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Erythema Multiforme (Clinical)

Erythema Multiforme (Clinical)

Erythema Erythema Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of disease processes. Chalazion multiforme (EM) is an acute hypersensitivity reaction characterized by targetoid skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions lesions with multiple rings and dusky centers. Lesions may be accompanied by systemic symptoms (e.g., 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 mucosal lesions (e.g., bullae Bullae Erythema Multiforme). The majority of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with EM have a history of recent viral (especially 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) or bacterial infection (usually Mycoplasma pneumoniae Mycoplasma pneumoniae Short filamentous organism of the genus mycoplasma, which binds firmly to the cells of the respiratory epithelium. It is one of the etiologic agents of non-viral primary atypical pneumonia in man. Mycoplasma). Erythema Erythema Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of disease processes. Chalazion multiforme is diagnosed clinically and treatment is directed toward removing the causative agent and alleviation of symptoms.

Last updated: Mar 4, 2024

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Contents

Overview

Epidemiology[1,2,7]

  • Estimated annual 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 far less than < 1%
  • More common in young adults (20‒40 years of age)
  • Men > women

Etiology[1–3,7]

Erythema Erythema Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of disease processes. Chalazion multiforme (EM) is a cell-mediated immune reaction (type IV reaction) directed against the antigens of the offending agent, which deposit 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.

A significant number of cases are idiopathic Idiopathic Dermatomyositis; however, there are many etiologies that may be identified:

Classification Etiologies Examples
Infectious causes (most common, 90% of cases) Bacterial
  • Mycoplasma Mycoplasma Mycoplasma is a species of pleomorphic bacteria that lack a cell wall, which makes them difficult to target with conventional antibiotics and causes them to not gram stain well. Mycoplasma bacteria commonly target the respiratory and urogenital epithelium. Mycoplasma pneumoniae (M. pneumoniae), the causative agent of atypical or “walking” pneumonia. Mycoplasma 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(2nd most common cause)
  • Rickettsia Rickettsia Rickettsiae are a diverse collection of obligate intracellular, gram-negative bacteria that have a tropism for vascular endothelial cells. The vectors for transmission vary by species but include ticks, fleas, mites, and lice. Rickettsia
  • Chlamydophila psittaci
  • Salmonella typhi Salmonella typhi A serotype of Salmonella enterica which is the etiologic agent of typhoid fever. Enteric Fever (Typhoid Fever)
  • Mycobacterium tuberculosis Mycobacterium tuberculosis Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis
  • Histoplasma capsulatum Histoplasma capsulatum Histoplasma/Histoplasmosis
Viral
  • 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 ( HSV HSV Herpes simplex virus (HSV) is a double-stranded DNA virus belonging to the family Herpesviridae. Herpes simplex virus commonly causes recurrent infections involving the skin and mucosal surfaces, including the mouth, lips, eyes, and genitals. Herpes Simplex Virus 1 and 2) types 1 and 2
    • Most common cause
    • Approximately 50% of cases
  • Infectious mononucleosis Mononucleosis Infectious mononucleosis (IM), also known as “the kissing disease,” is a highly contagious viral infection caused by the Epstein-Barr virus. Its common name is derived from its main method of transmission: the spread of infected saliva via kissing. Clinical manifestations of IM include fever, tonsillar pharyngitis, and lymphadenopathy. Mononucleosis ( EBV EBV Epstein-barr virus (EBV) is a linear, double-stranded DNA virus belonging to the herpesviridae family. This highly prevalent virus is mostly transmitted through contact with oropharyngeal secretions from an infected individual. The virus can infect epithelial cells and B lymphocytes, where it can undergo lytic replication or latency. Epstein-Barr Virus, CMV)
  • Hepatitis C Hepatitis C Hepatitis C is an infection of the liver caused by the hepatitis C virus (HCV). The infection can be transmitted through infectious blood or body fluids and may be transmitted during childbirth or through IV drug use or sexual intercourse. Hepatitis C virus can cause both acute and chronic hepatitis, ranging from a mild to a serious, lifelong illness including liver cirrhosis and hepatocellular carcinoma (HCC). Hepatitis C Virus
Fungal
  • Vulvovaginal candidiasis Vulvovaginal candidiasis Infection of the vulva and vagina with a fungus of the genus candida. Candida/Candidiasis
  • Histoplasmosis Histoplasmosis Histoplasmosis is an infection caused by Histoplasma capsulatum, a dimorphic fungus. Transmission is through inhalation, and exposure to soils containing bird or bat droppings increases the risk of infection. Most infections are asymptomatic; however, immunocompromised individuals generally develop acute pulmonary infection, chronic infection, or even disseminated disease. Histoplasma/Histoplasmosis
  • Dermatophytes Dermatophytes Tinea infections are a group of diseases caused by fungi infecting keratinized tissue (hair, nails, and skin). These infections are termed dermatomycoses and are caused by the dermatophyte fungi. There are approximately 40 dermatophyte fungi that are part of 3 genera, including Trichophyton, Epidermophyton, and Microsporum. These infections can affect any part of the body but occur most often in warm, moist regions like the groin and the feet. Dermatophytes/Tinea Infections
Noninfectious causes Drugs
  • 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
  • Sulfonamides Sulfonamides A group of compounds that contain the structure so2nh2. Sulfonamides and Trimethoprim
  • Anticonvulsant Anticonvulsant Anticonvulsant drugs are pharmacological agents used to achieve seizure control and/or prevent seizure episodes. Anticonvulsants encompass various drugs with different mechanisms of action including ion-channel (Na+ and Ca+2) blocking and GABA reuptake inhibition. First-Generation Anticonvulsant Drugs drugs
  • Nonsteroidal anti-inflammatory drugs ( NSAIDs NSAIDS Primary vs Secondary Headaches)
  • Vaccines
Malignancy Malignancy Hemothorax
Miscellaneous
  • Menstruation Menstruation The periodic shedding of the endometrium and associated menstrual bleeding in the menstrual cycle of humans and primates. Menstruation is due to the decline in circulating progesterone, and occurs at the late luteal phase when luteolysis of the corpus luteum takes place. Menstrual Cycle
  • Inflammatory bowel disease
  • Sarcoidosis Sarcoidosis Sarcoidosis is a multisystem inflammatory disease that causes noncaseating granulomas. The exact etiology is unknown. Sarcoidosis usually affects the lungs and thoracic lymph nodes, but it can also affect almost every system in the body, including the skin, heart, and eyes, most commonly. Sarcoidosis
  • Systemic lupus erythematosus Systemic lupus erythematosus Systemic lupus erythematosus (SLE) is a chronic autoimmune, inflammatory condition that causes immune-complex deposition in organs, resulting in systemic manifestations. Women, particularly those of African American descent, are more commonly affected. Systemic Lupus Erythematosus
  • Polyarteritis nodosa Polyarteritis nodosa A form of necrotizing non-granulomatous inflammation occurring primarily in medium-sized arteries, often with microaneurysms. It is characterized by muscle, joint, and abdominal pain resulting from arterial infarction and scarring in affected organs. Polyarteritis nodosa with lung involvement is called churg-strauss syndrome. Vasculitides

Classification[3,5]

Erythema Erythema Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of disease processes. Chalazion multiforme is classified based on the presence of mucosal lesions and systemic symptoms into EM minor and major.

Cutaneous lesions Mucosal involvement Systemic symptoms
EM minor Present Absent, or limited to 1 surface Absent (or mild)
EM major Present Severe, involving ≥ 2 surfaces Common, more pronounced

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Clinical Presentation

Erythema Erythema Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of disease processes. Chalazion multiforme usually resolves spontaneously within 1 month, with no long-term sequelae. Rarely, EM may recur around 6 times/year for up to 10 years, on average (usually associated with HSV HSV Herpes simplex virus (HSV) is a double-stranded DNA virus belonging to the family Herpesviridae. Herpes simplex virus commonly causes recurrent infections involving the skin and mucosal surfaces, including the mouth, lips, eyes, and genitals. Herpes Simplex Virus 1 and 2 infection).[1,2,5,7]

Cutaneous lesions[1,2,5]

  • Begin as erythematous macules that develop over 3–5 days into papules → target lesions with 3 different zones
    • Central zone: dark and erythematous 
    • Middle zone: pale surrounding ring
    • Peripheral zone: erythematous outer ring with well-defined margins 
  • Location of lesions:
  • Centripetal spread (distal to proximal)
  • Rounded, < 3 cm in diameter
  • Pruritus Pruritus An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. Atopic Dermatitis (Eczema) or burning sensation can be present.
  • Atypical lesions:
    • Only 2 distinct zones
    • Raised edematous lesions
    • Poorly defined borders
Erythema multiform clinical presentation

Target lesions with a regular, round shape and 3 concentric zones: a central, darker-red area; a paler pink zone; and a peripheral red ring

Image: “Erythema multiforme” by Pediatric Unit, Maternal & Infant Department, S. Chiara University-Hospital, Via Roma 67, Pisa 56126, Italy. License: CC BY 2.0, edited by Lecturio.

Mucosal lesions[1,2,5]

  • Present in 25‒60% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship
  • Bullous → painful erosions Erosions Corneal Abrasions, Erosion, and Ulcers/ulcers
  • Diffuse areas of mucosal erythema Erythema Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of disease processes. Chalazion
  • 3 locations:
    • 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 (most common)
    • Ocular mucosa
    • Genital mucosa

Systemic symptoms[1,2]

Systemic symptoms are common with mucosal involvement (EM major):

Diagnosis

Clinical diagnosis[1–3]

EM is usually diagnosed clinically based on: 

  • Acute appearance of classic target lesions, typically persisting for 7‒14 days
  • +/– Mucosal involvement
  • +/– Systemic symptoms
  • Signs/symptoms associated with recent 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 (especially HSV HSV Herpes simplex virus (HSV) is a double-stranded DNA virus belonging to the family Herpesviridae. Herpes simplex virus commonly causes recurrent infections involving the skin and mucosal surfaces, including the mouth, lips, eyes, and genitals. Herpes Simplex Virus 1 and 2 or M. pneumoniae)
  • History of new, potentially causative medications

Laboratory and imaging[1,2,5]

  • Often not needed to make the diagnosis
  • Nonspecific findings may include elevations in:
    • WBC count
    • Erythrocyte sedimentation rate Erythrocyte Sedimentation Rate Soft Tissue Abscess ( ESR ESR Soft Tissue Abscess)
    • 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 enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body’s constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes
  • May be indicated to look for potential causes:
    • M. 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: serologic testing, chest X-ray X-ray Penetrating electromagnetic radiation emitted when the inner orbital electrons of an atom are excited and release radiant energy. X-ray wavelengths range from 1 pm to 10 nm. Hard x-rays are the higher energy, shorter wavelength x-rays. Soft x-rays or grenz rays are less energetic and longer in wavelength. The short wavelength end of the x-ray spectrum overlaps the gamma rays wavelength range. The distinction between gamma rays and x-rays is based on their radiation source. Pulmonary Function Tests, 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 swab
    • HSV HSV Herpes simplex virus (HSV) is a double-stranded DNA virus belonging to the family Herpesviridae. Herpes simplex virus commonly causes recurrent infections involving the skin and mucosal surfaces, including the mouth, lips, eyes, and genitals. Herpes Simplex Virus 1 and 2 (especially in recurrent EM): serologic testing, swab of suspicious lesions for 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)/culture
    • Selected tests to rule out other inflammatory, autoimmune, or malignant disorders

Skin biopsy Skin Biopsy Secondary Skin Lesions[1,2,5] 

Skin biopsy Skin Biopsy Secondary Skin Lesions is usually reserved for cases of diagnostic uncertainty.

  • Microscopy may show:
    • Vacuolated degeneration of basal cells
    • Scattered keratinocyte necrosis Keratinocyte Necrosis Stevens-Johnson Syndrome
    • 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 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
  • Direct immunofluorescence:
    • Findings in EM are nonspecific.
    • Can help differentiate EM from autoimmune blistering diseases (e.g., 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), which have more specific findings
Epidermal changes in erythema multiforme

Epidermal changes in EM with vacuolated degeneration of basal cells (arrow) and scattered individual keratinocyte necrosis (arrowhead)

Image: “Epidermal Changes in Erythema Multiforme” by Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan. License: CC BY 2.5

Management

Erythema Erythema Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of disease processes. Chalazion multiforme is often self-limiting Self-Limiting Meningitis in Children and does not require treatment. Management may vary based on local guidelines and treatment availability. The following information is based on US and UK guidelines.

General considerations[1,11]

  • Primary indication for hospitalization Hospitalization The confinement of a patient in a hospital. Delirium: severe disease leading to ↓ oral intake → likely to need IV fluids IV fluids Intravenous fluids are one of the most common interventions administered in medicine to approximate physiologic bodily fluids. Intravenous fluids are divided into 2 categories: crystalloid and colloid solutions. Intravenous fluids have a wide variety of indications, including intravascular volume expansion, electrolyte manipulation, and maintenance fluids. Intravenous Fluids and electrolyte repletion
  • Eliminate/address etiology:
    • Adjust/discontinue inciting medications
    • Treat 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 with appropriate antimicrobials

Symptomatic therapy[1,2,9–11]

The majority of cases will require only supportive therapy. The following may be used for relief of pruritus Pruritus An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. Atopic Dermatitis (Eczema) and discomfort due to lesions:

  • Oral sedating 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 (e.g., hydroxyzine Hydroxyzine A histamine h1 receptor antagonist that is effective in the treatment of chronic urticaria, dermatitis, and histamine-mediated pruritus. Unlike its major metabolite cetirizine, it does cause drowsiness. It is also effective as an antiemetic, for relief of anxiety and tension, and as a sedative. Antihistamines)
  • Topical antiseptics/ anesthetics Anesthetics Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. Anesthesiology: History and Basic Concepts
  • Topical corticosteroids Corticosteroids Chorioretinitis applied twice daily to affected areas:
    • Severe cutaneous disease (e.g., associated with mucosal involvement): high-potency (group 1 or 2)
    • Extremities and trunk: medium-potency (group 4 or 5) 
    • Face and intertriginous areas Intertriginous areas Malassezia Fungi: low-potency (group 6 or 7) 
  • Mucosal lesions:
    • Basic treatment:
      • High-potency corticosteroid gel (group 1 or 2, e.g., fluocinonide Fluocinonide Glucocorticoids 0.05% gel)
      • Oral anesthetic rinses (e.g., lidocaine Lidocaine A local anesthetic and cardiac depressant used as an antiarrhythmic agent. Its actions are more intense and its effects more prolonged than those of procaine but its duration of action is shorter than that of bupivacaine or prilocaine. Local Anesthetics)
      • Oral antiseptic rinses 
    • Severe mucosal lesions:
      • Oral corticosteroids Corticosteroids Chorioretinitis
      • Typical regimen: prednisone Prednisone A synthetic anti-inflammatory glucocorticoid derived from cortisone. It is biologically inert and converted to prednisolone in the liver. Immunosuppressants 40‒60 mg/day, followed by a taper over 2‒4 weeks
    • Ocular lesions:
      • Urgent ophthalmology consult
      • Topical ophthalmic preparations (e.g., dexamethasone Dexamethasone An anti-inflammatory 9-fluoro-glucocorticoid. Antiemetics 0.1%)

Management of recurrent EM

In cases of recurrent EM, consider specialty consultation for assistance.

HSV-associated EM:[1,4,9‒11]

  • Daily suppressive antiviral Antiviral Antivirals for Hepatitis B therapy; typical regimens:
    • Acyclovir Acyclovir A guanosine analog that acts as an antimetabolite. Viruses are especially susceptible. Used especially against herpes. Herpes Zoster (Shingles):
      • Adults: 400 mg twice daily
      • Pediatric: 10 mg/kg/day in divided doses
    • Valacyclovir Valacyclovir A prodrug of acyclovir that is used in the treatment of herpes zoster and herpes simplex virus infection of the skin and mucous membranes, including genital herpes. Herpes Zoster (Shingles) 500 mg twice daily
    • Famciclovir Famciclovir An aminopurine derivative and prodrug of penciclovir which is a competitive inhibitor of herpes simplex 2 DNA polymerase. It is used to treat herpes simplex virus infection. Antivirals for Herpes Virus 250 mg twice daily
  • Standard treatment is for ≥ 6 months.

Treatment-resistant EM (typically at least a 6-month course):[2,4,10,11]

  • Mycophenolate Mycophenolate Immunosuppressants mofetil
  • Azathioprine Azathioprine An immunosuppressive agent used in combination with cyclophosphamide and hydroxychloroquine in the treatment of rheumatoid arthritis. According to the fourth annual report on carcinogens, this substance has been listed as a known carcinogen. Immunosuppressants
  • Dapsone Dapsone A sulfone active against a wide range of bacteria but mainly employed for its actions against Mycobacterium leprae. Its mechanism of action is probably similar to that of the sulfonamides which involves inhibition of folic acid synthesis in susceptible organisms. It is also used with pyrimethamine in the treatment of malaria. Antimycobacterial Drugs
  • IV immunoglobulin Iv Immunoglobulin Dermatomyositis
  • Thalidomide Thalidomide A piperidinyl isoindole originally introduced as a non-barbiturate hypnotic, but withdrawn from the market due to teratogenic effects. It has been reintroduced and used for a number of immunological and inflammatory disorders. Thalidomide displays immunosuppressive and anti-angiogenic activity. It inhibits release of tumor necrosis factor-alpha from monocytes, and modulates other cytokine action. Immunosuppressants
  • Hydroxychloroquine Hydroxychloroquine A chemotherapeutic agent that acts against erythrocytic forms of malarial parasites. Hydroxychloroquine appears to concentrate in food vacuoles of affected protozoa. It inhibits plasmodial heme polymerase. Immunosuppressants
  • 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
  • Cimetidine Cimetidine A histamine congener, it competitively inhibits histamine binding to histamine h2 receptors. Cimetidine has a range of pharmacological actions. It inhibits gastric acid secretion, as well as pepsin and gastrin output. Antihistamines

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Differential Diagnosis

  • 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): a self-limiting Self-Limiting Meningitis in Children disease consisting of superficial, erythematous, pruritic lesions resulting from mast cell Mast cell Granulated cells that are found in almost all tissues, most abundantly in the skin and the gastrointestinal tract. Like the basophils, mast cells contain large amounts of histamine and heparin. Unlike basophils, mast cells normally remain in the tissues and do not circulate in the blood. Mast cells, derived from the bone marrow stem cells, are regulated by the stem cell factor. Angioedema activation and histamine release in 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. Lesions may last < 24 hours up to > 6 weeks. Commonly caused by viral 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 or by allergic reactions Allergic Reactions Type I hypersensitivity reaction against plasma proteins in donor blood Transfusion Reactions to drugs or food, other 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, stress, cold/ heat Heat Inflammation, and autoimmune disorders. Treatment, besides addressing the underlying condition, includes 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 and 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.
  • 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 immune-mediated condition characterized by the destruction of extracellular adhesive proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis (e.g., hemidesmosomes) by immunoglobulin G autoantibodies Autoantibodies Antibodies that react with self-antigens (autoantigens) of the organism that produced them. Blotting Techniques. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship present with 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 eczematous papules during the prodromal stage. After that, cutaneous, tense bullae Bullae Erythema Multiforme develop. This may last months to years, and treatment is focused on supportive, symptomatic care with 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 and 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. 
  • 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 ( 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): a life-threatening immune-mediated hypersensitivity reaction that involves the mucous membranes 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 (< 10% of body surface area). Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship generally have a history of taking certain medications (e.g., sulfa drugs) or recent infection. Clinical presentation involves macular skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions lesions with 2 zones of color change, vesicles Vesicles Female Genitourinary Examination, bullae Bullae Erythema Multiforme, and systemic symptoms (e.g., 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). Treatment comprises supportive 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 eye care and symptom control. 
  • Toxic epidermal necrolysis Toxic Epidermal Necrolysis Stevens-Johnson Syndrome (TEN): a life-threatening immune-mediated hypersensitivity disease process that is an extension Extension Examination of the Upper Limbs of 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. Toxic epidermal necrolysis Toxic Epidermal Necrolysis Stevens-Johnson Syndrome is an immune-mediated hypersensitivity reaction with mucocutaneous involvement (> 30% of body surface area). Mortality Mortality All deaths reported in a given population. Measures of Health Status rate depends on severity in both 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, at approximately 10% for 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 up to 50% for TEN. Both conditions require admission to a burn unit Burn unit Specialized hospital facilities which provide intensive care for burn patients. Staphylococcal Scalded Skin Syndrome (SSSS) for skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions care.

References

  1. Trayes, K. P., Love, G., Studdiford, J. S. (2019). Erythema multiforme: recognition and management. American Family Physician, 100(2), 82–88. https://www.aafp.org/dam/brand/aafp/pubs/afp/issues/2019/0715/p82.pdf 
  2. Sokumbi, O., Wetter, D. A. (2012). Clinical features, diagnosis, and treatment of erythema multiforme: a review for the practicing dermatologist. International Journal of Dermatology, 51(8), 889–902. https://doi.org/10.1111/j.1365-4632.2011.05348.x 
  3. Zoghaib S., Kechichian E., Souaid K., et al. (2019). Triggers, clinical manifestations, and management of pediatric erythema multiforme: a systematic review. Journal of the American Academy of Dermatologists, 81(3), 813‒822. https://doi.org/10.1016/j.jaad.2019.02.057 
  4. de Risi-Pugliese, T., Sbidian, E., Ingen-Housz-Oro, S., Le Cleach, L. (2019). Interventions for erythema multiforme: a systematic review. Journal of the European Academy of Dermatology and Venereology, 33(5), 842–849. https://doi.org/10.1111/jdv.15447 
  5. Huff, J. C., Weston, W. L., Tonnesen, M. G. (1983). Erythema multiforme: a critical review of characteristics, diagnostic criteria, and causes. Journal of the American Academy of Dermatologists, https://www.jaad.org/article/S0190-9622(83)80003-6/pdf
  6. Weston, W. L. (2005). Herpes-associated erythema multiforme. Journal of Investigative Dermatology, 124(6), xv–xvi. https://doi.org/10.1111/j.0022-202X.2005.23764.x 
  7. Wetter, D. A. (2021). Erythema multiforme: pathogenesis, clinical features, and diagnosis. UpToDate. Retrieved November 15, 2022, from https://www.uptodate.com/contents/erythema-multiforme-pathogenesis-clinical-features-and-diagnosis 
  8. Wetter, D. A. (2021). Erythema multiforme: Management. UpToDate. Retrieved November 15, 2022, from https://www.uptodate.com/contents/erythema-multiforme-management 
  9. Primary Care Dermatology Society. (2021). Erythema multiforme. Retrieved January 15, 2023, from https://www.pcds.org.uk/clinical-guidance/erythema-multiforme
  10. King, C. (2022). Erythema multiforme. DermNet. Retrieved January 15, 2023, from https://dermnetnz.org/topics/erythema-multiforme
  11. Soares, A., Sokumbi, O. (2021). Recent updates in the treatment of erythema multiforme. Medicina (Kaunas), 57(9):921. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8467974/
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