Photomedicine

Actinic Prurigo (AP)

Snapshot
Other common terms: AP, Hutchinson prurigo
ICD-10 classification: Not defined, L55-59
Prevalence: Unknown. More common in Latin and Indigenous Americans
Causes: Not well understood. Suggested that an immune-mediated response to UV light is responsible.
Symptoms: Extremely itchy skin rash, red and inflamed bumps (papules), thickened patches (plaques) and/or lumps (nodules) following exposure of skin to sunlight.
Treatments/cures: In some cases, actinic prurigo may resolve itself. Topical steroids, emollients, phototherapy, thalidomine and oral immunosuppressants.
Differential diagnosis: Polymorphous light eruption, prurigo nodularis, lupus
Actinic Prurigo (AP) is a rare chronic, idiopathic skin condition, which is characterised by abnormal cutaneous responses to ultraviolet radiation (i.e. photosensitivity). AP is thought to be mediated by an abnormal immune response in the background of genetic predisposition. AP is a rare condition and is usually seen in certain populations of the Americas. Skin lesions can appear hours to days after sun exposure and rarely, non-exposed skin can be affected. AP is also known as Hutchinson prurigo. Although AP is not associated with mortality, it can cause significant morbidity in afflicted individuals.

Incidence

Typically, AP first appears in the sunnier months and patients often report exacerbations in symptoms during summer and spring. Rarely, however, the symptoms are worse during winter and autumn, and immunological tolerance during summer is thought to be responsible for this phenomenon. AP tends to occur equally in both the sexes in children and adolescents. In adults, however, females are twice as frequently affected as males. A positive family history of AP or PLE is present in one-fifth of individuals with APThe prevalence of AP in the general population is not known, but is thought to be less than 5% in the above-mentioned populations. In Europe and the Asia-Pacific, where a pathogenetically similar but clinically distinct disease known as polymorphic light eruption (PLE) is more common, rare cases of AP have been reported.AP usually begins in childhood. In some individuals, it may resolve before adulthood. In others, however, it is chronic and tends to recur persistently. Rarely, the disease may arise in adults and the clinical course in these cases is usually chronic.Actinic prurigo can affect the skin of all races, although it is more commonly observed in Latin-American Mestizo and Native American populations. Sporadic cases have been reported in the United Kingdom, the United States, Europe, Australia and Japan.

Causes

Sun-exposure, i.e. exposure to ultraviolet A and B radiation, is the predominant cause of actinic prurigo, yet the reason for the abnormal response to sun exposure is not fully understood. AP is believed to be delayed-type hypersensitivity reaction to antigens exposed or changed following exposure of the skin to ultraviolet radiation. The exact nature of these antigens is not known. It is also believed that genetic predilection may play a role in the pathogenesis of AP, with up to 90% of patients with AP showing various human leukocyte antigen (HLA) variants. In particular, HLA type DRB1*0401 and HLA type DRB1*0407 have been associated with AP.

Cellular involvement in actinic prurigo

Langerhans cells (LC) are believed to play a role in the pathogenesis of AP. LC are antigen presenting cells that are involved in the induction of cell-mediated immune responses to antigens located in the skin. LCs in patients with AP show a reduced susceptibility to ultraviolet radiation. UV-resistant LCs in patients with AP activate immune responses via putative antigens. Because of the presence of UV-resistant LCs, the putative antigens may be delivered to lymphocytes in large amounts or in a chronic fashion, leading to inflammation seen in AP. Thus, a combination of altered expression of adhesion molecules and UV-resistant LCs may be involved in the pathogenesis of AP. Further studies are required to elucidate the identity of these putative antigens and to gain a better understanding of the disease process.Expression of cell adhesion and activation molecules has been shown to be increased in AP. This suggests that lymphocytes in skin lesions of AP are, therefore, activated and may play a role in the damage observed in this condition. An increased adhesiveness of lymphocytes, as a result of increased expression of adhesion molecules, enables them to migrate through the endothelium and extracellular matrix. Similarly, the activation molecules can act on their respective receptors to induce lymphocyte proliferation and activation. Ultraviolet radiation is thought to activate adhesion molecules, such as ICAM-1, via activated lymphocyte infiltrates in keratinocytes, leading to inflammation that is observed in AP.Skin lesions in AP have been shown to be infiltrated by CD4+ T cells. An abnormal immune sensitization occurs against epidermal antigens in AP. AP can be considered as an autoimmune disease, because lymphocyte activation occurs in response to patient’s own ultraviolet-irradiated keratinocytes.

Symptoms

The symptoms of actinic prurigo include:
  • Extremely itchy (pruritic) skin rash;
  • Red and inflamed bumps (papules);
  • Thickened patches (plaques); and/or
  • Lumps (nodules)
The symptoms of AP are often described as similar to those seen in atopic dermatitis (eczema).
In addition to the symptoms listed above, skin ulcerations, crusting and scaling can occur.
Although areas exposed to the sun, such as the cheeks, nose and hands, are more commonly affected, non-exposed areas can rarely occur in severe AP. Pseudo-alopecia of the eyebrows can occur if the face is constantly scratched. In severe cases, permanent mild scarring and hypopigmented lesions may develop.
In about 65% of the patients affected with AP, the lips are affected. Inflammation of the lip (cheilitis) and pruritis are commonly observed. Other features such as oedema, crusting, ulceration and scales may be present. Interestingly, in 10% of the patients with AP, the lips are the only sites that are affected.
In about 45% of AP patients conjunctivae of the eyes are affected. Hyperaemia, brown pigmentation, photophobia, epiphora (excess production of tears), and formation of pseudopterygium (where the conjunctiva adheres to the cornea) are potential symptoms associated with the involvement of conjunctivae.

Diagnosis

Observational diagnosis of actinic prurigo

Nevertheless, blood tests may be performed to rule out systemic diseases with involvement of the skin. The presence of HLA type DRB1*0401, or DRB1*0407 in genetic testing is suggestive of AP. Histological studies may be helpful. As a skin disease that does not involve internal organs, no blood tests are available to diagnose AP.Histologically, mild acanthosis, exocytosis, and spongiosis of the epidermis are observed. Lymphocyte infiltration and lymphoid follicles may be present. Eosinophils are often present. With the conjunctival histology, the epithelium appears thinned and atrophied. The basal cells are vacuolised with lymphocytic infiltration in the sub-mucosal follicles. Eosinophils are conjunctival pigmentation are common findings. The presence of lymphoid follicles in the mucosal and conjunctival laminae is the most characteristic pathological finding in AP.AP is diagnosed based on clinical assessment and the pathological study of the mucosae of the lips, conjunctivae, or the skin.

Phototesting and actinic prurigo

Other laboratory tests are used to rule out other systemic diseases with a photosensitivity component, rather than to diagnose AP. The presence of anti-nuclear antibodies and extractable nuclear antibodies should be undertaken to rule out lupus. The highly contagious Scabies should always be ruled out prior to diagnosing AP. When the skin on the nose is not affected, the condition is more likely to be photosensitive atopic dermatitis than AP. Polymorphic light eruption and prurigo nodularis are other morphologically similar diseases that should be excluded during the diagnosis of AP.Phototesting may help with the diagnosis, but is non-specific and does not rule out other photosensitive disorders. The minimal erythema dose, the minimum dose of narrow-band ultraviolet (UVB) radiation that is required to produce redness 24 hours after exposure, is reduced in patients with AP. It should be noted that a negative cutaneous phototesting does not exclude the diagnosis of AP.

Treatments

Actinic prurigo is seldom cured and so preventative measures are important in managing actinic prurigo. The disease may resolve before adulthood in some individuals. In others, however, it is persistent and seasonal outbreaks during summer and spring may occur. Rarely, AP may arise in adulthood and persist throughout life. Treatment is aimed at prevention and controlling symptoms. Avoiding UV exposure and appropriate sun protection measures may be beneficial. Prophylactic phototherapy may be helpful in some cases. Other treatment options include:
  • Emollients to relieve itching.
  • Topical steroids as anti-inflammatories. Oral steroids may be necessary in more severe disease. Hypersensitivity and infections are possible side-effects of steroid use.
  • Anti-malarial drugs, such as chloroquine, may be effective in some cases. These drugs have anti-inflammatory and photoprotective effects. Also, topical calcineurin inhibitors, such as tacrolimus, may be used to treat relatively mild AP
  • Oral thalidomide, an immune suppressant, is usually effective in treating more resistant AP in all age groups. Adverse effects include drowsiness, headache and weight gain. Nerve conduction studies should be performed regularly to assess for peripheral neuropathy, another side-effect of thalidomine treatment. Thalidomide is teratogenic and pregnancy must be avoided.
  • Oral immunosuppressants, such as azathioprine or cyclosporine.
  • Prophylactic phototherapy with UVB or PVB in spring, when the symptoms usually worsen, may be effective in some patients.

Prevention

Actinic prurigo is an idiopathic disease – i.e. the precise cause(s) of AP are unknown. As sun exposure is the primary trigger of the disease, prudent steps must be taken to reduce or avoid exposure to the sun. The use of sunglasses, wearing appropriate clothing, and the appropriate use of sunscreen may be beneficial. In case of excoriations, sunscreen should be used cautiously. Patients should be taught about the appropriate application of sunscreens. Patients should also be made aware that even minor exposure to ultraviolet radiation may result in outbreaks or exacerbations of symptoms. Annual prophylactic phototherapy may be of benefit in some patients.

Prognosis

Actinic prurigo usually arises in childhood, and persists into adulthood. In some individuals, AP can improve or resolve before adulthood. Rarely, it may arise in adulthood, and persist chronically. Although not a fatal disease, AP can lead to significant morbidity, with exacerbations during the sunnier months. Secondary infections and impetigo are potential complications. Irritant contact dermatitis can manifest with inappropriate use of sunscreens.

References

  • dermnetnz.org (2008) Actinic Prurigo. [Online]. Available online [Accessed 10/12/2008].
  • emedicine.com (2008) Actinic Prurigo. [Online]. Available online [Accessed 10/12/2008].
  • Hawk, J L & Ferguson, J (2008). ‘Chapter 90. Abnormal Responses to Ultraviolet Radiation: Idiopathic, Probably Immunologic, and Photo-Exacerbated’. In Wolff, K, Goldsmith, L A, Katz, S I, Gilchrest, B, Paller, A S & Leffell, D J: Fitzpatrick’s Dermatology in General Medicine, 7th Edition. Available online [Accessed 10/12/2008].
  • McGregor, J M, Grabczynska, S, Vaughan, R, Hawk, J L, Lewis, C L (2000). ‘Genetic Modeling of Abnormal Photosensitivity in Families with Polymorphic Light Eruption and Actinic Prurigo’. The Journal of Investigative Dermatology, Vol 115, pp. 471-476.
  • Ortiz-Castillo, J V, Boto-de Los-Bueis, A, de Lucas-Laguna, R, Pastor-Nieto, B, Pelaez-Restrepo, N, & Fonseca-Sandomingo, A (2006). ‘Topical cyclosporine in the treatment of ocular actinic prurigo’. Archivos de la Sociedad Espanola de Oftalmologia, Vol 81, pp. 661-664.
  • Torres-Alvarez, B, Baradana, L, Fuentes, C, Delgado, C, Santos-Martinez, L, Portales-Perez, D, Moncada, B & Gonzalez-Amaro, R (1998). ‘An immunohistochemical study of UV-induced skin lesions in actinic prurigo: Resistance of Langerhans cells to UV light’. European Journal of Dermatology, Vol 8(1), pp. 24-28.

Associations and online resources

Snapshot
Other common terms: VZV, chickenpox (varicella), shingles (herpes zoster)
ICD-10 classification: B01, B02
Prevalence: Very common with up to 1,500:100,000 reported.
Causes: Airborne transmission
Symptoms: Incubation period (2 weeks): fever, general malaise, abdominal pain, headache. Followed by skin lesions; a rash which eventually crust and heal.
Treatments/cures: No known cure. Treatment is generally avoided except in extreme cases. Relief of rash is mainstay of treatment.
Skin lesion (chickenpox) from VZV infection
Skin lesion (chickenpox) from VZV infection
The varicella zoster virus (VZV) is the cause of chickenpox (varicella), and shingles (herpes zoster). Varicella occurs as the primary infection, more commonly in childhood but can occur in adulthood. Herpes zoster is a result of reactivation of latent infection of nerve ganglia. The rate of infection is currently trending downwards with the introduction of a varicella zoster virus vaccine. Prognosis of the primary infection is generally good except in some instances. Patients who acquire the infection in adulthood have a higher mortality risk. Patients who are immunocompromised are also at risk. A developing foetus may acquire congenital problems if a primary infection occurs during pregnancy. Neonatal infections may also result in chronic complications.

Incidence

VZV infection was quite common prior to the introduction of the vaccine in 1995. Incidence rates of 1,500-1,600 per 100,000 have been reported in the USA. Since the introduction of the vaccine, reported incidence rates have markedly decreased. Where varicella was the principal problem, the hospitalization rate was 2.3-6.3: 100,000. The case-fatality rate was reported as 0.8 per 100,000 in children aged 1-4 years, and 21.3 per 100,000 in adults aged more than 20 years. A separate series reports a mortality rate of 9.22 per 100,000 consultations related to varicella. However, adults accounted for 81% of deaths despite representing only 19% of consultations. The majority of primary infections occur in children. While adults are less likely to acquire varicella, adults who do acquire the infection have a higher mortality rate. Current post-vaccine surveillance data is available from the Department of Health and Ageing (with the exception of the Australian Capital Territory, Victoria, and New South Wales). A total of 1,514 cases of varicella were reported in 2006. The highest incidence rates of varicella were 93.4:100,000 in the Northern Territory, and 48.9:100,000 in South Australia (Department of Health and Ageing, 2006). The highest incidence occurred in children aged 0-4 years (120:100,000). The overall Australian incidence was not available. A total of 1,052 cases of herpes zoster were reported in the same year. The overall rate was 5.2:100,000. Similarly, the highest rates were in South Australia (40.2: 100,000) and Northern Territory (38.7:100,000) (Department of Health and Ageing, 2006). Surveillance data prior to the introduction of the varicella vaccine in Australia is unavailable.

Causes

Skin lesion (chickenpox) from VZV infection
Skin lesion (chickenpox) from VZV infection
The main route of VZV infection is airborne transmission. In addition, direct contact may also transmit the virus. Unfortunately, even without the characteristic skin problems, a patient can still produce and spread the virus. The prodrome of varicella (non-specific symptoms such as fever and general malaise) gives little clue as to the proceeding illness. As such, preventing transmission can be difficult. Herpes zoster is a reactivation of latent VZV infection. The risk of reactivation increases with age. In addition, reactivation is associated with immune compromise. HIV infection, bone marrow disease, or immune-suppressing medications may all predispose to reactivation and severe complications. However, reactivation may also occur randomly with no discernible cause. VZV belongs to the family of herpesviruses and specifically the alphaherpesviruses. Their genome consists of double-stranded deoxyribonucleic acid (DNA) within an icosahedral nucleocapsid. The outermost layer is a lipid membrane. This confers a susceptibility to environmental factors such as heat, and detergents or solvents. Transmission between hosts usually occurs via inhalation of aerosols containing varicella zoster virus. Transmission via direct contact is less frequent but may also occur. VZV is hypothesized to be spread via leukocytes in the lymphatic system. People with obvious varicella are advised to remain at home to minimize spread of the virus. It is advised that patients not attend their usual occupation until a crust has formed over the initial lesions. Virus shedding is minimized once this has occurred. The virions first spread to local lymph nodes, where a primary viraemia occurs. The virus then infects other leukocytes and hepatocytes before producing a secondary viraemia to infect mucous membranes and skin epithelia. The time up to this point is considered to be the incubation period, which lasts approximately 14 days. Infection of the skin epithelia results in the characteristic lesions seen in varicella. Transmission of the virus is actually possible before the onset of these lesions. Following this, the virus forms a latent infection within nerve ganglia. Viral replication occurs within host cells. The virus binds to proteins on the surface of cells which induces its entry into host cells; the receptors used by VZV to facilitate cellular entry have not been identified. The host’s cellular mechanisms are then utilized to reproduce new viruses. Both humoral and cellular immunity is important in containing the infection. In immunocompromised patients, severe complications of VZV are more likely to occur

Symptoms

Skin lesion (shingles) from VZV infection
Skin lesion (shingles) from VZV infection
The incubation period of VZV is approximately 14 days, during which the patient may experience a number of non-specific symptoms such as:
  • Fever
  • General malaise
  • Abdominal pain
  • Headache
Following these symptoms, the characteristic skin lesions evolve, beginning with a macular rash, progressing to vesicles, which rupture and form hard crusts that eventually heal. Ulcerated lesions are often painful. These lesions typically develop around the entire body, but are concentrated centrally on the trunk. Lymphadenopathy is also seen. These lesions occur throughout the body, but are more concentrated around the trunk than the limbs. While this pattern is suggestive of varicella, abnormal distributions may occur. Complications of varicella include secondary bacterial infection, transient hepatitis, respiratory and neurological involvement, haemorrhagic complications, and nephritis. Congenital varicella syndrome may also occur. Patients with neurological complications may have cerebral signs, cerebellar signs, or a combination of both. Signs of meningitis such as photophobia, headache, and neck stiffness may also occur. Congenital varicella syndrome is characterized by microcephaly, limb hypoplasia, cutaneous defects, hypopigmented skin, and autonomic neuropathy. Herpes zoster: The skin lesions that occur in herpes zoster are similar to those in varicella. However, because reactivation of the virus typically occurs from one particular ganglion, the lesions occur in the distribution of a specific dermatome. The typical prodromal symptoms of fever and general tiredness may or may not be evident. However, pain in the same distribution as the skin lesions is likely, and may last even after the lesions have healed. Complications of herpes zoster include postherpetic neuralgia, and neurological involvement. Approximately 9% of patient with herpes zoster develop postherpetic neuralgia, which is characterised by pain persisting for long periods of time despite resolution of skin lesions. Only 0.2-0.5% of patients have neurological involvement; the majority recover without permanent impairment.

Treatments

Treatment for VZV infection is generally not required. However, guanosine analogues (such as acyclovir) are available. These are generally used in certain cases such as in immunocompromised patients, or in patients in whom severe infection or complications have developed. Passive immunization is also available. Immunoglobulin (antibodies) against VZV is administered to patients who are at risk of developing serious complications. This immunoglobulin is pre-formed and thus works even for immunocompromised patients. Treatment of immunocompromised adults with varicella with acyclovir does not improve skin healing rates, but can significantly reduced visceral complications. Acyclovir 10mg/kg for 7-10 days has been recommended. Administration via intravenous route over eight hours is preferred. The mainstay of treatment for VZV infection is prevention. A live attenuated vaccine was introduced in 1995. This vaccine has markedly reduced the rate of varicella. In addition, complication and mortality rates have also decreased. A similar vaccine is also available to prevent herpes zoster. Treatment is required for all patients with herpes zoster. The following regimens are recommended by Therapeutic Guidelines Ltd. (2004):
Drug Dose (oral) Frequency (Duration of 7 days)
Acyclovir 20mg/kg for children Five times daily
Acyclovir 800mg for adults Five times daily
Famiciclovir 250mg 8 hourly
Valacylovir 1000mg 8 hourly

Prevention

Individuals at high risk (e.g. pregnant women, immunocompromised individuals) should avoid patients with active disease. Children who acquired varicella should stay at home until the skin lesions have healed or crusted.

Vaccination

Active immunization:

Skin lesion (chickenpox) from VZV infection
Skin lesion (chickenpox) from VZV infection
A live-attenuated vaccine for the prevention of varicella is currently available. This vaccine works by mimicking a viral infection; the strain used is not as virulent, and does do not cause disease readily. The body is still able to recognize the foreign components of the virus, and develop an immune response and long term immunity against it. In Australia, it is recommended that newborns receive the vaccine between the ages of 12-15 months, followed by a second immunization at 4-6 years. Older children and adults who have not received the vaccine and have not previously been infected are advised to obtain the vaccine, unless there is a specific contraindication. The vaccine is available for free in Australia for those who fit the eligibility criteria (Department of Health and Ageing, 2008):
  • All children born on or after 1 May 2004 at 18 months of age
  • A one year cohort of children aged between 10 and 13 years who have not received varicella vaccine and who have not had the disease – commencement date and specific age group varies between States and Territories
The vaccine has been reported by Seward et al. (2002) to reduce mortality rates in America from 2.7-4.2:100,000 to 0.6-1.5:100,000. Other authors also support the cost-effectives of providing vaccination during infancy (Scuffham et al., 1999). Contraindications to the varicella vaccine include (Zimmerman, 1996):
  • Immuno-compromised individuals – Patients with HIV infection – Patients undergoing immunosuppressive therapy (such as high dose corticosteroid) – Patients with congenital immune deficiencies
  • Individuals with a history of anaphylaxis
  • Pregnancy
  • Untreated tuberculosis
A similar vaccine is also available for prevention of herpes zoster (reactivation of latent VZV). This vaccine is similar to the varicella vaccine, but has a higher dose of live virus. It has been shown to reduce reactivation of latent VZV (Holcomb & Weinberg, 2006). Where reactivation occurs, the rate of post-herpetic neuralgia was reduced. In addition to the contraindications listed above for the varicella vaccine, the herpes zoster vaccine should not be given to children as it has a higher viral load.

Passive immunization:

Administration of intravenous immunoglobulin against VZV is sometimes used for immunocompromised patients who have been exposed to VZV. Active immunization (i.e. live attenuated vaccine) is contraindicated in these cases as the patient would be unable to mount an adequate immune response, and may in fact develop an infection instead.

Prognosis

The mortality and morbidity rates of VZV infection have been significantly reduced since the introduction of the live attenuated vaccine in 1995. However, significant complications may still occur. Primary infection in adulthood holds a poorer prognosis than childhood infection. Higher mortality rates have been reported (Rawson, 2001). Data on the rate of severe complications is limited. A German study estimated severe complications to occur at 8.5 per 100,000 cases (Ziebold et al., 2001). Of 119 cases in the study, neurologic complications occurred in 73 children (61.3%), infectious complications occurred in 46 children (38.6%). Only eight patients reported long term complications; six due to infectious causes, and two due to neurologic complications (Ziebold et al., 2001). Immunocompromised patients have much poorer prognosis. The rate of developing congenital varicella syndrome is low. In a cohort of 362 women (15 with herpes zoster, and 347 with primary VZV infection), only one case of definite congenital varicella and two foetal deaths were documented (Harger et al., 2002). The incidence of herpes zoster increases with age. Incidence ranges from 4.2 per 1,000 person-years (age group 50-59) to 10.7 per 1,000 person-years (age group ?80) (Yawn et al., 2007). The most common complication of herpes zoster is associated pain and post-herpetic neuralgia. On average, 18% of patients may experience pain for more than 30 days. Again, this proportion increases with age Yawn et al., 2007). Other complications include ocular complications (4%), and neurological complications (3%). Less than 1% develop disseminated infection (Yawn et al., 2007).

References

  • Arvin, A M (1996). ‘Varicella-zoster virus’. Clinical microbiology reviews, 9(3), 361-381. Available online.[Accessed on 9/12/2008].
  • Balfour, H H Jr, McMonigal, K A & Bean, B (1983). ‘Acyclovir therapy of varicella-zoster virus infections in immunocompromised patients’. Journal of Antimicrobial Chemotherapy, 12(B), 169-179. Abstract available online [Accessed on 9/12/2008].
  • Department of Health and Ageing (2006). Australia’s notifiable diseases status, 2006: Annual report of the National Notifiable Diseases Surveillance System – Results: Vaccine preventable diseases. Communicable Diseases Intelligence, 3(2). Available online. [Accessed on 9/12/2008].
  • Department of Health and Ageing (2008). Varicella (chickenpox) vaccination program – common questions & answers for providers [Online]. [Accessed on 9/12/2008, no longer online].
  • Harger, J H, et al. (2002). ‘Frequency of congenital varicella syndrome in a prospective cohort of 347 pregnant women.’ Obstetrics & Gynecology, 100, 260-265. Available online. [Accessed on 9/12/2008. Link no longer active.].
  • Holcomb, K & Weinberg, J M (2006). ‘A novel vaccine (Zostavax) to prevent herpes zoster and postherpetic neuralgia’. Journal of Drugs in Dermatology, 5(9), 863-866. Abstract available online. [Accessed on 10/12/2008].
  • Marin, M, Meissner, H C & Seward, J F (2008). ‘Varicella prevention in the United States: A review of successes and challenges’. Pediatrics, 122(3), 744-751. Available online. [Accessed on 9/12/2008].
  • Rawson, H, Crampin, A & Noah, N (2001). ‘Deaths from chickenpox in England and Wales 1995-7: Analysis of routine mortality data.’ British Medical Journal, 323, 1091-1093. Abstract available online. [Accessed on 9/11/2008].
  • Scuffham, P A, Lowin, A V & Burgess, M A (1999). ‘The cost-effectiveness of varicella vaccine programs for Australia’. Vaccine, 18(5-6), 407-415. Abstract available online [Accessed on 9/12/2008].
  • Seward, J F, Watson, B M, Peterson, C L, Mascola, L, Pelosi, J W & Zhang, J X (2002). ‘Varicella disease after introduction of varicella vaccine in the United States, 1995-2000’. Journal of the American Medical Association, 287(5), 606-611. Abstract available online. [Accessed on 9/11/2008].
  • Spear, P G & Straus, S E (2007). ‘Alphaherpesviruses: Herpex simple virus and varicella-zoster virus’. Schaecter’s Mechanisms of Microbial Disease. 406-414. Lippincott Williams & Wilkins.
  • Therapeutic Guidelines Ltd. (2004). Infectious diseases. Therapeutic Guidelines: Dermatology 2nd Edition. 201-220. Therapeutic Guidelines Limited.
  • Yawn, B P, Saddier, P, Wollan, P C, StSauver, J L, Kurland, M J & Sy, L S (2007). ‘A population-based study of the incidence and complication rates of herpes zoster before zoster vaccine introduction’. Mayo Clinic Proceedings, 82, 1341-1349. [Accessed on 10/12/2008]
  • Ziebold, C, von Kries, R, Lang, R, Weigl, J & Schmitt, H J (2001). ‘Severe complications of varicella in previously healthy children in Germany: A 1-year survey’. Pediatrics, 108(5), e79. Available online. [Accessed on 10/12/2008]
  • Zimmerman, R K (1996). ‘Varicella vaccine: Rationale and indications for use’. American Family Physician [Online]. [Accessed on 10/12/2008, no longer online].

Online resources

Better Health Channel, Victoria:

Online associations

Snapshot

Other common terms:AP, Hutchinson prurigo
ICD-10 classification: Not defined, L55-59
Prevalence: Unknown. More common in Latin and Indigenous Americans
Causes: Not well understood. Suggested that an immune-mediated response to UV light is responsible.
Symptoms: Extremely itchy skin rash, red and inflamed bumps (papules), thickened patches (plaques) and/or lumps (nodules) following exposure of skin to sunlight.
Treatments/cures: In some cases, actinic prurigo may resolve itself. Topical steroids, emollients, phototherapy, thalidomine and oral immunosuppressants.
Differential diagnosis: Polymorphous light eruption, prurigo nodularis, lupus

Actinic Prurigo (AP) is a rare chronic, idiopathic skin condition, which is characterised by abnormal cutaneous responses to ultraviolet radiation (i.e. photosensitivity). AP is thought to be mediated by an abnormal immune response in the background of genetic predisposition. AP is a rare condition and is usually seen in certain populations of the Americas. Skin lesions can appear hours to days after sun exposure and rarely, non-exposed skin can be affected. AP is also known as Hutchinson prurigo. Although AP is not associated with mortality, it can cause significant morbidity in afflicted individuals.

Incidence

Typically, AP first appears in the sunnier months and patients often report exacerbations in symptoms during summer and spring. Rarely, however, the symptoms are worse during winter and autumn, and immunological tolerance during summer is thought to be responsible for this phenomenon. AP tends to occur equally in both the sexes in children and adolescents. In adults, however, females are twice as frequently affected as males. A positive family history of AP or PLE is present in one-fifth of individuals with APThe prevalence of AP in the general population is not known, but is thought to be less than 5% in the above-mentioned populations. In Europe and the Asia-Pacific, where a pathogenetically similar but clinically distinct disease known as polymorphic light eruption (PLE) is more common, rare cases of AP have been reported.AP usually begins in childhood. In some individuals, it may resolve before adulthood. In others, however, it is chronic and tends to recur persistently. Rarely, the disease may arise in adults and the clinical course in these cases is usually chronic.Actinic prurigo can affect the skin of all races, although it is more commonly observed in Latin-American Mestizo and Native American populations. Sporadic cases have been reported in the United Kingdom, the United States, Europe, Australia and Japan.

Causes

Sun-exposure, i.e. exposure to ultraviolet A and B radiation, is the predominant cause of actinic prurigo, yet the reason for the abnormal response to sun exposure is not fully understood. AP is believed to be delayed-type hypersensitivity reaction to antigens exposed or changed following exposure of the skin to ultraviolet radiation. The exact nature of these antigens is not known. It is also believed that genetic predilection may play a role in the pathogenesis of AP, with up to 90% of patients with AP showing various human leukocyte antigen (HLA) variants. In particular, HLA type DRB1*0401 and HLA type DRB1*0407 have been associated with AP.

Cellular involvement in actinic prurigo

Langerhans cells (LC) are believed to play a role in the pathogenesis of AP. LC are antigen presenting cells that are involved in the induction of cell-mediated immune responses to antigens located in the skin. LCs in patients with AP show a reduced susceptibility to ultraviolet radiation. UV-resistant LCs in patients with AP activate immune responses via putative antigens. Because of the presence of UV-resistant LCs, the putative antigens may be delivered to lymphocytes in large amounts or in a chronic fashion, leading to inflammation seen in AP. Thus, a combination of altered expression of adhesion molecules and UV-resistant LCs may be involved in the pathogenesis of AP. Further studies are required to elucidate the identity of these putative antigens and to gain a better understanding of the disease process.Expression of cell adhesion and activation molecules has been shown to be increased in AP. This suggests that lymphocytes in skin lesions of AP are, therefore, activated and may play a role in the damage observed in this condition. An increased adhesiveness of lymphocytes, as a result of increased expression of adhesion molecules, enables them to migrate through the endothelium and extracellular matrix. Similarly, the activation molecules can act on their respective receptors to induce lymphocyte proliferation and activation. Ultraviolet radiation is thought to activate adhesion molecules, such as ICAM-1, via activated lymphocyte infiltrates in keratinocytes, leading to inflammation that is observed in AP.Skin lesions in AP have been shown to be infiltrated by CD4+ T cells. An abnormal immune sensitization occurs against epidermal antigens in AP. AP can be considered as an autoimmune disease, because lymphocyte activation occurs in response to patient’s own ultraviolet-irradiated keratinocytes.

Symptoms

The symptoms of actinic prurigo include:

  • Extremely itchy (pruritic) skin rash;
  • Red and inflamed bumps (papules);
  • Thickened patches (plaques); and/or
  • Lumps (nodules)
The symptoms of AP are often described as similar to those seen in atopic dermatitis (eczema).
In addition to the symptoms listed above, skin ulcerations, crusting and scaling can occur.
Although areas exposed to the sun, such as the cheeks, nose and hands, are more commonly affected, non-exposed areas can rarely occur in severe AP. Pseudo-alopecia of the eyebrows can occur if the face is constantly scratched. In severe cases, permanent mild scarring and hypopigmented lesions may develop.
In about 65% of the patients affected with AP, the lips are affected. Inflammation of the lip (cheilitis) and pruritis are commonly observed. Other features such as oedema, crusting, ulceration and scales may be present. Interestingly, in 10% of the patients with AP, the lips are the only sites that are affected.
In about 45% of AP patients conjunctivae of the eyes are affected. Hyperaemia, brown pigmentation, photophobia, epiphora (excess production of tears), and formation of pseudopterygium (where the conjunctiva adheres to the cornea) are potential symptoms associated with the involvement of conjunctivae.
Diagnosis

Observational diagnosis of actinic prurigo

Nevertheless, blood tests may be performed to rule out systemic diseases with involvement of the skin. The presence of HLA type DRB1*0401, or DRB1*0407 in genetic testing is suggestive of AP. Histological studies may be helpful. As a skin disease that does not involve internal organs, no blood tests are available to diagnose AP.Histologically, mild acanthosis, exocytosis, and spongiosis of the epidermis are observed. Lymphocyte infiltration and lymphoid follicles may be present. Eosinophils are often present. With the conjunctival histology, the epithelium appears thinned and atrophied. The basal cells are vacuolised with lymphocytic infiltration in the sub-mucosal follicles. Eosinophils are conjunctival pigmentation are common findings. The presence of lymphoid follicles in the mucosal and conjunctival laminae is the most characteristic pathological finding in AP.AP is diagnosed based on clinical assessment and the pathological study of the mucosae of the lips, conjunctivae, or the skin.

 

Phototesting and actinic prurigo

Other laboratory tests are used to rule out other systemic diseases with a photosensitivity component, rather than to diagnose AP. The presence of anti-nuclear antibodies and extractable nuclear antibodies should be undertaken to rule out lupus. The highly contagious Scabies should always be ruled out prior to diagnosing AP. When the skin on the nose is not affected, the condition is more likely to be photosensitive atopic dermatitis than AP. Polymorphic light eruption and prurigo nodularis are other morphologically similar diseases that should be excluded during the diagnosis of AP.Phototesting may help with the diagnosis, but is non-specific and does not rule out other photosensitive disorders. The minimal erythema dose, the minimum dose of narrow-band ultraviolet (UVB) radiation that is required to produce redness 24 hours after exposure, is reduced in patients with AP. It should be noted that a negative cutaneous phototesting does not exclude the diagnosis of AP.

Treatments

Actinic prurigo is seldom cured and so preventative measures are important in managing actinic prurigo. The disease may resolve before adulthood in some individuals. In others, however, it is persistent and seasonal outbreaks during summer and spring may occur. Rarely, AP may arise in adulthood and persist throughout life. Treatment is aimed at prevention and controlling symptoms. Avoiding UV exposure and appropriate sun protection measures may be beneficial.

Prophylactic phototherapy may be helpful in some cases. Other treatment options include:

  • Emollients to relieve itching.
  • Topical steroids as anti-inflammatories. Oral steroids may be necessary in more severe disease. Hypersensitivity and infections are possible side-effects of steroid use.
  • Anti-malarial drugs, such as chloroquine, may be effective in some cases. These drugs have anti-inflammatory and photoprotective effects. Also, topical calcineurin inhibitors, such as tacrolimus, may be used to treat relatively mild AP
  • Oral thalidomide, an immune suppressant, is usually effective in treating more resistant AP in all age groups. Adverse effects include drowsiness, headache and weight gain. Nerve conduction studies should be performed regularly to assess for peripheral neuropathy, another side-effect of thalidomine treatment. Thalidomide is teratogenic and pregnancy must be avoided.
  • Oral immunosuppressants, such as azathioprine or cyclosporine.
  • Prophylactic phototherapy with UVB or PVB in spring, when the symptoms usually worsen, may be effective in some patients.
Prevention

Actinic prurigo is an idiopathic disease – i.e. the precise cause(s) of AP are unknown. As sun exposure is the primary trigger of the disease, prudent steps must be taken to reduce or avoid exposure to the sun. The use of sunglasses, wearing appropriate clothing, and the appropriate use of sunscreen may be beneficial. In case of excoriations, sunscreen should be used cautiously. Patients should be taught about the appropriate application of sunscreens. Patients should also be made aware that even minor exposure to ultraviolet radiation may result in outbreaks or exacerbations of symptoms. Annual prophylactic phototherapy may be of benefit in some patients.

Prognosis

Actinic prurigo usually arises in childhood, and persists into adulthood. In some individuals, AP can improve or resolve before adulthood. Rarely, it may arise in adulthood, and persist chronically. Although not a fatal disease, AP can lead to significant morbidity, with exacerbations during the sunnier months. Secondary infections and impetigo are potential complications. Irritant contact dermatitis can manifest with inappropriate use of sunscreens.

References
  • dermnetnz.org (2008) Actinic Prurigo. [Online]. Available online [Accessed 10/12/2008].
  • emedicine.com (2008) Actinic Prurigo. [Online]. Available online [Accessed 10/12/2008].
  • Hawk, J L & Ferguson, J (2008). ‘Chapter 90. Abnormal Responses to Ultraviolet Radiation: Idiopathic, Probably Immunologic, and Photo-Exacerbated’. In Wolff, K, Goldsmith, L A, Katz, S I, Gilchrest, B, Paller, A S & Leffell, D J: Fitzpatrick’s Dermatology in General Medicine, 7th Edition. Available online [Accessed 10/12/2008].
  • McGregor, J M, Grabczynska, S, Vaughan, R, Hawk, J L, Lewis, C L (2000). ‘Genetic Modeling of Abnormal Photosensitivity in Families with Polymorphic Light Eruption and Actinic Prurigo’. The Journal of Investigative Dermatology, Vol 115, pp. 471-476.
  • Ortiz-Castillo, J V, Boto-de Los-Bueis, A, de Lucas-Laguna, R, Pastor-Nieto, B, Pelaez-Restrepo, N, & Fonseca-Sandomingo, A (2006). ‘Topical cyclosporine in the treatment of ocular actinic prurigo’. Archivos de la Sociedad Espanola de Oftalmologia, Vol 81, pp. 661-664.
  • Torres-Alvarez, B, Baradana, L, Fuentes, C, Delgado, C, Santos-Martinez, L, Portales-Perez, D, Moncada, B & Gonzalez-Amaro, R (1998). ‘An immunohistochemical study of UV-induced skin lesions in actinic prurigo: Resistance of Langerhans cells to UV light’. European Journal of Dermatology, Vol 8(1), pp. 24-28.
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