Stevens-Johnson Syndrome

Overview

Classification

• Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe mucocutaneous reactions. 
• Considered a continuum of the same disease
• Classified based on the percentage of body surface affected by blisters, erosions Erosions Corneal Abrasions, Erosion, and Ulcers, and 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 detachment:

Epidemiology

• 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:
  • 1–7 cases per million people per year
  • Higher 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 and active cancer
  • SJS is more common.
• Mortality Mortality All deaths reported in a given population. Measures of Health Status rate:
  • SJS: 10%
  • TEN: 50%
• More common in women than men, with a ratio of 2:1
• Can occur at any age

Etiology

• Medications
  • Approximately 70% of cases
  • Occurs within 8 weeks of medication onset
• 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
  • 2nd-most common trigger Trigger The type of signal that initiates the inspiratory phase by the ventilator Invasive Mechanical Ventilation
  • Frequent cause in children
• Idiopathic Idiopathic Dermatomyositis
  • > ¹/₃ of cases
• Genetics Genetics Genetics is the study of genes and their functions and behaviors. Basic Terms of Genetics
  • Some HLA types are associated with an increased risk.
• Other risk factors
  • Malignancy Malignancy Hemothorax 
  • Lupus 
  • Ultraviolet light Ultraviolet light That portion of the electromagnetic spectrum immediately below the visible range and extending into the x-ray frequencies. The longer wavelengths (near-uv or biotic or vital rays) are necessary for the endogenous synthesis of vitamin D and are also called antirachitic rays; the shorter, ionizing wavelengths (far-uv or abiotic or extravital rays) are viricidal, bactericidal, mutagenic, and carcinogenic and are used as disinfectants. Bullous Pemphigoid and Pemphigus Vulgaris stimulus 
  • 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 therapy

The following table lists the major common medication and infectious causes of SJS/TEN:

Pathogenesis

The exact mechanism is unknown, but there are several theories:

1. Drug, or infectious, antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination in the skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions tissue → stimulates cytotoxic Cytotoxic Parvovirus B19 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, natural killer T cells Natural killer T cells A specialized subset of T-lymphocytes that exhibit features of innate immunity similar to that of natural killer cells. They are reactive to glycolipids presented in the context of the major histocompatibility complex (MHC) class i-like molecule, cd1d antigen. T cells: Types and Functions (NKT), and natural killer (NK) cells → granulysin release → 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 death
2. 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 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 → epidermal separation from the dermis Dermis A layer of vascularized connective tissue underneath the epidermis. The surface of the dermis contains innervated papillae. Embedded in or beneath the dermis are sweat glands; hair follicles; and sebaceous glands. Skin: Structure and Functions → characteristic 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 detachment of SJS/TEN
3. Dying cells and necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage → ↑ antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination load → triggers 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 to continue the inflammatory response → development of fluid-filled blisters 

This impaired 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 integrity can lead to:

• Water loss
• Secondary bacterial 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 and 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

Clinical Presentation

Clinical manifestations

Prodrome Prodrome Symptoms that appear 24–48 hours prior to migraine onset. Migraine Headache: 

• 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 (often > 39°C)
• Myalgia Myalgia Painful sensation in the muscles. Ion Channel Myopathy and arthralgia Arthralgia Pain in the joint. Rheumatic Fever
• Keratoconjunctivitis ( 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 cornea Cornea The transparent anterior portion of the fibrous coat of the eye consisting of five layers: stratified squamous corneal epithelium; bowman membrane; corneal stroma; descemet membrane; and mesenchymal corneal endothelium. It serves as the first refracting medium of the eye. Eye: Anatomy and conjunctiva Conjunctiva The mucous membrane that covers the posterior surface of the eyelids and the anterior pericorneal surface of the eyeball. Eye: Anatomy)
• Sore throat Sore throat Pharyngitis is an inflammation of the back of the throat (pharynx). Pharyngitis is usually caused by an upper respiratory tract infection, which is viral in most cases. It typically results in a sore throat and fever. Other symptoms may include a runny nose, cough, headache, and hoarseness. Pharyngitis
• 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
• Malaise Malaise Tick-borne Encephalitis Virus

Acute phase Acute phase Short Bowel Syndrome: 

• 1‒3 days after the prodrome Prodrome Symptoms that appear 24–48 hours prior to migraine onset. Migraine Headache
• Lasts 8‒12 days
• Cutaneous lesions
  • Begin as ill-defined, coalescing macules with purpuric centers or diffuse erythema Erythema Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of disease processes. Chalazion
    • Start on the face and thorax, then spread symmetrically
    • Typically spare scalp, palms, and soles
    • Tender to touch
  • Vesicles Vesicles Female Genitourinary Examination and bullae Bullae Erythema Multiforme form as the disease progresses
  • 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 begins to slough within days
  • Nikolsky sign Nikolsky Sign Dermatologic Examination: extension Extension Examination of the Upper Limbs 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 sloughing by applying pressure
• Mucosal lesions
  • Occur in approximately 90% of cases
  • Includes oral, pharyngeal, ocular, and urogenital erosions Erosions Corneal Abrasions, Erosion, and Ulcers

Complications

• Significant fluid loss
  • Severe dehydration Severe Dehydration Fluid Replacement Therapy in Children 
  • Hypovolemic shock Hypovolemic Shock Types of Shock 
  • Renal failure Renal failure Conditions in which the kidneys perform below the normal level in the ability to remove wastes, concentrate urine, and maintain electrolyte balance; blood pressure; and calcium metabolism. Renal insufficiency can be classified by the degree of kidney damage (as measured by the level of proteinuria) and reduction in glomerular filtration rate. Crush Syndrome
• Bacterial infection
  • 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 and septic shock Septic shock Sepsis associated with hypotension or hypoperfusion despite adequate fluid resuscitation. Perfusion abnormalities may include, but are not limited to lactic acidosis; oliguria; or acute alteration in mental status. Sepsis and Septic Shock are the main cause of death in SJS/TEN patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship.
  • Most often caused by Staphylococcus aureus Staphylococcus aureus Potentially pathogenic bacteria found in nasal membranes, skin, hair follicles, and perineum of warm-blooded animals. They may cause a wide range of infections and intoxications. Brain Abscess and Pseudomonas aeruginosa Pseudomonas aeruginosa A species of gram-negative, aerobic, rod-shaped bacteria commonly isolated from clinical specimens (wound, burn, and urinary tract infections). It is also found widely distributed in soil and water. P. Aeruginosa is a major agent of nosocomial infection. Pseudomonas
• Tracheobronchial epithelial involvement
  • Pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia 
  • Interstitial 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) 
• Protein loss: edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema
• Electrolyte imbalances
• Epithelial necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage of the gastrointestinal tract
  • Diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea 
  • Melena Melena The black, tarry, foul-smelling feces that contain degraded blood. Gastrointestinal Bleeding 
  • Colonic perforation Perforation A pathological hole in an organ, blood vessel or other soft part of the body, occurring in the absence of external force. Esophagitis 
  • Small bowel Small bowel The small intestine is the longest part of the GI tract, extending from the pyloric orifice of the stomach to the ileocecal junction. The small intestine is the major organ responsible for chemical digestion and absorption of nutrients. It is divided into 3 segments: the duodenum, the jejunum, and the ileum. Small Intestine: Anatomy intussusception Intussusception Intussusception occurs when a part of the intestine (intussusceptum) telescopes into another part (intussuscipiens) of the intestine. The condition can cause obstruction and, if untreated, progress to bowel ischemia. Intussusception is most common in the pediatric population, but is occasionally encountered in adults. Intussusception

Diagnosis

The diagnosis is clinical, based on history and physical exam findings.

• Skin biopsy Skin Biopsy Secondary Skin Lesions
  • Not required for diagnosis, but can confirm and rule out other conditions
  • 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 necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage is the hallmark finding.
    • Can be partial or full-thickness
    • Apoptotic 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 are scattered in the basal layer of the epidermis Epidermis The external, nonvascular layer of the skin. It is made up, from within outward, of five layers of epithelium: (1) basal layer (stratum basale epidermidis); (2) spinous layer (stratum spinosum epidermidis); (3) granular layer (stratum granulosum epidermidis); (4) clear layer (stratum lucidum epidermidis); and (5) horny layer (stratum corneum epidermidis). Skin: Structure and Functions in early lesions.
    • Full-thickness epidermal necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage and subepidermal bullae Bullae Erythema Multiforme later in the disease
  • Lymphocytic inflammatory infiltration
  • Direct immunofluorescence is negative.
• Supporting workup 
  • Aids AIDS Chronic HIV infection and depletion of CD4 cells eventually results in acquired immunodeficiency syndrome (AIDS), which can be diagnosed by the presence of certain opportunistic diseases called AIDS-defining conditions. These conditions include a wide spectrum of bacterial, viral, fungal, and parasitic infections as well as several malignancies and generalized conditions. HIV Infection and AIDS in monitoring treatment and complications
  • Basic metabolic panel Basic Metabolic Panel Primary vs Secondary Headaches → evaluate for electrolyte imbalance and renal failure Renal failure Conditions in which the kidneys perform below the normal level in the ability to remove wastes, concentrate urine, and maintain electrolyte balance; blood pressure; and calcium metabolism. Renal insufficiency can be classified by the degree of kidney damage (as measured by the level of proteinuria) and reduction in glomerular filtration rate. Crush Syndrome
  • Complete blood count → significant leukocytosis Leukocytosis A transient increase in the number of leukocytes in a body fluid. West Nile Virus may signal an infection
  • Bacterial and fungal cultures Fungal cultures Dermatophytes/Tinea Infections → bacterial superinfection and 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
  • Chest radiograph → pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia or interstitial pneumonitis Pneumonitis Human Herpesvirus 6 and 7

Treatment

• Immediate hospital admission
  • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship typically require intensive care or a burn unit Burn unit Specialized hospital facilities which provide intensive care for burn patients. Staphylococcal Scalded Skin Syndrome (SSSS).
  • SCORTEN score (score of toxic epidermal necrolysis) is calculated to determine severity, prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas, and appropriate setting for management (see table below).
• Withdrawal of causative agent is required.
• Supportive care:
  • Wound care
    • Debridement 
    • Moisturizers 
    • Antibacterial Antibacterial Penicillins ointments
  • Fluid and electrolyte management
  • Nutritional support
    • Parenteral nutrition Parenteral nutrition The administering of nutrients for assimilation and utilization by a patient who cannot maintain adequate nutrition by enteral feeding alone. Nutrients are administered by a route other than the alimentary canal (e.g., intravenously, subcutaneously). Central Venous Catheter for those with dysphagia Dysphagia Dysphagia is the subjective sensation of difficulty swallowing. Symptoms can range from a complete inability to swallow, to the sensation of solids or liquids becoming “stuck.” Dysphagia is classified as either oropharyngeal or esophageal, with esophageal dysphagia having 2 sub-types: functional and mechanical. Dysphagia and odynophagia Odynophagia Epiglottitis 
    • Transition to oral feeds when tolerated
  • Ocular care
    • Ophthalmology consultation
    • Corticosteroid and antibiotic eye drops 
    • Artificial tears for lubrication 
  • Temperature management
  • Pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways control 
    • Acetaminophen Acetaminophen Acetaminophen is an over-the-counter nonopioid analgesic and antipyretic medication and the most commonly used analgesic worldwide. Despite the widespread use of acetaminophen, its mechanism of action is not entirely understood. Acetaminophen and ibuprofen Ibuprofen A nonsteroidal anti-inflammatory agent with analgesic properties used in the treatment of rheumatism and arthritis. Nonsteroidal Antiinflammatory Drugs (NSAIDs) for mild pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways 
    • Opioids Opioids Opiates are drugs that are derived from the sap of the opium poppy. Opiates have been used since antiquity for the relief of acute severe pain. Opioids are synthetic opiates with properties that are substantially similar to those of opiates. Opioid Analgesics for severe pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways
  • Monitoring and treatment of superinfections
    • Bacterial and fungal cultures Fungal cultures Dermatophytes/Tinea Infections of blood, wounds, and mucosal lesions
    • Appropriate antibiotics and antifungals, as necessary
  • Education on future drug avoidance, including closely related agents
• Controversial treatments:
  • 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
  • Systemic corticosteroids Corticosteroids Chorioretinitis
  • Plasmapheresis
  • Intravenous immunoglobulin ( IVIG IVIG Dermatomyositis)

The SCORTEN score is used to help determine the severity, prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas, and appropriate setting for management in SJS/TEN patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship.

• Score 0‒1: 94% survival, may be treated in non-specialized wards
• Score 2: 87% survival, should be transferred to an intensive care unit, burn unit Burn unit Specialized hospital facilities which provide intensive care for burn patients. Staphylococcal Scalded Skin Syndrome (SSSS), or specialized dermatology unit
• Score 3: 53% survival, should be transferred to an intensive care unit, burn unit Burn unit Specialized hospital facilities which provide intensive care for burn patients. Staphylococcal Scalded Skin Syndrome (SSSS), or specialized dermatology unit
• Score 4: 25% survival, should be transferred to an intensive care unit, burn unit Burn unit Specialized hospital facilities which provide intensive care for burn patients. Staphylococcal Scalded Skin Syndrome (SSSS), or specialized dermatology unit
• Score 5‒7: 17% survival, should be transferred to an intensive care unit, burn unit Burn unit Specialized hospital facilities which provide intensive care for burn patients. Staphylococcal Scalded Skin Syndrome (SSSS), or specialized dermatology unit

Differential Diagnosis

• Erythema Erythema Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of disease processes. Chalazion multiforme: an acute, immune-mediated 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 eruption with typical targetoid lesions; may be accompanied by systemic symptoms and mucosal involvement. Etiology is usually due to infection from the herpes simplex Herpes Simplex A group of acute infections caused by herpes simplex virus type 1 or type 2 that is characterized by the development of one or more small fluid-filled vesicles with a raised erythematous base on the skin or mucous membrane. It occurs as a primary infection or recurs due to a reactivation of a latent infection. Congenital TORCH Infections 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, unlike SJS/TEN, which is usually caused by a medication. Diagnosis is clinical and will differentiate this condition from SJS. Treatment includes supportive care.

• Staphylococcal scalded skin syndrome Staphylococcal Scalded Skin Syndrome Staphylococcal scalded skin syndrome (SSSS), also known as Ritter disease and staphylococcal epidermal necrolysis, is a toxin-mediated condition caused by Staphylococcus aureus. The exfoliative toxin produced disseminates and cleaves desmoglein 1 in the epidermis, causing separation and detachment of the skin. Staphylococcal Scalded Skin Syndrome (SSSS) ( SSSS SSSS Staphylococcal scalded skin syndrome (SSSS), also known as Ritter disease and staphylococcal epidermal necrolysis, is a toxin-mediated condition caused by Staphylococcus aureus. The exfoliative toxin produced disseminates and cleaves desmoglein 1 in the epidermis, causing separation and detachment of the skin. Staphylococcal Scalded Skin Syndrome (SSSS)): presents with a painful, desquamative 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 rash Rash Rocky Mountain Spotted Fever, especially around the nose Nose The nose is the human body’s primary organ of smell and functions as part of the upper respiratory system. The nose may be best known for inhaling oxygen and exhaling carbon dioxide, but it also contributes to other important functions, such as tasting. The anatomy of the nose can be divided into the external nose and the nasal cavity. Nose Anatomy (External & Internal), mouth, and anus. The condition results from a staphylococcal toxin, and is usually seen in children. Unlike SJS/TEN, there is no mucosal involvement. Diagnosis is clinical and confirmed with bacterial cultures. A biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma will show noninflammatory, superficial splitting Splitting Defense Mechanisms of the epidermis Epidermis The external, nonvascular layer of the skin. It is made up, from within outward, of five layers of epithelium: (1) basal layer (stratum basale epidermidis); (2) spinous layer (stratum spinosum epidermidis); (3) granular layer (stratum granulosum epidermidis); (4) clear layer (stratum lucidum epidermidis); and (5) horny layer (stratum corneum epidermidis). Skin: Structure and Functions. Treatment includes antibiotics, wound care, and supportive care.

• Exfoliative dermatitis Dermatitis Any inflammation of the skin. Atopic Dermatitis (Eczema): a generalized, symmetric, erythematous rash Rash Rocky Mountain Spotted Fever caused by an underlying cutaneous disease ( 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, atopic dermatitis Dermatitis Any inflammation of the skin. Atopic Dermatitis (Eczema)), medications, and malignancy Malignancy Hemothorax ( lymphoma Lymphoma A general term for various neoplastic diseases of the lymphoid tissue. Imaging of the Mediastinum). The condition can mimic the early stages of SJS; however, there is no mucosal involvement (which will differentiate the condition from SJS). Diagnosis is made clinically, and treatment focuses on treating the underlying cause, withdrawal of implicated medications, and supportive care.

• Toxic shock syndrome Toxic Shock Syndrome Toxic shock syndrome (TSS) is an acute, multi-systemic disease caused by the toxin-producing bacteria, Staphylococcus aureus and Streptococcus pyogenes. Staphylococcal TSS is more common and associated with tampons and nasal packing. Toxic Shock Syndrome: a systemic syndrome caused by staphylococcus Staphylococcus Staphylococcus is a medically important genera of Gram-positive, aerobic cocci. These bacteria form clusters resembling grapes on culture plates. Staphylococci are ubiquitous for humans, and many strains compose the normal skin flora. Staphylococcus or 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 endotoxins Endotoxins Toxins closely associated with the living cytoplasm or cell wall of certain microorganisms, which do not readily diffuse into the culture medium, but are released upon lysis of the cells. Bacteriology. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship present with 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, shock Shock Shock is a life-threatening condition associated with impaired circulation that results in tissue hypoxia. The different types of shock are based on the underlying cause: distributive (↑ cardiac output (CO), ↓ systemic vascular resistance (SVR)), cardiogenic (↓ CO, ↑ SVR), hypovolemic (↓ CO, ↑ SVR), obstructive (↓ CO), and mixed. Types of Shock, and multisystem organ dysfunction. Cutaneous manifestations include a diffuse, erythematous rash Rash Rocky Mountain Spotted Fever and desquamation Desquamation Staphylococcal Scalded Skin Syndrome (SSSS). Diagnosis is based on blood culture results, clinical history, and exam, which will differentiate this condition from SJS. Treatment includes hemodynamic support, fluid resuscitation Resuscitation The restoration to life or consciousness of one apparently dead. . Neonatal Respiratory Distress Syndrome, and antibiotics.

• Pemphigus vulgaris Pemphigus vulgaris Bullous pemphigoid and pemphigus vulgaris are two different blistering autoimmune diseases. In pemphigus vulgaris, autoantibodies attack the desmosomal proteins, which connect the keratinocytes to one another. This attack results in a more severe, potentially fatal condition with fragile, flaccid blisters, usually with significant mucosal involvement. Bullous Pemphigoid and Pemphigus Vulgaris: an autoimmune disorder Autoimmune Disorder Septic Arthritis causing intraepidermal blistering and erosions Erosions Corneal Abrasions, Erosion, and Ulcers of the skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions and mucous membranes. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship will have cutaneous bullae Bullae Erythema Multiforme appearing on normal-appearing 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 and painful mucocutaneous erosions Erosions Corneal Abrasions, Erosion, and Ulcers. Diagnosis involves a biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma with immunofluorescence testing showing immunoglobulin G ( IgG IgG The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of igg, for example, igg1, igg2a, and igg2b. Hypersensitivity Pneumonitis) antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions against 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, differentiating this condition from SJS. Treatment includes corticosteroids Corticosteroids Chorioretinitis, immunosuppressants Immunosuppressants Immunosuppressants are a class of drugs widely used in the management of autoimmune conditions and organ transplant rejection. The general effect is dampening of the immune response. Immunosuppressants, and IVIG IVIG Dermatomyositis.

• Bullous pemphigoid Bullous pemphigoid Bullous pemphigoid and pemphigus vulgaris are two different blistering autoimmune diseases. In bullous pemphigoid, autoantibodies attack the hemidesmosomes, which connect epidermal keratinocytes to the basement membrane. This attack results in large, tense subepidermal blisters. Bullous Pemphigoid and Pemphigus Vulgaris: an autoimmune 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 disorder causing pruritus Pruritus An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. Atopic Dermatitis (Eczema), erythematous plaques, and tense, bullous lesions. Mucous membrane Mucous membrane An epithelium with mucus-secreting cells, such as goblet cells. It forms the lining of many body cavities, such as the digestive tract, the respiratory tract, and the reproductive tract. Mucosa, rich in blood and lymph vessels, comprises an inner epithelium, a middle layer (lamina propria) of loose connective tissue, and an outer layer (muscularis mucosae) of smooth muscle cells that separates the mucosa from submucosa. Barrett Esophagus involvement is rare. Triggers include medications, trauma, 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 conditions, and systemic disease. Biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma with immunofluorescence shows IgG IgG The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of igg, for example, igg1, igg2a, and igg2b. Hypersensitivity Pneumonitis and complement deposits along the basement membrane Basement membrane A darkly stained mat-like extracellular matrix (ecm) that separates cell layers, such as epithelium from endothelium or a layer of connective tissue. The ecm layer that supports an overlying epithelium or endothelium is called basal lamina. Basement membrane (bm) can be formed by the fusion of either two adjacent basal laminae or a basal lamina with an adjacent reticular lamina of connective tissue. Bm, composed mainly of type IV collagen; glycoprotein laminin; and proteoglycan, provides barriers as well as channels between interacting cell layers. Thin Basement Membrane Nephropathy (TBMN), which differentiates the condition from SJS. Treatment includes 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, immunosuppressants Immunosuppressants Immunosuppressants are a class of drugs widely used in the management of autoimmune conditions and organ transplant rejection. The general effect is dampening of the immune response. Immunosuppressants, and anti-inflammatory medications.