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Official reprint from UpToDate
www.uptodate.com ©2014 UpToDate
Author
Antonio A T Chuh, MD, FRCP,
FRCPCH
Section Editors
M...
to three-quarters of cases in some series [12,24-28]. The clinical manifestations and treatment of EBV infection are
discu...
associated disease. Skin biopsy may be useful in cases that are clinically confusing.
Course — Most children with GCS have...
immunization status of the child, and local prevalence of HBV infection are factors to consider in making a decision
about...
TREATMENT — The treatment of Gianotti-Crosti syndrome (GCS) is supportive, consisting of symptomatic
treatment of pruritus...
Topical corticosteroids have been tried in GCS but there is no evidence that the disease course is modified by such
therap...
Use of UpToDate is subject to the Subscription and License Agreement.
REFERENCES
1. GIANOTTI F. [Report on a special case ...
20. Colombo M, Rumi MG, Sagnelli E, et al. Acute hepatitis B in children with papular acrodermatitis. Pediatr
Pathol 1986;...
and Bartonella henselae infection]. An Esp Pediatr 2000; 52:299.
49. Baldari U, Cattonar P, Nobile C, et al. Infantile acr...
76. Grilli R, Izquierdo MJ, Fariña MC, et al. Papular-purpuric "gloves and socks" syndrome: polymerase chain
reaction demo...
GRAPHICS
Characteristic eruption of Gianotti-Crosti syndrome
(papular acrodermatitis)
The characteristic rash of Gianotti-...
Gianotti-Crosti syndrome
Multiple papules and papulovesicles on the extremities of a child.
Reproduced with permission fro...
Gianotti-Crosti syndrome
Multiple papules and papulovesicles on the face of a child with Gianotti-Crosti syndrome.
Reprodu...
Gianotti-Crosti syndrome
Papular and papulovesicular eruption with a predilection for the face
and extremities in a child ...
Gianotti-Crosti syndrome
Papules and papulovesicles in Gianotti-Crosti syndrome.
Reproduced with permission from: www.visu...
Gianotti-Crosti syndrome
Papules and papulovesicles on the buttocks of a child with Gianotti-Crosti syndrome.
Reproduced w...
Slapped cheek rash of parvovirus B19
A child with the characteristic malar ("slapped cheek") rash associated
with parvovir...
Erythema infectiosum
Reticulating pattern of an erythematous eruption on the extremities
due to parvorvirus B19. Rash is m...
Erythema multiforme
Characteristic target lesions of the palm in erythema multiforme begin
with a central vesicle.
Courtes...
Hand-foot-and-mouth disease - buccal mucosa
Small ulcers are present on the oral mucosa.
Reproduced with permission from: ...
Hand-foot-and-mouth disease - tongue
Multiple small ulcers are present on the tongue.
Reproduced with permission from: www...
Hand-foot-and-mouth disease - foot
Multiple vesicular lesions on an erythematous base are present on the
foot.
Reproduced ...
Interdigital lesions of scabies
The essential lesion is a small, erythematous, nondescript papule.
Courtesy of John T Cris...
Lichen planus
Lichen planus is characterized by flat-topped, violaceous papules.
Courtesy of Andrew Samel, MD.
Graphic 598...
Lichen planus
Note discrete polygonal scaling erythematous papules on the wrist.
Courtesy of Beth G Goldstein, MD and Adam...
Gloves and socks syndrome secondary to
parvovirus B19 infection
Papular-purpuric rash on the hands and feet of a patient w...
Acrodermatitis enteropathica
Acrodermatitis enteropathica in an infant. Moist erythematous plaques are
present on the chee...
Skin manifestations of Henoch-Schönlein purpura (IgA
vasculitis)
This picture shows the classic skin manifestations of Hen...
Skin manifestations of Henoch-Schönlein purpura (IgA
vasculitis)
Courtesy of Susan Kim, MD.
Graphic 72094 Version 4.0
Disclosures: Antonio A T Chuh, MD, FRCP, FRCPCH Nothing to disclose. Moise L Levy, MD Grant/Research/Clinical Trial Suppor...
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Gianotti-Crosti syndrome vs PPGSS syndrome

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Characteristic viral exanthems
Fever with skin rash

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Gianotti-Crosti syndrome vs PPGSS syndrome

  1. 1. Official reprint from UpToDate www.uptodate.com ©2014 UpToDate Author Antonio A T Chuh, MD, FRCP, FRCPCH Section Editors Moise L Levy, MD Morven S Edwards, MD Deputy Editor Abena O Ofori, MD Gianotti-Crosti syndrome (papular acrodermatitis) All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jul 2014. | This topic last updated: May 22, 2014. INTRODUCTION — Gianotti-Crosti syndrome (GCS), also known as papular acrodermatitis, papular acrodermatitis of childhood, and infantile papular acrodermatitis, is a symmetric papular eruption with an acral distribution (cheeks, buttocks, and extensor surfaces of the forearms and legs) (picture 1A-F). It was first described by Gianotti in 1955, and by Crosti and Gianotti in 1957 [1,2], and was initially believed to occur only in infants and children [3-5]. It has since been reported in adults [6-8]. TERMINOLOGY — In the original descriptions, Gianotti-Crosti syndrome (GCS) had three cardinal manifestations [1-5]: Gianotti referred to papular or papulovesicular acral eruptions, with or without itching, associated with reactive lymphadenitis, but not hepatitis, as "papulovesicular acrolocated syndrome" [4]. However, it is not possible to distinguish between GCS and papulovesicular acrolocated syndrome solely on the basis of cutaneous findings [9]. With current terminology, neither lymphadenopathy nor hepatitis is mandatory for the diagnosis of GCS. The term "Gianotti-Crosti disease" is sometimes reserved for patients with GCS that is documented to be related to hepatitis B virus (HBV) infection [10]. EPIDEMIOLOGY — The incidence and prevalence of Gianotti-Crosti syndrome (GCS) are unknown. Because many children with GCS may be diagnosed with a "viral rash" or "nonspecific viral exanthem," GCS is probably underdiagnosed [11]. (See 'Differential diagnosis' below.) GCS primarily affects children younger than five years of age. During childhood, boys and girls are equally affected [12,13]. However, in adulthood, females may be more prone than males to develop GCS [10]. Most reports of GCS describe isolated cases. However, several outbreaks have been described [14-18]. Three outbreaks in Japan were associated with HBV and involved 153, 54, and 14 patients [14-16]. The remaining two outbreaks were associated with Epstein-Barr virus (EBV) infection, and each involved five patients [17,18]. A mini- epidemic with four patients was reported, but the underlying virological cause was not found [19]. ETIOLOGY — Gianotti-Crosti syndrome (GCS) usually occurs in association with a viral illness. HBV and EBV are the most common causes. In a review of 308 cases, 22 percent were caused by HBV and 78 percent by other viruses [9]. Hepatitis B virus — The association of GCS with HBV infection is well known [9,14-16,20-23]. However, HBV is an uncommon cause of GCS in the United States and in other countries where universal hepatitis B vaccination during infancy is routine [10]. In infants and young children with acute HBV infection, GCS may be the only clinical manifestation. The clinical manifestations, treatment, and prevention of hepatitis B virus are discussed separately. (See "Overview of hepatitis B virus infection in children" and "Epidemiology, transmission, and prevention of hepatitis B virus infection" and 'Complications' below.) Epstein-Barr virus — Epstein-Barr virus is another common cause of GCS, accounting for approximately one-half ® ® Nonrelapsing erythemato-papular dermatitis localized to the face and limbs, lasting about three weeks● Paracortical hyperplasia of lymph nodes● Acute hepatitis, usually anicteric, which could last for months and progress to chronic liver disease●
  2. 2. to three-quarters of cases in some series [12,24-28]. The clinical manifestations and treatment of EBV infection are discussed separately. (See "Clinical manifestations and treatment of Epstein-Barr virus infection" and 'Complications' below.) Other infections — GCS is less commonly reported in association with other pathogens, including enteroviruses [29,30], cytomegalovirus [31-33], parvovirus [34,35], parainfluenza virus [36,37], hepatitis A virus [38,39], rotavirus [40,41], molluscum contagiosum [34,42], respiratory syncytial virus [30], human immunodeficiency virus [43], human herpesvirus 6 (mainly 6B) [44,45], Mycoplasma pneumoniae [46,47], beta-hemolytic streptococci [30], Bartonella henselae [48], and Borrelia burgdorferi [49]. (See appropriate topic reviews). Vaccines — GCS has been reported to occur after the administration of various vaccines, including influenza virus vaccine [50], measles-mumps-rubella vaccines [51], hepatitis B and measles vaccines [52,53], oral polio vaccine [54], hepatitis A vaccine [55], and Japanese encephalitis vaccine [56]. However, many children receive vaccinations before any disease event; such temporal associations may be purely coincidental and cannot be taken as definitive evidence for a causal association. PATHOGENESIS — The pathogenesis of Gianotti-Crosti syndrome (GCS), including the mechanism for the acral distribution of lesions, is unknown. Lesional histopathologic changes are nonspecific, and include focal spongiosis (collections of fluid in the epidermis) and parakeratosis with perivascular lymphocytic infiltrates in the upper dermis [57]. The clinical manifestations of GCS may represent a final common pathway for infections caused by several viruses. One hypothesis suggests that the clinical manifestations result from a delayed hypersensitivity reaction to viral illness [58]. The significance of IgE-mediated immunity in the pathogenesis of GCS and other viral exanthems is another area of investigation. A case-control study noted that children with GCS were significantly more likely to have had atopic dermatitis and to have a family history of atopy than control children who were being evaluated for recurrent infections (24 versus 7 percent for atopic dermatitis and 52 versus 31 percent for family history of atopy) [59]. CLINICAL FEATURES — Gianotti-Crosti syndrome (GCS) usually occurs in children younger than five years, but older children, adolescents, and adults also may be affected. Most patients have an upper respiratory or gastrointestinal illness in the week before the onset of the rash [10]; the initial illness may have resolved by the time the child presents with the rash. Dermatologic findings — GCS presents as a sudden symmetric eruption of multiple small papular or papulovesicular lesions. The lesions are monomorphous, flat-topped, pink-brown papules or papulovesicles, 1 to 10 mm in diameter; they may coalesce into plaques (picture 1A-F) [10,60]. The face, buttocks, extensor aspects of forearms and legs, and feet are predominantly affected. Truncal lesions are commonly present, although more transient and fewer in number than acrally distributed lesions. The presence of truncal lesions does not exclude a diagnosis of GCS [61]. The mucosal surfaces and nails are not involved [62,63]. The appearance of lesions at sites of trauma (ie, the Koebner phenomenon) may be seen during the early phase [12,63]. Pruritus usually is of mild to moderate severity; however, the spectrum ranges from absent to severe. Hemorrhagic changes occasionally occur, particularly in areas subject to trauma [10,60,63]. It has been suggested that patients with petechial lesions are more likely to have HBV [64]. However, the cutaneous findings of GCS are not helpful in determining whether GCS is caused by HBV, EBV, or another etiologic agent [9]. (See "Overview of hepatitis B virus infection in children".) Other findings — Affected patients may have concurrent malaise, low-grade fever, or diarrhea [10]. Lymphadenopathy is present in 25 to 35 percent of patients, usually in the cervical, axillary, or inguinal regions [12,65]. The frequency of hepatic involvement is not known [10]. When hepatitis is present, it usually is anicteric (without clinically recognized jaundice) [5,66]. Splenomegaly may occur, but is uncommon [10]. Neither lymphadenopathy nor hepatomegaly is necessary to make a diagnosis of GCS. (See 'Diagnosis' below.) Laboratory findings — There are no laboratory features characteristic of GCS. Patients with GCS may have modest lymphocytosis or lymphopenia [10]. Liver enzymes may be elevated in patients with EBV, CMV, or hepatitis-
  3. 3. associated disease. Skin biopsy may be useful in cases that are clinically confusing. Course — Most children with GCS have an excellent prognosis, although the course may be prolonged [10]. Spontaneous remission of the rash without active intervention is the rule. The rash usually lasts from 10 days to 6 months; however, durations ranging from 5 days to 12 months have been reported [65]. Pruritus may last for weeks. In the initial two to three weeks, new papules and papulovesicles continue to occur, and the areas of involvement expand. The distribution of eruption is most classic in the middle phase of the disease. Near the end of the course, slow resolution of the lesions occurs. There may be mild postinflammatory hyperpigmentation or hypopigmentation. However, scarring and/or pigment changes usually are not permanent. Recurrences are possible, but rare [67]. Lymphadenopathy and hepatomegaly (or hepatosplenomegaly) usually take longer to resolve than the cutaneous lesions [21,63]. Complications — Postinflammatory hypopigmentation or hyperpigmentation occurs frequently in children with darker skin types and can persist for months after resolution of the rash, but eventually resolves [10,68]. Permanent scarring is infrequent, even for children with facial involvement. Other potential complications are related to the underlying etiology. Complications related to EBV infection, including splenic rupture, or lymphoproliferative disorders, are theoretically possible. (See "Clinical manifestations and treatment of Epstein-Barr virus infection", section on 'Complications'.) Children with acute HBV infection may progress to chronic infection [14]. The age at the time of acute infection is the main determinant of the risk of progression: more than 90 percent of infants infected perinatally, and 25 to 50 percent of children infected between one and five years of age, develop chronic HBV infection [69]. The natural history of chronic HBV infection in children is variable, depending upon age, mode of acquisition, and ethnicity. (See "Overview of hepatitis B virus infection in children", section on 'Natural history'.) DIAGNOSIS — Gianotti-Crosti syndrome (GCS) is a clinical diagnosis. Laboratory investigations are not helpful in establishing the diagnosis in young children, but may be necessary to determine the etiology or to exclude other conditions in the differential diagnosis, particularly if the eruption or course is atypical for GCS. (See 'Differential diagnosis' below.) Clinical diagnosis — A diagnosis of GCS is strongly suggested by the sudden onset of a symmetrically distributed papular or papulovesicular eruption in a young child that primarily involves the face, buttocks, and/or extensor surfaces of the extremities and does not have another identifiable cause (picture 1A-F). The presence of extracutaneous signs and symptoms (eg, malaise, fever, diarrhea, lymphadenopathy) is variable. The establishment of diagnostic criteria would help to facilitate the clinical diagnosis of GCS and future studies of the disease. It remains to be determined whether diagnostic criteria proposed by the author and others are the ideal criteria for the diagnosis of this disease [70]. Skin biopsy — Lesional histopathologic changes are nonspecific and cannot confirm the diagnosis. However, lesional skin biopsy may be necessary to exclude other considerations in the differential diagnosis if the rash is atypical (eg, more prominent truncal than acral distribution or lack of spontaneous resolution in six months). (See 'Differential diagnosis' below.) Etiologic diagnosis HBV — Whether HBV serology and liver function tests are indicated for children with a diagnosis of GCS is controversial. On the one hand, HBV is an uncommon cause of GCS in countries where universal hepatitis B vaccination during infancy is routine [10]; HBV also appears to be an uncommon cause of GCS in some developing countries, such as India [71]. On the other hand, GCS may be the only clinical manifestation of acute HBV in infants and young children. The presence of jaundice cannot be used to indicate the need for HBV testing, since the hepatitis associated with GCS is usually anicteric. (See "Overview of hepatitis B virus infection in children", section on 'Acute HBV infection' and 'Other findings' above.) The ethnic origin, HBV carrier status of parents and family members (if known), physical status of the child,
  4. 4. immunization status of the child, and local prevalence of HBV infection are factors to consider in making a decision about testing for HBV. (See "Epidemiology, transmission, and prevention of hepatitis B virus infection".) We suggest the following tests for patients who are at increased risk for hepatitis B virus or who have hepatomegaly [10]: Other viruses — Investigations for EBV such as polymerase chain reaction for EBV DNA in peripheral blood mononuclear cells and serologic testing are generally unnecessary, since they do not affect clinical management. However, identification of an etiologic agent may be indicated in immunocompromised patients and/or patients with close contact with immunocompromised patients or pregnant women [72]. (See 'Other infections' above.) DIFFERENTIAL DIAGNOSIS — The constellation of clinical features in Gianotti-Crosti syndrome (GCS) is usually so characteristic that the diagnosis can be made relatively easily [10]. However, early in the course, during resolution, or in atypical cases, a number of other conditions may warrant consideration. Common conditions in the differential diagnosis of GCS include erythema infectiosum or other viral exanthems, erythema multiforme (early in the course), hand-foot-mouth disease, papular urticaria, scabies, diffuse lichen planus, and cutaneous drug eruptions. Less common, but important, conditions to consider in the differential diagnosis of GCS (because of the different implications for treatment, prognosis, and spread of infection) include papular purpuric gloves and socks syndrome, acrodermatitis enteropathica, Henoch-Schönlein purpura (IgA vasculitis), and Kawasaki disease. Clinical features that may help to differentiate these conditions from GCS include the onset, duration, distribution, and color of the rash; the presence and intensity of pruritus; and the involvement of the mucosa or nails [63]. Liver function tests — Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, and gammaglutamyl transpeptidase (GGT). ● Hepatitis B serology — Hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb), and hepatitis B core antibody (HBcAb). (See "Diagnosis of hepatitis B virus infection".) ● Erythema infectiosum − Erythema infectiosum (EI, also known as "fifth disease") is a common childhood exanthem caused by parvovirus B19. Like GCS, EI begins with nonspecific prodromal illness and acral eruption. However, the rash of EI, which begins on the cheeks (picture 2) and spreads to the extremities (picture 3), is usually macular rather than papular. By the time the rash develops, the child is no longer contagious. (See "Clinical manifestations and pathogenesis of human parvovirus B19 infection", section on 'Erythema infectiosum'.) ● Erythema multiforme − Erythema multiforme (EM) typically affects adolescents and young adults, but 20 percent of cases occur in children [60]. EM is often caused by herpes simplex virus or Mycoplasma infection. Although target lesions are characteristic of EM (picture 4), the lesions may be papular early in the course. Mucosal lesions are present in 25 to 50 percent of children with EM [60] and may help to distinguish it from GCS. ● Hand, foot, and mouth disease − Hand, foot, and mouth disease (HFM) is a common childhood illness that is usually caused by the group A coxsackieviruses. HFM is characterized by fever; oral vesicles on the buccal mucosa and tongue; and peripherally distributed small, tender cutaneous lesions on the hands, feet, buttocks, and (less commonly) genitalia (picture 5A-C). It usually resolves in around seven to ten days. The mucosal lesions and clinical course of HFM distinguish it from GCS. (See "Clinical manifestations and diagnosis of enterovirus and parechovirus infections", section on 'Hand, foot, and mouth syndrome'.) ● Scabies − Scabies is an infestation of the skin by the mite Sarcoptes scabiei that results in an intensely pruritic eruption (picture 6). The degree of pruritus distinguishes scabies from GCS: GCS never itches as severely as virtually every case of scabies does. (See "Scabies".) ● Papular urticaria − Papular urticaria (also known as insect bite-induced hypersensitivity reaction) is defined by chronic or recurrent eruptions of papules, vesicles, target lesions, or wheals caused by hypersensitivity to insect bites (eg, fleas, mosquitoes, bedbugs, mites) in children between 2 and 10 years of age. The lesions are symmetric and usually grouped in crops or clusters on exposed areas; they may take weeks to years to ●
  5. 5. TREATMENT — The treatment of Gianotti-Crosti syndrome (GCS) is supportive, consisting of symptomatic treatment of pruritus and education of the parents regarding the typically benign clinical course. Supportive care Pruritus — Symptomatic relief for pruritus is the only necessary treatment for most children with GCS. Various treatments for pruritus in GCS have been described in observational studies; none has been studied in a randomized controlled trial. In our experience, topical emollients provide adequate relief for most children. We suggest topical calamine lotion for children with pruritus of moderate severity. We suggest a nocturnal dose of a systemic sedating antihistamine (eg, diphenhydramine) for children with severe pruritus. resolve. Management is reviewed separately. (See "Insect bites", section on 'Papular urticaria'.) Lichen planus − Diffuse lichen planus might mimic GCS in adults. Distinguishing features of lichen planus include intense pruritus, pale violet color (picture 7), frequent involvement of the mucosal surfaces, and tendency to occur on the volar surface of the wrists (picture 8) [10]. (See "Lichen planus".) ● Cutaneous drug eruption − Cutaneous drug eruptions begin in dependent areas and generalize, often with associated mucus membrane erythema. Pruritus is the most common symptom. Blood eosinophilia may be present but is not a reliable finding. The most commonly prescribed medications (eg, antibiotics) are implicated most often. The clinical course distinguishes drug eruption from GCS. The onset of drug eruptions is almost always within two weeks of beginning a new drug, and within days of reexposure to a drug to which an individual is sensitized; chemically related compounds can cause cross reactions. Discontinuing the offending drug leads to resolution of the rash. (See "Drug eruptions", section on 'Drug-induced exanthems'.) ● Papular purpuric gloves and socks syndrome − Papular purpuric gloves and socks syndrome (PPGSS) typically occurs in young adults, but may occur in children [60,73,74]. It may be caused by several viruses including parvovirus B19, EBV, and CMV [75,76]. It is characterized by rapidly progressive symmetric painful swelling and erythema of hands and feet, often with a petechial or purpuric component [60]. There is a sharp demarcation at the wrists and ankles (picture 9). Systemic features may include anorexia, fever, and arthralgias [72]. Mucosal lesions, which do not occur in GCS, are a characteristic feature of PPGSS. In contrast to patients with EI, patients with parvovirus B19- related PPGSS may remain viremic, and therefore contagious, during the exanthem [60]. (See "Clinical manifestations and pathogenesis of human parvovirus B19 infection", section on 'Erythema infectiosum'.) ● Acrodermatitis enteropathica − Acrodermatitis enteropathica is a recessively inherited partial defect in intestinal zinc absorption. The clinical features include hyperpigmented skin lesions on the acral surfaces of the upper and the lower extremities, as well as the face and buttocks (picture 10). Acrodermatitis enteropathica is usually associated with other clinical manifestations (eg, alopecia, night blindness, diarrhea, impaired taste, growth retardation, and immune dysfunction) and has a different clinical course from GCS. (See "Zinc deficiency and supplementation in children and adolescents", section on 'Acrodermatitis enteropathica'.) ● Henoch-Schönlein purpura (IgA vasculitis) − Henoch-Schönlein purpura (HSP, IgA vasculitis [IgAV]) is the most common form of systemic vasculitis in children. It is characterized by palpable purpura in patients with neither thrombocytopenia nor coagulopathy (picture 11A-B), arthritis/arthralgia, abdominal pain, and renal disease. The clinical manifestations may develop over the course of days to weeks and may vary in their order of presentation. When present, the noncutaneous manifestations of HSP (IgAV) distinguish it from GCS. (See "Henoch-Schönlein purpura (IgA vasculitis): Clinical manifestations and diagnosis".) ● Kawasaki disease − Kawasaki disease is another common vasculitis of childhood. It is characterized by systemic inflammation manifested by fever, bilateral nonexudative conjunctivitis, erythema of the lips and oral mucosa, rash, extremity changes, and lymphadenopathy. The mucosal lesions of Kawasaki disease help to distinguish it from GCS. (See "Kawasaki disease: Clinical features and diagnosis".) ●
  6. 6. Topical corticosteroids have been tried in GCS but there is no evidence that the disease course is modified by such therapy [36]. Nonetheless, they may be helpful in controlling pruritus. Education — Parents of children with GCS should be provided with information about the etiology, prognosis, complications, and potential spread of the eruption to other children. As a general rule, complications of GCS are rare, the course is benign, and the prognosis is good. (See 'Etiology' above and 'Course' above and 'Control measures' below.) Monitoring — Children with GCS due to HBV infection should be followed-up regularly. In patients who recover from acute hepatitis B infection without progression to chronic infection, normalization of serum aminotransferases usually occurs within one to four months. Persistent elevation of serum ALT for more than six months indicates chronic hepatitis. (See "Clinical manifestations and natural history of hepatitis B virus infection", section on 'Acute hepatitis'.) Children with chronic hepatitis B infection should be referred to a pediatric gastroenterologist or hepatologist. (See 'Referral indications' below.) Control measures — The likelihood that the eruption will spread to other children depends to some extent upon the underlying etiology. However, for most of the causative infections, children are no longer contagious once the rash appears. Exclusion from child-care or school is unnecessary for most children with typical GCS. Children who are hepatitis B surface antigen positive can be admitted to child-care without restrictions provided that they have no behavioral or medical risk factors (eg, aggressive behavior, biting, bleeding disorder) [69]. (See "Overview of hepatitis B virus infection in children", section on 'Counseling and prevention'.) Referral indications — Referral to a pediatric dermatologist may be indicated if the diagnosis is uncertain or the disease course is exceptionally prolonged (eg, longer than six months). Referral to a pediatric gastroenterologist or hepatologist is indicated for children with persistently elevated liver enzymes or chronic hepatitis B infection. (See "Overview of hepatitis B virus infection in children".) SUMMARY AND RECOMMENDATIONS Gianotti-Crosti syndrome (GCS) is a symmetric papular eruption with an acral distribution (cheeks, buttocks, and extensor surfaces of the forearms and legs). (See 'Introduction' above.) ● GCS primarily affects children younger than five years, but can occur in adolescents and adults. (See 'Epidemiology' above.) ● GCS usually occurs in association with a viral illness. Hepatitis B virus (HBV) and Epstein-Barr virus are the most common causes. HBV is an uncommon cause of GCS in the countries where immunization of infants against HBV is routine. (See 'Etiology' above.) ● Although GCS has been reported to occur after the administration of various vaccines, a causal association has not been established. (See 'Vaccines' above.) ● The diagnosis of GCS is clinical. The characteristic rash of GCS consists of symmetric monomorphous, flat- topped, pink-brown papules or papulovesicles, 1 to 10 mm in diameter, that occur on the face, buttocks, feet, and extensor aspects of forearms and legs (picture 1A-F). (See 'Clinical features' above.) ● Noncutaneous findings include malaise, low-grade fever, and diarrhea. Lymphadenopathy is present in 25 to 35 percent of patients, typically in the cervical, axillary, or inguinal regions. Hepatitis, when present, is usually anicteric. (See 'Other findings' above.) ● An etiologic diagnosis for GCS should be pursued in patients with increased risk for hepatitis B virus infection, immunocompromised patients, and patients who have close contact with immunocompromised individuals or pregnant women. (See 'Etiologic diagnosis' above.) ● The constellation of clinical features in GCS is usually characteristic. However, a number of other conditions may warrant consideration early in the course, during resolution, or in atypical cases. These include erythema ●
  7. 7. Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. GIANOTTI F. [Report on a special case of toxic infection characterized by a desquamative erythemato- infiltrative eruption with lenticular foci and a selective localization at the extremities]. Soc Ital Dermatol Sifilogr Sezioni Interprov Soc Ital Dermatol Sifilogr 1955; 96:678. 2. CROSTI A, GIANOTTI F. [Eruptive dermatosis of probable viral origin situated on the acra]. Dermatologica 1957; 115:671. 3. Gianotti F. [Viral anicteric hepatitis in infantile papular acrodermatitis]. Epatologia 1966; 12:171. 4. Gianotti F. [Infantile papular acrodermatitis. Acrodermatitis papulosa and the infantile papulovesicular acrolocalized syndrome]. Hautarzt 1976; 27:467. 5. Gianotti F. Papular acrodermatitis of childhood and other papulo-vesicular acro-located syndromes. Br J Dermatol 1979; 100:49. 6. Claudy AL, Ortonne JP, Trepo C, Bugnon B. [Adult papular acrodermatitis (Gianotti's disease). Report of 3 cases]. Ann Dermatol Venereol 1977; 104:190. 7. Niitsuma H, Ishii M, Ojima T, et al. [A case of acute hepatitis infected with hepatitis B virus during pregnancy and complicated by Gianotti-Crosti syndrome]. Nihon Shokakibyo Gakkai Zasshi 1999; 96:423. 8. Gibbs S, Burrows N. Gianotti-Crosti syndrome in two unrelated adults. Clin Exp Dermatol 2000; 25:594. 9. Caputo R, Gelmetti C, Ermacora E, et al. Gianotti-Crosti syndrome: a retrospective analysis of 308 cases. J Am Acad Dermatol 1992; 26:207. 10. Brandt O, Abeck D, Gianotti R, Burgdorf W. Gianotti-Crosti syndrome. J Am Acad Dermatol 2006; 54:136. 11. Jindal T, Arora VK. Gianotti-crosti syndrome. Indian Pediatr 2000; 37:683. 12. Taïeb A, Plantin P, Du Pasquier P, et al. Gianotti-Crosti syndrome: a study of 26 cases. Br J Dermatol 1986; 115:49. 13. Brown J, Rentiers P. The Gianotti-Crosti syndrome: a distrinctive exanthem. Can Med Assoc J 1969; 100:773. 14. Toda G, Ishimaru Y, Mayumi M, Oda T. Infantile papular acrodermatitis (Gianotti's disease) and intrafamilial occurence of acute hepatitis B with jaundice: age dependency of clinical manifestations of hepatitis B virus infection. J Infect Dis 1978; 138:211. 15. Ishimaru Y, Ishimaru H, Toda G, et al. An epidemic of infantile papular acrodermatitis (Gianotti's disease) in Japan associated with hepatitis-B surface antigen subtype ayw. Lancet 1976; 1:707. 16. Kanzaki S, Kanda S, Terada K, et al. Detection of hepatitis B surface antigen subtype adr in an epidemic of papular acrodermatitis of childhood (Gianotti's disease). Acta Med Okayama 1981; 35:407. 17. Baldari U, Monti A, Righini MG. An epidemic of infantile papular acrodermatitis (Gianotti-Crosti syndrome) due to Epstein-Barr virus. Dermatology 1994; 188:203. 18. 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; 145:843. 19. Demattei C, Zawar B, Lee A, et al. Spatial-temporal case clustering in children with Gianotti-Crosti syndrome. Systematic analysis led to the identification of a mini-epidemic. Eur J Pediat Dermatol 2006; 16:159. infectiosum, erythema multiforme, hand-foot-mouth disease, scabies, papular urticaria, lichen planus, papular purpuric gloves and socks syndrome, acrodermatitis enteropathica, Henoch-Schönlein purpura (IgA vasculitis), and Kawasaki disease. (See 'Differential diagnosis' above.) The treatment of GCS is supportive. We suggest the following supportive measures (Grade 2C):● Topical emollients for mild pruritus• Topical calamine lotion for moderate pruritus• A nighttime dose of sedating antihistamine (eg, diphenhydramine) for severe pruritus• Children with GCS due to HBV infection should be followed-up regularly. (See 'Monitoring' above.)● Referral to a pediatric gastroenterologist or hepatologist is indicated for children with persistently elevated liver enzymes or chronic hepatitis B infection. (See 'Referral indications' above.) ●
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  9. 9. and Bartonella henselae infection]. An Esp Pediatr 2000; 52:299. 49. Baldari U, Cattonar P, Nobile C, et al. Infantile acrodermatitis of Gianotti-Crosti and Lyme borreliosis. Acta Derm Venereol 1996; 76:242. 50. Cambiaghi S, Scarabelli G, Pistritto G, Gelmetti C. Gianotti-Crosti syndrome in an adult after influenza virus vaccination. Dermatology 1995; 191:340. 51. Velangi SS, Tidman MJ. Gianotti-Crosti syndrome after measles, mumps and rubella vaccination. Br J Dermatol 1998; 139:1122. 52. Andiran N, Sentürk GB, Bükülmez G. Combined vaccination by measles and hepatitis B vaccines: a new cause of Gianotti-Crosti syndrome. Dermatology 2002; 204:75. 53. Karakaş M, Durdu M, Tuncer I, Cevlik F. Gianotti-Crosti syndrome in a child following hepatitis B virus vaccination. J Dermatol 2007; 34:117. 54. Erkek E, Senturk GB, Ozkaya O, Bükülmez G. Gianotti-Crosti syndrome preceded by oral polio vaccine and followed by varicella infection. Pediatr Dermatol 2001; 18:516. 55. Kolivras A, André J. Gianotti-Crosti syndrome following hepatitis A vaccination. Pediatr Dermatol 2008; 25:650. 56. Kang NG, Oh CW. Gianotti-Crosti syndrome following Japanese encephalitis vaccination. J Korean Med Sci 2003; 18:459. 57. Milbradt R, Nasemann T. [Entity of the Gianotti-Crosti's syndrome and its relation to hepatitis B infection]. Hautarzt 1975; 26:471. 58. Magyarlaki M, Drobnitsch I, Schneider I. Papular acrodermatitis of childhood (Gianotti-Crosti disease). Pediatr Dermatol 1991; 8:224. 59. Ricci G, Patrizi A, Neri I, et al. Gianotti-Crosti syndrome and allergic background. Acta Derm Venereol 2003; 83:202. 60. Paller AS, Mancini AJ. The exanthematous diseases of childhood. In: Hurwitz Clinical Pediatric Dermatology: A Textbook of Skin Disorders of Childhood and Adolescence, 3rd ed, WB Saunders, Philadelphia 2006. p.423. 61. Chuh AA. Truncal lesions do not exclude a diagnosis of Gianotti-Crosti syndrome. Australas J Dermatol 2003; 44:215. 62. Baleviciené G, Maciuleviciené R, Schwartz RA. Papular acrodermatitis of childhood: the Gianotti-Crosti syndrome. Cutis 2001; 67:291. 63. Tilly JJ, Drolet BA, Esterly NB. Lichenoid eruptions in children. J Am Acad Dermatol 2004; 51:606. 64. Spear KL, Winkelmann RK. Gianotti-Crosti syndrome. A review of ten cases not associated with hepatitis B. Arch Dermatol 1984; 120:891. 65. Chuh A, Lee A, Zawar V. The diagnostic criteria of Gianotti-Crosti syndrome: are they applicable to children in India? Pediatr Dermatol 2004; 21:542. 66. Colombo M, Gerber MA, Vernace SJ, et al. Immune response to hepatitis B virus in children with papular acrodermatitis. Gastroenterology 1977; 73:1103. 67. Patrizi A, Di Lernia V, Neri I, Ricci G. An unusual case of recurrent Gianotti-Crosti syndrome. Pediatr Dermatol 1994; 11:283. 68. Gabrielsen TO, Rajka G, Rustenberg B. [Acrodermatitis papulosa eruptiva infantum as a prodrome in hepatitis B infection]. Z Hautkr 1985; 60:1793. 69. American Academy of Pediatrics. Hepatitis B. In: Red Book: 2009 Report of the Committee on Infectious Diseases, 28th ed, Pickering LK (Ed), American Academy of Pediatrics, Elk Grove Village, IL 2009. p.337. 70. Chuh A, Zawar V, Law M, Sciallis G. Gianotti-Crosti syndrome, pityriasis rosea, asymmetrical periflexural exanthem, unilateral mediothoracic exanthem, eruptive pseudoangiomatosis, and papular-purpuric gloves and socks syndrome: a brief review and arguments for diagnostic criteria. Infect Dis Rep 2012; 4:e12. 71. Zawar V, Chuh A. Gianotti-crosti syndrome in India is not associated with hepatitis B infection. Dermatology 2004; 208:87. 72. Nelson JS, Stone MS. Update on selected viral exanthems. Curr Opin Pediatr 2000; 12:359. 73. Stone MS, Murph JR. Papular-purpuric gloves and socks syndrome: a characteristic viral exanthem. Pediatrics 1993; 92:864. 74. Harms M, Feldmann R, Saurat JH. Papular-purpuric "gloves and socks" syndrome. J Am Acad Dermatol 1990; 23:850. 75. Hsieh MY, Huang PH. The juvenile variant of papular-purpuric gloves and socks syndrome and its association with viral infections. Br J Dermatol 2004; 151:201.
  10. 10. 76. Grilli R, Izquierdo MJ, Fariña MC, et al. Papular-purpuric "gloves and socks" syndrome: polymerase chain reaction demonstration of parvovirus B19 DNA in cutaneous lesions and sera. J Am Acad Dermatol 1999; 41:793. Topic 4040 Version 9.0
  11. 11. GRAPHICS Characteristic eruption of Gianotti-Crosti syndrome (papular acrodermatitis) The characteristic rash of Gianotti-Crosti syndrome consists of symmetric pink- brown papular or papulovesicular lesions that are flat-topped and range from 1 to 10 mm in diameter. The face, buttocks, extensor aspects of forearms and legs, and feet are predominantly affected. Courtesy of Moise L Levy, MD. Graphic 67780 Version 2.0
  12. 12. Gianotti-Crosti syndrome Multiple papules and papulovesicles on the extremities of a child. Reproduced with permission from: www.visualdx.com. Copyright © 2014 Logical Images, Inc. Graphic 95217 Version 1.0
  13. 13. Gianotti-Crosti syndrome Multiple papules and papulovesicles on the face of a child with Gianotti-Crosti syndrome. Reproduced with permission from: www.visualdx.com. Copyright © 2014 Logical Images, Inc. Graphic 95218 Version 1.0
  14. 14. Gianotti-Crosti syndrome Papular and papulovesicular eruption with a predilection for the face and extremities in a child with Gianotti-Crosti syndrome. Reproduced with permission from: www.visualdx.com. Copyright © 2014 Logical Images, Inc. Graphic 95219 Version 1.0
  15. 15. Gianotti-Crosti syndrome Papules and papulovesicles in Gianotti-Crosti syndrome. Reproduced with permission from: www.visualdx.com. Copyright © 2014 Logical Images, Inc. Graphic 95220 Version 1.0
  16. 16. Gianotti-Crosti syndrome Papules and papulovesicles on the buttocks of a child with Gianotti-Crosti syndrome. Reproduced with permission from: www.visualdx.com. Copyright © 2014 Logical Images, Inc. Graphic 95221 Version 1.0
  17. 17. Slapped cheek rash of parvovirus B19 A child with the characteristic malar ("slapped cheek") rash associated with parvovirus B19 (erythema infectiousum, fifth disease). Courtesy of Moise L Levy, MD. Graphic 71737 Version 1.0
  18. 18. Erythema infectiosum Reticulating pattern of an erythematous eruption on the extremities due to parvorvirus B19. Rash is more common in children. The presence of intense erythema (a slapped cheek appearance) on the face is highly characteristic. Courtesy of Lee T Nesbitt, Jr. The Skin and Infection: A Color Atlas and Text, Sanders CV, Nesbitt LT Jr (Eds), Williams & Wilkins, Baltimore, 1995. http://www.lww.com Graphic 75125 Version 5.0
  19. 19. Erythema multiforme Characteristic target lesions of the palm in erythema multiforme begin with a central vesicle. Courtesy of Lee T Nesbitt, Jr. The Skin and Infection: A Color Atlas and Text, Sanders CV, Nesbitt LT Jr (Eds), Williams & Wilkins, Baltimore 1995. http://www.lww.com Graphic 74095 Version 5.0
  20. 20. Hand-foot-and-mouth disease - buccal mucosa Small ulcers are present on the oral mucosa. Reproduced with permission from: www.visualdx.com. Copyright Logical Images, Inc. Graphic 58566 Version 4.0
  21. 21. Hand-foot-and-mouth disease - tongue Multiple small ulcers are present on the tongue. Reproduced with permission from: www.visualdx.com. Copyright Logical Images, Inc. Graphic 71314 Version 3.0
  22. 22. Hand-foot-and-mouth disease - foot Multiple vesicular lesions on an erythematous base are present on the foot. Reproduced with permission from: www.visualdx.com. Copyright Logical Images, Inc. Graphic 53423 Version 4.0
  23. 23. Interdigital lesions of scabies The essential lesion is a small, erythematous, nondescript papule. Courtesy of John T Crissey, MD. Graphic 51161 Version 1.0
  24. 24. Lichen planus Lichen planus is characterized by flat-topped, violaceous papules. Courtesy of Andrew Samel, MD. Graphic 59807 Version 1.0
  25. 25. Lichen planus Note discrete polygonal scaling erythematous papules on the wrist. Courtesy of Beth G Goldstein, MD and Adam O Goldstein, MD. Graphic 50579 Version 1.0
  26. 26. Gloves and socks syndrome secondary to parvovirus B19 infection Papular-purpuric rash on the hands and feet of a patient with acute parvovirus B19 infection. Reproduced with permission from: Anderson DJ, Fangman W, Fowler VG, et al. A returning traveler with fever and rash. Clin Infect Dis 2005; 41:1453. Copyright © 2005 University of Chicago Press. Graphic 51856 Version 2.0
  27. 27. Acrodermatitis enteropathica Acrodermatitis enteropathica in an infant. Moist erythematous plaques are present on the cheeks and buttocks. The buttock lesions are typically symmetric. (Panel A) Reproduced with permission from: www.visualdx.com. Copyright Logical Images, Inc. (Panel B) Courtesy of Robert Sidbury, MD. Graphic 71329 Version 6.0
  28. 28. Skin manifestations of Henoch-Schönlein purpura (IgA vasculitis) This picture shows the classic skin manifestations of Henoch-Schönlein purpura (IgA vasculitis), with clusters of typical ecchymoses, petechiae, and palpable lesions on the legs in a typical distribution (gravity/pressure-dependent areas). IgA: immunoglobulin A. Courtesy of Susan Kim, MD. Graphic 63367 Version 5.0
  29. 29. Skin manifestations of Henoch-Schönlein purpura (IgA vasculitis) Courtesy of Susan Kim, MD. Graphic 72094 Version 4.0
  30. 30. Disclosures: Antonio A T Chuh, MD, FRCP, FRCPCH Nothing to disclose. Moise L Levy, MD Grant/Research/Clinical Trial Support: GSK [psoriasis (calcipotriene)]; Anacor [atopic dermatitis (investigational drug)]. Consultant/Advisory Boards: Galderma [acne (epiduo)]. Patent Holder: Incontinentia pigmenti (NEMO gene mutations). Morven S Edwards, MD Grant/Research/Clinical Trial Support: Novartis Vaccines [Group B Streptococcus]. Consultant/Advisory Boards: Novartis Vaccines [Group B streptococcal vaccine development]. Abena O Ofori, MD Employee of UpToDate, Inc. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy Disclosures

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