AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

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INTRODUCTION

Section 2 of 11  

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Background

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 where skin lesions appear minutes after UV exposure. It is commonly associated with cheilitis and conjunctivitis.^{2, 3}

Pathophysiology

No systemic or local photosensitizer is known in patients with AP, and a hypersensitivity implicating immunoglobulin E (IgE) has not been demonstrated.

AP has many features of a type IV hypersensitivity reaction. Skin lesions associated with AP are infiltrated with T lymphocytes, mostly CD4⁺, and some of the T-cells express activation markers.⁴ AP 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 AP may be the fact that Langerhans cells in persons with AP 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 AP. 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 through Southern blot analysis 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

Although different series are searching for a specific HLA, studies have shown associations with B40 and CW3 alleles in some populations, especially Amerindians.^{9, 10} For instance, in the Chimila Indians from Colombia,¹¹ a high frequency of HLA-Cw4 was found. However, in Cree Indians from Saskatchewan, Canada,¹² 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 AP.¹³ Another series also found HLA-DR4 DRB1*0407 in Colombian patients.¹⁴ Related alleles such as DRB*0407 have been found in British populations,¹⁵ and DRB1*14 has been found in the Inuit Indians of Canada.⁹

English patients with polymorphic light eruption (PMLE)¹⁶ have not shown an association with any HLA, which suggests that HLA-DR4 (DRB1*0407) could be used as a marker to distinguish PMLE from AP. Therefore, the association with HLA in AP but not in PLE suggests that AP represents an immunologically mediated disease with strong genetic determinants for its expression.^{11, 13}

Frequency

United States

AP 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.¹⁷ AP is well known in the United States among Native Americans.^{11, 17, 10, 18}

International

In Mexico, AP represents 1.34% of consultations with pediatric dermatologists and 4% of consultations with general dermatologists.¹ AP is common in Mexico, Central America, and South America, and it is well known in Canada among Native Americans.^{11, 18, 10} AP rarely occurs in Europe and Asia, where PLE (a disease with pathogenetic features similar to AP) is more regularly seen. Isolated cases have been reported in France,¹⁹ Germany,²⁰ Japan,²¹ Singapore,²² Thailand,²³ and Australia.²⁴ However, the prevalence rate of AP in photodermatology clinics around the world varies from 0-5%.²²

Mortality/Morbidity

AP is not associated with mortality.

Race

AP frequently affects 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.^{17, 1}

Age

AP can occur at any age; however, one third of patients are children.¹

CLINICAL

Section 3 of 11  

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• Clinical
• Differentials
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History

AP is clinically different from 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.^{17, 18}
• 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}

Physical

Lesions are erythematous papules, appear singly or in itchy groups, and can form large plaques. 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.

• 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.
• Conjunctival involvement is manifested by hyperemia, brown pigmentation, photophobia, epiphora, and formation of pseudopterygium. This finding is present in 45% of patients.
• Lesions on the lips are manifested by cheilitis, and pruritus, edema, scales, fissures, crusts, and ulceration may be present. This finding occurs in 60-70% of patients.^{2, 3}
• When the skin on the nose is not affected, photosensitized atopic dermatitis is more likely than AP.

Causes

• UV-A and UV-B 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.^{17, 25, 18}
• Some authors are considering a food photosensitizer or a nutritional selective deficiency as a cause; however, no evidence proves this theory.²⁵

DIFFERENTIALS

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Other Problems to be Considered

Chronic actinic dermatitis
Photosensitized atopic dermatitis

WORKUP

Section 5 of 11  

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Lab Studies

• AP 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.

Other Tests

• In a similar way to what happens in PLE, the minimal erythema dose (MED) is decreased in patients with AP.
• Great variation exists in the literature concerning protocols and results of phototesting for photodermatoses, such as PLE and AP. 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 AP, this phototest protocol may be avoided; however, this protocol may be useful for clinical research studies.
• 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 Findings

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.¹⁸ When lesions are experimentally reproduced, histopathologic findings are similar those mentioned.

TREATMENT

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Medical Care

• The cornerstone of pharmacologic treatment is 100 mg/d of thalidomide. Studies have shown that this drug modulates its effect on PA through suppression of tumor necrosis factor-alpha synthesis and modulation of interferon-gamma–producing CD3⁺ cells.²⁶ Thalidomide can be gradually reduced and then reinstituted in cases of relapse. Women in their childbearing years must use contraceptives because of the teratogenic potential of thalidomide. On some occasions, topical steroids or immunosuppressors are indicated, especially in acute exacerbated cases. Once the skin lesions remit, sunscreens should be used.^{27, 28, 1}
• Other medications frequently used with moderate results, because of their anti-inflammatory action, are antimalarials and pentoxyphilline,²⁹ although these drugs are more useful as topical corticosteroid-sparing agents.
• Less favorable results are obtained with antihistaminics, beta-carotenes, and psoralen plus UV-A light.
• If complications (eg, secondary infection, eczema) occur, patients can be treated with oral antibiotics or topical Burow solution.

Activity

Patients affected by AP 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.

MEDICATION

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Treatment is mainly aimed at 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.

Drug Category: Immunosuppressant agents

These agents inhibit key steps responsible for initiating immune activity.

Drug Category: Corticosteroids

These agents have anti-inflammatory properties and cause profound and varied metabolic effects. Corticosteroids modify the body's immune response to diverse stimuli.

Drug Category: Antimalarial agents

These agents are used for their anti-inflammatory and photoprotective effects.

FOLLOW-UP

Section 8 of 11  

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Further Inpatient Care

• The need of inpatient care for patients with AP is extremely infrequent.

Deterrence/Prevention

• 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 (UV-A 315-400 nm). This is especially problematic when people who are affected work close to windows.

Complications

• Common complications are secondary infection and irritant contact dermatitis, mainly due to the use of sunscreens. Impetigo is another typical complication.

Prognosis

• The prognosis is poor, with frequent relapses, especially during spring and summer. AP does not improve with time, contrary to what happens in PLE.

Patient Education

• 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.
• 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 AP is not a dose-dependent disease, and, similar to all immune-mediated hypersensitivity disorders, a minor amount of the offensive agent may provoke outbreaks.

MISCELLANEOUS

Section 9 of 11  

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Medical/Legal Pitfalls

• Failure to regularly supervise patients and to inform them of the possibility of exacerbation during spring and summer months is a pitfall.
• Failure to monitor the use of thalidomide in women, especially those of childbearing age, is a pitfall. Birth control measures must always be implemented.

Special Concerns

• Certifying to proper authorities that patients do not have a contagious or infectious disease is important.
• Women of childbearing age must be supervised monthly if oral drugs are being administrated.

MULTIMEDIA

Section 10 of 11  

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Media file 1:  Itchy plaques mainly on photoexposed areas of the face; these plaques are characteristic of actinic prurigo.
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Media file 2:  Photodistribution of lesions over the body.
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Media file 3:  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.
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Media file 4:  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.
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Media file 5:  One half of patients have bilateral conjunctivitis. Eye protection is needed to avoid disease progression.
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Media file 6:  About 75% of patients have cheilitis, which can take the form of solid lesions or erosions.
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Media file 7:  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.
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Media file 8:  Histologic examination shows acanthosis, mild spongiosis, edema of the lamina propria, and a moderate-to-dense perivascular lymphocytic inflammatory infiltrate.
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Media file 9:  A close-up view shows edema of the lamina propria as well as a lymphocytic inflammatory infiltrate in the dermis.
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Media file 10:  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.
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Media file 11:  Actinic cheilitis resulting from actinic prurigo.
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REFERENCES

Section 11 of 11

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13. Hojyo-Tomoka T, Granados J, Vargas-Alarcon G, Yamamoto-Furusho JK, Vega-Memije E, Cortes-Franco R, et al. Further evidence of the role of HLA-DR4 in the genetic susceptibility to actinic prurigo. J Am Acad Dermatol. Jun 1997;36(6 Pt 1):935-7. [Medline].
14. Surez A, Valbuena MC, Rey M, de Porras Quintana L. Association of HLA subtype DRB10407 in Colombian patients with actinic prurigo. Photodermatol Photoimmunol Photomed. Apr 2006;22(2):55-8. [Medline].
15. Menage H duP , Vaughan RW, Baker CS, Page G, Proby CM, Breathnach SM, et al. HLA-DR4 may determine expression of actinic prurigo in British patients. J Invest Dermatol. Feb 1996;106(2):362-7. [Medline].
16. Grabczynska SA, McGregor JM, Kondeatis E, Vaughan RW, Hawk JL. Actinic prurigo and polymorphic light eruption: common pathogenesis and the importance of HLA-DR4/DRB1*0407. Br J Dermatol. Feb 1999;140(2):232-6. [Medline].
17. Hojyo-Tomoka T, Vega-Memije E, Granados J, Flores O, Cortes-Franco R, Teixeira F, et al. Actinic prurigo: an update. Int J Dermatol. Jun 1995;34(6):380-4. [Medline].
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24. Crouch R, Foley P, Baker C. Actinic prurigo: a retrospective analysis of 21 cases referred to an Australian photobiology clinic. Australas J Dermatol. May 2002;43(2):128-32. [Medline].
25. Magana M. Actinic or solar prurigo. J Am Acad Dermatol. Mar 1997;36(3 Pt 1):504-5. [Medline].
26. Estrada-G I, Garibay-Escobar A, Nunez-Vazquez A, Hojyo-Tomoka T, Vega-Memije E, Cortes-Franco R, et al. Evidence that thalidomide modifies the immune response of patients suffering from actinic prurigo. Int J Dermatol. 2004;43:893-897. [Medline].
27. Londono F. Thalidomide in the treatment of actinic prurigo. Int J Dermatol. Sep-Oct 1973;12(5):326-8. [Medline].
28. Moncada B, Baranda ML, Gonzalez-Amaro R, Urbina R, Loredo CE. Thalidomide--effect on T cell subsets as a possible mechanism of action. Int J Lepr Other Mycobact Dis. Jun 1985;53(2):201-5. [Medline].
29. Torres-Alvarez B, Castanedo-Cazares JP, Moncada B. Pentoxifylline in the treatment of actinic prurigo. A preliminary report of 10 patients. Dermatology. 2004;208(3):198-201. [Medline].
30. Millard TP, Kondeatis E, Cox A, Wilson AG, Grabczynska SA, Carey BS, et al. A candidate gene analysis of three related photosensitivity disorders: cutaneous lupus erythematosus, polymorphic light eruption and actinic prurigo. Br J Dermatol. Aug 2001;145(2):229-36. [Medline].

Article Last Updated: Oct 2, 2006