Actinic prurigo is a photodermatosis that involves the skin, lips, and conjunctival mucosa mainly found in native and admixed populations of Latin America. Usually, it is diagnosed during childhood following extended solar exposure. It has a chronic course where pruriginous papules, nodules, and excoriated plaques on photoexposed skin areas are clearly evident. This morphology usually is accompanied by ocular pseudopterygium and cheilitis.
There is a lack of knowledge regarding its pathophysiology, but current histological and research findings suggest that it is an ongoing type IV hypersensitivity reaction with still unknown other immunopathogenic processes. They include the involvement of HLA-DR4 genes and the infiltration of CD4 lymphocytes, eosinophils, mast cells, and a serum increase of IgE.
Clinical manifestations are usually sufficient to diagnose this condition; however, phototesting can help diagnose undetermined or less severe cases. Although the presence of lymphoid follicles in the mucosa is not a frequent finding, its presence highly suggests a diagnosis of actinic prurigo.
Treatment includes intensive photoprotection, anti-inflammatories, and immunomodulators.
Actinic prurigo (AP) is a chronic, pruritic skin disease caused by an abnormal reaction to sunlight. In 1954, Escalona first described it in Mexico.[1] Lesions appear hours or days following sun exposure, contrary to what happens in solar urticaria, in which skin lesions appear minutes after UV exposure. It is commonly associated with cheilitis and conjunctivitis.[2, 3] See the images below.
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Itchy plaques mainly on photoexposed areas of the face; these plaques are characteristic of actinic prurigo.
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About 75% of patients have cheilitis, which can take the form of solid lesions or erosions.
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One half of patients have bilateral conjunctivitis. Eye protection is needed to avoid disease progression.
No systemic or local photosensitizer is known in patients with actinic prurigo, and a hypersensitivity implicating IgE has not been demonstrated.
Actinic prurigo has many features of a type IV hypersensitivity reaction. Skin lesions associated with actinic prurigo are infiltrated with T lymphocytes, mostly CD4+, and some of the T-cells express activation markers.[4] Actinic prurigo falls in the category of autoimmune diseases because lymphocytes from patients have been proven to be stimulated in a thymidine incorporation assay when confronted with their own UV-irradiated keratinocytes or UV-irradiated epidermal homogenates.[5]
At this point, the antigen that provokes the inflammatory reaction is not clear, but an epidermal protein is believed to be transformed by UV exposure. In the series by Santos-Martinez et al,[6] the presence of transforming growth factor-beta interleukin 13, and interleukin 10 was demonstrated in a non–type-TH1, non–type-TH2 pattern, similar to what has been shown in lesions of psoriasis and in the synovial fluid of rheumatoid arthritis.
Another potentially important finding in the pathogenesis of actinic prurigo may be the fact that Langerhans cells in persons with actinic prurigo show resistance to UV exposure when compared with those in healthy individuals.[7] This same finding has been shown in patients with a similar disease, polymorphous light eruption (PLE). Because these cells are resistant to their demise after UV exposure, they might handle and deliver UV-modified cutaneous antigens to T cells in larger amounts or in a more persistent way; this process could cause or augment the inflammatory phenomenon that is observed in the skin of patients with actinic prurigo. The apoptotic mechanism in these cells may be somewhat altered, facilitating their survival.
On the other hand, the polyclonal cellular immune response found in biopsy samples from Mexican patients may involve an imbalance linked to a specific hyperimmunity, in which the proportion of autoimmune cells is increased and the proportion of other cells is decreased.[8] This response is characterized by infiltration of CD4 lymphocytes, eosinophils, mast cells, and a serum increase of IgE.[9, 10]
Although different series are searching for a specific HLA, studies have shown associations with B40 and CW3 alleles in some populations, especially Amerindians.[11, 12] For instance, in the Chimila Indians from Colombia,[13] a high frequency of HLA-Cw4 was found. However, in Cree Indians from Saskatchewan, Canada,[14] the most common antigens were HLA-A24 and HLA-Cw4.
Other studies have shown a strong association with HLA-DR4. The more precise finding appears to be in the Mexican series, in which HLA-DR4 DRB1*0407 is found in more than 90% of patients with actinic prurigo.[15] Another series also found HLA-DR4 DRB1*0407 in Colombian patients.[16] Related alleles such as DRB*0407 have been found in British populations,[17] and DRB1*14 has been found in the Inuit Indians of Canada.[11]
Additional to the role of HLA-DR4 DRB1*0407 in the genetic susceptibility to develop actinic prurigo, HLA-DRB1*1406 could also be involved, and HLA-DRB1*0802 may possibly have a protective role. The existence of an HLA-B39-DRB1*0407 haplotype suggests a susceptibility region within the sixth human chromosome, at least among Amerindians affected by actinic prurigo.[18]
English patients with PLE[19] have not shown an association with any HLA, which suggests that HLA-DR4 (DRB1*0407) could be used as a marker to distinguish PLE from actinic prurigo. Therefore, the association with HLA in actinic prurigo but not in PLE suggests that actinic prurigo represents an immunologically mediated disease with strong genetic determinants for its expression.[13, 15]
Actinic prurigo occurs in persons of all skin types, but its prevalence in the general population is unknown. It probably represents less than 5% of referrals to photodermatologic clinics.[20] Actinic prurigo is well known in the United States among Native Americans.[12, 13, 20, 21]
International
In Mexico, actinic prurigo represents 1.34% of consultations with pediatric dermatologists and 4% of consultations with general dermatologists.[1] Actinic prurigo is common in Mexico, Central America, and South America, and it is well known in Canada among Native Americans.[12, 13, 21] Actinic prurigo rarely occurs in Europe and Asia, where PLE (a disease with pathogenetic features similar to actinic prurigo) is more regularly seen. Isolated cases have been reported in France,[22] Germany,[23] Japan,[24] Singapore,[25] Thailand,[26] and Australia.[27] However, the prevalence rate of actinic prurigo in photodermatology clinics around the world varies from 0-5%.[25]
Race
Actinic prurigo frequently affects admixture populations (eg, mestizos) of Latin America and American Indians with skin phototypes IV or V.
Sex
In children and adolescents, no differences in prevalence exist between the sexes. However, in adults, women are more frequently affected than men, with a female-to-male ratio of 2:1.[1, 20]
Age
Actinic prurigo can occur at any age; however, one third of patients are children.[1] The impact on quality of life in this population is serious. By means of the children's dermatology life quality index (CDLQI), children with actinic prurigo show high scores and closer to those obtained in children with xeroderma pigmentosum.[28]
The prognosis is poor, with frequent relapses, especially during spring and summer. Actinic prurigo does not improve with time, contrary to what happens in PLE.
Patients should always avoid sun exposure. Daily activities should be performed before 9 am and after 6 pm in tropical areas. In these regions of the world, sunlight can cause lesions to flare even with minor exposures (15 minutes [5 J/cm2UVA]).[29] Therefore, when outdoors, patients must wear dark-colored protective clothing such as pants, long sleeves, high neck, big-brimmed hat, and sunglasses.
Sunscreens should be used with caution, particularly commercial ones composed mainly with chemical filters, as these can worsen irritation on excoriated areas of the exposed skin. Thus, mineral sunscreens are more suitable in these cases. Teaching patients how to apply sunscreen is important. In the early phases of treatment, patients may not apply it properly; they may spread the cream all over their skin without allowing it to fully absorb. Therefore, teach patients to try to reach at least a 2-mg/cm2 dose on the exposed areas. A full UV coverage (290-400 nm) sunscreen is necessary to avoid exacerbations.
The patient should be aware of the UV index. The UV index forecast is usually available on the Internet or through the media in many parts of the world.
Patients should know that actinic prurigo is not a dose-dependent disease, and, similar to all immune-mediated hypersensitivity disorders, a minor amount of the offensive agent may provoke outbreaks.
Actinic prurigo is clinically different from polymorphous light eruption (PLE) and is characterized by an intensely itchy, excoriated papular and nodular eruption that lasts longer than PLE. It can affect any area that is exposed to the sun.
Patients typically report onset or exacerbation in spring and summer, but many patients have clinical symptoms that persist during autumn and winter, particularly in tropical areas.[20, 21]
In 65% of patients, the lips are involved, and, in 10% of patients, the lips are the only sites of involvement. In 45% of patients, the conjunctivae are affected.[2, 3]
Lesions are erythematous papules, appear singly or in itchy groups, and can form large plaques, as shown below. Lesions have serosanguineous crusting, and, because the ailment is chronic, lichenification is eventually seen. Chronic scratching of the face can produce pseudoalopecia of the eyebrows.
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Multiple itchy papules coalescing into plaques on the neck. These lesions are similar to lesions of polymorphous light eruption. Note the excoriations....
The dermatitis is generally disseminated, bilateral, and symmetric. It affects sun-exposed areas, such as the cheeks, the dorsum of the nose, the forehead, the chin, the ear lobes, the V of the neck and the chest, the extensor surfaces of the arms and the forearms, and the dorsum of the hands. In severe and long-standing disease, lesions in covered areas can also be seen, although this finding is infrequent. See the images below.
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One third of patients are children. The nose is frequently affected. This clinical feature is useful in distinguishing it from other entities, such as....
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Photodistribution of lesions over the body. Note the hypopigmented areas of the skin, which are very common after intense scratching in children.
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Lichenified plaques, excoriated nodules, and atrophic scars on the dorsal aspect of hands are frequently seen in children.
Conjunctival involvement, as shown below, is manifested by hyperemia, brown pigmentation, photophobia, epiphora, and formation of pseudopterygium. This finding is present in 45% of patients.
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One half of patients have bilateral conjunctivitis. Eye protection is needed to avoid disease progression.
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Erythematous and very itchy plaques on solar exposure areas of the face and pseudopterygium are commonly observed in actinic prurigo.
Lesions on the lips are manifested by cheilitis (as shown below), and pruritus, edema, scales, fissures, crusts, and ulceration may be present. This finding occurs in 60-70% of patients.[2, 3]
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Actinic cheilitis resulting from actinic prurigo.
When the skin on the nose is not affected, photosensitized atopic dermatitis, as shown below, is more likely than actinic prurigo.
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Young girl with a history of atopic dermatitis and itchy, lichenified plaques on her face for the last 3 months. Atopic dermatitis with photosensitivi....
UVA and UVB light seem to be the main provoking agents. This observation is supported by the fact that most patients live at high altitudes (>1000 m above sea level), and the condition improves in many patients when they move to lower altitudes. However, some patients who are affected already live at sea level.[20, 21, 30]
Some authors are considering a food photosensitizer or a nutritional selective deficiency as a cause; however, no evidence proves this theory.[30]
Common complications are secondary infection and irritant contact dermatitis, mainly due to the use of sunscreens. Impetigo is another typical complication. See the images below.
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Contact dermatitis due to sunscreen in a patient with actinic prurigo.
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Impetiginous area located on the right ear lobe due to intense scratching following an acute relapse.
Actinic prurigo is not a systemic disease, and no anomalous results occur in routine laboratory workup. Laboratory tests are performed to rule out systemic diseases with photosensitivity, such as lupus erythematosus.
Antinuclear antibody levels, anti-Ro and anti-La titers, and porphyrin levels are in the reference range.
Direct immunofluorescence study results are negative. These findings should support the diagnosis on the basis of the clinical picture.
In a similar way to what happens in polymorphous light eruption (PLE), the minimal erythema dose (MED) is decreased in patients with actinic prurigo.
Great variation exists in the literature concerning protocols and results of phototesting for photodermatoses, such as PLE and actinic prurigo. Lesions can be reproduced on healthy skin when it is irradiated with 10-20 times the MED with solar simulated light in 75% of cases. A delayed reading at 4-7 days confirms the presence of induced lesions. Patients in all the series reported from the authors' institution are based on these criteria.[6, 7] Although for routine treatment of patients with actinic prurigo, this phototest protocol may be avoided; however, this protocol may be useful for clinical research studies. See the image below.
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A phototest with UV-B light shows reproduction of lesions on the inner aspect of the arm. The result from the phototest with UV-A light was negative.
Another common phototesting protocol consists of irradiating the volar aspect of the forearm with 0.75 MED for 3-5 consecutive days; the lesions show similar reproduction rates.
Photopatch testing is negative.
A negative phototesting result does not exclude the diagnosis.
Histologic examination shows acanthosis, mild spongiosis, edema of the lamina propria, a moderate-to-dense in a bandlike lymphocytic inflammatory infiltrate, and, occasionally, lymphoid follicles. This latter finding is somewhat more common in the mucosa, the conjunctivae, and the lips (15-20%).[2] Abundant eosinophils are usually present. The affected conjunctivae show epithelial hyperplasia alternating with atrophy. Vacuolization of the basal cell layer and dilated capillaries in the dermis are also noted.[21] When lesions are experimentally reproduced, histopathologic findings are similar those mentioned. See the images below.
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Histologic examination shows acanthosis, mild spongiosis, edema of the lamina propria, and a moderate-to-dense perivascular lymphocytic inflammatory i....
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A close-up view shows edema of the lamina propria as well as a lymphocytic inflammatory infiltrate in the dermis.
The cornerstone of pharmacologic treatment in adult patients is 100-200 mg/d of thalidomide.[21, 34] Children aged 8-15 usually are treated with 12.5-100 mg/d.[1] Studies have shown that this drug modulates its effect on actinic prurigo through suppression of tumor necrosis factor-alpha synthesis and modulation of interferon-gamma–producing CD3+ cells.[35] Thalidomide can be gradually reduced to the minimal dose that can alleviate symptoms (eg, 25-50 mg/wk) and then reinstituted in cases of relapse. Women in their childbearing years must use at least two contraceptive methods, because of the teratogenic potential of thalidomide. On some occasions, topical steroids or immunosuppressors are indicated, especially in acute exacerbations. Once the skin lesions remit, sunscreens should be used.[1, 34, 36]
Other medications frequently used with moderate results, because of their anti-inflammatory action, are antimalarials and pentoxifylline,[37] although these drugs are more useful as topical corticosteroid–sparing agents.
Localized symptoms such as ocular signs of severe limbitis and conjunctivitis have been successfully controlled with sustained topical therapy using 2% cyclosporine A.[31]
Less favorable results are obtained with antihistamines, beta-carotenes, and psoralen plus UVA light.
If complications (eg, secondary infection, eczema) occur, patients can be treated with oral antibiotics or topical Burrow solution.
The need for inpatient care for patients with actinic prurigo is extremely infrequent.
Patients affected by actinic prurigo should not have restrictions in any areas, such as employment and education. However, changing from outdoor to indoor occupations is important if the patient is not improving with treatment.
Long-term precautions are important to avoid worsening of the condition. Therefore, patients should be aware of the sunniest months of the year to reduce outbreaks.
Photoprotection is important. Explaining the nature of the disease to patients is mandatory because they must protect themselves from the sun with sunglasses, hats, umbrellas, long sleeves, high neck shirts, and appropriate clothing on a daily basis. Patients must also avoid sun exposure between 9:00 am and 6:00 pm, even during the winter.
Sunscreens are only an adjunctive treatment. They do not represent a reliable control treatment. Physical sunscreens could be better than chemical sunscreens, especially in cases where excoriation is present and a burning sensation can be elicited.
Outdoor shade is not enough to provide photoprotection. Regularly, trees reduce ultraviolet light only by half.
Staying indoors could also be unsafe because window glasses do not filter long wavelengths (UVA 315-400 nm). This is especially problematic when people who are affected work close to windows.
The primary component of treatment is avoiding sun exposure. However, oral and topical corticosteroids are frequently used for short periods. Thalidomide is used, either alone or with topical corticosteroids, for resistant or multiple-relapse cases.
Clinical Context:
Thalidomide is an immunomodulatory agent that may suppress activated lymphocytes or prevent their activation. It also down-regulates excessive production of tumor necrosis factor-alpha and selected cell-surface adhesion molecules involved in leukocyte migration.
Clinical Context:
Prednisone is an immunosuppressant for the treatment of autoimmune disorders; it may decrease inflammation by reversing increased capillary permeability and suppressing PMN activity. Prednisone stabilizes lysosomal membranes and suppresses lymphocytes.
Clinical Context:
Betamethasone topical is for inflammatory dermatoses responsive to steroids. It decreases inflammation by suppressing the migration of polymorphonuclear leukocytes and reversing capillary permeability. It affects the production of lymphokines and has an inhibitory effect on Langerhans cells.
These agents have anti-inflammatory properties and cause profound and varied metabolic effects. Corticosteroids modify the body's immune response to diverse stimuli.
Clinical Context:
Hydroxychloroquine exerts anti-inflammatory activity by suppressing lymphocyte transformation and may have photoprotective effect. Use in actinic prurigo requires small doses once a day for long periods.
Clinical Context:
Chloroquine phosphate inhibits chemotaxis of eosinophils and locomotion of neutrophils, and it impairs complement-dependent antigen-antibody reactions. It may also have a photoprotective effect.
Clinical Context:
Cyclosporine ophthalmic is used to relieve dry eyes caused by suppressed tear production secondary to ocular inflammation. It is thought to act as a partial immunomodulator. The exact mechanism of action is not known.
Juan Pablo Castanedo-Cazares, MD, MSc, Photobiology Unit Director, Assistant Professor, Department of Dermatology, Hospital Central, Universidad Autonoma de San Luis Potosi, Mexico
Disclosure: Nothing to disclose.
Coauthor(s)
Bertha Torres-Alvarez, MD, Assistant Professor of Dermatology, Hospital Central, Universidad Autonoma de San Luis Potosi
Disclosure: Nothing to disclose.
Specialty Editors
David F Butler, MD, Former Section Chief of Dermatology, Central Texas Veterans Healthcare System; Professor of Dermatology, Texas A&M University College of Medicine; Founding Chair, Department of Dermatology, Scott and White Clinic
Disclosure: Nothing to disclose.
Lester F Libow, MD, Dermatopathologist, South Texas Dermatopathology Laboratory
Disclosure: Nothing to disclose.
Chief Editor
Dirk M Elston, MD, Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine
Disclosure: Nothing to disclose.
Additional Contributors
Craig A Elmets, MD, Professor and Chair, Department of Dermatology, Director, Chemoprevention Program Director, Comprehensive Cancer Center, UAB Skin Diseases Research Center, University of Alabama at Birmingham School of Medicine
Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: University of Alabama at Birmingham; University of Alabama Health Services Foundation<br/>Serve(d) as a speaker or a member of a speakers bureau for: Ferndale Laboratories<br/>Received research grant from: NIH, Veterans Administration, California Grape Assn<br/>Received consulting fee from Astellas for review panel membership; Received salary from Massachusetts Medical Society for employment; Received salary from UpToDate for employment. for: Astellas.
Acknowledgements
The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous authors, Veronica Lepe Murillo, MD, and Benjamin Moncada, MD, to the development and writing of this article.
References
Cazarin-Barrientos J, Roman D, Messina M. Talidomida en ninos con prurigo solar refractario. Actas Dermatol Dermatopatol. 2002. 1:11-5.
Itchy plaques mainly on photoexposed areas of the face; these plaques are characteristic of actinic prurigo.
About 75% of patients have cheilitis, which can take the form of solid lesions or erosions.
One half of patients have bilateral conjunctivitis. Eye protection is needed to avoid disease progression.
Multiple itchy papules coalescing into plaques on the neck. These lesions are similar to lesions of polymorphous light eruption. Note the excoriations induced by scratching.
One third of patients are children. The nose is frequently affected. This clinical feature is useful in distinguishing it from other entities, such as atopic dermatitis.
Photodistribution of lesions over the body. Note the hypopigmented areas of the skin, which are very common after intense scratching in children.
Lichenified plaques, excoriated nodules, and atrophic scars on the dorsal aspect of hands are frequently seen in children.
One half of patients have bilateral conjunctivitis. Eye protection is needed to avoid disease progression.
Erythematous and very itchy plaques on solar exposure areas of the face and pseudopterygium are commonly observed in actinic prurigo.
Actinic cheilitis resulting from actinic prurigo.
Young girl with a history of atopic dermatitis and itchy, lichenified plaques on her face for the last 3 months. Atopic dermatitis with photosensitivity is the main differential diagnosis with actinic prurigo in children.
Contact dermatitis due to sunscreen in a patient with actinic prurigo.
Impetiginous area located on the right ear lobe due to intense scratching following an acute relapse.
A phototest with UV-B light shows reproduction of lesions on the inner aspect of the arm. The result from the phototest with UV-A light was negative.
Histologic examination shows acanthosis, mild spongiosis, edema of the lamina propria, and a moderate-to-dense perivascular lymphocytic inflammatory infiltrate.
A close-up view shows edema of the lamina propria as well as a lymphocytic inflammatory infiltrate in the dermis.
Itchy plaques mainly on photoexposed areas of the face; these plaques are characteristic of actinic prurigo.
Photodistribution of lesions over the body. Note the hypopigmented areas of the skin, which are very common after intense scratching in children.
Multiple itchy papules coalescing into plaques on the neck. These lesions are similar to lesions of polymorphous light eruption. Note the excoriations induced by scratching.
One third of patients are children. The nose is frequently affected. This clinical feature is useful in distinguishing it from other entities, such as atopic dermatitis.
One half of patients have bilateral conjunctivitis. Eye protection is needed to avoid disease progression.
About 75% of patients have cheilitis, which can take the form of solid lesions or erosions.
A phototest with UV-B light shows reproduction of lesions on the inner aspect of the arm. The result from the phototest with UV-A light was negative.
Histologic examination shows acanthosis, mild spongiosis, edema of the lamina propria, and a moderate-to-dense perivascular lymphocytic inflammatory infiltrate.
A close-up view shows edema of the lamina propria as well as a lymphocytic inflammatory infiltrate in the dermis.
Young girl with a history of atopic dermatitis and itchy, lichenified plaques on her face for the last 3 months. Atopic dermatitis with photosensitivity is the main differential diagnosis with actinic prurigo in children.
Actinic cheilitis resulting from actinic prurigo.
Erythematous and very itchy plaques on solar exposure areas of the face and pseudopterygium are commonly observed in actinic prurigo.
Lichenified plaques, excoriated nodules, and atrophic scars on the dorsal aspect of hands are frequently seen in children.
Contact dermatitis due to sunscreen in a patient with actinic prurigo.
Impetiginous area located on the right ear lobe due to intense scratching following an acute relapse.
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