Generalized and Localized Rashes

Overview

Definition

A rash Rash Rocky Mountain Spotted Fever is an abnormal change 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’s color or texture Texture Dermatologic Examination.

Epidemiology

One of the most common conditions encountered by primary care physicians Physicians Individuals licensed to practice medicine. Clinician–Patient Relationship
In 2016, 1 in 4 people in the United States (84.5 million) were affected by 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 disease.
1 in 3 people required a dermatology evaluation.
Maculopapular Maculopapular Dermatologic Examination rashes are the most commonly seen generalized rash Rash Rocky Mountain Spotted Fever (95%).
Diagnostic errors Diagnostic Errors Incorrect or incomplete diagnoses following clinical or technical diagnostic procedures. Patient Safety: Types of Medical Errors in generalized rashes are common.

Etiology

The list of etiologies for rashes is long but can include irritants, allergens, 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 inflammatory conditions.

Classification

Rashes are described and classified based on certain characteristics, which can assist with forming a differential diagnosis when evaluating a patient.

Configuration

The configuration refers to the shape or outline of lesions.

Circinate: round, circular
Arciform: forms a partial circle
Linear: appears straight
Serpiginous: meandering appearance
Annular Annular Dermatologic Examination: round or circular with central clearing
Target: a series of concentric rings
Gyrate: a series of connecting arcs
Zosteriform: appears to follow a dermatome Dermatome Spinal Disk Herniation

Rash configurations — Visualization of different rash configurations
Image by Lecturio.

Morphology

The morphology is based on the size and consistency Consistency Dermatologic Examination of the lesions.

Flat lesions:
- Macule: nonpalpable lesion < 1 cm in diameter
- Patch: nonpalpable lesion > 1 cm in diameter
Raised lesions:
- Papule: elevated lesion < 1 cm in diameter
- Plaque Plaque Primary Skin Lesions: flat-topped elevated lesion > 1 cm in diameter
- Nodule Nodule Chalazion: deep, solid or cystic Cystic Fibrocystic Change, elevated lesion > 1 cm in diameter
- Wheal Wheal Urticaria (Hives): irregularly shaped, edematous, raised, transient plaque Plaque Primary Skin Lesions
Blistering lesions:
- Vesicle Vesicle Primary Skin Lesions: blister Blister Bullous Pemphigoid and Pemphigus Vulgaris filled with clear fluid, < 1 cm diameter
- Bulla: blister Blister Bullous Pemphigoid and Pemphigus Vulgaris filled with fluid, > 1 cm diameter
- Pustule: blister Blister Bullous Pemphigoid and Pemphigus Vulgaris filled with pus
Disruption 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:
- Erosion: partial-thickness loss 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
- Fissure: a crack Crack The purified, alkaloidal, extra-potent form of cocaine. It is smoked (free-based), injected intravenously, and orally ingested. Use of crack results in alterations in function of the cardiovascular system, the autonomic nervous system, the central nervous system, and the gastrointestinal system. The slang term ‘crack’ was derived from the crackling sound made upon igniting of this form of cocaine for smoking. Cocaine Use Disorder or split that extends into 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
- Ulcer: full-thickness loss 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 that extends into 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

Rash morphology — Visualization of different rash morphologies
Image by Lecturio.

Rash morphology flowchart — Schematic to help differentiate different morphologies based on their size and characteristics
Image by Lecturio.

Small, flat macules due to rubella
Image: “Rubella” by CDC. License: Public Domain

Large patches of hypopigmentation in vitiligo — Small, flat macules due to rubella
Image: “Rubella” by CDC. License: Public Domain

Secondary characteristics

Crust Crust Dried exudate of body fluids (blood, pus, or sebum) on an area of damaged skin Secondary Skin Lesions: dried exudate Exudate Exudates are fluids, cells, or other cellular substances that are slowly discharged from blood vessels usually from inflamed tissues. Pleural Effusion on the skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions
Scale Scale Dermatologic Examination: flakes or plates of desiccated 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
Lichenification Lichenification Atopic Dermatitis (Eczema): leathery thickening 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 with exaggerated 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 markings
Excoriation Excoriation Mastitis: linear 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 erosions Erosions Corneal Abrasions, Erosion, and Ulcers, often caused by scratching
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: swelling Swelling Inflammation of the tissue
Scar Scar Dermatologic Examination: fibrous Fibrous Fibrocystic Change tissue development after an injury

Demonstration of an overlying crust — An overlying crust
Image: “Diabetic dermopathy (“shin spots”) and diabetic bullae (“bullosis diabeticorum”) at the same patient” by Brzezinski P, Chiriac AE, Pinteala T, Foia L, Chiriac A. License: CCC BY 3.0

Scale on a herald patch of pityriasis rosea — An overlying crust
Image: “Diabetic dermopathy (“shin spots”) and diabetic bullae (“bullosis diabeticorum”) at the same patient” by Brzezinski P, Chiriac AE, Pinteala T, Foia L, Chiriac A. License: CCC BY 3.0

Distribution

Localized: Lesions are confined to a specific area.
Generalized: Lesions are dispersed throughout the body.
Symmetric: similarly affects both sides of the body
Asymmetric: unilateral or affects both sides of the body differently
Discrete: separate, distinct lesions
Grouped: clusters of lesions
Confluent (coalescing): Smaller lesions merge together.
Cleavage plane: Lesions are arranged along the lines 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 tension.

Clinical Presentation and Diagnosis

The diagnosis for many conditions is purely clinical and based on the patient’s history and physical exam.

History

Onset (including the location of initial onset)
Time frame:
- Acute or chronic
- Relapsing-remitting
Progression
Aggravating and alleviating factors
Associated symptoms:
- 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
- Pruritus Pruritus An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. Atopic Dermatitis (Eczema)
- Pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways
- Malaise Malaise Tick-borne Encephalitis Virus
- Cough
Other pertinent history:
- Allergies Allergies A medical specialty concerned with the hypersensitivity of the individual to foreign substances and protection from the resultant infection or disorder. Selective IgA Deficiency
- Recent travel
- Insect, plant, or animal exposure
- Occupational history
- New home products
- Drug exposure
- Sick contacts
- Chronic illnesses
- Sexual history

**Table: Summary of possible conditions based on patient’s history**
Patient’s history	Associated disease
Chronic illness	Dermatitis herpetiformis Dermatitis herpetiformis Rare, chronic, papulo-vesicular disease characterized by an intensely pruritic eruption consisting of various combinations of symmetrical, erythematous, papular, vesicular, or bullous lesions. The disease is strongly associated with the presence of hla-b8 and hla-dr3 antigens. A variety of different autoantibodies has been detected in small numbers in patients with dermatitis herpetiformis. Celiac Disease Seborrheic dermatitis Dermatitis Any inflammation of the skin. Atopic Dermatitis (Eczema)
Contact with ill persons	5th disease Meningococcemia Meningococcemia Terminal Complement Pathway Deficiency Rubella Rubella An acute infectious disease caused by the rubella virus. The virus enters the respiratory tract via airborne droplet and spreads to the lymphatic system. Rubella Virus Roseola Rubeola Rubeola Measles (also known as rubeola) is caused by a single-stranded, linear, negative-sense RNA virus of the family Paramyxoviridae. It is highly contagious and spreads by respiratory droplets or direct-contact transmission from an infected person. Typically a disease of childhood, measles classically starts with cough, coryza, and conjunctivitis, followed by a maculopapular rash. Measles Virus Scarlet fever Scarlet fever Infection with group a Streptococci that is characterized by tonsillitis and pharyngitis. An erythematous rash is commonly present. Scarlet Fever Varicella
Drug exposure	Lupus Drug eruption Urticaria Urticaria Urticaria is raised, well-circumscribed areas (wheals) of edema (swelling) and erythema (redness) involving the dermis and epidermis with associated pruritus (itch). Urticaria is not a single disease but rather is a reaction pattern representing cutaneous mast cell degranulation. Urticaria (Hives) Stevens-Johnson syndrome Stevens-Johnson syndrome Stevens-Johnson syndrome (SJS) is a cutaneous, immune-mediated hypersensitivity reaction that is commonly triggered by medications, including antiepileptics and antibiotics. The condition runs on a spectrum with toxic epidermal necrolysis (TEN) based on the amount of body surface area (BSA) involved. Stevens-Johnson Syndrome
Occupational or environmental exposure	Contact dermatitis Contact dermatitis A type of acute or chronic skin reaction in which sensitivity is manifested by reactivity to materials or substances coming in contact with the skin. It may involve allergic or non-allergic mechanisms. Male Genitourinary Examination
Insect and arthropod exposure	Insect bites Lyme disease Lyme disease Lyme disease is a tick-borne infection caused by the gram-negative spirochete Borrelia burgdorferi. Lyme disease is transmitted by the black-legged Ixodes tick (known as a deer tick), which is only found in specific geographic regions. Patient presentation can vary depending on the stage of the disease and may include a characteristic erythema migrans rash. Lyme Disease Rickettsialpox Rickettsialpox Rickettsia Rocky Mountain spotted 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 Scabies Scabies Scabies is an infestation of the skin by the Sarcoptes scabiei mite, which presents most commonly with intense pruritus, characteristic linear burrows, and erythematous papules, particularly in the interdigital folds and the flexor aspects of the wrists. Scabies
Recent systemic symptoms	5th disease HIV HIV Anti-HIV Drugs acute exanthem Exanthem Diseases in which skin eruptions or rashes are a prominent manifestation. Classically, six such diseases were described with similar rashes; they were numbered in the order in which they were reported. Only the fourth (Duke’s disease), fifth (erythema infectiosum), and sixth (exanthema subitum) numeric designations survive as occasional synonyms in current terminology. Varicella-Zoster Virus/Chickenpox Kawasaki disease Kawasaki disease An acute, febrile, mucocutaneous condition accompanied by swelling of cervical lymph nodes in infants and young children. The principal symptoms are fever, congestion of the ocular conjunctivae, reddening of the lips and oral cavity, protuberance of tongue papillae, and edema or erythema of the extremities. Kawasaki Disease Meningococcemia Meningococcemia Terminal Complement Pathway Deficiency Roseola Rubella Rubella An acute infectious disease caused by the rubella virus. The virus enters the respiratory tract via airborne droplet and spreads to the lymphatic system. Rubella Virus Rubeola Rubeola Measles (also known as rubeola) is caused by a single-stranded, linear, negative-sense RNA virus of the family Paramyxoviridae. It is highly contagious and spreads by respiratory droplets or direct-contact transmission from an infected person. Typically a disease of childhood, measles classically starts with cough, coryza, and conjunctivitis, followed by a maculopapular rash. Measles Virus Scarlet fever Scarlet fever Infection with group a Streptococci that is characterized by tonsillitis and pharyngitis. An erythematous rash is commonly present. Scarlet Fever Varicella
Sexual history	HIV HIV Anti-HIV Drugs acute exanthem Exanthem Diseases in which skin eruptions or rashes are a prominent manifestation. Classically, six such diseases were described with similar rashes; they were numbered in the order in which they were reported. Only the fourth (Duke’s disease), fifth (erythema infectiosum), and sixth (exanthema subitum) numeric designations survive as occasional synonyms in current terminology. Varicella-Zoster Virus/Chickenpox Secondary syphilis Secondary Syphilis Syphilis Disseminated gonorrhea Gonorrhea Gonorrhea is a sexually transmitted infection (STI) caused by the gram-negative bacteria Neisseria gonorrhoeae (N. gonorrhoeae). Gonorrhea may be asymptomatic but commonly manifests as cervicitis or urethritis with less common presentations such as proctitis, conjunctivitis, or pharyngitis. Gonorrhea
Travel	Insect bites Lyme disease Lyme disease Lyme disease is a tick-borne infection caused by the gram-negative spirochete Borrelia burgdorferi. Lyme disease is transmitted by the black-legged Ixodes tick (known as a deer tick), which is only found in specific geographic regions. Patient presentation can vary depending on the stage of the disease and may include a characteristic erythema migrans rash. Lyme Disease Rickettsialpox Rickettsialpox Rickettsia Rocky Mountain spotted 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

HIV: human immunodeficiency virus

Physical exam

A full 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 exam should be performed.

Appearance:
- Number of lesions
- Configuration and borders
- Morphology
- Color
- Presence of scale Scale Dermatologic Examination or crusts
Distribution:
- Diffuse or localized
- Symmetrical Symmetrical Dermatologic Examination or asymmetrical
- Dermatomal Dermatomal Dermatologic Examination
- Clustered or grouped
- Mucosal involvement
- Atypical sites (e.g., palms and soles)
Palpation Palpation Application of fingers with light pressure to the surface of the body to determine consistency of parts beneath in physical diagnosis; includes palpation for determining the outlines of organs. Dermatologic Examination of lesions:
- Raised
- Flat
- Texture Texture Dermatologic Examination changes
- Induration Induration Dermatologic Examination
- Blanching Blanching Dermatologic Examination with pressure
In patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with bullae Bullae Erythema Multiforme, check for 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 blistering or sloughing by applying pressure
- Demonstrates 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
In patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with plaques, check for Auspitz sign Auspitz Sign Psoriasis: pinpoint bleeding after scraping plaques
Other physical exam findings to evaluate for:
- Vital signs
- 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
- 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
- Pharyngitis Pharyngitis 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
- Heart murmur
- Hepatosplenomegaly Hepatosplenomegaly Cytomegalovirus
- Joint swelling Swelling Inflammation
- Neurologic deficits Neurologic Deficits High-Risk Headaches

Testing

A diagnostic workup may be performed if the history and physical exam do not provide enough clues to the diagnosis. The differential diagnosis will dictate which studies should be performed.

Biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma with microscopic examination:
- There are no widely accepted guidelines with indications for skin biopsy Skin Biopsy Secondary Skin Lesions.
- Immunofluorescence can be helpful.
Laboratory tests are indicated if there are systemic symptoms.
- CBC → evaluate for eosinophilia Eosinophilia Abnormal increase of eosinophils in the blood, tissues or organs. Autosomal Dominant Hyperimmunoglobulin E Syndrome, neutrophilia, or thrombocytopenia Thrombocytopenia Thrombocytopenia occurs when the platelet count is < 150,000 per microliter. The normal range for platelets is usually 150,000-450,000/µL of whole blood. Thrombocytopenia can be a result of decreased production, increased destruction, or splenic sequestration of platelets. Patients are often asymptomatic until platelet counts are < 50,000/µL. Thrombocytopenia
- Basic metabolic panel Basic Metabolic Panel Primary vs Secondary Headaches and 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 function panel → evaluate for systemic renal and hepatic involvement
- ANAs → a good initial test if an autoimmune etiology is being considered
- Serologic testing for various infectious causes
Allergy Allergy An abnormal adaptive immune response that may or may not involve antigen-specific IgE Type I Hypersensitivity Reaction testing:
- Patch testing
- 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 prick testing
- Serum IgE IgE An immunoglobulin associated with mast cells. Overexpression has been associated with allergic hypersensitivity. Immunoglobulins: Types and Functions studies

Management

The management of a rash Rash Rocky Mountain Spotted Fever depends on the underlying condition. Many rashes will be self-limited and may not require any treatment.

Basic management:
- Identify and avoid aggravating factors.
- Supportive therapies:
  - Low-heat baths
  - Mild soaps
  - 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
  - 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 moisturizers
Symptom management for pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways and pruritus Pruritus An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. Atopic Dermatitis (Eczema):
- 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
- NSAIDs NSAIDS Primary vs Secondary Headaches
- Antihistamines Antihistamines Antihistamines are drugs that target histamine receptors, particularly H1 and H2 receptors. H1 antagonists are competitive and reversible inhibitors of H1 receptors. First-generation antihistamines cross the blood-brain barrier and can cause sedation. Antihistamines
For inflammatory conditions:
- Infection should be ruled out.
- 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:
  - 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
  - Clobetasol Clobetasol A derivative of prednisolone with high glucocorticoid activity and low mineralocorticoid activity. Absorbed through the skin faster than fluocinonide, it is used topically in treatment of psoriasis but may cause marked adrenocortical suppression. Glucocorticoids
  - Betamethasone Betamethasone A glucocorticoid given orally, parenterally, by local injection, by inhalation, or applied topically in the management of various disorders in which corticosteroids are indicated. Its lack of mineralocorticoid properties makes betamethasone particularly suitable for treating cerebral edema and congenital adrenal hyperplasia. Glucocorticoids
- Systemic steroids Steroids A group of polycyclic compounds closely related biochemically to terpenes. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (sterols), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus. Benign Liver Tumors
For infectious causes:
- Antibiotics
- Antifungals
- Antivirals
Appropriate management for underlying systemic conditions

Comparison of Generalized Rashes

Noninfectious conditions

**Table: Summary of common noninfectious generalized rashes**
Condition	Features	Diagnosis	Management
Atopic dermatitis Dermatitis Any inflammation of the skin. Atopic Dermatitis (Eczema) ( eczema Eczema Atopic dermatitis, also known as eczema, is a chronic, relapsing, pruritic, inflammatory skin disease that occurs more frequently in children, although adults can also be affected. The condition is often associated with elevated serum levels of IgE and a personal or family history of atopy. Skin dryness, erythema, oozing, crusting, and lichenification are present. Atopic Dermatitis (Eczema))	Type IV hypersensitivity reaction Type IV hypersensitivity reaction Type IV hypersensitivity reaction, or delayed-type hypersensitivity, is a cell-mediated response to antigen exposure. The reaction involves T cells, not antibodies, and develops over several days. Presensitized T cells initiate the immune defense, leading to tissue damage. Type IV Hypersensitivity Reaction Ranges from erythema Erythema Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of disease processes. Chalazion to lichenification Lichenification Atopic Dermatitis (Eczema) to erythroderma Scaly patches Patches Vitiligo or plaques Pruritus Pruritus An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. Atopic Dermatitis (Eczema) Distribution is typically over flexor surfaces.	Clinical diagnosis Serum IgE IgE An immunoglobulin associated with mast cells. Overexpression has been associated with allergic hypersensitivity. Immunoglobulins: Types and Functions levels 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 prick tests Patch tests	Avoid triggers. Symptomatic therapy 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 Topical corticosteroids Corticosteroids Chorioretinitis Topical calcineurin inhibitors Calcineurin Inhibitors Compounds that inhibit or block the phosphatase activity of calcineurin. Immunosuppressants Phototherapy Phototherapy Treatment of disease by exposure to light, especially by variously concentrated light rays or specific wavelengths. Hyperbilirubinemia of the Newborn 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
Drug eruption	Often an immune-mediated hypersensitivity reaction Ranges in severity from urticaria Urticaria Urticaria is raised, well-circumscribed areas (wheals) of edema (swelling) and erythema (redness) involving the dermis and epidermis with associated pruritus (itch). Urticaria is not a single disease but rather is a reaction pattern representing cutaneous mast cell degranulation. Urticaria (Hives) and maculopapular Maculopapular Dermatologic Examination eruptions to EM, SJS SJS Stevens-Johnson syndrome (SJS) is a cutaneous, immune-mediated hypersensitivity reaction that is commonly triggered by medications, including antiepileptics and antibiotics. The condition runs on a spectrum with toxic epidermal necrolysis (TEN) based on the amount of body surface area (BSA) involved. Stevens-Johnson Syndrome, and TEN Lesions may include: Edematous wheals Diffuse maculopapular Maculopapular Dermatologic Examination lesions Target lesions Cutaneous bullae Bullae Erythema Multiforme Sloughing 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 and mucosa Systemic symptoms	Clinical diagnosis Skin biopsy Skin Biopsy Secondary Skin Lesions is rarely needed.	Withdrawal of the offending drug Symptomatic therapy Supportive care
Pityriasis rosea Pityriasis rosea Pityriasis rosea is an acute, self-limited skin disease. The etiology is not known, and it commonly occurs in young adults. Patients initially present with a single, ovoid “herald patch.” This is followed by diffuse, pruritic, scaly, oval lesions over the trunk (often in a “Christmas tree” distribution on the back) and extremities. Pityriasis Rosea	Idiopathic Idiopathic Dermatomyositis Single round, ovoid, salmon-colored patch (“ herald patch Herald Patch Pityriasis Rosea”) Followed by a widespread exanthem Exanthem Diseases in which skin eruptions or rashes are a prominent manifestation. Classically, six such diseases were described with similar rashes; they were numbered in the order in which they were reported. Only the fourth (Duke’s disease), fifth (erythema infectiosum), and sixth (exanthema subitum) numeric designations survive as occasional synonyms in current terminology. Varicella-Zoster Virus/Chickenpox with scale Scale Dermatologic Examination “Christmas tree” distribution on back Pruritus Pruritus An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. Atopic Dermatitis (Eczema)	Clinical diagnosis	No intervention is needed. Symptomatic management
Lichen planus Lichen planus Lichen planus (LP) is an idiopathic, cell-mediated inflammatory skin disease. It is characterized by pruritic, flat-topped, papular, purple skin lesions commonly found on the flexural surfaces of the extremities. Other areas affected include genitalia, nails, scalp, and mucous membranes. Lichen Planus	Idiopathic Idiopathic Dermatomyositis Cell-mediated inflammatory disease Flat-topped, papular, purple lesions Pruritus Pruritus An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. Atopic Dermatitis (Eczema) Includes genitalia, nails, scalp, and mucous membranes	Clinical diagnosis Biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma for confirmation	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
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	Cell-mediated inflammatory disease Well-circumscribed, salmon-colored plaques Silvery scales Scales Dry or greasy masses of keratin that represent thickened stratum corneum. Secondary Skin Lesions Seen on the scalp and extensor surfaces	Clinical diagnosis Biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma is rarely needed.	Local therapy: 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 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 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 Phototherapy Phototherapy Treatment of disease by exposure to light, especially by variously concentrated light rays or specific wavelengths. Hyperbilirubinemia of the Newborn Systemic therapy: 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 Biologic agents Biologic Agents Immunosuppressants

Note: Although pityriasis rosea and lichen planus are considered idiopathic, they have been associated with certain viruses.
EM: erythema multiforme
SJS: Stevens-Johnson syndrome
TEN: toxic epidermal necrolysis

Erythema and lichenification in the kneefolds of a patient with atopic dermatitis
Image: “Role of the skin microbiome in atopic dermatitis” by Salava A, Lauerma A. License: CC BY 4.0

Edematous wheals suggestive of urticaria. This can be a manifestation of a drug eruption. — Erythema and lichenification in the kneefolds of a patient with atopic dermatitis
Image: “Role of the skin microbiome in atopic dermatitis” by Salava A, Lauerma A. License: CC BY 4.0

Infectious conditions

**Table: Summary of common infectious generalized rashes**
Condition	Features	Diagnosis	Management
Hand-foot-and-mouth disease	Caused by coxsackievirus Coxsackievirus Coxsackievirus is a member of a family of viruses called Picornaviridae and the genus Enterovirus. Coxsackieviruses are single-stranded, positive-sense RNA viruses, and are divided into coxsackie group A and B viruses. Both groups of viruses cause upper respiratory infections, rashes, aseptic meningitis, or encephalitis. Coxsackievirus type A Painful oval-shaped vesicles Vesicles Female Genitourinary Examination on hands, feet, buttocks, and oral mucosa Oral mucosa Lining of the oral cavity, including mucosa on the gums; the palate; the lip; the cheek; floor of the mouth; and other structures. The mucosa is generally a nonkeratinized stratified squamous epithelium covering muscle, bone, or glands but can show varying degree of keratinization at specific locations. Stomatitis Associated 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	Clinical diagnosis	Symptomatic treatment
Roseola infantum Roseola infantum An acute, short-lived, viral disease of infants and young children characterized by a high fever at onset that drops to normal after 3-4 days and the concomitant appearance of a macular or maculopapular rash that appears first on the trunk and then spreads to other areas. It is the sixth of the classical exanthematous diseases and is caused by HHV-6. Human Herpesvirus 6 and 7 ( exanthem Exanthem Diseases in which skin eruptions or rashes are a prominent manifestation. Classically, six such diseases were described with similar rashes; they were numbered in the order in which they were reported. Only the fourth (Duke’s disease), fifth (erythema infectiosum), and sixth (exanthema subitum) numeric designations survive as occasional synonyms in current terminology. Varicella-Zoster Virus/Chickenpox subitum)	Caused by HHV-6 HHV-6 Human herpesvirus (HHV)-6 and HHV-7 are similar double-stranded DNA viruses belonging to the Herpesviridae family. Human herpesviruses are ubiquitous and infections are commonly contracted during childhood. Human Herpesvirus 6 and 7 or -7 Rose-pink maculopapular Maculopapular Dermatologic Examination rash Rash Rocky Mountain Spotted Fever Mostly on the chest and abdomen but the back, face, and extremities can be involved Preceded by high 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 cervical 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	Clinical diagnosis	Symptomatic treatment
Measles Measles Measles (also known as rubeola) is caused by a single-stranded, linear, negative-sense RNA virus of the family Paramyxoviridae. It is highly contagious and spreads by respiratory droplets or direct-contact transmission from an infected person. Typically a disease of childhood, measles classically starts with cough, coryza, and conjunctivitis, followed by a maculopapular rash. Measles Virus ( rubeola Rubeola Measles (also known as rubeola) is caused by a single-stranded, linear, negative-sense RNA virus of the family Paramyxoviridae. It is highly contagious and spreads by respiratory droplets or direct-contact transmission from an infected person. Typically a disease of childhood, measles classically starts with cough, coryza, and conjunctivitis, followed by a maculopapular rash. Measles Virus)	Caused by the measles Measles Measles (also known as rubeola) is caused by a single-stranded, linear, negative-sense RNA virus of the family Paramyxoviridae. It is highly contagious and spreads by respiratory droplets or direct-contact transmission from an infected person. Typically a disease of childhood, measles classically starts with cough, coryza, and conjunctivitis, followed by a maculopapular rash. Measles Virus 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 Maculopapular Maculopapular Dermatologic Examination rash Rash Rocky Mountain Spotted Fever that begins on the face and spreads to the trunk and extremities Koplik spots on the buccal membrane Associated with a high 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, cough, coryza Coryza Inflammation of the nasal mucosa, the mucous membrane lining the nasal cavities. Rhinitis, and 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	Clinical diagnosis	Symptomatic treatment
Rubella Rubella An acute infectious disease caused by the rubella virus. The virus enters the respiratory tract via airborne droplet and spreads to the lymphatic system. Rubella Virus ( German measles German measles An acute infectious disease caused by the rubella virus. The virus enters the respiratory tract via airborne droplet and spreads to the lymphatic system. Rubella Virus)	Caused by rubella Rubella An acute infectious disease caused by the rubella virus. The virus enters the respiratory tract via airborne droplet and spreads to the lymphatic system. Rubella Virus 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 Fine, pink macules on the face and neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess Becomes pinpoint and spreads to the trunk and extremities Less extensive than measles Measles Measles (also known as rubeola) is caused by a single-stranded, linear, negative-sense RNA virus of the family Paramyxoviridae. It is highly contagious and spreads by respiratory droplets or direct-contact transmission from an infected person. Typically a disease of childhood, measles classically starts with cough, coryza, and conjunctivitis, followed by a maculopapular rash. Measles Virus Forschheimer spots ( petechiae Petechiae Primary Skin Lesions on the soft palate Soft palate A movable fold suspended from the posterior border of the hard palate. The uvula hangs from the middle of the lower border. Palate: Anatomy) Associated 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, 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, and 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	Clinical diagnosis Serologic testing	Symptomatic treatment
5th disease ( erythema Erythema Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of disease processes. Chalazion infectiosum)	Caused by parvovirus B19 Parvovirus B19 Primate erythroparvovirus 1 (generally referred to as parvovirus B19, B19 virus, or sometimes erythrovirus B19) ranks among the smallest DNA viruses. Parvovirus B19 is of the family Parvoviridae and genus Erythrovirus. In immunocompetent humans, parvovirus B19 classically results in erythema infectiosum (5th disease) or “slapped cheek syndrome.” Parvovirus B19 Initial prodromal symptoms Initial Prodromal Symptoms Erythema Infectiosum “Slapped cheek” rash Rash Rocky Mountain Spotted Fever Followed by a morbilliform Morbilliform Erythema Infectiosum rash Rash Rocky Mountain Spotted Fever on the torso and extremities	Clinical diagnosis IgM IgM A class of immunoglobulin bearing mu chains (immunoglobulin mu-chains). Igm can fix complement. The name comes from its high molecular weight and originally being called a macroglobulin. Immunoglobulins: Types and Functions or PCR PCR Polymerase chain reaction (PCR) is a technique that amplifies DNA fragments exponentially for analysis. The process is highly specific, allowing for the targeting of specific genomic sequences, even with minuscule sample amounts. The PCR cycles multiple times through 3 phases: denaturation of the template DNA, annealing of a specific primer to the individual DNA strands, and synthesis/elongation of new DNA molecules. Polymerase Chain Reaction (PCR) testing is rarely needed.	Symptomatic treatment
Scarlet fever Scarlet fever Infection with group a Streptococci that is characterized by tonsillitis and pharyngitis. An erythematous rash is commonly present. Scarlet Fever	Caused by 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 pyogenes Begins 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 and 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 Flushed cheeks Cheeks The part of the face that is below the eye and to the side of the nose and mouth. Melasma Strawberry tongue Strawberry tongue Kawasaki Disease Sandpaper-like rash Rash Rocky Mountain Spotted Fever on neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess, trunk, and extremities Pastia’s lines	Clinical diagnosis Rapid antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination or throat Throat The pharynx is a component of the digestive system that lies posterior to the nasal cavity, oral cavity, and larynx. The pharynx can be divided into the oropharynx, nasopharynx, and laryngopharynx. Pharyngeal muscles play an integral role in vital processes such as breathing, swallowing, and speaking. Pharynx: Anatomy culture to confirm	Penicillin Penicillin Rheumatic Fever Amoxicillin Amoxicillin A broad-spectrum semisynthetic antibiotic similar to ampicillin except that its resistance to gastric acid permits higher serum levels with oral administration. Penicillins
Chickenpox Chickenpox A highly contagious infectious disease caused by the varicella-zoster virus. It usually affects children, is spread by direct contact or respiratory route via droplet nuclei, and is characterized by the appearance on the skin and mucous membranes of successive crops of typical pruritic vesicular lesions that are easily broken and become scabbed. Chickenpox is relatively benign in children, but may be complicated by pneumonia and encephalitis in adults. Varicella-Zoster Virus/Chickenpox	Caused by varicella-zoster virus Varicella-Zoster Virus Varicella-zoster virus (VZV) is a linear, double-stranded DNA virus in the Herpesviridae family. Varicella-zoster infections are highly contagious and transmitted through aerosolized respiratory droplets or contact with infected skin lesions. Varicella-Zoster Virus/Chickenpox Rash Rash Rocky Mountain Spotted Fever appears in crops and progresses from macules to papules to vesicles Vesicles Female Genitourinary Examination on a red base Lesions eventually crust Crust Dried exudate of body fluids (blood, pus, or sebum) on an area of damaged skin Secondary Skin Lesions. Intense pruritus Pruritus An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. Atopic Dermatitis (Eczema) Begins on trunk and spreads to the face and extremities Prodrome Prodrome Symptoms that appear 24–48 hours prior to migraine onset. Migraine Headache of 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 malaise Malaise Tick-borne Encephalitis Virus	Clinical diagnosis Serologic testing may be done to confirm the diagnosis.	Symptomatic treatment Consider antiviral Antiviral Antivirals for Hepatitis B therapy ( acyclovir Acyclovir A guanosine analog that acts as an antimetabolite. Viruses are especially susceptible. Used especially against herpes. Herpes Zoster (Shingles)).

HHV: human herpesvirus
PCR: polymerase chain reaction

Painful vesicles on a hand (a) and foot (b) due to hand-foot-and-mouth disease — Painful vesicles on a hand (A) and foot (B) due to hand-foot-and-mouth disease
Image: “Hand, foot and mouth disease: changing Indian scenario” by Rao PK, Veena K, Jagadishchandra H, Bhat SS, Shetty SR. License: CC BY 3.0, edited by Lecturio.

Diffuse maculopapular rash on the chest and abdomen due to roseola infantum — Painful vesicles on a hand (A) and foot (B) due to hand-foot-and-mouth disease
Image: “Hand, foot and mouth disease: changing Indian scenario” by Rao PK, Veena K, Jagadishchandra H, Bhat SS, Shetty SR. License: CC BY 3.0, edited by Lecturio.

Comparison of Common Localized Rashes

**Table: Summary of common localized rashes**
Condition	Features	Diagnosis	Management
Contact dermatitis Contact dermatitis A type of acute or chronic skin reaction in which sensitivity is manifested by reactivity to materials or substances coming in contact with the skin. It may involve allergic or non-allergic mechanisms. Male Genitourinary Examination	Type IV hypersensitivity reaction Type IV hypersensitivity reaction Type IV hypersensitivity reaction, or delayed-type hypersensitivity, is a cell-mediated response to antigen exposure. The reaction involves T cells, not antibodies, and develops over several days. Presensitized T cells initiate the immune defense, leading to tissue damage. Type IV Hypersensitivity Reaction from allergens or irritants Maculopapular Maculopapular Dermatologic Examination or vesicular rash Rash Rocky Mountain Spotted Fever Erythema Erythema Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of disease processes. Chalazion and swelling Swelling Inflammation Weeping, scaling, or crusting Pruritus Pruritus An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. Atopic Dermatitis (Eczema) or burning pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways	Clinical diagnosis Patch testing	Avoid causative agents. 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 Antihistamines Antihistamines Antihistamines are drugs that target histamine receptors, particularly H1 and H2 receptors. H1 antagonists are competitive and reversible inhibitors of H1 receptors. First-generation antihistamines cross the blood-brain barrier and can cause sedation. Antihistamines 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
Tinea corporis Tinea corporis Dermatophytes/Tinea Infections	Caused by a dermatophyte infection Annular Annular Dermatologic Examination patches Patches Vitiligo or plaques with raised, scaly borders Expand peripherally Central clearing Pruritus Pruritus An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. Atopic Dermatitis (Eczema)	KOH preparation KOH preparation Primary Skin Lesions Fungal culture	Topical or oral antifungals
Seborrheic dermatitis Dermatitis Any inflammation of the skin. Atopic Dermatitis (Eczema)	Unknown etiology Erythematous, well-demarcated plaques Greasy yellow scales Scales Dry or greasy masses of keratin that represent thickened stratum corneum. Secondary Skin Lesions Found on the scalp, face, trunk, and intertriginous areas Intertriginous areas Malassezia Fungi	Clinical diagnosis Biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma to confirm	Topical antifungals 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 Calcineurin inhibitors Calcineurin Inhibitors Compounds that inhibit or block the phosphatase activity of calcineurin. Immunosuppressants Keratolytic agents
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	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 S. pyogenes Evolution of papules to vesicles Vesicles Female Genitourinary Examination to pustules Honey-colored crusts Bullous form: large, flaccid bullae Bullae Erythema Multiforme	Clinical diagnosis Cultures are rarely needed.	Mild-to-moderate cases: topical antibiotics Bullous or severe cases: oral antibiotics
Cellulitis Cellulitis Cellulitis is a common infection caused by bacteria that affects the dermis and subcutaneous tissue of the skin. It is frequently caused by Staphylococcus aureus and Streptococcus pyogenes. The skin infection presents as an erythematous and edematous area with warmth and tenderness. Cellulitis	Bacterial infection of 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 and subcutaneous tissues Erythema Erythema Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of disease processes. Chalazion and induration Induration Dermatologic Examination Warm to the touch Poorly demarcated	Clinical diagnosis Blood cultures if 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 is present	Penicillins Penicillins Beta-lactam antibiotics contain a beta-lactam ring as a part of their chemical structure. Drugs in this class include penicillin G and V, penicillinase-sensitive and penicillinase-resistant penicillins, cephalosporins, carbapenems, and aztreonam. Penicillins Vancomycin Vancomycin Antibacterial obtained from streptomyces orientalis. It is a glycopeptide related to ristocetin that inhibits bacterial cell wall assembly and is toxic to kidneys and the inner ear. Glycopeptides for MRSA MRSA A strain of Staphylococcus aureus that is non-susceptible to the action of methicillin. The mechanism of resistance usually involves modification of normal or the presence of acquired penicillin binding proteins. Staphylococcus
Erysipelas Erysipelas Erysipelas is a bacterial infection of the superficial layer of the skin extending to the skin’s superficial lymphatic vessels. This infection presents as a raised, well-defined, tender, and bright red rash. Typically on the legs or face, but erysipelas can occur anywhere on the skin. Erysipelas	A more superficial bacterial infection than cellulitis Cellulitis Cellulitis is a common infection caused by bacteria that affects the dermis and subcutaneous tissue of the skin. It is frequently caused by Staphylococcus aureus and Streptococcus pyogenes. The skin infection presents as an erythematous and edematous area with warmth and tenderness. Cellulitis Involves the upper 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 and superficial lymphatics Well-defined erythema Erythema Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of disease processes. Chalazion with raised demarcation Pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways and tenderness	Clinical diagnosis Blood cultures if 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 is present	Penicillins Penicillins Beta-lactam antibiotics contain a beta-lactam ring as a part of their chemical structure. Drugs in this class include penicillin G and V, penicillinase-sensitive and penicillinase-resistant penicillins, cephalosporins, carbapenems, and aztreonam. Penicillins Vancomycin Vancomycin Antibacterial obtained from streptomyces orientalis. It is a glycopeptide related to ristocetin that inhibits bacterial cell wall assembly and is toxic to kidneys and the inner ear. Glycopeptides for MRSA MRSA A strain of Staphylococcus aureus that is non-susceptible to the action of methicillin. The mechanism of resistance usually involves modification of normal or the presence of acquired penicillin binding proteins. Staphylococcus
Necrotizing fasciitis Necrotizing fasciitis Necrotizing fasciitis is a life-threatening infection that causes rapid destruction and necrosis of the fascia and subcutaneous tissues. Patients may present with significant pain out of proportion to the presenting symptoms and rapidly progressive erythema of the affected area. Necrotizing Fasciitis	Life-threatening bacterial infection of the subcutaneous tissues and fascia Fascia Layers of connective tissue of variable thickness. The superficial fascia is found immediately below the skin; the deep fascia invests muscles, nerves, and other organs. Cellulitis Rapidly progressive erythema Erythema Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of disease processes. Chalazion, swelling Swelling Inflammation, and 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 Severe pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways Bullae Bullae Erythema Multiforme 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 Systemic toxicity Toxicity Dosage Calculation	Clinical diagnosis Blood and tissue culture Imaging studies	Surgical debridement Debridement The removal of foreign material and devitalized or contaminated tissue from or adjacent to a traumatic or infected lesion until surrounding healthy tissue is exposed. Stevens-Johnson Syndrome Broad-spectrum Broad-Spectrum Fluoroquinolones IV antibiotics Hemodynamic support
Herpes zoster Herpes Zoster Varicella-zoster virus (VZV) is a linear, double-stranded DNA virus in the Herpesviridae family. Shingles (also known as herpes zoster) is more common in adults and occurs due to the reactivation of VZV. Varicella-Zoster Virus/Chickenpox ( shingles Shingles Varicella-zoster virus (VZV) is a linear, double-stranded DNA virus in the Herpesviridae family. Shingles (also known as herpes zoster) is more common in adults and occurs due to the reactivation of VZV. Varicella-Zoster Virus/Chickenpox)	Caused by reactivation Reactivation Herpes Simplex Virus 1 and 2 of the varicella-zoster virus Varicella-Zoster Virus Varicella-zoster virus (VZV) is a linear, double-stranded DNA virus in the Herpesviridae family. Varicella-zoster infections are highly contagious and transmitted through aerosolized respiratory droplets or contact with infected skin lesions. Varicella-Zoster Virus/Chickenpox Vesicular eruption in a dermatomal Dermatomal Dermatologic Examination distribution Rash Rash Rocky Mountain Spotted Fever is preceded by pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways. Complicated by postherpetic neuralgia Postherpetic neuralgia Pain in nerves, frequently involving facial skin, resulting from the activation the latent varicella-zoster virus. The two forms of the condition preceding the pain are herpes zoster oticus; and herpes zoster ophthalmicus. Following the healing of the rashes and blisters, the pain sometimes persists. Herpes Zoster (Shingles)	Clinical diagnosis PCR PCR Polymerase chain reaction (PCR) is a technique that amplifies DNA fragments exponentially for analysis. The process is highly specific, allowing for the targeting of specific genomic sequences, even with minuscule sample amounts. The PCR cycles multiple times through 3 phases: denaturation of the template DNA, annealing of a specific primer to the individual DNA strands, and synthesis/elongation of new DNA molecules. Polymerase Chain Reaction (PCR) Tzanck smear Tzanck smear Herpes Simplex Virus 1 and 2	Prevented by vaccine Vaccine Suspensions of killed or attenuated microorganisms (bacteria, viruses, fungi, protozoa), antigenic proteins, synthetic constructs, or other bio-molecular derivatives, administered for the prevention, amelioration, or treatment of infectious and other diseases. Vaccination Antiviral Antiviral Antivirals for Hepatitis B agents may reduce duration of symptoms. Symptomatic therapy

IV: intravenous
MRSA: methicillin-resistant S. aureus
PCR: polymerase chain reaction
KOH: potassium hydroxide

A pruritic, vesicular eruption due to contact dermatitis
Image: “Neoprene Orthopaedic Supports: An Underrecognised Cause of Allergic Contact Dermatitis” by Hawkey S, Ghaffar S. License: CC BY 3.0

Annular, scaling lesion of tinea corporis — A pruritic, vesicular eruption due to contact dermatitis
Image: “Neoprene Orthopaedic Supports: An Underrecognised Cause of Allergic Contact Dermatitis” by Hawkey S, Ghaffar S. License: CC BY 3.0

References

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Fleischer AB Jr, Feldman SR, Bullard CN. Patients can accurately identify when they have a dermatologic condition. J Am Acad Dermatol. 1999;41(5 pt 1):784–786.
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Bircher, A. (2020). Exanthematous (maculopapular) drug eruption. UpToDate. Retrieved Feb 10, 2021, from https://www.uptodate.com/contents/exanthematous-maculopapular-drug-eruption
Armstrong, C.A. (2021). Approach to the clinical dermatologic diagnosis. In Corona, R. (Ed.), UpToDate. Retrieved February 26, 2021, from https://www.uptodate.com/contents/approach-to-the-clinical-dermatologic-diagnosis
Bickers DR, Lim HW, Margolis D, Weinstock MA, Goodman C, Faulkner E et al. (2006). The burden of skin diseases: 2004 a joint project of the American Academy of Dermatology Association and the Society for Investigative Dermatology. Journal of the American Academy of Dermatology 55:490-500.
Ely, J. and Stone, M. (2010). The Generalized Rash: Part I. Differential Diagnosis. American Family Physician. 81(6):726-734.
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