AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Background

Gianotti-Crosti syndrome is a self-limited childhood exanthem that manifests in a characteristic acral distribution. It is rarely associated with systemic findings. The original cases, described in Italy by Gianotti in 1955, were associated with hepatitis B virus infection, although other viral infections currently account for most cases.

The 2 older, descriptive designations, papular acrodermatitis of childhood (PAC) and papulovesicular acrolocated syndrome (PAS), described indistinguishable clinical entities. PAC is the term most commonly used today.

Also see the eMedicine Pediatrics article Gianotti-Crosti Syndrome.

Pathophysiology

Although the original reports of this syndrome were attributed to acute infection with the hepatitis B virus, more recent studies have demonstrated that Gianotti-Crosti syndrome is more commonly associated with a number of other infectious agents, both viral and bacterial. In the United States, the agent that has been reported most frequently in association with Gianotti-Crosti syndrome is Epstein-Barr virus (EBV). See

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. Deposition of circulating immune complexes in the dermis may play a role. Several studies have failed to demonstrate deposition of viral particles or bacteria within the dermis.

Frequency

United States

Gianotti-Crosti syndrome occurs sporadically in the clinical setting, with no apparent genetic or familial predisposition. It appears to be uncommon and may go unrecognized because of its generally benign and self-limited course. It is more commonly seen in the spring and summer, possibly as a result of a concomitant increase in viral illness seen in the general population.

International

The distribution of the disease is worldwide, with cases reported in Great Britain, France, Germany, Spain, Russia, Turkey, India, Hong Kong, China, and Japan.

In one series of 20,000 patients younger than 5 years seen over a 5-year period in Bordeaux, France, 26 patients with features consistent with Gianotti-Crosti syndrome were identified, yielding an annual incidence of 0.13%.¹

Mortality/Morbidity

• Gianotti-Crosti syndrome is generally a benign, self-limited condition.
• In the original cases of hepatitis B virus-associated disease, anicteric hepatitis developed in a proportion of patients. Anicteric hepatitis may also be seen in cases associated with other viral illnesses such as EBV.
• In extremely rare cases, chronic liver disease has followed the initial phase of infection with hepatitis B virus.

Race

• No racial predilection is apparent.

Sex

• In children, males and females are equally affected.
• Reported cases in adults have been seen exclusively in females.

Age

• The onset of the eruption typically occurs in children aged 3 months to 15 years, with an average age of 2 years and a peak incidence at 1-6 years. Adult cases are rare but have been reported in women aged 17-46 years.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

History

Children usually present with 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. Recurrences are rare.
• Pruritus accompanies the eruption in 23% of patients.
• Other symptoms related to the primary viral syndrome or underlying bacterial infection may include mild constitutional symptoms such as low-grade fever and malaise, pharyngitis and/or mucosal lesions, or symptoms of an upper respiratory tract infection.
• When associated with a hepatitis B virus, EBV, or CMV infection, an anicteric acute hepatitis may be present.
• A case control study of 29 children with Gianotti-Crosti syndrome from Bologna, Italy demonstrated a higher prevalence of atopic dermatitis in patients versus controls (24.1% vs 6.8%). They also found that patients were more likely than controls to have elevated levels of total and specific immunoglobulin E and a family history of atopy.²

Physical

The cutaneous eruption is characterized by monomorphous pale, pink-to-flesh–colored or erythematous 1- to 10-mm papules or papulovesicles localized symmetrically and acrally over the extensor surfaces of the extremities, the buttocks, and the face. The number of lesions ranges from few to many. The trunk, knees, elbows, palms, and soles are rarely involved, and, in general, extensive involvement of the trunk is not consistent with a diagnosis of Gianotti-Crosti syndrome. Individual papules may coalesce to form larger plaques. Uncommonly, the eruption may develop a petechial or purpuric appearance. Partial involvement of only the face or the extremities is not uncommon, especially in older children. Over days to weeks, the papules may acquire a smooth-topped, polished, or lichenoid appearance. Other findings upon physical examination include the following:

• Fever (27%)
• Lymphadenopathy (31%)
• Hepatosplenomegaly (4%)
• Pharyngeal erythema, oropharyngeal ulcers or vesicles, or tonsillar swelling in cases secondary to infections of the upper respiratory tract

Causes

Gianotti-Crosti syndrome has been associated with the following infectious agents:

• Hepatitis B virus, most commonly ayw strain
• Epstein-Barr virus (probably the most common etiology)³: Gianotti-Crosti syndrome has been associated with both primary infection and with endogenous reactivation of EBV.⁴
• Respiratory syncytial virus⁵
• Coxsackieviruses,^{1, 6} echoviruses, and other enteroviruses⁵
• Parainfluenza virus
• Parvovirus B19⁷
• Poxvirus⁷
• Cytomegalovirus¹
• Human herpesvirus 6, both primary infection and reactivation of latent infection⁸
• Rotavirus⁹
• Human immunodeficiency virus
• Group A beta-hemolytic streptococci
• Neisseria meningitidis¹⁰
• Mycoplasma pneumoniae
• Bartonella henselae
• Borrelia burgdorferi

Gianotti-Crosti syndrome has also been reported to occur after vaccination for the following:

• Hepatitis A virus¹¹
• Hepatitis B virus^{12, 13, 14}
• Measles, mumps, rubella viruses (MMR)¹⁵
• Influenza virus¹⁶
• Oral poliovirus vaccine¹⁷
• Japanese encephalitis virus¹⁸

The Medscape Vaccines Resource Center may be of interest. Additionally, see the CME course Promoting Vaccine Safety: Answers to Common Questions.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Other Problems to be Considered

Unilateral laterothoracic or asymmetric periflexural exanthem of childhood - Initially manifests as a unilateral papular exanthem in the axilla, the flank, and/or the antecubital fossa, characterized by minute, 1- to 2-mm papules, that become bilateral and more generalized over the course of several days

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Lab Studies

• Laboratory studies are not generally indicated.
• Blood counts may reveal a lymphocytosis and a relative monocytosis or a lymphopenia secondary to the underlying viral infection.
• In cases associated with acute infection with the hepatitis B virus, EBV, or CMV, anicteric hepatitis is evident by elevations in the levels of hepatic transaminases and antiviral antibodies.
• A viral agent can be identified in approximately one third of cases. If a specific infectious etiology is suspected, testing can be directed at potential etiologies.
• • EBV - Monospot, immunoglobulin M (IgM) and immunoglobulin G (IgG) titers, or serum polymerase chain reaction (PCR)
  • CMV - IgM and IgG titers, serum CMV antigen levels, or serum PCR
  • RSV, parainfluenza virus, other respiratory viral pathogens - Nasal washing for fluorescent antibody testing
  • Enterovirus - Culture or polymerase chain reaction from serum
  • Parvovirus B19 - IgM and IgG titers or serum PCR
  • HHV-6 - Serum PCR
  • Group A beta-hemolytic streptococci - Serum PCR or throat culture

Histologic Findings

The histology of skin biopsy specimens is nonspecific. Mild epidermal acanthosis and spongiosis with focal parakeratosis can be seen. A lymphocytic exocytosis may also be seen. Edema of the papillary dermis and a superficial lymphohistiocytic infiltrate, sometimes with a perivascular localization or a lichenoid appearance, is common. Rarely, features of a lymphocytic vasculitis have been noted.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Medical Care

Education and reassurance are usually sufficient for concerned parents. Some children may require general supportive and symptomatic care for the associated viral or streptococcal infection.

• Application of soothing, anti-itch topical preparations with menthol, colloidal oatmeal, or pramoxine in conjunction with oral antihistamines may be useful for relief of pruritus.
• Avoidance of topical steroid use is advised.
• If an associated streptoccocal infection is identified, a course of an appropriate systemic antibiotic should be initiated.

Consultations

In rare instances of persistent liver dysfunction in the setting of acute hepatitis B infection, consultation with a pediatric gastroenterologist should be considered.

Activity

Isolation is not necessary.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

The goals of pharmacotherapy are to reduce associated symptoms, in particular pruritus. These agents do not shorten the course of the disease or prevent complications.

Drug Category: Antihistamines

These agents prevent histamine response in sensory nerve endings and blood vessels. They are more effective in preventing histamine response than in reversing it.

Drug Name	Hydroxyzine hydrochloride (Atarax, Vistaril)
Description	Offers a mild degree of relief from pruritus. Antagonizes H1 receptors in periphery. May suppress histamine activity in the subcortical region of CNS.
Adult Dose	25-50 mg PO q6h prn
Pediatric Dose	0.6 mg/kg/dose PO q6h prn
Contraindications	Documented hypersensitivity
Interactions	CNS depression may increase with alcohol or other CNS depressants
Pregnancy	C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions	Associated with clinical exacerbations of porphyria (may not be safe for porphyric patients); ECG abnormalities (alterations in T waves) may occur; may cause drowsiness; use caution in patients with narrow-angle glaucoma, prostatic hyperplasia, bladder neck obstruction, asthma, or COPD

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Further Outpatient Care

• A follow-up visit after 2 months for evaluation of persistent signs or symptoms is advisable.
• Children with atypical presentations should also be reevaluated after 2-4 weeks to evaluate progression and to confirm the diagnosis.

Complications

• In rare cases, chronic liver disease can occur after the initial phase of infection with hepatitis B virus.

Prognosis

• The prognosis is excellent. This syndrome is generally a benign, self-limited condition with only rare complications. The eruption usually starts to resolve after 6-8 weeks.

Patient Education

• 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.

MULTIMEDIA

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Media file 1:  Characteristic erythematous papules of Gianotti-Crosti syndrome appear on the face of this child. The child does not have a toxic appearance.
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Media file 2:  Characteristic erythematous papules of Gianotti-Crosti syndrome can be seen on the extremities, as is the case in this young child (same patient as in Media File 1).
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Media file 3:  A 9-year-old girl who recently returned from a trip to Europe with her family. She developed a low-grade fever, malaise, and some lymphadenopathy. An eruption limited to her face, arms, legs, and buttocks was noted.
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Media type:  Photo

Media file 4:  A mildly pruritic eruption characterized by erythematous papules localized to the face, arms, legs, and buttocks.
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Media type:  Photo

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

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23. Chuh AA. Diagnostic criteria for Gianotti-Crosti syndrome: a prospective case-control study for validity assessment. Cutis. Sep 2001;68(3):207-13. [Medline].
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25. Hurwitz S. Papular acrodermatitis of childhood. In: Clinical Pediatric Dermatology. Philadelphia, Pa: WB Saunders; 1993:128-30.
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Article Last Updated: Mar 24, 2008