Chickenpox differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Michael Maddaleni, B.S. João André Alves Silva, M.D. [2] Aravind Reddy Kothagadi M.B.B.S [3]

Overview

Chickenpox must be differentiated from various rash-causing conditions like Coxsackievirus, Stevens-Johnson syndrome (SJS), measles, rubella, Rocky mountain spotted fever and syphilis.

Differentiating Chickenpox from other Diseases

Chickenpox must be differentiated from other diseases presenting with diffuse papulovesicular rash in a febrile patient. The various conditions that should be differentiated from chickenpox include:^[1]^[2]^[3]^[4]^[5]^[6]^[7]

Common conditions to be differentiated from chickenpox:

Common Conditions	Features
Coxsackievirus	The most commonly caused disease is the Coxsackie A disease, presenting as hand-foot-mouth disease. It may be asymptomatic or cause mild symptoms. There may be 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.
Stevens-Johnson syndrome	The symptoms may include fever, sore throat and fatigue. Commonly presents as ulcers and other lesions in the mucous membranes, almost always in the mouth and lips but also in the genital and anal regions. The lesions in the mouth are extremely painful and reduce the patient's ability to eat or drink. Conjunctivitis of the eyes occurs in about 30% of children. A rash measuring about an inch across, may arise on the face, trunk, arms and legs, and soles of the feet, but usually not on the scalp.
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 of the skin of hands, feet and genital area.
Measles	Prodrome of high fever, cough, coryza and conjunctivitis, with oral mucosal lesions (Koplik's spots), followed by widespread skin rash.
Syphilis	It commonly presents with gneralized systemic symptoms such as malaise, fatigue, headache and fever. Skin eruptions may be subtle and asymptomatic It is classically described as: Non-pruritic bilateral symmetrical mucocutaneous rash Non-tender regional lymphadenopathy Condylomata lata Patchy alopecia
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.
Cytomegalovirus	The common symptoms include sore throat, swollen lymph nodes, fever, headache, fatigue, weakness, muscle pain and loss of appetite.
Meningococcemia	It commonly presents with rash, petechiae, headache, confusion, and stiff neck, high fever, mental status changes, nausea and vomiting.
Meningitis	It commonly presents with headache, nuchal rigidity, fever, petechiae and altered mental status.
Rocky Mountain spotted fever	The symptoms may include maculopapular rash, petechial rash, abdominal pain and joint pain.
Molluscum contagiosum	The lesions are commonly flesh-colored, dome-shaped and pearly in appearance. They are often 1-5 millimeters in diameter, with an umblicated 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

Less common conditions to be differentiated from chickenpox:

Chickenpox must also be differentiated from other conditions presenting with

Less Common Diseases	Features
Atypical measles	The 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.
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.
Rickettsial pox	The 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, with a generalized distribution.
Toxic erythema	It is a common rash in infants, with clustered and vesicular appearance.
Monkeypox	The 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.
Rat-bite fever	It commonly presents with fever, chills, open sore at the site of the bite and rash, which may show red or purple plaques.
Scarlet fever	It 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.

Differentiating chickenpox infection in immunocompromised host

Varicella Zoster virus infection is common among immunocompromised patients who are at high risk for other fungal, bacterial, and viral infections. It should be differentiated from the following diseases, which may present as confusion, fever and headache in immunocompromised patients:

Disease	Differentiating signs and symptoms	Differentiating tests
CNS lymphoma^[8]	Patient is immunocompetent Focal symptoms indicative of a mass lesion Seizure	Single solitary ring enhancing lesion on CT or MRI
Disseminated tuberculosis^[9]	Prior history of residence in an endemic area Chronic cough, weight loss, hemoptysis	PCR of CSF for tuberculosis Mycobacterial culture of CSF Brain biopsy for acid-fast bacilli staining Culture and acid stain positive for acid-fast bacilli CXR shows cavitations
Aspergillosis^[10]	Pulmonary lesions in addition to CNS lesions Symptoms may include cough, chest pain, and hemoptysis	CSF fungal culture, galactomannan
Cryptococcosis	Symptoms include cough, chest pain, and hemoptysis	Cryptococcal antigen from CSF and serum CSF fungal culture
Chagas disease^[11]	History of residence in Central or South America Acute infection is rarely symptomatic Encephalitis or focal brain lesions Myocarditis Chronic infections in immunocompromised patients develop into encephalitis with necrotic brain lesions causing a mass effect	Trypanosoma cruzi in blood, tissue, or CSF, PCR of tissue or body fluids, and serologic tests
CMV infection^[12]	Most common CNS opportunistic infection in AIDS patients Presents with encephalitis, retinitis, progressive myelitis, or polyradiculitis In disseminated disease, it involves both the liver and kidneys	Brain CT/MRI/biopsy: location of lesions is usually near the brain stem or periventricular areas PCR of CSF with detectable virus is diagnostic Brain biopsy with + staining for CMV or evidence of owl's eyes is also diagnostic, but it is rarely performed because of the location of brain lesions
HSV infection^[13]	Seizures, headache, confusion and/or urinary retention can be seen in disseminated disease, which usually affects only the immunocompromised or acute infections In pregnant women, it may be associated with concurrent genital/oral lesions; can be spread to the neonate during acute infection in the mother, or via viral shedding in the birth canal Neonatal HSV can range from localized skin infections to encephalitis, pneumonitis, and disseminated disease	Brain CT/MRI/biopsy: location of lesions is usually the medial temporal lobe or the orbital surface of the frontal lobe. PCR of CSF with detectable virus is diagnostic
Varicella Zoster infection^[14]	Multifocal involvement has subacute course, usually only in immunosuppressed, with headache, fever, focal deficits, and seizures Unifocal involvement is more typically seen in immunocompetent hosts, occurring after contralateral cranial nerve herpes zoster, with mental status changes, TIAs, and stroke Disseminated varicella zoster virus can occur in adults during primary infection, presenting with pneumonitis and/or hepatitis Disease is a vasculopathy with hemorrhage and stroke	PCR of CSF with detectable virus is diagnostic
Brain abscess^[15]^[16]	Associated with sinusitis (abutting the sinuses) or with bacteremia Signs and symptoms includes fever and necrotizing brain lesions with mass effect	CSF culture or culture of brain abscess
Progressive multifocal leukoencephalopathy^[17]	Symptoms are often more insidious in onset and progress over months. Symptoms include progressive weakness, poor coordination, with gradual slowing of mental function. Only seen in the immunosuppressed. Rarely associated with fever or other systemic symptoms	PCR of CSF for JC virus Biopsy reveals white matter lesions and not well-circumscribed lesions.

Oral lesions to be differentiated from chicken pox:

Oral lesions caused by chickenpox must be differentiated from other diseases presenting with pain and blistering within the mouth (gingivostomatitis). The differentials include:

Disease	Presentation	Risk Factors	Diagnosis	Affected Organ Systems	Important features	Picture

Coxsackie virus	Fever Sores in the mouth Rash with blisters Aches	Pregnancy immunodeficiency	History and Physical exam Throat swabs Swabs from the lesion Tzanck test	Oral cavity Skin	Symptomatic treatment
Chicken pox	Conjunctival symptoms Catarrhal symptoms Characteristic spots on the trunk appearing in two or three waves Itching	Pregnancy Premature infants born to susceptible mothers All infants born at less than 28 weeks gestation or who weigh ≤1000 grams Immunocompromised	History and physical exam PCR to detect VZV in skin lesions (vesicles, scabs, maculopapular lesions)	Oral cavity Skin	Sodium bicarbonate in baths or antihistamines for itching Paracetamol (acetaminophen) for fever Prednisolone is contraindicated
Measles	Fever Rash Cough Coryza (runny nose) Conjunctivitis (pink eye) Malaise Koplick spots in mouth	Unvaccinated individuals^[18]^[19] Crowded and/or unsanitary conditions Traveling to less developed and developing countries Immunocompromized Winter and spring seasons Born after 1956 and never fully vaccinated Health care workers	History and examination PCR for Measles-specific IgM antibody PCR for Measles RNA	Oral cavity Skin Respiratory tract Eyes Throat	Caused by Morbillivirus Primary site of infection is the respiratory epithelium of the nasopharynx Transmitted in respiratory secretions, via aerosol droplets containing virus particles
Herpangina	Sudden fever Sore throat and dysphagia- These can occur several hours(up to 24 hours), before the appearance of the enanthem. Vomiting Abdominal pain Myalgia Headache Pharyngeal lesions	Attendance at a kindergarten/child care center Contact with herpangina cases Residence in rural areas Overcrowding Poor hygiene Low socioeconomic status	Clincial diagnosis Pharyngeal viral and bacterial cultures can be taken to exclude HSV infection and streptococcal pharyngitis.	Skin Oral Cavity	Characteristic enanthem- Punctate macule which evolve over a period of 24 hours to 2-4mm erythematous papules which vesiculate, and then centrally ulcerate. The lesions are usually small in number, and evolve rapidly. The lesions are seen more commonly on the soft palate and uvula. The lesions can also be seen on the tonsils, posterior pharyngeal wall and the buccal mucosa.	Erythema, vesicles and ulcerating lesions in herpangina
Primary herpetic gingivoestomatitis^[20]	Pin-head vesicles rupture to form painful irregular ulcerations covered by yellow-grey membrane Severe pain Submandibular lymphadenopathy Halitosis It involves buccal mucosa, tongue, posterior pharynx, and gingival and palatal mucosa	Direct contact HIV infection	Tzanck test demonstrates multinucleated epithelial giant cells^[21] Viral culture is the gold standard for diagnosis Direct immunofluorescence	Oral cavity Mucous membranes	Ulcers are common on lips, gums, throat, front of tongue, inside of the cheeks and roof of the mouth Treatment is with antiviral agents such as Valacyclovir and Famciclovir
Oral Candidiasis	Dysphagia or odynophagia White patches on the mouth and tongue		Clinical diagnosis Confirmatory tests rarely needed	Localized candidiasis Oral and esophageal candidasis Candida vulvovaginitis Chronic mucocutaneous candidiasis Invasive candidasis Candidaemia Candida endocarditis Candida osteoarticular disease	Oral candidiaisis is a benign self limiting disease unless accompanied by immunosuppression.	Tongue infected with oral candidiasis - By James Heilman, MD - Own work, CC BY-SA 3.0, httpscommons.wikimedia.orgwindex.phpcurid=11717223.jpg

References

↑ Hartman-Adams H, Banvard C, Juckett G (2014). "Impetigo: diagnosis and treatment". Am Fam Physician. 90 (4): 229–35. PMID 25250996.
↑ Mehta N, Chen KK, Kroumpouzos G (2016). "Skin disease in pregnancy: The approach of the obstetric medicine physician". Clin Dermatol. 34 (3): 320–6. doi:10.1016/j.clindermatol.2016.02.003. PMID 27265069.
↑ Moore, Zack S; Seward, Jane F; Lane, J Michael (2006). "Smallpox". The Lancet. 367 (9508): 425–435. doi:10.1016/S0140-6736(06)68143-9. ISSN 0140-6736.
↑ Ibrahim F, Khan T, Pujalte GG (2015). "Bacterial Skin Infections". Prim Care. 42 (4): 485–99. doi:10.1016/j.pop.2015.08.001. PMID 26612370.
↑ Ramoni S, Boneschi V, Cusini M (2016). "Syphilis as "the great imitator": a case of impetiginoid syphiloderm". Int J Dermatol. 55 (3): e162–3. doi:10.1111/ijd.13072. PMID 26566601.
↑ Kimura U, Yokoyama K, Hiruma M, Kano R, Takamori K, Suga Y (2015). "Tinea faciei caused by Trichophyton mentagrophytes (molecular type Arthroderma benhamiae ) mimics impetigo : a case report and literature review of cases in Japan". Med Mycol J. 56 (1): E1–5. doi:10.3314/mmj.56.E1. PMID 25855021.
↑ CEDEF (2012). "[Item 87--Mucocutaneous bacterial infections]". Ann Dermatol Venereol. 139 (11 Suppl): A32–9. doi:10.1016/j.annder.2012.01.002. PMID 23176858.
↑ Gerstner ER, Batchelor TT (2010). "Primary central nervous system lymphoma". Arch. Neurol. 67 (3): 291–7. doi:10.1001/archneurol.2010.3. PMID 20212226.
↑ von Reyn CF, Kimambo S, Mtei L, Arbeit RD, Maro I, Bakari M, Matee M, Lahey T, Adams LV, Black W, Mackenzie T, Lyimo J, Tvaroha S, Waddell R, Kreiswirth B, Horsburgh CR, Pallangyo K (2011). "Disseminated tuberculosis in human immunodeficiency virus infection: ineffective immunity, polyclonal disease and high mortality". Int. J. Tuberc. Lung Dis. 15 (8): 1087–92. doi:10.5588/ijtld.10.0517. PMID 21740673.
↑ Latgé JP (1999). "Aspergillus fumigatus and aspergillosis". Clin. Microbiol. Rev. 12 (2): 310–50. PMC 88920. PMID 10194462.
↑ Rassi A, Rassi A, Marin-Neto JA (2010). "Chagas disease". Lancet. 375 (9723): 1388–402. doi:10.1016/S0140-6736(10)60061-X. PMID 20399979.
↑ Emery VC (2001). "Investigation of CMV disease in immunocompromised patients". J. Clin. Pathol. 54 (2): 84–8. PMC 1731357. PMID 11215290.
↑ Bustamante CI, Wade JC (1991). "Herpes simplex virus infection in the immunocompromised cancer patient". J. Clin. Oncol. 9 (10): 1903–15. doi:10.1200/JCO.1991.9.10.1903. PMID 1919640.
↑ Hambleton S (2005). "Chickenpox". Curr. Opin. Infect. Dis. 18 (3): 235–40. PMID 15864101.
↑ Alvis Miranda H, Castellar-Leones SM, Elzain MA, Moscote-Salazar LR (2013). "Brain abscess: Current management". J Neurosci Rural Pract. 4 (Suppl 1): S67–81. doi:10.4103/0976-3147.116472. PMC 3808066. PMID 24174804.
↑ Patel K, Clifford DB (2014). "Bacterial brain abscess". Neurohospitalist. 4 (4): 196–204. doi:10.1177/1941874414540684. PMC 4212419. PMID 25360205.
↑ Tan CS, Koralnik IJ (2010). "Progressive multifocal leukoencephalopathy and other disorders caused by JC virus: clinical features and pathogenesis". Lancet Neurol. 9 (4): 425–37. doi:10.1016/S1474-4422(10)70040-5. PMC 2880524. PMID 20298966.
↑ Feikin DR, Lezotte DC, Hamman RF, Salmon DA, Chen RT, Hoffman RE (2000). "Individual and community risks of measles and pertussis associated with personal exemptions to immunization". JAMA. 284 (24): 3145–50. PMID 11135778.
↑ Ratnam S, West R, Gadag V, Williams B, Oates E (1996). "Immunity against measles in school-aged children: implications for measles revaccination strategies". Can J Public Health. 87 (6): 407–10. PMID 9009400.
↑ Kolokotronis, A.; Doumas, S. (2006). "Herpes simplex virus infection, with particular reference to the progression and complications of primary herpetic gingivostomatitis". Clinical Microbiology and Infection. 12 (3): 202–211. doi:10.1111/j.1469-0691.2005.01336.x. ISSN 1198-743X.
↑ Chauvin PJ, Ajar AH (2002). "Acute herpetic gingivostomatitis in adults: a review of 13 cases, including diagnosis and management". J Can Dent Assoc. 68 (4): 247–51. PMID 12626280.

[pmid25250996-1] Hartman-Adams H, Banvard C, Juckett G (2014). "Impetigo: diagnosis and treatment". Am Fam Physician. 90 (4): 229–35. PMID 25250996.

[pmid27265069-2] Mehta N, Chen KK, Kroumpouzos G (2016). "Skin disease in pregnancy: The approach of the obstetric medicine physician". Clin Dermatol. 34 (3): 320–6. doi:10.1016/j.clindermatol.2016.02.003. PMID 27265069.

[MooreSeward2006-3] Moore, Zack S; Seward, Jane F; Lane, J Michael (2006). "Smallpox". The Lancet. 367 (9508): 425–435. doi:10.1016/S0140-6736(06)68143-9. ISSN 0140-6736.

[pmid26612370-4] Ibrahim F, Khan T, Pujalte GG (2015). "Bacterial Skin Infections". Prim Care. 42 (4): 485–99. doi:10.1016/j.pop.2015.08.001. PMID 26612370.

[pmid26566601-5] Ramoni S, Boneschi V, Cusini M (2016). "Syphilis as "the great imitator": a case of impetiginoid syphiloderm". Int J Dermatol. 55 (3): e162–3. doi:10.1111/ijd.13072. PMID 26566601.

[pmid25855021-6] Kimura U, Yokoyama K, Hiruma M, Kano R, Takamori K, Suga Y (2015). "Tinea faciei caused by Trichophyton mentagrophytes (molecular type Arthroderma benhamiae ) mimics impetigo : a case report and literature review of cases in Japan". Med Mycol J. 56 (1): E1–5. doi:10.3314/mmj.56.E1. PMID 25855021.

[pmid23176858-7] CEDEF (2012). "[Item 87--Mucocutaneous bacterial infections]". Ann Dermatol Venereol. 139 (11 Suppl): A32–9. doi:10.1016/j.annder.2012.01.002. PMID 23176858.

[pmid20212226-8] Gerstner ER, Batchelor TT (2010). "Primary central nervous system lymphoma". Arch. Neurol. 67 (3): 291–7. doi:10.1001/archneurol.2010.3. PMID 20212226.

[pmid21740673-9] von Reyn CF, Kimambo S, Mtei L, Arbeit RD, Maro I, Bakari M, Matee M, Lahey T, Adams LV, Black W, Mackenzie T, Lyimo J, Tvaroha S, Waddell R, Kreiswirth B, Horsburgh CR, Pallangyo K (2011). "Disseminated tuberculosis in human immunodeficiency virus infection: ineffective immunity, polyclonal disease and high mortality". Int. J. Tuberc. Lung Dis. 15 (8): 1087–92. doi:10.5588/ijtld.10.0517. PMID 21740673.

[pmid10194462-10] Latgé JP (1999). "Aspergillus fumigatus and aspergillosis". Clin. Microbiol. Rev. 12 (2): 310–50. PMC 88920. PMID 10194462.

[pmid20399979-11] Rassi A, Rassi A, Marin-Neto JA (2010). "Chagas disease". Lancet. 375 (9723): 1388–402. doi:10.1016/S0140-6736(10)60061-X. PMID 20399979.

[pmid11215290-12] Emery VC (2001). "Investigation of CMV disease in immunocompromised patients". J. Clin. Pathol. 54 (2): 84–8. PMC 1731357. PMID 11215290.

[pmid1919640-13] Bustamante CI, Wade JC (1991). "Herpes simplex virus infection in the immunocompromised cancer patient". J. Clin. Oncol. 9 (10): 1903–15. doi:10.1200/JCO.1991.9.10.1903. PMID 1919640.

[pmid15864101-14] Hambleton S (2005). "Chickenpox". Curr. Opin. Infect. Dis. 18 (3): 235–40. PMID 15864101.

[pmid24174804-15] Alvis Miranda H, Castellar-Leones SM, Elzain MA, Moscote-Salazar LR (2013). "Brain abscess: Current management". J Neurosci Rural Pract. 4 (Suppl 1): S67–81. doi:10.4103/0976-3147.116472. PMC 3808066. PMID 24174804.

[pmid25360205-16] Patel K, Clifford DB (2014). "Bacterial brain abscess". Neurohospitalist. 4 (4): 196–204. doi:10.1177/1941874414540684. PMC 4212419. PMID 25360205.

[pmid20298966-17] Tan CS, Koralnik IJ (2010). "Progressive multifocal leukoencephalopathy and other disorders caused by JC virus: clinical features and pathogenesis". Lancet Neurol. 9 (4): 425–37. doi:10.1016/S1474-4422(10)70040-5. PMC 2880524. PMID 20298966.

[pmid11135778-18] Feikin DR, Lezotte DC, Hamman RF, Salmon DA, Chen RT, Hoffman RE (2000). "Individual and community risks of measles and pertussis associated with personal exemptions to immunization". JAMA. 284 (24): 3145–50. PMID 11135778.

[pmid9009400-19] Ratnam S, West R, Gadag V, Williams B, Oates E (1996). "Immunity against measles in school-aged children: implications for measles revaccination strategies". Can J Public Health. 87 (6): 407–10. PMID 9009400.

[KolokotronisDoumas2006-20] Kolokotronis, A.; Doumas, S. (2006). "Herpes simplex virus infection, with particular reference to the progression and complications of primary herpetic gingivostomatitis". Clinical Microbiology and Infection. 12 (3): 202–211. doi:10.1111/j.1469-0691.2005.01336.x. ISSN 1198-743X.

[pmid12626280-21] Chauvin PJ, Ajar AH (2002). "Acute herpetic gingivostomatitis in adults: a review of 13 cases, including diagnosis and management". J Can Dent Assoc. 68 (4): 247–51. PMID 12626280.

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