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AlexanderSalava

Exanthem (Eruptive Skin Rash)

Essentials

  • An exanthem may be due to an infection or a drug or both, but the cause cannot be deduced on the basis of the external characteristics alone.
  • A temporal association with the cause (drug or symptoms of infection) is essential.
  • A distinction should be made between a typical maculopapular exanthem and other, atypical (vesicular, pustular, papular, purpuric) exanthems.
  • Various skin disorders or spread and aggravation of an existing skin disorder may resemble an exanthem.
  • Remember to examine the mucosa and to identify any severe drug reaction.

Clinical picture and symptoms

  • An exanthem is an extensive acute eruptive rash usually caused by an infection or drug reaction (drug exanthem).
  • Exanthems may take various forms, and several clinical subtypes have been described. In addition, many skin disorders may spread like exanthems. Features that are characteristic of exanthems are extensive skin changes, rapid eruption and an acute course.
  • A classic maculopapular exanthem causes acute, symmetric, monomorphic erythematous small coin-sized lesions on extensive skin areas, often primarily on the trunk.
    • A maculopapular exanthem is symmetric and spreads from the trunk towards the limbs. Small lesions merge to form an even, erythematous area.
  • A severe reaction may produce rosette-like lesions resembling those seen in erythema multiforme (exanthema multiforme).
  • The site where the lesions first appear (e.g. the face), and the dynamics of spreading and recovery may be of differential diagnostic significance.
  • Presence of lesions on the mucosa (mouth, lips, eyes, genital area) may also help in differential diagnosis. This may also suggest a severe form of disease.
  • The patient may have systemic symptoms (fever, fatigue) suggestive of an infection or severe drug reaction. In uncomplicated, drug-induced exanthem no systemic symptoms are usually seen.

Diagnosis

  • The cornerstones of diagnosis are good history taking (course and spread of the disease, association with drugs Hypersensitivity to Drugs, possible contact persons, vaccination status) and clinical examination (appearance and symptoms of exanthem), as well as possible laboratory tests, depending on what cause is suspected.
  • Does the patient have symptoms of infection? Did he/she run a fever before the onset of the exanthem (strongly suggestive of an infectious exanthem if there is no association with any drug)?
  • Is there a temporal association with any drug (new drug started 1 to 3 weeks before the onset of the exanthem)?
  • Temporal association with travelling?
  • Are there any local signs or symptoms of infection (respiratory, urinary tract or gastrointestinal)?
  • Skin lesions should be examined close-up, too, paying attention to the following:
    • Localization (symmetricity, unilaterality, etc.)
    • Are the lesions scaly (suggesting a skin disorder, such as psoriasis or pityriasis rosea) or are there papules or pustules (chickenpox, extensive folliculitis)?
    • Are the lesions clearly defined? Are there erythematous spots, individual blisters or blistered surfaces?
  • Also check the scalp, nails, ears, genital area, oral mucosa, eyes (often of differential diagnostic significance).
  • Various types of exanthem and their possible causes are presented in table T1.

Types of exanthem and their causes

Typical maculopapular exanthem
Drug-induced exanthemTypesSimple drug-induced exanthem Hypersensitivity to Drugs 1 2
  • Resembling measles, morbilliform
Multiform drug-induced exanthem
  • Annular lesions 3 4
  • Rosette lesions 5
Severe drug reactions
  • Often also mucosal lesions 6
Most common causes in FinlandAntimicrobial drugs
  • Beta-lactam antibiotics, sulfonamides, fluoroquinolones and terbinafine
NSAIDs
Drugs with CNS effect
  • Phenytoin, carbamazepine 7 and lamotrigine are the most common
Exanthems triggered by infectionsMost common causes in FinlandMononucleosis Mononucleosis
  • 10 to 15% of those with mononucleosis develop an exanthem.
  • If amoxicillin is administered, nearly every patient develops an exanthem 8.
Streptococcal infections in connection with tonsillitis Pharyngitis and Tonsillitis in Children, for instance
  • Classic scarlet fever, for example, causing scaling of the palms and soles while healing
Viral infections of the upper respiratory tract
  • Influenza, parainfluenza, adenoviruses, coronaviruses, e.g. COVID-19, etc.
Gastrointestinal virus infections
  • E.g. enteroviruses and arboviruses
Bacterial infections of the upper respiratory tract
  • Mycoplasma, etc.
Rare causesBorreliosis
  • Multilocular erythema migrans 9 Lyme Borreliosis (LB) with several larger erythematous lesions may trigger a reactive exanthem.
Acute cytomegalovirus infection
Acute HIV infection HIV Infection
  • Typical roseola-like rash
Viral hepatitis Viral Hepatitis
Secondary syphilis Syphilis
  • Syphilis II, roseola-like rash 10
Toxic exanthems caused by Staphylococcus infections
  • Toxic shock syndrome, staphylococcal scalded skin syndrome in the newborn
  • Impaired general condition, large erythematous lesions on the trunk and limbs, on recovery scaling of the palms and soles, for example
Classic pox diseases (check vaccination)
Tularaemia Tularaemia 13
  • Ulcerous papule at site of infection, enlarged regional lymph nodes
Pogosta disease Pogosta Disease 14
  • Pogosta disease, exanthem with small lesions and few systemic symptoms
Causes in childrenExanthema subitum Exanthema Subitum 15 16
Erythema infectiosum Erythema Infectiosum 17
  • Some patients have fever, a sore throat and muscle pain before developing the exanthem.
  • The exanthem usually begins on the face ("slapped cheek") and spreads in a few days to the upper and sometimes lower limbs.
  • It may show a lacy, net-like pattern.
  • The exanthem may disappear and reappear repeatedly for several weeks.
Kawasaki disease Kawasaki Disease
  • Fever, enlarged lymph nodes, conjunctival, oral and pharyngeal symptoms
  • Complex exanthem, usually consisting of flushing erythematous lesions, erythema and swelling of the hands and feet
Atypical exanthem
Exanthem with blisters or papulopustules (vesicular or pustular)CommonChickenpox 18
  • May also occur in adults
Extensive hand, foot and mouth disease 19 20
  • May spread from palms and soles to other sites on the limbs and sometimes also to the trunk.
Extensive folliculitis (furunculosis) 21
RarePustular or acneiform exanthems triggered by medication
  • Caused, for instance, by systemic glucocorticoids
Papular exanthemTypesPapular acrodermatitis of childhood (Gianotti-Crosti syndrome) 22 23
  • Buttocks, elbows and knees, can also appear in cheeks, often symmetric
  • Often triggered by a viral respiratory infection
Laterothoracic exanthem of childhood
  • Unilateral, asymmetric, primarily on the trunk, for example on one flank
Molluscum contagiosum (wide-spread) 24
Purpuric exanthem (petechiae and extensive purpura in addition to the exanthem)More commonPurpuric exanthems triggered by infections
  • Viral respiratory and intestinal tract infections
Parvovirus B19 infections
  • Various types, such as the purpuric gloves and socks syndrome (symmetric purpuric exanthem of hands and feet)
Epidemic nephropathy (Puumala virus infection)
  • Purpuric exanthem in about 5 to 10% of cases
Drug rashes Hypersensitivity to Drugs
Pigmented purpuric dermatoses
RareThrombocytopenia
Vasculitis
  • Leukocytoclastic vasculitis of the skin 25
  • Henoch-Sch�nlein purpura 26
Septic infections, such as
  • meningococcal meningitis (impaired general condition, neurological symptoms, purpuric exanthem, extensive haemorrhagia on the skin)
  • gonococcus

Exanthems associated with febrile infections in tourists. The causes are given in order of frequency from the most to the least common.

InfectionPossible dermatological symptoms
Dengue Viral Diseases in Warm ClimatesIn the beginning transient erythema of the face and neck, then, at 3 to 5 days from the onset of symptoms and fever, maculopapular exanthem that spreads from the trunk to the face and limbs. Petechiae may occur. Often coalesces into general erythema that has small lighter areas of healthy skin, "white islands in a sea of red".27
Typhoid and paratyphoid fever Diarrhoeal Diseases Caused by MicrobesMild exanthem with small macules usually on weeks 2-4 after the onset of fever and abdominal pain, individual small macules (rose spots) on the trunk and limbs, typically on the chest and abdomen.
Relapsing fever Bacterial Diseases in Warm ClimatesVery variable, often maculopapular exanthem, may also resemble erythma multiforme, usually appears at the end of the febrile stage and lasts for 1-2 days.
Spotted fevers Bacterial Diseases in Warm ClimatesPurpuric exanthem, on days 3-5 after the onset of the disease, in some cases preceded by ”tache noire” 28.Maculopapular and vesicular exanthems also occur (may resemble chickenpox).
Chikungunya Viral Diseases in Warm ClimatesMaculopapular or vesicular exanthem at the acute febrile stage, on days 2-3 of the disease; aphthae in mouth and groin are also common; symmetric strong pain in joints
Leptospirosis Bacterial Diseases in Warm ClimatesPurpuric exanthem of short duration (< 24 hours) on trunk and limbs, Petechiae in the palate; in severe disease jaundice, conjunctivitis and extensive purpura of the skin.
West Nile virus infectionMaculopapular exanthem with small macules on weeks 1-2 of the disease, on trunk and limbs, may be centred on limbs; often roseola-like.
Zika virus infection Viral Diseases in Warm ClimatesMaculopapular exanthema 3-5 days after symptom onset, often itching, usually starting on the trunk and spreading to limbs, conjunctivitis
Rare haemorrhagic fevers Viral Diseases in Warm ClimatesEcchymosis and haemorrhages on the skin and mucosa; bleeding diathesis; large haematomas and petechiae may occur on the skin, in mild cases purpuric exanthem
Yellow fever Viral Diseases in Warm ClimatesReddish facial flushes, jaundice, conjunctivis, purpuric exanthem and petechiae on the skin; in severe disease ecchymoses and haemorrghages

Skin disorders that may spread like an exanthem

  • Acute urticaria or acute exacerbation of chronic urticaria (itching, single lesions changing location in the course of the day) Hives (Urticaria) 29
  • Psoriasis, such as guttate psoriasis (white, lamellar scales) 30; pustular exanthem in pustular psoriasis 31
  • Pityriasis rosea (single scaly lesion a few weeks before the eruption of more scaly spots) 32
  • Eczemas (acute exacerbation of atopic eczema 33, spreading allergic eczema 34, nummular eczema 35
  • Acne (extensive, severe, acute disease of the trunk, back and chest may resemble a pustular or papular exanthem
  • Paraneoplastic exanthems
  • Rashes associated with connective tissue disorders (such as cutaneous lupus erythematosus 36)
  • Erythema multiforme Erythema Multiforme

Workup

  • Basic blood count with platelet count, CRP, ESR
  • If streptococcal infection is suspected, culture from pharyngeal secretions
  • A complete blood count may be useful for differential diagnosis (for example, eosinophilia in drug reactions, lymphocytosis or lymphocytopenia and sometimes thrombocytopenia in viral infections, increased mononuclear cell levels [atypical lymphocytes] in mononucleosis).
  • If a septic infection is suspected, blood culture should be performed twice. Targeted antibody tests based on clinical suspicion, such as EBV, HIV, Treponema.
  • Early stage clinical viral infections, such as HIV or EBV, can be diagnosed by PCR technology instead of the slower antibody test. This should be borne in mind when choosing the test.
  • Histological examination of a skin biopsy sample may be useful in diagnosing skin disorders resembling exanthem (such as guttate psoriasis).

Treatment

  • In patients who are in good condition and have no risk factors, it is often sufficient to withdraw the offending medication and to arrange a follow-up visit, as necessary.
  • For drug rashes and infectious exanthems, a cooling non-medicated lotion or gel can be applied topically as symptomatic treatment.
    • For example, a non-medicated ointment stored in a refrigerator or an extemporaneously prepared 2 to 3% menthol ointment (prescribe: menthol. 2.0%, make up to 100.0% with non-medicated ointment)
    • Commercial ointments are also available.
  • Antihistamines, such as 10 mg cetirizine once daily, can be used for symptomatic treatment of itching.
  • If a drug reaction is probable and severe infections have been excluded, oral glucocorticoids, such as a 1- to 2-week course of 0.5 mg/kg prednisolone, can be given as symptomatic treatment.
  • For some patients, mid-potent to potent (Class II-III) glucocorticoid ointments in courses of 1 to 2 weeks may be sufficient.
  • Treatment of any triggering infection

Specialist consultation

  • If the patient's general state is getting worse or a severe infection or drug reaction is suspected, emergency referral to hospital is indicated.
  • An infectious diseases specialist should be consulted if, for example, measles, viral or bacterial diseases from a warm climate, haemorrhagic fever or severe septic infection is suspected or if a diagnosis of HIV infection is either confirmed or strongly suspected.
  • A dermatologist should be consulted if symptoms persist or do not respond to treatment (suspicion of a skin disorder resembling exanthem).
  • An allergologist should be consulted if the reaction is probably drug-induced and the drug in question will be therapeutically important for the patient in the future.

    References

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    • Stern RS. Clinical practice. Exanthematous drug eruptions. N Engl J Med 2012;366(26):2492-501. [PubMed]
    • Rawlin M. Exanthems and drug reactions. Aust Fam Physician 2011;40(7):486-9. [PubMed]
    • Demoly P, Adkinson NF, Brockow K et al. International Consensus on drug allergy. Allergy 2014;69(4):420-37. [PubMed]
    • Keighley CL, Saunderson RB, Kok J ym. Viral exanthems. Curr Opin Infect Dis 2015;28(2):139-50. [PubMed]
    • Korman AM, Alikhan A, Kaffenberger BH. Viral exanthems: An update on laboratory testing of the adult patient. J Am Acad Dermatol 2017;76(3):538-550. [PubMed]
    • Drago F, Ciccarese G, Gasparini G ym. Contemporary infectious exanthems: an update. Future Microbiol 2017;12():171-193. [PubMed]
    • Drago F, Paolino S, Rebora A ym. The challenge of diagnosing atypical exanthems: a clinico-laboratory study. J Am Acad Dermatol 2012;67(6):1282-8. [PubMed]