths. Hyperbilirubinemia of the Newborn^[5,6]

Phototherapy Phototherapy Treatment of disease by exposure to light, especially by variously concentrated light rays or specific wavelengths. Hyperbilirubinemia of the Newborn is an older therapy known to be beneficial for psoriatic lesions.

Benefits:

• Inhibits keratinization
• Has antiinflammatory effects
• Induces apoptosis Apoptosis A regulated cell death mechanism characterized by distinctive morphologic changes in the nucleus and cytoplasm, including the endonucleolytic cleavage of genomic DNA, at regularly spaced, internucleosomal sites, I.e., DNA fragmentation. It is genetically-programmed and serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. Ischemic Cell Damage of pathogenic T cells T cells Lymphocytes responsible for cell-mediated immunity. Two types have been identified – cytotoxic (t-lymphocytes, cytotoxic) and helper T-lymphocytes (t-lymphocytes, helper-inducer). They are formed when lymphocytes circulate through the thymus gland and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen. T cells: Types and Functions within the psoriatic plaques

Indications:

• Generalized plaque Plaque Primary Skin Lesions 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
• Guttate psoriasis Guttate Psoriasis Psoriasis
• Pregnant women (should take folate Folate Folate and vitamin B12 are 2 of the most clinically important water-soluble vitamins. Deficiencies can present with megaloblastic anemia, GI symptoms, neuropsychiatric symptoms, and adverse pregnancy complications, including neural tube defects. Folate and Vitamin B12 supplements during treatment)

Modalities:

• Narrowband (NB) ultraviolet B (UVB):
  • Wavelengths from 311 to 313 nm
  • Can be used as monotherapy or in combination with most other therapies (exception: cyclosporine Cyclosporine A cyclic undecapeptide from an extract of soil fungi. It is a powerful immunosupressant with a specific action on T-lymphocytes. It is used for the prophylaxis of graft rejection in organ and tissue transplantation. Immunosuppressants due to ↑ risk of cancer)
  • Preferred over psoralen Psoralen Melanoma ultraviolet A (PUVA) despite slightly lower efficacy
  • Home NB-UVB units are available.
• Excimer UVB laser:
  • Wavelength: 308 nm 
  • Used for targeted, localized lesions
  • More efficacious than NB-UVB for localized lesions
• PUVA:
  • Photochemotherapy: ultraviolet A (UVA) radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma given with a photosensitizing agent (oral or bath psoralen Psoralen Melanoma)
  • Higher risks compared to NB-UVB, especially 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 cancer
  • Recommended in palmoplantar pustular psoriasis Pustular Psoriasis Psoriasis and localized plaque Plaque Primary Skin Lesions 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
• Broadband (BB) UVB:
  • Wavelengths from 270 to 390 nm, with peak emission at 313 nm
  • An older, less effective form of phototherapy Phototherapy Treatment of disease by exposure to light, especially by variously concentrated light rays or specific wavelengths. Hyperbilirubinemia of the Newborn compared to NB-UVB
  • Used when NB-UVB is not available

Regimen:

• Usual: 3 times a week during treatment, then tapered to the lowest frequency that controls symptoms (typically once weekly)
• Estimating starting dose is based on Fitzpatrick 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 type (tables available from AAD)

Risks:

• Ocular toxicity Toxicity Dosage Calculation → use eye protection during treatments
• Photocarcinogenesis

Climatotherapy: 

• Using the natural environment of several unique geographic regions as part of dedicated programs involving sun exposure (and, frequently, salt baths)
• Geographic sites:
  • Black Sea
  • Blue Lagoon in Iceland
  • Canary Islands

Systemic therapies

Systemic therapies are often indicated for moderate-to-severe disease and are generally managed by specialists (e.g., rheumatology, dermatology). Choice of systemic therapy is typically based on a combination of individual patient factors (including risks of potential adverse effects), patient preference, and cost.

Nonbiologic agents:^[1,6,9,10]

• 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 ( MTX MTX 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):
  • Competitively inhibits dihydrofolate reductase Dihydrofolate Reductase Sulfonamides and Trimethoprim → inhibits rapidly dividing cells
  • Indications:
    • Moderate-to-severe arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis in adults
    • Concurrent peripheral (but not axial Axial Computed Tomography (CT)) psoriatic arthritis Psoriatic Arthritis A type of inflammatory arthritis associated with psoriasis, often involving the axial joints and the peripheral terminal interphalangeal joints. It is characterized by the presence of hla-b27-associated spondyloarthropathy, and the absence of rheumatoid factor. Psoriasis
  • Formulations:
    • Oral (most common)
    • Subcutaneous
    • IM
  • Experts recommend supplementing with folic acid (or folinic acid) to decrease GI adverse effects:
    • Given daily except on days when patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship take MTX MTX 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 therapy or as a larger dose once weekly 24 hours after MTX MTX 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 administration
    • May slightly decrease the efficacy of 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 treatment → avoid large doses
  • Toxicities (and monitoring):
    • GI distress
    • Immunosuppression (perform baseline hepatitis B Hepatitis B Hepatitis B virus (HBV) is a partially double-stranded DNA virus, which belongs to the Orthohepadnavirus genus and the Hepadnaviridae family. Most individuals with acute HBV infection are asymptomatic or have mild, self-limiting symptoms. Chronic infection can be asymptomatic or create hepatic inflammation, leading to liver cirrhosis and hepatocellular carcinoma (HCC). Hepatitis B Virus and C, HIV HIV Anti-HIV Drugs, and tuberculosis Tuberculosis Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis testing)
    • Myelosuppression Myelosuppression Oxazolidinones (monitor CBC)
    • Hepatotoxicity Hepatotoxicity Acetaminophen (monitor liver function tests Liver function tests Liver function tests, also known as hepatic function panels, are one of the most commonly performed screening blood tests. Such tests are also used to detect, evaluate, and monitor acute and chronic liver diseases. Liver Function Tests)
    • Teratogenic (ensure adequate contraception in reproductive-aged women; avoid pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care for at least 3 months after stopping MTX MTX 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)
• Apremilast Apremilast Phosphodiesterase Inhibitors:
  • Phosphodiesterase 4 inhibitor → results in downregulation of inflammatory responses involving Th1 Th1 A subset of helper-inducer T-lymphocytes which synthesize and secrete interleukin-2; interferon-gamma; and interleukin-12. Due to their ability to kill antigen-presenting cells and their lymphokine-mediated effector activity, th1 cells are associated with vigorous delayed-type hypersensitivity reactions. T cells: Types and Functions, Th17 Th17 A subset of helper-effector T-lymphocytes which synthesize and secrete interleukins il-17; il-17f; and il-22. These cytokines are involved in host defenses and tissue inflammation in autoimmune diseases. T cells: Types and Functions, and interferon pathways
  • Can also be used in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with psoriatic arthritis Psoriatic Arthritis A type of inflammatory arthritis associated with psoriasis, often involving the axial joints and the peripheral terminal interphalangeal joints. It is characterized by the presence of hla-b27-associated spondyloarthropathy, and the absence of rheumatoid factor. Psoriasis
  • Adverse effects:
    • GI distress
    • Upper respiratory 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
    • Dehydration Dehydration The condition that results from excessive loss of water from a living organism. Volume Depletion and Dehydration (especially in the elderly)
    • Depression
    • Weight loss Weight loss Decrease in existing body weight. Bariatric Surgery
    • 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
• Cyclosporine Cyclosporine A cyclic undecapeptide from an extract of soil fungi. It is a powerful immunosupressant with a specific action on T-lymphocytes. It is used for the prophylaxis of graft rejection in organ and tissue transplantation. Immunosuppressants:
  • Inhibits calcineurin Calcineurin A calcium and calmodulin-dependent serine/threonine protein phosphatase that is composed of the calcineurin a catalytic subunit and the calcineurin B regulatory subunit. Calcineurin has been shown to dephosphorylate a number of phosphoproteins including histones; myosin light chain; and the regulatory subunits of camp-dependent protein kinases. It is involved in the regulation of signal transduction and is the target of an important class of immunophilin-immunosuppressive drug complexes. Vitiligo and proinflammatory signaling
  • Best/typical uses:
    • Severe recalcitrant disease
    • Acute flares
    • As induction/bridging therapy to safer long-term options
    • Can also be used in erythrodermic, pustular, and palmoplantar psoriasis Palmoplantar Psoriasis Psoriasis
  • Obese patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship should be dosed according to actual body weight
  • Many adverse effects, including:
    • Nephrotoxicity Nephrotoxicity Glycopeptides
    • Hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension 
    • Paresthesias Paresthesias Subjective cutaneous sensations (e.g., cold, warmth, tingling, pressure, etc.) that are experienced spontaneously in the absence of stimulation. Posterior Cord Syndrome and musculoskeletal pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways
    • Lymphoproliferative and cutaneous malignancies 
    • Hypertriglyceridemia Hypertriglyceridemia A condition of elevated levels of triglycerides in the blood. Lipid Disorders 
    • Electrolyte abnormalities
    • GI effects (tend to be milder/shorter-lived than with some other agents)
  • Monitoring:
    • Blood pressure
    • CBC
    • Renal function tests and electrolytes Electrolytes Electrolytes are mineral salts that dissolve in water and dissociate into charged particles called ions, which can be either be positively (cations) or negatively (anions) charged. Electrolytes are distributed in the extracellular and intracellular compartments in different concentrations. Electrolytes are essential for various basic life-sustaining functions. Electrolytes (K⁺, Mg²⁺)
    • Liver function tests Liver function tests Liver function tests, also known as hepatic function panels, are one of the most commonly performed screening blood tests. Such tests are also used to detect, evaluate, and monitor acute and chronic liver diseases. Liver Function Tests
    • Uric acid Uric acid An oxidation product, via xanthine oxidase, of oxypurines such as xanthine and hypoxanthine. It is the final oxidation product of purine catabolism in humans and primates, whereas in most other mammals urate oxidase further oxidizes it to allantoin. Nephrolithiasis
    • Lipids Lipids Lipids are a diverse group of hydrophobic organic molecules, which include fats, oils, sterols, and waxes. Fatty Acids and Lipids
    • Pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care test
• Acitretin:
  • An oral retinoid that is not immunosuppressive (often used in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with HIV HIV Anti-HIV Drugs)
  • More efficacious if combined with phototherapy Phototherapy Treatment of disease by exposure to light, especially by variously concentrated light rays or specific wavelengths. Hyperbilirubinemia of the Newborn (allows for lower doses of each)
  • Slow-acting, may take 3‒6 months for full response to be seen
  • Contraindications Contraindications A condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks). Noninvasive Ventilation:
    • Pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care (should be avoided for up to 3 years after completing treatment due to teratogenicity) and breastfeeding Breastfeeding Breastfeeding is often the primary source of nutrition for the newborn. During pregnancy, hormonal stimulation causes the number and size of mammary glands in the breast to significantly increase. After delivery, prolactin stimulates milk production, while oxytocin stimulates milk expulsion through the lactiferous ducts, where it is sucked out through the nipple by the infant. Breastfeeding
    • Severely impaired liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy and/or kidney function (avoid alcohol use)
  • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship should not donate blood while taking (and within 36 months after last dose)
  • Adverse effects:
    • Mucocutaneous issues: xerosis Xerosis Sjögren’s Syndrome, dry eyes and mucosa, itching/burning 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, brittle nails, hair loss
    • Hyperlipidemia
  • Monitoring:
    • CBC
    • Liver function tests Liver function tests Liver function tests, also known as hepatic function panels, are one of the most commonly performed screening blood tests. Such tests are also used to detect, evaluate, and monitor acute and chronic liver diseases. Liver Function Tests
    • Lipid panel
    • Pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care test
• Deucravacitinib:^[20]
  • A selective tyrosine Tyrosine A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine; thyroid hormones; and melanin. Synthesis of Nonessential Amino Acids kinase 2 inhibitor
  • Most common adverse effect: nasopharyngitis
• Other immunosuppressive agents sometimes used:
  • Hydroxyurea Hydroxyurea An antineoplastic agent that inhibits DNA synthesis through the inhibition of ribonucleoside diphosphate reductase. Antimetabolite Chemotherapy
  • Azathioprine Azathioprine An immunosuppressive agent used in combination with cyclophosphamide and hydroxychloroquine in the treatment of rheumatoid arthritis. According to the fourth annual report on carcinogens, this substance has been listed as a known carcinogen. Immunosuppressants
  • 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
  • Mycophenolate Mycophenolate Immunosuppressants mofetil
  • Thioguanine
  • Tofacitinib

Biologic agents Biologic Agents Immunosuppressants:^[4,6–9]

• Monoclonal antibodies Monoclonal antibodies Antibodies produced by a single clone of cells. Ebolavirus and Marburgvirus and fusion proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis that inhibit specific cytokines Cytokines Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. Adaptive Immune Response or cytokine receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors → play important roles in psoriatic 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
• Considered the most effective agents for moderate-to-severe 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
• Typically much more expensive
• Prescribing biologics:^[7]
  • Should be used as prescribed by specialists
  • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship should avoid pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care; reliable contraception is required if pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care is possible.
• Indications:
  • People who cannot take 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 and cyclosporine Cyclosporine A cyclic undecapeptide from an extract of soil fungi. It is a powerful immunosupressant with a specific action on T-lymphocytes. It is used for the prophylaxis of graft rejection in organ and tissue transplantation. Immunosuppressants or for whom such therapy has failed
  • Preference
  • Can be used for scalp, nail, palmoplantar, pustular, erythrodermic, and inverse psoriasis Inverse Psoriasis Psoriasis
  • Psoriatic arthritis Psoriatic Arthritis A type of inflammatory arthritis associated with psoriasis, often involving the axial joints and the peripheral terminal interphalangeal joints. It is characterized by the presence of hla-b27-associated spondyloarthropathy, and the absence of rheumatoid factor. Psoriasis (especially TNF-alpha inhibitors and IL-17 inhibitors IL-17 inhibitors Ankylosing Spondylitis)
• Cautions:
  • Increased risk of malignancy Malignancy Hemothorax when biologics are used in combination with other immunosuppressant agents
  • Immunosuppressed patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship (e.g., HIV HIV Anti-HIV Drugs)
  • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with chronic 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 (recommend baseline testing for HIV HIV Anti-HIV Drugs, hepatitis B Hepatitis B Hepatitis B virus (HBV) is a partially double-stranded DNA virus, which belongs to the Orthohepadnavirus genus and the Hepadnaviridae family. Most individuals with acute HBV infection are asymptomatic or have mild, self-limiting symptoms. Chronic infection can be asymptomatic or create hepatic inflammation, leading to liver cirrhosis and hepatocellular carcinoma (HCC). Hepatitis B Virus and C, tuberculosis Tuberculosis Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis)
  • TNF-alpha inhibitors:
    • Moderate-to-severe heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR)
    • Multiple sclerosis Sclerosis A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. Wilms Tumor
  • IL-17 inhibitors IL-17 inhibitors Ankylosing Spondylitis:
    • Inflammatory bowel disease
    • Recurrent candida Candida Candida is a genus of dimorphic, opportunistic fungi. Candida albicans is part of the normal human flora and is the most common cause of candidiasis. The clinical presentation varies and can include localized mucocutaneous infections (e.g., oropharyngeal, esophageal, intertriginous, and vulvovaginal candidiasis) and invasive disease (e.g., candidemia, intraabdominal abscess, pericarditis, and meningitis). Candida/Candidiasis
• These drugs require regular Regular Insulin monitoring, typically:
  • Labs: CBC, liver function tests Liver function tests Liver function tests, also known as hepatic function panels, are one of the most commonly performed screening blood tests. Such tests are also used to detect, evaluate, and monitor acute and chronic liver diseases. Liver Function Tests, serum creatinine, pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care test (if applicable)
  • Exams to check 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 cancer and lymphadenopathy Lymphadenopathy Lymphadenopathy is lymph node enlargement (> 1 cm) and is benign and self-limited in most patients. Etiologies include malignancy, infection, and autoimmune disorders, as well as iatrogenic causes such as the use of certain medications. Generalized lymphadenopathy often indicates underlying systemic disease. Lymphadenopathy
  • Appropriate cancer screening Screening Preoperative Care

Psoriatic arthritis Psoriatic Arthritis A type of inflammatory arthritis associated with psoriasis, often involving the axial joints and the peripheral terminal interphalangeal joints. It is characterized by the presence of hla-b27-associated spondyloarthropathy, and the absence of rheumatoid factor. Psoriasis^[1,7,21]

Management of psoriatic arthritis Psoriatic Arthritis A type of inflammatory arthritis associated with psoriasis, often involving the axial joints and the peripheral terminal interphalangeal joints. It is characterized by the presence of hla-b27-associated spondyloarthropathy, and the absence of rheumatoid factor. Psoriasis should be guided by rheumatology.

• Symptomatic therapy:
  • NSAIDs NSAIDS Primary vs Secondary Headaches for mild disease 
  • Glucocorticoids Glucocorticoids Glucocorticoids are a class within the corticosteroid family. Glucocorticoids are chemically and functionally similar to endogenous cortisol. There are a wide array of indications, which primarily benefit from the antiinflammatory and immunosuppressive effects of this class of drugs. Glucocorticoids (systemic and injections)
• Pharmacologic therapy:
  • Biologics ( infliximab Infliximab A chimeric monoclonal antibody to tnf-alpha that is used in the treatment of rheumatoid arthritis; ankylosing spondylitis; psoriatic arthritis and Crohn’s disease. Disease-Modifying Antirheumatic Drugs (DMARDs), etanercept Etanercept A recombinant version of soluble human tnf receptor fused to an IgG Fc fragment that binds specifically to tumor necrosis factor and inhibits its binding with endogenous tnf receptors. It prevents the inflammatory effect of tnf and is used to treat rheumatoid arthritis; psoriatic arthritis and ankylosing spondylitis. Immunosuppressants, adalimumab Adalimumab A humanized monoclonal antibody that binds specifically to tnf-alpha and blocks its interaction with endogenous tnf receptors to modulate inflammation. It is used in the treatment of rheumatoid arthritis; psoriatic arthritis; Crohn’s disease and ulcerative colitis. Disease-Modifying Antirheumatic Drugs (DMARDs)) 
  • Disease-modifying antirheumatic drugs Disease-modifying antirheumatic drugs Disease-modifying antirheumatic drugs are antiinflammatory medications used to manage rheumatoid arthritis. The medications slow, but do not cure, the progression of the disease. The medications are classified as either synthetic or biologic agents and each has unique mechanisms of action and side effects. Disease-Modifying Antirheumatic Drugs (DMARDs) ( 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, leflunomide Leflunomide An isoxazole derivative that inhibits dihydroorotate dehydrogenase, the fourth enzyme in the pyrimidine biosynthetic pathway. It is used an immunosuppressive agent in the treatment of rheumatoid arthritis. Disease-Modifying Antirheumatic Drugs (DMARDs)) 
• Nonpharmacologic therapy:
  • Physical and occupational therapy Occupational Therapy Skilled treatment that helps individuals achieve independence in all facets of their lives. It assists in the development of skills needed for independent living. Fetal Alcohol Spectrum Disorder 
  • Exercise 
  • Orthotics 
  • Joint protection
  • Weight reduction