Continuing Education Activity

Actinic prurigo, also known as prurigo or hydroa aestivale or Hutchinson summer, is a photodermatosis that is characterized by intensely pruritic papulonodular lesions, primarily but not exclusively affecting sun-exposed areas. The condition is usually seen in prepubescent females and typically in the spring and can persist through winter. In severe cases, excoriations, cheilitis, conjunctival disease, and scarring may develop. The disease has a strong genetic component and is commonly seen in American Indians of North, Central, and South America. This activity reviews the evaluation and management of actinic prurigo and highlights the interprofessional team's role in caring for patients with this condition.

Objectives:

• Describe the pathophysiology of actinic prurigo.
• Explain how to evaluate a patient with suspected actinic prurigo.
• Identify treatment considerations for actinic prurigo.
• Outline how an interprofessional team approach to evaluating, managing, and counseling patients with actinic prurigo will improve outcomes.

Introduction

Actinic prurigo (AP) is a rare form of idiopathic photodermatosis that primarily affects sun-exposed areas of the skin. The affected regions of the skin typically include the face, neck, and dorsal surface of the upper extremities. Sun-protected areas of the skin, such as the buttocks, have also been described. Actinic prurigo typically manifests in the spring as symmetric intensely pruritic papulonodular dermatitis and can persist into the winter months. In severe cases, excoriations, cheilitis, conjunctival disease, and scarring may develop. Actinic prurigo is typically described in prepubescent females but can occur at any age or gender. The disease has a strong genetic component and is more commonly seen in American Indians of North, Central, and South America. The diagnosis is mainly clinical. Disease management begins with sun protection and sunlight avoidance. Treatment involves topical antihistamines, corticosteroids, photochemotherapy (PUVA), as well as systemic therapies for severe cases. Without treatment, this disease course remains chronic and can persist into adulthood.[1][2][3]

Etiology

The etiology remains unclear, but there is a strong genetic component suggesting an autoimmune basis for actinic prurigo. The human leukocyte antigen DR4 allele variant is present in 90% of the cases, especially the DR4 subtype DRB1*0407, which is seen in 60% of cases.[4] Aside from a genetic predisposition, environmental exposure, especially to ultra-violet light, seems to be a major provoking factor. Older studies suggested an increased prevalence of actinic prurigo in populations residing in high-altitude areas with an improvement in the disease severity if the affected individual moved to lower altitudes.[5]

Epidemiology

Actinic prurigo is a rare photodermatosis in the United States. However, actinic prurigo is more common in the American Indian populations of North, Central, and South America. The disease can affect both genders but is more commonly described in female patients. Actinic prurigo can manifest at any age, although the disease typically presents in prepubescent individuals with the mean onset before age 10. Some studies suggest an increased prevalence of actinic prurigo in certain geographic areas with dry, warm climates at an altitude of at least 1000 meters above sea level.[6][7][8]

Pathophysiology

The pathophysiology of actinic prurigo remains largely unclear. Still, evidence suggests the disease process is driven by a delayed type-IV hypersensitive response to ultraviolet A and B (UVA and UVB) radiation in genetically predisposed individuals. Both TH1 and TH2 lymphocytic processes have been implicated in the disease process. Multiple studies note the presence of eosinophils and mast cells in the dermal layers of involved tissue, which suggests a type-IVb (TH2)-driven response specifically. TH2 lymphocytes secrete IL-4, IL-5, and IL-13, which promote IgE and IgG4 production by B cells. These immunoglobulins stimulate eosinophils and mast cells. Individuals with moderate to severe actinic prurigo have been found to have markedly elevated IgE levels, further supporting a type-IVb (TH2) hypersensitive reaction.[9]

Histopathology

Biopsy alone is not sufficient to diagnose actinic prurigo, but histopathology can help aid diagnosis and exclude other disease processes with similar presentations. Skin biopsies will show hyperkeratosis, spongiosis, and acanthosis in the epidermis with lymphocytic perivascular infiltration in the dermis. A lip biopsy will show lymphoid germinal centers in the lamina propria, which can help distinguish actinic prurigo from the polymorphous light eruption. Studies have also described an infiltration of eosinophils and mast cells in the underlying mucosa of affected lesions, which correlate with a delayed type-IVb hypersensitive response.

History and Physical

Patients with actinic prurigo will typically present in early spring as sunlight becomes more prevalent, and individuals spend more time exposing their skin to sunlight. Patients will present with intensely itchy, erythematous papulonodular lesions on predominantly sun-exposed areas of the skin. The face, especially over the zygomatic arches, nasal bridge, lower lip, and conjunctiva, is typically affected. However, lesions may develop anywhere on the neck, trunk, extremities, and even non-sun exposed areas such as the buttocks. Since the lesions are intensely pruritic, excoriations, skin thickening, scarring, and hyper- or hypopigmentation may occur.

Actinic cheilitis has been described as a hallmark finding in patients with actinic prurigo. Individuals may present with actinic cheilitis as a solitary finding or in concurrence with more widespread papulonodular lesions.

Evaluation

Actinic prurigo is typically diagnosed clinically with a detailed history and physical exam. Patients will report the characteristic symptoms of severely pruritic papulonodular erythematous skin lesions that began in the spring or summer months. Patients may or may not report a direct correlation between exposure to sunlight and disease onset. Diagnosis can be aided by skin photo-testing, histologic evaluation, and genetic screening for the HLA DR4 allele variant. Clinicians often perform laboratory testing and immunofluorescence studies to rule out lupus erythematosus and other photosensitive dermatoses.[9]

Treatment / Management

Minor cases of actinic prurigo can be treated with sun-avoidance alone. Proper sun protection includes avoiding sunlight by staying indoors or in shaded areas, wearing protective clothing, sunglasses, and wide-brim hats, and using a broad-spectrum sunscreen. Topical corticosteroids and non-sedating antihistamines will provide relief for acute episodes. The more severe and persistent disease requires treatment with systemic therapies such as antimalarials, tetracyclines, and systemic corticosteroids.

Thalidomide has been described as the hallmark therapy for severe refractory cases of actinic prurigo. Treatment with thalidomide has a major limiting side effect profile, which includes peripheral neuropathy and teratogenicity. Treatment with thalidomide is contraindicated during pregnancy or in individuals trying to become pregnant. Females of childbearing age must use contraception during therapy with thalidomide. Screening for peripheral neuropathy is typically initiated pre-treatment and continued throughout the treatment process.

Alternative immunosuppressive regimens with agents like cyclosporine A have been described as successful as well. Photochemotherapy with psoralen and ultraviolet A (PUVA) has also been shown to successfully manage symptoms and treat skin changes caused by actinic prurigo.[10][11]

Differential Diagnosis

Originally, actinic prurigo was thought to be a hereditary type of polymorphous light eruption (PMLE), more common idiopathic photodermatoses. Genetic testing and the unique clinical presentation of actinic prurigo now support two separate disease entities. The HLA-DR4 allele, specifically the DRB1*0407 subtype, is strongly associated with actinic prurigo and not PMLE. Actinic prurigo also has an earlier age of onset and frequently presents with cheilitis and sometimes conjunctivitis, which is never seen in patients with PMLE. When suspecting actinic prurigo, laboratory tests are also necessary to rule out systemic diseases such as lupus erythematosus or porphyria.

• Polymorphous light eruption
• Systemic lupus erythematosus
• Porphyria

Prognosis

Actinic prurigo is a chronic disease process and can reoccur with repeated sun exposure. Treatment with immunosuppressive agents like thalidomide and cyclosporine A has been shown to be effective at long-term suppression of symptoms. Some adolescents may have spontaneous resolution of symptoms and may not demonstrate disease progression into adulthood.

Complications

Complications of actinic prurigo include:

• Secondary bacterial infections
• Contact dermatitis
• Impetigo

Deterrence and Patient Education

Patients require education on avoiding sun exposure and using adequate protection when outdoors. They also need to be made aware of potential complications, especially with the application of sunscreen on irritated skin. The importance of prevention by avoiding unprotected sun exposure cannot be overstated with this disease. Due to the general prevalence of this disease in a younger age group, repeated counseling is needed to ensure behavior modification. In addition to prevention, patients require education on potential complications of therapy, especially with the use of thalidomide in young females. Ensuring compliance with contraception while on thalidomide is mandatory to avoid its teratogenic side-effects. 

Enhancing Healthcare Team Outcomes

Actinic prurigo does not resolve with time and is marked by frequent relapses. For most patients with actinic prurigo, the outcomes are poor. The condition is associated with frequent relapses, especially during the warmer months of the year. The condition rarely spontaneously resolves and is chronic. The overall quality of life is poor.[12][13] [Level 3] It presents in young patients and without proper treatment and education can lead to significant long-term complications. Hence the role of an interprofessional team to provide coordinated and integrated care is critical.

The specialty-trained nurse can help educate the patient on avoiding unprotected sun exposure, understanding the UV index, and the proper use of commercially available sunscreens. The nurse can help educate the patient on the importance of compliance with treatment and UV protection as even going out during the day can cause a relapse of the condition within minutes. The clinical pharmacist plays a critical role in educating the patient on potential complications and adverse reactions from therapy, especially with high potency treatments such as systemic immunosuppressants. The pharmacist can also assist the clinicians by reviewing medications prescribed and evaluating for any potential drug-drug interactions. The patient must also receive education regarding the proper use of appropriate sunscreens, as most commercially available sunscreens are not recommended. Only mineral sunscreens can be used. An integrated interprofessional care team can help provide multifaceted education required by the patient to ensure optimal outcomes. [Level 5]

Actinic prurigo is labile, and even minor exposure to the sun can lead to an outbreak.[14][15] [Level 3] Communication between clinicians and nurses can help ensure adequate patient education and behavior modification to help achieve disease remission. Communication coupled with coordinated action plans between clinicians, mid-level practitioners (PAs, NPs), nurses, and pharmacists can help ensure safe and adequate treatment of the disease without adverse events, resulting in improved patient outcomes. [Level 5]