Continuing Education Activity

Papular acrodermatitis of childhood (Gianotti-Crosti syndrome) is a benign, self-limiting rash that occurs in childhood. It exhibits a distinct acral distribution, comprising monomorphic skin-colored to pink-red papules primarily found on the face, buttocks, and extremities' extensor surfaces. The condition is associated with multiple viral illnesses, including Epstein-Barr virus, cytomegalovirus, coxsackievirus, adenovirus, influenza, enteroviruses, echovirus, hepatitis A virus, herpes simplex viruses, human herpesvirus 6, HIV, mumps, parainfluenza virus, parvovirus B19, poxviruses, respiratory syncytial virus, and rotavirus. Additionally, it has been reported after vaccination, including influenza, Calmette-Guerin bacillus, diphtheria-pertussis-tetanus, poliomyelitis, hepatitis B, Japanese encephalitis, and measles vaccines. In the United States, the Epstein-Barr virus is the most commonly reported cause of papular acrodermatitis of childhood; however, in many cases, no infectious trigger is identified.

This activity reviews the evaluation and management of papular acrodermatitis of childhood, as well as its diverse viral associations and potential correlation with vaccinations. Learners will explore the syndrome's evolving etiology and engage with current evidence-based practices for diagnosing it, focusing on the distinguishing features of the rash and its associated systemic symptoms. Additionally, the session highlights the self-resolving nature of the rash and the role of the interprofessional team in treating patients with this condition.

Objectives:

• Evaluate the presentation of a patient with papular acrodermatitis of childhood (Gianotti-Crosti syndrome), distinguishing it from other pediatric rashes like viral exanthems, allergic reactions, or drug eruptions.

• Determine the risk factors for developing Gianotti-Crosti syndrome, including its association with recent viral infections or vaccinations in pediatric patients presenting with characteristic skin lesions.

• Determine the pathophysiology of papular acrodermatitis of childhood to interpret clinical presentations and laboratory findings consistent with the immune-mediated process causing the condition.

• Implement effective collaboration and communication among interprofessional team members to improve outcomes and treatment efficacy for patients affected by papular acrodermatitis of childhood.

Introduction

Papular acrodermatitis of childhood, otherwise known as Gianotti-Crosti syndrome, is a benign rash associated with various viral illnesses.[1] Although historically thought to be solely a manifestation of hepatitis B infection, it has been demonstrated to occur following many viral illnesses and vaccination, which suggests that this is an immunologic response rather than a primary manifestation of infection. [2] Papular acrodermatitis of childhood is characterized by the acute eruption of monomorphic skin-colored to pink-red papules on the face, buttocks, and extensor surfaces of the extremities. The lesions usually spontaneously resolve, and treatment is supportive.[3][4][5]

Etiology

When papular acrodermatitis of childhood was initially described in the 1950s, it was believed to be a manifestation of hepatitis B virus infection. This was in large part due to the prevalence of anicteric hepatitis in these patients. Although this association is still common in hepatitis B endemic areas, it has been rare in the United States since the advent of the hepatitis B vaccine.

Ongoing studies have demonstrated that papular acrodermatitis of childhood can occur following a wide variety of viruses. These viruses include but are not limited to Epstein-Barr virus, cytomegalovirus, coxsackievirus, adenovirus, influenza, enteroviruses, echovirus, hepatitis A virus, herpes simplex viruses, human herpesvirus 6 (HHV-6), HIV, mumps, parainfluenza virus, parvovirus B19, poxviruses, respiratory syncytial virus, coronavirus, and rotavirus.[6][7] 

The condition has been reported after vaccination, including influenza, Calmette-Guerin bacillus, diphtheria-pertussis-tetanus, poliomyelitis, hepatitis B, Japanese encephalitis, yellow fever, and measles vaccines.[8] The Epstein-Barr virus is the most commonly reported cause of papular acrodermatitis of childhood in the United States. However, in many cases, no infectious trigger is identified. The relationship between these potential triggers and the manifestation of papular acrodermatitis of childhood is not well defined but is presumed to be immunologically mediated.[9][10][11][12][13][14]

Epidemiology

Reports of papular acrodermatitis of childhood are most common in children younger than 4 to 6 years of age, consistent with its viral etiology. In children, there is no sex predilection; however, in adulthood, it is slightly more common in female patients. There does not appear to be a genetic or familial predisposition in papular acrodermatitis of childhood. Most cases occur in spring and summer. Papular acrodermatitis of childhood occurs more often in children with atopic diseases, including atopic dermatitis. Although the disease is observed worldwide, the etiological agents exhibit geographic variations.[12][15][16]

Pathophysiology

The precise pathophysiology of papular acrodermatitis is unknown, but it is presumed to be immunologically mediated, given its association with viral infections and vaccination. Its increased prevalence in patients with a history of atopic disease, family history of atopic disease, or elevated immunoglobulin E also supports an immune-mediated pathology.[17] Proposed processes include immune complexes or delayed hypersensitivity reactions, but this has not been well defined to date.

Histopathology

Biopsy samples are not frequently taken from a patient of popular acrodermatitis as it is a benign condition and clinical diagnosis. The primary histological findings involve the dermis, reflecting the underlying immune response and vasculitic processes associated with the condition. Skin biopsies typically show a perivascular lymphocytic infiltrate, indicating an inflammatory reaction centered around blood vessels. This infiltrate consists mainly of lymphocytes. Additionally, there may be evidence of mild spongiosis and exocytosis in the epidermis, suggesting a secondary response to the immune activation.

The inflammatory changes in the blood vessel walls, consistent with a vasculitic component, may include endothelial swelling and perivascular fibrin deposition. Notably, the histopathological features are not pathognomonic for papular acrodermatitis and may overlap with other viral exanthems. Therefore, clinical correlation and consideration of the patient's medical history remain crucial for an accurate diagnosis. Overall, the histopathology of papular acrodermatitis underscores its immunologically mediated nature, emphasizing the transient and self-resolving nature of the skin lesions in this childhood dermatosis.[18]

History and Physical

As its name implies, papular acrodermatitis of childhood clinically manifests as an acute, symmetric eruption of flat-topped papules in an acral distribution. These monomorphic papules most commonly occur on the extensor surfaces of the extremities. Arms are more commonly involved than legs; the face, buttocks, palms, and soles may also be affected. The trunk and scalp are relatively spared, as are the popliteal and antecubital fossae. However, the involvement of any of these areas does not preclude the diagnosis of papular acrodermatitis of childhood.

The lesions are usually pale pink to flesh-colored and 1 to 10 mm in size. They tend to be larger in younger children and smaller in older children and adolescents. Rarely, lesions may be vesicular or hemorrhagic. They are firm and discrete; however, rarely, they can become confluent over pressure points like knees and elbows. Koebner phenomena, the accentuation of lesions at sites of trauma, has also been reported. Mild to moderate pruritus may also be present. 

Symptoms frequently last 2 to 4 weeks. In some cases, new lesions may appear for up to 8 to 11 weeks after the onset of illness. Importantly, the appearance of the rash itself may not help to distinguish the variously associated etiologies of papular acrodermatitis of childhood; however, careful assessment of associated or antecedent symptoms is essential for recognizing possible infectious triggers that may require further evaluation or isolation.

Usually, the rash resolves without any residual effects or scarring. Occasionally, hyperpigmentation or hypopigmentation may persist after the rash resolves.[12][19][20][21] There is no associated mucosal enanthem, but mucocutaneous features of the underlying viral trigger may be present.[21] Fever, lymphadenitis, and other symptoms such as hepatosplenomegaly or pharyngitis may be seen in association with the rash or preceding it. This is consistent with a variety of viral triggers for this entity.

There may also be a history of vaccination preceding the onset of the rash.[19][22] There are no specific laboratory findings seen in papular acrodermatitis of childhood. However, modest lymphocytosis or lymphopenia and elevated liver enzymes may be seen in Epstein-Barr virus, cytomegalovirus, or hepatitis-associated disease.[19]

Evaluation

In general, papular acrodermatitis of childhood is a clinical diagnosis with no laboratory testing indicated unless there are symptoms or physical exam findings, such as hepatomegaly, to suggest an underlying viral illness, such as hepatitis, that may require further management.

Proposed diagnostic criteria include:

• Lesions lasting at least 10 days
• 1- to 10-mm papules or papulovesicular lesions with involvement of 3 of the 4 following sites:
  • Extensor surfaces of the forearms
  • Extensor surfaces of the legs
  • Cheeks
  • Buttocks
• Symmetrical distribution of lesions

Practitioners may need to further evaluate the causative virus in children who are immunocompromised or who reside in endemic areas. If a patient presents with jaundice, hepatomegaly, or generalized lymphadenopathy, evaluation for other viral infections, including hepatitis B or Epstein-Barr virus, may be indicated. Rarely, a skin biopsy may be performed to exclude other conditions in immunocompromised or other high-risk patients. Normally, biopsy findings are nonspecific, with dermal perivascular mononuclear cell infiltrates and capillary endothelial swelling.[23][24]

Treatment / Management

Practitioners should reassure patients that papular acrodermatitis of childhood is a benign and self-limited illness. The majority of cases spontaneously resolve without active intervention. Symptomatic management of itching may be helpful. Patients may use emollients or oral antihistamines. Since infectious agents do not directly cause skin lesions, mild-to-moderate potency topical steroids may be used in patients who fail to achieve relief of itching with emollients and oral antihistamines. However, treatment with topical steroids or oral antihistamines does not shorten the course of illness. Any underlying disorder, such as hepatitis B, that requires further management should be addressed. Lesions resolve without scarring, although postinflammatory pigmentary alteration may persist in some patients.[25]

Differential Diagnosis

The differential diagnosis of papular acrodermatitis of childhood includes other viral exanthems such as erythema infectiosum and hand, foot, and mouth disease, insect bites, scabies, papular urticaria, atopic dermatitis, erythema multiforme, Langerhans cell histiocytosis, lichenoid dermatoses, and immunoglobulin A (IgA) vasculitis.

Prognosis

Papular acrodermatitis of childhood is a benign and self-limited disease that typically persists for 10 days to 6 months. The majority of skin manifestations resolve within 2 weeks to 2 months. Extracutaneous manifestations tend to persist longer than cutaneous lesions. Recurrences are rare.[22][26][27]

Complications

Postinflammatory hypopigmentation or hyperpigmentation may occur in darker skin phenotypes and persist for up to 6 months. Permanent scarring is uncommon. Complications may arise secondary to the underlying viral etiology.[19][28]

Deterrence and Patient Education

It is important to reassure parents about the benign nature of papular acrodermatitis of childhood to avoid unnecessary invasive testing or treatments. Further laboratory work-up is only indicated in high-risk patients, including those who are immunocompromised or from hepatitis B endemic areas. Additional testing is also suggested in those with extracutaneous symptoms suggestive of an underlying viral etiology, such as the Epstein-Barr virus. Excluding children from daycare, school, or social activities is not recommended.

Enhancing Healthcare Team Outcomes

Healthcare workers, including nurse practitioners and clinicians, need to be aware that papular acrodermatitis of childhood is a benign viral-induced skin disorder. It is often confused with other skin infections of childhood. If there is any doubt about the diagnosis, the patient should be referred to a dermatologist. Papular acrodermatitis of childhood is not person-to-person transmissible and does not require isolation beyond standard precautions or restrictions from school or other community activities. However, the associated viral infection may be contagious; thus, isolation may need to be considered based on other symptoms suggestive of infectious disease. The dermatologist and dermatologist nurse specialist should provide a team effort to educate patients and their families about the disease and the necessary precautions.