Herpes zoster differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; L. Katie Morrison, MD; Associate Editor(s)-in-Chief: Varun Kumar, M.B.B.S. [2] João André Alves Silva, M.D. [3]

Overview

Diagnosis of Herpes zoster might not be possible in the absence of a rash (i.e., before rash or in cases of zoster without rash). It is sometimes confused with herpes simplex, and, occasionally, with impetigo, contact dermatitis, folliculitis, scabies, insect bites, papular urticaria, candidal infection, dermatitis herpetiformis, and drug eruptions.

Differentiating Herpes Zoster from other Diseases

Skin lesions caused by Herpes Zoster infection must be differentiated from:

Disease	Findings
Atopic dermatitis	The skin of a patient with atopic dermatitis reacts abnormally to irritants such as food and environmental allergens The skin on the flexural surfaces of the joints (elbows and knees) are most commonly affected regions It usually present with red, flaky and very itchy skin It also becomes vulnerable to surface infections caused by bacteria
Pyoderma gangrenosum	It usually occurs on the legs Ulcers initially look like small bug bites or papules, and later progress to larger ulcers that may become necrotic Ulcers can cause pain and scarring
Herpes simplex	Primary orofacial herpes/HSV-1 presents itself as multiple, round, superficial oral ulcers Genital herpes/HSV-2 can be more difficult to diagnose than oral herpes since most HSV-2-infected persons have no classical signs and symptoms Adults with non-typical presentation are more difficult to diagnose. However, prodromal symptoms that occur before the appearance of herpetic lesions helps to differentiate HSV from other conditions Herpes infection can recur even after successful initial treatment. The first episode is usually longer (two to four weeks) more painful and severe than the recurrent episodes
Contact dermatitis	Skin reaction resulting from exposure to allergens, irritants or sunlight It usually presents as a localized rash or irritation of the skin only on the superficial regions of the skin
Folliculitis	It starts when hair follicles are damaged by friction from clothing, blockage of the follicle, or shaving In most cases of folliculitis the damaged follicles are then infected with the bacteria Staphylococcus
Scabies	Transmissible ectoparasite skin infection characterized by superficial burrows, intense pruritus and secondary infection
Papular urticaria	Skin condition, commonly caused by an allergic reaction commonly caused by direct contact with an allergenic substance, or an immune response to food, other allergen, or emotional stress The rash can be triggered by quite innocent events, such as mere rubbing or exposure to cold. It is characterized by raised red skin welts. Welts from hives can appear anywhere on the body (face, lips, tongue, throat, and ears) Welts may vary in size from about 5 mm to the size of a dinner plate, typically itch severely, sting, or burn, and often have a pale border
Candidal infection	Fungal infection (mycosis) of any of the Candida species, of which Candida albicans is the most common Candidiasis thereby encompasses infections that range from superficial, such as oral thrush and vaginitis, to systemic and potentially life-threatening diseases Superficial infections of skin and mucosal membranes by Candida causing local inflammation and discomfort is common in many human populations
Dermatitis herpetiformis	Systemic condition, usually extremely itchy. In many people the vesicles or papules appear on pressure points, such as the elbows, knees, back and buttocks. Symptoms sometimes appear to be symmetrical (most prevalent at pressure points) It may also present as a patch of red skin with little water blisters scattered about The unpredictable skin rash may appear or be exacerbated by any irritation such as dry skin, scratching or clothing that is rough or scratchy
Drug eruptions
Kawasaki disease	Commonly presents with high and persistent fever, red mucous membranes in mouth, "strawberry tongue", swollen lymph nodes and skin rash It also presents with peeling off of the skin of the hands, feet and genital area
Measles	Commonly presents with high fever, coryza and conjunctivitis with the observation of oral mucosal lesions (Koplik's spots), followed by widespread skin rash Positive serologic test for serum measles IgM antibody, isolation of measles virus in culture, or detection of measles virus RNA by reverse transcription polymerase chain reaction (RT-PCR) is diagnostic
Rubella	Presents with a facial rash which then spreads to the trunk and limbs, fading after 3 days, low grade fever, swollen glands, joint pains, headache and conjunctivitis. The rash disappears after a few days with no staining or peeling of the skin Forchheimer's sign occurs in 20% of cases, and is characterized by small, red papules on the area of the soft palate.
Hand foot and mouth disease	Most commonly caused disease is the Coxsackie A It may be asymptomatic or cause mild symptoms, or it may produce fever and painful blisters in the mouth (herpangina), on the palms and fingers of the hand, or on the soles of the feet. There can also be blisters in the throat or above the tonsils Adults can also be affected and can present with High grade fever Sore throat Painfull Itchy rash especially on the hands/fingers and bottom of feet, several days after high temperature
Monkeypox	Presentation is similar to smallpox, although it is often a milder form, Presents with fever, headache, myalgia, back pain, swollen lymph nodes, a general feeling of discomfort, and exhaustion. Within 1 to 3 days after the appearance of fever, the patient develops a papular rash, often first on the face (lesions usually develop through several stages before crusting and falling off)
Cytomegalovirus	Commonly asymptomatic , but it may present with sore throat, swollen lymph nodes, fever, headache, fatigue, weakness, muscle pain and loss of appetite Diagnostic tests are essential for the management of CMV infection in immunocompromised patients which include serology, polymerase chain reaction|polymerase chain reaction (PCR), culture, and histopathology
Acne	Typical of teenagers, usually appears on the face and upper neck, but the chest, back and shoulders The upper arms can also have acne, but lesions found there are often keratosis pilaris, not acne The typical acne lesions are comedones and inflammatory papules, pustules, and nodules
Syphilis	Commonly presents with gneralized systemic symptoms such as malaise, fatigue, headache and fever. Skin eruptions may be subtle and asymptomatic, classically described as Non-pruritic bilateral symmetrical mucocutaneous rash Non-tender regional lymphadenopathy Condylomata lata Patchy alopecia
Molluscum contagiosum	Lesions are commonly flesh-colored, dome-shaped, and pearly in appearance (often 1-5 millimeters in diameter, with a dimpled center) Generally not painful, but they may itch or become irritated. In about 10% of the cases, eczema develops around the lesions
Mononucleosis	Mononucleosis is an acute clinical manifestation of EBV Initially presents with malaise, headache, and low-grade fever After progression of the disease, it may present with more specific signs of tonsillitis and/or pharyngitis, cervical lymph node enlargement and tenderness, and moderate to high fever In most cases of infectious mononucleosis is a clinical diagnosis EBV serology test should be done if mononucleosis is suspected The laboratory hallmark of the disease is the presence of atypical lymphocytes
Toxic erythema	Common rash in infants, with clustered and vesicular appearance
Rat-bite fever	Commonly presents with fever, chills, open sore at the site of the bite and rash, which may show red or purple plaques
'Parvovirus B19	The rash of fifth disease is typically described as "slapped cheeks," with erythema across the cheeks and sparing the nasolabial folds, forehead, and mouth
Stevens-Johnson syndrome	Symptoms may include fever, sore throat and fatigue. Commonly presents ulcers and other lesions in the mucous membranes (mouth, lips, genital, and anal) Mouth are usually extremely painful and reduce the patient's ability to eat or drink Conjunctivitis of the eyes occurs in about 30% of children A rash may arise on the face, trunk, arms and legs, and soles of the feet, but usually not on the scalp
Rocky Mountain spotted fever	Symptoms may include maculopapular rash, petechial rash, abdominal pain, and joint pain
Impetigo'	Commonly presents with pimple-like lesions surrounded by erythematous skin. Lesions are pustules, filled with pus, which then break down over 4-6 days and form a thick crust Associated with insect bites, cuts, and other forms of trauma to the skin
Scarlet fever'	Commonly includes fever, punctate red macules on the hard and soft palate and uvula (Forchheimer's spots), bright red tongue with a "strawberry" appearance, sore throat, headache, and lymphadenopathy
'Meningococcemia	Commonly presents with rash, petechiae, headache, confusion, and stiff neck, high fever, mental status changes, nausea, and vomiting
Rickettsialpox '	First symptom is commonly a bump formed by a mite-bite, eventually resulting in a black, crusty scab Many of the symptoms are flu-like including fever, chills, weakness and muscle pain Most distinctive symptom is the rash that breaks out, spanning the person's entire body

• Atopic dermatitis - The skin of a patient with atopic dermatitis reacts abnormally and easily to irritants, food, and environmental allergens and becomes red, flaky and very itchy. It also becomes vulnerable to surface infections caused by bacteria. The skin on the flexural surfaces of the joints (for example inner sides of elbows and knees) are most commonly affected regions in people.

• Pyoderma gangrenosum - disease that causes tissue to become necrotic, causing deep ulcers that usually occur on the legs. When they occur, they can lead to chronic wounds. Ulcers usually look like small bug bites or papules initially, and they progress to larger ulcers. Though the wounds rarely lead to death, they can cause pain and scarring.

• Herpes simplex - Primary orofacial herpes / Herpes simplex type 1 presents itself as multiple, round, superficial oral ulcers Adults with non-typical presentation are more difficult to diagnose. However, prodromal symptoms that occur before the appearance of herpetic lesions helps to differentiate HSV from other conditions with similar symptoms like allergic stomatitis. Genital herpes can be more difficult to diagnose than oral herpes since most genital herpes/HSV-2-infected persons have no classical signs and symptoms.. They present with blisters and ulcers in genital area that are similar to orofacial herpes. Herpes infection can recur even after successful initial treatment. The first episode is usually longer (two to four weeks) more painful and severe than the subsequent/recurrent episodes.

• Contact dermatitis - skin reaction resulting from exposure to allergens (allergic contact dermatitis) or irritants (irritant contact dermatitis).Phototoxic dermatitis occurs when the allergen or irritant is activated by sunlight. Contact dermatitis is a localized rash or irritation of the skin caused by contact with a foreign substance. Only the superficial regions of the skin are affected in contact dermatitis.

• Folliculitis - Folliculitis starts when hair follicles are damaged by friction from clothing, blockage of the follicle, or shaving. In most cases of folliculitis the damaged follicles are then infected with the bacteria Staphylococcus.

• Scabies - transmissible ectoparasite skin infection characterized by superficial burrows, intense pruritus and secondary infection.

• Papular urticaria - skin condition, commonly caused by an allergic reaction, that is characterized by raised red skin welts. It is also known as nettle rash or uredo. Welts from hives can appear anywhere on the body, including the face, lips, tongue, throat, and ears. Welts may vary in size from about 5 mm (0.2 inches) in diameter to the size of a dinner plate; they typically itch severely, sting, or burn, and often have a pale border. Urticaria is generally caused by direct contact with an allergenic substance, or an immune response to food or some other allergen, but can also appear for other reasons, notably emotional stress. The rash can be triggered by quite innocent events, such as mere rubbing or exposure to cold.

• Candidal infection - fungal infection (mycosis) of any of the Candida species, of which Candida albicans is the most common. Candidiasis thereby encompasses infections that range from superficial, such as oral thrush and vaginitis, to systemic and potentially life-threatening diseases. Candida infections of the latter category are also referred to as candidemia and are usually confined to severely immunocompromised persons, such as cancer, transplant, and AIDS patients, whereas superficial infections of skin and mucosal membranes by Candida causing local inflammation and discomfort is common in many human populations. While clearly attributable to the presence of the opportunistic pathogens of the genus Candida, candidiasis describes a number of different disease syndromes that often differ in their causes and outcomes.

• Dermatitis herpetiformis - systemic condition, usually extremely itchy. In many people the vesicles or papules appear on pressure points, such as the elbows, knees, back and buttocks. It may also present as a patch of red skin with little water blisters scattered about. The unpredictable skin rash may appear or be exacerbated by any irritation such as dry skin, scratching or clothing that is rough or scratchy. The fact that the rash is most prevalent at pressure points may be why the symptoms sometimes appear to be symmetrical.

• Drug eruptions - Cutaneous drug eruptions are the most frequent type of adverse drug reactions and the overwhelming majority of these reactions are thought to be allergic in origin.

• Insect bites - In an insect bite, the insect injects formic acid, which can cause an immediate skin reaction often resulting in a rash and swelling in the injured area, often with formation of vesicles.

• Kawasaki disease - commonly presents with high and persistent fever, red mucous membranes in mouth, "strawberry tongue", swollen lymph nodes and skin rash in early disease, with peeling off of the skin of the hands, feet and genital area.

• Measles - commonly presents with high fever, coryza and conjunctivitis, with observation of oral mucosal lesions (Koplik's spots), followed by widespread skin rash.

• Monkeypox - presentation is similar to smallpox, although it is often a milder form, with fever, headache, myalgia, back pain, swollen lymph nodes, a general feeling of discomfort, and exhaustion. Within 1 to 3 days (sometimes longer) after the appearance of fever, the patient develops a papular rash, often first on the face. The lesions usually develop through several stages before crusting and falling off.

• Rubella - commonly presents with a facial rash which then spreads to the trunk and limbs, fading after 3 days, low grade fever, swollen glands, joint pains, headache and conjunctivitis. The rash disappears after a few days with no staining or peeling of the skin. Forchheimer's sign occurs in 20% of cases, and is characterized by small, red papules on the area of the soft palate.

• Atypical measles - symptoms commonly begin about 7-14 days after infection and present as fever, cough, coryza and conjunctivitis. Observation of Koplik's spots is also a characteristic finding in measles.

• Coxsackievirus - the most commonly caused disease is the Coxsackie A disease, presenting as hand, foot and mouth disease. It may be asymptomatic or cause mild symptoms, or it may produce fever and painful blisters in the mouth (herpangina), on the palms and fingers of the hand, or on the soles of the feet. There can also be blisters in the throat or above the tonsils. Adults can also be affected. The rash, which can appear several days after high temperature and painful sore throat, can be itchy and painful, especially on the hands/fingers and bottom of feet.

• Acne - typical of teenagers, usually appears on the face and upper neck, but the chest, back and shoulders may have acne as well. The upper arms can also have acne, but lesions found there are often keratosis pilaris, not acne. The typical acne lesions are comedones and inflammatory papules, pustules, and nodules. Some of the large nodules were previously called "cysts"

• Syphilis - commonly presents with gneralized systemic symptoms such as malaise, fatigue, headache and fever. Skin eruptions may be subtle and asymptomatic Classically described as 1) non-pruritic bilateral symmetrical mucocutaneous rash; 2) non-tender regional lymphadenopathy; 3) condylomata lata; and 4) patchy alopecia.

• Molluscum contagiosum - lesions are commonly flesh-colored, dome-shaped, and pearly in appearance. They are often 1-5 millimeters in diameter, with a dimpled center. Generally not painful, but they may itch or become irritated. Picking or scratching the lesions may lead to further infection or scarring. In about 10% of the cases, eczema develops around the lesions. They may occasionally be complicated by secondary bacterial infections.

• Mononucleosis - Common symptoms include low-grade fever without chills, sore throat, white patches on tonsils and back of the throat, muscle weakness and sometime extreme fatigue, tender lymphadenopathy, petechial hemorrhage and skin rash.

• Toxic erythema - common rash in infants, with clustered and vesicular appearance.

• Rat-bite fever - commonly presents with fever, chills, open sore at the site of the bite and rash, which may show red or purple plaques.

• Parvovirus B19 - the rash of fifth disease is typically described as "slapped cheeks," with erythema across the cheeks and sparing the nasolabial folds, forehead, and mouth.

• Cytomegalovirus - common symptoms include sore throat, swollen lymph nodes, fever, headache, fatigue, weakness, muscle pain and loss of appetite.

• Scarlet fever - commonly includes fever, punctate red macules on the hard and soft palate and uvula (Forchheimer's spots), bright red tongue with a "strawberry" appearance, sore throat and headache and lymphadenopathy.

• Rocky Mountain spotted fever - symptoms may include maculopapular rash, petechial rash, abdominal pain and joint pain.

• Stevens-Johnson syndrome - symptoms may include fever, sore throat and fatigue. Commonly presents ulcers and other lesions in the mucous membranes, almost always in the mouth and lips but also in the genital and anal regions. Those in the mouth are usually extremely painful and reduce the patient's ability to eat or drink. Conjunctivitis of the eyes occurs in about 30% of children. A rash of round lesions about an inch across, may arise on the face, trunk, arms and legs, and soles of the feet, but usually not on the scalp.

• Varicella-zoster virus - commonly starts as a painful rash on one side of the face or body. The rash forms blisters that typically scab over in 7-10 days and clears up within 2-4 weeks.

• Chickenpox - commonly starts with conjunctival and catarrhal symptoms and then characteristic spots appearing in two or three waves, mainly on the body and head, rather than the hands, becoming itchy raw pox (small open sores which heal mostly without scarring). Touching the fluid from a chickenpox blister can also spread the disease.

• Meningococcemia - commonly presents with rash, petechiae, headache, confusion, and stiff neck, high fever, mental status changes, nausea and vomiting.

• Rickettsialpox - first symptom is commonly a bump formed by a mite-bite, eventually resulting in a black, crusty scab. Many of the symptoms are flu-like including fever, chills, weakness and muscle pain but the most distinctive symptom is the rash that breaks out, spanning the person's entire body.

• Meningitis - commonly presents with headache, nuchal rigidity, fever, petechiae and altered mental status.

• Impetigo - commonly presents with pimple-like lesions surrounded by erythematous skin. Lesions are pustules, filled with pus, which then break down over 4-6 days and form a thick crust. It's often associated with insect bites, cuts, and other forms of trauma to the skin.

For pain symptoms depending on the location:

• Angina
• Cholecystitis
• Appendicitis
• Trigeminal neuralgia
• Renal calculi
• Glaucoma
• Spinal cord compression

Herpes zoster can be more difficult to diagnose in children, younger adults, and immunocompromised persons who are more likely to have atypical presentations.