Gianotti-Crosti Syndrome

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Gianotti-Crosti syndrome (GCS) is a distinct infectious exanthem with associated lymphadenopathy and acute anicteric hepatitis. [1] 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. [2]

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. [3] However, more information is needed in order to define the precise mechanism involved. No genetic or familial predisposition is apparent. [4]  An association with oral polio vaccination has been reported. [5]

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. [6]

No racial predilection has been noted; however, the underlying infection correlates with the endemic pathogens of a specific geographic region.

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. [7] Thus, hormonal influences may play a role in GCS. [8]

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. [7]

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.

Baleviciene G, Maciuleviciene R, Schwartz RA. Papular acrodermatitis of childhood: the Gianotti-Crosti syndrome. Cutis. 2001 Apr. 67(4):291-4. [Medline].

Caputo R, Gelmetti C, Ermacora E, et al. Gianotti-Crosti syndrome: a retrospective analysis of 308 cases. J Am Acad Dermatol. 1992 Feb. 26(2 Pt 1):207-10. [Medline].

Caltabiano R, Vecchio GM, De Pasquale R, Loreto C, Leonardi R, Vasquez E. Human ß-defensin 4 expression in Gianotti-Crosti. Acta Dermatovenerol Croat. 2013. 21(1):43-7. [Medline].

Tagawa C, Speakman M. Photo quiz. Papular rash in a child after a fever. Gianotti-Crosti syndrome. Am Fam Physician. January 2013. 87(1):59-60. [Medline].

Al Dhaheri HS, Al Kaabi A, Kara Hamo Y, Al Kaabi A, Al Kaabi S, Al Tatari H. Unusual Presentation of Gianotti-Crosti Syndrome due to Epstein-Barr Virus Infection. Case Rep Dermatol Med. 2016. 2016:1017524. [Medline].

Marcassi AP, Piazza CAD, Seize MBMP, Cestari SDCP. Atypical Gianotti-Crosti syndrome. An Bras Dermatol. 2018 Mar. 93 (2):265-267. [Medline].

Iorizzo LJ 3rd, Scott G, Tausk FA. Gianotti-Crosti syndrome: a case report in an adult. Cutis. April 2012. 89(4):169-72. [Medline].

Brandt O, Abeck D, Gianotti R, Burgdorf W. Gianotti-Crosti syndrome. J Am Acad Dermatol. January 2006. 54(1):136-45. [Medline].

Metelitsa AI, Fiorillo L. Recurrent Gianotti-Crosti syndrome. J Am Acad Dermatol. 2011 Oct. 65(4):876-7. [Medline].

Yoshida M, Tsuda N, Morihata T, et al. Five patients with localized facial eruptions associated with Gianotti-Crosti syndrome caused by primary Epstein-Barr virus infection. J Pediatr. 2004 Dec. 145(6):843-4. [Medline].

Mendoza N, Diamantis M, Arora A, et al. Mucocutaneous manifestations of Epstein-Barr virus infection. Am J Clin Dermatol. 2008. 9(5):295-305. [Medline].

Draelos ZK, Hansen RC, James WD. Gianotti-Crosti syndrome associated with infections other than hepatitis B. JAMA. 1986 Nov 7. 256(17):2386-8. [Medline].

Atanasovski M, Dele-Michael A, Dasgeb B, Ganger L, Mehregan D. A case report of Gianotti-Crosti post vaccination with MMR and dTaP. Int J Dermatol. 2011 May. 50(5):609-10. [Medline].

Kroeskop A, Lewis AB, Barril FA, Baribault KE. Gianotti-Crosti syndrome after H1N1-influenza vaccine. Pediatr Dermatol. 2011 Sep-Oct. 28(5):595-6. [Medline].

Chuh A, Zawar V, Sciallis GF, Lee A. The diagnostic criteria of pityriasis rosea and Gianotti-Crosti syndrome – a protocol to establish diagnostic criteria of skin diseases. J R Coll Physicians Edinb. 2015 Sep. 45 (3):218-25. [Medline].

Retrouvey M, Koch LH, Williams JV. Gianotti-Crosti syndrome following childhood vaccinations. Pediatr Dermatol. Jan-Feb 2013. 30(1):137-8. [Medline].

Sören A Craig-Müller, MD Resident Physician, Department of Dermatology and Department of Internal Medicine, University of Minnesota Medical School

Sören A Craig-Müller, MD is a member of the following medical societies: Alpha Omega Alpha, American Medical Association

Disclosure: Nothing to disclose.

Dirk M Elston, MD Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Robert A Schwartz, MD, MPH Professor and Head of Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, Rutgers New Jersey Medical School; Visiting Professor, Rutgers University School of Public Affairs and Administration

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, New York Academy of Medicine, American Academy of Dermatology, American College of Physicians, Sigma Xi

Disclosure: Nothing to disclose.

Dirk M Elston, MD Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Kevin P Connelly, DO Clinical Assistant Professor, Department of Pediatrics, Division of General Pediatrics and Emergency Care, Virginia Commonwealth University School of Medicine; Medical Director, Paws for Health Pet Visitation Program of the Richmond SPCA; Pediatric Emergency Physician, Emergency Consultants Inc, Chippenham Medical Center

Kevin P Connelly, DO is a member of the following medical societies: American Academy of Pediatrics, American College of Osteopathic Pediatricians, American Osteopathic Association

Disclosure: Nothing to disclose.

Howard Pride, MD Associate Physician, Departments of Pediatrics and Dermatology, Geisinger Medical Center

Howard Pride is a member of the following medical societies: American Academy of Dermatology and Society for Pediatric Dermatology

Disclosure: Nothing to disclose.

Gianotti-Crosti Syndrome

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