Gianotti Crosti Syndrome 

Gianotti Crosti Syndrome 

Introduction

• Self-limited rash of childhood characterized by acute onset and symmetrical distribution of papules, vesicles, or papulovesicles predominantly affecting face and extensor surfaces of arms, legs, and buttocks^(1,2)
• Usually spontaneously resolves in 2-12 weeks^(1,2)

Synonyms

•  Papular acrodermatitis
•  Papular acrodermatitis of childhood
•  Acrodermatitis papulosa infantum

Epidemiology

Who Is Most Affected

•  Young children aged 1-6 years^(1,2)

Incidence/Prevalence

• Likely underreported due to benign and self-limited nature and misdiagnosis as nonspecific exanthem (Prim Care 2015 Dec;42(4):517)

What are the Risk Factors?

• Vaccinations implicated
  • Gianotti-Crosti syndrome diagnosed 1 week after H1N1 intranasal vaccine in 9-year-old boy with negative viral cultures in case report (Pediatr Dermatol 2011 Sep-Oct;28(5):595)
  • Gianotti-Crosti syndrome diagnosed based on clinical findings and consistent histology in 19-month-old boy 2 days after measles, mumps, and rubella vaccine in case report (Pediatr Dermatol 2013 Jan-Feb;30(1):137)

Associated Conditions

• history of atopic conditions including atopic dermatitis and asthma more common in children with Gianotti-Crosti syndrome compared to controls
  •  based on retrospective cohort study
  •  37 children (mean age 4.5 years) with Gianotti-Crosti syndrome (GCS group) and 37 matched controls had medical records reviewed
  • comparing history of atopic conditions in GCS group vs. control group
    • atopic dermatitis in 28 vs. 9 (p < 0.001)
    •  asthma in 14 vs. 6 (p = 0.06)
    • allergic rhinitis in 18 vs. 11 (not significant)
    •  atopic urticaria in 4 vs. 0 (not significant)
    • allergic conjunctivitis in 2 vs. 4 (not significant)
    •  ≥ 1 atopic condition in 31 vs. 19 (p = 0.006)
    •  ≥ 2 atopic conditions in 21 vs. 9 (p = 0.009)
    •  ≥ 3 atopic conditions in 11 vs. 2 (p = 0.01)
  •  Reference – Pediatr Dermatol 2016 Sep;33(5):488

Etiology and Pathogenesis

Causes

•  immune response to infection of nonspecific etiology⁽¹⁾
• most commonly associated with^(1,2)
  • Epstein-Barr virus (EBV) (most commonly associated virus in the United States)
  • hepatitis B virus (HBV)
  • Gianotti-Crosti syndrome has been less commonly reported with
    • other viral infections
      • hepatitis A virus (HAV)
      • coxsackie virus B (CVB)
      • molluscum contagiosum
      • rotavirus
      •  respiratory syncytial virus (RSV) infection in children or in adults
      • parvovirus B19
      •  parainfluenza virus
      • mumps virus
      • cytomegalovirus (CMV); Gianotti-Crosti syndrome as presenting sign of CMV in 3-year-old immunocompetent girl in case report (J Clin Virol 2016 May;78:120)
    • bacterial infections⁽²⁾
      •  Bartonella henselae
      • Mycoplasma pneumoniae
      • group A Streptococcus
      • Borrelia burgdorferi (J Am Acad Dermatol 2006 Jan;54(1):136)

Pathogenesis

•  unknown⁽²⁾

History and Physical

Clinical Presentation

•  acute onset of characteristic rash most commonly occurs in young children but has been reported in adults⁽²⁾
•  rash is not painful but is commonly accompanied by mild pruritus that can be severe in rare cases^(1,2)
• most children are otherwise asymptomatic, but some children may have^(1,2)
  •  fever
  •  symptoms of upper respiratory infection
  •  hepatomegaly
  •  lymphadenitis
  •  diarrhea (Prim Care 2015 Dec;42(4):517)
•  rash may be preceded by upper respiratory or gastrointestinal illness (Prim Care 2015 Dec;42(4):517)
• proposed diagnostic criteria may help diagnose Gianotti-Crosti syndrome (GCS) in children (level 2 [mid-level] evidence)
  •  based on diagnostic case-control study
  •  23 children (mean age 3.1 years) from India with GCS and 74 controls from India (mean age 4.4 years) with alternate diagnosis after suspected GCS or were diagnosed with any of the differential diagnoses considered in GCS were evaluated with proposed diagnostic criteria
  • GCS diagnosed if
    • all positive clinical features occurred on ≥ 1 occasion
      •  monomorphous, flat-topped, pink-brown papules or papulovesicles 1-10 mm in diameter
      •  ≥ 3 affected sites among cheeks, buttocks, extensor surfaces of forearms, or extensor surfaces of legs
      •  symmetrical
      •  lasting ≥ 10 days
    • rash does not have any negative clinical features
      •  extensive truncal lesions (compared to acral eruption)
      •  scaly lesions
    •  GCS considered more likely than differential diagnoses (acrodermatitis enteropathica, erythema infectiosum, erythema multiforme, hand-foot-and-mouth disease, Henoch-Schonlein purpura, Kawasaki disease, lichen planus, papular urticaria, papular purpuric gloves and sock syndrome, scabies)
    •  findings consistent with GCS on biopsy if performed
  •  for distinguishing children with GCS from controls, clinical prediction rule had 100% sensitivity and 100% specificity
  •  Reference – Pediatr Dermatol 2004 Sep-Oct;21(5):542

History

History of Present Illness (HPI)

•  ask about recent illness^(1,2)

Physical

General Physical

•  patients are sometimes feverish⁽²⁾

Skin

• look for distinctive erythematous rash^(1,2)
  •  symmetrical distribution on face and extensor surfaces of arms, legs, and buttocks
  •  trunk is also often involved, but to a lesser extent than acral areas
  • discrete lesions are typically
    •  1-10 mm in size
    •  vesicular, papular, or papulovesicular (may be edematous)
    •  red-brown in color
    •  flat-topped but can be dome-shaped
  •  rash can coalesce and form larger plaques (Prim Care 2015 Dec;42(4):517)
  •  may include Koebner phenomenon (accentuation of lesions at site of trauma)

Neck

•  assess for lymphadenitis⁽²⁾

Abdomen

•  assess for hepatomegaly⁽²⁾

Diagnosis

Making the Diagnosis

• diagnosis is made based on clinical findings including^(1,2)
  •  acute onset of characteristic rash
  •  otherwise asymptomatic presentation or one that includes symptoms of lymphadenitis, hepatomegaly, fever, and upper respiratory infection

Differential Diagnosis

• Henoch-Schonlein purpura⁽¹⁾
• erythema multiforme⁽¹⁾
• hand-foot-and-mouth disease⁽¹⁾
•  acral pityriasis lichenoides⁽¹⁾
•  asymmetric periflexural exanthem (APE)/unilateral laterothoracic exanthem (ULE)⁽¹⁾
• other differential diagnoses may include
  • Kawasaki disease
  • erythema infectiosum (parvovirus B19 infection)
  • lichen planus
  •  papular purpuric gloves and socks syndrome
  • scabies
  •  acrodermatitis enteropathica
  •  papular urticaria
  •  Reference – Infect Dis Rep 2012 Jan 2;4(1):e12

Testing Overview

•  diagnosis usually based on clinical findings; proposed diagnostic criteria may help diagnose Gianotti-Crosti syndrome in children (level 2 [mid-level] evidence)
• lesional biopsy is typically only performed if presentation is unusual; findings include⁽²⁾
  •  dense lichenoid lymphohistiocytic infiltrate
  •  strong, staining for beta-defensin-4 in stratum corneum, granulosum, and spinosum
•  if infection with Epstein-Barr virus or hepatitis B virus is suspected, consider serological testing if available⁽¹⁾
• nonspecific laboratory findings include
  •  elevated liver enzymes
  •  elevated lactate dehydrogenase
  •  elevated alkaline phosphatase without hyperbilirubinemia
  •  Reference – Prim Care 2015 Dec;42(4):517

Management

Management Overview

•  Gianotti-Crosti syndrome is self-limited, and there is no effective treatment for altering disease course⁽¹⁾
• supportive treatment measures⁽¹⁾
  •  if child has pruritus, consider topical calamine
  •  if child has severe pruritus affecting sleep, consider nocturnal dose of sedating systemic antihistamine such as diphenhydramine or hydroxyzine
  •  topical steroids or rarely oral corticosteroids may be considered in select cases
  •  symptomatic remission reported after 5-day treatment with ribavirin 300 mg/day orally in 6-year-old girl with 4-month history of highly pruritic rash clinically consistent with Gianotti-Crosti in case report (J Dermatol Case Rep 2008 Dec 27;2(4):63full-text)
•  if underlying virus is implicated, treat any associated complications of virus⁽¹⁾
• if Gianotti-Crosti syndrome is due to⁽¹⁾
  • hepatitis B virus (HBV), consider monitoring for hepatitis due to chronic infection
  • Epstein-Barr virus (EBV), consider monitoring for complications due to long-term infection
•  Gianotti-Crosti itself is not contagious, but the viruses that trigger it can be⁽²⁾

Complications and Prognosis

Complications

• complications of chronic hepatitis B infection, although rare, can occur in children with Gianotti-Crosti syndrome caused by hepatitis B infection including^(1,2)
  •  subacute or chronic hepatitis
  •  cirrhosis
  •  hepatocellular carcinoma
•  long-term complications of Epstein-Barr virus (EBV) infection include Burkitt and Hodgkin lymphomas, nasopharyngeal carcinoma, and multiple sclerosis; association between Gianotti-Crosti syndrome in childhood and these EBV complications has not been established⁽¹⁾

Prognosis

• rash
  •  self-limited and typically resolves within 2-12 weeks (Prim Care 2015 Dec;42(4):517)
  •  range of rash duration in cohort of 23 children in India with Gianotti-Crosti syndrome was 14 days to 12 months (Pediatr Dermatol 2004 Sep-Oct;21(5):542)
  •  no anticipated scarring after lesions heal (J Am Acad Dermatol 2006 Jan;54(1):136)
• cases associated with hepatitis B virus infection
  •  after resolution of acute infection, most children reported to have hepatitis B surface antigenemia and remain infectious
  •  development of chronic hepatitis or ultimate death from hepatitis B infection in children who have recovered from Gianotti-Crosti syndrome is very rare
  •  Reference – J Am Acad Dermatol 2006 Jan;54(1):136
•  case report findings of recurrent Gianotti-Crosti syndrome after hepatitis B vaccination can be found in (Future Sci OA 2021 Mar 4;7(6):FSO695)
• cohort study evaluating relationship between serum IgE and clinical course of Gianotti-Crosti syndrome in 29 children can be found in Front Pediatr 2021;9:643341

Prevention and Screening

•  not applicable

Guidelines and Resources

Guidelines

• no relevant guidelines for “Gianotti-Crosti syndrome” found 2017 Oct 17 on MEDLINE search using guidelines limiter

Review Articles

•  review of viral skin diseases can be found in Prim Care 2015 Dec;42(4):517
•  review of viral exanthems can be found in Dermatol Ther 2013 Nov-Dec;26(6):433
•  review can be found in J Am Acad Dermatol 2006 Jan;54(1):136

MEDLINE Search

•  to search MEDLINE for (Gianotti-Crosti syndrome) with targeted search (Clinical Queries), click therapy, diagnosis, or prognosis

Patient Information

•  handout from Australasian College of Dermatologists
•  handout from American Osteopathic College of Dermatology
•  handout from National Organization for Rare Disorders
•  handout on first aid for rashes from KidsHealth

References

1. Fölster-Holst R, Zawar VP, Chuh A. Paraviral exanthems. Expert Rev Anti Infect Ther. 2016 Jun;14(6):601-11.
2. Arango CA, Jones R. 8 viral exanthems of childhood. J Fam Pract. 2017 Oct;66(10):598-606.