Practice Essentials
Gianotti-Crosti syndrome (GCS) is a self-limited childhood exanthem that manifests in a characteristic acral distribution. It is rarely associated with systemic findings. Other descriptive designations, papular acrodermatitis of childhood (PAC) and papulovesicular acrolocated syndrome (PAS), described indistinguishable clinical entities. PAC is the term most commonly used today.
The original cases, described by Gianotti in 1955, were associated with hepatitis B virus infection, although other viral infections and vaccinations currently account for most cases. In the United States, the agent that has been reported most frequently in association with Gianotti-Crosti syndrome is Epstein-Barr virus (EBV).
The pathophysiologic process underlying Gianotti-Crosti syndrome remains unknown, although it is believed to represent an immunologic response to transient viremia or bacteremia, possibly a delayed-type hypersensitivity response. Children with a history of atopic dermatitis are at increased risk for developing GCS. [1, 2]
The most common presentation is an acute, symmetric, exanthematous, asymptomatic cutaneous eruption that develops over several days. The eruption typically lasts at least 10 days but can last longer than 6 weeks in more than 50% of patients. Complete resolution typically takes more than 2 months. Pruritus accompanies the eruption in 23% of patients. Systemic findings related to the primary viral syndrome or underlying bacterial infection may include malaise, fever, diarrhea, lymphadenopathy, and upper respiratory symptoms. [3]
Recurrences are rare, although a recurrent case associated with influenza virus vaccination has been reported. [4] Chronic cases lasting more than 12 months have been reported. [3]
Diagnostic criteria for Gianotti-Crosti syndrome have been proposed. All of the following positive clinical features must be present [5] :
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Monomorphous, flat-topped, pink-brown papules or papulovesicles 1-10 mm in diameter
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At least three of the following four sites involved: cheeks, buttocks, extensor surfaces of forearms, extensor surfaces of legs
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Symmetric eruption
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Duration of at least 10 days
In addition, extensive truncal lesions and scaling are absent, alternative diagnoses based on clinical judgment have been excluded, and histopathologic findings are compatible, if skin biopsy is performed.
Treatment is primarily supportive. Topical steroids are generally not effective, although anecdotal responses have been reported. Systemic treatment with antihistamines has been moderately helpful in relieving pruritus. Some children may require symptomatic care for the associated viral or bacterial infection. Follow-up appointments are required to monitor the lesions and address parental concerns.
Discussion with the parents regarding the benign, self-limited course is advisable. If a particular viral or bacterial infection is suspected as the etiology, the course of the associated infection should also be discussed.
Background
Gianotti and Crosti initially described GCS as associated with a hepatitis B virus exanthem, which they termed papular acrodermatitis of childhood. A similar constellation of characteristics was later found to be associated with several infectious agents and immunizations that were called papulovesicular acrolocated syndromes. Subsequent retrospective studies have shown that these 2 entities are indistinguishable from one another, and they are now consolidated under the unifying title of GCS. [6]
Also see Dermatologic Manifestations of Gianotti-Crosti Syndrome.
Pathophysiology
The most likely explanation for the exanthem is a local type IV hypersensitivity reaction to the offending viral or bacterial antigen within the dermis. This is based on the immunohistochemical characterization of the cutaneous inflammatory infiltrate. Findings on direct immunofluorescence examination of the skin are always negative. Electron microscopy has never revealed virus particles that suggested a reactive process other than an autoimmune phenomenon or direct infection of the skin. Inciting factors include various viral and bacterial infections, as well as recent immunizations. The rarity of Gianotti-Crosti syndrome (GCS) in adults suggests lifelong immunity to a common viral triggering agent. GCS is more common among children with atopic dermatitis, suggesting an immune mechanism. Increased human beta-defensin-4 (hBD-4) activity in the epidermis has been reported, indicating viral antigenemia rather than a type IV hypersensitivity reaction, as a possible cause of GCS in some viral cases. [7] However, more information is needed in order to define the precise mechanism involved. No genetic or familial predisposition is apparent. [8] An association with oral polio vaccination has been reported. [9]
Etiology of Gianotti-Crosti Syndrome
In the United States, the agent that has been reported most frequently in association with Gianotti-Crosti syndrome is Epstein-Barr virus (EBV). Gianotti-Crosti syndrome has been associated with both primary infection and with endogenous reactivation of EBV. [9, 10]
Other associated viral infections are as follows:
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Hepatitis A, B, and C
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Rotavirus
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Coxsackieviruses A16, B4, and B5
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Adenovirus
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Enterovirus
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Parainfluenza virus type 1 and type 2 [12]
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Parvovirus B19
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Paravaccinia (milker's nodules)
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Human herpesvirus 6
Associated bacterial infections are as follows:
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Mycobacterium avium-intracellulare
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Bartonella henselae
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Borrelia burgdorferi
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Meningococcemia
Associated immunizations are as follows:
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Polio [9]
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Diphtheria [15]
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Smallpox
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Hepatitis B
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H1N1 [16]
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COVID-19 [17]
Epidemiology
Frequency
United States
Because of the benign self-limited nature of Gianotti-Crosti syndrome (GCS), most cases are not reported, and the overall incidence is unknown. Frequency probably parallels the incidence of a precipitating infection in a specific geographic region.
International
The underlying infection correlates with the endemic pathogens of a specific geographic region.
For example, in Japan and Mediterranean countries, GCS is more commonly associated with hepatitis B virus infection. With the advent of more universal hepatitis B immunization, Epstein-Barr virus is now the most common etiologic factor worldwide. [18, 19]
Race
No racial predilection has been noted; however, the underlying infection correlates with the endemic pathogens of a specific geographic region.
Sex
In the pediatric population, GCS affects males and females with equal frequency. However, affected adults have been almost exclusively female, with only 3 documented cases affecting men. [20] Thus, hormonal influences may play a role in GCS. [12]
Age
GCS primarily occurs in children aged 3 months to 15 years, with a peak in children aged 1-6 years. More than 90% of patients are younger than 4 years, with a mean age of diagnosis of 15 months to 2 years. [20] Adult cases are rare but have been reported mainly in women aged 17-65 years and in immunocompromised adults with HIV-infection or following bone marrow transplantation. [21, 22]
Prognosis
Prognosis is excellent. Lesions clear within 4-12 weeks. No long-term complications are associated with Gianotti-Crosti syndrome (GCS). The mere presence of a rash does elicit some degree of social morbidity, depending on the age of the affected child. Although typically nonpruritic, some reports document pruritus in the later stages of the rash. The only significant morbidity involves the underlying infectious process, particularly the hepatitis B virus.
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Multiple erythematous flat-topped papules on the cheeks of an 18-month-old boy with Gianotti-Crosti syndrome.
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Arm of a 3-year-old boy with Gianotti-Crosti syndrome demonstrating well-defined erythematous lichenoid papules on the arm and forearm.
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Thigh of the 3-year-old boy with Gianotti-Crosti syndrome.
