Genetic modeling of abnormal photosensitivity in families with polymorphic light eruption and actinic prurigo

Actinic prurigo and polymorphic light eruption are two of the so-called idiopathic photodermatoses, resulting from abnormal cutaneous responses to ultraviolet radiation (photosensitivity). Whereas they are clinically distinct in most cases, there are sufficient similarities between them to suggest they may be related conditions. To take this further, we examined the prevalence of polymorphic light eruption in families ascertained through actinic prurigo probands, as evidence of a shared pathogenesis. We then determined the heritability of photosensitivity in 420 individuals from families ascertained through polymorphic light eruption and actinic prurigo probands using segregation analysis. Across 58 pedigrees the prevalence of photosensitivity in first-degree relatives was 20.9% compared with a population prevalence of 13.6%, giving a relative risk of 1.5 (confidence interval 1.15-2.0) and providing evidence of clustering within families. The prevalence of photosensitivity (predominantly polymorphic light eruption) in relatives of actinic prurigo probands was 23.7%, with a relative risk of 1.74 (confidence interval 1.24-2.36). Modeling for polymorphic light eruption across all pedigrees revealed a strong genetic component with polymorphic light eruption showing a dominant mixed mode of inheritance. The model parameters estimate that 72% of the U.K. population carry a low penetrance polymorphic light eruption susceptibility allele, but that among this highly prevalent genotype only 24% of susceptible females and 13% of susceptible males will have polymorphic light eruption. Expression of polymorphic light eruption in genetically susceptible individuals (intergenotype variance) is determined in large part by a polygenic component, with an important additional environmental component. In summary, this study provides clear evidence that polymorphic light eruption is an inherited condition. It also suggests that polymorphic light eruption and actinic prurigo share a common genetic background, supporting the view that actinic prurigo may represent a human leukocyte antigen-restricted subset of polymorphic light eruption.     

Actinic prurigo, tropical (South-East Asian) variant.

Actinic prurigo is a chronic familial photodermatitis found predominantly among the Amerindians. It has been reported from North and South America, Britain and Japan. We report a case of actinic prurigo seen in Singapore. A 20-year-old Malay female presented with a persistent pruriginous eruption in the sun-exposed parts and on her abdomen. She also had lower lip cheilitis and thinning of the outer eyebrows, features often seen in actinic prurigo. The minimal erythema dose to ultraviolet A (UVA) and UVB were persistently lowered. We propose that this condition be called actinic prurigo, tropical (South-East Asian) variant.     

A case of actinic prurigo in Thailand

Actinic prurigo is a separate entity from the polymorphous light eruption that affects American Indians. It has been reported mainly from North and South America, with only few reported cases from Britain or Asia. We report a case of actinic prurigo in a Thai girl who showed cheilitis and pruritic papules on exposed areas for three years. We were able to induce populovesicular lesions by three consecutive irradiations with 100 J/cm2 UVA and 2 minimal erythematous dose of UVB. However, three weeks after irradiation, a prurigo papule developed at the UVB irradiated site.     

Successful thalidomide therapy for actinic prurigo in a European woman

Actinic prurigo is a rare, often difficult‐to‐treat, idiopathic photodermatosis. Actinic prurigo is divided into a hereditary form appearing in the Native American population and a sporadic form occurring in non‐Native Americans. We present a 28‐year‐old Caucasian woman who developed typical clinical signs and symptoms of actinic prurigo, just as had her mother and grandmother. The patient and her mother were HLA‐A24 and HLA‐DR 4 with the subtype HLA‐DRB1*0408. Based on clinical symptoms and the HLA pattern, the diagnosis of actinic prurigo was made. Treatment with thalidomide led to resolution of the disease. This case report of a Caucasian woman suffering from a hereditary form of actinic prurigo questions the established classification of actinic prurigo into a hereditary Native American form and a sporadic form occurring in the non‐Native American population.     

Effectors of inflammation in actinic prurigo

BACKGROUND: Actinic prurigo is a specific familial photodermatosis of uncertain pathogenesis. OBJECTIVE: Our purpose was to investigate the immunohistologic presentation of actinic prurigo to explore the involved pathomechanisms. METHODS: The present immunohistochemical study was performed on biopsy specimens from 20 Mexican patients presenting with a severe and perennial form of the disease. RESULTS: The dense inflammatory infiltrate was composed predominantly of helper T type 1 lymphocytes admixed with scattered B-cell lymphoid follicles and numerous dermal dendrocytes. Keratinocytes contained abundant tumor necrosis factor-alpha and calprotectin. CONCLUSION: In subjects genetically predisposed to actinic prurigo, ultraviolet light may trigger excessive tumor necrosis factor-alpha production by keratinocytes whose sustained release in turn exerts its proinflammatory activity and deleterious epidermal effects. Such a cascade of events is in line with the therapeutic benefit already reported when thalidomide is used to treat actinic prurigo.     

Primary cutaneous B-cell lymphoma associated with actinic prurigo

We describe two patients with a diagnosis of actinic prurigo who subsequently developed cutaneous B-cell lymphoma. This is the first report, to our knowledge, of this association. We propose that chronic antigenic stimulation by ultraviolet radiation, in the context of actinic prurigo, may have been causal in the development of these unusual lymphomas.     

Coexistence of adult-onset actinic prurigo and shampoo dermatitis: A case report

Actinic prurigo is a rare and acquired idiopathic photodermatosis. It usually shows childhood onset and female predominance. Here, we present an unusual case of a male patient with coexistence of adult-onset actinic prurigo and shampoo-induced allergic contact dermatitis. He was initially diagnosed with actinic prurigo. However, after detailed examination of the distribution of the rash, careful collection of his history, and interpretation of the results of histopathologic analysis, photo test, patch test, and photopatch test, coexistence of adult-onset actinic prurigo and shampoo-induced allergic contact dermatitis associated with cocamidopropyl betaine was diagnosed. The rash improved after appropriate use of sunscreen and avoidance of shampoo containing this allergen. Dermatologists should be aware of the possibility of concurrent photodermatitis and contact dermatitis.     

Lymphocyte subtypes and adhesion molecules in actinic prurigo: observations with cyclosporin A

BACKGROUND: Actinic prurigo is a photodermatitis in which UV light is implicated by an unknown mechanism. METHODS: Skin biopsies of 19 patients with actinic prurigo and 11 controls were analyzed by immunohistochemistry. RESULTS: In actinic prurigo patients, there was a significant increase in the number of CD3, CD4, CD8, CD45RA, CD45RO, and CD45RB lymphocytes and Langerhans cells, as well as in the level of human leukocyte antigen-DR (HLA-DR) expression and cell adhesion molecules lymphocyte functional antigen-1 (LFA-1), intercellular adhesion molecule-1 (ICAM-1), and endothelial leukocyte adhesion molecule-1 (ELAM-1). Actinic prurigo patients were treated with cyclosporin A (CsA), and a final skin biopsy was taken after 6 months of treatment. All the cell populations and markers studied, except for the CD4 lymphocytes, Langerhans cells, and HLA-DR expression, returned to normal levels. CONCLUSIONS: CsA was found to be effective in relieving the clinical symptoms of actinic prurigo.     

Diagnosis and treatment of the common idiopathic photodermatoses

The idiopathic photodermatoses are the most common cause of photosensitivity and the commonest of these are polymorphic light eruption, actinic prurigo, chronic actinic dermatitis and solar urticaria. The clinical presentation, investigation and treatment of these four disorders are presented. Spontaneous improvement does occur.     

Patch testing in actinic prurigo

42 out of 93 Saskatchewan Indians (32 female (F) and 10 male (M] with actinic prurigo were patch tested to standard series allergens between 1983 and 1987. Positive reactions were most frequently seen with nickel (3F:2M) and colophony. All 3 positive patch tests to colophony were in males. The same patients were also patch tested to extracts of 21 Saskatchewan plants and 3 Hollister-Stier plant extracts. Only 1 male and 2 females had positive patch tests. None of these 3 had rashes on the eyelids, behind the ears or under the chin. We conclude that plant contact dermatitis is unlikely to be mistaken for actinic prurigo in Saskatchewan.     

A case of severe actinic prurigo successfully treated with thalidomide

Actinic prurigo is an uncommon and usually persistent idiopathic photodermatosis with typical human leukocyte antigen (HLA) associations (HLA-DR4, particularly subtypes DRB1*0407 and DRB1*0401). Although its mechanism of action is not clearly understood, thalidomide has been shown to be particularly efficacious in treating actinic prurigo, among other conditions. A 31-year-old Australian woman who had suffered actinic prurigo for most of her life was treated with two courses of thalidomide (50-100 mg nocte) over consecutive summers. Remission was observed after cessation of the second course of thalidomide and had continued 4 years later. Abnormalities in the cutaneous response to ultraviolet radiation at the time of diagnosis, detected by monochromator phototesting, reverted to normal following treatment.     

A case of actinic prurigo showing hypersensitivity of skin fibroblasts to ultraviolet A (UVA)

We here report a patient with actinic prurigo. He had had erythematous papulovesicular eruptions on the sun-exposed sites from fall to early summer for 4 years. The lesions healed leaving atrophic scars. The histology showed epidermal necrosis and dermal dense perivascular lymphohistiocytic infiltration and edema. His minimal erythema doses to ultraviolet B (UVB) and UVA were normal and lowered, respectively. Skin lesions were produced by repeated irradiation with UVA plus UVB, but not with UVA alone. Then he was diagnosed as having actinic prurigo. Skin fibroblasts from the patient were hypersensitive to UVA. We believe that the hypersensitivity relates to the pathomechanisms of the photosensitivity in the case. UVA sensitivity of fibroblasts may be useful for differentiating actinic prurigo, hydroa vacciniforme, and other similar photosensitive disorders.     

Actinic prurigo: a case report with successful induction of skin lesions

A 7-year-old girl with actinic prurigo, probably the first ever published case in Japan, is reported. Intensive irradiation of UV-B and light application of carbon dioxide snow induced the characteristic papules indicating that the patient seemed to respond to various kinds of external stimuli. However, pruritus did not always accompany the appearance of these induced skin lesions. The presentation of skin lesions of actinic prurigo on covered skin and in the winter may partly be explained by these observations.     

Asociación entre HLA-DR4 y prurigo actínico: una revisión exploratoria

IntroductionDifferent studies on actinic prurigo suggest that this pathology may have an autoimmune component. Alterations have been found in peripheral blood cell subpopulations, increased lymphocytes and the expression of adhesion molecules in dermal lesions, in addition to a strong association with HLA class II.ObjectiveDescribe the current status of the association of HLA class II and actinic prurigo in the scientific literature published.Material and methodsScoping review that included PubMed, Scopus y LILACS. Empirical and theoretical publications, without a time limit written in English and Spanish were included.Result26 documents were included there are original research articles (n = 11), congress presentation (n = 1), narrative reviews (n = 6), letters to the editor (n = 4), comment (n = 1), case report (1), and case series (n = 2).ConclusionA strong association between actinic prurigo and HLA-DR4 and subtype DR4 DRB1*0407 is described. It is necessary to conduct a major number of studies for typification in other populations in order to establish the presence of unknown alleles associated with actinic prurigo. Simultaneously, it is important to increase the sample of patients with the disease and control the patient's sample to explore a possible influence of an environmental factor that modulates presence of the actinic prurigo.     

Thalidomide in actinic prurigo

Fourteen patíents sufferíng from actíníc prurígo were treated with thalidomide. Eleven patients showed lasting improvement on the drug and three of these remained symptom-free after discontinuing therapy. No major side-effects were observed. Thalidomide is an effective drug in the treatment of actinic prurigo but it must be used with adequate contraception in women of child-bearing age.     

HLA typing in polymorphous light eruption

Human leukocyte antigen typing of 41 white patients with polymorphous light eruption (limited concept) showed no significant differences when compared with the typing of 51 white control subjects. We previously found that actinic prurigo, an idiopathic photodermatosis particularly associated with Amerindians, has a positive association with antigens A24 and Cw4 and a negative association with A3. We suggest, on the basis of both laboratory and clinical findings, that polymorphous light eruption (limited concept) and actinic prurigo are two different and distinct diseases.     

Association of HLA subtype DRB10407 in Colombian patients with actinic prurigo

BACKGROUND: Human leukocyte antigen (HLA) DRB1*0407 had been associated with actinic prurigo in different populations. This class II HLA-DR subtype had not been studied in Colombia. OBJECTIVE: The objective of this study was to establish whether there was an association of actinic prurigo with HLA DR in a Colombian population. MATERIALS AND METHODS: Forty patients with a clinical diagnosis of actinic prurigo and 40 healthy subjects, paired by age, sex and birthplace, were studied. HLA typing for HLA DRB1 and DRB1*04, if necessary, was performed by the PCR-SSP method using blood samples. RESULTS: A high frequency of HLA DRB1*0407 was found in the patients (97.5% vs. 30%; P<0.00001). The allelic frequency of HLA DRB1*0407 was 63.8% in the case group, and 14.5% in the controls (P<0.00001). In the control group, there was a higher frequency of the alleles DRB1*01 (14.5% vs. 1.25%; P=0.0027) and DRB1*13 (23.7% vs. 2.5%; P=0.00013). LIMITATIONS: The small number of controls does not allow us to drive conclusions about other HLA alleles. CONCLUSIONS: HLA subtype DRB1*0407, found in actinic prurigo patients in studies conducted in England, Scotland, Ireland and Mexico, was also associated in Colombian patients. This finding, concordant in patients from different ethnic groups, could be helpful in the diagnosis of this disease and probably important in its pathogenesis. DRB1*01 and DRB1*13 alleles were more frequent in controls than in patients; we do not know whether they play any role in the resistance to the disease.     

Treatment of actinic prurigo with PUVA: mechanism of action

Five patients with actinic prurigo were treated twice weekly with PUVA. One area on the back was shielded from UVA throughout the 15-week treatment period. Before PUVA, all patients had increased erythemal sensitivity to UVA and showed abnormal augmentation of UVB erythema by topical indomethacin. After PUVA, all patients were free of photosensitive symptoms and skin that had been exposed to UVA showed normal erythemal responses. By contrast, the areas of skin that had been protected from UVA showed erythemal responses that were unchanged from pre-PUVA values. Augmentation of UVB erythema by topical indomethacin persisted, both on UVA exposed and UVA protected skin. These results show that, although PUVA is an effective treatment in actinic prurigo, it does not alter the underlying mechanism of photosensitivity. The protective effect is local and is due presumably to an increase in melanin pigmentation and epidermal thickness.     

Clearance of pediatric actinic prurigo with dupilumab

Actinic prurigo is a rare, idiopathic chronic photodermatosis of childhood characterized by excoriated papules, nodules, and plaques in sun-exposed areas. It is notoriously difficult to treat. The disorder involves a type IV hypersensitivity reaction driven by both Th1 and Th2 inflammatory pathways, the latter of which leads to secretion of IL-4, IL-5, IL-13, and production of B cells, IgE, and IgG4. Dupilumab, an IL-4 receptor antagonist, disrupts the Th2 pathway. We present a pediatric patient with severe, recalcitrant actinic prurigo who achieved rapid and sustained clearance with dupilumab.     

Narrow-band ultraviolet B phototherapy in patients with recalcitrant nodular prurigo

Management of nodular prurigo has been less than satisfactory. Conventional therapies such as systemic antihistamines and topical steroids have not been particularly successful. The effects of narrow-band ultraviolet B (NB-UVB) phototherapy in the treatment of various inflammatory dermatoses have been proven, however, no data exist on the efficacy and the duration of remission in NB-UVB monotherapy for nodular prurigo. The aim of this study was to evaluate the effect of NB-UVB phototherapy on recalcitrant nodular prurigo. NB-UVB phototherapy was performed once a week on 10 patients with recalcitrant nodular prurigo. The initial dose was 0.4 J/cm(2), and the dose was increased by 0.1 J/cm(2) for each treatment. The treatment was performed until the eruption was almost clear. In each patient, a mean cumulative dose of 23.88 J/cm(2) was applied over a mean of 24.3 irradiations. The mean maximum daily dose of ultraviolet B was 1.2 +/- 0.4 J/cm(2). NB-UVB phototherapy notably improved the eruption of nodular prurigo in all patients. Follow up at 1 year revealed that only one patient had relapsed. The remaining nine patients continued to derive long-term benefits. NB-UVB phototherapy appears to be an effective treatment for recalcitrant nodular prurigo, offering long-term benefits in the majority of those treated.